On the cover: Transmission electron photomicrographic image of a 

dispersed suspension of single-walled carbon nanotubes labeled with 

10-nm colloidal gold. This labeling technique allows these nanoparticles 

to be more easily tracked and visualized in various tissues and organs 

following exposure. Image courtesy of Robert Mercer, NIOSH. 
Progress Toward Safe 

Nanotechnology in the 

Workplace 

A Report from the NIOSH 

Nanotechnology Research Center 

DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Centers for Disease Control and Prevention 

National Institute for Occupational Safety and Health 
This document is in the public domain and may be freely 

copied or reprinted. 

Disclaimer 

Mention of any company or product does not constitute endorsement by the 

National Institute for Occupational Safety and Health (NIOSH). In addition, 

citations to Web sites external to NIOSH do not constitute NIOSH endorsement of the sponsoring organizations or their programs or products. Furthermore, NIOSH is not responsible for the content of these Web sites. 

Ordering Information 

To receive documents or other information about occupational safety and 

health topics, contact NIOSH at 

NIOSH—Publications Dissemination 

4676 Columbia Parkway 

Cincinnati, OH 45226–1998 

Telephone: 1–800–35–NIOSH (1–800–356–4674) 

Fax: 513–533–8573 

E-mail: pubstaft@cdc.gov 

or visit the NIOSH Web site at www.cdc.gov/niosh 

DHHS (NIOSH) Publication No. 2007–123 

(Reissued with minor modifications) 

June 2007 

safer • healthier • peopletm 

ii 
 

 

 

 

 

Foreword

As with any new technology, the earliest and most extensive exposures to engineered nanoparticles are most likely to occur in the workplace. Workers are 

currently producing and using nanoparticles. Society requires assessment of 

whether these exposures present any threat to workers. The National Institute 

for Occupational Safety and Health (NIOSH) is mandated by law to conduct 

research and develop guidance on worker safety and health. NIOSH, in collaboration with partners in other government agencies, countries, academia, 

industry, labor, and nongovernmental organizations, has been conducting research and developing guidance to address the occupational safety and health 

of workers exposed to nanomaterials. This document is a report of the progress 

of the NIOSH Nanotechnology Research Center (NTRC) since its inception 

in 2004 through 2006. Using only internally redirected resources, the NTRC 

has begun to make contributions to all the steps in the continuum from hazard 

identification to risk management. 

Understanding the occupational safety and health issues of nanotechnology is a 

complex endeavor. The types of nanomaterials and the opportunities for workplace exposure are growing rapidly. The challenge is to effectively address the 

safety and health issues of nanotechnology while helping society realize the farreaching potential benefits. NIOSH will continue to respond to this challenge. 

John Howard, M.D. 

Director, National Institute for

 Occupational Safety and Health 

Centers for Disease Control and Prevention 

iii 
Executive Summary 

The National Institute for Occupational Safety and Health (NIOSH) is the Federal agency responsible for conducting research and making recommendations 

to prevent work-related injury, illness, and death. As such, NIOSH is active in 

(1) identifying critical issues related to possible health hazards of nanomaterials, (2) protecting the safety and health of workers involved in this emerging 

technology, and (3) implementing a strategic plan to develop and disseminate 

methods for safely advancing the technology through workplace controls and 

safe handling procedures, and (4) investigating the possible applications of 

nanotechnology to solve workplace safety and health issues. Because of their 

small size and large surface area, engineered nanoparticles may have chemical, physical, and biological properties distinctly different from larger particles 

of similar chemical composition. Those properties may include the ability to 

reach the gas exchange regions of the lung, travel from the lung throughout 

the body, penetrate dermal barriers, cross cell membranes, and interact at the 

molecular level. NIOSH is investigating all of these properties, as it would with 

any new technology or material in the workplace, to provide the necessary 

guidance to ensure a safe and healthy workplace. 

NIOSH is mandated by the Occupational Safety and Health Act to determine 

whether materials in a workplace constitute any harm and to provide recommendations for preventing injury and illness. NIOSH is taking the first steps 

in assessing hazards posed by various types of nanoparticles by attempting 

to understand the mechanisms of action of nanoparticles in living systems 

and assessing risks to workers. The research being conducted by the NIOSH 

Nanotechnology Research Center (NTRC) was funded by redirecting existing NIOSH programmatic funds: $3.0 million in FY 2005, $3.7 million in FY 

2006, and $4.6 million in FY 2007. This budgetary constraint has made a more 

comprehensive research program specific to nanomaterials difficult to implement. Even with the budgetary constraints, NIOSH investigators have laid the 

foundation for an evidence-based strategy for providing safe nanotechnology 

in the workplace. This effort is consistent with the following guidance from 

the U.S. Office of Science and Technology Policy (OSTP) and the Office of 

Management and Budget (OMB): to ensure that nanotechnology research leads 

to the responsible development of beneficial applications, high priority should 

be given to research on societal implications, human health, and environmental 

issues related to nanotechnology and to develop, where applicable, cross-agency 

approaches to the funding and execution of this research [July 8, 2005 memorandum for the Heads of Executive Departments and Agencies]. Because of 

iv 
 

Executive Summary 

its mission and the active program of research it has started, NIOSH has been 

identified as a lead agency in several high priority areas by the Nanotechnology 

Environmental and Health Implications (NEHI) Working Group within the 

National Nanotechnology Initiative (NNI). 

Nanotechnology Research Center 

NTRC was established in 2004 to coordinate and facilitate research in nanotechnology and develop guidance on the safe handling of nanomaterials in the 

workplace. It is a ‘virtual center’ in which NIOSH scientists and engineers at 

geographically dispersed locations are linked by shared computer networks 

and other technologies. This approach surmounts the logistical complications 

that traditionally arise when scientists and engineers collaborating on common research are not physically in the same locations. This approach has also 

allowed NIOSH to jump-start research and facilitate ongoing studies. The goals 

for NTRC are as follows: 

1.	 Determine whether nanoparticles and nanomaterials pose risks of 

injuries and illnesses for workers. 

2.	 Conduct research on applying nanotechnology to the prevention of 

work-related injuries and illnesses. 

3.	 Promote healthy workplaces through interventions, recommendations, 

and capacity building. 

4.	 Enhance global workplace safety and health through national and international collaborations on nanotechnology research and guidance. 

As evidenced by the full report, progress has been made toward each of these 

goals. The following paragraphs present highlights of each goal. 

1. Determine whether nanoparticles and nanomaterials pose risks 

of injuries and illnesses for workers. 

Since 2004, the NTRC has conducted toxicology research on the properties 

and characteristics of nanoparticles that are relevant for predicting whether 

these particles pose a risk of adverse health effects in workers (see Appendix 

A for the status of ongoing research and published results). These research 

projects have involved characterizing occupationally relevant nanoparticles— 

particularly the toxicity of carbon nanoparticles. Preliminary work by NTRC 

investigators demonstrated that exposures to specific nanotubes had harmful 

pulmonary effects (such as a fibrotic response) in mice soon after exposure 

to relatively low doses. NTRC investigators have evaluated the potential for 

v 
NIOSH Nanotechnology Research Center 

nanoparticles to enter the bloodstream and move to systemic tissues after being deposited in the lungs. NTRC is also assessing the impact of dermal exposure to nanoparticles. In addition, NTRC established a nanoparticle aerosol 

generation system and began conducting animal inhalation studies during the 

summer of 2006. These studies will help scientists determine whether some 

engineered nanomaterials pose risks to human health in the work setting. They 

will also help determine the mechanisms by which they operate. Although the 

results of these studies are preliminary and limited, more research is needed to 

predict whether they signal a health risk to humans. The data support the need 

to address that question and provide promising leads for strategic, ongoing 

studies. 

NTRC investigators have evaluated exposure-response information and developed quantitative risk assessment methods for nanoscale titanium dioxide; 

these efforts may serve as a model for assessing the risk of other nanoparticles. 

To gain further knowledge about exposure and control practices, the NTRC 

has established a field team (see Appendix B) to conduct assessments of workplaces where exposure to engineered nanoparticles may occur. To date, this 

team has partnered with various companies that produce or use engineered 

nanoparticles to obtain useful information about potential worker exposures, 

control technologies, and risk management practices. 

2. Conduct research on applying nanotechnology to the prevention 

of work-related injuries and illnesses. 

NTRC has identified various possibilities for applying nanotechnology to occupational safety and health, including the application of this technology in 

fabricating more efficient filters, sensors, and protective clothing. NTRC has 

also conducted numerous discussions with academia and the private sector 

on other potential projects. Efforts are underway between NTRC, other CDC 

personnel, and the Georgia Institute of Technology to identify collaborative 

projects involving nanotechnology applications to occupational and public 

health problems. 

3. Promote healthy workplaces through interventions, recommendations, and capacity building. 

NTRC has provided seminal guidance for workers and employers in nanotechnology through the document entitled Approaches to Safe Nanotechnology: An 

Information Exchange with NIOSH. This document was posted on the NIOSH 

Web site in 2005 and updated in August 2006 (see Appendix H for a summary). The document concludes the following: 

vi 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

Executive Summary 

■	 Given the limited amount of information for determining with confidence whether adverse human health effects may be associated with 

production and use of engineered nanoparticles, interim precautionary 

measures should be taken to minimize worker exposures. 

■	 For most processes and job tasks, the control of airborne exposure to 

nanoaerosols can be accomplished using a wide variety of engineering 

control techniques (e.g., exhaust ventilation, process enclosure) similar 

to those used in reducing exposure to other types of aerosolized particulates. 

■	 Implementing a risk management program in workplaces where 

workers are exposed to nanomaterials can help to minimize the 

potential for exposure to nanoaerosols. Elements of such a program 

should include engineering control techniques and good work practices. Engineering controls such as source enclosure (i.e., isolating 

the generation source from the worker) and local exhaust ventilation systems should be effective for capturing airborne nanoparticles. 

Current knowledge indicates that a well-designed exhaust ventilation 

system with a high-efficiency particulate air (HEPA) filter should effectively remove nanoparticles. The use of good work practices (e.g., 

handling and transfer practices, using wet methods, cleaning of contaminated surfaces), the education and training of workers, and the 

use of personal protective equipment (PPE) when needed should help 

reduce the potential for exposure. 

■	 Respirators may be necessary when engineering and administrative 

controls do not adequately prevent exposures. Currently, there are no 

specific exposure limits for airborne exposures to engineered nanoparticles, although occupational exposure limits exist for larger particles 

of similar chemical composition. Preliminary evidence shows that for 

respirator filtration media, particulates as small as 2.5 nm in diameter 

are efficiently captured, in keeping with single fiber filtration theory. 

Although this evidence needs confirmation, it suggests that it is likely 

that NIOSH-certified respirators will be useful for protecting workers 

from nanoparticle inhalation when properly selected and fit tested as 

part of a complete respiratory protection program. 

Other information products on the NIOSH Web site include the Nanotechnology topic page (with an extensive section on Frequently Asked Questions) and 

the Nanoparticle Information Library (NIL), which is a resource on particle information, including physical and chemical characteristics. In addition, NTRC 

vii 
 

 

 

 

 

 

 

 

NIOSH Nanotechnology Research Center 

has convened a cross-Federal group to develop a framework document for 

health surveillance of workers exposed to nanomaterials. This document will 

also involve the business community to identify the range of issues involved in 

occupational health surveillance. 

Nationally and internationally, NTRC has delivered a wide range of presentations on occupational safety and health issues associated with nanotechnology. These have included presentations at scientific conferences, 

trade associations, and professional associations; meetings of government 

agencies and nongovernmental organizations (NGOs); and special panels 

convened by government agencies, NGOs, and professional associations 

(see Appendix A for a listing of NTRC presentations and other activities). 

NIOSH has cosponsored the three major international meetings on occupational safety and health involving nanomaterials. These research summits 

furthered the exchange of the latest information among leading scientists and 

promoted the application of research findings to actual workplace practice for 

minimizing occupational exposures. The third meeting will be held in Taiwan 

in 2007, and two NTRC scientists serve on the planning committee. NIOSH 

also cosponsored a major occupational safety and health research-to-practice 

(r2p) conference in Cincinnati, Ohio during December 2006, which drew 

more than 450 participants from 11 countries. In addition, NTRC is collaborating with the U.S. Environmental Protection Agency (EPA), the Occupational Safety and Health Administration (OSHA), and other government agencies 

to obtain and evaluate exposure and good work practice information. 

4. Enhance global workplace safety and health through national 

and international collaborations on nanotechnology research 

and guidance. 

NTRC has established several national and international collaborations to 

advance understanding of occupational safety and health for nanotechnology 

workers. NTRC participates in the NNI and has contributed to the nanotechnology strategic plan for the Nation through the working group of NEHI. Occupational Safety and Health has been a major priority of the NEHI effort, and 

the NIOSH strategic research plan and activities are addressing most of the 

major issues in the NEHI plan. 

The NTRC has collaborated with the Organization for Economic Cooperation 

and Development (OECD) to build cooperation, coordination, and communication between the United States and 30 OECD member countries (including 

the European Union), and with more than 180 nonmember economies as well. 

viii 
Executive Summary 

NTRC is part of the U.S. leadership on the International Organization for Standardization (ISO) TC 229 Nanotechnology Working Group on Health, Safety, 

and the Environment. NTRC also works with the World Health Organization 

(WHO) Collaborating Centers on global projects of information dissemination 

and communication. 

Together, the research and guidance efforts of the NTRC are expected to enhance the safe use of nanotechnology in the workplace and safe work-related 

handling of nanomaterials. However, until more information becomes available, it is appropriate to take precautions and apply recognized occupational 

exposure control measures where nanoparticle exposure may occur. 

Steps to Addressing Occupational Safety 

and Health Implications 

The NTRC research and guidance effort has been initiated to fill the knowledge 

gaps in prevention and control of workplace exposures to engineered nanoparticles. To accomplish this, the NTRC has focused its research program on hazard identification and characterization, exposure assessment, risk assessment, 

and risk management. While research continues, NIOSH partners and stakeholders have urged NIOSH to provide interim guidance for risk management 

until scientists understand those properties, characteristics, and behaviors of 

nanomaterials that may pose occupational safety and health risks. NTRC has 

provided such interim guidance and will continue to do so as research is being 

conducted. 

The NTRC research program has identified 10 critical topic areas important 

for understanding the potential health risks and developing and disseminating 

recommendations. The report describes each of these critical topic areas and 

the research being conducted. These 10 topic areas are the core of the NTRC 

research program and represent the areas that are most critical to addressing 

occupational safety and health issues. They include toxcity and internal dose, 

risk assessment, epidemiology and surveillance, engineering controls and PPE, 

measurement methods, exposure assessment, fire and explosion safety, recommendation and guidance, communication and education, and applications. 

By working in these 10 critical areas, NIOSH has comprehensively begun to 

address the information and knowledge gaps necessary to protect workers and 

responsibly move nanotechnology forward so that its far-reaching benefits may 

be realized. 

ix 
 

 

 

 

 

 

 

 

NIOSH Nanotechnology Research Center 

NIOSH Resource Limitations 

Since its inception in 2004, the NTRC has published more than 70 papers in the 

peer-reviewed scientific literature (see specific research projects in the appendices) and provided a broad range of information and guidance. Publications in 

the area of hazard identification and characterization, exposure assessment, risk 

assessment, and risk management have provided a framework for beginning to 

address the potential hazards and risks from engineered nanoparticles. While 

these accomplishments have contributed significantly to our understanding of 

the potential health risks to nanoparticles, NIOSH research and subsequent 

development and dissemination of interim guidance efforts are limited by 

the amount of funding available. To the best of its ability in allocating limited 

resources to competing priorities, NIOSH has redirected funds internally over 

the past 3 years to build modest increases in nanotechnology research program 

support. New infusions of funding beyond the current NIOSH budget, specifically directed toward the program, would be needed for significant expansion 

of research to address the following research gaps: 

1. 	 Although NIOSH toxicology studies have provided better understanding of the ways in which some types of nanoparticles may enter the 

body and interact with the body’s organ systems, the breadth and depth 

of such research efforts have been limited to a few nanoparticle types. 

More types of nanoparticles need to be assessed for characteristics and 

properties relevant for predicting potential health risk. 

2	 NIOSH field investigators have assessed exposure to engineered 

nanoparticles in some workplaces, but few data exist on the extent and 

magnitude of exposure to other types of nanoparticles in workplaces that 

manufacture or use nanomaterials, nanostructures, and nanodevices. 

3.	 NIOSH guidance is a first step toward controlling nanoparticles in the 

workplace; however, more research is needed on the efficacy and specificity of engineering and work practice control measures. NIOSH needs 

support to conduct more field investigations. 

4.	 An increasing number of workers are involved with the research, development, production, and use of nanomaterials, but there is a lack of 

specific guidance for occupational health surveillance. NIOSH needs 

support to conduct research on the short- and long-term potential 

health risks in nanotechnology workers. This may involve the conduct 

of large-scale prospective epidemiologic studies and the establishment 

of exposure registries. 

x 
 

 

 

 

Executive Summary 

5.	 The utility of nanotechnology to support the development of new technologies (such as sensors, more efficient filters, and better protective 

materials) that can enhance the protection of workers requires further 

research and development and can be advanced by additional resources. 

In summary, the NTRC has advanced the scientific knowledge in understanding the possible health risks of engineered nanoparticles. Continuing research 

will help to expand this knowledge and provide opportunities for advancing 

the safe use of nanotechnology. 

xi 
xii 
 

Contents 

Foreword. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii
 

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iv
 

Abbreviations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiv
 

Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii
 

Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
 

Chapter 1: Toxicity and Internal Dose . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
 

Chapter 2: Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
 

Chapter 3: Epidemiology and Surveillance . . . . . . . . . . . . . . . . . . . . . . . 23
 

Chapter 4: Engineering Controls and Personal Protective


 Equipment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
 

Chapter 5: Measurement Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
 

Chapter 6: Exposure Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
 

Chapter 7: Fire and Explosion Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
 

Chapter 8: Recommendations and Guidance . . . . . . . . . . . . . . . . . . . . . 47
 

Chapter 9: Communication and Education. . . . . . . . . . . . . . . . . . . . . . . 53
 

Chapter 10: Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
 

Appendices 

A. Project-Specific Progress Reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
 

B. Field Research Team Progress Report . . . . . . . . . . . . . . . . . . . . . . . . . 131
 

C. Occupational Health Surveillance for Nanotechnology Workers . . 137
 

D. Review of the NIOSH Extramural Nanotechnology Research


 Program: Fiscal Years 2001–2006. . . . . . . . . . . . . . . . . . . . . . . . . . . 139
 

E. Nanotechnology Information Dissemination. . . . . . . . . . . . . . . . . . . 151
 

F. Other NTRC Partnership Activities and Presentations . . . . . . . . . . . 159
 

G. Projected Timeframe for Addressing Critical Areas . . . . . . . . . . . . . 165
 

H. Executive Summary—Approaches to Safe Nanotechnology: An 


 Information Exchange with NIOSH. . . . . . . . . . . . . . . . . . . . . . . . . 171
 

xiii 
Abbreviations
 

AIHA American Industrial Hygiene Association 

AIHce American Industrial Hygiene Conference and Exposition 

ANSI American National Standards Institute 

ASSE American Society of Safety Engineers 

ASTM American Society for Testing and Materials 

BIA Berufsgenossenschafliches Institut für Arbeitsschutz 

CDC Centers for Disease Control and Prevention 

CIB Current Intelligence Bulletin 

CMPND Center for Multifunctional Polymer

 Nanomaterials and Devices 

CNF carbon nanofiber 

CNT carbon nanotube 

COPD Chronic obstructive pulmonary disease 

CPC Condensation Particle Counter 

CSHEMA Campus Safety, Health and Environment

 Management Association 

DART Division of Applied Research and Technology 

DEP Diesel exhaust particulate 

DSHEFS Division of Surveillance Hazard Evaluation

 and Field Studies 

DRDS Division of Respiratory Diseases 

DSR Division of Safety Research 

EHS Environmental Health Sciences 

EID Education and Information Division 

EPA U.S. Environmental Protection Agency 

EU European Union 

FAQs Frequently Asked Questions 

FMPS Fast Mobility Particle Sizer 

FY Fiscal year 

HELD Health Effect Laboratory Division 

HEPA High-Efficiency Particulate Air Filter 

xiv 
 

 

Abbreviations 

HHE Health Hazard Evaluation 

HHPC hand-held particle counter 

IAPA Industrial Accident Prevention Association 

ICMAT International Conference on Materials for

 Advanced Technologies 

ICON International Council on Nanotechnology 

INRS Institut National de la Recherche Scientifique 

ISO International Organization for Standardization 

kW kilowatt 

LDH lactate dehydrogenase 

MCE mixed cellulose ester 

MIST man-in-simulation test 

MOU memorandum of understanding 

MOUDI micro-orifice-uniform-deposit impactor 

NASA National Aeronautics and Space Administration 

NATO North Atlantic Treaty Organization 

NCER National Center for Environmental Research 

NEHI Nanotechnology Environmental and Health Implications 

NFPA National Fire Protection Association 

NGO non-governmental organization 

NIH National Institutes of Health 

NIEHS National Institute of Environmental

 Health Sciences 

NIL Nanoparticle Information Library 

NIOSH National Institute for Occupational Safety and Health 

NIST National Institute of Standards and Technology 

nm nanometer(s) 

NNI National Nanotechnology Initiative 

NNIN National Nanotechnology Infrastructure Network 

NORA National Occupational Research Agenda 

NPPTL National Personal Protective Technology Laboratory 

NRC National Research Council 

NSET Nanoscale Science, Engineering, and Technology 

xv 
NIOSH Nanotechnology Research Center 

NSF National Science Foundation 

NTRC NIOSH Nanotechnology Research Center 

OD Office of the Director 

OECD Organization for Economic Cooperation

 and Development 

OEP Office of Extramural Programs 

ORC Organization Resource Council 

OSH occupational safety and health 

OSHA Occupational Safety and Health Administration 

PAS passive aerosol sampler 

PPE personal protective equipment 

PRL Pittsburgh Research Laboratory 

PSLT poorly soluble, low toxicity 

QD quantum dot 

QRA quantitative risk assessment 

r2p research to practice 

REL recommended exposure limit 

RFA request for application 

RTI Research Triangle Institute 

SBIR Small Business Innovative Research 

SNORA Small National Occupational Research Agenda

 on personal protective equipment 

SRL Safety Research Laboratory 

SWCNT single-walled carbon nanotube 

TEM Transmission Electron Microscopy 

TEM/EDS Transmission Electron Microscopy/

 Energy Dispersive Spectroscopy 

TERA Toxicology for Excellence in Risk Assessment 

TiO2 titanium dioxide 

TSCA Toxic Substances Control Act 

WHO World Health Organization 

xvi 
Acknowledgments 

This report was developed by the scientists and staff of the National Institute 

for Occupational Safety and Health (NIOSH) who participate in the NIOSH 

Nanotechnology Research Center (NTRC). Paul Schulte, Ph.D., is the coordinator of the NTRC. Special thanks go to Vincent Castranova, Ralph Zumwalde, Charles Geraci, Mark Hoover, and Amanda Harney Gust for organizing 

this report. Other NIOSH staff who conducted or contributed to the work 

described here include the following: James Antonini, Paul A. Baron, Stephen 

Berardinelli Jr., Eileen M. Birch, Fred Blosser, George R. Bockosh, Aleksandar 

D. Bugarski, David W. Chrislip, Keith G. Crouch, Brian D. Curwin, Gregory 

A. Day, Gregory J. Deye, Ming Ding, Clayton B. Doak, Kevin H. Dunn, Kelley Durst, G. Scott Earnest, Cherie F. Estill, Douglas E. Evans, Michael Galvin, 

Pengfei Gao, John Howard, Ann Hubbs, DeLon R. Hull, Vijia K.Karra, Bon-Ki 

Ku, Eileen Kuempel, Pramod S. Kulkarni, Li-Ming Lo, Max Lum, Michael 

Luster, John McKernan, Walter H. Mengel, Robert Mercer, Mark M. Methner, 

Paul Middendorf, Arthur L. Miller, Diane B. Miller, Vladimir Murashov, James 

O’Callaghan, Andrea Okun, Dale Porter, Larry Reed, Dori Reissman, Appavoo 

Rengasamy, Allen Robinson, Ronald Shaffer, Anna Shvedova, Petia Simeonova, 

Aleksandr Stefaniak, Virginia Sublet, Douglas Trout, Leonid A. Turkevich, and 

Mary L. Woebkenberg. 

NIOSH would also like to acknowledge the seminal contribution of Andrew 

Maynard (formerly with NIOSH) to the NTRC and the early leadership of 

Mary Lynn Woebkenberg. 

Vanessa Becks, Gino Fazio, Steve Leonard, and Anne Stirnkorb performed 

desktop publishing, and graphic design. Anne Hamilton, Susan Afanuh, and 

Jane Weber edited the report. Brenda Proffitt provided word processing support. 

xvii 

Introduction
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

NIOSH Nanotechnology Research Center 

Background 

Nanotechnology is a system of innovative methods to control and manipulate 

matter at near-atomic scale to produce new materials, structures, and devices. 

Nanoparticles are a specific class or subset of these new materials that have at 

least one dimension that is less than 100 nm. They exhibit unique properties 

because of their nanoscale dimensions. Nanotechnology offers the potential for 

tremendous improvement and advances in many areas that may benefit society, such as integrated sensors, semiconductors, medical imaging, drug delivery systems, structural materials, sunscreens, cosmetics, coatings, and many 

others. Nanotechnology is one of the most rapidly growing industries across 

the world. By 2015, the global market for nanotechnology-related products 

is predicted to reach $1 trillion and employ 1 million workers in the United 

States alone. The properties of nanoparticles (e.g., size, surface area, reactivity) 

that yield many of the far-reaching societal benefits may also pose risks. Currently, increasing numbers of workers are potentially exposed to nanomaterials 

in research laboratories, startup companies, production facilities, and operations where nanomaterials are processed, used, disposed of, or recycled. The 

challenges are to determine whether the nature of engineered nanostructured 

materials and devices presents new occupational safety and health risks. At the 

same time, the need is to realize the benefits of nanotechnology while proactively minimizing the risk. 

Multiple Federal agencies are fostering the development and use of nanotechnology. The President’s Council of Advisors on Science and Technology has collaborated with the interagency National Science and Technology 

Council to create the National Nanotechnology Initiative (NNI). This initiative supports basic and applied research and development in nanotechnology to create new nanomaterials and to disseminate new technical capabilities to industry. The purpose of NNI is to facilitate scientific breakthroughs 

and maintain U.S. competitiveness in nanoscience. A stated goal of this 

interagency program is to ensure that nanotechnology research leads to the 

responsible development of beneficial applications by giving high priority to 

research on societal implications, human health, and environmental issues 

related to nanotechnology. 

The National Institute for Occupational Safety and Health (NIOSH) is the Federal agency responsible for conducting research and making recommendations 

to prevent work-related injury, illness, and death. NIOSH is a member of the 

Nanoscale Science, Engineering, and Technology (NSET) Subcommittee of the 

National Science and Technology Council. As such, NIOSH is active in (1) identifying critical issues related to possible hazards of nanomaterials, (2) protecting 

2 
 

 

 

 

Introduction 

worker safety and health in this emerging technology, and (3) implementing a 

strategic plan for conducting research and for developing guidance documents. 

Because of their small size and large surface area, engineered nanoparticles 

may have chemical, physical, and biological properties distinctly different from 

and greater than fine particles of similar chemical composition. Such properties may include a high rate of pulmonary deposition, the ability to travel from 

the lung to systemic sites, the ability to penetrate dermal barriers, and a high 

inflammatory potency per mass. At a time when materials and commercial 

applications are being conceived, NIOSH is well positioned to proactively 

identify, assess, and resolve potential safety and health issues posed by nanotechnology. NIOSH has 35 years of experience in conducting research and 

formulating recommendations for occupational safety and health. During this 

period, NIOSH has developed considerable expertise in measuring, characterizing, and evaluating new processes and new materials by conducting quantitative exposure assessments and evaluating health effects. NIOSH also has 

expertise in developing control systems and prevention strategies for incidental 

nanoparticles (for example, diesel exhaust, welding fume, smelter fume, and 

fire smoke particles). NIOSH is using this experience to address similar issues 

for engineered nanoparticles. 

NIOSH has redirected programmatic funds ($3.0 million in FY 2005, $3.7 

million in FY 2006, and $4.6 million in FY 2007) to resolve occupational 

safety and health knowledge gaps in the field of nanotechnology by conducting 

a broad program of research and guidance development. This report describes 

the progress of the NIOSH Nanotechnology Research Center (NTRC). The 

Center is a matrix of activities and projects consisting of and supported by 

more than 30 scientists from various divisions and laboratories in NIOSH who 

have developed and implemented a strategic plan (available at www.cdc.gov/ 

niosh/topics/nanotech) to address occupational health issues of nanotechnology. See Appendix G for a projected timeline of activities. 

The NIOSH Role in Occupational Safety and Health of 

Nanotechnology Workers 

A complete process for managing occupational safety and health implications 

during the development of new technologies and materials consists of a set of 

progressive elements: identifying and characterizing the hazard, assessing the 

extent of exposure, characterizing the risk, and developing control and management procedures. As exposure assessment data become available, it can be 

determined whether an occupational risk exists; if so, the risk can be assessed 

and characterized. The risk characterization should make it possible to 

3 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

NIOSH Nanotechnology Research Center 

determine whether workplace exposure to a given technology or material (in 

this case, nanoparticles) is likely to result in adverse health effects. The exposure 

assessment data will also provide a means to determine what controls are effective in preventing exposure that could cause adverse effects. The NTRC is involved in answering questions posed in each element in the risk management 

process (Figure 1). Particularly as this report illustrates, the NTRC has begun 

to answer questions about hazards by assessing exposures to nanoparticles in 

surrogate animals using well established scientific principles. Toxicological 

research is one element that forms the foundation for occupational safety and 

health. The critical routes of exposure (respiratory and skin) and their targets 

(lungs, cardiovascular, skin, brain, systemic) are being identified, and research 

is being conducted on the health effects and mechanisms of action of specific 

nanoparticles. 

Meanwhile, research is being conducted on measuring nanoparticles in air, 

determining what measures are appropriate, and using this information in field 

assessments. Parallel efforts have been undertaken to address the control of 

airborne nanoparticles and the strengths and weaknesses of control approaches. Similar efforts are underway for personal protective equipment (PPE) such 

as respirators and gloves. 

The findings of field investigations and laboratory research are continually used 

to update guidance for thinking about, evaluating, and managing potential nanotechnology risks. This information is being widely disseminated by NIOSH. 

The problem is that it is difficult to proceed in a classic step-by-step fashion 

from hazard identification to risk management because each day more workers may be exposed to nanomaterials as nanotechnology permeates industrial and commercial sectors. Thus the challenge is to conduct research to 

address knowledge gaps while drawing on all available information to provide interim guidance. Fortunately, a body of knowledge exists on hazards, 

risks, and controls for particles between 100 nm and 1μm. Nanomaterials 

that are currently manufactured apparently have no major physical features 

that would make them behave differently from fine and ultrafine particles 

when controlling them in the workplace. However, the limits of this assumption need continued evaluation. 

Despite a comprehensive approach, NIOSH research and guidance is limited 

by resource constraints. Workplace applications of nanotechnology are numerous and diverse. At this time, it is difficult to understand whether broad, 

homogenous classes of nanoparticles can be identified for testing and 

control purposes. The vast diversity of nanoparticles presents a challenge 

4 
5

Figure 1. Steps to protect workers involved with nanotechnology. Adapted from Gibbs, 2006.

Introduction
 

 

 

 

 

NIOSH Nanotechnology Research Center 

for determining which ones should be the focus of research. NIOSH has 

primarily been addressing the growing categories of carbon nanotubes, 

carbon nanofibers, metal oxides, and quantum dots in laboratory and field 

investigations. However, within each category is a broad range of combinations, surface characteristics, and physical and chemical parameters that can 

and are being altered by researchers and manufacturers. Although specific 

nanoparticles are being assessed in toxicologic research, the NTRC field team 

is proceeding to identify and assess the growing range of nanoparticles in the 

workplace. 

Critical Topic Areas 

NTRC has identified 10 critical topic areas (Figure 2) to (1) guide its research 

in areas where knowledge gaps exist, (2) develop strategies, and (3) provide 

recommendations. Each chapter (1–10) provides a brief description of the 

research that NTRC is conducting in the topic area and the applications and 

Toxicity and internal dose 

Risk assessment 

Epidemiology and surveillance 

Applications 

Exposure Fire and explosion

 assessment safety 

Measurement Recommendations

 methods and guidance 

Engineering Communication

 controls and PPE and education 

Figure 2. The 10 critical areas identified by the NTRC. 

6 
Introduction 

implications of nanomaterials in the workplace. Research needs for each topic 

area are listed as follows: 

1. Toxicity and Internal Dose 

■	 Investigating and determining the physical and chemical properties 

(e.g., size, shape, solubility) that influence the potential toxicity of 

nanoparticles 

■	 Determining what happens to nanomaterials once they enter the 

body. 

■	 Evaluating short- and long-term effects that nanomaterials may 

have in organ systems and tissues (e.g., lungs, brain, cardiovascular) 

■	 Determining biological mechanisms for potential toxic effects 

■	 Creating and integrating models to help assess hazards 

■	 Determining whether a measure other than mass is more appropriate for determining toxicity 

2. Risk Assessment 

■	 Determining how existing exposure-response data for fine and 

ultrafine particles (human or animal) may be used to identify and 

assess occupational hazards and risks 

■	 Developing a framework for evaluating potential hazards and predicting the occupational risk of exposure to nanoparticles 

3. Epidemiology and Surveillance 

■	 Evaluating existing epidemiological studies in the workplace where 

nanomaterials are used 

■	 Identifying knowledge gaps that could be filled by epidemiological 

studies to advance the understanding of nanomaterials and evaluating the feasibility of conducting new studies 

■	 Integrating nanotechnology safety and health issues into existing 

hazard surveillance methods and determining whether additional 

screening methods are needed 

■	 Using existing systems to share data and information about nanotechnology 

4. Engineering Controls and PPE 

■	 Evaluating the effectiveness of engineering controls in reducing occupational exposures to nanoaerosols and developing new controls 

when needed 

7 
NIOSH Nanotechnology Research Center 

■	 Evaluating the suitability of control banding techniques when additional information is needed, and evaluating the effectiveness of 

alternative materials 

■	 Evaluating and improving current PPE 

■	 Developing recommendations to prevent or limit occupational exposures to nanomaterials (e.g., recommending respiratory protection) 

5. Measurement Methods 

■	 Evaluating methods for measuring the mass of respirable particles 

in the air and determining whether this measurement can be used 

to measure nanomaterials 

■	 Developing and field-testing practical methods to accurately measure airborne nanomaterials in the workplace 

■	 Developing, testing, and evaluating systems to compare and validate sampling instruments 

6. Exposure Assessment 

■	 Determining key factors that influence the production, dispersion, 

accumulation, and re-entry of nanomaterials into the workplace 

■	 Determining how possible exposures to nanomaterials differ by 

work process 

■	 Assessing possible exposure when nanomaterials are inhaled or 

settle on the skin 

NIOSH monitoring of a worker 

during a nanomaterial powder 

production and collection. 

8 
Introduction 

7. Fire and Explosion Safety 

■	 Identifying physical and chemical properties that contribute to 

dustiness, combustibility, flammability, and conductivity of nanomaterials 

■	 Recommending alternative work practices to eliminate or reduce 

workplace exposures to nanomaterials 

8. Recommendations and Guidance 

■	 Using the best available science to make interim recommendations 

for workplace safety and health practices during the production, 

use, and handling of nanomaterials 

■	 Evaluating and updating mass-based occupational exposure limits 

for airborne particles to ensure good, continuing precautionary 

practices 

9. Communication and Education 

■	 Establishing partnerships to allow for identifying and sharing research needs, approaches, and results 

■	 Developing and disseminating training and education materials to 

workers, employers, and occupational safety and health professionals 

10. Applications 

■	 Identifying uses of nanotechnology for application in occupational 

safety and health 

■	 Evaluating and disseminating effective applications to workers, 

employers, and occupational safety and health professionals 

The remainder of this report provides an update describing the research and 

guidance efforts in each of the 10 critical topic areas of the NTRC. In addition, 

ongoing partnerships and collaborations are identified along with accomplishments and areas where future research is needed. The appendices provide 

details of each intramural project and they outline published research and 

presentations of the NTRC staff. Appendix D provides information regarding the nanotechnology research being funded through the NIOSH Office of 

Extramural Programs. 

9 

Toxicity and Internal Dose 

1 
NIOSH Nanotechnology Research Center 

Background 

NIOSH has studied in great detail the toxicity of incidental exposures to 

nanoparticles generated from processes involving combustion, welding, or 

diesel engines. However, less is known about nanoparticles that are intentionally produced (engineered) with diameters smaller than 100 nm. Many uncertainties exist as to whether the unique properties of engineered nanomaterials 

pose occupational health risks. These uncertainties arise because of gaps in 

knowledge about the potential routes of exposure, movement of nanomaterials 

once they enter the body, and the interaction of the materials with the body’s 

biological systems. Results from existing animal and human studies of exposure to incidental nanoscale and other respirable particles provide preliminary 

information about the possible adverse health effects from exposures to similar 

engineered nanomaterials. 

The NTRC is conducting research to address the following questions: 

■	 Is particle surface area a more appropriate measure of exposure than 

particle mass? 

■	 Does a high deposition of nanoparticles in the lungs affect clearance 

and movement of nanoparticles from airspaces into cells, tissues, and 

blood vessels? 

■	 Can nanoparticles get into various organs once they are in the bloodstream? 

■	 By what mechanisms do nanoparticles generate reactive oxygen species? 

■	 Do nanoparticles cause adverse health effects in workers if they penetrate the skin? 

■	 How do shape, durability, and chemical composition of nanoparticles 

affect their biological activity? 

■	 Do nanoparticles that are bound together separate into smaller, possibly more potent structures in biological fluids? 

■	 Are in vitro assays predictive of in vivo responses to nanoparticles? 

NTRC Toxicology and Internal Dose Projects 

The NTRC has built a comprehensive research program focused on the question of whether nanomaterials pose occupational health risks. Currently, sev12 
 

 

 

 

 

 

 

Chapter 1 ■ Toxicity and Internal Dose 

eral projects are underway and are primarily studying the effects of inhalation and dermal exposure to 

nanoparticles. Projects include the following: 

■	 Measuring how nanoparticles deposit in and 

clear out of the lungs after intratracheal instillation, pharyngeal aspiration, or pulmonary 

exposure 

■	 Monitoring how nanoparticles move from 

the airways into tissue and blood through 

the use of labeled nanoparticles 

■	 Measuring pulmonary damage, oxidant 

stress, inflammation, and fibrosis after pulmonary exposure to nanoparticles of various compositions and shapes 

■	 Measuring the cardiovascular effects of pulmonary exposure to nanoparticles of various compositions and shapes 

■	 Measuring how nanoparticles move from 

the lung to brain tissue and determining 

whether this results in neural effects 

■	 Determining the role of surface area in biological activity 

■	 Determining the ability of lung lining fluid 

to separate nanoparticles that are bound 

together 

■	 Determining whether in vitro measurement of the oxidant-generating capacity of 

nanoparticles predicts in vivo response 

■	 Determining dermal effects of exposure to 

nanoparticles of various compositions and 

shapes 

For more information about the NTRC nanotoxicology projects, see Appendix A, Projects 1 through 10. 

Collaborations and Partnerships 

NTRC scientists working in the area of toxicity and 

internal dose have established external collaborations 

Transmission electron micrograph (TEM) of 

dispersed multiwalled carbon nanotubes. 

Magnification=4,350X 

800 nm 

20 μm 

Collagen 

SWCNT 

Alveolar granulomas containing single-walled 

carbon nanotube (SWCNT) with collagen detected 

in granuloma, indicating a fibrotic response. The 

tissue sample was collected 7 days following exposure to 40 μg of SWCNT by pharyngeal aspiration in rats. 

13
 
14

NIOSH Nanotechnology Research Center 

with universities, private industries, and other government agencies. Collaborations are intended to advance knowledge and understanding of the factors 

that are critical for determining whether nanoparticles pose an occupational 

risk of harmful effects. NTRC is collaborating with organizations such as the 

National Aeronautics and Space Administration (NASA), the University of 

Pittsburgh, West Virginia University, IBM, and Mitsui Incorporated. These collaborations provide a multidisciplinary approach to addressing research needs 

and ensure high-quality research. 

Accomplishments

The NTRC Toxicity and Internal Dose team has had significant accomplishments over the last several years to advance knowledge and understanding of 

exposure to nanomaterials. The team has accomplished the following: 

■ Developed a method for improved dispersion of nanoparticles for in 

vitro and in vivo exposure 

■ Determined the in vitro effect of single-walled carbon nanotubes or 

metal oxide nanoparticles on dermal cells in culture 

■ Determined the pulmonary effect of exposure to single-walled carbon 

nanotubes

■ Labeled single-walled carbon nanotubes and tracked their deposition 

and migration in the lung in laboratory animals

■ Developed systems to generate aerosolized ultrafine titanium dioxide 

(TiO2) particles and single-walled carbon nanotubes (SWNCTs) at a 

controlled size and concentration 

■ Determined cardiovascular response in laboratory animals to pulmonary exposure to single-walled carbon nanotubes and TiO2 nanoparticles 

20 μm 20 μm

Right: Microvessel in rat 

muscle showing a buildup of 

polymorphonuclear neutrophils (PMNs) on the vessel 

wall 24 hours after intratracheal installation exposure to 

Ti02. The vessel wall is less 

responsive to vasodilators and 

blood flow is restricted. Left:

Microvessel from a control rat 

showing no buildup of PMNs 

and free-flowing blood cells.
Chapter 1 ■ Toxicity and Internal Dose 

For more information about the NTRC nanotoxicology accomplishments, see 

Appendix A, Projects 1 through 10. 

Additional Research Needs and Future Direction 

Although the NTRC has made significant advancements in understanding the 

potential harmful effects of exposure to nanomaterials, much more research is 

needed. The NTRC is focusing its research efforts in the following four primary areas: 

1.	 Determining the nature and severity of effects on the lung from inhaled 

nanoparticles 

2.	 Determining whether nanoparticles can move to other parts of the 

body (e.g., the heart or brain) after the particles are inhaled 

3.	 Determining whether exposure to nanoparticles has any effect on the 

immune system 

4.	 Determining whether the unique physical and chemical properties of 

nanoparticles affect how the body responds when exposed to these 

particles 

200 nm 

200 nm 

Fullerenes—These are TEMs of 

nanoparticles suspended in water 

and sonicated. 

SWCNTs produced by the high-pressure decomposition of carbon monoxide (HiPCO) method. 

Arrows note iron contamination of the unpurified 

SWCNT. 

15
 

Risk Assessment 

2 
NIOSH Nanotechnology Research Center 

Background 

In the context of occupational safety and health, risk assessment can be described as a scientific evaluation of the potential for adverse safety and health 

effects to workers exposed to hazardous substances. When assessing risk, it 

must be determined whether a hazard is present and the extent to which a 

worker is likely to be exposed to the hazard. Risk occurs only when a hazardous agent is present and a worker is exposed to that agent. Quantitative and 

qualitative risk assessment methods are used to evaluate risk. 

Quantitative risk assessment methods are used when adequate data are available concerning the relationship between the amount of exposure received 

and the reaction to that exposure. This relationship is known as dose-response. 

Quantitative methods are useful to estimate exposure concentrations that are 

likely (or unlikely) to cause adverse health effects. The estimates are then used 

Risk assessment paradigm. (Based on National Research Council [1983]. Risk assessment in the Federal government: managing the process. Committee on the Institutional 

Means for Assessment of Risks to Public Health, Commission on Life Sciences, National 

Research Council. Washington, DC: National Academy Press, 191 pp.) 

18
 
Chapter 2 ■ Risk Assessment 

in conjunction with occupational exposure data (1) to characterize the health 

and safety risk to workers, (2) to form a basis for risk management decisions, 

and (3) to evaluate the effectiveness of engineering controls and other occupational safety and health measures. When adequate dose-response data are not 

available, qualitative risk assessment methods such as comparative or hazardranking approaches may be used. 

To develop appropriate risk assessment models and methods, risk assessors 

work closely with experimental scientists to design laboratory experiments that 

will provide useful data for estimating risk and uncertainty. They also work 

with risk managers to provide the analyses needed to develop effective risk 

reduction strategies. 

NTRC Risk Assessment Projects 

The goal of occupational risk assessment is to predict conditions in the work 

environment that could lead to safety and health hazards for workers. This information is used by risk managers to develop appropriate preventive measures 

Predicted deposition of inhaled particles in the human respiratory tract— 

ICRP [1994] model: light exercise, nose breathing; 0.1–5 μm, minimal 

inertial and diffusion deposition mechanisms. (Source: ICRP, International 

Commission on Radiological Protection [1994]. ICRP Publication 66: Human respiratory tract model for radiological protection. Elsevier Science, 

Inc. Tarrytown, NY.) 

19 
 

 

 

NIOSH Nanotechnology Research Center 

to reduce or eliminate the risk. In a new industry such as nanotechnology, human data are not yet available for estimating the risk of exposure to engineered 

nanoparticles. Therefore, NTRC is scientifically extrapolating existing animal 

data to humans to evaluate dose-response relationships and estimate the risk to 

workers who are producing or using nanoparticles. 

To advance understanding of this risk and to provide improved scientific models 

and methods that assess the risk of exposure to nanoparticles, the NTRC Risk 

Assessment team is currently focusing its research efforts in the following three 

areas: 

1.	 Extending current rodent lung models to describe the fate of inhaled 

nanoparticles and their increased potential for translocating to other 

organs in the body 

2.	 Investigating models to describe biologically based relationships between internal dose and biological response 

3.	 Developing state-of-the-art statistical methods to consolidate risk estimates from a number of equally plausible dose-response models 

The NTRC is also investigating quantitative and qualitative risk assessment 

methods for occupational exposure to nanoparticles. Information currently 

available includes (1) toxicology and epidemiology studies of respirable airborne particles and fibers and (2) toxicology studies of in vitro and in vivo 

responses to nanoparticles. Existing studies provide the NTRC with a basis for 

developing interim occupational safety and health guidance, and for comparing the effects of well-studied materials to the effects of new nanoparticles, as 

data become available. 

For more information about the NTRC nanotechnology risk assessment projects, see Appendix A, Project 12. 

Collaborations and Partnerships 

Risk assessors who are part of the NTRC have established both internal and 

external collaborations with other researchers and organizations. External 

partners include CIStems Institute of Information Technology (CIIT) Centers 

for Health Research, the Institute of Occupational Medicine, and Toxicology 

for Excellence in Risk Assessment. Research collaborations are underway in areas such as (1) study design for risk assessment of nanoparticles, (2) evaluation 

of dose metric, (3) translocation of labeled nanoparticles, (4) region-specific 

deposition of inhaled nanoparticles, and (5) biomathematical lung modeling of 

nanoparticle deposition and early biological responses. 

20 
 

 

 

 

 

 

 

Chapter 2 ■ Risk Assessment 

Accomplishments 

Between 2004 and 2006, NTRC risk assessors had significant accomplishments 

in their research projects. The Risk Assessment Team has accomplished the 

following: 

■	 Performed quantitative risk assessment using data from existing studies 

of fine and ultrafine particles 

■	 Developed partnerships with external researchers in an effort to fill 

data gaps and obtain the scientific information needed to achieve occupational safety and health research objectives 

■	 Published research findings in scientific, peer-reviewed publications 

■	 Presented research findings at scientific meetings 

More specifically, a quantitative risk assessment of fine and ultrafine TiO2 

particles was used as the basis for recommended exposure limits (RELs) in a 

NIOSH Current Intelligence Bulletin. Modifications to a lung deposition model were completed to provide enhanced capabilities for lung dosimetry modeling and research of nanoparticles. Finally, NTRC researchers were invited to 

provide expert advice and consultation to national and international working 

groups evaluating occupational safety and health issues of nanoparticles. 

Additional Research Needs and Future Direction 

During FY 2007, NTRC risk assessors will initiate research efforts involving 

nanoparticles in two primary ways: 

1.	 Investigating the application of risk assessment methods using existing 

data to provide a framework for developing preliminary risk management strategies 

2.	 Exploring biomathematical modeling approaches to fill data gaps concerning occupational health risks of exposure to nonspherical nanoparticles (i.e., carbon nanotubes) 

These research efforts, in conjunction with ongoing projects, will provide NTRC 

with a sound scientific basis for determining interim estimates of the potential 

safety and health hazards to workers exposed to engineered nanoparticles. It will 

also assist NTRC in providing prudent interim guidelines for using engineering 

controls, work practices, and other risk management strategies to protect workers responsible for producing and/or using nanomaterials. These assessments 

may be refined as research is finalized and new data become available. 

21 

3 

Epidemiology and 

Surveillance 
 

 

 

 

NIOSH Nanotechnology Research Center 

Background 

Human studies of exposure and response to engineered nanomaterials are not 

currently available. Gaps in knowledge and understanding of nanomaterials 

must be filled before epidemiologic studies can be performed. For example, 

improvements in exposure assessment will allow researchers to identify groups 

of workers who are likely to be exposed to nanomaterials. In turn, health 

studies conducted on these worker groups can provide useful information 

about the health risks associated with nanomaterials. Until such studies can be 

conducted effectively, studies of humans exposed to other aerosols (e.g., larger 

respirable particles) can be used to evaluate the health risks of exposure to 

airborne nanomaterials. 

The available health data on workplace exposure to airborne respirable particles and fibers, and the air pollution data from epidemiology literature may 

provide valuable insight into the hazards of nanoparticle exposure. However, 

applying these data to workplace exposures to nanomaterials presents a number of challenges, including the following: 

■	 Determining the relative importance of particle size (less than 100 nm) 

as a cause of the observed health effect 

■	 Determining whether nanoparticles move throughout the body and 

potentially affect organ systems other than the one through which they 

entered the body 

The NTRC hopes to address these and other challenges as information is 

gained from epidemiologic and other health studies of workers exposed to 

nanomaterials. 

NTRC Epidemiology and Surveillance Projects 

The lack of information about potential effects of workplace exposures to 

nanomaterials underscores the need for occupational health surveillance to 

be considered for nanotechnology workers. NTRC is addressing this lack of 

exposure and health effects data by developing guidance for employers and 

workers concerning the implementation of occupational health surveillance in 

workplaces where nanomaterials are handled. 

Every workplace involved in the production, use, and/or handling of engineered 

nanomaterials should conduct a needs assessment to make a qualitative risk 

determination. The guidance being developed by NTRC will consist of a framework for approaching such a needs assessment and applying existing hazard 

24 
25

Chapter 3 ■ Epidemiology and Surveillance

and medical surveillance methods in workplaces. It will provide information to 

improve existing occupational health surveillance programs and methods for 

initiating programs where none exist. As the field of nanotechnology advances, 

it is likely that this guidance and framework will need to be revised and updated, as will any existing occupational health surveillance programs. 

Collaborations and Partnerships

The NTRC has partnered with other Federal agencies to develop guidance related to occupational health surveillance for nanotechnology workers. Partners 

include the following:

■ U.S. Environmental Protection Agency

■ U.S. Department of Energy

■ U.S. Department of Defense

■ Occupational Safety and Health Administration

■ Lawrence Berkeley National Laboratory 
NIOSH Nanotechnology Research Center 

Accomplishments 

The NTRC has convened a cross-Federal group to develop guidance for nanotechnology employers and workers on implementing occupational health 

surveillance programs in the workplace. For more information about the development of an occupational health surveillance program for nanotechnology 

workers, please see Appendix C. 

Additional Research Needs and Future Direction 

A well-recognized need exists for an improved ability to assess relevant exposures to nanoparticles (e.g., we need to determine how to appropriately measure nanoparticle exposure and to assess particle size distribution and composition). Improved exposure assessment will involve a series of important first 

steps and will be closely tied with improvements in identifying worker cohorts 

likely to be exposed to nanomaterials. These gaps in our current knowledge 

about nanomaterials must be filled before epidemiologic studies can be effectively carried out. In addition, toxicologic and health effects research is needed 

to identify potential health problems to be addressed through medical surveillance programs. 

26 
4 

Engineering Controls 

and Personal Protective 

Equipment 
 

NIOSH Nanotechnology Research Center 

Background 

Because of the current lack of exposure standards for nanomaterials, an alternative rationale is required to evaluate the need for and effectiveness of 

engineering controls. In addition, the success of emerging nanotechnology 

industries will depend on production and development costs, including the 

installation of new exposure controls. Minimizing occupational exposure is 

the most prudent approach to controlling materials of unknown toxicity such 

as nanomaterials. Typically, these approaches include substituting a less toxic 

material if possible, enclosing the hazardous process, removing workers from 

exposure by automating the process, isolating workers from the hazard, and/or 

using local exhaust ventilation where nanomaterials are handled. Improved 

control approaches will become more evident as the risks of exposure to nanomaterials are better understood. 

When engineering controls are not feasible for reducing exposure to nanoparticles, PPE such as respirators, protective clothing, and gloves should be considered. The use of PPE should be based on a combination of professional 

judgment and assessment of the hazard. A concern has been raised that 

nanoparticles could pass through the protective barrier of PPE at a higher rate 

than larger particles because of their smaller size and unique properties. Therefore, NTRC is conducting research to address this concern. 

NTRC Engineering Controls and PPE Projects 

Engineering Controls 

The published literature contains only a limited number of studies on the 

implementation and effectiveness of engineering controls in the nanotechnology industry. Therefore, a group of NTRC researchers is assessing multiple 

approaches for controlling occupational exposure to nanoparticles. As part of 

this assessment, standard engineering controls are being thoroughly assessed 

to determine how controlling nanoparticle exposure differs from controlling 

larger particle exposure. In addition, a group of NTRC researchers is conducting walk-through technical evaluations at a variety of facilities that handle 

nanomaterials. Scientists are evaluating the potential for occupational exposure to nanoparticles and the use of engineering controls at these facilities. 

They also provide interim recommendations on safe work practices and work 

with the company to evaluate the its engineering controls when applicable. 

For more information about the field investigations, see Appendix A, Project 13. 

28 
Chapter 4 ■ Engineering Controls and Personal Protective Equipment 

pler that will be used in small-scale laboratory studies and testing of human 

A flat plate test system for measuring 

respirator filter penetration of 3 to 20 nm 

silver particles 

Respirators and Other PPE 

Scientific information is available to characterize 

the efficiency of respirator filtration for particles 

larger than 20 nm in diameter. However, less is 

known about smaller particles. To increase knowledge and understanding of these smaller particles, 

NIOSH funded a study in 2005 at the University 

of Minnesota’s Center for Filtration Research. The 

purpose of this study was to measure the penetration of nanoparticles between 3 and 20 nm in size 

through various filter media, including glass fiber, 

electret, and nanofiber. The respirator filter media 

tested in this study effectively collected nanoparticles as small as 3 nm. There was no evidence that 

particles in this size range pass through filter media 

at a higher rate than the larger particles. The NTRC 

is planning studies to validate these findings using NIOSH-approved respirators and to evaluate 

worker exposures to nanoparticles when respirators do not fit correctly. 

The NTRC is also developing innovative methods to measure the penetration of nanoparticles 

through protective clothing and ensembles. The 

NTRC developed a prototype passive aerosol samsubjects. The sampler will be used to evaluate the penetration of nanoparticles 

through commercially available protective ensembles; iron oxide aerosols 

down to 20 nm will be used. Once this study is complete, the NTRC will develop a statistical model based on study results. 

For more information about the NTRC PPE studies, see Appendix A, Projects 

15 and 16. 

Collaborations and Partnerships 

Engineering Controls 

NTRC engineers, scientists, and industrial hygienists have established external collaborations to evaluate the effectiveness of engineering controls. These 

assessments have been conducted by the NTRC Field Research team through 

29
 
NIOSH Nanotechnology Research Center 

surveys conducted at various types of industries that handle engineered nanomaterials. One such collaboration is being used to evaluate the reduction in 

airborne exposure to nanomaterials after implementing engineering controls 

or safe work practices. 

Respirators and Other PPE 

NIOSH and E.I. du Pont de Nemours & Co. (DuPont) signed an agreement in 

June 2006 under a memorandum of understanding (MOU). The purpose of 

the MOU is to establish a formal partnership to conduct research and increase 

knowledge and understanding of nanomaterials to reduce potential occupational exposures to nanoparticles. This MOU is effective through December 

2007. 

Accomplishments 

Engineering Controls 

In December 2005, NTRC conducted a comprehensive evaluation at a research 

facility that incorporates carbon-based nanomaterials into composites. NTRC 

collected numerous airborne and surface samples and operated a set of realtime aerosol instrumentation as part of a task-based sampling approach. Engineering controls and work practices were observed and qualitatively evaluated. 

A report has been completed and will be made publicly available. 

Checking for fiber release 

during destructive testing of 

nanofibers deposited on a 

substrate using optical and 

condensation particle counters. 

30
 
 

 

 

 

Chapter 4 ■ Engineering Controls and Personal Protective Equipment 

In March 2006, NTRC conducted an extensive study 

at a primary manufacturer of nanoscale metal oxides. 

The purpose was to characterize potential occupational 

exposure to nanomaterials and evaluate use of engineering controls and safe work practices. An interim 

report has been prepared for the manufacturing facility 

that includes results of the evaluation and provides 

recommendations about where improvements can 

be made to minimize exposure. NTRC is working 

with this company to demonstrate the effectiveness of 

implementing recommended changes to engineering 

controls and work practices. 

In July 2006, NTRC conducted a screening survey at a 

manufacturing facility where quantum dots are produced and encapsulated into small display units. The 

survey collected basic information about the types of 

processes employed, exposure control methods, and 

exposure measurement data. NTRC has drafted a report for the company that includes results from air and 

surface samples and provides recommendations for 

improving exposure controls and work practices where 

necessary. 

Results obtained from the evaluation of engineering 

control practices at nanomaterial facilities will be used 

to update recommendations in the NIOSH draft document Approaches to Safe Nanotechnology: An Information Exchange with NIOSH (available at www.cdc. 

gov/niosh/topics/nanotech/safenano/). 

Respirators and Other PPE 

Results of respirator and filtration research were 

reported in several media outlets and have been 

presented at national and international conferences. 

Findings will continue to be shared as the information 

becomes available. 

Enclosing hood with HEPA exhaust 

constructed to control possible emission 

of nylon nanofibers during destructive 

testing. 

Local exhaust ventilation controlling fugitive emissions during precursor mixing at a 

primary nanoscale metal oxide production 

facility. 

31
 
NIOSH Nanotechnology Research Center 

Additional Research Needs and Future Direction 

NTRC will focus its efforts on conducting in-depth field surveys and other 

research studies that document the effectiveness of various exposure controls 

and work practices for nanotechnology industries. To assist in developing 

sampling procedures, NTRC will continue collaborating with researchers who 

develop measurement protocols. NTRC will also continue its research of the 

potential for nanoparticles to penetrate respirators and other PPE. Findings 

will be used to develop standards and methods to protect workers from exposure to nanomaterials. 

32 
Measurement Methods 

5 
NIOSH Nanotechnology Research Center 

Background 

Sound scientific measurement methods are essential to effectively anticipate, 

recognize, evaluate, and control potential occupational health risks from current and emerging nanotechnologies. Traditional measurement approaches, 

such as determining total and respirable dust concentrations, may not be 

adequate for nanomaterials because of their unique physical, chemical, and 

biological properties. 

NTRC scientists are conducting research to identify and validate a comprehensive set of methods suitable for measuring nanomaterials. This area of research 

is known as nanometrology. To fill gaps in nanometrology, the Measurement 

Methods Team within the NTRC has identified three critical measurement 

goals: 

1.	 Evaluate methods used to measure total and respirable dust concentrations to determine whether the same methods can be used to measure 

nanomaterials. 

2.	 Develop and field test practical methods to evaluate their accuracy in 

measuring airborne nanomaterials in the workplace. 

3.	 Develop testing and evaluation systems to compare and validate sampling instruments. 

NTRC Measurement Methods Projects 

The Measurement Methods team is focusing its efforts on building a knowledge base of methods suitable for measuring nanomaterials in the workplace. 

The team has a wide variety of research projects underway; within its projects 

the team is doing the following: 

■	 Establishing a controlled laboratory environment to generate nanoparticles and evaluate the effectiveness of instruments that measure the 

size and morphology (structure and form) of these particles (this laboratory will allow researchers to conduct evaluations existing and new 

instruments using different nanomaterials) 

■	 Evaluating instruments to monitor nanoparticle aerosols in real time 

■	 Investigating innovative methods to estimate surface area of aerosols 

and demonstrating that these methods provide comparable results for 

nanoparticles of different shapes and sizes 

34 
Chapter 5 ■ Measurement Methods 

■	 Evaluating different measurement methods to determine worker exposure to TiO2

 particles smaller than 2.5 and 0.1 μm in diameter (fine and 

ultrafine nanoparticles, respectively). 

■	 Developing new direct-reading instruments to measure size distribution, surface area, and mass concentration of nanoaerosols. 

In addition, the NTRC Measurement Methods Team supports the activities of 

the Field Research Team in characterizing exposures to nanomaterials in the 

workplace and evaluating the effectiveness of controls used to reduce exposures. 

The above research activities will provide a better understanding of the nature 

and extent of potential exposure to nanoparticles in the workplace. Results 

from these activities will help explain how nanoparticles are generated and 

dispersed. In addition, the results from ongoing research will help the occupational health community develop scientifically sound health protection strategies and provide information necessary for establishing voluntary national and 

international standards for emerging nanotechnologies. 

For more information about the NTRC measurement methods projects, see 

Projects 1, 5, 11, 13, 14, and 17 in Appendix A, and the Field Research Project 

in Appendix B. 

Air sampling filter in 

close proximity during 

tear-testing of nanofiber 

coated cellulose. 

35 
 

 

 

 

NIOSH Nanotechnology Research Center 

Collaborations and Partnerships 

Scientists within the NTRC Measurement Methods team are collaborating internally, as well as with external agencies and organizations, to characterize the 

potential for nanoparticle exposure in the workplace, evaluate sampling instruments, characterize the physical and chemical properties of nanomaterials, and 

evaluate methods for controlling exposure. 

NTRC has established several partnerships with industries conducting research 

of ultrafine nanomaterials, as well as with national and international government agencies and standards organizations, academia, labor unions, and aerosol 

instrument manufacturers. External partnerships include the following: 

■ National Institute of Standards and Technology 

■ U.S. Environmental Protection Agency 

■ U.S. Department of Energy 

■ U.S. Department of Defense 

■ American National Standards Institute 

■ ASTM International 

Comprehensive aerosols measurements conducted at different production processes within a primary nanoscale metal oxide production facility. A number of aerosol sampling methods and instruments are used 

simutaneously to better understand particle characteristics. 

36 
 

Chapter 5 ■ Measurement Methods 

In addition, NTRC collaborates with several national and international committees and working groups, as well as with commercial instrument manufacturing companies. Additional partnerships are noted within the specific projects listed in Appendix A. 

Accomplishments 

Between 2004 and 2006, scientists within the NTRC Measurement Methods 

team made significant advancements in characterization, implementation, and 

evaluation of measurement tools and techniques. The Measurement Methods 

team has accomplished the following: 

■	 Developed laboratory-based techniques for characterizing nanoparticles 

■	 Evaluated innovative instrumentation for nanometrology in controlled 

laboratory settings 

■	 Tested a set of measurement methods in nanotechnology workplaces 

■	 Developed nanoparticle reference materials in collaboration with the 

National Institute of Standards and Technology (NIST) 

■	 Disseminated research findings through scientific peer-reviewed publications, presentations, and the media 

■	 Provided expert advice and consultation to stakeholders through personal interactions and the NIOSH Nanotechnology Web page 

■	 Developed a prototype aerosol sampler that was submitted internally 

within NIOSH’s technology transfer channels for possible patenting 

For an expanded account of the accomplishments achieved within the NTRC 

Measurement Methods Program, see Appendix A, Projects 1, 5, 11, 13, 14, 

and 17. 

Additional Research Needs and Future Direction 

The Measurement Methods team will focus its short-term efforts on supporting the field- and laboratory-based research plans outlined in the NTRC projects listed in Appendix A. In addition, the group plans to strengthen NTRC’s 

capabilities for characterizing nanoparticles (e.g., development of nanoaerosol 

samplers), ensure that research findings are incorporated into national and international consensus standards, and expand both field- and laboratory-based 

research plans developed through the NTRC measurement projects. 

37 

Exposure Assessment 

6 
 

 

 

 

 

 

 

 

 

 

NIOSH Nanotechnology Research Center 

Background 

Exposure assessment is a critical component in determining whether nanomaterials pose occupational safety or health risks. Therefore, it is necessary to conduct 

exposure assessments in the workplace to identify the ways that workers may be 

exposed to nanomaterials, the amount of exposure that may occur, and the frequency of potential exposure. Without workplace exposure data, it is difficult to 

accurately characterize the work environment, identify sources that are emitting 

nanomaterials, or estimate the amount of nanoparticle exposure that workers 

may receive. In addition, exposure data can be beneficial when making decisions 

concerning risk management or evaluating the effectiveness of engineering controls and work practices in reducing worker exposures. 

The NTRC Exposure Assessment team has initiated workplace evaluations of 

worker exposure to nanomaterials in industries that produce and handle different types of nanomaterials. Several exposure assessment methods are being 

used to characterize exposures, including methods that will identify the size, 

shape, structure, and chemistry of airborne nanomaterials. This information is 

typically gathered after a walk-through evaluation of the facility. 

To the extent possible, personal breathing-zone samples are taken to ensure 

that each worker’s exposure is measured accurately. Unfortunately, many of the 

instruments currently available to detect nanomaterial exposures are too large 

to attach to the worker to collect breathing-zone samples. Therefore, general 

area air samples are taken in conjunction with personal samples to estimate the 

magnitude of nanomaterial exposure in areas occupied by workers. 

Sampling for airborne 

nanoparticles during a drum 

changing operation in a 

commercial nanomaterial 

production facility. 

40
 
 

Chapter 6 ■ Exposure Assessment 

NTRC Exposure Assessment Projects 

NTRC is currently conducting both qualitative and quantitative exposure assessment surveys in a variety of producers and end-users of nanomaterials. For 

more information about these activities, see Appendix B. 

Collaborations and Partnerships 

Scientists within the NTRC Exposure Assessment team are collaborating 

internally and with external agencies and organizations to develop and apply 

state-of-the-art methods to identify and characterize workplace exposures to 

nanomaterials, develop estimates of these exposures for exposure-response and 

risk assessment studies, and evaluate the significance of occupational exposure 

to nanomaterials and the effectiveness of intervention strategies. 

NTRC has also established partnerships with national and international 

government agencies and standards organizations, aerosol instrument manufacturers, and industries conducting research on nanoscale particles. External 

partners include the following: 

■	 Exposure Assessment Strategies Committee of the American Industrial 

Hygiene Association (AIHA) 

■	 Nanotechnology Working Group of AIHA 

■	 American Association for Aerosol Research and its international affiliates 

■	 American National Standards Institute (ANSI) 

■	 International Organization for Standardization (ISO) Technical Committee 229 on nanotechnologies 

Sampling and data collection during a mixing 

operation. 

41 
NIOSH Nanotechnology Research Center 

Accomplishments 

As part of the NTRC, the Exposure Assessment team has made significant recent accomplishments in characterizing workplace exposures to nanomaterials. 

In the past year, NTRC has completed four exposure assessment surveys with 

the following organizations: 

■	 A university composite material research laboratory that integrates 

carbon nanofibers to strengthen plastic materials 

■	 A manufacturer of TiO2 

■	 A research laboratory that handles quantum dots 

■	 A filter manufacturer that applies nylon nanofibers to a cellulose base 

material to increase filtration efficiency 

For more information about these exposure assessment surveys, see the Field 

Research Team Progress Report in Appendix B 

Additional Research Needs and Future Direction 

The NTRC Exposure Assessment team has identified several areas where additional research is needed. NTRC plans to continue its efforts conducting 

initial onsite exposure assessment surveys using handheld particle size and 

concentration instrumentation in various nanotechnology facilities, and investigating work processes and practices that could potentially lead to exposure to 

nanomaterials. Upon completion of the initial surveys, NTRC plans to conduct 

additional exposure characterization studies using more sophisticated instrumentation capable of measuring particle size distributions, particle surface 

area, and the mass of particles for various size ranges. Measurements obtained 

during the detailed surveys are expected to allow NTRC to determine the 

extent of workplace exposure to nanomaterials and estimate their potential for 

causing health effects. 

In addition, NTRC will continue to work with partners to develop personalsized sampling instruments that are able to measure particle size, shape, surface area, concentration, electrical charge, and other nanoparticle characteristics that may influence the conditions and potential health effects of workplace 

exposure. The development and validation of small sampling instruments to 

accomplish these characterizations are critical to the field of exposure assessment, and in understanding the health effects that exposure to nanomaterials 

may have on workers. 

42 
Fire and Explosion Safety 

7 
NIOSH Nanotechnology Research Center 

Background 

The field of nanotechnology is relatively new, and therefore little is known 

about the potential occupational safety hazards that may be associated with 

engineered nanomaterials. However, the information that is available about the 

properties of nanoscale particles indicates that under given conditions, engineered nanomaterials may pose a dust explosion hazard and be spontaneously 

flammable when exposed to air because of their large surface area and overall 

small size. Until more specific data become available, NTRC is using findings 

from research studies involving particles smaller than 100 nm to evaluate the 

potential risk for fire and explosion of airborne nanoparticles. 

About 20 dust explosions occur in industry settings each year and result in 

property damage, worker injury, and death. Dust explosions burn rapidly and 

with extreme intensity. During these explosions, settled surface dust may get 

resuspended in the air and create an environment suitable for further combustion. Processes that generate engineered nanomaterials in the gas phase or use 

or produce nanomaterials as powders, slurries, suspensions, or solutions, are 

likely to release nanoparticles into the air and therefore create the greatest risk 

for fire and explosion. Currently, the primary safety concerns associated with 

nanomaterials in the workplace are fire and explosion. 

Fire and Explosion 

Nanomaterials present a safety concern for potential fire and explosion because data show that decreasing the particle size of combustible materials may 

increase the risk for explosion. For many dust particles, the explosion risk 

appears to plateau at particle sizes on the order of tens of microns. However, 

some nanomaterials are designed specifically to generate heat through the progression of reactions at the nanoscale; this too may present a fire hazard that is 

unique to engineered nanomaterials. 

The ability of nanomaterials to become electrostatically charged during transport, handling, and processing introduces a unique explosion hazard when 

dealing specifically with nanopowders. Their tendency to charge has been 

found to drastically increase as particle surface area increases. As a result, their 

large surface area may become highly charged and become their own ignition 

source if the powder is dispersed in the air. 

Nanoparticles and nanostructured porous materials have been used for many 

years as effective catalysts for increasing the rate of reactions or decreasing the 

necessary temperature for reactions to occur in liquids and gases. Depending 

44 
Chapter 7 ■ Fire and Explosion Safety 

on their composition and structure, some nanomaterials may initiate catalytic 

reactions and increase the fire and explosion potential that would not otherwise be anticipated from their chemical composition alone. 

NTRC Safety Projects 

NTRC has not yet begun any research projects to investigate the explosivity 

and risk of fire from airborne exposures to nanomaterials in the workplace. At 

present, NTRC has reviewed the relevant literature and has initiated the development of a research study protocol. 

Collaborations and Partnerships 

Collaborative efforts are underway to identify stakeholders and organizations 

(e.g., National Fire Protection Association [NFPA]) with expertise in areas associated with the potential safety hazards of airborne dust exposures (e.g., fire, 

explosion). Through established collaborations and partnerships, NTRC will 

develop a research plan to determine the physical and chemical characteristics 

of nanoscale powders that may pose the greatest risk for fire and explosion in 

the workplace. 

Accomplishments 

In the absence of data to predict the risk of fire and explosion from airborne 

nanoparticles, NTRC has developed and published interim guidance in a document entitled Approaches to Safe Nanotechnology: An Information Exchange 

with NIOSH. This document can be obtained on the NIOSH Web site at: www. 

cdc.gov/niosh/topics/nanotech/safenano/. 

Additional Research Needs and Future Direction 

NTRC has identified several areas within the nanotechnology fire and explosion safety initiative where additional research is needed. These areas of research include the following: 

■	 Understanding the chemical, physical, and reactive properties of nanomaterials
 

■	 Determining the potential for airborne nanomaterials to cause fire or 


explosion
 

45 
NIOSH Nanotechnology Research Center 

■	 Understanding the extent to which combustible nanomaterials pose a 

higher risk of fire and explosion than coarser material of similar composition and quantity 

■	 Determining any chemical and/or physical characteristics of nanomaterials that may initiate catalytic reactions and increase the potential of 

fire and explosion 

46 
8 

Recommendations 

and Guidance 
 

 

 

NIOSH Nanotechnology Research Center 

Background 

NIOSH is responsible for (1) conducting research and making recommendations to protect the safety and health of workers, and (2) providing guidance to 

workers and employers on how to control potential occupational health hazards. In addition, NIOSH is dedicated to translating its research findings into 

recommendations and guidance that are scientifically sound and practical for 

the workplace. 

The national and international research community has identified the development of sound scientific recommendations for nanotechnology workers 

and employers as a key research priority. These recommendations should help 

workers and employers better understand the potential risks associated with 

exposure to nanomaterial and provide guidance on ways to manage and eliminate these risks. NTRC has identified the following goals to ensure that workers are protected from the potential safety and health hazards from exposure to 

nanomaterials: 

■	 Make interim scientific recommendations for prudent workplace safety 

and health practice during production and use of nanomaterials based 

on the best available scientific knowledge. 

■	 Validate experience-based recommendations using scientific, field- and 

laboratory-based research. 

■	 Develop partnerships with employers, workers, government agencies, 

and those in academia to disseminate recommendations and solicit 

feedback for improvement. 

■	 Issue periodic updates and revisit interim recommendations based on 

new research findings. 

■	 Evaluate Material Safety Data Sheets for informative and precautionary 

language that reflects current classification, toxicity data, and recommendations for working with nanomaterials. 

■	 Evaluate and update recommended occupational exposure limits (e.g., 

mass-based airborne particles) to ensure that good prudent practices 

are used. 

NTRC Recommendations and Guidance Projects 

NTRC has several ongoing projects aimed at providing recommendations to 

employers, workers, and safety and health professionals involved or interested in the field of nanotechnology. The primary project is a document 

48 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chapter 8 ■ Recommendations and Guidance 

entitled Approaches to Safe Nanotechnology: An Information Exchange with NIOSH. This document was first issued 

in October 2005 and updated in July 2006. Currently, this 

document draws from the ongoing NTRC assessment of 

the potential health risks from exposure to nanomaterials 

and the best practices for minimizing worker exposure. 

This document will continue to be updated as more data 

become available about the potential safety and health 

risks, as well as measures that can be used to control workplace exposure to nanomaterials. 

NTRC is also participating in the Nanotechnology 

Environmental and Health Implications (NEHI) effort 

to develop national research priorities. NTRC is participating in the following five areas: (1) instrumentation, 

metrology, and analytical methods; (2) nanomaterials 

and human health; (3) nanomaterials and the environment; (4) health and environmental surveillance; and (5) 

risk management methods. 

NIOSH developed this document Collaborations and Partnerships to provide an overview of what is 

known about nanomaterial hazards 

NTRC has established internal and external collabora­ and measures that can be taken to 

tions to gather information necessary to develop sound minimize workplace exposures. 

scientific recommendations and guidelines concerning the 

safe handling of nanomaterials. National and international 

collaborations and partnerships include the following: 

■	 NNI through National Science and Technology Council’s Subcommittee on Nanoscale Science, Engineering and Technology
 

■	 Organization for Economic Cooperation and Development (OECD) 

■	 New England Healthcare Institute 

■	 U.S. Environmental Protection Agency 

■	 International Organization for Standardization 

■	 American National Standards Institute 

■	 ASTM International 

■	 U.S. Department of Energy National Laboratories 

49
 
 

NIOSH Nanotechnology Research Center 

In addition, the NTRC is collaborating with academic institutions, manufacturers, and employers to ensure that current recommendations on the potential 

safety and health hazards of nanomaterials are available to workers in the field 

of nanotechnology. 

Accomplishments 

NTRC has developed interim recommendations for workers and employers on 

the safe handling of nanomaterials, and it continues to publish findings from 

ongoing research. The Recommendations and Guidance team has accomplished the following: 

■	 Developed and disseminated an interim guidance document for safety 

and health professionals entitled Approaches to Safe Nanotechnology: 

An Information Exchange with NIOSH 

■	 Developed a draft Current Intelligence Bulletin with recommended 

exposure limits for workplace exposure to TiO2

 nanoparticles 

■	 Established partnerships with national and international researchers, 

manufacturers, and industry leaders 

■	 Provided expert advice and consultation as well as disseminated recommendations and guidance through invited participation in national 

and international working groups and expert panels 

■	 Disseminated research findings and recommendations through peerreviewed journal articles 

Additional Research Needs and Future Direction 

Currently, few quantitative data are available on occupational exposure to 

nanomaterials. To fill the gaps in the knowledge and understanding of nanomaterials, NTRC created the Nanotechnology Field Research Team. This team 

has conducted onsite investigations at facilities that produce and/or handle 

nanomaterials. 

NTRC plans to continue its onsite field investigations in order to collect experiential data and develop a complete and accurate risk-based approach to 

managing nanomaterials. However, additional research is needed to fill several 

remaining information gaps to better understand the occupational safety and 

health implications of nanomaterials. Additional research and information are 

needed in the following areas: 

50 
 

Chapter 8 ■ Recommendations and Guidance 

■	 Overall characterization of nanomaterial processes 

■	 Prudent work practices to minimize and manage exposure to nanomaterials 

■	 Engineering controls and PPE 

■	 Worker training that addresses potential hazards that may be associated with nanomaterials 

■	 Evaluation of analytical instruments and methods used to measure 

exposure to nanomaterials 

■	 Quantitative and qualitative measurements of exposure to nanomaterials 

In addition, NTRC is developing guidance for the occupational health surveillance of workers exposed to engineered nanomaterials. This guidance will 

address medical and biological monitoring, health record review, and the effectiveness of exposure registries. 

For more information about recommendations and guidance on the safe handling, use, manufacturing, and processing of nanomaterials, visit the NIOSH 

nanotechnology Web site at www.cdc.gov/niosh/topics/nanotech. 

51 

9 

Communication
 

and Education
 
 

NIOSH Nanotechnology Research Center 

Background 

Communication and education are integral components infused throughout 

the NTRC research program, and they are closely related to the NIOSH research-to-practice (r2p) program, which is geared towards converting research 

results into safety and health information useful for workers and employers. As 

a result, communication and education is one of the 10 critical topic areas in 

addressing knowledge gaps, developing strategies, and providing recommendations concerning nanotechnology exposure. 

NTRC has identified the following goals and deemed them as critical to ensuring that relevant and applicable safety and health information is available to 

various target audiences: 

■	 Establish partnerships to identify and share research needs and findings 

■	 Develop communication materials that provide the target audience 

with useful and appropriate scientific information 

54
 
 

 

 

 

 

 

 

 

 

Chapter 9 ■ Communication and Education 

■	 Disseminate research findings through communication methods suitable to the target audience 

■	 Develop effective communication and educational materials to assist in 

reducing occupational exposure to nanomaterials 

■	 Develop a global collaboration with partners interested in nanotechnology communication and education 

NTRC communicates with a broad range of audiences including employers, 

workers, safety and health professionals, researchers, congressional offices, and 

the media. Therefore, it is important to ensure that each audience (1) receives 

information in a way that is appropriate and beneficial and (2) has the potential 

to increase occupational safety and health within the field of nanotechnology. 

NTRC Communication and Education Projects 

Communication and education has a role in each of the critical topic areas. To 

advance knowledge and understanding of the potential impact that nanotechnology and exposure to nanomaterials has in the workplace, NTRC is doing 

the following: 

■	 Developing and maintaining an in-depth Web page dedicated to nanotechnology research on the NIOSH public Web site 

■	 Creating and disseminating a brochure that describes the NTRC research 

program and provides general information about nanotechnology 

■	 Establishing and managing an online information library that contains resources about nanoparticles (Nanoparticle Information Library 

[NIL]) 

■	 Sponsoring international symposia on nanotechnology 

■	 Developing documents that contain guidance and recommendations 

on the applications and implications of exposure to nanomaterials in 

the workplace 

■	 Publishing research findings in scientific, peer-reviewed publications 

For more information about communication and education as well as nanotechnology information dissemination strategies by NTRC, see Appendix E. 

Collaborations and Partnerships 

To leverage resources and maximize the number of employers and workers who receive information about potential safety and health effects of 

55 
NIOSH Nanotechnology Research Center 

nanomaterials, NTRC has built global collaborations with stakeholders and 

organizations. These collaborations encourage researchers, industries, government officials, and labor organizations to develop sound communication and 

education strategies that increase knowledge, awareness, and understanding of 

emerging nanotechnologies and the potential health implications of exposure 

to nanomaterials in the workplace. NTRC has built collaborations with groups 

such as the following: 

■ Nanoparticle Occupational Safety and Health Consortium 

■ Nanoscale Science, Engineering, and Technology Subcommittee of the 

U.S. National Science and Technology Council 

■ National Toxicology Program 

■ AIHA 

■ International Council on Nanotechnology 

■ ISO 

■ ASTM International 

■ World Health Organization (WHO) 

■ OECD 

In addition, NTRC is a member of several national and international committees and working groups, including the Organization Resource Council (ORC) 

Nanomaterials Work Practices Workgroup, the ISO Technical Committee on 

Nanotechnology, the International Advisory Committee for the Third International Symposium on Nanotechnology in Taiwan, and the International 

Commission on Occupational Health Meeting Session on Nanotechnology in 

Milan, Italy. 

Accomplishments 

NTRC has developed several communication and educational products that 

provide workers with up-to-date information about nanotechnology and the 

potential safety and health risks from exposure to nanomaterials. These products include a nanotechnology topic page on the NIOSH Web site, documents 

and brochures, presentations, and an electronic resource that contains information about nanoparticles. 

The NIOSH Nanotechnology topic page (www.cdc.gov/niosh/topics/nanotech) 

was updated in 2006 and currently includes the following information: 

56 
 

Chapter 9 ■ Communication and Education 

■	 The NIOSH role in nanotechnology 

■	 Ten critical topic areas for NIOSH nanotechnology research 


■	 Interim recommendations (Approaches to 


Safe Nanotechnology: An Information Exchange with NIOSH) that invite the public to 


provide comments 


■	 Frequently Asked Questions about nanotechnology 


■	 News and events 

■	 A nanoparticle information library (NIL) 


developed by NTRC in partnership with 


national and international agencies. NIL is 


a searchable database that will help occupational health professionals, industry users, 


worker groups, and researchers organize and 


share information about nanomaterials. 


NTRC has conducted training and education courses on occupational safety 

and health within nanotechnology for various national and international organizations. In addition, NTRC has participated in professional development 

courses with the American Society of Safety Engineers (ASSE), AIHA, the 

Industrial Accident Prevention Association (IAPA), and several North Atlantic Treaty Organization (NATO) countries. NTRC staff have also provided 

presentations and participated in expert panel discussions at numerous meetings, workshops, and conferences about nanotechnology both nationally and 

internationally, and published more than 70 manuscripts in scientific, peerreviewed journals. 

Additional Research Needs and Future Direction 

NTRC will continue to expand and update its communication and educational 

products as more data become available on the exposures to nanomaterials in 

the workplace, and on the impact that exposure to nanomaterials has on workers. These products will be available to provide information and education to 

workers, companies, and educational institutions to prevent worker exposure 

to nanomaterials and reduce potential risk of occupational injury and illness. 

57
 

Applications 

10 
 

 

 

 

NIOSH Nanotechnology Research Center 

Background 

The unique properties and characteristics of nanomaterials may provide the basis 

for innovative new devices, products, or processes to reduce risks of work-related 

injuries and illnesses. Such innovations may have properties or capabilities that 

cannot be created or manufactured using conventional materials. 

NTRC Application Projects 

NIOSH has funded a number of research projects looking at applications of 

nanotechnology to develop advanced protective gear and sensors, both intramurally and extramurally. For more information about programs funded 

through the NIOSH Office of Extramural Programs, see Appendix D. 

Collaborations and Partnerships 

To advance the application of nanotechnology in the workplace, NTRC is 

building and establishing national and international partnerships. Currently, 

NTRC is collaborating with Carnegie Mellon University to develop a sensor 

that can be placed in a respirator to warn the user of inward chemical leakage 

through the respirator filter. NTRC is also working with the Georgia Institute 

of Technology to develop a thermal warning system to protect firefighters from 

extreme temperatures, and a sensor that can be used by emergency responders 

to detect biological threats. 

Accomplishments 

The NTRC Applications research program is in its early development stages. 

Research is primarily focused on improving worker safety and health by applying emerging nanotechnologies in the workplace such as sensors to warn 

workers of a hazardous exposure or develop better materials that can be used 

in making protective equipment and clothing. 

Within NTRC and through partnerships and collaborations, the Applications 

Team has accomplished the following: 

■	 Developed a methodology to identify emerging nanotechnologies that 

may pose a safety and health risk to workers 

■	 Developed a prototype sensor that can detect organic vapors and be 

embedded into respirator cartridges 

60 
Chapter 10 ■ Applications 

■	 Developed a noninvasive bio-monitoring capability to evaluate exposure to organophosphorus insecticides 

■	 Developed an extremely sensitive, low-temperature, low-cost, and miniaturized sensor that can be mounted inside a respirator to warn users 

when toxic organic vapors are inside the respirator 

■	 Designed, developed, and demonstrated improved sensor technology 

for detecting hydrogen sulfide 

Additional Research Needs and Future Direction 

NTRC will continue to monitor the emergence of new nanotechnologies and 

evaluate their implications for improving and/or harming worker safety and 

health. Such evaluations may lead to new recommendations to protect workers 

from exposure to nanomaterials. 

61 

Appendix A
 

Project-Specific
 

Progress Reports
 
NIOSH Nanotechnology Research Center 

Table 1 identifies the 10 critical topic areas that are addressed within each of 

the research projects conducted by NTRC. Details about each project (including accomplishments, publications and presentations, and partnership activities) are also described following this table. 

64 
Table 1. Overview of the 10 critical topic areas addressed in research projects

Toxicology Risk Epidemiol- Engineer- Measure- Exposure Fire and Recommen- CommuniProject number and inter- assess- ogy and ing controls ment assess- explosion dations and cation and

and/or category nal dose ment surveillance and PPE methods ment safety guidance education Applications 

Project 1 x x Project 2 x Project 3 x Project 4 x Project 5 x x Project 6 x Project 7 x Project 8 x Project 9 x Project 10 x Project 11 x x x x 

Project 12 x x x x 

Project 13 x x x x x Project 14 x x Project 15 x x 

Project 16 x x 

Project 17 x x x x x 

Nanotechnology infor x x x x mation dissemination

Office of the director

x x partnership activities 

­

65 
 

 

NIOSH Nanotechnology Research Center 

Research Program (Projects 1-10): Nanotechnology 

Safety and Health Research Program 

Program Coordinator: Vincent Castranova, Ph.D., HELD/ 

NIOSH/CDC 

Progress Report: FY 2004–FY 2006 

Background 

Nanotechnology is one of the fastest growing emerging technologies in the 

United States and across the world. Defined as the manipulation of matter 

at near-atomic scales to produce new materials, structures, and devices with 

unique properties, nanotechnology has potential applications for integrated 

sensors, semiconductors, medical imaging, drug delivery systems, structural 

materials, sunscreens, cosmetics, and coatings. By 2015, the global market for 

nanotechnology-related products is predicted to reach $15 trillion and to employ 1 million workers in the United States. 

Engineered nanoparticles are defined as having one dimension smaller than 

100 nm. Because of their small size, nanoparticles exhibit unique physical and 

chemical properties not associated with similar materials in the micrometer 

scale. These unique properties, small size, and high surface area may result in 

biological responses to exposure not observed with fine particles of the same 

composition. 

To address the critical need to determine whether workers could be at risk of 

adverse health effects as a result of exposure to nanomaterials, NIOSH funded 

the Nanotechnology Safety and Health Research Program in February 2004. 

The original research program included the first six projects listed below: 

Project 1 

■	 Generation and Characterization of Occupationally Relevant Airborne 

Nanoparticles 

■	 Principal Investigators: Bon-Ki Ku, Ph.D., and Doug Evans, Ph.D. 

Project 2 

■	 Pulmonary Toxicity of Carbon Nanotube Particles 

■	 Principal Investigators: Anna Shvedova, Ph.D., and Paul Baron, Ph.D. 

66 
Appendix A ■ Project-Specific Progress Reports 

Project 3 

■	 Role of Carbon Nanotubes in Cardiopulmonary Inflammation and 

COPD-Related Disease 

■	 Principal Investigators: Michael Luster, Ph.D., and Petia Simeonova, 

Ph.D. 

Project 4 

■	 Particle Surface Area as a Dose Metric 

■	 Principal Investigator: Vincent Castranova, Ph.D. 

Project 5 

■	 Ultrafine Aerosols from Diesel-Powered Equipment 

■	 Principal Investigator: Aleksander Bugarski, Ph.D. 

Project 6 

■	 Nanotechnology Safety and Health Research Coordination 

■	 Principal Investigator: Vincent Castranova, Ph.D. 

Research activities of this program cover aerosol generation and characterization studies in the laboratory 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. 

In October 2005, the original research program was augmented with the approval of a program expansion “Research Gaps Unaddressed in the Initial 

Nanotechnology Safety and Health Research Program.” This expansion added 

the following three projects to the original program: 

Project 7 

■	 Systemic Microvascular Dysfunction: Effect of Ultrafine vs. Fine Particles 

■	 Principal Investigator: Vincent Castranova, Ph.D. 

Project 8 

■	 Pulmonary Deposition and Translocation of Nanomaterials 

■	 Principal Investigators: Robert Mercer, Ph.D., and James Antonini, 

Ph.D. 

67 
NIOSH Nanotechnology Research Center 

Project 9 

■	 Dermal Effects of Nanoparticles 

■	 Principal Investigators: Anna Shvedova, Ph.D., and Min Ding, Ph.D. 

These additional three projects augment the original research program by 

investigating the ability of nanoparticles, once deposited in the lung, to enter 

the blood and translocate to systemic tissue. Effects on systemic microvascular 

function and resistance will be evaluated. These new projects will also evaluate 

effects of nanoparticles on the skin. 

In FY 2006, a new project was added to investigate the pulmonary and neural 

effects of pulmonary exposure to an incidental nanoparticle welding fume. 

Project 10 

■	 Neurotoxicity after Pulmonary Exposure to Welding Fumes Containing 

Manganese 

■	 Principal Investigators: James Antonini, Ph.D.; Diane Miller, Ph.D.; and 

James O’Callaghan, Ph.D. 

1.4 nm in diameter 

Micrometers in length 

Unique physical, chemical and 

electronic properties 

■ 

■ 

■ 

TEM 

68 
 

Appendix A ■ Project-Specific Progress Reports 

Project 1: Generation and Characterization of 

Occupationally Relevant Airborne Nanoparticles 

Accomplishments 

■	 Developed and fully characterized an in-situ nanoparticle generation 

facility for evaluating instrument response to tightly controlled particle 

morphology and size. 

■	 Evaluated aerosol instrumentation for monitoring nanoparticle aerosols in real time. 

■	 Evaluated three methods of estimating aerosol surface area (diffusion 

charging, transmission electron microscopy, and differential mobility 

analysis) and showed that these methods provide comparable measurements of aerosol surface area for particles smaller than 100 nm in 

diameter over a range of particle shapes. 

■	 Characterized the morphology of SWCNTs in aqueous suspension in 

support of Project 2. 

■	 Characterized the morphology of a SWCNT aerosol generated for a 

mouse inhalation study in support of Project 2. 

■	 Selected and obtained various commercially available nanomaterials 

and performed preliminary screening of physical properties through 

collaboration with Project 11 and in support of Project 4. 

■	 Developed and conducted preliminary testing of a nanomaterial redispersion system for nanoscale TiO2 in support of Project 4. The system 

includes a flexible nonradioactive aerosol neutralization device. 

■	 Constructed a flow and humidity control system for the nanomaterial 

redispersion system above in support of Project 4. Determined that 

high humidity has a serious adverse effect on redispersion of powdered 

nanomaterials. 

■	 Completed preliminary testing of an electro-spray aerosol generation 

system to produce aerosols of nanoparticles in support of Project 4. 

■	 Evaluated the airborne levels of SWCNTs during synthesis and handling in a laboratory setting. 

■	 In collaboration with the University of Minnesota, used real-time new 

instrumentation (serial measurements of particle mobility and mass) 

combined with TEM analysis to obtain information about the relationship between particle morphology and particle properties of irregularly 

shaped nanoparticles. 

69 
NIOSH Nanotechnology Research Center 

■	 Observed anomalous behavior in state-of-the-art aerosol measurement 

instrumentation. These findings are anticipated to lead to the development of effective monitoring methods and new and improved instrument designs that are needed for accurate characterization of worker 

exposures. 

■	 Evaluated particle sizing instrument responses to airborne carbon 

nanotubes and nanofibers. 

■	 In support of a NIOSH extramural project, collaborated with University of Cincinnati researchers in the performance evaluation of a wetelectrostatic precipitator for diesel engine exhaust after-treatment. 

■	 In collaboration with the University of Iowa: 

1.	 Conducted the first workplace study of ultrafine and nanoparticle mapping. Mapped ultrafine number concentration, active 

surface area and respirable mass concentration in an engine 

machining facility. 

2.	 Demonstrated the appropriate selection and use of mobile 

sampling equipment for effective monitoring of ultrafine and 

nanoparticles in workplaces. 

3.	 Demonstrated that the contribution of emissions from direct 

gas-fired heating systems can dominate ultrafine particle concentrations within a workplace. 

4.	 Mapped ultrafine number concentrations, active surface area, 

and respirable mass concentrations in an automotive foundry 

and demonstrated some limitations in mapping procedures. 

5.	 Conducted field research to help identify cause of high ultrafine 

particle concentration formation from direct gas-fired heating 

systems. 

Publications and Abstracts 

■	 Evans DE, Maynard AD, Peters TM, Heitbrink WA [2005]. Estimating 

aerosol surface area in the automotive industry. 24th Annual AAAR 

Conference, Austin, TX, October 17–21, p. 293. 

■	 Ku BK, Maynard AD [2005]. Physical characterization of airborne carbon nanofibers. 2nd International Symposium on Nanotechnology and 

Occupational Health, Minneapolis, MN, October 3–6, p. 119. 

■	 Ku BK, Maynard AD [2005]. Comparing aerosol surface-area measurement of monodisperse ultrafine silver agglomerates using mobility 

70 
Appendix A ■ Project-Specific Progress Reports 

analysis, transmission electron microscopy and diffusion charging. J 

Aerosol Sci 36:1108–1124. 

■	 Ku BK, Maynard AD [2006]. Generation and investigation of airborne 

silver nanoparticles with specific size and morphology by homogeneous nucleation, coagulation, and sintering. J Aerosol Sci 37:452–470. 

■	 Ku BK, Emery MS, Maynard AD, Stolzenburg MR, McMurry PH 

[2006]. In situ structure characterization of airborne carbon nanofibers 

by a tandem mobility-mass analysis. Nanotechnol 17:3613–3621. 

■	 Ku BK, Maynard AD, Evans DE [2005]. Methods for measuring the 

active surface area of ultrafine particles as an exposure metric. 9th 

International Symposium on Neurobehavioral Methods and Effects 

in Occupational and Environmental Health, Gyeongju, South Korea, 

September 26–29, p. 26. 

■	 Ku BK, Maynard AD, Baron PA, Deye G [2005]. Anomalous responses 

(arcing, electrical discharge) in a differential mobility analyzer caused 

by ultrafine fibrous carbon aerosols. 24th Annual AAAR Conference, 

Austin, TX, October 17–21, p. 43. 

■	 Ku BK, Emery MS, Maynard AD, Stolzenburg MR, McMurry PH 

[2006]. Measurement of airborne carbon nanofiber structure using a 

tandem mobility-mass analysis. 7th International Aerosol Conference, 

Minneapolis, MN, September 10–15. 

■	 Maynard AD [2004]. Nanotechnology—a new occupational health 

challenge for a new generation? Int Commission Occup Health Newsletter 2(3):4–6. 

■	 Maynard AD [2004]. Responsible nanotech at work. Nanotechnology: 

A Materials Today Supplement, p. 56. 

■	 Maynard AD [2005]. Characterizing exposure to nanomaterials. The 

Toxicologist 84:A649. 

■	 Maynard AD, Kuempel ED [2005]. Airborne nanostructured particles 

and occupational health. J Nanopart Res 7:587–614. 

■	 Maynard AD, Baron PA, Foley M, Shvedova AA, Kisin ER, Castranova 

V [2004]. Exposure to carbon nanotube material during the handling 

of unrefined single walled carbon nanotube material. J Toxicol Environ 

Health Part A 67:87–107. 

■	 Peters TM, Heitbrink WA, Evans DE, Slavin TJ, Maynard AD [2006]. 

The mapping of fine and ultrafine particle concentrations in an engine 

machining and assembly facility. Ann Occup Hyg 50(3):249–257. 

71 
NIOSH Nanotechnology Research Center 

■	 Ramsey D, Ku BK, Maynard AD, Evans DE, Bennett J [2005]. Evaluation of nanoparticle de-agglomeration by disc centrifuge. 2nd International Symposium on Nanotechnology and Occupational Health, 

Minneapolis, MN, October 3–6, p. 120. 

■	 Stolzenburg M, McMurry PH, Emery MS, Ku BK, Maynard AD [2006]. 

Obtaining dispersion of an intensive particle property from a tandemsizing experiment. 7th International Aerosol Conference, Minneapolis, 

MN, September 10–15. 

Invited Presentations 

■	 Maynard A [2005]. Working with engineered nanomaterials: Towards 

developing safe work practices. University of Cincinnati. Cincinnati, 

OH, May. 

■	 Maynard A [2005]. Working with engineered nanomaterials: Towards 

developing safe work practices. Korean Occupational Safety and Health 

Agency (KOSHA), Daejeon, South Korea, May 11. 

■	 Maynard A [2005]. Nanotechnology and occupational health—addressing potential health risks. Korean Society of Toxicology Annual 

Conference, Seoul, Korea, May 13. 

■	 Maynard A [2005]. Nanotechnology: Overview and relevance to occupational health. AIHce, Anaheim, CA, May 24. 

■	 Maynard A [2005]. Nanotechnology and occupational health. AIHce, 

Anaheim, CA, May 24. 

■	 Maynard A [2005]. Working at the nanoscale: nanotechnology and 

potential health risk. AIHce, Anaheim, CA, May 24. 

■	 Maynard A [2005]. Nanomaterials and occupational health. Establishing a healthy working environment. The World Environment Center 

International Environment Forum, New York, NY, March 10. 

■	 Maynard A [2005]. Responsible nanotechnology and the working environment. National Research Council review of the US NNI, Meeting 

on responsible nanotechnology, Washington, DC, March 24. 

■	 Maynard A [2005]. Generating and characterizing airborne nanoparticles. American Association for the Advancement of Science: Nanoaerosol Exposure, Washington, DC, February 20. 

72 
 

 

 

 

Appendix A ■ Project-Specific Progress Reports 

■	 Maynard A [2005]. Understanding the potential impact of nanotechnology on occupational health. University of Cincinnati, Cincinnati, 

OH, February 23. 

■	 Maynard A [2004]. Working with engineered nanomaterials: Towards 

developing responsible work practices in an uncertain world. National 

Nanotechnology Infrastructure Network (NNIN) meeting Nanosafe: 

A Workshop on Environmental Health and Safety in Nanotechnology 

Research. Georgia Institute of Technology, Atlanta, GA, December 2. 

■	 Maynard A [2004]. NORA Liaison Committee Meeting. Nanotechnology at NIOSH. Washington DC, December 2. 

■	 Maynard A [2004]. Laboratory safety and disposal issues. Nanotoxicology Workshop. Gainesville, FL, November 3. 

■	 Maynard A [2004]. Working at the nanoscale: nanotechnology and 

potential health risks. CDC/Environmental & Occupational Health & 

Injury Prevention Coordination Center, Atlanta, GA, November 9. 

■	 Maynard A [2004]. Nanotechnology: Challenges and Opportunities. 

OSHA/NIOSH Interagency Health Outcome Conference. Washington, 

DC, November 16. 

■	 Maynard A [2004]. Nanotechnology and occupational health. Professional Conference of Industrial Hygienists. Montreal, Canada, October 5. 

■	 Maynard A [2004]. Nanotechnology and occupational health. Am. 

Chemical Council Nanotechnology Workshop, Atlanta, GA, October 20. 

■	 Ku BK [2005]. Physical characterization of ultrafine particles: Nanoaerosol surface area measurement. Korea Occupational Safety and 

Health Agency (KOSHA), Incheon, Korea, September 22–23. 

■	 Ku BK [2006]. Physical characterization of occupationally relevant 

nanoparticles. University of Kentucky, Lexington, KY, March 9. 

■	 Evans D [2006]. Field measurement of nano-aerosols. International 

Conference on Nanotechnology. Occupational and Environmental 

Health & Safety: Research to Practice. Cincinnati, OH, December 4–7. 

73 
 

NIOSH Nanotechnology Research Center 

Project 2: Pulmonary Toxicity of Carbon Nanotube 

Particles 

Accomplishments 

■	 Measured the generation of hydroxyl radicals by unpurified SWCNTs. 

Determined that this radical generation was due to iron contamination 

of the nanotubes. 

■	 Measured oxidant stress and injury to human keratinocytes and human 

bronchial epithelial cells exposed to unpurified single-walled carbon 

nanotubes in culture. 

■	 Determined that acid treatment removes contaminating iron from 

SWCNTs. Found that these purified nanotubes do not generate radicals 

and are not avidly phagocytized by macrophages in culture. 

■	 Exposed mice to purified SWCNTs by pharyngeal aspiration. Observed 

transient inflammation and damage but a rapid and progressive fibrotic 

response in the lungs. Agglomerates were associated with fibrosis in 

granulomatous lesions; while more dispersed structures resulted in 

progressive diffuse interstitial fibrosis. 

■	 In vitro exposure of macrophages to purified SWCNTs indicates that 

the nanotubes are not avidly phagocytized and do not stimulate an 

oxidative burst reaction. In vivo exposure of the lung also supports the 

lack of avid phagocytosis by the alveolar macrophages that correlates 

with the absence of persistent inflammation. 

■	 Adsorption of phosphatidylserine (but not phosphatidylcholine) on the 

SWCNT surface makes them recognizable by macrophages indicating 

potentially promising approaches to modulating their fate in the lung. 

■	 A generation system was developed to produce aerosols of SWCNTs for 

an inhalation study. Inhalation exposure studies have been taking place 

during the summer of 2006. 

Publications and Abstracts 

■	 Baron PA [2006]. Description of an aerosol calculator. 7th International 

Aerosol Conference, Minneapolis, MN, September 10–15. 

■	 Baron PA, Deye GJ, Shvedova AA, Castranova V [2005]. Generation of 

very low density fibrous carbon powders (single-walled carbon nanotubes and Pyrograf III). 24th Annual AAAR Conference, Austin, TX, 

October 17–21, p. 214. 

74 
 

 

 

 

Appendix A ■ Project-Specific Progress Reports 

■	 Baron PA, Deye GJ, Shvedova AA, Castranova V [2005]. Generation of 

very low density fibrous carbon powders (single-walled carbon nanotubes and Pyrograf III). 2nd International Symposium on Nanotechnology and Occupational Health, Minneapolis, MN, October 3–6, p. 40. 

■	 Feng WH, Tyurina YY, Bayir H, Shvedova AA, Kagan VE [2007]. 

Phosphatidylserine enhances recognition and uptake of single-walled 

carbon nanotubes by rat microglial cells. The Toxicologist 91(1). 

■	 Heck DE, Kagan VE, Shvedova AA, Laskin JD [2005]. An Epigrammatic (abridged) recounting of the myriad tales of astonishing deeds 

and dire consequences pertaining to nitric oxide and reactive oxygen 

species in mitochondria with an ancillary missive concerning origin of 

apoptosis. Toxicol 208(2):259–271. 

■	 Kagan VE, Bayir H, Shvedova AA [2005]. Nanomedicine and nanotoxicology: Two sides of the same coin. J Nanomedicine: Nanotechnol Biol 

Med 1(4):313–316. 

■	 Kagan VE, Potapovich AN, Osipov YY, Tyurina ER, Kisin E, Schwegler-Berry D, Mercer R, Castranova V, Shvedova AA [2006]. Direct 

and indirect effects of single-walled carbon nanotubes on RAW 264.7 

macrophages: Role in iron. Toxicol Lett 165:88–100. 

■	 Kagan V, Tyurina YY, Konduru N, Basova L, Stolz D, Kisin E, Murray 

A, Fadeel B, Shvedova A [2007]. Targeted delivery of phosphatidylserine-coated single-walled carbon nanotubes to macrophages. The 

Toxicologist 91(1). 

■	 Kisin E, Murray AR, Johnson V, Gorelik O, Arepalli S, Gandelsman 

VZ, Hubbs AF, Mercer RR, Baron P, Kagan VE, Castranova V, Shvedova AA [2005]. Pulmonary toxicity of carbon nanotubes. The Toxicologist 84:A1041. 

■	 Kisin E, Murray AR, Castranova V, Kagan VE, Shvedova AA [2006]. 

Single-wall carbon nanotubes induce oxidative stress, acute inflammation, and progressive pulmonary fibrosis. Toxicol 90(1):A1556. 

■	 Mercer RR, Scabilloni J, Kisin E, Gorelik O, Arepalli S, Murray AR, 

Castranova V, Shvedova AA [2005]. Responses of lung parenchyma to 

carbon nanotubes. The Toxicologist 84:A1042. 

■	 Shvedova AA, Castranova, V, Kisin E, Schwegler-Berry D, Murray AR, 

Gandelsman VZ, Maynard A, Baron P [2003]. Exposure to carbon 

nanotube material: Assessment of nanotube cytotoxicity using human 

keratinocyte cells. J Toxicol Environ Health, 66(Part A):1901–1918. 

75 
 

NIOSH Nanotechnology Research Center 

■	 Shvedova AA, Kisin ER, Murray AR, Schwegler-Berry D, Gandelsman 

VZ, Baron P, Maynard A, Gunther MR, Castranova V [2004]. Exposure 

of human bronchial epithelial cells to carbon nanotubes caused oxidative stress and cytotoxicity. Proceedings of the Society for Free Radical 

Research Meeting. European Section, Ioannina, Greece, June 26–29, 

2003, pp. 91–103. 

■	 Shvedova AA, Kisin E, Murray AR, Gorelik O, Arepalli S, Gandelsman 

VZ, Mercer B, Hubbs A, Kagan VE, Castranova V [2004]. Oxidative 

stress and pulmonary toxicity of carbon nanotubes. Free Radical Biol 

Med 37(1). 

■	 Shvedova AA, Kisin E, Murray A, Maynard A, Baron P, Gunther M, 

Keshava N, Schwegler-Berry D, Gandelsman V, Gorelik O, Aperalli S, 

Kagan V, Castranova V [2004]. Assessment of carbon nanotube cytotoxicity using human cells and animal models. Proceedings of The 

Toxicology Forum’s 29th Toxicology Annual Winter Meeting, Washington, DC, February 2–4. 

■	 Shvedova A, Kisin E, Mercer R, Murray A, Johnson VJ, Potapovich A, 

Tyurina Y, Gorelic O, Arepalli S, Schwegler-Berry D, Antonini J, Evans 

DE, Ku B-K, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P 

[2005]. Unusual inflammatory and fibrogenic pulmonary responses to 

single walled carbon nanotubes in mice. Am J Physiol: Lung Cell Mol 

Physiol 289:L698–L708. 

■	 Shvedova AA [2005]. Comparative toxicity of nanomaterials in vivo 

and in vitro. 229th American Chemical Society Meeting, San Diego, 

CA, March 12–16. 

■	 Shvedova AA, Potapovich AL, Osipov AN, Tyurina YY, Kisin E, 

Schwegler-Berry D, Mercer RR, Castranova V, Kagan VE [2006]. Oxidative interactions of single walled carbon nanotubes with RAW 264.7 

macrophages: role of iron. Toxicol 90(1):A1557. 

■	 Shvedova AA, Kisin ER, Murray A, Gorelik O, Arepalli S, Castranova 

V, Young S-H, Gao F, Tyurina YY, Oury T, Kagan VE [2007]. Vitamin E 

deficiency enhances pulmonary inflammatory response and oxidative 

stress induced by single-walled carbon nanotubes in C57B6/L mice. 

The Toxicologist 91(1). 

Invited Presentations 

■	 Baron P [2006]. Measurement and generation of single-walled carbon 

nanotubes. Particle Workshop at NIST, Gaithersburg, MD, April 24–26. 

76 
Appendix A ■ Project-Specific Progress Reports 

■	 Baron P, Schulte P, Evans D [2006]. The nanotechnology program at 

NIOSH. Presented at the Emerging Needs in Aerosol Research for Occupational Hygiene. INRS, Nancy, France, November 22. 

■	 Castranova V [2005]. Pulmonary response to exposure to carbon nanotubes. Korean Society of Toxicology, Seoul, South Korea, May 13. 

■	 Castranova V [2005]. Pulmonary toxicity of single-walled carbon 

nanotubes. The Centre for Nanoscience and Nanotechnology. University of Melbourne, Melbourne, Australia, July 14. 

■	 Castranova V [2005]. Pulmonary toxicity of single walled carbon 

nanotubes. Research School of Physical Sciences and Engineering. The 

Australian National University, Canberra, Australia, July 27. 

■	 Castranova V [2005]. Pulmonary toxicity of single walled carbon 

nanotubes. National Industrial Chemicals Notification and Assessment 

Scheme. Sydney, Australia, July 29. 

■	 Castranova V [2005]. Pulmonary toxicity of single walled carbon nanotubes. Oak Ridge National Laboratory, Oak Ridge, TN, June 24. 

■	 Castranova V [2006]. Pulmonary toxicity of single-walled carbon 

nanotubes. Material Sciences Conference, San Francisco, CA, April 29. 

■	 Castranova V [2006]. Pulmonary toxicity of single-walled carbon 

nanotubes. 7th International Conference on the Science and Application of Nanotubes, Nagano, Japan, June 19–23. 

■	 Shvedova A [2004]. Pulmonary toxicity of carbon nanotubes. International Congress on Nanotechnology, San Francisco, CA, November 

7–10. 

■	 Shvedova A [2004]. Pulmonary toxicity of SWCNT. National Nanotechnology Infrastructure Network (NNIN) meeting Nanosafe: A 

Workshop on Environmental Health and Safety in Nanotechnology 

Research, Georgia Institute of Technology, December 2. 

■	 Shvedova A [2004]. Pulmonary toxicity of carbon nanotubes: what 

we know and what we do not know. National Nanotechnology Infrastructure Network (NNIN): Nanosafe: A Workshop on Environmental 

Health and Safety in Nanotechnology Research, Atlanta, GA, December 1–3. 

■	 Shvedova A [2005]. Pulmonary oxidative stress, inflammation, and 

fibrosis induced by single wall carbon nanotubes. 2nd International 

Symposium on Nanotechnology and Occupational Health, Minneapolis, MN, October 3–6. 

77 
NIOSH Nanotechnology Research Center 

■	 Shvedova A [2005]. Pulmonary toxicity of carbon nanotubes. 8th 

International Conference on Mechanisms of Action of Inhaled Fibers, 

Particles, and Nanoparticles in Lung and Cardiovascular Diseases, Research Triangle Park, NC, October 25–28. 

■	 Shvedova A [2005]. Comparative toxicity of nanomaterials in vivo and 

in vitro. 229th American Chemical Society Meeting. San Diego, CA, 

March 12–16. 

■	 Shvedova A [2005]. Pulmonary response to carbon nanotubes. 44th Society of Toxicology Meeting, New Orleans, LA, March 6–10. 

■	 Shvedova A [2005]. Unusual pulmonary response to carbon nanoparticles. First Annual Meeting of American Academy of Nanomedicine. 

John Hopkins University, MD, August 15–16. 

■	 Shvedova A [2005]. Pulmonary oxidative stress, inflammation, and 

fibrosis induced by single wall carbon nanotubes. 2nd International 

Symposium on Nanotechnology and Occupational Health, Minneapolis, MN, October 3–6. 

■	 Shvedova A [2005]. Pulmonary toxicity of carbon nanotubes. 8th International Conference on Mechanisms of Action of Inhaled Fibers, Particles, and Nanoparticles in Lung and Cardiovascular Disease, Research 

Triangle Park, NC, October 25–28. 

■	 Shvedova A [2005]. Oxidative stress and pulmonary toxicity of carbon 

nanotubes. 1st International Meeting Nanotoxicology: Biomedical Aspects, Miami Beach FL, January 28–February 1. 

■	 Shvedova A [2006]. Single-walled carbon nanotubes induced oxidative 

stress, acute inflammation and progressive pulmonary fibrosis. 45th 

Society of Toxicology Meeting, San Diego, CA, March 12–18. 

■	 Shevedova A [2006]. Pulmonary effects of single-walled carbon nanotubes. International Conference on Nanotechnology, Occupational and 

Environmental Health & Safety; Research to Practice, Cincinnati, OH, 

December 4–7. 

■	 Shevedova A [2006]. Pulmonary toxicity of single-walled carbon nanotubes. Karolinska Institute Nanotechnology Symposium. Stockholm, 

Sweden, November 15. 

78 
 

 

 

 

 

 

Appendix A ■ Project-Specific Progress Reports 

Project 3: Role of Carbon Nanotubes in Cardiopulmonary 

Inflammation and COPD-Related Diseases 

Accomplishments 

■	 Mice were exposed to purified SWCNTs by pharyngeal aspiration and 

cardiopulmonary responses at 1, 7, 28, 56, and 180 days post-exposure 

were monitored. 

■	 At days 7, 28, 56, and 180 post-exposure to carbon nanotubes, observed mitochondrial DNA damage and increased production of reactive oxygen species in aortic tissue. 

■	 Found that pulmonary exposure to carbon nanotubes induced similar 

oxidative modification in aortic tissue of ApoE-1-mice, an atherosclerosis model. 

■	 Pulmonary exposure to carbon nanotubes induced activation of the 

oxidative gene, heme-oxygenase-1, in lung, heart, and aortic tissue. 

■	 Chronic exposure of mice (four instillations of 20 μg per mouse every other week for 2 months) to purified SWCNTs induced enhanced 

atherosclerosis progression in ApoE-/- mice especially if the mice were 

fed a fat chow. 

■	 The body weights, plasma cholesterol, glucose, and lactate dehydrogenase 

(LDH) levels were comparable in SWCNT- and vehicle-exposed mice 

under both diet regimens indicating that the enhanced progression of 

cardiovascular disease by SWCNTs is not due to altered lipid profiles. 

■	 The plaque area analyzed by aortic morphometric en face analysis demonstrated a significant increase in the atheroma formation in SWCNTexposed mice compared with the control-treated mice. 

■	 Histological assessment of the lesion size in the brachiocephalic arteries 

of these mice confirmed that SWCNT exposure accelerated atherosclerosis progression compared with the control treatment. 

■	 Although the plaques were larger in the SWCNT-exposed mice, the cellular composition of the plaques was similar to that of control-exposed 

mice. 

■	 SWCNT-induced atherosclerosis acceleration was not associated with 

significant differences in the plasma levels of inflammatory cytokines 

including IL–6, IL–10, MCP–1, TNF–α, and IFN–y. 

■	 Preliminary data demonstrated that SWCNT-induced atherogenic effects are associated with mitochondrial distress mediated endothelial 

79 
 

 

NIOSH Nanotechnology Research Center 

dysfunction and alterations in platelet properties (increased thrombogenic potential). 

Publications and Abstracts 

■	 Li Z, Salmen R, Hulderman T, Kisin E, Shvedova A, Luster M, Simeonova P [2004]. Pulmonary carbon nanotube exposure and oxidative 

status in vascular system. Free Radical Biol Med 37(1):S142. 

■	 Li Z, Salmen R, Hulderman T, Kisin E, Shvedova AA, Luster MI [2005]. 

Pulmonary exposure to carbon nanotubes induces vascular toxicity. 

The Toxicologist 84:A1045. 

■	 Li ZJ, Chapman R, Hulerman T, Salmen R, Shvedova, A, Luster MI, 

Simeonova PP [2006]. Relationship of pulmonary exposure to multiple 

doses of single wall carbon nanotubes and atherosclerosis in APOE-/­

mouse model. The Toxicologist 90(1):A1555. 

■	 Simeonova PP [2006]. Nanomaterial exposure and risk for systemic effects. 

Toxicology and Risk Assessment Meeting, Cincinnati, OH, April, p. 59. 

■	 Simeonova P, Li J, Luster MI, Shvedova A, Salmen R [in press]. Carbon 

nanotube exposure and cardiovascular outcomes. 2nd International 

Symposium on Nanotechnology and Occupational Health, Minneapolis, MN, 2005. 

Invited Presentations 

■	 Luster M [2004]. Nanoparticles toxicity testing issues. Nanotoxicology 

Workshop, Gainesville, FL, November 3–4. 

■	 Luster M [2005]. Nanoparticles toxicity issues. Ramazzini Collegium, 

Bologna, Italy, September. 

■	 Luster M [2006]. Nanomaterials workshop, project on emerging nanotechnologies. Woodrow Wilson International Center for Scholars, 

Washington, DC, March. 

■	 Simeonova P [2005]. Nanoparticles-systemic and vascular effects. 

Nano-toxicology: Biomedical Aspects, Miami, FL. 

■	 Simeonova P [2005]. Nanoparticles—toxicological approaches. First 

Annual Scientific Meeting of the American Academy of Nanomedicine, 

Baltimore, MD, August 15–16. 

■	 Simeonova P [2006]. Nanomaterial exposure and risk for systemic 

effects. Toxicology and Risk Assessment Conference, Cincinnati, OH, 

April 24–27. 

80 
Appendix A ■ Project-Specific Progress Reports 

■	 Simeonova P [2006]. Nanoparticles and cardiovascular toxicity. Allegheny-Erie Chapter, Society of Toxicology (A-E SOT), Pittsburgh, PA, 

April 7. 

■	 Simeonova P [2006]. Cardiovascular effects of nanoparticles. International Conference on Nanotechnology Occupational and Environmental Health and Safety: Research on Practice, Cincinnati, OH, December 

4–7. 

81 
 

 

NIOSH Nanotechnology Research Center 

Project 4: Particle Surface Area as a Dose Metric 

Accomplishments 

■	 Measured the particle surface area and mass of ultrafine and fine TiO2, 

ultrafine and fine carbon black, and fine and coarse crystalline silica 

samples. 

■	 Measured the surface area and cell numbers of primary rat alveolar 

macrophages and a human alveolar type II epithelial cell line in culture. 

■	 Evaluated the toxicity of silica, TiO2, and carbon black of different 

particle sizes using a mass-based and a surface-based dose metric with 

macrophages and type II cells. Found that silica was the most toxic of 

the particles tested. 

■	 Evaluated the ability of the above particles to stimulate production of 

an inflammatory chemokine (IL–8 or MIP–2) by human type II cells or 

rat alveolar macrophages, respectively. Found that silica was the most 

potent stimulant of chemokine production. 

■	 Evaluated the dose-dependent pulmonary response to intratracheal 

instillation of ultrafine and fine carbon black 24 hours post-exposure. 

Found that on an equivalent mass basis ultrafine carbon black was 

more inflammatory. 

■	 Developed an improved method to disperse nanoparticles using bronchoalveolar lavage fluid for in vitro and in vivo testing. 

■	 Demonstrated that the improved dispersal method increased the inflammatory potency of ultrafine carbon black after intratracheal instillation. 

Publications and Abstracts 

■	 Castranova V [2007]. Comparison of pulmonary responses to singlewalled vs. multi-walled carbon nanotubes. The Toxicologist 91(1). 

■	 Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick 

J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, MonterioRiviere N, Warheit D, Yang H [2005]. Principles for characterizing the 

potential human effects from exposure to nanomaterials: elements of 

screening strategy. Particle Fibre Toxicol 2:8. 

■	 Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick 

J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, MonterioRiviere N, Warheit D, Yang H [2005]. Principles for characterizing the 

potential human effects from exposure to nanomaterials: elements of a 

screening strategy. Toxicol 90:A2333. 

82 
Appendix A ■ Project-Specific Progress Reports 

■	 Sager T, Robinson VA, Poster DW, Schwegler-Berry DE, Lindsley W, 

Castranova V [2007]. An improved method to prepare suspensions of 

nanoparticles for treatment of lung cells in culture or in vivo exposure 

by pharyngeal aspiration or intratracheal instillation. The Toxicologist 

91(1). 

■	 Sager T, Porter DW, Robinson VA, Lindsley WG, Schwegler-Berry DE, 

Castranova V [2007]. Improved method to disperse nanoparticles for 

in vitro and in vivo investigation of toxicity. Nanotoxicity 1. 

■	 Shvedova AA, Sager T, Murray AR, Kisin E, Porter DW, Leonard SS, 

Schwegler-Berry D, Robinson VA, Castranova V [2007]. Critical issues 

in the evaluation of possible adverse pulmonary effects resulting from 

airborne nanoparticles. In: Monteiro-Riviere N, Tran L, eds. Nanotechnology: Characterization, Dosing and Health Effects. New York: Taylor 

and Francis. 

■	 Sriram K, Porter DW, Tsuruoka S, Endo M, Jefferson AM, Wolfarth 

MG, Rogers GM, Castranova V, Luster MI [2007]. Neuroinflammatory 

responses following exposure to engineered nanomaterials. The Toxicologist 91(1). 

Invited Presentations 

■	 Castranova V [2004]. Nanotechnology safety and health research in 

NIOSH. First International Conference on Nanotoxicology: Biomedical 

Applications, Miami, FL, January 29–February 1. 

■	 Castranova V [2004]. Potential toxicity of nanoparticles. 2004 Northwest Occupational Health Conference, Portland, OR, October 14. 

■	 Castranova V [2005]. General toxicological issues of potential concern 

with nanoparticles, an overview. Nanotechnology Building Block for 

Tomorrow’s Advanced Technology, Perth, Australia, July 18. 

■	 Castranova V [2005]. Health issues for nanoparticles and nanotubes. 

Australian National Council Nanotechnology Network, Canberra, 

Australia, July 25. 

■	 Castranova V [2005]. Nanotechnology safety and health research in 

NIOSH. Korean Occupational Safety and Health Administration, Daejeon, South Korea, May 12. 

■	 Castranova V [2005]. Toxicity of ultrafine particles. Australian Institute 

for Bioengineering and Nanotechnology, University of Queensland, 

Brisbane, Australia, July 14. 

83 
NIOSH Nanotechnology Research Center 

■	 Castranova V [2005]. Toxicity of ultrafine particles. Centre for Nanoscience and Nanotechnology, University of Melbourne, Melbourne, 

Australia, July 14. 

■	 Castranova V [2005]. Toxicity of ultrafine particles. Ian Wark Research 

Institute, University of South Australia, Adelaide, Australia, July 26. 

■	 Castranova V [2005]. Toxicity of ultrafine particles. NASA Scientific 

Group, January 19. 

■	 Castranova V [2006]. Nanotoxicology program in NIOSH. NANOMIST Workshop. London, England, November 15. 

■	 Castranova V [2006]. Nanotoxicology research in NIOSH. American 

Industrial Hygiene Conference, Chicago, IL, May 16. 

■	 Castranova V [2006]. Nanotoxicology research in NIOSH. Nanobusiness 06, New York, May 19. 

■	 Castranova V [2006]. Nanotechnology safety and health research in 

NIOSH. EPA, Research Triangle Park, NC, July 25. 

■	 Castranova V [2006]. Pulmonary effects of exposure to single-walled carbon nanotubes. Wright Patterson Air Force Research Center. 

Dayton OH, October 31. 

■	 Castranova V [2006]. Pulmonary toxicology studies with nanoparticles: 

experimental issues. Informa Learning’s Conference on Nanotoxicology, Cambridge, MA, April 25. 

■	 Castranova V [2006]. Toxicity of ultrafine particles. Nanotechnology 

Center, Ohio State University, Columbus, OH, February 24. 

■	 Castranova V [2006]. Toxicity of ultrafine particles. Nanotox Consortium, University of Kentucky, Lexington, KY, September 19. 

■	 Porter D [2006]. Overview of NIOSH nanotoxicology research. Michigan Regional Chapter of the National Society of Toxicology, Augusta, 

MI, May 19. 

■	 Porter D [2005]. Particulate handling in the human lung. Biological Effects of Lunar Dust Workshop, Sunnyvale, CA, March 29–31. 

■	 Porter D [2005]. Toxicity of ultrafine particles. Nanotechnology: Occupational Safety and Health Perspectives. 21st Annual Kentucky 

Governor’s Safety and Health Conference and Exposition, Louisville, 

KY, May 11. 

84 
 

 

 

 

 

 

Appendix A ■ Project-Specific Progress Reports

 Project 5: Ultrafine Aerosols from Diesel-Powered

 Equipment 

Accomplishments 

■	 Developed a diesel and nanoparticle research facility at the Lake Lynn 

Laboratory. Designed and built 150- and 400-kw engine/dynamometer 

systems; designed and built downstream, upstream, and tailpipe sampling and measurement stations; designed and built ventilation control 

and measurement facilities; developed and evaluated particle sampling, 

measurement, and analysis methodologies. 

■	 Selected, acquired, and evaluated instrumentation for characterization 

of physical and chemical properties of diesel aerosols and gases. 

■	 Conducted a field study in an underground mine using diesel mining vehicles. The Scanning Mobility Particle Sizer, Tapered Element 

Oscillating Microbalance, and carbon analysis were used to determine 

and characterize particulate matter in the mine air downstream of the 

tested vehicles. 

■	 Developed protocols and conducted preliminary evaluation of the effects of emission controls, clean engines, and fuel formulations on the 

emission of fine and ultrafine diesel particles. 

■	 Developed methods for sampling and analysis of in vitro mutagenic 

and DNA and chromosomal damage activity by surfactant dispersion 

or solvent extract of a diesel aerosols. 

Publications and Abstracts 

■	 Bugarski A [2004]. Characterization of diesel aerosols in an underground metal mine. Proceedings of 8th ETH-Conference on Combustion Generated Nanoparticles (CD-ROM), August 16–18. 

■	 Bugarski A, Mischler S, Schnakenberg G [2005]. Affects of alterative fuels 

on concentrations of nanometer and ultrafine particles in an underground 

mine. In: Proceedings of 9th ETH-Conference on Combustion Generated 

Nanoparticles (CD-ROM), Zurich, Switzerland, August 15–17. 

■	 Bugarski A [2006]. Characterization of combustion generated nanometer and ultrafine aerosols emitted in work environment. 10th ETHConference on Combustion Generated Nanoparticles (CD-ROM), 

Zurich, Switzerland, August 21–23. 

■	 Bugarski AD, Schnakenberg GH Jr., Noll JD, Mischler SE, Patts LD, Hummer JA, Vanderslice SE [2006]. Effectiveness of selected diesel particulate 

85 
NIOSH Nanotechnology Research Center 

matter control technologies for underground mining applications: isolated zone study, 2003. Cincinnati, OH: U.S. Department of Health and 

Human Services, Centers for Disease Control and Prevention, National 

Institute for Occupational Safety and Health, NIOSH RI 9667. 

■	 Mischler S, Bugarski A, Schnakenberg G [2005]. Analysis of diesel 

particulate matter control technologies and measurements in US metal 

mines. Proceedings of 8th International Mine Ventilation Congress, 

Brisbane, Queensland, Australia, July 6–8. 

■	 Shi, XC, Keane M, Ong T, Harrison J, Gautam M, Bugarski A, Wallace 

W [2006]. In vitro mutagenic and DNA and chromosomal damage 

activity by surfactant dispersion or solvent extract of a reference diesel 

exhaust particulate material. 12th Diesel Engine-Efficiency and Emission Research (DEER), August 20–24. 

86 
 

Appendix A ■ Project-Specific Progress Reports 

Project 6: Nanotechnology Safety and Health Research 

Coordination 

Accomplishments 

■	 Organized a retreat of NIOSH aerosol scientists August 25–27, 2004 to 

formulate a strategic plan and discuss research progress in nanotechnology. Dr. Lang Tran from the Institute of Occupational Medicine, 

Edinburgh, Scotland was the guest speaker. 

■	 Organized a second retreat of NIOSH aerosol scientists August 23–25, 

2005 to update the strategic plan and discuss research progress in 

nanotechnology. Dr. Pratim Biswas from Washington University in St. 

Louis, Missouri, was the guest speaker. 

■	 Submitted annual reports to the Office of the Director, NIOSH. 

87 
 

 

 

 

 

NIOSH Nanotechnology Research Center 

Project 7: Systemic Microvascular Dysfunction—Effect of 

Ultrafine versus Fine Particles 

Accomplishments 

■	 Constructed and tested a generator of ultrafine TiO2 for rat inhalation 

studies. A stable output was achieved. 

■	 Initiated dose-response inhalation studies. Monitored the pulmonary 

response to the first test concentration. Monitored the systemic microvascular response to the first two test concentrations. Thus far, the 

systemic microvascular response to ultrafine TiO2 is greater than to fine 

TiO2

. 

Publications and Abstracts 

■	 Nurkiewicz TR, Porter DW, Barger M, Hubbs AF, Millecchia L, Rao K, 

Chen BT, Frazer D, Castranova V, Boegehold MA [2006]. Peripheral 

microvascular dysfunction follows ultrafine titanium dioxide inhalation. Health Effects Institute Annual Conference, San Francisco, CA, 

April. 

■	 Nurkiewicz TR, Porter DW, Barger M, Millecchia L, Rao KM, Marvar 

PJ, Hubbs AF, Castranova V, Boegehold MA [2007]. Systemic microvascular dysfunction and inflammation after pulmonary particulate 

matter exposure. Environ. Health Perspect. 114:412–419. 

■	 Nurkiewicz TR, Porter DW, Hubbs AF, Millecchia L, Stone S, Chen BT, 

Frazer D, Castranova V, Boegehold M [2007]. Inhalation of ultrafine 

titanium dioxide augments particle-dependent microvascular dysfunction. FASEB J 21. 

Invited Presentations 

■	 Castranova V [2005]. Microvascular dysfunction resulting from pulmonary exposure to particles. Research School of Physical Sciences 

and Engineering, Australian National University, Canberra, Australia, 

July 27. 

■	 Castranova V [2005]. Microvascular dysfunction resulting from pulmonary exposure to particles. Asan Medical College, Seoul, Korea, May 16. 

■	 Castranova V [2005]. Microvascular dysfunction resulting from pulmonary exposure to particulate matter. 2005 Conference on the Application of Systems Biology Methodologies to Environmental Research, 

Morgantown, WV, August 1. 

88 
Appendix A ■ Project-Specific Progress Reports 

Project 8: Pulmonary Deposition and Translocation of 

Nanomaterials 

Accomplishments 

■	 Developed a method to improve dispersal of SWCNTs for pharyngeal 

aspiration. 

■	 Developed a method to label SWCNTs with colloidal gold or quantum 

dots to track their distribution and fate upon pulmonary exposure. 

■	 Demonstrated that low doses of purified and dispersed (sub-micron) 

SWCNTs are capable of widely distributing in the lungs where they 

are incorporated into the alveolar interstitium and produce a fibrotic 

response. 

■	 Demonstrated that iron-rich SWCNTs induce elevated biomarkers of 

oxidative stress. 

Publications and Abstracts 

■	 Kagan VE, Tyurina YY, Tyurin VA, Konduru NV, Potapovich AI, 

Osipov AN, Kisin ER, Schwegler-Berry D, Mercer RR, Castranova V, 

Shvedova AA [2006]. Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: Role of Iron. Toxicol Lett 

165:88–00. 

■	 Mercer RR, Scabilloni JF, Wang L, Schwegler-Berry D, Shvedova A, 

Castranova V [2007]. Dispersion significantly enhances the pulmonary 

toxicity of single walled carbon nanotubes. The Toxicologist 91(1). 

■	 Roberts JR, Mercer RR, Young S-H, Porter DW, Castranova V, Antonini JM [2007]. Inflammation and fate of quantum dots following pulmonary treatment of rats. The Toxicologist 91(1). 

■	 Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs 

AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, 

Castranova V, Baron P [2005]. Unusual inflammatory and fibrogenic 

pulmonary responses to single walled carbon nanotubes in mice. Am J 

Physiol Lung Cell Mol Physiol 289:698–708. 

Invited Presentations 

■	 Mercer R [2005]. Lung parenchymal responses to carbon nanotubes. 

2nd International Symposium on Nanotechnology and Occupational 

Health, Minneapolis, MN, October 3–6. 

89 
NIOSH Nanotechnology Research Center 

■	 Mercer R [2006]. Distribution of SWCNT in the lungs. Nanotoxicology: Biomedical Aspects, Miami, Fl, January 28–February 1. 

■	 Mercer R [2006]. Inhalation toxicity of single-walled carbon nanotubes. 

Society for Risk Assessment. Tripartite teleconference, June. 

■	 Mercer R [2006]. SWCNT distribute and injure the lungs in a size dependent manner. New York Occupational Safety and Health Research 

Center, New York, April. 

90 
Appendix A ■ Project-Specific Progress Reports 

Project 9: Dermal Effects of Nanoparticles 

Accomplishments 

■	 Demonstrated that exposure of human keratinocytes in vitro to unpurified SWCNTs resulted in significant cytotoxicity. Purification of 

SWCNT to remove the iron catalyst particles resulted in less toxicity. 

■	 Demonstrated that exposure to murine epidermal cells to unpurified 

SWCNT activated the transcription factor AP–1. Such activation was 

not seen with purified SWCNT. 

■	 Demonstrated that exposure of mouse skin in vivo to unpurified SWCNT caused oxidant stress and inflammation. 

■	 Demonstrated that in vitro exposure of epidermal cells to nanosized 

TiO2 generated hydroxyl radicals, and activated AP–1 through phosphorylation of MAP kinase signaling pathways. 

Publications and Abstracts 

■	 Ding M, Lu Y, Bowman L, Leonard S, Castranova V, Vallyathan V 

[2006]. Titanium nanoparticles induces AP-1 activation through ROS 

and MAPKS pathways. 1st International Toxicology of Nanomaterial: 

Biomedical Aspects Meeting, Miami Beach, FL, January 29–February 1, 

p. 101. 

■	 Murray AR, Kisin E, Castranova V, Kommineni C, Kagan VE, Shvedova AA [2006]. Oxidative stress and inflammatory response in dermal 

toxicity of single-walled carbon nanotubes. 1st International Toxicology of Nanomaterial: Biomedical Aspects Meeting, Miami Beach, FL, 

January 29–February 1, p. 50. 

■	 Murray AR, Kisin E, Kommineni C, Kagan VE, Castranova V, Shvedova AA [2007]. Single-walled carbon nanotubes induce oxidative stress 

and inflammation in skin. The Toxicologist 91(1). 

91 
NIOSH Nanotechnology Research Center 

Project 10: Neurotoxicity after Pulmonary Exposure to

 Welding Fumes Containing Manganese 

Accomplishments 

■	 Characterized the physical and chemical properties of generated welding aerosol. 

■	 Compared the pulmonary, inflammatory, and immune responses after 

exposure to stainless steel and mild steel welding fumes. 

■	 Designed and constructed a robotic welding fume generator and inhalation exposure system for laboratory animals. 

■	 Initiated animal inhalation toxicity studies. 

■	 Evaluated the translocation of welding fume metals from the lungs to 

other organ systems (e.g., central nervous system and cardiovascular 

system). 

■	 Evaluated the potential neurotoxic effects in animals after inhalation of 

welding fume. 

Publications and Abstracts 

■	 Antonini JM, Taylor MD, Zimmer AT, Robert JR [2004]. Pulmonary 

responses to welding fumes: Role of metal constituents. J Toxicol Environ Health 67:233–249. 

■	 Antonini JM, Taylor MD, Millecchia L, Ebeling AR, Robert JR [2004]. 

Suppression in lung defense responses after bacterial infection in rats 

pretreated with different welding fumes. Toxicol Appl Pharmacol 

200:206–218. 

■	 Antonini JM, Leonard SS, Robert JR, Solano-Lopez C, Young S-H, Shi 

X, Taylor MD [2005]. Effect of stainless steel manual metal arc welding 

fume on free radical production, DNA damage, and apoptosis induction. Mol Cell Biochem 279:17–23. 

■	 Antonini JM, Afshari AAA, Stone S, Chen B, Schwegler-Berry D, 

Fletcher WG, Goldsmith WT, Vandestouwe KH, McKinney W, Castranova, V, Frazer DG [2006]. Design, construction, and characterization 

of a novel robotic welding fume generation and inhalation exposure 

system for laboratory animals. J Occup Environ Hyg 3:194–203. 

■	 Antonini JM, Santamaria A, Jenkins NT, Albini E, Lucchini R [2006]. 

Fate of manganese associated with the inhalation of welding fumes: 

Potential neurological effects. Neurotoxicol 27:304–310. 

92 
Appendix A ■ Project-Specific Progress Reports 

■	 Antonini JM, O’Callaghan JP, Miller DB, Miller DB [in press]. Development of an animal model to study potential neurotoxic effects associated with welding fume inhalation. Neurotoxicol. 

■	 Santamaria AB, Cushing CA, Antonini JM, Finley BL, Mowat FS [in 

press]. Potential neurological effects of manganese exposure during 

welding: a state-of-the-science analysis. J Toxicol Environ Health. 

■	 Solano-Lopez C, Zeidler-Erdely PC, Hubbs AF, Reynolds SH, Roberts JR, Taylor MD, Young S-H, Castranova V, Antonini JM [in press]. 

Welding fume exposure and associated inflammatory and hyperplastic 

changes in the lungs of tumor susceptible A/J Mice. Toxicol Pathol. 

■	 Antonini JM, Roberts JR [2007]. Comparison of lung injury and inflammation after repeated treatment with welding fumes collected from 

different welding processes. The Toxicologist 91(1). 

■	 Zeidler-Erdely PC, Young S-H, Roberts JR, Antonini JM [2007]. Acute 

lung inflammatory response following pharyngeal aspiration of stainless steel welding fume or soluble chromium in A/J and C57Bl/6J mice. 

The Toxicologist 91(1). 

Invited Presentations 

■	 Antonini J [2004]. Effect of workplace particulates on the susceptibility 

to bacterial infection and the suppression of lung defense responses in 

rats. Society of Toxicology Annual Meeting, Baltimore, MD, March. 

■	 Antonini J [2004]. Bioavailability of manganese associated with the 

inhalation of welding fumes: potential neurological effects. Conference 

on Health Effects, Clinical Research, and Industrial Hygiene Issues in 

Occupational Exposure to Manganese, New Orleans, LA, April. 

■	 Antonini J [2004]. Bioavailability of manganese associated with the 

inhalation of welding fumes: potential neurological effects. Conference 

on Welding—Industrial Hygiene and Occupational Health, American Industrial Hygiene Association, Pacific Northwest Section, Spring 

Meeting, Olympia, WA, April. 

■	 Antonini J [2004]. Effect of welding fume metal composition and solubility on free radical production and lung inflammation and injury. 3rd 

Conference on Molecular Mechanisms of Metal toxicity and Carcinogenesis, NIOSH, September. 

■	 Antonini J [2005]. Health effects on welding. American Industrial Hygiene Association Annual Meeting: AIHce 2005, Anaheim, CA, May. 

93 
NIOSH Nanotechnology Research Center 

■	 Antonini J [2005]. Development of an animal model to study the health 

effects of welding. Health Effects of Welding International Conference, 

sponsors: NIOSH, NIEHS, and West Virginia University, Morgantown, 

WV, July. 

■	 Antonini J [2005]. Characterization of welding fumes and their neurotoxic effects. 22nd International Neurotoxicology Conference: Manganese Symposium, Research Triangle Park, NC, September. 

■	 Antonini J [2005]. Development of an animal model to assess the effect of occupational particles on the susceptibility to bacterial lung 

infection. 8th International Meeting on Effects on Mineral Dusts and 

Nanoparticles, Research Triangle Park, NC, October. 

■	 Antonini J [2006]. Suppression of lung defense responses after bacterial infection in rats exposed by inhalation to stainless steel welding 

particles. 1st International Conference on Nanotoxicology: Biomedical 

Aspects, Miami, FL, January. 

■	 Antonini J [2006]. Characterization of welding fumes and their potential neurotoxic effects. International Workshop: Neurotoxic Metals— 

Lead, Mercury, and Manganese: From Research to Prevention: Brescia, 

Italy, June. 

94 
 

 

 

Appendix A ■ Project-Specific Progress Reports 

Nanotechnology Safety and Health Research 

Program (Projects 1–10) 

National and International Activities and Conferences 

■	 Maynard A [2004]. Co-organized the First International Conference 

First International Symposium on Occupational Health Implications of 

Nanomaterials from October 12–14 in Buxton, UK. The conference is 

co-sponsored by the UK Health and Safety Executive and NIOSH. 

■	 Maynard A [2005]. Co-organized the Second International Symposium of Nanotechnology and Occupational Health, Minneapolis, MN, 

October 3–6. 

■	 Castranova V [2005]. Co-organized the conference Mechanisms of Action of Inhaled Fibers, Particles, and Nanoparticles in Lung and Cardiovascular Disease, Research Triangle Park, NC, October 25–28. 

■	 Castranova V, Maynard A [2005]. Served on an EPA Workgroup 

through the International Life Sciences Institute to draft a document 

entitled Screening Protocols for Nanomaterial Toxicity. 

■	 Maynard A [2005]. Served as the NIOSH representative on the Nanomaterial Science Engineering and Technology Subcommittee of the 

National Science and Technology Council that develops guidance for 

the direction of Federal research in nanotechnology. 

■	 Castranova V [2005 to present]. Serves on a scientific advisory committee 

for the Nanotechnology Research Institute at the University of Rochester. 

■	 Castranova V [2006]. Served as an expert panel member: Health and 

Environmental Issues in Nanotechnology. Wilson Institute, Washington, DC, April 6. 

■	 Castranova V [2006]. Served as a participant: National Nanotechnology Coordination Office Workgroup on Public Dissemination, Education, and Outreach. Arlington, VA, May 30–31. 

■	 Shvedova A, Castranova V [2006]. Co-organized the Nanotoxicology: 

Biomedical Aspects Conference in Miami, FL, January 28–February 1. 

(The conference was co-sponsored by NIOSH and the University of 

Pittsburgh). 

■	 Antonini J [2005]. Co-organized a NIOSH-sponsored international 

conference Health Effects of Welding, Morgantown, WV, July. The conference was co-sponsored by the National Institute of Environmental 

95 
NIOSH Nanotechnology Research Center 

Health Sciences (NIEHS), the Association of Occupational and Environmental Clinics, and West Virginia University. 

■	 Antonini J [2006]. Serves as Vice Chair of the Safety and Health Committee for the American Welding Society. 

■	 Simeonova P [2006]. Co-director of a NATO-funded Advanced Research Workshop Nanotechnology-Toxicological Issues and Environmental Security (CBP.EAP.ARW 982043), Varna, Bulgaria, August 

12–17. 

■	 Simeonova P [2006]. Co-chaired the Nanoparticles: Toxicology, Health 

Effects, Hazard Identification Session, Toxicology and Risk Assessment 

Conference, Cincinnati, OH, April 24–27. 

■	 Simeonova P [2006]. Organized a presentation and discussions with 

Dr. Hussain, Air Force Laboratory on nanotoxicology risk assessment 

for NIOSH scientists. June 7. 

■	 Simeonova P, Luster M [2006]. Organized a presentation and discussions on Nanomaterial Safety for NIOSH scientists with Dr. N. Walker, 

National Toxicology Program, July 12. 

Dissemination (interviews and articles in lay press) 

A. Maynard (Project 1), A. Shvedova (Project 2), and/or V. Castranova (Project 

6) have been interviewed by the following press concerning NIOSH activities 

in Nanotechnology: 

■	 Nanobiotech News 2, 20, pp. 2–3 (May 19, 2004) 

■	 Small Times (May 19, 2004) 

■	 CN&E News 82, 24 pp. (June 14, 2004) 

■	 Environmental Health Perspectives 112, pp. A741–A749 (2004) 

■	 Science News: Particular Problems: Assessing Risks of Nanotechnology, 

May 6, Vol. 169, pp. 280–281 (2006) 

■	 Science News: How ‘toxic’ nanotubes were faking it. Interview with Science News writer from UK Mason Inman on June 3, 2006, published 

on NewScientist.com news service (June 5, 2006). 

J. Antonini has been interviewed by the following press concerning the NIOSH 

welding project: 

■	 The Courier (Louisiana), Business section (October 27, 2002) 

■	 Science 300(5621):927 (May 9, 2003) 

96 
 

 

Appendix A ■ Project-Specific Progress Reports 

■	 National Law Journal 127(238) 3 (December 10, 2003) 

■	 Forbes, p. 44 (February 2, 2004) 

■	 The Tennessean (Nashville, TN), Business section, p. 1E (July 16, 2005). 

■	 The Synergist 16(9):48–49 (October 2005) 

■	 The Plain Dealer–Cleveland (June 2, 2006) 

■	 Associated Press (June 12, 2006) 

P. Simeonova was interviewed by the following press on research being conducted with SWCNTs: 

■	 NanoHazard, Science News (March 19, 2005) 

Partnerships and Collaborations 

■	 J. Antonini established an interagency agreement with National Toxicology Program (NTP) to aid in the construction of a welding fume 

generation and animal exposure system to be used for NTP-sponsored 

chronic animal studies. 

■	 J. Antonini has established a collaboration with the Manganese Health 

Research Program and Vanderbilt University (funded by the U.S. 

Department of Defense) to evaluate the effect of manganese in welding 

fume on neurotoxicity in laboratory animals. 

■	 V. Castranova (Project 4) is collaborating with G. Oberdorster at the 

University of Rochester on the ability of nanoparticles to generate radical species. 

■	 V. Castranova and D.W. Porter (Project 4) are collaborating with Dr. 

Chen at Oak Ridge Laboratory to evaluate the pulmonary toxicity of 

nanoparticles. 

■	 A. Shvedova and V. Castranova (Projects 2 and 4) are collaborating with 

V. Kagan at the University of Pittsburgh on the toxicity of nanomaterials. 

■	 Dr. Luster (Project 3) is collaborating with NIEHS/NIH and the Department of Defense on nanotoxicology. 

■	 V. Castranova and D.W. Porter (Project 4) and P. Simeonova are collaborating with Mitsui Inc. and Dr. Endo (Japan) on pulmonary and 

cardiovascular toxicity of multi-walled carbon nanotubes. 

■	 V. Castranova and D. Frazer are co-investigators on the extramural 

grant Microvascular dysfunction resulting from pulmonary exposure 

to fine versus ultrafine titanium dioxide funded by the Health Effects 

Institute, (7/05–6/08). Dr. Nurkiewicz, West Virginia University, PI. 

97 
NIOSH Nanotechnology Research Center 

■	 D. Evans collaborated with the University of Iowa on mapping measurement and characterization of airborne nanoparticles in the workplace. 

■	 D. Evans collaborated with the University of Cincinnati for conducting 

a performance evaluation of a wet-electrostatic precipitator for diesel 

engine exhaust after-treatment. 

■	 J. Ku and D. Evans established a partnership with the University of 

Minnesota on real-time measurement of nanomaterial structure. 

■	 E. Kuempel and R. Mercer are collaborating on a model for nanoparticle deposition with Dr. Owen Price at CIIT, Research Triangle Park, 

NC. 

■	 NIOSH PRL formed the Metal/Nonmetal Diesel Partnership with the 

National Mining Association (NMA), the National Stone Sand and 

Gravel Association (NSSGA), the United Steel Workers of America 

(USWA), the MARG Diesel Coalition and the Industrial Minerals Association—North America (IMA-NA) with the objective of reducing 

exposure of underground mines to diesel aerosols and gases. 

■	 NIOSH PRL Diesel team is collaborating with the Mechanical and 

Aerospace Engineering Department of West Virginia University on 

modeling dispersion of diesel aerosol plume in underground mining 

environment. 

■	 A. Shvedova (Project 2) has a MOU with NASA to evaluate the toxicity 

of single walled carbon nanotubes. 

■	 A. Shvedova is collaborating with Dr. Bengt Fadeel, Karolinska University, Stockholm, Sweden; Dr. Kadiiska, NIEHS, Research Triangle Park, 

NC; and Dr. P. Quinn, Professor of the Department of Biochemistry, 

Kings College, University of London, London, UK; on oxidant generation by nanoparticles and resultant oxidant stress in exposed cells. 

■	 A. Shvedova and V. Castranova are co-investigators on the extramural grant Oxidant stress induced by nanomaterials funded by NIOSH 

(7/05–6/08). Dr. Kagan, University of Pittsburgh, PA. 

■	 P. Simeonova is collaborating with WVU, Medical School and Engineering Department, on nanomaterial toxicity and physicochemical 

properties. 

■	 P. Simeonova is collaborating with the University of Rochester, Rochester, NY, Department of Environmental Medicine, with Dr. Gunter 

Oberdorster. 

98 
Appendix A ■ Project-Specific Progress Reports 

■	 P. Simeonova is collaborating with NIEHS/NTP, Research Triangle 

Park, NC, on fullerene toxicity and metal oxide nanomaterials. 

NTRC Critical Research Topic Areas Addressed 

1. Toxicity and Internal Dose [Projects 2–4 and 6–10] 

2. Measurement Methods [Projects 1 and 5] 

99 
NIOSH Nanotechnology Research Center 

Research Project 11: Nanoparticles in the 

Workplace 

Principal Investigator: Mark Hoover, Ph.D., DRDS/NIOSH/ 

CDC 

Project Duration: FY 2004–FY 2009 

Background 

The scope of the NIOSH Nanoparticles in the Workplace project is to foster the 

development of partnerships, exposure monitoring instrumentation, operational protocols, and a comprehensive and detailed database of nanoparticles 

and their properties. These activities are intended to provide NIOSH and the 

occupational safety and health community with a better understanding of the 

nature and extent of potential occupational exposures to nanoparticles. The 

results from these activities are expected to foster the development of comprehensive and scientifically sound occupational health protection strategies 

for emerging nanotechnologies. This work also supports NIOSH toxicology 

studies of nanomaterials. This project will enable NIOSH and the nanotechnology industries to better anticipate, recognize, evaluate, and control potential 

occupational exposures to nanoparticles during their manufacturing and use. 

Accomplishments 

■	 Partnerships were developed with nanotechnology industries, academia, government agencies, labor, and voluntary consensus standard 

committees to conduct joint research and develop guidelines on working safely with nanomaterials. 

■	 Sampling protocols and safety management guidelines were developed 

to help characterize the extent of exposure to nanoparticles in the 

workplace. 

■	 Partnerships were established with a fullerene research facility, an industrial nano-TiO2

 production facility, a cosmetics company, an industrial producer of ultrafine beryllium oxide materials, and a university 

research facility engaged in polymer work with carbon nanofibers to 

characterize occupational exposure to nanomaterials. 

■	 Assistance was provided to the ISO in creating the new ANSI nanotechnology program, including the establishment of a nanotechnology 

technical committee. 

100 
Appendix A ■ Project-Specific Progress Reports 

■	 A new carbon nanotube reference material was developed and evaluated in collaboration with NIST. 

■	 A new ultrafine beryllium oxide standard reference was developed in 

collaboration with NIST and the U.S. Department of Energy. 

■	 The in-house capabilities for physico-chemical characterization of 

nanoparticles, especially as it relates to surface area, were established. 

■	 The NIL Project (Web-based) was initiated to develop a database on 

nanomaterials. 

■	 Partnership was established with TSI Incorporated on the characterization, under actual industrial field conditions, of the lung-deposited 

surface area aerosol sampling instrument. 

Publications and Abstracts 

■	 Castranova V, Hoover MD, Maynard A [2005]. NIOSH nanotechnology safety and health research program, in nanoparticles: a risk to health 

at work? Final Report of the First International Symposium on Occupational Health Implications of Nanomaterials, David Mark, ed., June, 

p. 117, http://www.hsl.gov.uk/media/1646/nanosymrep_final.pdf. 

■	 Hoover MD [2005]. Mixed exposure issues for nanotechnology safety, 

in nanoparticles: a risk to health at work? Final Report of the First International Symposium on Occupational Health Implications of Nanomaterials, David Mark, ed., June, p. 115, 

http://www.hsl.gov.uk/media/1646/nanosymrep_final.pdf

. ■	 Hoover MD, Miller AL, Lowe NT, Stefaniak AB, Day GA, Linch KD 

[2005]. Information management for nanotechnology safety and 

health, in nanoparticles: a risk to health at work? Final Report of the 

First International Symposium on Occupational Health Implications 

of Nanomaterials, David Mark, ed., June, p. 110, 

http://www.hsl.gov.uk/media/1646/nanosymrep_final.pdf

. ■	 Northage C, Hoover MD [2005]. Report of workshop Group F on 

regulatory implications, in nanoparticles: a risk to health at work? Final 

Report of the First International Symposium on Occupational Health 

Implications of Nanomaterials, David Mark, ed., June, pp. 145–147, 

http://www.hsl.gov.uk/capabilities/nanosymrep_final.pdf. 

■	 Phalen RF, Hoover MD [2006]. Aerosol dosimetry research needs. Inh 

Toxicol 18(7–10):841–843. 

101 
NIOSH Nanotechnology Research Center 

■	 Stefaniak AB, Day GA, Scripsick RC, Hoover MD [2005]. Comprehensive characterization strategies for ultrafine particles: lessons from 

beryllium health and safety studies, in nanoparticles: a risk to health at 

work? Final Report of the First International Symposium on Occupational Health Implications of Nanomaterials, David Mark, ed., June, p. 

118, http://www.hsl.gov.uk/media/1646/nanosymrep_final.pdf. 

■	 Stefaniak AB, Hoover MD, Day GA, Ekechukwu AA, Whitney G, Brink 

CA, Scripsick RC [2005]. Characteristics of beryllium oxide and beryllium metal powders for use as reference materials. J. ASTM International, 2(10):doi 10.1520/JAl13174. 

■	 Watters RL, Hoover MD, Day GA, Stefaniak AB [2006]. Opportunities 

for development of reference materials for beryllium. J. ASTM International, 3(1):doi 10.1520/JAl13171. 

Invited Presentations 

■	 Eshelman JC, Hoover MD, Petsonk EL, Antao VC, Trout DB, Schulte 

PA [2006]. Occupational Medicine Issues for Nanotechnology, American Occupational Health Conference, Los Angeles, CA, May 10. 

■	 Hoover MD [2005]. NIOSH Nanotechnology Informatics Overview, 

NIOSH—Altair Nanotechnologies, Inc. Information Exchange Meeting, Reno, NV, April 19. 

■	 Hoover MD [2004]. Mixed Exposure Issues for Nanotechnology Safety, 

1st International Symposium on Nanotechnology and Occupational 

Health, Buxton, UK, October 11–14. 

■	 Hoover MD [2004]. NIOSH Approaches to Safe Nanotechnology, 2006 

NIST Safety Day Symposium, National Institute for Standards and 

Technology, Gaithersburg, MD, June 15. 

■	 Hoover MD, Miller AL, Lowe NT, Stefaniak AB, Day GA, Linch KD 

[2004]. Information Management for Nanotechnology Safety and 

Health, 1st International Symposium on Nanotechnology and Occupational Health, Buxton, UK, October 11–14. 

■	 Hoover MD, Hearl FA [2005]. NORA Mixed Exposures Research 

Agenda, Society of Toxicology Workshop on Contemporary Concepts 

In Toxicology Charting the Future: Building the Scientific Foundation 

for Mixtures Joint Toxicity and Risk Assessment, Atlanta, GA, February 

16–17. 

102 
Appendix A ■ Project-Specific Progress Reports 

■	 Hoover MD [2005]. An Introduction to Nanotechnology and the Possible Hazards, Institute of Occupational and Environmental Health 

Lecture, West Virginia University, Morgantown, WV, March 1. 

■	 Hoover MD [2005]. Lung Dosimetry of Boundary Fire Smoke Samples, 

Wildfire Symposium, Morgantown, WV, March 31. 

■	 Hoover MD [2005]. Informatics for Nanotechnology Safety and Health, 

Round Table on the Role of the Occupational Safety and Health Professional in the Emerging Nanotechnology Industry, American Industrial 

Hygiene Conference and Exposition, Anaheim, CA, May 24. 

■	 Hoover MD [2005]. Nanotechnology: Addressing Potential Health 

Impact, Council of State and Territorial Epidemiologists, Albuquerque, 

NM, June 6. 

■	 Hoover MD [2005]. Planning for the Next Decade of NORA: Opportunities to translate Research into Practice through the National Occupational Research Agenda, Annual Meeting of the Health Physics Society, 

Spokane, WA, July 13. 

■	 Hoover MD [2005]. Nanotechnology: Understanding and Addressing 

Potential Health Impacts, National Association of Scientific Materials 

Managers, Reno, NV, July 25. 

■	 Hoover MD [2005]. Nanoparticles in the Workplace, NIOSH NanoAerosols 2005 Workshop, Oglebay, WV, August 24. 

■	 Hoover MD [2005]. Nanotechnology: Understanding and Addressing 

Potential Health Impacts, Southern California Environmental Safety, 

Hygiene, and Health Joint Technical Symposium, Long Beach, CA, 

October 27. 

■	 Hoover MD, Murashov V [2005]. National and International Standards 

Activities Related to Nanotechnologies, NIOSH NanoAerosols 2005 

Workshop, Oglebay, WV, August 25. 

■	 Hoover MD, Murashov V [2005]. Overview of National and International Standards Activities Related to Nanotechnologies and Draft 

Ideas for Discussion, U.S. Technical Advisory Group Meeting for ISO 

TC 229 Nanotechnologies, National Institute for Standards and Technology, Gaithersburg, MD, September 8. 

■	 Hoover MD [2006]. Exposure Assessment for Nanotechnology, American Industrial Hygiene Conference, Chicago, IL, May 13–18. 

■	 Hoover MD [2006]. Characterization of Nanoparticles in the Workplace, Ask the Expert session on the NIOSH Nanotechnology Research 

103 
 

 

 

 

 

 

NIOSH Nanotechnology Research Center 

Program, American Industrial Hygiene Conference, Chicago, IL, May 

13–18. 

■	 Hoover MD [2006]. NIOSH Approaches to Safe Nanotechnology, 2006 

NIST Safety Day Symposium, National Institute of Standards and Technology, Gaithersburg, MD, June 15. 

■	 Hoover MD [2006]. Nanoparticles in the Workplace, Campus Safety 

Health and Environmental Management Meeting, Anaheim, CA, 

July 19. 

■	 Miller AL, Hoover MD [2006]. Building a Nanoparticle Information 

Library, National Occupational Research Agenda Symposium, Washington, DC, April 18–20. 

■	 NIOSH NTRC [2006]. Approaches to Safe Nanotechnology: An Information Exchange with NIOSH. Conference on Commercialization of 

NanoMaterials 2006, Pittsburgh, PA, September 18–20. 

■	 Schulte P, Geraci C, Zumwalde R, Hoover M, Castranova V, Murashov 

V, Howard J [2006]. Occupational Safety and Health Issues in Nanotechnology, 28th International Congress on Occupational Health, 

Milan, Italy, June 8–16. 

■	 Miller AL, Hoover M [2005]. Building a Nanomaterial Information 

Library. Second International Symposium on Nanotechnology and Occupational Health, Minneapolis, MN, October 3–6. 

■	 Birch ME, Evans DE, Methner MM, McCleery RE, Crouch KG, Ku B-K, 

Hoover MD [2006]. Workplace Assessment of Potential Exposure to Carbonaceous Nanomaterials. Second International Symposium on Nanotechnology and Occupational Health, Minneapolis, MN, October 3–6. 

■	 Stefaniak AB, Day GA, Hoover MD [2006] Measurement Issues for 

Evaluating and Relating Nanoparticle Surface Properties to Bioaccessibility and Health. Workshop on Instrumentation, Metrology, and 

Standards for Nanomanufacturing, Gaithersburg, MD, October 17. 

■	 Miller AL, Hoover MD [2006]. Building a Nanoparticle Information 

Library. Workshop on Instrumentation, Metrology, and Standards for 

Nanomanufacturing, Gaithersburg, MD, October 17. 

■	 NIOSH NTRC [2006]. Approaches to Safe Nanotechnology: An Information Exchange with NIOSH. Workshop on Instrumentation, 

Metrology, and Standards for Nanomanufacturing, Gaithersburg, MD, 

October 17. 

104 
Appendix A ■ Project-Specific Progress Reports 

■	 NIOSH NTRC [2006]. NIOSH Nanotechnology Safety and Health Research Program. Workshop on Instrumentation, Metrology, and Standards for Nanomanufacturing, Gaithersburg, MD, October 17. 

■	 NIOSH Control Banding Working Group [2006]. Potential Application 

of “Control Banding” for Safe Handling of Engineered Nanoparticles in 

the Workplace. Workshop on Instrumentation, Metrology, and Standards for Nanomanufacturing, Gaithersburg, MD, October 17. 

■	 Hoover MD, Stefaniak AB, Methner MM, Ku BK, Geraci CL, Maher 

TV, Singh M [2006]. Evaluation of a Real-Time Surface Monitor in a 

Nanotechnology Workplace, International Conference on Nanotechnology Occupational and Environmental Health and Safety: Research 

to Practice, Cincinnati, OH, December 4–7. 

■	 Hoover MD [2006]. Science and Research Issues for Nanoparticle 

Measurements and Control, International Conference on Nanotechnology Occupational and Environmental Health and Safety: Research to 

Practice, Cincinnati, OH, December 7. 

■	 Hull MS, Hoover MD, Geraci CL [2006]. Update on Understanding 

and Assessing an Emerging Technology in Practice: Continuation of an 

Innovative Industry/Government Partnership. International Conference on Nanotechnology Occupational and Environmental Health and 

Safety: Research to Practice, Cincinnati, OH, December 4–7. 

■	 Miller AL, Hoover MD [2006]. Building a Nanoparticle Information 

Library. International Conference on Nanotechnology Occupational 

and Environmental Health and Safety: Research to Practice, Cincinnati, OH, December 4–7. 

■	 Stefaniak AB, Day GA, Hoover MD [2006] Measurement Issues for 

Evaluating and Relating Nanoparticle Surface Properties to Bioaccessibility and Health. International Conference on Nanotechnology Occupational and Environmental Health and Safety: Research to Practice, 

Cincinnati, OH, December 4–7. 

■	 Birch ME, Evans DE, Methner MM, McCleery RE, Crouch KG, Ku BK, 

Hoover MD [2006] Workplace Assessment of Potential Exposure to 

Carbonaceous Nanomaterials. International Conference on Nanotechnology Occupational and Environmental Health and Safety: Research 

to Practice, Cincinnati, OH, December 4–7. 

105 
NIOSH Nanotechnology Research Center 

■	 NIOSH NTRC [2006]. Approaches to Safe Nanotechnology: An Information Exchange with NIOSH. International Conference on Nanotechnology Occupational and Environmental Health and Safety: Research 

to Practice, Cincinnati, OH, December 4–7. 

■	 NIOSH NTRC [2006]. NIOSH Nanotechnology Safety and Health 

Research Program. International Conference on Nanotechnology Occupational and Environmental Health and Safety: Research to Practice, 

Cincinnati, OH, December 4–7. 

■	 NIOSH Control Banding Working Group [2006]. Potential Application 

of “Control Banding” for Safe Handling of Engineered Nanoparticles 

in the Workplace. International Conference on Nanotechnology Occupational and Environmental Health and Safety: Research to Practice, 

Cincinnati, OH, December 4–7. 

Future Presentations 

■	 Hoover MD [2007] Characterizing and Controlling Exposures to 

Nanoparticles in the Workplace, American Industrial Hygiene Association Teleweb Nanoparticle Update: Measuring, Evaluating, and Managing Exposures, March 8. 

■	 Hoover MD [2007] Measurement of Nanoparticles in the Workplace, 

Ask the Experts: An Update on NIOSH Research in Nanotechnology, 

American Industrial Hygiene Conference and Exposition, Philadelphia, 

PA, June 4. 

■	 Hoover MD [2007] Exposure Assessment and Sampling Issues for 

Nanotoxicology and Safe Handling of Nanoparticles in the Workplace, 

American Industrial Hygiene Conference and Exposition, Philadelphia, 

PA, June 4. 

National and International Activities 

■	 Participated in the formation and activities of the ANSI Nanotechnology Standards Steering Panel, including activities resulting in the formation of the new ISO Technical Committee 229 on Nanotechnologies. 

■	 Participating in the American Industrial Hygiene Association Nanotechnology Working Group, which is bringing together industrial 

hygiene expertise to develop educational programs, develop best practices, and share lessons learned. 

■	 Participated on the organizing committee for the Frontiers in Respiratory Dosimetry meeting, which was held at the National Academies 

Center at the University of California, Irvine, CA, October. 

106 
Appendix A ■ Project-Specific Progress Reports 

■	 Co-organized the Nanotechnology and Health Symposium for the 2006 

International Aerosol Conference in St. Paul, MN. 

■	 Participated in the writing group to develop the new American Society 

of Testing and Materials (ASTM) International Committee E56 standard on Safe Handling of Unbound Nanoparticles. 

Dissemination (interviews and articles in lay press) 

Project participants were interviewed by the press for the following journals 

and articles concerning NIOSH activities in nanotechnology: 

■	 Inside OSHA, 12(16):10–11 (August 8, 2005) 

■	 Journal of the American Medical Association (September 2005). 

■	 National Journal Technology Daily (September 2005) 

■	 BNA Daily Report for Executives, Nanotechnology: Small Nanotechnology Firms can be Leaders on Health, Safety Issues, Advisory Firm Says, 

205:A8 (October 25, 2005) 

■	 The Synergist 

■	 Small Times 

■	 Washington Post 

Partnerships and Collaborations 

■	 Partnership with NIST to develop new standard reference materials for 

nanoparticles 

■	 Partnership with Luna Innovations to characterize fullerenes in a nanotechnology research facility. 

■	 Partnership with a primary nanoscale metal oxide manufacturer to 

characterize nanometal oxides in a commercial manufacturer setting. 

■	 Partnership with a commercial cosmetics manufacturer to characterize 

and control exposures to nanomaterials in the production of cosmetics. 

NTRC Critical Research Topic Areas Addressed 

1. Exposure Assessment 

2. Measurement Methods 

3. Communication and Education 

4. Applications 

107 
 

NIOSH Nanotechnology Research Center 

Research Project 12: Nanoparticles—Dosimetry 

and Risk Assessment 

Principal Investigator: Eileen D. Kuempel, Ph.D., EID/ 

NIOSH/CDC 

Project Duration: FY 2004–FY 2009 

Background 

Risk assessment of occupational exposure to nanoparticles is needed to protect 

workers’ health. Human data are limited on exposure, dose, and response to 

nanoparticles. However, data from studies in rodents are available to evaluate 

the dose-response relationships and estimate the exposures in workers that 

would be unlikely to cause adverse health effects. Using these data in risk assessment requires a scientifically reasonable approach to extrapolating the animal data to humans. One such approach is the use of biologically based lung 

dosimetry models. However, these models have not been fully evaluated and 

validated for predicting the deposition and clearance of inhaled nanoparticles. 

Furthermore, these models currently have limited capability to describe the 

translocation of nanoparticles beyond the lungs, as observed in rodent studies. 

In this project, a current rat lung dosimetry model will be extended to include 

biologically relevant paths for the transport of nanoparticles to the blood 

and other organs as well as excretion. Data from the literature will be used to 

calibrate this model, and data from new studies at NIOSH and elsewhere will 

be used to validate the model. The model will be extrapolated to humans using 

human data where available (e.g., physiological parameters), and biologically 

based approaches to interspecies extrapolation will be applied to estimate from 

the rat model the parameter values not available in humans. These lung dosimetry models will be used in conjunction with rodent dose-response data to estimate risk of adverse health effects in workers and working lifetime exposure 

concentrations that are not expected to cause adverse health effects. 

Specific objectives include the following: 

1.	 Evaluate the dose-response relationships of inhaled particles by size 

and type and estimate the lung disease risks in workers using available 

data from existing studies. 

2.	 Revise and extend a current rat lung dosimetry model to include 

particle size-specific clearance and translocation beyond the lungs. 

108 
Appendix A ■ Project-Specific Progress Reports 

3.	 Validate the extended rat model using in vivo and in vitro data from 

ongoing studies at NIOSH and elsewhere. 

4.	 Quantify variability and uncertainty in parameter values of the human 

lung dosimetry models. 

5.	 Extrapolate the validated rat model to humans. 

6.	 Perform quantitative risk assessment for occupational exposure to 

nanoparticles.

 Accomplishments 

■	 Performed quantitative risk assessment (QRA) of working lifetime 

exposure to various poorly-soluble particles using dose-response data 

from chronic and subchronic inhalation studies in rats (ED Kuempel, 

M Wheeler, D Dankovic, AJ Bailer) (Objective 1). 

	 Performed QRA for a NIOSH “Current Intelligence Bulletin: 

Evaluation of Health Effects Data on Occupational Exposure to 

Titanium Dioxide,” which provided the scientific basis for developing particle size-specific RELs for fine and ultrafine TiO2

. 

	 Presented findings at scientific conferences and in published papers in peer-reviewed journals. Excess risk estimates for poorlysoluble nanoparticles were greater than those for larger respirable particles of similar composition; thus lower workplace 

exposure concentrations were estimated to be necessary for the 

nanoparticles evaluated to protect workers’ health. 

	 Stimulated a related project to develop quantitative methods for 

summarizing and interpreting multiple models fit to quantal 

response data using Bayesian model averaging (M Wheeler and 

J Bailer). 

■	 Initiated research project, Develop and Extend a Biomathematical Model in Rats to Describe Particle Size-Specific Clearance and Translocation 

of Inhaled Particles and Early Biological Responses (Objectives 2 and 3). 

	 Awarded research contract in 2005 to Dr. Lang Tran, Institute 

of Occupational Medicine, Edinburgh, United Kingdom. 

	 Designed extended rat dosimetry model for inhaled nanoparticles with clearance and translocation pathways based on biological and kinetic data from the scientific literature. 

	 Currently planning the calibration and validation of the extended rat model. 

109 
 

 

NIOSH Nanotechnology Research Center 

■	 Initiated and managed research project, Development of Specific Modifications to Multi-path Particle Deposition Model and Software Interface 

(Objectives 2–5). 

	 Awarded in 2005 to Drs. Bahman Asgharian and Owen Price, 

CIIT Centers for Health Research, Research Triangle Park. 

	 Completed in 2006 the beta version of the new model, which 

enables batch runs, variable exposure scenarios, lung regionspecific deposition estimates, and model predictions output in a 

format compatible with other models or software. Provides detailed deposition estimates for the rat and human lung models 

being developed for nanoparticles. Currently finalizing model 

for public release. 

	 Identified need for additional region-specific deposition estimates in the nasal region and initiated follow-on research 

contact to extend this capability, with Drs. Julie Kimbell and 

Bahman Asgharian, CIIT Centers for Health Research, in 2006. 

■	 Developed research proposal, Development and Application of Methods 

to Quantify Variability and Uncertainty in Lung Dosimetry Models for 

Use in Risk Assessment of Nanoparticles (Objectives 4 and 5). Awarded 

in 2006 to Dr. Eric Hack, Toxicology for Excellence in Risk Assessment 

(TERA). 

■	 Developed research proposal, Development of a Method for Predicting the Inhalability and Internal Dose of Airborne Carbon Nanotubes 

in Workers (Objective 4). Awarded in 2006 to Dr. Bahman Asgharian, 

CIIT Centers for Health Research, Research Triangle Park. 

■	 Results from research in Objectives 1–5 will be used in Specific Aim 6. 

Publications and Abstracts 

■	 Dankovic D, Kuempel E, Wheeler M [2006]. An approach to risk assessment for TiO2

. In: Proceedings of the 10th International Inhalation Symposium on Airborne Particulate Matter: Relevance of Particle 

Components and Size for Health Effects and Risk Assessment, held in 

Hannover, Germany, May 31–June 3. 

■	 Kuempel ED, Tran CL, Castranova V, Bailer AJ [2006]. Lung dosimetry 

and risk assessment of nanoparticles: evaluating and extending current 

models in rats and humans. Inhal Toxicol 18(10):717–724. 

■	 Kuempel ED, Wheeler M, Smith R, Bailer AJ [2005]. Quantitative 

risk assessment in workers using rodent dose-response data of fine 

110 
 

 

 

 

Appendix A ■ Project-Specific Progress Reports 

and ultrafine titanium dioxide. [Abstract]. In: Nanomaterials: a risk to 

health at work? First International Symposium on Occupational Health 

Implications of Nanomaterials,12–14 October 2004, Buxton, Derbyshire, UK, Report of Presentations at Plenary and Workshop Sessions 

and Summary of Conclusions. Buxton: Health and Safety Executive, 

UK, p. 111. 

■	 Kuempel ED, Aitken RJ [2005]. Regulatory implications of nanotechnology: summary of discussion and recommendations from Workshop 

G. In: Nanomaterials: A Risk to Health at Work? 1st International 

Symposium on Occupational Health Implications of Nanomaterials,12­

14 October 2004, Buxton, Derbyshire, UK Report of Presentations at 

Plenary and Workshop Sessions and Summary of Conclusions. Buxton: 

Health and Safety Executive, UK, pp. 142–143. 

■	 Maynard AM, Kuempel ED [2005]. Airborne nanostructured particles 

and occupational health. J Nanoparticle Res 7(6):587–614. 

■	 Maynard AM, Kuempel ED [2006]. Addressing the potential environmental and human health impact of engineered nanomaterials. In: The 

Symposium Q. Proceedings of the 3rd International Conference on 

Materials for Advanced Technologies (ICMAT), Singapore, July 3–8. 

Invited Presentations 

■	 Dankovic DA [2006]. An approach to risk assessment for TiO2

, by 

D Dankovic, E Kuempel, and M Wheeler. 10th International Inhalation Symposium on Airborne Particulate Matter: Relevance of Particle 

Components and Size for Health Effects and Risk Assessment. Hannover, Germany, June 3. 

■	 Kuempel ED [2004]. Assessing the health risks of nanomaterials in 

workers: current knowledge and research gaps. National Research 

Council, Board on Environmental Science and Toxicology. Woods 

Hole, MA, October 12. 

■	 Kuempel ED [2005]. Lung dosimetry and risk assessment for nanoparticles: use of in vitro and in vivo data to extend current models in rats 

and humans, by Kuempel E, Tran C, Bailer AJ, Castranova V. Frontiers in 

Aerosol Dosimetry Research Conference. Irvine, CA, October 24–25. 

■	 Kuempel ED [2006]. Quantitative risk assessment methods for 

nanoparticles: strategies and data needs. Nanotoxicology: Biomedical 

Aspects. Miami, FL, February 1. 

111 
NIOSH Nanotechnology Research Center 

■	 Kuempel ED [2006]. Estimating nanoparticle dose in humans: issues 

and challenges. Overcoming obstacles to effective research design in 

nanotoxicology. Cambridge, MA, April 25. 

■	 Kuempel ED [2006]. Risk assessment approaches and research needs 

for nanoparticles: an examination of data and information from current studies, by E Kuempel, C Geraci, P Schulte. NATO Advanced 

Research Workshop on Nanotechnology: Toxicological Issues and 

Environmental Security, Varna, Bulgaria, August 14. 

■	 Kuempel ED [2006]. Risk assessment approaches for nanoparticles. 

International Conference on Nanotechnology Occupational and Environmental Health & Safety: Research to Practice. Cincinnati, OH, 

December 6. 

National and International Activities and Conferences 

■	 Kuempel ED [2006]. Served as an invited working group participant 

and contributor to the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 93: Carbon Black, Titanium Dioxide and 

Non-Asbestiform Talc, Lyon, France, February 7–14. The carbon black 

and TiO2

 evaluated include ultrafine or nanoparticle forms. 

■	 Kuempel ED [2006]. Served as an invited participant and presenter at 

the NATO Advanced Research Workshop on Nanotechnology: Toxicological Issues and Environmental Security, in Varna, Bulgaria, August 

12–17. The scientific presentations, summary of workgroup discussions 

and recommendations will be published. 

Dissemination (interviews and articles in the lay press) 

ED Kuempel was interviewed for two magazine articles concerning NIOSH 

activities in nanotechnology: 

■	 Parsons J [2004]. Small wonders, big questions. Am Ind Hyg Assoc J, 

The Synergist 15(10):36–39. 

■	 Agencies publishing, generating data to protect against nanoparticle exposure [2004]. Occupational Safety and Health Reporter 34(42):1069– 

1070. 

Partnerships and Collaborations 

■	 ED Kuempel is collaborating with Dr. Lang Tran at the Institute of 

Occupational Medicine, in Edinburgh, U.K., on a research project to 

112 
Appendix A ■ Project-Specific Progress Reports 

develop and extend a biomathematical lung dosimetry model in rats to 

describe clearance and retention of nanoparticles. 

■	 ED Kuempel and RR Mercer are collaborating with Drs. Bahman Asgharian, Owen Price, and Julie Kimbell at the CIIT Centers for Health 

Research, Research Triangle Park, NC, on research projects to develop 

specific software modifications to the Multi-path Particle Deposition 

Model to enable integration of deposition estimates into the lung clearance and retention models for nanoparticles, to extend current models 

to include region-specific deposition of nanoparticles in the nasal region, and to explore deposition models for nonspherical nanoparticles. 

■	 ED Kuempel is collaborating with Dr. Eric Hack at Toxicology Excellence for Risk Assessment (TERA) to develop and apply methods to 

quantify the variability and uncertainty in lung dosimetry models for 

use in risk assessment of nanoparticles. 

NTRC Critical Research Topic Areas Addressed 

1. Exposure Assessment 

2. Toxicity and Internal Dose 

3. Risk Assessment 

4. Recommendations and Guidance 

113 
NIOSH Nanotechnology Research Center 

Research Project 13: The Measurement and 

Control of Workplace Nanomaterials 

Principal Investigators: Doug Evans Ph.D., and Kevin Dunn 

M.S., CIH, DART/NIOSH/CDC 

Co-investigators: Eileen Birch, Keith Crouch, Bon-ki Ku, 

and Paul Baron 

Project Duration: FY 2006–FY 2009 

Background 

The current version of this project was initiated in FY 2006 to address key research gaps in the NIOSH, CDC-NORA, and NIOSH-NTRC research portfolios on engineered nanomaterials. A shift in focus of a previous NTRC-approved 

and funded project (An Ultrafine Particle Intervention Study in Automotive Production Plants, approved February 2005) was made following suggestions from 

the NIOSH-NTRC steering committee (the funding source of this research). 

This project will provide a fundamental basis for understanding how nanomaterials are released and dispersed into the workplace, demonstrate the way 

nanomaterials can be monitored, and the way nanomaterial exposure can be 

controlled. Furthermore, this work provides NIOSH with the tools for making 

recommendations for reducing workers’ exposures to nanomaterials. Specific 

goals include the following: 

Conduct detailed nanomaterial workplace evaluations to provide the following: 

■	 A comprehensive workplace characterization of airborne nanomaterial 

release and exposure. 

■	 A determination of nanomaterial migration within the workplace. 

■	 A comprehensive qualitative and quantitative (where possible) assessment of engineering controls, ventilation systems, and work practices. 

■	 Recommendations for improvements in engineering controls and work 

practices where applicable. 

■	 Quantitative assessments of the efficacy of implemented engineering controls and work practices, where applicable, through workplace 

monitoring. 

114 
 

 

 

Appendix A ■ Project-Specific Progress Reports 

Accomplishments (FY 2006) 

■	 A NIOSH Health Hazard Evaluation (HHE) was conducted at a nanomaterial research facility in December 2005, where carbon-based nanomaterials were incorporated into polymers and resins to produce novel 

nanocomposites. On the basis of extensive experience gained from previous activities supported by Project 1, the exposure characterization, 

engineering control, and work practice evaluation were conducted by 

participants supported under this project. An HHE report of the study 

is available at: www.cdc.gov/niosh/hhe/reports 

■	 A large comprehensive exposure characterization, engineering control, 

and work practice evaluation was conducted at a primary manufacturer 

of nanoscale metal oxides in March 2006. An interim report has been 

prepared detailing observations, engineering controls, and work practice evaluations together with recommendations for improvements. 

A full report, detailing the comprehensive exposure characterization 

(size distributions, number concentrations, active surface area, mass 

concentrations, particle morphology, and material migration) is being prepared. Work continues with this company to demonstrate the 

efficacy of implemented recommended changes to engineering controls 

and work practices. 

■	 A screening survey was conducted at a quantum dot manufacturing 

facility in July 2006, where quantum dots were produced and encapsulated into small display units. The survey involved the collection of 

some basic information about the types of processes employed, exposure control methods, and exposure measurement data. A limited 

number of samples were collected for characterizing the nanomaterials 

in the workplace. A report of the survey is being prepared. 

Publications and Abstracts 

■	 Birch ME, Evans DE, Methner MM, McCleery RE, Crouch KG, Ku B-K, 

Hoover MD [2006]. Workplace assessment of potential exposure to 

carbonaceous nanomaterials. Poster presentation at the International 

Aerosol Conference. St. Paul, MN, September. 

■	 Dunn KH, Methner MM, Evans DE, Crouch KG, Stefaniak A, Ku B-K, 

Hoover MD, Curwin BD [2006]. Interim site survey report for a metal 

oxide and ceramic nanomaterials manufacturer. 

Invited Presentations 

■	 Dunn KH [2006]. Nanotech exposure controls and best practices. 

Presented at the International Conference on Nanotechnology, 

115 
NIOSH Nanotechnology Research Center 

Occupational and Health & Safety: Research to Practice. Cincinnati, 

OH, December 4–7. 

■	 Dunn KH, Evans DE, Ku B-K, Baron PA Birch ME, Crouch KG [2006]. 

Overview of NIOSH research on nanomaterial characterization and 

control technology. Presented at the 2006 American Industrial Hygiene 

Conference and Exposition, Chicago, IL, May 14–18. 

■	 Evans DE, et al. [2006]. Field measurement of aerosols at the nanoscale. 

Presented at the International Conference for Nanotechnology. Occupational and Environmental Health & Safety; Research to Practice. 

Cincinnati, OH, December 4–7. 

National and International Activities and Conferences 

■	 DE Evans is collaborating with researchers at the Health and Safety 

Laboratory (United Kingdom), at INRS (France) and BIA (Germany) 

on issues related to nanomaterial/ultrafine exposure measurement in 

workplaces. 

Dissemination (interviews and articles in the lay press) 

Washington Post Staff Writer, Rick Weiss, spoke at length with project participants during a site survey. The survey was the subject of a Post article by Mr. 

Weiss, which was published soon thereafter. 

■	 The DART project Measurement and Control of Workplace Nanomaterials was highlighted in the March 2006 edition of NIOSH eNews. The 

summary article discussed goals of the field project and issued a request for potential collaborators. 

■	 An article appeared in Occupational Hazards [2006]. This latter article 

covered results of related research identifying direct-fired, natural gas 

heating systems as sources of high concentrations of ultrafine particles 

in workplaces. The study was conducted with collaborators at the University of Iowa, (www.occupationalhazards.com/articles/14139). 

Partnerships and Collaborations 

NIOSH researchers are working with the three nanomaterial manufacturers/ 

processors mentioned above, The University of Iowa, The University of North 

Carolina, The Woodrow Wilson International Center for Scholars, International Truck and Engine Corporation, and the United Auto Workers Union. 

116 
117

Appendix A ■ Project-Specific Progress Reports

NTRC Critical Research Topic Areas Addressed

1. Exposure Assessment

2. Measurement Methods

3. Engineering Controls and Personal Protective Equipment

4. Fire and Explosion Safety

5. Recommendations and Guidance
NIOSH Nanotechnology Research Center 

Research Project 14: TiO2 Exposure 

Assessment Study 

Principle Investigator: Brian Curwin, DSHEFS/NIOSH/CDC 

Project Duration: FY 2006–FY 2009 

Background 

TiO2

, a poorly soluble, low-toxicity (PSLT) white powder, is used extensively 

in many commercial products, including paint, cosmetics, plastics, paper, and 

food as an anti-caking or whitening agent. Production in the United States was 

an estimated 1.43 million metric tons per year in 2004 [DOI 2005]. 

Ultrafine particles are hypothesized to penetrate the epithelial lining and lung 

interstitial spaces to a greater extent, more readily enter cells, and cause greater 

lung inflammation and oxidative stress compared with larger particles. Furthermore, it is hypothesized that the dose of particles, expressed as particle 

surface area, is associated with lung responses and this relationship is similar 

across PSLT particles. Persistent inflammation, tissue damage, fibrosis, and 

lung cancer have been observed in rats at doses of PSLT particles that impair 

lung clearance. Particle surface area dose has been shown to be a better predictor of lung clearance inhibition. 

NIOSH has identified critical research needs for workers exposed to ultrafine 

and fine TiO2

, including measuring workplace airborne exposures to ultrafine 

TiO2

 in manufacturing and end-user facilities and evaluating the exposure 

response relationship between TiO2

 and human health effects. The goal of 

this study is to measure workplace exposure to fine and ultrafine TiO2

 in both 

manufacturing and end-user facilites. The specific objectives are to (1) quantify 

the airborne particle size distribution of TiO2

 by job or process in manufacturing and end-user facilities and (2) obtain quantitative estimates of exposure in 

workers to fine and ultrafine TiO2

 particle sizes in manufacturing and end-user 

facilities. A task-based sampling scheme consisting of various real-time and 

mass based area and personal aerosol sampling will be employed. In addition, 

each participant will be asked to provide information about their work practices and PPE use. 

Accomplishments 

■ Protocol for TiO2 study has been written and is undergoing review. 

118 
Appendix A ■ Project-Specific Progress Reports 

■	 Critical exposure assessment equipment has been purchased including 

a TSI 3007 condensation particle counter and an Ecochem DC2000 CE 

portable diffusion charger. 

■	 A contract has been awarded to assist in identifying companies for 

study. 

Publications and Abstracts 

The field work has not begun and no data have been collected. Therefore, no 

publications or abstracts have been published. 

Invited Presentations 

This project is in its early stages and therefore no invitations to present results 

from this project have been offered. 

National or International Activities and Conferences 

No national or international activities have occurred or are planned at this 

time. 

Dissemination (interviews and articles in the lay press) 

This project is in its early stages. No results are available for dissemination. 

Partnerships and Collaborations 

■	 Consultations were held with Dr. Dirk Brouwer, Netherlands Organization for Applied Scientific Research (TNO), Netherlands, on study 

protocol development. 

■	 Collaboration with a manufacturer and an end user of ultrafine TiO2 

has been established for conducting possible exposure characterization 

studies. 

NTRC Critical Research Topic Areas Addressed 

1. Exposure Assessment 

2. Measurement Methods 

119 
 

 

NIOSH Nanotechnology Research Center 

Research Project 15: Evaluation of Nanoparticle 

Penetration Through Respirator Filter Media 

Principle Investigator: Samy Rengasamy, Ph.D., NPPTL/ 

NIOSH/CDC 

Project Duration: FY 2005–FY 2008 

Background 

The objective of this project is to evaluate the penetration of nanoparticles 

through respirator filter media. Nanoparticles smaller than 100 nm in size can 

behave differently from larger particles of the same material. NIOSH has initiated research projects on nanoparticle exposure, health effects, and respiratory 

protection. For respiratory protection against various particles, particulate 

respirators are commonly used in different workplaces. Although NIOSH-approved respirators efficiently capture particles greater than 20 nm, few data 

exist on their efficiency for particles smaller than 20 nm. Some studies suggest the penetration of smaller particles through filters by a thermal rebound 

mechanism. The results will be confirmed by testing NIOSH-approved respirators against particles smaller than 20 nm. This study will ensure that respirators provide adequate protection for workers in the nanotechnology industries. 

Accomplishments 

In 2005, the research proposal was approved for a pilot project study, and a 

contract was awarded to the University of Minnesota. Preliminary results from 

the project were presented at the 2nd International Symposium on Nanotechnology and Occupational Health in Minneapolis, MN, October 2005. Silver 

nanoparticles of 3-20 nm in diameter were generated for testing respirator 

filter media. Preliminary results indicated that filtration efficiency increased 

with decreasing particle size as expected according to the Brownian deposition theory. No evidence for thermal rebound of nanoparticles was observed. 

The results of this study suggest that respirator filters may efficiently capture 

nanoparticles greater than 3 nm in diameter. To confirm these results, further 

studies with silver and/or sodium chloride aerosol particles will be used to test 

for penetration through particulate filtering facepieces and cartridges. 

Publications and Abstracts 

■	 Kim SC, Harrington M, Rengasamy S, Pui D [2005]. Collection efficiency 

of filter media for nanoscale particles. Presented at the 2nd International 

120 
Appendix A ■ Project-Specific Progress Reports 

Symposium on Nanotechnology and Occupational Health in Minneapolis, MN. 

■	 Gardner P, Rengasamy S, Richardson A [2005]. Efficiency of respirator 

filters against nano-aerosols under high flow rate conditions. Presented 

at the 2nd International Symposium on Nanotechnology and Occupational Health in Minneapolis, MN, October 3–6. 

■	 Kim SC, Harrington M, Rengasamy Samy, Pui D [2006]. Collection efficiency of filter media for nanoscale particles. Presented at the American Industrial Hygiene Conference and Exposition, Chicago, IL, May 

14–18. 

■	 Shaffer R, Gao P, Rengasamy S [2006]. Penetration of nanoparticles 

through protective clothing and respirator filters. Presented at the 

Elevated Wind Studies International Conference, Arlington, Virginia, 

September 25–26. 

■	 Shaffer R, Rengasamy S, Gao P [2006]. Penetration of nanoparticles 

through protective clothing and respirator filter media. Presented at 

the International Conference on Nanotechnology, Occupational and 

Environmental Health & Safety: Research to Practice. Cincinnati, OH 

December 4–7. 

National and International Activities and Conferences 

S. Rengasamy arranged a Round Table meeting on Nanotechnology and PPE 

issues for the 2006 AIHCE meeting in Chicago. For this session, PPE experts 

from academic, industrial, and nongovernmental organizations were invited. 

Highlights of the presentations include studies on nanoparticle penetration 

through filter media and respirator filters. Other presentations included developing highly adsorbent and reactive nanoparticles for protective clothing for 

chemical and biological warfare agents and the evaluation of protective gloves 

and PPE for handling nanomaterials. 

Dissemination (interviews and articles in the lay press) 

■	 S. Rengasamy and R. Shaffer had an interview with Occupational 

Hazards magazine and discussed nanoparticle filtration. An article 

entitled NIOSH-funded Study Looks at Filter Efficiency for Nanoparticles 

was published in September 2005 (67:42). The growth of nanotechnology across different industries and the effects of nanoparticles on 

respiratory protection and were discussed. Single fiber theory and the 

mechanisms of penetration of different size particles through respirator 

121 
 

 

NIOSH Nanotechnology Research Center 

filters were also shared. The lack of knowledge about the penetration 

of nanoparticles smaller than 20 nm sizes and the importance of this 

research were highlighted. NIOSH collaboration with the University of 

Minnesota to study the penetration of particles smaller than 20 nm was 

shared. This interview highlighted current understanding of nanoparticles, and the importance of NIOSH nanoparticle filtration research 

work with the University of Minnesota. 

■	 S. Rengasamy and R. Berryann of NPPTL had an interview with the 

Bureau of National Affairs (BNA), Inc. in October 2005, and highlighted the current developments on respiratory protection against 

nanoparticles. An article entitled NIOSH Planning More Respirator 

Studies after Nanoparticle Tests Find Penetration was printed in a BNA 

publication, October 19, pp. 8–22. 

■	 S. Rengasamy and R. Shaffer of NPPTL had an interview with the 

AIHA publication The Synergist in October 2005, and discussed current nanotechnology research activities in NPPTL that address worker 

safety and issues. An article entitled Accelerating Research Sizes up the 

Implications of Nanotechnology in the Workplace was published in The 

Synergist [2005] 17(1):37–39. 

■	 S. Rengasamy and R. Shaffer of NPPTL were interviewed by Chemical 

and Engineering News in April 2006. The aim of the interview was to 

better understand the current developments in respiratory protection 

against nanoparticles. An article entitled How Well do Gloves and Respirators Block Nanoparticle was published in the May 1 issue of Chemical 

and Engineering News, pp.14–15. 

■	 K. Williams and A. Maynard were interviewed by The Synergist and 

highlighted the lack of complete information about nanoparticles and 

the performance of personal protective equipment against nanomaterials. An article titled Small Wonders, Big Questions was published in The 

Synergist [2004] 15(10):37–39. 

Partnerships and Collaborations 

■	 In January 2005, K. Williams assisted the EPA by reviewing a manufacturer’s application to manufacture a nanosized product that was 

submitted to EPA for approval under the Toxic Substances Control 

Act (TSCA). He provided input regarding the selection of appropriate 

PPE for the manufacturing process that was valuable to the EPA in the 

evaluation and approval of the manufacturer’s application. 

122 
Appendix A ■ Project-Specific Progress Reports 

■	 Partnership with the ISEA Filter Research Task Group was established 

to achieve the goals of this project. ISEA Filter Research critically reviewed the proposal in January 2005. The proposal was revised taking 

into consideration the comments and suggestions of the ISEA Filter 

Research Task Group. 

■	 S. Rengasamy, R. Shaffer, and P. Gao are actively participating in the 

DuPont Nanoparticle Occupational Safety and Health Consortium. The 

objectives of this consortium include the generation of nanoparticles, 

the measurement, filter penetration, and development of a portable 

device to measure nanoparticles in workplaces to provide safety and 

health to workers. An MOU between NIOSH/NPPTL and DuPont was 

officially executed in June 2006. This will allow NIOSH to collaborate 

with the DuPont Consortium and exchange information about PPE 

(clothing and respirators) and nanoparticles research. 

NTRC Critical Research Topic Areas Addressed 

1. Engineering Controls and PPE 

2. Recommendations and Guidance 

123 
 

 

 

NIOSH Nanotechnology Research Center 

Research Project 16: Development of Bench and 

Mist Protocols for Particulate Penetration Measurements of Protective Clothing and Ensembles 

Principle Investigator: Pengfei Gao, Ph.D., C.I.H., NPPTL/ 

NIOSH/CDC 

Project Duration: FY 2006–FY 2009 

Background 

Protective clothing and ensembles are critically important items for workers 

when exposed to hazardous conditions. In order to determine how well ensembles protect wearers, it is necessary to test the entire suit system while it 

is worn to measure potential leakage through seams, closures, areas of transition to other protective equipment, and any leakage due to movement and 

activities. The objective of this project is to develop innovative methodology 

for standardizing both bench-scale testing and man-in-simulant test (MIST) 

procedures for aerosol particle penetration through protective clothing and 

ensembles. A test method for aerosol particles including nanoparticles that 

does not depend on filtration will be developed. A passive aerosol sampler 

(PAS) using magnetic force will be developed and iron (II, III) oxide particles 

will be used to generate challenge aerosols. An aerosol chamber will be fabricated for evaluating the particulate penetration for particle sizes between 20 

and 500 nm; a wind tunnel will be used for larger particles up to 10 μm. Iron 

oxide collected on the PAS will be quantified using a colorimetrical method or 

TEM. Performance of the PAS will be evaluated under various test conditions, 

including particle size, particle concentration, wind speed, exposure duration, 

relative humidity, and sampler orientation. A disposition velocity model will 

be developed to calculate sampling rates of the PAS. Penetration of nanoparticles through fabrics and protective clothing swatches will be measured with 

other reference samplers to compare the performance of the PAS. The research 

findings will be used for revised and new American Society for Testing Materials (ASTM) and NFPA standards. The project duration is proposed to last 

for 4 years (FY 2006–FY 2009). 

Accomplishments 

■	 A prototype passive aerosol sampler using magnetic force has been 

developed at NPPTL to more accurately determine aerosol particle 

124 
Appendix A ■ Project-Specific Progress Reports 

penetration including nanoparticle penetration through ensembles. 

Preliminary evaluation of the sampler performance indicates the ability 

to collect nanoparticles down to 20 nm by the sampler. Appropriate 

sampler coatings were identified to facilitate analysis of collected aerosol. Experiments to allow an improved assessment of sampler performance were completed. 

■	 An Employee Invention Report (I–015–05) for the passive aerosol sampler was submitted to CDC Technology Transfer Office in March 2005. 

■	 A research proposal has undergone external peer review. 

Publications and Abstracts 

■	 King WP, Gao P, Shaffer R [2006]. Review of chamber design requirements for testing of personal protective clothing ensembles. Submitted 

to the Journal of Occupational and Environmental Hygiene for publication. 

Invited Presentations 

■	 Shaffer R, Rengasamy S, Gao P [2006]. Penetration of nanoparticles 

through protective clothing and respirator filter media. Presented at 

the International Conference on Nanotechnology, Occupational and 

Environmental Health & Safety: Research to Practice. Cincinnati, OH, 

December 4–7. 

■	 Shaffer R, Gao P, Rengasamy S [2006]. Penetration of nanoparticles 

through protective clothing and respirator filters. Presented at the Elevated Wind Studies International Conference. Arlington, VA, September 25–26. 

■	 Geraci C, Castranova V, Hoover M, Dunn K, Gao P [2006]. Ask the 

Expert—An update on NIOSH research in nanotechnology. Presented 

at a roundtable section at the American Industrial Hygiene Conference 

and Exposition, Chicago, IL, May 16. 

■	 King B, Gao P [2005]. A passive aerosol sampler for evaluation of personal protective ensembles. Presented at the Advanced Personal Protective Equipment: Challenges in Protecting First Responders Conference. Blacksburg, VA, October16–18. 

■	 King WP, Gao P [2006]. Coating evaluation for a newly developed 

passive aerosol sampler based on magnets for determination of particle 

penetration through protective ensembles. Presented at the American 

Industrial Hygiene Conference and Exposition, Chicago, IL, May 17. 

125 
NIOSH Nanotechnology Research Center 

Partnerships and Collaborations 

■	 Efforts have been initiated to establish research collaborations between 

NPPTL and the Research Triangle Institute (RTI) in North Carolina, 

Battelle in Columbus, OH, and the Center for Health-Related Aerosol 

Studies at the University of Cincinnati. The project officer visited RTI 

in May 2006 to discuss possible collaborative efforts. 

■	 A partnership has been arranged with the DuPont Nanoparticle Occupational Safety and Health Consortium. An MOU between NIOSH/ 

NPPTL and DuPont was officially executed in June 2006. The MOU 

provides a formal mechanism for exchanging information on PPE 

(clothing and respirators) and nanoparticles research. 

NTRC Critical Research Topic Areas Addressed 

1. Engineering Controls and PPE 

2. Recommendations and Guidance 

126 
Appendix A ■ Project-Specific Progress Reports 

Research Project 17: Web-based Nanoparticle 

Information Library Implementation 

Principal Investigator: Arthur Miller, Ph.D., SRL/NIOSH/ 

CDC 

Project Duration: FY 2004–FY 2008 

Background 

The primary objective of this project is to design, build, and implement the 

Web-based NIL. The NIL is being developed as a global source for information concerning the properties and associated health and safety implications 

of the myriad nanomaterials that are being developed. This work also supports 

efforts ongoing in the Nanoparticles in the Workplace project. It is intended to 

provide NIOSH and the occupational safety and health community with access 

to knowledge as to the variety and extent of nanomaterials being produced 

worldwide, along with information concerning their physical and chemical 

properties, processes of origin, and possible health effects. 

Accomplishments 

■	 Collaborated with the International Council on Nanotechnology 

(ICON) for the development of a knowledge management hub for 

nanotechnology. 

■	 Participated in the planning of the nanotechnology field team investigation effort and assisted with developing protocols. 

■	 Provided input for redesigning the nanotechnology topic page on the 

NIOSH Web site. 

■	 EIR document (patent application) titled, A Portable Hand Held Electrostatic Precipitator for Particle Sampling. 

■	 Developed two protocols for analyzing workplace aerosol samples 

using Transmission Electron Microscopy/Energy Dispersive Spectroscopy (TEM/EDS). 

■	 Provided consultation on the characterization of welding fume and 

worker exposure to the welding fume. 

■	 Based on preliminary work conducted by participants under Project 1, 

developed a protocol for nano-aerosol characterization fieldwork at a 

metal refinery, including real time mapping of particle concentrations 

in the workplace. 

127 
NIOSH Nanotechnology Research Center 

■	 Developed a project to map concentrations of airborne particles in the 

workplace using the Fast Mobility Particle Size (FMPS) instrument. 

This work includes the preliminary design of a (non-GPS) spatial mapping system to be used in indoor environments. 

■	 Built and tested an instrumentation cart for evaluating a prototype 

system for quasi-real-time spatial mapping of nanoparticles in the 

workplace. 

■	 Incorporated a mailing interface and a newsletter interface in the design of the nanoparticle information library. 

■	 Launched the nanoparticle information database on the NIOSH Web 

site. The prototype version went live in February 2006. 

Publications and Abstracts 

■	 Donggeun L, Miller A, Park K, Zachariah MR [in press]. Effects of trace 

metals on particulate matter formation in a diesel engine: metal contents from ferrocene and lube oil. Int J Automotive Technology. 

■	 Lee D, Miller A, Kittelson DB, Zachariah MR [2005]. Characterization 

of metal-bearing diesel nanoparticles using single particle mass spectrometry. J Aerosol Sci 37(2):88–110. 

■	 Lee D, Miller A, Zachariah M, Kittelson DB [2004]. Single particle 

mass spectrometry of metal-bearing diesel nanoparticles. ACS Symposium Series No. 890–Nanotech and the Environment: Applications and 

Implications. Chapter 17, pp.142–151, ISBN: 0–8412–3877–4. 

Papers Submitted for Publication 

■	 Miller A, Ahlstrand G, Kittelson DB, Zachariah MR [2006]. The fate 

of metal (Fe) during diesel combustion: morphology, chemistry and 

formation pathways of nanoparticles. Unpublished. Submitted to the 

journal of Combustion and Flame, March. 

■	 Miller AL, Habjan MC, Park K [2006]. Real-time estimation of elemental carbon emitted from a diesel engine: a preliminary study. Unpublished. Submitted to Environmental Science and Technology, August. 

■	 Ng A, Miller A, Ma H, Kittelson DB [2006]. Comparing measurements 

of carbon in diesel exhaust aerosols using the aethalometer, NIOSH 

Method 5040, and SMPS. Unpublished. Submitted to the SAE journal 

for publication as a Technical Paper, June. 

128 
Appendix A ■ Project-Specific Progress Reports 

Posters 

■	 Miller AL, Hoover M [2005]. Nanotechnology—assessing and controlling potential health impacts. Poster session for the XVIIth World Congress on Safety and Health at Work, Orlando, FL, September 19–22. 

■	 Maher TV, Omaye ST, Geraci CL, Zumwalde RD, Miller All, Hoover 

MD [2006]. A case study in partnering to develop a nanotechnology 

occupational safety program in a nanotechnology manufacturing environment. Poster session at the 2006 NORA Symposium. 

■	 Miller AL [2004]. Novel techniques for characterization of ultrafine 

metal aerosol formation: lessons from diesel combustion. Poster session at the first annual international symposium, Occupational Health 

Implications of Nanomaterials, co-sponsored by NIOSH, Buxton, UK, 

October. 

Invited Presentations 

■	 Miller AL [2005]. NIOSH’s role in improving health and safety in nanotechnology workplaces. Presentation given as part of a multi-agency 

panel session on nanotechnology at the SAMPE–2005 conference in 

Seattle, WA, November 3. 

■	 By special invitation, attended the 2006 the spring meeting of the 

ICON and gave two presentations: 

	 Development of a Web-based NIL 

	 Working Toward an Integrated Management Tool for Nanotechnology-related EHS Data 

■	 By invitation, gave a presentation in 2006 to the NanoIGERT members 

at the University of Minnesota, covering the proposed NIOSH work to 

build a nanomaterial information library, and solicited input to same. 

National and International Activities and Conferences 

■	 Miller AL, Hoover M [2005]. Building a Nanomaterial Information 

Library. Presentation for the Second International Symposium on 

Nanotechnology and Occupational Health, co-sponsored by NIOSH, 

Minneapolis, MN, October 3–6. 

Dissemination (interviews and articles in the lay press) 

TEM images of nanoparticles prepared by Art Miller were highlighted in the 

TSI 2005 aerosol instrumentation catalogue, which won an award sponsored 

by the Society for Technical Communication in 2006. 

129 
NIOSH Nanotechnology Research Center 

Partnerships and Collaborations 

■	 Sunshine Metal Refinery, WA, hosted a 2006 field study in which 

NIOSH staff characterized nanoparticles in the workplace. 

■	 NIOSH is collaborating with researchers in the Atmospheric Science 

Division at the Desert Research Institute (DRI), regarding instrument 

comparisons and measurement methods for airborne carbon particulates. 

■	 NIOSH is collaborating with EPA to study nano-fuel additives and 

their influence on particle generation by internal combustion engines. 

■	 Art Miller provided instruction to engineering students at Gonzaga 

University on the design, building, and testing a novel hand-held electrostatic nanoparticle sampler. 

■	 Assistance was provided by the following companies and Universities 

in designing the NIL: 

 Altair Nano 

 University of Minnesota 

 Washington University at St. Louis 

 Seattle University 

 Rice University/ICON consortium 

 A primary nanoscale metal oxide manufacturer 

NTRC Critical Research Topic Areas Addressed 

1.	 Toxicology and Internal Dose 

2.	 Risk Assessment 

3.	 Fire and Explosion Safety 

4.	 Communication and Education 

5.	 Recommendations and Guidance 

130 
Appendix B
 

Field Research Team 

Progress Report 
 

 

NIOSH Nanotechnology Research Center 

Summary of Field Research Progress 

Prinicpal Investigators: Mark Methner, PH.D., CIH; Charles 

L. Geraci, PH.D., CIH; Mark Hoover, PH.D., CIH 

Evaluation of Carbon Nanofiber Composite Material at a Polymer 

Research Facility 

Following a series of walk-through and planning visits, an in-depth survey was 

conducted on December 6, 2005 at a research facility evaluating the incorporation of nanomaterials into polymers. The purpose of the survey was to 

determine whether fugitive emissions and subsequent nanomaterial migration occurred during various laboratory processes involving both raw carbon 

nanofibers (CNF) and CNF bound within a composite matrix. Task-based air 

and surface sampling was conducted using a vacuum method. Real-time aerosol instrumentation was used to measure particle number, active surface area, 

mass concentration, and particle size distribution. In addition, air and surface 

samples were collected by NIOSH Method 5040 for subsequent total carbon 

analysis, as were air samples for analysis by TEM. A qualitative evaluation of 

engineering controls and work practices was also conducted and recommendations were made to the company. Preliminary results indicate that some release 

of CNF occurred during raw fiber transfer to a rotary-stirred mixing vessel. In 

addition, material was released during a cutting operation of CNF-laden epoxy 

polymer using a wet saw. A poster describing the methodology used to collect 

filter-based air and surface samples was presented in September 2006 at the 

International Aerosol Conference in St. Paul, Minnesota. Interim results have 

been provided to the facility. A final report has been issued (See http://www. 

cdc.gov/niosh/hhe/reports/pdfs/2005-0291-3025.pdf). Research activities were 

supported under Projects 11 and 13. 

Preliminary Screening Survey Using Handheld Direct Reading 

Instrumentation and Air Filter/Wipe Samples at a Quantum Dot 

Research and Development Laboratory 

A site survey was conducted on July 10, 2006, at a research and development 

laboratory engaged in the development of optical products with Quantum Dot 

(QD) coatings after several detailed conference calls. The purpose of the survey 

was to determine whether QD between 2 nm and 8 nm (monodisperse) were 

released during various laboratory treatments and processes. All processes 

were very well controlled by ventilation (i.e., laboratory hoods, glove boxes, 

Class 10,000 Clean Rooms). A total of 13 surface wipe samples were collected 

132 
Appendix B ■ Field Research Team Progress Report 

using Ghostwipe® substrates and 8 high-volume air samples were collected on 

mixed cellulose ester (MCE) filters. The surface and air samples are currently 

being analyzed for elemental metals in accordance with NIOSH Method 7300. 

Direct reading instruments (condensation particle counter [CPC] and handheld particle counter model HHPC-6; ART instruments) were also used to assess airborne particle concentrations in the work areas. No noticeable releases 

of QD were noted during any process. A final report has been submitted to the 

company. Research activities were supported under Project 13. 

Evaluation of Nanoscale Metal Oxide Release at a Commercial 

Technology Development and Powder Production Facility 

A comprehensive survey was conducted from March 12–17, 2005, at a commercial nanoscale metal oxide development and powder production facility 

following a series of walk-through and planning visits. The purpose of the 

survey was to assess the adequacy of engineering controls and work practices, 

characterize particle releases in the work area, and evaluate the performance of 

a range of nanoparticle characterization instruments and approaches. A series 

of recommendations for improved particle control and worker protection were 

provided to the facility. Detailed evaluation of particle size distribution, surface 

area, morphology, and other results are underway. Research activities were 

supported under Projects 11, 13, and 14. 

Evaluation of Nanoscale Nylon 6 Fiber Deposition and Potential 

Release during Engine Filter Media Manufacturing 

A recent survey (September 2006) of a filter manufacturer (electro-spinning 

deposition of nanoscale Nylon 6 onto cellulose substrate) has been completed. 

The final report is being drafted. 

Preliminary Evaluation of Nanomaterial Handling Practices at a 

Research Facility Engaged in State-of-the-Art Materials Characterization 

A series of walk-through visits have been made to a state-of-the-art materials 

characterization facility to assess the nature and adequacy of control practices 

being implemented in a newly developing nanotechnology research program at 

the facility. Presentations were also made to the industrial hygiene professional 

staff and to workers about the need for, and the nature of, good work practices 

for safe handling of nanomaterials. Collaborative work on documenting and 

improving work practices is underway. 

133 
NIOSH Nanotechnology Research Center 

The Many Faces of Nanotechnology 

134 
 

 

 

Appendix B ■ Field Research Team Progress Report 

Assessment of Work Practices in a Facility Developing Specially 

Formulated Fullerenes for Biomedical Applications 

A walk-through survey was conducted on July 28, 2005, at a research and 

development laboratory engaged in the development of specially formulated 

fullerenes for biomedical applications. Through collaboration with a local university, a detailed industrial hygiene survey was conducted and then presented 

at the International Aerosol Conference in September 2006, in St. Paul, MN. In 

addition, results of the survey and detailed observations of nanomaterial handling work practices were presented jointly by NIOSH and the company at the 

October 2005 International Symposium on Nanotechnology and Occupational 

Health in Minneapolis, MN. Frequent communication between NIOSH and 

the company are continuing to develop further recommendations on comprehensive management and work practice approaches to safe handling of nanomaterials. Involvement was supported under Project 11. 

Assessment of Work Practices at Universities Engaged in Research 

on Nanomaterials 

A series of walk-through investigations have been conducted at two universities engaged in materials science, aerosol science, and biomedical research on 

nanomaterials. The purpose of the investigations has been to learn more about 

the actual research and work practices underway, and to advise industrial 

hygiene professionals, researchers, and students about effective measures for 

controlling nanomaterials and preventing exposure. Opportunities for additional collaborative research are being discussed. 

Evaluation of the Performance of the State-of-the-Art Nanoparticle 

Sampling Equipment in a Nanoparticle Aerosol Generation Laboratory 

In July 2006, NIOSH and a commercial instrumentation company collaborated 

to evaluate the performance of a new nanoparticle real-time surface area 

analysis instrument under actual conditions of particle generation in an aerosol inhalation toxicology facility (supported by Project 11). Valuable lessons 

were learned about instrument performance, maintenance and trouble-shooting requirements, and comparison of instrument results with conventional 

nanoparticle characterization instrumentation. Data reduction and report 

writing are underway. Collaboration efforts were supported by Project 11. 

Invited Presentations 

■	 Methner MM [2006]. NIOSH nanoparticle exposure characterization 

and assessment. Society of Advanced Material Processing and Engineering (SAMPE). Dallas, TX. 

135 
NIOSH Nanotechnology Research Center 

■	 Methner MM [2006]. Health hazard evaluations of engineered 

nanoparticle exposures. Presented at the International Conference on 

Nanotechnology, Occupational and Environmental Health & Safety: 

Research to Practice. Cincinnati, OH, December 4–7. 

■	 Hoover MD, Stefaniak AB, Methner MM [2006]. Evaluation of a realtime surface area monitor in a nanotechnology workplace. Presented 

at the International Conference on Nanotechnology, Occupational and 

Environmental Health & Safety: Research to Practice. Cincinnati, OH, 

December 4–7. 

■	 Methner MM, Zimmer A, Baron P [2005]. Nanotechnologies: Occupational health considerations and controls. Presented at the United 

States Air Force Institute of Technology (AFIT), Wright-Patterson Air 

Force Base, Dayton, OH. 

136 
Appendix C 

Occupational Health 

Surveillance for 

Nanotechnology Workers 
NIOSH Nanotechnology Research Center 

Research Program: Occupational Health 

Surveillance For Nanotechnology Workers 

Program Coordinator: Douglas Trout, M.D., DSHEFS/ 

NIOSH/CDC 

Program Duration: FY 2005–Present 

The unique physical and chemical properties of nanomaterials, the increasing 

growth of nanotechnology in the workplace, and information suggesting that 

engineered nanomaterials may pose a safety and health hazard to workers all 

underscore the need for medical and hazard surveillance for nanotechnology. 

Every workplace dealing with engineered nanomaterials and nanotechnology 

should consider an occupational health surveillance program. NTRC has convened a cross-Federal group to develop a document as a framework for using 

existing medical and hazard surveillance mechanisms to create occupational 

health surveillance programs for nanotechnology workers. This guidance is not 

a prescriptive recommendation for a specific type of surveillance program, but 

rather is provided to present information that can be used to create appropriate 

occupational health surveillance to fit the needs of workers and organizations 

involved with nanotechnology. This framework presents information to help 

initiate occupational health surveillance where none exist. It is likely that as the 

field of nanotechnology changes over time modifications to any initial surveillance program will need to be considered periodically. 

138 
Appendix D 

Review of the NIOSH 

Extramural Nanotechnology 

Research Program: 

FY 2001–FY 2006 
 

NIOSH Nanotechnology Research Center 

NIOSH Nanotechnology Research Program Review 

for FY 2001–FY 2006 

Office of Extramural Research Programs 

Program Administrator: W. Allen Robison, Ph.D., NIOSH 

Office of Extramural Programs 

Background 

During 2001–2006, the Office of Extramural Programs (OEP) funded 

nanotechnology-related research through R01 and R43/44 mechanisms. Since 

FY 2005, OEP has participated in two collaborative requests for applications 

(RFA) for nanotechnology research grants investigating environmental and human health issues. The U.S. EPA National Center for Environmental Research 

(NCER) and the National Science Foundation (NSF) participated in FY 2005. 

NIEHS joined in FY 2006. Funding was available to support Research (R01) 

grants for 3 years and Exploratory (R21) grants for 2 years. 

Purpose 

OEP funding of nanotechnology-related research has been undertaken to help 

increase the knowledge of nanotechnology and manufactured nanomaterials 

as they relate to occupational safety and health. Research areas supported by 

NIOSH/OEP include assessment methods for nanoparticles in the workplace, 

toxicology of manufactured nanomaterials, and the use of nanotechnology for 

improved workplace monitoring. 

Status and Progress 

From FY 2001 to FY 2004, OEP funded three R43/44 projects for a total funding commitment of almost $950K (Table 1). In FY 2005, OEP began participating in the nanotechnology-related RFAs previously mentioned. For the 

first RFA, 83 applications were received; 19 of these were recommended for 

funding. Fourteen met NIOSH criteria for relevance to occupational safety 

and health, five were in the competitive range for funding consideration, and 

two were funded by NIOSH (Table 1). In FY 2005, EPA funded 14 projects and 

NSF funded 2 projects under this RFA. NIOSH also funded a nanotechnology 

research application through the R01 Program Announcement (Table 1) in FY 

2005. 

140 
 

 

 

 

Appendix D ■ Review of the NIOSH Extramural Nanotechnology Research Programs FY 2001–FY 2006 FY 2001–FY 2006 

In FY 2006, 81 applications were received in response to the RFA; 29 of these 

were recommended for funding. Six of the 29 met NIOSH criteria for relevance, 

three were in the competitive range for funding consideration, and one of these 

was funded by NIOSH (Table 1). EPA funded 21 projects, NSF funded four, and 

NIEHS funded three projects under this RFA. NIOSH also funded a nanotechnology research application through the Small Business Innovative Research 

(SBIR) Program Announcement. Summaries of projects funded by NIOSH/OEP 

are described below. 

To date, NIOSH/OEP has committed about $3.5 million dollars to nanotechnologyrelated research. Projects have been funded on applications and implications of 

nanotechnology. Contact information for the principal investigators of the projects 

funded by NIOSH/OEP is provided in Table 2. 

Next Steps 

In FY 2007 and FY 2008, NIOSH/OEP will continue collaborative efforts with 

EPA/NCER, NSF, NIH/NIEHS, and other international agencies to support 

nanotechnology research with occupational safety and health implications. OEP 

will confer with the NTRC regarding issues, knowledge gaps, and future directions. 

Additional Information 

Extramural investigators interested in pursuing nanotechnology studies related 

to occupational safety and health can learn more about the interests of NIOSH 

in this area by visiting the following Web pages: 

■ http://www.cdc.gov/niosh/topics/nanotech/ 

■ http://www.cdc.gov/niosh/topics/nanotech/NIL.html 

■ http://es.epa.gov/ncer/rfa/2005/2005_star_nano.html 

■ http://es.epa.gov/ncer/rfa/2004/2004_manufactured_nano.html 

Information about the NIOSH goal to transfer research findings, technologies, 

and information into prevention practices and products in the workplace can be 

found at http://www.cdc.gov/niosh/r2p/. The emphasis on r2p is intended to reduce occupation-related illness and injury by increasing the use of findings from 

NIOSH-funded research in the workplace. 

NIOSH conducts a wide range of efforts in the areas of research, guidance, information transfer, and public service. Additional information about the diverse 

activities of NIOSH can be found at the NIOSH home page (http://www.cdc. 

gov/niosh/homepage.html) and the program portfolio Web site (http://www.cdc. 

gov/niosh/programs/). 

141 
Table 1. Extramural nanotechnology research funded by NIOSH*, 2001–2006 

1st year Total projected Grant number Investigator Institution	 Project title Start End funding funding 

Before FY 2004 NIOSH/SBIR:

1R43OH007471–01 Hooker	 Nanomaterials Research Novel Hydrogen Sulfide Sensors for Portable 9/30/2001 3/31/2002 $100,000 $100,000 

LLC, Longmont, CO Monitors 

2R44OH007471–02 Williams Synkera Technologies Novel Hydrogen Sulfide Sensors for Portable 9/16/2003 9/15/2006 $373,430 $749,995 

Inc., Longmont, CO Monitors 

Pre-FY 2004 total: $473,430 $849,995 FY 2004 Exposure assessment (NIOSH/SBIR):

1R43OH007963–01A1 Rajagopalan	 Nanoscale Materials, From Nanoparticles to Novel Protective 9/1/2004 5/15/2005 $100,000 $100,000 

Inc., Manhattan, KS Garments 

FY 2005 Emerging technologies (NIOSH program announcement):

1R01OH008282–01A Kagan University of Pittsburgh	 Lung Oxidative Stress/Inflammation by 7/1/2005 6/30/2009 $363,975 $1,458,862

Carbon Nanotubes

FY 2005 Emerging technologies RFA (EPA STAR–2005–B1):

1R01OH008806–01 O’Shaughnessy University of Iowa Assessment Methods for Nanoparticles in 7/1/2005 6/30/2008 $132,903 $392,574 

the Workplace 

1R01OH008807–01 Xiong New York University Monitoring and Characterizing Airborne 8/1/2005 7/31/2008 $158,185 $396,401 

School of Medicine Carbon Nanotube Particles 

FY 2005 total: $655,063 $2,247,837 FY 2006 Nanotechnology RFA (EPA G2006–STAR F1 to F7):

1R01OH009141–01 Dutta Ohio State University	 Role of Surface Chemistry in the Toxicological 9/1/2006 8/31/2009 $119,700 $359,100 

Properties of Manufactured Nanoparticles

FY 2006 Nanotechnology (NIOSH/SBIR):

1R43OH008939–01 Deininger Synkera Technologies New Nanostructured Sensor Arrays for 8/1/2006 2/28/2007 $99,998 $99,998 

Inc., Longmont, CO Hydride Detection

FY 2006 total — — — — — $219,698 $459,098 

Grand total: $3,556,932

 FY 2007 Nanotechnology (NIEHS RFA–ES–06–008):

Release date	 September — Set aside $500K; maximum project $300K;


29, 2006 maximum length 4 years


 FY 2008 Nanotechnology RFA (EPA)—U.S./Europe:

Anticipated	 April 2007 — Set aside $500K; maximum project $250K;release date	 maximum length 3 years

*Abbreviations: EPA=Environmental Protection Agency; NIEHS=National Institue of Environmental Health Sciences; NIOSH=National Institute for Occupational Safety and Health; 

 RFA=request for application; SBIR=small business innovative research; STAR= science to achieve results. 

142 
Appendix D ■ Review of the NIOSH Extramural Nanotechnology Research Programs FY 2001–FY 2006 

Extramural Nanotechnology Research Project Summaries 

These brief project summaries were excerpted from the project descriptions. 

For additional information, please contact the identified investigator(s) for the 

specific project. Investigator contact information is provided in Table 2; however, information for Dr. Hooker was not available. 

Hooker 7471 (R43), Williams 7471 (R44) 

Novel Hydrogen Sulfide Sensors for Portable Monitors 

The primary objective for this project is the design, development, and demonstration of better sensor technology for the detection of hydrogen sulfide. 

Hydrogen sulfide is a highly toxic, colorless, flammable gas that reacts with 

enzymes that inhibit cell respiration. At high concentrations hydrogen sulfide 

can literally shut off the lungs, while lower levels can burn the respiratory tract 

and cause eye irritation. 

This gas is encountered in a wide range of industries, and a number of standards have been established for occupational exposure. The OSHA Permissible 

Exposure Limit (PEL) is 10 parts per million (ppm), the Short Term Exposure 

Limit (STEL) is 15 ppm, and exposures of 300 ppm or greater are considered 

immediately dangerous to life and health (IDLH). Because of the potential for 

adverse health effects at low concentrations, the industrial hygiene community 

is continually seeking improved performance from hydrogen sulfide sensors. 

Specific requirements include reliable and accurate detection in real-time, 

quantitative measurement capabilities, low purchase and life cycle costs, and 

low power consumption for portability. Sensors meeting these requirements 

will find numerous applications within the safety and health field. In addition, 

there are several potential spin-off opportunities in leak detection, emission 

monitoring, and process control. Alternative ceramic oxide materials and a 

unique multi-layer fabrication process to accomplish the objectives of this 

project will be used. The work plan includes optimization of the sensor materials, sensor element fabrication, sensor element packaging, in-house and 

external evaluation of the sensors, and establishing the foundation for new 

instrument development. The ultimate aim is a low-cost, low-power sensor 

that can be used in a new type of personal monitor. The envisioned monitor is 

a low-profile, credit card sized “smart-card” that cannot only alert the wearer 

when unsafe concentrations have been encountered but also track cumulative 

individual worker exposure to a particular toxic gas species. 

143 
NIOSH Nanotechnology Research Center 

Progress 

The early portions of this project focused on developing nano-structured sensor materials and morphologies targeted toward chemiresistive-based sensors. 

This work resulted in a commercial sensor that is being incorporated into the 

fixed-system H2S detection products of multiple partnering instrument manufacturers. The middle portion of the project focused on developing solid-state 

electrochemical sensors utilizing micro and nano-sized morphologies and 

structures. This has resulted in a working sensor currently being incorporated 

into an inexpensive, portable personal monitor as described above. 

Rajagopalan (7963) 

From Nanoparticles to Novel Protective Garments 

The overall objectives of this collaborative Phase I research between NanoScale 

and Gentex Corp. are to (1) investigate the use of highly adsorbent and reactive nanoparticles in protective garments and (2) create and test new materials 

for use in the production of protective clothing. During routine chemical use 

it is not always apparent when exposure occurs. Many chemicals pose invisible 

hazards and offer no warnings. More importantly, terrorists and saboteurs use 

a variety of toxic industrial chemicals to create improvised explosives, chemical 

agents, and poisons. When dealing with hazardous materials released either by 

accident or intentionally, protective clothing is critical in guarding against the 

effects of toxic or corrosive products that could enter the body by inhalation or 

skin absorption and cause adverse effects. 

This project seeks to (1) establish the feasibility of incorporating highly adsorbent and reactive nanoparticles into lightweight, permeable textiles and (2) 

evaluate the utility of the resultant fabric as protective clothing using standard 

industry testing procedures. These novel protective garments will be tailored 

specifically toward personnel associated with Federal, State, or local emergency 

agencies as well as fire fighters and civilian first responders. 

To achieve the overall objective, reactivity of selected nanoparticle formulations to various toxic industrial chemicals will be explored by use of a quartz 

spring balance to determine adsorption capacity. Based on the outcome of this 

research, a single reactive nanoparticle formulation will be chosen for use in 

fabrics. The selected nanoparticle formulation will then be incorporated into 

suitable fabrics using two established techniques. Next, fabric test swatches 

will be evaluated for a number of criteria using industry recognized ASTM test 

methods. Finally, the top four nanoparticle embedded fabrics will be tested for 

physical and chemical resistance against two representative toxic chemicals using a standard ASTM procedure. 

144 
 

 

 

 

 

 

Appendix D ■ Review of the NIOSH Extramural Nanotechnology Research Programs FY 2001–FY 2006 FY 2001–FY 2006 

Kagan (8282) 

Lung Oxidative Stress/Inflammation by Carbon Nanotubes 

Background 

Specific Aim 1: Establish the extent to which SWCNTs alone are pro-inflammatory to lung cells and tissue and characterize the role of iron in these effects using 

genetically manipulated cells and animals as well as antioxidant interventions. 

Specific Aim 2: Determine the potential for SWCNTs and microbial stimuli to 

synergistically interact to promote macrophage activation, oxidative stress, and 

lung inflammation. 

Specific Aim 3: Reveal the extent to which SWCNTs are effective in inducing apoptosis and whether apoptotic cells exert their macrophage-dependent 

anti-inflammatory potential during in vitro and in vivo SWCNT exposure. The 

project involves a team of interdisciplinary scientists with expertise in redox 

chemistry and biochemistry, cell and molecular biology of inflammation and its 

interactions with microbial agents, and pulmonary toxicology of nanoparticles. 

Progress 

Two types of SWCNTs were used (iron-rich and iron-stripped) to study their 

interactions with RAW 264.7 macrophages. Following ultrasonication of the 

SWCNTs to separate strands, neither type was able to generate intracellular production of superoxide radicals or nitric oxide by macrophages observed by flowcytometry and fluorescence microscopy. SWCNTs with different iron content 

displayed different redox activity in a cell-free model system. In the presence of 

microbial (zymosan) stimulated macrophages, nonpurified iron-rich SWCNTs 

were more effective in generating hydroxyl radicals than purified SWCNTs. The 

presence of iron in SWCNTs may be important in determining redox-dependent 

responses of macrophages. Dose and time-dependence studies of inflammatory 

responses in mice using pharyngeal aspiration of SWCNTs demonstrated that 

they elicited unusual pulmonary effects in C57BL/6 mice that combined a robust 

but acute inflammation with early onset yet progressive fibrosis and granulomas. It was demonstrated that occupationally relevant dose-dependent effects 

of SWCNTs may exert toxic effects in the lungs of exposed animals in vivo. 

SWCNT-induced inflammation and exposure caused altered pulmonary function. Microbial stimulation and clearance from the lungs of SWCNT-exposed 

mice were compromised. An unusual and robust inflammatory and fibrogenic 

response was correlated with the progression of oxidative stress and apoptotic signaling. The toxic effects of SWCNTs were important to consider, and 

also the role of transitional metals, particularly iron, should be investigated. 

145 
 

 

 

NIOSH Nanotechnology Research Center 

O’Shaughnessy (8806) 

Assessment Methods for Nanoparticles in the Workplace 

Background 

The primary objectives are to (1) provide the scientific community and practicing industrial hygienists with verified instruments and methods for accurately 

accessing airborne levels of nanoparticles and (2) assess the efficacy of respirator use for controlling nanoparticle exposures. 

Objectives will be satisfied through a combination of laboratory and field studies centered on the following aims: identify and evaluate methods to measure 

airborne nanoparticle concentrations; characterize nanoparticles using a 

complementary suite of techniques to assess their surface and bulk physical 

and chemical properties; and determine the collection efficiency of commonlyused respirator filters when challenged with nanoparticles. 

Progress

Several methods were used to aerosolize nanoparticles from bulk powders in 

the laboratory. An apparatus was developed to inject the aerosol into a mainflow of dry, filtered air through a charged neutralizing device. The amount 

and size distribution of the aerosol in the chamber is sampled with a scanning 

mobility particle sizer. Samples from the chamber are also being analyzed by 

TEM. While the primary particle size of these powders average 20 nm, an 

aerosol with a median size of 120 nm is generated. These findings have significance in occupational settings since agglomeration of the particles in this size 

range will have consequences in pulmonary deposition and respirator filtration. Nanosized particles were also found as contaminants in the water used. 

A variety of instruments are being compared for use in the field studies of 

nanoparticle exposure concentrations in two facilities; one in Minnesota and 

one in Texas. 

Xiong (8807) 

Monitoring and Characterizing Airborne Carbon Nanotube (CNT) 

Particles 

Background 

The proposed research will develop a comprehensive yet practical method for 

sampling, quantification, and characterization of CNT particles in air. This 

method will be capable of (1) classifying sampled particles into three categories: 

146 
Appendix D ■ Review of the NIOSH Extramural Nanotechnology Research Programs FY 2001–FY 2006 FY 2001–FY 2006 

tubes, ropes (bundles of single-walled CNT bounded by Van der Waals attraction force), and nontubular particles (soot, metal catalysts, and dust, etc.), and 

(2) measuring the number concentrations, size distributions for each type, and 

the shape characters (diameter, length, aspect ratio and curvature) of CNT. 

The method will use available instrumentation to build an air monitoring 

system that is capable of sampling and sizing airborne CNT particles in a 

wide size range by using a 10-stage Micro-Orifice Uniform Deposit Impactor 

(MOUDI) and an Integrated Diffusion Battery previously developed in this 

laboratory. 

Successful completion of this project will produce (1) a validated method for 

sampling airborne CNT in the workplace and (2) a practical method to classify 

sampled CNT particles by type through quantifying and characterizing each 

type separately using Atomic Force Microscopy image analysis technology. 

These methods are needed to determine potential health risks that may result 

from worker exposure to the various types (CNTs, nanoropes, and nontubular 

nanoparticles). The results will also provide a foundation for field and personal 

sampling devices for CNT. 

Progress 

Instrumentation and materials are essentially ready. Years 2 and 3 will focus on 

method development for sampling, quantifying, and characterizing airborne 

CNT aerosol particles. 

Dutta (9141) 

Role of Surface Chemistry in the Toxicological Properties of Manufactured Nanoparticles 

Background 

The objectives of this program are to verify two hypotheses: (1) the quantifiable 

differences in surface reactivity of nanoparticles, as measured by acidity, redox 

chemistry, metal ion binding and Fenton chemistry as compared with micronsized particles of similar composition cannot be explained by the increase in 

surface area alone, and (2) the oxidative stress and inflammatory response 

induced by nanoparticles upon interaction with macrophages and epithelial 

cells depends on their surface reactivity. The basis of these hypotheses is that 

nanoparticles contain a significantly higher number of “broken” bonds on the 

surface that provide different reactivity as compared to larger particles. 

147 
NIOSH Nanotechnology Research Center 

The experimental approach focuses on three classes of manufactured nanoparticles; catalysts (aluminosilicates), titania, and carbon. For the catalysts and 

titania samples, nanoparticles (<100 nm) and micron-sized particles of similar 

bulk composition will be studied. For carbon, carbon black and single-walled 

CNTs are chosen. Nanoparticles of aluminosilicates and titania will be synthesized, whereas the other particles will be obtained from commercial sources. 

Characterization will involve electron microscopy, surface area, and surface 

and bulk composition. 

Reactivity of well-characterized particles in regards to their acidity, reaction 

with antioxidants simulating the lung lining fluid, coordination of iron, and 

Fenton chemistry will be carried out using spectroscopic methods. Particular 

attention will be paid to surface activation as may exist during manufacturing and processing. In vitro oxidative stress and inflammatory responses upon 

phagocytosis of the particles by macrophages and pulmonary epithelial cells 

will form the toxicological/biological end points of the study. Methods include 

gene array techniques, assays for reactive oxygen species, and adhesion molecules on endothelial cells. 

Deininger (8939) 

New Nanostructured Sensor Arrays for Hydride Detection 

Background 

The goal of the proposed project is to develop improved sensors for the detection of hydrides (including arsine, phosphine, and diborane) for protection 

of worker safety and health. Current sensors suffer from severe limitations 

including lack of selectivity and limited accuracy and lifetime. An electronic 

sensor system, capable of automatically warning workers of the presence of one 

of these toxic gases, would provide a substantial benefit for worker safety and 

health. 

This project will take advantage of advances in nanotechnology, ceramic micromachining, and materials chemistry to create sensors that are substantially 

better than current state of the art. These improved sensors will be the basis for 

improved personal and permanent monitors for increased protection of workers in the semiconductor industry. 

148 
 

Appendix D ■ Review of the NIOSH Extramural Nanotechnology Research Programs FY 2001–FY 2006 FY 2001–FY 2006 

Table 2. Nanotechnology principal investigators funded by
 

NIOSH/OEP; FY 2001–FY 2006
 

Debra J. Deininger 

Synkera Technologies, Inc. 

2021 Miller Drive, Suite B 

Longmont, CO 80501 

(720) 494–8401 (T)/(720) 494–8402 (F) 

ddeininger@synkera.com 

1R43OH008939–01 (2006) 

Prabir K. Dutta 

The Ohio State University 

Department of Chemistry 

1960 Kenny Road 

Columbus, OH 43210 

(614) 292–4532 (T)/(614) 292–1685 (F)
 

dutta.1@osu.edu
 

1R01OH009141 (2006)
 

Professor Valerin E. Kagan, Ph.D., D.Sc. 

University of Pittsburgh 

Department of Environmental and

 Occupational Health 

Bridgeside Point 

100 Technology Drive, Suite 350 

Pittsburgh, PA 15129 

(412) 624–9479 (T)/(412) 624–9361 (F)
 

kagan@pitt.edu
 

1R01OH008282–01A (2005)
 

Patrick Thomas O’Shaughnessy 

University of Iowa 

Department of Occupational

 and Environmental Health 

100 Oakdale Campus, 137 IREH 

Iowa City, IA 52242–5000 

(319) 335–4202 (T)/(319) 335–4225 (F) 

Patrick-Oshaughnessy@uiowa.edu 

1R01OH008806–01 (2005) 

Shymala Rajagopalan 

NanoScale Materials, Inc. 

1310 Research Park Dr. 

Manhattan, KS 66502 

(785) 537–0179 (T)/(785) 537–0226 (F) 

srajagopalan@nanoactive.com 

www.nanoactive.com 

1R43OH007963–01A1 (2004) 

Stephen Williams 

Synkera Technologies, Inc. 

2021 Miller Drive, Suite B 

Longmont, CO 80501 

(720) 494–8401 (T)/(720) 494–8402 (F) 

swilliams@synkera.com 

2R44OH007471–02 (2003) 

Judy Xiong 

New York University School of Medicine

 Environmental Medicine 

57 Old Forge Road 

Tuxedo, NY 10987 

(845) 731–3627 (T)/(845) 351–5472 (F) 

xiongj@env.med.nyu.edu 

1R01OH008807–01 (2005) 

149 

Appendix E 

Nanotechnology Information 

Dissemination 
NIOSH Nanotechnology Research Center 

Research Project: Nanotechnology Information 

Dissemination 

Prinicipal Investigator: Charles L. Geraci, Ph.D., C.I.H., 

EID/NIOSH/CDC 

Project Duration: FY 2006–FY 2010 

Background 

Guidance and recommendations for managing and preventing occupational 

exposure to nanoparticles is needed to protect the health of workers. This 

project will produce and disseminate educational information about current 

best practices for minimizing occupational exposure risks during the various 

phases of nanomaterial research, development, production, and use. The types 

of communication products and vehicles to be used include the following: 

■	 Interim recommendations on the NIOSH Web site to provide a vehicle for presenting the latest information about nanotechnology, and 

to provide customers a means to provide feedback, ask questions, and 

provide examples of work; a Nanoparticle Information Library (NIL) 

that contains chemical and physical properties of specific nanoparticles 

■	 A Current Intelligence Bulletin on Working with Engineered Nanomaterials that will present NIOSH’s current knowledge and recommendations on health effects, exposure limits, exposure monitoring, PPE, 

respiratory protection, and engineering controls 

■	 Educational materials that will be used to teach the safety and health 

components of nanotechnology and nanomaterial processing at the 

graduate and undergraduate level 

■	 Nano-safe training tool kits that can be used as part of an overall risk 

management program by nanotechnology companies or companies 

who incorporate nanomaterials into their products 

This information will be valuable to the much larger population of secondary users of nanomaterials who may not be producing the materials, but are 

incorporating them into existing products. In addition to materials developed 

by NIOSH, partnerships with universities and businesses will be developed 

to incorporate their experience and share practices they have developed that 

have been effective. This project will allow for a direct translation of r2p by 

152 
Appendix E ■ Nanotechnology Information Dissemination 

communicating NIOSH research and field observations in training documents 

and tools. The time frame for this project extends into FY 2010 and will be the 

primary means to communicate NIOSH research results to the nanotechnology industry, and to maintain an active dialogue with that community. 

Accomplishments 

■	 Collected and assembled NTRC information and research results into 

the original version of Approaches to Safe Nanotechnology: An information Exchange with NIOSH. This document was posted on the NIOSH 

Web site on October 3, 2005. 

■	 Developed a Nanotechnology Information Development and Dissemination project as part of the WHO coordinating centers portfolio. 

■	 Developed an initial sampling protocol as part of the TiO2 CIB to address possible contribution of nano-sized particles to workplace exposure. 

■	 Established a working partnership with a metal oxide nanoparticle 

production facility to evaluate work practices and develop protocols to 

assess workplace exposures. 

■	 Produced an update to Approaches to Safe Nanotechnology and posted it 

on the NIOSH Web site on June 4, 2006. 

■	 Updated the NIOSH Nanotechnology Web topic page to highlight the 

ten critical research areas identified in the Strategic Research Plan. 

Charles L. Geraci’s activities in the NIOSH 

Nanotechnology Research Program 

Accomplishments 

■	 National and international promotion of NIOSH leadership in the area 

of nanotechnology occupational safety and health research 

■	 Member of ISO TC 229 on Nanotechnologies, Working Group 3 in 

Health, Safety and Environment 

■	 Expert reviewer to the ORC Nanotechnology Workgroup developing 

best practices for nanomaterial processes 

■	 Nanotechnology expert contact for the memorandum of understanding 

between NIOSH and AIHA 

153 
 

 

 

 

NIOSH Nanotechnology Research Center 

■	 Project officer on the NIOSH project Nanotechnology Information 

Dissemination 

■	 Developer and co-leader of the NIOSH Nanotechnology Field Research 

team 

■	 Facilitated visits to three nanomaterial facilities 

Invited Presentations 

■	 Regulatory and risk overview [2006]. International Conference on 

Nanotechnology, Occupational and Environmental Health and Safety: 

Research to Practice. Cincinnati, OH, December 4–7. 

■	 Managing nanomaterials along the product life cycle [2006]. International Conference on Nanotechnology, Occupational and Environmental Health and Safety: Research to Practice. Cincinnati, OH, December 

4–7. 

■	 Evaluation of a real-time surface area monitor in a nanotechnology 

workplace [2006]. Co-author on a poster presented at the International 

Conference on Nanotechnology, Occupational and Environmental 

Health and Safety: Research to Practice. Cincinnati, OH, December 4–7. 

■	 Update on understanding and assessing an emerging technology in 

practice: continuation of an innovative industry/government partnership [2006]. Co-author on a poster presented at the International Conference on Nanotechnology, Occupational and Environmental Health 

& Safety; Research to Practice. Cincinnati, OH, December 4–7. 

■	 Health issues associated with nanotechnology [2006]. Continuing 

Medical Education Seminar Series, College of Medicine, University of 

Cincinnati, November 29. 

■	 Managing nanomaterials in the workplace: what do we know? [2006]. 

The American Society of Safety Engineers’ Solutions in Safety Through 

Technology Symposium, Scottsdale, AZ, November 16–17. 

■	 What is nanotechnology and should you be concerned? [2006]. Fall 

meeting of the Building Environment Council of Ohio, Columbus, OH, 

October 26. 

■	 What every industrial hygienist should know about nanotechnology 

[2006]. Ohio Valley Section—American Industrial Hygiene Association, Cincinnati, OH, October 24. 

■	 Risk based approach to nanoparticle management [2006]. Greater St. 

Louis Safety and Health Conference, St. Louis, MO, October 1. 

154 
 

 

 

 

Appendix E ■ Nanotechnology Information Dissemination 

■	 The NIOSH field effort to evaluate practices in nanotechnology [2006]. 

Commercialization of Nanomaterials, Pittsburgh, PA, September 20. 

■	 The NIOSH nanotechnology research program: applicability to nanocomposites [2006]. Center for Multifunctional Polymer Nanomaterials 

and Devices, Board of Advisors Meeting, National Composites Center, 

Kettering, OH, August 15. 

■	 The NIOSH nanotechnology research program: overview with emphasis 

on areas of industry collaboration [2006]. Joint Memorandum of Understanding Meeting: NIOSH and DuPont, NIOSH National Personal 

Protective Technology Laboratory (NPPTL), Pittsburgh, PA, August 3. 

■	 Nanotechnology in the workplace: promoting innovation through better risk management [2006]. Campus Safety, Health and Environment 

Mangers Association Annual Conference, Anaheim, CA, July 19. 

■	 Nanotechnology in the workplace: the NIOSH research program 

[2006]. NPE International Plastics Exposition, Special Educational session on Nanotechnology, Chicago, IL, June 20, 2006 

■	 Occupational health risks of nanoparticles in the workplace [2006]. 

Nanocomposites 2006, Special Forum on Health Issues of Nanotechnology, Chicago, IL, June 19. 

■	 Nanotechnology: ensuring workplace health and safety through better 

risk management [2006]. Nanotechnology in Food and Agriculture, Inaugural Conference by Food Chemical News, Washington, DC, June 7. 

■	 The NIOSH nanotechnology research program: progress through 

industry partnerships [2006]. NanoBusiness Alliance, New York, NY, 

June 19. 

■	 Nanotechnology research at NIOSH and applications to the pharmaceutical industry [2006]. AIHA Pharmaceutical Forum, American 

Industrial Hygiene Conference and Exposition, Chicago, IL, May 17. 

■	 NIOSH nanotechnology program update: ask the experts—(arranged 

the session and presented updates): NIOSH information resources update and NIOSH Field Research Activities [2006]. American Industrial 

Hygiene Conference and Exposition, Chicago, IL, May 16. 

■	 Nanotechnology: government initiatives [2006]. Special Symposium 

on Occupational Safety and Health Issues of Nanotechnology in the 

Workplace, American Industrial Hygiene Conference and Exposition, 

Chicago, IL, May 13. 

155 
NIOSH Nanotechnology Research Center 

■	 Nanotechnology health and safety professional development course 

[2006]. Health and Safety Canada, Industrial Accident Prevention Association Conference, Toronto, Canada, May 4. Delivered the following 

modules: 

	 Physical and chemical characteristics, metrology, and exposure 

assessment 

	 Risk management, work practices, safety, PPE 

	 Information resources 

■	 Overview of key NIOSH nanotechnology research projects: Building 

a nanoparticle information library, Potential application of control 

banding to nanotechnology, Nanotechnology information resources on 

the NIOSH Web, and Nanotechnology: a coordinated NIOSH research 

program [2006]. National Occupational Research Agenda Symposium, 

Washington, DC, April 18–20. 

■	 Health and safety practices for nanotechnology [2006]. Special Panel 

Session, the Ohio Nanotechnology Summit 2006, Columbus OH, 

March 4. 

■	 The NIOSH nanotechnology research program: an overview for Ohio 

[2006]. Nanotechnology Primer Session, the Ohio Nanotechnology 

Summit, Columbus, OH, March 4. 

■	 A case study in partnering to develop a nanotechnology occupational 

safety and health program in a nanotechnology manufacturing environment [2006]. Co-author on poster presented at the Second International Symposium Nanotechnology and Occupational Health, Minneapolis, MN, October 4. 

Future Presentations 

■	 Nanotechnology: current knowledge for effective risk management 

[2007]. Oregon Governor’s Occupational Safety & Health Conference, 

Salem, OR, March 12–15. 

■	 Nanotechnology: what do we know for effective hazard communication? [2007]. Society for Chemical Hazard Communication, San Antonio, TX, April 25. 

■	 NIOSH nanotechnology research update: ask the experts [2007]. Philadelphia, PA, June 5. 

156 
 

 

 

Appendix E ■ Nanotechnology Information Dissemination 

■	 Developing information for effective exposure evaluation and risk 

management in the production of nanoparticles [2007]. ASSE National 

Conference, Special Symposium on Developing Business Models for 

Managing Nanotechnology, Orlando, FL, June 2–7. 

National and International Activities 

■	 C. Geraci is a member of the ISO Technical Committee 229 on Nanotechnologies, Work Group 3 Technical report on current safe practices in 

occupational settings relevant to nanotechnologies. 

■	 C. Geraci was the Co-Organizer of the Conference Planning Committee and Co-Chair of the Applications Session of the International Conference on Nanotechnology, Occupational and Environmental Health 

and Safety: Research to Practice, Cincinnati, OH, December 4–7, 2006. 

■	 C. Geraci is the U.S. member of the International Advisory Committee 

Member for the U.S. for the Third International Symposium on Nanotechnology: Occupational and Environmental Health, Taipei, Taiwan, 

August 29 to September 1, 2007. 

■	 C. Geraci is a member of the American Industrial Hygiene Association 

Nanotechnology Working Group. 

■	 C. Geraci served as an Expert Peer Reviewer to the ORC Nanomaterials Work Practices Workgroup. 

Partnerships and Collaborations 

■	 Developed a partnership with an international cosmetic product manufacturer to evaluate exposures, work practices, and controls during the 

introduction of nanoparticle materials. 

■	 Ongoing partnership with a primary metal oxide manufacturer: characterization of exposures to metal oxide nanoparticles; develop work 

practices and controls; evaluate effectiveness of controls; develop a 

return-on-investment study for controls and health safety and environmental improvements. 

■	 Planned investigations in the nanocomposites industry through a partnership with the Center for Multifunctional Polymer Nanomaterials and 

Devices (CMPND) and the University of Dayton Research Institute. 

■	 Participated in an inaugural workshop on nanotechnology with the 

Campus Safety, Health and Environment Management Association 

(CSHEMA) and developed a strategy for Web-casting workshops. 

157 
NIOSH Nanotechnology Research Center 

NTRC Critical Research Topic Areas Addressed 

1. Exposure Assessment 

2. Communication and Education 

3. Recommendations and Guidance 

4. Measurement Methods 

158 
Appendix F 

Other NTRC Partnership 

Activities and Presentations 
NIOSH Nanotechnology Research Center 

Other NTRC Staff, Activities in the NIOSH 

Nanotechnology Research Program 

John Howard, M.D. 

Presentations 

■	 The NIOSH nanotechnology initiative: ensuring a safe and healthful 

workforce in a changing environment. Kansas City Safety and Health 

Conference, ASSE, Kansas, MO, July 14–15. 

■	 The NIOSH nanotechnology initiative: ensuring a safe and healthful 

workforce in a changing environment. The Art of Safety: the 10th Anniversary Commemorative Safety & Health Congress and Expo, Isla 

Verde, PR. The NIOSH Nanotechnology Initiative: Ensuring a safe and 

healthful workforce in a changing environment, July 30–August 5. 

■	 The NIOSH nanotechnology initiative: ensuring a safe and healthful 

workforce in a changing environment [2005]. OSHA Health Forum, 

Denver, CO, August 31. 

■	 Perspectives on nanotechnology ‘[2006]. NIOSH and Nanotechnology, 

Woodrow Wilson International Center for Scholars, Washington, DC, 

February 23. 

■	 National CleanRooms Contamination Control [2006]. Nanotechnology 

and Risk: The NIOSH Perspective. Technology Conference & Exposition on 15 March, Boston MA, March 15. 

■	 Mt. Sinai annual ERC meeting on toxicity and control issues [2006]. 

Nanotechnology and risk: the NIOSH perspective. April 7. 

■	 NIOSH at 5 years of NNI [2006]. International Nanotechnology Conference on Communication and Cooperation. Arlington, VA, May 

15–17. 

■	 Nanotechnology and risk: the NIOSH perspective [2006]. Congress 

of Nanobiotechnology and Nanomedicine (NanoBio 2006). San Francisco, CA, June 19–21. 

Vladimir Murashov, Ph.D. 

Publications and Abstracts 

■	 ISO/TC 229/WG3 Summary of U.S. research and development activities on nanotechnology related to environmental health and safety 

[2006]. NANO TAG N 221–2006, ANSI. 

160 
 

 

 

Appendix F ■ Other NTRC Partnership Activities and Presentations 

■	 Report of the OECD workshop on the safety of manufactured nanomaterials building Co-operation, Co-ordination, and Communication 

[2005]. Washington DC, December 7–9. Environment Directorate, Organisation for Economic Cooperation and Development, Paris [2006]. 

■	 Murashov VV [2006]. Comments on Particle surface characteristics 

may play an important role in phytotoxicity of alumina nanoparticles 

(by Yang L and Watts, DJ, published in Toxicol Lett [2005] 158:122– 

132). Toxicol Lett 164:185–187. 

Presentations 

■	 Nanotechnology: preparing for public health assessment [2006]. George 

Washington University, School of Public Health. Introductory environmental and occupational health course, Washington, DC, June 5. 

■	 Nanotechnology: research perspective/current knowledge [2006]. National Response Team Worker Safety and Health Technical Conference, 

Washington, DC, May 31. 

■	 Nanotechnology: government initiatives [2006]. Nanotechnology Symposium: Nanoparticles in the Workplace, Chicago, IL, May 13. 

■	 Safe nanotechnology [2006]. NSTI Nanotech 2006, Boston, MA, May 9. 

■	 NIOSH nanotechnology program: funding [2006]. International Conference on Nanotechnology. Technical Association for the Pulp and 

Paper Industry, Atlanta, GA, April 28. 

■	 NIOSH nanotechnology program: research [2006]. International Conference on Nanotechnology. Technical Association for the Pulp and 

Paper Industry, Atlanta, GA, April 26. 

■	 NIOSH nanotechnology program [2006]. Office of Extramural Programs, NIOSH, Atlanta, GA, April 25. 

■	 Nanotechnology and risk: NIOSH perspective [2006]. RIMS 2006 Annual Conference and Exhibition. Honolulu, HI, April 24. 

■	 Nanotechnology: ensuring a safe and healthful workplace [2006]. PDC 

Piedmont Chapter of the ASSE, SC, March 16. 

■	 NIOSH Nanotechnology Program [2006]. NanoBusiness Alliance, 

Washington, DC, February 17. 

■	 NIOSH Nanotechnology Program [2006]. American Insurance Association, Washington, DC, February 8. 

161 
NIOSH Nanotechnology Research Center

■	 NIOSH Current Intelligence Bulletin on TiO2

 [2006]. Particles and 

Cancer, MIT Conference, San Juan, PR, January 11. 

■	 Nanotechnology: ensuring a safe and healthful workplace [2005]. 2005 

MRS Fall Meeting, Symposium S: Nanomaterials and the Environment, 

Boston, MA, December 1. 

■	 Occupational safety and health and nanotechnology: knowns and unknowns, Nanotechnology: are the health and safety concerns as small 

as the particles? [2005].AIHA Texas Hill Country Section 2005 Symposium, Austin, TX, November 3. 

■	 NIOSH Nanotechnology Research Program [2005]. Nanotechnology 

and the Environment: Applications and Implications Progress Review 

Workshop III, Arlington, VA, October 26–28. 

■	 NIOSH and National Nanotechnology Initiative [2005]. Aerospace 

Industries Association ES&H Fall 2005 Meeting, Redondo Beach, CA, 

October 12–14. 

■	 NIOSH Nanotechnology Research Program [2005]. American Chemistry Council Nanotechnology Panel, Arlington, VA, September 20. 

National and International Activities 

■	 Member of NSET Subcommittee of the National Science and Technology Council’s Committee on Technology and its working groups. 

■	 Member of the NNI-Chemical Industry Consultative Board for Advancing Nanotechnology. 

■	 Member of the National Electrical Manufacturers Association’s Nanotechnology Advisory Council. 

■	 Member of the external peer-review panel for EPA White Paper on 

Nanotechnology, June 2006. 

Paul Schulte, Ph.D. 

Publications 

■	 Schulte PA, Salamanca-Buentello F [2006]. Ethical and scientific issues 

of nanotechnology in the workplace. Environmental Health Perspectives. 

available at http://www.ehponline.org/docs/2006/9456/abstracts.html 

Invited Presentations 

■	 Occupational Safety and Health Issues in Nanotechnology [2006]. International Commission on Occupational Health. Milan, Italy, June 12. 

162 
Appendix F ■ O ix F ■ Other NTRC Partnership Activities and Presentations

■	 NIOSH Nanotechnology Research [2005]. Nanoparticle Occupational 

Health and Safety Workshop sponsored by the Massachusetts Toxics 

Use Reduction Institute and the Center for High-Rate Nanomanufacturing. Westborough, MA. December 2. 

Presentations 

■	 Nanotechnology and Occupational Safety and Health and Ethical/ 

Medical Issues [2006]. Presentations at the International Conference on 

Nanotechnology Occupational and Environmental Health and Safety: 

Research to Practice. Cincinnati, OH. December 4–7. 

■	 Nanotechnology [2006]. Health and Safety Professional Development 

Course, Health and Safety Canada 2006, Industrial Accident Prevention Association Conference, Toronto, Canada, May 4. Delivered the 

following modules: 

	 Overview 

	 Toxicology 

	 Risk Assessment 

	 Medical Surveillance 

	 Ethical Issues 

■	 Panel Member. Ethical and legal aspects of nanomaterials and environmental regulation [2005]. Materials Research Society Fall Meeting, 

Boston, MA, December 1. 

NTRC Critical Research Topic Areas Addressed 

1.	 Communication and Education 

2.	 Recommendation and Guidance 

163 

Appendix G 

Projected Timeframe for 


Addressing Critical Areas
 
Projected timeframe for addressing critical areas

Calendar year NIOSH

10 critical areas 2005 2006 2007 2008 2009 

Exposure assessmentToxicity and internal dose 

DEP* generation and Data and preliminary Nanoparticle evaluations Dosimetry lung model in

characterization studies dosimetry for DEP (HELD in an automotive plant rats and humans, begin(NORA-PRL, HELD base) base, NORA-PRL) (NTRC-DART) phase II: calibration and

validation with transloWildfire ultrafine aerosol Data and preliminary TiO2 workplace expo- cation data (NTRC-EID and firefighter exposure dosimetry for firefighters sure assessment report pending) studies (SNORA-DRDS) (SNORA-DRDS) (DSHEFS unfunded)Continue evaluation

Dosimetry lung model in Continue evaluation and characterization ofrats and humans, begin and characterization of nanoparticle exposures phase I: structure and nanoparticle exposures in workplaces handling calibration w/ existing in workplaces handling nanomaterialsdata (NTRC-EID) nanomaterials Initiate TiO2 workplace


exposure assessment
(DSHEFS unfunded)
Initiate field surveys of
workplaces handling
nanomaterials
 

Preliminary results from Hazard ID information Preliminary cardiovas- Complete dose and timetoxicity testing in labora- on carbon nanotubes cular endpoints (NORA- information on carbon

tory animal and in vitro (NORA-HELD) HELD pending) nanotubes (NORA-HELD)systems (NORA-HELD) Surface area-mass met- Nanometal hazard ID

ric results (NORA-HELD) (NORA-HELD)Dose-response data for Dermal informationdiesel exhaust particles (NORA-HELD)(HELD) Neurological effects

(HELD base)Translocation results in laboratory animals afterpulmonary and dermalexposure to nanomaterials (NORA-HELD) 

Continue evaluationand characterizationof workplaces handlingnanomaterialsDevelopment of firmcardiovascular endpoints(NORA-HELD)Quantification of systemic nanoparticle concentrations in laboratoryanimals after pulmonaryexposure to nanospheresand nanofibers (NORAHELD) 

(Continued) 

166 
Projected timeframe for addressing critical areas

Calendar year NIOSH

10 critical areas 2005 2006 2007 2008 2009 

Epidemiology and surveillanceRisk assessment 

Phase I—baselineinformation gathering(NTRC-DRDS) Preliminary QRA on TiO2

from existing studies (EIDbase)Initiate collaborative research on lungmodel development andnanoparticle dose estimation (NTRC-EID)External review draftof CIB developed with separate RELs for fineand ultrafine TiO2 based 

on NIOSH QRA 

Survey of uses andworkers (DRDS-DSHEFSunfunded)Phase I—baselineinformation gathering(NTRC-DRDS)Correlation of healtheffects with ultrafineaerosol exposures inauto workers (NTRCDART-DSHEFS pending) Perform QRA on other fine and ultrafine materials from existing studies(EID base)Publish scientific paperson QRA methods fornanoparticles includingTiO2

Develop lung depositionmodel enhancements 

Phase I—baseline information gatheringPhase II—populationstudiesContinue QRA of fine andultrafine particles (EID)Initiate hazard/risk evaluation for nanomaterialsin workplace (EID)Extend and calibrate ratlung dosimetry model fornanoparticles (NTRC-EID)Start estimation ofnanoparticle depositionin nasopharyngeal region(NTRC-EID)Start evaluation andmodeling of CNT inhalability and lung deposition (NTRC-EID) 

Phase I—baseline information gatheringLevels of exposure androutesQRA for nanoparticlesusing new NIOSH data(EID pending)Validate rat dosimetry model for nanoparticlesusing new NIOSH data(NTRC-EID)Human lung model variability and uncertaintyresults (NTRC-EID)Nasopharyngeal deposition results (NTRC-EID)CNT inhalability modeling preliminary results(NTRC-EID)Use hazard/risk evaluation in NIOSH guidancedocument (EID-pending) 

Further correlation of health effects with ultrafine aerosol exposures inauto workersExtend human lungdosimetry model fornanoparticle estimation(NTRC-EID)Initiate CNT human lungdosimetry model basedon preliminary results(NTRC-EID pending)Preliminary QRA for CNTbased on rodent data(EID pending) 

(Continued) 

167 
Projected timeframe for addressing critical areas

Calendar year NIOSH

10 critical areas 2005 2006 2007 2008 2009 

Measurement methodsEngineering controls andPPEFire and explosion safetyCommunication andeducation 

Pilot studies of nanoparticles in the workplace(DRDS)Development of techniques for online surfacearea measurement(DART)Identification of key control issuesIdentification of key safety issues (DSR-NPPTL)Basic set of FAQs (NTRC, OD base)Web site updates (NTRCEID, OD, others base)Public presentations(NTRC and many divisions base)NIL pilot (SRL-DRDS) 

Measurement studiesof nanoparticles in theworkplace (DRDS andothers)Analyses of filter efficiency (NPPTL-DRDS)Evaluation of controlbanding options (NTRCEID-DRDS-DART) Initiate efforts to investigate fire and explosionhazards of nanomaterialsExpanded set of FAQs 

(DART, NTRC and many divisions base)Web site updates (NTRC, EID, OD, others base)Public presentations(NTRC and many divisions base)NIL updates (SRL-DRDS) 

Established suite of instruments and protocols(NTRC-DRDS)Measurement studies of nanoparticles in the workplace (DRDS and others)Further development of online and offlinenanoparticle measurement methods (DRDSDART)Testing controls in auto plants (DART-DSHEFS)Respirator performanceevaluations (NPPTL)Good safety handlingpractices (NTRC-DSRNPPTL)Web site updates (NTRC, EID, OD, others base)Public presentations(NTRC and many divisions base)NIL updates (SRL-DRDS) 

Viable and practicalworkplace samplingdevice for nanoparticles(affordable, portable,effective) (NTRC-DARTDRDS and others)

Evaluation of controlimprovements in autoplants (DART-DSHEFS)Evaluation of clothingand otherWeb site updates (NTRC, EID, OD, others base)Public presentations(NTRC and many divisions base)NIL updates (SRL-DRDS) 

Performance results for nanoparticle measurement instruments andmethods (DRDS andothers)Summary of controlstrategies (NTRC-DART) Summary of nanotechnology safety experience(NTRC-DSR) Web site updates (NTRC, EID, OD, others base)Public presentations(NTRC and many divisions base)NIL updates (SRL-DRDS)

(Continued) 

168 
Projected timeframe for addressing critical areas

Calendar year NIOSH

10 critical areas 2005 2006 2007 2008 2009 

Recommendations and External review of NIOSH Publication of TiO2 CIB Good working practices New or updated Nano- New or updated Nanoguidance TiO2 CIB (EID base) (EID base) guidelines (DART base) materials document materials document

(NTRC base) (NTRC base) Nanomaterials document

(NTRC base) 

Applications NIOSH education series Roadmap up and running	 Prioritized list of short Further r2p Further r2p
 

term impact r2p
 

* CIB=Current Intelligence Bulletin; CNT=carbon nanotube; DART=Division of Applied Research and Technol­ Abbreviations:

ogy; DEP=diesel exhaust particulate; DRDS=Division of Respiratory Diseases; DSHEFS=Division of Surveillance Hazard Evaluation and Field Studies; EID=Education and Information Division; FAQs=Frequently Asked Questions; HELD=Health Eff ect Laboratory Division; ID=identifi cation; NIL=Nanoparticle Information Library; NIOSH=National Institute for Occupational Safety and Health; NORA=National Occupational Research Agenda; NPPTL=National Personal Protective Technology Library; NTRC=Nanotechnology Research Center; OD=Offi ce of the Director; PPE=personal protective equipment; PRL=Pittsburgh Research Laboratory; QRA=quantitative risk assessment; r2p=research to practice; SNORA=Small National Occupational Research Agenda (on PPE); SRL=Safety Research Laboratory; TiO =titanium dioxide. 2

169 

Appendix H 

Executive Summary 

Approaches to Safe 

Nanotechnology: An 

Information Exchange 

with NIOSH 
NIOSH Nanotechnology Research Center 

Approaches to Safe Nanotechnology: 

An Information Exchange with NIOSH 

The Executive Summary is distributed solely for the purpose of pre-dissemination 

peer review under applicable information quality guidelines. The draft document 

“Approaches to Safe Nanotechnology: An Information Exchange with NIOSH” 

has not been formally disseminated by CDC/NIOSH and should not be construed 

to represent any agency determination or policy. A copy of the draft document 

can be found at the NIOSH Web site: http://www.cdc.gov/niosh/topics/nanotech/ 

Executive Summary 

Nanotechnology has the potential to dramatically improve the effectiveness 

of a number of existing consumer and industrial products and could have 

a substantial impact on the development of new applications ranging from 

disease diagnosis and treatment to environmental remediation. Because of the 

broad range of possible nanotechnology applications, continued evaluation of 

the potential health risks associated with exposure to nanomaterials is essential 

to ensure their safe handling. Nanomaterials are engineered materials having 

at least one dimension between 1 and 100 nanometers. Nanomaterials often 

exhibit unique physical and chemical properties that impart specific characteristics essential in making engineered materials, but little is known about 

what effect these properties may have on human health. Research has shown 

that the physiochemical characteristics of particles can influence their effects 

in biological systems. These characteristics include particle size, shape, surface area, charge, chemical properties, solubility, and degree of agglomeration. 

Until the results from research studies can fully elucidate the characteristics of 

nanoparticles that may potentially pose a health risk, precautionary measures 

are warranted. 

NIOSH has developed this document to provide an overview of what is known 

about nanomaterial toxicity and measures that can be taken to minimize 

workplace exposures. NIOSH is seeking comments from occupational safety 

and health practitioners, researchers, product innovators and manufacturers, 

employers, workers, interest group members, and the general public so that 

appropriate existing safety and health guidance can be further refined and disseminated. Opportunities to provide feedback and information are available 

throughout the document. 

172 
Appendix H ■ Executive Summary: Approaches to Safe Nanotechnology 

The following is a summary of findings and key recommendations: 

Potential Health Concerns 

■	 The potential for nanomaterials to enter the body is among several factors that scientists examine in determining whether such materials may 

pose an occupational health hazard. Nanomaterials have the greatest 

potential to enter the body if they are in the form of nanoparticles, agglomerates of nanoparticles, and particles from nanostructured materials that become airborne or come into contact with the skin. 

■	 Based on results from human and animal 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 other organs. 

■	 Experimental studies in rats have shown 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 the biological responses observed in animals. 

■	 Cytotoxicity and experimental animal studies have shown that changes 

in the chemical composition, structure of the molecules, or surface 

properties of certain nanomaterials can influence their potential toxicity. 

■	 Studies in workers exposed to aerosols of manufactured microscopic 

(fine) and nanoscale (ultrafine) particles have reported lung function 

decrements and adverse respiratory symptoms; however, uncertainty 

exists about the role of ultrafine particles relative to other airborne contaminants (e.g., chemicals, fine particles) in these work environments 

in causing adverse health effects. 

■	 Engineered nanoparticles whose physical and chemical characteristics 

are like those of ultrafine particles need to be studied to determine if 

they pose health risks similar to those that have been associated with 

the ultrafine particles. 

Potential Safety Concerns 

■	 Although insufficient information exists to predict the fire and explosion risk associated with nanoscale powders, nanoscale combustible 

173 
 

 

NIOSH Nanotechnology Research Center 

material could present a higher risk than coarser material with a 

similar mass concentration given its increased particle surface area and 

potentially unique properties due to the nanoscale. 

■	 Some nanomaterials may initiate catalytic reactions depending on their 

composition and structure that would not otherwise be anticipated 

from their chemical composition alone. 

Working with Engineered Nanomaterials 

■	 Nanomaterial-enabled products such as nanocomposites and surface 

coatings, and materials comprised of nanostructures such as integrated 

circuits are unlikely to pose a risk of exposure during their handling 

and use. However, some of the processes (formulating and applying 

nanoscale coatings) used in their production may lead to exposure to 

nanoparticles. 

■	 Processes generating nanomaterials in the gas phase, or using or 

producing nanomaterials as powders or slurries/suspensions/solutions pose the greatest risk for releasing nanoparticles. Maintenance on 

production systems (including cleaning and disposal of materials from 

dust collection systems) is likely to result in exposure to nanoparticles 

if it involves disturbing deposited nanomaterial. 

■	 The following workplace tasks may increase the risk of exposure to 

nanoparticles: 

	 Working with nanomaterials in liquid media without adequate 

protection (e.g., gloves) will increase the risk of skin exposure. 

	 Working with nanomaterials in liquid during pouring or mixing operations, or where a high degree of agitation is involved, 

will lead to an increase likelihood of inhalable and respirable 

droplets being formed. 

	 Generating nanoparticles in the gas phase in non-enclosed systems will increase the chances of aerosol release to the workplace. 

	 Handling nanostructured powders will lead to the possibility of 

aerosolization. 

	 Maintaining equipment and processes used to produce or fabricate nanomaterials or the clean-up of spills or waste material 

will pose a potential for exposure to workers performing these 

tasks. 

	 Cleaning of dust collection systems used to capture nanoparticles can pose a potential for both skin and inhalation exposure. 

174 
Appendix H ■ Executive Summary: Approaches to Safe Nanotechnology 

	 Machining, sanding, drilling, or other mechanical disruptions 

of materials containing nanoparticles can potentially lead to 

aerosolization of nanomaterials. 

Exposure Assessment and Characterization 

■	 Until more information becomes available about the mechanisms 

underlying nanoparticle toxicity, it is uncertain as to what measurement technique should be used to monitor exposures in the workplace. 

Current research indicates that mass and bulk chemistry may be less 

important than particle size and shape, surface area, and surface chemistry (or activity) for nanostructured materials. 

■	 Many of the sampling techniques that are available for measuring airborne nanoaerosols vary in complexity but can provide useful information for evaluating occupational exposures with respect to particle size, 

mass, surface area, number concentration, composition, and surface. 

Unfortunately, relatively few of these techniques are readily applicable 

to routine exposure monitoring. 

■	 Regardless of the metric or measurement method used for evaluating 

nanoaerosol exposures, it is critical that background nanoaerosol measurements be conducted before the production, processing, or handling 

of the nanomaterial/nanoparticle. 

■	 When feasible, personal sampling is preferred to ensure an accurate 

representation of the worker’s exposure, whereas area sampling (e.g., 

size-fractionated aerosol samples) and real-time (direct reading) exposure measurements may be more useful for evaluating the need for 

improvement of engineering controls and work practices. 

Precautionary Measures 

■	 Given the limited amount of information about the health risks associated with occupational exposure to engineered nanoparticles, it is 

prudent to take measures to minimize worker exposures. 

■	 For most processes and job tasks, the control of airborne exposure to 

nanoaerosols can be accomplished using a wide variety of engineering control techniques similar to those used in reducing exposure to 

general aerosols. 

■	 The implementation of a risk management program in workplaces 

where exposure to nanomaterials exists can help to minimize the 

potential for exposure to nanoaerosols. Elements of such a program 

should include the following: 

175 
NIOSH Nanotechnology Research Center 

	 Evaluating the hazard posed by the nanomaterial based on 

available physical and chemical property data and toxicology or 

health effects data 

	 Assessing potential worker exposure to determine the degree of 

risk 

	 The education and training of workers in the proper handling 

of nanomaterials (e.g., good work practices) 

	 The establishment of criteria and procedures for installing and 

evaluating engineering controls (e.g., exhaust ventilation) at 

locations where exposure to nanoparticles might occur 

	 The development of procedures for determining the need and 

selection of PPE (e.g., clothing, gloves, respirators) 

	 The systematic evaluation of exposures to ensure that control 

measures are working properly and that workers are being provided the appropriate PPE 

■	 Engineering control techniques such as source enclosure (i.e., isolating the generation source from the worker) and local exhaust ventilation systems should be effective for capturing airborne nanoparticles. 

Current knowledge indicates that a well-designed exhaust ventilation 

system with a HEPA filter should effectively remove nanoparticles. 

■	 The use of good work practices can help to minimize worker exposures 

to nanomaterials. Examples of good practices include; cleaning of work 

areas using HEPA vacuum pickup and wet wiping methods, preventing 

the consumption of food or beverages in workplaces where nanomaterials are handled, and providing facilities for hand-washing and showering and changing clothes. 

■	 No guidelines are currently available on the selection of clothing or 

other apparel (e.g., gloves) for the prevention of dermal exposure to 

nanoaerosols. However, some clothing standards incorporate testing 

with nanoscale particles and therefore provide some indication of the 

effectiveness of protective clothing with regard to nanoparticles. 

■	 Respirators may be necessary when engineering and administrative 

controls do not adequately prevent exposures. Currently, no specific 

exposure limits exist for airborne exposures to engineered nanoparticles although occupational exposure limits exist for larger particles of 

similar chemical composition. The decision to use respiratory protection should be based on professional judgment that takes into account 

176 
Appendix H ■ Executive Summary: Approaches to Safe Nanotechnology 

toxicity information, exposure measurement data, and the frequency 

and likelihood of the worker’s exposure. Preliminary evidence shows 

that for respirator filtration media there is no deviation from the classical single-fiber theory for particulates as small as 2.5 nm in diameter. 

While this evidence needs confirmation, it is likely that NIOSH certified respirators will be useful for protecting workers from nanoparticle 

inhalation when properly selected and fit tested as part of a complete 

respiratory protection program. 

Occupational Health Surveillance 

■	 The unique physical and chemical properties of nanomaterials, the 

increasing growth of nanotechnology in the workplace, available 

information about biological and health effects in animals associated 

with exposures to some types of engineered nanoparticles in laboratory 

studies, and available information about the occupational health effects 

of incidental ultrafine particles all underscore the need for medical 

and hazard surveillance for nanotechnology. Every workplace dealing with nanoparticles, engineered nanomaterials, or other aspects of 

nanotechnology should consider the need for an occupational health 

surveillance program. NIOSH is in the process of formulating guidance 

relevant to occupational health surveillance for nanotechnology. 

177