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A cleanroom or clean room is an environment, typically used in manufacturing or

scientific research, with a low level of environmental pollutants such as dust, airborne microbes,
aerosol particles, and chemical vapors. More accurately, a cleanroom has a controlled level of
contamination that is specified by the number of particles per cubic meter at a specified particle
size. To give perspective, the ambient air outside in a typical urban environment contains
35,000,000 particles per cubic meter in the size range 0.5 m and larger in diameter,
corresponding to an ISO 9 cleanroom, while an ISO 1 cleanroom allows no particles in that size
range and only 12 particles per cubic meter of 0.3 m and smaller. In the pharmaceutical
industry, clean rooms play a crucial role in the manufacturing of pharmaceutical products which
are required to be free from microbial and particulate contamination and required to be protected
from moisture. Such pharmaceutical products are manufactured and manipulated in cleanrooms,
which are fitted with HEPA and, if required, ULPA filters as well as dehumidifier systems
Cleanrooms can be very large. Entire manufacturing facilities can be contained within a
cleanroom with factory floors covering thousands of square meters. They are used extensively in
semiconductor manufacturing, biotechnology, Nanotechnologythe, life sciences, and other fields
that are very sensitive to environmental contamination.
The air entering a cleanroom from outside is filtered to exclude dust, and the air inside is
constantly recirculated through high-efficiency particulate air (HEPA) and/or ultra-low
particulate air (ULPA) filters to remove internally generated contaminants.
Staff enter and leave through airlocks (sometimes including an air shower stage), and
wear protective clothing such as hoods, face masks, gloves, boots, and coveralls.
Equipment inside the cleanroom is designed to generate minimal air contamination. Only
special mops and buckets are used. Cleanroom furniture is designed to produce a minimum of
particles and to be easy to clean.
Common materials such as paper, pencils, and fabrics made from natural fibers are often
excluded, and alternatives used. Cleanrooms are not sterile (i.e., free of uncontrolled microbes)
only airborne particles are controlled. Particle levels are usually tested using a particle counter
and microorganisms detected and counted through environmental monitoring methods.
Some cleanrooms are kept at a positive pressure so if any leaks occur, air leaks out of the
chamber instead of unfiltered air coming in.
Some cleanroom HVAC systems control the humidity to low levels, such that extra
equipment ("ionizers") is necessary to prevent electrostatic discharge problems.

Low-level cleanrooms may only require special shoes, with completely smooth soles that
do not track in dust or dirt. However, for safety reasons, shoe soles must not create slipping
hazards. Access to a cleanroom is usually restricted to those wearing a cleanroom suit.
In cleanrooms in which the standards of air contamination are less rigorous, the entrance
to the cleanroom may not have an air shower. An anteroom (known as a "gray room") is used to
put on clean-room clothing.
Some manufacturing facilities do not use fully classified cleanrooms, but use some
cleanroom practices to maintain their contamination requirements.
The purpose of the cleanroom is to isolate the product from contaminants that cause
product rejection by your quality control. This is done by keeping contaminants out of the
facility or, should they enter, by removing them before they do damage.

Cleanrooms are typically kept at an air pressure slightly higher than surrounding space to
provide a limited amount of exfiltration and thereby prevent leakage of contaminated air into the
cleanroom. A pressure on the order of 0.05 inches of water column is appropriate for your
starter clean room. Higher pressures are more expensive, produce higher air noise, and are
rarely required. A negative pressure clean room, one intended to prevent clean room air from
leaking outward is possible, but unusual, and the need for such a design should be carefully
studied before making an investment.
Other parameters, such as lighting level and quality, sound level, vibration, and air velocity,
should be addressed as appropriate for specific nanotech applications.
design of the conditioning system and of the filtered air recirculation system are usually best
addressed separately. Application of filter fan units offers a neat solution to the requirement for
high airflow rates of filtered air (Figure 2).


Nanotechnology product research and development eventually calls for a

pilot line that permits the production process to be examined, fine tuned, and
scaled up as volume increases. Often the facility serves to generate cash as small
lots of product are manufactured for introduction to the marketplace. The small
scale cleanroom facility offers the environment of a full scale production facility,
provides the stringent environment commonly required for nanotechnology
product manufacture, enables the process to be evaluated in a real environment,
and offers the opportunity to establish real yields upon which financial projections
can be based, all this at a reasonable cost per square foot so important to a start-up


Nanomaterials are defined as ultrafine particles with a dimension of one to
100 nanometers in diameter. One nanometer is one-billionth of a meter. Lowsolubility ultrafine particles are more toxic than larger particles on a mass-for-mass
basis. In addition to the hazardous properties of the chemical constituents, their

smaller dimensions, larger surface area, and ability to penetrate cell membranes
more easily than larger particles add to the hazardous properties of these materials.
Because of their small particle size, they can be deposited deep into the
lungs and, once in the bloodstream, may be able to cross the blood-brain barrier.
Exposure to these materials during synthesizing processes and use may occur
through inhalation, ingestion, and contact with the skin or eyes. Other hazards to
consider are catalytic effects and fire or explosion. Particles in the nanometer size
range are currently being evaluated for toxicity and critical exposure levels based
on mass, surface area, and the number of particles per unit volume. Until these
factors are determined workers should implement stringent controls on exposure
when working with them. The following guidelines, modified from the American
Chemical Society, are provided to educate and protect those working with


1.Use good general laboratory safety practices as found in this Laboratory
Chemical Safety Plan. Wear gloves, lab coats, safety glasses, face shields, closedtoed shoes as needed.
2.Be sure to consider the hazards of precursor materials in evaluating process
hazards. OSHA's "Particularly Hazardous Substances" (such as cadmium) must be
handled in a containment such as a fume hood or a glove box.
3.Avoid skin contact with nanoparticles or nanoparticle-containing solutions by
using appropriate personal protective equipment. Do not handle nanoparticles with
your bare skin.
4.If it is necessary to handle nanoparticle powders outside of a HEPA-filtered
powered-exhaust laminar flow hood, wear appropriate respiratory protection. The
appropriate respirator should be selected based on professional consultation with
5.Use fume exhaust hoods to expel fumes from tube furnaces or chemical reaction

6.Dispose of and transport waste nanoparticles according to the hazardous

chemical waste guidelines.
7.Vacuum cleaners used to clean up nanoparticles should be factory tested, HEPAfiltered units.
8.Equipment previously used to manufacture or handle nanoparticles should be
evaluated for potential contamination prior to disposal or reuse for another
9.Lab equipment and exhaust systems should also be evaluated prior to removal,
remodeling, or repair.
10.Given the differing synthetic methods and experimental goals, no blanket
recommendation can be made regarding aerosol emissions controls. This should be
evaluated on a case by case basis.
11.Consideration should be given to the high reactivity of some nanomaterials with
regard to potential fire and explosion hazards.
Steps Required for Implementing a Nanotechnology Research Safety Program
Amend the Laboratory Safety Plan (Appendix F) to include specific safety requirements for
work with Nanotechnology
This Laboratory Safety Plan (LSP) describes policies, procedures, equipment, personal
protective equipment and work practices that are capable of protecting employees from the
health hazards in laboratories. The LSP is intended to safely limit laboratory workers'
exposure to hazardous substances.

Evaluate workplaces for the presence of hazardous substances, harmful physical

agents, and infectious agents.
Monitor workplace exposure if there is reason to believe that the exposure will
exceed an action level, PEL or cause adverse health effects.
If exposures to any regulated substance routinely exceed an action level or
permissible exposure level there must also be employee medical exposure
Provide training to employees concerning those substances or agents to which
employees may be exposed.
Written information on agents must be readily accessible to employees or their
Labeling requirements for containers of hazardous substances and equipment or
work areas that generate harmful physical agents.

Nanoparticles are likely to be dangerous for three main reasons:
1. Nanoparticles may damage the lungs. We know that 'ultra fine' particles from diesel
machines, power plants and incinerators can cause considerable damage to human lungs.
This is both because of their size (as they can get deep into the lungs) and also because
they carry other chemicals including metals and hydrocarbons in with them.
2. Nanoparticles can get into the body through the skin, lungs and digestive system. This
may help create 'free radicals' which can cause cell damage and damage to the DNA.
There is also concern that once nanoparticles are in the bloodstream they will be able to
cross the blood-brain barrier.
3. The human body has developed a tolerance to most naturally occurring elements and
molecules that it has contact with. It has no natural immunity to new substances and is
more likely to find them toxic.
The danger of contact with nanoparticles is not just speculation. As more research is undertaken,
concerns increase. Here are some of the recent findings:

some nanoparticles cause lung damage in rats. Several studies have shown that carbon
nanotubes, which are similar in shape to asbestos fibres, cause mesothelioma in the lungs
of rats (see below)

other nanoparticles have been shown to lead to brain damage in fish and dogs

a German study found clear evidence that if discrete nanometer diameter particles were
deposited in the nasal region (in rodents in this case), they completely circumvented the
blood/brain barrier, and travelled up the olfactory nerves straight into the brain

inhaled carbon nanotubes can suppress the immune system by affecting the function of T
cells, a type of white blood cell that organises the immune system to fight infections.

What are the health and safety concerns about

It is a difficult question to answer as each nanoparticle (like each chemical) can have its
own unique effects. The effects of the nanoparticles are not only based on the chemical
characteristics - the shape, size, surface texture, surface charge and other factors can all impact
how the nanoparticles might affect our health. In addition, the nano-sized particle may not have
the same characteristics as its normal particles (including when the nanoparticle created from

the same chemical or material). Nanoparticles are also being studied for their ability to cause
fires or explosions, or if they can play a role as a catalyst (a substance that causes or accelerates a
chemical reaction).
The Health and Safety Executive (HSE) in the United Kingdom cautions "We do not recommend
that you rely on hazard information for 'similar' nanomaterials in your risk assessment unless you
have good data to confirm this approach is appropriate."
In 2010, the Institut de recherche Robert-Sauv en sant et en scurit du travail (IRSST)
reported the following:
"... the information available about the hazards specific to these substances is still very
fragmentary. The literature gives us very little information specific to NP [nanoparticles] relating
to their physical hazards like fires or explosions. As for health hazards, many toxicological
studies on different substances have demonstrated toxic effects on various organs. It is found that
in general, an NP will normally be more toxic than the same chemical substance of larger
dimensions, but it is currently impossible to determine which measuring parameter for exposure
is best correlated with the measured effects. The evaluation of occupational exposure must
therefore address a series of different parameters, and the exposure data available are relatively
rare. It should also be noted that at the present time, attention is particularly focused on carbon
nanotubes (CNT), which seem to show, in different animal studies, toxicity similar to that of
asbestos and consequently causing great concern in the international scientific community,
This concern regarding carbon nanotubes (CNTs) and other biopersistent high aspect ratio
nanomaterials (HARNs) is also noted by the HSE which states "in view of the evidence for lung
damage and lack of information on the effects of long-term repeated exposure, a higher level of
control is warranted for CNTs and biopersistent HARNs."
The National Institute for Occupational Safety and Health (NIOSH) reports that low solubility
nanoparticles are more toxic than larger particles on a mass for mass basis. It is likely that the
particle surface area and surface density are factors. NIOSH also states the following health

Animal and human studies have shown that airborne nanoparticles can be deposited in
the respiratory tract. Animal studies have also shown nanoparticles with the ability to
enter the blood and move to other organs.

Animal studies have shown that nanoparticles show more effects than large particles of
similar composition (showing pulmonary inflammation and lung tumors when inhaled).

Studies in animals and cells have shown changes in the nanoparticles chemical
composition, structure, and size make a difference in their properties and toxicity.

Workers exposed to fine or ultrafine particles have shown lung effects.

How can you control exposure to nanoparticles?

There have been limited studies done the possible exposure to nanoparticles to a worker. As with
any process, workers can be exposed through the manufacturing process, as well as the
maintenance and clean up of the equipment.
The exposure potential is dependant on the following:

Characteristics of the material.

Amount of the material.

Whether the particles are dry or in a solution.

Degree of containment.

Duration of use.

Many studies indicate that the toxicity of particles increase when there is a decrease in diameter
size and an increase in the surface area. This characteristic must be taken into account when
conducting risk assessments.
In the absence of any other evidence, precautionary measures should be used.
Control measures can be implemented using the hierarchy of control principles. First, try to
eliminate the exposure. If you are unable to eliminate the exposure, then engineering solutions
should be investigated including ventilation and source enclosures. NIOSH states that "current
knowledge indicates that a well-designed exhaust ventilation system with a high-efficiency
particulate air (HEPA) filter should effectively remove nanomaterials". Education and training in
safe handling is essential. Separate eating rooms and change facilities are good options. While
personal protective equipment (PPE) is being studied to determine if current models offer
adequate protection from nanoparticles, use of such equipment can be considered as part of a
complete health and safety risk management program. When any PPE is used, it should be done
so as part of a complete PPE program. Health monitoring may also be considered.
NIOSH indicates the following examples as areas or activities where exposure could occur:

Working with nanomaterials in liquid media without adequate protection (e.g., gloves).

Working with nanomaterials in liquid during pouring or mixing operations, or where a

high degree of agitation is involved.

Generating nanoparticles in non-enclosed systems.

Handling (e.g., weighing, blending, spraying) powders of nanomaterials.

Maintenance on equipment and processes used to produce or fabricate nanomaterials and

the cleaning-up of spills and waste material containing nanomaterials.

Cleaning of dust collection systems used to capture nanoparticles.

Machining, sanding, drilling, or other mechanical disruptions of materials containing


If nanoparticles are used in your facility, make the effort to find and understand the most current
research in this area. NIOSH encourages workplaces where employees may be exposed to
engineered nanoparticles to:

Take prudent measure to control workers exposures to nanoparticles.

Conduct hazard surveillance as the basis for implementing controls.

Continue use of established medical surveillance approaches.

Nanoparticles appear to enter the body the same way other particles - through inhalation,
ingestion or absorption through the skin. While there is no cut off in size that makes particles
toxic or non-toxic, some studies have shown that as particles become smaller, there is an
increased likelihood of injury to occur.
In all cases, more studies are needed to determine the health concerns for humans. How a
nanoparticle enters the body and the effect it may have depends on many factors including:

Surface area.



Composition / chemistry.




Current research indicates the following:


Nanoparticles can be deposited in all areas of the respiratory tract depending on the size and
composition of that particular nanoparticle. They can also enter the blood and lymph circulation
systems and be distributed throughout the entire body. When in the blood system, they can be
taken up by the liver, spleen, bone marrow, heart and other organs.

Nanoparticles can also cross the skin and possibly reach other organs. There are indicators that
particles can accumulate around hair follicles and when the follicle opens, the particles can reach
deeper levels.

There is also some animal study evidence that the nanoparticles may be able to enter the body
though nerves, usually the olfactory nerves and bulbs in the nose (the "nerves of smell"), and
move along the axons and neurons of the central nervous system.
Digestive system

While this area is not as well researched, early studies have shown nanoparticles tend to pass
through the gastrointestinal (GI) tract and are eliminated quickly. Again, this effect is dependant
on the properties of the specific nanoparticle.

Work Practices
Nanomaterial design
o Use synthetic wet methods, and bind nano materials to substrate,
whenever possible.
o Use green chemistry techniques to minimize toxicity of intermediates, and
of waste products.
o Always consult available literature on known, or suspected, hazards (bulk
and nanoscale).
o Establish laboratory standard operating procedures for specific, repeated,
operations that are believed to be high risk.
Laboratory safety equipment ensure availability, and train upon use, of standard
emergency equipment (e.g. eyewash, safety showers, extinguishing agents, and
emergency notification systems).
Laboratory Hygiene refer to the laboratory Chemical Hygiene Plan
o Do not eat, drink, or apply cosmetics in a laboratory.
o Never mouth pipet.
o Do not allow contaminated gloves to contact public surfaces expected to
be free of hazards.

o Wash hands frequently; especially upon completion of laboratory work,

and prior to the consumption of food or drink.
Labeling, Signage, and Designated Work Areas
o Control potential exposure by having clearly designated work areas for
activities of high, or unknown, risk. This is accomplished via signage,
caution tape, or other standard visible communication mechanisms that
will be understood by all staff (including non-scientist support staff).
o Label all containers, including hazardous wastes, to plainly indicate the
presence of all constituents, including nanomaterials (e.g. include the term
nano in the chemical descriptor).
Housekeeping, and Waste Generation
o Protect surfaces with disposable bench paper, and/or wet-wiping daily.
o Schedule regular cleaning of the entire work area either via wet-wiping, or
an approved laboratory HEPA vacuum. Note: change out HEPA
cartridges in a fume hood.
o Nanoparticle contaminated solid wastes should be managed as potentially
hazardous wastes.
Transportation of materials use sealed container, and secondary containment,
when transporting materials within the laboratory and between laboratories.