(NATO Science For Peace and Security Series C - Environmental Security) Igor Linkov, Jeffery A. Steevens-Nanomaterials - Risks and Benefits (NATO Science For Peace and Security Series C - Environm-1

Nanomaterials: Risks and Benefits
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Series C: Environmental Security

Nanomaterials:
Risks and Benefits
Edited by
Igor Linkov
US Army Engineer Research
and Development Center
Concord, Massachusetts
U.S.A.
and
Jeffery Steevens
US Army Engineer Research
and Development Center
Vicksburg, Mississippi
U.S.A.
Published in cooperation with NATO Public Diplomacy Division

Based on the papers presented at the NATO Advanced Research Workshop on
Nanomaterials: Environmental Risks and Benefits
Faro, Portugal
27-30 April 2008
Library of Congress Control Number: 2008941252
ISBN 978-1-4020-9490-3 (PB)

ISBN 978-1-4020-9489-7 (HB)
ISBN 978-1-4020-9491 -0 (e-book)
Published by Springer,
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CONTENTS
Preface .................................................................................................................... ix
Acknowledgements ................................................................................................ xi
Part 1. Human Health Risks
Human Health Risks of Engineered Nanomaterials: Critical Knowledge

Gaps in Nanomaterials Risk Assessment ................................................................. 3
A. Elder, I. Lynch, K. Grieger, S. Chan-Remillard, A. Gatti, H. Gnewuch,
E. Kenawy, R. Korenstein, T. Kuhlbusch, F. Linker, S. Matias, N. Monteiro-
Riviere, V.R.S. Pinto, R. Rudnitsky, K. Savolainen, A. Shvedova
Disposition of Nanoparticles as a Function of Their Interactions with
Biomolecules .......................................................................................................... 31
I. Lynch, A. Elder
Assessment of Quantum Dot Penetration into Skin in Different Species
under Different Mechanical Actions ...................................................................... 43
N.A. Monteiro-Riviere, L.W. Zhang
Nanotechnology: The Occupational Health and Safety Concerns......................... 53
S. Chan-Remillard, L. Kapustka, S. Goudey
Biomarkers of Nanoparticles Impact on Biological Systems ................................ 67
V. Mikhailenko, L. Ieleiko, A. Glavin, J. Sorochinska
Nanocontamination of the Soldiers in a Battle Space ............................................ 83
A.M. Gatti, S. Montanari
Part 2. Environmental Risk
SMARTEN: Strategic Management and Assessment of Risks and Toxicity

of Engineered Nanomaterials................................................................................. 95
C. Metcalfe, E. Bennett, M. Chappell, J. Steevens, M. Depledge, G. Goss,
S. Goudey, S. Kaczmar, N. O’Brien, A. Picado, A.B. Ramadan
Solid-Phase Characteristics of Engineered Nanoparticles:
A Multi-dimensional Approach ........................................................................... 111
M.A. Chappell
Nanomaterial Transport, Transformation, and Fate in the Environment:
A Risk-Based Perspective on Research Needs .................................................... 125
G.V. Lowry, E.A. Casman
v
vi CONTENTS
Visualization and Transport of Quantum Dot Nanomaterials

in Porous Media.................................................................................................... 139
C.J.G. Darnault, S.M.C. Bonina, B. Uyusur, P.T. Snee
Developing an Ecological Risk Framework to Assess Environmental Safety
of Nanoscale Products: Ecological Risk Framework........................................... 149
L. Kapustka, S. Chan-Remillard, S. Goudey
Development of a Three-Level Risk Assessment Strategy
for Nanomaterials ................................................................................................. 161
N. O’Brien, E. Cummins
Classifying Nanomaterial Risks Using Multi-criteria
Decision Analysis................................................................................................. 179
I. Linkov, J. Steevens, M. Chappell, T. Tervonen, J.R. Figueira, M. Merad
Part 3. Technology and Benefits
Nanomaterials, Nanotechnology: Applications, Consumer Products, and

Benefits................................................................................................................. 195
G. Adlakha-Hutcheon, R. Khaydarov, R. Korenstein, R. Varma,
A. Vaseashta, H. Stamm, M. Abdel-Mottaleb
Risk Reduction via Greener Synthesis of Noble Metal Nanostructures
and Nanocomposites............................................................................................. 209
M.N. Nadagouda, R.S. Varma
Remediation of Contaminated Groundwater Using
Nano-Carbon Colloids.......................................................................................... 219
R.R. Khaydarov, R.A. Khaydarov, O. Gapurova
A Novel Size-Selective Airborne Particle Sampling Instrument (WRAS)
for Health Risk Evaluation ................................................................................... 225
H. Gnewuch, R. Muir, B. Gorbunov, N.D. Priest, P.R. Jackson
Nanotechnologies and Environmental Risks: Measurement Technologies
and Strategies........................................................................................................ 233
T.A.J. Kuhlbusch, H. Fissan, C. Asbach
Part 4. International Perspectives
Processing of Polymer Nanofibers Through Electrospinning

as Drug Delivery Systems .................................................................................... 247
E. Kenawy, F.I. Abdel-Hay, M. H. El-Newehy, G.E. Wnek
Air Pollution Monitoring and Use of Nanotechnology Based Solid State
Gas Sensors in Greater Cairo Area, Egypt........................................................... 265
A.B.A. Ramadan
Advanced Material Nanotechnology in Israel...................................................... 275
O. Figovsky, D. Beilin, N. Blank
CONTENTS vii
Silver Nanoparticles: Environmental and Human Health Impacts ...................... 287

R.R. Khaydarov, R.A. Khaydarov, Y. Estrin, S. Evgrafova, T. Scheper,
C. Endres, S.Y. Cho
Developing Strategies in Brazil to Manage the Emerging
Nanotechnology and Its Associated Risks ........................................................... 299
A.S.A. Arcuri, M.G.L. Grossi, V.R.S. Pinto, A. Rinaldi, A.C. Pinto,
P.R. Martins, P.A. Maia
The Current State-of-the Art in the Area of Nanotechnology
Risk Assessment in Russia ................................................................................... 309
M. Melkonyan, S. Kozyrev
Environmental Risk Assessment of Nanomaterials ............................................. 317
A.A. Bayramov
Part 5. Policy and Regulatory Aspects
Considerations for Implementation of Manufactured Nanomaterial Policy

and Governance.................................................................................................... 329
F.K. Satterstrom, A.S.A. Arcuri, T.A. Davis, W. Gulledge, S. Foss Hansen,
M.A. Shafy Haraza, L. Kapustka, D. Karkan, I. Linkov, M. Melkonyan,
J. Monica, R. Owen, J.M. Palma-Oliveira, B. Srdjevic
The Safety of Nanotechnologies at the OECD..................................................... 351
P. Kearns, M. Gonzalez, N. Oki, K. Lee, F. Rodriguez
Nanomaterials in Consumer Products: Categorization
and Exposure Assessment .................................................................................... 359
S. Foss Hansen, A. Baun, E.S. Michelson, A. Kamper, P. Borling,
F. Stuer-Lauridsen
Strategic Approaches for the Management of Environmental
Risk Uncertainties Posed by Nanomaterials ........................................................ 369
R. Owen, M. Crane, K. Grieger, R. Handy, I. Linkov, M. Depledge
Methods of Economic Valuation of the Health Risks Associated
with Nanomaterials............................................................................................... 385
S. Shalhevet, N. Haruvy
Nanomaterials: Applications, Risks, Ethics and Society ..................................... 397
A. Vaseashta
Group Decision-Making in Selecting Nanotechnology Supplier: AHP
Application in Presence of Complete and Incomplete Information..................... 409
B. Srdjevic, Z. Srdjevic, T. Zoranovic, K. Suvocarev
Uncertainty in Life Cycle Assessment of Nanomaterials:
Multi-criteria Decision Analysis Framework for Single Wall Carbon
Nanotubes in Power Applications ........................................................................ 423
T.P. Seager, I. Linkov
viii CONTENTS
Knowing Much While Knowing Nothing: Perceptions and Misperceptions

About Nanomaterials............................................................................................ 437
J.M. Palma-Oliveira, R.G. de Carvalho, S. Luis, M. Vieira
Participants ......................................................................................................... 463
Author Index....................................................................................................... 471

PREFACE
Many potential questions regarding the risks associated with the development and
use of wide-ranging technologies enabled through engineered nanomaterials. For
example, with over 600 consumer products available globally, what information
exists that describes their risk to human health and the environment? What engi-
neering or use controls can be deployed to minimize the potential environmental
health and safety impacts of nanomaterials throughout the manufacturing and
product lifecycles? How can the potential environmental and health benefits of
nanotechnology be realized and maximized?
The idea for this book was conceived at the NATO Advanced Research
Workshop (ARW) on “Nanomaterials: Environmental Risks and Benefits and
Emerging Consumer Products.” This meeting – held in Algarve, Portugal, in April
2008 – started with building a foundation to harmonize risks and benefits
associated with nanomaterials to develop risk management approaches and
policies. More than 70 experts, from 19 countries, in the fields of risk assessment,
decision-analysis, and security discussed the current state-of-knowledge with
regard to nanomaterial risk and benefits. The discussion focused on the adequacy
of available risk assessment tools to guide nanomaterial applications in industry
and risk governance.
The workshop had five primary purposes:
Describe the potential benefits of nanotechnology enabled commercial
products.
Identify and describe what is known about environmental and human health
risks of nanomaterials and approaches to assess their safety.
Assess the suitability of multicriteria decision analysis for reconciling the
benefits and risks of nanotechnology.
Provide direction for future research in nanotechnology and environmental
science to address issues associated with emerging nanomaterial-containing
consumer products.
Identify strategies for users in developing countries to best manage this rapidly
developing technology and its associated risks, as well as to realize its benefits.
The organization of the book reflects major topic sessions and discussions
during the workshop. The papers in Part 1 review and summarize human health
impact of nanomaterials. Part 2 includes papers on environmental risks. Part 3
presents benefits associated with nanomaterial enabled technologies over a wide
range of applications. Part 4 encompasses a series of case studies that illustrate
different applications and needs across nanomaterial development and use
worldwide. The concluding Part 5 is devoted to policy implication and risk
management. Each part of the book reviews achievements, identifies gaps in
current knowledge, and suggests priorities for future research in topical areas.
Each part starts with a group report summarizing discussions and consensus
ix
x PREFACE
principles and initiatives that were suggested during the group discussions at the
NATO workshop. The wide variety of content in the book reflects the workshop
participants’ diverse views as well as their regional concerns.
Simultaneous advances in different disciplines are necessary to advance nano-
technology risk assessment and risk management. Risk assessment is an inter-
disciplinary field, but progress in risk assessment has historically occurred due to
advances in individual disciplines. For example, toxicology has been central to
human health risk assessment, and advances in exposure assessment have been
important for environmental risk assessment and risk management. Nanotechnology,
however, ideally involves the planned and coordinated development of knowledge
across fields such as biology, chemistry, materials science, and medicine.
The workshop discussions and papers in the book clearly illustrate that while
existing chemical risk assessment and risk management frameworks may provide
a starting point, the unique properties of nanomaterials adds a significant level of
complexity to this process. The goals of the workshop included the identification
of strategies and tools that could currently be implemented to reduce technical
uncertainty and prioritize research to address the immediate needs of the regulatory
and risk assessment communities. Papers in the book illustrate application of advan-
ced risk assessment, comprehensive environmental assessment, risk characteri-
zation methods, decision analysis techniques, and other approaches to help focus
research and inform policymakers benefiting the world at large.
U.S. Army Engineer Research and Development Center Igor Linkov
Concord, Massachusetts, USA
U.S. Army Engineer Research and Development Center Jeff Steevens

Vicksburg, Mississippi, USA
August, 2008
ACKNOWLEDGEMENTS
The editors would like to acknowledge Dr. Mohammed Haraza (NATO workshop
co-director) and organizing committee members (Drs. Vicki Colvin, Delara Karkan,
Abou Ramadan, Jeff Morris, Saber Hussain, Jose Figueira, Jose Palma-Oliveira
and Carlos Fonseca) for their help in the organization of the event that resulted in
this book. We also wish to thank the workshop participants and invited authors for
their contributions to the book and peer-review of manuscripts. We are deeply
grateful to Deb Oestreicher for her excellent management of the production of this
book. Additional technical assistance in the workshop organization was provided
by Elena Belinkaia and Eugene Linkov. The workshop agenda was prepared in
collaboration with the Society of Risk Analysis Decision Analysis and Risk Specialty
Group. Financial support for the workshop was provided mainly by NATO.
Additional support was provided by the U.S. EPA, U.S. Army Engineer Research
and Development Center, International Copper Association, American Chemistry
Council and University of Algarve.
xi
HUMAN HEALTH RISKS OF ENGINEERED NANOMATERIALS
Critical Knowledge Gaps in Nanomaterials Risk Assessment
A. ELDER
Department of Environmental Medicine
University of Rochester
575 Elmwood Avenue, Box 850
Rochester, NY 14642, USA
Alison_Elder@urmc.rochester.edu
I. LYNCH
Centre for BioNanoInteractions
School of Chemistry and Chemical Biology
University College Dublin
Belfield, Dublin 4, Ireland
K. GRIEGER
Technical University of Denmark
Department of Environmental Engineering
Building 113
Kongens Lyngby 2800, Denmark
S. CHAN-REMILLARD
Golder Associates Ltd./HydroQual Laboratories Ltd.
#4 6125-12th Street S.E.
Calgary T2H 2K1, Canada
A. GATTI
University of Modena & Reggio Emilia
Lab of Biomaterials
Via Campi 213 A
Modena 41100, Italy
H. GNEWUCH
Naneum Ltd.
Canterbury Enterprise Hub
Canterbury CT2 7NJ, UK
E. KENAWY
Polymer Research Group, Department of Chemistry
Faculty of Science, University of Tanta
Egypt
I. Linkov and J. Steevens (eds.), Nanomaterials: Risks and Benefits, 3

4 A. ELDER ET AL.
R. KORENSTEIN
Marian Gertner Institute for Medical Nanosystems
Department of Physiology and Pharmacology, Faculty of Medicine
Tel Aviv University
69978 Tel-Aviv, Israel
T. KUHLBUSCH
Institute for Energy and Environmental Technology
Bliersheimer Street 60
Duisburg 47229, Germany
F. LINKER
Occupational Health Care Services, DSM
ARBODienst DSM, Alert & Case Centre
Kerenshofweg 200
NL-6167AE Geleen, The Netherlands
S. MATIAS
Instituto Superior Téchnico
Universidade Téchnica de Lisboa
Av. Rovisco Pais
1049-001 Lisboa, Portugal
N. MONTEIRO-RIVIERE
Center for Chemical Toxicology Research and Pharmacokinetics
Department of Clinical Sciences, College of Veterinary Medicine
North Carolina State University
4700 Hillsborough Street
Raleigh, NC 27606, USA
V.R.S. PINTO
Rua Capote Valente 710
São Paulo 05409-002, Brazil
R. RUDNITSKY
Office of Space & Advanced Technology
US Department of State
OES/SAT, SA-23, 1990 K Street, NW, Suite #410
Washington, DC 20006, USA
K. SAVOLAINEN
Finnish Institute for Occupational Health, New Technologies and
Risks Topeliuksenkatu 41 aA
GI-00250 Helsinki, Finland
HUMAN HEALTH RISKS OF ENGINEERED NANOMATERIALS 5
A. SHVEDOVA
CDC/NIOSH
1096 Willowdale Road
Morgantown, WV 26505, USA
Abstract. There are currently hundreds of available consumer products that

contain nanoscale materials. Human exposure is, therefore, likely to occur in
occupational and environmental settings. Mounting evidence suggests that some
nanomaterials exert toxicity in cultured cells or following in vivo exposures, but
this is dependent on the physicochemical characteristics of the materials and the
dose. This Working Group report summarizes the discussions of an expert
scientific panel regarding the gaps in knowledge that impede effective human
health risk assessment for nanomaterials, particularly those that are suspended in a
gas or liquid and, thus, deposit on skin or in the respiratory tract. In addition
to extensive descriptions of material properties, the Group identified as critical
research areas: external and internal dose characterization, mechanisms of response,
identification of sensitive subpopulations, and the development of screening
strategies and technology to support these investigations. Important concepts in
defining health risk are reviewed, as are the specific kinds of studies that will
quickly reduce the uncertainties in the risk assessment process.1
1. Introduction
Nanomaterials are commonly described as having at least one dimension smaller

than 100 nm. A broader definition, though, refers to those materials that are
manipulated at the atomic, molecular, or macromolecular scales in order to
achieve functionality that is different from that found in the bulk or molecular
form [106].
Many consumer items are already available that contain nanomaterials, such as
electronics components, cosmetics, cigarette filters, antimicrobial and stain-resistant
fabrics and sprays, sunscreens, and cleaning products [115]. According to a recent
survey of the Wilson Institute web site [29], there are at least 580 consumer
products on the market, including four with FDA approval for therapeutic use.
Although the potential for human exposures has not been fully evaluated and is
likely to be low in many cases, the safety of nanomaterials at a wide range of
doses and throughout the product life cycle should be characterized to ensure
consumer, occupational, and environmental health.
Critical components of a systematic safety assessment for engineered nano-
materials include: evaluation of exposure concentrations in occupational and
1
Summary of the NATO ARW Working Group discussions.
6 A. ELDER ET AL.
environmental settings; the physicochemical characteristics of the material at the

portal of entry; the structure and function of epithelial barriers at the portals of
entry; interactions of materials with biomolecules (proteins, nucleic acids, lipids);
biodistribution and elimination kinetics and identification of possible target organs;
characterization of dose-response relationships; elucidation of mechanisms of
response; identification of target tissues for nanomaterials effects; and identifi-
cation of human subpopulations with unique susceptibility to the effects of
nanomaterials. These concepts are summarized in Figure 1. New products are
rapidly emerging in the nanotechnology industry without a parallel development
of critical information regarding their safety. Furthermore, risk assessments are
currently proceeding in many cases without adequate methodologies to define
risk.
It should be noted that the assumptions used in assessing risks at the early
stages of most emerging technologies are designed to be protective (precautionary
principle) and to emphasize potential problems so that more attention is focused
on managing or mitigating such risks. As the technology progresses through the
product life cycle, more data becomes available and, thus, the assumptions used in
risk assessment become more realistic [10, 94]. This article focuses on the critical
knowledge gaps that impede the risk assessment process as well as strategies for
rapid reductions in those uncertainties.
1 +
+ ? (in gas or liquid)
?
+
4
2 3
2 3
4
to blood, other organs? 5 6
Figure 1. Key issues in assessing human health risk following nanomaterials exposures. (1) What is the
nature of the nanomaterial at the portal of entry (e.g. agglomerated, charged, soluble, size?)?; (2) How
do the physicochemical characteristics of nanomaterials change after deposition in the body (specific
changes likely to depend on portal of entry)?; (3) Do nanomaterials penetrate epithelial barriers?; (4)
Are nanomaterials transported away from the portal of entry to other organs (how much is transported?
What are the target tissues?)?; (5) How do the nanomaterial properties changes as they are transported
in the body (dissolution; protein/lipid binding)?; (6) How do responses at the cellular/tissue level affect
transport of nanomaterials?
2. Characterization of Nanomaterial Exposure
Although there is potential for occupational and environmental exposures to

nanomaterials throughout their life cycle, very little is known about the concen-
trations of such exposures. Furthermore, the characteristics of nanoscale materials
(e.g. size, shape, surface charge, agglomeration state, presence of secondary
coatings from air or liquid carrier) as they might be encountered in the workplace
or the environment are largely unknown.
Workplace exposure data for nanoparticles is scarce. However, Maynard et al.
[59] reported peak airborne levels of respirable particles of single-walled carbon
nanotubes up to 53 μg/m3 in a small university laboratory. Han and colleagues
[28] reported airborne levels of multi-walled carbon nanotubes during spraying,
blending, and weighing operations in a research laboratory that ranged from
undetectable levels to ~400 μg/m3. However, these data are from total particulate
samples at the breathing zone and, thus, the total mass concentration was not
comprised exclusively of nanotubes. Nevertheless, incorporation of control
measures reduced the nanotube-containing dust concentrations to background
levels.
A recent leaflet from NIOSH regarding workplace exposures to nanomaterials
states that current methods for controlling exposures are adequate, but that current
measurement techniques “are limited and require careful interpretation” [69].
These somewhat contradictory statements reflect the need for personnel with
extensive experience and specialized training in the handling and sampling of
nanomaterials. Although NIOSH cites a lack of sufficient evidence as the basis for
not recommending specific surveillance of nanoparticle-exposed workers, a
framework for the safe exploitation of nanotechnology has recently been described
that includes recommendations for methods and instrumentation to assess exposure
levels, characterize particle size and surface area distributions, and to identify
sources of nanoparticle release [58, 67, 68].
2.1. NANOMATERIALS CHARACTERIZATION
One critical research need is the development of methods and equipment for
adequate nanomaterial characterization, as has been previously cited [4, 84, 95,
109, 110]. Nanomaterial properties may also be altered in both biotic and abiotic
environments. Therefore, tools to detect and characterize chemical or physical
modifications of nanomaterials in such environments are needed. There is also a
pressing need to develop standardized assessments of particle characteristics
including size, shape, size distribution, structure and surface area [70]. This would
ensure that the same set of characteristics is described across studies, ultimately
facilitating a comparison between materials and subsequent exposure. Another
critical need is viewed to be the development of a set of reference nanomaterials
that can serve as benchmarks for the investigation of other nanomaterials, thereby
providing a basis for comparison. Reference materials are commonly used in tradi-
tional risk assessment frameworks for effects and exposure analyses. Significant
efforts are being made in this regard, both by the National Institute of Standards
8 A. ELDER ET AL.
and Technology (US) and the Institute of Reference Materials and Measurements
(EU), although the initial focus is on reference materials for calibration of
instrumentation with respect to size determination, rather than reference materials
for benchmarking of potential toxicity. At present, the scientific community lacks
a set of commonly accepted reference materials, including consensus on suitable
positive and negative control nanoparticles for different testing systems.
2.2. CHARACTERIZATION OF EXPOSURES
Assessing external human exposure to nanomaterials requires knowledge regarding

the likelihood of exposure, changes in particle concentration over time, and identi-
fication and characterization of exposure directly prior to uptake. Workplace or
ambient exposures to air- or liquid-suspended nanomaterials may occur. Although
estimates have been reported for selected nanosized compounds [66], no data is
available about actual levels of engineered nanomaterials in ambient environments,
mainly due to the limitations of current measurement methods. There is clearly a
need for a comparative exposure assessment which differentiates the routes and
forms of exposure as well as the morphology of the nanomaterials. This section
will mainly address inhalation exposures in the workplace, because this is currently
seen as the most likely exposure scenario. However, skin and gastrointestinal tract
exposures to gas- or liquid-suspended particles are also possible. Further details
are provided in Kuhlbusch et al. [43] in this same edition.
2.2.1. Measurement Methods
Measurement methods for detection of airborne (nano-) particles can be char-

acterized as (1) online/offline detection methods that distinguish environmental
from product materials, (2) methods for different matrices (gas/liquid/solid), (3)
personal or fixed sampling methods, (4) methods for different exposure metrics
(mass, surface area or number concentration (total and size-resolved), chemical
composition, etc.), and (5) methods that predict lung regional deposited dose.
No optimal method is currently available for measuring nanomaterials exposures,
since, for example, the ideal metric is still a matter of debate. Certainly, the best
method would be a personal sampler that determines all relevant physical and
chemical properties in real time or near-real time within discrete particle size bins.
This is, however, currently unavailable. Nevertheless, first steps towards simul-
taneously determining these properties are ongoing and are of extreme importance
for realistic exposure assessment.
Most exposure measurements have either used an online technique to determine
particle size distribution [42, 46, 63, 114] or offline techniques like thermal or
electrostatic precipitation or diffusion/impaction and subsequent particle char-
acterization [23, 82]. The choice of using particle number-weighted, as opposed to
mass-weighted, size distribution measurements is driven by the expense and
availability of the equipment, the high sensitivity of number concentration
measurements towards nanosized particles, the possible relevance of particle
number concentration for health effects, and the requirement for speciation. Of
similar importance with regard to linking particle properties to health may be the
particle surface area, either as inhalable (Matter LQ 1-DC) or lung deposited
fraction (TSI NSAM). An overview on measurement methods for nanoparticle
detection can be found in Kuhlbusch et al. [44].
2.2.2. Measurement Strategies
One measurement challenge is the differentiation of environmental (background)

from engineered nanoparticles. When deciding on measurement strategies and
methods, the following points have to be taken into account. First, there is a need
for a dynamic detection range, from a single particle to high number concentra-
tions. Secondly, there is a need for particle physical and chemical characterization.
Lastly, the time resolution (online/offline) must be considered.
There are three particle concentration ranges in terms of number that can
currently be evaluated [43]: single particle detection, a concentration of 1,000–
100,000 particles per cm3, and a concentration of more than 100,000 particles per
cm3. Detection of single particles can be achieved using either single particle
aerosol mass spectrometry (AMS) [72] or filter sampling with subsequent single
particle analysis by TEM/EDX. Both techniques have their advantages and limita-
tions, for example, the degree of chemical analysis that is possible. These methods
would allow a differentiation of background from engineered nanoparticles.
Detection of the source of particle concentrations >100,000 particles per cm3
should generally be easy since the source must be in the vicinity of the point of
measurement. The source can either be visually identified or detected by determining
spatial particle number concentration profiles.
The difficulty in assessing nanoparticle exposure at levels between 1,000–
100,000 particles per cm3 is that background particle concentrations can be in the
same concentration range. A first assessment of possible nanoparticle exposure
can be conducted by concurrent measurements of ambient and workplace particle
number concentrations and calculation of ambient particle penetration into the
work area. This approach is possible for concentrations down to a few thousand
particles per cubic centimeter [45]. Hence, clear differentiation of nanoparticles
from environmental nanoscale particles can only be done by the methods described
for single particle analysis.
2.2.3. Levels of Exposure
The limited exposure measurements conducted thus far in the workplace generally
show low levels or levels below the detection limits for exposure during normal
production and handling of nanomaterials. However, the adequacy of existing
detection instrumentation needs to be considered. The exposure-related measure-
ments were conducted in all steps of production and handling from the reactor, to
processing and handling/bagging of, for example, carbon black and titanium
dioxide [38, 45]. Measurements conducted in the presence of a leak within the
palletizing line showed high exposure values indicating that exposure can be
10 A. ELDER ET AL.
possible, especially in cases where engineering controls fail or during cleaning and
maintenance work in large scale nanomaterial production.
Measurements of dustiness of powders containing nanomaterials were conducted
by Dahman and Monz [14] in the framework of the NanoCare Project. This
investigation showed that engineered particles below 100 nm were not normally
released using a counter flow system. However, there were exceptions depending
on the material investigated. This example shows that extrapolations from few
measurements and generalizations to other materials should be done carefully.
2.2.4. Future Tasks
Results are eagerly awaited from ongoing investigations focusing on possible

human exposure during the life cycle of nanomaterials, from production, to their
use in products, and during recycling. Several scenarios exist with different degrees
of likelihood of possible release of nanomaterials into the environment and
subsequent exposure. The following tasks are seen to bring advances in exposure
assessments for nanoscale materials: the development of cost-effective screening
methodologies for assessing exposure, the development of devices that measure
personal exposure, evaluation of the adequacy of health surveillance protocols,
strengthening current methods for assessing agglomerate stabilities in order to
predict the potential for nanoparticle release during handling, the evaluation of
nanoparticle aging during transport (e.g. airborne, in water), and improvements in
the link between exposure assessments and dose metrics.
3. Barrier Function of Skin, Gastrointestinal Tract, and Respiratory Tract
If it can be assumed that most exposures to nanomaterials will occur in air or via
the food chain/drinking water, then the respiratory tract, skin, and gastrointestinal
tract are the primary routes of exposure to nanomaterials. However, other routes
such as intravenous, intradermal, and ocular are important to consider for specialized
applications. A critical component in evaluating the health risks associated with
nanomaterials exposure is knowledge regarding barrier function at the portal of
entry.
3.1. GASTROINTESTINAL TRACT
The gastrointestinal (GI) tract is not likely to be a primary route of exposure to

nanomaterials. However, particles that deposit in the respiratory tract and taken up
by alveolar macrophages are cleared via the mucociliary escalator and then
expectorated or swallowed. Some of the particulate matter, then, that deposits in
the lungs could be cleared to the GI tract (see following discussion about
macrophage-mediated clearance of nanosized particles). However, the barrier function
of the GI tract with respect to nanoparticles is somewhat equivocal.
The transfer of nanoparticles into blood and subsequent tissue distribution is
likely to be very dependent on particle surface characteristics because of the
extreme shifts in acidity and the negatively charged mucous layer in the small
intestine. Early work described the process of persorption, whereby micron-sized
insoluble particles are transported from the intestinal lumen to the blood via
paracellular pathways [113]. This process has been shown in in vivo studies to be
size-dependent, with smaller particles (polystyrene microspheres, colloidal gold)
being absorbed to a greater degree than larger ones [32, 35]. However, studies
with highly insoluble radioactive metal nanoparticles have shown extremely low
transfer into blood following GI tract exposures [41, 103], with some evidence for
an inverse relationship between particle size and percent transfer as well as for
negatively-charged particles having higher transfer rates [97]. Recent studies
employing electron microscopy and elemental analysis have identified nanosized
particulates, possibly from combustion sources or food, in human tissues such as
liver, kidney, and colon [20–22]. Although it is not clear how the particles
accumulated in these organs, both digestive and respiratory tact exposures are
possible explanations. In vitro model systems are likely to have limited predictive
power due to the absence of a mucous layer, which traps charged particles and
potentiates their clearance via the feces.
3.2. SKIN
Skin is the largest organ of the body. Its permeability to engineered nanomaterials
with respect to depth of penetration and interactions with structural components as
well as nanoparticle absorption into blood are not well understood. Recent in vitro
studies have employed flow-through diffusion cells to assess nanoparticle
penetration and absorption through skin.
3.2.1. Potential for Nanomaterials Skin Penetration
Nanomaterials must penetrate the stratum corneum layer in order to exert toxicity
in the lower cell layers. The quantitative prediction of the rate and extent of per-
cutaneous penetration (into skin) and absorption (through skin) of topically
applied nanomaterials is complicated due to many biological complexities, such as
the diversity of the skin barrier function across species and body sites. The stratum
corneum affords the greatest deterrent to absorption. Although the dead, keratinized
cell layer itself is highly hydrophobic, the cells are also highly water-absorbing, a
property that keeps the skin supple and soft as water is evaporated from the
surface. Sebum appears to augment the water-holding capacity of the epidermis;
however, its hydrophobic nature cannot be assumed to retard the penetration of
xenobiotics, including nanomaterials. The rate of diffusion of topically-applied
materials across the stratum corneum is directly proportional to the concentration
gradient of the material across the membrane, the lipid/water partition coefficient
of the material, and the diffusion coefficient of the material. It should be noted that
organic vehicles may themselves penetrate into the intercellular lipids of the stratum
corneum, thus affecting diffusion. Depending on the specific characteristics of the
skin barrier, there is a functional molecular size/weight cut-off that prevents very
large molecules from being passively absorbed across any membrane. The total
12 A. ELDER ET AL.
flux of any material across the skin is also dependent upon the exposed area, with
dose expressed as mass per square centimeter. In vitro studies of nanomaterial
penetration of skin may only approximate the in vivo situation since a long period
of time may be required to achieve steady state conditions and, thus, exceed the
time constraints of in vitro evaluations.
Transdermal flux (penetration) with systemic absorption of topically applied
nanomaterials has obvious implications in toxicology and therapeutic drug
delivery. However, knowledge of the depth and mechanism of particle penetration
into the stratum corneum barrier is crucial. The skin provides an environment
within the avascular epidermis where particles could potentially lodge and not be
susceptible to removal by phagocytosis, yet be available for immune recognition
through interaction with resident Langerhans cells. In fact, it is this relative
biological isolation in the lipid domains of the epidermis that has allowed for the
delivery of drugs to the skin using liposomal preparations.
Several studies have evaluated the hypothesis that nanoparticles can get
through or get lodged within the lipid matrix of skin. Zinc oxide (ZnO, 80 nm) and
agglomerates of titanium dioxide (TiO2) smaller than 160 nm did not penetrate the
stratum corneum of porcine skin in static diffusion cells [19]. Likewise, in vitro
application of ZnO nanoparticles (26–30 nm) in a sunscreen formulation to human
skin led to accumulation of nanoparticles in the upper stratum corneum with
minimal penetration [13]. However, a pilot study conducted in humans about to
undergo surgery showed penetration to the dermis of “microfine” TiO2 that was
applied over a period of 2–6 weeks [105]. Block copolymer nanoparticles (40 nm)
that were topically applied to hairless guinea pig skin in diffusion cells were able
to penetrate the epidermis within 12 h [99]. Additional studies with spherical
(QD565, the number refers to the fluorescence emission maximum) and elliptical
(QD655) CdSe-ZnS semiconductor nanocrystals that were applied to porcine skin
in flow-though diffusion cells showed that penetration is dependent on surface
coating or charge. Polyethylene glycol (PEG)- and carboxylic acid-coated QD565
were localized primarily in the epidermis by 8 h, while the QD565 PEG-amine
penetrated to the dermis. However, shape was also shown to be a determinant of
nanocrystal localization by the fact that the carboxylic acid-coated elliptical
crystals (QD655) did not penetrate into the epidermis until 24 h of exposure [88].
Studies have also reported that nanocrystal surface coatings and charge can
influence their toxicity in human epidermal keratinocytes [89]. These results
highlight the diversity in terms of size and composition of particles that could
possibly penetrate the stratum corneum to reach the deeper, viable layers of skin.
3.2.2. Factors that Affect Penetration Through Skin
Recent studies have demonstrated that mechanical action and perturbations of the
skin barrier can affect the penetration of nanoparticles. For example, Tinkle et al.
[108] reported that even large (0.5 µm) FITC-conjugated dextran beads could
penetrate the stratum corneum of human skin and reach the epidermis following
30 min of flexing. However, the particles did not penetrate the skin at all if it was
not mechanically flexed. Smaller amino acid-derivatized fullerene nanoparticles
(3.5 nm) were able to penetrate to the dermis of porcine skin that was flexed for
60 min and placed in flow-through diffusion cells for 8 h; non-flexed control skin
showed penetration that was limited to the stratum granulosum layer of the
epidermis [65, 87]. QD655 and QD565 coated with carboxylic acid (hydrodynamic
diameters of 18 and 14 nm, respectively) were studied for 8 and 24 h in flow-
through diffusion cells with flexed, tape stripped and abraded rat skin. No pene-
tration occurred with the nonflexed, flexed, or tape-stripped skin. However,
penetration to the viable dermal layer occurred in abraded skin. In some cases,
retention of QD in hair follicles was observed in the abraded skin [117].
Another important consideration is the possible retention of nanoparticles in
hair follicles, as has been alluded to above. Lademann and colleagues [48] showed
that TiO2 microparticles and polystyrene nanoparticles could be localized near
orifices in human hair follicles. Agglomerates of iron oxide and maghemite
nanoparticles with organic coatings (primary particle sizes ~5 nm) have been
shown to penetrate hair follicles and the epidermis of previously frozen human
skin surgical samples, suggesting a potential capacity for nanoparticles to traverse
the dermal barriers [6]. Other studies with TiO2 and methylene bis-benzotriazoyl
tetramethylbutylphenol showed only 10% of the formulation remained in the
furrows of the stratum corneum and infundibulum of the hair follicle of human
skin [57]. QD621, nail-shaped PEG-coated CdSe-CdS nanocrystals that were
topically applied to porcine skin in flow-through diffusion cells for 24 h penetrated
the upper layers of the stratum corneum and were primarily retained in hair
follicles and in the intercellular lipid layers, a situation also seen with carbon
fullerenes [118]. Although it appears that only a small amount of the applied
nanomaterial is retained in hair follicles, the kinetics of this retention and the
possibility of subsequent systemic distribution must be evaluated.
3.2.3. Potential for Nanomaterials Absorption into Blood from Skin
The evaluation of nanomaterial absorption into blood is a complex matter, so

results from in vitro systems that do not have intact microcirculation should be
carefully interpreted. Furthermore, human and porcine skin may react differently
with respect to nanoparticle penetration as compared to smaller organic chemicals
and drugs where, as described above, human and porcine skin are very similar.
Nevertheless, most recent work has demonstrated that absorption into blood would
not be predicted following topical application of nanomaterials to skin. For
example, QD621 nanocrystals that were applied to porcine skin in flow-through
diffusion cells were not found in the perfusate at any time point or concentration
[118]. Likewise, studies with QD565 coated with PEG, PEG-amine, or carboxylic
acid that were topically applied to human skin in diffusion cells for 8 or 24 h
showed that all three QD preparations remained on the surface of the stratum
corneum or were retained within hair follicle invaginations, but were not detected
in the perfusate [64]. Similar observations were made by this same group with
porcine skin exposed to the same particles [88]. A recent in vivo study, though,
showed that nanosized TiO2 that was applied topically to pig skin in sunscreen
14 A. ELDER ET AL.
formulation did not accumulate in lymph node or liver tissue following exposures
for 5 days per week for 4 weeks [90].
These studies demonstrate the complexity of skin and the stratum corneum
lipid barrier with respect to assessing nanoparticle penetration and absorption into
blood. In most cases studied to date, topically applied nanoparticles have not been
shown to be absorbed into the systemic circulation. However, penetration into the
stratum corneum can occur in all animal species studied. This penetration could be
significant relative to immunological and carcinogenic endpoints. Current findings
suggest that surface coatings as well as nanoparticle geometry also seem to modulate
penetration. All of these factors must be studied further if realistic risk assessments
of manufactured nanomaterials are to be made.
3.3. RESPIRATORY TRACT
3.3.1. The Pulmonary Epithelial Barrier
Nanoparticles that are inhaled as singlets have high predicted deposition effici-
encies via diffusional processes in all regions of the respiratory tract [34]. For
singlet particles of ~20 nm, the highest fractional deposition occurs in the alveolar
region, where bulk air flow is low or absent [93]. Nanosized particles are not
efficiently taken up by resident phagocytic cells (alveolar macrophages) [1, 27]
unless they are agglomerated, thus promoting their retention in the lung and
increasing the likelihood of interactions with the epithelial barrier. The alveolar
epithelial barrier has a large surface area (80–140 m2 in humans) [92] and is
extensively vascularized. In a healthy lung, there are only a few cell types with
which nanomaterials might interact in the alveolus: type I epithelial cells (which
cover ~95% of the alveolar surface), type II epithelial cells, and macrophages. The
basement membranes of the type I epithelial cells are continuous with those of
endothelial cells in the pulmonary capillaries, so the total thickness through which
nanoparticles have to travel to reach the blood is 0.3–2.5 μm, including the
interstitial space [80].
The composition of lung lining fluid varies by region of the respiratory
tract. In the alveolar region, the lining fluid consists of surfactants and an
overlying aqueous phase. Pulmonary surfactant is ~90% lipids (mainly disaturated
dipalmitoylphosphatidyl-choline and phosphatidylglycerol with smaller amounts
of cholesterol) and 10% proteins, which are secreted by type II alveolar epithelial
cells [26]. The alveolar lining fluid also contains plasma-derived proteins (e.g.
albumin, transferrin, immunoglobulins) that are critical to host defense functions
[39]. The degree to which nanomaterials might interact with these lipids and
proteins in situ is largely unknown.
3.3.2. Fate of Nanoparticles that Cross the Alveolar Epithelial Barrier
An important factor in assessing the toxicity of nanomaterials is their distribution

throughout the body and persistence in tissues following exposure. Obviously, this
is an issue that is difficult to fully address using in vitro model systems. Trans-
location to extrapulmonary tissues, including the liver and various brain regions
(notably the olfactory bulb), has been demonstrated, albeit in small amounts, for
inhaled nanosized poorly-soluble Mn oxide, 13C, Ag, and 192Ir [18, 41, 77, 78,
104]. In the case of the Mn oxide and 13C nanoparticles, the observed targeting of
the olfactory bulb was reported to be due to transport along the olfactory nerve,
which has projections terminating directly into the nasal cavity. In regards to
targeting of neuronal structures, though, deposition in the nose or alveoli is not an
absolute requirement. Studies by Hunter and Undem [33] showed that nodose and
jugular ganglia of the vagus nerve could be targeted by the intratracheal instillation
of dye tracer particles.
Interestingly, Semmler and colleagues [96] showed that the retention and
clearance kinetics of insoluble radioactive Ir nanoparticles (15–20 nm, count
median diameter) was not different from reports in the literature for larger
particles (polystyrene beads), although this was a mathematical exercise and not a
direct comparison to larger particles with the same chemistry. However, later
studies by this group showed that what was different was the degree of intersti-
tialization of the nanosized 192Ir particles [98]. Oberdörster et al. [75] also reported
that the interstitialization rates were ~10 times higher for nanosized TiO2 particles
delivered to the lungs via intratracheal instillation as compared to larger particles
of the same composition. More recently, Shvedova and colleagues [102] demon-
strated that single-walled carbon nanotubes (SWCNT) delivered via inhalation
exposure (deposited dose of 5 mg/mouse) resulted in the deposition of small
SWCNT structures and the induction of cellular inflammation, LDH and protein
release, and cytokine production that was two- to fourfold greater than responses
that resulted from oropharyngeal aspiration exposure to larger agglomerated
SWCNT structures. Morphometric evaluation of Sirius red-stained lung sections
also showed that SWCNT inhalation caused a fourfold higher increase in fibrosis
compared with that seen after pharyngeal aspiration, with collagen deposition in
peribronchial and interstitial areas. Interestingly, Mercer et al. [60] demonstrated a
fourfold greater fibrotic potency after pharyngeal aspiration of a well dispersed
SWCNT compared to a less dispersed suspension. This potency difference was
associated with a greater potential for smaller SWCNT structures to enter the
alveolar walls and cause interstitial fibrosis. Overall, these results suggest that
inhalation of dispersed SWCNTs leads to greater interstitialization and inflam-
mation as compared to those delivered in an agglomerated bolus by aspiration.
Thus, not only is the persistence or retention of the nanomaterials of importance,
but so too is the distribution within an organ system.
The liver, kidneys, and spleen have been shown to be the organs with the
highest retention of nanoparticles that cross the alveolar epithelial barrier [96,
104]. It is not entirely clear, though, how primary particle size or in vivo dissolu-
tion may affect the accumulation of materials in extrapulmonary organs. Some
studies have reported very rapid accumulation of nanoparticles, as determined via
chemical means, in liver, kidney, and olfactory bulb following respiratory tract
exposures [17, 85, 104]. In comparison to the respiratory tract, nanomaterials that
16 A. ELDER ET AL.
are injected intravenously accumulate in almost all tissues that are harvested [12,
17], although this is somewhat size-and surface chemistry-dependent.
Not surprisingly, surface coating has been shown to be an important deter-
minant of nanoparticle tissue distribution. At least two studies have shown that the
attachment of polyethylene glycol (PEG) to the surface of the semiconductor
nanocrystals increases their circulatory half-life after intravenous injection [2, 5]
due to lowered uptake efficiency by the liver and spleen (reticulo-endothelial
system). Reduced efficiency of liver uptake has also been shown for PEGylated
nanosized magnetite particles [52]. At least for CdSe-ZnS nanocrystals, the
particle size has also been shown to be an important determinant of tissue
retention following intravenous injection. Particles with hydrodynamic diameters
smaller than ~5.5 nm are almost completely eliminated via urine within the first 4
h [12]. Partly due to the effective cut-off size of the kidney filter, somewhat larger
particles are exclusively eliminated over time via the feces [98].
4. Nanomaterials Interactions with Biomolecules
Data from in vivo and in vitro studies suggesting lipid and/or protein oxidation as
a result of nanomaterials exposure provides indirect evidence of interactions with
biomolecules. For example, Oberdörster et al. [74] demonstrated lipid peroxidation,
but not protein oxidation, in brain tissue obtained from largemouth bass that were
exposed to aggregated nC60 fullerenes in tank water. Should such interactions be a
surprise, though? It has long been known that implanted materials acquire a
protein coating that ultimately determines the fate of the implant in terms of
biocompatibility. While this is likely to be the case at the nanoscale, too, the
challenge will be to identify those proteins, lipids, and other biomolecules that
interact with nanoparticles in the target organs and then to characterize the kinetic
nature of those interactions [54]. Progress along these lines has been made
recently with detailed identification of the proteins bound to nanoparticles [8, 9,
16] and the first indications of inappropriate folding leading to protein aggregation
in the presence of nanoparticles [50]. A further challenge will be to understand the
predictive value of this information in the context of human risk assessment.
4.1. INTERACTIONS WITH PROTEINS
Within the medical device community, it is now well accepted that material
surfaces are modified by the adsorption of biomolecules such as proteins in a
biological environment, and there is some consensus that cellular responses to
materials in a biological medium reflect the adsorbed biomolecule layer, rather
than the material itself [25, 55, 73]. Interestingly, recent studies suggest that
nanomaterial surfaces, having much larger surface area than flat ones, are more
amenable to studies to determine the identity and residence times of adsorbed
proteins [9, 40]. The recently introduced concept of the nanoparticle-protein
corona sees the adsorbed protein (biomolecule) layer as an evolving collection of
proteins that associate with nanoparticles in biological fluids, and suggests that
this is the biologically relevant entity that interacts with cells [53].
A recent systematic study of interactions of polystyrene nanoparticles with no
modification (plain) or modified with positive (amine) or negative (carboxylic)
charges indicates that the surface and the curvature (particle size) both influence
the details of the adsorbed proteins, although in all cases, a significant fraction of
the proteins bound were common across all particles [51]. The significance of this
for safety assessment is clear, as it implies that detailed characterization of the
nanoparticles in the relevant biological milieu is vital.
Evidence is emerging in the scientific literature that coating of nanoparticles
with specific proteins can direct them to specific locations – apolipoprotein E, for
example, has been associated with transport of nanoparticles to the brain [61]. The
binding of serum albumin to the surface of carbon nanotubes has also been shown
to induce particle uptake and anti-inflammatory responses in a macrophage cell
line [15].
However, there are several complicating factors, such as the fact that the
biomolecule corona is not fixed, but is rather dynamic. The corona equilibrates
with the surroundings, with high abundance proteins binding initially, but being
replaced gradually by lower abundance, higher affinity proteins. Additionally,
changes in the biomolecule environment, such as during particle uptake and
distribution, will be reflected as changes in the corona. This makes for consi-
derable difficulty in determining the nanoparticle biomolecule corona in-situ, as
attempts to recover the particles for measurement by isolating them from their
surroundings will by their very nature alter the subtle balance of the biomolecule
corona. However, the situation is not all bad. A considerable portion of the
biologically relevant biomolecules – the so-called “hard-corona” [51] – will
remain associated with the nanoparticles for a sufficiently long time so as not to be
affected by the measurement processes.
First indications of a potential role for nanoparticles in misfolding and aggre-
gation events [7, 50] as well as inhibition of misfolding [83] are emerging. A
range of different nanoparticles, including polymer particles, cerium oxide, carbon
nanotubes and PEG-coated quantum dots, enhanced the rate of fibrillation of the
amyloidogenic protein β-2-microglobulin under conditions where the protein was
in the slightly molton-globular state at pH 2.5 [50]. A mechanism based on a
locally high concentration of the protein in the vicinity of the nanoparticle surface,
thus increasing the probability of formation of a critical oligomer, was proposed.
A recent report from Bellezza and colleagues [7] demonstrated the interaction of
myoglobin (Mb) with phosphate-grafted zirconia nanoparticles. Adsorption induced
marked rearrangements of Mb structure, particularly loss of the secondary structure
(α-helices). Two distinct structures were observed: (i) globular aggregates, similar
to those for the native protein, and (ii) very extensive, branching structures of Mb,
with morphological properties similar to Mb prefibrillar aggregates. In this case,
the authors suggest that the prefibril-like aggregates were always observed next to
the zirconia nanoparticles, suggesting that these structures develop from the bound
protein. Studies in animals have shown that C60 hydrated fullerene may have anti-
amyloidogenic capacity, as a single intracerebroventricular injection of a C60
18 A. ELDER ET AL.
hydrated fullerene significantly improved the performance of a cognitive task in

control rats, resulting from inhibition of the fibrillation of amyloid-beta 25-35
peptide [83]. These results may offer a significant therapeutic advantage towards
diseases of the brain, which are often intractable, as well as raising the potential
for risk.
A recent review has summarized much of the current state-of-the-art in
protein-nanoparticle interactions [54]. A major hope of this field of research is that
it will be possible in the future to predict biological impacts of nanoparticles based
on a screening of the proteins for which they have the highest affinity, and an
understanding of the role of these proteins in nanoparticle uptake, trafficking and
subcellular localization.
4.2. INTERACTIONS WITH LIPIDS
There are almost no reports of the interaction between nanoparticles and lipids to
date, although considerable work has been done to develop solid lipid nanoparticles
for targeted drug delivery [36, 81] or using lipids such as phosphorylcholine or
oleic acid to stabilize nanoparticles, including enabling their transfer from organic
solvents to aqueous solutions [11, 24]. Several reports on the use of lipid coatings
to reduce protein binding have also been published recently. Ross and Wirth [86]
reported that laterally diffusible phosphocholine bilayers inside the pores of
colloidal silica nanoparticles suppressed 93% of the binding of avidin relative to
the unmodified silica colloidal crystals. Another recent report shows that gold
nanorods can be coated with lipid bilayers and used as sensors for protein binding,
but that the process is complex and requires issues such as membrane curvature
and adhesion properties [3].
Some studies with the original aim of quantifying the binding of lipids to
nanoparticles have been used as controls within broader studies of protein binding
to nanoparticles. For example, a recent study of human serum albumin (HSA)
binding to polymeric nanoparticles found that the thermodynamics of binding was
very different in the presence and absence of oleic acid, which is a major binding
ligand of HSA. Using isothermal titration calorimetry, the authors found that HSA
binding to the polymeric particles is exothermic, whereas in the presence of oleic
acid the adsorption is endothermic. Binding of oleic acid to the particles was
found to be endothermic [49].
On the basis of the discovery that lipoproteins have a large affinity for
nanoparticles of many different surface compositions, an obvious question that
arises is whether the particles are actually binding the lipoprotein complexes.
Thus, apolipoproteins in blood associate with lipoprotein particles, e.g. chylomicrons
(>100 nm) and high density lipoproteins (8–10 nm), with diameters that are similar
to engineered nanoparticles [56]. These lipoprotein complexes are composed of
triglycerides and cholesterol esters in the core surrounded by proteins and a
monolayer of phospholipids. A study of the binding of cholesterol and triglycerides
to polymeric nanoparticles has shown that the ratio of bound cholesterol to bound
triglyceride corresponds to the ratio in high density lipoprotein, suggesting that the
nanoparticles bind the whole lipoprotein complex [31].
Binding of lipoprotein complexes to nanoparticles could potentially explain

why many of the nanoparticles that bind these proteins and complexes are not
recognized by the body as foreign and as such do not elicit a toxic or immune
response. However, it is early days yet, and considerably more research into
nanoparticle-biomolecule interactions is needed.
5. Mechanisms of Response to Nanomaterials
There is a plethora of studies in the literature regarding the in vitro and in vivo
effects of engineered nanomaterials. However, much of this data is difficult to
interpret because of inadequate particle characterization, exposure doses that are
not well-justified in terms of realistic exposure conditions, or the elution of
substances (impurities) of known toxicity (e.g. transition metals). Nevertheless,
several studies have pointed to oxidative stress as an important mechanistic process
related to nanomaterials toxicity.
For example, Sayes et al. [91] showed that as nC60 fullerenes became more
water-soluble through derivatization of the particle surface, toxicity was drama-
tically reduced. The reduction in cytotoxicity was correlated with a lowered
oxygen radical production by the fullerenes. Nanoparticle oxidative capacity, as
determined using acellular methods, has also been shown to correlate well with
oxidant-sensitive reporter activity in cultured cells and acute in vivo inflammatory
responses [76]. As mentioned above, Oberdörster’s study in bass [74] reported
evidence of brain tissue lipid oxidation and a trend towards reduced glutathione
depletion. Glutathione is an abundant tripeptide with broad antioxidant capacity
and is gradually depleted in favor of the oxidized form as the severity of oxidative
stress increases [71]. Shvedova and colleagues [101] exposed mice to single-
walled carbon nanotubes (SWCNTs) via oropharyngeal aspiration and showed
dose-related increases in granuloma formation (in association with SWCNT
aggregates in tissues), interstitial fibrosis (in areas where SWCNTs were not visible),
neutrophilic inflammation, glutathione depletion, increases in 4-hydroxynonenal,
and increases in soluble inflammatory mediators. Furthermore, in vitro studies
using cultured human keratinocytes and murine macrophages supported the role of
oxidant production in response to nanotubes, as evidenced by the intracellular
formation of lipid peroxidation products and antioxidant depletion. The same
studies also highlighted the role of trace amounts of iron from the synthetic
process in the observed responses [37, 100]. This latter study, in particular,
highlights the need to identify transition metals, either as contaminants or
structural components, in nanomaterial preparations as part of a safety evaluation.
In addition to the oxidative stress hypothesis, there is also compelling data
regarding the role of surface coating or charge as a determinant of particle
toxicity. Early studies using near micron-sized polystyrene micellar particles
(~750 nm) demonstrated the principle that a negative surface charge was
responsible for membrane depolarization and inflammatory cytokine induction in
bronchial epithelial cells [112]. Likewise, a negative surface charge of micron-
sized ambient particulate matter from diverse sources was correlated with
20 A. ELDER ET AL.
increases in intracellular calcium and cytokine induction [111]. These responses

were thought to be related to the activity of acid-sensitive receptors on the cell
surface, suggesting cell type specificity of response (e.g. neuroepithelial). Ryman-
Rasmussen and colleagues [89], though, recently showed that negatively-charged
CdSe-ZnS semiconductor nanocrystals were more cytotoxic in human epidermal
keratinocytes than positively-charged particles of the same size and composition.
The extent to which these mechanisms may be involved in the responses of
diverse cell types to nanosized particles remains to be determined.
Following in vivo exposures, a combination of factors will ultimately deter-
mine the toxicity of a given material: oxidative capacity is likely to be related to
acute responses and in vivo solubility; interactions with proteins and lipids may
modify these processes (either increase or decrease toxicity) and also determine
the biodistribution of the particles; and the persistence of the material will affect
the long-term clearance and effects.
6. Sensitive Subpopulations
Knowledge regarding the biodistribution of nanomaterials as well as the mecha-

nisms of response to them will lead to reasonable hypotheses regarding subpopu-
lations that might experience adverse effects following exposure where other
individuals will not. For example, individuals with underlying cardiopulmonary
disease are more susceptible to the effects of ambient particulate air pollution [47,
79, 107]. Pre-existing bacterial or viral infections or disease states (e.g. diabetes)
can contribute to oxidant-antioxidant imbalance or the activation status of
inflammatory cells such that nanomaterials exposure could lead to persistent and
overwhelming oxidative stress and tissue injury. In addition, inflammatory disease
states can affect epithelial barrier function [30, 62, 116], thus altering the
distribution of nanomaterials that are deposited in the respiratory tract or that are
circulating in the blood. Depending on the route of exposure and the character-
istics of the nanoparticles, many studies have demonstrated accumulation in major
organ systems and passage through epithelial barriers. This raises the possibility
that nanosized particles can also accumulate in germ line cells or the placenta and
perhaps be transferred to the developing fetus, although this is an issue that has
not received a great deal of attention.
7. Summarizing Concepts
7.1. ACCEPTABLE SCREENING STRATEGIES
In general, there are no commonly accepted screening assays for nanomaterials

health effects. The American Society for Testing and Materials recently adopted a
set a screening tests for the safety evaluation of nanomaterials intended for
therapeutic use, including blood cell hemolysis, cytotoxicity in porcine kidney and
human hepatocarcinoma cells, and the formation of mouse granulocyte-macrophage
colonies. For nanomaterials that may be encountered in the workplace or the envi-
ronment, though, any screening strategy needs to be related to known mechanisms
of response and/or aspects of the material physico-chemistry that predict in vivo
responses. Some examples could include measurements of the oxidative capacity
of the particle surface and assessment of protein binding. However, these kinds of
assays have not yet been validated.
7.2. SUMMARY OF URGENT RESEARCH NEEDS
The most pressing research needs for the purpose of reducing the uncertainties in
nanomaterials risk assessment are apparent from the preceding text. They include
characterizations of external and internal exposures and identifications of mechanisms
of response and sensitive subpopulations, all of which must be supported by
thorough physicochemical characterization of test materials. This knowledge is
likely to lead to useful screening approaches, as illustrated in Figure 2.
Exposure Assessment Target Organ Dose

Nanomaterial
Characterization
Mechanisms Sensitive
Subpopulations
Screening
Strategies
Figure 2. Overview of the immediate research needs in regards to human health risk assessment of
nanomaterials.
A full understanding of external exposure includes measurements of particle

concentrations and physicochemical properties over time in gas or liquid carriers.
In particular, the impact of agglomeration/deagglomeration behavior and soluble
forms of the material need careful attention. Critical information for determining
internal dose of nanomaterials includes an evaluation of the ability of the material
to breech physiological barriers, the dose to and retention in target organs and
cellular/subcellular structures, changes in the physicochemical properties of the
material as it is distributed in the body, and how the interactions of the material
with endogenous biomolecules ultimately affect target organ dose. Some of these
efforts will require the development of new technologies, particularly for
nanoparticle-containing aerosol characterization.
Although it has presented a challenge for particle toxicologists in the past, in
vivo-to-in vitro dose comparisons would be helpful not only in understanding the
relevancy of in vitro test results, but also in the development of screening assays.
Determinations of mechanisms of action also need to be clearly linked to realistic
external and internal doses. However, it should be recognized that mechanistic
22 A. ELDER ET AL.
information will be critical in identifying sensitive subpopulations that may have

lower thresholds for responding to nanomaterials because of, for example,
alterations in repair of tissue damage or oxidant/antioxidant imbalance.
Lastly, it is imperative that there is strong global commitment to funding these
essential research areas. It is more cost-effective in the long term to proactively
address these critical knowledge gaps than to be reactive in regards to
nanomaterials health risk assessment. Especially in light of significant scientific
uncertainty and a lack of clear regulation, such an approach will allow the
nanotechnology industry to flourish while increasing openness and transparency in
decision-making processes.
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DISPOSITION OF NANOPARTICLES AS A FUNCTION
OF THEIR INTERACTIONS WITH BIOMOLECULES
I. LYNCH
Centre for BioNano Interactions
School of Chemistry and Chemical Biology
iseult@fiachra.ucd.ie
A. ELDER
Department of Environmental Medicine, University of Rochester
575 Elmwood Avenue, Box 850
Alison_Elder@urmc.rochester.edu
Abstract. This review focuses on emerging concepts in the fundamental under-

standing of how particle surfaces interact with components in biological fluids,
with an emphasis on how these interactions may inform research regarding the
biodistribution of nanosized materials from the portal of entry to other organ systems.
The respiratory tract is given particular focus here because of expected occupational
and environmental exposure scenarios. Information regarding the biodistribution
of nanoparticles and how they might be altered during the process by their local
environment is a critical part of a complete human health risk assessment.
1. Introduction
Nanomaterials can be described as having at least one dimension smaller than 100
nm. More broadly, though, they are materials that are manipulated at the atomic,
molecular, or macromolecular scales in order to achieve unique functionality [39].
Many consumer items are available that contain nanomaterials, as is a small
number of FDA-approved therapeutic agents [42]. The likelihood of human exposures
has not been fully assessed for the full product life cycle and is likely to be low in
many cases (e.g. when the material is embedded in a solid). Nevertheless, the
safety of these materials must be assessed in a systematic way to ensure standards
of protection for consumer, occupational, and environmental health.
In assessing human health risk from nanomaterials exposure, it is important to
consider the likely routes of entry into the body. Such routes include the respiratory
tract, gastrointestinal tract, and skin [7] for consumer, occupational, and environ-
mental exposure scenarios. Determining the retained dose and effects at the portal

32 I. LYNCH AND A. ELDER
of entry are critical components of nanomaterials risk assessment, as are the

disposition of the material following exposure and effects in tissues distant from
the portal of entry. The disposition of nanomaterials and their effects are likely to
be dependent on properties of the surface, as this will determine interactions with
biomolecules.
This paper describes some of the current concepts and literature regarding how
nanoparticles (NPs) interact with biomolecules and tissues. Common themes are
highlighted, but not meant to be comprehensive, thus leaving room for new
insights as this field grows into maturity.
2. Interactions of Nanoparticles with Biomolecules
In the medical device community, it has long been understood than materials
surfaces are covered by a layer of biomolecules immediately upon contact with
physiological systems (e.g. upon implantation) which mediates the interaction of
the material with the surrounding tissue [41]. It is likely that this phenomenon will
also be the key to understanding much of the bio-nano-science world [25] and it
has recently been argued that the effective unit of interest in the cell–nanomaterial
interaction is not the NP per se, but the particle and its ‘corona’ of more or less
strongly associated proteins from serum or other body fluids [26]. Ultimately it is
this corona of more or less disrupted proteins ‘expressed’ at the surface of the
particle that is ‘read’ by living cells. The high surface to volume ratio of NPs
means that the adsorption potential is hugely amplified by the amount of surface
exposed to living tissue (for example, there are 800 m2 surface area per litre
solution at 1% concentration of 70 nm particles).
There are additional complications relating to the particulate nature of NPs,
and to the fact that (when sufficiently small) they can access almost every organ
(see Section 3) and then be taken up into cells as opposed to interacting only with
cell surface receptors, as is the case with the more traditional biomaterials. Thus, it
is the nature of the organization of the adsorbed proteins and other biomolecules
on the surface of NPs, and any subsequent colloidal instability of either the NPs
(e.g. particle aggregation, flocculation, precipitation etc.) or the adsorbed proteins
(such as protein aggregation, clustering, fibrillation etc.) that determines the initial
biological responses to the presence of NPs.
2.1. INTERACTIONS OF NANOPARTICLES WITH PROTEINS
Proteins constitute a major fraction of the dry mass of cells, and in fact represent
about 18% (with water accounting for 70%) of a typical mammalian cell. Lipids
(~5%), polysaccharides (~2%) and DNA and RNA are other macromolecular
components of cells [2]. It is estimated that there are more than 1 million different
proteins in the human proteome, while in plasma there are over 3,700 different
proteins [28]. Thus, it is clear that the diversity of NP–protein interactions is
enormous, and the potential impacts of NPs on protein functioning are significant.
The recently introduced concept of the NP-protein corona sees the adsorbed
DISPOSITION OF NANOPARTICLES 33
protein (biomolecule) layer as an evolving collection of proteins that associate

with NPs in biological fluids based on abundance (initially) and affinity (higher
affinity proteins are selectively enriched over time), and suggests that this is the
biologically relevant entity that interacts with cells [25].
If our understanding of the risks associated with NPs and nanomaterials is to
evolve, we need to begin to make serious connections between the nature of the
NP-protein complex following different routes of exposure and the biological
consequences of NP uptake and translocation. This has particular relevance in
terms of the portal of entry of NPs, which in many cases is the lung (based on
collective experience from ultrafine particles), and subsequent translocation to the
systemic circulation and extrapulmonary organs, as the particles will have initial
contact with biomolecules from the lungs, including surfactant proteins and lipids.
The protein and lipid milieu of the respiratory tract exhibits considerable
regional variability. In the alveolar region, the lining fluid consists of surfactants
and an overlying aqueous phase. Pulmonary surfactant is ~90% lipids and 10%
proteins. The main physiological role of surfactant is to keep both the alveoli and
bronchioles patent during respiration. The lipid component is composed largely of
disaturated dipalmitoylphosphatidylcholine and phosphatidylglycerol with smaller
amounts of cholesterol. Surfactant proteins are also associated with the lipid layer
and are secreted by type II alveolar epithelial cells [18]. The alveolar lining fluid
also contains plasma-derived proteins (e.g. albumin, transferrin, immunoglobulins)
that are critical to host defense functions [22]. For ultrafine pollution particles
(whose dimensions are similar to those of many NPs), it has been shown that
particles deposited in the hypophase may interact with lung surfactant proteins A
and D or glycoproteins [21]. This study identified 13 mass fragments, diagnostic
of the amino acids alanine, arginine, asparagine, aspartic acid, glutamic acid,
glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, serine, and
valine, providing evidence that amino acids related to opsonin proteins adsorb to
nonbiological particle surfaces exposed to human lung lining fluid.
There is already considerable evidence that adsorbed biomolecules can
(temporarily) mediate the effect of particles of known toxicity, such as quartz
silica and kaolin clays. For example, binding of serum proteins to cristobalite (a
form of crystalline silica) shifted the dose at which an inflammatory response was
observed to a higher concentration; the same effect was found with titanium
dioxide and asbestos [4]. Several studies have shown that simulated pulmonary
surfactant delays the onset of cytotoxicity, DNA-damaging activity, and apoptosis
induction by respirable quartz and kaolin in cultured cells [16, 17]. Another study
also demonstrated that Diesel exhaust particles, but not carbon black, could bind
to a pro-inflammatory molecule (interleukin-8) and that this binding was weakly
inhibited with high serum concentrations [33]. Thus, there already exist clear
linkages between adsorbed biomolecules and mediation of NP toxicity effects, and
a systematic evaluation of the nature of the proteins that adsorb to NPs upon
deposition in different sites in the lungs and correlation of this with biological
effects would offer enormous potential for screening of the estimated >30,000 NPs
that are under development in laboratories and industries worldwide.
In order to really understand the implications of NPs on living systems,

identification of the adsorbed proteins and their residence times is not sufficient,
as the situation is dynamic and evolves as the NPs are transported around the
system. As highlighted already in this volume [14], information is also required
about the binding affinities and stoichiometries, and on the nature of the groups of
proximate amino acid residues that are expressed at the outer surface of the
adsorbed protein layer (the biological identity). This will require significant efforts
from biophysicists and others over several years to really tease out these detailed
(so-called) epitope maps [25].
However, there are several complicating factors, such as the fact that the
biomolecule corona is not fixed, but is rather dynamic. The corona equilibrates
with the surroundings, with high abundance proteins binding initially, but being
replaced gradually by lower abundance, higher affinity proteins. Additionally,
changes in the biomolecule environment, such as during particle uptake and distri-
bution, will be reflected as changes in the corona. This makes for considerable
difficulty in determining the NP biomolecule corona in-situ, as attempts to recover
the particles for measurement by isolating them from their surroundings will by
their very nature alter the subtle balance of the biomolecule corona. However, the
situation is not all bad. A considerable portion of the biologically relevant
biomolecules – the so-called “hard-corona” [44] – will remain associated with the
NPs for a sufficiently long time so as not to be affected by the measurement
processes.
A recent review has summarized much of the current state-of-the-art in
protein–NP interactions [45]. A major hope of this field of research is that it will
be possible in the future to predict biological impacts of NPs based on a screening
of the proteins for which they have the highest affinity, and an understanding of
the role of these proteins in NP uptake, trafficking and subcellular localization.
2.2. INTERACTIONS OF NANOPARTICLES WITH LIPIDS
Pulmonary surfactant is a phospholipid-protein complex, components of which are

secreted by type II alveolar epithelial cells and Clara cells. Changes have been
found in phospholipid concentrations in bronchoalveolar lavage fluid (BALF) of
patients with pulmonary fibrosis, indicating that phospholipid is involved in fibrotic
processes, such as occurs following prolonged, high-dose particulate exposures.
Kuroda and colleagues [24] also demonstrated in rats that phospholipid concen-
trations in lung lavage fluid were increased significantly throughout a 6 month
period following crystalline silica exposure and that the increases correlated with
the severity of the inflammatory response.
The interactions of fine particles (urban PM2.5) and surfactant removed from
human lungs by bronchoalveolar lavage were studied using a surface analysis
technique to identify which of the chemical components of lung lining fluid deposit
on PM2.5. The most strongly associated mass fragment on PM2.5 surfaces
exposed to BALF was di-palmitoyl-phosphatidylcholine, a component of lung
surfactant [21].
Thus, while there is significant literature on the interactions of ultrafine

particles with lipids, evidence of engineered NPs interactions with lipids is only
beginning to emerge [3]. A very recent study of the interaction of 15 nm gold NPs
with semisynthetic pulmonary surfactant (dipalmitoyl-phosphatidylcholine (DPPC)/
palmitoyl-oleoyl-phosphatidyl-glycerol/surfactant protein B (SP-B) in the ratio
70:30) showed that low levels of gold NPs (3.7 mol% Au/lipid, 0.98% wt/wt)
impeded the surfactant’s ability to reduce surface tension (gamma) to low levels
during film compression and to re-spread during film expansion [3]. The authors
concluded that gold NPs can interact with and sequester pulmonary surfactant
phospholipids and, if inhaled from the atmosphere, could impede pulmonary
surfactant function in the lung. Carbon nanotubes have also been shown to adsorb
surfactant lipids and proteins, thereby modulating the function of pulmonary
surfactant [33]. It is not yet clear if all nanomaterials can alter the concentration –
as demonstrated for crystalline silica – or function of phospholipids in the lung or
if lipid–NP interactions will change the “biological identity” of the particle surface.
3. Disposition of Nanoparticles Following In Vivo Exposures
The physiological barriers with which nanomaterials are likely to interact –

namely skin and the gastrointestinal and respiratory tracts – are diverse both
structurally and physiologically. It is, therefore, somewhat unlikely that a single
NP physicochemical property will explain all interactions with target tissues. For
example, NPs that are taken up via the gastrointestinal tract are exposed to the
highly acidic environment of the stomach and then interact with a mucous gel
layer once they reach the intestines. These factors are not present in skin or lung,
nor are there such extreme environmental shifts. For each of the barriers, it is
important to understand how peculiarities of structure and physiology might
impact interpretations regarding the physicochemical characteristics that are
hypothesized to determine NP fate and effects following exposure. More details
about the three different barriers are provided in Elder et al. [14]. Likewise, the
unique protein and lipid environments at these barriers are likely to affect how
NPs are initially, at least, transported in the body. This section will focus on the
respiratory tract, as other papers in this book address skin and the gastrointestinal
tract.
3.1. THE RESPIRATORY TRACT BARRIER
It should be stated at the outset that in evaluating NP disposition, it is important to

consider what it is that is being detected chemically or microscopically: the
particle itself or a component of the particle (solute, tracer molecule). Obviously,
the former is more desirable. Materials that lend themselves well to disposition
and biokinetics studies are fluorescent (e.g. semiconductor nanocrystals, quantum
dots, QDs) and electron-dense metal NPs. Nevertheless, physicochemical char-
acteristics such as primary particle size, shape, surface coating, surface charge,
hydrophobicity, agglomeration state in relevant solutions, and solubility are
important parameters. QDs and metal NPs have been used extensively to evaluate
the barrier function of the skin and respiratory tract in regards to nanomaterials.
Another attractive feature of these two NP types is that it is possible to vary
surface chemistry without changing particle core chemistry, but studies taking
advantage of this are somewhat limited.
There are many ways to deliver nanosized particles to the respiratory tract
in order to gain information about their disposition, including intranasal and
intratracheal instillation, oropharyngeal aspiration, intratracheal microspray, and
nose-only, intratracheal, or whole-body inhalation. Both the dose rate and dose
distribution are artificial with the instillation and aspiration methods. However,
such delivery is acceptable for screening studies or when the exposure material is
precious and follow-up studies are planned [12]. For nanosized particles delivered
via inhalation as singlets, mathematical predictions suggest that they will effici-
ently deposit via diffusional processes in all regions of the respiratory tract,
although the highest fractional deposition for particles of ~10–100 nm occurs in
the alveolar region [20]. Two important anatomical features of this region of the
respiratory tract are (1) the large surface area of the alveolar epithelium and (2) its
high degree of vascularization. Deposition also occurs, though, in the tracheo-
bronchial and nasopharyngeal-laryngeal regions, which contain projections of
sensory nerves. Dendrites of the olfactory nerve, for example, project directly into
the nasal epithelium.
Clearly, then, given the different biological milieu represented by the various
deposition sites (detailed in Section 2.1 above), a systematic investigation of the
effects of NP size coupled to surface physicochemical properties and consequent
adsorbed biomolecule coronas on NP biodistribution is a key direction for
immediate research to begin to address one of the most significant gaps in current
knowledge related to NP safety assessment.
3.2. TRANSLOCATION OF NANOSIZED PARTICLES
In the alveolar region of the lung, where 10–100 nm diameter particles are
predicted to deposit efficiently, there is a limited number of cells with which to
interact in a healthy lung, namely alveolar macrophages and type I and type II
alveolar epithelial cells. Particles that agglomerate and remain in that state in
alveolar lining fluid may be taken up by alveolar macrophages and removed via
mucociliary clearance. However, this clearance mechanism does not work well for
NPs [1, 19], thus promoting their retention in the lungs and possibly leading to
interactions with epithelial cells. Via mechanisms such as endocytosis and passive
transcellular or paracellular translocation, NPs can gain access to the interstitial
space and the blood. In the upper respiratory tract and in the tracheobronchial
region, NPs can also be taken up by sensory neurons; the existence of sensory
neurons in the alveolar region of the lung is somewhat controversial.
Several studies have now shown that the alveolar epithelium, at least, permits
transfer of nanosized particles into the interstitial space. Oberdörster et al. [29]
showed that the interstitialization of nanosized TiO2 particles proceeded at a rate
that was ~10 times faster than larger particles of the same composition that were
delivered to the lungs via intratracheal instillation. Geiser et al. [15] reported that a
substantial fraction (~20%) of inhaled nanosized TiO2 particles could be found in
alveolar epithelial cells, the interstitium, and blood cells within 1 h of exposure.
Other recent studies have also shown a high degree of interstitialization for
nanosized 192Ir particles [35]. Evidence was also presented that suggested that the
interstitialized particles could then be transported back to the airway epithelium
for elimination. These studies have been done with spherical NPs, but work with
single-walled carbon nanotubes, which are fibrous in nature, suggests that those
particles that are better dispersed upon delivery to animals (e.g. via inhalation)
have a greater interstitial fibrotic potential [27, 36].
Although the amounts of deposited NPs that leave the alveolar surface and
travel into the interstitium and blood are small, several studies have demonstrated
that they accumulate in extrapulmonary organs [13, 23, 30, 31, 37, 38]. NPs of
various compositions were used (Ag, Au, Mn oxide, 13C, and 192Ir) and were
generated in the gas phase and delivered via whole-body or intratracheal inhalation.
It is important to note that it is likely that the NP itself and not a solute or label
was being tracked in these studies. With the exception of Mn oxide and Ag NPs,
which would be predicted to have limited in vivo solubility, the other particle
types are very poorly soluble. In addition to tissues such as liver and spleen, the
central nervous system was also shown to be a site of NP accumulation [13, 30,
31, 38]. It is proposed that NPs that are deposited onto the nasal epithelial surface
after inhalation exposures are translocated to the olfactory bulb via the olfactory
nerve and, possibly, to more distal brain structures [5, 6, 10, 11].
The liver, kidneys, and spleen have been shown to be the organs with the
highest retention of NPs that cross the alveolar epithelial barrier [34, 38]. Similar
to what was observed for NPs accessing the interstitium, it also appears that NPs
accumulate very rapidly in extrapulmonary organs [38]. In comparison to the
respiratory tract, nanomaterials that are intravenously injected accumulate in
almost all tissues [9], although this is somewhat dependent on particle size and
surface chemistry. It is to be expected that NPs will encounter very different
protein and lipid milieu as they are transported from the lungs to extrapulmonary
tissues, both in terms of distinct species and their relative abundances. The degree
to which biodistribution depends on interactions of the NP surface with
endogenous proteins and lipids is largely unknown, but is the subject of current
research.
One last issue is that the integrity of the epithelial barrier must be considered.
This is likely to be of importance for two reasons. For one, inflammation can alter
that the permeability of epithelial barriers [40, 43], thus potentiating transfer of
NPs from the site of deposition to more distal organs. Indeed, a recent study by
Chen and colleagues [8] showed that the transfer of radiolabeled nanosized, but
not 200 nm, polystyrene beads into the blood following intratracheal instillation
exposures in rats was potentiated by pre-exposure to bacterial lipopolysaccharide,
a known inflammatory stimulus. Secondly, soluble inflammatory mediators that
are present at the site of injury could become associated with the NP surface and
either affect distribution or induce effects in tissues where the particles accumulate.
Thus, the possibility exists that individuals with compromised barrier function
(e.g. ongoing inflammation due to underlying disease or concurrent exposure to

inflammatory stimuli) may be more susceptible to the effects of NPs.
4. Summary and Concluding Remarks
Several important concepts were reviewed here in regards to the biodistribution of

NPs that are deposited in the respiratory tract. First, translocation is dependent on
particle size. Secondly, the organs in which NPs accumulate is likely to reflect the
site of deposition in the lung and the physicochemical characteristics of the
NPs (agglomerate state, solubility, e.g.). These parameters (deposition site and
physicochemical characteristics) also determine the proteins and other biomole-
cules that adsorb onto the NPs immediately upon contact with the cells of the
lung, and thus confer a “biological identity” to the NPs, which interacts with the
cellular machinery and determines uptake and translocation pathways. The integrity
of epithelial barrier is also a critical factor (e.g. lung inflammation). Lastly, it
should be clear from the concepts reviewed herein that a well-done nanomaterials
risk assessment requires a multidisciplinary approach, a global commitment to
research funding, and a need for the development of new technologies such as
screening assays and measurement tools. Such an approach should result in a rapid
reduction in the uncertainties of the current risk paradigm and ensure the future
success of the nanotechnology industry.
Acknowledgements
The authors are supported by the following funding: NIEHS Center grant P30
ESO1247, EPA STAR grant RD 83172201, DoD MURI FA9550-04-1-0430, NIH
R01 CA134218, EU FP6 project NanoInteract (NMP4-CT-2006-033231), ESF
Network EpitopeMap, IRCSET, SFI SRC BioNanoInteract (07/SRC/B1155) and
HEA PRTLI4.
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ASSESSMENT OF QUANTUM DOT PENETRATION INTO SKIN
IN DIFFERENT SPECIES UNDER DIFFERENT MECHANICAL
ACTIONS
N.A. MONTEIRO-RIVIERE, L.W. ZHANG

Center for Chemical Toxicology Research and Pharmacokinetics
nancy_monteiro@ncsu.edu
Abstract. Skin penetration is one of the major routes of exposure for nanoparticles
to gain access to a biological system. QD nanoparticles have received a great deal
of attention due to their fluorescent characteristics and potential use in medical
applications. However, little is known about their permeability in skin. This study
focuses on three types of quantum dots (QD) with different surface coatings and
concentrations on their ability to penetrate skin. QD621 (polyethylene glycol
coated, PEG) was studied for 24 h in porcine skin flow-through diffusion cells.
QD565 and QD655 coated with carboxylic acid were studied for 8 and 24 h in
flow-through diffusion cells with flexed, tape stripped and abraded rat skin to
determine if these mechanical actions could perturb the barrier and affect
penetration. Confocal microscopy depicted QD621 penetration through the
uppermost layers of the stratum corneum (SC) and fluorescence was found in the
SC and near hair follicles. QD621 were found in the intercellular lipid layers of
the SC by transmission electron microscopy (TEM). QD565 and 655 with flexed
and tape-stripped skin did not show penetration; only abraded skin showed
penetration in the viable dermal layers. In all QD studies, inductively coupled
plasma-optical emission spectroscopy (ICP-OES) analysis for cadmium (Cd) and
fluorescence for QD did not detect Cd or fluorescence signal in the perfusate at
any time point, concentration or type of QD. These results indicate that porcine
skin penetration of QD621 is minimal and limited primarily to the outer SC layers,
while QD565 and 655 penetrated into the dermis of abraded skin. The anatomical
complexity of skin and species differences should be taken into consideration
when selecting an animal model to study nanoparticle absorption/penetration.
These findings are of importance to risk assessment for nanoscale materials
because it indicates that if skin barrier is altered such as in wounds, scrapes, or
dermatitis conditions could affect nanoparticle penetration deeper into the dermal
layers and skin is an important organ and can serve as a potential route of
exposure and should not be overlooked.

44 N.A. MONTEIRO-RIVIERE AND L.W. ZHANG
1. Background
Quantum dot (QD) nanoparticles have potential use in diagnostics, drug delivery
and imaging in biomedicine or therapeutic applications due to their optical
characteristics that result in strong fluorescence without photobleaching [1]. QD
conjugated with streptavidin have been bound to cytoskeletal elements and surface
receptors when visualized with monoclonal antibodies [2, 3]. A series of
carboxylic acid coated QD with different emission wavelengths are now
commercially available making QD a useful tool to mark certain proteins in cells.
Prostate tumors in mice were imaged with a QD-antibody conjugate that provided
a novel method of cancer labeling in vivo [4]. QD biocompatibility should be
evaluated in cells and in tissues before incorporating them into structures for
biomedical devices or implants. Currently, there is little information regarding QD
permeability in skin. Their potential for toxicity and interactions with biological
systems is needed before nanomaterial risk assessments can be made.
QD565/655 contain a cadmium/selenide (CdSe) core with a zinc sulfide (ZnS)
shell. By TEM, QD565 are spherical with a diameter of 4.6 nm, while QD655 are
ellipsoid with a diameter of 6 (minor axis) X 12 nm (major axis). The
hydrodynamic diameters for QD565 are 35 nm for the polyethylene glycol, (PEG),
uncharged, 14 nm for the carboxylic acid (COOH), negatively charged, and 15 nm
for the (PEG-amine (NH2), positively charged. The hydrodynamic diameters
QD655 were 45 (PEG), 18 (COOH), and 20 nm (NH2) [5]. In comparison,
QD621-PEG coated have a CdSe core and CdS shell coated with PEG polymer
coils, and are nail shaped by TEM with the mean width of 5.78 ± 0.97 nm and
length of 8.40 ± 1.9 nm with a hydrodynamic size of 39 ± 1 nm evaluated by size-
exclusion chromatography [6].
The heavy metals Cd and Se may have toxic effect on cells or tissues. QD have
been shown to degrade in oxidative environments [7, 8]. Therefore, QD
degradation and the potential Cd release in vivo may pose a toxic risk. Skin has
been shown to be permeable to some engineered nanomaterials in commercial
products, medicines, cosmetics and can serve as a portal of entry for localized or
systemic exposure to humans, especially in an occupational scenario. Therefore,
the objective of these studies was to assess if QD nanoparticles of different sizes,
shapes, and surface coatings could penetrate the skin of different species under
different mechanical actions.
2. Interaction of Different QD Topically Applied to Intact Skin
Our laboratory investigated the effects of penetration by QD565 and 655 with
diverse physicochemical properties in porcine flow-through diffusion cells.
QD565 with PEG, PEG-NH2, or COOH showed penetration into the stratum
corneum (SC) and localization within the epidermal and dermal layers by 8 h.
PEG and PEG-NH2 coated QD655 were localized within the epidermal layers by
8 h. The penetration of COOH coated QD655 into epidermal layers was evident
only at 24 h [5]. Recently, we have studied another type of QD, QD621 that has a
ASSESSMENT OF QUANTUM DOT PENETRATION INTO SKIN 45
different shape (nail shaped) and different shell coating (CdS shell). QD621 was
topically applied to porcine skin in flow-through diffusion cells to assess
penetration. At the low concentration of 1 μM, QD621 were located primarily in
the normal intact SC layers of the skin (Figure 1, left column). No QD621
fluorescence was detected in the stratum granulosum, stratum spinosum, or
stratum basale layers of the epidermis. At the high concentration of 10 μM (right
column) QD621 were primarily present in the SC layers or in between the stratum
granulosum-corneum interface, although a small amount of fluorescence was
detected in the upper epidermal layers. Occasionally, QD621 were seen in the
outer root sheath of the hair follicle [9].
Figure 1. QD621-PEG applied to porcine skin flow-through diffusion cells for 24 h. Left column: 1 μM
dose. Right column: 10 μM dose. Top row across: confocal-DIC images depicting the skin section by
DIC. Middle row across: fluorescence indicating QD621-PEG. Bottom row across: overlay of DIC and
fluorescence depicting QD on the surface and in the outer root sheath of the hair follicle (right). Bars =
100 μm.
The penetration differences seen with QD565, QD655 and QD621 in flow-
through diffusion porcine skin cells showed how differences in composition, size,
configuration, surface charge and other physicochemical parameters could
influence penetration. PEG-QD621 with a hydrodynamic diameter of 39 ± 1 nm
were capable of penetrating only the uppermost layers of the porcine SC after 24 h
of exposure, while confocal microscopy showed that all three surface coatings of
the QD565 penetrated at 8 and 24 h but only the QD655 COOH took 24 h to
penetrate the skin. No fluorescence was detected in the perfusate. The above study
showed that QD synthesized with the same core/shell with similar surface coatings
and hydrodynamic diameters but different shapes and penetration rates can
penetrate intact skin [5]. QD621-PEG was dissolved in water as stock solution,
while QD565-PEG and QD655-PEG were in a borate buffer (pH 8.0) to prevent
agglomeration and had a similar viscosity and similar pH with water. QD565 and
QD655 penetrated through porcine skin faster and deeper than QD621. The SC
layers remained intact and no other morphological alterations were noted by either
laser scanning confocal microscopy or TEM due to pH effects that possibly could
alter the skin barrier formation or cell morphology that would allow for
penetration. Therefore, QD565-PEG, QD655-PEG and QD621-PEG penetration
of porcine SC is independent of the vehicle or pH. These three QD have the same
chemical composition including a “rigid” core and a “soft” surface coating.
Penetration may not only be determined by size and charge, but also by the shape
of the rigid core and durability of the coating. It has been reported that elastic
particles were able to distribute through the epidermis faster, while rigid particles
were found to remain on the surface of the upper SC [10]. The most common
route of penetration in skin is via the intercellular lipid spaces between the
corneocytes. Our previous study showed the diameter of porcine corneocytes to be
32 μm and the vertical and lateral gaps between corneocytes are 19 nm [11].
Therefore, the QD could potentially pass through the corneocytes lateral
intercellular spaces since the QD621 has a rigid core length of 8.4 nm and width
of 5.8 nm but overall size of 39–40 nm. It is theoretically possible that the outer
PEG coating is a “soft” coating thereby allowing the QD621 to “squeeze” through
the intercellular space and remain lodged within the SC lipid bilayers (Figure 2A,
B). QD621-PEG penetration may be limited through the epidermis due to their
large size and irregular configuration and this fact could explain the different
behavior between the nail shaped QD621 (5.78 by 8.4 nm) and spherical QD565
(4.6 nm core) or elliptical QD655 (6 by 12 nm). Therefore, the 1 μM QD621 did
not penetrate deep into the SC or epidermis, while the QD565 and QD655 (smaller
and more regular in shape) would have less difficulty penetrating the lipid layers
of the stratum corneum.
QD nanoparticle studies in our lab reported on the penetration of QD into the
SC layers or outer root sheath of hair follicles, but not within the deeper layers of
skin [9, 12, 13] except for QD565/655 in porcine skin flow-through diffusion cells
[5]. Other types of nanoparticles have been topically applied to the skin to assess
penetration. TiO2 and ZnO nanoparticles are key ingredients that are added to
sunscreens to protect the skin from UV induced damage. Cross et al., 2007 [34]
Figure 2. TEM of QD621-PEG in the SC of flow-through porcine diffusion cells. (A) QD621-PEG in
the intercellular lipid layers of the SC. Bar = 250 nm. (B) Higher magnification of the enlarged area of
2A depicting individual nail-shaped QD621 (arrow) and some small agglomerates. Bar = 50 nm.
reported that most micronized transparent ZnO nanoparticles of 26–30 nm in

oil/water formulations topically applied to human skin in in vitro static cells for 24
h remained on the surface of the SC. Microfine ZnO of 80 nm and agglomerates of
titanium dioxide less than 160 nm did not penetrate the porcine SC layer in in
vitro static diffusion cells [14]. Maghemite nanoparticles of 5.9 nm have been
shown to penetrate hair follicles and the SC layer of the epidermis, suggesting a
potential route for nanoparticles to traverse the dermal barriers [16]. Polystyrene
nanoparticles of 20 nm tend to distribute in human hair follicles [15]. Minoxidil
loaded polymeric nanoparticles of 40 nm were able to penetrate the skin of hairy
guinea pigs, probably through hair follicles [17]. Hair follicles are often
envisioned as special channels for absorption of topical compounds, which could
by pass the SC barrier [18]. If hair follicles are a route of exposure for QD then
nanoparticles penetrating into the skin may be independent of particles size and
may be a safety issue. All of the above studies have demonstrated that the
penetration and distribution in skin for topical administration of QD or other
nanoparticles are minimal. However, it will be interesting to investigate if smaller
nanoparticles can penetrate deeper into the skin after repetitive applications and
for longer durations. However, these types of studies will need to be conducted
in vivo because there are limitations to in vitro cell systems.
3. QD Penetration in the Skin via Mechanical Forces
Species differences may be a function of intercellular lipid structure or hair follicle

density that could modify penetration processes [19]. Rat skin is sometimes used
in toxicity studies and widely used due to the ease of handling and low cost. Pig
and human skin have a sparse hair coat compared to that of rodent skin. Porcine
skin is widely used in penetration studies because it is anatomically, biochemically
and physiologically similar to human skin [20–22]. Skin from the back of pigs and
abdomen of humans have 11 ± 1 hair follicles/cm2, while rat has a 289 ± 21 [23].
Our laboratory investigated the penetration of QD655 and QD565 coated with
COOH in rat skin for 8 and 24 h in flow-through diffusion cells. Skin was flexed,
tape stripped and abraded to determine if these mechanical actions could perturb
the barrier and affect penetration. The hair was clipped on the back of rats 24 h
prior to experiment. Skin from the back was removed and placed dermal side
down on flow-through diffusion cells. QD655 or QD565 of 1 µM dosed for 8 or
24 h in intact skin showed both QD on the surface of the SC and on the hair
without penetration into the epidermal layers. The irregular and uneven staining of
QD on the surface of rat skin is probably due to the high hair follicle density that
prevents QD from reaching the SC surface, thereby showing fluorescence on the
surface of the hairs. Furthermore, QD655 or QD565 were found on the surface of
the SC in a homogeneous and continuous pattern, but there was no difference in
QD penetration between flexed skin and intact skin. Rat skin was tape stripped ten
times to remove the SC layers. In tape-stripped skin, QD were deposited evenly
and homogeneously on the surface of the viable epidermal layers. Rat skin was
also abraded with sandpaper 60 times, until the skin was slightly red but not
bleeding. This mechanical action removes the SC layers and viable epidermal
layers so that penetration of QD can be facilitated through skin. QD655 and
QD565 showed slight penetration into the dermis at both 8 and 24 h (Figure 3).
Since QD consist of a Cd core, we evaluated for Cd leaching from the QD to
detect absorption in the perfusate samples collected at different time points. No
fluorescence was emitted or Cd detected in any of the perfusate samples at any
time points. ICP-OES supported the fluorescence measurements that there was no
evidence of absorption in the flow-through diffusion cells. These results suggested
that barrier perturbation by flexion and tape stripping did not cause penetration of
QD, but only abraded skin allowed QD to penetrate deeper into the dermal layers
of skin. Additional studies in our laboratory with QD in tape stripped and intact
human skin in flow through diffusion cells found similar results. QD penetration
through human skin was minimal [13]. All of these observations demonstrate that
there are species differences and these anatomical complexities may interfere with
the penetration of QD in skin.
Skin exposed to different mechanical actions such as tape stripping or abrasion
is often used in skin pharmacokinetic research to study drug absorption in skin.
Tape stripping of the SC facilitates the percutaneous absorption of a compound
across skin providing a noninvasive procedure to predict human skin absorption
for the compound [24]. Tape stripping has been used to assess the absorption of
cosmetic products, heavy metals and other chemicals to determine the amount of a
compound that has been absorbed [25–27]. Rat skin was tape stripped and
investigated by its permeability of QD in flow-through diffusion cells. The
macroscopic and microscopic results depicted tape stripping ten times removed
most of the hairs and completely removed all the SC layers, and the effects of tape
stripping showed QD565 or QD655 deposited evenly and homogeneously on the
surface of viable epidermal layers without penetration into the epidermis at 24 h
[12].
Figure 3. QD565-COOH applied to abraded rat skin in flow-through diffusion cells for 24 h. Left
column: 1 μM dose of QD565-COOH. Bar = 100 μm. Right column: higher magnification of the left
column depicting QD565 in the dermal layers of the skin. Bar = 25 μm.
Skin abrasion is often used in clinical settings for skin resurfacing, drug
delivery [28, 29] or to increase vitamin C absorption [30]. We abraded the skin
and laser scanning confocal microscopy depicted penetration of QD565 and
QD655 into the dermis at 24 h. Rat epidermis typically contains one to two layers
of keratinocytes, and after abrasion, the epidermis was removed. In this study, QD
penetrated into the abraded skin but not tape stripped skin indicating that the
basement membrane had been partially removed so that QD could easily penetrate
into the dermis without the basement membrane acting as another selective
barrier.
Flexed skin and its permeability to nanoparticles are of interest especially in an
occupational setting. Skin flexion is a method that simulates flexing movements
such as repetitive wrist bending. Polymeric nanoparticles coated with a 40 nm
thick PEG block copolymer layer topically applied to hairless guinea pig skin for
12 h were able to penetrate the epidermis [17]. FITC-conjugated dextran beads of
0.5 μm penetrated the SC of human skin and reached the epidermis after 30 min of
flexing [31]. Studies in our lab have shown that a fullerene amino acid-derivatized
peptide nanoparticles of 3.5 nm were capable of penetrating the dermal layers of
porcine skin flexed for 60 min and placed in flow-through diffusion cells for 8 h,
while non-flexed control skin showed limited penetration to the upper epidermal
layers [32, 33]. TEM found the derivatized fullerene was localized within the
intercellular space of the stratum granulosum layer. In our study, rat skin was
flexed at 45° with a frequency of 20 flexes/min similar to the porcine study above.
The apparatus provides tension and compression that mimics repetitive skin
movement. After 60 min of flexing, QD655-COOH and QD565-COOH were
found on the surface of the SC in a homogeneous and continuous pattern in rat
skin. Perhaps flexion of the skin enhanced the rate of QD penetration along the
side of the hair shaft. Also, repetitive motions may alter the structural organization
of skin and lead to an increase in penetration by compromising the permeability
barrier.
4. Conclusion
In summary, we showed that QD621 penetration into skin was minimal and
limited to the uppermost SC layers and the outer root sheath of hair follicles. We
did not detect any Cd in the perfusate by ICP-OES or QD by fluorescence
indicating lack of dermal absorption or below the level of detection. When
different mechanical stressors were applied to rat skin, QD showed no penetration
in nonflexed control, flexed and tape stripped skin, but minimal penetration in
abraded skin. The above studies provided a better understanding on the
penetration of different types of QD with different types of surface coatings in
different species. QD penetration depends on its size, charge, shape and other
physicochemical parameters. Also, different mechanical actions on skin could
alter the barrier properties that would effect nanoparticles penetration into skin
and flexion could cause nanoparticles to penetrate deeper. This research suggests
that there is risk for potential health care workers that suffer defects in their skin
barrier such as atopic dermatitis, psoriasis or eczema on their hands and other
parts of their body with a compromised skin barrier that could be susceptible to
nanoparticle penetration. In addition, this study also provided information on
nanoparticle absorption that could occur in abraded skin that could relevant in
certain occupations exposure scenarios and potentially as a method of drug
delivery.
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NANOTECHNOLOGY
The Occupational Health and Safety Concerns
S. CHAN-REMILLARD
Golder Associates Ltd., and HydroQual Laboratories Ltd.
#4, 6125 – 12th Street S.E.
Calgary, Alberta T2H 2K1, Canada
sylvia_chanremillard@golder.com
L. KAPUSTKA
LK Consultancy
8 Coach Gate Place SW
Calgary, AB T3H 1G2 Canada
Kapustka@shaw.ca
S. GOUDEY
HydroQual Laboratories Ltd. #4, 6125 – 12th Street S.E
Calgary, Alberta T2H 2K1, Canada
Abstract. Nanotechnology is a rapidly emerging field. There are currently over

500 consumer products available in the marketplace and the field of nanotechnology
itself that will be worth over $1 trillion by 2012. However, with an increasing
number of products emerging, there is also a consequent rise in ecological and
human exposure. The risk and degree of exposure to nanoscale particles (NP) will
vary depending on the form of the particle, for example, powder, liquid or
encapsulated, when contact occurs. Although, general public exposure to NP is
increasing due to the shear number of products available, the majority of human
exposure still occurs in an occupational setting. Preliminary exposure studies
demonstrate that NP may enter the body via the gastrointestinal, respiratory and
integumentary systems and then translocate to other vital organs and systems (for
example via the olfactory bulb). Historical data on ultrafine particles have shown a
higher incidence of lung cancer and respiratory disorders associated with
exposure. Due to these data and evidence emerging directly on NP, precautionary
measures may be warranted to ensure worker safety. Regulatory agencies and
manufacturers are beginning to consider standard practices that adequately protect
workers from nanoscale particle exposure. The occupational hazards associated
with exposure and the current safety recommendations will be discussed.

54 S. CHAN-REMILLARD ET AL.
1. Introduction
The concept of nanoscale particles (NP) and processes in the nanoscale is not
novel. Humans have been exposed to NP from the natural environment long
before recorded history. However, it has only been in the last couple of decades
where exposures to NP that are anthropogenic in origin, specifically the engineered
forms, have become a potential health and safety issue. Nanotechnology has been
compared to the industrial and computer revolutions for its ability to change/create
many technologies and how we approach science. Many benefits may be realized
through the integration of nanotechnology in existing and previously unattainable
technologies. Although there is much excitement for nanotechnology within the
scientific and commercial/industrial communities, there is a large gap in our
knowledge regarding how NP exposure may impact living organisms. This lack of
toxicity data may seriously hamper the progression and commercialization of this
science.
Nanoscale particles can be classified according to their source origin. Under
this classification scheme they can be categorized as natural, incidental or
engineered NP. Natural NP, as the name implies, are found naturally in the
environment (e.g. viruses, products of bacterial processes, many of the functions
that occur within living organisms are within the nanoscale), incidental NP are
created as a function of industrial processes (e.g. combustion of diesel engines,
welding fumes) and engineered NP have been specifically created for a function or
property.
As compared to natural NP, incidental and engineered forms are both
anthropogenically introduced into the environment. Engineered NP are created
with a specific chemical signature, homogeneous morphology, and size. Often
times with specific functionality whereas incidental NP are a heterogeneous
mixture for each of these characteristics. Due to the unique physical-chemical
characteristics of engineered NP, our understanding of how they may react and
defenses against these particles in biological systems is not very well known.
Furthermore, the intrinsic toxicity of individual NP must also be factored into
health impact assessments.
2. Exposure
Although there are an increasing number of products with nanotechnology

incorporated into them available on the consumer marketplace exposure to
engineered NP is still occurring primarily within the occupational realm. Workers
are exposed to the NP either through manufacturing of the particles directly or
products that have these NP incorporated into them. Due to the lack of toxicity
information on how NP react within biological systems key questions regarding
the health and safety of frontline workers still remain. Do existing engineering
controls and personal protective equipment guidelines adequately protect workers
from NP exposure? Are the current tools/instruments used to measure exposure
levels sensitive enough for measuring such small particulate matter?
NANOTECHNOLOGY 55
The degree of exposure to NP is highly dependent on the initial form of the

particle and the organism that comes in contact with it. There are higher risks of
exposure to NP that are within the dust or aerosolized forms due to their increased
mobility, whereas exposure to particles that are immobilized within a liquid or a
more rigid matrix (e.g. steel) will have a much lower risk of exposure [1].
However, it must be noted that exposure to NP in an immobilized structure may
increase if the product breaks down resulting in the release of smaller particles
into the environment.
3. Routes of Entry
Nanoscale particles may enter into the body via three primary routes: inhalation,
skin exposure and ingestion where the toxicity targets are the respiratory, integu-
mentary and gastrointestinal systems respectively.
3.1. RESPIRATORY SYSTEM
Epidemiological studies into ultrafine/incidental particles are beginning to

demonstrate that there are some serious health effects associated with chronic
exposure. Occupational workers exposed to particles from combustion engines or
welding fumes for prolonged periods have higher incidences of lung cancer,
chronic obstructive pulmonary disease, fibroids and cardiovascular diseases [3, 11,
13] as compared to the general population. Studies on chronic inhalation of
ultrafine or incidental particles may provide some insight into the health impact of
chronic exposure to engineered NP.
The respiratory tract has three distinct regions: the nasopharyngeal, tracheo-
bronchial and the alveolar. The regional deposition rate of NP within each of these
compartments is highly dependent on the size of the particle. The deposition of NP
that are 1 nm in dimension is primarily within the nasopharyngeal region whereas
slightly larger particles (20 nm) deposit further down the respiratory tract in the
alveolar macrophage regions where it is much more difficult for the body’s
clearance mechanisms to remove these particles [23].
The respiratory tract has several clearance mechanisms for particulate matter.
The respiratory tract has a thick layer of mucus that traps particles as they are
inhaled. Within the tracheobronchial region, particles trapped in the mucus layer
are removed via the mucociliary escalator. The particles are either expelled
through expectoration or may enter the gastrointestinal tract through swallowing.
The primary clearance mechanism within the alveolar region is a phagocytic activity
through the action of alveolar macrophages. Alveolar macrophages phagocytose
the particles and move them upwards into the tracheobronchial region where they
are then removed by the mucociliary escalator.
Under normal circumstances these respiratory clearance mechanisms are
highly effective at clearing particulate matter that enters into the respiratory tract.
However, due to the unique physico-chemical properties and the size and aspect
ratio characteristics of NP the effectiveness of these clearance mechanisms is
uncertain. The impairment of phagocytic activity and cytotoxic action towards

alveolar macrophages exposed to several carbon based NP have previously been
observed [10].
The impairment of respiratory defense mechanisms may consequently result in
the persistence of NP in the lung, movement of the particles deeper into the lung
tissue or translocation to other target organs. The presence of nanoscale carbon
(black, nanofibers and multiwalled nanotubes) were toxic to human lung cells
after only 24 h of exposure; toxicity increased with prolonged exposure (5 days).
Morphological changes, such as decreased cellular contact, detachment from
cellular matrix, condensation of nuclei and cytoplasmic retraction were observed
in exposed cells [18]. The persistence of particles in lung tissue may result in an
elevated inflammatory response and ultimately various lung diseases as observed
in epidemiological studies on ultrafine particles [3, 11, 13].
Persistence of NP within the lung may increase the potential for translocation
to other target organs. Translocation of NP into the blood stream can occur via the
air/blood barrier, through the lymphatic system, move further into the lung tissue
or interstitium or via the sensory neurons (e.g. olfactory bulb or the vagus nerve
[24]). Nanoscale particles have been found to penetrate beyond the basement
membrane into the capillary lumen and then attach directly onto red blood cells
[29], which may explain the cardiovascular consequences of exposure. Inhaled NP
have been detected in the liver and bladder [20, 23], heart and spleen [28], lymph
nodes [24] and in the olfactory bulb and different regions of the brain [7] after
varying periods of exposure.
3.2. INTEGUMENTARY SYSTEM
Another major route of entry for NP is the integumentary system or the skin. The
skin is made up of three distinct layers: the epidermis, dermis and the subcutaneous
fatty layer. The epidermis is the top few layers of skin that includes the horny
outer layer composed of dead keratinized skin cells (stratum corneum), prickle cell
layer (stratum spinosum) and the basal cell layer (stratum basal). Collectively these
three layers of the epidermis form a tight protective barrier for the underlying
dermis that contains a rich blood supply, immune cells (macrophages/dendritic
cells), lymph vessels and sensory nerve endings.
Traditionally, the thick stratum corneum (0.5–1.5 mm thick) layer was thought
of as a relatively impermeable barrier to many compounds as experienced in the
pharmaceutical industry where creating effective topical medications with a high
absorbance rate is a challenge. Skin flexion studies demonstrate that smaller
particles (0.5–1 um) are able to penetrate into deeper skin layers than larger particles
(2–4 um) suggesting a size dependent gradient for penetration [30]. However, due
to the smaller size and unique physicochemical properties of NP is the epidermal
layer as effective of a barrier against penetration by NP based formulations? The
movement of NP into the dermal layer increases the chances of further translo-
cation via the blood supply, lymph system, immune cells and sensory neurons to
secondary target organs with potential unintended consequences.
NANOTECHNOLOGY 57
The most commonly used NP in topical applications are nanoscale titanium

dioxide and zinc oxide in sunscreens. These NP have been used for over 2
decades. Prior to the use of NP in sunscreen formulations the application of
sunscreen left a non-aesthetically pleasing white film on the skin. The advantage
of using NP for sunblocks is that in the nanoscale range, titanium dioxide and zinc
oxide still retain their UV blocking capabilities but are also transparent. This has a
major impact on improving public health.
Several studies have demonstrated that the epidermal layer is highly effective
in preventing the passage of NP. Nanoscale titanium dioxide and zinc oxide did
not penetrate beyond the stratum corneum of the protective outer epidermal layer
[8, 6, 19, 27]. In a presentation to the FDA public forum on nanomaterials, the
Cosmetic, Toiletry and Fragrance Association (CTFA) indicated that these
particles have been rigorously tested and are deemed safe for human usage [26].
Nohynek et al. [22] also conclude that titanium dioxide and zinc oxide that are
currently used in cosmetic preparation do not pose a risk to human health.
However, caution should still be taken with other types of NP through dermal
contact [4].
Another potential route for dermal penetration of NP is through the follicle.
The follicular pathway may represent a route for NP to bypass the protective
epidermal layer. The hair follicle penetrates deep into the dermal layer where there
is a rich supply of blood and immune cell activity directly connected to the
follicle. The potential for these particles to enter systemic circulation via the
follicle is a mechanism that many topical drug delivery systems exploit.
Lademann et al. [16] demonstrated that dyes carried by NP are able to penetrate
deeper and persist longer in hair follicles than non-particulate counterparts. They
also found that mechanical massage or motion aids the penetration of particles
deeper into the follicle. The follicle not only acts as a transit point but also as a
reservoir for topically applied medications. Although from a pharmaceutical
perspective, this is advantageous. The unintended consequences of non-
prescriptive particles depositing in the follicles may result in systemic circulation
of particles with unknown sequelae.
Follicular penetration studies using fluorescence microscopy found that larger
particles remained in the upper regions of the follicle, whereas, 40 nm particles
were found in the follicle as deep as the viable dermal layers. There was also
increase immune cell sampling for 40 nm particles than larger particles [31].
Deposits of iron NP in and around the follicle were observed as far as 30–170 um
below the viable epidermal layer [4]. With titanium dioxide (20 nm) deposition
was observed as deep as 400 um into the follicle, however, no particles were
found in the vital tissue or near sebaceous glands [17].
A key factor that may pose a challenge in the case of drug delivery systems or
protection in the case of penetration of non-prescriptive NP is the opened or
closed state of the follicle orifices. Follicles are open during periods of active
sebum production or hair growth but during the resting phase a protective layer of
sebum and desquamated cells covers the follicle opening [15, 25]. The open or
closed state of the follicles may be a factor in penetration and persistence of NP
inside the follicular orifice.
3.3. GASTROINTESTINAL SYSTEM
The third major route of entry for NP is via the gastrointestinal tract. Entrance of
NP into this system may occur via direct ingestion or as previously discussed, via
the mucociliary escalator. The entire gastrointestinal tract is approximately 6.5 m
in length. It is divided into the two distinct regions, the upper (mouth, pharynx,
esophagus and stomach) and lower gastrointestinal tract (large/small intestine and
anus). Not only do absorptive/digestive/defecation processes occur throughout the
tract, the digestive tract plays a prominent role in immune functioning via the gut
associated lymphoid tissue (GALT) and is intricately associated with key
accessory organs like the liver, gallbladder and pancreas.
Similar to the respiratory tract, the gastrointestinal tract is lined with a thick
mucus membrane that is in direct contact with the contents of the gastrointestinal
tract. When inhalation or whole body NP exposure occurs, there is a high
likelihood that these particles will be entering into the gastrointestinal tract.
Considering the large surface area involved for absorptive/digestive processes the
potential for ingested NP to disrupt this system may be considerable. What is the
fate of these NP once in the gastrointestinal tract? Are they excreted, do they
persist only in the intestinal tissue or do they translocate through the gut wall into
other secondary organs?
The efficacy of many oral pharmaceuticals is highly dependent on the ability
of the gastrointestinal system to absorb the active ingredients. Much of our current
understanding of how NP act at the gut wall/systemic circulation interface has
arisen from research looking at the use of NP to enhance the delivery of drugs
across the gut wall into systemic circulation. The implications of NP enhancing
drug absorption and is great, however, the absorption of particles that are not
physiologically relevant may have unintended consequences.
The mucosal lining is composed of millions of villus lined with cells
(enterocytes/epithelial) that are constantly and rapidly turned over. A key route to
systemic access by NP is the ability to penetrate through this lining. Gold NP (4
and 10 nm) were able to gain access through the gut wall via tiny little pores that
formed from enterocyte turnover through a process called persorption. The smaller
the NP the further they were able to penetrate into the gut wall. Gold NP were
observed on the apical and basolateral sections of the villi. There were also some
particles observed near lymph vessels, suggesting another potential mechanism
that NP may cross into the blood stream [12].
Through fluorescence imagery, nanoscale chitosan particles have been
observed in epithelial cells lining the jejunum, duodenum and ileum. Chitosan
were also found deeper in the lamina propria, suggesting movement of particles
through the epithelium. Similar to the study by Hillyer and Albrecht, NP were also
found in the peyer’s patches, which are key cells within the gut involved in
immune surveillance [5].
The movement of gold nanoparticles was not isolated just to the deeper layers
of the gut wall but was found in secondary organs. Four nanometer gold particles
were isolated in the blood, brain, lung heart, kidney, spleen, liver, small intestine
and stomach 7 days post exposure [12]. When compared to larger particles (58 nm),
NANOTECHNOLOGY 59
the 4 nm particles had the highest degree of translocation. Similar to the respiratory
tract, this suggests a size dependent gradient for translocation across the gut wall.
Yet others have found that ingested NP primarily transit through the gastrointestinal
system and are excreted in fecal matter and urine [14, 28].
4. Occupational Health and Safety
The previous section discusses the impact of NP on the three key target exposure
sites in humans illustrates the variability that the type of NP tested and the target
sites evaluated can have on conclusions regarding physiological effects/responses.
Although these studies contribute to the current database of information there is
still not a large enough body of evidence or consensus on the ultimate effects NP
have on living organisms to truly inform or regulate nanotechnology. This is one
of the key issues surrounding the nanotechnology industry and how it is to be
effectively regulated and the hazards and risks effectively managed. Until there is
enough information to effectively inform regulatory agencies and industry, health
and safety guidelines to the best of our knowledge must be developed and
implemented to prevent human exposure to the potential health hazards of NP.
Exposure to engineered NP will vary depending on the context of exposure.
Currently, the majority of human exposure to NP is isolated to frontline workers,
in the occupational setting, who are directly involved in producing or incorpo-
rating NP into products. Due to the rapid emergence of products containing NP
available for consumer consumption, there will be a parallel increase in exposure
levels among the general public.
However, general public exposure will differ from occupational exposure in
the form of the nanoparticle that exposure will occur. The majority of NP exposure
to the general public will occur in the form of products where NP are bound
within some sort of matrix. For example, titanium dioxide NP will be bound
within the liquid matrix of a lotion or carbon nanofibers will be bound within the
steel structure of an automobile frame. The matrix that binds the particles will
confer a degree of protection to the consumer against exposure to free NP.
Within the occupational setting, there is a higher likelihood of exposure to NP
that are in the free form. The adequacy of health and safety protocols within an
occupational setting remains uncertain due to our limited understanding of the
toxicity of NP.
4.1. NIOSH
There are several worldwide organizations (ASTM, NIOSH, ICON, SCENHIR)

involved in assessing the safety protocols for handling nanomaterials. A key
organization involved in this initiative is the National Institute of Occupational
Safety and Health (NIOSH), an organization within the Centers for Disease
Control and Prevention (CDC). The key mandate of NIOSH is to ensure that
beneficial applications of nanotechnology are developed in a responsible manner
with a high priority focus on the societal, human and environmental implications
of nanotechnology. In 2004, the Nanotechnology Research Center (NTRC) was

developed under the auspice of NIOSH. The NTRC was developed to specifically
focus on nanotechnology research. Since 2005 NIOSH has internally redirected
US$11 million of funding towards this initiative.
The role of the NTRC is to (1) Determine whether NP and nanomaterials pose
a human health risk to workers, (2) Conduct research on the use of nanotechnology
to prevent work related injuries and illnesses, (3) Promote healthy workplaces
through interventions, recommendations and capacity building and (4) Enhance
global workplace safety and health through national and international collaborations
on nanotechnology research and guidance. The research under the NTRC encom-
passes ten critical topic areas: (1) toxicity and internal dose, (2) risk assessment,
(3) epidemiology and surveillance, (4) engineering controls and personal protective
equipment, (5) measurement methods, (6) exposure assessment, (7) fire and explosion
safety, (8) recommendations and guidance, (9) communication and education and
(10) applications [1].
Currently, there is a knowledge gap in our understanding of the toxicity of NP
to living organisms. Are NP toxic and at what dose or exposure level do NP pose a
risk? Several different but complementary key critical topic areas have been
established to answer these key questions. Scientists involved in the first critical
topic area are investigating the physicochemical properties of NP that influence
toxicity, determining the fate of NP once they have entered into biological systems
and the short and long term effects of exposure to organ systems and tissues.
Scientists involved in the exposure assessment group are evaluating possible
inhalation and dermal exposure to nanomaterials, determining how exposure may
differ by work process and determining the key factors that influence the produc-
tion, dispersion, accumulation and re-entry of nanomaterials into the workplace
environment. Scientists within risk assessment work stream are evaluating whether
current exposure-response data for fine and ultrafine particles are adequate in
assessing/identifying the hazards related to NP and are developing a risk-based
framework for evaluating the potential hazards and occupational risk of exposure
to NP. Researchers funded under the third critical topic area are involved in
identifying what knowledge gaps can be filled with epidemiological studies to
further advance our knowledge of NP.
Scientists involved in the engineering controls and personal protective equipment
stream of research have a twofold mandate. They are actively evaluating whether
current engineering controls and personal protective equipment used are effective
at protecting workers from NP exposure. The second mandate of this group
involves looking at ways to enhance worker safety through incorporation of
nanotechnology into personal protective equipment. Research from scientist
working under the applications umbrella are also working on identifying ways to
apply nanotechnology to enhance occupational health and safety. Scientists
involved in the fifth work stream are actively involved in evaluating, developing
and testing methods and validating sampling instruments to accurately measure
airborne nanomaterials in the workplace.
Due to the different physicochemical properties of compounds in the nanoscale
range, there is a possibility that these materials may become flammable and
NANOTECHNOLOGY 61
explosive. An example of a compound that does not have explosive tendencies in

the macro form but is highly explosive and volatile upon contact with air and
water is zinc. One of the key research streams funded by the NTRC is identifying
the physicochemical properties of nanoscale that contribute to their combustibility
and flammability. This group then makes recommendations for alternative work
practices that decrease or eliminate exposure to such situations.
As previously discussed, the pace that nanotechnology products are emerging
on the consumer marketplace is not paralleled by toxicity research. This poses a
significant challenge to regulators and industry alike. A critical topic area under
the mandate of the NTRC is to provide interim recommendations and guidance for
workplace safety and health practices in handling nanomaterials using the current
state of knowledge. To aid in the collection and dissemination of the most up to
date information, the communication and education stream is actively involved in
fostering international partnerships to ensure the sharing of research needs, appro-
aches and results.
4.2. ENVIRONMENTAL HEALTH AND SAFETY PLANS
There are many companies worldwide that are engaged in some level of nanotech-
nology development or usage. Since nanotechnology is a relatively new field of
research, whether the health and safety plans of these organizations can adequately
protect workers from the potential hazards of nanotechnology must be evaluated.
In collaboration with the International Council on Nanotechnology (ICON), an
interdisciplinary team of scientists from the University of California at Santa Barbara
(UCSB) interviewed 64 organizations from private sector companies, research
labs, university labs and consultant companies within North America, Australia,
the Europe and Asia that claimed to work with nanotechnology in some capacity
on their environmental health and safety (EHS) plans regarding nanotechnology
[9].
Many of the respondents (38/64) to the survey had some sort of EHS program
in place ranging from having guideline documents, using risk assessment
approaches, EHS programs modeled after those for fine or ultrafine particles and
more sophisticated programs that monitor actual exposure to NP. The EHS training
programs included information on the safe handling and standard operating
procedures for nanomaterials, the proper use of personal protective equipment, the
hazards and toxicities associated with handling nanomaterials and engineering
controls for decreasing exposure to nanomaterials. Fewer programs included
information on emergency procedures to handle accidental exposure, proper waste
handling practices, the potential for/implications of environmental release of nano-
materials, consumer protection, exposure monitoring and regulations governing
nanomaterials.
There seemed to be an association between the size of the company and the
level of nano-specific safety training, with larger companies having more sophisti-
cated health and safety programs. When asked why their organizations administered
a nano-specific safety protocol, several organizations indicated that this was a
safety precaution against unknown hazards that include potential toxicity, the
minimization of employee exposure, a proactive approach to address potential

risks from nanomaterials exposure or the unique hazards related to nanomaterials
and compliance with safety regulations for fine particles.
However, 26 out of the 64 companies surveyed did not have a nano-specific
safety protocol in place. These companies sited reasons for not having EHS plans
ranged from planning to implement a training protocol, employees were not in
direct contact with the materials, they treated nanomaterials as a hazardous waste
to the companies that deem the nanomaterials were not dangerous or there was not
enough time or resources to implement a plan [9].
This report also describes internal and external barriers to implementing an
EHS program. The respondents cited the major external barrier to implementing
an EHS program was the lack of useful information and consistent guidelines
regarding the safe handling of nanomaterials, while less frequently the ineffective
techniques for detecting and measuring the presence of NP in the work place was
also cited as a barrier. The most frequently cited internal barrier to instituting a
health and safety plan was the costs that were associated with implementation. An
interesting internal barrier to implementation cited was the attitudes of the workers
towards EHS and nanomaterials risk. Workers either believed that implementation
of these plans required too much effort and did not acknowledge the importance of
safety protocols in handling nanomaterials, also described as the naïve approach or
they had a cavalier approach where they felt that the safety protocols were
ineffective and that there was little risk associated with handling the nanomaterials
[9].
The knowledge gaps identified by the NIOSH research initiatives and the lack
of toxicity data illustrates the many impediments that face regulators and industry
in assessing the level of safety protocols that need to be implemented to protect
occupational workers from being exposed to the potential hazards of handling NP.
4.3. NANOMATERIALS – OCCUPATIONAL HEALTH AND SAFETY

EXPOSURE CONTROLS
Although there are many barriers to implementing health and safety protocols,
interim guidelines based on the most current information available have been
developed to provide regulators and industry guidance on minimizing occupational
exposure [1, 2, 9, 21]. The current guidelines to minimize work place exposure to
NP suggest substituting or eliminating the hazardous material(s) from the process
or when that is not possible to implement engineering and administrative controls.
In the event that is not possible to implement or the effectiveness of engineering/
administrative controls is uncertain, the use of personal protective equipment
(PPE) is recommended.
Industrial hygiene specialists recommend the first line of defence against
exposure to hazardous materials is to completely eliminate or substitute a compound
for one that is less hazardous from a process. For example, the substitution of a
powdered form of a NP, which is easily aerosolized and has a high likelihood of
being inhaled or ingested, for a form that is bound within a liquid matrix would
decrease the risk of exposure. In some instances, the complete elimination of the
NANOTECHNOLOGY 63
compound from the process would remove the likelihood of exposure to a toxic
substance [1, 9]. However, in situations where elimination or substitution of a
compound in a product or process is not a realistic option, the implementation of
safety programs that incorporate engineering controls, administrative controls or
PPEs are necessary to ensure worker safety.
The use of engineering controls developed to control gases is the most
effective means of controlling the movement of NP out of designated workspaces.
The types of engineering controls that are recommended are local ventilation
systems for the immediate work area (e.g. total enclosures [e.g. glove box], partial
enclosures [e.g. chemical hoods, low flow vented balances], weigh hoods for dry
materials, and exterior hoods located adjacent to workspace [e.g. receiving or draft
hoods that draw in particles]), general exhaust ventilation (e.g. scrubbing systems,
negative pressure), specific designation of a workspace by encapsulating/isolating
the area as a nanomaterials zone or the use of specialized filters (e.g. HEPA
filters). Encapsulation/isolation of work processes that involve nanomaterials may
also be achieved through distance, physical separation/barriers or the use of
isolation or control rooms [1, 21].
An important supplement to engineering controls is the use of administrative
controls, which are driven by good laboratory practices and standard operating
procedures, will also decrease the risk of occupational exposure to NP. The
implementation of administrative controls involves extensive safety training of
personnel exposed to processes that involve the use of NP. Important elements of
administrative controls are the cleaning procedures that are used within a facility.
The use of wet wiping procedures and HEPA vacuums systems but not blowers or
fans to prevent the accumulation of NP within workspaces is recommended [1, 9,
21]. ASTM further suggests the use of surfactants during cutting/drilling to
minimize dust production and the requirement for workspaces/equipment/furniture
to be constructed of smooth, non-porous materials to simplify cleaning to further
decrease the risk of occupational exposure.
Another important facet of administrative controls is worker training and
education. Worker education and training into the potential hazards of NP may
help to decrease the previously described ‘naïve’ or ‘cavalier’ attitudes towards
health and safety experienced by workers. Educating workers to the hazards
associated with or suspected of NP may have a larger impact on attitudes towards
personal health and safety within an occupational setting than simply advising on
the need for protection. Educational programs should not only involve training/
education on proper handling procedures and safety issues surrounding NP, but
should also include information on the prevention of transfer (e.g. no eating
around NP workspaces, have designated lab coats/gloves/goggles, enclosed vessels),
proper hazard labeling procedure, the availability of material safety data sheets
and emergency response and medical surveillance procedures [1, 21].
The final method to control worker exposure to NP is through the use of PPEs.
Personal protective equipment is recommended as the primary defense against
exposure only in instances where engineering and administrative controls have
been deemed ineffective at minimizing occupational exposure to NP. Types of
PPEs used are respirators, eye protection and protective clothing and gloves that
are specifically designated for NP use. Respirators fitted with N100 filters are
recommended by NIOSH as being completely effective at blocking NP inhalation.
However, the type of respirator (e.g. half or full faced mask) and proper fitting of
the mask will affect the degree of protection offered by the respirator. If possible,
the use of powered air purifying respirators fitted with a HEPA filter is recom-
mended. When using the half faced masks, it is highly recommended that the type
of eye protection used include at a minimum side shields around the eye.
5. Conclusion
Many wonderful advances in science and technology have been or yet to be

realized through the use and manipulation of material within the nanoscale range.
In addition to the search for new applications for nanotechnology, there is also the
responsibility to understand the impact these NP have on living organisms and to
protect living organisms from potentially toxic exposure.
The toxicity of these particles still remains relatively unknown. The new
emerging science of nanotoxicology that studies how NP impact living organisms
is not progressing at a parallel pace to product development. The lack of toxicity
data introduces a serious gap in knowledge that may hamper our ability to further
develop/introduce products, ensure consumer safety and effectively regulate these
products.
Until there is adequate toxicity data available interim safety guidelines based
on the most current information have been developed. Proper education/training
programs and implementation of EHS programs based on these guidelines will
minimize the level of NP exposure to frontline workers. Further research needs to
be conducted to enhance worker safety and to ensure consumer and environmental
safety of nanotechnology.
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BIOMARKERS OF NANOPARTICLES IMPACT ON
BIOLOGICAL SYSTEMS
V. MIKHAILENKO, L. IELEIKO, A. GLAVIN,

J. SOROCHINSKA
R.E. Kavetsky Institute of Experimental Pathology, Oncology
and Radiobiology of National Academy of Sciences
45 Vasilkivska Street
03022 Kyiv, Ukraine
mvmik@yahoo.com
Abstract. Studies of nanoscale mineral fibers have demonstrated that the toxic
and carcinogenic effects are related to the surface area and surface activity of
inhaled particles. Particle surface characteristics are considered to be key factors
in the generation of free radicals and reactive oxygen species and are related to the
development of apoptosis or cancer. Existing physico-chemical methods do not
always allow estimation of the nanoparticles impact on organismal and cellular
levels. The aim of this study was to develop marker system for evaluation the
toxic and carcinogenic effects of nanoparticles on cells. The markers are designed
with respect to important nanoparticles characteristics for specific and sensitive
assessment of their impact on biological system. We have studied DNA damage,
the activity of xanthine oxidoreductase influencing the level of free radicals,
bioenergetic status, phospholipids profile and formation of 1H-NMR-visible
mobile lipid domains in Ehrlich carcinoma cells. The efficiency of the proposed
marker system was tested in vivo and in vitro with the use of C60 fullerene
nanoparticles and multiwalled carbon nanotubes. Our data suggest that multiwalled
carbon nanotubes and fullerene C60 may pose genotoxic effect, change energy
metabolism and membrane structure, alter free radical level via xanthine oxidase
activation and cause mobile lipid domains formation as determined in vivo and
in vitro studies on Ehrlich carcinoma cells.
1. Introduction
Among engineered nanoparticles (NP) currently being produced, the most

common are fullerenes C60 and carbon nanotubes (CNT). These materials possess
nanostructure-dependent properties that may potentially lead to unusual biological
activity which typically increases as the particle size decreases. Highly increased
surface area of NP may be toxicologically relevant. Studies of mineral particles
have demonstrated that the toxic and carcinogenic effects are mostly related to the
surface area of inhaled particles and their surface activity [1]. Data yielded from

68 V. MIKHAILENKO ET AL.
animal and cell culture studies pointed to an increase in pulmonary inflammation,

oxidative stress incidence, an increased risk of carcinogenesis, inflammatory
cytokine production, apoptosis, and activation of certain gene expression and cell
signaling pathways [2]. A common mechanism of NP impact on cell damage is
oxidative and nitrosative stress development. Fullerenes and CNT’s have been
shown to produce superoxide and induce free radical damage to cells [3–6].
However, currently the potential adverse effects of engineered NP on human health
and the environment can not be fully estimated due to insufficient knowledge of
mechanisms of action and lack of standardized testing protocols.
In our study we have develop a marker system to evaluate the toxic and
carcinogenic effects of nanoparticles on cells in order to address their involvement
into free radical processes, energy metabolism, membrane structural changes
and genotoxic mechanisms. We studied DNA damage, the activity of xanthine
oxidoreductase (XOR) influencing the level of free radicals, bioenergetics status,
phospholipids profile and formation of 1H-NMR-visible mobile lipid domains
(MLD) in Ehrlich ascites carcinoma (EAC) cells.
Xanthine oxidoreductase is a complex molybdoflavoprotein identified as a
terminal enzyme of purine catabolism, catalyzing the hydroxylation of hypoxanthine
to xanthine and of xanthine to urate. The XOR protein is apparently expressed as
xanthine dehydrogenase form (XDH; EC 1.1.1.204) but partially can be converted,
either reversibly or irreversibly, to xanthine oxidase form (XO; 1.1.3.22) by post-
translational modification [7, 8]. The forms of XOR enzyme are differentiated by
the preference of oxidizing substrate, and generation of reactive oxygen species
(ROS) – hydrogen peroxide and superoxide radical [7, 9]. XOR plays an important
role in maintaining the balance of free radicals, takes part in NO circulation,
decomposition of S-nitrosothiols and can be source of reactive nitrogen species
(RNS) – NO and peroxynitrite [8, 10]. In fact, peroxynitrite can be produced by
XOR itself [11].
At normal conditions, the XDH form predominates in vivo, producing the
potent antioxidant uric acid. Conversion of XDH to XO form results in overpro-
duction of the superoxide radicals in tissues and may cause intensification of lipid
peroxidation (LPO) and production of additional quantities of hydrogen peroxide
in tissues [12, 13]. Activation of XOR and conversion of its XDH form to XO
form leads to apoptosis and death of the damaged cells at pathological processes
[14]. At the same time connection between enzyme activation, ROS and RNS
production, and subsequent damage of a genetic material which can cause tissues
malignization was observed in a number of studies [15, 16].
1
H NMR-visible MLD increased formation are reported as a peculiar feature of
malignant cells in vitro and in vivo [17]. Cell membrane rearrangements coincident
with malignancy and proliferation of tumor cells may contribute to the increase in
the ratio of methylene (CH2 at 1.3 ppm) to methyl (CH3 at 0.9 ppm) resonance
signal intensity as observed by proton nuclear magnetic resonance (1H NMR).
Cellular origin of these resonances is related to lipid turnover and cell membrane
structure and arises from the isotropically tumbling molecules, with sufficient
molecular mobility. NMR signals from CH2 and CH3 groups originate mainly
from mobile fatty acyl chains of tissue triacylglycerides with lesser contributions
BIOMARKERS OF NANOPARTICLES IMPACT ON BIOLOGICAL SYSTEMS 69
from free fatty acids and cholesteryl esters. The presence of NMR-detectable
lipids in cells can originate from triacylglycerides in globular plasma membrane
microdomains (22–28 nm in diameter) or intracellular lipid bodies, either adjacent
to the plasma membrane or within the cytoplasm [18, 19].
Bioenergetic status of cells was characterized by 31Р-NMR spectroscopy by
phosphorylated metabolites and their ratios: inorganic phosphate/β-nucleoside
triphosphates (Рi/βNTP), inorganic phosphate/phosphocreatine (Рi/PCr), inorganic
phosphate/phosphomonoesters (Pi/PME) that characterize the level of energy
metabolism and phosphomonoesters/β-nucleoside triphosphates (PME/βNTP),
inorganic phosphate/phosphomonoesters (Pi/PME) that indicate the level of
hypoxia. The metabolism of membrane components was characterized by the
phosphomonoesters/phosphodiesters (PME/PDE) ratio. The increase in the
PME/PDE ratio indicates activation of membrane components synthesis, ratio
reduction point to an intensive breakdown of cells membranes.
Lipids profile was characterized by the contents of phosphor-containing lipids.
It is known that cardiolipin is involved in apoptosis and oxidative phosphorylation,
provides osmotic stability of mitochondria [20, 21]. Phosphatidylserine could
affect the regulation of protein kinase C activity and apoptosis [22]. Decrease of
phosphatidylinositol content may be caused by the processes of intensive degra-
dation or by the inhibition of its synthesis. Degradation of phosphatidylinositol
leads to the formation of such second messengers, as diacylglycerol and inositol-
1,4,5-triphosphate. Diacylglycerol is bound to the inner layer of the plasma
membrane and participates in activation of proteine kinase C. Inositol-1,4,5-
triphosphate diffuses through the plasma membrane into cytoplasm and binds to
the specific receptors on the endoplasmic reticulum causing the release of calcium
ions into the cytosol. Alterations of the phosphatidylcholine/sphingomyelin
(PtdCho/SpM) ratio points out to changes of the level of membrane structuring
[23]. Ratio increases reflect reduction of membrane structuring and increased
membrane permeability, whereas ratio decreases indicates increased membrane
viscosity.
The single-cell gel electrophoresis (or comet) assay is a rapid, simple and
sensitive technique for visualizing and measuring DNA damage in individual
cells. It is used as a primary method of screening for genotoxic compounds. The
method is based on detection of various mobility damaged DNA contained in cells
embedded in agarose gel and subjected to a constant electric field. Thus DNA
migrates to the anode, forming a trace reminding a “tail of a comet” which
parameters depend on the level of DNA damage [24].
The aim of this study was to develop marker system for complex evaluation
the toxic and carcinogenic effects of nanoparticles on cells. Existing physico-
chemical methods, due to insufficient knowledge of mechanisms of action, do not
always allow estimation of the nanoparticles impact on organismal and cellular
levels. The proposed marker system is based on studies of DNA damage, the
activity of XOR, bioenergetics status, phospholipids profile, and formation of
MLD in cells and is hypothesized to reveal mechanisms of NP damaging effects
on cells. The current marker system was used to test in vivo and in vitro the effects
of C60 fullerene nanoparticles and multiwalled carbon nanotubes (MWCNT) on

EAC cells.
2. Materials and Methods
Investigations were carried out on white inbred male mice weighting 19–22 g, 2–
2.5 months old, bred by vivarium of R.E. Kavetsky Institute of Experimental
Pathology, Oncology and Radiobiology of National Academy of Sciences of
Ukraine (Kyiv, Ukraine). All experiments with animals were approved by the
Regional Animal Ethics Committee.
2.1. ANIMAL STUDIES
Ehrlich ascites carcinoma (EAC) obtained from the Bank of Cell Line of the R.E.
Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology (Kyiv,
Ukraine). EAC were maintained and propagated by serial intraperitoneal trans-
plantation of EAC cells in an aseptic environment. Cells of EAC (106 cells/mice)
were injected intraperitoneally (i.p.) at the volume of 0.5 ml of physiologic solution.
All the experiments on tumor bearing mice were conducted 6 days after the EAC
transplantation. MWCNT’s suspension in physiologic solution was i.p. adminis-
tered (0.5 ml per mouse) in concentrations of 0.5 and 1.5 mg/mouse for 24 h.
2.2. CELL CULTURE
EAC cells were obtained from male mice with Ehrlich ascite tumor. Cells from
ascites, after washing, were suspended in Dulbecco’s modified Eagle’s medium
(DMEM, Sigma, St. Louis, MO, USA), supplemented with 10% fetal calf serum
(FCS, Gibco Laboratory, Carlsbad, CA, USA) and maintained by culturing in a
humidified atmosphere of 5% CO2 at 37°C for at least 12 h. EAC cells (7 105
cells/ml of DMEM) were treated for 24 h with carbon nanoparticles (CNP)
suspensions: MWCNTs (0.07 0.035 and 0.017 mg/ml) and fullerene C60 (0.066
mg/ml). The percentage of living and dead cells was determined by trypan blue
exclusion test.
2.3. NANOPARTICLES
Two different type of CNP were examined in this study. MWCNT, obtained from
Dr. J.I. Semencov and T.A. Alekseeva (TMSpetsmash Ltd., Kyiv, Ukraine), were
acid treated to reduce the catalyst impurity, washed and resuspended in
physiologic solution. Fullerene C60 was obtained from ALSI (Ukraine). All CNP
suspensions were freshly sonified under 4°C before administration (6 x 30 s) to
break up agglomerates.
2.4. NMR ASSAY
Dual extraction of cellular lipids and water-soluble metabolites from tissue

samples was made by the methanol-chloroform-water extraction method proposed
by Tyagi et al. [25]. This method facilitates the simultaneous extraction of both the
water-soluble metabolites and the organic-soluble lipid components from the same
tissue sample.
Water-soluble dried extract samples were re-dissolved in D2O, organic-soluble
lipid dried extract samples were re-dissolved in CDCl3. 31Р-NMR spectroscopy
allows simultaneous level assessment of the main phosphorylated metabolites.
31
P and 1H spectra of tissue extracts were acquired using Varian Mercury BB
NMR spectrometer (Varian, Palo Alto, CA, USA), operating at frequency 300
MHz. All NMR measurements were carried out at temperature 20°C and all
samples were spun at 20 Hz. Chemical shifts in 31P NMR spectra were recorded
with respect to methylenediphosphonic acid, trisodium salt (MDP, Sigma, St.
Louis, MO, USA), used as an external standard. The resonance of phosphocreatine
was set at 0 ppm. Chemical shifts in 1H NMR spectra were recorded with use of
0.1% solution of sodium 3-trimethylsilyl[2,2,3,3-D4] propionate in D2O as a
reference at 0 ppm.
The acquisition parameters of 1H spectra of water-soluble metabolites:
relaxation delay time 4 s; spectral width 6 kHz; number of points 7,218; 30° flip
angle. The intense water resonance was partially suppressed by the use of
presaturation of the residual water protons in the solvent.
The acquisition parameters of 31P spectra of water-soluble metabolites:
relaxation delay time 2.4 s; spectral width 6.5 kHz; number of points 6,503; 90°
flip angle. Proton scalar coupling interactions were removed by using continuous
low power proton coupling.
The acquisition parameters of 31P spectra of phospholipids: relaxation delay
time 5 s; spectral width 3 kHz; number of points 6,000; 90° flip angle. Proton
scalar coupling interactions were removed by using continuous low power proton
coupling.
2.5. THE ALKALINE COMET ASSAY
EAC cells were washed in PBS and suspended in agarose gel (0.5 · 106– 0.7 · 106
cells/ml). Cells were then lysed, subjected to alkaline denaturation, and electro-
phoresis [26]. Slides were stained with acridine orange solution (20 μg/ml). Comet
images were observed at 100x magnification with a fluorescence microscope
connected to a video camera (CCD, Webbers, USA). One hundred images were
randomly selected from each sample and analyzed by an image-analysis program
“CometScore” (TriTek Corp, Sumerduck, VA, USA).
The extent of DNA damage was estimated by the following parameters: Comet
Area (AC) – the area covered by the whole comet; Tail Length (lT) – the horizontal
distance from the centre of the head (start of tail) to the end of the tail; %DNA in
Tail (DNAT) – the DNA percentage in the tail – %DNAT = 100DNAT/( DNAT+
DNAH); Tail Moment (MT) – the product of tail length and fraction of DNA in the
tail – MT = lT% DNAT; Olive tail moment – the product of the proportion of tail
intensity and the displacement of tail centre of mass relative to the centre of the
head.
2.6. MLD ASSAY
Cells were harvested and washed once with PBS then washed twice with PBS
made with D2O to reduce protons signal from H2O. Cells (8–10 · 107 cells/ml)
were suspended in a final volume of 0.6 ml of PBS-D2O, transferred to a 5 mm
NMR tube and placed on ice until analysis. The percentage of viable cells,
determined by Trypan blue exclusion test, ranged between 85% and 95%, both
before and after NMR analyses. 1H NMR spectra were acquired using a 300 MHz
Varian Mercury 300BB NMR spectrometer (Varian, Palo Alto, CA, USA) at
20°C, 90° flip angle, repetition time 10 s, 200 excitations, 16000K data points and
5 kHz spectral width. A glass capillary with 0.1% solution of TSP in D2O was
used as a reference at 0 ppm for each sample. NMR spectra were obtained using
presaturation of the residual water protons in the solvent, and samples were spun
at 20 Hz to prevent settling of cells during the experiment. The standardized areas
of the methylene and methyl protons resonances (at 1.3 and 0.9 ppm, respectively)
were integrated using VNMR software (Varian, Palo Alto, CA, USA) and
expressed in relative units.
2.7. XOR ASSAY
Total XOR activity and activity of XO were examined in EAC cells [27]. Activity
of XOR enzyme was estimated by the production of uric acid from xanthine
(absorbance at 295 nm). Reaction kinetics were measured for 30 min at 26°С in
special 96-well plates on the microplate reader Synergy™ HT (Bio-Tek
Instruments, Winooski, VT, USA). In each well 250 μl of incubation mixture (50
mM sodium phosphate buffer with 0.3 mM EDTA, 0.5 mM xanthine, 0.5 mM
NAD+ and 0.24 mM oxonic acid) and 3.6 · 105 EAC cells in 50 μl of 50 mM
sodium phosphate buffer with 0.3 mM EDTA were added. Oxonic acid was used
as uricase inhibitor [28]. XOR activity was expressed in nM uric acid formed by
1 . 106 AEC cells during 1 h. Total protein concentration was determined according
to Greenberg and Craddock [29].
2.8. LPO ASSAY
Intensity of lipid peroxidation (LPO) was evaluated by spontaneous accumulation

of malonic dialdehyde (MDA) and expressed in nanomoles of MDA per gram of
cells per hour. The absorbance of the colored thiobarbituric acid-reactive
substances was measured at 532 nm on a Diode-matrix UV-Vis spectrophotometer
Agilent 8453 (Agilent, Santa Clara, CA, USA) [30, 31].
2.9. STATISTICAL ANALYSIS
Statistical analysis was performed in cases when experiments were carried out at
least in triplicate using Student’s t-test. Values are reported as mean ± standard
error.
3. Results and Discussion
The EAC cells used in our study are a well characterized biochemically and
morphologicaly tumor model and is commonly applied in toxicological studies.
The ascite form of EAC can be used for in vivo experiments and can be easy
transferred into culture for in vitro studies. The EAC cells were treated with CNPs
for 24 h in in vivo and in vitro experiments, after which the bioenergetics status,
phospholipids profile, DNA damage, XOR activity, LPO level, and MLD
formation were simultaneously quantified.
3.1. CHARACTERISATION OF BIOENERGETIC STATUS AND

PHOSPHOLIPIDS PROFILE OF EAC CELLS TREATED BY CNP
3.1.1. Energy Metabolism of EAC Cells
The bioenergetic status of cells was characterized by 1H and 31P NMR spectros-
copy. The quantity of individual phosphor-containing metabolites were determined:
Glucose 6-phosphate (G6-P), Phosphoethanolamine (PE), Phosphocholine (PC),
Inorganic Phosphate (Pi), Glycerophosphocholine (GPC), Glycerophosphoethano-
lamine (GPE), Phosphomonoesters (PME represented by PE + PC), Phospho-
diesters (PDE represented by GPC + GPE), Nucleoside triphosphate (NTP),
Nucleoside diphosphate (NDP), Choline (Cho), Creatine (Cr), and Phospho-
creatine (PCr), as shown in Figure 1.
Cells exposure to fullerene C60 caused a 2.6-fold decrease in the Pi/PME ratio
and 1.4-fold decrease in the PME/PDE ratio. Thus, fullerene C60 activated
energetic metabolism, leading to a decline in membrane component synthesis and
reduced hypoxia level (Figure 2B).
Exposure to fullerene C60 caused a decrease in lactate (1.2-fold) and taurine
(1.3-fold) contents, as well as an increase in Cho + PC + GPC (twofold) and Cr +
PCr (4.53-fold) contents. Such changes of lactate content indicated a decline in
anaerobic glycolysis (data not shown).
Treatment with low concentration of MWCNT caused 1.2-fold increase of the
Pi/β-NTP and PME/β-NTP ratios, that reflected inhibition of energetic metabolism
and intensification of hypoxia. High doses of MWCNT caused a 1.5-fold rise in
the PME/β-NTP ratio which indicates an intensification of hypoxia, however a
1.6-fold decline in the Pi/PME ratio indicates activation of energetic metabolism.
5 10
9
13
3 8
1 4
11 14
12
16
15
2 −2
PPM
−8.0 −9.0
PPM
7
PPM
8.0 7.0
−18.0 −18.5
PPM
6
PPM
20 18 16 14 12 10 8 6 4 2 0 −2 −4 −6 −8 −10 −12 −14 −16 −18
31
Figure 1. Typical P NMR spectra of water-soluble metabolites obtained by dual extraction of EAC
cells. 1 – MDP standard, 2 – G6-P, 3 – PE, 4 – PC, 5 – Pi, 6 – GPE, 7 – GPC, 8 – PCr, 9 – γNTP, 10 –
βNDP, 11 – αNDP, 12 – αNTP, 13 – NADP(H), 14 – UDP, 15 – DPDE, 16 – βNTP.
A B
10
51 0,3
8
6
34 0,2
4
2 17 0,1
1 2 3 4 0 0
3 4
Figure 2. Energy metabolism level in EAC cells treated in vivo with CNP. (A) Effect of MWCNT on
Pi/β-NTP, PME/β-NTP, Pi/PME and PME/PDE ratios in EAC cells – ■ – control cells; – MWCNT-
treated cells (0.5 mg/mouse); □ – MWCNT-treated cells (1.5 mg/mouse). (B) Effect of fullerene C60
(0.066 mg/ml) on Pi/PME and PME/PDE ratios – ■ – control cells; – fullerene C60 treated cells. 1 –
Pi/β-NTP, 2 – PME/β-NTP, 3 – Pi/PME, 4 – PME/PDE.
The PME/PDE ratio increased 1.6 and 2.9 times under the influence of low and
high doses of MWCNT, respectively. Increase in the PME/PDE ratio pointed to
the activation of membrane components synthesis (Figure 2A).
Low and high concentrations of MWCNT caused a modest decline of taurine
content. Exposure to low doses of MWCNT caused a 1.3-fold decrease of Cho +
PC + GPC content and a 1.2-fold increase of lactate content. However, high
concentration of MWCNT caused a 1.5-fold decline of lactate content (data not
shown).
3.1.2. Phospholipids Profile of EAC Cells
Phospholipids of EAC cells were characterized by the contents of phosphatidylcholine

(PtdCho), plasmalogen phosphatidylcholine (PlPtdCho), phosphatidylinositol
(PtdIns), sphingomyelin (SpM), phosphatidylserine (PtdSer), phosphatidylethano-
lamine (PtdEtn), plasmalogen phosphatidylethanolamine (PlPtdEtn) and cardiolipin
(Card) by 31Р-NMR spectroscopy (Figure 3).
Figure 3. Typical 31P NMR spectra of phospholipids obtained by dual extraction of EAC cells. 1 –
Card, 2 – PlPtdEtn, 3 – PtdEtn, 4 – PtdSer, 5 – SpM, 6 – PtdIns, 7 – PlPtdCho, 8 – PtdCho.
Exposure to fullerene C60 decreased PtdCho (1.2-fold), PlPtdCho (1.4-fold),

PtdSer (1.6-fold), PtdEtn (1.3-fold), and PlPtdEtn (1.5-fold). Treatment with fullerene
C60 was followed by a 1.4-fold decrease in the PtdCho/SpM ratio (Figure 4A).
Low concentration of MWCNT caused decreases in PtdCho (1.2-fold),
PlPtdCho (twofold), SpM (1.6-fold), PtdSer (1.4-fold), and PtdEtn (1.4-fold)
contents. The PtdCho/SpM ratio increased 1.3 times under the influence of low
doses of MWCNT. High concentration of MWCNT caused an increase in SpM
(1.2-fold), PtdSer (1.4-fold), PlPtdEtn (1.3-fold), and Card (1.5-fold). Treatment
with high doses of MWCNT caused small decrease of the PtdCho/SpM ratio
(Figure 4B).
Thus, fullerene C60 caused decrease of almost all phospholipids content and
increase of plasma membrane structuring as determined by the PtdCho/SpM ratio.
However, low doses of MWCNT caused decrease of phospholipids content and
increase of membrane permeability. On the contrary, high concentrations of
MWCNT caused increase of phospholipids content and a small rise of plasma
membrane structuring.
40
A
100 B
35
80
30
25 60
20
40
15
10 20
5
0
0
1 2 3 4 5 6 7 8
1 2 3 4 5 6 7 8
Figure 4. Phospholipids level in EAC cells treated with CNP: (A) Effect of fullerene C60 (0.066 mg/ml)
– ■, control cells; , fullerene C60 treated cells. (B) Effect of MWCNT – ■ – control cells; –
MWCNT treated cells (0.5 mg/mouse); □ – MWCNT treated cells (1.5 mg/mouse). 1 – PtdCho, 2 –
PlPtdCho, 3 – PtdIns, 4 – SpM, 5 – PtdSer, 6 – PtdEtn, 7 – PlPtdEtn, 8 – Card.
3.2. ASSESSMENT OF MLD BY PROTON NMR
The ratio of CH2/CH3 signal intensity was moderately increased (1.2 times) in
fullerene C60-treated EAC cells, but the choline resonance signal (at 3.2 ppm)
decreased twofold as compared with untreated EAC cells. This effect may be
related to apoptosis-associated changes in fullerene C60 treated cells. Exposure to
MWCNT was accompanied by small decreases in the CH2/CH3 ratio and choline
resonance signal (Figure 5A).
25
15
5
-5
-15
%
-25
-35
-45
-55
Cho CH2/CH3
Figure 5. Levels of MLD and Cho in EAC cells treated with CNP. (A) Typical 1H NMR spectra of
EAC cells. Peak assignments: 1 – CH3 signal mainly from protein residues and lipids at 0.9 ppm; 2 –
(-CH2)n signal from mobile lipids resonate at 1.3 ppm, 3 – creatine at 3.03 ppm and 4 – choline-based
metabolite signal at 3.23 ppm. (B) The ratio of treated to untreated cells for Cho and CH2/CH3, % ■,
fullerene C60 treated cells (0.066 mg/ml); , MWCNT treated cells (1.5 mg/mouse).
1
H NMR analysis revealed an increase in MLD formation in fullerene C60-
treated cultured cells in contrast with MWCNT effect after administration into
peritoneal cavity. Neither CNP caused any significant cytotoxicity in the range of
concentrations used, as evidenced by trypan blue exclusion test.
3.3. XOR ACTIVITY AND LPO LEVEL
The activity of XOR was studied in EAC cells. Formation of uric acid in samples
did not depend on the presence of NAD+ in incubation mixture. These data indicate
that nearly all XOR in cells was present in the oxidase form, and dehydrogenase
form was absent [32].
Presence of fullerene C60 in cultural medium resulted in a moderate increase of
enzyme activity (21.5%) and more distinct decrease of LPO intensity (49.2%).
Treatment with MWCNT also increased XO activity in EAC cells (Figure 6). The
maximum effect was observed at the middle concentration of MWCNT in cultural
medium (0.035 mg/ml), resulting in a 91.8% increase in XO activity. At MWCNT
concentrations 0.017 and 0.07 mg/ml XO activity was raised on 39.2% and 45.3%,
respectively. When MWCNT were administered into peritoneal cavity in
concentration of 1.5 mg/animal, the XO activation was lower (23.5%), and LPO
level in EAC was decreased to 86.5%.
200
150
100
%
50
-50
-100
1 2 3 4 5
Figure 6. XO activity and LPO intensity in EAC cells treated with CNP (the ratio of XO activity in
CNP treated to untreated cells, %). Experimental groups: 1 – fullerene C60 treated cells (0.066 mg/ml);
2 – MWCNT treated cells (1.5 mg/mouse); 3 – MWCNT treated cells (0.017 mg/ml); 4 – MWCNT
treated cells (0.035 mg/ml); 3 – MWCNT treated cells (0.07 mg/ml). ■ – XOR activity; – LPO
intensity.
Thus, effects of fullerene C60 and MWCNT on XOR activity and LPO intensity
of the EAC had unidirectional character. The activity of XOR was raised and level
of the LPO was decreased. The alteration of XOR activity depended on MWCNT
concentrations. Effects of MWCNT on XOR activity of EAC was more pronounced
in cell culture than in the peritoneal cavity of mice. Lower effect of MWCNT in
peritoneal cavity is probably related to adhesion of a considerable amount of
MWCNT on organs of experimental animals. The decrease in LPO was unexpected
and needs further investigation since the majority of publications observe the
opposite effect. Taking into account that such an effect was observed in parallel
with the activation of XO, which is capable of generating superoxide radicals,

hydrogen peroxide, NO. and peroxinitrite [7, 8, 10], the decrease in LPO was
probably caused by elimination of free radical compounds due to binding to CNP
surface [33].
3.4. DNA DAMAGE
The ability of CNP to induce the formation of DNA strand breaks was assessed
using the comet assay and the obtained results were compared to untreated EAC
cells (Figure 7). Treatment of EAC cells during 24 h with fullerene C60 (0.066
mg/ml) induced comet area threefold, the tail length 2.3-fold, and the tail moment
and Olive tail moment twofold.
1000 A B 35
800 30
600 25
20
400 15
200 10
5
0
0
1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8
Figure 7. DNA damage in EAC cells treated with CNP by comet assay. (A) Comet area and (B) tail
length. 1 – control cultured cells; 2 – fullerene C60 treated cells (0.066 mg/ml); 3 – MWCNT treated
cells (0.07 mg/ml); 4 – MWCNT treated cells (0.035 mg/ml); 5 – MWCNT treated cells (0.017
mg/ml); 6 – control ascitic cells; 7 – MWCNT treated cells (0.5 mg/mouse); 8 – MWCNT treated cells
(1.5 mg/mouse).
The effect of MWCNT on DNA damage was inversely related to doses used
for cells treatment. Treatment of EAC cells with MWCNT (0.07 mg/ml) induced
the moderate increase of DNA damage (1.2–1.3 times) compared to untreated
cells. At the time of analysis most of cells (98%) were not stained with Trypan
blue. Treatment cells with MWCNT at 0.035 mg/ml was followed by a moderate
rise in comet area, tail length, Olive tail moment increase of 1.5-fold, and tail
moment increase of twofold. The number of cells with comets was increased 17%.
Treatment cells with MWCNT in concentration of 0.017 mg/ml caused the largest
effect on DNA damage. The comet area was increased threefold, the tail length
and tail moment twofold, and the Olive tail moment 1.6-fold. The number of cells
with comets rose 38%.
The DNA damage was also assayed when EAC cells were treated with
MWCNT in vivo. Low concentration of MWCNT (0.5 mg/mouse) induced the
increase of the comet area in 1.5 times and the tail length and tail moment 1.3-
fold. The Olive tail moment did not change significantly. The higher MWCNT
dose (1.5 mg/mouse) induced an increase in the comet area of 1.6-fold, the tail
length 1.3-fold, the tail moment threefold, and the Olive tail moment twofold. The
number of cells with comets increased 4–10% in 0.5 ng MWCNT/mouse and 1.5
mg MWCNT/mouse, respectively.
4. Conclusion
Insufficient knowledge of NP mechanisms of action and large variety of inter-

actions with biological molecules require new approaches to estimate nanoparticle
impacts on organismal and cellular levels. The complex estimation of toxic and
carcinogenic effects of NP on cells was carried out to address their involvement in
free radical processes, energy metabolism, membrane structural changes and
genotoxic damage in EAC cells exposed to CNP. The use of EAC model provided
an opportunity to study CNP impact in vitro on cultured cells as well as in vivo
when NP were administered i.p. to tumor-bearing mice.
Our data suggest that MWCNT and fullerenes may pose genotoxic effect,
change energy metabolism and membrane structure, alter free radical level via XO
activation, and cause MLD formation, as determined in the in vivo EAC model
and in vitro cell culture. Exposures of cells to CNP (fullerene C 60 and MWCNT)
induced DNA damages both on in vivo and in vitro systems. MWCNT-induced
DNA damage was inversely related to doses used for cells treatment. Cells
exposed to MWCNT in vitro exhibited a greater degree of DNA damage than cells
exposed in vivo.
XOR enzymatic activity did not depend on the presence of NAD+ in incubation
mixture, this indicates that nearly all XOR in cells was present in the oxidase form
and dehydrogenase form was absent. The effect of fullerene C60 and MWCNT on
XOR activity and LPO intensity of the EAC had a unidirectional character. The
activity of XOR was raised and level of the LPO was decreased. The effects of
MWCNT on XOR activity in EAC was more pronounced in cell culture than in
peritoneal cavity of mice. This may be due to transperitoneal absorption of a
considerable part of substance or its adhesion to organs. Decrease of LPO levels
were unexpected, possibly caused by the elimination of free radical compounds
due to binding to CNP surface.
Treatment with MWCNT caused intensification of hypoxia and activation of
membrane component synthesis, yet fullerene C60 caused the opposite effect.
Fullerene C60 and high doses of MWCNT revealed activation of energy
metabolism and a reduction of membrane permeability, however low doses of
MWCNT caused opposite changes. Phospholipid metabolism decreased after
treatment with fullerene C60 or low concentration of MWCNT but conversely
exposure to high doses of MWCNT caused elevation of phospholipids content.
The obtained results demonstrate a possible link between cells exposed to CNP
and corresponding changes of the proposed markers. The use of a wide variety of
indicators allowed us to acquire information about major mechanisms of NP
damaging effect on organism. Thus, the developed system of biomarkers can be
suggested as a sensitive and efficient approach for assessment of toxic and
carcinogenic CNP impact on organism.
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NANOCONTAMINATION OF THE SOLDIERS IN A BATTLE
SPACE
A.M. GATTI
Laboratory of Biomaterials
University of Modena and ReggioEmilia
Via Campi 213 A
41100 Modena, Italy
antonietta.gatti@unimore.it
S. MONTANARI
Nanodiagnostics srl
Modena, Italy
Abstract. The paper deals with the unusual pathologies some soldiers contracted
after exposure in battle theatres in Iraq and in the Balkans, and considers the
hypotheses the Authors developed to explain the origin of those diseases, that
proved to be lethal in a few cases. The scenario of particulate nanopollution
generated by high-temperature combustions characteristic of some weapons is
described. The electron-microscopy observations carried out in 37 soldiers’
pathological tissues verified the internal dissemination of toxic metallic micro and
nano-particles. The article considers the way of entrance of those nanopollutants:
the lung for inhalation and the digestive system for the ingestion of polluted food.
Battle theatre pollution is also discussed.
1. Introduction
The actual number has never been published and probably is not known, but what
is unquestionable is that veterans from the first Gulf War, and most of them are
American and British, have come home ill and some of them died.
In a few instances, their symptoms, seemingly unhomogeneous and never
experienced together before, were not recognized as belonging to a definite
pathology. For that reason, they were either ignored or underestimated or, in the
best of circumstances, classed as the expressions of something new christened
“Gulf Syndrome” [1–13].
Something similar and sometimes even absolutely superimposable occurred
after the war fought in the Balkans. When that war was declared concluded, Italian
troops were sent to former Yugoslavia as peacekeepers and returned ill or, more
often, grew ill after having been repatriated.

84 A.M. GATTI AND S. MONTANARI
As far as we know, that pathology or, to be more accurate, that collection of

pathologies, looked to be shared by French, Hungarian, Danish, Spanish,
Portuguese, Belgian, Dutch and Greek soldiers [14] and, being a collection of
symptoms and pathologies, was called a syndrome: the “Balkans Syndrome”.
The symptoms observed can evolve into more serious diseases like, for
example, various forms of cancer, Hodgkin’s and non-Hodgkin’s lymphoma or
leukaemia. Also pathologies involving the blood have been diagnosed, pathologies
that did not look particularly important but that, after a certain lapse of time, could
result in a myeloma.
All those post-war illnesses started to appear in 1991, to show up again after
the second Gulf War among the American veterans, but also soldiers engaged in
another war theatre, Afghanistan, reported similar conditions.
As a rule, those soldiers leave in perfect health (such condition is testified by
medical report written before the mission begins and, in any case, a soldier on
active service must be in good health condition), but after a comparatively short
time of stay they may start to show symptoms, sometimes trivial, but growing
more and more serious and even fatal.
For information completeness’ sake it is necessary to mention how some
American and British soldiers who fell ill after the first Gulf War showed also
neurological symptoms, something not observed or, in any case, not reported in
Italian Balkans veterans.
This piece of evidence is particularly important as a clue, because it means
that, though the activities undertaken were unquestionably similar, there was
something that made them somehow different.
According to the Nuclear Regulatory Commission, Depleted Uranium (DU)
may not contain more than 0.711% of U235 and the one used to make DU
ammunitions contains less than 0.2%. Its radioactivity is so low that it is only
reasonable to rule it out as directly accountable for the pathologies observed. As a
matter of fact, people employed to work that metal where DU weapons are
manufactured do not show any of the symptoms reported by the veterans nor any
other particular pathology attributable to radioactivity. Nevertheless, it is
impossible to exclude and, rather, it is very reasonable to say that if radioactive
particles are ingested or inhaled, they find themselves in a particularly restricted
biological environment where they can easily induce adverse reactions.
If we look at the reports issued by the UNEP in 2003 about “DU in Bosnia ed
Erzegovina: Post Conflict Environmental Assessment “ by the United Nations
Environment Programme, Switzerland 2003 (www.unep.org), we read that places
exist where a residual radioactivity still persists (see map in the report [15]),
particularly when unexploded darts remain stuck or buried in the ground, but
nobody has ever checked and documented if Italian soldiers were stationed there
or had ever had a chance to come in contact with them.
In order to identify the causal agent of the pathologies we are dealing with, it is
imperative to locate place and possibility of exposure. Once determined those two
factors, it is necessary to verify if the hypothesis may fit to the same pathologies in
other cohorts of subjects like soldiers operating in firing grounds, people living
in proximity to those posts and, in particular, civilians and NGO effectives present
NANOCONTAMINATION OF THE SOLDIERS IN A BATTLE SPACE 85
in war theatres. It is only by evaluating the whole situation that we can single a
causal agent out shared by all those classes of subjects.
DU has been chosen because of a few favourable characteristics, among which
its hardness, high specific weight, high melting point, excellent armour-piercing
penetration and pyrophoricity. When the projectile is launched, its pointed
penetrator can pierce relatively thick armour plates or virtually any other mark,
and the explosion ensuing has part of the material involved vaporize, as the
temperature induced is in the range 3,036–3,063°C [16].
After sublimation, everything is present in the volume involved gives origin to
an aerosol and than to condensation dust that, because of the very high temperature,
is often of nanometric size. The chemical composition of those particles is the
result of the fortuitous combination of the elements present in the occasional
crucible represented by the target and, on a smaller scale, by the bomb itself. The
main factor conditioning the size of that particulate matter (sometimes within the
order of magnitude of the tens of nanometres) is temperature and, as a general
rule, the higher it is, the smaller the particles are. As a consequence, the particles
generated close to the core of the explosion will be smaller than those formed in a
more peripheral area. Similar results occur when a great quantity of conventional
ammunitions is used, an event common when weapons must be disposed of and
that is done by setting them off, or when an explosion in an arsenal occurs out of
control. Such an event has been reported, for example, in a site close to Baghdad
[17].
The ultramicroscopic analyses showed the presence of micro- and nanoparticles
with unusual chemical compositions, in all cases metallic. Among other composi-
tions, we found alloys of Lead and Tin, Zinc–Iron–Titanium, Lead–Bismuth and
Bismuth alone, Tin–Silver, Iron–Copper–Zinc, Titanium–Iron, Silicon–Zirconium,
Strontium–Sulphur, Cadmium–Silicon and also Uranium–Thorium. All these
compounds are toxic due to at least one of their components and, because of their
morphology and dimension, they show a physical aggressiveness towards the
organism.
The formation of a brand new pollution, never experimented before, with a
chemical composition that at times is certainly toxic as is composed by non
biodegradable, non biocompatible heavy metals represents a novel stimulus to
which the human body is not prepared to react in a positive way nor is likely to be
capable of adapting [18].
Our organism needs Oxygen to live, along with a variety of nutrients, and
without Oxygen our cells can survive only for a very short time. Particularly in
modern warfare, because of high-temperature weapons, a novel, particulate
pollution is created that permeates man, animals and the whole environment, and
that form of pollution can be inhaled with the air and ingested with the vegetables
grown under the inevitable fallout that ensues. The school of Leuven (Belgium)
[19] demonstrated that inhaling 100-nm particles is risky for our health, since dust
that size negotiates the alveolar barrier within 60 s reaching the blood stream and,
within an hour, the liver and all other tissues and organs. As has been observed by
our group, those particles are trapped in any tissues acting like any mechanical
filter or can penetrate cell nuclei where can induce adverse effects both as foreign
bodies and as being composed of toxic elements.
The evidence we found consistently in the pathological-tissue specimens of the
more than 100 cases of ill soldiers studied is the most irrefutable demonstration of
this theory [20].
Other Authors chose to keep looking for a Uranium contamination in the
soldiers’ urine [21].
To be sure, the measurements they carry out can verify a possible
contamination from Uranium radioactivity, but do not take into consideration the
unavoidable lack of information about the quantity of radiations each patient
absorbed before a presumed exposure in a war theatre (zero reference). For that
reason, the value found is at least partially independent of the Uranium that may
have entered that organism. In addition to that, that value depends on the
capability the subject’s kidneys have to get rid of Uranium as an ion resulting
from the solution of materials present in the body, nor can we know whether those
materials are of natural or anthropic origin, and, in the latter case, if they come
from the use of weapons. And that hypothesis does not offer any explanation
about how subjects showing similar excretion values come to suffer from different
pathologies and, in particular, offers no explanation about the neurological
diseases reported by American and British soldiers (no systematic observations
exist for other nationalities).
Symptomatology caused by radiations is very well-known and is amply
described in medical literature dealing with Japanese subjects exposed to A bomb
radiations in August 1945. The symptoms reported there do not coincide with
those found in the veterans from the Balkans and the Gulf and, therefore, the
hypothesis that those syndromes may be caused by radioactivity looks hard to
accept.
It is a fact that, if at the beginning the symptoms observed were hardly
attributable to a single disease, as the different pathologies develop, the soldiers
died for cancerous diseases of different districts of the body; but cancer is very
frequent among the population (the incidence now is that it affects 1 subject out of
3) who was never exposed to Uranium radiations. It is well known that chemicals,
but radiations as well, can cause cancer, but it sounds strange that in a battle
theatre that group if pathologies is triggered only by radiation.
These considerations should lead to search for a cause compatible with the
objective data and the events occurred, and equally shared by soldiers, civilians
and animals.
The analyses completed in our laboratory on the bioptical and autoptical
samples taken from American, French and Italian soldiers, those on the same kind
of samples from soldiers and civilians active in firing grounds along with the
environmental analyses carried out in war theatres and in firing grounds induce us
to sketch out a different scenario and another possible causal agent, i.e. the sub-
micronic pollution created by weapon and target together.
As briefly described above, a temperature like the one brought about by DU
explosions generates extremely fine inorganic particles that can be inhaled and
ingested by men and animals alike. One of the peculiarities of such anthropic
pollution is its small size, and to that size they owe their capability to penetrate so
easily virtually any organ and tissue, none excluded, from the lymph nodes to the
brain to the gonads. Our analyses on about 1,000 cases involving soldiers,
civilians and workers busy in polluted sites is evidence of the presence of such
particulate matter and its dissemination inside the organism. In some circumstances,
the assessment of their morphology and chemical composition identifies unambi-
guously those particles as coming from random and very particular combustions
like a high-temperature explosion. It is a matter of fact that those particles are
neither biodegradable nor biocompatible and can interact in a noxious way with
the organism.
For a long time medical literature has described pathologies due to small
foreign bodies: silicosis, the lung disease caused by inhalation of silica microparti-
cles; asbestosis and mesothelioma from the exposure to asbestos dust; foreign-
body granulomatosis of various tissues.
On the other hand, toxicology relevant to the exposure to nanoparticles is a
fairly new subject and is still a matter of tentative approach in all technologically
advanced countries. Proof of that are the several American and European projects
in the field of nanotoxicology in progress at the moment. From 2002 to 2005, one
of the Authors of this text (Dr. Gatti) was the coordinator of a European project
called Nanopathology (www.nanopathology.it) at is now the coordination of a
second project called DIPNA (Development of an integrated platform for the
nanoparticle risk assessment).
Yet, a number of studies exist about the easiness with which nanoparticulate
enters the organism and is disseminated once inhaled or ingested. Their entry in
the brain may even be possible through the olfactory nerve as described by
Öberdörster [22, 23]. As soon as they are in the brain, they can represent an
irritative factor because of their characteristic of acting as electrical conductors
and/or, occasionally, because of their magnetic properties. The whole of all those
anomalous activities and their non biodegradability can be the cause of local toxicity.
One of the characteristics of this kind of particulate is its capability of moving
from pregnant mother to foetus. We did not have the chance to examine tissues
taken from miscarried, malformed foeti, the offspring of veterans, but checked
those from stillborn, malformed lambs whose mothers grazed in meadows
occupied by firing grounds. Pregnant sheep fed on grass polluted by the dust
created by explosions, and that dust, delivered to the embryo, was then found in
the dead lamb. It is evident that particulate matter can be compatible with the
development of an embryo, but that development is abnormal and in most cases
incompatible with life outside the mother’s womb. Similar cases did we find in
human malformed foeti, but, in those circumstances, the cause was attributable to
industrial or urban pollution.
A few other hypotheses have been put forward to explain the so-called Balkans
and Gulf syndromes. One of them is the use of multiple, certainly too close in
time, vaccinations. That could be taken into account, but only if in those cases
where a temporal consequence can be demonstrated, i.e. when, immediately after
the vaccines have been administered, the subject shows an ailment that grows
worse.
It is a well-known fact that so-called adjuvants (http://www.emea.europa.eu/pdfs/

human/vwp/13471604en.pdf) are added to vaccines in order to improve the
immune response so a lesser quantity of drug is needed and enhance the organism
reaction because of their pyrogenicity. Adjuvants can be inorganic matter that can
be made up by heavy metals. Mercury was widely used before it was banned
because of its obvious toxicity.
As shown by our studies, inorganic, non biodegradable and non biocompatible
particulate like that used in vaccines cannot been disposed of by the organism and
the consequences of its introduction into the body are the ones mentioned above.
As briefly reported, it is not just soldiers who suffer from the Balkans and Gulf
syndromes or from similar collections of symptoms and diseases, but it is also
soldiers active in firing grounds or civilians living in war theatres. Especially
civilians were never subject to multiple vaccinations nor took cocktails of drugs
the way soldiers, in some circumstances, do, and, therefore, it is really hard to
blame the vaccines when only part of the patients were exposed to them.
Nevertheless, ruling out the possibility that using vaccines and drugs in a way
that is so concentrated and outside medical experience may be an aggravation and
make the onset of the disease easier, does not look correct and the hypothesis
deserves further investigation.
Hypotheses like the one linked to the use of sprays against bacteriological war
shows the same weak points as the theory above.
In conclusion, the analysis on pathological tissues aimed at detecting parti-
culate matter looks the most meaningful test to assess the exposure the subject
underwent.
2. The Contamination
The soldiers’ pathological tissues we analyzed showed the presence of micro- and,
more commonly, nanoparticles. The chemistry we came across was sometimes
unusual: Mercury–Selenium, Antimony–Cobalt, Zirconia. It was somewhat surprising
to find inside soldiers’ tissues particles we thought to be confined in nanotech-
nological laboratories.
Zirconia, for instance, as we found in a soldier’s spleen (see Figure 1), has a
melting point of about 2,400°C and the generation of nanoparticles of that
material, outside a nanotechnological laboratory, implies temperatures peculiar to
special combustions.
During the blast of high-technology weapons or of an accumulation of
ammunition, a very high temperature is created that can cause the formation of
aerosolized material that are disseminated in all the solid angle around the
explosion site. As a consequence of the blast power and the meteorological condi-
tions (presence of wind, rain, etc.) this fresh pollution can be disseminated to a
distance of many kilometres from its origin. A different stratification in the space
of the micro and nanoparticles is possible and logic, but no scientific data are
available in a battle theatre.
Figure 1. Zirconia micro and nanoparticles embedded in a spleen tissue in a patient affected by non-
Hodgkin lymphoma. The Energy Dispersive spectroscopy identifies the particles composed of Carbon,
Zirconium, Oxygen, Chlorine, Iron.
Immediately after the explosions a fresh contamination of the environment

occurs that can involve humans and animals for the pollution of air and soil. Grass
can act as a repository for the fall-out of this pollution and since it is a food for
animals, it can pollute them. That way, animals ingest biodegradable grass containing
not-biodegradable and non-biocompatible particles. The analyses we carried out
on malformed lambs born inside a firing range confirm the hypothesis of a
pollution in the mother and its translocation through the fetal circulation to the
embryo. Also the observations on cigarettes and tobacco leaves from Sarajevo
immediately after the bombing confirm the existence of a characteristics war
pollution on the flora. (The tobacco industry was the only manufacturing plant that
still operated during the siege and bombing of Sarajevo because, unlike other
industries, it did not need electricity that was very scarce.)
Figure 2 shows the so-called war contamination of a tobacco leaf where a
particle containing also uranium and thorium is visible.
As a conclusion, it is indispensable that the new wars take into account the
micro and nanopollution generated by the explosions [24].
Figure 2. Tobacco leaf surface with particles of environmental dust. The whiter debris is a compound
of Phosphorus, Oxygen Carbon, Cerium, Lanthanium, Neodymium, Silicon, Aluminum, Magnesium,
Chlorine, Potassium, Thorium, Uranium and Iron.
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SMARTEN
Strategic Management and Assessment of Risks and Toxicity of Engineered
Nanomaterials
C. METCALFE
Environmental and Resource Studies
Trent University
Peterborough, Ontario, Canada
cmetcalfe@trentu.ca
E. BENNETT
Intertox, Inc.
Salem, Massachusetts, USA
M. CHAPPELL, J. STEEVENS
Environmental Laboratory
U.S. Army Corps of Engineers
Vicksburg, Mississippi, USA
M. DEPLEDGE
Peninsula Medical School
Plymouth, UK
G. GOSS
Department of Biology
University of Alberta
Edmonton, Alberta, Canada
S. GOUDEY
HydroQual Laboratories
Golder Associates Ltd.
Calgary, Alberta, Canada
S. KACZMAR
O’Brien and Gere Engineers Inc.
Syracuse, New York, USA
N. O’BRIEN
School of Agriculture, Food Science and Veterinary Medicine
College of Life Sciences
Dublin, Ireland
A. PICADO
Instituto Nacional de Engenharia Tecnologia e Inovação
Lisbon, Portugal

96 C. METCALFE ET AL.
A.B. RAMADAN
National Egyptian Environmental and Radiation Monitoring Network
Cairo, Egypt
Abstract. Traditional risk assessment procedures are inadequate for predicting the
ecological risks associated with the release of nanomaterials (NM) into the
environment. The root of the problem lies in an inadequate application of solid
phase chemical principles (e.g. particle size, shape, functionality) for the risk
assessment of NMs. Thus, the “solubility” paradigm used to evaluate the risks
associated with other classes of contaminants must be replaced by a “dispersivity”
paradigm for evaluating the risks associated with NM. The pace of development
of NM will exceed the capacity to conduct adequate risk assessments using current
methods and approaches. Each NM product will be available in a variety of size
classes and with different surface functionalizations; probably requiring multiple
risk assessments for each NM. The “SMARTEN” approach to risk assessment
involves having risk assessors play a more proactive role in evaluating all aspects
of the NM life cycle and in making decisions to develop lower risk NM products.
Improved problem formulation could come from considering the chemical,
physical and biological properties of NMs. New effects assessment techniques are
needed to evaluate cellular binding and uptake potential, such as biological assays
for binding to macromolecules or organelles, phagocytic activity, and active/passive
uptake processes. Tests should be developed to evaluate biological effects with
multiple species across a range of trophic levels. Despite our best efforts to assess
the risks associated with NM, previous experience indicates that some NM
products will enter the environment and cause biological effects. Therefore, risk
assessors should support programs for reconnaissance and surveillance to detect
the impacts of NM before irreversible damage occurs. New analytical tools are
needed for surveillance, including sensors for detecting NMs, passive sampling
systems, and improved methods for separation and characterization of NMs in
environmental matrices, as well as biomarker techniques to evaluate exposure to
NMs. Risk assessors should use this information to refine data quality, determine
future risk assessment objectives and to communicate interim conclusions to a
wide group of stakeholders.1
1. Introduction
Engineered nanomaterials (NM) are generally regarded as man-made materials

with at least one dimension below 100 nm [6]. Nanoparticles can occur naturally
(e.g. ash, colloids, large biomolecules), or can be produced unintentionally (e.g.
diesel exhaust), but concern over the potential adverse environmental impacts of
1
SMARTEN 97
nanoparticles has been directed at engineered NMs. Engineered NM can be

divided into four different classes: carbon-based materials (e.g., fullerenes), metal-
based materials (e.g., gold or titanium dioxide nanoparticles), dendrimers (e.g.,
nano-sized polymers), and composites (i.e., mixtures of nanoparticles). Nanoparti-
cles typically have different physico-chemical properties compared to their
respective bulk material, including different optical properties, thermal behaviour,
material strength, solubility, conductivity and catalytic activity [8]. Probably the
most significant change in the properties of nanoparticles is the increase in surface
to volume ratio [4]. The proportion of atoms at the particle surface increases
inversely with particle size, so that the surface properties of nanoparticles can
dominate the properties of the bulk material [43]. These particles can also transfer
energy to nearby oxygen molecules, which leads to the formation of reactive
oxygen species (ROS). Exposure to oxyradicals can lead to cell damage and death
[12]. Nanoparticles are similar in size to biological macromolecules such as
proteins, DNA and phospholipids, so it is possible that NMs can cause disruptions
at the molecular and cellular level. Many other physical and chemical factors can
influence the toxicity of NMs, including surface reactivity, the dissolution ratio,
and particle shape [42].
2. Ecotoxicology and Risk Assessment Techniques
Ecotoxicology is an integrative field that includes evaluations of the environ-

mental fate and the biological effects of chemicals. Assessments of environmental
impacts are based on a weight-of-evidence approach that combines environmental
chemistry, acute and chronic toxicity testing with single species, evaluation of
biomarkers of exposure and effect, and studies of ecosystem-level responses.
Laboratory-based bioassays are typically performed using model species represen-
ting different feeding strategies and positions in food webs. Multiple species
toxicity tests are of value to identify sensitive species and to study the variations in
toxic effects across taxonomic groups.
Elements of ecotoxicology are also included in methods for ecological risk
assessment. In these procedures basic data gathering involves an “Exposure
Assessment” and an “Effects Assessment”. In the Effects Assessment, efforts are
made to determine the thresholds for toxicity in organisms, and in the Exposure
Assessment, efforts are made to determine the concentrations to which organisms
may be exposed in the environment. Risk Characterization involves comparing
the Exposure Assessment and Effects Assessment data to give an indication of the
“risk” of toxic effects occurring among organisms exposed to a chemical. In the
context of exposures to NM, risk assessments must be conducted to try to evaluate
the environmental hazards associated with new NM products that are to be
introduced into the marketplace, or to assess the hazards associated with existing
NM products that may already be present in the environment. For new NMs that have
not yet been introduced into the marketplace, there are no data regarding the con-
centrations in the environment, and so the predicted environmental concentrations
must be estimated. For NM that have the same elemental or chemical composition,
but differ in size, shape or surface properties, is not clear whether separate risk
assessments will be required for each individual product. Various jurisdictions
have called for integrated risk assessment procedures for nanomaterials [6, 35]. In
this review, we present a case for a fundamentally different approach to risk
assessments for NM released into the environment. The “SMARTEN” approach
requires that several elements of traditional risk assessments be abandoned or
reformulated in order to address the unique characteristics of NM.
3. The “Nano-effect” Paradigm
The “nano-effect” may be defined as unique or enhanced NM properties, reactions

or biological interactions that occur below a specific particle size threshold.
This term implies that such effects are not observed with larger particle sizes.
Enhanced properties are associated with decreasing particle size, as a function of
increased particle surface area. Incorporation of the principles of the nano-effect
into traditional environmental risk assessment procedures requires a paradigm shift
from the concepts that are applied to “conventional” environmental contaminants,
such as pesticides and industrial chemicals. Table 1 summarizes the novel char-
acteristics of nanoparticles that must be considered in an environmental risk
assessment, relative to the parameters that are considered in risk assessments of
other classes of contaminants.
TABLE 1. Characteristics of NM that must be considered for environmental risk assessments, relative
to the characteristics considered for “conventional” classes of contaminants.
Characteristic Nanoparticles Other contaminants
Distribution in water Dispersivity Solubility
Distribution in porous Filtration Adsorption/desorption
media
Biological availability Sorption? Lipophilicity
Cellular uptake Vesicular transport? Passive or facilitated diffusion
Toxic mechanisms Steric hindrance, photo-chemical Interactions with cellular
effects, oxidative damage, macromolecules and receptors,
inflammation narcosis
Target trophic systems Bottom of the food chain? Top of the food chain
3.1. DISTRIBUTION IN THE ENVIRONMENT
3.1.1. Interactions
NM may interact in the environment in the following ways:

(a) Flocculation: Most NMs tend to readily flocculate. NM dispersions may be
temporarily stabilized by severe agitation, such as sonication, but this has the
potential to introduce artifacts onto the NM surface. NM dispersions are also
stabilized by derivatizing the particle surface by introducing charged groups.
However, experimental evidence shows that adding very dilute salt is
sufficient for NMs to again readily flocculate. NM dispersions are readily
stabilized in the presence of dissolved humic substances. This behavior
SMARTEN 99
appears linked to the surfactive character of dissolved humic substances, which

minimizes NM particle size and poly-dispersivity [9]. Aggregation of carbon
nanotubes was inhibited by the addition of humic and fulvic acids [24].
Dissolved organic material commonly occurs at concentrations in natural
aqueous systems that are capable of stabilizing NM dispersions [34]. These
type of changes may alter the behavior of NMs in water and soils.
Nanoparticulate FeO coated with sodium dodecylsulphate was stable in a soil
suspension for 14 days, without changes in the particle size distribution [18].
In solid-gas systems (water-limited), the small size of NM makes them readily
aerosolized. For example, Murr and Garza [31] showed that so-called clean-
burning technologies produce extremely small-sized combustion products (i.e.,
carbon nanotubes) that easily form aerosols, compared to products created with
older technologies.
(b) Dissolution: Most NMs are highly insoluble, yet some material may dissolve
in the presence of organic chelators, resulting in the release of its metallic
constituents into the environment. For example, there is some evidence that
FeO nanoparticles are dissolved in the presence of acetate/lactate [33].
(c) Sorption: NMs may readily sorb other constituents in the aqueous phase. For
example, Madden et al. [29] observed that smaller FeO particles (7 nm)
undergo greater specific adsorption by Cu2+ ions than larger FeO particles (25
nm). NMs themselves may also be sorbed onto soil surfaces. In a sense, NM
sorption in a soil is analogous to flocculation of individual NM particles in
which NMs are simply “added” to the bulk environmental solids.
(d) Transformation and degradations: Most inorganic NMs are used in oxidized
forms that are stable under ambient conditions. On the other hand, organic
NMs may be degraded when exposed to the environment. For example,
fullerenes appear to be spontaneously but slowly oxidized in solution. Ozone
has proved much more reactive, however than molecular oxygen to fullerenes
[10], which may be a relevant transformation mechanism in advanced
treatment systems for water and wastewater. CNTs are highly resistant to
degradation (analogous to soil black carbon). However, manufacturers appear
to introduce limited functionalization in even so-called non-derivatized CNTs
in order to facilitate separation and purification during manufacturing.
There is little information available concerning the microbial transformation of
NMs. Redox reactions are often mediated by microorganisms; either directly through
enzymatic activity, or indirectly through the formation of biogenic oxidants or
reductants [28]. Biological modifications, as well as degradation of the surface
functionalization may result in modified NM structures and freed constituents.
3.1.2. Distribution
Perhaps the most important paradigm shift that must be understood for risk
assessments of NM relates to the concept of “solubility” of chemicals and the
“dispersivity” of nanoparticles in aqueous media. The capacity of nanoparticles to
disperse in aqueous media will govern their environmental fate. NM dispersed
within the aqueous phase are more mobile, and aggregation of NM reduces
mobility [17, 24]. This concept is fundamentally different from the solubility
paradigm that drives our predictions of the environmental fate and biological
availability of other classes of contaminants. Properties such as water solubility
and octanol/water partition coefficients (i.e. log Kow) are the basic parameters
used to assess the risks associated with exposure to contaminants that are
governed by the solubility paradigm. Similar key properties have not yet been
identified for risk assessment of nanoparticles, but the characteristics that
influence the “dispersivity” of nanoparticles in aqueous media include particle
size, charge, speciation, crystallinity, surface area, and adsorbed phase composition.
These properties are reviewed elsewhere in this book.
The distribution of NM in porous media, such as soils and sediments is also
governed by the size, shape and charge distribution of the particles. Filtration of
nanoparticles through porous media is influenced by electrostatic interactions
between the particles and soil/sediment. However, physical interactions that
“sieve” the particles within the media are also an important factor [13]. Data from
laboratory experiments indicate that NM may be relatively immobile in soils [41],
or they may be relatively mobile [26], depending on the characteristics and size of
the NM.
3.2. BIOLOGICAL AVAILABILITY AND UPTAKE
For small organic molecules, lipophilic compounds are more biologically available
than hydrophilic compounds, and uptake of lipophilic compounds occurs through
passive diffusion across the cell membrane. For metal cations, uptake occurs as a
result of facilitated diffusion of metal-protein complexes across cell membranes.
The factors governing the biological availability and cellular transport of NM are
less well understood. For fish, it has been suggested that the first step governing
biological availability is trapping of NM in the mucous layers of the skin, gills and
gut epithelium [20]. It is unlikely that NM are transported by passive or facilitated
diffusion across cellular membranes. Indeed, Moore [30] suggests that vesicular
transport (i.e. endocytosis, pinocytosis) may be the most important mechanism of
NM transport into cells. If this is the case, then some invertebrates (e.g. bivalves)
that have a high capacity for vesicular transport within gastrointestinal tissues may
be especially susceptible to uptake of NM. Fish are capable of greater uptake by
endocytosis in the gut than higher vertebrates. It is clear that some NM can be
transported through tissues, including the blood-brain barrier [25]. It is possible
that this type of transport occurs through para-cellular routes, such as transport
across tight junctions. However, much remains to be learned about the mechanisms
of uptake and transport of NM in organisms.
3.3. MECHANISMS OF TOXICITY
Once NM enter the tissues of organisms or are transported across cell membranes,
toxicity is likely to occur principally through one or a combination of four
mechanisms (Figure 1). The first mechanism involves the release of the chemical
SMARTEN 101
constituents from the NM, which produces toxicity through more or less
“conventional” processes, such as the release of toxic cadmium ions from CdTe
nanoparticles [11, 44]. The other three mechanisms of NM toxicity are typically
not observed for the classes of contaminants that are considered when using
traditional risk assessment methods. Thus, a second mechanism of NM toxicity is
related to the size and shape of the particle, which produces steric hindrances or
interferences with macromolecules such as phospholipids, nucleic acids and
proteins. For instance, the penetration and toxicity of CdTe quantum dots in vitro
in nerve and glial cells was more pronounced with small (2.2 nm diameter)
positively charged CdTe than large (5.2 nm diameter), equally charged CdTe.
[27]. A third mechanism involves the surface properties of the NM, such as
photochemical properties, local electric fields, charge densities, and electronic
semi-conductance. These surface properties may result in the formation of oxygen
radicals that can damage macromolecules [3, 36], but it is also possible that the
surface reactivity of NM could directly disrupt cellular processes, such as energy
production in mitochondria [28]. In some cases, it is not clear whether damage as
a result of the presence of oxyradicals is due to the direct effects of the NM (i.e.
mechanism 3), or due to the indirect effects of macrophage and granulocytes
involved in an inflammatory response induced by the presence of the NM in
tissues (i.e. mechanism 2). Duffin et al. [16] observed that the extent of lung
inflammation depended not only on the particle surface area, but also on the
surface reactivity in rats exposed to nanoparticles. The fourth mechanism of
toxicity is related to the capacity for NM to act as vectors for the transport of other
toxic chemicals to sensitive tissues. In a study with fish (i.e. carp), cadmium
accumulation was increased 2.5-fold when TiO2 nanoparticles were added
concurrently with cadmium salts [45].
3.4. VULNERABLE LOCI IN TROPHIC WEBS
Organisms occupying particular loci in trophic webs may be at increased risk of

nanotoxicity. Toxicity tests have been performed with NMs using a variety of test
organisms, ranging from bacteria to algae to benthic invertebrates and fish [7, 28].
In many cases, bacteria, plants and invertebrates were the most sensitive organisms
to the biological effects of NM. Adams et al. [1] evaluated the toxicity of three
photosensitive NMs (FeO, TiO 2, SiO2) to two bacterial species, Bacillus subtilis
and Escherichia coli, and the cladoceran, Daphnia magna. The most sensitive
species was the suspension feeding cladoceran. In a study of the toxicity of ultra-
fine TiO2, a green alga, Pseudokirchneriella subcapitata, was the most sensitive
species in comparison to rainbow trout and D. magna [42]. In addition, deposit
feeders or filter feeders are the most likely organisms to accumulate NM from
water, soil and sediments. There is considerable evidence that a range of NM
exhibit anti-bacterial activity [32].
Release of Physical effects of

NM constituents size and shape
Effects Effects on
on gene
membranes expression
Other Effects on Effects on Inflammatory

macro- enzyme Response
contaminants activity
molecules
Surface
Vector for other reactivity
contaminants
Light
Figure 1. Mechanisms of toxicity of nanomaterials in organisms.
These results indicate that the biological effects of NMs may be observed first
in organisms from lower trophic levels. In conventional risk assessments, more
weight is placed on toxicity testing using fish species, and special emphasis is
placed on chemicals that show potential for bioaccumulation and biomagnification
through food chains. For risk assessments of NM, it is logical to assume that bio-
logical effects will be observed among mainly invertebrate species and micro-
organisms at the lower levels of the food web, or organisms that are important in
geochemical and nutrient cycling. For instance, Tong et al. [40] observed that
fullerenes impacted the composition of soil microbial communities.
4. The Strategic Management and Assessment of Risks and Toxicity

of Engineered Nanomaterials (SMARTEN)
Risk assessments for NM will require a shift in approach from the methods of
exposure assessment and effects assessment that have been used previously for
other classes of contaminants [21, 37]. As discussed above, conventional risk
assessment procedures are hampered by adherence to paradigms that focus on the
solubility and partitioning of chemicals, and fate and exposure pathways that may
not be relevant for NM. Extensive use of lethality data for toxicity endpoints may
also be inappropriate as our greatest concerns for NM center around sublethal
effects, such as genotoxicity and inflammatory responses.
The diverse properties of NM and the lack of clearly defined approaches are
currently a major impediment to risk assessment of these materials. Among
companies producing NM products in Germany and Switzerland, 65% indicated
that they do not currently conduct risk assessments [23]. At the moment, there is a
relatively short list of NM products in commercial production that require
environmental risk assessment, but there is looming on the horizon a much greater
SMARTEN 103
challenge. As we approach the next few decades, the large investments made in
nanoscience around the world will yield a myriad of new products. The
penetration of many new NM products into the marketplace will outstrip the
ability to perform full risk assessments. Will a change of a single moiety on a
given nanomaterial that alters its physical characteristics (e.g. water solubility) but
not its functionality require a new risk assessment? Will the same NM product
marketed over different size ranges require an individual risk assessment for each
size class? The sheer magnitude of new materials will quickly outstrip the capacity
of the regulatory agencies and industry to respond in a timely manner, resulting in
reduced investment in the technology.
Methods are needed to prioritize new NM products and target them for
environmental risk assessment, while minimizing the potential for adverse
environmental effects. An overall goal should be to provide industry with
information on potential mechanisms of toxicity or biological interactions early in
the product development cycle. Thus, the specific properties of the product can be
tailored to minimize any unwanted effects, while maintaining the commercially
desirable properties of the material. This “green-nano” approach will allow
industry to develop their products using the best available information; regulators
to prioritize particles of concern and provide industry with a structure under which
they can introduce new products to the marketplace.
One approach to effective risk assessment of new NM products is to more
thoroughly examine the existing information available from the manufacturer,
such as anticipated volumes of production, the product life cycle and the basic
physical and chemical information available for the material. This conceptual
model should accommodate non-traditional measures that provide evidence
regarding the source, fate, expected media, exposure pathways, and potential
receptors. As illustrated in Figure 2, some of this information can be used to make
predictions about the likely transport processes into the environment, exposure
pathways and receptors for biological effects. In spite of a lack of fate, transport
and effects data normally associated with traditional risk assessment, this approach
may allow predictions to be made of the environmental hazards of NM.
To develop a strategy that provides this required information, it is absolutely
necessary that toxicologists and physical scientists work together to identify the
physical and chemical properties that make NMs hazardous. In a recent review,
Handy et al. [21] identified the need to understand the biological implications of
differences in NM shape, size, surface charge, coatings, attached functional
groups, core metals, intracellular dissolution, etc. A logical effort will require
specific manipulation of the physical characteristics of a singe base class of NM
(and repeated for different classes of NMs), followed by toxicity testing with a
number of in vitro and in vivo models. Moreover, similar testing should be cross-
validated in at least two independent laboratories to ensure the validity of the
results. While this effort seems extensive (and expensive), a logical hypothesis
based scientific approach offers a practical mechanism for the provision of
baseline data in the near and far term to understand the nature of biological
interaction with different NM classes.
2. Media and 3. Exposure Pathways

1. Sources Transport Processes and Receptors
Air Terrestrial
Inbalation Vertebrates
Aggregation /
Con n
UV Degradation
tact tio
es
Ing
Terrestrial
Invertebrates
Engineered Settling / suspension t
Nanostructures ac
nt ion
Soil Co est
g
In
Engineered Contact, Ingestion
Nanodevices Degradation
t
ac
Ing tact
ion
Reaction nt ion
Co est
est
n
Intermediates
Co
Sorption / desorption In
g
Ingestion
Aquatic
Production Invertebrates
Waste Water Contact
Aggregation/ Ingestion
Ingestion
Product Degradation Fish Fish
Degradation
n
tio
ge act
on
es
Settling / suspension
nt
sti
Ing
Co
In
Sediment
Contact Benthic Ingestion
Product use, Spills Degradation Ingestion Invertebrates
Intentional application,
disposal
Figure 2. Conceptual framework for utilizing information from the NM manufacturer to make
predictions about the environmental fate and effects of NM.
To address these issues, the SMARTEN approach involves thinking more

carefully about the likely fate, exposure and effects of NM, such as considering
the characteristics summarized in Table 1. For example, many NM with particle
sizes in excess of 4 nm that enter aquatic environments are likely to aggregate and
be deposited in sediments or floc layers that overly sediments. This suggests that it
might be wiser to investigate the effects of these NM on deposit feeding
organisms rather than species that live in the water column. Current laboratory
methods that have been developed to provide the data for conventional risk
assessments, such as the OECD test methods [14] may not be appropriate for
evaluating NM. It may be necessary to develop new test methods, such as assays
to evaluate binding to synthetic skin or nano-sensors, or uptake across biofilms.
Test systems to evaluate phagocytosis or inflammatory responses as a result of
exposure to NM may be more relevant endpoints than acute toxicity tests with
whole organism models.
5. Environmental Surveillance and Reconnaissance
The current regulatory frameworks in North America and Europe that require
environmental risk assessments to be conducted prior to the introduction of new
chemicals into the marketplace have only been in place for the past 15–20 years.
However, there are now several examples of the failure of these regulatory
approaches to predict the impacts of chemicals on ecosystems. For instance,
SMARTEN 105
perfluorinated substances used in fluoropolymer products are accumulating in the

environment [38] including in humans [2], despite earlier evaluation of the risks
that these substances might pose. Since it appears that current risk assessment
protocols are not adequate for the surveillance of conventional chemical classes, it
is reasonable to assume that some NM products will be approved for commercial
production that will have impacts in aquatic and/or terrestrial ecosystems. Environ-
mental surveillance and reconnaissance programs are required to safeguard against
these eventualities. The traditional analytical approaches that are used to detect
others classes of contaminants in the environment will not be appropriate and new
analytical techniques will be needed for surveillance purposes [22, 39]. Modified
and/or novel sampling devices may be needed, such as passive sampling devices or
nano-sensors that can be deployed in water, air or soil to detect the presence of NM.
Over the years, biomarkers have been developed that are efficient at providing
an early warning of deleterious effects on biological systems [15]. Goldberg and
Bertine [19] argued that the analysis of the detoxifying enzymes, cytochrome P-450
activity, metallothioneins and estrogenic responses can provide useful information on
the effects of contaminants in the aquatic environment. It may be possible to develop
a unique set of biomarkers that can be used in surveillance programs to monitor
for the biological effects of NM. Toxicogenomics methods may be valuable
biomarkers for evaluating exposure to NM.
6. Overview
The SMARTEN framework can also be integrated into wider concepts of

“Environmental Security”, which involves actions that guard against environ-
mental degradation in order to preserve or protect humans and natural resources at
scales ranging from global to local in a sustainable manner. Environmental security
can best be viewed as a response to one or more of three categories of events:
(a) Manmade gradual changes that slowly erode economic and environmental
sustainability, and, in some cases, may even be irreversible.
(b) Natural catastrophic events that, to some extent, may be predictable, so it is
possible to plan response and protection measures.
(c) Manmade catastrophic events, which are typically sudden and unpredictable.
The different perspectives on environmental security are time, spatial scales (i.e.
local, regional, national, trans-national, global). Nanotechnology risk management
challenges may be viewed according to the rankings illustrated in Figure 3.
The field of environmental security is changing rapidly. Government and
academic research in western countries appears to be undergoing a process of
reshaping on an annual basis as a result of public health scares and sudden tragic
world events. Environmental security will continue to change and evolve as new
threats, both manmade and natural, reveal themselves at local, national or interna-
tional spatial scales. Frameworks for organizing environmental security programs
for nanotechnology, therefore, must be flexible and must adapt as either current or
new challenges and response to those challenges manifest in additional or unforeseen

consequences.
Assessment and Ranking of Risks
Comprehensive, Qualitative to Semi-quantitative

but qualitative Integrative
semi-quantitative to quantitative
Rank risks in Integration of risk
Develop a list terms of Detailed analyses to identify
of potential potential costs analysis of shared attributes,
threats and (e.g., $, injuries, ranked risks in Common variables,
vulnerabilities fatalities, lost order of ranking and risk synergies.
opportunities)
and time scales Re-order
over which risks Ranking accordingly
occur
Figure 3. Rankings of risks associated with exposure to NM.
In addition to decision frameworks, new or improved technologies and

environmental monitoring programs are needed to enhance prevention, response,
and mitigation strategies and to anticipate or forecast when threats might occur. In
future, environmental surveillance programs must: (a) support real-time decision
making, (b) provide accurate and impartial data to avoid human interference, (c)
provide for stable, long-term safekeeping of data, (d) support other environmental
applications, and (e) support long-term planning schemes such as early warning
systems.
This paper presents a suggested framework for evaluating the potential
environmental and ecological hazards of NM. This framework, referred to as
SMARTEN outlines some ideas about the fundamental informational needs.
However, with recognition of the wide range of physical and chemical properties
of NM, their uses and the rate at which new products and applications are likely to
be developed, it is not intended to be a comprehensive “check list” of required
testing strategies that must be performed before NM products enter into
commercial production. SMARTEN is intended as a starting point of an iterative
process by which a NM product can be evaluated. The process features and
emphasizes decision points where the new information is combined with and
compared against previous information, as well as available data on similar
materials. In each step, a conceptual model of the potential hazards of the material
is refined, questions and data quality objectives are raised, and a decision is made
as to the need for and scope of additional testing. This approach is intended to
provide a degree of flexibility that reflects the current degree of uncertainty and
the need to provide a means for the expedited evaluation of products of
nanotechnology.
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SOLID-PHASE CHARACTERISTICS OF ENGINEERED
NANOPARTICLES
A Multi-dimensional Approach
M.A. CHAPPELL
U.S. Army ERDC
3909 Halls Ferry Road
Vicksburg, MS 39056, USA
Mark.a.chappell@usace.army.mil
Abstract. The challenge associated with determining the environmental fate and
risk of engineered nanomaterials lies in understanding the fundamentally
associated solid-phase chemistry. The solid phase represents the most complex,
most thermodynamically “powerful”, yet the least understood phase among the
three phases (solid, liquid, gas) commonly present in environmental systems. This
difficulty is compounded by the fact that the nanoparticle size range represents a
frontier field in itself in solid-phase chemistry, being the smallest size particles,
close to the solid-phase – macromolecule boundary yet the most chemically
reactive fraction in solid mixtures.
This chapter contains a brief review of some important properties or
characteristics of solid phase particles. These properties are presented theoretically
as directed interactions among multiple linkages of any single property to another.
Selected properties discussed in this chapter include particle charge, crystal
structure, surface and bulk speciation, surface area, and adsorption phase com-
position. This discussion is presented in the context of solid-phase characteristics
that influence nanoparticle dispersion stability and potential bioavailability by
controlling particle size.
1. Introduction
The intended purpose of this paper is to review solid phase chemical properties
of nanoparticles important for describing their reactivity in environmental
systems. In doing so, it is important to realize that the current level of knowledge
for solid-phase chemistry is far inferior to that of the chemical knowledge of
liquid and gas phase systems. This knowledge gap is attributed to the higher order
of complexity of the solid phase and the difficulty of probing these systems. When
studying solids, one not only deals with the unique chemistry of the solids’ con-
stituents, but the bonding and coordination environment among the constituents
confers a super-molecular complex that exhibits its own unique dynamics,

112 M.A. CHAPPELL
structural order, vibration, electronic, and magnetic properties, to name a few. It is

this ability that makes solid phase chemistry so formidable. Yet, it’s the power of
this behavior that makes the solid phase the dominant phase controlling geologic
and biological chemistry on the Earth’s surface.
A major obstacle to deciphering this chemistry lies in probing the solid phase
systems. While liquid and gas phases are easily captured and mobilized through
elaborate analytical systems, environmental solids are neither fluid nor (typically)
transparent. Numerous techniques have been developed to facilitate analysis of
solid phases. Chief among these are extraction techniques designed to transfer the
solid phase constituents to the liquid phase for ease of analysis. But aside from the
elemental analysis and stoichiometries, most of the fundamental information is
lost, particularly in terms of the constituent speciation (yet, there do exist some
liquid phase techniques for this), coordination environment, long-term order, and
macroscopic properties. More often than not, little is preserved of the solids’
inherent chemistry, often relegating atomic constituent speciation to arbitrary
delineations based on the properties of the extractant.
Adding to the complexity of solid phase analysis is the unique behavior of
solids at their surface interface. A solid surface, typically defined as the first few
atomic layers at the “outer edge” of the solid, is where most of the solid’s excess
energy is exhibited, and potentials are created to promote chemical and physical
work. While liquid and gas phase solutes enjoy high degrees of freedom of
movement to alleviate energy excesses, the confining environment of solid phases
forces these excesses to be transferred to the surface atomic layers. Three common
means by which surface excess energy is reduced are (1) phase transitions, (2)
surface reconstructions, and (3) adsorption of liquid or gas phases and associated
solutes [1]. The relative small size of the surface compared to the rest of the
material, termed the “bulk”, makes it difficult to probe as well.
Solids exhibit a variety of seemingly unrelated or even contradictory properties
so that adequate descriptions based on one or two properties are (if ever) adequate.
And in addition, these properties can seem contradictory to each other. For
example, a solid can be charged but behave hydrophically. Because the chief
defining property of engineered nanomaterials is particle size, this review will
focus on the relationship of solid phase properties to the particle size of
nanomaterials. Figure 1 shows a theoretical chart proposing relationships between
solid phase nanoparticle properties and linkages to particle size, and potentially
stabilizing nanoparticle dispersions [2]. This list is by no means complete nor
represents all of the properties of nanoparticles, but is presented to the reader as a
guide for the following discussion of different solid phase properties. Notice in the
schematic that particle size is predominantly represented as a property resulting
from other properties. Thus, this review focuses on the other properties viewed as
controlling nanoparticle size.
SOLID-PHASE CHARACTERISTICS OF ENGINEERED NANOPARTICLES 113
5 3
1 4
8 6
Figure 1. Schematic showing hypothetical relationships between solid-phase properties discussed in

this review and particle size (controlling dispersion potential). 1 = particle size, 2 = crystal structure, 3
= interior strain, 4 = species, 5 = surface area, 6 = surface charge density, 7 = surface electrical
potential, and 8 = adsorbed phase. For this paper, edge sizes are all assumed = 1.
2. Particle Charge
2.1. CHARGE DEVELOPMENT AND THE DDL
Perhaps, the best understood mechanism for influencing particle size is particle
charge. Charge can develop on the surface through different ways, such as at the
solid’s crystal edges or functionalization/degradation of the nanomaterial (NM)
surface. For example, NMs may be functionalized with external COOH groups,
which will deprotonate as the system pH is increased away from the functional
group’s pKa. A material that develops charge in this way is termed “variable-
charged” because the total charge of the solid phase is affected by the system pH.
Charge that arises from internal deficits in the particle bulk composition (such as
geologic isomorphous substitution) result in “constant-charge” materials. This
review will focus solely on descriptions of variably charged materials.
A variably charged surface experiences charge with a change in pH. Classical
colloidal theory describes a situation at the solid-solution interface where charge
developed on the surface is expressed out into the surrounding solution a certain
distance away from the particle. This charged volume around the particle is called
the “diffuse double layer” or DDL. The DDL is an electrical field driven by a
surface electrostatic potential, ψo [3], which has formed to electro-neutralize the
114 M.A. CHAPPELL
surface. In classical theory [4], the DDL is filled with oppositely charged
counterions swarming around the wetted surface, attempting to establish electro-
neutrality – the distribution of cations and anions matching the electrical potential
of the interfacial field.
The DDL is generally divided into two layers (although more layers have been
added on in modern times): The Stern layer and the diffuse layer (Figure 2). The
Stern layer is a very thin volume of the solid-solution interface directly adjacent to
the surface. The tight complexation of coordinating water and counterions makes
the Stern layer rigid and compact, forming what is known as the plane of slippage
or the plane of shear [5]. Beyond the Stern layer is a layer composed of more-
loosely complexed counterions and coordinating water called the diffuse layer.
Here, the influence of ψo pulls oppositely charged counterions toward the surface
while diffusion forces allow some same-charged ions to approach the surface as
well.
Much of the charge-related chemistry that occurs at particle surfaces is
controlled by the surface electrical potential and the distance in which that
potential “influences” the bulk solution. The extent in which the surrounding
solution “feels” ψo decays with distance from the surface. In the Stern layer, ψo
decays linearly with distance d to ψd (known as the Stern potential). In the diffuse
layer, ψo decays exponentially, beginning with ψd and approaching zero as d → ∞.
The decay of ψ0 with distance (x) from the surface (see Figure 2) is mathemati-
cally represented as:
ψ = ψoexp (-kx) (1)
where ψ = the surface potential expressed in the DDL with distance from the
surface (in nm) and k = inverse DDL thickness, which is equal to:
12
⎛ 8C O ⎞
k = ev ⎜⎜ ⎟⎟ (2)
⎝ DKT ⎠
where, Co = bulk solution concentration, K = Boltzmann constant, T = absolute
temperature, v = valence of ions in solution, D = medium dielectric constant, and e
= elementary charge of an electron. Equation 2 predicts that increasing the
concentration of counterions in solution (i.e., increasing the ionic strength) will
increase k or compress the DDL. With the DDL compressed, the repulsive
interactions from overlapping DDLs is minimized, thereby allowing the particle
surfaces to come within the distance of the Stern layer, and flocculating through
van der Waals forces.
2.2. DISPERSION/FLOCCULATION PROCESSES
Inter-particle repulsive forces (RF), are influenced by ionic concentration and ionic
valence. This response is described in the classical DLVO theory ([6], and
references therein) as
64 ⎛ vFψ o ⎞
RF = tanh ⎜ ⎟ C o RT exp (− k d ) (3)
K ⎝ 4RT ⎠
where, F = Faraday’s constant, R = molar gas constant, and d = separation

between planar surfaces. Equations 1–3 predict that increasing k will reduce RF by
reducing the DDL size. Note, however, in Eq. 3, the term CoRT represents the
expression for osmotic potential or pressure, showing that DDL size is also
affected by the osmotic pressure exerted by the constituents in the DDL. The
osmotic potential of the DDL is controlled by the concentration of counterions
adsorbed at the solid-liquid interface – which again is controlled by ψo – a
property of the surface. Thus, the DLVO theory models changes in repulsive
forces via two different mechanisms: One dependent on the properties of the solid,
the other dependent on the bulk solution. The net result is the effect of ionic
strength on the dispersion potential of differently charged colloids (e.g., one high
charge, the other low charge). When increasing the ionic strength of the bulk
Stern layer ~ plane of slippage
ψd Diffuse layer
Counterion conc.
ψ°
or
Low ionic strength
High ionic strength
Distance from surface (nm)

σ1 σ2
Bioavailability index
% Dispersion
ZPC
− 0 +
Zeta potential (mV)
or
pH − pHo
Figure 2. (Top) Theoretical plots showing the change in ψ(x) of charged NM particle with distance
from the surface and changing solution ionic strength. This plot is overlain with a plot showing the
distribution of counterions in the Stern and Diffuse layers. (Bottom) Relationship in the change in zeta
potential (ξ) away from the ZPC (the rate of change with respect to surface charge density σ where |σ1|
> |σ2|) and increase in particle dispersion and bioavailability. In both plots, it is assumed the solution
phase does not contain any specifically adsorbing solutes.
116 M.A. CHAPPELL
solution, Eq. 2 predicts the DDL size will reduce equivalently on both particles.
Yet, the higher osmotic pressure exhibited in the DDL of the higher charged solid
will enhance the pace of dispersion in the particles with higher ψo [7], as
represented in Figure 2.
2.3. ZETA POTENTIAL (ξ) AND ZPC
Zeta potential (ζ in mV) measurements are measures of the magnitude of charge

(ψ in Eq. 1) expressed in the DDL at the plane of slippage (x = d). When the
charged particle moves through aqueous media, all material within the plane of
slippage (also called the plane of shear) “slides” along with it. The plane of
shear/slippage is considered analogous to the Stern layer, which is roughly
equivalent to the distance of the first hydration shell surrounding a surface. Zeta
potential changes can be summarized by a property called the zero point-of-charge
or ZPC, which is the pH in which NM zeta potential = 0. If we set ζ ~ ψ0 (given
the very short distance of the plane of slippage from the surface), then the
relationship between ζ and the ZPC can be simply represented as,
ζ ~ ψ0 = 59.2 (pH0 – pH) (4)
where pH0 = pH of the ZPC and pH = the pH of the bulk solution. For surfaces
with mono-functionality, ZPC represents a minimum in which no charge is
expressed, analogous a functional group pKa. For surfaces with poly-functional
groups, ZPC represents the average of the different surface pKa values. It turns
out that as a matter of convenience, solids exhibiting a ZPC will buffer the
solution pH at that ZPC at equilibrium.
The ZPC provides a simple parameter for estimating NM bioavailability.
When ξ = 0, the pH is at the NM’s ZPC. Here, no charge is expressed at the plane
of shear, and the particle essentially behaves as a hydrophobic solid. On the other
hand, when ξ ≠ 0, the particle is charged at the plane of shear, and exhibits
hydrophilic behavior. This information is directly relevant to the bioavailability of
NM to organisms. Fully dispersed NMs are expected to exist at their minimum
particle sizes in solution. In this form, NMs are expected to be the most bioavailable.
At the ZPC, the material is expected to exhibit maximum flocculation. Thus, ZPC
provides an appropriate estimation of the dispersion behavior, and bioavailability
of NMs.
3. Surface Charge Density/Distribution
While ZPC gives a relative sense of what pH a variably charged surface will
exhibit charge at the plane of shear, the actual magnitude of charge controlling the
surface potential is given by the specific charge density. Surface charge density is
a measure of the total distribution of charged functional groups normalized to the
total surface area of the material. The relationship between the surface electrical
potential and the surface charge density (σ) is modeled as:
σ = [(2/π) CoDKT)]1/2 sinh(vFψ0/2RT) (5)

For simplicity’s sake, this equation can be reduced by assuming ψ0 is small (<25
mV) and by lumping constants in Eq. 5 into a single variable (λ):
σ = (λ1/2Co1/2 D/4π) ψ0 (6)
The above equations simulate the properties of variably charged systems.
Since σ is variable, changing pH is evaluated using Eq. 4, then in Eq. 6, ψ0 is held
constant as the change in C0 is evaluated on σ. Surface electrical potentials for
surfaces with high specific charge densities quickly decay so that zeta potential
approaches zero with small changes in ionic strength relative to surfaces with
lower specific charge densities, as represented in the bottom plot of Figure 2.
Specific charge densities can also impact the interaction of NM with other
contaminants or charged surfaces. In theory, a NM possessing a high charge
density describes a situation where the charge is dispersed through out the particle
surface, so that the particle overall behaves as a hydrophilic material. But, if a NM
has a low charge density, it suggests that charged domains exist sporadically on
the NM surface, surrounded by other noncharged domains, which are expected to
behave hydrophobically. Thus, NMs with lower charge densities may exhibit
some surfactive characteristics because of the limited separation of hydrophilic
and hydrophobic domains on the surface. This consideration is important from a
chemical standpoint as partial surfactive behavior enhances the complexity of
environmental domains in which the NM may associate in.
4. Crystal Structure
Crystallinity is a property that describes the regular, repeating arrangement of

constituent elements in a nanomaterial. Crystal structure of a NM can be described
by the unit cell, a component of the crystal that represents the whole crystal when
stacked together repeatedly [8]. Crystal structures can vary widely depending on
the elemental composition, elemental ratios, and packing geometry of constituents.
Crystallinity is important because it directly impacts the surface chemistry of
solid materials. For example, the catalytic reduction of organic molecules by Fe-
oxides varies with Fe mineralogy [9–11]. Fe-oxides nanoparticles exhibit enhanced
reactivity for degrading organics over the larger particles, yet this reactivity
exceeds the expectation based on the larger surface area for the smaller sized
particles. One contributing factor may be related to conditions that destabilize or
add strain to the internal crystal structure of NM relevant to bulk particles [1, 12,
13]. X-ray evidence reveals that the long-range order of ZnS (spheralite) solids
degrades as particle size is decreased to the nanoparticle range as evidenced by
translational shifts of atomic sheets in the crystal lattice [14]. Internal crystal strain
may be alleviated by surface complexation of solvents or specific solute on the
nanoparticle surface. For example, dried or MeOH-suspended ZnS nanoparticles
showed significant internal strain which was alleviated when particles were
resuspended in water [15, 16]. Internal crystal strain may also promote spontaneous
118 M.A. CHAPPELL
surface derivitization or functionalization. Gilbert et al. [16] observed decreased

interior strain of ZnS nanoparticles with increasing strength of surface solute
complexation. As surface sites generally show evidence of increased strain on the
crystal structure of surface atoms, interior crystal strain may only increase the
surface excess energy of nanoparticles [15].
5. Speciation
In general, speciation refers to the electron status of the atomic orbitals of an

element. For most elements, atomic species is defined by the element’s valence
state, which is an important distinction with respect to toxicity. For As, the
common valence states are 0, +3, and +5, each exhibiting their own particular
toxicity. But, in solid phase systems, the complexation environment of the
material must be also distinguished. For example, Cd(II) is toxic and bioavailable
to organisms as a soluble cation or weakly complexed on a surface. However,
Cd(II) bound to a Fe-oxide surface is extremely stable [17, 18] and generally non-
bioavailable. On the other hand, the growing concern over nano-Ag stems from its
ready leaching from fabrics containing the material [19]. This suggests that the
nano-Ag is very weakly complexed in the material. Thus, the benefits of nano-Ag
may be better realized if it can be added to textiles as a stronger complex.
For the graphene-based nanomaterials, speciation generally refers to the
surface functionalization, in terms of transformations of the surface carbons. For
example, reaction of carbon nanotubes in acid results in the formation of variably
4.5
3.5
pH
2.5
2
0 100 200 300 400
-1
OH consumed (cmol kg )
Figure 3. Titration of 100 mg l−1 MWCNT (freshly obtained from manufacturer) suspended in 5 mM
NaNO3 and titrated in pH-stat mode (180 s equilibrium period) using 50 mM HNO3 [32]. The pKa
centered at approx. pH 3.25 is indicative of COOH groups.
charged COOH groups from cleavage of some of the surface aromatic groups. In
this case, speciation has a direct impact on other properties (as represented in
Figure 1) such as particle size (which effects dispersion potential), particle
morphology, solubility, and particle charge [20–22]. Recent information has
revealed the common practice of manufacturers to partially functionalize the
surface of carbon nanotubes to facilitate separation and purification by acid
precipitation (Figure 3).
The net speciation of a nanomaterial is, in effect, the mean speciation of the
smaller domains on the material’s surface. Thus, nanomaterial speciation is
influenced by crystal structure and surface morphology. For example, edge sites
on clays and Fe-oxides exhibit a higher pKa than other sites on the material [23,
24]. While the reason for this behavior is not known, it is suspected to be
associated with the higher water coordination number and possibly greater
stability of OH groups at the high-angle sites.
6. Surface Area
Particle surface area is defined as area of particle surface per mass of particle. In
Figure 1, surface area is represented as the only characteristic of nanoparticles
influenced by particle size. As Oberdörster et al. [25] explain, particle surface area
increases exponentially as particle size decrease below 100 nm. This relationship
is important in controlling the chemical equilibrium of systems. If the nanoparticle
size is stable, NM particle chemistry could dominate the chemistry of the mixed
solid phase system because it possesses the dominant surface area, even at dilute
proportions of the total. However, if NM aggregates due to the composition of the
system, then surface area and control of the equilibrium is minimized unless the
concentration of the total NM is increased. For this reason, it is essential that NM
particle size be measured before and after experiments.
TABLE 1. Relationship between crystal structure, atomic composition, and surface area of iron oxide
minerals. (Information taken from Schwertmann and Cornell [26].)
Mineral name Formula Crystal system Surface area (m2 g−1)
Hematite α-Fe2O3 Trigonal 30–90
Magnetite Fe3O4 Cubic 4
Goethite α-FeOOH Ortho rhombic 20–130
Lepidocrocite γ-FeOOH Ortho rhombic 70–80
Ferrihydrite variable Trigonal 300
Feroxyhite δ´-FeOOH Hexagonal 200
Akaganeite β-FeOOH Monoclinic 30
NM surface area is also influenced by the material’s crystal structure (Figure 1).
Table 1 shows how the Fe-oxide minerals with similar compositions can have very
different surface areas because of their differences in crystallinity. Surface area
also serves as the denominator in charge density (σ) calculation. Decreasing particle
size is expected to decrease the charge density of the particle and according to
120 M.A. CHAPPELL
Figure 2, reduce the degree in which the NM flocculates with small changes in
(pH0–pH).
7. Adsorbed Phase
A very common way to probe the surface of any material is to study its sorption
abilities. Sorption of solutes with different properties (e.g., polarity, functional
group composition) provides the basis for arbitrary classification of sorbents by
the shape of the sorption isotherm. However, interpretation of sorption behavior is
complicated by the fact that the adsorbed phase promotes transitions in the solid
phase, such as influencing crystal strain. These complexities are experienced at the
simplest levels. For example, a common method for dispersion environmental
solids is to saturate the surface with Na+ cations. The high osmotic coefficient (Eq.
3) generated by packing the DDL with the Na osmolyte causes the DDL to swell,
and force individual particles apart through inter-particle repulsions. Thus,
saturating the adsorbed phase of the solid with Na forces the materials into
dispersion by decreasing the particle size. On the other hand, insufficient control
of the adsorbed phase can induce flocculation of the particles. Table 2 lists a
selection of articles taken from the toxicology literature. Out of the sixteen
articles, 13 record the NM size before experiments while four record the size after
the experiments. In all cases, the final particle sizes are different from the initial
sizes – a result that is attributable to the adsorbed phase on the particle as affect by
the system matrix.
TABLE 2. Example of the results of a brief survey of the scientific literature with respect to the
analysis of nanoparticle size in the experimental matrix.
Nanomaterial Initial size Size in Test matrix Dispersion Reference
system treatment
ZnO 30 nm OD: 102 nm 0.01 M Ca(NO3)2 in Teric N30 Franklin
to several Milli-Q water, et al., 2007
micrometers pH7.5 w/2 mM
PIPES
Lipid coated ~1.2 nm − MHW in 0–20 mg Lysophopha Roberts
CNT l−1 tidylcholine et al., 2007
/sonicate
SWCNT OD: 1 nm − Mouse serum Brief Lam et al.,

Length: shearing/so 2004
several nication
micrometers
Partially OH- 10–200 nm − Milli-Q water, Stirring Oberdorster
nC60 Aggregates RHW-freshwater or et al., 2005
Artificial sea water
(35 ppt)
SWCNT OD: 1.1 nm − Dechlorinated tap Sodium Smith et al.,
Length: 5– water dodecyl 2007
30 um sulphate
In SDS and
OD: 190– sonication
800 nm
Nanomaterial Initial size Size in Test matrix Dispersion Reference

system treatment
nC60 10–200 nm − RHW THF or Zhu et al.,
stirring 2006
Ag(0) 5–46 nm Stable in Incubated egg water Sodium Lee et al.,
~diameter 10 nM 1.2 nM NaCl citrate and 2007
11.6 nm NaCl but sodium
aggregated borohydride
in 100 mM
NaCl
SWCNT − − 30 g l−1 seawater Incorporatio Templeton
n of et al., 2006
hydroxyl
and
carboxylic
acid
functional
groups
Alumina ~13 nm − Milli-Q water − Yang and
N4+: 201 Watts, 2005
nm particles
aggregates
size
SWCNT OD: 1 nm − Buffered BSA Sonication Leeuw et al.,
Length: 102 2007
nm
nC60, TiO2 nC60: 10- − MHRW THF which Lovern et al.,
20nm was filter 2007
TiO2: 30nm off and
evaporated
three times
nC60 − 50–300 Milli-Q water Stirring and Henry et al.,
nm w/instant ocean sonication 2007
or THF
nC60 30–100nm − RHW THF Oberdorster,
aggregates 2004
TiO2 and OD: − MRHW THF or Lovern and
nC60 Filtered, sonication Klaper, 2005
10–20 nm
Sonicated,
20–100 nm
Filtered
TiO2, 30 nm
Sonicated
TiO2, 100–
500 nm
Fluorescent 39.4–42,000 474 nm in Medaka eggs in − Kashiwada,
latex nm eggs & oil ERM at pH 7.2 2006
particles droplets,
39.4 nm in
yolk &
gallbladder
SWCNT − − Filtered seawater Agitation Templeton,
AP-SWCNT 2006
122 M.A. CHAPPELL
Franklin, N.M., N.J. Rogers, S.C. Apte, G.E. Batley, G.E. Gadd, and P.S. Casey. 2007. Comparative
toxicity of nanoparticulate ZnO, bulk ZnO, and ZnCl2 to a freshwater microalga (Pseudokirchneriella
subcapitata): The importance of particle solubility. Environ. Sci. Technol. 41:8484-8490.; Henry, T.B.,
F.-M. Menn, J.T. Fleming, J. Wilgus, R.N. Compton, and G.S. Sayler. 2007. Attributing effects of
aqueous C60 nano-aggregates to tetrahydrofuran decomposition products in larval zebrafish by
assessment of gene expression. Environ. Health Perspectives 115:1059-1065.; Kashiwada, S. 2006.
Distribution of nanoparticles in the see-through medaka (Oryzias latipes). Environ. Health Perspectives
114:1697-1702.; Lam, C.-W., J.T. James, R. McClusky, and R.L. Hunter. 2004. Pulimonary toxicity of
single-walled carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol. Sci.
77:126-134.; Lee, K.J., P.D. Nallathamby, L.M. Browning, C.J. Osgood, and X.-H.N. Xu. 2007. In
vivo imaging of transport and biocompatibility of single silver nanoparticles in early development of
zebrafish embryos. Nano 1:133-143.; Leeuw, T.K., M. Reith, R.A. Simonette, M.E. Harden,
P. Cherukuri, D.A. Tsyboulski, K.M. Beckingham, and R.B. Weisman. 2007. Single-walled carbon
nanotubes in the intact organism: Near-IR imaging and biocompatibility studies in Drosophilia. Nano
Lett. 7:2650-2654.; Lovern, S.B., and R. Klaper. 2006. Daphna magna mortality when exposed to
titatium dioxide and fullerene (C60) nanoparticles. Environ. Toxicol. Chem. 25:1132-1137.; Lovern,
S.B., J.R. Strickler, and R. Klaper. 2007. Behavior and physiological changes in Daphnia magna when
exposed to nanoparticle suspensions (titanium dioxide, nano-C60, and C60HxC70Hx). Environ. Sci.
Technol. 41:4465-4470.; Oberdorster, E. 2004. Manufactured nanomaterials (fullerenes, C60) induce
oxidative stress in the brain of juvenile largemouth bass. Environ. Health Perspectives 112:1058-1062.;
Oberdörster, E., S. Zhu, T.M. Blickey, P. McClellan-Green, and M.L. Haasch. 2005. Ecotoxicology of
carbon-based engineered nanoparticles: effects of fullerene (C60) on aquatic organisms. Carbon
44:1112-1120.; Roberts, A.P., A.S. Mount, B. Seda, J. Souther, R. Qiao, S. Lin, P.C. Ke, A.M. Rao,
and S.J. Klaine. 2007. In vivo biomodification of lipid-coated carbon nanotubes by Daphnia magna.
Environ. Sci. Technol. 41:2657-2658.; Smith, C.J., B.J. Shaw, and R.D. Handy. 2007. Toxicity of
single walled carbon nanotubes to rainbow trout, (Oncorhynchus mykiss): Respiratory toxicity, organ
pathologies, and other physiological effects. Aquatic Toxicol. 82:94-109.; Templeton, R.C., P.L.
Ferguson, K.M. Washburn, W.A. Scrivens, and G.T. Chandler. 2006. Life-cycle effects of single-
walled carbon nanotubes (SWNTs) on an estuarine meiobenthic copepod. Environ. Sci. Technol.
40:7387-7393.; Yang, L., and D.J. Watts. 2005. Particle surface characteristics may play an important
role in phytoxicity of alumina nanoparticles. Toxicol. Lett. 158:122-132.; Zhu, S., E. Oberdörster, and
M.L. Haasch. 2006. Toxicity of an engineered nanoparticle (fullerene, C60) in two aquatic species,
Daphnia and fathead minnow. Marine Environ. Res. 62:S5-S9.
A number of papers have shown that NM dispersions can be stabilized by

addition of surfactants or soluble humic materials [27–31]. Our recent work [2]
demonstrated that NM particle size and polydispersivity minimized when
saturated with adsorbed surfactant. This saturation point was predictable by the
surfactant’s CMC based on the equilibrium concentration of surfactant in solution
because the hydrophobic moiety preferentially adsorbed to the graphene surface of
the carbon nanotubes tested. Humic materials were also shown to stabilize CNT
dispersions according to their ability to imitate surfactive behavior. Humic
material with highly carbohydrate-based carbon domains were shown to be poorly
surfactive.
Acknowledgements
Assistance with titration analysis in Figure 3 was provided by Aaron George

SpecPro, Inc., Huntsville, AL) and Cynthia Price (US Army ERDC). Table 2 was
prepared by Jen Chappell (SpecPro, Inc., Huntsville, AL).
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NANOMATERIAL TRANSPORT, TRANSFORMATION, AND
FATE IN THE ENVIRONMENT
A Risk-Based Perspective on Research Needs
G.V. LOWRY
Carnegie Mellon University, Civil & Environmental Engineering
Pittsburgh, PA 15213, USA
glowry@cmu.edu
E.A. CASMAN
Carnegie Mellon University, Engineering and Public Policy
Pittsburgh, PA 15213, USA
casman@andrew.cmu.edu
Abstract. The existing approaches for assessing the environmental risks of

nanomaterials need to be adapted to the behaviors of nanomaterials before they
can provide reliable information. Assessing or predicting these risks requires
understanding of the potential sources of these materials to the environment, their
distribution once released, their transformations and persistence, and their potential
negative effects. In this chapter we discuss the potential sources of nanomaterials
released to the environment, then we present potential physical and biogeochemical
processes that can affect the fate, transport, and transformations of manufactured
nanomaterials released into the environment. Finally, we discuss modifications of
existing risk analysis methods needed and the most important data gaps that must
be filled in order to assess the environmental risks associated with these materials.
1. Introduction
Nanomaterials are just now emerging into the global marketplace. They are found
in consumer goods, in cosmetics and health care products, recreational equipment,
paint, plastics, and electronics. The two most common nanomaterials currently
used in consumer goods are silver nanoparticles and titanium dioxide nanoparticles.
Silver nanoparticles are antibacterial. They appear in humidifiers, washing machines,
cutting boards, and even in food packaging. Titanium dioxide, which is a photo-
active surface coating, is found in cosmetics, paint, and batteries and is likely the
most prevalent manufactured nanomaterial. Many additional products are being
developed, and it is reasonable to assume that as goods penetrate the markets, their
nanomaterial components will enter the biosphere in large numbers. A 2004 report
by Lux Research [9] entitled “Sizing Nanotechnology’s Value Chain” estimates
that the value of nano-intermediates and nano-enabled products in 2008 is

126 G.V. LOWRY AND E.A. CASMAN
approximately US$0.2 trillion. This is projected to be more than US$2.5 trillion

by 2014. Even if a fraction of this estimate were to be realized, substantial
quantities of nanomaterials will enter the environment in the coming decade.
Given the impending releases of these materials, their known (and predicted)
biological activities, and our current ignorance of their effects on natural systems,
it is prudent to examine the risks to the environment and to human health
associated with these materials. Currently there are many unanswered questions
associated with their releases, their fate, transport, and transformation in the
environment, and in their potential toxic effects.
It is currently impossible to conduct a traditional environmental risk assessment
for these materials, which requires a well developed understanding of all these
factors. A traditional environmental risk assessment starts with a significant
observed negative effect. None have been reported to date. Moreover, regulators
have expressed the desire for a tool that will predict an as yet unidentified negative
effect. Just as there is no algorithm in the engineering toolkit that could have
linked DDT to thinning bald eagle egg shells a priori, we don’t know enough
about nanomaterials or biology to predict such a specific impact.
In the near term, regulators will have to resign themselves to more approachable
goals – to advance the science so at least we can predict with some confidence
where nanoparticles go in the environment, whether they persist, in what form, if
they accumulate, their interactions with other substances, and the kinds of
biological effects that are consistent with their chemical properties. We must begin
to develop new frameworks for describing the potential risks associated with these
materials. We must integrate laboratory results into a risk analytic framework as
they are generated. Such preliminary risk analyses will help to identify and
prioritize the most relevant data gaps that must be filled before a traditional risk
assessment is feasible.
In this chapter we focus mostly on the physical and biogeochemical processes
that can affect the fate, transport, and transformations of manufactured nanomaterials
released into the environment, and discuss the most important data gaps that must
be filled in order to assess the environmental risks potentially associated with
these materials.
2. Sources of Nanomaterials and Potential for Exposure
Many naturally occurring nanomaterials exist in the environment at concentrations

many orders of magnitude greater than any manufactured nanomaterial. Biological
systems have evolved coping mechanisms for recognizing and clearing these
particles, whereas manufactured nanomaterials present new challenges for environ-
mental systems. This is especially true if the manufactured nanomaterials do not
have any natural analog, e.g. quantum dots and the heavy metals they contain.
Further, man-made nanomaterials are often coated with a surfactant, polymer, or
polyelectrolyte. The combination of the particle and the organic surface coating,
often used to make the materials water soluble or biocompatible, are not likely to
have natural analogs.
NANOMATERIAL TRANSPORT, TRANSFORMATION, AND FATE 127
In some cases, manufactured nanomaterials may be used in products where

they would enter the environment as individual nanoparticles or small agglo-
merates (e.g., silica nanoparticles used as solid lubricants, fullerenes added to
cosmetics, metal and metal oxide nanoparticles injected for groundwater remedi-
ation). In other cases, manufactured nanomaterials may be incorporated into
consumer products as composites or mixtures that would likely initially be released
to the environment in an encapsulated form (e.g., nanotube composites used to
make tires, tennis rackets, and video screens). The form of the released nanomaterials
is an important consideration for risk assessment and risk prediction.
Accidental releases to the environment may come from point sources such as
nanomaterial manufacturing facilities, from the waste products from these facilities,
from intermediates and finished products containing them. Products disposed of in
landfills may serve as point sources of nanomaterials into the environment. Nano-
materials used for targeted drug delivery will be excreted and sent to wastewater
treatment plants which may ultimately serve as point sources of nanomaterials.
With appropriate controls, releases of nanomaterials from these point sources
should be minimal, but accidental releases are possible.
As with many environmental contaminants, non-point sources of nanomaterials
will be the most difficult to control and will likely be the majority of nanomaterial
releases to the environment. Many release mechanisms are possible including wet
deposition of particles from the atmosphere, attrition from products containing
nanomaterials, storm-water runoff from manufacturing sites or city roads and
highways. As nanotubes find their way into automobile tires and brake pads,
attrition from these products will constitute a large source of nanomaterials into
the environment.
Recent published works are developing the understanding of how the properties
of materials influence their transport, transformation and fate in the environment.
The locations, concentrations, and properties of the nanomaterials released to the
environment are all factors that will affect their distribution, concentration, and
ultimately their effects on the health of an ecosystem. Many nanomaterials will
transform either physically or biologically once released to the environment (e.g.,
aggregation, loss of surface coatings, photolysis, etc.) These transformations will
affect the distribution and concentration of these materials in the subsurface, and
ultimately will control the magnitude of the negative (or positive) effects that these
materials may have on the environment. A conceptual model of these processes is
shown in Figure 1. We will have to understand the sources of the materials, the
characteristics of those materials, as well as the transformations of those materials
and the effect on the surface properties of those materials in order to predict
or assess the risks that those materials may pose. Given the great variety in
nanomaterials properties, size, morphology, chemical composition, and the even
greater variability in the types of surface coatings, we will have to understand
these processes from first principles in order to generalize these findings across
classes or types of nanomaterials.
Finished Products
Intermediate
Raw NM products
Biotic
Releases
Transformations & Modified NM

NM Properties
Degradation Properties
Abiotic
Distribution, Concentration, and Effects

Figure 1. Schematic of processes affecting the distribution, concentration, and effects of nanomaterials
released to the environment.
3. Traditional Risk Assessment and the Need for a New Framework for
“Risk Prediction”
Traditional risk assessment starts with an observed effect on a specific organism

caused by a known pollutant. The emissions of the pollutant are quantitatively
tracked through the relevant parts of the environment, partitioned, degraded,
transformed and bioamplified, as appropriate, so exposure, dose, and morbidity
estimates for the affected species can be calculated. Currently for nanomaterials,
every part of this process is uncertain, from the emissions and their rates of entry
into the environment, through to the endpoint, e.g. toxicity to an organism, an
ecosystem, an acute effect, an evolutionary effect, or disruption of an ecosystem
service.
Nanomaterials do not behave like conventional chemicals. Properties, such as
solubility and octanol/water partition coefficients – so useful for describing the
movement of conventional materials in the environment in traditional risk
assessment – do not capture the behavior of nanomaterials, which congregate at
interfaces. Naturally occurring and anthropogenic chemicals in the environment
can alter a nanomaterial’s mobility, toxicity, bioavailability, and visa versa, invali-
dating single-chemical transport models. Matrix effects may be the most important
and complex problem of modeling nanomaterial fate in the environment, as the
matrix in which they are embedded in their initial product life imparts properties
that change as the matrix is degraded.
Traditional risk assessment requires specific end points for analysis. However,
for nanomaterials scientists are more confident talking about the properties of the
nanomaterials that give them their potential biological activity (ability to transport
electrons and create reactive oxygen species, penetration of the blood brain barrier,
immunostimulation, ability to carry other molecules, photo-catalytic activity) in
regards to toxicity testing (in many cases these are the same properties that make
nanoparticles so useful in their intended applications), rather than real ecotoxicity
end-points. It is currently unclear as to when these presumptive mechanisms of
biotoxicity rise to a level where precaution would dictate controls on nanomaterials,
especially as effects observed under laboratory conditions are often not reproducible
in nature.
For example, C60 was shown to be bactericidal in pure cultures, however,
addition of C60 to an extremely high concentration (1 g/kg or 1,000 ppm added to
a real soil) showed no effects on microbial survival and DGGE analysis suggested
limited effect on the diversity of the most prevalent organisms.
Despite impressive knowledge gaps, existing risk assessment tools may
provide some insight. A recent paper by Mueller and Nowack [10] is a good
example of a high level (in terms of abstraction) estimate of potential environ-
mental risk from nanomaterials. These authors estimated the expected average
concentrations of nanomaterials in the environment at the national level using a
conceptual compartmental model. By comparing these concentrations to published
no-effects levels for those materials, a rough risk ranking of the materials was
possible. We might quibble with every assumption in the paper, but the risk ranking
of the three nanomaterials studied seems nevertheless plausible. Such a highly
aggregated result cannot be used in a standard-setting context, but demonstrates
the creative use of judgment and fragmentary data to improve understanding.
Another risk ranking method, based on certain properties of the nanomaterials,
is proposed by Linkov, Figueira and Merad in this volume. These authors argue
that such a risk ranking should be used to prioritize nanomaterials for further
study, an urgent need, considering the proliferation of new nanomaterials.
To move the field forward, other risk frameworks capable of dealing with
preliminary data and missing information will have to be developed. The problem
can and should be approached from many angles, in anticipation of the time when
we have sufficient understanding to build and parameterize more traditional risk
assessment models. One such framing is the probabilistic network. These models
track probability rather than mass and are particularly useful for reasoning under
uncertainty. Their structure can integrate expert judgment with empirical observation
and accommodates updating as new data become available.
4. Primary Data Gaps for Risk “Prediction” and Assessment
4.1. BIOLOGICAL END-POINT
Assessing the risks of nanomaterials relies, at the very least, on understanding the
processes leading to exposure of organisms to the released materials, and on the
negative effects that they may have on an organism (toxicity). Exposure and
toxicity are not enough, however, to predict environmental risks of nanomaterials
to the environment. Some understanding of the effect of these materials at an
ecosystem level must also be determined. This requires a good understanding on
how the elements of an ecosystem function synergistically, and an understanding
of the natural redundancy existing in ecosystems to help maintain homeostasis
with respect to ecosystem services. This is currently out of range of our abilities,
and therefore risk prediction is a distant goal. Regardless, there are many primary
data gaps regarding the transport, transformation, and fate of nanomaterials that
can help lay the foundation for risk prediction, even in the absence of a systems
level understanding of ecosystem function. These data gaps are outlined briefly
here.
4.2. TRANSPORT
Once released in to the environment, nanomaterials may be transported away from

the point of release and be redistributed in the environment, or may not travel
significantly away from the point of release. Predicting the concentration of
nanomaterials in the environment requires some understanding of their transport
away from the point of release. If transport is facile, the materials may distribute
widely in the environment, and average concentrations would be relatively low. If
they do not readily migrate from the point of release, concentrations may be
locally high, forming “hot spots”. Thus the transport of nanomaterials in the
environment is inseparable from the risk prediction. Guestimates regarding the
transport of nanomaterials are insufficient. We need a better understanding of the
factor controlling the transport of nanomaterials in the environment in order to
predict the risks they may pose.
Aggregation and deposition are the primary processes affecting transport of
transformation of nanomaterials in the environment. Many nanomaterials are
produced as distinct particles with diameters of 1–100 nm, but these particles
aggregate to form much larger, colloidal aggregates in water. For example, 20-nm
titanium dioxide particles form aggregates in water and in biological fluids [7].
Similarly, fullerene C60 and hydroxylated C60 (fullerols) forms aggregates ~20–
200 nm in diameter in pure water which may be highly stable, showing little
propensity to continue to aggregate or to disaggregate over periods of several
months or more [1]. The basis for this stability is not clear. Hydrophobicity or
chemical bonding between nanoparticles can also promote their aggregation in
water. The rate and extent of aggregation depends on ionic strength, ionic
composition, and other environmental factors. Generally increasing ionic strength
and the presence of divalent cations such as Ca2+ and Mg2+ increases the rate and
extent of aggregation, and may affect the stable size of aggregates that are formed.
Thus nanoparticles will tend to aggregate more in seawater (high ionic strength)
than in fresh water. For some materials, the particle’s intrinsic properties can
affect their rate and extent of aggregation. For example, magnetic attractive forces
between Fe0 nanoparticles used for groundwater remediation cause them to
aggregate more rapidly than less magnetic iron oxide nanoparticles with similar
dimensions [13]. Aggregation can significantly affect the transport of particles in

porous media [17], the bioavailability of the materials to bacteria and to
eukaryotic cells [7, 8], and the potential for sedimentation from a water column
and ultimately the exposure to these materials. Aggregates or agglomerates of
nanoparticles that settle can be expected to accumulate in sediments of lakes or
rivers in the absence of nanoparticle degradation. Those that do not will travel
much further in the water column from the point of release. Some evidence
suggests that the deleterious effects on bacterial populations are greater for smaller
aggregates of C60 than for larger ones. Thus, aggregation of nanoparticles may
mitigate both exposure and toxicity in some cases.
Another critical, but often overlooked factor affecting the transport and
distribution of manufactured nanomaterials in the environment is the surface
coatings that are engineering onto the particles, or surface coatings that are
acquired upon release to the environment. For example, nanoscale zerovalent iron
used for groundwater remediation must be engineered with a polyelectrolyte,
surfactant, or polymer coating in order make them mobile in the subsurface [4,
15–17]. Quantum dots are engineered with an organic surface coating such as
polyethylene glycol to make them dispersible in water and biocompatible. It
should be no surprise that these surface coatings will also significantly affect their
distribution in the environment. The magnitude of the effect these surface coatings
on their transport will depend on the type of coating and the repulsive forces that
those coatings provide. For example, small molecular weight coatings such as the
surfactant sodium dodecylsulfate (SDS) commonly used to stabilize nanoparticles
against aggregation in water, provide primarily electrostatic stabilization by
imparting a surface charge to the particle. These are fairly weak repulsive forces
and are readily blocked by cations in solution, rendering them ineffective. Large
molecular weight polymers (uncharged) can provide steric repulsions that stabilize
particles against aggregation and enhance transport. Large molecular weight
polyelectrolytes such as polystyrene sulfonate (70000k molecular weight) provide
electrosteric stabilization that reduces sensitivity to changes in ionic strength and
composition of the water and provides much more resistance against aggregation,
enhancing transport more so than surfactants [12, 15].
Natural organic matter (NOM) such as humic and fulvic acids can also
stabilize particles against aggregation in water, which may enhance their transport
in aqueous environments and in groundwater. For example, Sewanee River fulvic
acids were shown to be much more efficient at stabilizing single-walled carbon
nanotubes in water than was SDS [3]. Nanoparticles have high surface-to-volume
ratios and therefore high surface energy. Any natural organic matter in a system
will tend to adsorb to the particle surfaces, altering their surface properties and
enhancing their mobility. Much of the natural organic matter in the environment is
similar in molecular weight and charge as a moderate to high molecular weight
polyelectrolyte, so the enhanced migration of polyelectrolyte modified Fe0
nanoparticles relative to the bare Fe0 nanoparticles observed by Saleh and co-
workers [15] may be a good indication of the effect of NOM on the transport of
manufactured nanoparticles in water. The mechanisms by which adsorbed organic
coatings affect aggregation and deposition are under investigation e.g. [12], but
the conditions under which enhanced transport will be observed is a current data
gap in our understanding of the behavior of manufactured nanomaterials in the
environment.
The same processes affecting transport of nanomaterials in the environment
affect the efficacy of water treatment systems that may be used to remove them.
For example, coagulation and sand and membrane filtration are used to remove
particles from drinking water. These traditional processes have been shown to be
ineffective at removing some manufactured nanomaterials (e.g. quantum dots)
from drinking water [19]. While not yet systematically evaluated, the engineered
and acquired coatings on manufactured nanoparticles will undoubtedly affect
these processes.
4.3. TRANSFORMATIONS AND FATE
Once released into the environment, manufactured nanomaterials can be transformed

biotically or abiotically. These transformations may alter the size, shape, and
surface chemistry of the particles and their coatings and will affect their ultimate
distribution in the environment. Some examples of biotic and abiotic transfor-
mations of manufactured nanomaterials include the removal of surface coatings
from single walled carbon nanotubes by freshwater Daphnia. Roberts et al. [14]
demonstrated that the lysophophatidylcholine coating on single-walled carbon
nanotubes was removed as the tubes moved through the guts of the Daphnia. The
Daphnids used the phospholipid coating on the nanotubes as a food source under
food limited conditions. The nanotubes excreted by the Daphnia were less
resistant to aggregation as a result of the removal of the lysophophatidylcholine
coating. There are a host of other types of biotransformations that may occur to
the particles, or to the coatings on the particles upon release to the environment.
For example, microbial transformations of nanomaterials or the bioavailability of
the surface coatings to bacteria are unexplored at this time. It is feasible that
bacteria can oxidize or reduce nanomaterials or the attached coatings via electron
transport in pili, or through direct reduction by membrane bound cytochromes
(Figures 2 and 3). For example, dissimilatory iron reducing bacteria are known to
respire on nanoparticulate iron oxides which could alter the particle surfaces by
reductively dissolving Fe-oxides or Fe-oxyhydroxides formed at the water/particle
interface [2] or by generating reactive surface-associated Fe(II) species [18].
Microbially induced corrosion could also ensure the localized dissolution of the
iron nanoparticles, thereby eliminating possible concerns from off-site migration
and risk. These microbial transformations are very likely to occur for many types
of nanomaterials (carbon, metals, and metal oxides), but have not yet been well
characterized. Transformations by fungi, nature’s decomposers, are also likely but
have not yet been explored in detail. It is these types of biological transformations
on the particle coatings that will affect their transport, and will determine the
ultimate fate of manufactured nanomaterials in the environment.
Figure 2. Microbial reduction/oxidation of nanoparticle coatings and functional surface coatings.

(Courtesy of Professor Kelvin Gregory.)
Figure 3. Hypothetical microbial reduction of surface groups on nanoparticles by geobacteraceae.

(Courtesy of Professor Kelvin Gregory.)
The physical and chemical transformations of manufactured nanomaterials that

may occur after release to the environment include dissolution, disaggregation,
photolysis, hydrolysis, and a variety of other non-biological redox transformations.
All of these transformations can affect the concentration, persistence, toxicity
effects on individual organisms and ecosystems. Very few of these abiotic reactions
have been studied in detail, given the novel nature of most nanomaterials, but
some examples do exist and illustrate the potential effect that these transforma-
tions may have on their distribution in the environment. For example, fullerenes
(or C60) aggregate and acquire a surface charge after stirring in water. Stable 50–
200 nm clusters of C60 known as n C60 are formed. The processes are not certain,
but the formation of these dispersible clusters is certain and may be the expected
for of C60 released to the environment. However, the interaction of these clusters
with carboxylic acids such as maleic acid, tends to dissolve or disaggregate these
clusters (Figure 4). It is clear that this process will affect the size, number, and
distribution of C60 in the environment. It is also likely that the adsorption of
carboxylic acids to the particles will change their surface chemistry.
Figure 4. Disaggregation or nC60 cluster due to exposure to carboxylic acid. (Courtesy of Professor
Peter Vikesland.)
Abiotic redox transformations of nanomaterials can also affect their fate. For
example, Fe0 nanoparticles used for in situ remediation of chlorinated solvent and
heavy metals are designed to oxidize, thereby supplying electrons for the reductive
Figure 5. TEM images of fresh nanoiron samples showing before reaction and after reaction with TCE
in water. Both particle types have an apparent core-shell morphology. RNIP, made from gas phase
reduction of Fe-oxides in H2, appear to have a shrinking core during reaction in water. Fe(B), made
from reduction of Fe2+ in a water/methanol solution using sodium borohydride appear to undergo
oxidative dissolution followed by precipitation of the dissolved Fe to hematite [5]. The shell on Fe(B)
is predominantly borate [11].
dechlorination of chlorinated solvents or reductive sequestration of heavy metals

[6]. The data thus far on the fate of nanoiron have been largely collected in the
laboratory in deionized water. They suggest that different types of Fe0 particles
will undergo different transformations (Figure 5). In one case, RNIP (a Fe0/Fe3O4
core/shell nanoparticle) is oxidized from the outside in, yielding particles of
similar size and shape, but the Fe0 has been oxidized to the Fe-oxides, magnetite
and maghemite. Another type of Fe0 synthesized by a different process and
nanocrystalline to amorphous appears to undergo reductive dissolution resulting in
Fe-oxide particles that are of a different size, shape, and chemical composition [5].
From a risk assessment point of view, it is essential to understand the ultimate fate
(end products) of the particles once released to the environment. Very few, if any,
well controlled in situ investigations of the fate of nanoiron or any other type of
nanoparticle in the subsurface have been conducted.
5. Summary and Conclusions
The emergence of nanotechnology and the incorporation or nanomaterials into

consumer goods, medications, etc. is currently in its infancy. The effects that these
products will have on the environment and on human health are unknown, and
precautionary measures are warranted until the risks that these materials may pose
have been elucidated. The co-evolution of a new technology along with the under-
standing of the potentially negative environmental consequences is unprecedented.
We typically forge ahead with the technology and manage the repercussions in the
future. In some cases the negative effects outweigh the positive ones.
There are many research needs with respect to environmental transport, fate,
and effects of nanomaterials. In particular we need to gain a fundamental under-
standing of the factors affecting the aggregation, deposition, and ultimately the
distribution of manufactured nanomaterials in the environment. The surface coatings
engineered or acquired upon release to the environment will dramatically affect all
of the process affecting the transport of these materials in the environment.
Transformations that affect these surface coatings, either biotic or abiotic, need to
be elucidated in detail. Processes affecting the persistence of these materials must
also be determined. Only then can we assess the potential for exposure and estimate
the concentrations that would be expected in different parts of the environment.
Once the potential for exposure is clear, and the nature of the material that an
organism may be exposed to is known, we can begin to estimate the potential
effects due to these exposures.
Performing traditional risk assessments for nanomaterials will not be possible
until these obstacles are overcome, but interim assessments using fragmentary
information will help us appreciate the environmental implications of the data as
they become available.
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VISUALIZATION AND TRANSPORT OF QUANTUM DOT
NANOMATERIALS IN POROUS MEDIA
C.J.G. DARNAULT, S.M.C. BONINA, B. UYUSUR

University of Illinois at Chicago
Department of Civil and Materials Engineering
842 W. Taylor Street, ERF# 2071
Chicago, IL 60607, USA
darnault@uic.edu
P.T. SNEE
University of Illinois at Chicago
Department of Chemistry
845 West Taylor Street
Chicago, IL 60607, USA
Abstract. This paper presents our research on the visualization and transport
phenomena of quantum dot nanomaterials in porous media. It includes the
development of a non-intrusive, high spatial and temporal resolution method to
visualize transport and measure quantum dot nanomaterials concentration in
porous media, allowing to characterize the mechanisms that control the transport,
or lack of mobility, of engineered nanomaterials – quantum dots – in subsurface
complex and heterogeneous environment. The visualization technique used to
explore the transport of quantum dot nanomaterials is a toolbox that allows to
characterize a wide range of flow and transport phenomena due to mesoscale
heterogeneities. The characterization of these flow and transport phenomena includes
the visualization and/or quantification of flow, fluid content and nanoparticle
concentrations. The visualization technique selected to investigate transport of
quantum dot nanomaterials in two-dimensional variably saturated porous media is
a non-intrusive method based on fluorescence resulting from the quantum dots
optical properties. The visualization procedure consists of exciting fluorescent
quantum dots in porous media by using a UV light located in the front of the
chamber and in characterizing the water content with the light transmitted through
the porous media by using light emitted devices (LEDs) as a light source placed in
the back of the chamber. The visualization, calibration and image analysis are
performed using an image software. Experiments investigating quantum dot nano-
materials transport in unsaturated zone demonstrates the effects of preferential
flow and gas-water interfaces on the transport of quantum dot nanomaterials
through the vadose zone.

140 C.J.G. DARNAULT ET AL.
1. Introduction
Nanomaterials are at the leading edge of the rapidly growing field of nanotech-
nology. Their unique size-dependent properties make these materials superior and
indispensable in many areas of human activity. Nanotechnology has considerable
global socio-economic value, and is expected to have significant impacts on
everyday life. Nanomaterials have numerous commercial and technological
applications in chemical, biomedical, energy, electronics and space industries. A
wide range of nanomaterials such as carbon nanotubes, fullerene derivatives, and
quantum dots are used in almost all industries and all areas of society and the
prevalence of these materials in society will be increasing, as will the likelihood of
exposures [11, 21, 22]. Once nanomaterials are released into the environment via
manufacturing, use or disposal, their transport is the critical parameter in assessing
their exposure and impact on the public health and the ecosystem, therefore
understanding the fate of nanomaterials in the environment is critical [1, 4, 27, 29,
31]. Initial work on nanomaterials mobility in saturated and homogeneous porous
media has shown that fullerol may be very mobile while nC60 mobility is very
limited [3, 15, 16]. Nanoscale iron particles designed for environmental remedia-
tion can flow with groundwater over 20 m distance [33]. pH and therefore surface
potential and aggregate dominate titania nanoparticles interaction with each other
and surface, while the transport speed of these nanoparticles aggregates did not
vary with pH [10]. Among the various types of nanomaterials, the semiconductors,
quantum dots are key enablers in nanosciences, engineering and technology. Since
they were discovered in early 1980s they have a longer impact on nanotechnology
compared to the other nanomaterials such as carbon nanotubes and composites
emerged in 1990s. Currently, the data and literature on the fate and transport of
quantum dots, currently is sparse and there is a great need for knowledge and
detailed information. Quantum dot nanomaterials are a potentially new source of
contaminants, and because of the broad suite of physical-chemical properties,
could exhibit a wide range of transport properties. Furthermore, their unique
fluorescence properties make them an excellent material to use for the investi-
gation of the transport of nanomaterials in porous media as it greatly facilitate
their detection and quantification through visualization. Therefore, our research
goal aims at developing a visualization method and imaging process to investigate
the fate and transport of quantum dot nanomaterials in variably saturated porous
media using a non-intrusive high spatial and temporal visualization technique
based on white light transmission and UV fluorescence detection.
2.1. SEMICONDUCTOR NANOCRYSTALS
The development of fluorescent probe technology is essential towards gaining a

fundamental understanding of many basic physical processes. While emissive organic
sensing dyes have existed for over 100 years, there are very few materials that are
VISUALIZATION OF QUANTUM DOT NANOMATERIALS 141
photochemically stable. This fact has generated enormous interest in the study and
development of highly fluorescent and photochemically robust inorganic nanocrystals
(NCs, also known as quantum dots) [30]. Since their discovery in the early 1980s,
semiconductor NCs have gained a large amount of attention due to their unique
optical and electronic properties [8, 23]. The effects of exciton quantum confine-
ment, the high crystallinity, and the organic surface passivation of semiconducting
NCs results in tunable and efficient emission quantum yields compared to the bulk
materials [2]. The size-dependent luminescent spectra are much narrower compared
to fluorescent organic dyes and are highly resistant to photobleaching. Further,
colloidal NC suspensions can be prepared using simple one-step chemical procedures
[18, 20]. Shown in Figure 1 is a TEM micrograph of cadmium sulfide overcoated
with zinc sulfide (CdS/ZnS) NCs. The nanoscopic size and sharp crystallinity of
the materials can be discerned from the image while the inset showcases the effect
of size and material composition on the emission wavelength. Although NCs are
intrinsically hydrophobic, the emission is not quenched using our method of water
solubilization as shown in the inset. For this study, we have specifically synthesized
~2.8 nm diameter CdSe NCs by injecting Trioctylphosphine Selenide into a 350°C
solution containing Cadmium Acetylacetonate, Tetradecylphosphonic acid (TDPA)
in a solution of Trioctylphosphine (TOP) and Trioctylphosphine Oxide (TOPO).
The NCs were then precipitated using methanol, resuspended in hexane and then
injected to a solution of Cadmium Acetylacetonate, TOPO, TOP, Decylamine and
TDPA. After removal of the hexane under vacuum, a layer of Cadmium doped
Zinc Sulfide was added through the slow (~2 h) addition of a solution of Diethyl
Zinc in 3 ml of TOP concurrently with a 3 ml solution of Hexamethyldisilathiane
in TOP at 150°C [5, 12]. The CdSe/CdZnS NCs are then precipitated, dried and
mixed with a 40% octylamine modified Poly(acrylic Acid) in chloroform. The
Figure 1. TEM micrograph of CdS/ZnS nanocrystals. Inset: Size and composition dependent emission
from CdS/ZnS (blue), small to large (green to red emitting) CdSe/ZnS NCs in aqueous solution.
chloroform is then removed under vacuum and the NCs are resuspended in water.
Excess polymer is removed using 100K high molecular weight centrifuge filters
from Millipore.
2.2. VISUALIZATION OF QUANTUM DOT NANOMATERIALS IN

VARIABLY SATURATED POROUS MEDIA
The visualization method was derived from a light transmission method developed
by Darnault et al. [7]. The visualization technique selected to investigate transport
of quantum dot nanomaterials in two-dimensional variably saturated porous media
is a non-intrusive method based on fluorescence resulting from the quantum dots
optical properties. The visualization procedure consists of exciting fluorescent
quantum dots in porous media by using a UV light on front side of the chamber
and by using a light emitted devices (LEDs) as a light source in the back of the
chamber and detecting the light transmitted through the porous media to characterize
the water content (Figure 2). Images were acquired through a Q-IMAGING
MicroPublisher RTV camera located in front of the chamber. The visualization,
calibration and image analysis was performed using IPLab software.
Figure 2. Visualization experimental set-up.
To calibrate the fluorescence intensity to the quantum dots concentration in

variably saturated sand, calibration cells were used. A stock solution of quantum
dot nanomaterials was prepared and diluted by 4, 6.6, 10, 13.3, 20, 50 and 100 to
obtain a wide range of concentrations (corresponding to 25%, 15%, 10%, 7.5%,
5%, 2% and 1% respectively of the stock solution concentration). Calibration cells
consist of plastic cuvettes (1.1 × 1.1 × 4.5 cm) filled with sand as porous media
and with various degree of water saturations to obtain both saturated and unsaturated
systems as well as a wide range of quantum dots concentrations. The saturated
cells were filled by five steps. Dry sand was poured into the cuvette and then the
quantum dots solution was added for saturation. 1.45 g of sand and 0.32 ml of
quantum dots solution were used in each step. For the unsaturated cells, the
quantum dots solution and the dry sand were first mixed in a beaker. Afterwards,
the mixture was put into the cuvettes. Two calibration curves were obtained to
determine the relationship between water saturation and intensity; as well as quantum
dots concentration and hue. Each experiment includes a two-step process. In the
first step, the light source placed behind the calibration cells is switched on in a
dark room and the resulting transmitted light from the cells is recorded with the
camera. In the second step, the UV light is placed in front of the calibration cells
(about 25 cm away) and the fluorescence resulting from the cells is recorded. Both
images are recorded in RGB format and processed with IPLab software as follow:
the image resulting from the light transmission is converted in intensity format to
relate the intensity parameter to water saturation, and the image resulting from the
cell fluorescence is converted in hue format to relate the hue parameter to
quantum dot nanomaterials concentration in variably saturated porous media.
3. Results
3.1. CALIBRATION
“Water content of each calibration cell was obtained from the intensity image
of the light transmitted and quantum dot concentration of each calibration cell was
obtained from the hue image representing the fluorescence detected with the UV
light (Figures 3 and 4). Calibration curves where developed to establish relationships
between intensity versus water content (Figure 5) and hue versus quantum dots con-
centrations (Figure 6). Quantum dots concentrations versus hue values for various
degrees of saturation of porous media are presented in Figure 6. The procedure to
Figure 3. Intensity image of the calibration cells resulting from transmitted light.
Figure 4. Hue image of the calibration cells under UV light.

200
150 25%QD
Intensity
15%QD
100 10%QD
7.5%QD
50 5%QD
2%QD
0 1%QD
0% 20% 40% 60% 80% 100%

% Saturation
Figure 5. Degree of saturation versus intensity values for various degrees of quantum dots concentrations.
quantify the quantum dots concentration in variably saturated porous media

includes two steps: first the water content in porous media is quantified using
intensity values resulting from the image obtained through light transmission
through porous and then, once the water content is determined, the quantum dots
concentration is obtained from hue values resulting from the image obtained
through fluorescence using the UV light. A linear relationship is observed between
hue value and quantum dots concentration for a constant water content (Figure 6).
200
180
160
140 100
75
120 50
25
Hue
100 Linear (25)

80 Linear (50)
Linear (75)
60 Linear (100)
40
20
0
0% 5% 10% 15% 20% 25% 30%
QD Concentration
Figure 6. Quantum dots concentrations versus hue values for various degrees of saturation of porous
media (25%, 50%, 75% and 100%).
Legend for Figure 5 should be “Figure 5. Degree of saturation versus intensity

values for various degrees of quantum dots concentrations.”
3.2. APPLICATION: QUANTUM DOTS TRANSPORT THROUGH

FINGERED FLOW IN VADOSE ZONE
Vadose zone processes play a pivotal role in the fate and transport of subsurface
contaminants as it is typically the first subsurface environment encountered by
contaminants before reaching the groundwater [17, 32]. Groundwater contamination
is influenced by the hydrodynamics of vadose zone system, and the two main
processes controlling water in the vadose zone are gravity which moves water
downward and capillary process that moves water in all directions, stores it and
releases it [9, 17]. As a result of the various geologic processes that lead to soils
formation, there are heterogeneities in these materials over a wide range of length
scales. These heterogeneities in the flow paths of the vadose zone are a critical
feature because they can lead to the development of preferential flow. Preferential
flow is a non-ideal behavior of flow in porous media that occurs in a non-volume-
averaged fashion along localized, preferential pathways, by-passing a fraction of
the porous space [28]. Preferential flow can be found to occur by a number of
different mechanisms, such as fingered flow, macropores flow [19]. Particles
migrating in the soil matrix can be filtered by small pores, but preferential flow
(e.g. soil macropore) leads to rapid breakthrough of the particles [6, 13, 14, 24–
26]. Once mobilized, particles move by advection and dispersion and may be
deposited by mass transfer reaction that take place at mineral–grain surfaces and at
air–water interfaces.
In this context, a two-dimensional flow experiment in homogeneous sand was
designed to assess the role of preferential flow – fingered flow – on the transport
of quantum dot nanomaterials in vadose zone. This experiment was analyzed and
processed by the visualization technique and imaging procedures. The experimental
system consisted of a two-dimensional chamber – height: 30 cm, width: 20 cm –
with 1 cm thick inner compartment that was filled with sand porous media and
various degree of water saturation were achieved through saturation and drainage.
The resulting initial experimental conditions simulated both vadose zone and
aquifer system. A quantum dots solution was applied as a point source on the sand
surface to simulate the release of nanomaterials in the subsurface environment.
This simulation resulted in the formation of a fingered flow phenomena. The fate
and transport of quantum dot nanomaterials in the vadose zone were observed and
analyzed with the visualization method. The image obtained under the UV light
exposure were converted to hue system to visualize and quantify the quantum dots
nanomaterials in porous media (Figure 7a, b). The mobility and transport of quantum
dot nanomaterials through the vadose zone by preferential flow phenomena –
fingered flow – were demonstrated (Figure 7a). The role of gas-water interfaces
on the retention of quantum dot nanomaterials at the capillary fringe was also
established (Figure 7b).
Figure 7. Fate and transport of quantum dots nanomaterials in vadose zone in Hue format (Quantum
dots are visualized in red color). Transport of quantum dots by fingered flow in vadose zone (a).
Retention of quantum dots nanomaterials by gas-water interface located at the capillary fringe (b).
4. Conclusions
A non-intrusive, high spatial and temporal resolution technique was developed to

visualize and quantify quantum dots nanomaterials in variably saturated porous
media. The impacts of preferential flow – fingered flow – as well as gas–water
interfaces on the fate and transport of engineered nanomaterials, such as quantum
dots in the vadose zone environment were demonstrated.
Acknowledgements
This research was funded by the University of Illinois at Chicago, U.S.A. and Regione
Puglia and High Cultural Activities, Italy (Assessorato al Lavoro, Copperazione e
Formazione Professionale POR Puglia 2000-2006, Asse III; Misura 3.7).
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DEVELOPING AN ECOLOGICAL RISK FRAMEWORK TO
ASSESS ENVIRONMENTAL SAFETY OF NANOSCALE
PRODUCTS
Ecological Risk Framework
L. KAPUSTKA
LK Consultancy
Kapustka@shaw.ca
S. CHAN-REMILLARD, S. GOUDEY
HydroQual Laboratory Ltd.
Calgary, Alberta, Canada
Abstract. The nanotechnology industry is developing rapidly and promises to

spawn many exciting products in the field of medicine, manufacturing, and various
environmental fields, such as bio-control agents, and remediation catalysts. However,
as legitimate questions of environmental safety go unanswered, opposition to the
industry is accelerating just as rapidly. Unique physico-chemical properties of
compounds within the nano-range present unknown toxicities relative to similar
substances of larger dimensions. There is a critical need for a framework to assess
risk of nanoscale particles that both the public and industry can accept.
1. Introduction
Nanotechnology is a rapidly developing industry that is capitalizing on the novel

physical and chemical characteristics of nanoscale particles (NPs). The novel
properties of NPs that hold the promise for revolutionary advances in medicine,
manufacturing, and numerous domestic uses also may present unanticipated environ-
mental consequences. Early indications are that some NPs can be assimilated into
organisms, translocated through vascular systems, and loaded into tissues and cells.
Though some preliminary laboratory investigations have shown toxic responses in
various test species, there are legitimate questions regarding the realism of these
tests conditions. Consequently, we still do not know if these test results portend
unacceptable risks or merely indicate intriguing curiosities.
Here we discuss the need for a risk framework that can guide decision-makers
through the critical nodes in the lifecycle of nanoscale products. We describe the

150 L. KAPUSTKA ET AL.
characteristics that such a framework should include and reflect on the many
efforts underway in industry, governments, academia, and public interest groups.
2. Public Perception of Risk
The successful development of new technologies, including nanotechnology,

requires input from diverse groups of stakeholders. Often, perception of risk
weighs heavily in the progression of the technology from early conceptualization
to the reduction to practice (Figure 1). The evolution of any technology begins
with an inspiration by theoreticians who develop the initial concept; this is
followed by scientists who move a theory from concept to the experimental stage.
Once the technology has taken on a tangible form, entrepreneurs and sometimes
venture capitalists begin to invest in the technology resulting in the emergence of
consumer products. Ideally, in the eyes of the entrepreneurs, a new technology
progresses through this product development curve in a direct, unhindered fashion.
As new participants enter, a linear path may take on a series of iterative loops.
This occurs as investors, regulators, or interested publics ask new questions,
explore additional scenarios, and seek comfort that any known or suspected risk,
including financial or environmental, are acceptable. With any new perspective
and any new question, the path to successful commercialization may be altered,
even blocked.
A major factor that may affect the realization of the full potential of nanotech-
nology is the publics’ perception of the risks associated with nanotechnology with
regard to socioeconomic and environmental health impacts [1, 2]. Prior experience
with the public backlash to genetically modified organisms (GMO) [3] and the
nuclear power industries [4] provide the nanotechnology industry with precedence
to consider these factors early in the evolution of product development [5].
The occurrence of an event that causes morbidity or mortality due to use of or
exposure to nanotechnology likely would trigger negative public perception and
bring heightened attention from news media and activists groups [6]. The question
is whether the nanotechnology industry will address consumer challenges candidly
and respectfully or will it be constrained in a manner similar to the GMO industry.
Much depends on the publics’ confidence that appropriate measures to manage
risks are being taken from the initial stages of product development through
product disposal. Although consumer products that incorporate nanotechnology
are rapidly emerging and already available [7] there is still opportunity to address
environmental concerns, manage risks, and engage in meaningful communications
with the interested public [8].
EFFECTIVENESS OF A RISK ASSESSMENT FRAMEWORK TO INFORM PUBLIC PERCEPTION
Effective Management of Risk and Perceptions Damage Control
CURRENT STATE OF NANOTECHNOLOGY

RESEARCH AND DEVELOPMENT
VE
Funding Sources: UR
• Academic Institutions TC Resolve Conflicts
M EN
• Entrepreneurs Interest Groups:
• Economic Development Programs OP Gain Publics' Confidence
• Regulatory Agencies EL
• Environmental Groups DEV
• Technology Companies T
D UC
PRO
OGY
N OL
CH
TE
NO
NA
Politicians Lose Publics' Confidence

Sales
Marketers
General Public / Activist Groups
Business Developers
Engineers
PROGRESS TOWARD VIABLE MARKETS

Applied Scientists Media Dissemination of Information
Theoreticians • Often erroneous
• Often incomplete
• May generate negative public perception
DEVELOPING AN ECOLOGICAL RISK FRAMEWORK
• May creates "crisis" mentality
Figure 1. Stages in the continuum from concept to commercialization.

BEST OPPORTUNITY TO SAVE
Triggering Event
RESOURCES, COST, REDUCE RISK
(e.g. accidental release raising fears of
AND NEGATIVE PUBLIC PERCEPTION
mortality/morbidity to receptors)
151
Anticipatory Crisis
3. Risk Assessment Framework
Modern-day risk assessment has evolved over the past two decades as a useful
tool to inform environmental management decisions [9–11]. In its basic form, risk
assessment examines one or more scenarios to characterize the likelihood of
occurrence. In this process, the magnitude of exposure that receptors may realisti-
cally experience is estimated. Next, the range of exposures to stressors is related to
expected effects. Finally, the likelihood of occurrence and consequences are weighed
against incertitudes. Though substantive inherent and contrived limitations exist in
the practice of risk assessment [12], the basic framework still provides the best
means of focussing information on specific stakeholder issues in the process of
developing coherent risk management and risk mitigation strategies.
Though ecological risk and human health risk assessment have largely
developed as independent disciplines, there has been substantial movement in
recent years toward an integrated approach consistent with the World Health
Organization [13] definition, which states “Health is a state of complete physical,
mental and social well-being and not merely the absence of disease or infirmity.”
An integrated risk assessment thus begins with the Problem Formulation stage by
inclusion of socioeconomic, psychological, spiritual, human health, and ecological
consideration into the guiding conceptual model. If broad stakeholder involvement
is fostered [14], proactive dialogue can be developed [15]. In this fashion, the
emerging nanotechnology industry would benefit from application of an integrated
decision framework that addresses the publics’ concerns over the full lifecycle of a
given product [16].
Public safety and environmental protection are important and shared obligations
of proponents and regulators in any industry. The risk assessment framework, as
noted above, provides one tool that can be used effectively to organize infor-
mation that can be useful to foster informed dialogue and to assist in making
critical decisions. There is growing recognition of the need for risk assessments of
NP [17–21].
The risk framework can be applied at different stages of a product beginning
with experimental work of formulation through disposal of all waste streams and
products. The degree of sophistication used in assessing risks should increase
along the product life-cycle. Characteristically, the assumptions used in assessing
risk at the early stages are designed to be protective, that is to trip flags about
possible problems so that more attention is focused on managing or mitigating
such risks. As one progresses through the product lifecycle, more data become
available and thus the assumptions used in the assessment become more realistic.
At any level of analysis, absence of data typically triggers precaution. In the
absence of solid defensible scientific information that addresses public concerns,
the nanotechnology industry likely will face restrictive measures based on
precautionary principles.
Clear communication on risk issues requires common understanding of terms.
Important aspects of such communications include distinguishing between hazard
and risk as well as exposure and effect.
DEVELOPING AN ECOLOGICAL RISK FRAMEWORK 153
Hazard – the inherent properties of a stressor (biological, chemical, or physical

agent) that can have an adverse effect on a receptor (humans, other animals,
plants, or microbes).
Exposure – the magnitude, concentration, dose, or other measure of the degree
of contact a receptor has with a hazard.
Effect – the biological response of an organism, population, or ecological
system to a stressor.
Risk – the likelihood of an adverse effect occurring as a result of being
exposed to a hazard.
Risk Assessment – a process (usually within a formalized framework) that
examines scenarios to evaluate the likelihood of an adverse event occurring.
This is accomplished through estimation of the magnitude of exposure and
relating effects that occur from such exposures to one or more hazards.
Studies of algae, invertebrates, plants, and fish have shown that organisms
incorporate NP into their tissues and, at the concentrations/doses tested, exhibit
some toxic responses [22]. A key outstanding question is whether the laboratory
test concentrations are realistic (i.e., will such concentrations occur in the
environment? if so, under what circumstances?).
At this stage in the development of the nanotechnology industry, we do not
know enough to judge whether adverse effects are likely to be manifested in occu-
pational settings or the environment. Therefore, there is some urgency to adapt the
risk framework to address the specific issues pertaining to the nanotechnology
industry. Concurrently, the need is equally urgent for data on toxicity (hazard),
fate and transport of particles across environmental media, and quantitation of
exposure for various receptors (human and ecological).
Finally, the output of an integrated risk assessment generally contains multiple
components that must be judged in terms of societal values. Thus, societal values
dictate both the structure of the questions addressed and the interpretation of the
results of the risk assessment. To do so requires getting the right questions right –
and this demands consideration of ecological imperatives [12, 23]. In particular,
ecological systems are dynamic, self-organizing entities that cannot be restored,
they can only be emulated. Change is inevitable and predictions of future conditions
are tenuous at best.
There also must be clear recognition of the interface between science and
public policy that lead to regulations [24, 25]. Though we all bring certain biases
to any analysis and discussion, the power of science, including ecology, derives
from the desire to provide objective explorations of how the world works, in other
words free of normative science [25]. We should remain cognizant that the
specific values of ecological resources, both goods and services, are contextual
(i.e., the values are based on human needs and desires, which vary among cultures,
ethnicities, economic status, age, gender, and many other sociological considerations).
Moreover, economies are based (whether acknowledged or not) on the flow of
ecological goods and services. Therefore, public policy that emerges with respect
to the nanotechnology industry should incorporate long-range objectives of
sustaining predictable flows of ecological goods and services along with the
shorter-term economic benefits accrued from specific nano-materials.
Information derived from a formal risk assessment approach is compatible
with multi-criteria decision analysis tools. Perhaps the most important feature that
comes from the marriage of risk assessment and decision analysis is the
opportunity to focus explicitly on the sufficiency of information required to make
a decision. Not only does this provide for a more satisfying result, but it also gives
added value to the risk assessment. From personal examination of risk assessments
conducted on hazardous waste sites (and Lee Nikl, Golder Associates, Vancouver,
British Columbia, Canada, personal communications, 2007), the value in savings
is $50 and $500 for every $1 spent on a risk assessment.
Communicating the results of a risk assessment and the decisions to be made
can be challenging. One of the most difficult barriers to overcome is to develop a
common language to translate highly technical jargon into a form that people
outside the immediate field can relate to. After all, the collection of persons who
contribute to a decision on such matters as those facing the nanotechnology area
range from physicists, chemists, economists, social scientists, sociologists, politicians,
ethicists, and many more. We have found it useful to classify the results of risk
assessment into a risk matrix that provides an expression of the likelihood of an
event occurring and the consequence if the event does occur [26]. Though
agreeing on the operational definitions of risk categories is far from trivial, once
basic agreement has been achieved, it becomes relatively easy for stakeholders,
regardless of their areas of expertise, to grasp the meaning of the risk categories
and to act accordingly in moving toward a decision.
4. A Risk-Based Life-Cycle Analysis Approach
We believe there is need for a comprehensive program to address issues emerging

in the broadly defined nanotechnology arena. This can be achieved by adapting
the basic constructs of the risk assessment framework by staging a sequence of
tiered assessments tailored to address different phases along the product commer-
cialization continuum.
4.1. CONCEPTUAL BEGINNING
At the earliest stages of designing a new nanoscale substance, whether achieved

through a directed theoretical focus or a serendipitous discovery, a few basic
considerations should be examined. Clearly at the outset, there are minimum data;
most information will be generalized deductions from rules of physical chemistry.
Nevertheless, some insights into potential hazards may be anticipated from know-
ledge of the expected behaviours of the substances in different media. Drawing
from experiences with conventional chemical substances, an initial characterization
may be attempted using correlative information from similar substances and
similar molecular configurations. As the body of information increases, something
akin to the quantitative structure activity relationships (QSAR) should emerge.
Clearly, in these early stages of amassing data, there will be large uncertainties,
but as the database grows, some classes of substances will be resolved such that
reasonable projections of risks to humans or to ecological resources should be
possible. We envision a check-list type analysis, based on QSAR-like decision
rules should be possible fairly soon that would serve as a pre-feasibility scoping
exercise that would serve a few large objectives:
Establish a basis for laboratory hygiene that is protective of staff who may
encounter the products and by-products of production
Identify types of data that could be confirmatory of hazard ranking (an espe-
cially useful way of demonstrating lower hazards that could lead to relaxation
of stringent safety requirements) and
Focus on gathering additional characterization data that would be useful in
assessing risks at later stages of the product development and commer-
cialization continuum
4.2. BENCH-SCALE TESTING
With successive stages of development, characterization data should continue to

address questions of potential hazards and fate of substances in the intended media.
During bench-scale production, generic measurements should provide better char-
acterization of the nanoscale particle structure and behaviour in aqueous and non-
aqueous media. The data gathered should confirm predictions based on QSAR-
like predictions and extend the database for future uses. The focus of bench-scale
testing should be on characterizing the environmental fate of both the primary
nano-material and on the waste-streams generated in production of the intended
product. Generally, these data should provide the foundation for predictions of
toxicity to different receptors (human and ecological), though at this stage,
laboratory toxicity tests similar to the safety tests used in conventional chemical
and pesticide registration guidelines would not be conducted.
4.3. PILOT PRODUCTION
At the time commercialization looks to be feasible and pilot production begins,
expanded safety testing in relevant media should be started. A small number of
tests that examine in-life toxicity responses would be warranted. The choice of test
methods is likely to evolve as more data are generated, but the focus of these early
tests will always be to ensure that Type II errors (i.e., declaring something to be
safe that is indeed harmful) are avoided.
Simplified conceptual models are needed at this stage to guide the selection of
tests appropriate to characterize risks to humans in the work place, other humans
that may be exposed to the substances, and ecological receptors. Generic concep-
tual models should be developed to achieve consistent decisions across the industry
with respect to the rigour of testing. We anticipate that these initial tests would use
species suspected to be maximally sensitive to the particular products being tested.
Currently, there is no consensus as to whether existing laboratory tests are
appropriate and robust for determining toxicity of NPs. Efforts are underway
within various research laboratories and standardization organizations to determine if

standardized test methods used for conventional product safety testing will require
modification. At a minimum, there is consensus that different methods are needed
to characterize the NPs including for particle size, aggregation, surface area, and
reactive surfaces; mere concentration of the base substance is insufficient.
4.4. COMMERCIALIZATION
Information gathered along the path to this point will be needed to construct more
detailed conceptual models for use in expanded safety testing and determination of
risks to humans and to ecological receptors. Specific scenarios relevant to both the
intended uses and accidental releases that occur during manufacturing, distribution,
use, and disposal would be required.
The product-specific conceptual model should be used to guide the data require-
ments for completion of a detailed, integrated risk assessment. Some scenarios, we
can anticipate, will be addressed through generalized narratives that draw upon
information already assembled up to this stage. However, parts of some scenarios
may require focused measurements of fate and transport of the NPs, by-products,
and break-down products. The suite of laboratory toxicity tests may need to be
expanded to develop relevant toxicity data for the specific scenarios.
The ultimate goal of this stage of the product risk assessment should be to
demonstrate safety to humans and ecological receptors. This should engender
sufficient confidence for regulators to write regulations and issue permits and for
the public to trust both the information and the decision to permit production and
commercialization.
4.5. POST-COMMERCIALIZATION
At least for the next several years, the industry will benefit from some form of
risk-based monitoring to validate the assumptions used to obtain the permits for
production and commercialization. The conceptual model that was used to guide
the risk assessments in the previous stage should inform the type of post-commer-
cialization monitoring that would be warranted. As the regulatory bodies and the
public become convinced that the permitting process is sufficiently protective, the
magnitude of monitoring is likely to be relaxed. If, however, unexpected indications
of human health or ecological injury are detected, such information logically
would flow back to earlier stages of the process and result in increased rigour in
characterizing risks. Such a risk-based approach meshes with the processes of
active adaptive management, a strategy that serves the dual goals of promoting
commercialization and maintaining environmental protection [27–29]. Findings in
such a monitoring program can be used in real time to avoid, minimize, or
mitigate adverse effects – especially if made part of the permitting process.
5. Contemporary Activities
Professional societies have rallied around the perceived need to address data gaps
that currently stymie characterization of risks associated with NPs. The Society for
Risk Analysis organized a Section on Nanotechnology at its annual North American
meeting in 2006. The Society of Environmental Toxicology and Chemistry (SETAC)
formed working group in 2007 that is examining five topical areas relevant to the
field. The topics being addressed by the more than 90 members from Europe,
North America, and Australia are (1) terminology, (2) environmental fate and
behaviour, (3) toxicokinetics and bioconcentration, (4) ecotoxicology, and (5) risk
assessment framework.
In addition to professional societies, government bodies such as the US EPA,
Environment Canada and Health Canada, and the European Community have
launched exploratory studies of nanoscale products. In the US, some states and
municipalities [30, 31] have considered policies pertaining to the nanotechnology
industry.
Collaboration between industry and consultancies has led to articulation of
policy needs (CIELAP) [32] as well as initial efforts to develop risk approaches
tailored to the nanotechnology industry [19].
The American Society for Testing and Materials-International (ASTM-I), the
Organization for Cooperation and Development (OECD), and the International
Standards Organization (ISO), have initiated work to develop standards for testing
and handling nanomaterials. ASTM-I for example is examining the full suite of
toxicity test methods to determine if the tests as described are adequate for
addressing the unique properties of NPs. Early emphasis will be to consider the
special characterization steps required to document exposure regimes. Other aspects
of the tests to be evaluated will include consideration of test volumes, relevant
endpoints, and interpretation of effects data. In all of these areas of interest, the
field is progressing rapidly. An important challenge faces all who work in this area
to remain current and to the extent practical, minimize duplication of effort.
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DEVELOPMENT OF A THREE-LEVEL RISK ASSESSMENT
STRATEGY FOR NANOMATERIALS
N. O’BRIEN, E. CUMMINS
Biosystems Engineering UCD School of Agriculture, Food Science
and Veterinary Medicine
College of Life Sciences, Agriculture and Food Science Centre
niall.obrien@ucd.ie
Abstract. The release of nanomaterials and, in particular, free nanoparticles into

the environment from secondary sources such as industrial manufacturing and
consumer products as well as from intentional environmental application has
compelled a need for a broad and pre-emptive analysis of nanomaterial fate and
transport in the environment and subsequent potential human exposure pathways.
The novel and potentially reactive characteristics of nanomaterials have lead to
predictions on potential undesirable ramifications of exposure to these materials
on human health. The three-level risk assessment strategy presented in this work
has its basis in qualitative model equations that represent the inter-relationships
between the different material and process characteristics and environmental
behaviors and their relationship to potential exposure scenarios. The factors that
influence these behaviors are examined, and the potential application of this risk
assessment strategy in a semi-quantitative model is considered.
1. Introduction
Nanomaterials have been developed for use in many environmental applications

such as nanoscale sensors for monitoring and detection of pollutants as well as
nanoparticle additives in coatings. Examples include TiO2 in paint to aid in oxidizing
volatile organic compounds and iron oxide based nanoparticle remediation of polluted
soil and groundwater. While these intentional releases into the environment are
intended to provide solutions to or pre-empt environmental problems, there is
concern that nanomaterials and free nanoparticles, particularly from unintentional
or incidental industrial and domestic releases, may result in the creation of new
environmental and subsequent human health hazards. There are two principle
concerns about nanomaterials. First, there is very little precedent to compare the
fate of such a potentially mobile group of materials, some of which are func-
tionalized especially to disperse in aqueous media [27]. Large scale environmental

162 N. O’BRIEN AND E. CUMMINS
fate studies are difficult to execute. The range of products into which nano-
research is currently being applied, such as cosmetics, electronics, fuel additives,
paints and coatings, means that an unprecedented number of routes of release and
exposure are possible. The second principle concern is that of potential reactivity.
Nanoparticles are found naturally in the environment, and man-made nanoparticles
have been produced incidentally in large amounts since the industrial revolution.
However, engineered nanomaterials are produced to undertake certain functions as
efficiently as possible, often involving maximizing and functionalizing the surface
area, which in turn increases their potential toxicity. It is this reactivity, coupled
with their potential mobility, which fuels concern over nanomaterial fate and
transport in the environment and subsequent human exposure.
An analysis of the development and release into the marketplace of any new
technology, especially those with environmental applications, often boils down to
an assessment of risk versus benefit. With nanomaterials, the environmental
benefits of nano-remediation and fuel additives are obvious but often it is difficult
to form a realistic picture of the potential risks associated with these new products
and processes due to the uncertainties associated with materials at this scale. This
is the problem faced by regulators in incorporating nanomaterials into current risk
assessment or regulatory frameworks or developing new frameworks in order to
ensure the responsible and sustainable development of nanotechnology and nano-
materials. A major obstacle in developing new frameworks, or adapting old ones,
is that those charged with assessing nanomaterial risk cannot as yet definitely
specify those common characteristics or mechanisms inherent in nanoscale materials,
or even those characteristics and mechanisms that demand that such a broad
grouping of materials should even be regulated as a single entity. The strategy for
nanomaterial exposure assessment presented here isolates five common behaviors
of nanomaterials in the environment. Characteristics which relate to these behaviors
and the human exposure scenarios resultant from these behaviors are presented,
and hence nanomaterial characteristics may be related to potential human exposure
scenarios by means of an assessment of nanomaterial behavior in the environment.
This assessment strategy is presented within a three-level framework in which the
exposure related questions/concerns to be addressed by the assessment are identified,
the characteristics associated with the particular material and process and its
behavior in the environment are isolated while the behavior and characteristics are
subsequently linked to potential exposure scenarios. The common behaviors of
nanomaterials in the environment that underpin this strategy and the material
characteristics and inter-relationships influencing these behaviors are discussed
and linked to exposure scenarios of possible concern. The strategy presented has
potential to form the basis of a user input based exposure model with which risks
from nano-materials may be evaluated, with potential use in providing regulators
with some measure of nanoparticle risk, an area in which there is little guidance at
present.
DEVELOPMENT OF A THREE-LEVEL RISK ASSESSMENT 163
2. Nanomaterial Exposure Analysis
Comprehensive fate studies are difficult to execute with novel substances such as
nanomaterials as there is very little risk assessment precedent associated with the
analysis of materials with such potential mobility and reactivity released into the
environment. Exposure models can become very complicated due to uncertainty,
assumptions and data gaps in our knowledge of the fate and characteristics of
these materials, environmental pathways and transformations, as well as detection
and analysis. Therefore, qualitative or semi-quantitative exposure models offer the
most realistic measures of potential hazard and exposure with our current level of
knowledge. The novel three level risk analysis strategy proposed here may aid in
overcoming this uncertainty and deficiency in data, as the most basic hazard and
exposure based questions to be answered by the risk assessment are identified and
potential realistic exposure scenarios are linked to these questions via the
treatment, transformation and environmental behavior of these nanomaterials.
A risk assessment model based on this strategy would involve the input of
particle and process characteristics by the user, which are correlated to potential
behavior in the environment and subsequent exposure scenarios derived from fate
and exposure studies from literature. The characteristic, process and treatment
variables presented in this strategy are not an exhaustive list of all possible factors
that may determine nanomaterial exposure, fate and transport, but is comprised of
variables that may be familiar to the user, applicable in many exposure scenarios
and about which a reasonable amount of research has been undertaken.
3. Three-Level Strategy
The proposed overall risk assessment strategy is comprised of three levels as seen
in Figure 1. The exposure related questions/concerns to be addressed by the
assessment are determined in level 1. The characteristics associated with the
particular material and process and its behavior in the environment are identified
in level 2 by means of three inter-related modules: characteristics, treatment and
behavior. These behaviors and characteristics are linked to potential exposure
scenarios in level 3, which comprises of a fourth module: exposure scenarios. The
strategy has its basis in qualitative model equations that represent the inter-
relationships between the different material and process characteristics and
behaviors. The qualitative model equations linking each module were derived
from literature and expert opinion. The individual modules associated with Levels
2 and 3 and their elements are discussed in later sections.
Example exposure questions to be answered by RA:
Level 1
1. E_con: Release of environmentally relevant concentrations?
2. E_sprd:Local Vs Widespread exposure?
3. E_freq: Exposure frequency?
4. E_rts: Primary routes of human exposure?
Particle:
C_sc: Surface charge
Characteristics module
C_mat: Material
C_sol: Solubility/ Persistence
C_form: Form
Process:
C_sd: Size distribution C_lcs: Life cycle stage
C_agg:Aggregate size C_con: Quantities/ Concentr
C_sa: Surface area C_freq: Frequency
Level 2
Treatment module Behaviour module
B_mda: Exposure media

T_dis: Disposal methods
B_trpt: Transport
T_ww: Wastewater treatment
T_wat: Water release
T_slg: Sludge release B_ads: Adsorption
T_fil: Filter efficiency B_rd /pht: Redox/Photoact
T_chr: Characteristic transform B_agg: Aggregation
B_acc: Accumulation
scenarios module
Answers to initial exposure questions:

Exposure
Level 3
1. E_con: Function of: C_lcs: C_con, C_freq, T_dis, T_fil

2. E_sprd: FII of: C_lcs, C_con, C_freq, T_dis, B_trpt, B_ads, B_agg, B_acc
3. E_freq: FII of: C_lcs, C_con, C_freq, T_dis, B_trpt, B_agg, B_acc
4. E_rts: FII of: B_trpt, B_agg, B_acc
Figure 1. Three-level risk assessment strategy.

3.1. LEVEL 1: RISK ASSESSMENT FOCUS
The exposure concentrations, frequencies, routes and spread/reach associated with

a particular nanomaterial are outlined in this section. Pertinent concerns are selected
for examination, the relevant material and process characteristics determined and
resultant potential environmental behaviors extrapolated, with the original concerns
addressed considering the predicted behaviors and initial material and process
characteristics. Some initial Level 1 questions/concerns, as can be seen in Figure
1, are outlined and addressed in Level 3.
3.2. LEVEL 2: CHARACTERISTICS MODULE
The characteristics module concerns the elements associated with the character-
istics of the material and process to be assessed and may be seen in Figure 1.
While the material and process characteristics this risk assessment strategy employs
are not exhaustive, considering the data gaps and uncertainty associated with
nanomaterial exposure and behavior, they may allow a preliminary assessment of
the materials potential mobility and behavior.
3.2.1. Material
The material assessed may be one intentionally released into the environment,
such as zero valent nanoscale iron used for remediation, or a material released
unintentionally or incidentally such as cerium oxide nanoparticles used as fuel
additives. The material in question will determine its possible environmental or
health risks. A survey into workplace health and safety practices in international
nanomaterial firms and laboratories indicated that when asked if they believed
there were any special risks associated with nanomaterials that they either handled
or produced, 35 organizations reported that there were none, 25 described risks,
and 12 reported either not knowing or not having enough information [5]. Of those
describing risks, 12 organizations specified inhalation, 6 reported flammability, 1
dermal, and 1 environmental, and 11 generalized regarding possible risk. All
organizations working with metals or metal oxides, 30, other than quantum dots
reported no risk. The model strategy is tailored to include common individual
nanoparticles likely to be used in the environment, such as those discussed above,
as well as broad particle groupings such as metals, metal oxides, carbonaceous,
organic and non-metals [20].
3.2.2. Form
Form relates to the form in which the particle is present in the particular product,
process or life cycle stage. An ICON workplace report [20] highlighted the
different forms such as dry powder, bound in solids and bound in liquids in which
nanomaterials are handled in the workplace. Each form is associated with a
different probability of release, exposure and behavior in the environment. Kaegi
et al. [21] traced 50–200 nm TiO2 particles, used as whiteners and for the
volatizing of organic compounds in paint, from their source on a building facade

to a retrieving sink, such as rivers and storm drains. The National Research Centre
for the Working Environment, Denmark have conducted tests on consumer pump
and spray products containing nanoparticles and have shown these products to
generate aerosols in the nanoparticle range, and the differing methods of application
to have a large effect on particle concentration [32].
3.2.3. Size Distribution
The size distribution of the individual particles within the nanomaterial is

associated with its uptake and behavior during treatment and aggregation and
accumulation within the environment. Information on shape may also be provided
here as this factor may prove important in inhalation exposure, where length and
bio-persistency are thought to determine inflammatory potential [8].
3.2.4. Aggregate Size
The initial aggregate size the particles within the nanomaterial occur is associated
with its uptake and behavior during treatment and aggregation and accumulation
within the environment. Initial particle size should be taken into account along
with aggregate size as studies with agglomerations of nano-sized and fine TiO2
particles with similar aerodynamic diameters showed the nano-sized agglomerations
to produce more adverse lung effects on a mass basis [37]. It must also be noted
that large nano-sized aggregates have a large physical diameter but a low density,
and so have a small aerodynamic diameter and therefore be respirable [7]. This
state of aggregation and resulting available surface area of nanomaterials may change
once introduced into biological media as a result of surface-tension-mediated
disaggregation of electrostatically or loosely agglomerated particulates [34].
3.2.5. Surface Area
The surface area of nanoparticles is generally larger than that for the same
material in greater than nano-size on a mass or volume basis. This larger surface
area correlates to more potential reactive sites on a mass or volume basis which in
turn is associated with a greater redox and photoactivity potential, adsorption
potential and aggregation potential, affecting transport properties within the environ-
ment and behavior during treatment. This high number of potential reactive sites
may also be associated with potential pulmonary inflammation upon inhalation
[28].
3.2.6. Surface Charge
The initial surface charge of the particles within the nanomaterial may affect the
aggregation state of nanoparticles, which in turn is associated with the transport,
accumulation and further agglomeration states of the nanomaterial once released
into the environment and during treatment. Surface charge may also play an
important role in adsorption and potential inflammatory effects once inhaled or
ingested. Studies by Veronesi et al. [36] have shown PM negative surface charge
to correlate with PM induced pulmonary inflammation. A review by Hoet et al.
[19] into nanoparticle health risks highlighted the poor bioavailability of ingested
positively charged particles through electro static repulsion and (negatively
charged) mucus entrapment.
3.2.7. Solubility/Persistence
The solubility or degrading ability of a material is associated with its persistence

in ecological and biological systems. The rate of dissolution may be considered
proportional to particle surface area, therefore nanoparticulate materials should
dissolve faster than larger-sized bulk materials, for the same mass, on surface area
considerations alone [12]. The dissolution of soluble metal ions from the surface
metal-based nanoparticles, and perhaps the eventual complete dissolution of the
particle upon entry into ecological systems, is of concern. Even with solubility of
a few percent, a 1 mg l−1 solution of a metal oxide NP might generate l µg l−1
concentrations of metal ions in solution, and so there are concerns that some
nanoparticles will act as delivery vehicles for free metal ions [17]. Active
functionalization of the nanomaterial surface or the addition of a surfactant may
alter the degradability of a material.
3.2.8. Life Cycle Stage
The life cycle stage of a particular product or process will be associated with the
form the material is associated with and its potential environment exposure targets,
quantities and treatment. The life cycle stages of note include nanomaterial manu-
facture, use as an ingredient in production, application of nano-containing product/
process and disposal.
3.2.9. Quantities/Concentrations
The quantities (t/year, g/p/day) and concentrations (ppm, µg/m3) in which a nano-
product or process occurs is associated with its likelihood of release, treatment,
transport and accumulation within the environment. A study of Swiss industry by
Schmid and Riediker [31] found that several types of nanoparticles were found to
be used in quantities of more than 1,000 kg/year per company, but the majority of
nanoparticle applications were of a much smaller production scale. An ICON
workplace report highlighted the scale in which nanoparticles are produced in
various sectors, varying from bench or laboratory scale to full commercial scale.
Remediation technologies typically use nanoparticles in the region of g/l [24]. A
report into nanoparticle exposure modelling [4] highlighted the concentrations of
engineered nanoparticles currently found in a range of consumer products, ranging
from 0.001 to 100 mg/g.
3.2.10. Frequency
The frequency (daily, single treatment) and location (rural, urban) in which a
nanoproduct or process occurs is associated with its likelihood of release, treatment,
accumulation and transport within the environment. A report into nanoparticle
exposure modelling [4] highlighted the current usage frequencies for consumer
products likely to contain nanoparticles in the future and the potential subsequent
nanoparticle release assuming different market penetrations. These products
ranged from personal care products to paints and cleaning products.
3.3. LEVEL 2: TREATMENT MODULE
3.3.1. Disposal Methods
The methods of disposal of a nano-product (wastewater, nano-specific, incineration

and landfill) are associated with its likelihood of release into the environment, the
media into which it is released (soil, water, air) and its accumulation, transport and
ultimate fate within the environment. An ICON report [20] highlighted industrial
disposal of nanomaterials as hazardous waste through a waste management company
and the incineration, agglomeration, storage or recycling of nanomaterials. However,
most companies did not separate nano-waste into separate containers and did not
label it as “nanomaterial,” but rather classified it by the bulk material.
3.3.2. Waste-Water Treatment
Where nanomaterials are released intentionally into the environment or are released
unintentionally from industrial facilities and domestic use, these materials are
likely to enter wastewater treatment facilities before direct human exposure through
ingestion and dermal exposure. The aggregation, surface charge and surface area
of the nanomaterials as well as the treatment method employed will affect their
removal efficiency and fate. Wastewater may be subjected to many different types
of treatment, including physical, chemical and biological processes. Nanosized
particles are most likely to be affected by sorption processes and chemical reactions.
Nanomaterials that escape sorption in primary treatment may be removed from
wastewater after biological treatment via settling in the secondary clarifier. The
rate of gravitational settling of particles in water is dependent on particle diameter,
and while nanoparticles may settle more slowly, their large surface to mass ratio
will encourage entrapment in larger sludge flocs, enhancing removal [35].
3.3.2.1. Treated Water Release
Many wastewater treatment processes are expected to remove nanomaterials very

efficiently, such as activated sludge [4], due to Brownian motion and their affinity
to organic colloid binding. Due to high removal efficiencies, along with significant
dilution factors upon release, it is expected that nanomaterials shall not be found
in significant amounts in the released, treated waters.
3.3.2.2. Sludge Release
Where large quantities of nanomaterials are removed in the wastewater treatment

process, this nanomaterial may be applied to soil within the treatment sludge.
Silver mass flows have shown a significant percentage of released silver may be
applied to agricultural soils, with nanomaterials likely to be removed in a similar
fashion [3]. The transport and fate of this soil applied sludge, and thus nanomaterials,
is an exposure route with potential effects on accumulation and secondary effects
on the food chain as well as cross-media contamination into water and subsequent
human exposure. A report into modelling exposure to engineered nanoparticles
has attempted to apply traditional equations, used for pesticide drift and wastewater
treatment amongst others, to potential intentional and unintentional nanoparticle
release scenarios [4]. These models attempt to predict nanomaterial application to
soils and release into waterways; however, the report concedes that much more
data is needed in order to refine these models.
3.3.3. Filter/Converter Efficiencies
Filter and catalytic converter efficiencies may have a large bearing on the amount
of nanomaterial released into the environment from processes such as fuel additive
and industrial manufacturing. Initial investigations into the efficiencies of filters
with a cerium additive show a slight chance of cerium release into the environment,
though simulations with worst case scenarios (all vehicles employing high levels
of cerium additive; 92% efficient filter) indicate a very low risk of cerium
inhalation [18]. Cerium levels in the air and soil in the vicinity of major transport
systems would increase, although this must be assessed in a risk-benefit
framework as cerium additives have also been shown to reduce the overall particle
mass level released from vehicles [18]. Fibrious filtration techniques, such as
HEPA standard filters used in industrial environments, have been shown to be
even more efficient with nanosized particles (<100 nm), due to these particles
being subject to Brownian motion enhancing collision probability with fibers. The
maximum particle penetrating size was observed at approximately 150–300 nm
[26].
3.3.4. Transformation of Characteristics
Treatment of nanomaterials may result in a transformation of their characteristics

such aggregation state and surface charge. This transformation may affect their
treatment removal efficiencies and subsequent environmental behavior such as
adsorption and transport. An example of transformation in the environment is that
of iron nanoparticles used for the dechlorination of organic pollutants. These
particles are oxidized to iron oxide during this reaction and other metal particles
are also converted to oxides in the presence of air and water. The resulting oxides
may even be more reactive then the original free metals. Metal compounds in the
environment may also be converted to more mobile compounds [35]. The effects
of environmental release of particles on surface charge will depend on the media
into which the nanoparticles are released. It has been noted in studies by
Mahmoodi et al. [25] that their TiO2 surfaces were positively charged in acidic
media (pH < 6.8), and as the pH of the system increased, the number of negatively
charged sites increased, increasing the adsorption potential to negatively charged
species.
3.4. LEVEL 2: BEHAVIOR MODULE
Table 1 lists the particle and process characteristics that may affect some typical
material behavior in the environment that may be of relevance in assessing the
human exposure risk posed by a nanomaterial according to available literature.
The exact theory of nanomaterial behavior in the environment has not yet been
elucidated so the relationships listed in Table 1 may be seen as subjective. The
actual characteristics considered shall change depending on which exposure media
is being considered. The characteristics indicated will have different effects on the
final behavior of the material, such as transport or adsorption, and in the final
assessment these different characteristics must be weighted in accordance to their
perceived relevance to specific nanomaterial behavior. The listed characteristics
and behaviors will have inter-relationships and layers of complexity, although this
strategy only considers those behaviors and characteristics which are reasonably
easy to define and have a potentially significant effect on the nanomaterials final
exposure risk.
TABLE 1. Nanomaterial characteristics and environmental behavior.
Behavior
Material Transpt/Mob. Aggreg. Accum. Adsorp. Redox/Ptact
Character. B_trpt B_agg B_acc B_abs B_rd/pt
C_mat X
C_form X
C_sd X X X
C_agg X X X
C_sa X X X X
C_sc X X X X X
C_sol X X X
C_lcs
C_con X X X
C_freq X X
T_dis X X X
T_ww X X X X
T_wat X X X X
T_slg X X X X
T_fil X
T_car X X X X X
3.4.1. Exposure Media
The exposure media relates to the environmental media into which the
nanomaterial is released or is transported within; air, water or soil. This will affect
the fate, aggregation, accumulation and human exposure probability of the
material in question. Release of nanomaterials into the environment may be direct
or through treatment facilities such as treated wastewater and sludge, as can be
seen in the two-way exposure pathways in Figure 1.
3.4.2. Transport/Mobility
The transport or mobility properties of a material will affect the potential area
exposed to a nanomaterial and thus the potential human exposure. The differing
characteristics of a material in different environmental media will affect its
transport potential. Fate and transport of nanomaterials in aqueous environments,
for example, is limited by the materials aqueous solubility, interactions between
the nanomaterial and natural and anthropogenic chemicals in the system, and
biological processes. Nanoparticles generally settle more slowly than larger
particles of the same material in aqueous systems, though nanosized particles have
a greater potential to be adsorbed onto soil and sediment particles, due to their
larger surface to mass ratio, thus affecting their transport potential [35]. Fate and
transport of nanoparticles in soil systems is affected by particle characteristics
such as particle concentration, surface area and aggregate size and system
characteristics such as pH and ionic strength [24]. A review by Nowack and
Bucheli [27] into surface modified nanoparticles concluded that these particles
were likely to be mobile under natural conditions, indicating the importance of
determining exact surface properties of nanomaterials and particles, as indicated in
this strategy, in order to assess their potential mobility in the environment.
3.4.3. Adsorption
The adsorptive properties or potential of a nanomaterial may relate to the potential

of materials to adsorb onto the nanomaterial or the potential of nanomaterials to
adsorb onto larger particles or materials. The adsorptive potential of a nanoma-
terial is influenced by its surface area, surface charge, aggregation state and
surface treatments. Adsorption of nanomaterials onto organic and soil particles
will influence their treatment removal potential and their transport potentials in
environmental media. Adsorption of materials such as transition metals and
organic compounds may result in secondary exposure scenarios such as the so-
called “Piggy-backing effect”, where a potentially harmful compound attaches to a
nanomaterial, resulting in a bioavailability that may not have been previously
available [9, 11]. A study by Zhang et al. [38] showed a much greater uptake of
cadmium in Carp in the presence of TiO2 nanoparticles than in the presence of
cadmium alone, highlighting this potential for enhanced bioavailability.
3.4.4. Aggregation
Aggregation of nanomaterials will affect their transport, redox, adsorption,

treatment and persistence potential. Particle aggregation will be affected by the
ionic strength of natural systems, which vary considerably, and this will thus
affect transport, as these aggregates are mobile. This must be taken into considera-
tion in nanoparticle-based environmental remediation systems, analyzing life
cycles of nanoparticles used in commercial products, and determining potential
exposure to nanoparticles for health and impact studies [10]. The chemistry of
engineered nanoparticles suggests they will aggregate in many types of natural
waters (e.g., hard freshwater and seawater), and ecotoxicologists have found it
virtually impossible to disperse these particles in pure water by physical means
alone [17]. Phenrat et al. [29] has suggested that, given the rapid aggregation of
nano-scale zero valent iron into micrometer-sized fractal aggregates in NaHCO3
at pH 7.4 they observed, it may be more appropriate to specify the aggregate size
for use in any filtration models since the choice of particle size greatly affects the
estimated effective mobility of the particles. In a study focusing on actual
nanomaterial emissions into the environment, Kaegi et al. [21] traced TiO2
nanoparticles from their source, painted facade, to their sinks, such as storm drains
and rivers. These particles were not found in aggregates but mostly isolated or in
organic binds.
3.4.5. Accumulation
Accumulation of nanomaterials in the environment will affect their transport

potential and exposure concentrations and frequencies, with aggregation and accu-
mulation likely to result in fewer, but more extreme, exposure events. Accumulation
of nanomaterials in media such as sediment and soil applied sludge may have
secondary effects on the food chain, such as organisms in the lower trophic levels
such as benthic worms and daphnia [17]. A cautionary tale into secondary affects
on the food chain is the introduction of a veterinary drug into cattle in the 1980s in
India leading to a 99–97% reduction in vulture numbers, with resultant rapid
escalation of scavenger populations such as feral dogs, rats and crows, which in
turn increased the risk of spreading disease amongst humans [16].
3.4.6. Redox/Photo-Activity
The redox or photo-activity of a nanomaterial may be seen as a potential indicator

of toxic potential upon human exposure, where behavioral characteristics may be
linked to cell toxicity mechanisms. Studies by Gojova et al. [13] on the inflamma-
tory effects of metal oxide particles on human aortic endothelial cells following
acute exposure showed that these effects depend on particle composition. Studies
specifically on nano-TiO2 have lead to different proposals as to the particular
characteristics that drive reactive oxygen species production and subsequent
inflammatory effects, depending on exposure routes. Singh et al. [33] have shown
these particles, even as aggregates/agglomerates, to have inflammatory properties
in lung epithelial cells that appear driven by their specific surface area. However,
Grassian et al. [15] found engineered nanoparticles, with the highest commercially
available surface area and smallest particle size for TiO2 used in the study, did not
show particularly toxic effects to rat lungs in a sub-acute inhalation study. These
results are in conflict with the notion that inflammatory response is expected to be
high with high surface area powders composed primarily of nanoparticles in the
lower size range. While any inflammatory effects in these studies were concluded
to be produced by oxidative stress, the responsible mechanism(s) could not be
elucidated. TiO2 nanoparticles may undergo surface treatments, such as alumina or
silica/alumina coatings that limit their chemical and photo-chemical activity.
Particles having undergone such a treatment would be expected to have a low risk
potential for producing adverse pulmonary health effects [37].
3.5. LEVEL 3: EXPOSURE SCENARIOS
The exposure scenarios examined in Level 3 relate to those primary questions

posed in Level 1 of the risk assessment strategy. These exposure scenarios typically
address exposure concentrations, frequencies and routes. Resultant exposure scenarios
are a result of the combination of process and treatment characteristic elements
and behavioral conclusions of the strategy in Level 2. Some typical exposure
scenario questions, such as those highlighted in Figure 1, are discussed below.
3.5.1. Environmentally Relevant Concentrations
The concentrations of a nanomaterial found in the environment will determine

whether this material poses a realistic environmental and subsequent human health
hazard. Level 2 strategy elements relevant to the concentrations of a nanomaterial
released into the environment include the life cycle stages considered, concen-
trations or quantities of a product or process in circulation, the material disposal
methods and the treatment and filtration methods employed. A study by Handy et
al. [17] into lethal dose values on the ecotoxicity of nanoparticles found very few
published studies, but studies on fish and invertebrates have suggested that C60
fullerenes and 10–20 nm TiO2 particles are toxic in the milligram per liter range,
but that the specific LC50 values were dependent on the preparation of the
material and the use of dispersants.
3.5.2. Local vs. Widespread Exposure
The extent to which an environmentally released nanomaterial is transported will

determine whether this material poses a realistic human exposure hazard. Level 2
strategy elements relevant to the extent of penetration of a nanomaterial released
into the environment include the life cycle stages considered, concentrations or
quantities of a product or process in circulation, the material disposal methods, the
treatment methods employed and the transport, aggregation and accumulation
behavior.
3.5.3. Exposure Frequency
The frequency of exposure to a nanomaterial is an important factor in accumu-

lation and fatigue effects through repeated exposure. Level 2 strategy elements
relevant to the likely frequency of exposure to a nanomaterial released into the
environment include the life cycle stages considered, concentrations or quantities
of a product or process in circulation, the material disposal methods, the treatment
methods employed and the transport, aggregation and accumulation behavior.
3.5.4. Primary Routes of Human Exposure – Inhalation, Ingestion, Dermal

Exposure
The route of exposure to a nanomaterial is an important factor in determining

characteristics, frequencies and concentrations of concern to human health. Level
2 strategy elements relevant to the likely routes of exposure to a nanomaterial
released into the environment include the transport, aggregation and accumulation
behavior.
4. Model Application
4.1. UNCERTAINTY, VARIABILITY AND ASSUMPTIONS
In the case of nanomaterials, and nanoparticles in particular, there is great uncer-

tainty as to their fate in the environment, the quantities these particles may be
present in at each exposure point and the potential ecotoxicological hazards and
transformations that may take place such as disaggregation and adsorption of
potentially harmful materials. Because of a lack of exposure and toxicological data
concerning nanoparticles, qualitative risk assessments employing probability
distributions, substitutions and even simulation in tandem with expert opinion and
critical literature reviews are required to fill these data gaps [14].
The case for eliciting expert opinion or critically analyzing literature in order
to overcome uncertainty and data gaps in risk assessment modelling is one which
has been examined in an assessment by Cooke et al. [6] on campylobacter
transmission in chicken processing lines. In this assessment, expert judgment on
predicted observable quantities in combination with probabilistic inversion was
used for validation and criticism of a general mathematical chicken processing
model. Study of the experts’ rationales led to a revision of the model and a good
fit between the experts’ and the re-predicted distributions. A qualitative model
derived from the strategy presented here may employ a critical analysis of
literature, in which the intrusion of subjectivity would be unavoidable, although
once critical exposure points such as fate during treatment processes and transport
in different environmental media are better understood and studies with universal
reference materials undertaken, this strategy may be converted to a quantitative
basis where a common risk ranking structure for nanomaterials may be developed.
Distributions allow us to account for the full spectrum of possible events in the
particles lifetime. For example, carbon nanotubes may adsorb significant amounts
of the catalytic metals used to produce them and particles in the environment may
adsorb bio-molecules. Both scenarios may result in inflammatory effects in the
human body [11]. Iterative simulations employing these distributions relating to
the various release and behavioral possibilities allow a true picture of the potential
exposure scenarios to be assembled. Any model using this strategy may tackle the
problem of deficiencies in initiating data by employing predefined distributions
for the particular entry derived from data sets according to the known initiating
parameters and their inter-relationships. These data sets may be derived from
literature, manufacturers’ information and expert opinion.
One of the major assumptions made in this three-level strategy is that the
material, process, treatment and behavioral characteristics presented alone are
involved in the exposure scenarios. The second is that any relationships employed
in a model derived from this strategy would by independent of all other physical
variables. Many of the potential model relationships employed may not be derived
from any firm underlying physical laws, nor may they as yet be verified by direct
observation or by experiment. Indeed, studies into compartmentalized models for
hazardous materials, such as exposure models concerning mass transfers over
time, have shown that the types of arguments leading to a choice of a specific
model depend entirely on the material in question [23]. Once a compartmental
model is chosen, the method for determining the relationships involved and values
of the underlying transfer coefficients is also highly specific to the problem at
hand and involves a great deal of qualitative reasoning. The absence of direct
physical measurements of these inter-relationships and transfer coefficients means
that relevant uncertainty inherent in a qualitative model derived from this strategy
could not be determined by objective statistical methods, but by the subjective
uncertainty of experts.
5. Discussion and Conclusions
The strategy presented here does not cover every material, process and environ-
mental characteristic that may be relevant to human exposure to nanomaterials,
though it does provide an overview of the principle factors, their inter-relationships
and effects on nanomaterial environmental behavior that need to be taken into
account before developing a nanomaterial or process for wide scale release, or
before developing regulatory frameworks for these materials. Due to its largely
qualitative basis, any model derived from this strategy would be of more use in
comparing two nanomaterials, or comparing the effects of changing one or more
material or process characteristics. As more information is generated on critical
exposure points such as fate during treatment processes and transport in different
environmental media, models with a quantitative basis may be constructed on this
basis, where nanomaterials may be compared on a common risk ranking structure,
while also removing the subjectivity associated with qualitative risk analyses. This
model strategy could find application in regulatory forecasting, where future

exposure scenarios may be explored and controls set where appropriate.
Another avenue of research that may be undertaken as part of this vein of
research is that of potential ecotoxicity, as alluded to in discussions on effects of
accumulation of nanomaterials in the environment, such as critical damage to vital
links in the food chain. The anti-bacterial effects of nano-silver are well reported
[2], but research by Adams et al. [1] into the ecotoxic potential of various nanoscale
metal oxides in water suspensions indicated varying degrees of antibacterial
activity to test organisms, highlighting the importance of nanomaterial environ-
mental exposure control until more is known about material characterisation and
potential toxic mechanisms. Models assessing potential ecotoxicity may incorporate
information on the characteristics of the ecological systems into which the specific
nanomaterial is to be introduced, such as salinity/ionic strength, pH, hardness,
dissolved organic matter, etc. [17].
Secondary effects of nanomaterials that may need to be taken into account in
undertaking a full human health impact analysis of nanomaterials is that of raw
material extraction and potential recyclability. The functionalization of nanoma-
terials at the nanoscale has opened up new avenues of exploitation for many materials,
and the extraction of the raw mineral materials that form these nanomaterials may
have secondary effects on the environment and subsequently human health [22,
30]. This functionalization enhances traditional material characteristics, such as
strength, melting temperature, etc. but also limit the traditional recycling routes
and methods available for these enhanced material and products [22]. The risk
assessment of nanomaterials may ultimately be an exercise of measuring risk vs.
benefit of a potential new enabling nanoproduct, process or technology.
Acknowledgements
The authors would like to acknowledge the financial support from the Irish
Environmental Protection Agency for this work.
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CLASSIFYING NANOMATERIAL RISKS USING
MULTI-CRITERIA DECISION ANALYSIS
I. LINKOV, J. STEEVENS, M. CHAPPELL

US Army Research and Development Center, CEERD-EP-R
Vicksburg, MS 39180, USA
igor.linkov@usace.army.mil
T. TERVONEN
Faculty of Economics and Business
University of Groningen
P.O. Box 800, 9700 AV Groningen, The Netherlands
t.p.tervonen@rug.nl
J.R. FIGUEIRA
CEG-IST, Centre for Management Studies, Instituto Superior
Técnico, Technical University of Lisbon
2780-990 Porto Salvo, Portugal
figueira@ist.utl.pt
M. MERAD
Societal Management of Risks Unit/Accidental Risks Division –
INERIS BP 2 - F60550 Verneuil-en-Halatte, France
myriam.merad@ineris.fr
Abstract. There is rapidly growing interest by regulatory agencies and stakeholders

in the potential toxicity and other risks associated with nanomaterials throughout
the different stages of the product life cycle (e.g., development, production, use
and disposal). Risk assessment methods and tools developed and applied to
chemical and biological material may not be readily adaptable for nanomaterials
because of the current uncertainty in identifying the relevant physico-chemical and
biological properties that adequately describe the materials. Such uncertainty is
further driven by the substantial variations in the properties of the original material
because of the variable manufacturing processes employed in nanomaterial pro-
duction. To guide scientists and engineers in nanomaterial research and application
as well as promote the safe use/handling of these materials, we propose a decision
support system for classifying nanomaterials into different risk categories. The
classification system is based on a set of performance metrics that measure both
the toxicity and physico-chemical characteristics of the original materials, as well
as the expected environmental impacts through the product life cycle. The stochastic

180 I. LINKOV ET AL.
multicriteria acceptability analysis (SMAA-TRI), a formal decision analysis

method, was used as the foundation for this task. This method allowed us to cluster
various nanomaterials in different risk categories based on our current knowledge
of nanomaterial’s physico-chemical characteristics, variation in produced material,
and best professional judgement. SMAA-TRI uses Monte Carlo simulations to
explore all feasible values for weights, criteria measurements, and other model
parameters to assess the robustness of nanomaterial grouping for risk management
purposes.1,2
1. Introduction
Nanotechnology is a rapidly growing field of research that is already demon-

strating a great impact on consumer products. The field of nanotechnology can be
defined as the production and use of materials at the nano-scale, normally
characterized as smaller than 100 nm in one dimension [28]. Nanomaterials are
formed through both natural (e.g., combustion by-products) and synthetic processes.
For the purposes of this paper, we focus our discussion solely on engineered
nanomaterials, which are currently used in more than 600 different consumer
products (Woodrow Wilson Institute http://www.nanotechproject.org/inventories/
consumer/). In spite of their potential commercial benefits, some nanomaterials
have been identified as toxic in in vivo and in vitro tests. Clearly, our knowledge
of the potential toxicity of these materials is far from comprehensive [28, 35]. The
potential environmental fate and toxicity (as well as potential for exposure and
risk) of nanomaterials may be strongly impacted by the material’s physico-
chemical characteristics. For example, potentially toxic nanoparticles that tightly
bind to soil surfaces may exhibit limited movement through the environment. In
this case, such materials may be deemed relatively safe for certain specific uses.
Such information is important as a lack of understanding of nanomaterial toxicity
and risks may delay full-scale industrial application of nano-enabled technologies.
Nanomaterial research and regulations could be guided by a systematic char-
acterization of factors leading to toxicity and risks in the absence of definitive
data. In this paper, we propose a risk-based classification system for nanomaterials
that takes into account several parameters commonly associated with nanoparticle
toxicity and risk. These parameters vary from nanomaterial physico-chemical
characteristics to expected environmental concentrations to fate and transport
mechanisms. In this work, we consider risk to both humans and to the environ-
ment in a broad ecological sense. This work does not attempt to draw exact
conclusions about the environmental risks associated with different nanomaterials,
but rather to provide reasonable recommendations about which nanomaterials may
need more precise measurements and testing to be safely deployed in consumer
products.
1
This paper is based on material submitted for publication in the Journal of Nanoparticle Research.
2
The views and opinions expressed in this paper are those of the individual authors and not those of
the US Army, NATO, or other sponsor agencies.
NANOMATERIAL RISKS USING MULTI-CRITERIA DECISION ANALYSIS 181
2. MCDA Approaches to Classification
Clustering nanomaterials into ordered risk categories can be treated as a sorting

problem in the context of multi-criteria decision analysis (MCDA). MCDA refers
to a group of methods used to impart structure to the decision-making process.
Generally, the MCDA process consists of four steps: (1) structuring the problem
by identifying stakeholders and criteria (nanomaterial properties in this case)
relevant to the decision at hand, (2) eliciting the parameters of the model (weights,
thresholds, etc.), and assigning measurements for each alternative (e.g., nanomaterial
risk group), (3) executing the model through computer software, and (4) inter-
preting results of the model and possibly re-iterating the process from step 1 or 2
by re-evaluating the model. The goal of this MCDA process was not to select a
single best alternative, but to rank or group alternatives through a structured
process. A detailed analysis of the theoretical foundations for different MCDA
methods and their comparative strengths and weaknesses is presented in [2].
A review of MCDA applications to environmental management can be found in [22].
The SMAA-TRI sorting method [32] is well suited for the proposed classification
system given the uncertain physico-chemical characteristics of nanomaterials.
Many of the characteristics attributed to nanomaterials are limited to a solely
qualitative assessment (see [14] for a review of other MCDA sorting methods).
We used SMAA-TRI, an outranking model based on ELECTRE TRI (see e.g.
[15]) for the assignment procedure. If an alternative outranked another, then the
alternative was considered at least as good or better than another alternative. We
preferred SMAA-TRI as it extends the capabilities of ELECTRE TRI by allowing
the use of imprecise parameter values. ELECTRE TRI assigns the alternatives
(different nanomaterials in this study) to ordered categories (risk classes). Three
types of thresholds are used to construct the outranking relationships by defining
preferences with respect to a single criterion. The indifference threshold defines the
difference in a criterion that is deemed insignificant. The preference threshold is
the smallest difference that would change the expert preference. Between these
two lay a zone of “hesitation” of indifference. The veto threshold is the smallest
difference that completely nullifies (raises a “veto” against) the outranking
relation. The assignment procedure involves comparing the properties associated
with a specific nanomaterial (g1, g2, …, gm) against a profile that includes ranges
of criteria metric values corresponding to several risk classes. Comparisons are
performed with respect to each criterion, taking into account the specified
thresholds. The final classification decision is based on the profile criteria weights
and specified cutoff level (lambda). For example, Class 4 represents the highest risk
while Class 1 is the lowest risk (Figure 1).
The assigned criteria weights represent the subjective importance of the
criteria. For this reason, ELECTRE TRI was particularly attractive for these
classifications because the weights represent “votes” for each criteria which are
not affected by criteria scales. The lambda cutting level represents the minimum
weighted sum of criteria that have to be in concordance with the outranking
relation for it to hold: the lambda cutting level is used to transform the “fuzzy”
gm
gm-1
s s4 ss
3
ss
2
ss
1
Cla Cla Cla Cla
g3
g2
g1
Figure 1. Example measurements of profiles for each criterion gj. Profiles are marked with horizontal
lines. (Adapted from [25])
outranking relation into an exact one (whether an alternative outranks a profile or

not). For example, a lambda cutting level of 0.6 means that 60% of the weighted
criteria have to be “at least as good” for the outranking relation to hold.
Alternatives were compared by accounting for the three thresholds. An alter-
native and profile with scores of 0.4 and 0.6 (for the same criterion) respectively,
and an indifference threshold of at least 0.2, demonstrates that this criterion fully
supports the conclusion that the alternative outranks the profile. Sometimes the
support is not binary, but is further affected by linear interpolation in the hesitation
zone of both veto and preference thresholds (see e.g. [31]). In this case the support
can have real values between 0 (no support) and 1 (full support).
All the parameters of ELECTRE TRI can be imprecise and represented by
arbitrary joint distributions in SMAA-TRI. This feature allows us to make conclusions
about risks related to different nanomaterials even though the information about
their characteristics is limited. Monte Carlo simulations were used in SMAA-TRI
to compute acceptability indices for alternative categorizations (i.e., for assigning
nanomaterials in different risk classes).
Output of SMAA-TRI comes as a set of category acceptability indices which
describes the share of feasible parameter values that assign alternatives to each
category. The category acceptability indices are measures indicating the stability
of the parameters, i.e., if the parameters are too uncertain to make informed
decisions. A high index (>95%) signals a reasonably safe assignment of the
alternative into the corresponding category. With lower indices, the risk attitude of
the decision maker defines the final assignment. For example, if an alternative has
a 80% acceptability for the lowest risk category, and a 20% acceptability for the
second lowest risk category, a risk-averse decision maker could assign the
alternative to the higher risk category.
SMAA-TRI conducts the numerical simulation by comparing the effect of
changing parameter values and criteria evaluations on the modeling outcomes.
Parameter imprecision can be quantified by Monte Carlo simulations using different
probability distributions (uniform, normal, log-normal, etc.). Gaussian or uniform

distributions are typically used (for more information about SMAA methods, see
[34]).
3. Criteria
Recent articles, as well as the frameworks reviewed in this study, generally use
several different characteristics in their assessment of nanomaterial risk. These
characteristics are generally based on extrinsic particle characteristics (size,
agglomeration, surface reactivity, number of critical function groups, dissociation
abilities) [3, 5, 6, 17, 21, 23, 27, 35]. Summary descriptions of five basic extrinsic
nanomaterial properties, agglomeration, reactivity/charge, critical functional groups,
particle size, and contaminant dissociation are presented below:
Agglomeration is an important criterion of risk because it includes a description of
the physical state of nanoparticles (NP) in the system. In aqueous solutions,
NP agglomeration generally occurs by two mechanisms: colloid settling and
flocculation. Flocculation occurs when Brownian-driven collisions bind unasso-
ciated particles together through van der Waals forces by dehydrating the inter-
acting surfaces. Consequently, the particle separates out of solution containing
the mass of the previously unassociated particles. Settling, on the other hand,
occurs due to the pull of gravity, as described by Stokes law relationships.
Particles may settle but remain non-flocculated, settling at interparticle
distances with the lowest free energies. In the absence of surfactive agents,
particle flocculation is fairly predictable by particle charge. Charged functional
groups give way to the development of a surface electrostatic potential which
extends out a few nanometers at the solid-liquid interface forming a diffuse
double layer or DDL [8, 36]. Classical DLVO theory predicts that repulsive
forces between particles (arising from overlapping DDLs) increase with
increasing ion concentrations (or increasing ionic strength, I) because of rising
osmotic pressures at the solid-solution interface force the DDL to swell ([13]
and references therein). Yet, classical Debeye–Huckel theory predicts a competing
case where increasing ion concentration decreases DDL thickness, throwing a
system into flocculation. Thus, at a fundamental level, the process of agglome-
ration represents the balance of these two competing charge interactions.
Reactivity/Charge. Charge may be expressed on NP either by design (such as
through functionalization) or by spontaneous degradative reactions. NPs may
be functionalized with various types of groups, such as COOH, NH2, and SH2
through standard organic synthesis methods. Such functionalizations may be
useful for manufacturing processes. For example, single-walled carbon nanotubes
(SWNTs) are typically carboxylated at their ends as part of the isolation/
purification process (Anita Lewin, RTI International, personal communication,
2007). The type of charge occurring on functionalized NPs is called variable
charge, which means that the magnitude of the surface electrostatic potential
varies with solution pH [36]. Variably charged groups characteristically exhibit a
surface pKa. Thus, variably charged surface groups may be speciated (e.g.,
protonated vs. deprotonated) by the classical Henderson-Hasselbauch equation.

Furthermore, the magnitude of the surface electrical potential may be suppressed
by increasing I, as described previously. Thus, the reactivity of variably
charged functional groups varies with the difference in solution pH from the
surface pKa and the magnitude of I.
Critical functional groups: Related to the reactivity/charge, critical functional
groups make up an important criterion given the fact that nanomaterial
functionality and bioavailability is directly related to chemical species. Basing
risk criteria on elemental speciation is superior to elemental composition alone
because it identifies the unique set of reactions available to each species. For
example, suspended zero-valent Fe nanoparticles have been shown to catalyze
reductive degradations of aqueous organic contaminants [19]. The same
degradative ability has been shown for structural Fe2+ (higher oxidation state
than zero-valent Fe but different speciation in terms of its complexation
environment) domains at clay-edge and -interlayer nano-sites in soil [18]. The
Cd2+ cation in quantum dots exhibits no toxicity to organisms as long as it
remains complexed with Se [11]. Speciation also determines solubility or
potential dissociation of nanomaterials.
Contaminant dissociation: This criterion describes risk associated with residual
impurities contained within the NP. For example, Fe oxide NP may contain S
impurities depending on whether FeCl3 or Fe2(SO4)3 was used in manufacturing.
Carbon nanotubes may contain Ni, Y, or Rb metal cation impurities [7, 10],
which may either be entrained within or adsorbed onto the surface of the tubes.
However, little is actually known about the extent in which metallic and
organic contaminants remain with the manufactured product. Thus, the
assignment of this risk criterion could change depending on better information.
Size: Particle size is a criterion related to the agglomeration and reactivity
criteria. Obviously, smaller particles agglomerate at slower rates. However,
agglomeration is also related to the particle size distribution or polydispersivity.
For example, greater monodispersivity of particles sizes appears to promote
more stable dispersions [9]. Also, nanoparticle reactivity is also impacted by
the size of NP surface relative to the bulk of the solid. While the surface is the
reactive portion of solids, the bulk component may suppress the surface reactivity
through internal reorganizations, etc. NPs are essentially surfaces with limited
bulk. Thus, the smaller particle size, the lower bulk to potentially limit surface
reactivity. Surfaces with low accompanying bulk have been shown to possess
enhanced reactivities, such as high-affinity adsorption of metals or unique
structures of assembly during agglomeration [1, 12]. Particle size is particularly
important in terms of distinguishing the unique size-dependent chemistry of
nanoparticles from classical colloid chemistry.
Processes that may influence the potential hazards of engineered nanomaterials
include bioavailability potential, bioaccumulation and translocation potential, and
potential for toxicity. These processes have been described in empirical studies
and are dependent on the characteristics of the particles as described above. It is
difficult to predict the behavior of these materials, however, in the future computa-
tional approaches are expected to provide additional tools to estimate these
processes from the physical and chemical parameters.
Bioavailability potential: Bioavailability describes the amount of material

absorbed across cell membranes from the various exposure routes (e.g.,
dermal, inhalation, and oral exposures) into system circulation in an organism
[24]. This process is controlled by the characteristics described above. For
example, charge of the particles may influence the agglomeration of the
particles and hence limit the ability of the particle to cross the gastrointestinal
membranes after oral ingestion. There are however, several pathways which
nanoparticles may cross cell membranes ranging from pinocytosis, endocytosis,
and diffusion as summarized in [37]. The mechanisms by which these particles
are absorbed are highly dependent on the particle composition, surface modifi-
cation, size, shape, and agglomeration.
Bioaccumulation potential: Bioaccumulation is the net accumulation of particles
absorbed from all sources (soil, water, air, and food) and exposure routes listed
above into an organism. Accumulation must consider the temporal aspects of
exposure and include kinetic factors such as exposure concentration, duration
of exposure, clearance, biotransformation, and degradation. Most studies to
date have focused on the potential for uptake and translocation in specific
tissues [20, 30] and have not addressed the toxicokinetics of nanoparticles.
Toxic potential: Toxicity of engineered nanomaterials and particles in mammalian
and other animal systems has been assessed primarily through cytotoxicity
screening assays; although some in vivo studies have been completed. Effects
of nanomaterials occurs through oxidative stress, inflammation from physical
irritation, dissolution of free metal from metal nanoparticles, and from impurities
in nanomaterials (e.g., catalysts) [28]. The characteristics of nanoparticles that
influence toxicity include the size, surface area, morphology, and dissolution.
To date, screening studies using in vitro approaches have observed toxicity
from metal nanoparticles at lower concentrations [4] than toxicity from
carbon-based nanoparticles [16, 26].
4. Proposed Classification Framework
The purpose of the proposed classification system is to preliminarily group

nanomaterials in risk classes for screening level risk assessments. Such groupings
should aid in prioritizing materials for further study. In this paper, we considered five
risk categories: extreme, high, medium, low, and very low risk. In order to assign
particular nanomaterials to these categories, we need to define criteria scales,
thresholds, and measurements.
The quantitative criterion, particle size, was evaluated as the mean size of the
material in units of nanometers as obtained from literature review and expert
estimates. Bioavailability, bioaccumulation, and toxic potential were measured
through subjective probabilities that the nanomaterial has significant potential in
the criterion. These, as well as rest of the criteria (agglomeration, reactivity/charge,

critical function groups) were measures based on expert judgments. The qualitative
criteria, agglomeration, reactivity/charge, and critical function groups, were measured
in terms of ordinal classes: 1 was the most favorable (least risk) value class, while
5 the least favorable (highest risk).
For the qualitative criteria, we encoded the classes with integers. The
indifference thresholds were set to 0 and the preference thresholds to 1. This
choice of thresholds represented an ordinal scale: a smaller number was preferred
to a larger one, but the intervals did not carry any information (e.g. 1 is as much
preferred to 2 as 1 is to 3). If there were multiple possible classes for an alter-
native, the measurement was modeled with a uniform distribution, meaning that
the integers corresponding to these classes were equiprobable within specified
range. Veto thresholds were not used in this phase of the framework, but will be
added later when more information about the criteria becomes available. Size is a
criterion that should have some veto associated with it, so that very small
materials cannot be assigned to the safer (lower risk) categories.
Even though nanomaterial size is believed to be a factor influencing toxicity,
there is little specific information available characterizing toxic effects relative to
the 1–100 nm size range [29]. More research is needed to define the thresholds in
a more exact manner. If a “smaller”-sized nanoparticle represents higher risk, it
follows that a larger size is “more preferable” because of its inherently lower risk.
Due to these knowledge gaps, imprecise thresholds were used for nanomaterial
size with indifference threshold of 10 ± 5% and preference threshold of 25 ± 5%.
Bioavailability, bioaccumulation, and toxic potential were all measured using a
cardinal but subjective scale as described in the previous section. Because of the
subjectivity of this scale, we applied imprecise thresholds. Indifference thresholds
were set to vary uniformly from 0 to 10, and preference thresholds from 10 to 20.
The SMAA-TRI model separated the risk categories using profiles formed
from measurements of the same criteria as the alternatives. In our framework, the
profile measurements were all exact (Table 1).
Our model applied imprecise preference information in the form of weight
bounds. For more information on how these were implemented, see [33]. We
judged the toxic potential to be the most important criterion, and thus it was
assigned weight bounds of 0.3–0.5. Bioavailability and bioaccumulation potentials
were deemed the least important criteria, and as a result, we were undecided on
their relative importance. Both of these criteria were given weight bounds ranging
from 0.02–0.08. The rest of the criteria were assigned weight bounds of 0.05–0.15.
We used imprecise values for the lambda cutting level within the range of
0.65–0.85. Lambda defines the minimum sum of weights for the criteria that must
be in concordance with the outranking relation to hold. The classification was
performed according to the pessimistic assignment rule, which in risk assessment
applications represents a more conservative approach.
TABLE 1. Profile measurements. Each row corresponds to a profile differentiating the categories presented in the first column.
Agglomeration Reactivity/ Crit. Contaminant Bioavailability Bioaccumulation Toxic Size

charge function dissociation potential pot. pot.
Profile groups
Extreme- 4 4 4 4 100 100 100 5
high
High- 3 3 3 3 80 80 80 50
medium
Medium- 2 2 2 2 70 70 70 100
low
Low-very 1 1 1 1 60 60 60 200
low
TABLE 2. Criteria measurements. The first four criteria are measured as ordinal classes. Measurements of reactivity/charge have associated uncertainty in that the
materials can belong to either of the indicated classes. The following three criteria have linear imprecision of 10 in both directions from the indicated mean value.
Size has uncertainty of 10% of the shown mean value.
Agglomeration Reactivity Crit. Contaminant Bioavailability Bioaccumulation Toxic Size

/charge function dissociation pot. (±10) pot. (±10) pot. (±10%)
groups (±10)
C60 4 2,3 3 2 25 50 10 100
MWCNT 4 2,3 4 3 25 50 25 50
CdSe 4 4,5 1 4 50 75 75 20
Ag NP 3 4,5 1 4 50 75 75 50
Al NP 5 1,2 1 1 25 75 10 50
5. Example
We demonstrated application of the framework by classifying five nanomaterials:

nC60 (a fullerene), MWCNT (Multi-Walled Carbon Nanotube), CdSe (quantum
dot), Ag NP (Silver-Nanoparticles), and Al NP (Aluminum Nanoparticles).
Typical size ranges for these materials were estimated based on in situ
measurements from the available literature. Other properties were assessed using
authors expert judgments, taking into account the characteristics for each criterion
described in Section 3. Metrics for the five materials used in our case study
(Table 2) were input into the SMAA-III software.
Category acceptability indices obtained from the simulation are presented in
Figure 2. These indices show that the data was too imprecise to make definite
decisions about the risks related to the different nanomaterials. However, there
was sufficient data to make preliminary classifications. For example, CdSe
exhibited a very high index in the high risk-class. On the other hand, Al NP may
be considered relatively safe, its category acceptability indices for low and very low
risk were 34 and 34, respectively. Summing these indices gave the material an
estimated 68% probability of being classified as “low to very low risk”. C60 showed a
reasonable acceptability index (49%) for the low risk category. In terms of making risk-
aware decisions for C60 and Al NPs, we feel that further studies into expanding
the potential applications of Al NP and C60 (as opposed to CdSe) are justified.
It is important to point out that in spite of the high uncertainty of the above
results, this work represents a reasonable starting point for a more thorough follow-
up analysis. And indeed, more data is required to improve our estimates. Risk
estimates based on acceptability indices below 80% should be viewed with caution.
Extreme risk High risk Medium risk Low risk Very low risk
C60 0 0 51 49 0
MWCNT 0 26 73 1 0
CdSe 0 98 1 1 0
Ag NP 0 29 71 1 0
AI NP 0 0 33 34 34
Figure 2. Category acceptability indices of the example. A high index means, that the material is
assigned to that category with a large share of possible parameter values (weights, measurements,...).
For example, should C60 be deemed viable for further research and application,
additional measurements will be required to further refine the risk estimates. In
spite of its limitations, the quantified risk values determined from our simulations
are helpful in characterizing the risk and uncertainty for limited and variable data.
6. Concluding Remarks
Nanotechnology is a fast growing research field with an increasing impact on our

everyday lives. Although nanomaterials are used in common consumer products,
the lack of information about human health and environmental risks may hamper
the full-scale implementation of this technology. We presented in this paper a
systematic multi-criteria approach that allows for assigning nanomaterials into
ordered risk classes. Materials assigned to the highest risk class potentially repre-
sent areas of important future toxicological studies while materials exhibiting low
risk may be recommended for direct commercial use. The proposed framework
takes into account measurements and expert estimates for multiple criteria that are
known to impact the toxicity of the material.
The use of SMAA-TRI approach allows for the explicit incorporation of
uncertainty parameters in the model. An appealing characteristic of the outranking
model applied in SMAA-TRI is that it allows veto effect to be modeled, meaning
that a nanomaterial’s poor performance in one criterion cannot be compensated by
good performance in other criteria (as is the case for compensatory MCDA
models, e.g. utility theory). This convention prevents decisions about the risk of a
particular nanomaterial being unduly based on one particular criterion (such as
size vs. surface reactivity relationships) as the material may have other physico-
chemical characteristics related to size that exhibit a greater impact on its toxicity.
Acknowledgements
The studies described and the resulting data presented herein were obtained from
research supported by the Environmental Quality Technology Program of the US
Army Engineer Research and Development Center (Dr. John Cullinane, Technical
Director).
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NANOMATERIALS, NANOTECHNOLOGY
Applications, Consumer Products, and Benefits
G. ADLAKHA-HUTCHEON
Defence R&D Canada
Ottawa, Ontario, Canada
Gitanjali.Adlakha-Hutcheon@drdc-rddc.gc.ca
R. KHAYDAROV
INP, Uzbekistan Academy of Sciences
Tashkent, Uzbekistan
R. KORENSTEIN
Faculty of Medicine, Tel-Aviv University
Tel-Aviv, Israel
R. VARMA
United States Environmental Protection Agency
Cincinnati, Ohio, USA
A. VASEASHTA
Nanomaterials Laboratories & Characterization Labs
Marshall University
One John Marshall Drive
Huntington, WV 25575, USA
H. STAMM
Joint Research Centre
European Commission
Ispra, Italy
M. ABDEL-MOTTALEB
Department of Chemistry, Faculty of Science
Ain Shams University
11566 Abbassia
Cairo, Egypt
Abstract. Nanotechnology is a platform technology that is finding more and more

applications daily. Today over 600 consumer products are available globally
that utilize nanomaterials. This chapter explores the use of nanomaterials and

196 G. ADLAKHA-HUTCHEON ET AL.
nanotechnology in three areas, namely Medicine, Environment and Energy. Given

the large number of applications being designed that utilize nanomaterials and
nanotechnologies, and the perception that nanotechnology can (or will) provide
the ultimate solution for the world’s problems; questions arise regarding who
benefits from these technological advances. Additionally, within the popular press
all nanotechnology products are generally portrayed as being beneficial to society
without necessarily distinguishing between real and potential benefits of the
technology. Lastly, the benefits and implications of these technological advance-
ments in society are explored.1
1. Introduction
The NATO Advanced Research Workshop titled “Risk, Uncertainty and Decision
Analysis for Nanomaterials: Environmental Risks and Benefits and Emerging
Consumer Products” had five primary objectives. The Working Group (WG) on
“Nanotechnology and its benefits” discussed two off the five, namely: “The potential
benefits of nanotechnology enabled commercial products”; and “Identifying
strategies for users in developing countries to best manage this rapidly developing
technology and its associated risks, as well as to realize its benefits”. The subject
of the WG’s deliberations primarily revolved around the former and the latter only
to the extent that it pertained to benefits.
2. Definition of Nanotechnology
The late Dr. Richard Smalley defined Nanotechnology as the art and science of
building stuff that does stuff at the nanometer scale. This definition is therefore
inclusive of science in speaking of nanotechnologies; for our purposes here
reference to nanotechnology included science in its fold.
3. Nanotechnology: New Name for Old Products?
Nanomaterials have been used for centuries – from the use of nanometer-size gold
particles for red stained glass to soot from candles in inks. Nanoparticles can be
both man-made and naturally occurring. What is different today is that technological
advancements have enabled us to produce and detect these materials and begin to
understand how their shape and size can be used to good effect, and with this
ability, we can begin to change them so that they are more exploitable. This
1
Summary of the NATO ARW Technology Working Group discussions. Co-chairs – Gitanjali
Adlakha-Hutcheon and Rafi Korenstein; Members – Mohamed Abdel-Mottaleb, Azad Bayramov, John
Cullinane, Oleg Figovsky, Nava Haruvy, Renat Khaydarov, Mikhail Kondratyev, Hermann Stamm,
Rajender Varma, Ashok Vaseashta, Teresa Vieira.
NANOMATERIALS, NANOTECHNOLOGY 197
development is best summed up by The Royal Society and the Royal Academy of
Engineering, UK – they define Nanotechnology as the ability to measure, see,
manipulate and manufacture things between 1 and 100 nm (1 billionth of a meter)
– is seen as the driver of a new industrial revolution emerging with the
development of materials that exhibit new properties and potential new risks and
benefits at this tiny scale [27].
4. Applications
Nanotechnology is a platform technology that utilizes the inherently unique

properties of matter that arise at the nanoscale. Applications of this technology can
be found in areas of material sciences, medicine, energy, environment, communi-
cations and electronics among others. The enormous international S&T investment
in nanotechnology research has evolving, and potentially endless possibilities.
Researchers continue to find new applications for nanomaterials. Whether it is
using carbon nanotubes to make vehicle composites stronger than steel, but lighter
(thereby improving fuel economy), or creating medicines that can target and treat
specific cells in the body, or purifying water at point of use – nanotechnology
could revolutionize some of these sectors. One of the challenges is to garner
benefits without risk. In this section applications of nanotechnology in the fields
of nanomedicine, energy and environment will be elaborated.
5. Nanomedicine – Answering Clinical Needs
The European Technology Platform (ETP) group has defined nanomedicine as the
application of nanotechnology to achieve breakthroughs in healthcare [8]. Nano-
medicine consists of several subdomains including diagnostics and imaging; drug
delivery; and regenerative medicine.
An important subdomain of nanomedicine is the field of in-vivo diagnosis
based on imaging technologies. One of the most promising applications is molecular
imaging, which refers to the characterization and measurement of biological
processes at the cellular and/or molecular levels, and has emerged as a powerful
tool to visualize molecular events of an underlying disease. The merging of
nanotechnology with molecular imaging provides a versatile platform for novel
design of nano-probes that will have tremendous potential to enhance the
sensitivity, specificity, and signaling capabilities of various biomarkers in human
diseases. Nanoengineered platforms possess unprecedented potential for early
detection, accurate diagnosis, and personalized treatment of diseases. Such
platforms have been employed in many biomedical imaging modalities, namely,
optical imaging, computed tomography, ultrasound, magnetic resonance imaging,
single-photon-emission computed tomography, and positron emission tomography
[4]. Multifunctionality is the key advantage of nanoplatforms over traditional
approaches. Targeting ligands, imaging labels, therapeutic drugs, and many other
agents can all be integrated into the nanoplatform to allow for targeted molecular
imaging and molecular therapy by encompassing many biological and biophysical
barriers [4]. Moreover, the technological advancement in miniaturizing medical

devices in conjunction with microelectromechanical systems (MEMS) technology
provides foundations for the nanoelectromechanical systems (NEMS). The
application of medical devices in nanomedicine can be envisioned in four areas of
applications consisting of minimally invasive surgery, heart assisting devices,
drug delivery on demand and finally pain therapy.
Drug delivery aims to employ nanoscale carrier particles or molecules
developed to improve the bioavailability and pharmacokinetics of therapeutics.
Drug-delivery systems can be synthesized with controlled composition, shape,
size and morphology as demonstrated by examples such as programmable
fusogenic vesicles [1]. The surface properties of nanocarriers can be manipulated
to increase solubility, immunocompatibility and cellular uptake. The limitations of
current drug delivery systems include suboptimal bioavailability, limited effective
targeting and potential cytotoxicity. Examples of drug delivery systems include
liposomes, polymer nanoparticles, nano-suspensions and polymer therapeutics.
The pharmaceutical industry is interested in these delivery systems owing to their
unique properties: (1) Nanoparticles can be used for passive tumor targeting; (2)
They have the potential to improve penetration through biological barriers, such as
the blood brain barrier, for drug delivery; (3) They can be used to increase the
solubility of drugs; and (4) They can even possess characteristics of contrast
agents for improved imaging (e.g., the use of nanometer-sized superparamagnetic
iron oxide particles as cellular contrast agents allows the non-invasive detection of
labeled cells on high-resolution magnetic resonance images). Thus, the production
of multifunctional targeted drug carriers, also possessing imaging characteristics
enables the possibility of combining the diagnostic properties with the therapeutic
ones (“theranostics”) [8].
Today, our surgical tools are large and crude at the molecular scale, yet the
cellular and molecular machinery in our tissue is small and precise. The only
reason that modern surgery works is the remarkable ability of cells to regroup,
bury their dead, and heal over the wound. However, the possibility of spontaneous
tissue regeneration is limited. Recent advances in stem cell research, opens promising
pathways towards regeneration of injured organs. There are two major strategies
for inducing regeneration in the damaged tissue: (i) activation of the endogenous
regenerative capacity, and (ii) cell transplantation therapy. Cell transplantation is
approaching clinical reality. To continue to enhance the benefits of cell transplan-
tation it has been proposed that nanobiotechnology possesses a unique potential
that will aid considerably in overcoming obstacles including: identifying a
universal cell source that can be differentiated into specific cellular phenotypes,
developing techniques to enhance integration of the transplant within the host
tissue, improving strategies for in vivo detection and monitoring of the cellular
implants, and developing new techniques to deliver genes to cells [6]. These enhance-
ments will benefit considerably from understanding, visualizing, and controlling
cellular interactions through the manipulation of materials, tissues, cells, and DNA
at the level of and within the individual cell. As such, nanobiotechnology is well
suited to optimize the generally encouraging results already achieved in cell
transplantation.
Nanomedicine therefore has the potential, by enabling earlier diagnosis, for

better therapy and improved follow-up care, to make healthcare more effective in
terms of clinical outcome and more affordable for the society in general.
6. Nanotechnology and the Environment
Two types of applications of nanotechnology are possible with respect to the

environment, environmental technology applications that help solve environmental
problems like pollution: and those that support sustainability. According to the US
Environmental Protection Agency’s (US EPA) White Paper [28], nanotechnology
presents new opportunities to improve how contaminants in the environment are
measured, monitored, managed, and minimized [28]. This paper discusses the
potential environmental benefits of nanotechnology, describing environmental
technologies as well as other applications that can foster sustainable use of
resources. It further encourages the US EPA to engage resources and expertise to
encourage, support, and develop approaches that promote pollution prevention,
sustainable resource use, and good product stewardship in the production, use and
end of life management of nanomaterials. Additionally, it asks the Agency to draw
on new, “next generation” nanotechnologies to identify ways to support environ-
mentally beneficial approaches such as green energy, green design, green chemistry,
and green manufacturing. Responsible manufacturing which incorporates principles
of green chemistry and environmentally responsible production of nanomaterials
(such as making use of reusable and recyclable materials, restricting the use of
chemicals or other harmful materials) is now being referred to as “Green Nanotech-
nology” [30, 31]. In this area there has also been increasing interest in identifying
environmentally friendly materials such as reducing agents, capping agents and
dispersants etc. that are multifunctional. Examples of green manufacturing range
from processes employing environmentally friendly chemicals with minimum
energy requirements to producing silver and gold nanoparticles, among other
noble nanometals, using benign reagents such as vitamin B2, [19], vitamin C [20]
and tea and coffee extract [21].
7. Energy
Energy security is the largest challenge facing humankind in the twenty-first

century. Eighty-five percent (85%) of energy consumption worldwide is provided
by fossil fuels, while the current rate of discovery of fossil fuels is almost half the
rate of consumption. Further, for every oil field, either new or in use, only ca. 60%
of the oil is recovered [33]. These facts clearly indicate the urgent need for
systematically addressing this challenge. The energy issue can be generally divided
into two main sectors, namely, securing new sustainable energy sources, and an
effective, clean and rational use of existing energy resources. Nanotechnology
(NT) has the potential to revolutionize the entire energy sector both in terms of
finding new resources and maximizing the utilization of existing ones [31].
In terms of maximizing current energy resources, NT offers two main approaches.

First, an ability to secure more resources at a cheaper cost for example, the
possibility of retrieving more than 95% of the oil out of the well. Several
examples of how NT achieves this goal include subsurface sensors that can be
used to improve both the discovery and the recovery of hydrocarbons; better
materials to make it easier, cheaper and faster to extract oil. Corrosion problems
caused by bacteria during oil production can be solved with the help of self-
assembled layers that contain silver nanoparticles which in turn inhibit or kill the
corrosive bacteria. Nanotechnology also offers alloys and additives that increase
material performance, making drilling bits and pipes stronger, more wear-
resistant, and lighter, thus decreasing drilling costs. Additionally, NT can produce
smart materials able to respond to external conditions (e.g. poreholes that can
respond to water presence by changing the diameter of the hole, thus stopping a
“lifting response”, or smart pipelines that detect leaks and self-heal [18]).
Secondly, NT can enable more efficient use of the existing energy resources. Huge
energy savings can be obtained by lowering the operational temperature of
industrial chemical reactions or by increasing the selectivity of such reactions.
Since catalysis mainly depends on maximizing surface area per volume (S/V [7,
26]), nanomaterials are good sources to achieve high S/V and to study catalytic
processes [10]. For a long time the fundamental study of catalysis in the laboratory
was carried out using much idealized model systems far removed from the
complex three-dimensional (3D) systems in real applications [14, 23]. NT offers
the tools and mechanisms to build controlled 3D catalytic systems mimicking real
application conditions while still providing the conditional control necessary for
laboratory studies [15, 34].
NT’s impact on the field of catalysis goes beyond fundamental studies; it can
provide completely new catalysts – for example, gold which is an inert material in
bulk conditions is found to have a high catalytic activity when applied in
nanometer sized structures [13, 29].
In terms of finding new resources, Filipponi and Sutherland ([9]) present an
overview of the applications of nanotechnology that may have the potential to help
within the Energy sector. Nanotechnology will cut cost both of the solar cells and
the equipment needed to produce and deploy them, making solar power
economical and hence a more useable alternative to fossil fuels. For this
application one needs to able to make solar cells inexpensively – NT has such a
potential and could therefore help move solar power into the mainstream. There is
also the potential for nanotechnology to contribute to reductions in energy demand
through lighter materials for vehicles; materials and geometries that contribute to
more effective temperature control; technologies that improve manufacturing
process efficiency; materials that increase the efficiency of electrical components
and transmission lines; and materials that could contribute to a new generation of
fuel cells (FC) and a step closer towards a hydrogen economy.
Fuel cells represent an important research direction for clean energy
production. These devices convert fuel such as hydrogen directly into electricity
through an electro-catalytic process rather than by combustion, which yields
higher energy efficiency. In such devices, the electrodes play a very important
role. Thus the stability of the electrodes against electrochemical processes and
impurity poisoning, and high-charge carrier mobility are important [12]. The
structure of such electrodes is very complex, which makes fundamental studies of
structure/performance relationship very difficult. NT offers the tools to
systematically study this problem. Further, the precise positioning capabilities
offered by NT allow the construction and manipulation of such complex
electrodes [5, 11].
In summary, NT offers more diverse approaches to the pressing energy issue
than any other technology to date. Not just in terms of actual energy production,
but even in terms of energy savings on every level, for example, smart-windows
that can control the amount of light transmitted into the building thus controlling
the temperature. Furthermore, industrial processes with high energy consumption
are being modified using NT to lower the energy demand. Thus, nanotechnology
may indeed offer mankind hope towards energy security.
8. Nanotechnology and Emerging Consumer Products
Nanotechnology is a growing global enterprise that will have large economic and
social impacts as can be observed with the ever emerging products that utilize
some form of nanotechnological application whether it is a coating on cars to self-
cleaning windows.
Consumer products containing nanomaterials are entering the marketplace at a
rapid pace. “Nanotechnology is no longer simply a science of the future, but it is a
way of producing and using materials at a tiny scale that is rapidly entering our
everyday lives in cosmetics, medicine, food, sports equipment, computers, auto-
mobiles, and many other consumer products”. Nanoscale materials are in some
sunscreens, house paints, clothing, and computers being sold in stores around the
world (Project on emerging nanotechnologies [25]).
9. Consumer Products
As cited in the sections above, nanotechnology heralds a world of better and more
durable consumer products. In 2006, nanotechnology was incorporated into more
than $50 billion worth of manufactured goods. The Project on Emerging Nanotech-
nologies maintains an inventory of consumer products that utilize nanomaterials.
As of May 15, 2008, this inventory contained 610 products or product lines
produced by 322 companies located in 20 countries. This online list of company-
identified nanotechnology consumer products includes merchandise from such
well known brands as Samsung, Black & Decker, Eddie Bauer, and others [25].
Since this list relies on manufacturers self-identifying products that may contain
nanomaterials or use nanotechnologies in the manufacturing process, it is not an
all-inclusive inventory. Other inventories are maintained, for instance, in Japan,
although these cannot be easily or completely accessed due to language differences
(e.g. [2]).
10. Benefits of Nanotechnology
Rapid advances in material sciences and technology that enable manipulation of

matter at the nanometer scale will continue to allow the realization of many
benefits of this technology. Foremost among these will be a new manufacturing
paradigm.
Present day activity for manufacturing and use of nanomaterials is 49% in the
United States, 30% in the European Union, and 21% in other parts of the world
[3]. Although techniques for manufacturing nanomaterials are as varied as the
materials themselves, they can be divided into two main types of approaches:
“bottom-up” and “top-down” procedures. Bottom-up manufacturing is based on
the building of structures, atom-by-atom or molecule-by-molecule and can be split
into three categories: chemical synthesis, self-assembly, and positional assembly
[27]. Bottom-up methods are widely used for manufacturing of metal nanoparticles,
nanofilms, fullerenes, nanotubes, quantum dots etc. Top-down manufacturing
involves starting with a micrometer- to millimeter-sized piece of material and
etching, milling or machining fine, nanosized structures from it by removing
material using for instance, precision engineering or lithography techniques. Top-
down manufacturing can be used for obtaining computer chips, precision-
engineered surfaces, metal oxanes etc. [32].
11. Paradigm Shift for Manufacturing
What would it mean if one could inexpensively make things with every atom in
the right place? For starters, one could continue the revolution in computer
hardware right down to molecular gates and wires – something that today’s
lithographic methods (used to make computer chips) could never hope to do. One
could inexpensively make very strong and very light materials: shatterproof
diamond in precisely the shapes one wants, in large volumes, and over 50 times
lighter than steel of the same strength. One could make a Cadillac that weighed 50
kg, or a full-sized sofa you could pick up with one hand. One could make surgical
instruments of such precision and deftness that they could operate on the cells and
even molecules from which one is made – something well beyond today’s medical
technology. The list goes on – it is projected that almost every manufactured
product could be improved, often by orders of magnitude.
11.1. THE ADVANTAGES OF POSITIONAL CONTROL
The reason that such revolutionary changes in manufacturing would be possible is

due to positional control – a basic principle of nanotechnology. At the macro-
scopic scale, the idea that one can hold parts in our hands and assemble them by
properly positioning them with respect to one another goes back to prehistory: we
celebrate ourselves as the tool using species. At the molecular scale, the idea of
holding and positioning molecules is new and almost outrageous.
Nanotechnology, employing positional control, will dramatically reduce the

costs and increase the capabilities of spacecrafts and space flight. The strength-to-
weight ratio and the cost of components are absolutely critical to the performance
and economy of space ships: with nanotechnology, both of these parameters will
be improved by one to two orders of magnitude. Improvements in these two
parameters alone should improve the overall cost/performance ratio by over three
orders of magnitude. This has led NASA to support nanotechnology by initiating
projects examining molecular manufacturing systems and molecular machines
using computational models.
Beyond inexpensively providing remarkably lighter and stronger materials for
spacecrafts, nanotechnology will also provide extremely powerful computers that
are small relative to their computing powers with which to guide both those ships
and a wide range of other activities in space.
12. Quantum Computing
Nanotechnology will take us to the post-lithographic era. In futuristic computers

each logic element will be made from just a few atoms. One would be able to
economically build and interconnect trillions upon trillions of small and precise
devices in a complex three dimensional pattern. Further enabling us to build mass
storage devices that can store more than a 1020 bytes in a volume the size of a
sugar cube; RAM that can store a mere 1018 bytes in such a volume; and massively
parallel computers of the same size that can deliver a1018 instructions per second.
Such enhanced computing could open up areas for innovation within the defence
and security domains such as: secure messaging through quantum encryption;
intelligent and completely autonomous short and long-range weapons; self-
repairing military equipment; global information networks through quantum
computing; miniature high energy battery and power supplies; and highly sensitive
miniature biological and chemical sensors among others. According to Merkle
[17] today, “smart” weapons are fairly big – we have the “smart bomb” but not the
“smart bullet.” In the future, even weapons as small as a single bullet could pack
more computer power than the largest supercomputer in existence today, allowing
them to perform real-time image analysis of their surroundings and communicate
with weapons tracking systems to acquire and navigate to targets with greater
precision and control. We’ll also be able to build weapons both inexpensively and
much more rapidly. Rapid and inexpensive manufacture of great quantities of
stronger more precise weapons guided by massively increased computational
power will alter the way wars are fought. Changes of this magnitude could
destabilize existing power structures in unpredictable ways. While molecular
manufacturing will not arrive for many years to come, it’s obvious that military
potential will increasingly attract the interest of planners.
One can now see the fundamental shape of a molecular manufacturing
technology. Self replicating assemblers, operating under computer control, let us
inexpensively build more assemblers. The assemblers can be reprogrammed to
build other products. The assemblers use programmable positional control to
position molecular tools and molecular components, permitting the inexpensive

fabrication of most structures consistent with physical law. Diamondoid materials
in particular have become inexpensive and its remarkable properties usher the
technology in what has been called the Diamond Age [17].
The obvious leap in our manufacturing capabilities will come from positional
control leading to faster miniaturization and precision. Along with all the obvious
manufacturing benefits, there are also many potential medical and environmental
benefits.
13. Global Implications
Benefits through nanotechnology for the environment as was eluded to earlier,

will include: reduction of waste products generated, and energy used, during
manufacturing of conventional materials as well as nanomaterials; research
applications of nanomaterials in areas of green energy approaches, including solar
energy, hydrogen, power transmission, diesel, pollution control devices, and
lighting; environmental remediation/treatment research supporting improvement
of pollutant capture or destruction by exploiting novel nanoscale structure-
property relations for nanomaterials used in environmental control and
remediation applications; development of nanotechnology-enabled devices for
measuring and monitoring contaminants and other compounds of interest,
including nanomaterials. Examples of the latter would involve development of
new nanoscale sensors for the rapid detection of virulent bacteria, viruses, and
protozoa in aquatic environments [28].
Nanotechnology could let us make almost every manufactured product better
(faster, lighter, stronger, smarter, safer and cleaner). One can already see many of
the possibilities as the examples above illustrate. New products that solve new
problems in new ways are more difficult to foresee, yet their impact is likely to be
even greater. Could Edison have foreseen the computer, or Newton the communi-
cations satellite? The development of higher quality materials, more efficient
energy storage, better water quality, and more effective delivery of pharmaceuticals
all have the potential to improve everyday life for many people.
Product development using nanotechnology today far exceeds the body of
knowledge concerning the safety of nanomaterials or the implications for human
or environmental health. New generations of nanomaterials will evolve, and with
them new and possibly unforeseen health and environmental issues. It will be
crucial that the regulatory bodies while leveraging the benefits of nanomaterials
continue to evolve in parallel with the expansion of and advance in these new
technologies.
Given the large number of applications being designed that utilize nanoma-
terials and nanotechnologies, and the perception that nanotechnology is (or will
be) a panacea for the world’s problems, questions about who benefits from these
technological advances arise. The popular press generally touts all nanotechnology
products as beneficial to society, while not necessarily distinguishing between real
and potential benefits of the technology. On economic grounds, current projections
put the global market for nanotechnology and nanomaterial-containing products at

an estimated $2.6 trillion by 2014 [16]. Consequently, a very significant challenge
is ensuring an even distribution of benefits throughout the world community.
These implications led to the Technology and Benefits WG at the NATO ARW
discussing the potential for nanotechnology to sustain world resources as another
benefit.
14. Conclusions and Future Recommendations
The WG acknowledged that technological advances are largely being driven by

the promise of economic benefits. Taking three examples, namely: applications of
nanotechnology in medicine, environment and energy the risks to health and
environment; total investment; health and environmental benefits; return on
investment; and the size of population impacted were evaluated. Preliminary
predictions, based on arbitrary economic numbers, showed that benefits were not
evenly distributed across the world.
The Advanced Research Workshop at large felt that concurrent advances in
methods to protect human and environmental health will be essential so that
asymmetric benefits to society are not created. There was a clear recognition
among all workshop participants that resolving the question of who benefits from
nanotechnology lies in pulling together multidisciplinary expertise from multiple
nations. Probably the most significant strength of Nanotechnology is that the
approach is crossdisciplinary. Simply put, ideas and products originally developed
for medical and biological purposes find applications in electronics or energy
industries. This has in turn pushed scientists, medical doctors and engineers to
significantly revise and modify their approach to problem solving to rapidly adopt
new ideas and techniques. The ultimate beneficiary of such a paradigm shift will
be humanity.
For the first time in history, a new technology holds forth the promise of
providing inexpensive energy, food and clean water for everyone on the planet
thereby it could also be used in innovative ways to encourage political stability
and responsibility [24].
Acknowledgements
We acknowledge the NATO ARW on “Nanomaterials: Environmental Risks and

Benefits and Emerging Consumer Products” held in Faro, Portugal from 27–30
April 2008 and the Participants of the Working Group on Nanotechnology and its
benefits.
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RISK REDUCTION VIA GREENER SYNTHESIS OF NOBLE
METAL NANOSTRUCTURES AND NANOCOMPOSITES
M.N. NADAGOUDA, R.S. VARMA

Sustainable Technology Division, US Environmental Protection
Agency
National Risk Management Research Laboratory
26 West Martin Luther King Drive, MS 443
Cincinnati, OH 45268, USA
varma.rajender@epa.gov
Abstract. Aqueous preparation of nanoparticles using vitamins B2 and C which

can function both as reducing and capping agents are described. Bulk and shape-
controlled synthesis of noble nanostructures via microwave (MW)-assisted spon-
taneous reduction of noble metal salts using α-D-glucose, sucrose, and maltose
has been achieved. The MW method also accomplishes the cross-linking reaction
of poly (vinyl alcohol) (PVA) with metallic systems such as Pt, Cu, and In;
bimetallic systems, namely Pt-In, Ag-Pt, Pt-Fe, Cu-Pd, Pt-Pd and Pd-Fe; and
single-walled nanotubes (SWNT), multi-walled nanotubes (MWNT), and Buckmin-
sterfullerene (C-60). The strategy is extended to the formation of biodegradable
carboxymethyl cellulose (CMC) composite films with noble nanometals; such
metal decoration and alignment of carbon nanotubes in CMC is possible using a
MW approach. The MW approach also enables the shape-controlled bulk synthesis
of Ag and Fe nanorods in poly (ethylene glycol) (PEG).
1. Introduction
Lately, much effort has been devoted to the controlled synthesis of nanostructured
materials because of their unique chemical and physical properties. Metal nano-
materials have attracted considerable attention because of their unique magnetic,
optical, electrical, and catalytic properties and their potential applications in
nanoelectronics. Hierarchical assembly of solution-based nanocrystals as building
blocks is of great interest because of their potential in controlling morphologies of
nanostructures and, hence, their properties wherein structured nanoparticle assemblies
such as wires, rings, and superlattices, have been prepared. However, the challenge
of synthetically controlling particle shape had limited success. Nevertheless, some
physical and solid state chemical methods have been developed for making
semiconductor, metal nanowires, nanobelts, and nanodots in addition to wet
chemical methods.

210 M.N. NADAGOUDA AND R.S. VARMA
Herein, we report a simple and general strategy using a wide variety of

relatively benign solvents under which noble metal nanoparticles effectively self
assemble into spheres, nanowires, and nanorods in presence of vitamin B2
(Riboflavin), vitamin B1 and vitamin C. The approach also serves the need for a
greener protocol as there is a renewed interest in using green chemistry to
synthesize metal nanoparticles [1]. Green chemistry is the design, development,
and implementation of chemical products and the process to reduce or eliminate
the use and generation of substances hazardous to human health and the
environment. A primary driver for newer synthetic endeavors is the development
of efficient and environmentally benign protocols for the synthesis of a variety of
materials. Strategies to address mounting environmental concerns with current
approaches include the use of environmentally benign solvents, biodegradable
polymers, and non-toxic chemicals. In the synthesis of metal nanoparticles by
reduction of the corresponding metal ion salt solutions, there are at least three
areas of opportunity to engage in green chemistry: (i) choice of solvent, (ii) the
reducing agent employed, and (iii) the capping agent (or dispersing agent). In this
area there has also been increasing interest in identifying environmentally friendly
materials that are multifunctional. For example, vitamin B2 functions both as a
reducing and capping agent for metal nanostructures in addition to its high water
solubility, low toxicity and biodegradability [2].
As the pressure to produce materials in a rapid and benign fashion has
continued to increase, so microwave (MW)-assisted chemistry has emerged as a
valuable tool that permeates various aspects of chemistry including material
synthesis. The major objectives are to maximize the efficient use of safer raw
materials and to reduce waste. The use of emerging MW-assisted chemistry
techniques in conjunction with greener reaction media is dramatically reducing
chemical waste and reaction times in several chemical syntheses and chemical
transformations [3]. MW irradiation provides rapid and uniform heating of
reagents, solvents, and intermediates and this homogeneous heating also provides
uniform nucleation and growth conditions, resulting in the formation of homo-
geneous nanomaterials with small sizes. Power dissipation is fairly uniform
throughout with ‘deep’ inside-out heating of the solvent, which leads to better
crystallinity.
2. MW-Assisted Shape-Controlled Bulk Synthesis of Ag and Fe Nanorods

in PEG Solutions
Recently, bulk syntheses of Ag and Fe nanorods using PEG under MW irradiation

conditions have been accomplished [4]. Favorable conditions to make Ag nanorods
were established and the process was extended to make Fe nanorods with uniform
size and shape. The nanorods formation depended upon the concentration of PEG
used in the reaction with metal salts. Ag and Fe nanorods crystallized in face
centered cubic symmetry. The method uses no surfactant or reducing agent and is
greener in nature which could open a myriad of applications. In a typical
procedure, aqueous silver nitrate (AgNO3) solution (0.1 M) and different mol ratio
RISK REDUCTION VIA GREENER SYNTHESIS OF NOBLE METAL 211
of PEG (molecular weight 300) were mixed in a 10 ml test tube at room tempe-
rature to form a clear solution. The reaction mixture was irradiated in a CEM
Discover focused MW synthesis system maintaining a temperature of 100°C
(monitored by a built-in infrared sensor) for 1 h with a maximum pressure of 280
psi. The resulting precipitated Ag nanorods were then washed several times with
water to remove excess PEG. The obtained Ag nanorods are shown in Figure 1.
In summary, bulk synthesis of silver and iron nanorods can be achieved in
PEG medium under MW irradiation conditions. The results clearly demonstrate
that the concentration of PEG controls the final shape and size of the nanostruc-
tures which act as reducing agent as well as capping agent. The nanorod formation
depends upon the concentration of PEG used in the reaction with respect to the
silver or iron salts.
Figure 1. SEM images of Ag nanorods obtained via MW irradiation for 1 h using (a) 4 ml PEG + 4 ml
AgNO3 , (b) 5 ml PEG + 3 ml AgNO3, and (c) 3 ml PEG + 5 ml AgNO3.
3. MW-Assisted Synthesis of Noble Metals Using Natural Polymers
Bulk and shape-controlled synthesis of gold (Au) nanostructures with various

shapes such as prisms, cubes, and hexagons was accomplished via MW-assisted
spontaneous reduction of noble metal salts using an aqueous solution of α-D-
glucose, sucrose, and maltose [5]. The expeditious reaction was completed under
MW irradiation in 30–60 s and can be applied to the generation of nanospheres of

Ag, Pd, and Pt (see Figure 2 for TEM images). The noble nanocrystals underwent
catalytic oxidation with monomers such as pyrrole to generate noble nano-
composites, which have potential functions in catalysis, biosensors, energy storage
systems, nanodevices, and other ever-expanding technological applications. In a
typical experiment, an aqueous solution of HAuCl4 (0.01 N) was placed in a 20 ml
glass vessel and mixed with an appropriate amount of α-D-glucose. The reaction
mixture was exposed to high-intensity MW irradiation (1,000 W, Panasonic MW
oven equipped with invertor technology) for 30–45 s. Similarly, experiments were
conducted using 0.01 N PtCl4, 0.01 N PdCl2 and 0.1 N AgNO3.
Figure 2. TEM images of Au nanostructures synthesized (low concentration of sugar) using MW

irradiation with natural polymers such as (a) sucrose, (b) α-D-glucose, or (c, d) maltose. The insets
show corresponding electron diffraction patterns.
4. MW-Assisted Synthesis of CMC/Metal Biodegradable Nanocomposites
A green approach was established that generates bulk quantities of nanocomposites

containing transition metals such as Cu, Ag, In, and Fe at room temperature using
a biodegradable polymer, carboxymethyl cellulose (CMC), by reacting respective
metal salts with the sodium salt of CMC in aqueous media [6]. These nanocomposites
exhibit broader decomposition temperatures when compared with control CMC,
and Ag-based CMC nanocomposites exhibit a luminescent property at longer
wavelengths. The noble metals such as Au, Pt, and Pd do not react at room tempe-
rature with aqueous solutions of CMC, but do so rapidly under MW irradiation
conditions at 100°C. This environmentally benign approach, which provides facile
entry to the production of multiple shaped noble nanostructures (see Figure 3)
without using any toxic reducing agent such as sodium borohydride (NaBH4),
hydroxylamine hydrochloride, and so forth, and/or a capping/surfactant agent, and
which uses a benign biodegradable polymer CMC, could find widespread techno-
logical and medicinal applications.
Figure 3. Photographic image of CMC reduced Au, Pt and Pd (from left to right) synthesized using
MW at 100 °C for 5 min.
5. Preparation of Novel Metallic and Bimetallic Cross-Linked PVA

Nanocomposites Under MW Irradiation
A facile method utilizing MW irradiation was achieved that accomplishes the

crosslinking reaction of PVA with metallic and bimetallic systems [7]. Nanocom-
posites of PVA cross-linked metallic systems such as Pt, Cu, and In, and
bimetallic systems such as Pt-In, Ag-Pt, Pt-Fe, Cu-Pd, Pt-Pd and Pd-Fe were
prepared expeditiously by reacting the respective metal salts with 3 wt% PVA
under MW irradiation and maintaining the temperature at 100°C, a radical
improvement over the methods for preparing cross-linked PVA described in the
literature. The general preparative procedure is versatile and provides a simple
route to manufacturing useful metallic and bimetallic nanocomposites (see Figure
4) with various shapes, such as nanospheres, nanodendrites and nanocubes.
Figure 4. Photographic image of cross-linked PVA with various metallic and bimetallic systems:
(a) Pt, (b) Pt-In, (c) Ag-Pt, (d) Cu, (e) Pt-Fe, (f) Pt with higher concentration ratio, (g) Cu-Pd, (h) In,
(i) Pt-Pd and (j) Pd-Fe.
6. MW-Assisted Synthesis of Noble Metal Decoration and Alignment of

Carbon Nanotubes in CMC
A facile MW method that accomplishes alignment and decoration of noble metals

on carbon nanotubes (CNT) wrapped with CMC was achieved. CNT’s such as
SWNT, MWNT, and C-60 were well dispersed using the sodium salt of CMC
under sonication [8]. Addition of respective noble metal salts then generated noble
metal-decorated CNT composites at room temperature.
Figure 5. Aligned CNT’s in CMC polymer matrix upon MW irradiation.
However, aligned nanocomposites of CNTs could only be generated by exposing

the above nanocomposites to MW irradiation. The general preparative procedure
is versatile and provides a simple route to manufacturing useful metal coated CNT
nanocomposites (see Figure 5).
7. MW-Assisted Synthesis of Cross-Linked PVA Nanocomposites

Comprising SWNT’s, MWNT’s, and C-60
The cross-linking reaction of PVA with SWNTs, MWNTs, and C-60 using MW
irradiation afforded nanocomposites of PVA cross-linked with SWNT, MWNT
and C-60 expeditiously by reacting the respective CNT’s with 3 wt% PVA under
MW irradiation and maintaining a temperature of 100°C, representing a radical
improvement over literature methods to prepare such cross-linked PVA compo-
sites (see Figure 6 for SEM image) [9]. This general preparative procedure is
versatile and provides a simple route to the manufacture of useful SWNT, MWNT
and C-60 nanocomposites.
Figure 6. SEM images of SWNT cross-linked PVA nanocomposites.
8. A Greener Synthesis of Core (FE, CU)-Shell (AU, PT, PD, and AG)
Nanocrystals Using Aqueous Vitamin C
A greener method to fabricate novel core (Fe and Cu)-shell (noble metals) metal
nanocrystals using aqueous ascorbic acid (vitamin C) is described [10]. Transition
metal salts such as Cu and Fe were reduced using ascorbic acid, a benign naturally
available antioxidant; addition of noble metal salts then resulted in the formation
of the core–shell structure depending on the core and shell material used for the
preparation (see Figure 7). Pt yielded a tennis ball kind of structure with a Cu
core, whereas Pd and Au formed regular spherical nanoparticles. Au, Pt, and Pd
formed cube-shaped structures with Fe as the core. Inversely, transition metals
Figure 7. TEM images of core (Fe)-shell with (a) Au, (b) SAED of Au, (c) Pd, and (d) Pt core–shell
bimetallic nanostructures.
with noble metals, such as Pd, as the core also formed interesting structures; these
structures were brushlike with indium as the shell and needle-like when Cu was
employed as the shell. The method is general uses no surfactant or capping agent
and can be extended to noble metals as cores and transition metals as shells. The
core–shell nanocrystals were characterized using transmission electron micro-
scopy (TEM) and selected area electron diffraction (SAED). These nanocrystals
have unique properties that are not originally present in either the core or shell
materials and may have potential functions in catalysis, biosensors, energy storage
systems, nanodevices, and ever-expanding other technological applications.
9. Green Synthesis of Noble Nanospheres, Nanowires, and Nanorods Using

Vitamin B2: Catalytic Polymerisation of Aniline and Pyrrole
For the first time, a new green chemistry approach is described that uses vitamin
B2 in the synthesis of silver (Ag) and palladium (Pd) nanospheres, nanowires, and
Figure 8. TEM image of Ag and Pd nanoparticles synthesized using vitamin B2. (a) Ag (average size
6.1 ± 0.1 nm) in ethylene glycol, (b) Pd (average size 4.1 ± 0.1 nm) nanoparticles in ethylene glycol, and
(c), (d) Ag (average size 5.9 ± 0.1 nm, and average size 6.1 ± 0.1) nanoparticles in acetic acid and NMP,
respectively. Inset shows corresponding particle size distribution, electron diffraction, and UV excitation.
nanorods at room temperature without using any harmful reducing agents, such as
sodium borohydride (NaBH4) or hydroxylamine hydrochloride, or any special
capping or dispersing agent [2]. In ethylene glycol, the average particle size of Ag
nanoparticles was found to be 6.1 ± 0.1 nm; the average particle size of Pd
nanoparticles was found to be 4.1 ± 0.1 nm. In acetic acid and NMP, average sizes
of Ag nanoparticles were 5.9 ± 0.1 and 6.1 ± 0.1 nm, respectively (see Figure 8).
10. Conclusion
We have demonstrated the use of various environmentally benign reagents such as

sugars, vitamins and renewable polymers for the greener production of a wide
variety of metal nanoparticles as well as nanocomposites. The use of MW energy
coupled with the use of eco-friendly solvents enables the expeditious generation of
nanomaterials and their nanocomposite forms with utmost ease.
References
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wires and rods,” Green Chem., 8, 516–518 (2006).
2. M. N. Nadagouda and R. S. Varma “Green synthesis of Ag and Pd nanospheres,
nanowires and nanorods using vitamin B2: catalytic polymerisation of aniline and
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REMEDIATION OF CONTAMINATED GROUNDWATER USING
NANO-CARBON COLLOIDS
R.R. KHAYDAROV
Institute of Nuclear Physics
Ulugbek, 100214
renat2@gmail.com
R.A. KHAYDAROV, O. GAPUROVA

Abstract. The paper deals with a novel method of obtaining nano-carbon colloids
(NCC). The method allows synthesizing aqueous dispersions of NCC with the
sizes in the range of 1–100 nm, concentration of 150–400 ppm and pH of 2.8–3.1.
Due to functional carboxyl groups the ion exchange capacity of carbon colloids
obtained is very high – 7.4 mmol/g for a monovalent cation. NCC can be used for
effective removal of metal ions (Zn, Ni, Cu, Sb, Co, Cd, Cr, etc.) from conta-
minated water.
1. Introduction
Using metals and chemicals in process industries has resulted in the generation of
large quantities of effluent containing high levels of toxic heavy metals, meanwhile
mining and mineral processing operations also generate toxic liquid wastes [2].
The presence of different organic and heavy metal contaminants in groundwater
has a large environmental, public health and economic impact. Most of the
traditional technologies such as solvent extraction, activated carbon adsorption,
biological degradation and common chemical oxidation, whilst effective, very
often are costly and/or time-consuming [3]. Over the last decade usage of nano-
particles, structures from 1 to 100 nm in size, have been studied in this regard due
to their large surface areas and high surface reactivity [1]. For instance, nanoscale
iron particles have been considered as a new generation of environmental
remediation technologies that could provide cost-effective solutions to some of the
most challenging environmental cleanup problems [4].
This paper deals with synthesizing nano-carbon colloids (NCC), it also discusses
their usage for the extraction of pollutants from industrial wastes. The colloidal
carbon with functional groups such as carboxyl, hydroxyl and keto-groups can be
particularly useful being applied jointly with micro and ultra-filtration processes
for conducting separations not achievable by microporous activated carbons. The

220 R.R. KHAYDAROV ET AL.
commercially available activated carbons are heterogeneous in nature; hence new

carbons with well defined chemical groups are required.
Although it is not possible to form colloids of unoxidized carbon, colloids of
oxidized graphite or graphite oxide are widely known [5]. Nitric acid, hypochlorite
and ammonia are usually used for surface modification of carbon. Here, we describe
an electrochemical oxidation method to produce the water-based NCC with
sufficient stability without mixing the nitric acid with a surfactant. The capability
of NCC in removing metal ions and radionuclides from water is also discussed.

High-density isotropic graphites are used as an anode and a cathode. The dimen-
sions of electrodes are chosen as follows: 65 mm (W) × 30 mm (H) x 15 mm (Th).
The distance between electrodes immersed in a distilled water bath is able to be
varied from 10 to 120 mm in the current density range 0.1–3 mA/cm2. The electric
power applied to the electrodes is 60 V (DC). Two anodes and one cathode between
anodes are used to increase the surface of working electrodes and to decrease
dimensions of the device. Total working area of the anodes is 24 cm2.
The constructed apparatus includes an electrolytic cell 120 mm (W) × 140 mm
(H) × 105 mm (Th) made of plastic. The cell contains distilled water as an electrolyte
and three carbon electrodes immersed into the electrolyte. The deionized water is
most preferable for cost-effective production of pure carbon colloids. The electro-
lytic cell is installed on the magnetic stirrer. The electrolyte is passed between the
electrodes to provide the electrolyte with carbon particles and discharge the gas
generated via electrolysis from the electrodes.
The process of the device operation consists of two stages. The first stage is
the electrolysis during 10 min. The second stage is the electrolyte stirring during
60 s. This process is executed automatically. Twin timer ST-T (Korea) is used to
control the process.
Radionuclides used as the label of ions during the study of water purification
process are given in Table 1. Radionuclides were produced by irradiating salts of
ions in nuclear reactor of the Institute of Nuclear Physics (Tashkent, Uzbekistan).
Ge(Li) detector with a resolution of about 1.9 keV at 1.33 MeV and the 4096-
channel multichannel analyzer were used to detect γ-quantum from radionuclides.
Areas under γ-peaks of radionuclides were measured to calculate the amount of
ions.
The exchange capacity Q, mmol/g, was calculated as follows:
Q = (A0 – Ae )/(A0 – AB) . B/W, (1)
where B is amount of carrier, mmol; W is weight of exchanger, g; A0 is a count
rate of the original solution, Ae is a count rate of the solution at equilibrium, AB is
a background count.
The distribution coefficient Kd and the percent adsorption P were calculated by
Eqs. 2 and 3:
REMEDIATION OF CONTAMINATED GROUNDWATER 221
Kd = ((A0 – AB )/ (Ae – AB) – 1). V/W, (2)

.
P = 100 (1 - (Ae – AB) /(A0 – AB)), (3)
where V is a total volume of the solution, ml.
TABLE 1. Radionuclides used as labels (T1/2 is the half-life of the radionuclides, Eγ is the energy of the
γ-peaks).
Elements Radionuclides T1/2 Eγ, MeV
51
Cr(VI) Cr 27.73 days 0.320
60
Co(II) Co 5.27 years 1.17, 1.33
65
Ni(II) Ni 2.5 h 1.480
64
Cu(II) Cu 12.7 h 0.511
65
Zn(II) Zn 244.1 days 1.115
89
Sr(II) Sr 50.5 days 0.909
115
Cd(II) Cd 53.5 h 0.336
124
Sb(II) Sb 60.2 days 1.691
134
Cs(I) Cs 2.07 years 0.605
3. Mechanism of NCC Formation
In the graphite structure, each carbon atom is covalently bonded with other carbon
atoms so that they form flat sheet-like sequential hexagonal structures. However,
the parallel flat sheets of hexagonal-structured carbon atoms are weakly bonded
together due to attractive van der Waals forces. Thus the parallel carbon flat sheets
are easy to split by relatively weak external forces; other functional groups can
also easily enter between the graphite flat sheets.
During the electrochemical oxidization in the water, an anion (OH−) formed
from the cathode with the excess of electrons moves toward the anode with the
deficit of electrons. At the anode, the electrons are removed at the surface of
carbon nanoparticles, and simultaneously, the oxidation process was occurred.
Since the oxidation is imposed on the surface of carbon in the electrochemical
process, the magnitude of repulsion forces formed between the stacked layers get
larger than that of van der Waals attraction forces between the layers. Carbon
nanoparticles are charged negatively and after switching off the electric power the
oxidized particles come away from the anode and the functional groups such as
carbonyl (>C=O) , hydroxyl (-OH), and carboxyl (-COOH) group are formed on
the surface of carbon particles. Thus the resulting NCC nanofluid is able to
maintain its stability as long as the hydrophilic functional groups exist.
4. NCC Preparation Technique
The electrolysis is executed by two stages: activation of the anode and the carbon
nanoparticles generation.
At the first stage the electrolyte has low conductivity, value of electric current
is small, about 0.1–0.2 mA/cm2 and the oxidization reaction is slow. Duration of
this stage is about 50 h and depends on the quality (density) of graphite. At this
stage a voltage between electrodes can be high, about 60–100 V.
As the reaction proceeds, the conductivity of the electrolyte is abruptly increased,
electric current can increase up to 10 mA/cm2 and higher and the oxidization
reaction is activated. As a result, the carbon is finely split, and then is covered by
the carboxyl group. At the second stage the electric current between electrodes
must be about 3–4 mA/cm2. If current density values greater than 8–10 mA/cm2,
the rate of oxygen evolution is greater than the rate of its diffusion through the
electrode; hence there is a pressure build-up within the electrode causing the
electrode to disintegrate. NCC is not stable, in 2–3 weeks the precipitation of NCC
is to be observed. Similarly, at current density less than 3–4 mA/cm2 the rate of
oxygen evolution is such that, although some pressure builds up in the electrode,
the gas is able to diffuse out of the electrode before disintegration occurred, small
pieces of carbon broke off in the process to form colloidal carbon and very small
amount of slurry. The NCC is stable during 150 days at least.
The rate of diffusion of hydrogen at the cathode is such that little or no pressure
built up within the electrode and therefore no colloid is produced at this electrode.
The colloidal carbon is produced only at the anode and remains within the vicinity
of the electrode, indicating that the carbon is negatively charged. Reversal of the
electrode polarity results in the surrounding carbon migrating slowly to the new
anode.
Carbon nanoparticles are removed from the anode during the electrolyte stirring
stage. Figure 1 demonstrates the process of carbon nanoparticles splitting. pH of
the NCC is 2.8–3.1 and depends on the concentration of carbon nanoparticles;
concentration of carbon nanoparticles is 150–400 ppm and depends on duration of
the process; ion exchange capacity is 7.4 mmol/g for a monovalent cation. The
typical TEM image for NCC obtained is shown on Figure 2.
Figure 1. Process of carbon colloids splitting.

REMEDIATION OF CONTAMINATED GROUNDWATER 223
Figure 2. Typical TEM image of carbon colloids obtained (the scale is 200 nm).
5. Water Decontamination by Carbon Nanoparticles
Removing heavy metal ions (Zn, Ni, Cu, Sb, Co, Cd, Cr, etc.) from water was
studied. pH of the NCC was 2.8, concentration of carbon nanoparticles was 250
ppm Dependence of the distribution coefficient Kd for different ions at pH = 7.1 of
the solutions is presented in Table 2.
TABLE 2. Distribution coefficient Kd (ml/g) and percent adsorption P (%) for different ions
(concentration of ions C0 = 10 mg/l, V = 50 ml, W = 0.5 g, pH = 7.1, contact time 1 h).
Elements P Kd, 105
Cr(III) >99 140
Co(II) >99 170
Ni(II) >99 1,300
Cu(II) >99 1,400
Zn(II) >99 4,000
Sr(II) >99 3,800
Cd(II) >99 100
Sb(II) >99 400
Cs(I) 60 0.6
The results given in Table 2 demonstrate high ion-exchange potential of the

colloidal carbons. In real water which contains different ions, the colloidal particles
are coagulated within some time depending on the concentration of salts. Before
and during coagulation process the nanoparticles as the ion exchangers react with
cations. After coagulation water can be easily filtered from particles with attached
cations. This means that the colloidal particles are quite effective for removal of
the metal cations and may provide a useful alternative for example to method of
flocculation of metal hydroxides and oxides.
6. Conclusion
The described method allows producing NCC with concentration of carbon

nanoparticles of 150–400 ppm and pH of 2.8–3.1. The concentration of nanoparti-
cles depends on duration of the process and pH of NCC depends on concentration
of carbon nanoparticles. The ion exchange capacity of carbon nanoparticles due to
functional carboxyl groups is very high, 7.4 mmol/g for a monovalent cation.
NCC can be used for effective removing metal ions (Zn, Ni, Cu, Sb, Co, Cd, Cr,
etc.) from contaminated water.
References
1. Bönnemann, H., and Richards, R. (2001) Nanoscopic metal particles – synthetic

methods and potential applications, Eur. J. Inorg. Chem. 10, 2455 and 2480.
2. Coetser, S.E., Heath, R.G., and Ndombe, N. (2007) Diffuse pollution associated with the
mining sectors in South Africa: A first-order assessment. Water Sci. Technol. 55: 9–16.
3. Theron, J., Walker, J.A, and Cloete, T.E. (2008) Nanotechnology and water treatment:
applications and emerging opportunities, Crit. Rev. Microbiol. 34, 43–69.
4. Zhang, W. (2003) Nanoscale iron particles for environmental remediation: an overview,
J. Nanopart. Res. 5, 323–332.
5. Peckett et al. (2000) Electrochemically oxidised graphite. Characterisation and some ion
exchange properties. Carbon 38, 345–353.
A NOVEL SIZE-SELECTIVE AIRBORNE PARTICLE SAMPLING
INSTRUMENT (WRAS) FOR HEALTH RISK EVALUATION
H. GNEWUCH, R. MUIR, B. GORBUNOV

Naneum Limited, CEH, University of Kent
Canterbury, Kent CT2 7NJ, UK
robert.muir@naneum.com
N.D. PRIEST
Urban Pollution Research Centre, Middlesex University
Queensway, Enfield, Middlesex EN3 4SA, UK
P.R. JACKSON
CERAM
Queens Road, Penkhull
Stoke-on-Trent, Staffordshire ST4 7LQ, UK
Abstract. Health risks associated with inhalation of airborne particles are known
to be influenced by particle sizes. A reliable, size resolving sampler, classifying
particles in size ranges from 2 nm–30 µm and suitable for use in the field would
be beneficial in investigating health risks associated with inhalation of airborne
particles. A review of current aerosol samplers highlighted a number of limitations.
These could be overcome by combining an inertial deposition impactor with a
diffusion collector in a single device. The instrument was designed for analysing
mass size distributions. Calibration was carried out using a number of recognised
techniques. The instrument was tested in the field by collecting size resolved
samples of lead containing aerosols present at workplaces in factories producing
crystal glass. The mass deposited on each substrate proved sufficient to be detected
and measured using atomic absorption spectroscopy. Mass size distributions of
lead were produced and the proportion of lead present in the aerosol nanofraction
calculated and varied from 10% to 70% by weight.
1. Introduction
The high health risk associated with the inhalation of airborne particles has been
recognised and documented, see e.g. Brown et al. [1]; Pope et al. [15]. Many
epidemiological studies have shown associations between exposure to particulate
matter in the air and increases in morbidity and mortality [4]. There is a growing
concern that health risk associated with airborne particles is influenced by size.
Some studies indicate that nanoparticles (less than 100 nm in diameter) having

226 H. GNEWUCH ET AL.
increased toxicity relative to larger particles composed of the same materials [5–7,
14].
Size-resolved sampling of airborne particles often requires various techniques
to be employed [11]. There would be a significant benefit in a sampler that could
reliably collect size resolved samples across the entire size range which is consi-
dered to be relevant to health effects. There are many technical difficulties in size-
resolved sampling of particles smaller than 100 nm – especially under real conditions
of variable and/or high humidity. Pressure drop in low-pressure cascade impactors
corrupts size distributions and causes condensation of water as well as other atmos-
pheric constituents on substrates, e.g., Hart and Pankow [9] have estimated that the
gas-particle mass exchange for PAHs could cause errors in measurements of up to
40%. Large mass changes were directly observed by Moor et al. [13] in experiments
where atmospheric aerosol particles collected onto substrates of a cascade impactor
were exposed to conditions with lowered partial pressures of semi-volatile compounds.
2. Methods
In this paper, we describe a novel size-selective aerosol sampling instrument,

WRAS (Wide Range Aerosol Sampler), based upon diffusion deposition coupled
with inertial deposition in a single apparatus (www.naneum.com). This enables
the size-selective sampling of aerosol particles in a wide range of airborne particle
sizes without employing low-pressure cascade impactor technology.
The WRAS instrument comprises an inertial unit similar to a May [12] cascade
impactor having the lowest stage cut off diameter 0.25 μm and a specially designed
diffusion deposition unit (nano-selector) for smaller particles. Operating flow rate
is 20 l/min. First, aerosol particles are drawn into an isokinetic inlet of the cascade
impactor where those greater than 0.25 μm in aerodynamic diameter are collected
according to their aerodynamic diameter. Collection efficiency of particles in an
inertial cascade impactor increases with size, therefore, the largest particles are
removed from the flow by the first stage and the smaller particles are deposited
onto following stages, stages 6–12 (Table 1).
TABLE 1. The characteristics of the stages of the WRAS sampler.*

Stage Min. size (µm) Max. size (µm) Unit
1 0.001 0.0015 Nano-selector
6 0.25 0.5 Cascade impactor
11 8.1 20 Cascade impactor
12 20 ~35 Cascade impactor
*Latest model of the WRAS sampler
AIRBORNE PARTICLE SAMPLING INSTRUMENT 227
The flow emerging out of the cascade impactor contains particles smaller than
0.25 μm. These particles are collected by sets of Nylon nets. Collection efficiency
of particles in a diffusion unit decreases with the size, therefore, the smallest
particles are collected at the first net and the larger particles are deposited onto
following nets according to cut off diameters shown in Table 1 (Sections 1–5).
Nano-selector units have been designed to collect particles sequentially in the
size range from 1 nm to 0.25 μm. In practice, this is achieved by selecting nets
with differing fibre diameters, fibre densities and by varying the number of nets
per stage and the flow velocity. The nano-selector deployed in the WRAS sampler
has a cylindrical cross-section (ID = 4.7 cm) and contains five stages. From Table
1 the cut off diameters of the WRAS sampler covers the size range from 1 nm to
35 μm. Thus it is the first universal size-selective sampling apparatus which
enables airborne particles to be collected in the entire aerosol size range that is of
concern with respect to health risks.
Artificial lead and tungsten aerosols were employed to calibrate the WRAS
sampler according to the approach described by Sinclair et al. [16] and Cheng
et al. [2]. The cut off diameters in the nanoparticle size range were calculated
according to Cheng and Yeh [3] and were compared with the cut-off diameters
found from the size distributions measured (with SMPS) before and after a net.
The calculated and measured cut-off diameters were in good agreement (Table 2).
TABLE 2. Calculated/measured cut off diameters of WRAS diffusion collector stages.*
Stage Di (nm) calculated Di (nm) measured
2 17 16.5 + 1
3 80 80+ 5
4 120 110 + 10
*Previous model of WRAS sampler
A case study is presented here to illustrate the potential of the novel sampling
system. The developed WRAS sampling unit (previous model) was employed to
sample airborne particles at various working places in the crystal glass industry.
Aerosol particles were collected in a range of sizes from 2 nm to 20 μm (11 size
fractions) at a flow rate 20 l/min and at a controlled relative humidity of 80%. The
sampling time employed varied from 2 to 24 h (according to aerosol concentration
levels). The mass of lead collected was determined by atomic absorption
spectroscopy [8]. Aerosol mass size distributions of lead were obtained from the
samples collected.
Size distributions are crucial for the evaluation of health risk. It is known that
particle deposition efficiency in the human respiratory system is influenced by the
size of particles. An example compiled from experimental and theoretical data is
shown in Figure 4 [10]. The efficiency is a V-shaped function with a high degree
of deposition for nanoparticles and for particles in micro-range (close to 100%). In
the sub-micron range, the efficiency falls to about 10–20 %. Therefore, when the
mass of airborne particles is concentrated in the sub-micron range (as in Figure 3)
the dose of deposited particles is proportionally less than from an aerosol with a
maximum positioned towards the nano size range (Figure 2). This shows the
importance of size-resolved sampling for correct evaluation of health risk.
3. Results
The total mass concentration of lead aerosols determined at working places ranged
from 0.6 to 50 μg/m3. The nanoparticle mass fraction of aerosols (sizes less than
100 nm) was found to vary from 10% to 70%. A typical aerosol size distribution
of lead (sampled at the glass smelting area at plant A) is shown in Figure 1. The
size distribution has a maximum at about 0.35 μm. but there is a noticeable
amount of Pb associated with nanoparticles in the range below 0.1 μm. Even more
nanoparticle mass fraction was observed at plant B where melting of lead
compounds also takes place (Figure 2). In contrast, at plant C, involved in glass
polishing, airborne particle size distributions contain much less mass fraction in
the nanoparticle range (Figure 3). Thus, size distribution of lead at workplaces
may vary considerably depending on production processes.
Figure 1. Airborne lead particle size distribution obtained at a plant A involved in hot lead processing.
Figure 2. Airborne lead particle size distribution obtained at a plant B involved into hot lead processing.
Figure 3. Airborne lead particle size distribution obtained at a plant C involved into hot lead
processing.
The size distribution of the number of particles deposited in the respiratory

system Nl(D) is a product of the ventilation rate Q, exposure time t, airborne
particle size distribution fa(D) and the deposition efficiency of particles E(D)
N l ( D) = Q t f a ( D) E ( D) (1)
Nl(D), therefore, represents the mass distribution of particles that were

deposited in the respiratory system. The fraction of particles captured by the
respiratory tract calculated for distributions shown in Figures 1–3, and for the
efficiency presented in Figure 4 showed that the fraction of deposited total particle
mass varied from 16% (Figure 3) to 37% (Figure 1) to 51% (Figure 2).
100%
90%
80%
70%
Efficiency
60%
50%
40%
30%
20%
10%
0%
0 1 2 3 4
LogD, D - nm
Figure 4. Efficiency E(D) of airborne particles deposition in the human respiratory tract.
4. Conclusions
The principles of inertial and diffusion deposition have been employed in the
design and construction of a new instrument (WRAS) that was developed to size-
selectively collect aerosol particles across a wide aerosol size range relevant to
health effects. The instrument developed does not require low pressure to collect
nanoparticles and, therefore, can be employed to sample size-selectively aerosol
particles across the entire aerosol size range down to nanometer-sized particles
with minimal sampling artefacts caused by evaporation/condensation of volatile
and semi-volatile compounds.
Data shows that the size distributions of lead containing particles in the aerosol
at workplaces are influenced by manufacturing processes in the crystal glass
industry. The nanoparticle mass fraction of aerosols (sizes less than 100 nm) was
found to vary from 10% to 60%. It was found that the fraction of mass of lead
deposited in the respiratory system depends on the mass distribution of lead and
varies from 16% to 51%. This result is important for air quality assessment and
health risk evaluation. It shows that standard, non-size-resolving OH sampling
techniques, used by the crystal glass industry and others will overestimate the total
health risk considerably.
References
1. Brown J. S., Kirby L. Z. and William D. B. (2002) Ultrafine particle deposition and
clearance in the healthy and obstructed lung. Am J Resp Crit Care Med, 166:1240–
1247.
2. Cheng Y. S., Keating J. A. and Kanapilly G. M. (1980) Theory and calibration of a
screen-type diffusion battery, J Aerosol Sci., 11:549–556.
3. Cheng Y. S. and Yeh H. C. (1980) Theory of a screen-type diffusion battery. J. Aerosol
Sci. 11:313–320.
4. Dockery D. W., Pope C. A., Xu X., Spengler J. D., Ware J. H., Fay M. E., Ferris B. G.
and Speizer F. E. (1993) An association between air pollution and mortality in six US
cities. N Engl J Med 329:1753–1759.
5. Donaldson K., Li X. Y. and MacNee W. (1998) Ultrafine (nanometer) particle-
mediated lung injury. J Aerosol Sci 29:553–60.
6. Ferin J. (1994) Pulmonary retention and clearance of particles. Toxicol Lett 72:121–
125.
7. Ferin J., Oberdorster G. and Penny D. P. (1992) Pulmonary retention of ultrafine and
fine particle in rats. Am J Resp Cell Mol Biol 6:535–542.
8. Gorbunov B., Priest N., Jackson P. R. and Cartlidge D. (2000) Aerosol size distribution
of lead at working places. J Aerosol Sci 31(Suppl. 1):S520–521.
9. Hart K. M. and Pankow J. F. (1994) High-volume air sampler for particle and gas
sampling. 2. Use of backup filters to correct for the adsorption of gas-phase polycyclic
aromatic hydrocarbons to the front filter. Environ Sci Technol 28:655–661.
10. Hinds W. C. (1999) Aerosol technology. Properties, Behaviour and Measurement of
Airborne Particles. New York: Wiley, pp. 233–259.
11. John W. (2001) Size Distribution Characteristics of Aerosols. In: Aerosol
Measurement. Principles, Techniques and Applications. Ed. PA Baron and K Willeke.
New York: Wiley, pp. 99–116.
12. May K. R. (1982) A personal note on the history of the cascade impactor. J Aerosol Sci
13:37–47.
13. Moore M., Gorbunov B. and Williams I. (1998) A new method to study interaction of
semi-volatile compounds with aerosol particles. J Aerosol Sci 29(Suppl. 1):S887–888.
14. Oberdorster G., Ferin J. and Lehnert B. E. (1994) Correlation between particle-size, in-
vivo particle persistence, and lung injury. Environ Health Perspect 102(Suppl. 5):173–
179.
15. Pope C. A., Dockery D. W. and Schwartz J. (1995) Review of epidemiological
evidence of health effects of particulate air pollution. Inhal Toxicol 7:1–18.
16. Sinclair D., Countess R. J., Liu B. Y. H. and Pui D. Y. H. (1976) Experimental
verification of diffusion battery theory. J Air Poll Control Assoc 26:661–663.
NANOTECHNOLOGIES AND ENVIRONMENTAL RISKS
Measurement Technologies and Strategies
T.A.J. KUHLBUSCH, H. FISSAN, C. ASBACH

Air Quality & Sustainable Nanotechnology Unit
Institute for Energy and Environmental Technology (IUTA) e. V.
Bliersheimerstr. 60
47229 Duisburg, Germany
tky@iuta.de
Abstract. Assessments of nanoparticle exposure are needed to enable risk assess-

ments which are needed to achieve a sustainable development of nanotechnology
including public perception. Therefore an overview of measurement techniques,
needed data quality, comparability, and measurement strategies is given. Addi-
tionally some results of exposure related studies are summarized. Overall it is
demonstrated that an integrated approach towards nanoparticle exposure assess-
ments in workplaces, but also in the environment is needed, despite the current
published results indicating mainly release of nanoparticle agglomerates in the
size range larger than 100 nm.
1. Introduction
Nanoparticles and nanoobjects, intentionally produced particles of nanoscale in

three or two dimensions, have specific properties possibly altering the (eco-)
toxicological potential when compared to larger particles or the corresponding
bulk material. The detailed assessment of this potential risk is a prerequisite to
accomplish sustainable nanotechnology since it directly influences the public
perception. The risk is generally a function of potential hazard and exposure. The
importance of the latter is given by (a) that no risk exists if no exposure, (b) the
dose, leading to possible health effects, is directly linked to the exposure, and (c)
correct exposure determination is also of importance for e.g. epidemiological
studies. To assess exposure it is also necessary to clarify the areas (e.g. workplace,
environment), subjects (e.g. humans, animals, ecosystems) and exposure media
(air, liquid, solid) of interest.
This paper focuses on the human exposure mainly in workplace environments
since highest exposure can be expected in these areas. Also, measurement techno-
logies and strategies can be evaluated and tested in workplace environments since
possible sources and hence particle material is known and can be differentiated
from ambient nanoscale particles.

234 T.A.J. KUHLBUSCH ET AL.
The currently discussed main exposure route of nanoparticles is via the airborne
state by inhalation. Other discussed routes of exposure such as via the skin or
gastrointestinal tract possibly leading to an uptake are currently seen as of minor
importance [4] but still have to be investigated.
Two major pieces of information are necessary for the assessment of exposure
and possible nanoparticle implications:
The exposure leading to a dose
The hazard, influenced by the particle properties
Hence, assessments of exposure to nanoparticles have a twofold task. One task
is the general determination of an exposure and to quantify the ‘relevant’ aerosol
property. The second task is the characterization of the nanoparticle properties
since these may have been influenced or changed during the transport period after
release. Any changes in these particle properties may have a significant influence
on the possible hazard of nanoparticles. Spatial and time resolution of the
measurements can therefore play a crucial role in the exposure determination and
its evaluation.
This background puts certain demands onto the measurement techniques for
airborne nanoparticles as well as the measurement strategies.
2. Measurement Techniques
Basically, various physical and/or chemical properties of nanoparticles and aerosols

can be determined with especially particle size and concentration being physical
properties of importance in the case of nanoparticles (<100 nm in three dimensions)
and nanoobjects (<100 nm in two dimensions). For a decision on the instrumen-
tation to be used for exposure measurement the scheme shown in Figure 1 was
introduced in Borm et al. [2]:
This scheme indicates the different steps of possibilities when choosing the
instrumentation for exposure assessment. Certainly, the ideal sampling for exposure
assessment would be a personal sampler measuring and reporting continuously the
physical and chemical characteristics of all single particles (agglomerates or primary
particles) as well as their concentrations entering the measurement system. Since
this is not possible, decisions have to be made based on the task to perform and
Figure 1. Scheme of particle characterization for exposure measurements [2].

NANOTECHNOLOGIES AND ENVIRONMENTAL RISKS 235
the corresponding availability of adequate measurement technology. If e.g. the

question is limited to whether primary particles of a specific nanoparticle product
are present in the work area it may be sufficient to use a device determining
particle number concentration or particle number size distributions. If, on the other
hand, exposure should be determined in the framework of epidemiological studies,
possibly certain particle properties such as lung deposited particle surface area
become important. Hence, currently an array of stationary instruments and
measurement technologies are employed to study exposure and possible effects of
nanoparticles.
To assess particle properties such as morphology or chemical composition,
mainly offline methods, namely single particle analysis following particle deposition,
commonly by electrostatic precipitation [7], are usually required. The analytical
techniques may comprise electron microscopic (SEM, TEM), atomic force micro-
scopic analysis for physical properties and energy-dispersive x-ray spectroscopy
(EDX) for single particle or total reflection x-ray fluorescence spectrometry
(TXRF) [10] for total chemical analysis. While the determination of particle con-
centrations and size distributions from the sample deposits is generally possible by
electron microscopy, this method is very limited in its concentration range and
also very time consuming.
Technically mature online instrumentation for the determination of various
aerosol properties is commercially available. The aerosol properties of interest
include particle number and surface area concentration and their size distributions.
Mass concentration determination is of minor importance for nanoparticle
detection due to the low sensitivity and low mass involved. Total particle number
concentrations are commonly determined with a Condensation Particle Counter
(CPC), sometimes also called Condensation Nucleus Counter (CNC). In a CPC,
particles get exposed to an atmosphere supersaturated with vapour of its working
fluid, commonly butanol, isopropyl alcohol or water. The vapour condenses on the
particle surface and causes the particles to grow to a size that can scatter a laser
beam downstream of the condensation chamber. The number of impulses from the
scattering of the laser beam is counted in order to determine the particle number
concentration. [17]. The lower detection limit for these devices reaches down to
3 nm [9] and below.
There are no instruments available that can determine airborne concentrations
of geometric particle surface area. In electrical diffusion chargers such as the
LQ1DC (Matter Engineering) particles are exposed to a unipolar ionic atmosphere
and ions are attached to the particle surface due to Brownian diffusion. The
current, measured upon deposition of the charged particles, is proportional to the
so-called Fuchs surface area [11], i.e. the surface area of particles available for ion
attachment. This “surface area” is proportional to dp1.39 and therefore smaller than
the geometric surface area, being proportional to dp2. Another instrument, called
Nanoparticle Surface Area Monitor, NSAM (TSI) also uses an electrical diffusion
charger but manipulates the size distribution such that the measured current is
proportional to the geometric particle surface area concentration that gets
deposited in either the alveolar or tracheobronchial region of the lung [8, 19].
Number size distributions of airborne particles with diameters down to a few

nanometers can be determined using electrical mobility analysis. Particles are
initially brought to a known charge distribution (equilibrium) in a neutralizer
which can be based on radioactive decay or corona discharge. The particles then
enter a Differential Mobility Analyzer (DMA), a concentric, cylindrical set up,
near the outer electrode. Charged particles are deflected in the electric field
between the two electrodes. The electrical mobility is a function of particle size
and charge. Particles of high electric mobility, i.e. small and/or highly charged
particles move faster towards the inner electrode than particles of low electrical
mobility, i.e. the location where they hit the inner electrode is a function of their
electrical mobility. At the other end of the inner electrode, particles of certain
mobility are withdrawn through an outlet slit. The withdrawn mobility is
determined by the voltage applied to the electrodes. In a Scanning Mobility
Particle Sizer, SMPS [20], the voltage is continuously ramped and the particle
concentration in the sample flow through the slit measured with a CPC. An
algorithm is used to relate the measured concentrations to the corresponding
electrical mobilities and along with the known charge distribution to determine the
number size distribution as a function of electrical mobility diameter. If the
relationship between particle mobility diameter and particle surface area is know,
the number size distribution can easily be converted into surface area size
distribution. Integration over a desired size range can also provide total number or
surface area concentration.
Another, for work related exposure interesting measurement technique is also
based on the electrical mobility of charged particles. It is implemented in the Fast
Mobility Particle Sizer (FMPS, TSI) which is based on work conducted by Mirme
et al. [18]. The main difference to the SMPS described above is that the particle
detection is based on an array of 22 electrometers, placed along the outer electrode
in a DMA. Simultaneous detection of particles within the entire size range covered
(5.6–560 nm) allows for a time of resolution of 1 s. For comparison, a comparable
size scan by an SMPS would take at least 2 min, because the different sizes are
measured sequentially. The downside of the FMPS is the lower size resolution, 16
channels per decade, compared to e.g. possible 64 channels per decade for the
SMPS. Nevertheless, the FMPS may be preferred if size distribution have to be
determined in work areas with quickly varying work processes and therefore size
distribution fluctuations shorter than the time resolution of the SMPS. Extended
information on measurement techniques may also be found in Kuhlbusch et al.
[14].
3. Comparability and Data Quality
Measurements to assess exposure of e.g. humans should be comparable to actually

allow for comparisons between different work environments, different work pro-
cesses, to enable the evaluation of exposure reduction measures etc. Still, the
comparability between different instruments, instruments from different manu-
facturers, or even between two similar instruments but two different users is not
always sufficient. Comparison studies as e.g. reported by Dahman et al. [5] clearly
showed the differences between various instruments and the need of ‘understanding’
the equipment.
Fitted Size Distributions

SMPS-T1 (0.3/3 lpm)
3.5x105
SMPS-T2 (0.6/6 lpm)
3.0x105 SMPS-G1 (L-DMA)
SMPS-G1 (M-DMA)
2.5x105 FMPS
dN/dlog(dp) [nm]
2.0x105
1.5x105
1.0x105
5.0x104
0.0
10 100
Particle Diameter dp [nm]
Figure 2. Example of NaCl particle size distribution determined with various SMPS (different
providers, volume flow, and type of DMA) and FMPS. (Adapted from Asbach et al. [1].)
An example of a comparison for sodium chloride test particles is given in

Figure 2. This figure clearly shows the comparability of (a) number concentration
<100 nm, (b) modal diameter, and (c) width of the size distribution. This com-
parability for the ideal test condition is general in the range of around 40% and
better. More detailed analysis of the comparability will soon be published.
Nevertheless, it has to be stated that comparability and reproducibility are
currently more in an infant state and that standardization as well as good under-
standing of the measurement devices are still needed.
4. Measurement Strategies
The difficulties in the determination of nanoparticles in air, water or soils are

manifold. In all three matrices the problems of the specific nanoparticles have to
be overcome. In all cases single particle analyses are necessary to enable identifi-
cation. The problem may be reduced if nanoparticles with very specific and robust
properties or specific chemical components, not or only rarely present in the
corresponding matrix, are used. Nevertheless, in some cases clear differentiation
of the source of the nanoscale particle, natural or manmade, may not be possible
as e.g. for iron particles.
Identification (and differentiation from natural nanoscale particles)
Characterization
And quantification
Another problem, difficult to be covered with “normal” measurement methods

is the alteration of surfaces of nanoparticles. Surfaces of nanoparticles are altered
after the production to achieve specific particle properties and to enhance e.g.
dispersion of nanoparticles during certain production steps. These surface
properties are currently discussed to be of possible importance for toxicological
effects. No study, to the knowledge of the authors, has so far been conducted to
investigate whether particle surface properties are stable after e.g. accidental
release to the environment.
The above two paragraphs briefly explain the difficulties in the measurements
and hence in the set up of measurement strategies for nanoparticles exposure.
While the latter case (persistence of particle surface properties) is only of interest
if particles are released we may first focus on the task of the general assessment
whether nanoparticle exposure exists or not. This is of importance since no risk
exists when no exposure is given.
To allow for first tests and evaluations of measurement strategies as well as
measurement techniques we first focus on exposure related measurements in work
areas since there we know which kind of nanoparticle to determine and we can
expect the highest exposure concentrations compared to e.g. in the environment.
Two of the first questions to tackle in the case of exposure measurements are
the questions of measurement metric and necessary lower detection limit. Table 1
gives an overview of possible particle metrics and concentration ranges of interest.
TABLE 1. Particle metrics and concentrations of interest for exposure measurements.

Number Surface
(N/cm³) (µm²/cm³)
<1,000 <10
1,000–100,000 10–1,000
>100,000 >1,000
The concentrations given in the first row of Table 1 (<1,000 N/cm³ or <10
µm²/cm³) are in our view concentration ranges with no or only little effects unless
particle specific toxicity as e.g. for asbestos is given. The latter may be assessed in
toxicological screening tests. In those cases where such low limits of detection are
needed only single particle analysis by microscopes coupled with e.g. EDX can
currently be employed as is already used for asbestos. Due to this detection
technique it is normally possible to discriminate environmental nanoscale particles
from engineered ones. Nevertheless, this method is very time consuming, expensive,
and can hardly be employed in routine monitoring.
In cases of particle concentrations exceeding 100,000 N/cm³ (or 1,000 µm²/µm³)
a source has to be close to the measurement point and should be identifiable by
simple aerial particle number concentration measurements with a CPC.
The most difficult and maybe most important case for exposure assessments is
the intermediate concentration range of 1,000–100,000 N/cm³ (or 10–1,000 µm²/cm³).
This concentration range covers the usual ambient particle number concentrations
which may range from a few hundreds particles per cm³ in clean air conditions,
e.g. mountainous regions or sea sides, around 10,000–30,000 N/cm³ in urban
background situations, up to possibly 100,000 N/cm³ close to high traffic areas

(e.g. Dingenen et al. [6]). Hence, to assess nanoparticle exposure in this concen-
trations range neither microscopic single particle analysis nor simple number or
surface area concentration measurements are really an option due to potentially
high background contributions and variability. A measurement strategy is therefore
needed to overcome this problem but still to allow for a relatively practicable
assessment of possible nanoparticle exposure.
The following approach briefly summarized here is described in detail in
Kuhlbusch et al. [15] and is based on the strategy used in studies at several carbon
black production facilities [12, 13].
One of the basic assumptions of this strategy is that the intrusion of ambient
particles into a work area can be calculated by a constant, but size dependent
‘penetration factor’. This factor is determined by e.g. measuring with an SMPS
concurrently at a comparison site and in the work area when no work activity is
taking place. By calculating the ratio of the two measured size distributions a size
dependent ‘penetration factor’ is derived.
80,000
70,000
3
Number concentration / #/cm
60,000
50,000
40,000
Outside area
30,000
20,000
10,000
0
Inside area
08:00
09:00
10:00
11:00
12:00
13:00
14:00
15:00
16:00
Time
Outside area
Environment
Working area
(Inside area)
Traffic
subtract
Production
process
Other workings ?
Figure 3. Penetration of particles from outside area into the work area. (Adapted from Kuhlbusch et al. [15].)
The same measurements are performed when the work activity of interest is
ongoing. Now, the measurements conducted in the work area show the particle
size distribution with work activity. The size distribution to be present in the work
area when no work activity would have been ongoing can be calculated based on
the measurement at the comparison site and the ‘penetration factor’ determined
before. The comparison of the two values, in this example particle size distri-
bution, show (a) whether nanoscale particles were released by the work activity
and (b) the size distribution emitted by the process. So far, this value is only
indicative, whether nanoparticles may have been released. No nanoparticles have
been released by the process if no increased particle concentration is determined.
If increased particle concentrations are determined further investigations based on
e.g. single particle analysis or time of release (does it correlate with the specific
work activity?) are needed. This basic idea is sketched in Figure 3.
5. Results from Previous Studies
Several studies have now been conducted to assess possible exposure to particles
below 100 nm. Most of these studies however deal with unintentionally produced
particles such as welding and soldering fumes (e.g. Brouwer et al. [3]). Only a
limited number of measurements have so far been conducted determining possible
exposure to nanoparticles or nanoobjects in real nanotechnology work areas [12,
13, 15].
The results of the measurements conducted at three different industrial plants
are summarized in Table 2.
TABLE 2. Summary of particle release below 100 nm at three different carbon black plants. (Adapted
from Kuhlbusch and Fissan [13].)
Observed
Likely origin
increases
Plant 1 Reactor No
Pelletizer No
Bagging No
Plant 2 Reactor Yes Nearby traffic
Pelletizer Yes Nearby traffic
Bagging Yes Propane fork lifts
Plant 3 Reactor Yes condensed oil vapors
Pelletizer Yes Flue gas–leak
Diesel fork lifts,
Bagging Yes
gas heater
Measurements to determine possible nanoparticle exposure were conducted at

overall nine sites. Six of these sites showed elevated concentrations of nanoscale
particles. In two cases this could be attributed to nearby traffic by e.g. analyzing
the wind direction dependency, in further two cases other sources than the
nanoparticle production were the reason for the elevated concentrations, namely
forklifts and gas heater. Finally in two cases the reason for the higher concentra-
tions was found to be related with the production facility. One time it was con-
densed oil vapors coming from maintenance work. These particles were nanoscale
particles but no nanoparticles. In the last case a leak in the production facility was
the reason for the very high concentrations. In this case true nanoparticles were
present.
Another study which investigated the possible exposure to carbon nanotubes
was conducted by Maynard et al. [16]. This study showed that there was no
evidence of an increase in particle number concentration during the handling of
carbon nanotube material. Rather, in all cases, the field number concentration
decreased during the periods when the material was handled. But they also state
that laboratory investigation showed that nanoparticles, or better here nanoobjects
can become airborne when vigorously agitated.
Yeganeh et al. [21] on the other hand reported significant increases of sub-100
nm particle number concentrations during the handling of carbonaceous nano-
materials including fullerenes. Anyhow, no quantification of release was done due
to the highly variable background and hence the actual contribution of engineered
nanoparticles to the determined number concentration is not known.
Wake et al. [22] investigated nanoscale particles at different workplaces in
various industries, including workplaces with nanoparticle production. They conclude
that there was no evidence of significant ultrafine particle release in unagglomerated
form when working with nanoscale powders. In contrast, processes involving heat,
such as welding, released high levels of nanoscale particles.
The examples above show that nearly no or little exposure was determined in
the field. This may well be due to the materials being produced and the safe work
conditions at the investigated work places. It now becomes necessary to get
comparable measurement technologies and measurement strategies in place to
investigate the various work places in nanoparticle production facilities. Exposure
to nanoparticles and nanoobjects has to be carefully screened to ensure a safe and
sustainable development of this technology.
6. Summary
An array of measurement techniques for the determination of airborne nanoscale

particles exists. Still, the demand on these techniques, namely measurements of all
possibly health relevant particle parameters online as personal dose (personal
sampler) is extremely high and currently not fulfilled. Only few devices exist for
personal sampling (only offline and use of imaging techniques) and measurements
of the dose. Especially the latter may vary significantly since particle uptake is
size dependent (even within the size range below 100 nm) but also dependent of
physiochemical characteristics such as solubility and hygroscopicity.
The main techniques currently used are stationary systems such as the
SMPS. First assessments of comparability and reproducibility of size distribution
measurement devices show discrepancies in e.g. number concentrations, modal

size in the range of 30–40%. Uncertainties can be expected to be larger since no
protocols on data correction (e.g. diffusion losses, multiple charge correction), and
only limited information on influence of state of agglomeration on the measure-
ment results exist.
Measurement strategies are currently needed beside reproducible and comparable
measurement techniques to allow for a first assessment if product nanoparticles/
nanoobjects were released. The measurement strategy is crucial to allow for an
assessment of uncertainty and of lower detection limits.
Despite all the above problems, which still have to be dealt with, first measure-
ment results indicate that
1. Measurements are currently feasible
2. Monitoring on a routine base can also be done and
3. No or only limited release of nanoscale particles or objects has been detected
Nevertheless, it has to be kept in mind that the information base for exposure
assessment is currently built on an uncertain and limited data base which has to be
improved in size, comparability, reproducibility. This can be achieved by working
on the feasibility for routine assessments, development of reliable measurement
techniques, standardization of measurement techniques, measurement strategies,
and implementation of screening/monitoring of nanoscale particles in sensitive
work areas.
Future challenges are currently especially seen in the detection of product
nanoparticles in the environment, which we believe to be currently nearly impossible
for airborne particles.
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PROCESSING OF POLYMER NANOFIBERS THROUGH
ELECTROSPINNING AS DRUG DELIVERY SYSTEMS
E. KENAWY, F.I. ABDEL-HAY, M.H. EL-NEWEHY

Chemistry Department, Polymer Research Group
Faculty of Science, Tanta University
Tanta 31527, Egypt
ekenawy@yahoo.com
G.E. WNEK
Department of Chemical Engineering
Case Western Reserve University
Cleveland, OH 44106-7217, USA
Abstract. The use of electrospun fibers as drug carriers could be promising in the
future for biomedical applications, especially postoperative local chemotherapy. In
this research, electrospun fibers were developed as a new system for the delivery
of ketoprofen as non-steroidal anti-inflammatory drug (NSAID). The fibers
were made either from polycaprolactone (PCL) as a biodegradable polymer or
polyurethane (PU) as a non-biodegradable polymer, or from the blends of the two.
The release of the ketoprofen was followed by UV–VIS spectroscopy in phosphate
buffer of pH 7.4 at 37°C and 20°C. The results showed that the release rates from
the polycaprolactone, polyurethane and their blend were similar. However, the
blend of the polycaprolactone with polyurethane improved its visual mechanical
properties. Release profiles from the electrospun mats were compared to cast films
of the various formulations.
1. Introduction
Controlled drug delivery systems have gained much attention in the last few
decades. This is due to the many advantages compared with the conventional
dosage forms such as improving therapeutic efficacy, reducing toxicity by delivering
them at a controlled rate. Recently, electrospun fibers were explored as new
device for drug delivery [1–5]. The main advantages of the fibrous carriers are that
they offer site-specific delivery of drugs to the body. Also, more than one drug can
be encapsulated directly into the fibers. Due to the high surface area and porous
structure of the electrospun fibers, they find applications in many fields such as
medicine [6–18], biosensors, catalysts, photonic, sensitized solar cells, tissue
engineering, nanocomposites, antimicrobial materials and membranes [9–31].

248 E. KENAWY ET AL.
Recently, we reported the first drug delivery system for the antibiotic
tetracycline hydrochloride from nanofibrous membranes based on poly(ethylene-
co-vinyl acetate), poly(lactic acid) and their blends [1]. Kim et al. incorporated a
hydrophilic antibiotic into poly (lactide-co-glycolide) to produce nanofibrous
scaffolds [32], while Brewster et al. used polymer based electrospun nanofibers
containing dispersions of poorly water-soluble pharmaceuticals as delivery
systems [33]. Biodegradable polymers are good candidates for applications in the
biomedical field due to their biocompatibility, their degradation and mechanical
properties.
Polycaprolactone (PCL) (Figure 11) is a rather hydrophobic semi-crystalline
polymer with a high molecular weight. It may be used in diffusion-controlled
delivery systems. The main mode of degradation for caprolactone polymers is
hydrolysis. This degradation proceeds first by diffusion of water into the material,
followed by random hydrolysis fragmentation of the material, and finally more
extensive hydrolysis accompanied by phagocytosis, diffusion, and metabolism.
The hydrolysis is affected by the size, hydrophilicity, and crystallinity of the
polymer and the pH and temperature of the environment [34].
[O(CH2)5CO]n
Figure 1. Chemical structure of polycaprolactone (PCL).
On the other hand, polyurethanes, as non-biodegradable polymer, have many

medical applications. The applications includes external devices such as wound
dressing to many types of catheters and feeding tubes to long term implants such
as pacemakers. Generally, polyurethanes are made of hard and soft domains
(Figure 22).
O O
(O CH2CH2)x O C NH CH2 NH C O CH2CH2CH2CH2 O
Polyol Isocyanate Extender
Figure 2. Chemical structure of polyurethane (PU) (Tecophilic Resin HP-60D-60).
The diisocyanate and extender make up the hard domains and the macrodiol
makes the soft domain. Tecophilic is a reaction product synthesized from hydro-
genated methylene diisocyanate (HMDI) (diisocyanates), poly (ethylene glycol)
(macrodiols) and 1, 4-butanediol (chain extenders).
In this work, fibrous membranes containing ketoprofen based on polycapro-
lactone (PCL), polyurethanes and their blends were prepared from electrospinning.
Various blends were prepared and the release of the ketoprofen from the various
PROCESSING OF POLYMER NANOFIBERS THROUGH ELECTROSPINNING 249
membranes was investigated at body temperature (37°C) and at room temperature

(20°C).
2. Experimental
2.1. GENERAL EXPERIMENTAL PROCEDURE
2.1.1. Materials
Polycaprolactone (PCL) (average Mw 80,000k g/mole), methanol, chloroform,

sodium phosphate dibasic (Na2HPO4) and potassium phosphate monobasic
(KH2PO4) were purchased from Aldrich (USA). Polyurethane (PU) (Mw 120,000k
g/mole, was measured by GPC using PMMA or PS standard) was purchased from
Thermedics Polymers Products, a division of VIASYS Healthcare (USA).
Ketoprofen was purchased from Sigma (USA). All these materials were used as
received without further purification.
2.1.2. Characterization Techniques
The morphology of a dried mats and films were investigated with a JSM-820
scanning electron microscope (SEM) (JEOL Ltd., USA). The thickness of
electrospun mats and films was measured using a Precision Micrometer, Model
No. 49-61, Range: 0–1.270 mm, Testing Machines, INC. AMITVILLE N.Y.
(USA). UV spectra were recorded using GENESYS™ 6 Spectrophotometer
(USA).
2.1.3. Preparation of Phosphate Buffer Solution (PB)

The phosphate buffer solution (pH 9.0) was prepared as described previously [35]
by dissolving sodium phosphate dibasic (Na2HPO4) (35.49 g) in 1 l deionized
water and the pH was adjusted to 9.0 using 0.1N sodium hydroxide and 0.1N
hydrochloric acid solutions. The phosphate buffer solution (pH 7.4) was prepared
by dissolving sodium phosphate dibasic (Na2HPO4) (21.70 g) and potassium
phosphate monobasic (KH2PO4) (2.60 g) in 1 l deionized water and the pH was
adjusted to 7.4 using 0.1N sodium hydroxide and 0.1N hydrochloric acid
solutions. The pH 2.0 buffer solutions were adjusted with 0.1N hydrochloric acid
and the pH was adjusted to 2.0 using 0.1N sodium hydroxide and 0.1N
hydrochloric acid solutions.
2.2. ELECTROSPINNING
2.2.1. Preparation of Polymer Solution and Fiber Aggregates

2.2.1.1. Polyurethane (PU)
Polyurethane (PU) solution was prepared by dissolving PU in chloroform by
heating at 65–70°C for 3–4 h with stirring to obtain a concentration of 10%
solution by weight (w/w). Ketoprofen in concentration of 5% w/w PU was

dissolved in a small amount of methanol and was added to PU solution and was
stirred for 20–30 min before electrospinning.
2.2.1.2. Polycaprolacton (PCL)
Polycaprolactone (PCL) solution was prepared by dissolving PCL in chloroform
at room temperature overnight with vigorous stirring to obtain a concentration of
10% w/w. Ketoprofen in concentration of 5% w/w PU was dissolved in a small
amount of methanol and was added to PCL solution and was stirred for 20–30 min
before electrospinning.
2.2.1.3. Polyurethane/Polycaprolactone) Blend
Blend of PU/PCL with different ratio (PU/PCL: 75/25, 50/50 and 25/75) was
prepared as following: Polyurethane (PU) solution was prepared by dissolving PU
in chloroform on heating at 65–70°C for 3–4 h with stirring. The solution was
cooled to room temperature and then polycaprolactone (PCL) was added and the
solution was stirred at room temperature overnight to give a total concentration of
10% w/w. Ketoprofen in concentration of 5% w/w PU/PCL blend was dissolved
in a small amount of methanol and was added to the solution and was stirred for
20–30 min before electrospinning.
2.3. GENERAL PROCEDURE FOR ELECTROSPINNING PROCESS
A schematic diagram of the electrospinning process is shown in (Figure 3). It

consists of a syringe with a flat-end metal needle cut, a syringe pump (model 100
KD scientific Inc., New Hope, PA) for controlled feeding rates, a grounded
cylindrical stainless steel mandrel, and a high voltage DC power supply
(Spellman, CZE1000R, Spellman High voltage Electronics Corp., Hauppauge,
NY). The solution was placed in a syringe; positive or negative voltage was
applied to initiate the jet. The feeding rate was controlled by the syringe pump and
the tip-to-collector distance (TCD) was adjusted. The electrospun mats was dried
in a hood at room temperature overnight. For the purpose of comparison, casting
film containing the same materials was made onto Petri dish.
Figure 3. Schematic of electrospinning system.

2.4. IN VITRO DRUG RELEASE TESTS
2.4.1. Determination of Total Ketoprofen Content
Ten milligram of mat or film were suspended in 10 ml basic solution of pH 9.0

(sodium hydroxide solution). The mixture was maintained at 60°C and the amount
of ketoprofen released by hydrolysis was determined by UV spectrophotometer at
λmax = 260 nm.
2.4.2. In Vitro Drug Release
The release of ketoprofen was determined by UV spectrophotometer at λmax = 260

nm as a function of time. The procedure used was as following: 10 mg of
electrospun mat or film was placed in 10 ml phosphate buffer (PB) of pH 7.4 and
was shacked in a shaking water bath (Shaker Water bath, Model #25, USA) at
37°C and 20°C.
3. Results and Discussions
Non-steroidal anti-inflammatory drugs (NSAIDs) are used for controlling pain and
inflammation in rheumatic diseases. Administration of acidic NSAIDs to arthritic
patients relieves pain and inflammatory swelling [36]. While NSAIDs have many
advantages, one of their few disadvantages is a relatively short plasma half-life.
This results in short activity duration, and a pronounced ulcerogenic potency
[37-38]. Ketoprofen (Figure 4), our drug model, is one of NSAIDs group. It is
effective as anti-inflammatory agent in humans with floristic diseases.
O
CH3
=
CHCOOH
Figure 4. Chemical structure of ketoprofen.
In the current work, new systems of controlled drug release via electrospinning
technique were developed. Electrospun polycaprolactone as biodegradable system
and polyurethane as non-biodegradable system for drug delivery were prepared.
Polycaprolactone has poor mechanical properties; therefore, it was blended with
polyurethane to improve its mechanical properties.
3.1. PREPARATION OF FIBER AGGREGATES
3.1.1. Polyurethane (PU)

Polyurethane with ketoprofen entrapped on it was electrospun from 10% w/w
solution with feeding rate 5–11 ml/h when 20 kV was applied with TCD 20 cm. A
(a) (b)
(c) (d)
(e)
Figure 5. SEM micrograph of electrospun PU, PCL and their blends containing ketoprofen drug,
(a): PU; (b): PCL; (c): PU/PCL 75/25, (d): PU/PCL 50/50 and (e): PU/PCL 25/75.
rotating metal drum was used to collect the resulting fiber to give a white sheet of
non-woven fiber. The non-woven fiber diameters ranged from 3.12 to 6.25 μm.
The sheet thickness ranged from 104 to 143 μm. The SEM of electrospun fiber is
shown in (Figure 5). The electrospun mat is opaque due to light scattering from
the fibrous structure. Casting film was prepared and the film thickness ranged
from 200 to 269 μm.
3.1.2. Polycaprolactone (PCL)
Polycaprolactone with ketoprofen entrapped on it was electrospun from 10% w/w

solution with feeding rate 6–7 ml/h when 20 kV was applied with TCD 15 cm. A
rotating metal drum was used to collect the resulting fiber to give a white sheet of
non-woven fiber. The non-woven fiber diameters ranged from 2 to 6.66 nm and
the sheet thickness ranged from 113 to 120 μm. The SEM of electrospun fiber is
shown in Figure 5. The electrospun mat is opaque due to light scattering from the
fibrous structure. SEM detected no ketoprofen crystals on the surface of the fibers,
indicating this indicated that ketoprofen was perfectly embedded in the fibers.
Casting film was prepared and the film thickness ranged from 196 to 204 μm.
3.1.3. Polyurethane/Polycaprolactone (PU/PCL) Blend
Blends of polyurethane and polycaprolactone with different ratios (PU/PCL:

75/25, 50/50 and 25/75) with ketoprofen entrapped on it were electrospun from
10% w/w solution. Generally, the electrospun mat is opaque due to light scattering
from the fibrous structure.
3.1.3.1. PU/PCL (75/25) Blend
PU/PCL (75/25) blend with ketoprofen entrapped on it was electrospun with
feeding rate 6 ml/h when 20 kV was applied with TCD 15 cm. The produced non-
woven fiber diameters ranged from 1 to 7 μm. The sheet thickness range was 65–
88 μm. The SEM of electrospun fiber before and is as shown in Figure 5. This
indicated that there ketoprofen was perfectly embedded in the fibers. For
comparison studies, casting film was prepared and the film thickness ranged from
200 to 255 μm.
3.1.3.2. PU/PCL (50/50) Blend
When voltage of 22 kV was applied to solution of PU/PCL: 50/50 with ketoprofen
entrapped on it with feeding rate 6–8 ml/h and TCD 15 cm, non-woven fiber of
diameters ranged from 1.75 to 6.45 μm were obtained. The sheet thickness ranged
from 85 to 106 μm. The SEM of electrospun fiber is as shown in Figure 5. The
film thickness ranged from 238 to 297 μm.
3.1.3.3. PU/PCL (25/75) Blend

Non-woven fiber of (PU/PCL: 25/75) with ketoprofen entrapped on it from 10
wt% solution was obtained when a voltage of 21 kV was applied, with feeding
rate 6 ml/h and TCD 15 cm. The non-woven fiber diameters ranged from 1 to 4.25
μm. The sheet thickness ranged from 74 to 112 μm. The SEM image of electrospun
fiber is shown in Figure 5. The cast film thickness ranged from 160 to 179 μm.
3.2. DETERMINATION OF TOTAL KETOPROFEN CONTENT
To evaluate the total content of ketoprofen in the samples, they were hydrolyzed
by heating or sonication of a known amount of the mat or film in alkaline solution
of pH 9.0. The amount released of ketoprofen from the sample was determined by
UV spectrophotometer at λmax = 260 nm, at room temperature within 30 min.
Then, the samples were heated at 60°C. The drug concentration was monitored by
UV spectrophotometer until it reaches a constant concentration for the drug.
3.2.1. Polyurethane (PU)
The fast release studies of ketoprofen trapped in the polyurethane (PU) in the
alkaline solution of pH 9.0 at 60°C showed that, the total ketoprofen content of
PU-spun was 49.97 (mg ketoprofen)/(g polymer) and for PU-film was 51.12 (mg
ketoprofen)/(g polymer) (TABLE 1).
3.2.2. Polycaprolactone (PCL)
Based on the fast release of ketoprofen studies from polycaprolactone in the

alkaline solution of pH 9.0 at 60°C, the ketoprofen content for electrospun PCL
was 52.30 (mg ketoprofen)/(g polymer) and 48.21 (mg ketoprofen)/(g polymer)
for PCL-film (TABLE 1).
3.2.3. PU/PCL (75/25)
The fast release studies of PU/PCL (75/25) blend with ketoprofen entrapped on it
in alkaline solution of pH 9.0 at 60°C, showed that the total ketoprofen content for
PU/PCL (75/25)-mat was 46.94 (mg ketoprofen)/(g polymer) and 48.62 (mg
ketoprofen)/(g polymer) for PU/PCL (75/25)-film (TABLE 1).
3.2.4. PU/PCL (50/50)
The studies of PU/PCL (50/50) blend in alkaline solution of pH 9.0 at 60°C

showed a total ketoprofen content of 50.44 (mg ketoprofen)/(g polymer) for
PU/PCL (50/50)-mat and 48.67 (mg ketoprofen)/(g polymer) for PU/PCL (50/50)-
film (TABLE 1).
3.2.5. PU/PCL (25/75)
PU/PCL (25/75) blend with ketoprofen entrapped on it in alkaline solution of pH

9.0 at 60°C, showed a total ketoprofen content for electrospoun PU/PCL (25/75)
of 49.68 (mg ketoprofen)/(g polymer) and 48.79 (mg ketoprofen)/(g polymer) for
PU/PCL (25/75)-film (TABLE 1).
TABLE 1. Ketoprofen content for electrospun mat and film made from PU, PCL and their blends after
sonication for 24 h at 60°C.
(mg ketoprofen)/(g polymer)
Polymer code
Found from hydrolysis Calculated
PU-spun 49.97 50.08
PU-film 51.12 51.78
PCL-spun 52.30 52.69
PCL-film 48.21 53.58
PU/PCL:75/25 spun 46.94 49.03
PU/PCL:75/25 film 48.62 49.03
PU/PCL:50/50 spun 50.44 50.86
PU/PCL:50/50 film 48.67 51.45
PU/PCL:25/75 spun 49.68 49.75
PU/PCL:25/75 film 48.79 49.95
3.3. IN VITRO DRUG RELEASE
The rate of ketoprofen released from electrospun fibers was studied at pH 7.4 and
various temperatures. The rate of release is likely to depend on the temperature.
The electrospinning technique is newly utilized in the field of drug delivery
[1–5]. It provides a unique and simple technique for the drug delivery. The
advantages of this technique are that it could be applied for wide range of
pharmaceutical compounds either functionalized or non-functionalized. It could be
used for more than one drug at the same time; in addition, more than one polymer
could be used to be electrospun at one jet at the same time. Also, it is possible to
be electrospun as layers. It could be applied directly for transdermal drug delivery,
used as a nerve guide or as a bag for the biohemostate devices.
3.3.1. Drug Release from Electrospun Fiber and Film Made from
Polyurethane (PU)
The release rates of ketoprofen from electrospun fiber and cast film made from
polyurethane were studied in pH 7.4 at 37°C and at 20°C. In general, the trend of
release from both electrospun mat and cast film showed initial fast release in the
first few hours followed by slower release rates as shown in (Figure 6).
Investigation of the release profiles showed that the electrospun polyurethane
exhibited initial burst release even at 20°C. However, the release rate of the
ketoprofen drug from the electrospun polyurethane mat showed relatively higher
release rate at 37°C than that at 20°C as shown in (Figure 6). It released a total
amount of 47.61 (mg drug)/(g polymer) which represents 95.28% of its drug
content at 37°C. Whereas, it released 43.80 (mg drug)/(g polymer) which
represents 87.64% of its drug content at 20°C. For comparison, film was cast from
polyurethane containing the same amount of ketoprofen. The release profile of the
drug from the cast film is as shown in (Figure 6). It also showed initial fast release
within the first few hours followed by a slower release rate. At 37°C, the total
amount released of ketoprofen from cast film was 44.96 (mg drug)/(g polymer)
which represents 87.96% of its drug content. At 20°C, the total amount released of
ketoprofen from cast film was 38.59 (mg drug)/(g polymer) which represents
75.51% of its drug content. Again, the effect of temperature here was clear. As it
increased, the amount of ketoprofen released from the cast polyurethane film
increased from 75.51% to 87.96% of its drug content. This is expected because the
release from the film is diffusion dependent and the temperature increases the
diffusion rate. Comparison between the amount released of ketoprofen from
the electrospun PU mat and the PU cast film is as shown in (Figure 6). At 37°C,
the difference between the amount released from both electrospun mat and cast
film was not high. This could be due to the effect of temperature on the diffusion
from the film, which increases the release rate. This increment due to temperature
effect diminishes the effect of high surface area of the electrospun fibers. While at
lower temperature, 20°C, the diffusion rate is lower. Consequently, the high
surface area of the electrospun fibers showed high release rate compared to the
cast film.
100
Cumulative drug released (%)
80
60 spun-20°C
spun-37°C
film-20°C
40 film-37°C
20
0
0 40 80 120 160 200 240 280 320 360
Time (h)
Figure 6. In vitro release profile of ketoprofen from electrospun mat and film made from PU in
phosphate buffer pH 7.4 at the 37°C and 20°C.
3.3.2. Drug Release from Electrospun Fiber and Film Made from
Polycaprolactone (PCL)
The ketoprofen released from the PCL mat and film was studied at 37°C
(approximate body temperature) and at 20°C in phosphate buffer of pH 7.4. The
release profiles are shown in Figure 7. The release from electrospun PCL at 20°C
was slower than that released at 37°C. It showed an initial fast release at both
temperatures. It released about 39.61% of its drug content within the first 2 h at
37°C, and then the release rate was slower as shown in Figure 7. It released 44.18
(mg drug)/(g polymer) which represents 84.48% of its drug content within 2
weeks at 20°C, whereas 50.65 (mg drug)/(g polymer) which represents 96.85% of
its drug content at 37°C was released within the same period. Cast film from PCL
showed a total release of 38.66 (mg drug)/(g polymer) which represents 80.36% of
its drug content at 37°C while it showed 36.64 (mg drug)/(g polymer) which
represents 76.16% of its drug content at 20°C. Comparison between the
electrospun mat and cast film showed initial fast release at both 20°C and 37°C
within the first few hours. After about 2 h, the profile showed a faster release from
the electrospun mat than the film. It showed a total release of 50.65 (mg drug)/(g
polymer) which represents 96.84% of its drug content after 2 weeks at 37°C and
44.18 (mg drug)/(g polymer) which represents 84.47% of its drug content at 20°C
after the same period. The same phenomenon was observed at 20°C for both PCL
mat and film.
100
80
60 spun-20°C
spun-37°C
film-20°C
40 film-37°C
20
0
0 40 80 120 160 200 240 280 320 360
Time (h)
Figure 7. In vitro release profile of ketoprofen from electrospun mat and film made from PCL in
phosphate buffer pH 7.4 at 37°C and 20°C.
3.3.3. Drug Release from Electrospun Fibers and Films Made from
Polyurethane/Polycaprolactone (PU/PCL) Blends
3.3.3.1. Polyurethane/Polycaprolactone (PU/PCL: 75/25) Blend.

The ketoprofen release profiles from electrospun fiber and film made from
(PU/PCL: 75/25) are shown in Figure 8. The ketoprofen release was studied at
37°C and at 20°C in phosphate buffer of pH 7.4. At 37°C, the amount released of
ketoprofen from electrospun fiber within the first 2 h was 29.46 (mg drug)/(g
polymer) which represents 62.76% of its drug content as shown in Figure 8, while
it released 42.68 (mg drug)/(g polymer) which represents 90.93% of its drug
content after 2 weeks. At 20°C, it released 23.94 (mg drug)/(g polymer) which
represents 51.01% of its drug content within the first 2 h. After 2 weeks, a slight
increase in the amount released of ketoprofen was observed, it released 36.33 (mg
drug)/(g polymer) which represents 77.40% of its drug content. Cast film of
(PU/PCL: 75/25) showed a total release of 79.88% of its drug content at 37°C
while it showed 59.35% of its drug content at 20°C. Comparison between the
amounts released of ketoprofen from the electrospun fiber and cast film. Both of
the electrospun fiber and cast film showed initial fast release at both 37°C and at
20°C within the first few hours. After 2 h, the release profile showed a faster
release for the electrospun mat than the film. Electrospun fiber showed a total
release of 42.68 (mg drug)/(g polymer) which represents 90.93% of its drug
content after 2 weeks at 37°C and cast film showed a total release of 38.84 (mg
drug)/(g polymer) which represents 79.88% of its drug content after the same
period. The initial fast release was also observed at 20°C for both electrospun mat
and film.
100
80
60 spun-20°C
spun-37°C
film-20°C
40
film-37°C
20
0
0 40 80 120 160 200 240 280 320 360
Time (h)
Figure 8. In vitro release profile of ketoprofen from electrospun mat and film made from (PU/PCL:
75/25) blend in phosphate buffer (pH 7.4) at 37°C and 20°C.
3.3.3.2. Polyurethane/Polycaprolactone Blend (PU/PCL: 50/50).

The ketoprofen release profiles from electrospun fiber and cast film of (PU/PCL:
50/50) are shown in (Figure 9). The release was studied at 37°C and 20°C in
phosphate buffer of pH 7.4. At 37°C, the amount released of ketoprofen from
electrospun fiber within the first 2 h was 30.24 (mg drug)/(g polymer) which
represents 59.95% of its drug content, while it released 44.63 (mg drug)/(g
polymer) which represents 88.49% of its drug content after 2 weeks. At 20°C, it
released 27.59 (mg drug)/(g polymer) within the first 2 h which represents 54.69%
of its drug content, while it showed a total release of 41.51 (mg drug)/(g polymer)
which represents 82.30% of its drug content after 2 weeks. The in vitro drug
released from (PU/PCL: 50/50) cast film was also investigated. The total amount
released of ketoprofen was 34.87 (mg drug)/(g polymer) which represents 71.66%
of its drug content after 2 weeks at 37°C and 24.12 (mg drug)/(g polymer) which
represents 49.57% of its drug content at 20°C. Comparison between the electrospun
fiber and cast film, showed initial fast release at both 37°C and 20°C within the
first 2 h. After about 2 h, the profile showed a faster release from the electrospun
mat than the film. This is due to the high surface area of the electrospun fibers
compared to the cast films. Electrospun fiber showed a total release of 30.24 (mg
drug)/(g polymer) which represents 59.95% of its drug content after 2 weeks at
37°C and cast film showed a total release of 21.48 (mg drug)/(g polymer) which
represents 44.14% of its drug content after the same period. The initial fast release
phenomenon was also observed for electrospun mat and the cast film of (PU/PCL:
50/50) at 20°C. The total amount released of ketoprofen from the blend 50:50 was
higher in case of electrospun mat than the film. This is again attributed to the high
surface area of the very fine fibers.
100
80
60 spun-20°C
spun-37°C
film-20°C
40 film-37°C
20
0
0 40 80 120 160 200 240 280 320 360
Time (h)
Figure 9. In vitro release profile of ketoprofen from electrospun mat and cast film made from
(PU/PCL: 50/50) blend in phosphate buffer pH 7.4 at 37°C and 20°C.
3.3.3.3. Polyurethane/Polycaprolactone Blend (PU/PCL: 25/75).

The ketoprofen release profiles from electrospun fiber and cast film of (PU/PCL:
25/75) are shown in (Figure 10). The ketoprofen release was studied at 37°C and
20°C in phosphate buffer pH 7.4. At 37°C, the amount released of ketoprofen
from electrospun fiber within the first 2 h was 33.09 (mg drug)/(g polymer) which
represents 66.61% of its drug content, while it showed a total release of 44.19 (mg
drug)/(g polymer) which represents 88.96% of its drug content after 2 weeks. At
20°C, it released 29.90 (mg drug)/(g polymer) within the first 2 h which represents
60.18% of its drug content, while it showed a total release of 40.73 (mg drug)/(g
polymer) which represents 81.99% of its drug content after 2 weeks. The in vitro
release profiles of ketoprofen from (PU/PCL: 25/75) cast film. The total amount
released of ketoprofen from cast film after 2 weeks at 37°C was 36.92 (mg
drug)/(g polymer) which represents 75.67% of its drug content and 33.73 (mg
drug)/(g polymer) released at 20°C which represents 69.15% of its drug content.
Comparison between the electrospun fiber and cast film, showed initial fast
release at both 37°C and 20°C within the first 2 h. After about 2 h, the profile
showed a faster release from the electrospun mat than the film. Electrospun fiber
showed a total release of 44.19 (mg drug)/(g polymer) which represents 88.96% of
its drug content after 2 weeks at 37°C and cast film showed a total release of 36.92
(mg drug)/(g polymer) which represents 75.67% of its drug content at 20°C after
the same period. The same effect for the device shape was explored; it was found
that electrospun mat showed faster release rate than the film, however, both
showed initial release.
100
80
60 spun-20°C
spun-37°C
film-20°C
40
film-37°C
20
0
0 40 80 120 160 200 240 280 320 360
Time (h)
Figure 10. In vitro release profile of ketoprofen from electrospun mat and film made from (PU/PCL:
25/75) blend in phosphate buffer pH 7.4 at the body temperature 37°C and 20°C.
4. Conclusion
New drug delivery systems for ketoprofen as non-steroidal anti-inflammatory drug

(NSAID) were developed. These systems were based on the encapsulation of
ketoprofen in the electrospun fibers. These fibers were either biodegradable, such
as polycaprolactone (PCL), or non-biodegradable polymers, such as polyurethane
(PU), or their blends. The ketoprofen release was monitored in phosphate buffer of
pH 7.4 at 37°C and 20°C. Generally, as the temperature increased, the amount
released of ketoprofen increased. The release rates from the polycaprolactone,
polyurethane and their blend are almost similar. However, the blend of the
polycaprolactone with polyurethane improved its visual mechanical properties.
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AIR POLLUTION MONITORING AND USE OF
NANOTECHNOLOGY BASED SOLID STATE GAS SENSORS
IN GREATER CAIRO AREA, EGYPT
A.B.A. RAMADAN
National Center for Nuclear Safety and Radiation Control
3 Ahmed El-Zomor Street, Nasr City 11762, P.O. Box 7551
Cairo, Egypt
ramadan58@yahoo.com
Abstract. Air pollution is a serious problem in thickly populated and

industrialized areas in Egypt, especially in greater Cairo area. Economic growth
and industrialization are proceeding at a rapid pace, accompanied by increasing
emissions of air polluting sources. Furthermore, though the variety and quantities
of polluting sources have increased dramatically, the development of a suitable
method for monitoring the pollution causing sources has not followed at the same
pace. Environmental impacts of air pollutants have impact on public health,
vegetation, material deterioration etc. To prevent or minimize the damage caused
by atmospheric pollution, suitable monitoring systems are urgently needed that
can rapidly and reliably detect and quantify polluting sources for monitoring by
regulating authorities in order to prevent further deterioration of the current
pollution levels. Consequently, it is important that the current real-time air quality
monitoring system, controlled by the Egyptian Environmental Affairs Agency
(EEAA), should be adapted or extended to aid in alleviating this problem.
Nanotechnology has been applied to several industrial and domestic fields, for
example, applications for gas monitoring systems, gas leak detectors in factories,
fire and toxic gas detectors, ventilation control, breath alcohol detectors, and the
like. Here we report an application example of studying air quality monitoring
based on nanotechnology ‘solid state gas sensors’. So as to carry out air pollution
monitoring over an extensive area, a combination of ground measurements
through inexpensive sensors and wireless GIS will be used for this purpose. This
portable device, comprising solid state gas sensors integrated to a Personal Digital
Assistant (PDA) linked through Bluetooth communication tools and Global
Positioning System (GPS), will allow rapid dissemination of information on
pollution levels at multiple sites simultaneously.

266 A.B.A. RAMADAN
1. Introduction
Most of industrial and nuclear activities, involving the use of energy and
transportation prominently among them, are accompanied by emission of air
pollutants. Urban air pollution, in turn, is the source of range of problems,
including health risks with inhalation of gases and particles, accelerated corrosion
and deterioration of materials. Greater Cairo is considered the most important city
in Egypt from demographical point of view. It encompasses 27% of the Egyptian
population, 64% of the industry and 45% of motor vehicles. Greater Cairo area
lies in a sub-tropical region with a dry climate, warm summers and mild winters. It
rarely gets rain. There are fairly substantial variations between daytime and
nighttime temperatures. The average summer temperature is 31°C, while that of
winter is 16°C with an average difference between day and night of 10°C. This
great temperature difference promotes the formation of dew at dawn as the relative
humidity of the air becomes generally high, especially during the winter season.
The prevailing wind velocity with an average of 3 m s−1, but gusts of up to 4–5
m s−1 may be experienced in early morning and late afternoon. Dust storms also
occur during April and May when the Khamasin winds blow over the Egyptian
western desert with a wind speed of the order of 10 m s−1. Relative humidity
fluctuates between 59% in June and 71% in December, with visibility of about 5
km. This restricted visibility is the result of the presence of solid particles in the
atmosphere. The strong emissions of trace gases and aerosol particles by vehicles
traveling on the city’s narrow roads, industry and resuspended soil dust, together
with secondary aerosol, coupled with the unfavourable natural conditions of
dispersion, are responsible for the high concentrations of pollutants observed in
the greater Cairo metropolitan area. Greater Cairo areas suffers from high ambient
concentrations of atmospheric pollutants [1–3], including particulates (PM),
carbon monoxide (CO), oxides of nitrogen (NOx), ozone (O3) and sulfur dioxide
(SO2). Nasralla [1] reported particulate lead concentrations ranged from 0.5 µg/m3
in a residential area to 0.3 µg/m3 at the city centre. Sturchio et al. [2] measured
total suspended particulate (TSP) and lead concentrations using stable isotopic
ratios (207Pb/204Pb and 208Pb/204Pb) at 11 sites in Cairo. Lead and TSP
concentrations ranged from 0.08 to 25 µg/m3, respectively at Helwan to over 3 and
1,100 µg/m3, respectively, at the city centre.
Rodes et al. [4] measured fine (PM2.5) and coarse (PM10-PM2.5) concentrations
as a part of a source apportionment study in Cairo from December 1994 to
November 1995. The annual average PM10 concentrations exceeded the 24 h
average US standard of 150 µg/m3 at all sites except Ma’adi and the background
site. In general, one can see that air pollution level is high during winter months
and create winter syndrome due to low temperature, low mixing depth, pollution
inversion, traffic density, driving habits or due to ratio of automobiles to trucks.
In recent years there has been considerable concern about the many adverse
effects of elevated air pollutants levels in the atmosphere, which are associated
with various anthropogenic and natural processes. In the meantime, photochemical
smog formation has been observed in Cairo metropolitan areas [2]. Photochemical
AIR POLLUTION MONITORING AND USE OF NANOTECHNOLOGY 267
smog is a complex mixture of atmospheric pollutants termed photo-oxidants,

which are rapidly formed on warm sunny days through reactions of volatile
hydrocarbons and other oxidisable organic compounds with nitrogen oxides under
the influence of sunlight [5].
The aims and objectives of this paper approach include: (1) To apply a suitable
gas sensing device coupled to a personal digital assistant for continuous
monitoring of urban air pollution and disseminate the information in real time
through wireless GIS. (2) To build up a simple monitoring system using low cost
portable gas sensing systems. (3) To assist in establishing priorities, measurements
of air pollution in greater Cairo area and increasing public awareness and
enhanced public participation.
2. Air Pollution in Greater Cairo Area
Greater Cairo area’s geographic location and its industrial and population deve-
lopment make it vulnerable to the problems caused by atmospheric particulate
matter and ozone. Because of the situation outlined above and Egypt’s location at
latitude 30o N with more than 340 days of sunshine per year, it is expected that
high levels of photochemical smog occur in Egypt, especially greater Cairo area
today, with higher levels predicated for the near future. Air quality in the streets of
greater Cairo area has become critical and the predominant cause of air pollution
in downtown street is vehicle emission. Crowded traffic density and flow conditions
in Cairo city have become worse and ambient air quality has deteriorated as a
result. A decade ago the health costs of exposure to lead (Pb), particulate matter
(PM), and carbon monoxide (CO) in Cairo were estimated to be equivalent to
between 8% and 12% of urban annual income. These pollutants are mostly
emitted by the transport sector. During the last years the ambient levels of key
pollutants – Pb, particulates, SO2 and CO-in Cairo and other urban centers have
fallen dramatically. Using as an example of visibility measurements at Helwan
area, air quality has improved since 2001, and even improvements are reported in
PM10 levels. Concentration levels of NOx and CO are stable and declining
respectively. SO2 concentrations are not so high but it can exceed the Air Quality
Limit value under certain conditions. Also SO2 levels have declined substantially
as new technology has been established at the country’s power plants. Ozone (O3)
levels are still causing concern with Maximum levels exceeding the standard [6].
Downwind transport of ozone precursors from heavily populated areas in Cairo
causes the high ozone concentrations at locations to the south. Diurnal variation of
ozone exhibits a seasonal variability, with the maximum diurnal variation during
summer. PM10 is still the most critical problem facing Egypt. It still giving very
high concentrations which can reach six times the Air Quality limit value as daily
average this may be due to the high background in Egypt which is mainly
generated by wind blown dust. Highest concentrations of PM10 are found in
industrial and traffic areas. PM10 exhibits two maxima during the year, each forced
by a different mechanism. The first occurs during the spring, is sharp and of
shorter duration, and is forced by the sand storms during Khamseen conditions.
268 A.B.A. RAMADAN
The second peak is during the fall, with longer duration and less amplitude, and is
due to pollution episodes associated with the more local meteorological conditions
of the season. All VOC group-totals are indoors higher than outdoors but only the
concentrations of alkanes and terpenes are statistically significant higher indoors
than outdoors [7]. The concentration of the group of aromatic hydrocarbons is in
Cairo indoors and outdoors nearly identical.
3. Air Quality Monitoring System
The EEAA has been measuring air quality levels through the automatic monitoring
system and reporting real time air quality levels through the Internet as air quality
index (AQI) maps (Figure 1). Air quality monitors comprise 40 permanent stations
and are set up at roadside and general sites. Unfortunately, the cost of establishing
and implementing traditional monitoring systems is extremely high. This air
quality monitoring system can measure and report air quality levels in real time;
nevertheless there is still a huge disadvantage that this monitoring system cannot
be implemented at many sites to monitor air pollution over an extensive area
Figure 1. Location of air quality monitoring stations in the greater Cairo area.
because of high costs. To substitute the typical analytical tools and adapt or extend
the air quality monitoring system of EEAA with a new generation of detectors,
nanotechnology based metal oxide semiconductors such as ZnO semiconductor
used in this study are a viable alternative. In fact these solid state gas sensors offer
an excellent opportunity for implementation in environmental monitoring due to
light weight, extremely small size, robustness, low cost and also as they can be
installed anywhere to collect data covering extensive areas. The air quality data
can eventually be transmitted through a Wireless GIS network system to the
general public.
4. Nanotechnology
The nanotechnology realm has traditionally been defined as lying dimensions

between 0.1 and 100 nm. Nanotechnology has been applied to industry for
example in textile, medicine and health, computing, transportation, aeronautics
and space exploration, environment, and so on. In the last decade the specific
demand for gas detection and monitoring has emerged especially as the awareness
of need to protect the environment has grown [8]. Gas sensors are applied in
numerous fields of applications [9]. In the present case, a nanotechnology based
gas sensors application for studying air pollution is described. The answer to why
use nanotechnology based solid-state gas sensor is that increasing the surface to
bulk atom ratio increases grain size dependence, meaning increasing gas
adsorption and more sensitivity [10].
4.1. SOLID STATE GAS SENSORS FOR AIR POLLUTION
Gas sensors for detecting air pollutants must be able to operate stably under
deleterious conditions, including chemical and/or thermal attack. Therefore, solid
state gas sensors appear to be the most appropriate in terms of their practical
robustness. The sensors used for detecting air pollutants are usually produced
simply by coating a sensing (metal oxide) layer on a substrate with two electrodes.
Typical materials are tin oxide (SnO2), zinc oxide (ZnO), titanium oxide (TiO2)
and tungsten oxide (WO3) with typical operating temperatures of 200–400°C [11].
The general mechanism for a metal oxide sensor is a change in the resistance (or
conductance) of the sensor when it is exposed to pollutant gas, relative to the
sensor resistance in background air. The sensor resistance is the best-known
sensor output signal and is in most cases determined at constant operation
temperature and by DC-measurement [11]. AC measurements have also been
reported [12] but are more frequently used in impedance spectroscopy [13] at a
modeling level. Figure 2 explains how metal oxide semiconductor detects
pollutant gases. The depletion zone at the surface of metal oxide sensor is due to
absorption of atmospheric oxygen. When the metal oxide sensor absorbs a
reducing gas (CO, H2), depletion area at the surface will be decreased, meaning
increasing conductivity. On the other hand, if a metal oxide sensor absorbs an
oxidizing gas (NO2), the depletion zone at the surface will be increased, meaning
270 A.B.A. RAMADAN
decreasing conductivity. In conclusion, a change of conductivity/resistance is

related to gas concentration. In the case of a ZnO sensor, conductivity decreases
that means resistance increases when the sensor absorbs NOx, dependent on NOx
concentration [11].
Figure 2. Schematic diagram of a metal oxide semiconductor following [11].
5. Internet GIS
Internet GIS is a relationship between GIS and Internet. Users will be able to
access GIS applications without purchasing GIS software by using a web browser.
Detailed maps can be generated from huge databases of spatial information and
distributed all over the world. The Web is a cost effective way to share or provide
public access to data worldwide on the Internet.
As shown in Figure 3, the wireless GIS Data Logging System being developed
in this study is composed of two parts, i.e. hardware and software. On the
hardware side, a Mandrake 9.1 Server provides the back-end support. A user has
in hand a Personal Digital Assistant operated on Pocket PC. So as to be complete,
a Global Position Receiver (GPS) and Digital camera can be also integrated
through proper extensions. On the software side, a Minnesota Map server 4.4.0
ensures Web Map Service (WMS), which is an Open Source Common Gateway
Interface (CGI) based development environment for building spatially enabled
Internet applications. The server setup is made up of Postgre SQL, Post GIS and
PHP, configured with each other to execute the client’s request and manage the
database. The client setup is composed of interfaces, developed using JavaScript
and Hyper Text Markup Language (HTML) [14]. For wireless Data Updating
System, it is composed of three tiers, including Front-End Tier, Middle-Tier and
Back-End Tier. On the Front-Tier is the client, making a request, Minnesota Map
Server in the Middle Tier passes the CGI-request over to the Back-End Tier where
PHP and PostgreSQL with PostGIS read the data and execute the request.
Update, Insert,
Delete GIS Request
PHP Compiler
Data With PostgreSQL
Function
Client
side
PostGIS (Browser)
PNG
Mapserver
PostgreSQL WMS
Server side GML
Shape file
GIS Data
Back-End Middle Front-End

Tier Tier Tier
Figure 3. Flow chart showing Internet GIS set up.
6. NOx Observation Using the ZnO Sensor
The data used for this study are composed of measured NOx concentration from
ten stationary air quality monitoring sites as shown in Figure 4. A limited number
of observation sites were taken to test the method at locations which are critical
for automobile pollution. The data were collected every hour from 0700 h until
1900 h, which were fed to the GIS for further processing. It is supposed that more
air sampling points are needed for more accurate interpolation techniques, or
interpolation by creating a buffer at each point is supposed to be more suitable
method for this study as shown in Figure 4.
7. Integrating GIS with Nanosensors
The solid-state gas sensor gives out electric signals, related to NOx concentration.
An A/D circuit converter converts the NOx concentration values from an analog to
digital signal. NOx concentration levels, acquired from monitoring sites, GIS base
maps and attributes were input into Personal Digital Assistant linked with GPS.
The results were utilized for air quality level modeling of the study area. The
model developed were used for acquiring and monitoring real time air quality
levels and also updating information through wireless GIS using WMS. The
information on the resulting air quality levels can operate as a monitoring system
and be displayed in the form of GIS database. The air quality levels were
272 A.B.A. RAMADAN
categorized into five classes, overlaid with Cairo GIS base maps. The five classes
of air quality level reported include hazardous, very unhealthy, unhealthy,
moderate and good. Hence, Internet users can browse and query air quality
interpolated maps, relating to geographic information, including districts, roads,
urban settlement, and historical air quality level. The Internet based GIS is useful
real time interaction on air quality levels and increases public awareness and
participation.
Nanosensors and Digital NOx

Evaluation Kit A /D converter Concentration
GIS base map of BKK Digital

- Admin. boundary PDA Camera
- Population
Ambient air
- Road GPS
smapling
- Urban settlement
Report real time AQ data

through wireless GIS
Figure 4. Conceptual framework for NOx monitoring using nanosensors integrated with internet GIS.
8. Conclusion and Discussion
Current air quality of greater Cairo area is better than a decade ago. However,
greater Cairo area still has been facing serious air pollution problems. As seen in
central Cairo, black and white smoke from truck and public bus exhaust still
occurs. This is attributed to the rapid economic and industrial growth, combined
with a lack of strict implementation of air quality and requires the EEAA to adapt
or extend the current EEAA’s air quality monitoring systems and also facilitate the
problem of analyzing and monitoring air pollution in greater Cairo area. The
traditional air quality monitoring system, controlled by the EEAA, is extremely
expensive. Analytical measuring equipment is costly and time consuming, and can
seldom be used for air quality reporting in real time. The EEAA has been
forecasting and reporting real time air quality levels through the Internet in the
form of maps. However, the air quality index of each monitoring site is just shown
by rather coarse levels; good, moderate, unhealthy, very unhealthy and hazardous.
The air quality report should be more in detail, including information such as air
quality interpolated maps, relating to other information for better understanding
the air quality level. For these reasons, this work is aimed to build up an easy
monitoring system using low cost portable gas sensing systems ‘solid state gas
sensors’ so as to carry out air pollution monitoring over an extensive area and to
be able to report real time air quality data through Wireless Internet GIS.
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ADVANCED MATERIAL NANOTECHNOLOGY IN ISRAEL
O. FIGOVSKY, D. BEILIN, N. BLANK

Polymate, Ltd.
International Nanotechnology Research Center
Migdal Ha’Emek, Israel
polymate@borfig.com
Abstract. One of the most interesting directions in material engineering during the
past few years is the technical development of nanocomposite materials consisting
from two or more phases with precise interphase border and nanostructured
materials based on interpenetrated polymer network. Israel is one of world leaders
in fundamental and industrial nanotechnology research, including fostering of
start-up companies. Some important developments in the field of nanotechnology
material engineering in Israel are summarized in the paper.
1. Introduction [1–6]
The economic, security, military, and environmental implications of molecular

manufacturing are diverse. Unfortunately, conflicting definitions of nanotechnology
and blurry distinctions between significantly different fields have complicated the
effort to understand those differences and to develop sensible, effective policy for
each.
The risks of today’s nanoscale technologies cannot be treated the same as the
risks of longer-term molecular manufacturing. It is a mistake to group them in
policy considerations – each is important to address, but they offer different
problems and will require far different solutions. The field of nanotechnology
usually involves a broad collection of diverse fields. Essentially, anything suffi-
ciently small and interesting can be called nanotechnology. It has been projected
that many of these materials are benign. Molecular manufacturing, by contrast,
will bring unfamiliar risks and new types of problems.
Desktop nanofactories will use vast arrays of tiny machines to fasten single
molecules together quickly and precisely, allowing engineers, designers, and
potentially anyone else to make powerful products at the touch of a button.
Although such a contraption has been envisioned in some detail for almost two
decades, with the basic concept dating back to 1959 when the physicist R. Feynman
first described it, it’s only in recent years that technology has advanced to the
point where we can begin to see the practical steps that might bring it into reality.

276 O. FIGOVSKY ET AL.
The essence of nanotechnology is the ability to work at the molecular level to

create large structures with fundamentally new molecular organization. Materials
with features on the scale of nanometers often have different properties from their
macroscale counterparts. The prospect of a new materials technology that can
function as a low-cost alternative to high-performance composites has, thus,
become irresistible around the world. By this means nanotechnology presents a
new approach to material science and engineering as well as for design of new
devices and processes. Figures 1–3 provide perspective on the global momentum
of nanotechnology development.
Composite materials are two- or multiphased with a well defined interphase
border. Such materials contain the reinforcing elements immersed into a polymeric,
ceramic or metal matrix. Mechanical properties of composites depend on structure
and properties of the interphase border. Phases of usual composite materials have
micron and submicron sizes. Important among these nanoscale materials are
nanocomposites in which the constituents are mixed on a nanometer-length scale.
They often have properties that are superior to conventional microscale composites
and can be synthesized using surprisingly simple and inexpensive techniques.
The tendency to reduce the phase’s sizes of a filler (a strengthening element) is
attributable to a decrease in its microscopic deficiency (the size of one of nano-
composite phase is less than 100 nm). The reinforced polymer remains transparent
since to the nanometer size of the particles is smaller than the wavelength range of
visible light. Other characteristics of the composites include high barrier
performance and improved thermal stability, which make these compounds
suitable for many applications. This nanocomposite technology is one of the most
promising directions in a material engineering, applicable to a wide range of
polymers including thermoplastics, thermosets and elastomers.
Israel is a world leader in Nanotechnology, that is involved in fundamental
academic research but focuses most on fostering industrial research and start-up
companies (Figure 4).
Figure 1. Global nanotechnology market 2007.

ADVANCED MATERIAL NANOTECHNOLOGY IN ISRAEL 277
Figure 2. Nanotechnology market evolution 2006–2012.
2000
Revenue (Million USS)
1800 2006
1600 2007
1400
1200 2008
1000 2009
800
600 2010
400 2011
200
0 2012
t k 2013
gy en ce
s
rin er
er nm en D th 2014
En iro ci & O
v S od 2015
En Li
fe Fo
Figure 3. Revenue forecasts of nanoporous materials demand (world), 2006–2015, million US dollars.
In the paper we present new developments within one of the lead Israeli
companies: Polymate Ltd., International Nanotechnology Research Center (Polymate
Ltd., INRC) which includes a branch in Berlin, Germany.
Polymate Ltd., INRC specializes in providing applied and fundamental research
and development (R&D) in the scientific and technological fields of material,
chemical and environmental engineering, with a focus on the development,
marketing, and commercialization of advanced nanocomposites. Polymate Ltd.,
INRC successfully operates on the basis of multi-sided partnerships in many
regions around the world, such as Europe, Japan, Canada, the Former Soviet
Union among others. Polymate Ltd., INRC’s latest Network Nanostructured
Polymer System has been named a winner in the third annual NASA Nanotech
Briefs®’ Nano 50™ Awards (2007) in the Technology category.
Figure 4. Nanotechnology material engineering companies in Israel.
2. General Comment
Nanostructured composite materials can be categorized depending on the location

of the nanoscale structure in the system (Figure 5).
After an initial literature review, and when considering the information needed
in order to describe a nanomaterial from a physical and chemical perspective when
estimating the hazard of nanomaterials, we propose the following nine properties
as being important:
Chemical composition
Size
Shape
Crystal structure
Surface area
Surface chemistry
Surface charge
Solubility
Adhesion, defined as “the force by which the nanoparticles and its components
are held together”
Figure 5. Classification of nanomaterials.
3. Nanostructured Composites Based on Interpenetrated Polymer Network

[7–11]
This project is oriented to prepare nanocomposites based on an interpenetrated

polymer network (IPN), such as polyurethanes, epoxies and acrylate by way of
creating nanoparticles of SiO2, TiO2 and other metal oxides during a techno-
logical stage from a liquid phase. Using an interpenetrating polymer network principle
in production of composite materials provides a unique possibility to regulate both
micro- and nano-structured properties. Formulation of a new class of nanocomposite
materials is characterized by the absence of contaminants for a network polymers
technology. As a main component of such technology we are using branched
(dendro)-aminosilanes that at the first stage are curing agents for many oligomers.
The proposed dendro-aminosilane hardeners provide potential to introduce the
siloxane fragments into aromatic structure of diphenylolpropane based epoxy-
amine network polymers. Additional hydrolysis of aminosilane oligomer creates
the secondary nano-structured network polymer that improves the service properties
of the compound. Branched (dendro) polyamine hardeners are a novel direction in
epoxy and cyclocarbonate and acryl resins chemistry.
The new hardeners give rise to formation of IPN of a polymerized resin with a
polysiloxane network by the hydrolytic polycondensation of silane groups. The
IPN network may be formed on the base of epoxy-cyclocarbonate oligomers. It
was found that at least 0.1 equivalent weight of silane per epoxy resin equivalent
weight may result in IPN formation. Epoxy resin has a low resistance to acetone
and methanol attack.
Novel hybrid nonisocyanate polyurethane based nanocomposites (HNIPU)
were produced by the following reaction.
Pilot production of two component paints, top coatings, adhesives and floorings
are obtained. Figure 6 illustrates industrial application of the IPN flooring. The
two-component compounds have unique properties that combine the best mecha-
nical properties of polyurethane and chemical resistance of epoxy binders.
4. Nanocomposites Based on Hybrid Organo-Silicate Matrix [12–17]
Important among nanoscale materials are hybrids or nanocomposites. They often

exhibit properties superior to conventional composites. Organic-inorganic hybrid
Figure 6. IPN flooring (Tosaf Compounding Co., Israel).

nanostructures have generated great interest by combining optical, magnetic or

electronic properties of inorganic crystals with mechanical properties and functio-
nality of organic compounds. They suggest a variety of potential applications such
as electrical, optical and medical markers.
By using a principle of forming nanostructure by creating nanoparticles during
a technological process from a liquid phase, Polymate Ltd., INRC has elaborated
a few composites based on different kinds of soluble silicates. Significant
increases in silicate matrix strength and durability were reached by incorporation
of special liquid additives, such as TFS, which serve as a microcrystallizing
nucleator on the technological stage and later deposit into the pores of silicate
matrix. Our last developments are mainly applying a novel type of soluble silicate
contained organic cations, for example, the DABCO (shown below)-based organic
alkali soluble silicate.
5. Polymer Nanocompsites with Very Low Permeability and High

Resistance to Adverse Environments [18–22]
Novel chemically resistant polymer materials were developed by adding nano-size

inorganic active fillers that react with aggressive media into which they are intro-
duced, forming a new phase of high-strength hydrate complexes. This enhanced
bonding occurs upon penetration of aggressive media into active nano-fillers
containing polymer material. The chemical resistant properties of the forming
polymer materials are activated by harsh environmental conditions where polymer
systems without additives remain susceptible to corrosion.
Figure 7 illustrates the effect of special powdered additives on chemical
resistance of nonisocyanate polyurethane covering.
12
0.8
0.6
0.4
0.2
0
0 6 12
With additives Time. months
Without additives
Figure 7. Chemical resistance of nonisocyanate polyurethane covering to 25% H2SO4 at 25°C.
Polymate Ltd., INRC has developed an extensive product range of such active
nano-fillers for upgrading the most common polymers against a wide variety of
aggressive media including acids, sea water, fluorine, alkalis and more.
6. Novel Metallic Matrix of Nanoreinforced Materials Produced by

Superdeep Penetration [23]
Technological process on the basis of new physical effect “superdeep penetration”

(SDP) allows applications ranging from the steel tools (for example, HSS) to new
composite materials (Figure 8).
Detonation
100− 180 mm
High-energy flow
The Steel bush

200 mm
Steel intermediates
Figure 8. Principal scheme of superdeep penetration of micro particles into metal body.
These materials can be used for replacement base steels in metal-cutting and
stamp tools. In some cases new materials can be used for replacement of a hard
metal (on the basis of WC) in the tools for mining (e.g., cutters of coal and mining
machines, Figure 9). The application of the new SDP technology allows an
increase in the service life of the tools up to 1.5–5.0 times compared to currently
used tools. The technology can be applied for the volume strengthening of
practically any type of instrumental steel.
Figure 9. The tools for coal cracking strengthened by SDP method.
Use of new physical effect SDP allows acquisition of special composite materials
on the basis of aluminum, with the set anisotropy of physical and chemical
properties. In micro-sized volumes of the aluminum matrix, the electrical conduc-
tivity in mutually perpendicular directions of an aluminum matrix can differ by a
factor of two. The new technology of volumetric reorganization of aluminum will
find wide application in the manufacturing of electric installations and electronic
devices.
7. Water-Dispersion Paint Composition with Biocide Properties Based on

Silver Nano-Powder [24]
We have developed an advanced bioactive coating using silver nanoparticles. As

found in numerous studies during the past 2 decades, particles with dimensions in
nanometer scale (10−9 to 10−8 m) possess unique properties that differ from those
of atoms and ions on the one hand and bulk substances on the other hand. These
silver nanoparticles were produced by the novel BAR-synthesis. The biological
activity of varnish-paint materials modified by silver nanoparticles was estimated
on the following microorganisms:
Escherichia coli (E. coli 1257) as a conventional device. Due to reduction in
cost of expensive materials, the use of these novel aluminum materials in
electric installations and control systems will save millions of U.S. dollars. The
preparation cost of aluminum structure rearrangement does not exceed
US$40/kg, a two- to threefold reduction in industrial production cost. An
individual preparation may lead to manufacture of tens to thousands of
electronic devices. Process SDP is high-efficiency and does not require
expensive equipment. The new technology of volumetric reorganization of
aluminum, creation zones of nano-structures, the materials received on this
basis, will find wide manufacturing applications for electric installations and
electronic devices.
Other applicable model species
Coliphage (RNA-phage MS-2) as a model of viral infection, including
influenza A and B, hepatitis A
Mold fungi (Penicillinum chrysogenum) as a typical representative of
microflora of the dwellings and a model of fungicidal contamination
Spores and other microflora
The test data confirms the significant advantages of elaborated water-born acrylic
bioactive coatings.
8. Nanocellulose and Biodegrable Composite Materials [25, 26]
Nanocellulose (NanoCell) with CI crystalline modification was prepared using an

advanced, environmentally friendly, efficient and cheap technology. The developed
technology permits producing NanoCell in bench scale and industrial amounts.
The NanoCell product can be manufactured in the form of dispersions, high solid
paste and dry powder.
The FDA-approved nanostructured aqueous polymer, GreenCoat, is applied
for protective covering of paper and wood. The coating layer imparts material
barrier properties against permeation of water, grease, oxygen and some other
substances (Figure 10). Waste of coated material can be re-pulped and used in
paper industry or decomposed in nature due to its biodegradability.
GreenCoat Layer
Cellulose base
Figure 10. The new nano-scale cellulose product.
The GreenCoat emulsion is coated on a cardboard surface by means of bar –

coater and dried at 150–170oC for 30–60 s. The GreenCoat W glazing hot melt
composition is then coated on the first layer by means of bar-coater at 130–135oC
and air cooled. The waste of the coated material can be re-pulped and used in
paper industry or decomposed in nature due to its biodegradability (Figure 11).
Figure 11. Recycling of the biodegradable coatings.
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Materials. Proceedings of International Conference on Composite Materials and
Energy (ENERCOMP - 95), Montreal, Canada, May 8–10, 1995, pp. 499–502.
14. O. Figovsky: New Polymer and Silicate Matrix for Composite Materials. Proceedings
of Ninth Annual International Conference on Composite Engineering. July 1–6, San
Diego, CA, USA, pp. 205–206.
15. O. Figovsky: Nanocomposite Bonding Composition Based on Hybrid Organic-Silicate
Matrix. Abstracts of the International Symposium on Bond Behaviour of FRP in
Structures, Hong Kong, China, 7–9 December, 2005, No. BBC S0064.
16. F. Buslov, L. Shapovalov, O. Figovsky: Advanced Synthesis of Organo-Inorganic
Nanohybrid Materials for Coatings. Proceedings of Third World Congress
“Nanocomposites 2003”, 10–12 November, 2003, San Francisco, CA, USA, pp. 32/1–7.
17. O. Figovsky, L. Shapovalov: Nanocomposite Coatings Based on Nonisocyanate
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Conference “New Fields in Colour and Coatings”, September 12–14, 2007, Tokyo,
Japan, pp. 34–37.
18. O. Figovsky: Composite Materials with a Microstructure which Gives the Possibility
Increasing Service Properties During Exploitation. The Structural Integrity of
Composite Materials & Structures, A Residential Meeting & Workshop, Isle of Capri,
Italy, 20–25 May, 2001.
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924.
20. R. Potashnikov, O. Birukov, O. Figovsky, A. De Shrijver: Nanostructured Acrylic Uv-
curable Foam - Sealant. Abstract of the 11th Israel Materials Engineering Conference,
December 24–25, 2003, Haifa, Israel, p. 134.
21. O. Figovsky, N. Blank: Novel active nanofillers for increasing chemical resistance and
durability of polymer composite materials. The 15th International Conference
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SILVER NANOPARTICLES
Environmental and Human Health Impacts
R.R. KHAYDAROV
Ulugbek, 100214
renat2@gmail.com
R.A. KHAYDAROV
Y. ESTRIN
ARC Centre of Excellence for Design in Light Metals
Department of Materials Engineering, Monash University
CSIRO Division of Materials Science and Engineering
Clayton, Victoria, Australia
S. EVGRAFOVA
V.N. Sukachev Institute of Forest SB RAS
Krasnoyarsk, Russia
T. SCHEPER, C. ENDRES
Institute of Technical Chemistry
Leibniz University
Hannover, Germany
S.Y. CHO
Yonsei University
Seoul, South Korea
Abstract. The bactericidal effect of silver nanoparticles obtained by a novel

electrochemical method on Escherichia coli, Staphylococcus aureus, Aspergillus
niger and Penicillium phoeniceum cultures has been studied. The tests conducted
have demonstrated that synthesized silver nanoparticles – when added to water
paints or cotton fabrics – show a pronounced antibacterial/antifungal effect. It was
shown that smaller silver nanoparticles have a greater antibacterial/antifungal
efficacy. The paper also provides a review of scientific literature with regard to

recent developments in the field of toxicity of silver nanoparticles and its effect on
environment and human health.
1. Introduction
Medicinal and preservative properties of silver have been known for over 2,000
years. The ancient Greek and Roman civilizations used silver vessels to keep
water potable. Since the nineteenth century, silver-based compounds have been
widely used in bactericidal applications, in burns and in wound therapy, etc. [11].
Over the last decades silver has been engineered into nanoparticles, structures
from 1 to 100 nm in size. Owing to their small size, the total surface area of the
nanoparticles is maximized, leading to the highest values of the activity to weight
ratio. Due to this property being distinctly different from that of the bulk metal,
silver nanoparticles have attracted much attention and have found applications in
diverse areas, including medicine [26], catalysis [14], textile engineering [14],
biotechnology and bioengineering [23], water treatment [30], electronics [12]
and optics [21]. Furthermore, currently silver nanoparticles are widely used as
antibacterial/antifungal agents in a diverse range of consumer products: air sanitizer
sprays, socks, pillows, slippers, respirators, wet wipes, detergents, soaps, shampoos,
toothpastes, air filters, coatings of refrigerators, vacuum cleaners, washing machines,
food storage containers, cellular phones, etc. [6].
Numerous synthesis approaches were developed to obtain silver nanoparticles
of various shapes and sizes, including laser ablation [13], gamma irradiation [18],
electron irradiation [3], chemical reduction by inorganic and organic reducing
agents [4], photochemical methods [19], microwave processing [31], and thermal
decomposition of silver oxalate in water and in ethylene glycol [22]. Having
compared minimum inhibitory concentration (MIC) values for bacterial cultures,
one can see that the antimicrobial activity of silver nanoparticles strongly depends
on the method of their synthesis.
This paper deals with the authors’ research in the field of antimicrobial pro-
perties of silver nanoparticles obtained by our recently suggested electrochemical
technique [10], which provides extremely low minimum inhibitory concentration
(MIC) values as well as a high efficacy of nanosilver as antimicrobial agent
against a range of microbes on the surface of paints and fabrics [7]. This paper
also provides a review of the most recent scientific publications regarding the
possible toxic effects of silver nanoparticles to the environment and human health.

The process of electrochemical synthesis of silver nanoparticles [10] is based on
using an inexpensive two-electrode setup in which the anode and the cathode
made from the bulk Ag are placed vertically, face-to-face, 10 mm apart. The
electrodes are immersed into an electrochemical cell filled with 500 ml of distilled
water obtained with water distiller (DE-25, Russia). In the tests reported here, the
SILVER NANOPARTICLES 289
electrolysis was performed during 1 h at the temperature range of 325–340 K with

a constant voltage of 20 V. Periodical changing the polarity of the direct current
between the electrodes with a period of 4 min and vigorous stirring during the
process of electrolysis were applied in order to reduce the agglomeration of particles.
Synthesized silver nanoparticle solutions were stored under ambient conditions in
glass containers. The morphology of the silver nanoparticles/ powders obtained
was studied using transmission electron microscopy (TEM), scanning electron
microscopy (SEM), and dynamic light scattering (DLS) measurements. The concen-
tration of silver nanoparticles in solutions was determined by neutron activation
analysis [29].
To evaluate the antibacterial and fungicidal properties of Ag nanoparticles
Escherichia coli was used as a representative Gram-negative bacterium;
Staphylococcus aureus was used as a Gram-positive bacterium; Aspergillus niger
and Penicillium phoeniceum were used to represent cosmopolitan saprotrophic
fungi. To assay the antimicrobial activity of silver nanoparticles in aqueous
solution against E. coli on solid media, the agar disk diffusion method was used.
Bacteria inocula were prepared from a log-phase culture of E. coli K12 grown in
LB-media on a rotary shaker (120 rpm) at 37°C. The inocula were diluted with
0.9% NaCl to the 0.5 McFarland standard and 100 μl were applied onto 9 cm
Mueller-Hinton agar plates with a depth of approximately 5 mm. Disks of
absorbent paper (5 mm in diameter) were impregnated with 10 μl of silver
nanoparticle solutions (47.5, 42.5, 22.6 and 11.3 ppm). For comparison, disks of
the same diameter with 10 μl Tetracycline, Penicillin G and Ampicillin (1 g/l
each) were used, leading to a concentration of the respective substance of 10
μg/disk. The freshly prepared disks were placed on the surface of the inoculated
agar plates. After incubation at 37°C for 18 h the zones of bacterial inhibition
were measured optically. In order to impregnate a cotton fabric with silver
nanoparticles, the simple padding procedure [12] was used. In a separate exercise,
commercially available water paint was mixed with silver nanoparticles solutions
in a ratio of 7:1 in order to impart antimicrobial properties to the paint. To
evaluate the antibacterial and fungicidal properties of Ag nanoparticles added to a
cotton fabric and a water paint, samples (1.5 × 1.5 cm) treated by different
compositions of Ag nanoparticles as well as control samples were immersed in a
thin layer of beef-extract agar. A 1 ml of suspension of approximately 105 CFU/ml
density of the microorganisms to be tested were distributed uniformly on agar
surface and incubated at 28°C (CFU = colony forming units). Antimicrobial
activity was evaluated according to the presence or absence of microbial growth
just above the sample after a 24-h incubation for bacteria and a 72-h incubation for
fungi. All microbiological tests were performed in triplicate.
MICs of silver nanoparticle solutions for various microbes were determined
using the macrodilution broth susceptibility test. Nutrient broth used in the
macrodilution method contained peptic digest of animal tissue 50.00 g/l; beef
extract 1.5 g/l; sodium chloride 5.00 g/l; glucose 5 g/l; pH 7.4 ± 0.2. A
standardized suspension of approximately 106 CFU/ml density was obtained by
inoculating the culture in nutrient broth (Hi-Media) and incubating the tubes at
37°C for 3 h. A serial dilution of our silver nanoparticles solution was prepared
within a desired range. Ten milliliter of the standardized culture suspension was
then inoculated and tubes were incubated at 37°C for 24 h. MIC was defined as
the lowest concentration of the inhibiting agent that completely inhibited bacterial
growth, the unit for MIC was chosen as mg(Ag)/l. MIC was examined visually, by
checking the turbidity of the tubes.
3. Results and Discussion
3.1. MORPHOLOGY OF THE SYNTHESIZED Ag NANOPARTICLES
It was shown by DLS measurements that a typical sample of silver nanoparticles

solution obtained by the two-electrode setup described above contains not only
nanoparticles, but also a small amount of large (>100 nm) colloidal silver
particles. In order to remove these coarse particles and to provide reduction of
silver ions present in the solution, we used filtration of the solution through a
3-μm pore size paper filter. The filter narrows the range of size distributions of
synthesized silver nanoparticles while providing additional reduction of Ag ions
according to the following reaction: Ag+1 + e → Ag0. As a result, the ratio of the
concentrations of silver ions and silver nanoparticles suspended in the solution is
reduced. A final stage of Ag nanoparticle synthesis involves additional treatment
of the smallest-size fraction of silver nanoparticles remaining in solution after the
filtering stage. It consists of adding hydrogen peroxide to a level of up to 0.005%
concentration of H2O2 to the solution. Due to the reaction Ag2O + H2O2 → 2Ag +
H2O + O2 silver oxide is reduced to Ag which is released in the solution. By this
process the size of the silver nanoparticles is reduced, while new Ag nanoparticles
may be forming as well. Examination of TEM images taken 2 weeks after the
addition of H2O2 revealed that silver nanoparticles suspended in water solution
were nearly spherical and that their size distribution fell in the range of 2–20 nm,
the average size being about 7 nm, cf. Figure 1.
Figure 1. Typical TEM image and size distribution of silver nanoparticles obtained by electrochemical
synthesis.
3.2. ANTIBACTERIAL ACTIVITY OF SILVER NANOPARTICLES
In Figure 2 the antibacterial effect of silver colloids with the concentrations of

47.5, 42.5, 22.6 and 11.3 ppm is presented vis-à-vis to that of known antibiotics.
The concentrations of silver were selected in such a way as to correspond to
maximum Ag concentrations used in consumer nanoproducts which are currently
available on the market. Comparing zones of growth inhibition around the disks
impregnated with various antibiotics and Ag nanoparticles, one can see that silver
nanoparticle solution demonstrates a certain antimicrobial effect. The intensity of
the effect is increased with the concentration of the solution.
Figure 3 demonstrates zones of growth inhibition around the disks impregnated
with various antibiotics and the disk with the largest Ag nanoparticles concen-
trations that we have used. Considering that the Ag concentration used in the
experiment was approximately 20 times lower than that of the antibiotics, one can
expect that silver nanoparticles would outperform Ampicillin, Penicillin and
Tetracycline antibiotics of the same concentration.
20
18
16
14
12
zone of inhibition
diameter [mm]
10
0
Am picillin Tetracycline Penicillin G Ag 47.5 ppm Ag 42.5 ppm Ag 22.6 ppm Ag 11.3 ppm
10 μ g/disk 10 μ g/disk 10 μ g/disk 0.475 μ g/disk 0.425 μ g/disk 0.226 μ g/disk 0.113 μ g/disk
Figure 2. Antibacterial activity of silver nanoparticles in aqueous solution against E. coli K12 deter-
mined by the agar disk diffusion method.
In order to reveal an effect of the size of silver nanoparticles on their bactericidal

efficiency the minimum inhibitory concentration (MIC) assays were conducted
against the gram-negative bacterium E. coli and the gram-positive bacteria S.
aureus and B. subtilis. The results for MIC assays shown in Table 1 demonstrate
that smaller silver nanoparticles had a greater antibacterial efficacy. The conducted
MIC assays have also shown clearly that the proposed electrochemical technique
Figure 3. Zones of growth inhibition around disks impregnated with silver nanoparticles and various
antibiotics.
provides very high antimicrobial activity of synthesized silver nanoparticles. For

example, Sarkar et al. [27] have recently proposed a method of synthesis of Ag
nanoparticles that provided the same MIC values for E. coli and S. aureus
varieties as in the present study. Sarkar and coauthors claimed that “such a low
value of MIC showed by silver nano particles is unprecedented”. The results
obtained for larger nanoparticles (with a mean size of 70 nm) are in good
agreement with MIC assays for E. coli for colloidal silver (32.2 mg/l in case of
average Ag-particle size of 63 nm) stabilized by sodium oleate (cf. [32]). On the
other hand, MIC values for the same bacteria obtained by Rupareli et al. [25] are
higher than those presented in Table 1, although they studied smaller silver
nanoparticles (3.32 ± 1.129 nm). We suppose that it is mainly connected with the
high purity of nanoparticles obtained by our electrochemical technique without
surfactants. Unfortunately, existing studies on nanotoxicity were concentrated on
empirical evaluation of the toxicity of various nanoparticles, with less regard
Table 1. Minimum inhibitory concentration (MIC) assay results for silver nanoparticles.
Bacterium MIC (mg(Ag)/l) MIC (mg(Ag)/l)
(average particle size of (average particle size of 70 nm)
7 nm)
E. coli 3 34
S. aureus 2 25
B. subtilis 19 no data
given to the relationship between nanoparticle properties and toxicity [6]. Thus, there
is an obvious need for further studies on the development of a database of bactericidal
efficacy of silver nanoparticles as a function of their size and composition.
3.3. ANTIMICROBIAL EFFECT OF COTTON AND PAINT SAMPLES

MODIFIED WITH SILVER NANOPARTICLES
Bactericidal activity has become a significant property of textiles and paints used
in applications such as medicine, clothing, and household products. We have
impregnated cotton fabrics and water paints with our nanosized silver colloids. As
one can see from Figure 4, most of initial silver nanoparticles had agglomerated
into clusters because of attractive interaction forces between them (6-month old
samples).
Figure 4. Samples of water paint (left) and cotton fabric (right) with immobilized silver nanoparticles.
The bactericidal action of the cotton fabric with immobilized silver nanoparticles
on S. aureus was also studied. Experiments with agar plates demonstrated that the
modified fabric (1 µg/cm2) can inhibit the growth of S. aureus on beef extract agar
(Figure 5).
Similar tests were conducted on S. aureus using pasteboard covered with water
paint modified with silver nanoparticles. These tests demonstrated that the
modified paint with the area concentration of Ag of 0.001 mg/cm2 could inhibit
the growth of S. aureus on beef extract agar.
Our recent microbiological tests [7] confirmed antifungal effect of the water
paint modified with silver nanoparticles on Aspergillus niger and Penicillium
phoeniceum cultures. It was shown in particular that a 20 ppm concentration of Ag
nanoparticles (mean size of 50 nm) and a 3 ppm concentration (mean size of 15
nm) have similar antifungal effects, i.e. smaller silver nanoparticles had a greater
antifungal efficacy. Tests on nanosilver-modified cotton fabrics, in which a 20
ppm solution of Ag nanoparticles with the mean size of 50 nm was used, also
confirmed their antibacterial/antifungal effect: growth of these species of fungi in
the vicinity of samples treated with a colloidal solution of Ag nanoparticles was
suppressed.
Figure 5. Growth of S. aureus culture on a cotton fabric sample modified by silver nanoparticles on the
first and the next day. (Note the white spots corresponding to S. aureus colonies.) The sample #1 is a
control sample, i.e. non-modified; other samples are modified with silver nanoparticles having various
average sizes.
4. Environmental and Human Health Impacts
Silver-based materials have been widely used over the last decades in medical
organizations, photographic laboratories etc. Not long ago, the annual silver
release into the environment from industrial wastes and emissions was estimated
at approximately 2,500 t, of which 150 t ended up in the sludge of wastewater
treatment plants with 80 t being released into surface waters [28, 24]. The
maximum concentrations of silver released into the environment are regulated at
various levels in different countries by their appropriate environmental protection
agencies. It was well documented in studies conducted in the twentieth century
that the toxicity of silver in the environment occurred mainly in the aqueous phase
and depended on the concentration of active, free Ag+ ions. [24]. As for the impact
on human health, the scientific literature of the last century cited mainly cases of
permanent bluish-gray discoloration of the skin (argyria) or eyes (argyrosis)
occurring when the accepted threshold values for silver and its compounds were
exceeded [1].
In the twenty-first century the significant growth of applications of nanosilver
in various branches of industry as well as its use in consumer products has caused
new concerns that silver nanoparticles may have a toxic effect on the environment
and human health. There is a public perception that silver nanoparticles do not
discriminate between different strains of bacteria and are likely to destroy microbes
beneficial to other organisms and ecological processes [2]. Unfortunately, only a
few scientific investigations on cytotoxicity of nanosilver have been conducted to
date. For example, in vitro toxicity assays of silver nanoparticles in rat liver cells
by Hussain et al. [9] have shown that low level exposure resulted in oxidative
stress, cellular shrinkage and impaired mitochondrial function. Silver nanoparticles
also turned out [5] to be highly toxic to in vitro mouse germline stem cells, as they
drastically reduce mitochondrial function and cause increased leakage of ions
through cell membranes. According to studies conducted by Soto [31], nanoparticulate
silver aggregates were more cytotoxic than asbestos. There is also an impact of
nanosilver exposure on development of the lymphatic system of embryos of
chickens, although the entire embryo development was not influenced by silver
nanoparticles [8].
Considering the studies on cytotoxicity of nanoparticles, it is important to keep
in mind that in vitro results can differ from what is found in vivo and are not
necessarily clinically relevant [15]. It should also be noted that some reported silver
cytotoxicity studies were performed using unrealistically high concentrations of
nanosilver.
It would be fair to say that the mechanism of the bactericidal effect of silver
nanoparticles is not well understood as yet. Lok et al. [17] have recently reported
that “Nanosilver represents a special physicochemical system which confers their
antimicrobial activities via Ag+”. If this conclusion is verified then most bioaccu-
mulation and toxicity issues relating to silver nanoparticles can be considered
from the point of view of the toxic potential of ionic silver, which is documented
sufficiently well. As under natural environmental conditions the ionic silver is
readily transformed to nonreactive compounds [24], this would mean that the envi-
ronmental risks of nanosilver toxicity is not as severe as the popular perception
may suggest.
By contrast, according to Morones et al. [20] the bactericidal effect of silver
nanoparticles on micro-organisms is connected not merely with the release of
silver ions in solution. Following their report, silver nanoparticles can also be
attached to the surface of the cell membrane and disturb its proper function
drastically. They are also able to penetrate inside the bacteria and cause further
damage by possibly interacting with sulfur- and phosphorus-containing compounds
such as DNA. It is interesting to note that silver nanoparticles have also demon-
strated synergistic effects with known antibiotics, such as amoxicillin [16].
Thus, there is an urgent need for further studies on the bactericidal mechanism
of silver nanoparticles, which will be a step forward to better understanding of
their environmental and human health impacts. As silver-based materials have a
great commercialization potential, we anticipate a large amount of reports from
various scientific groups in the field of nanosilver toxicity in near future. To quote
a recent review: “A full understanding of the hazards of nanoparticles will make a
major contribution to the risk assessment that is so urgently needed to ensure that
products that utilize nanoparticles are made safely, are exploited to their full
potential and then disposed of safely” [15].
5. Conclusion
An electrochemical technique for synthesis of silver nanoparticles with high anti-

microbial activity has been developed. Our studies have revealed that silver
nanoparticles suspended in water solution are nearly spherical, their average
diameter being 7 ± 3 nm. Due to their high purity, very low inhibitory
concentration (MIC) values for Escherichia coli (3 mg/l), Staphylococcus aureus
(2 mg/l) and Bacillus subtilis (19 mg/l) cultures have been obtained. The tests
conducted have demonstrated that synthesized silver nanoparticles added to water

paints or cotton fabrics show a pronounced antibacterial/antifungal effect, despite
the fact that they tend to be agglomerated into clusters. It has been shown that
smaller silver nanoparticles have a greater antibacterial/antifungal efficacy. A
brief review of the scientific literature on recent studies into the impact of silver
nanoparticles on environment and human health has been provided.
Acknowledgments
R. R. Khaydarov acknowledges partial support of this work through the INTAS

Fellowship Grant No. 5973 for Young Scientists under the “Uzbekistan – INTAS
2006” program.
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DEVELOPING STRATEGIES IN BRAZIL TO MANAGE THE
EMERGING NANOTECHNOLOGY AND ITS ASSOCIATED
RISKS
A.S.A. ARCURI, M.G.L. GROSSI, V.R.S. PINTO, A. RINALDI

Foundation on Occupational Safety and Health Researches and
Studies – FUNDACENTRO – Ministry of Labour and Employment
San Paolo 05409-002, Brazil
arline@fundacentro.gov.br
A.C. PINTO
IIEP – Intercâmbio, Informações, Estudos e Pesquisas
Rua Pedro Américo, 52, 13º andar
San Paolo, Brazil
P.R. MARTINS
RENANOSOMA, IPT – Instituto de Pesquisas tecnológicas do
estado de São Paulo
Av. Prof. Almeida Prado 532
Cid. Universitária. 05508-901 São Paulo, Brazil
P.A. MAIA
FUNDACENTRO – Ministry of Labour and Employment
Rua Marcelino Velez, 43
Campinas – 13020-200, Brazil
Abstract. Emerging countries, such as Brazil, are beginning to feel the impact of
nanomaterial production occurring in further developed countries. It is important
to identify strategies for the risk management of these products. For this reason,
Fundacentro, a Ministry of Labor and Employment institution, in Brazil is currently
working to develop management strategies for nanotechnology and its associated
risk.
One of Brazil’s first efforts to develop a nanotechnology management and risk
assessment plan occurred at the “Nanotechnology, Environment and Society for
a Possible New World” workshop held on January 25, 2004 at the 5th World
Social Forum in Porto Alegre. Within the same year, there was also the creation of
Renanosoma, a Brazilian research network involved in nanotechnology, socio-
logical issues, and environmental matters. The aim of Renanosoma is to research
potential effects of nanotechnology and increase public awareness of the social,

300 A.S.A. ARCURI ET AL.
economical, environmental, and ethical impacts. This network has also been res-
ponsible for four international seminars related to nanotechnology, and coordinated a
federally funded project titled “Public Engagement in nanotechnology”. Through
this project, conferences are held three times a week via the internet (http://www.
meebo.com/room/nanotecnologia/). In each conference, debates involving a main
speaker (a previously invited researcher), researchers from all over the country,
social scientist, and the interested public discuss different views and aspects of
nanotechnology’s implementations and impacts.
Since 2006, many other organizations have joined the Renanosoma network,
some of which include the IIEP (Information Exchange, Studies and Research),
DIESAT (Inter Union Department of Studies and Research on Health and
Workplace), DIEESE (Inter Union Department of Statistics and Socio-Economical
Studies), and FUNDACENTRO (Foundation on Occupational Safety and Health
Researches and Studies). The interest and participation of these organizations in
the Renanosoma network drove the momentum for two additional seminars to be
held on occupational safety and health. Additionally, FUNDACENTRO is funding
a project that is being developed to propose feasible controlling measures for
nanomaterial and identify impacts that nanotechnology may have on the general
working public and the environment. Several additional projects and activities are
planned for the year 2008 that may become developments of groups recently
added to Renanosoma.
1. Introduction
FUNDACENTRO is a foundation, created in 1966, that produces and disseminates

research studies in many different occupational fields. Since the foundation’s
creation, FUNDACENTRO main objective has been to foster a safe and healthy
work environment for industry employees by identifying main items of risk that
occur in the workplace. Currently, the foundation develops projects and activities
in the construction industry, chemical safety, small enterprises, the rural sector,
ergonomics, ionizing and non-ionizing radiations (mainly at the telecommunica-
tions field), machinery protection, fishing, silicosis elimination, and many others.
The creation of regulative norms for the safety and health of Brazilian workers
requires a great deal of research. In 1995, a legislation agreement was enacted to
prohibit the use of Benzene in anhydrous alcohol production and to admit only
0.1% (v/v) of benzene in products such as solvents, paints, and varnishes. The
development of this agreement was based on FUNDACENTRO’s intervention in
the sectors where Benzene was present. It was introduced a technological
reference value parameter for measuring the environmental concentration of the
benzene found in workplace air. This agreement was able to engage industry
workers, employers, and branches of the government. In addition to Benzene,
FUNDACENTRO developed studies that established awareness of the carcino-
genic effects of Asbestos, which helped drive the banishment of this highly toxic
substance.
MANAGE THE EMERGING NANOTECHNOLOGY 301
Nanotechnology is still considered an emerging field. Currently, several

nanoproducts available on the market but additional technology remain to be
introduced into product manufacturing and distribution. The production of these
materials can represent risks, even unknown ones, to society and exposed workers.
Risk can occur at any stage of the product’s life cycle such as the development,
production, and disposal/destruction of the material. Due to the extensive potential
for risk, FUNDACENTRO has the opportunity to intervene not only in facilities
where workers are currently being exposed to hazards, but also by implementing
effective prevention measurements. Research is currently being conducted to
identify the risk of new production methods and how the launch of these new
products could negatively impact exposed workers. From this preliminary
knowledge, FUNDACENTRO is in the process of developing information and
communication about nanomaterial risk that are typical actions of risk manage-
ment. This process is developing despite the fact that the foundation’s researchers
have just recently become aware of nanotechnology. FUNDACENTRO realizes
that precautions must be taken to establish risk management strategies in protec-
ting exposed workers and the general public. In the workshop “Risk, uncertainty
and decision analysis for nanomaterials: environmental risks and benefits and
emerging consumer products” one of the statements of purpose is defined as
“Identify strategies for users in developing countries to best manage this emerging
technology and its associated risks”. This statement gives a clear insight to the
intentions and actions developing in Brazil by FUNDACENTRO and its
stakeholders to try and manage possible associated risks from these technologies.
2. Risk Management
A classic model for risk management begins from hazard identification. NIOSH
(2006) NIOSH (2006a) published a figure with steps to protect workers involved
with nanotechnology. The NIOSH figure below depicts hazard identification as
the first step, hazard characterization as the second, exposure assessment as the
third, and risk characterization as the fourth. All of these sequential steps lead to
the end objective of the model that is to predict risk management.
When the topic is nanotechnology, it is difficult to follow the steps outlined in
this model. There are many unknown elements regarding the first step of the
model, which is hazard identification of nanostructured materials. Many
references exist that discuss issues pertaining to the lack of knowledge relative to
nanotechnology [1, 2, 6, 9–11, 13, 14, 16, 20, 21, 23, 24]. In the field of
nanotechnology there remains an abundance of material to be studied and
revealed. Despite the fact that there are currently wide gaps of knowledge, enough
information has already been produced to understand that there is a need in
minimizing or eliminating a person’s exposure to nanomaterial substances. It is
also important to point out that traditional protocols established in occupational
health may not be efficient for nanomaterial exposure due to their novel properties
and the questionable efficiency of past protocols.
Steps to protect workers

involved with
nanotechnology
Hazard identification
“Is there reason to believe this could be harmful?”
Hazard identification
“How and under what conditions could be harmful?”
Exposure assessment
“Will there be exposure in real-world conditions?”
Risk characterization
“is substance hazardous and will there be exposure?”
Risk management
“Develop procedures to minimize exposures?”
Recent information of nanoparticles and their potential effects was stated

below by NIOSH [17]:
“Nanomaterials have the greatest potential to enter the body if they are in the
form of nanoparticles, agglomerates of nanoparticles, and particles from
nanostructures materials that become airborne or come into contact with the
skin.
Based on results from human and animals studies, airborne nanomaterials can
be inhaled and deposit in the respiratory tract; and based on animal studies,
nanoparticles can enter the blood stream and translocate to others organs.
Experimental studies in rats show that equivalent mass doses of insoluble
ultrafine particles (smaller than 100 nm) are more potent than large particles of
similar composition in causing pulmonary inflammation and lung tumors in
those laboratory animals. However, toxicity may be mitigated by surface
characteristics and other factors. Results from in vitro cell culture studies with
similar materials are generally supportive of biological responses observed in
animals.
Cytotoxicity and experimental animal studies shown that changes in the
chemical composition, structure of molecules, or surface properties of certain
nanomaterials can influence their potential toxicity.
Studies in workers exposed to aerosols of manufactured microscopic (fine) and
nanoscale (ultra fine) particles have reported lung function decrements and
adverse respiratory symptoms; however, uncertainty exists about the role of
ultra fine particles relative to other airborne contaminants (e.g., chemicals, fine
particles) in these work environments in causing adverse health effects.”
This reference concludes that “Engineered nanoparticles whose physical and

chemical characteristics are like those ultra fine particles need to be studied to
determine if they pose health risks similar to those that have been associated with
ultra fine particles” [17]. In addition to the issues reported by NIOSH, many
additional reports have been published that address potential health concerns
relative to nanoparticles [3, 4, 5, 7, 8, 12, 15, 18, 19].
As we can see, engineered nanomaterials pose many new questions for risk
assessment that are not yet completely answered. Swiss researchers lead a study
[9] that gives an overview of the general properties of nanomaterial products in the
market. The study reveals that in general, industries working with nanomaterials in
Germany and Switzerland have approached the issue of risk and safety through
written surveys collected from over 40 companies. The characterization of particles
and safety measures returned in the surveys from each company was so diverse
that no categorization relative to risk and material specification could be deter-
mined. Twenty-six companies (65%) indicated that they did not perform any risk
assessment of their nanomaterials and 13 companies (32.5%) performed risk
assessments sometimes or always. Fate of nanomaterials in the use and disposal
stage received little attention by industry, and the majority of companies did not
foresee any unintentional release of nanomaterials throughout the life cycle.
The development of risk and safety decision framework in nanotechnology
industry is necessary to ensure that the potential risks of engineered nanomaterials
are taken into consideration. The Helland study reveals that the majority of com-
panies surveyed did not perform any form of risk assessment or proactive risk
assessment strategies. As revealed in cases such as this, it is becoming more
apparent that risk management strategies need to be implemented in industries
involved with nanotechnology manufacturing and development. Management
strategies need to be developed urgently not only to protect public and environ-
mental health, but also to protect the industry workers being exposed to the
materials.
3. Risk Management in Brazil
New technologies, especially in the nano field, are becoming instruments of life
style change in society. Therefore, before and after public acceptance, information
about nanomaterials has been released through the media in Brazil in addition to
many other countries. The media is describing nanotechnology as a science that
will improve human life and society at large. This publicity has played a large role
in propagating the potential impact that amplification and improvement of
nanomaterial products will have on the general public. An additional drive behind
nanotechnology may be the increase in wealth for most companies involved with
production of materials. Although there is much universal discussion concerning
the potential impacts of nanomaterials, very few discussions lead to the topic of
whether these materials should actually be available through the public market.
This universal discussion rarely stamps some negative point that leads the society
to a better decision.
On the other side, many research centres and universities conduct studies
solely for the purpose of determining the potential positive impacts of nano-
materials. Consequently, some facilities will study the potential harmful effects of
their materials only after the receiving results for their initial studies, which may
occur after products have already been released onto the market. This is the case
of many nano research facilities in Brazil founded by CNPq (Brazilian National
Council for the Scientific and Technological Development). Through the Micro-
electronic Laboratory of Polytechnic School of USP (University of San Paolo),
nanomaterial research will be conducted for developments in fields of medicine
and industry. In total, this lab will gather about 20 Brazilian researchers in the next
2 years
The Laboratory of Nanotechnology integrated with Synchrotron Light (located
in Campinas, South Brazil) is currently developing research focusing on nano-
material properties and characterizations. The fact that this laboratory is focusing
on material research and characterization sets it apart from other facilities con-
ducting nanomaterial research in Brazil. Research in the field of nanotechnology
may have the ability to promote the technological development of Brazil;
consequently this may exclude the public from debates concerning economic and
social implications as well as potential risks of such advancements.
Many teaching institutions, such as technical and high schools, are offering
nanotechnology classes that explore how the present pioneering initiative is aimed
at contributing knowledge to the scientific community and other graduate profes-
sionals faced with technological challenges. One institution developing programs
aimed at gaining student interest in the field of nanotechnology is the Multi-
disciplinary Centre for Ceramic Material, which gathers researchers from the
Federal University of San Carlos (UFSCar) and from Paulista State University
(UNESP). This institution has developed a game that gets players familiar with the
nanoscopic world. The participants are given games pieces that must be joined
together as quickly as possible to form a realistic scientific image.
Companies, even more than universities, are willing to develop new products
at nanometric scale based on profit. Products are often released into the public
market well before any research investigating the potential effects of these
products on man and the environment has been conducted. For instance, in May
2008, a symposium on automotive materials and nanotechnology was conducted
by SAE BRASIL, the theme of which was “The Re-invention of the Automobile
and New Components”. During this symposium they discussed replacing steel
with other materials, some of which may include materials from a new field such
as nanomaterial. Nanotechnology is stepping ahead in the car industry, especially
in plastics, paints, and electronic component fields. Although there are potential
new developments using nanotechnology in the automotive industry, the
symposium program does not plan to cover relevant damages that may be caused
to workers or the environment after exposure to materials used in production.
Additionally, products such as washing-machines, refrigerators, and hair dryers
bearing nanosilver particles can be currently found in use at several Brazilian
residences. Owners of these products often do not know enough information to
ask questions regarding the possible negative impacts that these particles could
have if released into the environment.
There is a national program created by the Ministry of Science and Technology,
“Nanotechnology and Nanoscience Development”. Among its priority actions, are
politics on ethical and social impact subjects. Unfortunately, budgets that would
normally fund the program have been allocated nearly 100% toward industrial
research and growth.
What can be concluded from this report is that there are not enough agents to
provide society knowledge of possible impacts from these new technologies.
RENANOSOMA projects, alongside with “Public Engagement on Nanotechno-
logy” and “FUNDACENTRO” have been exceptions. From 2006 on, Fundacentro
has studied as well as publicized the impacts of nanotechnology on workers and
the environment. Though significant, such efforts are too little to make the all of
the Brazilian population aware of the problems and possible risks from nano-
technology. The lack of knowledge may result, if persistent, to a scenario of un-
repairable damages and losses to the environment and human health, especially to
industry workers exposed to the materials.
Many difficulties are encountered when well established countries attempt to
follow the steps outlined for risk management due to the lack of knowledge about
the materials, but the risk management process is even more difficult to follow in
developing countries. Despites the difficulties, scientific researchers, the NGO,
and social representatives have put forth an effort to discuss problems that may be
encountered by nanomaterial production with public and industry workers. This
initiative is being considered the beginning of a risk management process in
Brazil, which has benefited from learning the challenges faced by classical risk
assessment actions.
4. FUNDACENTRO Project on Nanotechnology
In 2007, FUNDACENTRO began a project that took a preliminary survey about

nanotechnology and its potential impact to worker health and safety. Surveys were
taken in areas that conducted the greatest amount of nanotechnology work. As a
result of this project, many other areas on interest in nanotechnology were
developed. The seminar entitled “Nanotechnology, workers health, foods and
social and environmental impacts” consisted of lectures concerning nanotechnology.
Along with the seminar was also the production of a website, http://blog.iiep.
org.br/nanotecnologia/, which distributed related press material. This project is
continuing in 2008. This year we intend to prepare field research in nanomaterial
product development laboratories and enterprises. The target is assessment of
workplace conditions. Similar surveys had already been done by other researchers
[6, 9]. Through this project we will try to compare if the risk and safety decision
frameworks in Brazilian industry and laboratories are, or not, similar to those in
other countries.
We plan to continue propagating awareness about the impacts and information
associated with nanotechnology. Scheufele et al. [22] conducted research studies
concluding that scientists expressed more concerns than the general public about
two areas of potential risks of nanotechnology: more pollution and new health
problems. Due to these impending concerns, we believe it is important to inform
the public as well as nanomaterial industry workers about the potential impacts
that these products could have. The action items of this year are to produce events,
educational material, videos, and a website discussing the potential impacts of
nanotechnology. All information will be posted on the FUNDACENTRO website
and available to the public.
References
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THE CURRENT STATE-OF-THE ART IN THE AREA OF
NANOTECHNOLOGY RISK ASSESSMENT IN RUSSIA
M. MELKONYAN
A.V. Shubnikov Institute of Crystallography of RAS
59 Leninsky pr
119333 Moscow, Russia
nanotech@ns.crys.ras.ru
S. KOZYREV
Center for Advanced Studies
of the Saint-Petersburg State Polytechnical University
29 Polytekhnicheskaya ul
St. Petersburg 195251, Russia
Abstract. The purpose of this paper is to describe the first steps in the area of
Nanotechnology risk studies in Russia, to discuss the importance of joining Russia
to the bodies responsible for international cooperation on environmental, health
and safety impacts of N&N.
1. Introduction
In June 2004 an “International dialog on responsible research and development of

Nanotechnology” meeting took place in Alexandria (VA), USA. The meeting
discussed a wide range of topics, such as: benefits and risks of Nanosciences and
Nanotechnologies (N&N) to environment, human health and safety (EHS); socio-
economic and ethical implication; special consideration of N&N in developing
countries. It was highlighted that there is need and opportunity to address the
possible societal, health and environmental impact of N&N at an international
level. This event was the very positive starting point. Since that time many
important steps have been made and the real results were achieved in the further
discussions of the interested parties within OECD and some other international
organizations. They were related to exchange of information and best practices,
address issues of common interest, such as: nomenclature, methodologies for risk
assessment, toxicological and ecotoxicological studies. The OECD Working Party
of Manufactured Nanomaterials established in 2006 has developed some projects,
among them there is the development of OECD database on (EHS) research.
Some years ago the evaluation of Nanotechnology risks for the environment
and human health, the associated need to consider preventive measures was not a
priority in Russia. This was mainly due to the lack of scientific information,

310 M. MELKONYAN AND S. KOZYREV
relatively limited use of nanomaterials, and no apparent evidence of adverse impacts

on the environment and human health.
Currently the understanding of the importance of this problem has become the
key issue in Russia and the first steps have been undertaken. The goal of this paper
is to describe these steps in the area of Nanotechnology risks studies in Russia, to
discuss the importance of joining Russia to the bodies responsible for international
cooperation on environmental, health and safety impacts of N&N.
2. The Brief History of N&N in Modern Russia
The history of N&N in modern Russia can be divided into two periods: since 1991
until 2007 and since 2007 – till our days and beyond.
During the first period the main governmental investments in N&N were
relatively small, however some state programmes were launched:
1. State Programme of the Ministry of Education and Science (1992):
“Prospective technologies and devices for micro- and nanoelectronics”
2. Interdepartmental Programmes coordinated by the Ministry of Education and
Science (1993):
“Fullerenes and atomic clusters”
“The Physics of Solid State Nanostructures”
3. Programmes of Russian Academy of Sciences:
“Fullerenes and atomic clusters” (1998)
“Low-dimensional quantum structures” (2001)
“Fundamental problems of physico-chemistry of nanomaterials” (2002)
4. Federal Targeted Programme (FTP) 2002–2006 “Research & Development in
priority fields of Russia’s S&T Complex”, Priority “Industry of Nanosystems
and Materials” (since 2004)
5. Enterprising Projects funded by Russian Foundation for Basic Research (since
1992)
We note that the Interdepartmental Programme “Fullerenes and atomic clusters”
devoted to complex problem of nanocarbon was the first interdisciplinary nano-
program of modern Russia. In program section “Biological activity and medical
application of fullerenes” have been carried out toxicological researches of
fullerenes and fullerene soot, which were very important in that period of
becoming of fullerene technology.
On April 26, 2007 Vladimir Putin, the former President of Russia, announced a
national initiative on the development of nanoindustry in Russia in his address to
Parliament. The golden age of Russia N&N has started. The investments in this
area will be ~$7.5 billion by 2015. The strategic goal of this initiative is to create
the Russian nanoindustrial sector in national high-tech, which would be able to
compete with those of economically developed countries on the internal and
international markets of nanoproducts in key fields of State security and defensive
capacity, technological security and economical independence, as well as improving
people’s life quality (http://www.spbcas.ru/nanobio/Nanobio08/Abstracts_ all.pdf).
NANOTECHNOLOGY RISK ASSESSMENT IN RUSSIA 311
Main tools of the state support of investigations and developments of nano-

industry are the following programmes (http://www.fasi.gov.ru/fcp; S. Ostapyuk
in http://www.spbcas.ru/nanobio/Nanobio08/Abstracts_all.pdf):
Federal Targeted Programme “Research & Development in priority fields of
Russia’s S&T Complex 2007–2012”, priority “Industry of Nanosystems and
Materials”
Federal Targeted Programme “National technological base 2007–2011”
Federal Targeted Programme “Development of electronic component base and
electronics 2008–2015”
Federal Space Program of Russia for 2006–2015
Federal Program for the development of nanoindustry up to 2015
Specialized NanoProgramme of the Russian Academy of Sciences
Programme of the Russian Academy of Medical Sciences “Nanotechnologies
and Nanomaterials in Medicine” for 2008–2015
Specialized Projects of the Russian Foundation for Basic Research
Main tool for the development of the experimental and technological basis in
nanoindustry is the Federal Target Program “Development of the Infrastructure of
Nanoindustry in the Russian Federation for 2008–2010” (http://www.government.
ru/government/governmentactivity/rfgovernmentdecisions/archive/2007/08/09/86
03022.htm).
In 2007 the State Corporation “Russian nanotechnologies” was founded for the
support of the emerging high-tech companies in national nanoindustry (http://www.
rusnano.com).
The tool ensuring the effective scientific personnel training for the national
nanoindustry, the social protection of scientific personnel, attracting and keeping
young people in science, education, and high-tech technologies is the Federal
Target Program “Scientific and Pedagogical Personnel of the Innovative Russia”
for 2009–2013.
The main effect of the realization of the above-listed tools for nanoindustry
development will be formation of the competitive national sector of investigations
and developments in nanoindustry and ensuring conditions for the gradual raising
of the rate of production of new types of goods. And, as a result, the profile
Russian companies should get on in the world high-tech markets.
3. First Steps in Nanotechnology Risks Studies in Russia
In Russia there is not currently research Programme underway to address human

health and/or environmental safety aspects of Nanomaterials. But a number of
R&T projects on impacts of nanoparticles are funded by Russian Foundation for
Basic Research; by Federal Agency for Science and Innovation within the
thematic priority “The industry of nanosystems and materials” of the Federal
Target-oriented Programme “Research and Development in Priority Fields of S&T
Complex of Russia for 2007–2012”. Studies of physico-chemical properties of
Nanomaterials (in particular, nanoparticles) have been carried out within Russian
Academy of Sciences (RAS), especially in the frame of “Fundamental problems of

physico-chemistry of nanomaterials” Programme launched in 2002. Some researchers
are including toxicological, ecotoxicological and metrological aspects on Nano-
technology in their research, but there is no official network for these areas. A
number of Russian organizations are the partners of projects on analysis of toxicity
of nanomaterials that have been funded by ISTC (http://search.istc.ru/index.
jsp?v=7 ).
Consideration of projects funded by Russian Foundation for Basic Research
has demonstrated the interesting results (http://www.rfbr.ru/pics/22366ref/file.
pdf). First of all, the number of scientific papers in the area of nanosciences was
increased rapidly during 2003–2007 period (see Figure 1). The distribution of
papers among different areas of knowledge has shown that in 2003 the most
studies were accomplished in the area of physics (Figure 2a). In 2006 the situation
radically changed, and 3% of projects were devoted to problems of medicine and
biology (see Figure 2b). We can recognize that some of these projects were
relevant to studies of nanotechnology impacts on human health and environment.
The first event in Russia, devoted to the risks and benefits of Nanotechnology,
was organized by National contact point “Nanotech” (FP7-NMP NCP) in October
2006. It was the round table on risks of Nanotechnology for human health and
environment under the title “Nanomaterials may be reactive, but nanoscientists
should be proactive”. This event demonstrated that Russian scientific community
has recognized the importance of studies of Nanotechnology potential impacts on
human health and environment. The similar thematic workshop “Impact of
nanomaterials on (EHS)” was organized within the SCOPE-EAST Conference in
Moscow, December 3–4, 2007 (http://scope-east.net/?p=conference_w_nano).
Figure 1. The increase in the number of research projects in the area of N&N during the period
2003-2007.
Figure 2a. Distribution of nanoprojects among the different subject areas in 2003.
Figure 2b. Distribution of nanoprojects among the different subject areas in 2006.
In 2007 Federal Consumer Rights and Human well being Department

(Rospotrebnadzor; http://www.rospotrebnadzor.ru) issued the regulations concern-
ing the inspection of new products containing Nanomaterials (№ 53, 23.07. 2007);
regarding the approval and implementation of methodological recommendations
on the assessment of Nanomaterials safety (№ 280, 12.10.2007); regarding the
Conception of the toxicological studies, risk assessment methodology, methods of
identification and quantitative description of Nanomaterials (№ 79, 31.10.2007).
Nanotechnology Action Plan for Russia – 2015 will contain the special
subprogramme covering issues of nanosafety and potential impacts of Nano-
materials on health and environment.
Representatives of Russia participate in the work of ISO/229-Nanotechnology.
For last year the specialized working groups with focus on the development of
different aspects of Nanotechnology impacts on human health and environment
have been established in governmental structures and research organizations. For
example, the expert analytical group for nanosafety and nanorisks at the Center for
Advanced Studies of the Saint-Petersburg State Polytechnical University (http://
www.spbcas.ru).
«National Nanoindustry Association» (NCO «NNA»), a non-commercial organi-
zation was established in Russia, January 2008 (http://www.nanotech. ru/nan/).
One of the critical directions of the work is to promote studies of Manufactured
Materials impacts on EHS. NCO NNA organized two relevant workshops “Waste
Management using Nanotechnologies” (March 2008), “Nanotechnology in Chemical
industry” (April 2008).
According to its informal character the special session was not expected to
produce any formal conclusions, however it was highlighted that there is the need
and opportunity for Russia to join the international forum on the possible societal,
health and environmental impacts of nanotechnology. Russia is at the start point in
development of studies on Nanotechnology risks. Coordinating systematic
comparisons of research results and sharing of information between Russia and
other countries, laboratories across the world is of the great importance.
The expert analytical group at the Center for Advanced Studies and Russian
NCP “Nanotech” organized the special session “The international dialog on Nano-
technology risk assessment and management: opportunities for Russia” in the frame
of the Second International Conference on Nanobiotechnologies” “NanoBio’2008”
in Saint-Petersburg (June 16–18, 2008) (http://www.spbcas. ru/nanobio).
The main objectives of the special session are:
To present European and international activities in the area of nanotechnology
risk studies
To discuss how to promote joining of Russia to the bodies responsible for
international cooperation on impacts of nanotechnology to environment,
health safety (EHS)
To consider how to establish the national network for the area of nanotech-
nology risk studies and assessment, how to coordinate and manage different
activities in this area at national level
The summary of the special session has included the following points:
To establish the national forum for the area of impacts of Nanotechnologies
on environment, human health safety (EHS) in the frame of national network
for Nanotechnologies
The national forum will include scientific institutions experienced in risk
assessment, companies, innovative small and middle enterprises
This forum could support national coordination and participation of Russia in

international organizations, such as OECD, ISO, UNESKO, in relation to risk
assessment and risk management
The inventory of research studies in the area of Nanotechnology risks in Russia
will be reflected in the public report “the state-of-the-art”. This report could help
the further development of research strategies to investigate the EHS impacts of
manufactured nanomaterials: on one hand – fundamental studies of different
physico-chemical properties of nanomaterials and development of new methods in
predictive toxicology; on the other hand – targeted research is needed to ensure
adequate understanding of nanomaterials that are close to market.
A very important achievement could be the creation of national data base on
results of studies of toxicity, physico-chemical properties of nanoparticles, manu-
factured nanomaterials. This database should be with easy access and structured.
Detailed studies of Nanotechnology risks have suggested active dissemination
of information on European, national, international activities in this area (special
web-site, newsletters, publishing of booklet); wide dissemination of knowledge
about impacts of Nanotechnologies on EHS in Russia, covering the social aspects
of N&N, boosting the responsible and safe approach to development of this area in
the country; informing of all stakeholders in this area on international efforts and
activities in this area; launch of special; identifying knowledge gaps, facilitate
collaboration between projects, network and communicate; public consultations,
on-line survey on different aspects of Nanotechnology risks and benefits. More
actively participate in FP7 EU projects, calls dedicated to the problems of
Nanotechnology impacts on EHS.
ENVIRONMENTAL RISK ASSESSMENT OF NANOMATERIALS
A.A. BAYRAMOV
Institute of Physics
National Academy of Sciences of Azerbaijan
G.Javid 33
AZ1143 Baku, Azerbaijan
bayramov_azad@mail.ru
Abstract. In this paper, various aspects of modern nanotechnologies and, as a

result, risks of nanomaterials impact on an environment are considered. This very
brief review of the First International Conference on Material and Information
Sciences in High Technologies (2007, Baku, Azerbaijan) is given. The conference
presented many reports that were devoted to nanotechnology in biology and business
for the developing World, formation of charged nanoparticles for creation of func-
tional nanostructures, nanoprocessing of carbon nanotubes, magnetic and optical
properties of manganese-phosphorus nanowires, ultra-nanocrystalline diamond films,
and nanophotonics communications in Azerbaijan. The mathematical methods of
simulation of the group, individual and social risks are considered for the purpose
of nanomaterials risk reduction and remediation. Lastly, we have conducted studies
at a plant of polymeric materials (and nanomaterials), located near Baku. Assessments
have been conducted on the individual risk of person affection and constructed the
map of equal isolines and zones of individual risk for a plant of polymeric
materials (and nanomaterials).
1. Introduction
Nanotechnology can be defined as the control and restructuring of matter below

100 nm in size in order to create materials, devices, structures and functional
systems. Simply put, nanotechnology is the direct manipulation of matter at the
level of atoms and molecules [1]. Restructuring nature at the nanoscale leads to
materials with novel and exotic properties. For existing substances and materials
remade at the nanoscale, these properties are significantly different to their larger
equivalents. The novel properties of nanomaterials make them attractive for use in
industrial processes.
Many reports were devoted to nanotechnology in biology and business for the
developing World, formation of charged nanoparticles for creation of functional
nanostructures, nanoprocessing of carbon nanotubes, magnetic and optical properties
of manganese-phosphorus nanowires, ultra-nanocrystalline diamond films, and

318 A.A. BAYRAMOV
nanophotonics communications in Azerbaijan (2007, Baku, Azerbaijan) [2]. Several

are mentioned below.
Firstly, N. Mamedov from Institute of Physics National Academy of Sciences
of Azerbaijan has made the report, “Photonics (nanophotonics) and optical com-
munications in Azerbaijan: horizons for development”. He noted that current
optical research is directed towards the advanced design and fabrication of optical
fibers, integrated optics, optical amplifiers, optoelectronic devices and nanostruc-
tures, which are all photonic devices. Although research, education, and training
on photonics and nanophotonics in Azerbaijan can hardly be taken for fully adequate
to the word standards, the forecast given by the Ministry of Communications and
Information Technologies with regard to optical communications is optimistic
with a significant increase in the nearest future.
Secondly, Y. Nakavama from Osaka University (Japan) has made the report
“Preparation and nanoprocessing of carbon nanotubes”. He noted that because of
their structural perfection, tiny size, low density, excellent mechanical property
and unique electronic property, carbon nanotubes (CN‘I’s) have been placed in the
research and development of various applications such as reinforcement with
electric conductance for functionalized composites and building blocks for future
nanoscale electronic or electromechanical devices In his report he reviewed recent
works on the synthesis toward millimeter-long blush-like (vertically aligned)
CNTs and nanoscale-engineering of CNTs.
Finally, S. Habib from Nanotechnology Center King Abdul Aziz University
Saudi Arabia has made the report “Nanotechnology for the Developing World”.
He noted that the sheer size of global expenditure on research and development on
nanotechnology is a sure indicator attesting to the very promising economical
viability of nanotechnology worldwide. Presently, the private sector spends over
10 billion annually and the figure is projected to reach 12 billion in 2008, while
global governmental funding on nanotechnology research and development is
about 4 billion and rising. By no means this expenditure is evenly distributed
among the different countries and as a matter of fact the different regions and
contents of the world. A fact indicating how is the possible prime winners of
exploiting the emerging trillion dollar nanotechnology market. Competing for
market shares on the nanotechnology products projected to reach a trillion dollar
size, some countries are spending around €10 per capita annually to develop such
products.
In Azerbaijan, roughly US$10 million is spent each year on the research and
development of nanotechnology and nanomaterials. Nanomaterials in the form of
nanoscale powders and fibres are already being used in sunscreens, cosmetics,
food additives, packaging, scratch-proof and self-cleaning paints and glass,
clothing, sports equipment, disinfectants, fuel additives, batteries and a range of
other products. Table 1 below outlines the applications for nanomaterials that are
currently in use in Azerbaijan or close to commercialization.
ENVIRONMENTAL RISK ASSESSMENT OF NANOMATERIALS 319
Table 1. Nanomaterials currently in use in Azerbaijan.

Energy and environment Industrial catalysts
Fuel additives
Membrane separation
Water/air purification, fuel cells technologies
Electronic Semiconductors
Memory applications
Flexible displays
Manufacturing Coatings; catalysts
Coatings for food protection
Zinc oxide (ZnO) in paints, sunscreens
Mining and agribusiness Alumina platelets
Mineral Separation
Bioextraction; applications for particles, oxide powders
Health and medical Diagnostic markers
Particle engineering
Biosilicates for tissue engineering
Let us consider some common nanomaterials and their uses.
2. Some Common Nanomaterials and Their Uses
Zinc oxide and titanium dioxide powder have been used in sunscreens extensively
since their inception, lending them their distinctive thick white appearance [3].
While these conventional powders are opaque, nanoscale zinc oxide and titanium
dioxide particles in the order of (40–50) nm are transparent while still retaining
the ability to block UV rays. By substituting conventional powders of zinc oxide
and titanium dioxide with nanoparticles, manufacturers are able to produce a
sunscreen that is transparent when applied. In 2003 in Azerbaijan, the initial use of
nanoscale titanium dioxide and zinc oxide began.
Carbon nanotubes consist of carbon atoms arranged in a lattice and rolled into
a tube of variable length, but only a few nm in diameter. They are needle-like in
shape and have a structure similar to that of asbestos [2]. Carbon nanotubes are
extremely strong, up to ten times that of steel, while remaining very light. Their
high strength to weight ratio makes them especially suitable for reinforcing
materials ranging from tennis rackets and car tires, to military tanks. Carbon
nanotubes also exhibit novel electrical conductivity, and they are being developed
for use in high performance circuits and displays.
Catalytic nanomaterials are used in many different industrial processes ranging
from mineral refinement, chemicals production and the manufacture of polymers
(e.g. Chemical Plant of Polymer in Baku). Researchers at Rutgers University in
the United States have been developing nanoscale iron and cobalt particles for use
in the chemical conversion of coal to diesel [4]. With these new catalysts,
researchers hope to continue transport fuel production through the conversion of
coal.
During the manufacture, transport, use and disposal of nanomaterials and those
products containing nanomaterials, the release of these materials into the environment
is inevitable. As the use of nanomaterials increases, presence in the environment
will also. While pathways such as the waste stream from industrial processes or
320 A.A. BAYRAMOV
product disposal are similar to those for other substances, the use of nanomaterials
in sunscreens and cosmetics can also lead to the environmental presence of nano-
materials. In Europe, ecologists are detecting the active ingredients of sunscreens
and skin care products in inland lakes at levels that are starting to have an impact
on wildlife [5]. This suggests that even the use of these consumer products, which
are not traditionally seen as entering the environment after use, will likely lead to
the environmental release of nanomaterials. Since nanomaterials are, can and will
enter into the environment, it is crucial to assess the potential risk these materials
may have for human health and environmental harm.
3. The Risk Assessment of Nanomaterials
The unique properties and extremely small size of nanomaterials are such that
even determining the full extent of the risks to human health and environment is
currently beyond the means of existing risk assessment frameworks [3].
Given that nanomaterials can be more toxic than their conventional equivalents,
it is clear that the risks associated with nanomaterials cannot be inferred from the
relative risk or safety of their bulk equivalents. That is, although some nanomate-
rials are made of substances that have long been used in other forms, their very
different physical and chemical properties mean they may pose different risks than
conventional materials. The toxicity of a nanomaterial cannot be assumed by
comparison with another nanomaterial since toxicological properties arise from a
variety of features, such as their surface characteristics, size, shape, overall
composition and chemical reactivity. There are in essence several independent and
interdependent variables that dictate toxicity.
The dedicated testing of each individual nanomaterial will be particularly
pertinent when next-generation nanotechnology develops complex nanostructures
and devices those themselves actively interact and manipulate molecules and
organic compounds. The level of interactions possible with living organisms and
the wider environment will be so broad and complex that the data derived from
testing one next-generation nanomaterial cannot be used to determine the safety or
risk of any other next-generation nanomaterial due to the inordinate number of
variables in play.
While there is an established methodology for assessing the toxicity of conven-
tional substances, the report into the risks associated with Nanomaterials by
Britain’s Royal Society notes that current testing regimes are not entirely suitable
for nanomaterials [6]. For example, the European Commission’s Scientific Committee
on Emerging and Newly Identified Health Risks has suggested that any determina-
tion of the critical dose of nanomaterials must also take into account the number of
particles and total surface area, rather than just the exposure mass of a substance,
which is the current practice [3]. In addition, the effects of surface characteristics
and coatings, their size and shape, physical composition and chemical reactivity,
and the potential for aggregation (clumping) all need to be specifically tested to
develop a comprehensive assessment of the risks of nanomaterials. The Royal
Society flags as a priority the need to establish a standardized set of methodologies to
effectively assess the contribution of all these factors to nanotoxicity in both the
environment and in humans [6].
Current toxicological methodologies express toxicity with respect to a critical
mass concentration beyond which harm occurs. Yet hazardous dosages expressed
in mass concentrations do not give an accurate indication of the exposure amount
for nanomaterials above which harm is induced. The minimum toxic dose for
nanomaterials is also affected by the total surface area available for biological
reaction and the number of particles present.
The risk assessment of nanomaterials is further complicated by a lack of
established standardized indicators for nanotoxicity. While factors such as surface
characteristics and coatings, shape, physical composition and chemical reactivity,
and the potential for aggregation may all play a role in nanotoxicity, their exact
contribution is not known.
Researchers are still clarifying the way nanomaterials are transported within
living organisms and the regions and organs in which they concentrate. This
information is essential in establishing the risk of nanomaterials as it gives an
indication of which organs and processes are most vulnerable to toxic effects.
The extremely small size of nanomaterials puts them completely beyond the
ability of optical microscopes to detect and analyse. The instruments required to
track and observe nanomaterials, such as scanning tunneling microscopes and
atomic force microscopes, are extremely expensive machines that are confined to
the laboratory. Even for toxicological studies conducted within the lab using cell
cultures or test animals, these instruments are unsuitable for tracking and
analyzing nanomaterials within individual organisms or single cells. This makes it
difficult to study the behaviour of nanomaterials in living organisms and is one of
the reasons why this area of knowledge is so limited.
And so, without a coherent testing regime within which the risks of nanoma-
terials can be appropriately assessed, it is currently impossible to make informed
decisions regarding their handling and use. Not only is there not enough infor-
mation about the actual hazards of nanomaterials currently in use to effectively
manage these risks, but there are no established risk assessment regimes capable
of considering the unique characteristics and properties of these new materials.
4. Simulation of Risk Assessment of Nanomaterials
At normal functioning, the analysis of nanomaterials manufacture shows, the

influence of such objects on an environment is connected both to social–
psychological influence on people and with the potential danger of pollution of an
atmosphere and territory dangerous substances [8–12]. Therefore, the model of
risk should reflect all essential factors on which functioning system to the greatest
degree depends should be taken into account.
Output parameters of mathematical model of risk determine a mathematical
expectation of amount of the affected people living in area of industrial object
[13]. We shall consider possible analytical approaches to the decision of a
322 A.A. BAYRAMOV
problem. The mathematical expectation (risk R) of amounts of affected people can

be determined dependence.
2π ∞
R = ∫ ∫ r (ϕ , l ) ⋅ P(ϕ , l )dϕ ⋅ dl ,
ϕ =0 l =0
Where: r(ϕ,l) is a distance from a plant up to the person in polar coordinates (the
beginning of coordinates is superposed with plant); P(ϕ,l) is a probability of
affection of the person in a point with (ϕ,l) coordinates.
The probability of affection P(ϕ,l) is defined as follows:
P(ϕ,l) = P0(ϕ)⋅Pl(l,ϕ0),
Where: P0(ϕ) is a probability of that at the moment of emission the direction of
wind ϕ = ϕ0 will be realized; Pl(l,ϕ0) is a probability of affection on distance l
from a place of emission in direction ϕ0.
As a pollution is equiprobable at any moment then P0(ϕ) should be defined on
the basis of a wind rose in the given zone or region. If to neglect differences in
characteristics of an underlying surface on each of directions of possible
distribution of harmful emission and to enter concept of the average characteristic,
it is possible to simplify essentially a problem, having divided variables:
l =∞ ϕ = 2π
R = ∫ P(l )
l =0
∫ r (ϕ , l ) ⋅ P(ϕ )dϕ ⋅ dl
ϕ =0
This approach to calculation of risk criterion is one of possible variants of an

analytical method of assessment. In practice of risk assessment, the following
approaches to mathematical modelling risk are considered.
Modeling of individual risk. Individual risk is the probability of the person
affection in the course of year from the certain reasons in the certain point of
space. Results of the analysis of individual risk are displayed on a map of the plant
as the closed lines of equal values (isolines).
The construction of isolines of individual risk is carried out under the formula (1)
Ri ( x, y ) = ∑ ∑P ( Q x, y ) F ( Am ) (1)
m∈M l∈L
Where: PQ(x,y) is a probability of influence on the person in a point with

coordinates (х, у) of the damaging factor Q with the intensity corresponding to
affection of the person (healthy man of 40 years) under condition of realization of
Ат event (pollution); F (Am) is frequency of occurrence of Ат event per year; M is a
set of indexes which corresponds to considered events; L is a set of indexes which
correspond to the list of all damaging factors arising at considered events.
We have carried out researches at a plant of polymeric materials (and

nanomaterials), located near to Baku. Isolines of equal risk and zones of individual
risk are resulted on Figure 1 for this factory.
We can see from Figure 1, that near of plant (zone 1) the individual risk of
person affection is high, R = 10−4. In zone 2 R = 10−5 (the individual risk of person
affection is acceptable). Lastly, in zone 3 R = 10−6, i.e. the individual risk of
person affection is low.
Figure 1. Construction isolines of equal risk and zones of individual risk for a plant of polymeric
materials (and nanomaterials): 1, 2, 3 are zones of accordingly high, acceptable and low risk.
Modeling of social risk. The social risk is a dependence of occurrence frequency

of the events causing affection of people, on this number of people. Social risk R -
F (N) characterizes scale of possible extreme situations. The social risk can be
designed under the formula (2)
⎛ N ⎞ ⎛ Qm ⎞
Rs ( N ) = ∑ ∑ P⎜⎜ Q ⎟⎟ P⎜⎜ ⎟⎟ F ( Al ) , (2)
m∈M l∈L ⎝ m ⎠ ⎝ Al ⎠
⎛ N ⎞
Here: P⎜⎜ ⎟⎟ is a probability of N people affection from the damaging factor
⎝ Qm ⎠
⎛Q ⎞
Qm; P⎜⎜ m ⎟⎟ is a probability of occurrence the damaging factor Qm at realization
⎝ Al ⎠
events Al.
Modeling of risk at accidents on chemically dangerous plants manufacturing
of nanomaterials. On known toxic dose D in a point with coordinates (х, у) a
mathematical expectation of losses among population M (N) is determined under
the formula
324 A.A. BAYRAMOV
M (N ) = ∫ ∫ P[D(x, y )]⋅ψ (x, y )dxdy

Sr
(3)
Where: Sr is an integration domain, i.e. the area of a part of city within the limits
of which people affection is possible at accidents on the set plant; ψ(x,y) is a
density of people location in vicinities of a point with coordinates (x, y); P[D(x,у)]
is a probability of people affection depending on amount of a toxic doze in a point
of city with coordinates (х, у), determined from the parametrical law of people
affection harmful substances; D (x, у) is the toxic doze chemically dangerous
substance for a point with coordinates (х, у) under the formula
tk
D(x, y ) = ∫ Ω(x, y, t )dt

tn
Where: tn..........tk are intervals of time; Ω(х,у,t) is a concentration of chemically

dangerous substance in an atmosphere for a point with coordinates (х, у) during
the set moment of time (t).
Under the formula (3), mathematical expectation of losses is determined for a
case when the initial data are known. It is necessary to take into account
variability of a direction (θ) and speeds of a wind (v) within 1 year. Then losses
can be determined under the formula
2π Vmax
M (N ) = ∫ ∫ ∫ ∫ f (θ ,V )P[D(x, y )]ψ (x, y )dVdθdxdy
Sr 0 Vmin
(4)
Where: f(θv) is a function of density of distribution of a direction 0 and speed v a

wind; vmin and vmax are minimal and maximal possible values of speed of a wind; Sr
is an integration domain. Other designations are same, as in the formula (3).
Taking into account expression (4), the assessment of individual risk at a plant
can be carried out under the formula
2π Vmax
H
Re =
N ∫ ∫ ∫ ∫ f (θ ,V )P[D(x, y )]ψ (x, y )dVdθdxdy
Sr 0 Vmin
Where: H is a probability of pollution in the course of year; N is population size.
5. Conclusion
Various aspects of modern nanotechnologies and risks of nanomaterials impact on

an environment are considered. The mathematical methods of simulation of the
group, individual and social risks are considered for the purpose of nanomaterials
risk reduction and remediation. We have carried out researches at a plant of

polymeric materials (and nanomaterials), which is located near Baku.
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CONSIDERATIONS FOR IMPLEMENTATION
OF MANUFACTURED NANOMATERIAL POLICY
AND GOVERNANCE
F.K. SATTERSTROM
Harvard University School of Engineering and Applied Sciences
Cambridge, MA 02138, USA
satterst@fas.harvard.edu
A.S.A. ARCURI
Foundation on Occupational Safety and Health Researches and
Studies (FUNDACENTRO)
Ministry of Labour and Employment
São Paolo 05409-002, Brazil
T.A. DAVIS
Department of Chemistry, University of Montreal
C.P. 6128, succursale Centre-Ville
Montreal (QC) H3C 3J7, Canada
W. GULLEDGE
American Chemistry Council
1300 Wilson Blvd., Arlington, VA 22209, USA
S. FOSS HANSEN
Department of Environmental Engineering, Nano DTU
Building 113
Kgs. Lyngby DK-2800, Denmark
M.A. SHAFY HARAZA

Quality Assurance, Quality Control Department
National Center of Nuclear Safety and Radiation Control Atomic
Energy Authority
Ahmed El Zomor Street
Nasr City 11672 Box 7551
Cairo, Egypt
L. KAPUSTKA
LK Consultancy
Kapustka@shaw.ca
330 F.K. SATTERSTROM ET AL.
D. KARKAN
Nanotechnology Health Products and Food Branch
A.L. 2005A, Graham Spry Building
Ottawa, Ontario K1A 0K9, Canada
I. LINKOV
US Army Engineer Research and Development Center
Concord, MA 01742, USA
M. MELKONYAN
Institute of Crystallography of RAS
Leninsky pr., 59
Moscow 119333, Russia
J. MONICA
Porter Wright Morris & Arthur LLP
1919 Pennsylvania Avenue NW, Suite 500
Washington, DC 20006-3434, USA
R. OWEN
Department for Environment, Food and Rural Affairs (DEFRA)
Environment and Human Health Programme, UK Environment
Agency Block 1 Government Buildings
Burghill Road
Bristol BS10 6BF, UK
J.M. PALMA-OLIVEIRA
Faculty of Psychology and Sciences of Education (FPCE)
University of Lisbon, Alameda da Universidade
1100 Lisboa, Portugal
B. SRDJEVIC
Faculty of Agriculture, University of Novi Sad
Trg D. Obradovica 8
Novi Sad 21000, Serbia
Abstract. Many policy frameworks for risk assessment of manufactured nanomate-

rials have been developed worldwide. These frameworks range from voluntary
methods and self-regulation to prescriptive regulation. In our view, the regulatory
policies ideally need to include consideration of the risks and benefits of nanotech-
nology, as well as risk perception and risk communication efforts. Further, the
policies should: (a) take a holistic viewpoint, considering the entire lifecycle of a
manufactured nanomaterial, including use, production, transport, and disposal, and
MANUFACTURED NANOMATERIAL POLICY AND GOVERNANCE 331
(b) consider the ecological and human health effects for all of the reasonably
foreseeable exposures. There is a need for adaptive management to allow reaction
to new developments (e.g., new toxicology information) and to gain additional
information through policy.1– 2
1. Introduction
The authors of this chapter were members of the Considerations for Implemen-
tation of Manufactured Nanomaterial Policy and Governance Working Group at
the NATO Workshop on Nanomaterials Risks and Benefits (Faro, Portugal, April
2008). The working group (WG) focused on risk assessment and policy frameworks.
This chapter includes the original focus and also discusses guidance on methods
for policy development based on the best available science, as well as the infor-
mation and tools (e.g., databases, modeling software, and web portals) that (a) support
the development of policies by regulators, industry, and others, and (b) efficiently
disseminate information to the public and others.
The foundation for the WG’s efforts was a recent book chapter [24] that reviewed
current nanomaterial risk management frameworks and related documents developed
by regulatory agencies, trade associations, not-for-profit organizations, academics,
and companies, including an in-depth review of 13 such documents. Table 1 lists
11 documents reviewed by Linkov and Satterstrom, and the WG added one
additional recently published U.S. government multi-agency framework (National
Nanotechnology Initiative, NNI) and the European Union’s recently enacted
Registration, Evaluation, Authorisation, and restriction of CHemicals (REACH)
legislation. In all, the models and frameworks include comprehensive state-of-the-
science regulation framework documents, voluntary programs, documents on the
regulation and ethics of nanomaterials, and position statements.
The Linkov and Satterstrom chapter developed a list of criteria based on work
being undertaken by Health Canada on nanotechnology, with the categories being:
(1) Science and Research Aspects; (2) Legal and Regulatory Aspects; (3) Social
Engagement and Partnerships; and (4) Leadership and Governance. Within each
category, Linkov and Satterstrom modified Health Canada’s specific criteria to fit
their categories. For example, the “Science and Research Aspects” are adapted
from the US Nanotechnology Environmental and Health Implications Working
Group’s research needs categories, and the Legal and Regulatory Aspects are
adapted from the Woodrow Wilson Center. The WG also reviewed the NNI and
REACH in the same manner, with the results included in Table 1.
1
2
The views and opinions expressed in this paper are those of the individual authors and not those of the
US Army, NATO, or other sponsor agencies.
TABLE 1. Overview of papers discussing different aspects of the nanomaterial risk assessment process
in Linkov and Satterstrom [24], with information added by the Working Group for the NNI and
REACH. Elements of nanomaterial regulation frameworks discussed in each document (criteria are
numbered 1–4 under each category; for each document and criterion, ■ = document discussed the
criterion, ▪ = document mentioned the criterion, and (blank) = document did not address the criterion).
Sub-criteria for the table are as follows:

Science and research aspects Category 3: Social engagement and
partnerships
1. Development of methods for 1. Promotion of education and distribution of
detection/characterization/data collection information/use of risk communication tools
2. Assessment of environmental fate &
2. Use of stakeholder engagement tools
transport/impacts
3. Development of partnerships with academia,
3. Assessment of toxicology/human health
industry, public organizations, provinces, and
impacts
international regulators
4. Assessment of health and environmental
4. Emphasis of ethical conduct
exposure
Legal and regulatory aspects Category 4: Leadership and Governance
1. Voluntary regulatory and best-practices 1. Transparency in nanotechnology-related
measures decisions
2. Information-based regulatory tools (e.g.,
2. Consideration of benefits of nanotechnology
labeling)
3. Economic-based regulatory tools (e.g., tax or 3. Adaptive modification of existing or
fee for safety testing) development of new legislation
4. Liability-based regulatory tools (e.g., penalty
4. Consideration of precautionary principle
for pollution)
The WG agreed with the conclusion from the Linkov and Satterstrom chapter
that regulatory tools should be further assessed to ensure availability of the metho-
dology and knowledge base necessary to regulate manufactured nanomaterials.
Further, the WG agreed that the starting point for further development of these
tools is the set of risk assessment and risk management policies and procedures
already developed by regulatory agencies and industry for traditional industrial
materials, such as surfactants and other chemical substances.
2. Regulatory Gaps and Review of the Current Landscape
This section presents a summary of current regulatory frameworks and trends

reported and discussed at the NATO Workshop.
2.1. EU PERSPECTIVE
The identification of limitations of the current regulation of nanomaterials has been

subject to intense international scrutiny. European legislation covers nanomaterials in
principle [14, 15], and four areas are especially relevant to nanomaterial regulation:
(1) the new chemical legislation termed Registration, Evaluation and Authorisation
and restriction of CHemicals (REACH); (2) food laws; (3) the safety at workplace
directives, and, finally, (4) waste management directives [19].
REACH went into force in early 2007, establishing an authorizing system that
requires the registration and evaluation of existing and new chemical substances
marketed in the EU [17]. Under REACH, a chemical substance is defined as:
a chemical element and its compounds in the natural state or obtained by
any manufacturing process, including any additive necessary to preserve
its stability and any impurity deriving from the process used, but
excluding any solvent which may be separated without affecting the
stability of the substance or changing its composition [17].
In theory, the wide definition of a chemical substance under REACH covers
nanoscale substances [5]. However, REACH has at least two major limitations of
its potential application to nanoparticles. First, registration is based on chemical
composition, which means that, for instance, C60 and carbon nanotubes could in
theory be included under the same registration as carbon black, and nano-sized
TiO2 could be included under the same registration as micron-sized TiO2, despite
the fact that it is well-known that these have vastly different chemical and
biological properties [8, 19].
Another potential limitation of REACH is that requirements for producers and
importers to provide toxicological data and requirements for assessing environ-
mental exposure are based on mass thresholds. Data sets are not required until
production or imported volumes are above the threshold of 1 t/year of substance.
For many nanoparticles, this threshold would hardly be reached in the short term
[5, 19] low concentration of nanoparticles in a final product article is likely to
exclude many nanoengineered articles from the REACH legislation, since no
registration is required when the concentrations of a substance is lower than 0.1%
w/w [19].
Just as REACH in theory covers nanomaterials, so do EU food laws, since the
EU Food Law Regulation requires all food to be safe [18]. This in theory applies
to all foods and food packaging containing nanomaterials as well; however, the
laws have been criticized for being too loose [20]. None of the existing EU
regulations applicable to agriculture, food, or food packaging currently consider or
mention nanoscale products or materials, nor do they require new safety
assessment or labeling due to particle size [20].
Future regulation may include nanomaterials more explicitly. The European
Parliament’s Committee on the Environment, Public Health and Food Safety
stated last year that it wanted separate limit values for nanotechnologies and that
the permitted limits for a nanoparticle additives should not be the same as for
traditional food additives [21]. Additionally, in a recent proposal adopted by the
European Commission to revise the EU Novel Foods Regulation, the definition of

novel food includes foods modified by new production processes, such as
nanotechnology and nanoscience, which might have an impact on the food itself
[9]. The European Food Safety Authority (EFSA) is also currently preparing an
initial scientific opinion on the potential risks arising from the use of
nanotechnology in food, expected by 31 March, 2008 [20].
The Safety at Workplace Directives include no direct reference to workers’
potential exposure to engineered nanoparticles, nor does the communitarian and
national legislation on the protection of workers’ health at workplaces [19]. The
Framework Directive 89/31 and Directive 98/24 on the risks associated with
chemical substances set guidelines to establish Occupational Exposure Limits
(OELs) for workers [10, 11]. However, there are three main problems associated
with the establishment of OELs for workers at this point:
1. The establishment of OELs is typically based on a complete risk assessment
procedure which is presently not possible for engineered nanoparticles.
2. OELs are based on mass concentration being a proper metric for toxicity, but
the most optimal parameter(s) to determine nanoparticle toxicity is still
undefined.
3. Nanoparticles are not easily detected and monitored in the workplace and it is
unclear whether existing personal protective equipment is adequate [19].
Just as with the safety at workplace directives, there are no specific references
to engineered nanoparticles in existing laws. Hence, nanomaterial-including
wastes are tackled by waste management regulations in a non-specific way [19].
In some cases, the nano-waste can fall within a particular waste category; for
example, C60 in oil lubricants is specifically regulated [19]. If a certain nano-waste
falls within the scope of Council Directive 1991/689 on the management of
hazardous waste [12], more severe obligations would apply. Again, the lack of
(eco)toxicological data makes it difficult to state if nanoparticles meet the criteria
of hazardousness [19].
2.2. U.S. PERSPECTIVE
The regulation of engineered nanoscale materials at the federal level in the United
States is currently accomplished through the application of existing environmental,
health, safety, food, drug, and workplace laws. Engineered nanoscale materials are
primarily subject to the regulatory authorities enforced by the Environmental
Protection Agency (EPA), Food and Drug Administration (FDA), Occupational
Safety and Health Administration (OSHA), and the Consumer Product Safety
Commission (CPSC). Whether new nano-specific laws, regulations, and/or guidance
documents are needed is the subject of vigorous research, analysis, and debate.
2.2.1. EPA
The EPA currently uses existing laws and regulations to guard against any potential
nano-related environmental health and safety (EHS) risks. The most prominent
laws in this scheme are the Clean Air Act, Clean Water Act, Safe Drinking Water
Act, Resource Conservation and Recovery Act, Comprehensive Environmental
Response Compensation and Liability Act, Federal Insecticide, Fungicide, and
Rodenticide Act, and the Toxic Substances Control Act (“TSCA”). The EPA has
primarily relied upon TSCA thus far.
The EPA has comprehensive authority to regulate the production and use of all
chemical substances under TSCA, including engineered nanoscale materials. If the
EPA makes the requisite findings that a specific chemical substance poses a sub-
stantial EHS risk, it has full power to limit or ban that substance. No such findings
have been made (or asserted) for any engineered nanoscale material. Further, any
new chemical substance or significant new use of an existing chemical substance
requires premanufacturing review and approval by the EPA under TSCA. The
EPA determines whether an engineered nanoscale material is a new chemical
substance or significant new use of an existing chemical substance based on the
case-by-case approach that the Agency has historically applied in determining the
TSCA inventory status of chemical substances.
Under its TSCA powers, the EPA initiated a voluntary information collection
program for engineered nanoscale materials in January 2008. The EPA’s Nanoscale
Materials Stewardship Program (NMSP) is intended to provide a firm scientific
foundation for any future regulatory action by encouraging submission of hazard
and other information including risk management practices for nanoscale materials.
The EPA worked extensively with interested stakeholders on the NMSP’s design,
which has two levels: a “basic” and an “in-depth” program.
Basic program: Participants were invited to voluntarily report available infor-
mation (including material characterization, hazard, use, potential exposures,
and risk management practices) on any engineered nanoscale materials they
manufacture, import, process, or use. The EPA developed a data form for
submitting this information, but participants were asked to provide available
data in any convenient format. Additionally, the EPA did not ask participants
to develop any new information, only to submit existing data. Participants who
had already developed a risk management plan were invited to include the plan
as part of their submission under the basic program. The EPA further encouraged
participants who do not have a risk management plan to consider developing
one and provide it with their basic submission.
In-depth program: Participants are invited to voluntarily develop data (including
testing if needed) over a longer timeframe. Entities or consortia with an
interest in developing data for a specific nanoscale material(s) were requested
to notify the EPA at any time. Once potential participants are identified, the
EPA will facilitate a process leading to data development. The EPA states:
“The data and experience generated by the basic program, including input
from the interim program evaluation, will help to inform the types of in-depth
data that need to be developed.” As of late July 2008, the EPA has received
submissions under the Basic Program from 19 companies covering 90
nanomaterials. An additional 11 companies committed to the EPA to provide
information, also under the basic program. Three companies volunteered to

participate in the in-depth program.
2.2.2. FDA
Because it is already accustomed to dealing with products that interact with the
body at the nanoscale level, the FDA believes existing laws, regulations, and
product review and approval processes should be sufficient to ensure against any
potential EHS risks posed by the use of nanoscale materials in food, drugs,
medical devices, biologics, blood & vaccines, animal & veterinary products,
cosmetics, radiation-emitting products, and combination products. To this end,
FDA employs a “product-by-product” approach that may include one or more of
the following:
Premarket Approval: Prior to introduction into the marketplace, new phar-
maceuticals, high-risk medical devices, food additives, colors, and biological
substances require prior approval by the FDA. Typically, the producer/sponsor
of the product identifies and assesses the risks presented by the product and
addresses each risk and how it will be minimized in a product application.
FDA staff then reviews these documents, often with the assistance of an
Advisory Committee. A pre-approval inspection of the manufacturing plant is
often required.
Premarket “Acceptance”: These products are often similar to products that
were approved previously or are products prepared in accordance with
approved specifications, such as pharmaceuticals manufactured to existing
USP Monographs and medical devices marketed with 510(k) Premarket
Notifications. The review process of these products is significantly more rapid
than Pre-Market Approval.
Post-Market Surveillance: In this third category, the FDA manages the risks of
products like foods, cosmetics, radiation-emitting electronic products, and
materials such as food additives and food packaging that are “generally
recognized as safe” (GRAS). For these products, market entry and distribution
are at the discretion of the manufacturer/producer. All of these products are
generally regulated by the application of Good Manufacturing Practices. FDA
monitors the behavior of these products and takes regulatory action if adverse
events occur that threaten public or individual health.
2.2.3. OSHA
Potential workplace exposure risks are regulated under existing OSHA standards.
No nano-specific workplace exposure standards have been deemed necessary as of
the date of this paper. Additionally, the National Institute for Occupation Health
and Safety informs and advises OSHA regarding workplace exposure issues and
has published a strategic research plan and workplace handling guidance docu-
ments specifically addressing the use of engineered nanoscale materials in the
workplace.
2.2.4. CSPC
Certain widely-used consumer products containing engineered nanoscale materials

are regulated by the CPSC under existing laws. The CSPC’s resources are stretched,
although its FY 2009 budget contains its first ever nano-specific funding for research
and study. While the CSPS believes its existing laws are sufficient to cover nanoscale
materials, it also notes that the nanoscale products it regulates are not subject to
premarket approval; thus, the CPSC may not become aware of some potential
EHS risks involving these products until reported after the fact.
2.2.5. Municipalities and States
Finally, two American municipalities have created registries for engineered nanoscale
materials – Berkeley, California and Cambridge, Massachusetts. Several states are
contemplating similar initiatives.
Berkeley’s hazardous materials handling ordinance was amended in December
2006 to encompass engineered nanoscale materials. The ordinance requires:
All facilities that manufacture or use manufactured nanoparticles shall
submit a separate written disclosure of the current toxicology of the
materials reported, to the extent known, and how the facility will safely
handle, monitor, contain, dispose, track inventory, prevent release and
mitigate such material3 […] All manufactured nanoparticles defined as a
particle with one axis less than 100 nanometers in length, shall be
4
reported in the disclosure plan.
So far, only a handful of companies have submitted information responsive to
Berkeley’s ordinance.
Further, Cambridge, Massachusetts studied the same issue during 2008 and
determined that:
[i]n the absence of acceptable exposure standards, the Cambridge Public
Health Department, with the invaluable guidance offered by the
Nanomaterials Advisory Committee, has concluded that active and
constructive collaboration with firms and institutions in Cambridge that
currently manufacture, process, or conduct research on engineered
nanoscale materials is the most reasonable and effective strategy at this
time for reducing health risks to workers, students, and residents.
In keeping with this conclusion, in July 2008, Cambridge’s City Council
adopted a six-part plan for dealing with possible EHS risks related to engineered
nanoscale materials:
3
Berkeley, California, Municipal Code, Chapter 15.12, Hazardous Materials and Waste Management,
Section 15.12.040(I), Filing of disclosure information.
4
Berkeley, California, Municipal Code, Chapter 15.12, Hazardous Materials and Waste Management,
Section 15.12.050(C)(7), Quantities requiring disclosure.
1. Have the Cambridge Fire Department and the Local Emergency Planning
Committee establish an inventory of engineered nanoscale materials being
manufactured, handled, processed, or stored in the city
2. Work with academia and industry to offer assistance to companies to help
evaluate and limit potential workplace exposure to nanoscale materials
3. Educate the public concerning products containing nanoscale materials
4. Track nano-related EHS science and studies as they develop
5. Track the status of regulations and best practices concerning nanoscale
materials as they develop and
6. Report back to the City Council every 2 years on any new development in
these areas
2.3. CANADIAN PERSPECTIVE
The Canadian Environmental Protection Act, 1999 [7] is in place to contribute to

sustainable development through pollution prevention and the protection of
environment and human health. Under the Act, provisions are outlined for both
new and existing substances as well as establishing a legal regime for information
gathering and assessment powers. The Domestic Substance List (DSL) is the sole
basis for determining whether a substance is new in Canada, and any substance
not listed on the DSL is considered to be new, and thereby subject to New
Substances Notification Regulations (NSNR). These regulations ensure that any
new substance undergoes a risk assessment of its potential effects on the
environment and human health.
Currently in Canada, the Act and the Regulations apply to new nanomaterials
in the same way as any other substance, as outlined in the New Substances
Program Advisory Note 2007–06. Although there is no internationally recognized
definition of a nanomaterial, they can be described as substances having one or
more dimensions in a nanoscale range. Accordingly, nanomaterials which are
manufactured in or imported into Canada are subject to the same regulatory
requirements as chemicals and polymers. In this framework, nanomaterials which
are manufactured in or imported into Canada that are not listed on the Domestic
Substance List are considered new and thereby subject to the Regulations. The
nanoscale form of a substance on the DSL is viewed to be new if it has “unique
structures or molecular arrangements.” As an example, the nanomaterial fullerene
(CAS No. 99685-96-8) is not listed on the DSL and is therefore considered as a
new substance in Canada.
Under the “Proposed Regulatory Framework for Nanomaterials Under the
Canadian Environmental Protection Act, 1999” [6], Environment Canada and
Health Canada propose a two-phase approach for a regulatory framework for
nanomaterials. The proposal emphasizes the importance of being scientifically
robust as well as harmonized with international efforts. The two-phase approach is
based on short- and long-term objectives. Phase 1 (2006) consists mainly of
working with international partners to develop scientific and research capacities,
informing potential notifiers of their regulatory responsibilities under the current
framework, developing information-gathering initiatives, and considering whether
amendments to CEPA [7] or the New Substances Notification Regulations will be

needed. Phase 2 (beginning 2008) consists of a focus on terminology and
nomenclature by ISO TC229, consideration of data requirements under NSNR,
and consideration of the Significant New Activity (SNAc) provision of CEPA [7]
to require notification of nanoscale forms of substances already on the DSL.
2.4. OTHER GLOBAL PERSPECTIVES
The United Kingdom has been in the forefront of developing and implementing
voluntary environmental programs for nanomaterials, including one run by the UK
Department for Environment, Food and Rural Affairs (DEFRA). The DEFRA
voluntary reporting scheme is intended to:
develop a better understanding of what types of engineered nanoscale
materials are likely to be produced in the UK, and to build up an under-
standing of their properties and characteristics so that the potential
hazard, exposure and risks associated with these materials may be
determined [28].
The program is intended to run for 2 years. Industry is asked to submit existing
data on the characteristics of engineered nanoscale materials, including information
on material characterization, hazard, use and exposure potential, and risk manage-
ment practices. Submission of all available information is encouraged and lack of
a complete package of data should not keep companies from reporting under the
scheme [28]. However, DEFRA does not request that industry develop new data
and even discourages industry from generating any additional data that would
require animal testing [28]. After 6 months of implementation, only nine submis-
sions have been received by DEFRA, two from academia and seven from industry
[30].
The Brazilian co-author of this chapter, an occupational exposure expert, noted
potential special considerations regarding worker exposures when developing and
implementing policies and regulations for manufactured nanomaterials. Workers
may present the main exposure risk potential among humans, and they may be
involved in the entire product life cycle. These activities imply that workers may
be exposed to these products for a much longer time than the general population,
and to potentially much higher concentrations as well. This situation is of special
concern when there is the possibility of nanomaterial release to the atmosphere,
especially in the form of nanoparticles. It is also of special concern when activities
involve possible dermal contact with the nanoparticles. These possible workplace
exposures require specific regulations concerning the production and use of the
manufactured nanomaterials, aimed at eliminating or at least minimizing the
possibility of occupational exposures to these products. It is also important to
remember that the workers have the right to know the type of agents to which they
may be exposed. Recommendations about regulations should thus include
consideration of the workplace.
Additionally, the WG notes that developing countries may be affected by the
nanotechnology products manufactured in developed countries [1], that Russia has
taken initial steps in nanotechnology risk assessment, and that Israel is active in
nanotechnology research as well.
3. Considerations for Development and Implementation of Policy

and Governance
In addition to the prescriptive regulation discussed above, voluntary and other

programs have also been initiated to regulate nanomaterials.
3.1. VOLUNTARY ENVIRONMENTAL PROGRAMS
Given the gaps and limitations of the current regulation, the questions as to
whether or not or how to regulate the manufacture and commercialization of
nanomaterials have become the subject of heated debate internationally. Several
governments have opted to implement voluntary environmental programs (VEPs),
arguing that this is the only viable proportional option for the time being [22, 28,
29, 31, 33]. Two such VEPs, both already discussed, are the voluntary Nanoscale
Material Stewardship Program implemented in the US in 2008 and the voluntary
reporting scheme for engineered nanoscale materials implemented in the UK in
2006.
It remains to be seen whether voluntary measures will be enough to generate
up-to-date and relevant health and safety information to ensure protection of
health, safety, and the environment. It is generally known that key elements of any
successful VEP are incentives to participate for various stakeholders, agency
guidance and technical assistance, signed commitments and periodical reporting,
quality of information, and transparency in design, reporting, and evaluation.
However, Hansen and Tickner [22] recently found that many of these elements
have not been fully addressed in VEPs currently implemented on nanomaterials in
the UK and the US. After 2 years of the DEFRA program implementation and 6
months of implementation in the US, the number of submissions received remains
small [13, 30].
3.2. INTEGRATION OF RISK ASSESSMENT, COST-BENEFIT

ANALYSIS, AND MULTI-CRITERIA DECISION ANALYSIS
Conventional methods and decision-support tools such as risk assessment, cost-

benefit analysis, and risk-benefit analysis have a number of limitations and have
often proven inadequate to deal with complex and uncertain environment and
health problems such as the ones posed by nanotechnologies [16, 34]. For
instance, entities such as economists, governments, and public health agencies
tend to think in utilitarian terms, assuming that, when faced with risks, all
available information is used to calculate the expected value of costs and benefits.
The best choice is then assumed to be the one with the greatest expected net
benefits. However, in realistic political discourse, people tend to include values
such as distribution of risks and benefits, dread of the unknown, fear of the
uncontrollable, and anger at unfairness as well as the expected value of harm [26,
27, 34].
Conventional decision-support tools might be used in decision-making processes
to help inform the often challenging decisions about competing risks. However,
this requires due consideration of their limitations, and it is important to remember
that the decisions need to be informed by public values (that is to say, value
conflicts cannot be solved by science alone) [32, 34]. Past efforts have focused on
identifying the exact quantitative risk or cost-/risk-benefit ratio of particular risks
rather than providing guidance to decision-makers on how to interpret risk numbers
and decision alternatives. Furthermore, they have provided little guidance on what
to do with available information or on what actions might be warranted given the
information, thus falling short of its ultimate aim [34].
Instead of going to great lengths trying to use and adapt conventional decision-
support tools for nanomaterials, a trade-off analysis for manufactured nanomaterials
could be focused on mapping and understanding known and suspected risks and
benefits, and the availability of risk-superior alternatives (through alternatives
assessment) without necessarily translating them into a common metric cost [2].
All effects should be described in their natural units and the time period in which
each effect is experienced should be fully revealed, as should the uncertainties,
e.g., in risk and probability distributions [2].
Group Economic effects Health/safety effects Environmental effects

Producers C$
Workers C$ BH/S
Consumers C$ BH/S
Others C$ BH/S EH/S
In order to make the trade-off analysis successful, a broad stakeholder represen-

tation should be sought to enable a holistic analysis of the known and suspected
risks and benefits. The lack of information for “red flags” such as persistence or
bioaccumulation of nanomaterials should be considered as indicators of a strong
potential for negative surprises. A wide range of preventive regulatory options
must then be explored and implemented. Tradeoffs should not seem as inevitable,
but rather spark additional research and investment into risk-superior alternatives,
exploiting the fact that proactive regulatory measures to improve public health can
spark innovation within industry [3, 4, 25].
4. Policy Challenges
4.1. CHALLENGES
The WG agreed that the challenges for manufactured nanomaterial-related policies

include consideration of the risks and benefits of these materials and their uses.
However, instead of focusing on estimating the exact risks and benefits, the WG
noted that the efforts should be directed toward understanding tradeoffs and
finding superior risk alternatives given information currently available.
Another challenge is how to include a thorough understanding of risk

perceptions, which can depend on the applications in which the technologies are
being used, and then developing appropriate risk communication efforts. Public
perception of the risks stemming from nanotechnology is important, not only with
regard to a person’s own personal risk, but also with regard to perception of risk
toward others (e.g., family) and the environment. In recent years, several studies
have examined public perception of nanotechnology. Generally speaking, there
seems to be little knowledge about nanotechnology in parallel with a low level of
risk perception. Results from more detailed experiments show a much more
complex picture (see Palma-Oliveira et al., this volume). The results demonstrate
that the main factors which could explain most of the variance in the judgment
data are related to notions of harm and benefits, the number of people exposed, the
level of scientific knowledge, the fact that nanomaterials applied to biotechnology
represent a new risk, the potential damage to the environment, and the degree to
which the consequences were voluntary or observable. Furthermore, experts
significantly and systematically perceived less risk for all of the seven biotech
applications. Additionally, the risk from food-related applications was considered
higher by both groups than the risk from medical applications. The WG also noted
the challenges of considering the risk perceptions of policy makers and risk
assessors, and that any differences with public perceptions should be highlighted
and used to inform communication efforts.
Such a pattern of results seems to indicate that despite the current positive
view of nanotechnology, this picture could be easily be reversed if something
negative and globally significant should happen. The need for improved public
knowledge and good risk management and communication is therefore stressed.
Several additional challenges were noted by the WG. For example, as with
other substances in the environment, nanotechnology regulators need to consider
the differences between natural and both engineered and non-engineered anthro-
pogenic nanomaterials, and the associated scientific and legal challenges associated
with separating these materials for risk assessment, risk management, and policy
purposes. Another challenge discussed by the WG was the need to understand the
complex relationships between sources and the related exposure pathways to many
potential receptors. Further, the WG noted a need for a common, standardized
taxonomy and terminology for nanomaterials, including capturing key aspects of
their physical and chemical characteristics, together with the establishment of
standardized “use categories.”
4.2. STRATEGIES FOR ADDRESSING POLICY CHALLENGES
The WG generally agreed with the strategies noted in the Linkov and Satterstrom
[24] book chapter. These include that, to best manage nanotechnology risk,
regulatory agencies need an adaptive, tiered framework. The framework should
employ multiple tools at different levels of the regulatory pyramid, with specific
tools chosen on a case-by-case basis. The adaptive framework should be utilized
to react to new developments and to gain additional information through policy.
Further, a “regulatory pyramid” (with self-regulation at the pyramid’s base and
prescriptive legislation at the apex) is needed. However, some members of the

WG noted that the huge diversity of possible materials in nanotechnology makes
the pyramid approach very challenging, and that it would be impossible to develop
a “one-way-to-go” methodology to support the development of policies. This is
especially true in countries where more than one regulatory agency is involved in
the regulatory process for manufactured nanomaterials.
In addition, the WG noted that information-based tools or economics-based
tools would help the nanotechnology industry from the bottom up (i.e., self-
regulation), in addition to the top-down approach (i.e., prescriptive regulation)
offered by traditional risk assessment. Further, it was noted that multi-criteria
decision analysis, including stakeholder engagement, can be used to prioritize
regulatory knowledge gaps, select specific regulatory tools, and also to allocate
limited resources and focus follow-up activities. The WG also felt that an
adaptive, tiered integration of risk management with decision support would thus
be ideal.
Further, the WG agreed that a common, standardized taxonomy and terminology
for nanomaterials, including the capturing of key aspects of their physical and
chemical characteristics, together with the establishment of standardized “use
categories,” should be the global goal. This would facilitate the development of
information resources (e.g., publications and other documents, and databases) that
provide easy access and sharing across countries as regulators attempt to under-
stand and assess the properties of new materials compared to similar materials.
Attempts could be made to have a leading global organization(s) for key aspects
of this effort.
Other challenges and needs noted by the WG included:
The differences between sources and intended uses of nanoscaled particles
(naturally occurring vs. manufactured) need to be acknowledged and considered
when developing policies and frameworks.
Interactions and collaborations among regulators, scientists, and other stake-
holders need to continue to be encouraged to develop coherent, adequate
policies to address such a dynamic field.
The ideal policy should take a holistic viewpoint, considering the entire
lifecycle of a nanomaterial, including not only use but also the production,
transport, and disposal/recycling.
The main exposure considerations for policy development include occupa-
tional, consumer, and general population exposures of humans, as well as
environmental exposures of ecological receptors.
Ecological and human health effects should be considered for all reasonably
foreseeable multimedia exposures.
Attempts should continue to be made by both companies and regulatory agencies
to communicate information about manufactured nanomaterials to the public.
The WG noted the efforts of the not-for-profit GreenFacts (http://www.
greenfacts.org) to provide information.5
5
See http://copublications.greenfacts.org/en/nanotechnologies/index.htm.
Development of a crisis-/catastrophe plan for manufactured nanomaterials

should be considered by both companies and regulatory agencies. The recent
case of the Magic Nano consumer products in Germany being associated with
respiratory problems was discussed by the WG as both a good and bad
example of how such crisis could/should not be addressed by the material
6
supplier, consumer product company, and a regulatory agency.
5. Progress in Bridging Gaps and Overcoming Challenges
5.1. PROGRESS IN DEVELOPING THE NOMENCLATURE

AND TAXONOMY
The rapid development of nanotechnology has meant an accompanying and

equally rapid increase in the number of terms used in both nanoscience and
nanotechnology. These terms need to be organized and accurately described to
avoid the development of different terms to describe the same material or property
so that consistency can be ensured between all stakeholders. Examples of such
terms include nanotube, nanoshell, nano-onion, etc. Along with these ambiguous
terms, there needs to be an unambiguous system to describe specific nanomaterials
to avoid duplication of work between researchers, allow industry to protect
patents, and regulators/governments to accurately assess the risk of a specific
material. These specific names take the form of a nomenclature system, similar to
the ones currently in place for other materials, such as Chemical Abstract Service
(CAS) and International Union of Pure and Applied Chemistry (IUPAC) for
chemicals and polymers, and International Union of Biochemistry and Molecular
Biology (IUBMB) for biological systems.
The development of such terms and nomenclature has come under the auspices
of the International Standards Organization (ISO) Technical Committee on nano-
technologies 229 (TC/229). TC/229 was mandated by the Organisation for Economic
Co-operation and Development (OECD) Working Party on Manufactured
Nanomaterials (WPMN) to develop standards for three themes: (1) terminology
and nomenclature (TC/229 working group 1); (2) measurement and metrology
(TC/229 working group 2); and (3) environmental health and safety (TC/229
working group 3). The scope of working group 1 (WG1) is defined as “(to) define
and develop unambiguous and uniform terminology and nomenclature in the field
of nanotechnologies to facilitate communication and to promote common under-
standing.” (ISO/TC229 N230 Business Plan).
5.1.1. Taxonomy
Under Working Group 1(WG1), work is currently underway to develop a systematic

procedure (i.e., taxonomy) to address terminologies dealing with nanomaterials.
6
See http://www.smalltimes.com/Articles/Article_Display.cfm?ARTICLE_ID=270664&p=109 and
http://www.bfr.bund.de/cm/279/frequently_asked_questions_on_nanotechnology.pdf.
There exist specific projects, such as (1) developing a hierarchy of terms (i.e., core
and secondary terms) used to describe nanomaterials; and (2) defining these core
and secondary terms. Once completed, the combination of these documents will
provide a knowledge databank of all terms, consisting of appropriate definitions
that describe nanomaterials and nanotechnologies, thereby enabling stakeholders
to accurately describe their nanomaterials.
5.1.2. Nomenclature
There is currently a Task Group set up under WG1 (Canadian lead) that is
examining the development of a nomenclature system for nanomaterials. This
nomenclature system would allow interested parties to unambiguously organize
and identify nanomaterials based on a specific naming system. The Task Group
involved in this project includes representatives from different nomenclature
bodies (e.g., IUPAC and CAS), along with other stakeholders (academia, research,
and government) as well as various ISO member states. This work is crucial for all
stakeholders dealing with nanomaterials. For example, researchers in the field of
nanotechnology require an accurate and systematic way to name materials so that,
for example, extrapolation of effects (prediction) and their implicit assumptions
can be both made and communicated in a meaningful way. In the case of industry,
it must be possible to differentiate between the various nanomaterials for the
purpose of patent protection as well as avoiding generalizations with regard to
nanomaterial hazard and effects characterizations. Regulatory bodies will also
require a consistent nomenclature system in order to make amendments to current
legislation or write new legislation enabling nano-specific legal instruments.
5.2. PROGRESS IN DEVELOPING ACCESS TO CONSUMER PRODUCT

INFORMATION, INCLUDING EXPOSURE SCENARIOS
In addition to the progress described above in developing the nomenclature

and taxonomy, progress has occurred in providing information about how materials,
including manufactured nanomaterials, are used in various products. The Project
on Emerging Nanotechnologies (http://www.nanotechproject.org/inventories/
consumer/) from the Woodrow Wilson International Center for Scholars and the
Pew Charitable Trusts is an example of the development of Web-based access to
global information about the uses of nanomaterials in consumer products and, as
of mid-2008, its Consumer Products Inventory contained information on over 600
products, produced by over 320 companies located in 20 countries.
For development of exposure assessments, the European Information System
on “Risks from chemicals released from consumer products/articles” (EIS-
ChemRisks, http://web.jrc.ec.europa.eu/eis%2Dchemrisks/index.cfm) provides
infrastructure, methods, and tools to help understand and assess the exposures to
substances and materials associated with the reasonably foreseeable uses and
misuses of consumer products and articles (e.g., clothing and toys). Developed
since 2003 by the European Commission’s Joint Research Centre (JRC), Institute
of Health and Consumer Protection (IHCP), Physical and Chemical Exposure Unit
(PCE), EIS-ChemRisks, as of mid-2008, is being expanded for use in occupa-

tional, professional product, environmental, and life-cycle exposure assessments.
These types of assessments are useful for addressing the European Union’s
General Product Safety Directive (GPSD, 2001/95/EC), the EU’s REACH legislation,
and for other purposes such as industry-led proactive risk assessments of new
substances, materials, and consumer products. The EIS-ChemRisks “EU Exposure
Assessment Toolbox” provides: (a) Web-based access and a central user interface,
(b) standard formats for information entry and retrieval, and for developing
scenario-based exposure assessment dossiers, (c) detailed product-, substance-,
material-, and data-specific taxonomies, (d) “knowledge-based” data queries, and
(e) the ability to generate detailed reports. The EIS-ChemRisks Toolbox includes
examples of how information from nanomaterial-related publications can be
placed into the Toolbox databases/modules, and used to develop exposure scenarios.
5.3. PROGRESS IN DEVELOPING THE LIFECYCLE ASSESSMENTS
There is a growing list of efforts involving assessment of environmental impact

through the life-cycle analysis (LCA) of manufactured nanomaterials. For
example, the goals of a U.S. EPA-sponsored LCA project included (a) evaluating
the life-cycle environmental profile of candidate nanomaterials for photovoltaic
(PV) applications, (b) comparing these profiles with those of the micro-sized
counterparts that they may replace, and (c) establishing a process-based approach
that will be valuable for comparing nano- to micro-materials within groups of
thin-film materials (e.g., semiconductors and superconductors). One source of
ongoing information about LCA-related projects is http://nanotechproject.us/
inventories/ehs/browse/projects/. Another example investigated how carbon
nanotubes (CNTs) might be released during their life-cycle in lithium-ion
secondary batteries and synthetic textiles. The findings suggest that releases of
CNTs might occur in the production, usage, and disposal phases, with the
likelihood and form of release is determined by the way CNT are incorporated
into the CNT-containing material [23].
Despite this progress, the life cycle is currently employed only as way to
organize or identify potential source terms, rather than a formal life cycle
assessment that encompasses a broader range of impact criteria. In the context of
extraordinarily high uncertainty that is currently characteristic of nanotechnology,
traditional LCA approaches may not be applicable. Seager and Linkov (2008 and
chapter in this volume) stress the importance of carrying LCA forward through the
impact assessment stage and developing new tools for life cycle impact
assessment that draws upon a wide range of formal MCDA techniques.
5.4. PROGRESS IN CREATING WEB-BASED ACCESS TO

INFORMATION IN LOCAL LANGUAGES, AND IN PUBLICLY
UNDERSTOOD WORDING
The current and future uses of and exposures to nanomaterials are global in scope,
yet key publications and other forms of knowledge (e.g., web sites) may not be
available in the native language of a country, and the nanomaterial-containing

products may be manufactured in one country and imported into other countries.
For general public knowledge, and for the benefit and use by experts and policy
makers, it will be important to establish nanomaterial-related web sites that
attempt to provide information in key languages, and ideally in the native
languages of most of the world’s population. The European Union has made great
strides in doing this in recent years for the citizens in its 27 Member States; for
example, the web site for the European Chemicals Agency presents information in
all 23 official EU languages. Similar efforts are also being made in Europe (and
useful globally) by the not-for-profit GreenFacts organization, which provides
web-based access in multiple languages to complex scientific reports on health
and the environment for reading by non-specialists.
6. Conclusions and Additional Policy-Related Needs
This chapter noted that many policy frameworks for manufactured nanomaterials
have been developed globally, and that these frameworks range from voluntary
methods and self-regulation to prescriptive regulation. It also noted that: (a) the
methods can be from different levels of the regulatory pyramid, (b) the policies
ideally need to include consideration of the risks and benefits of nanotechnology,
(c) that risk perception and risk communication need to be considered, (d) the
policies should consider the entire lifecycle of a manufactured nanomaterial,
including use, and (e) that the ecological and human health effects for all
reasonably foreseeable exposures should be considered. Finally, an ongoing need
is for the establishment and sharing of skills for both developed and developing
countries. Some important sets of skills (e.g., toxicologists) may not be available
at all in some countries, both in industry and in government agencies. Ideally, this
expertise would be developed in upcoming years, but it is realistic to assume that
countries will continue to need to try to work together as much as possible to share
information and expertise. This would allow for the development of risk assess-
ments and policies within developed and developing countries that are based on
the prevailing knowledge around the world. Global professional societies and
other types of global organizations (e.g., World Health Organization and Organi-
sation for Economic Co-operation and Development) can play roles in facilitating
the information sharing and the development of expertise.
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THE SAFETY OF NANOTECHNOLOGIES AT THE OECD
P. KEARNS, M. GONZALEZ, N. OKI, K. LEE, F. RODRIGUEZ

OECD, Environment, Health and Safety Division
2 rue André-Pascal
75775 Paris Cedex 16, France
Peter.KEARNS@oecd.org
Abstract. This paper introduces the work of OECD’s Working Party on Manu-
factured Nanomaterials. In particular, it describes its “sponsorship programme”
through which OECD member countries and other stakeholders are collaborating
to fund and manage the safety testing of 14 manufactured nanomaterials. The
paper describes the endpoints which will be addressed during the safety testing
which cover both human health and environmental safety. There is also reference
to supporting work including a preliminary review of existing test guidelines as
well as work on alterative test methods which ultimately aims to avoid the use of
animal testing.
(This paper does not necessarily represent the views of OECD or its member
countries.)
1. A Brief Introduction to OECD
The Organisation for Economic Co-operation and Development (OECD) was

founded in 1961. Today the OECD has 30 member countries.1 Its principal aim is
to promote policies for sustainable economic growth and employment, a rising
standard of living and trade liberalisation. By “sustainable economic growth”, the
OECD means growth that balances economic, social and environmental consi-
derations.
The OECD brings together its member countries to discuss and develop both
domestic and international policies. It analyses issues, recommends actions, and
provides a forum in which countries can compare their experiences, seek answers
to common problems, and work to co-ordinate policies.
1
OECD member countries are: Australia, Austria, Belgium, Canada, the Czech Republic, Denmark,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Japan, Korea, Luxembourg,
Mexico, the Netherlands, New Zealand, Norway, Poland, Portugal, the Slovak Republic, Spain,
Sweden, Switzerland, Turkey, the United Kingdom and the United States. The European Commission
also takes part in the work of the OECD.

352 P. KEARNS ET AL.
The OECD’s work is overseen by several governing bodies. At the highest

level is the OECD Council, made up of Ambassadors from all member countries.
The Council’s main role is to review and approve the OECD budget and
programme of work. It can also adopt Council Decisions (which legally bind all
member countries to a particular course of action) and Council Recommendations
(which strongly encourage action within governments). The Council and all other
OECD bodies work on many issues by consensus.
Under the Council, work in the OECD is directed by specialised committees,
and under these, there are subsidiary bodies (working parties and working groups),
which are composed of experts representing member countries. The Chemicals
Programme, for example, is managed by the Chemicals Committee.
2. OECD’s Working Party on Manufactured Nanomaterials (WPMN)
The Working Party on Manufactured Nanomaterials (WPMN) was established in

2006 by OECD’s Chemicals Committee.
The WPMN brings together more than 100 experts from governments and
other stakeholders. The participants are from the OECD member countries and
certain non-member economies such as Brazil, China, the Russian Federation,
Singapore and Thailand. In addition, there a number of observers and invited
experts from other intergovernmental organizations (for example, UNEP and
WHO) as well as the International Standardization Organization (ISO). Other
stakeholders include industry whose participation is organized by BIAC,2 trade
3
unions whose participation is organized by TUAC and environmental NGOs.
The objective of the WPMN is to promote international co-operation in human
health and environmental safety related aspects of manufactured nanomaterials
(MN), in order to assist in the development of rigorous safety evaluation of
nanomaterials. The main focus of the work is on the industrial chemicals sector.
The Working Party is currently implementing its work through the eight projects
listed below:
Safety testing of a representative set of manufactured nanomaterials
Manufactured nanomaterials and test guidelines
The role of alternative methods in nanotoxicology
Co-operation on voluntary schemes and regulatory programmes
Co-operation on risk assessment
Exposure measurement and exposure mitigation
Development of a database on human health and environmental safety research
and
Research strategies on manufactured nanomaterials
2
The Business and Industry Advisory Committee to the OECD.
3
Trade Union Advisory Committee to OECD.
THE SAFETY OF NANOTECHNOLOGIES AT THE OECD 353
These eight projects are being managed by eight steering groups of the WPMN
which are implementing their “operational plans”, each with their specific
objectives and timelines. For the most part, these steering groups (which average
around 20 participants) are being led/chaired by members of the WPMN, with
support from the OECD secretariat. Much of the work has been (and is being)
undertaken through teleconferences and electronic means. At the same time, there
are close linkages amongst the projects, and for this reason, “face-to-face”
meetings of steering groups are organized as the need arises. The results of each
project are evaluated and endorsed by the entire WPMN.
3. Safety Testing of a Representative Set of Manufactured Nanomaterials –

A Sponsorship Programme
The focus of this paper is on the project of the WPMN entitled, Safety Testing of a
Representative Set of Manufactured Nanomaterials. This project was one of the
first developed by the WPMN and is built around the concept that much valuable
information on the safety of manufactured nanomaterials, as well as the methods
used to assess safety, can be derived by testing specific nanomaterials for human
health and environmental safety effects. The objective of this project, therefore,
has been to develop a programme to create an understanding of the kind of
information on intrinsic properties that may be relevant for exposure and effects
assessment of nanomaterials through testing.
As a first step in this project, the WPMN selected a priority list of manufactured
nanomaterials for testing (see Table 1).
This list has also been referred to as a “representative set” of manufactured
nanomaterials. The word “representative” refers to those manufactured nanomate-
rials now, or soon to enter into commerce, for inclusion in a set of reference
materials to support measurement, toxicology and risk assessment of nanomaterials.
Although the list was mainly selected taking into account those materials which
are in commerce (or close to commercial use), other criteria were also considered:
for example, production volume, the likely availability of such materials for
testing and the existing information that is likely to be available on such materials.
In developing this list, the WPMN recognized that it should remain flexible. It
emphasized, for example, that certain nanomaterials not included may become
important in the future and certain nanomaterials currently on the list may have
(over time) reduced production and/or use. Accordingly, the list should be
TABLE 1. Representative set of manufactured nanomaterials.

Fullerenes (C60) Aluminium oxide
Single-walled carbon nanotubes (SWCNTs) Cerium oxide
Multi-walled carbon nanotubes (MWCNTs) Zinc oxide
Silver nanoparticles Silicon dioxide
Iron nanoparticles Polystyrene
Carbon black Dendrimers
Titanium dioxide Nanoclays
considered as a “snapshot in time”, of those nanomaterials in commerce or

likely to enter into commerce in the near term.
At the same time, some nanomaterials on the list may have variants that the
WPMN may wish to consider in detail in the future. For example, C60 could be
broadened to other fullerenes as well as chemically modified varieties of C60; it
may also be important to analyze chemically modified single- and multi-walled
carbon nanotubes; and the influence of surface coatings of elemental and metal
oxide nanomaterials, and/ or their different shapes.
As a second step in this project, the WPMN developed and agreed a list of
endpoints for which these nanomaterials should be tested (see Table 2). They
include a range of endpoints relevant to human health and environmental safety.
Addressing this set should ensure consistency between the various tests to be
carried out on specific nanomaterials. It should also lead to the development of
“dossiers” for each nanomaterial including information on, for example, basic
characterization, environmental fate, ecotoxicity and mammalian toxicity.
In order to undertake this testing work, the WPMN launched a “sponsorship
programme” at the end of 2007. This sponsorship programme is an international
effort by which delegations to the WPMN will share the testing of those
manufactured nanomaterials selected by the WPMN. There are three levels of
participation available. For each nanomaterial, a lead sponsor(s) is designated who
will conduct or co-ordinate all of the testing deemed to be appropriate and feasible
to address the endpoints (Table 2) for a specific nanomaterial (Table 1). In
addition, a co-sponsor may conduct some of the testing for a specific nanomaterial.
Finally, a contributor may provide test data, reference or testing materials or other
relevant information to the lead and co-sponsors. The current list of lead sponsors,
co-sponsors and contributors is shown in Table 3. It is expected that other
participants will join the programme as the work evolves.
It is envisaged that this sponsorship programme will proceed in two phases.
The first phase will test each nanomaterial (Table 1) for the set of endpoints
(Table 2).
This work is being supported by the development of a guidance manual for
sponsors of the testing programme. It is also expected that the list of endpoints
will be refined based on the practical results obtained through the testing
programme. As such, phase one testing is expected to be of an exploratory nature,
science-based and without any consequences for existing regulatory datasets. In
addition, it is expected that this will identify those cross-cutting issues or tests,
that will need further consideration, which will be undertaken during phase 2.
TABLE 2. List of endpoints for testing.
Physical–chemical
Nanomaterial
properties and Environmental
information/identifi- Environmental fate Mammalian toxicology Material safety
material toxicology
cation
characterization
Nanomaterial name Agglomeration/aggre- Dispersion stability in Effects on pelagic Pharmacokinetics Flammability*
(from list) gation water species (short (ADME)
term/long term)
CAS number Water solubility Biotic degradability Effects on sediment Acute toxicity Explosivity*
Ready species (short
term/long term)
Structural Crystalline phase Ready biodegradability Effects on soil species Repeated dose toxicity Incompatibility*
formula/molecular (short term/long term)
structure
Composition of Dustiness Simulation testing on Effects on terrestrial Chronic toxicity*
nanomaterial being ultimate degradation in species
tested (including surface water
degree of purity,
known impurities or
additives)
Basic morphology Crystallite size Soil simulation testing Effects on Reproductive toxicity*
microorganisms
Description of surface Representative TEM Sediment simulation Other relevant Developmental toxicity*
chemistry (e.g., coating picture(s) testing information (when
or modification) available)
Major commercial uses Representative TEM Sewage treatment Genetic toxicity*
picture(s) simulation testing
THE SAFETY OF NANOTECHNOLOGIES AT THE OECD
Known catalytic Particle size Identification of Experience with human

activity distribution degradation product(s) exposure*
355
356
Physical–chemical
Nanomaterial
properties and Environmental
information/identifi- Environmental fate Mammalian toxicology Material safety
material toxicology
cation
characterization
Method of production Specific surface area Further testing of Other relevant test data*
(e.g., precipitation, gas degradation product(s)
phase) as required
Zeta potential (surface Abiotic degradability
charge) and fate
Surface chemistry Hydrolysis, for surface
(where appropriate) modified nanomaterials
Photocatalytic activity Adsorption- desorption

Pour density Adsorption to soil or
sediment
Porosity Bioaccumulation
potential
P. KEARNS ET AL.
Octanol-water partition Other relevant

coefficient, where information (when
relevant available)
Redox potential
Radical formation
potential
Other relevant
information (where
available)
*where available
THE SAFETY OF NANOTECHNOLOGIES AT THE OECD 357
TABLE 3. Sponsorship arrangements (as of 13 June 2008).
Lead sponsor(s) Co-sponsor(s) Contributor
Fullerenes(C60) Japan, United States

(US)
SWCNTs Japan, US Germany, Canada,

European Commission
(EC), France
MWCNTs Japan, US Korea, BIAC (Business Germany, Canada, EC,
and Industry) France
Silver nanoparticles US, Korea Germany, Canada Australia, EC, France
Iron nanoparticles Canada, US
Carbon black Germany, US
Titanium dioxide Germany Canada, Spain, BIAC, France

Korea, US
Aluminium oxide Germany, US
Cerium oxide United Kingdom (UK), Netherlands, Australia, Germany,

Business and Industry EC
(BIAC), United States
Zinc oxide UK, BIAC BIAC Australia, Canada,
Silicon dioxide BIAC, Korea EC, France
Polystyrene Korea
Dendrimers Spain US
Nanoclays US
4. Other Projects Related to the Testing and Assessment of Nanomaterials
It is important to know whether existing test guidelines (used for “traditional

chemicals”) can be successfully applied to manufactured nanomaterials. Some
information on this question will be derived from the sponsorship programme. In
parallel, however, the WPMN has undertaken a preliminary review of existing test
guidelines (especially the 115 OECD Test Guidelines [TGs]) with view to esta-
blishing whether they are suitable for nanomaterials. This preliminary review,
which is expected to be published in early 2009, covers test guidelines for: physical
chemical properties; effects on biotic systems; degradation and accumulation; as

well as health effects.
At the same time, the WPMN has initiated work on the role of alternative
methods in nanotoxicology, which will avoid animal testing. As a first step, a
report is being prepared including: (i) a list of in vitro endpoints on human health
and ecotoxicity; (ii) the kind of information that the in vitro tests will provide; (iii)
a list of validated in vitro tests that might be used for testing nanomaterials; and
(iv) a background document on the feasibility for validating further in vitro
methods and to consider the development of further in vitro tests.
5. Additional Information
OECD’s WPMN has agreed that its work should be as open and transparent as
possible. With this in mind, information derived from its projects will be made
available in a timely way on its web site: www.oecd.org/env/nanosafety/.
NANOMATERIALS IN CONSUMER PRODUCTS
Categorization and Exposure Assessment
S. FOSS HANSEN, A. BAUN

Department of Environmental Engineering, NanoDTU
Technical University of Denmark, Building 113
Kgs. Lyngby DK-2800, Denmark
sfh@env.dtu.dk
E.S. MICHELSON
Project on Emerging Nanotechnologies
Woodrow Wilson International Center for Scholars
Washington, DC, USA
A. KAMPER, P. BORLING, F. STUER-LAURIDSEN

DHI
Hørsholm, Denmark
Abstract. Exposure assessment is crucial for risk assessment for nanomaterials.

We propose a framework to aid exposure assessment in consumer products. We
determined the location of the nanomaterials and the chemical identify of the 580
products listed in the inventory maintained by the Woodrow Wilson International
Center for Scholars. It was found that in 19% of the products the nanomaterial
were nanoparticles bound to the surfaces. Nanoparticles suspended in liquids were
used in 37% of the products, whereas 13% used nanoparticles suspended in solids.
One percent were powders containing free potentially airborne nanoparticles.
Based on the location of the nanostructure we were able to further group the
products into categories of: (1) Expected to cause exposure; (2) May cause exposure;
and (3) No expected exposure to the consumer. Most products fall into the
category of expected exposure, but we were not able to complete the quantitative
exposure assessment mainly due to the lack of information on the concentration of
the nanomaterial in the products – a problem that regulators and industry will have
to address if we are to have realistic exposure assessment in the future. To
illustrate the workability of our procedure, we applied it to a product scenario –
the application of sun lotion – using best estimates available and/or worst case
assumptions.
The quantity of the active substance on the skin per application for a 2 year old
child is found be Ader = 260 mg for a particle concentration of 10% if the amounts
applied correspond to the European Commission’s recommendations on use of
sunscreen. This value is about three times less than that for an adult. The potential

360 S. FOSS HANSEN ET AL.
worst case dermal uptake assuming full skin penetration is found to be 63 mg kg−1
bw day−1 for a particle concentration of 10% for a 2 years old child, which is twice
the dermal uptake for an adult.1
1. Introduction
Despite the fact that nanotechnology is often described as a future technology, few
realize that nanomaterials are actually already being used in a wide variety of
consumer products, and that the number of commercially available products seem
to be increasing rapidly.
In 2006, the Project for Emerging Nanotechnologies at the Woodrow Wilson
International Center for Scholars (i.e. Project on Emerging Nanotechnologies)
launched an inventory of the consumer products available to consumers (i.e.
Woodrow Wilson inventory). Originally the inventory contained 212 different
products in 2006, which has increased to 580 products in 2007. Projections are
that this number will continue to increase as the unique properties of nanomaterials
are explored further and translated into commercial products. At first glance, it
might seem straight forward to conclude that since the number of consumer
products is increasing, the levels of consumer exposure are too and as a
consequence the risks related to nanomaterials would also be increasing should
nanomaterials turn out to have hazardous properties. We argue that the situation
may be more complex as the potential risks related to consumer products depend
on other factors than the use and the properties of the nanomaterials. More
specifically, determining the location of the nanomaterial in the product will be a
key parameter for identifying likely exposure pathways and make realistic
exposure assessments. For instance, the risk scenarios will be different for a free
airborne nanoparticle that can be directly inhaled and for a nanoparticle suspended
in liquids where dermal exposure maybe is the most relevant pathway.
In this paper we propose a framework to aid exposure characterization and
assessment of nanomaterials in consumer products. As an illustrative case study
we apply it to the products currently listed in the inventory created by the Project
on Emerging Nanotechnologies at the Woodrow Wilson Center for International
Scholars.
2. Location of Nanomaterials in Consumer Products
While knowledge on the chemical identity and the product categories are required
for any risk assessment of consumer products, we propose that exposure
assessment of products containing manufactured nanomaterials has to take into
account the location of the nanomaterial in the products. Elsewhere we have
1
For a full version of the work and results presented in this paper see Hansen, S.F. et al [12].
NANOMATERIALS IN CONSUMER PRODUCTS 361
shown that nanomaterials can be categorized depending on the location of the

nanostructure [3]. This divides all nanomaterials into three overall categories: (1)
in the bulk; (2) on the surface; and (3) as particles. Each of these categories has a
number of subcategories. Materials structured on the nanoscale in the bulk
included one phase material (such as for instance nanocrystalline copper) and
multiphase material (such as ceramic zeolites [porous] and diblock copolymers
[non-porous]). Materials with nanoscale structures on the surface include: (a) one
phase material structured on the nanoscale; (b) nanoscale thick, un-patterned film;
(c) patterned film as films of nanoscale thickness or as surface pattern having
nanoscale dimensions. Finally, the category of particles includes: (a) surface
bound nanoparticles; (b) nanoparticles suspended in liquids; (c) nanoparticles
suspended in solids; and (d) as free airborne particles (for a full explanation of this
categorization framework see Hansen et al. [3]).
Using the categorization framework to each of the 580 products in the
consumer products inventory we were able to categorize about 75% of all the
products in the inventory. Figure 1 shows the distribution of all the products
categorized according to the location of the nanostructure in the products. It was
found that in 19% of the products the nanomaterial were nanoparticles bound to
the surfaces. Nanoparticles suspended in liquids were used in 37% of the products,
whereas 13% used nanoparticles suspended in solids. One percent were powders
containing free potentially airborne nanoparticles whereas we were not able to
determine the location of the nanomaterial for 140 products given the available
information from producers or through the data in the inventory.
Distribution of products into various categories of nanomaterials

200 Bulk Surface Particles
150
Number of products
100
50
0
Structure
Film
Structure
Suspended
Suspended
Airborne
Surface
Unclassifiable
Multi phase
One phase
bound
surface
in liquids
in solids
film
Figure 1. Products in the Woodrow Wilson inventory categorized depending on the location of the
nanostructure. Thirteen percent, 19%, 37% of the products used nanoparticles suspended in solids,
bound to the surfaces, suspended in liquids, respectively. About 1% were powders containing free
potentially airborne nanoparticles [12].
3. Potential of Consumer Exposure to Nanomaterials
The categorization of the consumer products according to location of the nano-

material enables the surveyed products to be grouped into three different exposure
categories:
1. Expected to cause exposure – these products either requires or makes direct
human exposure possible. For products belonging to this category the human
exposure can be quantified based on the expected applied quantity of the
product combined with the application frequency. The categories “Nanoparticles
suspended in liquids” (IIIb) and “Airborne Nanoparticles” (IIId) fall into this
exposure category.
2. May cause exposure – although the particles in the products are not meant to
be released, a certain wear and tear must be anticipated leading to release
of nanomaterials. For these products it is not possible to estimate a daily or a
yearly consumption of products and there are currently no data available on the
release of particles from this type of products. The category ‘Surface-bound
nanoparticles’ (IIId) falls into this exposure category.
Figure 2. Distribution of the products with no, possible and expected exposure within each of the
various products categories depending on the location of the nanomaterial in the product.
3. No expected exposure to the consumer – expected negligible exposure because

the nanoparticles are encapsulated in the product. The category of ‘Nanoparticles
suspended in solids’ (IIIc) falls into this category (see Figure 2).
Using the data behind Figure 1 in combination with the exposure grouping
illustrated in Figure 2, it is found that expected consumer exposure is highest for
products in the products categories “Appliances” and “Health and Fitness”. This is
shown in Figure 3. Expected exposure 36% for products that fall into the category
of home and garden whereas it is 58% for cross-cutting products. For the other
categories of products the expected exposure ranges between these two percentages
except for appliances for which exposure is only expected for 17% of the products.
Possible exposure percentages are equally high ranging between 20–30% except
for food and beverages and electronics and computers for which about 10% fall
into the category of possible exposure.
Figure 3. Distribution of the products with no-, possible- and likely exposure within each of the
various products categories [12].
The exposure grouping is based on the physical state in the application phase
when the consumer exposure is expected to highest. It should be noted that some
consumer products will change their exposure potential during the product life-
cycle e.g. for paints where nanoparticles will be in liquid form when the paint is
applied but in solid form once the paint has dried. In this case the major consumer
exposure is expected to be from the liquid paint, but weathering and physical
abrasion of the dried surface could potentially lead to an exposure.
4. Quantitative Exposure Assessment
The approach described above can form the basis for exposure characterization of
consumer products based on nanomaterials. However, to complete an exposure
assessment it is necessary to include a quantification of the level of exposure. This

kind of assessment is hampered by the fact that the content of nano-sized materials
is only publicly available for a very limited number of consumer products.
To illustrate the applicability of the framework outlined above, we have chosen to
quantify the potential human exposure to the nanomaterials for a realistic product
scenario, namely the application of a sunscreen lotion containing nano-sized TiO2
particles. The potential exposure and dermal uptake is calculated for an adult man
and woman as well as a 2 year old child and are based on default values and
equations taken from Part 1, Appendix II – “Consumer Exposure”, in the Technical
Guidance Document (TGD) on risk assessment for existing substances [1].
Very few producers/distributors provide information about the content of the
nanomaterials in the products. However, from a survey on the industrial
production and application of nanotechnology in the Danish industry we know
that producers of sun lotions use 10–20 nm TiO2 particles with a specific surface
area of 50–200 m2/g as UV absorber and that the nanoparticles are present in
concentrations up to 10% [11].
The route of exposure for a sun lotion will mainly be dermal contact. Intake of
smaller quantities by contact with the area around the mouth is not taken into
consideration. As the product is a “leave on” product, which should neither be
TABLE 1. Equations, explanations, and default values for dermal exposure assessment of TiO2 applied
in sunscreen lotion.
Symbol Explanation Equation Scenario
Concentration of active
Fprod 10% [11]
substance in the product
Body weight (adult ♀/♂/2 year 60/70 [1]/12.34
Bw
old) [4] kg
N Number of applications 3 per day [1]
The quantity of active substance
Ader Qprod * Fprod (1)
on the skin per application (mg)
Potential daily uptake of quantity
Uder pot of active substance (mg/kg (Ader * n)/bw (2)
bw/day)
The quantity of product per
Qprod child (kchild * Qprod, adult)/kadult (3)
application for a child
Qprod
application for an adult
Qprod adult 8,000 mg [1]
application for an adult
The quantity of recommended
Qprod adult product per application for an 36,000 mg [2]
adult
Body area of a 2 year old child,
kchild weighting 12.34 kg and 0.55 [4]
measuring 86.8 cm (m2)
Body area of an adult woman
kadult 1.69 [1]
(m2)
diluted when used nor washed off, the quantity of active substance on the skin
(Ader) for an adult can be estimated by Eq. 1 in Table 1 to be Ader = 800 mg for a
sun lotion containing 10% of nanomaterial.
Assuming that all nanoparticles penetrate the skin Eq. 2 in Table 1 can be used
to estimate the potential uptake per kilogram body weight per day. Uder, pot is equal
to 40 mg kg−1 bw day−1 nano-TiO2 for women if the sun lotion contains 10%
nanoparticles. For men Uder, pot is equal to 34 mg kg−1 bw day−1.
The conversion of the value of applied sun lotion in an adult compared to a
child can be calculated using Eq. 3 in Table 1. The quantity of the active substance
on the skin per application for a 2 year old child is found be Ader = 260 mg for a
particle concentration of 10%. This value is about three times less than for an adult.
Uder, pot would on the other hand be two times higher i.e. 63 mg kg−1 bw day−1.
The above calculated estimates for Ader and Uder, pot are based on the default
values indicated in the TGD for the quantity of the actually applied sun lotion.
However according to the recommendation of the European Commission of 22
September, 2006 on the effectiveness of sun protection preparations, sun lotion
must be applied in quantities corresponding to 4.5 times what TGD stipulates in
order to reach the protection level indicated by the sun protection factor. The
quantity per application mentioned is therefore approximately 36 g for an average-
sized adult [2].
Thus, for adult consumers that apply the recommended quantity, the quantity
of active substance on the skin per application would 3,600 mg per application of
sun lotion of sun lotion containing 10% of nanomaterials, whereas Uder, pot would
be 102 mg kg−1 bw day−1. For a 2 year old child Ader would be 1,171 mg per
application of sun lotion whereas the daily uptake of active substance is Uder, pot =
285 mg kg−1 bw day−1.
5. Discussion
Consumer exposure assessment for products containing nanomaterials has been

acknowledged as an important knowledge gap [7, 9] and we have presented a
categorization framework to aid such exposure assessment. Depending on the
location of the nanostructure in the product (e.g. in the bulk; on the surface; or as
particles) the categorization framework divides products into three different
exposure categories: (1) Expected to cause exposure; (2) May cause exposure; and
(3) No expected exposure to the consumer.
Even despite the sometimes very limited information available in the Woodrow
Wilson inventory on consumer products, we were still able to categorize 75% of
the 580 products. Forty-five percent of the products fall into category of expected
exposure and that almost 25% of the products could not be categorized regarding
exposure. This is an element of concern given that the level of knowledge about
the hazardous properties of nanomaterials is currently very limited [3, 5, 7].
Our use of scenarios based on best estimates and worst-case assumptions show
how the methodology outlined in the Technical Guidance Document can be used
to obtain overall estimates of the potential human exposure of nanomaterials
through consumer products. Using this methodology we estimated the quantity of
the active substance on the skin per application for a 2 year old child to be Ader =
260 mg for a particle concentration of 10% if the amounts applied correspond to
the European Commissions recommendations on use of sunscreen. This value is
about three times less than for an adult. The potential dermal uptake is found to be
285 mg kg−1 bw day−1 for a particle concentration of 10% for a 2 years old child,
which is twice the amount compared an adult.
It should be noted that these uptake values are worst-case scenarios assuming
full skin penetration of nanoparticles. In its latest opinion on the safety of nano-
materials in cosmetic products the European Scientific Committee on Consumer
Products stated that there is inadequate information on among other uptake of
nanoparticles via physiologically normal and compromised human skin [9]. The
extent to which nanoparticles actually do penetrate the skin is currently a matter of
considerable debate internationally and will probably depend on specific particle
properties and the local environment in which it is used [8].
The general lack of information about the kinds of nanomaterials used, how
they are used, and in which concentrations hampers full scale, quantitative
exposure assessments. One thing is that this information is not publicly available,
another is that this information is often not available to regulators and that they
have limited authority to obtain such information unless the health risk of these
products has been assessed [6, 10]. This means that not even regulators have
access to the information needed to do realistic exposure assessment in support of
their overall decision-making process. The lack of information about chemical
identifies of the nanomaterials used and the concentration of the material in the
product is something that regulators and industry will have to address if realistic
exposure assessments are to be possible in the future.
Acknowledgements
We thank Torben Dolin for the technical assistance with the graphic design.
References
1. European Commission JRC (2003) Technical Guidance Document in Support of

Commission Directive 93/67/EEC on Risk Assessment for New Notified Substances
and Commission Regulation (EC) 1488/94 on Risk Assessment for Existing
Substances. European Commission, Brussels
2. European Commission (2006) Commission Recommendation of 22 September 2006 on
the Efficacy of Sunscreen Products and the Claims Made Relating Thereto (Notified
Under Document Number C(2006) 4089) (Text with EEA Relevance) (2006/647/EC).
Official Journal of the European Union L 265/39
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Hazard Identification of Nanomaterials. Nanotox 1: 243–250
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Scholars, Washington, DC
6. National Materials Advisory Board (2006) A Matter of Size Triennial Review of the
National Nanotechnology Initiative. National Materials Advisory Board, National
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Washington, DC
7. SCENIHR (2006) Scientific Committee on Emerging and Newly Identified Health
Risks (SCENIHR modified Opinion (After Public Consultation) on the Appropriateness
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and Adventitious Products of Nanotechnologies. 002/05. European Commission Health
& Consumer Protection Directorate-General
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Accordance with the Technical Guidance Documents for new and existing substances
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Nanomaterials in Cosmetic Products Adopted by the SCCP after the public consultation
on the 14th plenary of 18 December 2007 SCCP/1147/07. European Commission,
Brussels
10. Taylor M.R. (2006) Regulating the Products of Nanotechnology: Does FDA Have the
Tools It Needs? Project on Emerging Nanotechnologies. Woodrow Wilson
International Center of Scholars, Washington, DC
11. Tønning K., Poulsen M. (2007) Nanotechnology in the Danish Industry - Survey on
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(2008) Categorization Framework to Aid Exposure Assessment of Nanomaterials in
Consumer Products. Ecotox 17: 438–447
STRATEGIC APPROACHES FOR THE MANAGEMENT OF
ENVIRONMENTAL RISK UNCERTAINTIES POSED BY
NANOMATERIALS
R. OWEN
School of Biosciences
University of Westminster
115 New Cavendish Street
London W1W 6UW, UK
UK Environment Agency
Block 1 Government Buildings
Burghill Road, Bristol BS10 6BF, UK
richard.owen@environment-agency.gov.uk
M. CRANE
WCA Environment Limited
23 London Street
Faringdon, Oxfordshire, UK
K. GRIEGER
Institute of Environment & Resources
Lyngby, Denmark
R. HANDY
School of Biological Sciences, University of Plymouth
Drake Circus
Plymouth, UK
I. LINKOV
U.S. Army Engineer Research and Development Center
83 Winchester Street
Brookline, Massachusetts, USA
M. DEPLEDGE
Peninsula Medical School
John Bull Building, Research Way
Plymouth, UK

370 R. OWEN ET AL.
Abstract. Central to the responsible development of nanotechnologies is an

understanding of the risks they pose to the environment. As with any novel
material or emerging technology, a scarcity of data introduces potentially high
uncertainty in to the characterisation of risk. Early priorities are the identification
of key areas of risk uncertainty and the strategic approach for managing and
reducing these. This is important as the information subsequently gathered
supports decision making and policy development. We identify one important
source of uncertainty for the quantification of both hazard and exposure for
nanomaterials, the complexity of their behaviour in natural systems. We then
outline two approaches for managing this uncertainty, based on experiences with
chemicals: one that primarily focuses on hazard and one that initially focuses on
exposure. While each approach places emphasis on different information
requirements a common feature is the considerable time lag between information
gathering and subsequent decision making based on the evidence gathered.
Complementary environmental surveillance approaches can act as a safety net,
although it is not as yet clear how fit for purpose current monitoring programmes
are in this regard.1
1. Introduction
In recent years there has been considerable debate concerning the potential
environmental risks posed by nanomaterials, and in particular manufactured
nanoparticles (see for example [13, 16, 17, 22, and references therein]. There are
at least two factors contributing to this: firstly the unprecedented growth in the
development, manufacture and use of diverse nanomaterials in many sectors and
secondly the altered and in some cases emergent properties that nanomaterials
may possess in comparison with the bulk form of the same material. The concern
is that such altered properties may result in enhanced or novel adverse impacts to
environment and to human health arising from increased toxicity, bioavailability
or environmental persistence of the nanomaterial, or that they may interact with
other chemicals in the environment, influencing the toxicity of those chemicals
(e.g. [1]).
With the advent of any novel material or new technology an early priority is
the identification of significant areas of risk uncertainty, and nanomaterials are no
exception to this. The Royal Society and Royal Academy of Engineers 2004
report was, for example, one important document that identified key uncertainties
and others have followed, often describing these in terms of research needs (e.g.
[11]). Since that report, one important source of risk uncertainty is emerging from
laboratory studies of the fate, behaviour and ecotoxicity of manufactured
nanoparticles [2, 9, 14]. Once they enter the natural environment (as with many
so-called ‘non-conservative’ chemicals), complex changes can occur to their
structure and physico-chemical behaviour. This complexity is influenced by a
1
ENVIRONMENTAL RISK UNCERTAINTIES POSED BY NANOMATERIALS 371
number of abiotic and biotic factors which themselves may vary, depending on the
environment in which a nanoparticle occurs [9]. Complex behaviour in natural
systems raises significant issues for ecotoxicological hazard assessment and the
modelling of environmental exposure for nanomaterials [3, 6], some of which we
describe in more detail below. An important consequence of complexity is the
introduction of potentially high uncertainty to assessments of their environmental
risks [3].
2. Complexity of Behaviour: A Major Source of Uncertainty in

Nanomaterials Hazard and Exposure Assessment in Natural Systems
Two key areas in environmental risk assessment where the complexity of

nanomaterials behaviour in natural systems poses significant issues are in the
quantification of hazard and exposure. Central to this are firstly establishing the
relationship between exposure and toxicity (dose-response) and calculation of
predicted no effects concentrations (PNECs) and secondly, the calculation of predic-
ted environmental concentrations (PECs) to which PNECs may be compared in a
risk assessment scenario. These calculations form the cornerstones of environmental
risk characterisation.
By way of an example, we might consider the development of an Environ-
mental Quality Standard (EQS) for a manufactured nanoparticle. A chemical EQS
is a value (generally defined by regulation) which specifies the permissible
concentration of a chemical over a period of time in environmental samples, and is
a primary tool for chemical regulation. By comparing a measurement of the
chemical with the EQS it is possible to determine whether the chemical poses an
environmental risk and, if so (i.e. if the EQS is exceeded), to advocate risk
management. The development of the EQS itself is based almost entirely around
hazard assessment. A PNEC is usually calculated from Lowest Observed Effect
Concentration (LOEC) or No Observed Effect Concentration (NOEC) data using
standard ecotoxicity tests (for example those recommended by the Organisation
for Economic Co-operation and Development, OECD), to which ‘assessment’ (or
‘uncertainty’) factors have been applied.
The key issue is that the LOEC and NOEC for a manufactured nanoparticle
derived from laboratory studies is likely to be strongly influenced by the abiotic
(and biotic) composition of the environmental matrix in which exposure occurs,
variations in which may influence nanoparticle structure, form and behaviour [9].
In aquatic systems some relevant abiotic factors are pH, ionic strength and the
concentration of humic substances in the aquatic matrix [9], Figure 1. These are
known to influence and modify physico-chemical characteristics of the particle.
Of these, one of the more important is the surface charge of the nanoparticle, as
this will influence how particles will agglomerate. Such abiotic factors are likely
to play critically important roles in mediating the bioavailability, bioaccumulation
and toxicity of nanomaterials when exposure occurs in natural settings.2
2
In fact this may be a more general phenomenon: for example dermal penetration by a nanoparticle is
influenced by the surface charge of the particle concerned.
372 R. OWEN ET AL.
Figure 1. Aggregation of iron oxide nanoparticles in water as a function of pH. (Images courtesy of
Jamie Lead and Mohammed Baalousha, University of Birmingham, U.K.)
Perhaps the best example of how abiotic and biotic factors are known to influence
bioavailability, bioaccumulation and toxicity of nanomaterials is that of asbestos
fibres. Here, it is a combination of the aspect ratio of the fibre (or shape) i.e.
length and width, and the durability or biopersistence of the nanofibre, in the
context of the physiological response in the airways and the macrophages in the
lung (i.e. clearance), that are critical determinants of subsequent toxicity and
pathology [19]. This demonstrates the need to understand complexity and biological
interaction when predicting toxicity and pathogenicity for nanomaterials, when
exposure occurs in natural settings.
A consequence of complexity is that laboratory exposures of organisms to
nanomaterials following standard test protocols, for example using (standard)
de-ionised water, may have only limited environmental relevance when compared
with the natural environment in which exposure occurs.3 Issues of complexity and
3
Such issues of relevance are not restricted to nanomaterials: it might be argued that similar issues
exist for chemicals in general.
the associated environmental relevance of standard tests will also apply to terrestrial
systems although, based on the experience with ‘conventional’ chemicals, aquatic
toxicity data are likely to be the primary information required for assessing risks
to both aquatic and terrestrial environments in many regulatory contexts [6].
The implications of complexity and environmental relevance are that these
may introduce a considerable measure of uncertainty to any LOEC or NOEC
when calculated using current standard tests employed for chemicals. Further
uncertainty in hazard assessment will result from, for example, the paucity of data
on adsorption, distribution, metabolism and excretion (ADME) in organisms and
the lack of information on chronic effects.
In a similar way, the complexity of environmental nanomaterial behaviour will
introduce uncertainty into determinations of predicted environmental concentrations
(PECs) in complex environmental settings. Of note here is that receiving environ-
ments for nanomaterials (e.g. estuaries where pH and ionic strength can vary
considerably) and indeed some sources of exposure such as complex industrial
effluents can be highly complex in nature.
As a consequence, uncertainties in predictions of exposure (PEC) and hazard
(PNEC) will be propagated during characterisation of environmental risk,
amplifying overall uncertainty when these are compared.
An important point to note is that uncertainty in both hazard and exposure
assessment is likely to vary with the nanomaterial concerned and its degree of
functionalisation. This implies that uncertainty is not likely to be uniform across
nanomaterials and that the contributing sources of uncertainty may vary with the
nanomaterial concerned and the context of exposure. However, given the scarcity
of data on fate, behaviour and effects it seems likely that for many nanomaterials,
at least in the short to medium term, current uncertainties in hazard and exposure
will continue to be large [21, 22]. This combination of scarcity of risk data and
associated high risk uncertainty will be a recurring feature of many novel
materials and technologies in the early phases of their innovation.4
A key issue for nanomaterials (and indeed any emerging technology or novel
material) is how risk uncertainty should be managed i.e. what is the strategic
approach to reducing risk uncertainty.
3. Approaches for Managing Environmental Risk Uncertainties for

Nanomaterials
Experience with ‘conventional’ chemicals allows us to identify a number of options

for managing uncertainties in the environmental risk assessment of nanomaterials,
two of which we highlight below. Each of these approaches has a different emphasis
in terms of the type of information that would be collected, the first focussing on
hazard and the second initially on exposure.
4
Note emerging debates concerning converging technologies e.g. synthetic biology.
374 R. OWEN ET AL.
3.1. HAZARD-DRIVEN APPROACH
One approach for managing risk uncertainty is to take the view that the com-
plexity of nanomaterials behaviour in the environment is so poorly understood,
and detection methods so poorly advanced, that it would be unwise to rule out any
potential exposure route for a nanomaterial i.e. make no a priori assumptions
regarding environmental exposure at all. This would place the focus of data
provision onto hazard, with potentially extensive toxicity assessments, with many
types of organisms using endpoints that cover all potential exposure routes. This
approach is somewhat counter to the tiered approach to risk assessment taken for
conventional chemicals, where the exposure scenario guides hazard assessment
and, within this, endpoint selection (see Section 3.2. below), and in this regard the
case for making nanomaterials an exception would have to be made.
One benefit of such an approach would be that it might be possible to assemble
a comprehensive dataset of combined hazard and intrinsic properties of nano-
materials, and thereby ascertain which of these properties are important for
governing toxicity. On the other hand, the burden of hazard testing, for both the
nanomaterial and its functionalised variants, might be extensive, time consuming
and costly. There also remain two outstanding issues with such an approach: the
environmental relevance of a number of the tests that would be employed and the
large residual uncertainty this introduces (discussed above), and the fact that some
of the potential novel, indirect or chronic impacts might not necessarily be identified
under current testing requirements, no matter how extensive these may be.
Risk assessors have a useful tool that can be employed to address the issue of
complexity and relevance and the associated uncertainty this introduces to hazard
assessment: the use of uncertainty factors. This is a conventional and quantitative
approach for managing high uncertainty associated with hazard (e.g. LOEC and
NOEC calculations), where uncertainty factors of up to x1,000 can be applied to
the LOEC or NOEC (e.g. [3] when calculating PNECs. This approach is recom-
mended for managing uncertainty when hazard data are scarce or poor in quality,
or where extrapolations are necessary (for example extrapolating from effects
observed in laboratory rodent models to humans, or extrapolating from simple test
systems to exposure in complex environments).
The application of uncertainty factors to derive nanomaterial PNECs may
appear to offer the risk assessor and risk manager an immediately applicable and
pragmatic approach for defining a regulatory threshold, even where data are very
scarce. However this approach is not without its limitations, not least of which is
that the PNEC derived may be over precautionary. Additionally, where calculated
PNECs are very low, characterising risk in the environment may require the
development and optimisation of highly challenging or expensive analytical
measurement methods (with very low limits of detection) to enable monitoring
against the PNEC value. Such methods are either not available or require
considerable optimisation for complex environmental matrices [10], all of which
will take time. These are of course also similar issues for a number of ‘conven-
tional chemicals’, such as endocrine disrupting oestrogens (e.g. ethinyl oestradiol),
where experience indicates that such analytical challenges can pose significant
feasibility questions when the implementation of very low EQS’s and associated
costs are considered.
3.2. EXPOSURE-DRIVEN APPROACH
In this approach the initial strategy is to gain a better understanding of environ-

mental fate, behaviour, interaction and (importantly) bioavailability, with the
premise that without exposure in a bioavailable form there can be no risk to
organisms.
A primary focus is in the initial development and subsequent validation of a
conceptual model of exposure for the nanomaterial concerned, underpinned by a
life cycle assessment approach that considers sources and pathways of exposure
during production, use and end-of-life (e.g. waste disposal) [12]. Such models can
be used to develop emission scenarios and mass flows in the environment [3] and
suggest areas where better understanding of behaviour, form and fate in natural
systems can reduce associated uncertainties5; these can be subsequently investi-
gated to allow model refinement.
To give one example of this, Blaser et al. [3] attempted to assess the risk of
silver released from nano-functionalised plastics (i.e. silver from nanoparticles in a
fixed form released via leaching). In developing a model of exposure they were
able to observe that silver ions occur in solution at only low concentrations in the
aquatic environment, with most silver occurring as silver-sulphide clusters; they
noted however that most toxicological studies use silver nitrate (which forms
silver ions in aqueous solution) and that the effects of the more environmentally –
relevant forms of silver i.e. the clusters, have been only little studied. Their recom-
mendation was that uncertainty in the environmental chemistry of silver per se and
scarcity of toxicological studies that considered silver in its most environmentally-
relevant form posed the greatest uncertainties for risk assessment. This exemplifies
one of the biggest challenges for environmental risk assessment of nanomaterials;
a priority need to understand behaviour and bioavailability in natural systems.
In developing a conceptual exposure model for a given nanomaterial, an
understanding of sources to the environment, pathways and environmental fate are
important, underpinned by an understanding of material physico-chemical
properties. Measurements of such properties are recommended by OECD for risk
assessments of conventional chemicals. It is likely that some currently required
measurements (e.g. KOW, or octanol – water partition coefficient used to assess
potential bioaccumulation and trigger sediment toxicity tests) may not be suitable
for nanoparticles [6]). However, in general, measuring properties such as surface
charge, chemical composition, particle size range and so on are a useful and
established starting point for building the exposure scenario for any given
nanomaterial, based on fundamental properties of the material itself.
5
It should be noted however that increasing knowledge within a complex system may initially reduce
some uncertainties, but may also serve to increase other uncertainties simultaneously due to exposed
knowledge-gaps that were previously unrecognized.
376 R. OWEN ET AL.
In this approach a premium is placed on tools and data that allow better
prediction of bioavailability through an understanding of the complexity of
behaviour and speciation of nanomaterials in complex natural environments. To
give an example from the world of ‘conventional chemicals’, the development of
biotic ligand models for assessing hazards due to metals and the need to
understand factors such as pH and DOC in receiving waters resulted from an
understanding that bioavailability and toxicity must account for metal speciation
and the factors that influence this [18]. In this regard the issues posed by
nanomaterials have been faced before for chemicals such as metals in non
particulate form.
What is discussed above, including the development of a conceptual model of
exposure, is in fact an important aspect of what is called risk ‘problem formulation’:
this is the initial phase of a tiered environmental risk assessment approach that is
accepted on a global basis. Problem formulation helps define the source-pathway-
receptor connectivity and, through an understanding of exposure routes and
bioavailability, which endpoints should be assessed in subsequent quantitative risk
assessment. Of course, hazard assessment remains an integral aspect of this approach,
but rather than immediately measuring all endpoints, the selection of these is
guided by an initial evaluation of exposure and bioavailability, with the emphasis
initially being on collecting data that help reduce uncertainty in this area.
To date, while there have been important considerations of the appropriateness
of test methods for nanomaterials (e.g. Crane et al. [6]) less attention has been
given to the problem formulation phase of environmental risk assessment and how
this could be strengthened [17]. This initial phase is fundamentally important in
setting the context and boundaries of the subsequent qualitative and quantitative
risk assessments, and (importantly) justifies the intent to undertake such assess-
ments [7]. While it is acknowledged that poor problem formulation results in
inappropriate risk analysis [20], this aspect of risk assessment is an area which has
to date received only limited consideration in the context of nanomaterials.
The need for effective problem formulation is further emphasised by a defining
feature of nanomaterials: the cosmopolitan nature of these group of substances.
Not only is there an ever growing number of materials, from carbon nanotubes to
metal oxides, but individual nanomaterials can be functionalised (e.g. by surface
modification and ligand chemistry), which may in turn influence their environ-
mental behaviour and effects. There are also potential impurities within nanoparticles,
the quantity and nature of which may vary depending on the manufacturing
process. It seems unfeasible to undertake full quantitative risk assessments for
every nanoparticle, and its functionalised variants. Nor may this be necessarily
desirable, if effective problem formulation suggests it is not justified.
Tools that can support problem formulation for nanomaterials go beyond those
that can help with understanding exposure and bioavailability. Grouping and read-
across approaches could also help, and may indeed allow defensible testing of
only a representative substances within a category (e.g., see OECD QSAR
Application Toolbox6 [15]). Structure–activity relationships may also play an

important role. The value of structure–activity relationships in chemicals risk
assessment is in fact best exemplified by a nanomaterial: asbestos fibres. The
fibre–pathogenicity model is probably one of the most studied and robust
structure–activity models in chemicals risk assessment. In this model, an
understanding of asbestos pathogenicity has led to development of a structure–
activity model for high aspect ratio nanofibres that have specific dimensions (i.e.
>20 µm in length and <3 µm in diameter) and that are biopersistent. Nanofibres
that exhibit these properties are known to be potentially harmful to human health
if exposure is via the airways. There is a reasonable basis within problem
formulation to prioritise high aspect ratio nanotubes and fibres for quantitative
hazard and exposure assessment, based on both the structure –activity relationship
and the source–pathway–receptor connectivity i.e. justifying the intent. Indeed
recent work by Poland et al. [19] based on this structure–activity model suggests
its applicability for some carbon nanotubes which exhibit a high aspect ratio.
However, when moving beyond this specific scenario, the lack of data linking
nanomaterials properties to effects suggests that the application of traditional
QSAR models may be as yet limited for emerging chemicals. The results of
important initiatives such as the OECD safety testing of a representative set of
nanomaterials may perform a useful role to this end.
The above approach, in which problem formulation and development of a
conceptual model of exposure drive the risk assessment process, defining the
endpoints for hazard assessment, is in line with established thinking for environ-
mental risk assessment of chemicals in general. However, the ever changing
innovation landscape and diversity of nanomaterials and the convergence of
technologies (e.g. bio and nano) suggests that such problem formulation needs to
be iterative, and interfaced with horizon scanning activities and technology
roadmaps (Figure 2).
Figure 2. Interfacing horizon scanning and iterative problem formulation to justify the intent to
undertake quantitative environmental risk assessment.
6
However, for this approach to be acceptable the key physical and chemical parameters that influence
toxicity within a nanoparticle category will need to be known.
378 R. OWEN ET AL.
4. Incremental Research to Reduce Risk Uncertainties – The Right

Strategy?
In outlining the options for managing large risk uncertainties in an initially data
scarce environment, we are challenged with the question, what sort of information
should be assembled to enable confident decision making about risks? Each of the
two approaches outlined above places different emphasis on the information
gathered, for example through the commissioning of research from public or
private budgets. This is an important question, because the nature and quality of
the information gathered, and the way this information is framed socially, will
form the evidence base on which decisions concerning the development or
amendment of regulation will be made.
Many research programmes on nanomaterial Safety, Environment and Health
have been established over recent years with the intention of providing the
evidence base to inform development of policy and appropriate controls. These
programmes provide an important mechanism to reduce risk uncertainties, and
although the information gathered cuts across both the strategic options outlined
above, it is becoming clear that understanding exposure and bioavailability is a
growing priority. However, irrespective of the strategic approach taken, pragmatism
and experience suggest that the development of models of exposure and bioavaila-
bility, the establishment of mechanisms of toxicity, pathogenicity and ecological
effects, and the development of structure–activity models and their subsequent
validation through empirical research all suffer from one common and critical
issue, the time required to obtain the information on which subsequent decisions
are made, relative to the pace of innovation of the technology [13, 23], Figure 3.
This issue is becoming increasingly recognised: for example, a recent review of
the US EPA Nanomaterial Research Strategy [24] highlighted the fact that
decisions on the safe use of engineered nanomaterials in the near-term need to be
made within a data-poor environment; it further recognised the potential value of
approaches such as Expert Judgment and Multi-Criteria Decision Analysis to
address this issue [13], the latter being an approach that allows the structuring of
fragmented information for application in environmental management.
In some cases, for example when a large environmental impact is observed or
a laboratory study suggests a material is very harmful (e.g. [19]) management
decisions are made over shorter timescales, often through the invoking of the
precautionary principle. In general however, incremental research to advocate
amendment or development of new regulation is an inherently slow process, and
(as seen with nanomaterials), follows the introduction of the technology into
society. Given this, it might be argued that a strategy of reducing risk uncertainties
through incremental, often reductionist research may provide important informa-
tion to support confident decision making, but this may only extend to a small
number of nanomaterials and even then, take many years to realise.
Figure 3. Time lags in emergence of nanoproducts, generation and analysis of environment, health and
safety data and regulatory decision making [13].
It might also be argued, based on our experience with chemicals in the past, that
even with the most comprehensive programme of research to reduce risk uncer-
tainties, some nanomaterials may ‘fall between the cracks’, due to unforeseen,
novel or indirect impacts. Could it have been predicted, for example, that the
automobile internal combustion engine would have such wide impacts on society
and the environment through greenhouse gas mediated climate change? Experience
has taught us that the nature of the potential chronic and indirect environment,
health, safety and social impacts of novel chemicals and technologies are some-
times difficult to identify early on in the development of a technology [5]. In this
regard the concern may be less about making a priori assumptions concerning
exposure and more about making a priori assumptions of the nature of impacts
that might ensue. In part, this further emphasises the need to ensure problem
formulation is iterative and not static, developing a weight of evidence that in turn
guides the risk assessment process through an adaptive learning architecture,
allowing management and control at an early stage, before irreversible entrenchment
of the technology within society [5]. However, it also cautions us to develop a
safety net around a strategy that seeks to manage risk uncertainties through
incremental research. The question then becomes, what would that safety net be?
5. The Case for Environmental Reconnaissance and Surveillance
One potential safety net is through reconnaissance and surveillance, enacted for
example through environmental monitoring programmes. One approach might be
380 R. OWEN ET AL.
to amend ongoing programmes to monitor levels of one or more nanomaterials,

particularly where inputs to the environment are significant. However, as discussed
above, while sophisticated measurement techniques do exist, they are currently
very expensive to use, or not optimised for use in complex matrices, or not widely
available for use by regulators. Even assuming that the problems of appropriate
field instruments can be overcome, monitoring would have to address both the
nanomaterial itself and any breakdown products. The latter is key as some of the
secondary products could turn out to be more harmful than the parent nano-
material itself. A particular technical challenge to be overcome is that current
concentrations of manufactured nanoparticles in ecosystems are likely to be small,
compared with concentrations of naturally occurring nanoparticles. Consequently,
monitoring programmes would need to be capable of detecting quite low concen-
trations of manufactured nanoparticles against a relatively high background
concentration of naturally occurring nanomaterials.
However, the very high level of investment in nanotechnologies suggests that
in the future nanomaterials will continue to be released, intentionally or uninten-
tionally into our ecosystems. This highlights the importance of determining where
manufactured nanomaterials accumulate and for how long they will persist. One
approach might be to actively look for sites at which nanomaterials might be
expected to accumulate, thereby enhancing the exposure assessment process. This
active, intelligence-led reconnaissance deserves much more attention than it has
received in the past. Here, a challenge is to develop tools that permit a rudimentary,
conceptual life cycle model of environmental exposure to be undertaken by manu-
facturers and users of nanomaterials that allow identification of where important
environmental sinks for those nanomaterials may be. This might then allow the
targeted deployment of reconnaissance tools (e.g. the deployment of passive
sampling devices in aquatic environments, especially in sediments, which might
allow nanomaterials to be concentrated and detected more readily).
In reality however, without a regulatory driver, the justification to develop
analytical techniques and to amend routine monitoring programmes would follow
the results of incremental research, whereby curiosity driven studies would drive
the development or optimisation of those techniques to detect nanomaterials in the
form in which they occur in the environment, and subsequently apply them to
quantify environmental burdens. Where these were found to be significant and
above levels thought to be harmful (see Section 3.1 above) regulatory monitoring
would be enacted and programmes amended accordingly. This seems unlikely to
address the issue of the time lag between innovation, information gathering and
decision making described above.
An alternative approach would be to monitor primarily for biological impacts
in the environment, and subsequently apportion observed impacts to nanomaterials
through confirmatory analyses (so called Toxicity Identification and Evaluation).
Indeed, ecotoxicologists have thought long and hard about this, in their search for
an approach that can help to pragmatically manage high risk uncertainties
associated with known and unknown chemicals in complex natural environments,
where toxicity or bioavailability are poorly understood. To give one example, the
development and implementation of Direct Toxicity Assessment (DTA) within the
Pollution Prevention and Control legislation in the UK reflected the need to

quantify hazards and risks of discharges of complex chemical mixtures into the
aquatic environment that are of unknown or uncertain bioavailability and toxicity
(this might include many current nanomaterials in production).
It is worth expanding slightly on DTA (also known as Whole Effluent
Assessment), as it potentially offers a promising approach in this regard. It begins
with ‘whole discharge’ toxicity testing to assess the integrated effects of chemicals
as complex mixtures. DTA is applied where a discharge contains one or more
unknown chemicals and their breakdown products, or where the toxicity of these
substances is unknown or has been insufficiently evaluated. This would at first
glance apply to many nanomaterials for which environmental bioavailability and
toxicity data are scarce. It takes the form of acute, and where necessary chronic,
standard ecotoxicity tests on the discharge itself (perhaps addressing the issue of
environmental relevance of tests discussed before). Where toxicity is found, an
assessment of risk accounting for effluent dilution in the receiving waters is
undertaken. Of course, it goes without saying that the subsequent toxicity
identification and evaluation (TIE) process necessary to define the source of the
toxicity in the effluent and apportion this to the constituent nanomaterials in the
waste stream would be associated with the same sort of analytical challenges
discussed above. However, end of pipe DTA approaches may at the very least
allow a toxicological screening of direct sources of nanomaterials into the
environment without an immediate need for these highly sophisticated analytical
techniques.
Such an approach, which could be quite rapidly extended to cover nanomaterials
in waste streams, might afford a level of protection for the environment, through
the identification of the most significant point sources of nanomaterials in terms of
toxicity, and screening out of those effluents where toxicity is not observed. The
argument against such an approach is that there is still, at least in the U.K., a
reliance on largely acute toxicity tests (e.g. using Daphnia immobilisation or algal
growth), which may not address any indirect or novel impacts, but this is a more
general issue for chemicals and is not specific to nanomaterials. In addressing this,
it might be possible for example to amend standard tests used in DTA to assess
genotoxicity [4], which along with oxidative stress are two toxic impacts that have
been associated with exposure to at least some nanomaterials.
Whether the endpoints chosen are entirely appropriate or not, the principle
behind DTA is to place an emphasis on measuring biological effects first and then
understanding the causes of toxicity where this is observed.
When considering novel materials or technologies and their potential to cause
environmental impacts, it seems sensible to consider such biological effects
surveillance approaches as a safety net for the management of risk uncertainties
through incremental research. Such surveillance is best enacted if it is undertaken
within the context of an integrated risk assessment approach, for example combining
ecological monitoring in a water body with measures of toxic impact at an
organismal level (using for example appropriate biomarkers), both undertaken
within the context of an understanding of sources of chemicals to that water body
and modelling of the potential for exposure [8]. In Europe, there is a vehicle for
382 R. OWEN ET AL.
this through the most important piece of legislation for managing and conserving
water resources, the Water Framework Directive. It would be worth considering
which of the surveillance systems currently in place could offer an effective safety
net to ensure environmental impacts are first monitored and then apportioned to
nanomaterials, whether they need amending and, if so, what amendments might be
made.
There have been numerous examples of chemicals that have slipped through
the risk assessment process in the past (e.g. DDT, methyl mercury, endocrine
disruptors, etc.) and it is probably unrealistic to imagine that at least some forms
of nanomaterials will not pose new kinds of problems in the environment. If
applied appropriately, such biological surveillance approaches could provide some
added security that these unexpected effects are detected early and are dealt with
rapidly.
6. Conclusions
As with any emerging technology or novel material the risk scenario for
nanomaterials is one of data scarcity and associated high risk uncertainty. Several
strategies for managing risk uncertainties are available to risk assessors and risk
managers, each of which places emphasis on different information requirements.
The key issue becomes, with the advent of any new technology or novel material,
what sort of information should be assembled to enable confident decision making
about risks and the associated development of proportionate controls. Irrespective
of the strategy employed for managing and reducing the uncertainties identified,
each suffers from a common issue: the potentially large time lag between
innovation, uncertainties identification and the acquisition of data to reduce uncer-
tainties. This suggests the need to develop or optimise environmental surveillance
approaches that can act as a safety net, although how fit for purpose current
monitoring and surveillance programmes are to meet this objective has yet to be
evaluated.
Acknowledgements
We thank Peter Van der Zandt (European Commission) Rick Canady (US Food
and Drug Adminstration), Sophie Rocks and Simon Pollard (Cranfield University),
Paul Whitehouse and Steve Robertson (Environment Agency, UK) for their
insightful discussions.
Disclaimer
The views here do not necessarily represent those of the Environment Agency.
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METHODS OF ECONOMIC VALUATION OF THE HEALTH
RISKS ASSOCIATED WITH NANOMATERIALS
S. SHALHEVET
SustainEcon – Environmental Economics Consulting
126 Thorndike Street
Brookline, MA 02446, USA
sarit.shalhevet@gmail.com
N. HARUVY
Netanya Academic College
1 University Street
Netanaya, Israel 42365
Abstract. The worldwide market for nanomaterials is growing rapidly, but

relatively little is still known about the potential risks associated with these
materials. The potential health hazards associated with exposure to nanomaterials
may lead in the future to increased health costs as well as increased economic
costs to the companies involved, as has happened in the past in the case of
asbestos. Therefore, it is important to make an initial estimate of the potential
costs associated with these health hazards, and to prepare ahead with appropriate
health insurance for individuals and financial insurance for companies. While
several studies have examined the environmental and health hazards of different
nanomaterials by performing life cycle impact assessments, so far these studies
have concentrated on the cost of production, and did not estimate the economic
impact of the health hazards. This paper discusses methods of evaluating the
economic impact of potential health hazards on the public. The proposed method
is based on using life cycle impact assessment studies of nanomaterials to estimate
the DALYs (Disability Adjusted Life Years) associated with the increased
probability of these health hazards. The economic valuation of DALY’s can be
carried out based on the income lost and the costs of medical treatment. The total
expected increase in cost depends on the increase in the statistical probability of
each disease.
1. Introduction
The worldwide market for nanomaterials is growing rapidly, and is expected to

reach nearly $2.6 trillion by 2014, up from $50 billion in 2006 [1]. But despite the
growing usage, relatively little is still known about the potential risks associated
with these materials. So far, information on the health risks associated with

386 S. SHALHEVET AND N. HARUVY
nanomaterials is available mostly from studies of pollution-derived incidental

nanoparticles exposure. Many studies show that exposure to particulate air pollutants
increases the risk of pulmonary, cardiovascular, and central nervous system (CNS)
disease. Some studies show that exposure to the nanoparticle component of the
particulate pollution increases the health risks at much lower exposure concen-
trations than the exposure to micron-sized particles [26]. Moore [20] quotes a
large body of research showing that ultrafine particles can be dangerous to human
health. The US Environmental Protection Agency has attributed 60,000 deaths per
year to the inhalation of atmospheric nanoparticles, and there is evidence for direct
transfer into the brain. For example, several studies have found potentially
significant pulmonary toxicity of carbon nanotubes [26], and other studies have
found that carbon fullerenes (buckyballs), currently being used in some face
creams and moisturizers, can cause damage to fish, and may be toxic to humans
[6].
Weisner et al. [29] point out that most of the human exposure to nanomaterials
is likely to be caused during the manufacturing process, putting the workers at the
greatest risk. However, some exposure is possible from the use of nanomaterials
and their release into the atmosphere and accumulation in soil and water resources.
The exposure to nanomaterials may be through inhalation of particles in the air,
ingestion of food or water containing nanomaterials or even of the materials them-
selves. Some damage may also occur through dermal exposure to sunscreen or
cosmetics [29], although significant dermal absorption seems to be unlikely [27].
The potential health hazards associated with exposure to nanomaterials may
lead in the future to increased health costs as well as increased economic costs to
the companies involved, as has happened in the past in the case of asbestos.
Furthermore, fear of the unknown health hazards may cause consumers to reject
the use of nanotechnology, similarly to the widespread consumer rejection of
agricultural biotechnology products. The rejection of GMO foods based on the
perception of risk had cost some biotechnology companies billions of dollars [19],
and there are signs of a similar phenomena developing in nanotechnology. For
example, the Soil Association, a British organic agriculture association, announced in
January 2008 that it has banned human-made nanomaterials from the organic
cosmetics, food and textiles that it certifies [4]. A widespread public rejection of
nanomaterials could result in even greater losses, because the technology is being
incorporated into a greater variety of industries. Therefore, it is important to make
an initial estimate of the potential costs associated with these health hazards, and
to prepare ahead with appropriate health insurance for individuals and financial
insurance for companies.
Currently, the data on the health impacts of nanomaterials needed to make these
estimates is rather limited. A survey of nanotechnology firms in the Massachusetts
region found that the greatest barrier to understanding and managing the EHS
risks is the lack of quantitative information available. This barrier is compounded
by the shortage of material and staff resources in the smaller firms [17]. The
survey found that firms rely mostly on data from suppliers, expert judgement, best
practices, or current regulations as guidelines for risk assessment and management.
HEALTH RISKS ASSOCIATED WITH NANOMATERIALS 387
One of the common methods of evaluating the environmental impacts of new

products is life cycle assessment (LCA), which takes into accounts all the inputs
used in production and the outputs generated throughout the product’s life cycle.
The input and output analysis starts with the inputs used to extract the raw
materials and build the machinery used for production, transportation of materials,
and continues up until the point that the final product is disposed of as waste at the
end of its life cycle. This method is generally considered most useful as a tool to
compare the impacts of different products that serve similar functions and can
substitute for each other.
A general general framework for incorporating life cycle assessments in
nanotechnology risk management was suggested by Sweet and Strohm [27], based
on their review of the existing findings on health and environmental impacts. But
one of the most comprehensive attempts to date to build a system for data
assessment and life cycle assessment was carried out jointly by Environmental
Defense Fund and DuPont, who published a joint proposal for a Nano Risk
Framework that includes a detailed process of evaluating and addressing the
potential risks of nanoscale materials [18]. DuPont applied this framework to three
nanomaterials it produces: DuPontTM Light Stabilizer 210, a s titanium dioxide
that acts as a UV stabilizer and UV screener for polymers; carbon nanotubes
(CNTs), cylindrical carbon molecules that have a variety of applications; and a
nano-sized zero-valent iron (nano-Fe0), which may potentially be used to destroy
contaminants in groundwater. The results of their life cycle assessments are posted
on their website (www.NanoRiskFramework.com).
Other studies have made life cycle assessments of nanomaterials, combined
with economic assessments of their profitability. For example, Roes et al. [25]
conducted a life cycle impact assessment of the use of a polypropylene (PP)/layered
silicate nanocomposite as packaging film, agricultural film, and automotive panels.
They found that the incorporation of nanoclays in nanocomposites can have an
impact on the environment, but that impact can be compensated for if the
environmental benefits are large enough (in this case, the benefits from a lower
weight of the produced film). The life cycle costs depend on the specific appli-
cation, and were found to be higher than those of conventional products in the
case of packaging film and lower in the case of agricultural film and automative
panels.
However, these studies concentrated on the cost of production, and did not
estimate the economic impact of the health hazards on the general population.
Economic evaluation of the health impacts is important in order to make decisions
comparing products based on nanomaterials with conventional products.
2. Methods of Economic Evaluation
A full comparison of different products with different types of impacts needs to

consider the economic aspects as well. Environmental economics methodologies
are commonly employed to take into account the environmental impacts of a product
in the final comparison of the economic costs and benefits from comparative
products. The analysis of the economic impacts of the health risks associated with
production relies on a variety of methods, such as estimating people’s willingness
to pay to reduce their health risks. Similarly, health economics methodologies are
commonly employed to compare the outcomes of products or services that may
improve population’s health, relying on methods of estimating the value of
changes in quality of life for individuals. The discussion in this section focuses
mostly on concepts from health economics, but the basic principles are very
similar in both environmental and health economics [14].
A general framework for decision analysis based on economic valuation of
health impacts is presented in Figure 1. The process is based on data collected
from epidemiological studies on the health impacts of different materials. This
data is translated into health risk assessments, taking into account exposure at
varying amounts and the probabilities of different health outcomes. Economic
analysis is based on combining these results with economic data in order to
estimate the economic value of different health impacts. At the micro (company)
level, the results of economic evaluation of their products may be used to assess
the risk involved, as well as the scope of insurance which may be needed to cover
these risks. At the macro (national) level, the results may be used to determine
national policies on regulations and investments in different nanotechnologies.
Epidemiological data Economic data
Health risk assessment Economic analysis
Results
Micro level: Company risk management;
Insurance decisions.
Macro level: Public investments;
National policies & standards.
Figure 1. Risk management model.
Evers et al. [5], Kenkel [14], Kuper et al. [15], Rice and Hammitt [24], and
others summarize the methodologies of economic evaluation of health impacts.
An economic evaluation usually compares the product in question with the
alternative, which may be an existing product or an alternative new development.
There are four basic types of economic evaluation of health impacts: cost-
minimization, cost-benefit, cost-effectiveness and cost utility [15, 16]. In cost

minimization it is assumed that the products have similar impacts and differ only
in their costs; this method would generally not be appropriate for evaluating
products based on emerging technologies, such as nanotechnology based products.
Cost effectiveness analysis (CEA) and cost-utility analysis are illustrated in
Figure 2. Both methods are based on comparing the physical health impacts rather
than their economic value of the benefits, and making a monetary evaluation only
of the costs involved. Cost effectiveness analysis compares specific alternative
products with different health impacts, and is therefore most suitable for micro-
level comparisons of one company’s product against its alternative. The basic unit
of measurement is time – health impacts are measured by the impact on a person’s
time. This includes the impact (positive or negative) on longevity – extension of
life years due to improved health, or reduced life expectancy due to the product
examined. This measure also includes the time lost due to the disability – lost time
due to illness or time spent on additional health care. The total time of life years
lost is termed Disability Adjusted Life Years (DALY). Cost utility analysis
provides a measure of the value people place on their life and on different states of
health [3]; and assigns different weights to different periods of life, based on one’s
health. A state of perfect health is assigned a weight of 1; death is assigned a value
of 0; and disabilities of varying degrees are assigned weights between zero and
one. It is also possible to assign a negative weight, to a state defined as worse than
death. The total sum of life years multiplied by life quality weight for each period
is termed Quality Adjusted Life Years (QALY) [24].
Cost effectiveness analysis is less suitable for comparing products with
different types of impacts [22]. For decisions involving different categories of
impacts, or comparisons with a multitude of different options for investments,
cost-benefit analysis should be carried out. This method, as illustrated in Figure 3,
requires an economic evaluation of the benefits as well as the costs involved in
each alternative. In this case, the health impacts are expressed in monetary rather
than in time units. The economic valuation of the health impacts is based on
assigning an economic value to life years as measured in DALY or QALY, by
applying one or more of the range of economic methods for monetary valuation of
societal & environmental benefits. The monetary valuation can be based either on
the Human Capital Approach (HCA) or the Value of Statistical Life (VSL)
method.
The Human Capital Approach (HCA), is based on calculating the value of
disability time based on a total of the costs of treatment and the loss of potential
earnings. Treatment costs may include direct costs of providing health care, such
as emergency room visits, hospital stay and subsequent treatment; as well as the
indirect costs, or patient time costs, of restricted activity days, and the cost of
workday loss [3, 24]. The loss of potential earnings includes both the loss of annual
earnings and the assigned value for the loss of household services performed, In
cases where the health impacts of the exposure of pregnant women or children
may result in impaired development, the cost of developmental delays is calcu-
lated by multiplying the probability of each type of developmental delay with its
expected impacts on lifetime earnings. The example in Figure 4 shows the
economic impact of developmental delays as a result of exposure to mercury. The

IQ deficit resulting from fetal exposure or exposure as small child to mercury is
estimated based on epidemiological data; and the economic evaluation is presented
under both the Human Capital Approach (HCA) and the Value of Statistical Life
(VSL) method.
The Value of Statistical Life (VSL) is defined as the willingness to pay to
avoid a small change in risk of dying – that is, the incremental value of a minor
increase in risks and NOT the value of saving the individual’s life. There are many
methods of estimating the value of statistical life. One of these methods is
contingent valuation – disseminating surveys asking people what they are willing
to pay to avoid a small increase in specific risk. Another method is averting
behaviour measurement – examining people’s investments in preventive measures
as an indicator of willingness to pay for risk avoidance. A third method is hedonic
valuation, which looks at the relationship between some market price and risk,
usually by performing a regression analysis between risk and independent
Level of Comparing specific

Micro
Analysis alternatives with
different health
impacts
CEA Identifying the

Method Cost Effectiveness/Utility alternative with
Analysis highest benefit/cost
ratio
Measuring health
Unit of benefits in time
measurement Time units (cost per life
year saved)
Cost Effectiveness Analysis:

DALY
Disability Adjusted Life Years
Methods of
evaluation
QALY
Figure 2. Economic analysis methods: cost-effectiveness analysis.

Level of Analysis Macro
CBA
Method Cost Benefit
Analysis
Applies economic
methods for monetary
Unit of
Money valuation of societal &
Measurement
environmental benefits
Human Capital
HCA Approach:
Methods of Cost of illness
Evaluation
Value of
VSL Statistical Life:
Willingness to pay
Figure 3. Economic analysis methods: cost-benefit analysis.
variables. An example of the latter method is hedonic valuation based on wages –

that is, observing the risk premiums paid for riskier jobs as an indicator of
people’s willingness to accept a monetary compensation for increased risk.
Researchers estimate that the value of a lost productive day, using the human
capital approach, is about $150/day [9]. Estimates of the Value of Statistical Life
(independent of age), range between $3–9 million; The US Environmental
Protection Agency (EPA) uses an estimate of $5.9 million for its calculations [24].
As a general rule, economic valuations of the Value of Statistical Life usually
yield much higher values than the Human Capital Approach. An example of the
discrepancy between the two values, for the health impacts of exposure to mercury
by gender, is shown in Figure 4, which is based on the data published by Rice and
Hammitt [24]. Gyrd-Hansen [10] notes that even within the VSL measure,
different estimation can result in variations by a factor of 40, and that the results
are affected by the respondents’ income level. Despite these limitations, he
concludes that using contingent valuation methods for economic evaluation of
health impacts is a useful, if imprecise, tool for decision-making.
3500
VSL: Females
3000
VSL: Males
2500
Billion US$ (2000)
2000
1500
1000
500
HCA: Males HCA: Females
0
Figure 4. Valuation of health risks from exposure to mercury in consumers of commercial fish (total
for the US). (Prepared from data in [24], Tables 71 and 80.)
Economic analysis is an essential component in determining public health

policy, but it is often unclear how it should be carried out, and with whom the
responsibility lies. John Graham, administrator of the Office of Information &
Regulatory Affairs at the Executive Office of the US President, states that “... cost-
effectiveness analysis and cost-benefit analysis ... can help us accomplish more
public health and medical protection at less cost than will occur when decisions
are made without good analysis ... it is fair to say that their influence on practical
decision making in both the public sector and the private sector has been limited to
date” [8]. Furthermore, Graham suggests that university-based scientists’ ability to
offer solutions to emerging health issues is limited, because addressing these
issues requires multidisciplinary teams of the type university students find difficult
to put together.
3. Application to Nanomaterials
The neglect of economic analysis in the formulation of public health policies is

particularly notable in the field of nanotechnology, because of the special
difficulties involved in analysing emerging technologies [8]. However, although
there is little direct data available, it is possible to compare the known hazards of
nanoparticles with other toxic agents, in order to evaluate the statistical probability
of different health hazards, such as the impact of carbon nanotubes (CNTs) on
pulmonary toxicity. Von Gleich et al. [7] suggest an approach to making life cycle
assessments of nanomaterials that takes into consideration the limitations of
available information. Mueller and Nowack [21] present exposure models of
engineered nanoparticles of different types that may be used to model risk
assessments. Quantifying the disability adjusted life years can be done based on
the known health hazards of similar components, and its economic valuation can
be done based on the income lost and the costs of medical treatment. The total
expected increase in cost depends on the increase in statistical probability of each
disease.
Existing research on life cycle impact assessment has yielded enough
information to enable a simplified initial evaluation of a variety of nanomaterials.
For example, Pietrini et al. [23] published a life cycle assessment of poly (3-
hydroxybutyrane) (PHB) based composites, incorporated into cathode ray tube
(CRT) monitor housing and the internal panels of an average car, as compared
with the conventional, currently used products. Vince et al. [28] conducted a
comparative life cycle assessment of different desalination methods, including
nanofiltration-based desalination. Krishnan et al. [13] conducted a detailed life
cycle inventory study for semiconductor fabrication based on nanofabrication
technologies, and incorporated the results in a life cycle assessment of a complete
set of semiconductor manufacturing processes. Bauer et al. [2] conducted life
cycle assessments of PVD coatings (a type of vacuum coating techniques) and
CNT-based FED screen (carbon nanotube field emission displays for screen
displays). Several additional life cycle assessments of nanomaterials were
published in a special issue on sustainable nanotechnology development in the
Journal of Cleaner Production [12].
These life cycle assessments include, by definition of the LCA methodology,
estimates of the Disability Adjusted Life Years associated with the increased
probability of health hazards from the products examined. The DALY data can be
used for economic evaluation of the health impacts of these materials. This
method has been applied in other fields, for example, to carry out an economic
evaluation of the health impacts found in a life cycle assessment of agricultural
crops [11].
Further research should be done in multidisciplinary teams, composed of
economists, LCA analysts and nanotechnology experts to assess the possible
health impacts and their economic implications for the companies and for society
in general, and to establish recommendations for public health policy based on
both scientific and economic considerations.
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NANOMATERIALS
Applications, Risks, Ethics and Society
A. VASEASHTA
Nanomaterials Laboratories & Characterization Labs
Marshall University
One John Marshall Drive
prof.vaseashta@marshall.edu
Abstract. This study is conducted to provide a balanced, concise yet comprehen-

sive perspective of potentials and risks associated with the use of nanotechnology.
Risk assessment modality is based on parameters that evolve as a result of
interaction of reduced dimensional materials with its environment and observed
toxicological effects, as compared to the one based on conjecture. An overview of
the fate and transport of nanomaterials in air, water, and soil, resulting in environ-
mental impacts, human health, and ecology is briefly discussed. A three pillared
approach to assessing nanotechnology risk is discussed, viz.: to develop a framework
for assessing nanotechnology risk; to develop a survey instrument for assessing
risks from expert elicitation; and to conduct a Delphi based study to build upon
initial survey results. A framework for developing a comprehensive survey instru-
ment is discussed.
1. Introduction
Materials approaching nanoscale dimensions exhibit characteristics with numerous

unique and hitherto unexploited applications. Advances in synthesis and char-
acterization methods have provided the means to study, understand, control, or even
manipulate the transitional characteristics between isolated atoms and molecules
and bulk materials. Fundamental understanding and technological advances arise
from the potential of nanoscale materials to exhibit properties that are attributable
to their small size, physical characteristics, and chemical composition. Furthermore,
the nanoscale geometrical dimensions are comparable to the smallest engineered
entity, the largest molecules of living systems, and several fundamental physical
quantities. Unique characteristics and functionalities of nanomaterials have already
been utilized in cosmetics, apparel, and sports industries; while proof-of concept
electronic and optical devices have been demonstrated and further progress will
lead to commercialization.
Recently, functional and architectural innovations in nanoscale materials have
initiated applications in chemical and biological sensing [1, 2] environmental

398 A. VASEASHTA
pollution sensing [2, 3] monitoring [4], mitigation and remediation [5], advanced
energy generation and storage devices [2, 6], nano-biotechnology [7], nanophotonics
[8], in-vivo analysis of cellular processes [9], and futuristic health and clinical
medicine platforms [10]. A nanotechnology based sensor platform enables direct
electrical detection of biological and chemical agents in a label-free, highly multi-
plexed format over a broad dynamic range. Nucleic acid layers combined with
nanomaterials-based electrochemical or optical transducers produce affinity biosensors
such as the “DNA Biosensor” or “Genosensor” that are attractive devices for conver-
ting the hybridization event into an analytical signal for obtaining sequence-
specific information in connection with clinical, environmental, or forensic
investigations [11]. Further, applications of nanotechnology in material sciences,
health care, and information technology will likely have a positive impact on our
society.
The transformational potential of nanotechnologies has also been a cause of
concern since the dimensions are comparable to biological molecules, thus possibly
leading to toxicological effects. The new paradigm of collaborative research environ-
ment and virtual shared resources produce innovations faster than the Federal
agencies can either produce standards, safety instructions or informed policies that
address risks associated with use of nanotechnology based products. Often,
“voluntary codes of conducts” are adopted or employed to address societal concerns.
These complex dynamics may lead to possible erosion of public confidence, thus
tipping of the playing field from “potentials” to “risks.
The objective of this investigation is to provide balanced, concise, yet com-
prehensive and objective perspective of potentials and risks associated with the
use of nanotechnology. A comprehensive list of parameters that may determine
toxic potential of nanomaterials is provided, which may provide better perspective
of toxicological investigations as compared to isolated studies. Also, a discussion
concerning fate and transport further provides guidance about the dispersal and
transport of these materials in the environment, water streams, and soil. Scientists
share additional responsibility to address societal concerns by keeping the public-
at-large informed with a balanced perspective. Risk assessment employing expert
elicitation is primarily aimed to provide a balanced perspective.
2. Present and Future of Applications of Nanomaterials
Nanotechnology is a transformational technology that utilizes inherently unique

properties of matter in reduced dimensions. Applications of nanotechnology range
from material sciences, medicine, energy, environment, communications and elec-
tronics among others. A comprehensive list of applications is beyond the scope of
this section but is provided as a working group recommendation in this proceeding
[12]. Some of the applications in the context of health and environment vis-à-vis
risk scenarios are provided below.
Nanoengineered platforms possess unprecedented potential for early detection,
diagnosis, and site-specific and time-controlled cure for diseases. Multifunc-
tionality provides a key advantage to nanoengineered platforms, where targeting,
NANOMATERIALS 399
imaging, site and time specific therapeutics and drug delivery, and numerous other
functionalities can be integrated to allow for site-specific and targeted molecular
imaging, therapy and diagnostics probes, demonstrating tremendous potential to
enhance the sensitivity, specificity, and signaling capabilities of various biomarkers
in human diseases. Furthermore, nano-biotechnology will help identify cell-source
to be divided by specific cellular phenotypes, thus improving strategies for in-vivo
detection and monitoring of the cellular implants, techniques to enhance integration
of the transplant within the host tissue, and deliver genes to cells. Nanomaterials
have also been used for bactericidal, antibiotics, and drug-resistant strains. Quite
to the contrary, this investigation also deals with risk scenarios and assessment
instruments associated with interaction of nanomaterials with human body.
Nanomaterials have been studied in the context of environmental applications
to solve problems such as pollution and issues that support sustainability. Nano-
materials have been used as active, anti-reflective, and spectrum-shifting layers to
produce high efficiency solar cells inexpensively. Work has also been reported to
use nanomaterials to reduce energy load by using lightweight materials for
vehicles; materials and geometries that contribute to more effective temperature
control; technologies that improve manufacturing process efficiency; materials
that increase the efficiency of electrical components and transmission lines;
materials that contribute to new and improved fuel cells (FC) – for hydrogen
economy; and biodegradable materials for reduced and benign landfill volume.
Nanoscale materials are used for cosmetics – viz. sunscreens, house paints,
clothing, and computers. Despite of its abundant use and potential, there exists a
societal concern that nanomaterials pose health hazards, thus necessitating risk
assessment and guidelines for using engineered nanomaterials. The challenge of
nanotechnology is to deploy the benefits with minimal risks.
There is a significant gap in our knowledge of the environmental, health, and
ecological impacts associated with nanostructured materials. Since innovations in
the field of nanotechnology occur faster than policymakers can develop safe
handling practices; a comprehensive and fundamental investigation is necessary
based on dynamic transport of nanomaterials in the environment and its impact on
human health and ecology. It is imperative, therefore, to put the entire subject in a
balanced perspective to provide end-users of nanotechnology unbiased and fair
choices.
3. Risk Scenarios
Origin, physical dimensions, and characteristics of nanomaterials vary significantly.

Nanomaterials are produced by nature, commercial and industrial processes (not
intended for nanomanufacturing), and laboratory, industrial, and commercial process
designed to produce nanomaterials (also known as engineered nanomaterials). At
present, there is insufficient information to predict dispersal and distribution of
nanomaterials in mediums such as air, water, and soil. Hence, toxicity scenarios
leading to exposure to nanomaterials in the workplace environment are rendered
rather complicated to define, especially as they relate to the point of origin. For
400 A. VASEASHTA
lack of detailed scientific studies, some of the risks reported in literature range
from legitimate concerns to pure fiction or rather exaggerated extrapolation from
results tangentially related to nanomaterials. An understanding of the toxicity of
nanomaterials related to human beings, environment, and perhaps for sustainable
use in the future requires understanding the interface between nanomaterials and
its environment. More specifically, an understanding of the agglomeration and
dispersion, i.e. how nanomaterials transport themselves in the environment, the
fate and transport and life-cycle analysis of nanomaterials is critical.
3.1. NANOMATERIALS–ENVIRONMENT INTERFACE
Size and surface collectively control characteristics of nanoscale materials due to

the existence of large boundaries adjoining their surrounding medium and interplay
of physicochemical interactions. The surface free-energy is size-dependent and
hence increases almost inversely with the decreasing feature sizes of the material.
Collective response of a nanomaterial-medium system that is attributable to reduced
dimensions, viz. size, and surface structure, physical, chemical, and biological
interactions is vital to developing a scientific basis to predict its pathways for
toxicity. It is an exceedingly complex task due to a large matrix of parameters
consisting of nanomaterials, the surrounding environment, and influencing mecha-
nisms of interactions. Further complexities arise due to production and diversity of
nanoparticles. Hence, to develop guidelines for occupational exposure it will
become increasingly important to understand how nanoparticles and biological
systems interact in terms of bio-physico-chemical properties of nanoparticles
produced by nature, engineered, and produced as a result of routine industrial and
commercial processes. An extensive investigation is underway in the context of
specific functions ranging from bio-nanomaterials interface to toxic potential of
industrial pollution. Figure 1 shows environments of a NP and various bio-
physico-chemical interactions scenarios.
The characteristics which provide beneficial aspects are also believed to be
responsible for toxicity of nanomaterials. Consequently, NP toxicity is studied in
context of its ability to induce tissue damage through the generation of oxygen
radicals, electron-hole pairs, and oxidant stress by abiotic and cellular responses,
mitochondrial injury and cellular effects in the lung, cardiovascular system and
brain [13]. Some studies suggest that NPs absorb cellular proteins which could
induce protein unfolding, fibrillation, and thiol cross-linking; leading to neuro-
toxicity and reduced enzymatic activity [14]. Nanoparticles which are cationic are
also believed to induce toxicity via acidifying endosomes that lead to cellular
toxicity and apoptosis in epithelial lung, mitochondrial targeting, and cytosolic
deposition. Nanomaterials composed of redox-active elements are particularly reactive
and can initiate potentially detrimental chemical transformations. Furthermore,
even chemically benign NPs may become activated by light absorption. Hence,
fundamental understanding of a nanomaterial-surrounding medium is vital to
sustaining technological advances of nanoscale materials as a catalyst for new
scientific and technological avenues.
NANOMATERIALS 401
Figure 1. Nanoparticles/medium/cell interaction – physico-chemical characteristics.
3.2. FATE AND TRANSPORT
Despite beneficial effects and major developments in the field of nanomaterials,

there is a significant gap in our knowledge of the environmental, health, and eco-
logical impacts associated with nanostructured materials. A comprehensive and
fundamental investigation into the dynamic transport of nanomaterials in the
environment and its impact on human health and ecology is needed to guard
public welfare. The complex nature of naturally occurring and engineered nano-
materials and transport, either in the environment or via different exposure routes
with human body necessitates further studies. A matrix of parameters which
govern fate and transport modeling of nanomaterials such as exposure routes,
chemical composition, surface structure, solubility, size and shape effects, toxicity,
absorption, distribution, metabolism, agglomeration, and excretion rate and mecha-
nisms is under investigation via three most common routes – inhalation, ingestion,
and dermal exposure.
The accumulation, dispersion, and functional surface groups play an important
role in cytotoxicity and in evaluating pathways of cellular uptake, sub-cellular
localization, and targeting of sub-cellular organelles. Studies relating to the
thermodynamic properties, interfaces, and free energy of nanoparticles as a
function of particle size, composition, phase and crystallinity influence particle
dissolution in a biological environment. This investigation in conjunction with
plume modeling and predictive modeling approaches will assist in prioritizing,
testing, and correlating with in-vivo exposure models. A comprehensive investigation
402 A. VASEASHTA
will prove beneficial to development of risk assessment tools and ensuring safe
practice in nanotechnologies.
4. Preliminary Framework for Risk Analysis
In business management, decisions are made even though there is an element of

uncertainty about the outcome, often estimated as probability in mathematics.
Nanotechnology poses a rather unique challenge due to rapid development in this
relatively new field and rather insufficient studies of the effect of nanoparticles
with human health. The environment consists of nanomaterials produced by the
nature, industrial and transportation exhaust emission, and to some extent
inadvertent release of engineered nanomaterials. To help understand the structure
of this rather vast and complicated task, a preliminary framework is developed for
this investigation. A more detailed overview of basis, influence diagrams, and
corresponding survey instrument, is discussed elsewhere.
Effective risk analysis involves identifying, assessing, and mitigating risk to a
satisfactory level. Risk analysis is a process of evaluating critical assets and
systems, threats, vulnerabilities, and controls for mitigating threats. Outcomes of
risk assessment form a strategic plan for managing risks. Three pillars of risk
analysis are to assess, manage, and communicate. Assessment is the process of
identifying risk. Managing is the process of mitigating risks in an optimal manner.
Communication ensures that policy and decision makers and the general public
understand outcomes of risk assessment and risk management. Nanotechnology
risk assessment occurs in a climate of uncertainty and change; therefore, effective
decision making by participating experts is critical for a successful outcome.
According to Howard [15], high quality decisions are characterized by the
following elements:
1. Appropriate framing of decisions
2. Analysis of creative alternatives
3. Accurate information and sound models
4. Clear preferences for future status
5. Sound logic
6. Commitment to process and outcomes
Policy and decision makers are increasingly relying on expert-opinion elicitation
techniques for forecasting advances, reliability, and risks related to science and
technology [16]. Structured expert-opinion elicitation techniques effectively support
complex decision-making in the face of risk and uncertainty [17]. Since nano-
technology risk assessment is in its infancy, incorporating formal expert-opinion
elicitation methods within the risk assessment process may help to prevent
cognitive biases and faulty cognitive processes attributing to poor decision quality.
This report introduces the concept of using a structured expert-opinion elicitation
technique, a computerized Delphi technique to assess nanotechnology risks by
expert panels. Tversky and Kahneman [18] investigated factors contributing to
poor quality decisions arising from risk analysis processes. First, unreliable
NANOMATERIALS 403
information including incomplete, inaccurate, unrepresentative historical data

about threats, vulnerabilities, and occurrences leads to poor quality risk analysis
decisions. Second, unreliable forecasting including bad estimates of probabilities
and excluding outlier events impacts the quality of risk analysis decisions. Third, a
host of cognitive biases including representativeness, availability, anchoring and
adjusting, optimistic biases, risk biases, and a false sense of control may nega-
tively affect risk analysis processes. Finally, dysfunctional group dynamics arising
from strong personalities, organizational hierarchies, and miscommunications
impede the risk analysis process and resulting decisions. The Delphi Technique is
a structured interactive group communications technique effective for reaching
consensus about judgments, forecasts, or decisions from expert panels [19]. The
Delphi process occurs as follows:
Facilitator distributes survey to the expert panel.
Survey is answered anonymously and independently by an expert panel.
Facilitator summarizes and distributes results and rationale.
Expert panel anonymously and independently reviews summarized results and
rationale. Panelists may revise individual responses, optional.
The process of eliciting, summarizing, and distributing anonymous and inde-
pendent responses continues until consensus, stable responses, or a given number
of rounds is met. The Delphi Technique benefits decision making and forecasting
processes involving expert panelists in many ways. First, the Delphi technique
supports expert panels ranging from a few participants to a few thousand parti-
cipants. Second, the Delphi technique effectively overcomes constraints in time,
geographic location, cost, or anonymity needs. Third, the Delphi technique proves
effective when actuarial, technical, or economic data is unavailable thus mandating
expert judgment. Fourth, the Delphi technique has proven effective in the explo-
ration and forecasting of novel, complex, or uncertain problems or events. Finally,
the Delphi technique overcomes social barriers related to diversity, hierarchy,
personality, or hardened conflicts. Because the Delphi technique has proven merit
in forecasting trends and risks for many scientists, researchers, policy, and
decision makers; the authors propose a future investigation involving a Delphi
Study for assessing NT risks.
Efforts are underway to prepare an initial comprehensive survey. Then, a pilot
study will be conducted comprising a small group of experts at a forthcoming
nanotechnology conference. Then, the survey will be reviewed and revised accor-
dingly. A large number of nanotechnology scientists, researchers, industry, and
government experts will be contacted to participate in a formal Delphi Study for
Assessing Nanotechnology Risks. The Delphi Study for Assessing Nanotechno-
logy Risks will be conducted and results will be published. Figure 2 conceptually
shows various means to receive input from the survey instrument (shown in Figure 3).
404 A. VASEASHTA
Figure 2. Conceptualization of expert elicitation using Delphi.
4.1. RISK ASSESSMENT SURVEY INSTRUMENT
Every technology that mankind has adopted has risks associated with it. The
understanding of environmental effects and health risks associated with nanotech-
nology is very limited and sometimes contradictory. At present, a well defined risk
assessment modality is needed, as the “voluntary code of conduct” for using
nanomaterials is somewhat trepidation based and not entirely on scientific
methodology.
Effective risk analysis involves identifying, assessing, and mitigating risk to a
satisfactory level. Outcomes of risk assessment form a strategic plan for managing
risks. Nanotechnology risk assessment occurs in a climate of uncertainty and
change; therefore, effective decision making by participating experts is critical for
successful outcomes. Strategic planning encompasses seven categories, viz.:
taxonomy, significance, implementation, sustainability, precaution, inclusiveness,
and accountability. Risk analysis is a process of evaluating critical assets and
systems, threats, vulnerabilities, and controls for mitigating threats.
High quality decisions are characterized by the following elements: appropriate
framing of decisions; analysis of creative alternatives; accurate information and
sound models; clear preferences for future status; sound logic; and commitment to
process and outcomes. Policy and decision makers are increasingly relying on
expert-opinion elicitation techniques for forecasting advances, reliability, and risks
related to science and technology. Structured expert-opinion elicitation techniques
effectively support complex decision-making in the face of risk and uncertainty.
Since nanotechnology risk assessment is in its infancy, incorporating formal
expert-opinion elicitation methods within the risk assessment process may help to
prevent cognitive biases and faulty cognitive processes attributing to poor decision
quality.
NANOMATERIALS 405
Figure 3. A sample of questions used for expert elicitations.
The Delphi Technique is a structured interactive group communications technique

effective for reaching consensus about judgments, forecasts, or decisions from
expert panels. The Delphi process occurs as follows: a facilitator distributes survey to
the expert panel; the survey is answered anonymously and independently by the
expert panel; a facilitator summarizes and distributes results and rationale, and the
expert panel anonymously and independently reviews summarized results and
rationale, and panelists are allowed to revise individual responses. The process of
eliciting, summarizing, and distributing anonymous and independent responses
continue until consensus, stable responses, or a given number of rounds are met.
406 A. VASEASHTA
The Delphi technique has proven merit in forecasting trends and risks for many
scientists, researchers, policy, and decision makers.
5. Conclusion and Future Directions
Nanotechnology presents the promise of a diverse array of manufactured goods

and products that incorporate improved and innovative properties. National and
international governmental agencies, companies and research organizations have
all recognized significance of proactive steps to identify potential undesirable
health consequences of nanomaterials and to minimize impact in occupational
environments. Due to advantages offered by such materials and associated uncer-
tainty about untoward health effects from exposures should not impede tremendous
momentum and significant advantage towards applications in medical, security,
environment, and energy generation and storage.
Development of proposed survey instrument, its analysis, and efforts by com-
panies to develop worker safety programs based on the guidelines will minimize
potential health effects. Such an approach can further minimize the likelihood of
worker exposures to nanomaterials and subsequent financial liability claims and
litigation. Hence, exposure assessment using the proposed tools and data
collection by expert elicitation is important for the elucidation of potential health
risks assessment.
References
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and Systems, Springer Science and Business Media, Dordrecht, The Netherlands.
2. Vaseashta, A., Dimova-Malinovska, D., and Marshall, J. (2005) Nanostructured and
Advanced Materials, Springer Science and Business Media, Dordrecht, The Netherlands.
3. Pummakarnchana, O., Phonekeo, V., and Vaseashta, A. (2007) Sensors & Transducers
Journal 77(3), 1065–1072.
4. Pumakaranchana, O., Phonekeo, V., and Vaseashta, A., “Semiconducting Gas Sensors,
Remote Sensing Techniques, and Internet GIS for Air Pollution Monitoring in Residential
and Industrial Areas”, pp: 339 (2008) in “Functionalized Nanoscale Materials, Devices,
and Systems”, ed. Vaseashta, A. and Mihailescu, I. Springer, Dodretcht, The Netherlands.
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Pummakarnchana, O. (2007) Science and Technology of Advanced Materials 8, 47–59.
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Photonics, and Energy Generation and Storage”, pp: 3 (2008) “Functionalized Nanoscale
Materials, Devices, and Systems”, ed. Vaseashta, A. and Mihailescu, I. Springer, Dodretcht,
The Netherlands.
7. Vogel, V., and Baird, B. (Eds.) (2003) Nanobiotechnology: Report of the National
Nanotechnology Initiative Workshop, October 9–11, Arlington, VA.
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9. Prasad, P. (2004) Nanophotonics. Wiley, Hoboken, NJ.
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11. Erdem, A., and Vaseashta, A. (2008) NANO: Brief Reports and Reviews (in press).
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H., and Abdel-Mottaleb, M. This proceeding.
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and Butterfield, D. (2005) Free Radical Research 39(11), 1147–1154.
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Controlled Release, 94(1), 217–227.
15. Howard, R. (2007) Decision analysis: A personal account of how it got started and
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by W. Edwards, R. Miles, Jr., and D. von Winterfeldt (Eds.) (Cambridge University
Press, New York), pp. 32–56.
16. Ayyub, B. (2001) Elicitation of Expert Opinions for Uncertainty and Risks. CRC Press,
Boca Raton, FL.
17. Rowe, G., and Wright, G. (2001) Expert opinions in forecasting: The role of the Delphi
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Practitioners, edited by J. S. Armstrong (Kluwer, Norwell, MA), pp. 125–144.
18. Tversky, A., and Kahneman, D. (1974) Science, 185(4157), 1124–1131.
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Applications. Retrieved (October 10, 2007), from New Jersey Institute of Technology
Web site; http://is.njit.edu/pubs/delphibook/
GROUP DECISION-MAKING IN SELECTING
NANOTECHNOLOGY SUPPLIER
AHP Application in Presence of Complete and Incomplete Information
B. SRDJEVIC
Faculty of Agriculture
University of Novi Sad
Trg Dositeja Obradovica 8
21000 Novi Sad, Serbia
bojans@polj.ns.ac.yu
Z. SRDJEVIC, T. ZORANOVIC, K. SUVOCAREV

Faculty of Agriculture
University of Novi Sad
Trg Dositeja Obradovica 8
21000 Novi Sad, Serbia
Abstract. A group decision-making context is created to enable assessment of the

Analytic hierarchy process (AHP) performance in presence of complete and
incomplete information. To illustrate it, four recognized nanotechnology suppliers
are evaluated across seven commonly used company/product attributes (net price,
delivery, quality, production facilities, technical capability, management and
organization, and geographical location) to identify the best one in multicriteria
sense. Broad overview of applicable selection criteria and related MCDM metho-
dologies is also presented.
1. Introduction
Selecting the right supplier is difficult task, because each potential supplier has its
advantages and disadvantages. One can have good price, but low availability of a
skilled labor force necessary to produce the component. Other supplier can be
more reliable. Third one can have the best technical support for maintaining the
components. It is up to purchasing managers to define selection criteria and to
evaluate potential supplier according to them. To make the right decision,
managers must have reliable, trustworthy and comprehensive decision framework.
Decision making nowadays assumes scientifically supported process, which in
most cases includes several decision makers and interest groups. To successfully
deal with different attitudes and opinions of different people, variety of methods is
in use. Not many of them can involve quantitative, qualitative and semi-qualitative

410 B. SRDJEVIC ET AL.
criteria as the Analytic Hierarchy Process (AHP) can do; and this is probably the
main reason why it is popular worldwide.
The major advantage of AHP is that it involves a variety of tangible and
intangible goals. For instance, it reduces complex decisions to a series of pair-wise
comparisons, implements a structured, repeatable and justifiable decision making
approach and build consensus [26].
Method is used in business and industry, by the governmental bodies and even
by politicians, in individual and group contexts. Problems addressed are prioriti-
zation and selection, planning and budgeting, project and portfolio selection,
vendor and source selection, trade studies, performance and risk assessment,
market research, resources allocation, etc. Here we use AHP as a group decision
support tool in the supplier selection problem, with complete and incomplete
information.
First part of the paper gives brief overview of the supplier selection problem;
analyses selection criteria and selection methods. AHP basics are given next, with
emphasis on the a priori and a posteriori aggregation of individual judgments and
on the meaning and influence of complete and incomplete information on the final
decision. Illustrative example is given in the following section, while discussion
and conclusions close the paper.
2. Supplier Selection
2.1. SELECTION CRITERIA
The first step in the supplier selection process is to define selection criteria.
Pioneering work on this subject is done by Dickson [9], when he asked 170
purchasing agents and managers to evaluate 23 supplier selection criteria using the
five point scale: extreme (4), considerable (3), average (2), slight (1) and no
importance (0). Average value for each criterion is then calculated from all 170
assessments, as given in Table 1. Five top ranked are: quality, delivery, perfor-
mance history, warranties and claim policies and production facilities. Price is
ranked as the 6th criterion.
Similar results were obtained in 1991, when eight senior buyers in engineering
company made assessments of the same criteria [32].
Weber et al. [30] analyzed 74 papers and found that the most discussed criteria
for supplier selection are net price, delivery and quality (last column of Table 1).
Also, production facilities, technical capability, management and organizations
and geographical location are mentioned as selection criterion in more then ten
papers, with recommendation that they should be considered as decision elements
in the selection process.
GROUP DECISION-MAKING IN SELECTING NANOTECHNOLOGY SUPPLIER 411
TABLE 1. Supplier selection criteria [32].
2.2. SELECTION TECHNIQUES
The vast majority of the methods suggested in the related literature can be classified
into three categories: mathematical programming models, rating/linear weighting
models and artificial intelligence (AI) techniques [2]. Table 2 shows the supplier
selection techniques by methodological area.
TABLE 2. Supplier selection techniques. (Selected from [2].)
References
Ellram [12], Bhutta and Huq [3], Dogan and
Total cost of ownership
Sahin [10]
Wang et al. [29], Amid et al. [1], Kumar et al.
Mathematical programming techniques
[22]
AI methods Choy et al. [6], Choy et al. [7]
AHP Kahraman et al. [21], Liu and Hai [23]
Linear weighting techniques and other MCDM Grando and Sianesi [17], Chen et al. [4]
methods
Outranking techniques De Boer et al. [8], Dulmin and Mininno [11]
DEA Weber et al. [31], Talluri and Narasimhan [28]
The selection of the most appropriate method for a particular priority setting
situation, with regard to criteria depends on (1) the time available for the study, (2)
the availability of data in relation to the degree of analysis, (3) analytical capacity,
(4) participation in the process, and (5) transparency within the process [14].
Degree of intensity: Time

1: low
2: moderate 3 Mathematical programming / Simulation
3: high
Economic surplus
2
Analytic Hierarchy Process
1 Scoring
3 2 1 1 2 3
Partcipation Transparency
1
Data and analysis
Figure 1. Priority setting methods compared [14].
Figure 1 [14] illustrates a comparison of five different priority setting methods:

mathematical programming, simulation, economic surplus, analytic hierarchy process
(AHP) and scoring. Scoring and AHP are more transparent and participatory,
while mathematical programming, simulation, and economic surplus require more
time, resources, and data analysis. As we are looking for a tool allowing especially
participation, the latter are not considered as candidates for selection methodology
in our case.
Although scoring can be conducted in a relatively short period of time, is
transparent, allows participation, and does not require advanced quantitative skills,
AHP is selected as a solution framework since it minimizes the shortcomings of
scoring (for example poorly measured or overlapping criteria for determining the
best alternative) through careful structuring the decision hierarchy.
The major advantage of AHP is that it involves a variety of tangible and
intangible goals. For instance, it reduces complex decisions to a series of pair-wise
comparisons, it implements a structured, repeatable and justifiable decision-making
approach, and it builds consensus. An introduction to the method and its theoretical
foundations is given in Saaty [24]; for this reason only the basic properties of the
method that are necessary for understanding the decision-making process will be
described in the next section.
3. Analytic Hierarchy Process
The AHP is a multicriteria decision-making method which requires a well-

structured problem, represented as a hierarchy. Usually, at the top of the hierarchy
is the goal; the next level contains the criteria and sub-criteria, while alternatives
lie at the bottom of the hierarchy. AHP determines the preferences among the set
of alternatives by employing pair-wise comparisons of the hierarchy elements at
all levels, following the rule that, at given hierarchy levels, elements are compared
with respect to the elements in the higher level by using the Saaty’s importance
scale (Table 3).
TABLE 3. The fundamental Saaty’s scale for the comparative judgments.

Num. values Verbal terms
1 Equally important
3 Moderately more important
5 Strongly more important
7 Very strongly more important
9 Extremely more important
2, 4, 6, 8 Intermediate values
By assumption, value 1 corresponds to the case in which two elements

contribute in the same way to the element in the higher level. Value 9 corresponds
to the case in which one of the two elements is significantly more important than
the other. Also, if the judgment is that B is more important than A, the reciprocal
of the relevant index value is assigned. For example, if B is felt to be notably more
important as a criterion for the decision than A, then the value 1/7 would be
assigned to A relative to B. The results of the comparison are placed in comparison
matrices. After all judgments are made, the local priorities of the criteria, sub
criteria and alternatives can be calculated using the principal eigenvector of a
comparison matrix, as suggested by Saaty [24]. The synthesis is performed by
multiplying the criteria specific priority vector of the alternatives with the
corresponding criterion weight, and then appraising the results to obtain the final
composite alternatives priorities with respect to the goal. The highest value of the
priority vector indicates the best-ranked alternative.
3.1. GROUP DECISION MAKING
In the case of the group decision making, the aggregation can be performed on
individual priorities (1a) and individual judgments (1b) by the Geometric Mean
Method (GMM) [16].
If priorities are aggregated, AHP methodology is followed for each decision
maker separately till final alternatives’ priorities are obtain. Priorities are then
aggregated by equation:
K
ziG = ∏ z (k )α
k =1
i
k
(1a)
where K stands for the number of decision makers, zi (k) for the priority of i-th
alternative for k-th decision maker, αk for the ‘weight’ of k-th decision maker, and
ziG for the aggregated group priority value. Notice that weights αk should be
additively normalized prior to their use in Eq. 1a and that the final additive
normalization of priorities ziG is required.
To aggregate individual judgments and form combined (group) matrix AG =
G
{ a ij }, judgments from K matrices on each (i,j) position are aggregated by:
K
aijG = ∏ a (k )α
k =1
ij
k
(1b)
where aij (k ) is individual judgment of the decision maker k on the position i,j in
his/her decision matrix, αk for the ‘weight’ of k-th decision maker, and aijG
combined (group) judgment on position i,j in combined matrix. Final alternatives’
priorities are calculated using combined matrices as there is only one decision
maker.
Both mentioned methods assume that all positions in decision matrices a ij (k )
exist, i.e. that input is complete.
4. Complete and Incomplete Inputs
Decision matrix is, as described above, filled with decision-maker’s individual

judgments. If all matrix elements in the upper triangle exist, input matrix is consi-
dered complete and standard AHP synthesis procedure for calculating priorities
can be performed. If at least one element is missing, input is incomplete. Harker
[18] discussed three reasons why one would want to make fewer than the full set
of judgments for each of one or more sets of factors in an AHP model:
To reduce the time to make the judgments
Because of an unwillingness to make a direct comparison between two
particular elements
Because of being unsure about some comparisons
In such cases, it is not possible to calculate priorities and it is necessary to
estimate missing element using the existing ones. There are different methods
used for solving this problem: consistency optimization [15]; back-propagation
multi layer perceptron – neural network based method [20]; connecting paths [19,
5]; characteristic polynomial-based method [25]; and revised geometric mean
method [18]; to name but a few.
Simulation employed in [20] comparing the efficiency of four methods (connecting

paths, revised geometric mean method , characteristic polynomial-based method
and back-propagation multi layer perceptron), showed that connecting paths can
be considered as most efficient for small size matrices such are incomplete
matrices in our example.
4.1. CONNECTING PATHS
If aij (i ≠ j) is missed in a positive reciprocal matrix, aij can be determined by a

connecting path of size k, CPk, as follows:
CPk = ai,p1 ap1,p2 ... apk,j (2)
Missing element aij is a geometric mean of all connecting paths related to aij:
q
aij = q ∏ CP
k =1
k (3)
where CPk is a connecting path, k defines the number of elements in the connec-
ting path, and q is the number of all possible connecting paths.
Major drawback of this method is that the number of connecting paths can be
high for large matrices. For example, for matrix of size 10, number of connecting
paths is 109,000.
4.2. INCOMPLETE INPUT AND GROUP DECISION-MAKING
If incomplete matrix appears in the group decision framework, one solution is to

use existing individual judgments to estimate the missing one by the connecting
paths method and then to aggregate priorities or judgments using the Eq. 1a or b.
Another solution is proposed in [27]. Missing judgment aijG is estimated by using

the existing judgments a ij (l ) on the same positions in the decision matrices of
the other decision makers in the group. It is assumed that at least one judgment
exist on the analyzed position in M decision matrices for M members of the group.
Aggregation is then performed by using the following equation:
a ijG = [∏ a ij (l )]1 / M (4)

l∈L
where L denotes set of group members that have made pairwise comparison of the
elements (Ei, Ej), and M is number of those group members. Since matrix A is
reciprocical, aggregated values are also reciprocical and it is not necessary to
aggregate values for the position (j,i); element (j,i) is reciprocical value of (i,j).
Figure 3. Comparison matrices of criteria regarding goal for: (a) Evaluator 1, (b) Evaluator 2 and
(c) Evaluator 3.
Next step in the evaluation process was to compare alternatives regarding

criteria. As an illustration, comparison matrix of alternatives vs. criterion PRICE
for Evaluator 2 is presented on Figure 4.
Figure 4. Comparison matrix: alternatives vs. PRICE, Evaluator 2.
Applying the AHP methodology for each evaluator separately, priority vectors
of alternatives are calculated and given in Table 4.
TABLE 4. Alternatives’ weights and rankings.
Evaluator 1 Evaluator 2 Evaluator 3

Alternatives
Weight Rank Weight Rank Weight Rank
Keithley Instruments Inc. 0.381 1 0.238 2 0.331 1
Orthodyne Electronics 0.232 3 0.175 4 0.236 2
AIXTRON AG 0.234 2 0.225 3 0.211 4
Centrotherm Thermal Solutions 0.152 4 0.363 1 0.222 3
As expected, evaluators have quite different perspective of the problem and

that resulted in differences in alternatives’ rankings. For example, Evaluator 1
believes that Centrotherm Thermal Solutions is the least favorable supplier
according to given criteria, while Evaluator 2 believes it is the best one.
Since Evaluator 2 is more experienced, his weight is set to 0.5 (α2 = 0.5).
Weights of the other two evaluators are set to 0.25 giving α1 = α3 = 0.25. After
applying Eq. 1b, group decision is obtained as given in Table 5.
TABLE 5. Group decision.

Group
Alternatives
Weight Rank
Keithley Instruments Inc. 0.299 1
Orthodyne Electronics 0.215 4
AIXTRON AG 0.227 3
Centrotherm Thermal Solutions 0.260 2
Highest overall weight has Keithley Instruments Inc. (0.299) and should be
considered as the best supplier. It is followed by Centrotherm Thermal Solutions,
having the overall weight of 0.260, and by AIXTRON AG (0.227). Lowest
position is of the Orthodyne Electronics.
5.2. INCOMPLETE INPUT
Assuming that Evaluator 1 does not have all information needed to compare
suppliers Keithley Instruments Inc. and Centrotherm Thermal Solutions vs.
criteria Facility, incomplete matrix appeared as given in Figure 5.
Figure 5. Incomplete matrix: alternatives vs. Facility, Evaluator 1.
To calculate missing judgment a14, a total of four connecting paths is constructed

(Eq. 2)
CP1 = a12 a24 = 3 ⋅ 1/3 = 1
CP2 = a13 a34 = 1 ⋅ 4 = 4
CP3 = a12 a23 a34 = 3 ⋅ 1/3 ⋅ 4 = 4
CP4 = a13 a32 a24 = 1 ⋅ 3 ⋅ 1/3 = 1.
By using Eq. 3,
4
a14 = 4 ∏ CP
k =1
k = 4 CP1 ⋅ CP2 ⋅ CP3 ⋅ CP4
missing matrix element is then calculated as a14 = 2.

Weights of alternatives regarding criterion Facility have changed if missing
element is estimated, as given in Table 6.
TABLE 6. Alternatives’ weights regarding criterion facility.
Complete input Incomplete input
Alternatives
Weight Weight
Keithley Instruments Inc. 0.357 0.280
Orthodyne Electronics 0.094 0.144
AIXTRON AG 0.394 0.264
Centrotherm Thermal Solutions 0.156 0.311
The final alternatives’ weights and ranks remain unchanged. Change in local
priorities does not influence the final decision in this case, because:
(1) Evaluator 1 has the weight 0.25 in the group. During the aggregation,
judgments of Evaluator 1 are brought to power 0.25 and the difference between
30.25 (3 was the Evaluator 1 judgment on position a14) and 20.25 (2 is estimated
value on position a14) is not significant.
(2) There were 24 pondered matrices (8 for each evaluator); combined (final)
matrix elements aij are obtained as mean value of powered judgments and change
in one position can not cause significant change in the final result.
6. Discussion and Conclusion
To evaluate potential suppliers, one must have methodology that will involve
quantitative, qualitative and semi-qualitative criteria in the process. Also, most
frequently, decision have to be made as the group decision, by several decision
makers. The Analytic Hierarchy Process meets both of these requirements, as
presented in this paper.
Three evaluators participated in the selection process. First, complete infor-
mation situation is analyzed. Applying the AHP methodology for each evaluator
separately, three different alternatives’ rankings were obtained. Only one rank was
the same: Evaluator 1 and Evaluator 3 ranked nanotechnology supplier Keithley
Instruments Inc. as the first ranked. All other ranks differ. To select the best
supplier by the group, aggregation on individual judgments is performed and the
group (final) decision is obtained.
Example included also the case of the incomplete information. We have
analyzed the situation when only one judgment is missing in the matrix of size 4.
Estimation of the missing matrix element is made by the connecting paths method.
For the larger size matrices, one should consider some other estimation method
since computation time can considerably increase if connecting paths method is
used.
Another problem with the larger incomplete matrix is that the more comparisons
one makes, the more likely is that the matrix will be estimated accurately. On the
other hand, the more comparisons one makes, the longer it will take, and the
possibility of errors in the judgments increases.
If too many elements are missing, incomplete matrices should be discarded
and decision process repeated.
Acknowledgment
The authors wish to thank The Serbian Ministry of Science and Secretariat for
Science and Technological Development (Province of Vojvodina) for supporting
this research.
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UNCERTAINTY IN LIFE CYCLE ASSESSMENT
OF NANOMATERIALS
Multi-criteria Decision Analysis Framework for Single Wall Carbon Nanotubes in
Power Applications
T.P. SEAGER
Golisano Institute for Sustainability
Rochester Institute of Technology
thomas.seager@rit.edu
I. LINKOV
US Army Engineer Research and Development Center
Concord, Massachusetts, USA
Igor.Linkov@usace.army.mil
Abstract. Despite concerns regarding environmental fate and toxicology,

engineered nanostructured material manufacturing is expanding at an increasingly
rapid pace. In particular, the unique properties of single walled carbon nanotubes
(SWCNT) have made them attractive in many areas, including high-tech power
applications such as experimental batteries, fuel cells or electrical wiring. The
intensity of research interest in SWCNT has raised questions regarding the life
cycle environmental impact of nanotechnologies, including assessment of: worker
and consumer safety, greenhouse gas emissions, toxicological risks associated
with production or product emissions and the disposition of nanoproducts at end
of life. However, development of appropriate nanotechnology assessment tools has
lagged progress in the nanotechnologies themselves. In particular, current
approaches to life cycle assessment (LCA) – originally developed for application
in mature manufacturing industries such as automobiles and chemicals – suffer
from several shortcomings that make applicability to nanotechnologies proble-
matic. Among these are uncertainties related to the variability of material
properties, toxicity and risk, technology performance in the use phase,
nanomaterial degradation and change during the product life cycle and the impact
assessment stage of LCA. This chapter expounds upon the unique challenges
presented by nanomaterials in general, specifies sources of uncertainty and
variability in LCA of SWCNT for use in electric and hybrid vehicle batteries and
makes recommendations for modeling and decision-making using LCA in a multi-
criteria decision analysis framework under conditions of high uncertainty.1
1

424 T.P. SEAGER AND I. LINKOV
1. Introduction
The concept of the product life cycle in an environmental context refers to the
total, aggregated impact of all the economic or industrial activities engendered by
meeting product demands including: raw materials and energy extraction, benefac-
tion, parts manufacture, assembly, distribution and sale, use and final disposition
(such as disposal, remanufacturing, recycling or energy recovery of obsolete
products). The advantage of the life cycle perspective is that it avoids problem
shifting, in which solutions to environmental problems at one life cycle stage
create new problems at other stages (e.g. [9]). Failure to conduct a thorough life
cycle assessment (LCA) of a critical policy or design decision can sometimes
result in catastrophic consequences, such as the addition of MTBE to oxygenated
gasoline that was intended to improve tailpipe emissions (use phase), but also
resulted in extensive groundwater contamination resulting from leaking under-
ground storage tanks in the distribution phase [4].
The idea that the product life cycle is the proper perspective for assessing the
environmental implications of materials, including engineered nanostructured
materials, is now nearly universally accepted (e.g. [14, 40, 43]). However, there
remains a paucity of research regarding LCA of nanomaterials, per se. The primary
focus of scientific literature concerning environmental aspects of engineered
nanomaterials consists of toxicological studies that screen or compare different
materials in an effort assess dose-response relationships (e.g. [5, 27, 28]). In this
context, the ‘life cycle’ is employed only as way to organize or identify potential
source terms, rather than a formal life cycle assessment that encompasses a
broader range of impact criteria such as ozone depletion, climate change, eutro-
phication, smog or acidification. Compared with conventional products, such as
electronics, automobiles, chemicals, or even biofuels, where LCA has been applied
extensively, there is practically no understanding of the broader environmental
implications of nanomaterial substitution in products such as sports equipment,
cosmetics, or clothing.
In power applications the life cycle perspective is especially important. As
another example related to energy applications, there is the problem of coal. From
an energy independence perspective, the vast coal reserves of the United States
present an opportunity to reduce petroleum imports, spur the domestic economy,
narrow trade and current account deficits and reduce energy costs. But from an
environmental standpoint, coal is problematic. It results in higher life cycle
greenhouse gas emissions than other fossil-based alternatives such as petroleum or
natural gas. It is typically contaminated with trace minerals and metals such as
sulfur, mercury or arsenic that can be released to the environment through the
production of fine particles, vapors or ash. And coal mining can be a dangerous
and/or land intensive enterprise. Consequently, the use of coal in the United States
is not expanding as rapidly as alternative or renewable energy sources such as
wind, solar and biofuels. Nonetheless, if development of SWCNT-enhanced
lithium ion batteries for electric or plug-in hybrid vehicles is successful, there may
be widespread deployment of vehicles that depend upon coal-fired electric power
plants as a primary or supplemental energy source – as well as increased demand
UNCERTAINTY IN LIFE CYCLE ASSESSMENT OF NANOMATERIALS 425
from the manufacturing sector for large scale battery production. Both coal con-
sumption and concomitant environmental impacts are likely to increase. The
purpose of life cycle assessment in this case would be to compare the relative
increase in adverse environmental effects in the power generation sector with the
benefits realized in the use phase of the transportation sector.
Similarly, the extraordinary controversy regarding alternative automotive fuels
such as ethanol and biodiesel has, to a great extent, focused on whether the
investment of energy required to produce crop-based fuels (e.g., natural gas for
fertilizer production, diesel fuel for operation of farm equipment, and electricity
and/or heat for fuel processing) is justified by the energy content in the fuels
themselves (e.g. [11, 44]). More recently, as new policies encourage the rapid
expansion of biofuel crops cultivation, the boundaries of scientific interest have
expanded even further to include issues such as land clearing (e.g. [6]), eutrophi-
cation (e.g. [15]) and indirect greenhouse gas emissions (e.g. [3, 37]) that manifest
at stages of the life cycle far upstream from fuel consumption itself.
Use of SWCNT (or other nanomaterials) in power applications such as solar
cells, batteries or wires presents a set of problems that are analogous to biofuels in
several ways. For example, the energy required to manufacture SWCNT – and
especially pure phase SWCNT materials – is considerable. In addition to the
energy consumed in preparation of pure carbon feedstocks, metal catalysts, and
inert gas, energy is consumed in the vaporization of solid carbon and purification
of the resultant SWCNT. Material yields are typically low – e.g., less than 30% at
the laboratory scale [32]. Ultimately, only power applications that result in a high
return of energy during the use phase can justify the energy ‘invested’ during
earlier stages on a thermodynamic or economic basis (e.g. [2]. In static energy
production devices, such as photovoltaic solar cells, the adoption of nanotechno-
logies (beyond niche applications, such as spacecraft) is dependent upon whether
an improvement in photon conversion efficiency results in increased total energy
output over the life of the device. However in batteries, e.g. for hybrid or electric
vehicles, because they only store energy and do not produce energy of their own,
the critically important improvement that must be provided by nanotechnology is
increased energy density (kW-h/kg). Given constraints such as the maximum
vehicle range between recharge or refuel, increased energy density in a vehicle
battery would result in improved energy economy (i.e., mileage) due to the lighter
vehicle weight. Therefore, to the extent that hybrid or electric vehicles may be a
direct technological substitute for gasoline, ethanol or biodiesel vehicles, a
comparative life cycle investigation into the suitability of SWCNT technologies
for hybrid vehicle batteries is essential – albeit problematic.
2. LCA for SWCNT: Challenges
Originally developed for application in mature industries such as plastics, auto-

mobiles petroleum and metals, LCA was originally envisioned as a tool for
comparing or improving technologies that were fairly well understood. Later,
LCA was successfully applied to newer technologies such as semiconductors (e.g.
[45]). In contrast, nanotechnologies are barely in the nascent stages of research,

development and commercialization. As is typical of rapidly growing industries,
nanotechnology manufacturers are more focused on maximizing production and
technological development than on environmental efficiency or sustainability.
Moreover, the analytical techniques of LCA are not fully adapted to domains of
such extraordinary uncertainty. Nevertheless, application of LCA in an emerging
industry such as nanotechnology may present a unique opportunity to avoid the
types of environmental crises that are the legacy of the industrial revolution (e.g.
[35]) by applying appropriate life cycle risk measures early. Therefore, at least
three significant challenges to existing LCA techniques must be overcome:
material variability, uncertainty in toxicity and risk and uncertainty in functional
performance [36]. Each of these is described in separate sections below.
Material Variability. Even within a seemingly narrow class of nanomaterials
such as SWCNT, there are an incredible variety of material possibilities and
characteristics. It is inappropriate to make generalizations based upon studies that
fail to carefully differentiate SWCNT purity, length, diameter, chirality or state of
agglomeration [31, 42]. Almost any important performance property is dependent
upon the characteristics of the SWCNT employed. From an environmental risk
perspective, one of the most important characteristics of SWCNT may be their
toxicity. Nevertheless, with few exceptions, toxicity studies using SWCNT have
failed to robustly characterize the materials under investigation [10]. A typical
toxicological protocol might involve comparison of SWCNT to positive (e.g.,
ultra fine quartz) and negative (e.g., carbon black) controls, or comparison of
SWCNT from different sources (e.g. [12]). Some of these studies have shown
positive (i.e., deleterious to health) responses that are sensitive to SWCNT
dosages (e.g. [25]). However, where characterization is poor or non-existent, it is
not possible to understand the mechanism or determining factors causing toxicity.
For example, even SWCNT sold as “purified” may contain biologically significant
concentrations of metals [20]. There are currently no industry standard specifica-
tions to aid in characterization of SWCNT – making cross-comparison of different
toxicological (or other) findings problematic. Characterization procedures are still
evolving [49]. However, in LCA the properties of the materials themselves are no
more important than the processes employed to manufacture them. In this regard,
there is significant variety in approaches to synthesis of SWCNT, including: laser
ablation, arc discharge, flame, chemical vapor deposition and high pressure carbon
monoxide, to name a few (e.g. [36, 38]). Each process is expected to have a
unique life cycle environmental profile [47].
Uncertainty in Toxicity and Risk. Toxicological risk assessment typically
emphasizes characterization of exposure, dose and health response relationships.
(For a review relevant to nanomaterials, see Oberdörster et al. [28, 48]). By
contrast, LCA places particular emphasis on quantification of source terms, which
constitute the inventory of chemicals released into the environment. Only in the
impact assessment stage of LCA is information regarding the environmental fate
and transport, exposure, dose and response (for health impacts) considered in the
analysis. In the first step of impact assessment, the chemical emissions inventory
must be aggregated into several midpoint categories that are representative of the
types of impacts that are relevant to the study (e.g. [13]). The mathematics
employed is a simple weighted sum, in which all emissions related to a particular
midpoint, such as global warming or ozone depletion, are compared to a single
chemical standard representative of the impact category. For example, all emissions
that impact climate are expressed in equivalent kilograms of carbon dioxide,
whereas the ozone depletion category is expressed as equivalent kilograms of
CFC-11 (a chlorofluorocarbon that was frequently used as a refrigerant, foam-
blowing agent or in other applications prior to the production ban promulgated in
the Montreal Protocol). For health impacts, midpoints may be expressed in terms
of kilogram benzene (or other chemical) equivalents, kilogram PM10 (particles less
than 10 µm in diameter) or both. In some cases, there are extraordinary uncer-
tainties related to characterization of inventory data, which may be viewed as
justification for truncating life cycle impact assessment at the midpoint characteri-
zation stage, rather than continuing the analysis to complete damage assessment
(e.g., in terms of disability adjusted life-years, or DALYs), normalization and
weighting (e.g. [46]).
However, selection of standard LCA midpoint equivalencies pre-dated the
explosion of interest in nanomanufacturing. In the case of nanostructured materials,
even the characterization framework itself may not be inappropriate. For example,
without understanding the mode of action of toxicity, characterization of SWCNT
emissions in relation to benzene equivalents may be wildly incorrect. Similarly,
characterizing nanomaterials in terms of kilogram PM10 (or even PM2.5) may be
wholly unjustified, as it is not yet clear that mass concentration drives toxicity at
the nanoscale. Surface properties, functionalization, interaction with environ-
mental media, and microbial activation may all play roles in nanomaterial toxicity
that can not be captured in terms of mass, volume or even surface area concen-
trations. As a result, characterization factors for nanomaterials in the context of
life cycle impact assessment do not exist; nor is their development trivial. The idea
of benchmarking nanomaterial toxicity in terms of characterization factors relating
to existing LCA midpoint equivalencies may be unrealistic.
Uncertainty in Functional Performance. In determining the scope and boundaries
of a life cycle assessment, it is necessary to select the functional unit that repre-
sents the economic demand motivating the life cycle activities. Misrepresentation
of the functional unit can lead to misunderstanding of the production system. It is
important (when selecting a functional unit) to view life cycle problems from the
perspective of the consumer in the use phase, rather than from the perspective of
the manufacturer at the point of sale. For example, automobile manufacturers
often normalize operations data (such as man-hours, lost-time accidents or product
defects) in terms of vehicles produced. It may seem natural to the manufacturer to
consider life cycle data in the same terms such as carbon dioxide equivalents per
vehicle produced. Similarly, SWCNT manufacturers may track environmentally
relevant data relative to the total mass of SWCNT produced. But from the
consumer’s perspective, the vehicles or the SWCNT themselves are not the object
of demand (except in rare cases, such as collectors). Consumers only purchase
cars so that they can be driven. Consequently, a vehicle LCA is best expressed in
terms of vehicle-miles traveled, although nearly equivalent results can be obtained
when a functional unit is expressed in terms that are essentially equivalent to

vehicles-miles, such as total battery energy. On this basis, Matheys [23] estimated
that lead-acid, nickel-cadmium and nickel-metal hydride batteries all have
comparable environmental impacts, whereas lithium-ion batteries may have lower
impacts. However, the performance of lithium-ion batteries employing SWCNT
(e.g., as an anode) are still largely untested on all but laboratory scales. Moreover,
nanomaterials are rarely used in the pure phase. More typically, they are additives
or substitutes in composite materials. In many cases, the type and quantity of
nanomaterials have not been optimized and the mechanisms of functionality may
not be entirely understood. In other cases, laboratory-scale processes have not yet
been sufficiently scaled up to understand the potential environmental implications
of high-rate manufacturing. Depending on the end-use application, they may
require different levels of purification effort to remove metals or surface coatings
(e.g., of adsorbed carbon). Additionally, the relationship between SWCNT content
and functionality in the final application may be dependent upon the synthesis
methods and purification techniques employed. Because the synthesis, purification
and separation processes employed in manufacture can result in important changes
in the nanotube characteristics, these processes can not be assessed independently
of the end-use application.
3. Life Cycle Impact Assessment in High Uncertainty Applications
Although engineered nanomaterials represent a serious challenge to traditional

approaches to both toxicological risk and life cycle assessment, to some extent
these challenges can be met by employing a “decision-directed” approach to the
analysis, as has been recommended in chemical toxicology for over a decade (e.g.
[39]). This approach emphasizes a relative or comparative rather than absolute
approach. Already, a comparative screening of nanotech to other more mature
industries estimates that nanomanufacturing risks may be relatively low [33].
There may be several advantages to a decision-directed, comparative approach
under conditions of high uncertainty [18]. First, it requires a finite set of
alternatives and well-defined decision criteria, both of which serve to bound the
analysis. Second, analysis can be focused on areas in which the decision may be
sensitive to a narrowing of uncertainty bounds. Analytical effort may be conserved
and the sensitivity of decision outcomes to both uncertainty and variability can be
explored. Lastly, a decision directed approach implies coupling of the assessment
with a structured decision aid, such as cost-benefit or multi-criteria decision
analysis (MCDA). It is this latter aspect that may prove most challenging, as
decision analysis demands incorporation of knowledge from social science fields
(e.g. [8]) that are outside the domain of physical science and engineering, where
much of the expertise regarding nanotechnology, toxicology and power
technologies resides. Moreover, LCA is much less fully developed in impact
assessment (the stage that applies MCDA techniques, such as normalization and
weighting) than data gathering. Consequently, advances in both the theory and
practice of LCA that expand the role of cutting-edge MCDA techniques are
required [36].
4. Stochastic Decision Tools for MCDA
With its emphasis on broad systems boundaries, LCA necessarily requires the analyst
to consider a set of incommensurate decision criteria and the viewpoints of multiple
stakeholders or decision makers [1]. In power applications, criteria as diverse
as climate change, economy, human and ecological health, water quality, energy
independence, efficiency and renewability may be brought to bear. Under such
conditions, utility-based, normative decision analytic techniques such as cost
benefit analysis (which is a single criterion approach) are typically less likely to be
informative than more practical decision strategies that elucidate trade-offs and
contrast opposing points of view. In particular, MCDA approaches such as outranking
are especially suitable for problems where there are a large number of alternatives,
strong heterogeneity exists between criteria (making aggregation difficult) and
compensation of loss in a given criteria by gain in another is unacceptable (e.g.
[41]). An example applying outranking to nanomaterials has been reported [17,
19] and MCDA has been recommended as one of the most promising nanotechno-
logy risk governance tools [34]. However, the sources and implications of high
variability and uncertainty in MCDA are still not fully understood.
A decision directed approach allows consideration of uncertainty and
variability beyond those due to material variability, toxicity and risk, or functional
performance: namely, the preferences of the decision-makers or stakeholder
vested in the decision. In the United States, policy and decision-making has been
dominated by a utilitarian approach that draws heavily on microeconomic theory,
which posits that where preference functions are known, maximization of risk-
adjusted utility is a logical decision objective. However, in the case of environ-
mental decision making, preference functions are rarely (if ever) known or
describable. Environmental preferences are typically constructed by decision
makers as they progress through the process of decision analysis, rather than pre-
existing in the minds of the decision makers and revealed at the end of the analytic
process [30]. That is, people often change their minds. Or their thinking evolves.
Whether there are stable preference functions for any good or service is a matter
of debate among economists – but for environmental goods such as those repres-
ented in the decision criteria of LCA, decision makers have precious little experi-
ence exploring their own state of mind. Even the decision context can influence
the preferences [24] and decision makers may express seemingly contradictory
preferences for similar criteria in two different decision problems (e.g. [16]).
Because LCA has been promulgated by the International Standards Organization
as an objective, scientific tool, the methodology of techniques for incorporating
stakeholder preferences has lagged other aspects of LCA. For example, the impact
and decision analytic tools offered practitioners in automated software packages
are generally simplistic, if extant at all. In some cases, current decision analytic
tools in LCA may even be counter-productive by masking relevant aspects of a
problem [50]. However, there has been some effort to investigate the sensitivity of
LCA results to stakeholder preferences in green building applications, where it has
been reported that a group of LCA experts may weight global warming as little as
7% or as much as almost 70% of an overall merit function, depending on the time
horizon of interest [7]. The clear conclusion is that there is considerable variability
between different decision makers and that even within a narrow group (or single
decision maker) there may be variability or uncertainty with regard to preference
for trade-offs in performance of technological alternatives. The ultimate conclusion
of a comparative study may depend upon a subjective preference for one type of
impact at the expense of another.
To more accurately represent uncertain human values in risk and life cycle
impact assessment, the decision criteria weights in MCDA should be modeled
stochastically using Monte Carlo Analysis [50]. Explicit incorporation of uncertainty
in the weighting and impact assessment stage of LCA would allow for a more
accurate representation of how stakeholders actually perceive environmental
trade-offs. Moreover, it allows a rapid exploration of multiple views for screening
or comparison of alternatives without extensive value function elicitation [41].
The general approach, called stochastic multi-attribute acceptability analysis
(SMAA) is appropriate for situations in which the weights may be only partially
or even completely unknown due to the number of decision-makers (i.e., vari-
ability), high uncertainty, or characterized by mixed qualitative and quantitative
preference information. In these cases, reducing uncertainty or describing vari-
ability may be prohibitively expensive. However, it is still possible to explore the
sensitivity of alternative rank preferences to different weight spaces or constraints
and whether a technological alternative is likely to be preferred relative to other
alternatives.
5. Incorporating Uncertainty and Variability into LCA
Figure 1 depicts a general approach to collecting and aggregating data for LCA of
SWCNT anode vehicle batteries. The life cycle stages are listed horizontally in the
middle of the figure, with the resource inputs at each stage depicted in columns
below. Consequently, the figure reads best from bottom to top (depicting the flow
of data) and from left to right (depicting the flow of materials). Elements of the
analysis that are common to both conventional graphite anodes and SWCNT anodes
have been grayed out, inside the bubbles. These aspects of the system need not be
quantified in a comparative approach, as they are identical under each alternative.
Different types of data uncertainty and variability manifest at different stages
of LCA. Process yields, functional performance and material variability are all
represented in the inventory data. Table 1 lists several of the sources of uncer-
tainty and/or variability relevant to SWCNT in vehicle batteries at this stage.
However, toxicological information is represented in data characterization and
aggregation (Table 2). Lastly, uncertainty in criteria weightings is represented in
the final stages of impact assessment (depicted in Figure 1 at the top as SMAA).
Life Cycle Impact Assessment
Stochastic Multi Attribute Assessment
Human/Ecology Energy Use Society /

Economy Environment
Health Regulation
Impact Criteria
Data Characterization and Aggregation
SWCNT Anode Battery

Vehicle Use End of Life
Manufacturing Production
Free Carbon
Removal Battery Recovery
Cathode Vehicle Electricity
Production Manufacturing Generation and
Metals Removal
Transmission Vehicle
Electrodes, Recovery
Supplies, Casing
Acid Reflux
Half and
Separators
Inventory Data Acquistion

Soot Production
Electrolytic
Figure 1. Aggregation of data variability and uncertainty in LCA of SWCNT for vehicle batteries.
432
TABLE 1. Sources of variability & uncertainty in inventory data acquisition for LCA of SWCNT Li-ion batteries.
Free carbon Battery
Nanotube soot production Acid reflux Metals removal removal production Use phase End-of-life
Catalyst (e.g., Ni, Fe, Co) Filter membrane
Consumables
and consumption rate consumption
Energy sources (e.g., source
Energy of electricity, gas Heating requirements & heat source Energy losses
consumption)
Vaporization technique Cathode
Technology
(e.g., arc, flame, laser) selection
Tailpipe &
Solvent (e.g., acetone and/or Disposition of
Solvents & Inert gas (e.g., Ar, N2) & Acid type (e.g., electricty
water) requirements, waste materials
wastes waste gas disposition HCl, HNO3) generation
disposition of metals (i.e., CO2)
emissions
Production yield (i.e., tube SWCNT paper Recovery
Extent of metals
Process vs. free or amorphous Purity requirements anode thickness, Battery weight & recycling
dissolution
carbon) content rates
Lifetime (i.e.,
T.P. SEAGER AND I. LINKOV
Scale Technological learning curves, experimental vs. high-rate manufacturing rates vehicle range &
charge cycling)
e.g., closed refrigerant, Weight & energy
Cooling open water loop, consumption for
evaporative cooling
TABLE 2. Sources of variability & uncertainty in data characterization for LCA of SWCNT vehicle
batteries.
Process &
Material variability Toxicology & risk performance
Environmental fate & Proximity of sources
Quantity equivalencies transport (e.g. (e.g., manufacturers,
Human &
for dose determination agglomeration), exposure users, recyclers) to
ecological
(e.g., mass, surface area, routes, toxicological receptors (e.g.,
health
volume) equivalency benchmarks workers, consumers,
(e.g., kg PM2.5 equivalents) ecosystems)
Discount rates,
Experience curves, Mitigation, worker depreciation
Economy
scale-up costs protection, remediation costs schedules, salvage
values
Quality of energy aggregation measures (e.g., energy, exergy, cost), renewability,
Energy
imported vs. domestic
Source term interactions,
(e.g., nitrogen & phosphorus
Environment
for eutrophication, VOCs &
NOx for smog)
Public & regulatory
Socio-political
responses, attitudes
The SMAA approach has the advantage of applying stochastic methods to

preference modeling in a mathematical approach that is consistent with uncertainty
modeling in other aspects of LCA. Although most life cycle inventories use point
estimates, where information is available, Monte Carlo analysis is sometimes used
to propagate uncertainty and/or variability through several analytic phases [22] –
albeit few studies incorporate uncertainty through a complete impact assessment
[21]. Consequently, a combined inventory and impact assessment Monte Carlo
model can be used to explore which uncertainties drive the final preference
ordering of alternatives.
However, where multiple types of uncertainty are extraordinarily high, tradi-
tional Monte Carlo analysis alone is inadequate [26]. Probability distributions
under conditions of model and boundary uncertainty lack meaning (at best) or may
lead to overconfidence (at worst). In the case of SWCNT, stochastic analysis
should be combined with scenario analysis, in which certain parameters may be
fixed (sometimes at extreme or improbable boundary conditions) by decision
makers to explore a range of possibilities (e.g. [29]). The focus in scenario
analysis can be on exploring possible outcomes, rather than identifying the most
likely outcomes.
The critically important aspect of the integrated SMAA-LCA approach is that
it allows exploration of different types of uncertainty and variability in an
integrated, systematic way. Without considering the entire system in a specific
decision context, it is impossible to ascertain whether additional research effort
into reducing uncertainty or characterizing uncertainty is relevant to the final
outcome. Only by exploring the sensitivity of the decision outcome to all types of
uncertainty in concert can those with the greatest influence be discovered, as
uncertainties in one aspect of the analysis may overwhelm those in other areas that
may have otherwise been considered important areas to investigate further. The
overall result of a comparative life cycle exploration of uncertainty and variability

that is tightly coupled with a SMAA decision-analytic approach can be a better
understanding of the sensitivity of the system to important design variables or
parameters, a reprioritization of research and development efforts, a better
understanding of decision-maker preferences and ultimately, better decisions and
environmentally advantageous technologies.
Acknowledgements
The authors thank Drs. Brian Landi and Ryne Raffaelle at the Nanopower Research
Laboratory, Rochester Institute of Technology for helpful conversations regarding
purification and characterization of SWCNT for anode materials. Matt Ganter and
Kali West contributed to Table 1. Alexander Tkachuk prepared Figure 1. Permission
was granted by the Chief of Engineers to publish this information. The studies
described and the resulting data presented herein were obtained from research
supported by the Environmental Quality Technology Program of the US Army
Engineer Research and Development Center (Dr. John Cullinane, Technical
Director).
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KNOWING MUCH WHILE KNOWING NOTHING
Perceptions and Misperceptions About Nanomaterials
J.M. PALMA-OLIVEIRA, R.G. DE CARVALHO, S. LUIS,

M. VIEIRA
Faculty of Psychology and Educational Sciences (FPCE)
University of Lisbon
Alameda da Universidade
1100 Lisboa, Portugal
palma@veritas.pt
Abstract. Nanomaterials are not technological newcomers. However the use of an

integrative concept to describe the diverse and complex array of these very small
products is new. This chapter aims to describe some of the attitudes and risk
perception studies about these materials. Furthermore it will be presented an
empirical research where we will introduce some of the psychological factors that
could help in understanding the psychometrics of the nanomaterials risk perception.
One could conclude that despite the agreement that there is a widespread lack of
knowledge, people can still apply attitudes and deduce a risk perception estimate
that differs essentially according to the application domains. Furthermore risk
perception about nanomaterials can be easily modified if some new negative
phenomena arrive. In this context the design of a good risk communication
strategy is particularly important especially because according to many studies and
the one to be presented, the nano experts have difficulty in understanding what the
factors that underlie lay people’s judgments are.
1. Knowing Much
European citizens seem to be generally optimistic about the contribution of

technology to our way of life. An index of optimism shows a high and stable level
for computers and information technology and solar energy from 1991 to 2005.
Over the same period the index for biotechnology declined steeply from 1991 to
1999. From 1999 to 2005 the trend reversed, and now biotechnology is back to the
same level of optimism seen in 1991. Optimism about nanotechnology has
increased since 2002 – the ratio of optimists to pessimists being eight to one.

438 J.M. PALMA-OLIVEIRA ET AL.
Will improve No effect Will deteriorate Don’t know
Computers and information technology 79 11 6 4
Solar energy 78 14 3 6
Wind energy 74 16 3 7
Mobile phones 58 23 15 4
Biotechnology / genetic engineering 52 13 12 22
Space exploration 44 35 9 12
Nanotechnology 40 13 5 42
Nuclear energy 32 18 37 13
0 20 40 60 80 100
Percentage
Figure 1. Optimism and pessimism for eight technologies in 2005 [33].
According to an Eurobarometer study [33] (see Figure 1), the European public
is not risk-averse about technological innovations that are seen to promise tangible
benefits. In fact, in all of the areas studied (except for nanotechnology, in which
the percentage of non-response was high in all countries), most respondents
declared that they believed the new technologies development will have a positive
effect in society in the next 20 years.
While the majority is willing to delegate responsibility on new technologies to
experts, making decisions on the basis on the scientific evidence, a substantial
minority would like to see greater weight given to moral and ethical considera-
tions in decision taking about science and technology and to the voices of the
public. As an example, there is widespread support for medical (red) and industrial
(white) biotechnologies, but general opposition to agricultural (green) biotechno-
logies in all but a few countries.
Europeans support the development of nanotechnology, pharmacogenetics and
gene therapy. All three technologies are perceived as useful to society and morally
acceptable. Neither nanotechnology nor pharmacogenetics are perceived to be risky.
While gene therapy is seen as a risk for society, Europeans are prepared to discount
this risk as they perceive the technology to be both useful and morally acceptable.
In a set of questions asking for opinions on these four technologies (gene
therapy; pharmacogenetics; GM food; and nanotechnology), respondents were
first asked if they had ever heard of them.
Figure 2 shows the percentages of respondents in each EU Member State who
said they had heard of each of the applications.
Respondents were then asked whether they thought the different technologies
were morally acceptable, useful for society, risky for society, and whether they
should be encouraged. Figure 3 shows EU-wide mean scores for assessments of
these applications, on a scale ranging from +1.5 to −1.5.
KNOWING MUCH WHILE KNOWING NOTHING 439
GM foods Gene therapy Nanotechnology Pharmacogenetics
EU25 80 45 44 27
Netherlands 89 73 61 30
Denmark 87 55 69 39
Sweden 92 47 61 47
Luxembourg 79 63 63 41
Austria 79 68 56 39
France 91 47 55 26
Belgium 78 51 49 31
Italy 75 56 40 39
Finland 84 36 61 27
Germany 89 41 50 22
United Kingdom 92 43 44 14
Hungary 70 51 46 22
Estonia 63 54 36 36
Cyprus 72 36 46 35
Slovakia 74 40 41 32
Czech Republic 72 32 51 29
Slovenia 75 46 30 26
Latvia 73 45 28 29
Greece 72 38 28 29
Portugal 55 46 29 33
Spain 59 39 33 31
Poland 73 35 28 24
Ireland 68 40 26 21
Lithuania 52 32 28 26
Malta 55 22 28 20
0 50 100 150 200 250 300
Percentage
Figure 2. Familiarity with four technologies [33].
The figure shows varying levels of support for these technologies. The European
public is most positive about nanotechnology, followed by pharmacogenetics, and
then gene therapy, though on balance it regards the latter as risky. By contrast,
GM food is predominantly perceived as negative.
Morally acceptable Useful Risky Should be encounraged
1.0
0.8
0.5
0.3
0.0
−0.3
−0.5
Nanotechnology Pharmacogenetics Gene therapy GM Foods
Figure 3. Evaluations of four technologies [33].
As the judged usefulness of technologies declines perceived risk increases,

along with a decline in perceptions of moral acceptability and overall levels of
support. For nanotechnology and pharmacogenetics, agreement that they should
be encouraged goes along with the perception that they are not risky. This is
mirrored in the case of GM food, for which overall opposition is accompanied by
perceptions of relatively high risk. By contrast, gene therapy is supported despite
the tendency for it to be perceived as risky; it seems that the risk attached to gene
therapy is tolerable, whereas for GM food it is unacceptable.
There is clear evidence of differences in evaluations between those who have
heard of a technology and those who have not. Specifically, those who say they
have heard of gene therapy, pharmacogenetics and nanotechnology tend to express
notably more positive views than those who are unfamiliar with them. For these
Nanotechnology Pharmacogenetics Gene therapy GM foods
EU25 55 52 50 27
Czech Republic 71 60 56 46
Belgium 71 69 60 27
Finland 72 58 51 35
ltaly 54 62 58 34
Cyprus 65 67 58 15
Denmark 64 61 50 28
France 66 61 55 20
Luxembourg 61 69 55 13
Netherlands 69 52 45 25
Sweden 67 59 43 22
Slovakia 57 55 46 30
Greece 46 67 57 14
Spain 42 53 53 34
Germany 60 46 49 21
Portugal 39 49 47 38
Estonia 48 52 52 18
Hungary 52 47 46 23
United Kingdom 50 40 44 30
Austria 55 44 38 21
Poland 46 46 43 23
Malta 51 35 32 36
Latvia 43 42 45 15
Lithuania 40 34 32 23
Ireland 33 33 34 29
Slovenia 44 31 33 20
0 50 100 150 200 250

Percentage
Figure 4. Support for four technologies [33].

technologies people who are familiar with them are more likely than people who
are not familiar with them to agree that they are morally acceptable, useful and
should be encouraged, and more likely to disagree that they are risky.
Looking a little more closely at overall levels of approval (whether the tech-
nologies should be encouraged) we see varying levels of support across countries.
Figure 4 shows the stacked percentages of respondents who either ‘agree’ or
‘totally agree’ that each application should be encouraged.
These different attitudes towards this category of new technologies according
to the type of the specific applications is a very important feature that will come
across the whole chapter. Specifically, despite the global positive evaluation of
these new technologies, the attitudes and, for that matter, the risk perception is
strongly qualified by the specific attitudes towards the particular application. This
psychological framing will be discussed in the next sections.
2. While Knowing Nothing
Previously, we showed that people’s knowledge of nanotechnologies is low and

people have a positive opinion about its usefulness and moral acceptance, showing
slight concerns about its risks. However, how can people have these evaluations
about nanotechnologies not knowing what they actually are?
This section’s aim is to answer this question and discuss possible social-
technical implications that are relevant to risk management. To begin with, a
review of some research about the nature of human judgment and decision under
uncertainty will be presented, focusing on three features: (1) the evaluations
formation process, (2) how affect strongly influences evaluations, (3) and judgmental
heuristics involved in these.
First of all, if people never heard of “nanotechnology” before how can they
evaluate its risk? People can form judgments in two different ways [1]. If they
already have some information about the evaluation target, let’s say “nanotechno-
logy”, they can form an evaluation based on the data stored in memory. Otherwise,
the evaluation can be formed on-line after the acquisition of an initial piece of
information and then revised and updated as each subsequent piece of information
is acquired [12]. For example, in our own research participants were first told
“Nanotechnology deals with the development of procedures in which materials are
created or manipulated in the atomic and molecular scale” and latter on, by filling
the questionnaire they could infer that nanotechnologies deal with general
applications (“food, military…”) and different products (“sunscreen, toys, cancer
treatments”). Even if one might think that this information was kind of poor, with
the respondents themselves stating their perceived knowledge regarding general
nanotechnologies applications as low (M = 2.06; SD = 0.91), results illustrate that
even with this minimal amount of information they still formed opinions that were
consistent throughout the sample.
In fact, when not privy to specific and direct evidence necessary for an
inductive inference about an attribute, people tend to draw from whatever sources
of information they have available [11]. In some instances, attributes are inferred
from more global judgments or expectancies, such as a superordinate categorization

of the target (e.g., [2]) or an overall attitude towards the target [4, 18]. Besides
that, stronger inferences or evaluations are drawn with the passage of time, as
memory of the absence of initial information fades [19]. This means people can
simply judge nanotechnologies as technologies in general for example, and as time
goes by, this judgment becomes less doubtful. We highlight that the first pieces of
information that people receive tends to have more impact on evaluations than
latter information [7, 13]. Even if the original information may be forgotten or
inaccessible, its evaluation remains in memory and available for recall when it is
needed. First impressions do matter!
It’s also important to note that negative information has more impact than
positive information [13]. Risk managers should pay special attention to this issue:
one single and unfortunate accident involving nanotechnologies might be more
remembered than years of good practice and improvements on nanotechnologies
different applications.
Continuing our discussion, how can people make a consistent risk estimate
based on poor information? To make an evaluation we don’t necessarily gather all
relevant information and deliberate about it. Many times our evaluations follow
much easier and faster paths. If we analyze most our evaluations and decisions we
can notice they reflect an apparent lack of “rationality”. Human decision “fail” to
be explained by economic models: people do not decide in order to maximize
profit or minimize costs all of the time [22]. For example, think about your house
or car. Did you search all your options and settle for the better price/quality option
or did you just knew that there was “something” about it that made it worthy?
This “something”, sometimes has to do with affect. Many times people
intuitively use it instead of reason because usually rational choices consume more
cognitive resources and time, while affect-based decisions and judgments allow
the opposite. This means that instead of comparing nanotechnologies advantages
and disadvantages, people might rely on their spontaneous feelings towards it. The
point is that these feeling can be the result of very simple and basic psychological
process, such as the degree of exposure or familiarity with the subject [10, 31],
which influence people are usually not aware of. Because they derive not from
conscious evaluations but from unconscious and automatic affective evaluations
towards the object, they can produce an “I don’t like it, but I don’t know why”
phenomena. This justifies that “liking” may support attitudes or choices that
cannot be justified by people’s “rational” beliefs. This doesn’t mean that people
are irrational! It means that in certain cases their judgments are based on affect.
Functionally, these judgments are easier and faster and, in “known” situations,
they prove to be “correct”. So, to the question: “Do you think nanotechnologies
are risky?” we can unknowingly be answering “Oh yes, I don’t like it!”
Other times, this “something” might have to do with the “boundaries” of
intuitive rationality. The research program on judgmental heuristics, by the Nobel
Prize Daniel Kahneman and his colleague Amos Tversky, illustrates that people’s
intuitive judgments (the judgments that spontaneously and effortlessly come to
mind) are biased by factors that “reasonably” should be irrelevant. Specifically,
the researchers found (a) persistent errors in estimates of known quantities and
statistical facts and (b) systematic discrepancies between the regularities of intuitive
judgments and the principles of probability theory, Bayesian inference, or regression
analysis. This means that when an individual has to judge a risk, his intuitive
judgment probably will not have correspondence to its statistical meaning. We
emphasize that this happens both to lay people and to people with statistical
knowledge! Surprisingly, even the intuitive judgments of statistically sophisticated
researchers don’t conform to statistical principles with which they are thoroughly
familiar [26].
So, how do people judge things intuitively? In making predictions and
judgments people rely on a set of heuristics or rules of thumb. Sometimes these
yield reasonable judgments, other times they lead to severe and systematic errors.
One can distinguish between “individuals” heuristics, such as the availability or ease
with which particular mental contents come to mind [27], seriously influenced by
the mass medias coverage’s and “contextual” heuristics, like anchoring, the presence
of contextual information that temporary raise its availability in individuals
memory [27], and framing, with alternative formulations of the exactly same
situation making different aspects of it accessible in memory, thus leading to
different judgments [29]. On top of that, people don’t’ seem to be aware of these
biases and tend to have a great confidence on the accuracy of their judgments
[27]! So, when asked “Do you think nanotechnologies are risky?” we can
unknowingly be answering “Oh yes, I’m absolutely sure they are risky! Just
yesterday I saw on TV what a nanotechnology produced sunscreen did to a little
child’s skin.”
3. Going Beyond Knowledge: Predicting Nanotechnologies Acceptance

and Risk Perception
To answer this question we must comprehend the intuitive rules of risk perception.
Fischhoff et al. [5], followed the work on judgmental heuristics and combined a
compendium of hazards situational characteristics known to cause, at least, “strange”
risk perceptions, i.e., perceptions that diverge from risk technical assessments.
Introducing the so called Psychometric Paradigm, the researchers describe nine
characteristics which allow us to predict risk perception across specific hazards:
(1) voluntariness of risk (do people get into risky situations voluntarily?), (2)
immediacy of effect (to what extent is the risk of death immediate – or is death
likely to occur at some later time?), (3) knowledge about risk to those exposed (to
what extent are the risks known precisely by the persons who are exposed to
them?), (4) science knowledge about risk (to what extent are the risks known to
science?), (5) control over risk (if people are exposed to each risky activity or
technology, to what extent can they, by personal skill or diligence, avoid death
while engaging in the activity?), (6) newness (are risks new and novel or old and
familiar?), (7) chronic-catastrophic (is this a risk that kills people one at a time –
chronic risk – or a risk that kills large numbers of people at once – catastrophic
risk?), (8) common-dread (is this a risk that people have learned to live with and
can think about reasonably calm, or is it one that people have great dread for – on
the level of a gut reaction?), (9) severity of consequences (when the risk from the
activity is realized in the form of a mishap or illness, how likely is it that the
consequence will be fatal).
Testing across a wide range of hazards, research has shown that considering
these dimensions in addition to perceived benefits, it is possible to predict lay
people’s risk perceptions and acceptance judgments, despite people’s individual
differences. Furthermore, these characteristics tend to be highly intercorrelated
(for example, hazards judged to be voluntary tend also to be judged as controllable)
and can be effectively reduced to two factors by means of factor analysis [23].
One first factor, that explains most of the data and is usually labeled “dread risk”,
apparently discriminates between high- and low- risk technology activities, with
the high end being characterized by perceived lack of control, dread, catastrophic
potential, fatal consequences, and the inequitable distribution of risks and benefits
(e.g., nuclear weapons technology). The second factor, “unknown risk”, is defined
at its high end by hazards judged to be unobservable, unknown, new, and delayed
in their manifestation of harm (e.g., chemical technologies). Many studies have
also found a third factor, related to the number of people exposed to risk.
Lay people’s risk perceptions and attitudes are closely related to the position of
a hazard within this type of factor space. The higher a hazard’s score first on
“dread risk” and second on “unknown risk”, the higher its perceived risk and the
more people wish to reduce it.
Siegrist et al. [21] have adapted this paradigm for the examination of nanotech-
nology hazards (adding characteristics such as “trust in governmental agencies”
and “ethical justification”). Their results shown that perceived dreadfulness of
applications and trust in governmental agencies are also important factors in
determining perceived risk, with the author’s suggestion that public concerns
about nanotechnology would diminish if measures were taken to enhance
laypeople’s trust in governmental agencies.
We followed this psychometric paradigm and developed a study in order to
understand different nanotechnologies risk perceptions, partially replicating the
study by Siegrist et al. [21] and adding other variables and general nanotechno-
logy applications not considered by them.
Two hundred and sixty-nine participants filled a two-part web based
questionnaire on “nanotechnologies and society” voluntarily. From these, 24.8%
were males and 75.2% were females, 74.5% had a high-school degree, 21.8% a
university degree, 3.3% a master’s degree and 0.4% a Ph.D. The mean age was
24.9 and participants were mostly from the Lisbon area. Initially, they received the
first part of the questionnaire, in which they were given a definition of
nanotechnologies (“Nanotechnology deals with the development of procedures in
which materials are created or manipulated in the atomic and molecular scale, in
order to create new products whose properties have different characteristics
compared to materials created or manipulated on the basis of other types of
technologies”) and nanoparticles (“Particles with a dimension less than 100 nm
that can be formed by natural processes or manufactured trough nanotechnology
processes, having applications in various fields such as medicine, pharmacy,
clothing, food and telecommunications”). The aim was to give baseline information
that was equal to all participants, independent of their prior knowledge. Following
this information, they rated six general nanotechnology applications in a five point
scale based on eight risk perception attributes: Probability of health damage (1 =
very improbable; 5 = very probable); Worries about risks (1 = not worried; 5 =
very much worried); Voluntariness of risk (1 = voluntary; 5 = involuntary);
Knowledge of risk to those exposed (1 = known precisely; 5 = not known);
Adverse health effects strength (1 = not at all; 5 = very strong); Control over risk
(1 = controllable; 5 = uncontrollable); Trust in institutions responsible for
protecting people’s health regarding the technology (1 = no trust; 5 = much trust);
Ethically justifiable to develop the application (1 = absolutely justifiable; 5 = not
at all justifiable).
In the second part, participants had to rate 20 specific nanotechnology appli-
cations, in the same 8 risk perception attributes. However, given the length of the
questionnaire with the 20 specific nanotechnology applications, we divided it in
two parts with 10 specific applications each, with the participants being randomly
ascribed to one of them.
From these, seven scales were created by averaging results on each item,
creating composite measures with good psychometric properties overall and
reliability indexes (Cronbach’s Alpha). The scales are as follows: General
Nanotechnology Risk (α = 0.73); Clothes Nanotechnology Risk (α = 0.73); (α =
0.72); Food Nanotechnology Risk (α = 0.78); Communications Nanotechnology
Risk (α = 0.74); Medical Nanotechnology Risk (α = 0.68); Military Nano-
technology Risk (α = 0.81); Overall Nanotechnology Risk Perception, developed
through the aggregation of all these general and specific nanotechnology risk
ratings (α = 0.81).
The results show that the Overall Nanotechnology Risk Perception (considering
both general and specific applications) is neutral (neither positive nor negative)
with this view being highly consistent across the sample (M = 3.00; SD = 0.44),
the same happening for the General Nanotechnology Risk (M = 2.89; SD = 0.55).
Of these general applications, food (M = 3.38; SD = 0.63) and military
applications (M = 3.39; SD = 0.74) are perceived as significantly more threatening
than any of the others (p < .000). The lowest perceived level of threat is obtained
for the clothes application (M = 2.79; SD = 0.58), followed by the communi-
cations application (M = 2.95; SD = 0.63) and the medical application (M = 3.08;
SD = 0.56). These results seem to highlight more the general evaluations toward
the applications than the specific evaluations regarding their risks.
The results concerning the eight psychometric risk attributes for the Overall
Nanotechnology Risk Perception are presented in Table 1. As we were expecting,
results show that the “Knowledge of Risk to those Exposed” is the attribute with
the highest mean and, in the absence of knowledge, the attribute “Ethically
Justifiable to Develop the Application” is the one with the lowest.
Analyzing these eight psychometric attributes for the general nanotechnology
risk applications, some major differences arise.
For the clothes application, the results show that the participants consider that
there is a high lack of “Knowledge of Risk to those Exposed” (M = 3.63; SD = 1.05),
with the lowest results being for the “Worries about risks” (M = 2.41; SD = 1.01),
“Probability of health damage” (M = 2.44; SD = 1.04), “Adverse health effects

strength” (M = 2.56; SD = 0.78) and “Control over risk” (M = 2.52; SD = 0.91),
and the other attributes being around a medium point.
TABLE 1. Means and standard deviations for the eight psychometric risk attributes.
M SD
Lack knowledge 3.4907 0.72977
Involuntary 3.1838 0.60379
Lack trust 3.0148 0.64362
Health damage 3.0023 0.65461
Effects strength 2.9870 0.54246
Worries 2.9164 0.66749
Uncontrollable 2.8519 0.63891
Ethic unjustifiable 2.7047 0.62721
For the food application, results in Figure 5 show a high lack of “Knowledge
of Risk to those Exposed”, as well as medium-high “Worries about risks”,
“Probability of health damage”, lack of “Voluntariness of risk”, “Adverse health
effects strength”, with the other attributes being around a medium point.
Food risk
5,00
4,50
4,00
$
$
Mean Values
3,50 $ $ $
$ $
$
3,00
2,50
2,00
1,50
1,00
Health dama ge La ck of knowledge La ck of trust
Worries E ffec ts s trengh E thic ally unjustifiable
Involunta ry Uncontrollable
Figure 5. Nanotechnologies food risk.

For the communications application, the results show a medium-low lack of

“Knowledge of Risk to those Exposed” (M = 3.41; SD = 1.10), with the lowest
results being for the “Ethically justifiable to develop the application” which a low
value in this scale meaning that people consider it to be justifiable (M = 2.41; SD
= 1.10), for “Control over risk” (M = 2.75; SD = 0.99) and “Worries about risks”
(M = 2.76; SD = 1.07), with the other attributes being around a medium point.
For the medical application, the results show a medium-low lack of “Knowledge
of Risk to those Exposed” (M = 3.53; SD = 1.02), with the lowest result being for
the “Ethically justifiable to develop the application”, being this the most ethically
justifiable application of all the general applications (M = 2.29; SD = 0.92), with
the other attributes being around a medium point.
For the military application, results in Figure 6 show the highest consistency
comparing to the other applications, with all the attributes scoring medium-high or
medium-low (all results are above point 3 in the scale).
Military risk
5,00
4,50
4,00
Mean Values
3,50 $ $ $
$ $ $ $
$
3,00
2,50
2,00
1,50
1,00
Health dama ge La ck of knowledge La ck of trust
Worries E ffec ts s trengh E thic ally unjustifiable
Involunta ry Uncontrollable
Figure 6. Nano military risk.
Regarding the specific applications, mean values for the perceived risks can be
seen in Table 2. The one perceived as more threatening is Ammunition with a
medium-high perceived level of threat, followed by Water Sterilization, Sunscreen
and Toys Coating. The one’s perceived as less threatening were Cancer Treatment
with Nanocapsules, Medical Nanorobots, Data memory and Storage of Hydrogen
as a Gasoline Substitute. Once again, these results seem to reflect more the general
evaluations regarding the applications than the specific evaluations regarding their
risks.
TABLE 2. Perceived risks for the 20 specific applications.
M SD
Ammunition 3.5329 0.67142
Water sterilization 3.2412 0.56518
Sunscreen 3.2103 0.63596
Toys coating 3.1159 0.53760
Food packaging 3.0365 0.55487
Textiles coating 3.0251 0.60469
Building materials protection 2.9990 0.53873
Car paint 2.9461 0.56479
Photographic paper 2.9091 0.58095
Release of medication 2.8844 0.55434
Implants coating 2.8805 0.61551
Monitors 2.8565 0.59994
Food biosensors 2.8510 0.61244
Tires 2.8471 0.62260
Lightweight building materials 2.8318 0.55332
Skis 2.7996 0.56768
Hydrogen storage 2.7975 0.57061
Data memory 2.7653 0.59224
Medical nanorobots 2.7418 0.56440
Cancer treatment 2.6684 0.54212
A Principal Components Analysis (PCA) was performed to assess the

underlying psychological factors in the risk assessment of the general and specific
applications of nanotechnology. For this we averaged the ratings for each of the
eight attributes over participants and aggregated the data across applications
(following the procedure suggested by Willis et al. [31], and performed a PCA on
this data with a varimax rotation.
Given the results on the screen-test and the percentage of variance explained
considering the factors extraction, as seen in Table 3 we decided for three factors
with 84.78% of variance explained: Factor 1 – Dread (including “Probability of
health damage”, “Worries about risks” and “Adverse health effects strength”);
Factor 2 – Unknown (including “Knowledge of risk to those exposed” and “Control
over risk”); Factor 3 – Trust & Ethics (including “Trust in institutions responsible
for protecting people’s health regarding the technology” and “Ethically justifiable
to develop the application”).
TABLE 3. PCA loadings with a varimax rotation.
Dread Unknown Trust & ethics

Health damage 0.656 0.486 −0.120
Worries 0.932 0.120 −0.032
Involuntary 0.085 0.876 0.298
Lack of knowledge −0.173 0.896 0.301
Effects strength 0.878 −0.142 0.324
Uncontrollable 0.879 −0.130 0.284
Lack of trust 0.253 0.486 0.691
Ethically unjustifiable 0.106 0.272 0.895
Loadings above 0.50 are signaled
Following the PCA analysis, a spatial representation of the general and specific
nanotechnology applications was performed. For the sake of parsimony and clarity
and of the interpretation, we performed another PCA analysis with only two
factors, explaining 74.22% of the variance, with the attributes reorganized in this
way: Factor 1 – Dread (including “Probability of health damage”, “Worries about
risks”, “Adverse health effects strength” and “Control over risk”); Factor 2 –
Unknown, trust and ethics (including “Knowledge of risk to those exposed”,
“Trust in institutions responsible for protecting people’s health regarding the
technology”, “Ethically justifiable to develop the application” and “Voluntariness”).
Figure 7 represents all the applications in this two-dimensional plot, developed
from the two factors scores, labelled by application.
From this representation, we can see that the most trustworthy institutions
responsible for protecting people’s health regarding the technology are associated
with general and specific medical applications, with these being the applications
also with a higher knowledge of risk to those exposed, more control over exposure
and where is more ethically justifiable to develop the application. However, at the
same time, they also have a medium level of dread.
The applications with higher perceived risk are the ones where there is the
lowest knowledge, control over exposure, trust and ethical justification, combined
with a high perceived dread risk, namely the one’s associated with general and
specific military applications and general food applications.
The applications perceived as safer or with the lowest perceived risk, are the
ones where there is a higher knowledge, control over exposure, trust and where is
more ethically justifiable to develop the technology, combined with low levels of
perceived dread risk, namely data memory, food biosensors and hydrogen storage.
3,000
Factor 2 - Unknown + lack of trust and unethical
2,000
Ammunition
Military
Water Sterilization Food
1,000 Building materials protection
Car paint
Lightweight building
Toys coating Sunscreen
Photographic paper Textiles coating Food packaging
Skis
Clothes Tires Monitors Medical
0,000 Communication
Food biosensors
Data memory
Hydrogen storage
Release of medication
-1,000 General
Implants coating
-2,000
Medical nanorobots
Cancer treatment
-3,000
-3,000 -2,000 -1,000 0,000 1,000 2,000 3,000

Factor 1 - Dread
Figure 7. Spatial factorial representation of the general and specific nanotechnology applications –
laypeople.
Thus, even in the absence of information, people did judge nanotechnologies

in a consistent way, in accordance with intuitive judgments rules, and currently
they perceived them as moderately risky. Some applications stand out (military,
food), we believe not because people had more knowledge about them but because
of their evaluations towards technologies operating in those fields, along with a
low sense of control over exposure, distrust in institutions and perceived poor
ethical justifications.
4. Coping with Nanotechnologies Perceived Risk
In a negative scenario, if risk management isn’t successful it’s possible that

when people hear more about nanotechnologies in the future they will start
evaluating it as risky, because it is not only a matter of information but also
attitudes. The point is that even if public concerns about risks don’t turn out to be
true, as might be the case for nanotechnologies, the perception of being in risky
circumstances is a stressful situation [15] that might actually induce psychological,
physical and behavioral consequences (e.g. [32]).
How might people act in this situation? One way to cope with it is by means of
social comparison [6]. There are evidences that in certain groups under threat,
people who cope better are the ones who perform explicit self-evaluation against a
less fortunate target (downward evaluations), expressing peoples clear efforts to
regulate emotions by making the person feel better in comparison with worse-off
others [25]. For example, cancer patients that engage in this kind of comparisons
cope better with the disease than those who don’t. As Taylor and Brown [25]
argue, the healthy human mind seems to cordon off negative information, creating
positive illusions that help coping and are particularly adaptive when one is
threatened by adversity. In our case people might compare nanotechnologies with
other events, reevaluate them and psychologically accept being in a risky
situation.
A way to cope is reflected in the so-called “NIMBY” effect. This acronym
stands for “Not In My Backyard”. It’s a phenomenon that strikes whenever a
community has been chosen to host a hazardous facility or a facility that will carry
some cost for the local residents. Describes the fact that people usually agree with
the need to build some hazards facility but are against building that construction
near their home (e.g. [9, 17]). In this case, people cope with the situation not by
reevaluating it but by changing it. We argue that nanotechnologies, due to its
“nano” operative nature, can put people into a somehow similar phenomenon:
“Not In My Body” (NIMB) [1]. NIMB would describe people agreeing with the
general need to use nanotechnologies but refusing to use nanotechnologies that
would “enter” their body, (consider, for example, the differences in the clothes
and food applications). We recall the psychometric analysis of our data illustrated
that most of its variance was explained by a factor that combined attributes
concerning people’s health (“Dread” factor).
So, we analyzed if it might be important to isolate the risk perception of
nanotechnologies to the body level, comparing it with the risk for the self, other
people and family. Participants in our study evaluated the risk of nanotechnologies
in general to self, to their own body, to their family and to other people, perceived
general control regarding the general applications, the adverse health effects due
to nanoparticules entering the body to evaluate the NIMB effect, and the
knowledge perception, in Likert type 5 point scales (1 = Totally disagree; 5 =
Totally agree).
Once again we created scales by averaging results on each item, creating
composite measures with good psychometric properties overall and reliability
indexes (Cronbach’s Alpha). The scales are as follows: Perceived Nanotechnology
Risk to the Body, for the general applications (α = 0.81); Perceived Nanotechnology
Risk to Self, for the general applications (α = 0.81); Perceived Nanotechnology Risk to
the Family, for the general applications (α = 0.80); Perceived Nanotechnology Risk
to Other People, for the general applications (α = 0.86); Perceived Control over
Nanotechnology Risk for the general applications (α = 0.73); NIMB effect (α =
0.88); Perceived Knowledge of Nanotechnology Risk for the general applications
(α = 90.).
To what concerns an assessment of the general applications the results for
other variables show no significant differences in the level of perceived exposure
to the risk, namely between the perceived risk to self, to their own body, to their
family and to other people, with all having a medium value and the highest value
being the perceived risk to self (M = 3.09; SD = 0.76). Also the perceived level of
general control over the nanotechnologies risk is medium (M = 2.95; SD = 0.77),
the same happening with the perceived adverse health effects due to nanoparticules
entering the body (NIMB, M = 3.03; SD = 0.83).The level of knowledge,
however, is perceived as low (M = 2.06; SD = 0.91). Besides that, this scale has
the highest internal consistency index (α = 90.): people’s knowledge toward
general applications is only slightly differentiated.
These results confirm our suspicions: with the current state of lack of knowledge
people do not evaluate nanotechnologies in general as threatening and have a
moderate perceived level of general control. Currently there are also no differ-
ences between the perceived risk to them (or their body) and their family (usually
comparatively higher when people are in stress) and the risk to other people
(usually comparatively higher when people are successfully coping with stress).
We also performed a Multiple Regression Analysis to find out how the
perceived risk for the five applications could be better explained by these
variables. As previously theorized, the model that explained most data variability
(52.7%; p < .001) predicts the mean risk for the five applications raises when there
is an increase both in Perceived Nanotechnology Risk to Self (β = 0.379; p < .001)
and Perceived Nanotechnology Risk to the Family (β = 0.247; p < .05) and vice-
versa; at the same time decreases when there is an decrease in Perceived Control
over Nanotechnology Risk (β = −0.220; p < .001) and vice-versa. Thus, by
analyzing risk to self, family and control, we can predict people’s risk perception
for these five applications. Perceived control might play a leading role in
nanotechnologies risk management.
5. What the Experts Think Laypeople Think: Perceptions and

Misperceptions About Nanomaterials
Nanotechnologies possible “dread” and actual “lack of knowledge” makes it highly

vulnerable to the impact of an unfortunate event (such as an accident, sabotage,
contamination or a product tampering). Even if its specific or direct impact is
small, the indirect effect might be extremely powerful and even tamper with the
field’s development. This might happen because of the social informativeness or
“signal potential” of that event that might be perceived as a harbinger of further
and possibly catastrophic mishaps [23]. An example refers to the consequences of
GMO contamination of natural non-modified plants in the surrounding fields and
the negative publicity it brought to GMO production.
As for any activity or technology with a certain probability of risk associated
to it, experts in the field acknowledge the need to develop risk management and
communication strategies for the general public. Given the newness of this tech-
nology and its present neutral perceived level of threat, we are at the right moment
to develop them and prevent the negative impact of an unfortunate event. The
problem is that, in spite of being new it shares one characteristic with other older
technologies, which makes the process of risk management and communication
more difficult, if not paid attention to. This characteristic is that there seems to be
a huge gap between how technicians and lay people evaluate risks, with this gap
existing whether the risk is known or not, i.e. it is not only a matter of knowledge
level but also of perceptual and cognitive processes that technicians and lay people
privilege in order to “calculate” risk [23, 28].
The work on risk perception has systematically highlighted the differences
between the expert’s and laypeople’s assessments, emphasizing the formers
technical and objective character and the latter’s biases, inconsistencies and risk
perception illusions [14]. There is no doubt that the concept “risk” means different
things to different people. For example, when experts judge risk their responses
correlate highly with technical estimates of annual fatalities, with their assessment
being based on the factual data they have. Lay people usually go beyond this
information with their judgment of “risk” being based on other criteria, such as the
perceived threat to future generations or the equity in the distribution of risks [23],
as identified by the psychometric risk paradigm. Moreover, this perception is
systematically influenced by socio-demographic and cultural variables (e.g. [8]).
This is not surprising, since people and technicians are “trained” to evaluate
risks in different ways. In fact, experts are trained during their education and work
to evaluate risks in a set of established, shared and standardized criteria (i.e. all
professionals in the field are supposed to evaluate in the same manner). This level
of agreement is not so high when we talk about laypeople since that different
cultural experiences, frequency of exposure to the risks, socio-demographic char-
acteristics, personality type and other individual and social group differences
makes them use different criteria in different contexts for different risks. This
means that the difference between laypeople and experts is not only a matter of
knowledge but also about the framing with which they assess risks. Therefore,
both groups were “trained” either through experience, knowledge or both, to
evaluate with different criteria and eventually reached a point in which they could
do this spontaneously, without much rational thought associated with it. Particu-
larly, the experts were trained to frame and judge the risks and the situation in a
less intuitive way but, again, this is only a question of training since that given the
right conditions, laypeople can also evaluate under the same criteria as the experts
and experts can also fall prey to their intuitive assessments and judge under the
same criteria as laypeople. We will get back to this point later on. For now, we
will give next some examples of these different risk judgments between experts
and laypeople.
One example comes from Savadori et al. [20] who used the psychometric
paradigm to examine the difference between expert and layperson risk perception
on different biotechnology applications, specifically food and medical applica-
tions. Results regarding food applications showed that lay people judged the risk
as higher than the experts did. The main factors which could explain most of the
judgment’s variance both for laypeople and experts were related to perceived harm,
dread and usefulness. Additionally to these, people also made their evaluation in
terms of newness and level of scientific knowledge of the risk associated with
biotech food applications, having a broader perception than the experts for this
application. Results regarding medical applications also showed that lay people
judged it as higher than the experts, however here the factors considered by lay
people were less, when compared to the experts. The factors that explained
laypeople’s evaluation of the risk associated with medical biotech applications
were perceived harm and usefulness, while the experts considered these but also
the level in which would expose themselves and many people to the risk, its
newness and level of scientific knowledge.
These results show that although the risk’s newness and level of scientific and
social knowledge about it are important factors, people can still judge a risk as
high, even though these factors are not considered in the judgment, as it was the
case for people’s evaluation of medical biotech applications risk. Therefore,
although people appear to be irrational, since they systematically evaluated the
risks for the medical and food biotech applications as long as five other applica-
tions as higher than the experts did, their evaluation depends on the nature of the
hazards, with different judgment criteria being used for different hazards. Equally
interesting, the experts have gone beyond their specialized knowledge and expertise
to make their judgements, using the same criteria as people did, but for different
types of applications.
In a different study also comparing expert and laypeople, Siegrist et al. [21]
used the same psychometric paradigm to analyze the risk perception for various
nanotechnology applications. Results showed that people’s nanotechnology risk
judgements were higher and their trust in authorities responsible for protecting
people’s health regarding the technology was lower, than for the experts. However,
results regarding perceived benefits were not significantly different between
laypeople and experts. To what concerns the factors influencing individual differ-
ences, the best predictors of people’s perceived risk regarding nanotechnologies in
general were: perceived nanotechnology benefits, social trust and attitudes
regarding technology in general (perceived benefits and fears). For the experts risk
perception, the best predictor was only social trust, basing their judgements only
on this but not on their attitudes or perceived benefits. We consider this to be an
expected result given the fact that they work in the area and apparently consider
that the control over these risks should be handed in to the people in the same area
as them, since that they are the ones with the highest knowledge level.
Considering all this, we can infer that if some unfortunate negative event
happens regarding some kind of nanotechnology application, as long as it doesn’t
undermine the perceived trust in authorities responsible for protecting people’s
health regarding the technology, experts risk perception regarding nanotechno-
logies should remain “untouched”, independently of the type of application. The
same is not expected to happen with laypeople’s perception, given that their
judgements are also based on their attitudes and perceived nanotechnology benefits
and that even in the absence of specific knowledge about the nanotechnology
application for which the unfortunate negative event might happen, they can still
make their judgments.
Moreover, the magnitude of the risk perception increase should be higher for
those applications identified as more dreadful, unknown and distrusted, as identified
in Siegrist et al. [21] and in our own study presented before, based on the
psychometric paradigm (although this should happen only until a certain level, due
to a ceiling effect resulting from the presence of normal adaptation processes [15,
16]).
Finally, given the similarities of some nanotechnology applications in terms of
their perceived dreadfulness, lack of knowledge, trust and ethical assurance that
we identified (e.g. food and military general applications), it is expected that if an
unfortunate negative event happens for one of them, a spreading activation effect
should be expected [3] translating into a heightened risk perception for the other
applications perceived as similar in terms of these psychometric attributes (as it
might happen for example with any activity associated with the term “nuclear”).
For the reason presented before, regarding the maintenance of a high level of trust
as perceived by the experts, these changes aren’t expected to occur so suddenly
and with such a high magnitude, for the experts.
In spite all of this, there are still many misconceptions in the literature
regarding the differences between experts and lay people. It is a fact that, as we
seen, they both evaluate risks in a different way but that doesn’t mean, as
sometimes is implicit in the literature and most of the times explicit in the real
world, that experts are better than people at judging risks. In fact, this is somewhat
of an illusory conclusion, since for example laypeople can also evaluate annual
fatalities if they are asked to [23] and perform accurate frequency estimates of
causes of death, making difficult estimations based only on their judgments, in the
absence of any other information [14]. The opposite is also true, in the sense that
experts are “only humans” and there is no assurance that their judgments are
immune to biases, when they are forced to make evaluations that go beyond the
data they have [24].
As the psychometric approach shows, these divergences occur systematically
but can be successfully framed in a participated risk management process, as long
as we consider both expert and lay people different “languages” and “valuations”,
that go beyond the level of existing knowledge about a technology.
However, most of the times what hampers with risk communication and
management strategies it is not the existence of these different ways in which
experts and people evaluate risks. What often does the harm is that these strategies
are designed on a misperception of these differences and are based on the expert’s
expectations and implicit knowledge about how people think and perceive risks.
This implies the design of strategies in order to match how the experts think
people think or how people will react to a certain level of risk, and not to match
how people actually think or might react.
It is obvious from what we have shown before that the experts evaluate risks in
a different way from the lay people and that both, given the right conditions, can
have similar risk evaluations. However, how good are they to evaluate how people
perceive risks i.e., how much of a good intuitive psychologist are they?
To answer this question we performed a study with an expert sample asked to
fill the questionnaire while attending our nanotechnology meeting, with all partici-
pants giving their informed consent after a brief explanation of the research aims.
This sample was comprised of 24 experts with interests and/or experience in the
nanotechnology area, which answered a questionnaire on “nanotechnologies and
society” voluntarily. From these, 60.9% were males and 39.1% were females and
the mean age was 47.59, with 34.8% coming from Europe, 26.1% from the USA,
17.4% from Canada, 13.0% from Brazil and 8.7% from other countries. These
experts worked in areas such as Nanotoxicology and nanomaterials (N = 6),
Ecotoxicology (N = 5), Risk assessment (N = 5) and other nanotechnology and
risk assessment related areas.
In this study, the participants had to fill the same questionnaire as in our study
presented before but without the 20 specific applications. However, differently
from study 1, they were presented a set of statements, for which they were asked
to choose the response (from the possible 5) that most matched the opinion of the
general public, i.e., what nanotechnology experts believe to be the laypeople’s
perceptions on this field. This is an original framing, since most of the literature
on risk assessment analyses how the experts perceive the risks but not how the
experts perceived how people in general perceive the risks, i.e. what the experts
think laypeople think.
The introduction was stated as follows: “As you’re probably aware one of the
most recent fields of technological research is the field of nanotechnology. Like
several other technological breakthroughs nanotechnology is likely to prompt
specific perceptions and attitudes by the general public. In this study we are
interested in studying what nanotechnology experts believe to be the perceptions
of the general public on this field, i.e., the layperson’s beliefs about several
features of nanotechnology.” Therefore, the items were similar to study 1 but with
a different framing, as seen in the following example: “The general public views
the probability of health damage derived from nanotechnology as (1 = Very
unlikely 5 = Very likely)”.
The results showed that the experts consider the layperson’s General Nano-
technology Perceived Risk to be moderate (M = 3.21; SD = 0.47) but significantly
higher than the risk perception level that laypeople reported in study 1 (M = 2.89;
SD = 0.55; p = .005), which shows that they think people consider nanotech-
nologies more threatening than laypeople actually consider. However, to what
concerns the general applications, experts have an accurate view by considering
that food (M = 3.40; SD = 0.46) and military applications (M = 3.36; SD = 0.68)
are seen as the most threatening, while the applications to clothing (M = 2.87; SD
= 0.43), medicine (M = 2.89; SD = 0.44) and communications (M = 2.92; SD =
0.45) considered to be the least threatening, with no significant differences
compared to what laypeople reported in study 1.
The results concerning the eight psychometric risk attributes for the General
Nanotechnology Risk Perception show that in the same way as in people’s perce-
ption in study 1, they also consider the “Knowledge of Risk to those Exposed” as
the attribute with the highest mean, meaning that the experts consider that there is
a high level of lack of knowledge in laypeople. However, they consider this lack
of knowledge to be higher (M = 3.75; SD = 58) than what people report (M =
3.49; SD = 73), although this being only marginally non-significant (p = .079).
The same happens for “Trust in institutions responsible for protecting people’s
health regarding the technology”, with the experts considering that this lack of
trust is perceived as higher (M = 3.27; SD = 1.02) than it actually is (M = 3.02;
0.64; p = .075).
The only significant misperception in these, refers to the “Voluntariness of

risk”, i.e. experts consider that people’s exposure to nanotechnologies risk is more
involuntary (M = 3.44; SD = 57) than actually people consider it to be (M = 3.18;
SD = 0.60; p = .035). This can be seen as the work of a defense mechanism, in
which people deny and try not to think about the fact that they might be exposed
to a risk unknown to them and to which they didn’t chose voluntarily to be
exposed to, showing a natural adaptation process that lowers the stress in this
sense [16, 25]. This was demonstrated in our study with the laypeople’s sample, in
which perceived control was one of the best negative predictors of perceived risk,
meaning that an increase in one implies a decrease in the other. Differently, the
expert’s defense mechanism regarding nanotechnologies is to trust the authorities
in controlling the risks, as seen in the Siegrist et al. [21] study.
When we consider the eight psychometric attributes for the five general
nanotechnology risk applications, the differences arise. We found a very good
level of expert’s accuracy in judging people’s perception for the communications
and military nanotechnology applications, with no significant differences between
laypeople and experts. Moreover, we found a good level of accuracy for the
clothes application, with the only difference being in terms of trust, with the
experts considering it to be significantly higher (M = 3.33; SD = 1.20) than
actually people perceive it (M = 2.92; SD = 0.83; p = .027) and also a rather good
accuracy regarding the food application, with the differences being in terms of
trust and voluntariness, with the experts considering trust to be significantly higher
(M = 3.46; SD = 1.10) than actually people perceive it (M = 3.10; SD = 0.88; p =
.056), and the involuntariness in the exposure to the risk to be significantly higher
0.026).
The lowest level of accuracy was for the medical nanotechnology application,
with the experts considering the worries about the risk to be significantly lower
.003), the effects strength to be significantly lower (M = 2.71; SD = 0.81) than
actually our sample perceive it (M = 3.23; SD = 0.88; p = .006), the health damage
to be significantly lower (M = 2.71; SD = 1.04) than actually people perceive it
(M = 3.22; SD = 1.08; p = .027), the lack of control over exposure to the risk to be
significantly higher (M = 3.38; SD = 1.17) than actually people perceive it (M =
2.84; SD = 0.95; p = .009), the involuntariness in the exposure to the risk to be
lower (M = 2.88; SD = 1.19) than actually people perceive it (M = 3.29; SD =
1.00; p = .059).
Concerning the general applications, the results for other variables showed
only one misperception. As we expected, the experts consider the perceived
adverse health effects due to nanoparticules entering the body (NIMB effect) to be
higher (M = 3.60; SD = 0.81) than actually people perceive it (M = 3.03; SD =
0.83; p = .001).
A PCA Analysis was performed to assess the underlying psychological factors
in the risk assessment the experts consider that the people have, regarding the five
general applications of nanotechnology. For this, we averaged the ratings for each
of the eight attributes over the expert sample and aggregated the data across
applications. A PCA was performed on this data with only one factor being extracted,
explaining 74.93% of the variance. All attributes saturated above 0.60 on this factor,
except for the attribute “control over exposure” (saturation of −0.926) which lost
its explanatory power among the others.
This shows that the expert’s judgments of people’s perception have an overall
narrower explanatory level, compared to the underlying factors for people’s actual
perception (given that there were three factors identified in study 1, for the
laypeople’s perception). This misperceptions and lack of knowledge about what
and how people think, significantly affects the experts intuitive and non-factual
predictions of how people will judge a certain risk for a certain nanotechnology
application, and consequently how they will react to that risk. This is a very
dangerous endeavor since that if experts do this without knowing anything about
human cognitive functioning and behavior, instead of managing and communi-
cating risk with the aim of reducing it, they will actually increase it and also the
possible negative reactions and manifestations associated to it.
These misperceptions are evident in Figure 8 which represents the general
applications in a two-dimensional plot, developed from the two factor scores
resulting from another PCA we performed, labeled by application. We should
1,500
General
1,000
Factor 2 - Exposure, trust and ethics
Food
Clothes
0,500 Military
0,000
-0,500
Communication
-1,000
Medical
-1,500
-1,500 -1,000 -0,500 0,000 0,500 1,000 1,500

Factor 1 - Dread
Figure 8. Spatial factorial representation of the general and specific nanotechnology applications –
experts.
warn however that the confidence in this analysis is lower than the one performed
in study 1, since that the two factors obtained in this one are not completely
independent, even after performing a varimax rotation, which can insert a certain
error level in the analysis. In spite of this, we’ll present the results since the
differences from the laypeople’s two-dimensional plot are very clear, even dis-
counting the measurement error.
In this figure, we can see that only the military and food applications are in the
same quadrant as in study 1. All the other applications are influenced by mispercep-
tions regarding the risks, especially to what concerns the medical applications,
which are considered to have a high level of knowledge, trust and ethical
justification and a low level of dreadness. However, according to laypeople’s
perception they would be in a different quadrant, characterized by a moderate
knowledge of risk to those exposed, control over exposure and ethical justification
but, at the same time, with a medium level of dread.
In a nutshell, we can see that while experts are accurate in analyzing lay people
perceived nanotechnologies risk in general considering the eight psychometric
attributes, this accuracy disappears when they have to consider the five applica-
tions based on these same eight attributes. This demonstrates that their implicit
knowledge about laypeople’s cognitive functioning cannot compensate for the
differences between applications, i.e. they think people evaluate the risks always
in the same manner.
Also, intuitively the experts judge the high level of lack of specific knowledge
to be the main cause of differences between applications and since that they
consider people to have similar lack of knowledge in every application, then there
shouldn’t be differences. Since that in the Siegrist’s et al. [21] study the experts
risk perception regarding nanotechnology was best predicted by social trust, we
can infer that experts expect that people in the absence of knowledge regarding the
applications, also use trust as a criteria for their judgments. However, as we saw in
our results, there is a misperception about the trust level in the food and clothes
nanotechnology applications. Moreover, as we know from the same study, people
use criteria as perceived nanotechnology benefits, social trust and attitudes
regarding technology in general (perceived benefits and fears) to make their risk
assessments. This might explain why the highest misperception was for medical
nanotechnology applications, which seems to be more influenced by attitudes and
perceived benefits than any of the others. This is exactly where the experts
implicit knowledge about laypeople’s functioning fails, by not considering that
differences in risk assessments might occur given the presence of attitudes and
other perceptions, i.e. they seem to be only accurate in assessing laypeople’s
perception when these influences are not so strong.
6. Conclusions
From the above results and discussion one can extract several important conclusions
that qualify the usual reflections about the nanomaterials’ risk perception and
attitudes.
The first point that is important to stress is that the widespread positive
attitudes about nanomaterials might actually be based on the global attitudes about
technology. When people are asked to evaluate specific nano applications this
global positive picture starts to fade. The details of this process were analyzed and
our revision and research was able to shed some light on the psychological process
that underlies the formation of specific attitudes and risk perception based on
small amounts of information.
Worth mentioning is the somewhat sharp differences within the evaluation of
global applications where food and military ones shown a different profile. When
we detailed even further the specificity of nano applications, a factorial picture
also illustrated that some applications like ammunition and food have higher risks,
while others have comparatively much lower risks (e.g., medical). Thus, and as
mentioned above, even in the absence of information, people did judge nano-
technologies in a consistent way, in accordance with intuitive judgments rules, and
currently they perceive them as moderately risky (i.e. people “know much” in
spite of their overall moderate to high lack of knowledge). Some applications
stand out (military, food), we believe not because people had more knowledge
about them but because of their evaluations towards technologies operating in
those fields, along with a low sense of control over exposure, distrust in institutions
and perceived poor ethical justifications. Additionally to this, the individual
perceived control was also one of the most important factors.
Comparing experts and lay people perceptions of nanotechnologies one can
easily conclude that experts have somewhat a misguided perception of people’s
evaluations. One of the reasons for this mismatch is the fact that the complexities
of the factors that guide lay risk perception are much more subtle and diverse than
expected by the experts. The complexity of values and perceived benefits that are
behind the attitudes and risk perceptions regarding specific applications are not
fully understand by the experts.
The data and literature revised above also points out a potential negative
scenario of hypothetical events related with nanomaterials. Given the lack of
knowledge shown by people across studies and the specific values and ethical
factors implied in the specific domain applications, a negative attitude and higher
risk perception can be facilitated in that context, if no risk management and
communication strategy is developed to address these specific factors.
All of this stresses the importance of a participated strategy that could take in
to account the specificities of lay people world views connected with the
nanotechnology application domain and also the factors that are important for risk
evaluation such as e.g., perceived control. The understanding of these processes
probably has to start within the nanotechnology expert’s community who, most
probably, will be in the front line of a potential crisis.
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PARTICIPANTS
Abdel- Department of Chemistry Tel.: + 2010 168 6244

Mottaleb, Faculty of Science Fax: + 202/ 2634 7683
Sabry Ain Shams University Emails: sabry.abdel-mottaleb@
11566 Abbassia, Cairo, Egypt daad-alumni.de;
Phochem08@photoenergy.org
Abdel-Shafy, Water Research & Pollution Control Email: husseinshafy@
Hussein Dept., National Research Centre Cairo, yahoo.com
Egypt
Adlakha- Defense Research and Development Tel.: 613-996-3183
Hutcheon, Canada Fax: 613-996-5177
Gitanjali 305 Rideau Street, Ottawa K1A 0K2, Email: Gitanjali.
Canada Adlakha-Hutcheon@
drdc-rddc.gc.ca
Arcuri, Arline Foundation on Occupational Safety and Tel.: 5511 3066 6140
Sydneia Abel Health Researches and Studies – Fax: 55 11 3066 6341
FUNDACENTRO – Ministry of Labour Email: arline@fundacentro.
and Employment gov.br
San Paolo 05409-002, Brazil
Bayramov, Institute of Physics Tel.: +994124394057
Azad National Academy of Sciences Fax: +994124470456
G.Javide 33 Email: bayramov_azad@
Baku AZ 1143, Azerbaijan mail.ru
Bayramova, Institute of Geology
Svetlana National Academy of Sciences of
Azerbaijan
G.Javide av. 29
Baku AZ 1143, Azerbaijan
Bennett, Erin Environmental Biologist Tel.: 978-740-0096 x529
18, Commercial Street Fax: 978-740-0097
Salem, MA 01970 Email: ebennettt@
bioengineering.com
Blank, Nelly International Nanotechnology Research Tel.: 972-50-653392

Center Polymate Fax: 972-4-8248050
Kibbutz Ind. Zone Email: newtech@borfig.com
Migdal Ha’Emeq
Haifa 23100, Israel
Chan- Golder Associates Ltd/HydroQual Tel.: 1.403.253.7121
Remillard, Laboratories Ltd Fax: 1.403.252.9363
Sylvia #4 6125-12th Street S.E. Email: sylvia_chanremillard@
Calgary T2H 2K1, Canada golder.com
463
464 PARTICIPANTS
Chappell, Mark Environmental Laboratory Tel.: 601-634-2802

U.S. Army Corps of Engineers Fax: 601-634-3410
3909 Halls Ferry Road Email: Mark.a.chappell@
Vicksburg, MS 39056, USA usace.army.mil
Colvin, Vicki ICON Tel.: 713-348-5741
Rice University Fax: 713-348-2578
141 Dell Butcher Hall Email: colvin@rice.edu
Houston, TX 77005, USA
Cullinane, John Environmental Laboratory Tel.: 601.634.3723
U.S. Army Corps of Engineers Fax: 601.634.2854
3909 Halls Ferry Road Email: John.M.Cullinane@
Vicksburg, MS 39180, USA usace.army.mil
Davis, J. National Center for Environmental Tel.: (919) 541-4162
Michael Assessment Fax: (919) 685-3331
Office of Research and Development Email: Davis.Jmichael@
U.S. Environmental Protection Agency epa.gov
Research Triangle Park, NC 27711, USA
Davis, Thomas Environment Canada and Tel.: (514) 343 6111 poste 4929
Department of Chemistry (514) 804 5957
University of Montreal Fax: (514) 343 7586
C.P. 6128, succursale Centre-Ville Email: ta.davis@umontreal.ca
Montreal (QC) H3C 3J7, Canada
Depledge, Peninsula Medical School Tel.: 44 (0) 1752 437402
Michael Plymouth, PL6 8BU, UK Fax: 44 (0) 1752 517842 Email:
Michael.depledge@pms.ac.uk
Elder, Alison University of Rochester Tel.: 585-275-2324
Department of Environmental Medicine Fax: 585-256-2631
575 Elmwood Avenue, Box 850, Email: Alison_Elder@
Rochester, NY 14610, USA urmc.rochester.edu
Figovsky, Oleg International Research Center Polymate Tel.: 972-4-8248072
3a Shimkin Street Fax: 972-4-8248050
Haifa 34750, Israel Email: figovsky@netvision.net.il
Figueira, José Instituto Superior Técnico Tel.: +351-21-423-35-07
Rui Technical University of Lisbon Fax: +351-21-423-35-68
DEG, Tagus Park, Avenue Cavaco Silva Email: figueira@ist.utl.pt
Porto Salvo 2780-990, Portugal
Figueira, 480 Boul. Armand-Frappier, Laval Tel.: (450) 680-3471
Marianne (Québec), Canada H7V 4B4 Fax: (450) 687-5860
Email: figueiramm@
hotmail.com
PARTICIPANTS 465
Fonseca, Carlos Department of Electronic Engineering Email: cmfonsec@ualg.pt

and Informatics
Faculty of Science and Technology
University of Algarve
Campus de Gambelas
Faro 8005-139, Portugal
Foss Hansen, Department of Environmental Tel.: +45 45 25 15 93
Steffen Engineering, NanoDTU Fax: + 45 45 93 28 50
Technical University of Denmark Email: sfh@er.dtu.dk
Building 113, Kgs. Lyngby DK-2800,
Denmark
Gatti, Laboratory of Biomaterials Tel.: +39059798778
Antonietta University of Modena & Reggio Emilia Fax: +390597579182
Via Campi 213 A, Modena 41100, Email: antonietta.gatti@
Italy unimore.it
Gnewuch, Naneum Ltd Tel.: +44 1227824631
Harald Canterbury Enterprise Hub +44 1227827778
Canterbury CT2 7NJ, Email: harald.gnewuch@
UK naneum.com
Goss, Greg Biological Sciences Building Tel.: 1-780-492-2381
University of Alberta greg.goss@ualberta.ca
Edmonton, Alberta T6G 2E9, Canada
Goudey, J. HydroQual Laboratories Tel.: (403) 253-7121
Stephen Golder Associates Ltd (403) 560-6028
#4, 6125 12th Street SE Fax: (403) 252-9363
Calgary, Alberta T2H 2K1, Canada Email: sgoudey@golder.com
Grieger, Khara Department of Environmental Tel.: +454525 2164
Engineering, NanoDTU Fax: +4545932850
Technical University of Denmark Email: kdg@er.dtu.dk
Building 115, Kgs. Lyngby DK-2800
Grossi, Maria University of Stuttgart Tel.: 0049 7131 6427616
Gricia Port-Talbot-Str. 17 Fax: 00 49 711 685 65495
Heilbronn 74081, Germany Email: gricia@gmx.de
Gulledge, American Chemistry Council Tel.: (703) 741-5613
William 1300 Wilson Blvd. Email: William_Gulledge@
Arlington, VA 22209, USA americanchemistry.com
Hakkinen, Senior Toxicologist Tel.: 301-827-4222
Pertti Bert National Library of Medicine Fax: 301-480-3537
National Institutes of Health Email: pertti.hakkinen@
6707 Democracy Boulevard nih.gov
Suite 510, Bethesda, MD 20892 USA
466 PARTICIPANTS
Haraza, Quality Assurance Quality Control Email: shafymahmoud@

Mahmoud Department yahoo.com
Ahmed Shafy National Center of Nuclea Safety and
Radiation Control
Atomic Energy Authority
Ahmed El Zomor Street, Nasr City 11672,
Box 7551
Cairo, Egypt
Haruvy, Nava Netanya Academic College Tel.: +972-8-946-3189
One University Street Fax: +972-8-936-5345
Netanya 42100, Israel Email: navaharu@
netvision.net.il
Kaczmar, O’Brien and Gere Engineers Inc. Tel.: 315-345-4545
Swiatoslav 5000 Brittonfield Pkwy Fax: 315-437-3555
Syracuse 13221, USA Email: kaczmasw@obg.com
Kadeli, Lek US Environmental Protection Agency, Tel.: (202) 564-6989 or 6620
1200 Pennsylvania Avenue, NW 8101R, Fax: (202) 564-2244
Washington, DC 20460, USA Email: Lek.kadeli@epa.gov
Kapustka, LK Consultancy Email: Kapustka@shaw.ca
Larry 8 Coach Gate Place SW
Calgary, AB T3H 1G2, Canada
Karkan, Delara Health Canada Email: Delara_karkan@
Canada hc-sc.gc.ca
Kearns, Peter ENV/EHS OECD Tel.: +33 1 4524 1677
2 rue Andre-Pascal Fax: +33 1 4524 1675
75775 Paris Cedex 16, France Email: peter.kearns@oecd.org
Kenawy, El- Polymer Research Group, Department of Tel.: +040-3344352
Refaie Chemistry +012 2372276
Faculty of Science Fax: +040-3350804
University of Tanta, Email: ekenawy@yahoo.com
Egypt
Khaydarov, Institute of Nuclear Physics Email: renat2@gmail.com
Renat Uzbekistan Academy of Sciences
Kondratyev, St. Petersburg Technical University Email: makond@mail.ru
Mikhail Russia, St. Petersburg, 198152 Tel.: +79213400875
Fax: +78122971639
Korenstein, Marian Gertner Institute for Medical Tel.: 972-3-6406042
Rafi Nanosystems Fax: 972-3-6408982
Department of Physiology and Email: korens@post.tau.ac.il
Pharmacology
Faculty of Medicine
Tel Aviv University
69978 Tel-Aviv, Israel
PARTICIPANTS 467
Kuhlbusch, Institute for Energy and Environmental Tel.: +49 2065 418 267
Thomas Technology, Air Quality & Sustainable Fax: +49 2065 418 211
Nanotechnology Unit, Bliersheimer Street Email: tky@iuta.de
60, Duisburg 47229, Germany
Linker, Manager Industrial Hygiene & Tel.: +31 (0)46 47 610 98
Fenneke Toxicology +31 (0)6 512 99 125
Occupational Health Care Services DSM Fax: +31 (0)46 47 647 62
ARBOdienst DSM Email: Fenneke.Linker@
Alert & Care Centre DSM.com
Kerenshofweg 200
NL-6167AE Geleen
The Netherlands
Linkov, Igor Environmental Laboratory Tel.: +1 617-233-9869
U.S. Army Corps of Engineers Email: Igor.linkov@
83 Winchester Street Suite 1 usace.army.mil
Brookline, MA 02446, USA
Lynch, Iseult Irish Centre for Colloid Science & Tel.: 00 353 1 7162418
Biomaterials Fax: 00 353 1 7162127
School of Chemistry & Chemical Biology Email: iseult@fiachra.ucd.ie
Ireland
Matias, Sara Instituto Superior Técnico, Universidade Tel.: +351 210 733 756
Técnica de Lisboa, Av. Rovisco Pais Email: Sara.matias@
1049-001 Lisboa, Portugal yahoo.com
McQuaid, NATO Environmental Security Panel Tel.: 0044 114 2365 349
James 61 Pingle Road Email: jim@mcquaid.
Sheffield S7 2LL, UK demon.co.uk
Melkonyan, Institute of Crystallography of RAS Tel.: +7(499)135-05-81
Marine Leninsky pr., 59 Fax: +7(499)135-10-11
Moscow 119333, Russia Email: nanotech@ns.crys.ras.ru
Metcalfe, Chris Trent University Tel.: 705-748-1011, x7272
1600 West Bank Drive Fax: 705-748-1569
Peterborough, Ontario K9J 7B8, Canada Email: cmetcalfe@trentu.ca
Monica, John Porter Wright Morris & Arthur LLP Tel.: (202) 778-3000
1919 Pennsylvania Avenue, NW (202) 778-3050
Suite 500 Fax: (202) 778-3063
Washington, DC 20006-3434, USA Email: jmonica@
porterwright.com
Monteiro- Center for Chemical Toxicology Tel.: 919-5136426
Riviere, Nancy Research and Pharmacokinetics Fax: 919-513-6358
Department of Clinical Sciences Email: Nancy_Monteiro@
College of Veterinary Medicine ncsu.edu
468 PARTICIPANTS
O’Brien, Niall Biosystems Engineering School of Tel.: 0035317165546

Agriculture, Food Science and Veterinary Fax: 0035314752119
Medicine, College of Life Sciences Email: niall.obrien@ucd.ie
Earlsfort Terrace
Dublin 2, Ireland
Owen, Richard DEFRA, Environment and Human Health Tel.: +44 (0) 7990 800051
Programme Fax: + 44 (0) 117 914 2673
UK Environment Agency Email: richard.owen@
Block 1 Government Buildings environment-agency.gov.uk
Burghill Road
Bristol BS10 6BF, UK
Palma-Oliveira, FPCE, University of Lisbon Tel.: +351 21 781 62 80
José Manuel Alameda da Universidade +351 96 150 44 44
1100 Lisboa, Fax: +351 21 781 62 89
Portugal Email: palma@veritas.pt
Picado, Ana Instituto Nacional de Engenharia, Tel.: 351 210 924 706
Tecnologia e Inovação, I.P. Fax: 351 217 166 966
Estrada do Paço do Lumiar, Edif. E - 1º Email: ana.picado@ineti.pt
Andar
Lisboa 1649-038, Portugal
Pinto, Valéria Foundation on Occupational Safety Tel.: +552125088548
and Health Researches Fax: +552125079041
and Studics-FUNDACENTRO Emails: valeria.pinto@
Av. Quintino Bocaiúva, 187 apto 302 fundacentro.gov.br;
São Francisco valeriarspinto@yahoo.com.br
Niterói 24360022, Brazil
Ramadan, National Egyptian Environmental Tel.: +202 27 48 787
Abou Bakr and Radiation Monitoring Network +2012 346 8077
3 Ahmed El Zomor Street Fax: +202 22876 031
Nasr City 11672 Emails: ramadan58@yahoo.com;
Box 7551 ramadan85@yahoo.com
Cairo, Egypt
Rudnitsky, Physical Science Officer Tel.: 202-663-2399
Robert Office of Space & Advanced Technology Fax: 202-663-2402
U.S. Department of State Email: RudnitskyRG@
OES/SAT, SA-23, 1990 K Street, state.gov
NW Suite #410
Washington, DC 20006, USA
Satterstrom, Harvard School of Engineering Tel.: (206) 919-9337
F. Kyle and Applied Sciences Email: satterst@
Engineering Sciences Laboratory 224 fas.harvard.edu
40 Oxford Street
Cambridge, MA 02138, USA
PARTICIPANTS 469
Savolainen, Kai Finnish Institute for Occupational Health Tel.: +358 30 474 2851
New Technologies and Risks Fax: +358 30 474 2114
Topeliuksenkatu 41 a A Email: Kai.Savolainen@ttl.fi
Helsinki FI-00250, Finland
Shalhevet, Sarit Sustain Econ – Environmental Economics Tel.: 617 879-0577
Consulting Fax: 617 879-0577
126 Thorndike Street Email: sarit.shalhevet@
Brookline, MA 02246, USA gmail.com
Shvedova, CDC/NIOSH Tel.: 304 285 6177
Anna 1096 Willowdale Road Fax: 304 285 5938
Morgantown, WV 26505, USA Email: ats1@cdc.gov
Srdjevic, Bojan Faculty of Agriculture, University Tel.: +381-21-4853-337
of Novi Sad Fax: +381-21-455-713
Trg D. Obradovica 8 Email: bojans@polj.ns.ac.yu
Novi Sad 21000, Serbia
Stamm, Institute for Health & Consumer Tel.: +39 0332 789030
Hermann Protection, EC Fax: +39 0332 785388
Via Fermi, Ispra 21020, Italy Email: hermann.stamm@
ec.europa.eu
Steevens, U.S. Army ERDC Tel.: 601-634-4199
Jeffery 3909 Halls Ferry Road Fax: 601-634-2263
Vicksburg, MS 39056, USA Email: Jeffery.A.Steevens@
us.army.mil
Tervonnen, CEG-IST, Centre for Management Tel.: +351 96 529 1326
Tommi Studies, IST +421 910 119 209
Technical University of Lisbon Fax: +351 214 233 568
Instituto Superior Técnico, Taguspark Email: tommi.tervonen@
Porto Salvo 2780-990, Portugal ist.utl.pt
Varma, Sustainable Technology Division National Tel.: (513) 487-2701
Rajender Risk Management Research Laboratory, Fax: (513) 569-7677
US EPA Email: Varma.Rajender@
Cincinnati, Ohio, USA epa.gov
Vaseashta, On Detail from Nanomaterials Tel.: 2026478548
Ashok Laboratories & Characterization Labs Fax: 2026474920
Marshall University Email: VaseashtaAK@
One John Marshall Drive state.gov
Vieira, Teresa Departamento de Mecânica Tel.: +351239790711
University of Coimbra Fax: +351239790701
Rua Luis Reis Santos Email: teresa.vieira@dem.uc.pt
Coimbra 3030-788, Portugal
Vieira, FPCE, University of Lisbon Tel.: +351 21 781 62 80
Mariana Alameda da Universidade +351 96 150 44 44
1100 Lisboa, Portugal Fax: +351 21 781 62 89
470 PARTICIPANTS
Wonkovich, US Environmental Protection Agency Tel.: (202) 564-6989 or 6620

Betty 1200 Pennsylvania Avenue, NW 8101R Fax: (202) 564-2244
Washington, DC 20460, USA Email: Wonkovich.Betty@
epamail.epa.gov
AUTHOR INDEX
A F
Abdel-Hay, F.I..........................247 Figovsky, O. .............................275
Abdel-Mottaleb, M...................195 Figueira, J.R..............................179
Adlakha-Hutcheon, G. .............195 Fissan, H. ..................................233
Arcuri, A.S.A. .................. 299, 329 Foss Hansen, S.................. 329, 359
Asbach, C. ................................233
G
B
Gapurova, O..............................219
Baun, A. ...................................359 Gatti, A.M............................... 3, 83
Bayramov, A.A. .......................317 Glavin, A. ...................................67
Beilin, D. ..................................275 Gnewuch, H. ......................... 3, 225
Bennett, E. ..................................95 Gonzalez, M..............................351
Blank, N. ..................................275 Gorbunov, B. ............................225
Bonina, S.M.C. .........................139 Goss, G. ......................................95
Borling, P. ................................359 Goudey, S. .................... 53, 95, 149
C Grieger, K. ............................3, 369
Grossi, M.G.L...........................299
Casman, E.A.............................125 Gulledge, W..............................329
Chan-Remillard, S. ......... 3, 53, 149
Chappell, M. ............... 95, 111, 179 H
Cho, S.Y. ..................................287 Handy, R. .................................369
Crane, M. . ................................369 Haruvy, N. ................................385
Cummins, E. .............................161
I
D
Ieleiko, L. ...................................67
Darnault, C.J.G. ........................139
Davis, T.A. ...............................329 J
de Carvalho, R.G. .....................437 Jackson, P.R. ............................225
Depledge, M. ...................... 95, 369
K
E
Kaczmar, S..................................95
Elder, A. ................................. 3, 31 Kamper, A. ...............................359
El-Newehy, M.H. .....................247 Kapustka, L. .............. 53, 149, 329
Endres, C. .................................287 Karkan, D..................................330
Estrin, Y. ..................................287 Kearns, P. .................................351
Evgrafova, S. ............................287 Kenawy, E. .......................... 3, 247
471
472 AUTHOR INDEX
Khaydarov, R.A................ 219, 287 R

Khaydarov, R.R. ....... 195, 219, 287
Ramadan, A.B.A. ............... 96, 265
Korenstein, R. ...................... 4, 195
Rinaldi, A..................................299
Kozyrev, S. ...............................309
Rodriguez, F. ............................351
Kuhlbusch, T.A.J.................. 4, 233
Rudnitsky, R. ................................4
L
S
Lee, K. ......................................351
Satterstrom, F.K. ......................329
Linker, F. ......................................4
Savolainen, K................................4
Linkov, I. .......... 179, 330, 369, 423
Scheper, T.................................287
Lowry, G.V. .............................125
Seager, T.P. ..............................423
Luis, S. .....................................437
Shafy Haraza, M.A. ..................329
Lynch, I. ................................. 3, 31
Shalhevet, S. .............................385
M Shvedova, A..................................5
Snee, P.T. .................................139
Maia, P.A. ................................299
Sorochinska, J. ...........................67
Martins, P.R..............................299
Srdjevic, B. ....................... 330, 409
Matias, S. ......................................4
Srdjevic, Z. ...............................409
Melkonyan, M. ................. 309, 330
Stamm, H. .................................195
Merad, M. .................................179
Steevens, J. ......................... 95, 179
Metcalfe, C. ................................95
Stuer-Lauridsen, F. ...................359
Michelson, E.S. . ......................361
Suvocarev, K. ...........................409
Mikhailenko, V...........................67
Monica, J. .................................330 T
Montanari, S. ..............................83
Tervonen, T. .............................179
Monteiro-Riviere, N.A. .......... 4, 43
Muir, R. ....................................225 U
N Uyusur, B..................................139
Nadagouda, M.N. .....................209 V
O Varma, R.S. ...................... 195, 209
Vaseashta, A. .................... 195, 397
O’Brien, N. .................................95
Oki, N. ......................................351 W
Owen, R............................ 330, 369
Wnek, G.E. ...............................247
P
Z
Palma-Oliveira, J.M. ........ 330, 437
Picado, A. ...................................95 Zhang, L.W. ...............................43
Zoranovic, T. ............................409
Pinto, A.C. ................................299
Pinto, V.R.S..........................4, 299
Priest, N.D. ...............................225

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Nanomaterials: Risks and Benefits

NATO Science for Peace and Security Series

A. Chemistry and Biology Springer

Series C: Environmental Security

Published in cooperation with NATO Public Diplomacy Division

Library of Congress Control Number: 2008941252

ISBN 978-1-4020-9490-3 (PB)

Printed on acid-free paper

All Rights Reserved

Part 1. Human Health Risks

Human Health Risks of Engineered Nanomaterials: Critical Knowledge

Part 2. Environmental Risk

SMARTEN: Strategic Management and Assessment of Risks and Toxicity

Visualization and Transport of Quantum Dot Nanomaterials

Part 3. Technology and Benefits

Nanomaterials, Nanotechnology: Applications, Consumer Products, and

Part 4. International Perspectives

Processing of Polymer Nanofibers Through Electrospinning

Silver Nanoparticles: Environmental and Human Health Impacts ...................... 287

Part 5. Policy and Regulatory Aspects

Considerations for Implementation of Manufactured Nanomaterial Policy

Knowing Much While Knowing Nothing: Perceptions and Misperceptions

Participants ......................................................................................................... 463

Author Index....................................................................................................... 471

U.S. Army Engineer Research and Development Center Jeff Steevens

I. Linkov and J. Steevens (eds.), Nanomaterials: Risks and Benefits, 3

Abstract. There are currently hundreds of available consumer products that

Nanomaterials are commonly described as having at least one dimension smaller

environmental settings; the physicochemical characteristics of the material at the

2. Characterization of Nanomaterial Exposure

Although there is potential for occupational and environmental exposures to

2.1. NANOMATERIALS CHARACTERIZATION

2.2. CHARACTERIZATION OF EXPOSURES

Assessing external human exposure to nanomaterials requires knowledge regarding

2.2.1. Measurement Methods

Measurement methods for detection of airborne (nano-) particles can be char-

2.2.2. Measurement Strategies

One measurement challenge is the differentiation of environmental (background)

2.2.3. Levels of Exposure

2.2.4. Future Tasks

Results are eagerly awaited from ongoing investigations focusing on possible

3. Barrier Function of Skin, Gastrointestinal Tract, and Respiratory Tract

3.1. GASTROINTESTINAL TRACT

The gastrointestinal (GI) tract is not likely to be a primary route of exposure to

3.2.1. Potential for Nanomaterials Skin Penetration

3.2.2. Factors that Affect Penetration Through Skin

3.2.3. Potential for Nanomaterials Absorption into Blood from Skin

The evaluation of nanomaterial absorption into blood is a complex matter, so

3.3. RESPIRATORY TRACT

3.3.1. The Pulmonary Epithelial Barrier

3.3.2. Fate of Nanoparticles that Cross the Alveolar Epithelial Barrier

An important factor in assessing the toxicity of nanomaterials is their distribution

4. Nanomaterials Interactions with Biomolecules

4.1. INTERACTIONS WITH PROTEINS

hydrated fullerene significantly improved the performance of a cognitive task in

4.2. INTERACTIONS WITH LIPIDS

Binding of lipoprotein complexes to nanoparticles could potentially explain

5. Mechanisms of Response to Nanomaterials

increases in intracellular calcium and cytokine induction [111]. These responses

Knowledge regarding the biodistribution of nanomaterials as well as the mecha-

7.1. ACCEPTABLE SCREENING STRATEGIES

In general, there are no commonly accepted screening assays for nanomaterials

7.2. SUMMARY OF URGENT RESEARCH NEEDS