ENVIRONMENTAL DEFENSE

Quantum Leaps:
Knowledge gaps in nanotechnology
health and safety
John M. Balbus, MD, MPH
Chief Health Scientist
ENVIRONMENTAL DEFENSE

Overview
• Introduction: growth of EH and S research
• Early answers to early questions
• First data addressing hypothetical risks
• Managing uncertain risks

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Research is beginning to
accumulate…
Scientific Journal Articles on Nanotechnology and Toxicity,
1982-2007
300
250
200
150
100
50
Number of Articles
0

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007*
1982-1995
Year of Publication

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And the budget for research is

growing…
Total 1500 125 EH&S
research research
funding 1250 100 funding
($M) ($M)
1000
75 NIOSH
OTHER
750 EPA
50 USDA
500 NASA
NIST
250 25 NIH
DOE

0 0 DOD
NSF
'00 '01 '02 '03 '04 '05 '06 07E 08P EH&S

Fiscal Year
Sources: National Science Foundation, National Science and Technology Council; NNI 2008 Budget (http://www.nano.gov/NNI_08Budget.pdf);
(
NNI 2007 Budget (http://www.nano.gov/NNI_07Budget.pdf)
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Why have special concerns with

nanoparticles?
• Analogy to fine particle
pollution
– Ability to move around the body
– Possible shared mechanisms of
toxicity
• Size is uniquely suited to
interact with biological
machinery

http://www.transportation.anl.gov/research/engine/diesel_structure.html
www.nanowerk.com/spotlight/spotid=2019.php Nanotechnology Project
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What we need to assure safety

• Reliable ways to detect and measure nanoparticles in
air, water, food
• Understanding of distribution and persistence of
nanomaterials in the body
• Reliable testing methods for both acute and chronic
toxicity
• Test results for range of materials and endpoints
• Assurance that protective technologies work for
nanoparticles

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Early findings of a young science…

• What properties affect the
transport and toxicity of a
nanoparticle?
• Do nanoparticles
accumulate in the body?
• How do nanoparticles
behave in the natural
environment?

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The superficial is
profound…

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Differential Penetration of QDs with

Different Surface Treatments

PEG-Coated NH2-Coated COOH-Coated

Ryan-Rasmussen, 2006

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Surface treatments of CNT’s

determine where they go

Liu et al., 2007

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QD size determines excretion

Choi et al., 2007 Nanotechnology Project

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Early data on key questions

• What properties affect the transport and
toxicity of a nanoparticle?
– Surface treatment, size critical
• Do nanoparticles accumulate in the body?
– Some do, some don’t; percent retained tends to
be low, no long term studies

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Agitation may be required to

generate high air concentrations

Maynard et al. 2004 Nanotechnology Project

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Sanding processes release nanoparticles
http://www.pnl.gov/nanotoxicology/capability.asp?id=20

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Early surprises in carbon

nanoparticle environmental fate
• Conventional wisdom:
– Carbon nanoparticles just stick to soil

• Studies show:
– Carbon nanotubes dissolve in Georgia river water
– Buckyballs form soluble, toxic nano-crystals

–Hyung et al. 2007

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Past as prologue? Learning by analogy

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Hypothetical: Nanoparticles scar

lungs like asbestos
• Carbon nanotubes are
fiber-like
• Early studies showed
inflammation,
activation of toxic
oxygen (ROS)

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What do early studies show?

• Nanoparticles poorly cleared by white blood cells
(macrophages) in the lung
• Carbon nanotubes cause short-term inflammation
– Iron contaminants lead to much greater inflammation
• Two CNT studies show surprising lung fibrosis or growths
– Appeared in the absence of ongoing inflammation
• No study has looked for effects longer than 90 days

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Hypothetical: nanoparticles harm the heart

like fine particle air pollution
• Nanoparticles are
small enough to go
through the lungs
• Early lab and
mouse studies
show similar types
of damage

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Carbon nanotubes caused aortic plaques

in mice
• Instilled SWCNTs damaged
lung, aorta, and heart tissue

• Mice developed aortic DNA

damage at 7, 28, and 60 days
after exposure

• Repeated exposure to SWCNTs

resulted in accelerated plaque
formation in mice fed high fat
diet

Li et al. 2007

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Hypothetical: Nanoparticles containing

toxic metals convey risk

http://www.orau.org/ptp/collection/shoefittingfluor/shoe.htm Nanotechnology Project

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Quantum dots vary in toxicity

• Studies have shown cellular
toxicity, DNA damage
(Hardman, 2007,Green 2005 )
– Longer exposure times more
likely to show toxicity
• Use of cadmium raises
concerns
– Long-term stability of caps
not certain
– Widespread applications may
lead to environmental loading

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Hypothetical: Nanoparticles disrupt

proteins like prions
• Nanoparticles
translocate to the
brain
• Uniform nature of
nanoparticles may
alter proteins within
cells

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Olfactory Nerve Translocation Pathway:

Slide courtesy Dr. Eva Oberdorster

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Images used with Project
permission
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Early studies suggest importance of

protein binding
• Serum protein binding
facilitated uptake in the liver
and spleen
• Two different types of
nanoparticles sped up the
creation of Alzheimer-like
protein fibrillation
– Study used extreme
conditions- needs to be
replicated in more life-like
conditions

Linse et al., 2007

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More than quantum leaps

• Enormous gaps remain
– Chronic toxicity-virtually no long-term test
results available
– Effects on development, nervous system,
immune system, etc., largely untested
– Very few data on environmental fate and
transport, ecotoxicity

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Temporary bridges
• Using the best available information to
make decisions
• Increasing the budget and focus of
governmental funded research
• Protecting workers and the environment in
the face of uncertainty

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Four Keys to Getting Nano Right

I. Significant increase in
government risk-research
investment
II. Close nano-loopholes in
regulations
III. Voluntary interim standards
IV. Meaningful stakeholder
engagement

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ED-DD Nano Risk Framework

Iterate

Profile
Lifecycle(s)

Describe Properties Decide,

Review
Material Evaluate Assess Risk Document
&
& Risks Mgmt &
Hazards Adapt
Application Act

Exposure

Assess, prioritize & generate data

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Conclusions
• Nanoparticles defy generalization
• Surface properties determine behavior and toxicity
• Few nanoparticles show significant short-term
toxicity
• Early studies suggest some novel and some known
toxic mechanisms
• Very little known about long-term effects
• Risk management guidance is available

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www.nanoriskframework.com

www.environmentaldefense.com\go\nano

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