sign in sign up
<<
Home , Impact of nanotechnology

Interim Guideline for Working Safely with (Based on the Most Current NIOSH Information at 01-Sep-2005. This Interim guideline will be revised on completion of the National Nanotechnology Research Agenda and NIOSH Recommendations)

What is Nanotechnology?

Nanotechnology is somewhat loosely defined, although in general terms it covers engineered structures, devices and systems that have a length scale of 1 – 100 nanometers1. At these length scales, materials begin to exhibit unique properties that affect physical, chemical and biological behavior. Researching, developing and utilizing these properties is at the heart of the new .

Nanotechnology is the understanding and control of matter at dimensions of roughly 1 to 100 nanometers, where unique phenomena enable novel applications1. A nanometer is one-billionth of a meter; a sheet of paper is about 100,000 nanometers thick. Encompassing nanoscale science, engineering and technology, nanotechnology involves imaging, measuring, modeling, and manipulating matter at this length scale.

At this level, the physical, chemical, and biological properties of materials differ in fundamental and valuable ways from the properties of individual atoms and molecules or bulk matter. Nanotechnology R&D is directed toward understanding and creating improved materials, devices, and systems that exploit these new properties.

Medical researchers work at the micro- and nano-scales to develop new drug delivery methods, therapeutics and pharmaceuticals. For instance, DNA, our genetic material, is in the 2.5 nanometer range, while red blood cells are approximately 2.5 micrometers1. Nanotechnology involves the creation and/or manipulation of materials at the nanometer (nm) scale either by scaling up from single groups of atoms or by refining or reducing bulk materials. A nanometer is 1 x 10-9 m or one millionth of a millimeter. To give a sense of this scale, a human hair is of the order of 10,000 to 50,000 nm, a single red blood cell has a diameter of around 5000 nm, viruses typically have a maximum dimension of 10 to 100 nm and a DNA molecule has a diameter of 2 – 12 nm1.

The use of the term “nanotechnology” can be misleading since it is not a single technology or scientific discipline. Rather it is a multidisciplinary grouping of physical, chemical, biological, engineering, and electronic, processes, materials, applications and concepts in which the defining characteristic is one of size.

Background

The past decade has seen intense interest in developing based on the unique behavior of nanometer-scale (nanoscale) structures, devices and systems, leading to the rapidly expanding and highly diverse field of nanotechnology. Interim Guideline for Working Safely with Nanotechnology

Although many are still in the pre-competitive stage, nanoscale materials are increasingly being used in optoelectronic, electronic, magnetic, medical imaging, drug delivery, cosmetic, catalytic and materials applications. Between 1997 and 2003, worldwide government investment in the field rose from $432 million a year to just under $3 billion a year, and the global impact of nanotechnology-related products is predicted to exceed $1 trillion by 20152.

NIOSH is unaware of any comprehensive statistics on the number of people in the U.S. employed in all occupations or industries in which they might be exposed to engineered, nano-diameter particles in the production or use of . Perhaps because of the relative newness of the nanotechnology industry, there appear to be no current, comprehensive data from official survey sources, such as the U.S. Bureau of Labor Statistics (BLS).

Occupational Risks

Existing research shows there is little evidence to suggest that the exposure of workers arising from the production, handling, and processing of has been adequately assessed6. Current knowledge is inadequate for purposes6. No information has been identified about worker exposures to nanoparticles in the university/research sector or in the new companies6.

Occupational health risks associated with and using nanomaterials are not yet clearly understood. The rapid growth of nanotechnology is leading to the development of new materials, devices and processes that lie far beyond our current understanding of environmental and human impact. Many nanomaterials and devices are formed from nanometer-scale particles (nanoparticles) that are initially produced as aerosols or colloidal suspensions. Exposure to these materials during manufacturing and use may occur through inhalation, dermal contact and ingestion. Minimal information is currently available on dominant exposure routes, potential exposure levels and material toxicity. What information does exist comes primarily from the study of ultrafine particles (typically defined as particles smaller than 100 nanometers).

Studies have indicated that low solubility ultrafine particles are more toxic than larger particles on a mass for mass basis. There are strong indications that particle surface area and surface chemistry are primarily responsible for observed responses in cell cultures and animals. There are also indications that ultrafine particles can penetrate through the skin, or translocate from the respiratory system to other organs. Research is continuing to understand how these unique modes of biological interaction may lead to specific health effects.

Workers within nanotechnology-related industries have the potential to be exposed to uniquely engineered materials with novel sizes, shapes and physical and chemical properties, at levels far exceeding ambient concentrations. To understand the impact of these exposures on health, and how best to devise appropriate exposure monitoring and

Page 2 of 11 Interim Guideline for Working Safely with Nanotechnology control strategies, much research is still needed. Until a clearer picture emerges, the limited evidence available would suggest caution when potential exposures to nanoparticles may occur.

NIOSH Activities

A number of active research programs within NIOSH are investigating ultrafine and nanoparticle behavior, and the health risks associated with nanomaterials. A NIOSH Nanotechnology Research Center is being developed that will coordinate institute-wide nanotechnology-related activities. The Institute is also working with other agencies to address health issues associated with nanotechnology, including participation in the National Nanotechnology Initiative3 and the Nanoscale Science, Engineering and Technology subcommittee of the National Science and Technology Council committee on technology (NSET). Building on these initiatives, NIOSH is developing a strategic plan to address immediate and long-term issues associated with nanotechnology and occupational health in partnership with other federal agencies, research centers and industry.

NIOSH, the Environmental Protection Agency, and the National Science Foundation are seeking applications proposing research about the potential implications of nanotechnology and manufactured nanomaterials on human health and the environment. Further information is available at http://es.epa.gov/ncer/rfa/2004/2004_manufactured_nano.html

NIOSH’s key role in conducting and partnering in research on occupational exposures to nanomaterials is noted in a new strategic plan under the National Nanotechnology Initiative. The National Nanotechnology Initiative Strategic Plan: December 2004 charts the vision, goals, and plans by which NIOSH and partner agencies will work to expedite the responsible advancement of nanotechnology over the next 5 to 10 years, and to ensure that the U.S. will remain a world leader in nanotechnology research and development. The strategic plan is available at http://www.nano.gov/NNI_Strategic_Plan_2004.pdf

The NIOSH Nanotechnology and Health & Safety Research Program.

NIOSH is conducting a five-year multidisciplinary study into the toxicity and health risks associated with occupational nanoparticle exposure. Research will cover aerosol generation and characterization studies in the lab and in the field, toxicity studies investigating the significance of aerosol surface area as a dose metric, and cardiopulmonary toxicity and lung disease related to carbon nanotubes, and other nanoparticles. The Nanotechnology Safety and Health Research Program is coordinated by Vincent Castranova, Ph.D., who provided information and current recommendations for this Interim Guideline.

Knowledge Gaps

1: The nanoparticle nomenclature is not sufficiently well described or

Page 3 of 11 Interim Guideline for Working Safely with Nanotechnology agreed Currently there are no agreed definitions for nanoparticles, nanoparticle aerosols, or for the various types of nanoparticles which are produced. Definitions proposed need to define a size interval to take account of the distribution in sizes likely to be present, to consider whether the definition should be based on physical dimensions (e.g. length, diameter, surface area) or on some behavioral property such as diffusivity and take account of agglomerated aerosols. Progress on nomenclature issues is usually best achieved based on consensus. The planned conference on nanoparticle health risks (organized by HSE and NIOSH) will provide an ideal forum to discuss these issues.

2: There are no convenient methods by which exposures to nanoparticles in the workplace can be measured or assessed For inhalation, the most appropriate metric for assessment of exposure to most nanoparticles is particle surface area. Currently there are no effective methods available by which particle surface area can be assessed in the workplace. There is a need for more research into the development of new improved methods, combinations and strategies to provide reliable assessments of exposure to nanoparticles and nanoparticle aerosols. Development of appropriate methods to evaluate dermal and ingestion exposure is also necessary. HSE should consider how best to promote the development of appropriate metrics and approaches.

3: Insufficient knowledge concerning nanoparticle exposure is available Much more information is needed regarding the exposure of workers involved in the production of all of the various types of nanoparticles via all of the production processes. In the absences of suitable measurements systems, coherent approaches as described above should be adopted. At this stage there is insufficient evidence to judge whether exposure to the various forms of nanoparticles is occurring at significant levels in nanoparticle production processes. HSE should consider how to encourage such data to be collected.

4: The effectiveness of control approaches has not been evaluated Better understanding is required relating to the effectiveness of control of nanoparticles. This will be better informed given the development of appropriate methods for assessment of exposure to nanoparticles and a better understanding on the levels of exposure that may be acceptable. This is true for both inhalation, dermal and ingestion risks. HSE should consider how to promote the evaluation of control approaches.

5: Knowledge concerning nanoparticle risks is inadequate for risk assessments Current knowledge is inadequate for risk assessment. Risk assessment approaches will have to consider how best to use information which is currently available, and plan to collect new information. An effective strategy for collecting, storing and disseminating this information is also necessary. Development of appropriate databases, and other information resources that can be used to collect and disseminate information on studies to investigate

Page 4 of 11 Interim Guideline for Working Safely with Nanotechnology

exposure or toxicological assessment of nanoparticles is a key element in this. Researchers must document, collate, maintain and disseminate information relevant to nanoparticle risk issues.

Carbon Nanotubes

Perhaps the most significant spin-off product of research, leading to the discovery of the C60 "buckyball" by the 1996 Nobel Prize laureates Robert F. Curl, Harold W. Kroto, and Richard E. Smalley, are nanotubes based on carbon or other elements. These systems consist of graphitic layers seamlessly wrapped to cylinders. With only a few nanometers in diameter, yet (presently) up to a millimeter long, the length-to-width aspect ratio is extremely high. A truly molecular nature is unprecedented for macroscopic devices of this size. Accordingly, the number of both specialized and large-scale applications is growing constantly.

Carbon nanotubes are fullerene-related structures that consist of graphene cylinders closed at either end with caps containing pentagonal rings. They were discovered in 1991 by the Japanese electron microscopist Sumio Iijima who was studying the material deposited on the cathode during the arc-evaporation synthesis of . He found that the central core of the cathodic deposit contained a variety of closed graphitic structures including nanoparticles and nanotubes, of a type never previously been observed. A short time later, Thomas Ebbesen and Pulickel Ajayan, from Iijima's lab, showed how nanotubes could be produced in bulk quantities by varying the arc- evaporation conditions. This paved the way to an explosion of research into the physical and chemical properties of carbon nanotubes in laboratories all over the world.

A major event in the development of carbon nanotubes was the synthesis in 1993 of single-layer nanotubes. The standard arc-evaporation method produces only multilayered tubes. It was found that addition of metals such as cobalt to the graphite electrodes resulted in extremely fine tube with single-layer walls. The availability of these structures should enable experimentalists to test some of the theoretical predictions that have been made about nanotube properties.

Smalley’s group described an alternative method of preparing single-walled nanotubes in 1996. Like the original method of preparing C60, this involved the laser-vaporization of graphite, and resulted in a high yield of single-walled tubes with unusually uniform diameters. These highly uniform tubes had a greater tendency to form aligned bundles than those prepared using arc-evaporation, and led Smalley to christen the bundles nanotube "ropes". Initial experiments indicated that the rope samples contained a very high proportion of nanotubes with a specific armchair structure. Subsequent work has suggested that the rope samples may be less homogeneous than originally thought. Nevertheless, the synthesis of nanotube ropes gave an important boost to nanotube research, and some of the most impressive work has been carried out on these samples.

Studies into the propensity for carbon nanotubes to form an aerosol, while being handled, and the toxicity of nanotubes were recently published 4,5.

Page 5 of 11 Interim Guideline for Working Safely with Nanotechnology

Reasonable Control Strategies for Working with Nanoparticles in Engineering Research within TEES Facilities

Strategies to control exposure to nanoparticles will include:

• Total enclosure of the process • Storage of all nano-materials in total enclosure • Local exhaust ventilation, with HEPA filtration • General ventilation • Limitation of numbers of workers and exclusion of others • Reduction in periods of exposure, via SOP’s and personnel training • Regular cleaning of wall and other surfaces; documented cleaning schedule • Use of appropriate personal protective equipment • Prohibition of eating and drinking in laboratories and controlled areas • Transport of nano-materials within secondary containment device • Immediate cleanup of all spills & discharges • Collection of all nanoparticle waste materials for disposal in compliance with the TAMU Hazardous Waste Management Plan.

CONTROL OF EXPOSURE BY INHALATION6

Engineering control For air velocities prevailing in workplaces, airborne nanoparticles can be considered as having no inertia. They will therefore behave in a similar way to a gas and if not fully enclosed will diffuse rapidly and will remain airborne for a long time. Because of their high diffusion velocity, these particles will readily find leakage paths in systems in which the containment is not complete. Engineering control systems designed for use to control nanoparticles such as enclosures, local exhaust ventilation (LEV), fume hoods and general ventilation therefore need to be of similar quality and specification to that which is normally used for gases rather than for particulate challenges. These systems do exist and are in common use in the chemical and other industry. Like all such systems effective performance of these systems will be highly dependent on appropriate use and maintenance.

Engineering controls are widely used to reduce exposure to welding fume. A variety of methods are recommended including general ventilation, LEV, fume hoods and on-gun extraction (HSE, 1990). The level of protection provided by these methods is considered to be quite variable and dependent on issues previously mentioned such as maintenance and worker behavior. of this type are also used in the carbon black industry but as indicated earlier, significant exposure in this industry still occurs.

Filtration Filtration plays an important role in the control of exposure to airborne particles. High Efficiency Particulate Arrester (HEPA) filters are used in engineering control systems to clean the air before returning it to the workplace. These filters are usually referred to as mechanical filters.

Page 6 of 11 Interim Guideline for Working Safely with Nanotechnology

Filtration theory is well understood and has been extensively described by several authors (e.g. Brown, 1992). As an aerosol penetrates through a filter, the trajectories of the particles deviate from the streamline due to various well-understood mechanisms. As a result, particles may collide with the filter elements (fibers) and become deposited on them. The mechanisms include diffusion, interception, initial impaction and gravitational settling. Electrostatic forces can also play a role in some filter types.

For particles less than 100nm, Brownian diffusion is the dominant mechanism (Lee and Mukund, 2001). Filtration efficiency due to Brownian diffusion increases as particle size decreases. Brownian diffusion is caused by collisions between particles and the air molecules to create random paths that the particles follow. The random motion increases the probability of a particle contacting one of the filter elements. Once the particle is collected onto a surface it will adhere to it due to the Van der Waals forces. Therefore filters are likely to be good collectors of nanoparticles.

Current methods for certification of HEPA filters and for filters do not routinely require testing at particle sizes in the nanometer size range. Internationally recognized standards for HEPA filters (DOE, 1998) require that the filter is challenged with an aerosol with a mass median diameter of 300nm and that the particle collection efficiency is greater than 99.97%. Three hundred nanometers is considered to be a much more penetrating aerosol for these filters than nanometer size particles due to the decrease of Brownian diffusion at this particle size. Similarly European Standards for respirator filter cartridges (CEN, 2001a) and for filtering face pieces (CEN, 2001b) require that these systems are tested against sodium chloride aerosols with a mass median diameter of 300nm. Again this is based on an expectation that this would be the most penetrating size.

Little work has been done to quantify the performance of filters against particles in the nanometer size range. It is still widely accepted, that with diffusion the dominant mechanism and the efficiency of filters will be high.

Use of Personal Protective Equipment (PPE) Use of PPE such as and air fed devices may be used (as a final option) as a method of control for any airborne . All of these devices depend on filtration as a means of cleaning the air prior to it being breathed by the worker. The discussion relating to filtration applies equally here. It is probable, for all but the smallest nanoparticles (<2nm) that the filtration efficiency will be high. It was not possible to identify any relevant research that has demonstrated this.

Air-purifying respirators are widely used in diverse workplaces, and thanks to decades of research and experience, occupational health professionals have confidence that a NIOSH-certified device with the correct filter, and properly fit-tested, will provide appropriate protection against silica dust and other traditional airborne contaminants. But what about particles in the nanoscale range, which are significantly tinier than traditional particles? Will the same filter be equally efficient in capturing them? To answer that question, NIOSH recently issued a contract for a laboratory study by

Page 7 of 11 Interim Guideline for Working Safely with Nanotechnology scientists at the University of Minnesota. NIOSH is funding the contract for one year, ending March 2006.

Conventional knowledge, based on a substantial body of evidence, holds that airborne particles 0.3 micrometers in size are more likely to penetrate a filter than particles of other sizes. Particles larger than 0.3 um will be blocked by filter fibers. Those smaller than 0.3 um will be stuck on and among the fibers through a process called “diffusional capture.” Consequently, if a filter captures particles 0.3 um in size, scientists could be confident that the filter would capture particles of any size.

However, little experimental work has been done to quantify the performance of filters against particles in the nanometer size range. The NIOSH-funded study aims to determine if the accepted theory of filtration remains valid for particles on the borders of nanosize and below. If the study finds that the effectiveness of filters begins to decrease for nanosize particles, it will attempt to identify at what size this decrease is likely to occur. Preliminary findings from the study are to be presented at the second International Symposium on Nanotechnology and Occupational Health, at Minneapolis, Minn., Oct. 3-6, 2005.

“NIOSH’s support for this study is part of our commitment with many partners to address current questions about nanotechnology and occupational health, and to design exemplary research to help answer those questions,” said NIOSH Director John Howard, M.D. “In so doing, we will help to ensure that the U.S. remains strong and competitive in the dynamic global nanotechnology market.”

It is well recognized in the science of Industrial Hygiene, however, that the determining factor governing the effectiveness of respiratory protection equipment (RPE) against particulate challenges is not absolute penetration through the filter, but rather face-seal leakage that bypasses the device. Face seal leakage is dependent on many factors including the fit of the mask to the face, duration of wearing, work activity etc. Since it is expected that nanoparticle aerosols will have high mobility, it is possible that enhanced leakage will occur although no more than might be expected for a gas. No relevant research to quantify this has been identified.

CONTROLS FOR DERMAL EXPOSURE Issues relating to dermal exposure have only relatively recently come to prominence in . Based on our understanding of the various processes by which nanoparticles can be synthesized there seems to be a strong possibility of dermal exposure occurring, most likely in the later stages of the process i.e. recovery or resulting from surface contamination. There is some evidence that dermal exposure to nanoparticles may lead to direct penetration of nanoparticles into the epidermis and possibly beyond into the blood stream. Therefore, it may be necessary to introduce control to exclude or limit the level of dermal exposure likely to occur.

As for inhalation exposure, COSHH provides a framework by which a strategy to prevent or control dermal exposure can be developed. However, it is acknowledged that prevention of dermal exposure is not covered so well in the guidance associated with COSHH.

Page 8 of 11 Interim Guideline for Working Safely with Nanotechnology

As with control of exposure by inhalation, the first approach is enclosure of the process. This should certainly be achievable as powder-handling processes can be enclosed successfully. However in practice, particularly with products or processes that are in development, the main emphasis is on investment and expenditure at the synthesis end of the process. This is likely to limit the expenditure on sophisticated control and automation processes to deal with what will be perceived as relatively mundane tasks such as harvesting and packing of nanomaterials.

In any case even where such processes are in place, the requirements for attention to breakdowns, maintenance etc means that the possibility of dermal exposure cannot be excluded at all times. In these and other instances protection against dermal exposure typically consists of the use of Skin Protective Equipment (SPE) i.e. suits, gloves and other items of protective clothing.

Even for powders in the macro scale, it is recognized that SPE is very limited in its effectiveness to reduce or control dermal exposure. Based on current understanding (Schnieder et al; 2000) multiple processes contribute to dermal exposure, and the relative ineffectiveness of SPE. In addition to the classical view that the failure of SPE results from direct penetration or permeation of an agent through the material from which the equipment is constructed, other process include transfer of substances by direct contact between surface, skin and outer respectively inner clothing or gloves, and redistribution of substances between compartments of the same type, e.g. redistribution of contaminants from one part of the skin contaminant layer to another as a result of touching the face with contaminated fingers.

Current European testing for certification of PPE against dermal exposure only takes account of permeation or penetration. Although recently, new tests have been proposed which take account of the other human factors based on simulations (Brouwer et al; 2004). Since it is likely that nanoparticles which escape into the workplace will become widely dispersed and will have high surface area, it is likely that the human factor element will be even more critical than for macrosize particles. In this case, it is quite likely that SPE will be less effective against nanoparticles than against macro size particles. It is also quite likely that direct penetration of nanoparticles through the material from which the protective clothing is made will be higher than for macro-sized particles.

CONTROLS FOR INGESTION EXPOSURE Understanding about exposure by ingestion in the workplace is not currently well developed. It is considered that ingestion exposure in the workplace results primarily from hand-to-mouth contact. It follows that strategies that tend to reduce dermal exposure in the workplace will also tend to reduce exposure by ingestion. The converse of this is also true. At this point in time we have identified no relevant research that has successfully quantified exposure to nanoparticles by ingestion in the workplace or the effectiveness of strategies to reduce this exposure.

Page 9 of 11 Interim Guideline for Working Safely with Nanotechnology

References

1. NNI, What is Nanotechnology? www.nano.gov/html/facts/whatIsNano.html.

2. Roco, M. C., Broader societal issues of nanotechnology, J. Nanoparticle Res. 5, 181-189, 2003.

3. NNI, The National Nanotechnology Initiative www.nano.gov.

4. Maynard, A. D., Baron, P. A., Foley, M., Shvedova, A. A., Kisin, E. R., and Castranova, V., Exposure to Material: Aerosol Release During the Handling of Unrefined Single Walled Carbon Nanotube Material, J. Toxicol. Environ. Health 67 (1), 87-107, 2004.

5. Shvedova, A. A., Kisin, E. R., Murray, A. R., Gandelsman, V. Z., Maynard, A. D., Baron, P. A., and Castranova, V., Exposure to carbon nanotube material: Assessment of the biological effects of nanotube materials using human keratinocyte cells., J. Toxicol. Environ. Health 66 (20), 1909-1926, 2003.

6. Aitken, R.J., K.S. Creely, and C.L. Tran, Nonoparticles: An Occupational Hygiene Review. Institute of Occupational . HSE Books, Riccarton, Edinburugh. 2004. ISBN 0 7176 2908 2.

7. An evaluation of a university lab producing single walled carbon nanotubes reported: “Estimates of the airborne concentration of nanotube material generated during handling suggest that concentrations were lower than 53 µg/m3 in all cases.” However, “laboratory studies indicated that with sufficient agitation unrefined SWCNT material can release fine particles into the air.” J. Toxicol. Environ. Health Part A, 67:87-107, 2004.

8. Unrefined SWCNT are contaminated by up to 30% iron by weight. This iron is redox reactive and can generate hydroxyl radicals which cause oxidant injury to human cells in culture. J. Toxicol. Environ. Health Part A, 66:1901-1918, 2003.

9. Pharyngeal aspiration of 10 – 40 ug of purified SWCNT (containing 0.2% iron) in a mouse model resulted in an interstitial fibrotic reaction that progressed through 60 days post-exposure. Am. J. Physiol.: Lung Cell Mol. Physiol. (in press, doi:10.1152/ajplung,00084.2005).

Page 10 of 11 Interim Guideline for Working Safely with Nanotechnology

Appendix

Subject: Draft response for comment Date: Thu, 1 Sep 2005 11:48:34 -0400 Thread-Topic: Draft response for comment Thread-Index: AcWvDJxG19srdPPtQ4q1nx6QSZT5BA== From: "Fominko, Irene" To: Cc: "Castranova, Vincent"

Dear Mr. Breeding,

Concerning your question about precautionary guidelines in the handling and storing of carbon nanotubes, NIOSH is looking into this issue, and best practices for handling nanomaterials is an active topic of the strategic NIOSH Nanotechnology Research Agenda. NIOSH is currently reviewing available information and intends to publish soon, on the NIOSH web site, interim discussion and recommendations for best practices. The interim web document will be subject to stakeholder comment and change as needed, as more information becomes available through continuing research.

In the meantime, if you are not familiar with them, the following are published, peer-reviewed results of NIOSH studies on single walled carbon nanotubes:

1. An evaluation of a university lab producing single walled carbon nanotubes reported: “Estimates of the airborne concentration of nanotube material generated during handling suggest that concentrations were lower than 53 µg/m3 in all cases.” However, “laboratory studies indicated that with sufficient agitation unrefined SWCNT material can release fine particles into the air.” J. Toxicol. Environ. Health Part A, 67:87-107, 2004.

2. Unrefined SWCNT are contaminated by up to 30% iron by weight. This iron is redox reactive and can generate hydroxyl radicals which cause oxidant injury to human cells in culture. J. Toxicol. Environ. Health Part A, 66:1901-1918, 2003.

3. Pharyngeal aspiration of 10 – 40 ug of purified SWCNT (containing 0.2% iron) in a mouse model resulted in an interstitial fibrotic reaction which progressed through 60 days post-exposure. Am. J. Physiol.: Lung Cell Mol. Physiol. (in press, doi:10.1152/ajplung,00084.2005).

These and other NIOSH studies will help lead to a better understanding of nanotechnology’s implications and applications for occupational health. I hope this information is useful.

Vince Castranova, Ph.D. Coordinator Nanotechnology Safety and Health Research Program National Institute of Occupational Safety & Health (NIOSH)

Page 11 of 11