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occupational safety and health topics, contact NIOSH atTo receive NIOSH documents or more information about 

 (1–800–232–4636)

or visit the NIOSH Web site at E-mail: cdcinfo@cdc.govTTY: 1–888–232–6348 

www.cdc.gov/niosh.

NIOSH eNewsFor a monthly update on news at NIOSH, subscribe to 

 by visiting www.cdc.gov/niosh/eNews. 

safer • healthier • peopleTMDHHS (NIOSH) Publication No. 2010–104through research and preventionsafety and health at work for all peopleDelivering on the Nation’s promise:

DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Centers for Disease Control and Prevention 

National Institute for Occupational Safety and Health 

4676 Columbia Parkway 

Cincinnati, Ohio 45226–1998 

Official Business 

Penalty for Private Use $300 
On the cover: Multi-walled carbon nanotubes (MWCNT) 

in the lungs of a mouse 56 days after exposure. The 

shorter fibers on the right are penetrating the lung wall 

from the alveolar space. The longer fibers on the upper 

and lower left have penetrated the outer wall of the 

lung into the pleural space. Image courtesy of Robert 

Mercer, NIOSH.
Progress Toward Safe 

Nanotechnology in the 

Workplace 

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health

A Report from the NIOSH

Nanotechnology Research Center 

Project Updates for 2007 and 2008
ii

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. All Web addresses referenced in this document were accessible as of the publication date.

Ordering Information

To receive documents or other information about occupational safety and 

health topics, contact NIOSH at

Telephone: 1–800–CDC–INFO (1–800–232–4636)

TTY: 1–888–232–6348

E-mail: cdcinfo@cdc.gov

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

For a monthly update on news at NIOSH, subscribe to NIOSH eNews by 

visiting www.cdc.gov/niosh/eNews.

DHHS (NIOSH) Publication No. 2010–104

November 2009

Safer • Healthier • PeopleTM
iii

Foreword

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

workers who produce and use nanoparticles. 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 and its partners 

in other government agencies, countries, academia, industry, labor, and nongovernmental organizations have been conducting research and developing 

guidance to address the occupational safety and health of workers exposed to 

nanomaterials. 

In February 2007, NIOSH issued its report on Progress Toward Safe Nanotechnology in the Workplace. That report described the progress of the NIOSH 

Nanotechnology Research Center (NTRC) since its inception in 2004 through 

2006. In this November 2009 update, we describe program accomplishments 

achieved in 2007 and 2008. The NTRC has, with limited resources, continued 

to make contributions to all the steps in the continuum from hazard identification to risk management.

Occupational safety and health issues of nanotechnology are complex. The 

types of nanomaterials and the opportunities for workplace exposure continue 

to grow rapidly. The challenge is to effectively address the safety and health issues of nanotechnology while helping society realize the far-reaching 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 
iv

Executive Summary

Occupational safety and health issues of nanomaterials are complex. Because 

engineered nanomaterials are small yet have a relatively large surface area, they 

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

larger particles of similar chemical composition. Those properties may affect 

the ability of the nanomaterials 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. The types of nanomaterials and the opportunities for workplace exposure to them continue to grow 

rapidly. The challenge is to effectively address the safety and health issues of 

nanotechnology while helping society realize nanotechnology’s far-reaching 

potential benefits. 

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 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 established the Nanotechnology Research Center (NTRC) in 2004 to 

coordinate and promote research in nanotechnology and to develop guidance 

on the safe handling of nanomaterials in the workplace. The NTRC 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 location. In 2007 the NTRC issued Progress Toward Safe 

Nanotechnology in the Workplace (DHHS NIOSH Publication No. 2007–123). 

That report describes the progress of the NTRC since its inception in 2004 

through 2006. This November 2009 update describes program accomplishments achieved in 2007 and 2008, and it includes summary updates from 43 

intramural projects and a comprehensive extramural program. The NTRC has, 

with limited resources, continued to make contributions to all the steps in the 

continuum from hazard identification to risk management (Figure 1).
v

Executive Summary

Figure 1. Steps in the continuum from hazard identification to risk management to protect workers 

involved with nanotechnology
vi

NIOSH Nanotechnology Research Center

The NTRC has four goals: 

1. Determine whether nanoparticles and nanomaterials pose risks of 

work-related injuries and illnesses. 

2. Conduct research to prevent work-related injuries and illnesses by applying nanotechnology products. 

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 continues to be made toward each of 

these goals. The following paragraphs present highlights of each goal. 

1. Determine whether nanoparticles and nanomaterials pose risks 

of work-related injuries and illnesses. 

Since 2004, the NTRC has pioneered research on the toxicological properties and characteristics of nanoparticles. This research is relevant for predicting whether these particles pose a risk of adverse health effects in workers. 

These research projects have involved characterizing occupationally relevant 

nanoparticles—particularly the toxicity of carbon nanoparticles. Preliminary 

work by the NTRC investigators demonstrated that mice exhibited harmful 

pulmonary effects (such as a fibrotic response) soon after low-dose aspiration 

exposure to specific nanotubes. The NTRC established a system for generating 

nanoparticle aerosol and began conducting animal inhalation studies during 

the summer of 2006. The inhalation studies verified the same fibrotic response 

seen in the aspiration studies. NTRC investigators have evaluated the potential for nanoparticles to enter the bloodstream and move to systemic tissues 

after being deposited in the lungs. 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 engineered nanomaterials operate. The results of these studies are preliminary and 

limited, and more research is needed to predict whether they signal a health 

risk to humans. The results obtained thus far support the need to address that 

question and provide promising leads for strategic, ongoing studies. 

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

established a field team to conduct assessments of workplaces where exposure 

to engineered nanoparticles may occur. By partnering in 2007 and 2008 with 

12 companies that produce or use engineered nanoparticles, this team collected useful information about potential worker exposures, control technologies, 

and risk management practices. 
vii

Executive Summary

2. Conduct research to prevent work-related injuries and illnesses 

by applying nanotechnology products. 

The 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. The NTRC 

and the Office of Extramural Programs at NIOSH are coordinating projects 

with academia and the private sector. 

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

Nationally and internationally, the NTRC has delivered a wide range of presentations on occupational safety and health issues associated with nanotechnology. These have included presentations to 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. Since its inception, 

the NTRC has published more than 170 papers in peer-reviewed scientific 

literature and provided a broad range of information and guidance. In addition, the NTRC has provided seminal guidance for workers and employers in 

nanotechnology through the following documents:

■ Interim Guidance for Medical Screening and Hazard 

Surveillance for Workers Potentially Exposed to Engineered Nanoparticles, DHHS NIOSH Publication No. 

2009–116

■ Approaches to Safe Nanotechnology: Managing the 

Health and Safety Concerns Associated with Engineered 

Nanomaterials, DHHS NIOSH Publication No. 2009–

125

■ Safe Nanotechnology in the Workplace: An Introduction 

for Employers, Managers, and Safety and Health Professionals, DHHS NIOSH Publication No. 2008–112

■ The Nanotechnology Field Research Team Update, DHHS 

NIOSH Publication No. 2008–120

■ NIOSH Nanotechnology Field Research Effort Fact Sheet, 

DHHS NIOSH Publication No. 2008–121

■ NIOSH Nanotechnology Metal Oxide Particle Exposure Assessment Study, DHHS NIOSH Publication No. 

2008–122
viii

NIOSH Nanotechnology Research Center

■ Draft Strategic Plan for NIOSH Nanotechnology Research: Filling the 

Knowledge Gaps, published February 2008 [www.cdc.gov/niosh/topics/

nanotech/strat_planA.html]

4. Enhance global workplace safety and health through national 

and international collaborations on nanotechnology research 

and guidance. 

The NTRC has established several national and international collaborations to 

advance understanding of occupational safety and health for nanotechnology 

workers. The NTRC participates in the National Nanotechnology Initiative 

(NNI) and has contributed to the nanotechnology strategic plan for the Nation through the Nanotechnology Environmental Health Implications (NEHI) 

working group. Occupational safety and health has been a chief 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 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. NIOSH led the development and publication of 

ISO TR/12885:2008, Health and Safety Practices in Occupational Settings Relevant to Nanotechnologies. The NTRC also works with the World Health Organization collaborating centers on global projects of information dissemination 

and communication. NIOSH co-led the World Health Organization project on 

best practices for safe handling of nanomaterials.

The NTRC has collaborated with the Organization for Economic Cooperation 

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

the European Union) and with more than 180 nonmember economies. NIOSH 

chaired the OECD Working Party for Manufactured Nanomaterials Steering 

Group 8, exposure measurement and exposure mitigation.

NIOSH cosponsored the 3rd International Symposium on Nanotechnology, 

Occupational and Environmental Health held in Taiwan in 2007 and serves 

on the planning committee for the 4th international conference scheduled for 

August 2009 in Helsinki, Finland. In addition, the NTRC is collaborating with 

the U.S. Environmental Protection Agency, the Occupational Safety and Health 

Administration, and other government agencies to obtain and evaluate exposure and good work practice information.
ix

Executive Summary

Critical Topic Areas

The NTRC research program has identified 10 critical topic areas for understanding the potential health risks and developing and disseminating recommendations: 

1. Toxicity and internal dose

2. Measurement methods

3. Exposure assessment

4. Epidemiology and surveillance

5. Risk assessment

6. Engineering controls and PPE

7. Fire and explosion safety

8. Recommendations and guidance

9. Communication and information

10. Applications

By working in these 10 critical areas, NIOSH has comprehensively begun addressing the information and knowledge gaps necessary to protect workers and 

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

be realized. 

Coordination with the National Nanotechnology Initiative

NIOSH participates in the NNI Strategy for Nanotechnology Environmental 

Health and Safety Research. Table 1 shows the alignment of the four NIOSH 

NTRC strategic goals and the 10 NTRC critical research areas with the NNI 

priority environmental health and safety research needs.

The research being conducted by the NIOSH NTRC continues to be funded by 

redirecting existing NIOSH programmatic funds: $4.4 million in FY 2007 and 

$ 5.7 million in FY 2008. A more comprehensive research program specific 

to nanomaterials has been difficult to implement because of this budgetary 

constraint. However, even with the budgetary constraints, NIOSH investigators 

have continued to build an evidence-based strategy for providing safe nanotechnology in the workplace.
x

NIOSH Nanotechnology Research Center

Table 1. Alignment of the four strategic goals and ten critical research areas of the 

NIOSH NTRC with the priority environmental health and safety research needs of the 

NNI*

NIOSH NTRC 

strategic goals

Determine if 

nanoparticles and 

nanomaterials 

pose risks for 

work-related injuries and illnesses

Conduct research 

on applying nanotechnology to the 

prevention of workrelated injuries and 

illnesses1

Promote healthy 

workplaces 

through interventions, recommendations, and 

capacity building

Enhance global 

workplace safety 

and health1

Toxicity and internal 

dose

3, A24, B1, B2, 

B3, B4, B5



Measurement 

methods

, A1, A2, A3, A4, 

A5, B2

 , E1 

Exposure assessment2

, A1, A2, D1, D4, 

D5, E1, E2

, E2 

Epidemiology and 

surveillance

, D1, D2, D3, 

D4, E4

, E4 

Risk 

assessment

, A2, B1, B2, 

D4, E3

, E3, E5 

Engineering controls 

and PPE

, D5  , E1 

Fire and explosion 

safety

, A2 

Recommendations 

and guidance

, E1, E5 

Communication and 

information

, E1, E5 

Applications  

1

The NNI EHS plan does not address applications or global activities pertaining to environmental health 

and safety of nanomaterials. However the NIOSH efforts described herein are consistent with the overall 

NNI strategy which does identify international opportunities for collaboration. 2

NIOSH is the lead agency for the NNI EHS Strategic area on human and environmental exposure assessment. 3

A  indicates that a goal is addressed by projects within the NIOSH critical research area 4

Alpha-numeric identifications indicate alignment of the NIOSH critical research area with the specific NNI 

priority research needs (see Appendix A). 
xi

Contents

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

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

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

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xviii

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

Partnerships and Collaborations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Project-Specific Progress Reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Project 1: Nanotechnology Research Center Coordination . . . . . . . . . . . 15

Project 2: Nanotechnology Safety and Health Research Coordination . . 22

Project 3: Systemic Microvascular Dysfunction: Effects of Ultrafine

vs. Fine Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Project 4: Particle Surface Area as a Dose Metric . . . . . . . . . . . . . . . . . . . . 29

Project 5: Role of Carbon Nanotubes in Cardiovascular and

COPD-Related Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Project 6: Investigations of Multi-Walled Carbon Nanotube Toxicity . . . 36

Project 7: Pulmonary Toxicity of Metal Oxide Nanospheres

and Nanowires . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

Project 8: WC-Co Nanoparticles in Initiating Angiogenesis by

Reactive Oxygen Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

Project 9: Evaluation of the Pulmonary Deposition and

Translocation of Nanomaterials . . . . . . . . . . . . . . . . . . . . . . . . 41

Project 10: Occupational Exposures and Potential Neurological Risks . . 43

Project 11: Lung Effects of Resistance Spot Welding Using Adhesives . . 46

Project 12: Neurotoxicity after Pulmonary Exposure to Welding Fumes . 47

Project 13: Potential Aneuploidy Following Exposure to

Carbon Nanotubes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

Project 14: Pulmonary Toxicity of Carbon Nanotube Particles . . . . . . . . 51

Project 15: Dermal Toxicity of Nanotube Particles . . . . . . . . . . . . . . . . . . 56

Project 16: Specific Biomarkers for Unusual Toxicity of Nanomaterials . . 58

Project 17: Pulmonary Toxicity of Diesel Exhaust Particles . . . . . . . . . . . 59

Project 18: Induction of Lung Fibrosis by Cerium Oxide in

Diesel Exhaust . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
xii

NIOSH Nanotechnology Research Center

Project 19: Potential Effects of Silicon-based Nanowires on

Lung Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

Project 20: Cell-based Assessment for Iron Nanoparticle-Induced

Health Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 

Project 21: Assessment of Carbonaceous Materials on Mutagenicity . . . 66

Project 22: Generation and Characterization of Nanoparticles . . . . . . . . 68

Project 23: Dustiness of Nanomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Project 24: Nanoaerosol Monitoring Methods . . . . . . . . . . . . . . . . . . . . . . 73

Project 25: Measurement of Nanoscale Carbonaceous Aerosols . . . . . . . 76

Project 26: Nanoparticle Reference Materials for Health Protection . . . . 78

Project 27: Calm Air Chamber and Wind Tunnel Evaluation of Personal

Aerosol Samplers for Nanoparticle Exposure Assessment . . . . . 80

Project 28: Ultrafine TiO2 Surface and Mass Concentration

Sampling Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

Project 29: Standard Determination of Nanoparticle Size . . . . . . . . . . . . . 82

Project 30: Development and Evaluation of Nanoaerosol Surface

Area Measurement Methods . . . . . . . . . . . . . . . . . . . . . . . . . . 83 

Project 31: Workplace Monitoring of Carbon Nanofibers/Nanotubes . . 84

Project 32: Ultrafine Aerosols from Diesel-Powered Equipment . . . . . . . 85

Project 33: Titanium Dioxide and Other Metal Oxides Exposure

Assessment Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

Project 34: Field Research Team . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

Project 35: Assessing the Feasibility of Industrywide Exposure and

Epidemiology Studies of Workers Exposed to

Engineered Nanomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

Project 36: Nanoparticles—Dosimetry and Risk Assessment . . . . . . . . . . 94

Project 37: Penetration of Nanoparticles through Respirators . . . . . . . . . 97

Project 38: Nanoparticle Penetration through Protective Clothing . . . . . 100

Project 39: Development of Personal Protective Equipment Ensemble

Test Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

Project 40: Web-based Nanoparticle Information Library

Implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

Project 41: Nanoparticles in the Workplace . . . . . . . . . . . . . . . . . . . . . . . . 106 

Project 42: New Sensor Technology Development for ESLI . . . . . . . . . . . 110
xiii

Contents

Project 43: Global Harmonization of Exposure Measurement and

Exposure Mitigation Approaches for Nanomaterials . . . . . . 112

Appendices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117

Appendix A: Projects by Critical Topic Area . . . . . . . . . . . . . . . . . . . . . . . . 119

Appendix B: NIOSH Extramural Nanotechnology Research Activities . 122
xiv

Abbreviations 

AIHA American Industrial Hygiene Association 

ACGIH American Conference of Governmental Industrial Hygienist

AM alveolar macrophage

AP-1 activator protein 1

APR air–purifying respirators

ASME American Society of Mechanical Engineers

ASSE American Society of Safety Engineers 

ASTM American Society for Testing and Materials 

ATP adenosine triphosphate

BAL bronchoalveolar lavage

CARB California Air Resources Board

CDC Centers for Disease Control and Prevention 

CNF carbon nanofiber

CNT carbon nanotube 

COPD Chronic obstructive pulmonary disease 

CPSC Consumer Product Safety Commission

DEP diesel exhaust particulate 

DEER Diesel Engine– Efficiency and Emissions Research

DEPE diesel exhaust particulate extract

DERT Developmental Engineering Research Team

DHHS U.S. Department of Health and Human Services

DIC different interference confocal

DNA dioxyribonucleic acid

DOE U.S. Department of Energy

DPF diesel particulate filter

EC–SOD extracellular superoxide dismutase

EHS Environmental Health and Safety

EPA U.S. Environmental Protection Agency

ESD electron spin resonance

ESLI end-of-service life indicator 

ESR erythrocyte sedimentation rate
xv

Abbreviations

FASEB Federation of American Societies for Experimental Biology

FCA–SS flux core arc–stainless steel

FDA U.S. Food and Drug Administration

FISH fluorescent in situ hybridization

GMA–MS gas metal arc–mild steel

HEI Health Effects Institute

HEPA high-efficiency particulate air 

HHE Health Hazard Evaluation

HPS Health Physics Society

IANH International Alliance for NanoEHS Harmonization

IDLH immediately dangerous to life and health

IEC International Electrotechnical Commission

IOM Institute of Occupational Medicine

ILO International Labor Organization

ILSI International Life Sciences Institute

ISO International Organization for Standardization 

IRSST Institut de recherché Robert–Sauvè en santé et en sécurité

 du travail

kW kilowatt

LDH lactate dehydrogenase

LLC limited liability company

LM Listeria monocytogenis

LNW long nanowire

MAPKs mitogen–activated protein kinase

MINChar Minimum Information Needed for Characterization

 of Nanomaterials

MMA–HS manual metal arc–hard surfacing

MOUDI micro–orifice uniform deposit impactor

MPPD multipath particle deposition

MWCNT multi-walled carbon nanotube

NADPH nicotinamide adenine dinucleotide phosphate

NASA National Aeronautics and Space Administration 

NATO North Atlantic Treaty Organization
xvi

NIOSH Nanotechnology Research Center

NCER National Center for Environmental Research 

NEAT nanoparticle emission assessment technique

NEHI Nanotechnology Environmental and Health Implications 

NFkB nuclear factor kB 

NGO non-governmental organization 

NIEHS National Institute of Environmental Health Sciences 

NIH National Institutes of Health

NIL Nanoparticle Information Library 

NIOSH National Institute for Occupational Safety and Health 

NIST National Institute of Standards and Technology 

NO nitric oxide

nm nanometer(s) 

NNI National Nanotechnology Initiative 

NORA National Occupational Research Agenda 

NS nanosphere

NSC National Safety Council

NSET Nanoscale Science, Engineering, and Technology 

NSF National Science Foundation

NSTC National Science and Technology Council

NTRC Nanotechnology Research Center

NSC National Safety Council 

OEP Office of Extramural Programs 

OECD Organization for Economic Cooperation and Development

OEP Office of Extramural Programs

OPN osteoponin

OSHA U.S. Occupational Safety and Health Administration 

PEL permissible exposure limit

PMN polymorphonuclear neutrophils

POSS polyhedral oligomeric silsesquioxanes

PPE personal protective equipment

r2p Research to Practice

RFA request for application 

RNS reactive nitrogen species
xvii

Abbreviations

ROS reactive oxygen species

SBIR small business innovation research

SMPS scanning mobility particle sizer

SNW short nanowire

SRM standard reference material

STEL short term exposure limit

SWCNT single-walled carbon nanotube 

TC technical committee

TEM transmission electron microscopy 

TGF–ß transforming growth factor beta

TiO2 titanium dioxide 

TR technical report

μg/m3 microgram per cubic meter

UK United Kingdom

USAF U.S. Air Force

VEGF vascular endothelial growth factor

Wc–Co tungsten carbide

WHO World Health Organization 

WT wild type
xviii

Acknowledgments 

This report was developed by the scientists and staff of NIOSH who participate 

in the NTRC. Paul Schulte is the manager, and Charles Geraci is the coordinator of the NIOSH National Occupational Research Agenda (NORA), Nanotechnology cross-sector program. Special thanks go to Laura Hodson and 

Ralph Zumwalde for writing and organizing the report.

Others who contributed substantially to the progress report include James 

Antonini, Eileen Birch, Aleksandar Bugarski, Vincent Castranova, Brian Curwin, Min Ding, Douglas Evans, Pengfei Gao, Mark Hoover, Bon-Ki Ku, Eileen 

Kuempel, Stephen Leonard, Jane Ma, Robert Mercer, Mark Methner, Arthur 

Miller, Vladimir Murashov, Terri Pearce, Dale Porter, Yong Qian, Appavoo 

Rengasamy, Jennifer Roberts, W. Allen Robison, Liying Wang Rojanasakul, 

Linda Sargent, Mary Schubauer-Berigan, Ronald Shaffer, Anna Shvedova, Petia 

Simeonova, Jay Snyder, Krishnan Sriram, Aleksandr Stefaniak, Jennifer Topmiller, Douglas Trout, and Leonid Turkevich. 

The NIOSH NTRC also acknowledges the contributions of Vanessa B. Williams, Gino Fazio, and Anne Stirnkorb for desktop publishing and graphic 

design and Elizabeth Fryer for editing the report.
Introduction
2

Background 

The NIOSH Nanotechnology Research Center (NTRC) was established in 2004 

to coordinate and promote research in nanotechnology and develop guidance 

on the safe handling of nanomaterials in the workplace. Since its inception, 

the NTRC has published more than 170 papers in peer-reviewed scientific 

literature and provided a broad range of information and guidance (see 2007 

Progress Report http://www.cdc.gov/niosh/docs/2007-123/ and Table 2). Publications in the areas of hazard identification and characterization, exposure 

assessment, risk assessment, and risk management have provided a framework 

for addressing hazards and risks from engineered nanoparticles. Although 

NTRC has contributed significantly to the understanding of health risks to 

nanoparticles, further research and subsequent development and dissemination of interim guidance efforts are limited by a lack of funding. NIOSH has 

to the best of its ability allocated limited resources to competing priorities and 

redirected funds internally over the past 4 years to build modest increases in 

support of the NIOSH Nanotechnology Research Program. 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:

■ 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 risks.

■ NIOSH field investigators have assessed exposure to engineered 

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

magnitude of exposure to other types of nanoparticles in workplaces 

that manufacture or use nanomaterials, nanostructures, and nanodevices.

■ 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. 

■ The number of workers involved with the research, development, 

production, and use of engineered nanomaterials is increasing, but 

there is a lack of specific guidance for occupational health surveillance. 

NIOSH needs support to conduct research on the short- and long-term 
3

Partnerships

health risks in nanotechnology workers. This may involve conducting 

large-scale prospective epidemiologic studies and establishing exposure 

registries.

■ The utility of nanotechnology to support 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. 

The NIOSH NTRC has advanced the scientific knowledge in understanding 

the possible health risks of engineered nanoparticles as demonstrated by the 

ongoing projects beginning on page 15. Table 2 (see Appendix B) lists the projects by number and critical topic areas researched (e.g., toxicity and internal 

dose, measurement methods, exposure assessment). These projects are also 

listed in Appendix A for each critical topic area. 
4

Partnerships and Collaborations

Integral to completing this research are the partnerships and collaborations 

NIOSH has forged with countries, academia, industry, labor, other government 

agencies, and nongovernmental organizations. These collaborations have provided expertise and resources critical for successfully completing research and 

for developing and disseminating health and safety information on engineered 

nanoparticles. The following are some of the ongoing NIOSH NTRC partnerships and collaborations in nanotechnology research:

Universities

■ The Ohio State University, evaluating workplaces, controls, and practices in the nanocomposites industry

■ University of Cincinnati, translating nanotechnology research into occupational and environmental health and safety activities

■ University of Dayton Research Institute, understanding and improving 

the control of carbon nanotubes

■ University of Iowa, measuring airborne concentrations of ultrafine 

particles

■ University of Nevada at Reno (with Altair Nano), understanding and 

improving the control of ultrafine metal oxides and engineered nanomaterials

■ University of Massachusetts at Lowell, collaborating on the development of good practices for handling nanomaterials in research laboratories and developing exposure assessment methods

■ University of Minnesota, measuring airborne concentrations of ultrafine particles

■ University of Montana, evaluating the toxicity of nanowires

■ University of Montreal, assessing and characterizing nanoparticles in 

the workplace 

■ University of Pittsburgh, evaluating the toxicity of nanomaterials

■ University of Rochester, measuring the ability of nanoparticles to generate radical species

■ University of Wisconsin, Madison, developing exposure assessment 

strategies and characterizing nanoparticles in friction stir welding and 

micromachining
5

Partnerships

■ Virginia Tech University (with Luna Nano Works), understanding and 

improving the control of fullerines and other engineered nanoparticles

■ West Virginia University Nanotechnology Center, evaluating the toxicity of metal oxide nanowires

■ West Virginia University Medical School, evaluating the effects of pulmonary exposure to nanoparticles, including the influence of exposure 

to titanium dioxide (TiO2) on systemic microvascular function

Safety and Health Organizations and Expert Groups

■ American Industrial Hygiene Association (AIHA), participating on 

working group activities and information exchange and dissemination 

for nanoparticle characterization and control

■ American Conference of Governmental Industrial Hygienists (ACGIH) 

■ American Society of Safety Engineers (ASSE)

■ Hamner Institutes for Health Sciences, modifying software for use in 

lung dosimetry modeling

■ Health Physics Society (HPS), participating in working group activities 

and information exchange and dissemination for nanoparticle characterization and control 

■ International Safety Equipment Association, collaborating on the respirator filter media work being conducted at the University of Minnesota 

to assess the filtration efficiency against nanoparticles

■ International Alliance for Nanotoxicology Harmonization (IANH), 

establishing protocols for reproducible toxicological testing of nanomaterials in both cell cultures and animals

■ National Safety Council (NSC)

■ The initiative on Minimum Information Needed for Characterization 

of Nanomaterials (MINChar), on encouraging adoption of a minimum 

set of physical and chemical material characterization parameters in 

nanotoxicology studies 

■ Institute of Occupational Medicine (IOM), Edinburgh, Scotland, 

revising rat lung dosimetry models to account for particle size-specific 

clearance and retention.
6

NIOSH Nanotechnology Research Center

Federal and Other Government Agencies

■ Environmental Protection Agency (EPA)

■ Occupational Safety and Health Administration (OSHA), evaluating 

the effectiveness of workplace control measures

■ Consumer Product Safety Commission (CPSC)

■ National Aeronautics and Space Administration (NASA), evaluating 

the toxicity of single-walled carbon nanotubes (SWCNTs)

■ U.S. Air Force

■ U.S. Army

■ Department of Energy (DOE) 

■ National Institute of Environmental Health Sciences/ National Institute 

of Health and the Department of Defense on nanotoxicology

■ National Institute of Standards and Technology (NIST), evaluating the 

toxicity of nanoparticles and developing nanoscale reference materials

■ National Nanotechnology Initiative (NNI) through active participation 

in NNI’s strategic and budget planning processes, and coordination of 

research into occupational safety and health of nanotechnology with 

other government agencies

■ National Toxicology Program, participating in the conduct of field assessments and toxicological research

■ Oak Ridge National Laboratory, evaluating the pulmonary toxicity of 

nanoparticles

■ Institut de Recherche Robert-Sauve en Santé et en Securite du Travail 

(IRSST), exchanging information on approaches to safe nanotechnology

■ Karolinska Institute, evaluating the effect of nanomaterials on immune 

cells

■ U.S. Nuclear Regulatory Commission, exchanging information on 

emerging application and health and safety issues for nanotechnology 

in the nuclear arena

■ World Health Organization (WHO)

■ Organization for Economic Cooperation and Development (OECD), 

collaborating on exposure measurement and exposure mitigation
7

Partnerships

■ International Labour Organization (ILO), developing information on 

nanotechnology for a revised edition of the Encylopaedia of Occupaitonal Health and Safety 

■ International Organization for Standardization (ISO) and the International Electrotechnical Commission (IEC), developing international 

standards for terminology, characterization, and safety practices for 

nanotechnology

Nanotechnology Industries

■ DuPont and the Nanoparticle Occupational Safety and Health industry 

consortium on issues related to the measurement of nanoparticles and 

the efficiency of filtration materials for engineered nanoparticles

■ Mitsui Co. Inc., evaluating the bioactivity of multi-walled carbon nanotubes (MWCNTs). 

■ IBM, evaluating the bioactivity of silicon nanowires

■ Luna Nano Works, understanding and improving the control of fullerines and other engineered nanoparticles

■ Altair Nano, understanding and improving the control of ultrafine 

metal oxides and engineered nanomaterials

■ Quantum Sphere, understanding and improving the control of nanoscale metals and metal oxides

■ QD Vision, understanding and improving the control of quantum dots

■ NanoMech LLC (Fayetteville, Arkansas), collaborating on a proposed 

EPA phase I SBIR project related to containment of airborne nanoparticles

Collaborative Workshops

■ In FY 2005, NIOSH cosponsored the first Symposium on Occupational 

Health Implications of Nanomaterials in Buxton, United Kingdom 

■ In FY 2006, NIOSH cosponsored the second Symposium on Occupational Health Implications of Nanomaterials in Minneapolis, MN.

■ In 2007, 

— NIOSH collaborated with the International Aerosol Research Assembly and the American Association for Aerosol Research to 

hold the Second International Symposium on Nanotechnology and 
8

NIOSH Nanotechnology Research Center

Occupational Health in conjunction with the international aerosol 

conference in St. Paul, MN. 

— NIOSH and the University of Cincinnati cosponsored the International Conference on Nanotechnology Occupational and Environmental Health and Safety: Research to Practice, in Cincinnati, OH. 

— NIOSH convened a collaborative workshop that included representatives from government, academia, labor, and industry in Washington, DC, to review a draft document developed by NIOSH and 

a cross-agency work group, titled Interim Guidelines on Medical 

Screening of Workers Potentially Exposed to Engineered Nanoparticles.

— NIOSH cosponsored the Third Symposium on Occupational Health 

Implications of Nanomaterials in Taipei, Taiwan. 

■ In 2008,

— NIOSH served as the agency lead to organize the program for the 

National Nanotechnology Initiative Workshop on Human and Environmental Exposure Assessment held February 2009, in Bethesda, 

MD. 

— NIOSH co-sponsored a National Institute of Standards and Technology Workshop on Enabling Standards for Nanomaterial Characterization in Gaithersburg, MD.

— NIOSH co-sponsored The Second International Conference on 

Nanotechnology in Zurich, Switzerland.

— NIOSH co-sponsored the Organization for Economic Co-operation 

and Development workshop on Exposure Assessment and Exposure 

Mitigation in Frankfurt, Germany.

— NIOSH participated in the planning of the Fourth International 

Conference on Nanotechnology—Occupational and Environmental 

Health held in August 2009, in Helsinki, Finland.

NIOSH Extramural Nanotechnology Research Activities

The NIOSH Office of Extramural Programs (OEP) manages the competitive 

process for awarding occupational safety and health grants and cooperative 

agreements to the research community outside the Institute. This process 

includes peer review, program relevance, and priorities from the National Occupational Research Agenda (NORA), the NIOSH r2p initiative, congressional 

mandates, and sector, or cross-sector areas of the NIOSH Program Portfolio 

(http://www.cdc.gov/niosh/programs).
9

Partnerships

From 2001 to 2009, the Office of Extramural Programs (OEP) has funded 

nanotechnology research through Occupational Safety and Health Research 

Program Announcements (R01) and Small Business Innovation Research 

Grants (R43/44). Since FY 2005, OEP has also participated in two joint Requests for Applications (RFAs) for Nanotechnology Research Grants Investigating Environmental and Human Health Issues. The US Environmental 

Protection Agency’s National Center for Environmental Research (NCER) and 

the National Science Foundation (NSF) participated in FY 2005. The National 

Institute of Environmental Health Sciences (NIEHS) joined in FY 2006. Funding was available to support Research (R01) grants for three years and Exploratory (R21) grants for two year.

In FY 2007, NIOSH/OEP participated in RFA-ES-06-008 Manufactured Nanomaterials: Physico-chemical Principles of Biocompatibility and Toxicity. This 

RFA was jointly sponsored by NIEHS, EPA, and NIOSH.

In FY 2009, nanotechnology related research proposals submitted to standing 

program announcements are being considered for funding by NIOSH/OEP.

To date, NIOSH/OEP has committed about $5.3 million dollars to research 

on applications and implications of nanotechnology. Summaries of the projects funded by NIOSH/OEP are included in Appendix B. NIOSH/OEP plans 

to 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 continue to confer with the 

NIOSH Nanotechnology Research Center regarding issues, gaps, and future 

directions.
10

Table 2. NTRC projects in the 10 critical topic areas for 2007–2008

Project 

number

Toxicology 

and Internal 

dose 

Measurement 

methods 

Exposure 

assessment

Epidemiology 

and

surveillance 

Risk

assessment 

Engineering 

controls and 

PPE*

Fire and 

explosion

Recommendations/ 

guidance

Communication and 

information Applications

1 X X X X X X X X X X

2 X

3 X4 X5 X6 X7 X8 X9 X10 X11 X12 X13 X14 X15 X16 X17 X18 X19 X20 X21 X22 X23 X X X

(Continued)
11

Project 

number

Toxicology 

and Internal 

dose 

Measurement 

methods 

Exposure 

assessment

Epidemiology 

and

surveillance 

Risk

assessment 

Engineering 

controls and 

PPE*

Fire and 

explosion

Recommendations/ 

guidance

Communication and 

information Applications

24 X X25 X X26 X27 X28 X29 X30 X31 X X32 X33 X X34 X35 X X36 X37 X38 X39 X40 X41 X X42 X43 X X X X

*PPE=personal protective equipment

Table 2 (Continued). NTRC projects in the 10 critical topic areas for 2007–2008

Project-Specific

Progress Reports

15

NIOSH Nanotechnology Research Center

Project 1: Nanotechnology Research Center 

Coordination

Principal Investigator: Charles Geraci, Ph.D.

Project Duration: FY 2006–2010

Critical Topic Areas: (1) toxicity and internal dose, (2) measurement 

methods, (3) exposure assessment, (4) epidemiology and surveillance, (5) risk 

assessment, (6) engineering controls and personal protective equipment, 

(7) fire and explosion safety, (8) recommendations and guidance, (9) communication and information, and (10) applications

Accomplishments and Research Findings 

■ Coordinated the NIOSH Nanotechnology Research Program across 10 

critical areas identified in the strategic research plan developed by the 

NTRC in 2005 to identify and prioritize nanotechnology research.

■ Sponsored and provided strategic direction to the Nanotechnology 

Field Research Team, which conducted 14 site visits in the reporting 

period.

■ Fostered collaboration among investigators across the entire NIOSH Nanotechnology Research Program.

■ Developed and maintained successful interagency agreements with

— Occupational Safety and Health Administration

— Consumer Product Safety Commission

— National Toxicology Program

■ Fostered collaboration in nanotechnology research with

— AIHA

— ASSE

— NSC

— U.S. Air Force

— U.S. Army

— NASA

— DOE

Benchtop weighing of CNT. Image 

courtesy of Mark Methner, NIOSH
16

NIOSH Nanotechnology Research Center

— International Alliance for NanoEHS Harmonization

— University of Massachusetts, Lowell

— The Ohio State University

— University of Dayton Research Institute

■ Represented NIOSH on several national and international working 

groups on nanotechnology, safety, and health.

■ Presented overviews of the NIOSH Nanotechnology Research Program 

to numerous organizations.

■ Provided briefings to the President’s Council of Advisors on Science 

and Technology.

Publications and Abstracts

■ Hoover MD, Stefaniak AB, Day GA, Geraci CL [2007]. Exposure 

assessment considerations for nanoparticles in the workplace. In: 

Monteiro-Riviere NA, Tran CL, eds. Nanotoxicology: characterization, 

dosing, and health effects. New York: Informa Healthcare USA Inc., pp. 

71–83.

■ Kuempel ED, Geraci CL, Schulte PA [2007]. Risk assessment approaches and research needs for nanomaterials: an examination of data and 

information from current studies. In: Simeonova PP, Opopol N, Luster MI, eds. Nanotechnology: toxicological issues and environmental 

safety, NATO security through science series book. New York: SpringerVerlag, pp. 119–145.

■ NIOSH [2008]. Safe nanotechnology in the workplace. An introduction 

for employers, managers, and safety and health professionals. Cincinnati, Ohio: U.S. Department of Health and Human Services, Centers 

for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Pub No. 2008–112.

■ NIOSH [2008]. The nanotechnology field research team update. Cincinnati, Ohio: U.S. Department of Health and Human Services, Centers 

for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Pub No. 2008–120.

■ NIOSH [2008]. NIOSH nanotechnology field research effort fact sheet. 

Cincinnati, Ohio: U.S. Department of Health and Human Services, 

Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Pub No. 2008–121.
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NIOSH Nanotechnology Research Center

■ NIOSH [2008]. NIOSH nanotechnology metal oxide particle exposure 

assessment study. Cincinnati, Ohio: U.S. Department of Health and 

Human Services, Centers for Disease Control and Prevention, National 

Institute for Occupational Safety and Health, DHHS (NIOSH) Pub. No. 

2008–122. 

■ NIOSH [2008]. Draft Strategic plan for NIOSH nanotechnology research: filling the knowledge gaps. Cincinnati, Ohio: U.S. Department 

of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, February 2008 [www.cdc.gov/niosh/topics/nanotech/strat_planA.html].

■ Schulte PA, Geraci CL, Zumwalde RD, Hoover MD, Kuempel ED 

[2008]. Occupational risk management of nanoparticles. J Occup Environ Hyg 5(4):239–249.

■ Schulte PA, Trout D, Zumwalde R, Kuempel E, Geraci CL, Castranova 

V, Mundt D, Mundt K, Halperin W [2008]. Options for occupational 

health surveillance of workers potentially exposed to engineered 

nanoparticles: state of the science. J Occup Med 50(5):517–526.

■ Schulte PA, Geraci CL, Zumwalde R, Hoover MD, Castranova VA, 

Kuempel E, Murashov V, Vainio H, Savolainen K [2008]. Sharpening 

the focus on occupational safety and health in nanotechnology. Scand J 

Work Environ Health 34(6):471–478.

■ NIOSH [2009]. Interim guidance for medical screening and hazard 

surveillance for workers potentially exposed to engineered nanoparticles. Cincinnati, Ohio: U.S. Department of Health and Human Services, 

Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Pub. No. 2009–116.

■ NIOSH [2009]. Approaches to safe nanotechnology: managing the 

health and safety concerns with engineered nanomaterials. Cincinnati, 

Ohio: U.S. Department of Health and Human Services, Centers for 

Disease Control and Prevention, National Institute for Occupational 

Safety and Health, DHHS (NIOSH) Pub. No. 2009–125. 

Invited Presentations

■ Geraci CL [2007]. Nanotechnology: an overview of health and safety 

issues “implications and applications.” Ohio Safety Congress and Expo, 

Columbus, OH, March 20.
18

NIOSH Nanotechnology Research Center

■ Geraci CL [2007]. The NIOSH Nanotechnology Research Program: 

occupational implications and applications. General Electric nanotechnology summit, Miskayuna, NY, April 18.

■ Geraci CL [2007]. Nanotechnology: using basic risk management 

concepts to address difficult questions. Society for Chemical Hazard 

Communication spring meeting, San Antonio, TX, April 25.

■ Geraci CL [2007]. The NIOSH Nanotechnology Research Program: 

occupational implications and applications. Northeastern University 

panel on nanotechnology and policy, Boston, MA, May 1.

■ Geraci CL [2007]. Nanomaterials in the workplace: applying basic risk 

management principles. American Society of Safety Engineers webinar, 

May 15.

■ Geraci CL [2007]. Nanotechnology: an international perspective from 

NIOSH. Education Safety Association of Ontario annual conference, 

Ontario, Canada, May 31.

■ Geraci CL, Hoover MD [2007]. Exposure assessment and sampling 

issues for nanotoxicology and safe handling of nanoparticles in the 

workplace. American Industrial Hygiene Association conference and 

exposition, roundtable 201: Toxicology and exposure assessment issues 

for nanotechnology: an update for industrial hygienists, Philadelphia, 

PA, June 2–7.

■ Geraci CL [2007]. One year later: an update of the NIOSH Nanotechnology Research Program. American Industrial Hygiene Association 

conference and exposition, roundtable 218: Ask the experts: an update 

on the NIOSH Nanotechnology Research Program, Philadelphia, PA, 

June 2–7.

■ Geraci CL [2007]. Building OS&H capability in nanomaterial manufacturing: an example of “research to practice.” American Society of Safety 

Engineers conference and exposition, Orlando, FL, June 25.

■ Geraci CL [2007]. Meeting the challenge: an update of the NIOSH 

Nanotechnology Research Program. ORC Worldwide Occupational 

Safety and Health joint meeting, Washington, DC, August 8.

■ Geraci CL, Methner MM, Dunn KH, Coe-Sullivan S [2007]. Occupational safety and health field study of workers potentially exposed 

to quantum dot nanomaterials. International symposium on nanotechnology: occupational and environmental health, Taipei, Taiwan, 

August 29.
19

NIOSH Nanotechnology Research Center

■ Geraci CL [2007]. Occupational risk management for nanomaterials 

along the product life cycle. International symposium on nanotechnology: occupational and environmental health, Taipei, Taiwan, September 1.

■ Geraci CL [2007]. International collaboration opportunities in nanotechnology research. International symposium on nanotechnology: 

occupational and environmental health, Taipei, Taiwan, September 1.

■ Geraci CL [2007]. Progress in addressing the occupational safety 

and health concerns of nanotechnology. President’s Council of Advisors on Science and Technology, briefing panel, Washington, DC, 

September 11. 

■ Geraci CL [2007]. Workplace risk management of nanomaterials: challenges and lessons learned. NanoTX’07, Dallas, TX, October 3.

■ Geraci CL [2007]. Nanotechnology: the new workplace, industrial 

hygiene implications. Professional conference on industrial hygiene, 

Louisville, KY, October 17. 

■ Geraci CL [2007]. Nanotechnology: the new workplace, Nano 101 for 

the industrial hygienist. Professional conference on industrial hygiene, 

Louisville, KY, October 23. 

■ Geraci CL [2007]. The NIOSH Nanotechnology Research Program. Professional conference for industrial hygiene, Louisville, KY, October 23.

■ Geraci CL [2007]. Nanotechnology: the new workplace, workplace 

exposure assessment challenges. American College of Occupational 

Medicine State-of-the-Art Conference/International Conference on 

Health Care Worker Health, Vancouver, British Columbia, Canada, October 27.

■ Geraci CL [2007]. Safe development of nanotechnology. Massachusetts 

governor’s panel on nanotechnology-office of technical assistance and 

technology, Boston, MA, November 15.

■ Geraci CL, Hoover MD [2007]. A risk assessment and control approach, teleweb on nanotechnology health and safety: case studies 

in the occupational setting. American Conference of Governmental 

Industrial Hygienists, December 4.

■ Hoover MD, Geraci CL [2008]. Nanotoxicology issues for assessing 

and managing occupational exposure risks for nanoparticles in the 

workplace. American Industrial Hygiene Association distance learning 

program, January 31.
20

NIOSH Nanotechnology Research Center

■ Geraci CL [2008]. Occupational safety and health issues and nanotechnology. Education Resource Committee program directors meeting, 

Galveston, TX, February 10.

■ Schulte PA [2008]. Occupational safety and health issues and nanotechnology. Food and Drug Law meeting, Washington, DC, February 18 

and 19.

■ Geraci CL [2008]. Progress in addressing the occupational safety and 

health concerns of nanotechnology. Meeting with Lockheed Martin, 

Baltimore, MD, February 1.

■ Geraci CL [2008]. Progress in addressing the occupational safety and 

health concerns of nanotechnology. Meeting with the New Jersey Technology Council, Rutgers University, Camden, NJ, March 4.

■ Geraci CL [2008]. Nanotechnology and occupational safety and health: 

What do we know? SESHA annual high technology environmental 

health and safety symposium, Portland, OR, March 27.

■ Geraci CL, Methner MM, Pearce TA, Hodson LL [2008]. Nanotechnology for industrial hygienists. American Industrial Hygiene Association—Central Ohio section meeting, Columbus, OH, April 22. 

■ Geraci CL, Hoover MD, Heidel DS, Pearce TA, Methner MM, Hodson 

LL [2008]. Nanoparticles in the workplace: assessing and managing 

risks. American Industrial Hygiene Association conference and exposition, Minneapolis, MN, May 31–June 5.

■ Geraci CL [2008]. Update on NIOSH research on the measurement of 

nanoparticles in the workplace. American Industrial Hygiene Association conference and exposition, roundtable 218: Ask the experts: an 

update on NIOSH Nanotechnology Research Program, Minneapolis, 

MN, May 31–June 5.

■ Geraci CL [2008]. NIOSH guidance on nanotechnology: protecting 

our workers environmental, health, and safety issues in nanomaterials 

workshop. Meeting sponsored by The American Ceramic Society/National Institute of Standards and Technology, Gaithersburg, MD, June 

8–10.

■ Geraci CL [2008]. Nanotechnology and occupational safety and health: 

What do we know? International conference on nanotechnology for the 

forest products industry, St. Louis, MO, June 25.

■ Geraci CL [2008]. The NIOSH nanotechnology field research team—

a brief summary and update of activities. DOE nanoscale science 
21

NIOSH Nanotechnology Research Center

research centers symposium: safe handling of engineered nanoscale 

materials, teleseminar to Argonne, IL, July 9.

■ Geraci CL [2008]. Engineering controls: the continuum of prevention 

through design, control banding, and engineering controls. OECD 

Working Party on Manufactured Nanomaterials Workshop on Exposure 

Assessment and Exposure Mitigation, Frankfurt, Germany, October 20. 

■ Geraci CL [2008]. Nanotechnology: real world challenges for the 

industrial hygienist. Professional Conference on Industrial Hygiene. 

Tampa, FL, November 11. 

■ Geraci CL [2008]. ]. Nanotechnology: real world challenges for the 

industrial hygienist. California Industrial Hygiene Council, San Diego, 

CA, December 8.

■ Methner MM, Hodson LL and Geraci CL [2008] Nanoparticle emission 

assessment technique (NEAT) used by NIOSH for Identifying Sources 

and Releases of Engineered Nanoparticles. Ohio Valley American Industrial Hygiene Association section, West Chester, OH, December 16.
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NIOSH Nanotechnology Research Center

Project 2: Nanotechnology Safety and Health

Research Coordination

Principal Investigator: Vincent Castranova, Ph.D.

Project Duration: FY 2004–2008

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Coordinated the NIOSH nanotoxicology program.

■ Fostered collaboration among investigators in the nanotoxicology program.

■ Fostered collaboration in nanotechnology research with

— The Consumer Products Safety Commission

— International Alliance for NanoEHS Harmonization

— Mitsui & Co.

— West Virginia University

— NASA

— University of Rochester

— University of Montana

— University of Pittsburgh

— Karolinska Institute

■ Represented NIOSH during involvement with several national and 

international working groups on nanotechnology safety and health.

■ Represented NIOSH during involvement with the National Nanotechnology Initiative nanotechnology environmental and health implication strategic planning group.

■ Presented overviews of the NIOSH nanotoxicology program to numerous organizations.

Publications and Abstracts

■ Mossman BT, Borm PJ, Castranova V, Costa DL, Donaldson K, Kleeberger SR [2007]. Mechanisms of action of inhaled fibers, particles, and 

nanoparticles in lung and cardiovascular diseases. Part Fibre Toxicol 4:4.
23

NIOSH Nanotechnology Research Center

■ Leonard SS, Castranova V, Chen BT, Schwegler-Berry D, Hoover M, 

Piacitelli C, Gaughan D [2007]. Particle size dependent generation 

from wildland fire smoke. Toxicol 236:103–113.

■ Balbus JM, Maynard AD, Colvin VL, Castranova V, Daston GP, Denison RA, Dreher KL, Goering PL, Goldberg AM, Kulinowski KM, 

Monteiro-Riviere NA, Oberdörster G, Omenn GS, Pinkerton KE, 

Ramos KS, Rest KM, Sass JB, Silbergeld EK, Wong BA [2007]. Meeting 

report: hazard assessment for nanoparticles. Environ Health Perspect 

115(11):1654–1659.

■ Schulte PA, Trout D, Zumwalde R, Kuempel E, Geraci CL, Castranova 

V, Mundt DJ, Mundt K, Halperin WE [2008]. Options for occupational health surveillance of workers potentially exposed to engineered 

nanoparticles: state of the science. J Occup Environ Med 50:517–526.

■ Papp T, Schiffmann D, Weiss D, Castranova V, Vallyathan V, Rahman Q 

[2008]. Human health implications of nanomaterial exposure. Nanotoxicol 2:9–27.

■ Ayres JG, Borm P, Cassee F, Castranova V, Donaldson K, Ghio A, Harrison RM, Hider R, Kelly F, Kooter I, Marano F, Maynard RL, Mudway I, Nel A, Sioutas C, Smith S, Baeza-Squiban A, Cho A, Duggan S, 

Froines J [2008]. Evaluating the toxicity of airborne particulate matter 

and nanoparticles by measuring oxidative stress potential—a workshop 

report and consensus statement. Inhal Toxicol 20:75–99.

■ Castranova V [2008]. The Nanotoxicology Research Program 

in NIOSH. J Nanopart Res [www.springerlink.com/content/

c302m62567162101/].

■ Pacurari M, Yin XJ, Zhao J, Ding M, Leonard SS, Schwegler-Berry 

D, Ducatman BS, Sbarra D, Hoover MD, Castranova V, Vallyathan V 

[2008]. Raw single-walled carbon nanotubes induce oxidative stress 

and active MAPKs, AP-1, NFkB, and Akt in normal and malignant human mesothelial cells. Environ Health Perspect 116:1211–1217.

■ Pacurari M, Yin XJ, Ding M, Leonard SS, Schwegler-Berry D, Ducatman BS, Chirila M, Endo M, Castranova V, Vallyathan V [2008]. 

Oxidative and molecular interactions of multi-walled carbon nanotubes in normal and malignant human mesothelial cells. Nanotoxicol 

2:115–170.

■ Vallyathan V, Pacurari M, Yin X, Zhao J, Ding M, Leonard S, Ducatman 

B, Castranova V [2008]. Alterations in molecular signaling of human 
24

NIOSH Nanotechnology Research Center

mesothelial cells exposed to raw single-walled carbon nanotubes. 

Respir Crit Care Med 177 Abs Issue:A219.

■ Pacurari M, Robinson V, Castranova V, Leonard SS, Chen F, Vallyathan 

V, Bargern M [2008]. Does sandblasted metal attenuate or enhance the 

toxicity of freshly fractured silica? Toxicologist 102:A300.

■ Castranova V [2008]. Comparison of in vitro, pharyngeal aspiration, 

and inhalation results for single-walled carbon nanotubes. Toxicologist 

102:A2356.

■ Hubbs AF, Mercer RR, Sriram K, Castranova V, Chen BT, McKinney W, 

Frazer DG, Batelli L, Willard P, Scabilloni J, Schwegler-Berry D, Porter 

D [2008]. Acute respiratory toxicolgic pathway of inhaled multi-walled 

carbon nanotubes. Vet Pathol 45:A220. 

■ Schulte PA, Geraci CL, Zumwalde R, Hoover M, Castranova V, Kuempel E, Murashov V, Vainio H, Savolainen K [2008]. Sharpening the 

focus on occupational safety and health of nanotechnology. Scand J 

Work Environ Health, 34(6):471–478.

Invited Presentations

■ Castranova V [2007]. Nanotoxicology research in NIOSH. Toxicology 

forum, Washington, DC, January 30.

■ Castranova V [2007]. Nanotechnology research in NIOSH. Meeting of 

the Northeastern chapter of the American Industrial Hygiene Association, Cleveland, OH, May 8.

■ Castranova V [2007]. Nanotoxicology research in NIOSH. NASA 

Glenn Research Center, Cleveland, OH, May 8.

■ Castranova V [2007]. Nanotoxicology research in NIOSH. American 

Industrial Hygiene Association conference and exposition, Philadelphia, PA, June 2–7.

■ Castranova V [2007]. Nanotoxicology research in NIOSH. West Virginia University Cancer Center, NTRC meeting in Morgantown, WV, 

February 21.

■ Castranova V [2007]. Critical toxicity parameters for nanoparticles vs. 

conventional particles. Presentation for the Department of Occupational 

Medicine, West Virginia University, Morgantown WV, August 28.
25

NIOSH Nanotechnology Research Center

■ Castranova V [2007]. Critical toxicity parameters for nanoparticles vs. 

conventional particles. Department of Physiology, West Virginia University, Morgantown, WV, August 30, 2007.

■ Castranova V [2007]. What do we know about exposure and human 

health effects on nanoparticles. Annual scientific conference of the Occupational and Environmental Medical Association of Canada, Banff, 

Alberta, Canada, October 15 and 16.

■ Castranova V [2007]. Critical toxicology parameters for nanoparticles 

vs. conventional particles. Conference on Bringing toxicology to global 

issues in occupational and environmental public health. Louisville, KY, 

October 18.

■ Castranova V [2007]. Biological effects of nanoparticles. State-of-theArt Conference/ International Conference on Health Care Worker 

Health, Vancouver, Canada, October 26–28.

■ Castranova V [2007]. NIOSH nanomaterials research activities. International Life Sciences Institute (ILSI) nanomaterials environmental 

health and safety project committee, Washington, DC, November 8.

■ Castranova V [2007]. Critical toxicity parameters for nanoparticles vs. 

conventional particles. Nanotechnology and occupational health and 

safety conference, Santa Barbara, CA, November 16 and 17.

■ Castranova V [2007]. NIOSH nanotoxicology research. European 

NanOSH conference—nanotechnologies: a critical area in occupational 

safety and health, Helsinki, Finland, December 3–5.

■ Castranova V [2008]. The Nanotoxicology Research Program in 

NIOSH. National Institute of Standards and Technology, Gaithersburg, 

MD, January 28.

■ Castranova V [2008]. Nanotoxicology research in NIOSH: nanotechnology update for industrial hygienists, American Industrial Hygiene 

Association distance learning program January 31.

■ Castranova V [2008]. Critical toxicity parameters for nanoparticles vs. 

conventional particles. Northern California Industrial Hygiene Society 

meeting, Palo Alto, CA, May 14.

■ Castranova V [2008]. NIOSH nanotoxicology program. American Industrial Hygiene Association Conference and Exposition, Minneapolis, 

MN, May 31–June 5.

■ Castranova V [2008]. NIOSH nanotoxicology research: biological 

activity of single-walled carbon nanotubes. American Industrial Hygiene Association conference and exposition, Minneapolis, MN, May 

31–June 5.
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NIOSH Nanotechnology Research Center

Project 3: Systemic Microvascular 

Dysfunction: Effects of Ultrafine 

vs. Fine Particle

Principal Investigator Vincent Castranova, Ph.D.

Project Duration: FY 2006–2010

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Designed, constructed, and tested a generation system to produce a 

stable airborne concentration of fine and ultrafine TiO2.

■ Conducted inhalation exposures evaluating the dose-independent 

systemic microvascular response to pulmonary deposition of fine vs. 

ultrafine TiO2 and found the following:

— Inhalation of TiO2 inhibited dilation of microvessels in the shoulder. 

— Inhalation of TiO2 resulted in inhibition of the ability of microvessels in the shoulder to respond to dilators.

— Systemic microvascular effects were demonstrated at lung burdens 

of TiO2, which did not cause widespread pulmonary inflammation 

as judged by BAL markers. 

— On an equivalent mass deposited basis, ultrafine TiO2 was approximately 10-fold more potent in causing systemic microvascular 

dysfunction than fine TiO2. 

— Inhalation of TiO2 inhibited nitric oxide production by systemic 

microvessels in response to dilators. 

— The inhibition of nitric oxide production by microvessels is reversed 

by inhibitors of reactive oxygen species.

— The inhibition of microvessel dilation is partially reversed by blockade of neural input to the microvessel.

— The inhibition of microvessel dilation is partially reversed by systemic depletion of neutorphils.

— Inhalation of TiO2 inhibited the ability of coronary vessel to dilate.
27

NIOSH Nanotechnology Research Center

Publications and Abstracts

■ Nurkiewicz TR, Porter DW, Hubbs AF, Stone S, Chen BT, Frazer D, 

Castranova V [2007]. Microvascular endothelium-dependent nitric 

oxide production is attenuated after inhalation of ultrafine particulate 

matter. FASEB J 21:A846.

■ Nurkiewicz TR, Porter DW, Hubbs AF, Cumpston JL, Chen BT, Frazer 

DG, Castranova V [2008]. Nanoparticle inhalation augments particledependent systemic microvascular dysfunction. Part Fibre Toxicol 5(1).

■ LeBlanc A, Hu Y, Muller-Delp J, Moseley A, Chen B, Frazer D, Castranova V, Nurkiewicz T [2008]. Particulate matter inhalation impairs 

coronary microvascular reactivity. Proc 25th Er Soc Microcir Conference, Budapest, Hungary, August 26–29, pp. 13–17. 

■ Nurkiewicz TR, Porter DW, Hubbs AF, Chen BT, Frazer DG, Castranova V [2008]. Ultrafine particulate matter inhalation attenuates microvascular endothelial nitric oxide production. Toxicologist 102:A1255.

Invited Presentations

■ Nurkiewicz TR, Porter DW, Hubbs AF, Millecchia LL, Donlin M, Chen 

TB, Frazer DG, Castranova V [2007]. Nanoparticle inhalation attenuates systemic microvascular endothelium-dependent nitric oxide production. World Congress for Microcirculation, Milwaukee, WI, August 

15–19.

■ Castranova V [2007]. Inhalation of ultrafine titanium dioxide augments particle-dependent microvascular dysfunction. Nanotoxicology 

conference, Venice, Italy, April 20.

■ Castranova V [2007]. Cardiovascular effects of pulmonary exposure to 

nanoparticles. Toxicology and risk assessment conference, Cincinnati, 

OH, April 25.

■ Castranova V [2007]. Inhalation of ultrafine titanium dioxide augments 

particle-dependent microvascular dysfunction. Center for Environmental Health, University of Montana, Missoula, MT, September 21.

■ Castranova V [2008]. Systemic microvascular effects of pulmonary exposure to fine vs. ultrafine particles. University of Connecticut, Storrs, 

CT, April 7.

■ Castranova V [2008]. Systemic microvascular effects of pulmonary 

exposure to fine vs. ultrafine particles. Meeting held at John Hopkins 

University, Baltimore, MD, June 10.
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NIOSH Nanotechnology Research Center

■ Castranova V [2008]. Ambient particulates and/or nanoparticles: 

cardiovascular and pulmonary toxic and morphologic manifestations. 

International Conference on Particles: Risks and Opportunities, September 2–5. 

■ Chen BT, McKinney W, Schwegler-Berry D, Castranova V, Frazer D 

[2008]. Aerosolization and characterization of multi-walled carbon 

nanotubes for inhalation studies. American Association for Aerosol 

Research annual conference, Orlando, FL, October 20–24.

■ Castranova V [2008]. Systemic microvascular effects of pulmonary 

exposure to particles. Presentation at the Harvard School of Public 

Health, Cambridge, MA, October 24. 

■ LeBlanc AF, Hu Y, Miller-Delp J, Chen D, Frazer BT, Castranova V, 

Nurkiewicz TR [2008]. Nanoparticle inhalation impairs endotheliumdependent vasoreactivity in coronary arterioles. American Heart Association conference, Washington DC, November 8–12.
29

NIOSH Nanotechnology Research Center

Project 4: Particle Surface Area as a Dose 

Metric

Principal Investigator: Vincent Castranova, Ph.D.

Project Duration: FY 2004–2008

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Developed a method to improve dispersion of nanoparticles in biologically compatible suspension media.

■ Determined that improved nanoparticle dispersion results in a greater 

inflammatory response after intratracheal instillation of ultrafine carbon black in rats.

■ Compared ultrafine TiO2 and carbon black to fine TiO2 and carbon 

black, respectively, and determined that the ultrafine particles of both 

are more inflammogenic on a mass-dose basis.

■ Determined that on an equivalent total particle surface area basis, the 

potencies of ultrafine versus fine TiO2 or carbon black were not significantly different.

■ Determined that pulmonary inflammation following intratracheal 

instillation of ultrafine TiO2 was more persistent than after installation 

of ultrafine carbon black.

■ Determined that in vitro treatment with ultrafine TiO2 stimulates oxidant production and induction of molecular signaling events in macrophages.

Publications and Abstracts

■ Shvedova A, Sager T, Murray A, Kisin E, Porter D, Leonard SS, SchweglerBerry D, Robinson V, Castranova V [2007]. Critical issues in the 

evaluation of possible effects resulting from airborne nanoparticles. In: 

Monteiro-Riviere NA, Tran CL, eds. Nanotechnology: characterization, 

dosing, and health effects. New York: Informa Healthcare USA Inc., pp. 

221–232.
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NIOSH Nanotechnology Research Center

■ Sager T, Porter D, Robinson V, Lindsley WG, Schwegler-Berry DE, Castranova V [2007]. An improved method to disperse nanoparticles for 

in vitro and in vivo investigation of toxicity. Nanotoxicol 1:118–129. 

■ Sager T, Robinson V, Porter D, 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. Toxicologist 

96:A1120.

■ Kang JL, Moon C, Lee HS, Park E-M, Kim HS, Castranova V [2008]. 

Comparison of the biological activity between ultrafine and fine titanium dioxide particles in RAW 264.7 cells associated with oxidative 

stress. J Toxicol Environ Health 71:478–485.

■ Porter DW, Sriram K, Wolfarth MG, Jefferson AM, Schwegler-Berry 

DE, Andrew ME, Castranova V [2008]. A biocompatible medium for 

nanoparticle dispersion. Nanotoxicology 2:144–154.

■ Kang JL, Moon C, Lee HS, Lee HW, Park E-M, Kim HS, Castranova 

V [2008]. Comparison of the biological activity between ultrafine and 

fine TiO2 particles in RAW 264.7 cells associated with oxidative stress. 

Toxicologist 102:A1486.

■ Sager T, Porter D, Castranova V [2008]. Pulmonary response to intratracheal instillation of fine or ultrafine carbon black or titanium dioxide: role of surface area. Toxicologist 102:A1491.

■ Sager T, Kommineni C, Castranova V [2008]. Pulmonary response to 

intratracheal instillation of ultrafine versus fine titanium dioxide: role 

of surface area. Particle Fibre Toxicol 5:17

Invited Presentations

■ Castranova V [2008]. Intratracheal instillation of rats to ultrafine TiO2

or ultrafine carbon black. Presentation at the Health and Environmental Sciences Institute, Washington, DC, May 8.
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NIOSH Nanotechnology Research Center

Project 5: Role of Carbon Nanotubes in 

Cardiovascular and COPD-Related 

Diseases

Principal Investigator: Petia Simeonova, Ph.D.

Project Duration: FY 2004–2008 

Critical Topic Area: toxicology and internal dose 

Accomplishments and Research Findings

■ Evaluated cardiovascular effects resulting from respiratory exposure to 

purified SWCNT and MWCNT. 

■ A single exposure resulted in a treatment-dose dependent, distressed 

mitochondrial homeostasis represented by mitochondrial DNA damage, 

glutathione depletion, and increased protein carbonyl formation in aortic 

tissue. Oxidative alterations of mitochondria can trigger endothelial dysfunction, a leading mechanism in atherosclerosis progression. 

SEM of macrophages treated with PC- or PS-coated SWCNT

SWCNT PC-coated SWCNT

PC-coated SWCNT

100 μm

1 μm

1 μm

1 μm
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NIOSH Nanotechnology Research Center

■ Multiple pulmonary exposures of apoE-/- mice, a model of human atherosclerosis, to SWCNT resulted in accelerated atherosclerosis.

■ Respiratory exposure to SWCNT and MWCNT resulted in acute and 

chronic systemic responses related to potential cardiovascular adverse 

effects. 

■ Currently, there is no evidence for translocation of carbon nanotubes, 

in a measurable amount, from the lung into the systemic circulation. 

SWCNT and MWCNT deposited in the lung induced acute systemic 

inflammatory and prothrombotic responses. These effects are portrayed 

by a complex pattern of gene expression and protein blood analyses.

■ Developed methodological approach used in the above studies for 

evaluating toxicity of respiratory exposure to particles. The approach 

will foster the development of predictive tests for estimating the toxicity of new nanomaterials based on their physiochemical characteristics 

and potential to induce oxidative stress, inflammation, and specific 

pulmonary and systemic toxicity.

■ Single exposure to CNTs is associated with a chronic and persistent 

release of osteopontin (OPN) into the systemic circulation. Preliminary 

data demonstrate a differential blood OPN response between female 

and male mice as a result of the CNT exposure. OPN may play a role in 

the CNT-induced local and cardiovascular responses. 

■ Evaluated cardiovascular effects of subchronic inhalation exposure to 

C60 particles (diameter 1 and 0.05 μm) in mouse and rat models (in 

collaboration with the National Institute of Environmental Health and 

Safety).

■ Found that the initial screening for cardiovascular toxicity demonstrated changes in the expression of several genes related to stress response, 

including c-fos, and heat shock proteins 25, 70, and 90 in the aortas of 

the exposed mice. Heat shock proteins are incremental in triggering 

many autoimmune/chronic inflammatory diseases. In this regard, it has 

been suggested that there is a multifaceted role for heat shock proteins 

in atherosclerosis. Wild type mice (not prone to develop atherosclerosis) exposed to fullerenes developed cardiovascular stress responses, 

which may indicate a predisposition to atherogenesis. 

■ Discovered that endothelial cells exposed to CNTs resulted in a direct 

effect. The findings of this study demonstrated actin cytoskeleton disruption, VE-cadherin disorganization, reduced tubule formation, and 

concomitant diminished viability of human aortic endothelial cells as a 

result of exposure to purified SWCNT or MWCNT. These effects were 
33

NIOSH Nanotechnology Research Center

dose dependent and most likely associated with mechanical damage of 

the cell membrane. The endothelial cells tolerate acute low concentrations of CNTs without changes in the viability, cytoskeleton, and function. 

■ Determined that study results demonstrate that the evaluation of systemic effects in parallel with pulmonary toxicity studies will provide a 

more complete toxicological assessment that can be used in predicting 

risk. 

Publications and Abstracts

■ Li Z, Hulderman T, Salmen R, Chapman R, Leonard SS, Shvedova 

A, Luster MI, Simeonova PP [2007]. Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes. Environ Health 

Perspect 115(3):77–82. Nomimated for Charles C. Shepard Science 

Award, 2008, and was highlighted and discussed in the section “Hotoff-the-Presses Peer-Reviewed Research Article” of the EH&S Nano 

News [www.ehsnanonews.com/] as one of the first investigations on the 

potential cardiovascular effects of pulmonary exposure to SWCNT. 

■ Simeonava PP and Luster MI [2007]. In: Simeonova PP, Opopol N, 

Luster MI, eds. Nanotechnology: toxicological issues and environmental safety, NATO security through science series book. New York: 

Springer-Verlag, Springer-Verlag.

■ NATO Security through Science Series Book Nanotechnologytoxicological Issues and Environmental Safety [2007]. Ed. Petia P. Simeonova, N. Opopol, MI Luster. Springer-Verlag. 

■ Simeonova PP [2007]. Nanoparticle exposure and cardiovascular 

effects—experimental data. In: Simeonova PP, Opopol N, Luster MI, 

eds. Nanotechnology: toxicological issues and environmental safety, 

NATO security through science series book. New York: Springer-Verlag. pp. 53–65. 

■ Simeonova PP, Erdely A, Li Z [2007]. Carbon nanotube exposure and 

risk for cardiovascular effects. In: Monteiro-Riviere NA, Tran CL, eds. 

Nanotoxicology: charaterization, dosing, and health effects. New York: 

Informa Healthcare USA Inc., pp. 237–246.

■ Simeonova PP, Li Z, Erdely A [2007]. Carbon nanotube respiratory 

exposure and risk from systemic effects. Toxicologist 96(1):137.
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NIOSH Nanotechnology Research Center

■ Erdely A, Hulderman T, Salmen R, Liston A, Zeidler-Erdely PC, Simeonova PP [2008]. Carbon nanotube acute lung exposure induces plasminogen activator inhibitor 1. Toxicologist 102(1):151.

■ Simeonova PP, Erdely A, Liston A, Roycroft J, Germolec D, Walker NJ, 

[abstract submitted]. Potential cardiovascular effects of Fullerene C60 

inhalation exposure. Society of Toxicology annual meeting, Baltimore, 

Maryland, March 2009.

■ Erdely A, Hulderman T, Salmen R, Liston A, Zeidler-Erdely PC, Simeonova PP [abstract submitted]. Time course of systemic effects following a single exposure to carbon nanotubes. Society of Toxicology 

annual meeting, Baltimore, Maryland, March 2009.

■ Walker VG, Hulderman T, Simeonova PP [abstract submitted]. Comparison of carbon nanotube-induced cytotoxicity in A549 and normal 

human bronchial epithelial (NHBE) cells. Society of Toxicology annual 

meeting, Baltimore, Maryland, March 2009.

■ Erdely A, Hulderman T, Salmen R, Liston A, Erdely P, Schwegler-Berry 

D, Castranova V, Koyama S, Kim Y-A, Endo M, Simeonova PP [2009]. 

Cross-talk between lung and systemic circulation during carbon 

nanotube respiratory exposure—potential biomarkers. Nano Lett 

14:9(1), pp. 36–43. 

■ Simeonova PP, Erdely A [in press]. Engineered nanoparticle respiratory 

exposure and potential risks for cardiovascular toxicity: predictive tests 

and biomarkers. Inhal Toxicol.

■ Walker VG, Hulderman T, Schwegler-Berry D, Simeonova PP [in 

review]. Potential direct effects of carbon nanotubes on human aortic 

endothelial cells.

Invited Presentations

■ Simeonova PP [2007]. Carbon nanotube respiratory exposure and risk 

from systemic effects. Society of Toxicology, Charlotte, NC, March, 

25–29.

■ Simeonova PP [2007]. Carbon nanotubes— toxicological evaluation. 

International meeting of nanotechnology, San Francisco, CA, November 5–7.

■ Erdely A, Hulderman T, Salmen R, Liston A, Zeidler-Erdely PC, Simeonova PP [2008]. Crosstalk between the lung and blood following 

carbon nanotube exposure; potential biomarkers and implications for 
35

NIOSH Nanotechnology Research Center

Scanning electron 

microscopy image of 

mouse macrophage 

with engulfed CNT

cardiovascular disease. Allegheny-Erie Chapter meeting, Society of 

Toxicology. Best overall poster award.

■ Walker VG, Hulderman T, Simeonova PP [2008]. Direct exposure to 

carbon nanotube induces cellular changes in primary human endothelial cells. The American Society for Cell Biology annual meeting, San 

Francisco, CA, December 13–17.

■ Simeonova PP [2008]. Engineered nanoparticle respiratory exposure 

and potential risk for cardiovascular toxicity. International inhalation 

symposium, Hanover, Germany, June 11–15.

■ Simeonova PP [2008]. Carbon nanotube pulmonary exposure—

cardiovascular effects. American Association for the Advancement of 

Science annual meeting, Boston, MA, February 14–18.

■ Simeonova PP [2008]. Air pollutants and atherosclerosis. Press briefing 

coordinated by the Director of the Office of Public Programs, American Association for the Advancement of Science, Boston, MA, February 14–18.

■ Simeonova PP, Erdely A, Walker V [2008]. Reports on MWCNT systemic 

toxicity and discussions about collaborations with Dr. Endo and Japanese 

scientist delegation visiting NIOSH. Morgantown, WV, March 12.

100 μm
36

NIOSH Nanotechnology Research Center

Project 6: Investigations of Multi-Walled 

Carbon Nanotube Toxicity

Principal Investigator: Dale Porter, Ph.D.

Project Duration: FY 2007–2009

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Developed and validated a biocompatible dispersion medium for use in 

nanotoxicology studies.

■ Investigated crystal structure of MWCNT using high resolution transmission electron microscopy.

■ Determined surface chemistry of the MWCNT using x-ray photoelectron spectroscopy.

■ Quantified metal contaminates and endotoxin levels preset in MWCNT.

■ Evaluated dispersion status of hydrosol MWCNT using low resolution 

transmission electron microscopy.

■ Determined zeta potential of hydrosol MWCNT.

■ Determined the length and diameter of MWCNT.

■ Conducted an in vivo dose-response and time-course study of 

MWCNT-induced toxicity after exposure by pharyngeal aspiration.

■ Aspiration exposure study results indicate that MWCNT exposure induces dose- and time-dependent changes in pulmonary inflammation, 

damage, and fibrosis in the lung.

■ Exposed mice by aspiration to gold-labeled MWCNT in order to determine MWCNT translocation. The samples have been collected and are 

currently being analyzed by neutron activation analyses.

■ Built a MWCNT inhalation system in conjunction with the Developmental Engineering Research Team (DERT).

■ Conducted a dose-response study to aerosolized MWCNT and found 

that inhaled MWCNT induces dose-dependent pulmonary inflammation and damage.
37

NIOSH Nanotechnology Research Center

Publications and Abstracts

■ Sager TM, 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. Nanotoxicol 1:118–129.

■ 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 NA, Tran CL, eds. 

Nanotoxicology: characterization, dosing, and health effects. New York: 

Informa Healthcare USA Inc., pp. 225–236.

■ 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. Toxicologist 96:A1390.

■ Sager T, Robinson V, Porter DW, Schwegler-Berry D, 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. Toxicologist 

96:A1120.

■ Porter DW, Sriram K, Wolfarth M, Jefferson A, Schwegler-Berry D, Andrew ME, Castranova V [2008]. A biocompatible medium for nanoparticle dispersion. Nanotoxicology 2:144–154.

■ Hubbs AF, Mercer RR, Sriram K, Castranova V, Chen BT, McKinney W, 

Frazer DG, Battelli L, Willard P, Scabilloni J, Schwegler-Berry D, Porter 

D [2008]. Acute respiratory toxicologic pathology of inhaled multiwalled carbon nanotubes. Vet Pathol 45:786.

■ Chen BT, McKinney W, Schwegler-Berry D, Castranova V, Frazer DG 

[2008]. Aerosolization and characterization of multi-walled carbon 

nanotubes for inhalation studies. American Association for Aerosol 

Research annual conference, Orlando FL, October 20–24.
38

NIOSH Nanotechnology Research Center

Project 7: Pulmonary Toxicity of Metal Oxide 

Nanospheres and Nanowires

Principal Investigator: Dale Porter, Ph.D.

Project Duration: FY 2007–2010

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Developed and validated a biocompatible dispersion medium for use in 

nanotoxicology studies.

■ Synthesized three engineered TiO2 nanoparticles—nanospheres, short 

nanowires, and long nanowires (Nianqiang Wu, West Virginia University).

■ Determined crystal structure of all three anatase TiO2 nanoparticles.

■ Characterized physical characteristics (diameter, length, width) of TiO2

nanoparticles.

■ Determined surface chemistry of the TiO2 nanoparticles using electron 

spin resonance spectroscopy.

■ Evaluated dispersion status of hydrosol TiO2 nanoparticles using low resolution transmission electron microscopy and dynamic light scattering.

■ Conducted an in vivo dose-response and time-course study of TiO2

nanoparticles after exposure by pharyngeal aspiration. Results from 

animal aspiration study indicate that exposure to TiO2 nanoparticles 

induces dose- and time-dependent changes in pulmonary inflammation and damage.

■ Acted as co-principal investigator on National Science Foundation 

(NSF) grant, Correlation among physicochemical properties, photochemical fate, and toxicity of TiO2 nanoparticles. Funding period 

September 1, 2008–August 31, 2011.

Publications and Abstracts

■ Sager TM, 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. Nanotoxicology 1:118–129.
39

NIOSH Nanotechnology Research Center

■ Sager T, Robinson V, Porter DW, Schwegler-Berry D, Lindsley WG, 

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. Toxicologist 

96:A1120.

■ Porter DW, Sriram K, Wolfarth M, Jefferson A, Schwegler-Berry D,

Andrew ME, Castranova V [2008]. A biocompatible medium for 

nanoparticle dispersion. Nanotoxicol 2:144–154.

■ Porter DW, Holian A, Sriram K, Wu N, Wolfarth M, Hamilton R, Buford M [2008]. Engineered titanium dioxide nanowire toxicity in vitro 

and in vivo. Toxicologist 102:306.

Invited Presentations

■ Hamilton R, Porter DW, Buford M, Sriram K, Wu N, Wolfarth M, 

Holian A [2008]. Engineered titanium dioxide nanoparticle bioactivity 

and toxicity are dependent on particle length and shape. Nanotoxicology—

second international conference, Zurich, Switzerland. September 7–10. 
40

NIOSH Nanotechnology Research Center

Project 8: WC-Co Nanoparticles in Initiating 

Angiogenesis by Reactive Oxygen 

Species

Principal Investigator: Min Ding

Project Duration: FY 2009–2011. (Preliminary data gathering started in FY2008) 

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ This project will investigate the potential pulmonary carcinogenesis in 

response to WC-Co particles exposure using cell culture and animal 

model.

■ Both fine and nanoparticles of WC-Co stimulate angiogenesis using 

the CEM assay. 

■ The mechanistic investigations (gene mutation, activation of transcription factors, reactive oxygen species [ROS] generation) indicate that 

WC-Co nanoparticles induce ROS production, which activates AKT 

and ERK signaling pathways in lung epithelial cells. 

■ ROS production results in transcriptional activation of AP-1, NF-κB, 

and VEGF through AKT and ERK1/2 activation with the greater effect 

observed in nanoscale WC-Co when compared to fine-sized WC-Co at 

the same concentration.
41

NIOSH Nanotechnology Research Center

Project 9: Evaluation of the Pulmonary 

Deposition and Translocation of 

Nanomaterials

Principal Investigator: Robert R. Mercer, Ph.D.

Project Duration: FY 2006–2010

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Found that aggregates of SWCNT disperse when deposited in the 

lungs.

■ Demonstrated that diffuse interstitial fibrosis following exposure to 

SWCNT is due to a dispersed submicron form of SWCNT that had not 

yet been identified.

■ Demonstrated that injury response (time course and resulting lesions) 

from the inhalation of SWCNT is similar to that produced by the aspiration of SWCNT, a less costly and more feasible delivery method.

■ Received the 2008 Charles C. Shepard Science Award for outstanding scientific paper, Alteration of Deposition Pattern and Pulmonary 

Response as a Result of Improved Dispersion of Aspirated Single-Walled 

Carbon Nanotubes in a Mouse Model.

■ Developed methods for labeling CNTs so that their potential translocation from the lungs to other organs can be studied.

The image on the left is from a 

normal mouse lung while the 

one on the right if from lungs 

30 days after exposure to 

SWCNT indicating an increase 

in collagen (stained bright 

yellow), the key element in 

fibrosis.
42

NIOSH Nanotechnology Research Center

Publications and Abstracts

■ Mercer RR, Scabilloni JF, Wand L, Schwegler-Berry D, Shvedova 

AA, Castranova V [2007]. Dispersion significantly enhances the 

pulmonary toxicity of single-walled carbon nanotubes. Toxicologist 

96(231):A1115.

■ Roberts JR, Mercer RR, Young S, Porter DW, Castranova V, Antonini 

JM [2007]. Inflammation and fate of quantum dots following pulmonary treatment of rats. Toxicologist 96(230):A1111.

■ Mercer RR, Scabilloni JF, Wang L, Battelli LA, Castranova V [2008]. 

Use of labeled single-walled carbon nanotubes to study acute translocation from the lungs. Toxicologist: 102(S-1), A1399.

■ Wang L, Castranova V, Rojanasakul Y, Lu Y, Scabilloni JF, Mercer RR 

[2008]. Direct fibrogenic effects of dispersed single-walled carbon 

nanotubes on human lung fibroblasts. Toxicologist: 102(S-1), A1499.

■ Wang L, Chanvorachote P, Toledo D, Stehlik C, Mercer RR, Castranova 

V, Rojanasakul Y [2008]. Hydrogen peroxide is a key mediator of Bcl-2 

down regulation and apoptosis induction by cisplatin in human lung 

cancer cells. Mol Cancer Thera Mol Pharmacol 73:119–127.

■ Mercer RR, Scabilloni J, Wang L, Kisin E, Murray A, Schwegler-Berry 

D, Shvedova A, Castranova V [2008]. Alteration of deposition pattern 

and pulmonary response as a result of improved dispersion of aspirated 

single-walled carbon nanotubes in a mouse model. Am J Physiol Lung 

Cell Mol Physiol 294:L87–97.

■ Shvedova AA, Kisin E, Murray E, Johnson V, Gorelik O, Arepalli S, 

Hubbs AF, Mercer RR, Keohavong P, Sussman N, Jin J, Stone S, Chen 

BT, Deye G, Maynard A, Castranova V, Baron P, Kagan VE [2008]. 

Inhalation versus aspiration of single-walled carbon nanotubes in 

C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Am J Physiol Lung Cell Mol Physiol 295:552–565.

Invited Presentations

■ Mercer RR [2007]. Inhalation toxicology of SWCNT. Society for Risk 

Assessment Teleseminar, June 7.

■ Mercer RR [2008]. Using labeled SWCNT to determine potential acute 

translocation from the lungs. Society of Toxicology annual meeting, 

March 16–20.
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NIOSH Nanotechnology Research Center

Project 10: Occupational Exposures and

 Potential Neurological Risks

Principal Investigator: Krishnan Sriram, Ph.D. 

Project Duration: FY 2008–2012

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings (Carbon nanotubes study)

■ Demonstrated the efficacy of a biocompatible dispersion medium for 

evaluating nanoparticle neurotoxicity. 

■ Evaluated neuroinflammatory responses following pulmonary and 

inhalation exposure to MWCNT.

■ Evaluated the effects of MWCNT on blood-brain barrier integrity. 

■ Demonstrated regional heterogeneity in the blood-brain barrier changes and neuroinflammatory responses following pulmonary and inhalation exposure to MWCNT. 

■ Evaluated the effects of MWCNT in eliciting Alzheimer-like pathology.

■ Demonstrated that pulmonary exposure to MWCNT up-regulates key 

genes involved in processing of the amyloid precursor protein, accumulation of which is a pathological hallmark of Alzheimer disease. 

Accomplishments and Research Findings (welding fume 

study)

■ Investigated the neurotoxicologic potential following pulmonary exposure to diverse welding fumes. Specifically, investigated the potential of 

welding fumes to cause dopaminergic neurotoxicity. 

■ Determined the regional metal distribution in the brain following pulmonary exposure to three types of welding fumes: gas metal arc-mild 

steel (GMA-MS), manual metal arc-hard surfacing (MMA-HS), and 

flux core arc-stainless steel (FCA-SS). 

■ Demonstrated the accumulation of manganese from welding fumes in 

target-dopaminergic brain areas.
44

NIOSH Nanotechnology Research Center

■ Demonstrated that with increasing solubility of welding fumes, a 

greater accumulation of manganese occurred in brain areas. 

■ Demonstrated that the potential to oxidize dopamine was directly proportional to the solubility of the welding fumes. 

■ Determined changes in T1 relaxation time (as an index of manganese 

accumulation) in specific brain areas using magnetic resonance imaging. 

■ Demonstrated that pulmonary exposure to GMA-MS, MMA-HS, and 

FCA-SS welding fumes caused loss of tyrosine hydroxylase protein, a 

marker of dopaminergic neurons.

■ Demonstrated that acute inhalation exposure to GMA-MS elicited 

neuroinflammation and gliosis in specific brain areas, including dopaminergic targets. 

■ Demonstrated that acute inhalation exposure to GMA-MS alters the 

expression of divalent metal transporters in distinct brain areas.

Accomplishments and Research Findings (titanium dioxide 

study)

■ Investigated the influence of nanoparticle size and shape on neurotoxicologic potential, using nanosphere and nanowire TiO2 particles. 

■ Evaluated neuroinflammatory responses following pulmonary exposure to TiO2 nanosphere (NS), short TiO2 nanowires (SNW) and long 

TiO2 nanowires (LNW).

■ Demonstrated that the potential of TiO2 nanomaterials to elicit neuroinflammation was LNW>SNW>NS, indicating that particle size and 

shape influenced the toxicological response.

Publications and Abstracts

■ 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. Society of 

Toxicology annual meeting, Charlotte, NC, March 25–29, Toxicologist 

96(1):288.

■ Antonini JM, Roberts JR, Sriram K, Benkovic SA, O’Callaghan JP, 

Miller DB [2008]. Extrapulmonary tissue distribution of metals following repeated lung exposures to welding fumes with different elemental 
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NIOSH Nanotechnology Research Center

profiles. Society of Toxicology annual meeting, Seattle, WA, March 

16–20. Toxicologist 102(1):226.

■ Porter DW, Holian A, Sriram K, Wu N, Wolfarth M, Hamilton R, 

Buford M [2008]. Engineered titanium dioxide nanowire toxicity in 

vitro and in vivo. Society of Toxicology annual meeting, Seattle, WA, 

March 16–20. Toxicologist 102(1):306.

■ Porter D, Sriram K, Wolfarth M, Jefferson A, Schwegler-Berry D, 

Andrew ME, Castranova V [2008]. A biocompatible medium for 

nanoparticle dispersion. Nanotoxicology 2(3):144–154.

■ Hubbs AF, Mercer RR, Sriram K, Castranova V, Chen BT, McKinney W, 

Frazer DG, Battelli L, Willard P, Scabilloni J, Schwegler-Berry D, Porter 

D [2008]. Acute respiratory toxicologic pathology of inhaled multiwalled carbon nanotubes. Vet Pathol 45:786. 
46

NIOSH Nanotechnology Research Center

Project 11: Lung Effects of Resistance Spot

 Welding Using Adhesives

Principal Investigator: James Antonini, Ph.D.

Project Duration: FY 2007–2010

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Designed a resistance spot welding generator for animal inhalation 

studies.

■ Nearly completed construction of the resistance spot welding generator.

■ Characterized the physical and chemical properties of aerosols generated after heating adhesives used in resistance spot welding.

Publications and Abstracts

■ Afshari AA, Antonini JM, Castranova V, Boylstein R, Kanwal R, Frazer 

DG [2008]. Design of an inhalation exposure system to study resistance spot welding fume characteristics and biological effects. Society 

of Toxicology annual meeting, Seattle, WA, March 16–20. Toxicologist 

102:226.

Invited Presentations

■ Chen BT, Stone S, Schwegler-Berry D, Frazer A, Donlin M, Cumpston 

J, Afshari A, Frazer D, Castranova V, Antonini JM [2007]. Characterization of welding fume particles generated from a robotic welding 

system. American Association for Aerosol Research annual conference, 

Reno, NV, September 24.

■ Antonini J [2008]. Health effects of welding. American Industrial Hygiene Association conference and exposition, Minneapolis, MN, May 

31–June 5. 
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NIOSH Nanotechnology Research Center

Project 12: Neurotoxicity after Pulmonary

 Exposure to Welding Fumes

Principal Investigator: James Antonini, Ph.D.

Project Duration: FY 2007–2010

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Characterized the physical properties of aerosol generated by welding 

and observed a significant number of welding particles in the nanoparticle-size range.

■ Observed that, after inhalation, stainless steel particles persist in the 

lung and induce greater lung damage than mild steel particles.

■ Observed the translocation of metals associated with welding fume 

(e.g., manganese and chromium) to other organ systems, including 

specific regions of the brain.

■ Observed some alterations in inflammatory mediators in brain tissue 

from specific lung region.

Publications and Abstracts

■ Santamaria AB, Cushing CA, Antonini JM, Finley BL, Mowat FS 

[2007]. Potential neurological effects of manganese exposure during 

welding: a state-of-the-science analysis. J Toxicol Environ Health, Part 

B, 10:417–465.

■ Antonini JM, Stone S, Roberts JR, Chen B, Schwegler-Berry D, Afshari 

AA, Frazer DG [2007]. Effect of short-term stainless steel welding 

fume inhalation exposure on lung inflammation, injury, and defense 

responses in rats. Toxicol Appl Pharmacol 223:234–245.

■ Antonini JM, Roberts JR [2007]. Comparison of lung injury and inflammation after repeated treatment with welding fumes collected from 

different welding processes. Society of Toxicology annual meeting, 

Charlotte, North Carolina, March 25–29. Toxicologist 96:103–104.

■ Antonini JM, Stone S, Roberts JR, Chen B, Frazer DG [2007]. Delayed 

inflammatory response after inhalation of stainless steel welding fume 
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NIOSH Nanotechnology Research Center

in rats. American Thoracic Society international conference, San Francisco, California, May 18–23. Am J Respir Crit Care Med 175:A429.

■ Zeidler-Erdely PC, Kashon ML, Battelli LA, Young S-H, Erdely AD, 

Roberts JR, Reynolds SH, Antonini JM [2008]. Lung inflammation and 

tumor induction in lung tumor susceptible A/J and resistant C57BL/6J 

mice exposed to welding fume. Part Fibre Toxicol 5:12.

■ Antonini JM, Roberts JR, Sriram K, Benkovic SA, O’Callaghan JP, 

Miller DB [2008]. Extrapulmonary tissue distribution of metals following repeated lung exposures to welding fumes with different elemental 

profiles. Society of Toxicology annual meeting, Seattle, WA, March 

16–20. Toxicologist 102:226.

■ Antonini JM, Stone S, Roberts JR, Schwegler-Berry D, Moseley A, 

Donlin M, Cumpston J, Afshari A, Frazer DG [2008]. Pulmonary 

effects and tissue distribution of metals after inhalation of mild steel 

welding fume. American Thoracic Society international conference, 

Toronto, Ontario, Canada, May 2008. Am J Respir Crit Care Med 

177:A910.

Invited Presentations

■ Antonini J [2008]. Manganese exposure during welding. Institute of 

Occupational and Environmental Health, West Virginia University, 

Morgantown, WV, Occupational Medicine Grand Rounds Seminar, 

March 4. 

■ Antonini J [2008]. Health effects of welding. American Industrial Hygiene Association conference and exposition 2008, Minneapolis, MN, 

May 31–June 5. 
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NIOSH Nanotechnology Research Center

Project 13: Potential Aneuploidy Following

 Exposure to Carbon Nanotubes

Principal Investigator: Linda Sargent, Ph.D.

Project Duration: FY 2007–2008

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Primary and immortalized human small airway epithelial cells were 

cultured and then exposed to SWCNTs or a positive control vanadium 

pentoxide to investigate the potential of CNTs to induce genetic damage in normal lung cells. The nanotubes had an average diameter of 1.1 

nanometer and a length of 100–1,000 nanometers. Cellular tubulin, 

mitotic spindle integrity, and centriole number were determined by 

immunofluorescence for beta-tubulin and centrin and photographed 

using fluorescent and confocal laser scanning microscopy. The chromosome number was examined by fluorescent in situ hybridization.

■ Binucleate cells, large polyploid appearing nuclei, bundled tubulin, and 

fragmented centrosomes were observed following 24 hours of exposure 

to either SWCNT or vanadium pentoxide.

■ The SWCNT-treated cells were further examined by fluorescent in situ 

hybridization (FISH) using large genomic probes labeled with fluorescent tags. FISH showed that the large nuclei were polyploid. The 

number of chromosomes per cell was not normal (aneuploid). Mitotic 

spindles were found to have multiple poles and many cells had anaphase bridges with fragmenting chromatin. Using different interference 

confocal microscopy (DIC), SWCNT were observed to be inside the 

cells. DIC combined with fluorescent confocal laser imaging showed 

that many of the cells had SWCNT in the nucleus and within the cellular and mitotic tubulin. Some of the binucleate cells appeared to be 

connected by SWCNT. CNTs in the mitotic spindle appear to distort 

the mitotic spindle apparatus. This damage was seen even at the lowest 

dose (24 μg/cm3). 

■ The researcher contacted Dr. Jeffrey Salisbury to obtain a construct for 

one of the centrosome genes with a green fluorescent protein tag to 

allow confirmation of the centrosome fragmentation and also to follow the changes of the centrosome during the cell cycle. Dr. Salisbury 
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NIOSH Nanotechnology Research Center

will send antibodies for the centrosome that are more specific than 

commercially available antibodies. These antibodies can increase the 

sensitivity of the detection of the centrosome. Dr. Salisbury will also 

participate in imaging the SWCNT treated cells by electron microscopy 

both in the cell and following isolation of the centrosomes by a gradient. The centrosome work will be published separately.

Invited Presentations

■ Sargent L [2008]. Genetic impact of carbon nanotubes and chemically 

specific genetic changes in lung adenocarcinoma. Naval Health Research Center, Detachment, Environmental Health Effects Laboratory, 

Wright-Patterson AFB, Dayton, OH, May 28. 

■ Sargent L [2008]. Genetic damage following carbon nanotube exposure. Mary Babb Randolph Cancer Center-National Institute of Occupational Safety and Health scientific retreat in cancer, February 12.
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NIOSH Nanotechnology Research Center

Project 14: Pulmonary Toxicity of Carbon

 Nanotube Particles

Principal Investigator: Anna Shvedova, Ph.D.

Project Duration: FY 2004–2008

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Low levels of antioxidants in vitamin E-deficient mice were associated 

with a higher sensitivity to SWCNT-induced acute inflammation, released LDH, total protein content, levels of proinflammatory cytokines, 

and enhanced profibrotic responses and collagen deposition. 

■ Exposure to SWCNTs markedly shifted the ratio of cleaved to fulllength extracellular superoxide dismutase (EC-SOD) in the lungs. 

Found no differences in the EC-SOD responses to SWCNT-induced 

oxidative stress between vitamin E-deficient and vitamin E-sufficient 

animals.

■ Sequential exposure to carbon nanotubes and bacteria enhanced pulmonary inflammation and infectivity. 

■ Decreased bacterial clearance in SWCNT-pre-exposed mice was associated with decreased phagocytosis of bacteria by macrophages and a 

decrease in nitric oxide production by these phagocytes. 

■ Failure of SWCNT-exposed mice to clear Lysteria led to a continued elevation in nearly all major chemokines and acute phase cytokines into 

the later course of infection.

Electron micrograph of 

carbon nanotubes at 

8,800x
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NIOSH Nanotechnology Research Center

■ An increased accumulation of neutrophils and decreased fibrosis was 

observed in the lungs of NADPH oxidase-deficient C57BL/6 mice 

exposed to CNTs. This corresponded to elevated levels of apoptotic 

cells in the lungs, production of proinflammatory cytokines, decreased 

production of the anti-inflammatory and profibrotic cytokine, TGFbeta, and reduced levels of collagen deposition. 

■ NADPH oxidase is an important regulator of the transition from the 

acute inflammation to the chronic fibrotic stage in response to SWCNT.

■ Developed a generation system that aerosolizes SWCNT for an inhalation study. The resulting aerosol was size-separated using a settling 

chamber and two cyclones to produce a respirable aerosol. 

■ The mass output efficiency of the entire system for producing a respirable aerosol from bulk material was estimated to be about 10%.

■ Completed inhalation study of SWCNT in C57BL/6 mice. 

■ The inhalation of nonpurified SWCNT (iron content of 17.7% by 

weight) at 5 mg/m3 5 hr/day for 4 days was compared with pharyngeal 

aspiration of varying doses (5–20 ug per mouse) of the same SWCNT. 

■ The chain of pathological events in both exposure routes was realized 

through synergized interactions of early inflammatory response and 

oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. 

■ SWCNT inhalation was more effective than aspiration in causing 

inflammatory response, oxidative stress, collagen deposition, and 

fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 

mice.

Publications and Abstracts

■ 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 from airborne 

nanoparticles. In: Monteiro-Riviere NA, Tran CL, eds. Nanotoxicology: 

characterization, dosing, and health effects. New York: Informa Healthcare USA Inc.

■ Kagan VE, Rao KMK, Kisin ER, Young S-H, Meighan T, Murray AR, 

Tyurina YY, Castranova V, Shvedova AA [2007]. Pulmonary effects 

of single-walled carbon nanotubes: inflammatory response, oxidative 

stress/signaling, and recognition by macrophages. In: Simeonova PP, 
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NIOSH Nanotechnology Research Center

Opopol N, Luster MI, eds. Nanotechnology: toxicological issues and 

environmental safety, NATO security through science series book, New 

York: Springer-Verlag, pp. 65–75.

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

V, Young SH, Gao F, Tyurina YY, Oury TD, Kagan VE [2007]. VitaminE deficiency enhances pulmonary inflammatory response and oxidative 

stress induced by single-walled carbon nanotubes in C57BL/6 mice. 

Toxicol Appl Pharmacol 221(3):339–348.

■ Fadeel B, Kagan V, Krug H, Shvedova A, Svartengren M, Tran L, 

Wiklund L [2007]. There’s plenty of room at the forum: potential 

risks and safety assessment of engineered nanomaterials. Nanotoxicol 

1(2):73–84. 

■ Kisin ER, Murray AR, Keane MJ, Shi XC, Schwegler-Berry D, Gorelik 

O, Arepalli S, Castranova V, Wallace WE, Kagan VE, Shvedova AA 

[2007]. Single-walled carbon nanotubes: geno- and cytotoxic effects in 

lung fibroblast V79 cells. J Tox Environ Health, Part A, 70(24):2071–

2079.

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

V, Young SH, 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 C57BL/6 mice. 

Toxicologist 96(1):A179.

■ Mercer RR, Scabilloni JF, Wang L, Schwegler-Berry D, Shvedova AA, 

Castranova V [2007]. Dispersion significantly enhances the pulmonary 

toxicity of single-walled carbon nanotubes. Toxicologist 96(1):A1115.

■ Baron PA, Deye GJ, Chen B-T, Schwegler-Berry D, Shvedova AA, Castranova V [2008]. Aerosolization of single-walled carbon nanotubes for 

an inhalation study. Inhal Tox 20(8):751–760.

■ Shvedova AA, Fabisiak JP, Kisin ER, Murray AR, Roberts JR, Tyurina 

YY, Antonini JM, Feng WH, Kommineni C, Reynolds J, Barchowsky A, 

Castranova V, Kagan VE [2008]. Sequential exposure to carbon nanotubes and bacteria enhances pulmonary inflammation and infectivity. 

Am J Respir Cell Mol Biol 38:579–590.

■ Shvedova AA, Kisin E, Murray AR, Kommineni C, Castranova V, 

Fadeel B, Kagan VE [2008]. Accumulation of neutrophils and decreased fibrosis in NADPH oxidase-deficient C57BL/6 mice exposed to 

carbon nanotubes. Tox Appl Pharm 231(2):235–240.
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NIOSH Nanotechnology Research Center

■ Shvedova AA, Kisin E, Murray AR, Johnson VJ, Gorerlik O, Arepalli 

S, Hubbs F, Mercer RR, Keohavong P, Sussman N, Jin J, Yin J, Stone 

S, Chen BT, Deye G, Maynard A, Castranova V, Baron PA, Kagan VE 

[2008]. Inhalation versus aspiration of single-walled carbon nanotubes 

in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Am J Physiol Lung Cell Mol Physiol 295(4):L552–565.

■ Kisin E, Murray A, Keane M, Shi X, Schwegler-Berry D, Gorelik O, 

Arepalli S, Castranova V, Wallace W, Kagan V, Shvedova A [2008]. 

Single-walled carbon nanotubes: geno- and cytotoxic effects in lung 

fibroblast V79 cells. Toxicologist 102(1):A441.

■ Murray AR, Kisin E, Fabisiak JP, Roberts JR, Antonini JM, Kommineni C, Reynolds J, Barchowsky A, Castranova V, Kagan V, Shvedova 

AA [2008]. Combined exposure to carbon nanotubes and bacteriaenhanced pulmonary inflammation and infectivity. Toxicologist 

102(1):A1494.

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

Hubbs AF, Mercer RR, Stone S, Frazer D, Chen T, Deye G, Maynard A, 

Baron P, Mason R, Kadiiska M, Stadler K, Mouithys-Mickalad A, Castranova V, Kagan VE [2008]. Inhalation of carbon nanotubes induces 

oxidative stress and cytokine response causing respiratory impairment 

and pulmonary fibrosis in mice. Toxicologist 102(1):A1497.

MWCNT in the lungs of 

a mouse 56 days after 

exposure. The shorter fiber 

on the right is penetrating the lung wall from the 

alveolar space. The longer 

fiber on the upper left has 

penetrated the outer wall 

of the lung into the pleural 

space.
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NIOSH Nanotechnology Research Center

Invited Presentations

■ Shvedova AA [2007]. Pulmonary toxicity of singled-walled nanotubes. 

International conference on nanotoxicology, Venice, Italy, April 19 and 

21.

■ Shvedova AA [2007]. Pulmonary toxicity of nanoparticles. Experimental biology meeting, Washington, DC, April 30–May 3.

■ Shvedova AA [2007]. Pulmonary toxicity of single-walled nanotubes in 

vivo: mechanisms and consequences. National Aeronautics and Space 

Administration/National Institute of Standards and Technology workshop on nanotube measurements. National Institute of Standards and 

Technology, Gaithersburg, MD, September 26–28.

■ Shvedova AA [2007]. Inhalation exposure to single-walled carbon 

nanotubes. European NanOSH conference—nanotechnologies: a critical area in occupational safety and health, Helsinki, Finland, December 

3–5.

■ Shvedova AA [2008]. Single-walled carbon nanotubes: are they mutagenic? Mary Babb Randolph Cancer Center—National Institute of Occupational Safety and Health scientific retreat in cancer, Morgantown, 

WV, February 12.

■ Shvedova AA, Kagan VE [2008]. Pulmonary toxicity of carbon nanotubes in vivo: mechanisms, regulations, and reality. Nanomaterials: 

environmental risks and benefits and emerging consumer products, 

Faro, Portugal, April 27–30. 

■ Shvedova AA [2008]. Carbon nanotube in the rodent lungs: recognition and modulation of toxicity. American Thoracic Society, international conference, Toronto, Canada, May 16–21.

■ Shvedova AA [2008]. Relevance of animal model studies: aspiration vs. 

inhalation. Second international conference: nanotoxicology, Zurich, 

Switzerland, September 7–10.
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NIOSH Nanotechnology Research Center

Project 15: Dermal Toxicity of Nanotube

 Particles

Principal Investigator: Anna Shvedova, Ph.D.

Project Duration: FY 2005–2010

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ SWCNTs induced geno- and cytotoxic effects in lung fibroblast V79 

cells when assessed using different test systems: the comet and micronucleus assays.

■ Engineered human skin exposed to unpurified SWCNT showed increased epidermal thickness and accumulation and activation of dermal fibroblasts with increased collagen level and release of proinflammatory cytokines. 

■ Exposure of murine epithelial JB6 P+ cells to unpurified SWCNT (30% 

iron) resulted in the production of ESR detectable hydroxyl radicals 

and caused a significant dose-dependent activation of AP-1. 

■ Detected no significant changes in AP-1 activation when partially purified SWCNT (0.23% iron) were introduced to JB6 P+ cells.

■ NF-κB was activated in a dose-dependent fashion by exposure to both 

unpurified and partially purified SWCNT. 

■ Topical exposure of SKH-1 mice to unpurified SWCNT induced free 

radical generation, oxidative stress, and inflammation, thus causing 

dermal toxicity.

Publications and Abstracts

■ Fadeel B, Kagan V, Krug H, Shvedova A, Svartengren M, Tran L, 

Wiklund L [2007]. There’s plenty of room at the forum: potential 

risks and safety assessment of engineered nanomaterials. Nanotoxicol 

1(2):73–84.

■ Kisin ER, Murray AR, Keane MJ, Shi XC, Schwegler-Berry D, Gorelik 

O, Arepalli S, Castranova V, Wallace WE, Kagan VE, Shvedova AA 

[2007]. Single-walled carbon nanotubes: geno- and cytotoxic effects in 

fibroblast V79 cells. J Tox Environ Health, Part A, 70(24):2071–2079.
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NIOSH Nanotechnology Research Center

■ Tyurina YY, Basova LV, Konduru NV, Tyurin VA, Potapovich AI, Cai 

P, Bayir H, Stoyanovsky D, Pitt BR, Shvedova AA, Fadeel B, Kagan VE 

[2007]. Nitrosative stress inhibits the aminophospholipid translocase 

resulting in phosphatidylserine externalization and macrophage engulfment: implications for the resolution of inflammation. J Biol Chem 

282(11):8498–8509.

■ Kagan VE, Tyurina YY, Konduru N, Basova LV, Stolz D, Kisin ER, 

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

Toxicologist 96(1):233.

■ Feng W, Tyurina YY, Bayir H, Shvedova AA, Kagan VE [2007]. Phosphatidlyserine enhances recognition and uptake of single-walled carbon nanotubes by rat brain microglial cells. Toxicologist 96(1):289. 

■ Murray AR, Kisin E, Kommineni C, Kagan VE, Castranova V, Shvedova AA [2007]. Single-walled carbon nanotubes include oxidative stress 

and inflammation in skin. Toxicologist 96:A1406.

■ Ding M, Zhao J, Bowman L, Leonard S, Lu Y, Kisin E, Murray A, 

Vallyathan V, Castranova V, Shvedova A [2008]. Induction of AP-1-

MAPKs and NF-KB signal pathways by tungsten carbide-cobalt particles. Toxicologist 102(1):A1031.

■ Feng W, Konduru NV, Tyurina YY, Clark K, Stolz DB, Bayir H, Fadeel 

B, Shvedova AA, Kagan VE [2008]. Involvement of endocytosis in uptake of phosphatidylserine-coated single-walled carbon nanotubes by 

RAW 264.7 macrophages. Toxicologist 102(1):213.

Invited Presentations

■ Shvedova AA [2008]. Single-walled carbon nanotubes: are they mutagenic? Mary Babb Randolph Cancer Center—National Institute of Occupational Safety and Health scientific retreat in cancer, Morgantown, 

WV, February 12.

■ Murray AR, Kisin ER, Leonard SS, Kommineni C, Kagan VE, Castranova V, Shvedova AA [2008]. Induction of oxidative stress and inflammation in the skin following exposure to single-walled carbon nanotubes. Zurich, Switzerland, March 12–15.
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NIOSH Nanotechnology Research Center

Project 16: Specific Biomarkers for Unusual

 Toxicity of Nanomaterials

Principal Investigator: Liying Wang Rojanasakul, Ph.D.

Project Duration: FY 2007–2008

Critical Topic Area: toxicology and internal dose 

Accomplishments and Research Findings

■ In vitro cellular models were developed for fibrogenic and biomarker 

studies of CNTs, such as collagen and collagenase production from 

fibroblasts and TGF-β production from lung epithelial cells.

■ Data from this project provided important preliminary findings used in 

obtaining NORA grant funding.

Publications and Abstracts

■ Wang L, Castranova V, Rojanasakul Y, Lu Y, Scabilloni J, Mercer RR 

[2008]. Direct fibrogenic effects of dispersed single-walled carbon 

nanotubes on human lung fibroblasts. Society of Toxicology annual 

meeting, Washington, DC, March 16–20. Toxicologist 102:A1499. 

■ Wang L, Castranova V, Mercer RR, Wu N, Tiao Li T, Li S, Hall J, Li M, 

Rojanasakul Y [abstract accepted]. Nanoparticle dispersion method 

using natural lung surfactant. Society of Toxicology annual meeting, 

Baltimore, Maryland, March 2009.

Invited Presentations

■ Wang L [2007]. Carbon nanotubes exhibit tumorigenic and fibrogenic 

potential in vitro. West Virginia University research meeting, Morgantown, WV, September. 

■ Wang L [2008]. Meeting with the National Institute of Occupational 

Health and Poison Control on nanotoxicology research, Beijing, China, 

November 16 and 17.

■ Castranova V [2008]. The ability of in vitro tests to predict pulmonary 

responses to SWCNT. John Hopkins University, Baltimore, MD, June 11.
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NIOSH Nanotechnology Research Center

Project 17: Pulmonary Toxicity of Diesel

 Exhaust Particles

Principal Investigator: Jane Ma, Ph.D.

Project Duration: FY 2003–2008

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Diesel-exhaust-particle (DEP) exposure induces lung inflammation 

and injury, which are mediated through reactive oxygen/nitrogen species (ROS/RNS) generation by alveolar macrophages (AM). 

■ C57B/6J wild type (WT) and iNOS knockout (iNOS KO) mice were 

exposed to saline, carbon black (35 mg/kg), or organic extract of DEP 

(DEPE) by aspiration and sacrificed at 1, 3, and 7 days postexposure. 

Carbon black, but not DEPE, significantly induced neutrophil infiltration in both WT and iNOS KO mice. 

■ Carbon black, but not DEPE, exposure results in inflammatory lung 

injury, suggesting that DEP-induced pulmonary inflammation is derived from the particulate. Nitric oxide (NO) does not play a significant 

role in Carbon-black-induced polymorphonuclear neutrophils (PMN) 

infiltration, air/capillary damage, and cytotoxicity. 

■ Carbon-black-exposed AM exhibited enhanced superoxide anion generation, peaking at 3 days post exposure. Carbon black exposure also 

induced mitochondrial damage, monitored as reduction of mitochondrial membrane potential in AM, which was not markedly affected 

by the NO deficiency. In contrast, DEPE did not significantly induced 

ROS generation or mitochondrial function in AM.

■ Carbon black and DEPE did not significantly affect adenosine triphosphate (ATP) levels in either WT or iNOS KO mice, because mitochondrial oxidative phosphorylation pathway is not the major energy source 

for AM. 

■ Transmission electron microscopy analysis has shown that animals exposed to DEP or carbon black, but not DEPE, were heavily laden with 

particle-filled vacuoles in the lung.
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NIOSH Nanotechnology Research Center

■ Vacuoles containing DEP from DEP-exposed animals were frequently 

associated with mitochondria or were in direct membrane-to-membrane contact with mitochondria, demonstrating that mitochondrial 

function was compromised. In contrast, carbon-black-filled vacuoles 

did not display functionally impaired mitochondria, and no intracellular vacuoles were found in animals exposed to DEPE.

■ DEP and carbon black both induced DNA damage in AM using comet 

assay. DEPE did not.

Publications and Abstracts

■ Ma JYC, Millecchia L, Barger MW, Ma JKH, Castranova V [2007]. 

Diesel exhaust particle-induced oxidant injury and cellular responses 

in wild type and inducible nitric oxide synthase-deficient (iNOS KO) 

mice: roles of particle core and adsorbed organics. Toxicologist 96(S1):A183.

■ Yin XJ, Dong CC, JYC, Roberts JR, Antoni J, Ma JKH [2007]. Suppression of phagocytic and bactericidal functions of rat alveolar macrophages by the organic component of diesel exhaust particles. J Toxicol 

Environ Health, Part A, 70(10):820–828.

Invited Presentations

■ Ma JYC [2008]. Effects of exposure to diesel exhaust particles on the 

susceptibility of the lung to infection. The Feinstein Institute for Medical Research, Manhasset, NY, April 8.
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NIOSH Nanotechnology Research Center

Project 18: Induction of Lung Fibrosis by

 Cerium Oxide in Diesel Exhaust

Principal Investigator: Jane Ma, Ph.D.

Project Duration: FY 2009–2012 (preliminary data gathering started in FY 2008) 

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

I. In vitro studies

■ Cerium oxide did not induce intracellular oxidant generation or alter 

mitochondrial function of alveolar macrophages (AM) but significantly damaged AM membrane integrity, induced apotosis, affected 

macrophage inflammatory responses, including increased TNF-α, but 

reduced IL-12 production. These results suggest that cerium oxide can 

cause direct cellular damage to AM.

■ Performed tests suggest that cerium oxide, under coexposure, may 

elicit new cellular toxicity in addition to DEP-induced toxicity and that 

cerium oxide suppresses cellular defense capability.

■ Previous studies have shown that nitric oxide plays an important role 

in the DEP-induced IL-12 production by AM. The decreased nitric 

oxide production in response to LPS challenge by cerium oxide is probably due to its redox characteristic, subsequently leading to the suppressed IL-12. In the coexposure cell culture, cerium oxide depressed 

DEP- and LPS-induced IL-12 secretion, suggesting that cerium oxide 

suppresses cellular defense capability.

II. In vivo studies

■ Cerium oxide administered intratracheally to Sprague Dawley rats 

induced significant neutrophil infiltration and elevated lactate dehydrogenase activity and albumin content in the BAL fluid, suggesting 

that these particles induced inflammation, cytotoxicity, and epithelial 

damage. 

■ Found a direct interaction of cerium oxide with AM, resulting in elevated AM phagocytic activity as monitored using confocal microscopy.
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NIOSH Nanotechnology Research Center

■ Cerium oxide exposure increased reactive oxygen species production 

in response to zymosan challenge as indicated by enhanced chemiluminescence generation.

■ Cerium oxide significantly reduced nitric oxide production by AM in 

response to ex vivo LPS challenge, demonstrating that these particles 

may modify AM host defense capability.

Publications and Abstracts

■ Ma JY, Hongwen Z, Barger M, Castranova V, Ma JK [2008]. Effects 

of cerium oxide on rat primary alveolar macrophages. Toxicologist 

102(1):A1513.

■ Ma JY, Zhao H, Barger M, Murali R, Meighan T, Castranova V, Ma JK 

[abstract accepted]. Pulmonary responses to diesel fuel catalyst cerium 

oxide nanoparticles. Society of Toxicology annual meeting, Baltimore, 

MD, March 2009.
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NIOSH Nanotechnology Research Center

Project 19: Potential Effects of Silicon-based

 Nanowires on Lung Toxicity

Principle Investigators: Stephen S. Leonard and Jenny R. 

Roberts

Project Duration: FY 2008–2010

Critical Topic Area: toxicology and internal dose 

Accomplishments and Research Findings

■ Completed physical characterization of silicon-based nanowires generated by IBM and titanium nanowires to be used as a control/reference 

material. 

■ Characterized and quantified nanowire-associated reactive oxygen 

species (ROS) using a cell-free model system and quantified nanowireinduced free radical generation in vitro in alveolar macrophages. 

■ Measured and evaluated pulmonary toxicity parameters in vivo using 

a titanium nanowire to assess the potential of the material as a control. 

The nanowires induced a transient, dose-dependent response in the 

lungs of rats that included increases in indicators of inflammation and 

oxidative stress. 

■ Evaluated the ability of pulmonary exposure to titanium nanowires 

to alter responses to a pulmonary infection. Only the highest dose of 

nanowires altered response to infection, inducing an increase in resolution of infection.

■ Evaluated a potential fluorescent marker, quantum dots, for tracking 

distribution of nanomaterials in the lung.

Publications and Abstracts

■ 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. Society of Toxicology annual meeting, 

Charlotte, North Carolina, March 25–29. Toxicologist 96:230.

■ Leonard SS, Castranova V, Chen BT, Schwegler-Berry D, Hoover M, 

Piacitelli C, Gaughan D [2007]. Particle-size-dependent radical generation from wildland fire smoke. Toxicol 236:103–113.
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■ Pacurari M, Yin XJ, Zhao J, Ding M, Leonard SS, Schwegler-Berry 

D, Ducatman BS, Sbarra D, Hoover MD, Castranova V, Vallyathan V 

[2008]. Raw single-wall carbon nanotubes induce oxidative stress and 

activate MAPKs, AP-1, NF-kB, and Akt in normal and malignant human mesothelial cells. Environ Health Perspect 116(9):1211–1217. 

■ Roberts JR, Schwegler-Berry D, Leonard SS, Karim A, Tirumala V, 

Antonini JM, Castranova V [2008]. Pulmonary toxicity associated with 

nondispersed titanium dioxide nanorods. Society of Toxicology annual 

meeting, Seattle, Washington, March 16–20. Toxicologist 102:308.

■ Ding M, Zhao J, Bowman LL, Leonard SS, Lu Y, Vallyathan V, Castranova V, Shvedova AA [2008]. Induction of AP-1-MAPKs and NF-kB 

signal pathways by tungsten carbide-cobalt particles. Toxicologist 

102:212, A1031.

■ Roberts JR, Antonini JM, Porter DW, Castranova V, Mercer RR [2008]. 

Characterization of pulmonary responses following treatment of rats 

with fluorescently labeled quantum dots with different surface functional groups. American Thoracic Society international conference, 

Toronto, Ontario, Canada, May 16–17, 2008. Am J Respir Crit Care 

Med 117:A49.

■ Roberts JR, Schwegler-Berry D, Chapman R, Antonini JM, Scabilloni 

JF, Castranova V, Mercer RR [abstract submitted]. Biodistribution of 

quantum dots after pulmonary exposure in rats. Society of Toxicology 

annual meeting, Baltimore, MD, March 2009.

■ Chapman R, Roberts JR, Castranova V, Leonard SS [abstract accepted]. 

Generation of reactive oxygen species by silicon nanowires. Society of 

Toxicology annual meeting, Baltimore, MD, March 2009.

■ Rushton EK, Jiang J, Leonard SS, Eberly S, Castranova V, Biswas P, 

Elder A, Gelein R, Finkelstein J, Oberdorster G [accepted for publication]. Predicting nanoparticle toxicity: evaluation of screening assays. 

Environ Health Perspect.
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Project 20: Cell-Based Assessment for Iron

 Nanoparticle-Induced Health

 Risks

Principal Investigator: Yong Qian

Project Duration: FY 2008–2010

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Developed a cell-based model for assessing nanoparticle particleinduced health risks.

■ Trained one post-doctoral fellow and one graduate student in nanotechnology research for advancement of their professional careers in 

the field.

■ Data from this project provided key preliminary results for a successful 

Pilot Funding Grant from the Mary Babb Randolph Cancer Center in 

the Health Sciences Center at West Virginia University.

Publications and Abstracts

■ Apopa PL, Qian Y, Guo NL, Schwegler-Berry D, Pacurari M, Porter 

D, Shi X, Vallyathan V, Castranova V, Flynn DC [in press]. Iron oxide 

nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule 

remodeling. Particle and Fibre Toxicology.

■ Apopa PL, Guo NL, Schwegler-Berry D, Pacurari M, Porter D, Shi X, 

Vallyathan V, Castranova V, Flynn DC, Qian Y [in press]. Iron oxide 

nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule 

remodeling. Annual Society of Toxicology Meeting.
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Project 21: Assessment of Carbonaceous

 Materials on Mutagenicity

Principal Investigator: Anna A. Shvedova, Ph.D., D.Sc.

Project Duration: FY 10/1/08–9/30/09

Critical Topic Area: toxicology and internal dose

Accomplishments and Research Findings

■ Inhalation exposure of C57BL/6 mice (5 mg/m3, 5 hr a day, 4 days) to 

respirable SWCNT caused formation of anuclear macrophages with 

fibrillar cytoplasm along with mitotic changes was seen in the lung interstitial cells. Pattern of anaphase bridges in macrophages was clearly 

detected at 7 and 28 days post inhalation. Therefore, such mitotic 

changes within macrophage with anaphase bridges indicated feasible 

spindle aberrations.

■ Post-exposure findings (7-days) revealed observable foci of bronchiolar 

epithelial cell hypertrophy in all exposed mice. Post-exposure findings 

(28-days) revealed bronchiolar epithelial cell hypertrophy and hyperplasia in all exposed mice.

■ Severe oxidative stress observed in the lung of mice exposed to inhalable SWCNT revealed depletion of GSH, protein thiol oxidation, 

accumulation of lipid peroxidation products, reduced total antioxidant reserves, and augmentation of 8-hydroxy-2’-deoxyguanosine 

(8-OHdG)—a marker of oxidative D damage. 

■ K-ras mutations were observed in the lung of C57BL/6 mice after 

inhalation exposure to SWCNT. The first 2 mutations in DNA samples 

corresponded to a change in the wild type K-ras gene codon 12 (GGT, 

glycine) to AGT (lane 2, serine) and GAT (lane 3, aspartate). The third 

mutation was a double mutation consisting of a GGT to GAT (glycine 

to aspartate at codon 12) and a GTG to ATG (valine to methionine at 

codon 8)].

■ One of the mutations found in SWCNT exposed mice by inhalation 

route (at day 28 post exposure) consisted of a double mutation occurring at codons 12 and 8 [GGT to GAT and GTG to ATG (valine to 

methionine), respectively. The role of this double mutation is unknown 

and may be specific for SWCNT exposure.
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Publications and Abstracts

■ Shvedova AA, Kisin E, Murray AR, Johnson, VJ, Gorerlik O, Arepalli 

S, Hubbs F, Mercer RR, Keohavong P, Sussman N, Jin J, Yin J, Stone 

S, Chen BT, Deye G, Maynard A, Castranova V, Baron PA, Kagan VE 

[2008]. Inhalation versus aspiration of single walled carbon nanotubes 

in C57BL/6 mice: inflammation, fibrosis, oxidative stress and mutagenesis. Am J Physiol Lung Cell Mol Physi 295(4):L552–65.

■ Elder A, Lynch I, Grieger K, Chan-Remillard S, Gatti A, Gnewuch H, 

Kenawy E-R, Korensten R, Kuhlbusch T, Linker F, Matias S, monteiroRiviere N, pinto V, Rudnitsky R, Savolainen K, Shvedova A [2008]. 

Deposition of nanoparticles as a function of their interactions with 

biomolecules. In “Nanomaterials Risks and Benefits”, Eds. Linkov & 

Steevens, Springer, The Netherland, pp. 3–29, (Proceedings of the 

NATO Advanced Research Workshop on Nanomaterials: Environmental Risks and Benefits Faro, Portugal, April 27–30.

■ Shvedova AA, Kisin ER, Porter D, Schulte P, Kagan VE, Fadeel B, 

Castranova V [2008]. Mechanisms of pulmonary toxicity and medical 

applications of carbon nanotubes: Two faces of Janus? Pharmacol Ther 

December 6, PMID:19103221. [Epub ahead of print].

Invited Presentation

■ Shvedova AA [2008]. Single-walled carbon nanotubes: Are they mutagenic? Mary Babb Randolph Cancer Center. National Institute of Occupational Safety and Health MBRCC, NIOSH Scientific Retreat in Cancer, Morgantown, WV, February 12.
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NIOSH Nanotechnology Research Center

Project 22: Generation and Characterization 

of Nanoparticles

Principal Investigator: Bon-Ki Ku, Ph.D.

Project Duration: FY 2004–2008

Critical Topic Area: measurement methods

Accomplishments and Research Findings

■ Developed an electrospray generation system to produce SWCNT aerosols with well-defined morphology for the purpose of evaluation instrument response to different morphology and possibly applying them to in 

vitro cell culture toxicity tests.

■ Field-tested size-selected nanoparticle measurement techniques and 

sampling methods in workplaces for physical and chemical analysis using transmission electron microscopy.

■ Characterized purified SWCNTs generated by electrospraying of suspensions. 

■ Conducted research on the relationship among electrical mobility, 

mass, and size for nanodrops 1–6.5 nm in diameter. 

■ Demonstrated that the established relation (which is used in the scanning mobility particle sizer) between electrical mobility and mass diameter for a sphere can be applied with confidence over the whole size 

range down to 1.3 nm.

■ Established significant partnerships with the University of Minnesota, 

University of Iowa, and Yale University.

■ Investigated the relationship between aerodynamic and mobility diameters of SWCNTs and MWCNTs and airborne carbon nanofiber.

■ In conjunction with the University of Minnesota, applied a new 

method to characterize the structure of airborne SWCNTs. The results 

obtained are expected to be used by toxicologists and other scientists 

to investigate and identify physical properties that may contribute to 

observed particle toxicity. 

■ Observed anomalous behavior in state-of-the-art aerosol instrumentation. This research is expected to lead to the development of effective 
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NIOSH Nanotechnology Research Center

monitoring methods and new/improved instrument designs that are 

needed for accurate characterization of worker exposures.

■ In conjunction with Yale University, contributed a large amount of data 

on mobility and mass relations for a significant number of different 

materials in the size range of a few nanometers. The data are valuable in 

giving a basis for accurate measurements of nanoparticles at very small 

sizes and are expected to be used in future research.

■ Characterized bipolar charging characteristics of carbon nanofibers to 

better understand particle charging-based instrument response to different particle morphologies, such as spherical and fiber shape.

Publications and Abstracts

■ Maynard AD, Ku B-K, Emery M, Stolzenburg M, McMurry P [2007]. 

Airborne single-walled carbon nanotube agglomerates show particle 

size-dependent physicochemical structure. J Nanopart Res 9:85–92.

■ Ku B-K, Maynard AD, Baron PA, Deye G [2007]. Observation and 

measurement of anomalous responses in a differential mobility analyzer by ultrafine fibrous carbon aerosols. J Electrostat 65:542–548.

■ Ku B-K [2008]. Nanomaterials and occupational health. Indust Health 

2:44–49 (in Korean). 

■ Ku B-K, Kulkarni P [in press]. Morphology of single-wall carbon 

nanotube aggregates generated by electrospray of aqueous suspensions. 

J Nanopart Res. 

■ Ku B-K, Fernandez de la Mora J [2009]. Relation between electrical mobility, mass, and size for nanodrops 1–6.5 nm in diameter in air. Aerosol Sci 

Technol 43(3), 241–249. 

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

Hubbs AF, Mercer RR, Keohavong P, Sussman N, Jin J, Yin J, Stone S, 

Chen BT, Deye G, Maynard A, Castranova V, Baron PA, Kagan VE [in 

press]. Inhalation versus aspiration of single-walled carbon nanotubes 

in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Am J Physiol Lung Cell Mol Physiol.

Invited Presentations

■ Ku B-K [2007]. Characterization of purified single-walled carbon 

nanotube aerosols generated by electrospraying of suspension. International symposium on nanotechnology, occupational, and environmental health, Taipei, Taiwan, August 29–September 1.
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NIOSH Nanotechnology Research Center

■ Ku B-K, Fernandez de la Mora J, Ude S [2007]. Relation between 

electrical mobility, mass, and size in the nanometer range of charged 

nanoparticles generated by electrosprays. American Association for 

Aerosol Research annual conference, Reno, NV, September 24–28.

■ Ku B-K [2007]. Nanoparticles and occupational health: toward safe 

nanotechnology conference. University of Kentucky, Lexington, KY, 

April 24. 

■ Ku B-K [2007]. Nanoparticles, occupational and environmental health: 

physical characterization of nanoparticles conference. Korea Institute 

of Machinery and Materials, Daejeon, Korea, September 3 and 4.

■ Ku B-K [2007]. Contemporary issues in occupational health: nanoparticles and occupational health conference. University of Yonsei, Seoul, 

Korea, September 5.

■ Ku B-K, Fernandez de la Mora J [2008]. Electrical mobility, mass, and 

size for nanodrops 1–3.5 nm in diameter. American Association for 

Aerosol Research annual conference, Orlando, FL, October 20–24.

■ Kulkarni P, Deye GJ, Ku B-K, Baron PA [2008]. Relationship between 

aerodynamic and mobility diameters of single- and multi-walled carbon nanotube aerosols. American Association for Aerosol Research 

annual conference, Orlando, FL, October 20–24.
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Project 23: Dustiness of Nanomaterials

Principle Investigator: Douglas E. Evans, Ph.D.

Project Duration: FY 2007–2009

Critical Topic Areas: measurement methods, exposure assessment, fire 

and explosion safety 

Accomplishments and Research Findings

■ Completed pilot phase of the research.

■ Evaluated novel method for testing powders and found it to be suitable 

for testing nanomaterials. Advantages of the method include

— Small powder samples required (mg quantities), allowing for a potentially greater number of materials to be tested

— Complete enclosure of the test system so that the operator is not 

exposed to potentially toxic materials

— Relevance to the workplace

■ Tested approximately 20 fine and nanoscale materials—consisting of at 

least three replicate tests—for total and respirable mass. Values span 

2 orders of magnitude.

■ Modified the testing system and protocol to investigate humidity effects 

on powder dispersal.

■ Designed a new dispersal chamber, allowing for a greater variety of 

measurements to be made.

■ In February 2007, visited the UK Health and Safety Laboratory in Buxton.

— Discussed issues related to workplace measurement of nanomaterials and dustiness testing methods.

— Conducted dustiness tests of the novel method in parallel with the 

more traditional (UK) rotating-drum method using the same materials. Technical issues were identified with both methods.

■ In early 2008, submitted a full NORA/NTRC proposal for the FY 2009 

solicitation to support continuing dustiness research.
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Invited Presentations

■ Evans DE [2007]. Working at the nanoscale: the occupational health 

and safety perspective. Health and Safety Laboratory, Buxton, United 

Kingdom, February 20.

■ Mark D, Bard D, Wake D, Hoover MD, Stefaniak AB, Methner MM, 

Evans DE, Geraci CL [2008]. Problems and experience of measuring 

worker exposure to engineered nanoparticles. International inhalation 

symposium: benefits and risks of inhaled engineered nanoparticles, 

Hanover, Germany, June 11–14
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Project 24: Nanoaerosol Monitoring Methods

Principle Investigators: M. Eileen Birch, Ph.D. and 

Douglas E. Evans, Ph.D.

Project Duration: FY 2005–2010

Critical Topic Areas: measurement methods, exposure assessment

Accomplishments and Research Findings (laboratory and 

field research) 

■ Collaborated on collection and analysis of diesel particulate samples 

from mines.

■ Collaborated on screening survey at a major producer of carbon nanofibers. Provided analytical data and submitted report to company (screening survey completed).

■ Completed walk-through at same facility. 

■ Completed survey on ultrafine aerosol sources at diesel engine manufacturing plant.

■ Completed in-depth survey at the University of Dayton Research 

Institute carbon nanofiber composite facility. Prepared report to the 

Institute.

■ Provided real-time data to Altair environmental health and safety 

facilitator for internal review in September 2007. Identified several 

areas where development of new/improved monitoring approaches is 

required. 

■ Completed construction of a novel instrument for fast measurement of 

nanoparticle size distribution (instrument evaluation under way).

Publications and Abstracts 

■ Heitbrink WA, Evans DE, Peters TM, Slavin TJ [2007]. Characterization and mapping of very fine particles in an engine machining and 

assembly facility. J Occup Environ Hyg 4(5):341–351. 

■ Baron PA, Estill CF, Beard JK, Hein MJ, Larsen L [2007]. Bacterial 

endospore inactivation caused by outgassing of vaporous hydrogen 

peroxide from polymethyl methacrylate (Plexiglas®). Lett Appl Microbiol 45:485–490.
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NIOSH Nanotechnology Research Center

■ Kulkarni P, Deye G, Baron P [2008]. Bipolar diffusion chargin 

of carbon nanotube aerosols. J Aerosol Sci, doi:10.1016/j.jaerosci.2008.09.008. 

■ Wang Z, Hopke PK, Ahamadi G, Cheng Y-S, Baron PA [2008]. Fibrous particle deposition in human and nasal passage: the influence of 

particle length, flow rate, and geometry of nasal airway. J Aerosol Sci 

39(12):1040–1054.

■ Baron P, Deye GJ, Martinez AB, Jones EN, Bennett JS [2008]. Size shifts 

in measurements of droplets with the aerodynamic particle sizer and 

the aerosizer. Aerosol Sci Technol 42(3):201–209.

■ Olfert J, Kulkarni P, Wang J [2008]. Rapid measurements of aerosol size 

distributions using a fast integrated mobility spectrometer. J Aerosol 

Sci [www.ecd.bnl.gov/pubs/BNL-79289-2007-AB.pdf].

■ Evans DE, Heitbrink WA, Slavin TJ, Peters TM [2008]. Ultrafine and 

respirable particles in an automotive grey iron foundry. Ann Occup 

Hyg 52(1):9–21.

■ Baron PA, Estill CF, Deye GJ, Hein MJ, Beard JK, Larsen LD, Dahlstrom GE [2008]. Development of an aerosol system for uniformly 

depositing bacillus anthracis spore particles on surfaces. Aerosol Sci 

Technol 42(3):159–172.

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

Hubbs AF, Mercer RR, Stone S, Frazer D, Chen T, Deye G, Maynard A, 

Baron P, Mason R, Kadiiska M, Stadler K, Mouithys-Mickalad A, Castranova V, Kagan VE [2008]. Inhalation of carbon nanotubes induces 

oxidative stress and cytokine response causing respiratory impairment 

and pulmonary fibrosis in mice. Toxicologi 102(1):307. 

■ Baron PA, Deye GJ, Chen B, Schwegler-Berry DE, Shvedova AA, Castranova V [accepted for publication]. Aerosolization of single-walled 

carbon nanotubes for an inhalation study. J Inhal Toxicol. 

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

Hubbs AF, Mercer RR, Keohavong P, Sussman N, Jin J, Stone S, Chen 

BT, Deye G, Maynard A, Castranova V, Baron PA, Kagan VE [in press]. 

Inhalation versus aspiration of single-walled carbon nanotubes in 

C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Amer J Physiol. 

■ Heitbrink WA, Evans DE, Ku B-K, Maynard AD, Slavin TJ, Peters 

TM [2009]. Relationships between particle number, surface area, and 
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respirable mass concentration in automotive engine manufacturing. J 

Occup Environ Hyg. 6(1):19–32. 

■ Kulkarni P, Deye G, Baron P [in press]. Bipolar diffusion charging characteristics of airborne carbon nanotube aerosols. J Aerosol Sci.

Invited Presentations

■ Birch ME, Evans DE, Ku B-K [2007]. Occupational monitoring of carbonaceous nanomaterials. American Association for Aerosol Research 

annual conference, Reno, Nevada, September 24–28.

■ Heitbrink WA, Evans DE, Ku B-K, Maynard AD, Peters TM, Slavin TJ 

[2007]. The relationship between particle surface area, number, and 

respirable mass concentration in an automotive foundry and engine 

machining facility. American Association for Aerosol Research annual 

conference, Reno, Nevada, September 24–28.

■ Kulkarni P, Deye G, Baron P [2007]. Bipolar diffusion charging characteristics of airborne, single-walled carbon nanotubes. American Association for Aerosol Research annual conference, Reno, NV, September 

24–28.

■ Evans DE [2007]. Working at the Nanoscale: The occupational health 

and safety perspective. NANOMIST meeting, Birmingham, United 

Kingdom, February 19. 

■ Baron PA [2008]. Aerosol science enabling nanomaterial research: experience in environmental and occupational health. Inaugural meeting 

of the student chapter of American Association for Aerosol Research, 

University of Cincinnati, Cincinnati, OH, April 29.
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NIOSH Nanotechnology Research Center

Project 25: Measurement of Nanoscale 

Carbonaceous Aerosols

Principle Investigator M. Eileen Birch, Ph.D. 

Project Duration FY 2007–2008

Critical Topic Areas: measurement methods, exposure assessment 

Accomplishments and Research Findings (laboratory and 

field research)

■ Completed preliminary investigations at two carbon nanofiber (CNF) 

facilities when this project began in June 2007. A NIOSH Health Hazard Evaluation (HHE) report on the first field study was published in 

2006. A report on the second study was sent to the company in February 2007. 

■ Completed design and assembly of a mobile aerosol sampling unit 

(cart) for performing real-time aerosol measurements in workplaces. 

The unit is equipped with sampling ports and battery power and accommodates a laptop and multiple aerosol instruments. 

■ Completed in-depth field study (five site visits during FY 2007 and 

FY2008) at a major CNF manufacturer. Found CNF dispersion within 

the facility. Identified production byproducts and informed company of 

them. Also provided recommendations to improve air quality. 

■ Began work on generation of a carbon black aerosol and its collection 

on filter sets in July 2008. This work will continue in FY 2009 under 

another project. 

■ Participated in the American Ceramics Society Workshop, nanoparticle 

measurement needs for environmental health and safety in Arlington, 

Virginia, June 9 and 10, 2008.

Publications and Abstracts

■ Methner MM, Birch ME, Evans DE, Ku B-K, Crouch KG, Hoover MD 

[2007]. Case study: identification and characterization of potential 

sources of worker exposure to carbon nanofibers during polymer composite laboratory operations. J Occup Environ Hyg 4(12):D125–D130.
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NIOSH Nanotechnology Research Center

■ Noll J, Birch ME [2008]. Effects of sampling artifacts on occupational 

samples of diesel particulate matter. Environ Sci Technol 42(14):5223–

5228.

■ Kulkarni P, Deye G, Baron P [2008]. Bipolar diffusion charging 

of carbon nanotube aerosols. J Aerosol Sci, doi:10.1016/j.jaerosci.2008.09.008.

■ Wang Z, Hopke PK, Ahamadi G, Cheng Y-S, Baron PA [2008]. Fibrous particle deposition in human and nasal passage: the influence of 

particle length, flow rate, and geometry of nasal airway. J Aerosol Sci 

39(12):1040–1054.

Invited Presentations

■ Birch ME, Evans DE, Ku B-K [2007]. Occupational monitoring of carbonaceous nanomaterials. American Association for Aerosol Research 

annual conference, Reno, NV, September 24–28.

■ Evans DE, Birch ME, Ku B-K, Ruda-Eberenz T [2008]. Occupational 

monitoring of carbonaceous nanomaterials. American Association for 

Aerosol Research annual conference, Orlando, FL, October 20–24. 

■ Ruda-Eberenz T, Birch ME, Evans DE, Ku B-K [2008]. Occupational 

monitoring of carbonaceous nanomaterials. Central Regional meeting 

of the American Chemical Society, Columbus, OH, June 10–14.
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NIOSH Nanotechnology Research Center

Project 26: Nanoparticle Reference 

Materials for Health Protection

Principle Investigator: Aleksandr B. Stefaniak, Ph.D.

Project Duration: FY 2007–2011

Critical Topic Area: measurement methods

Accomplishments and Research Findings

■ Developed a project protocol in collaboration with the National Institute of Standards and Technology (NIST) and Oak Ridge National 

Laboratory to develop reference materials.

■ Obtained external peer-review of study protocol.

■ Identified researchers at NIST who are leading nanoparticle reference 

material development initiatives.

■ Hosted Vince Hackley (NIST) at NIOSH-Morgantown to discuss NIOSH 

contributions to the development and qualification of a nanoscale TiO2

reference material. 

■ Identified a single-walled carbon nanohorn as an engineered nanoparticle with potential for development into reference material as a control 

material for toxicology studies.

■ Conducted a telephone conference call of NTRC working group on 

engineered nanoparticle classification schemes.

■ Participated in NIST-sponsored workshop on nanomaterial manufacturing, May 20–22, 2008 in Gaithersburg, MD.

— Participated in breakout session on separation and fractionation of 

nanomaterials.

— Reported output of workshop to the National Nanotechnology Initiative.

■ Participated in the American Ceramics Society workshop on nanoparticle measurement needs for environmental health and safety, June 9 

and 10, 2008 in Arlington, VA.

■ Co-sponsored with American National Standards Institute, National 

Cancer Institute, and NIST a workshop on enabling standards for 

nanomaterial characterization, October 8 and 9, 2008 in Gaithersburg, 
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NIOSH Nanotechnology Research Center

Maryland. Acted as codiscussion leader of breakout session—Reference 

and test materials, media and sample preparation.

■ Visited Luna NanoWorks (Danville, Virginia) to discuss workplace 

measurement issues.

Publications and Abstracts

■ Stefaniak AB, Schwegler-Berry D, Hoover MD, Goia DV, Rossner A, 

Postek MT, Poster DL [2007]. Development of nanoparticle size and 

surface area reference materials for exposure assessment. International 

symposium on occupational health implications of nanomaterials, 

Taipei, Taiwan, August.

■ Mark D, Bard D, Wake D, Hoover MD, Stefaniak AB, Methner MM, 

Evans DE, Geraci CL [2008]. Problems and experience of measuring 

worker exposure to engineered nanoparticles. International inhalation 

symposium: benefits and risks of inhaled engineered nanoparticles, 

Hanover, Germany, June 11–14.

Invited Presentations

■ Stefaniak AB [2008]. Methodological challenges of assessing bioavailability of emerging contaminants. University of North Carolina Superfund Basic Research Program workshop, assessing bioavailability as a 

determinant of pollutant exposure: building a multidisciplinary paradigm for the 21st century and beyond, Tampa, FL, February 18–20.

■ Stefaniak AB [2008]. Standards needs for occupational exposure assessment of nanomaterials. National Institute of Standards and Technology 

workshop on enabling standards for nanomaterial characterization, 

Gaithersburg, MD, October 8 and 9.

■ Stefaniak AB (presented by Hoover MD) [2008]. Minimal material 

characterization of nanomaterials. Workshop on ensuring appropriate material characterization in nanotoxicity studies, Washington, DC, 

October 28.
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Project 27: Calm Air Chamber and 

Wind Tunnel Evaluation of 

Personal Aerosol Samplers 

for Nanoparticle Exposure 

Assessment

Principal Investigator: Terri Pearce, Ph.D.

Project Duration: FY 2008–2010

Critical Topic Area: measurement methods

Accomplishments and Research Findings

■ Developed study protocol.

■ Obtained external peer-review for protocol.

Invited Presentation 

■ Pearce T [2008]. Direct-reading nanoaerosol instrument comparison. 

Abstract and poster for the American Association for Aerosol Research 

annual conference, Orlando, FL, October 20–24.
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NIOSH Nanotechnology Research Center

Project 28: Ultrafine TiO2 Surface and Mass 

Concentration Sampling Method

Principle Investigator: Aleksandr B. Stefaniak, Ph.D.

Project Duration: FY 2007–2011

Critical Topic Area: measurement methods

Accomplishments and Research Findings

■ Obtained external peer-review of study protocol.

■ Obtained bulk ultrafine TiO2 powder as a study material.

■ Characterized bulk powder physicochemical properties (density, morphology, primary particle size, particle cluster size, total surface area by 

gas adsorption, purity, and crystallinity).

■ Characterized intra- and inter-filter variability for three media: tracketched polycarbonate (0.4 μm pore), track-etched polycarbonate 

(0.8 μm pore) and Teflon (5 μm pore) including thermal integrity, pressure drop, mass stability, and collection efficiency.

■ Developed a protocol for determining background surface area of 

blank filter media using krypton gas isotherms.

■ Characterized intra- and inter-filter surface area variability for tracketched polycarbonate (0.4 μm pore), track-etched polycarbonate 

(0.8 μm pore) and Teflon (5 μm pore) filters.

■ Developed protocol for measuring ultrafine TiO2 surface area with 

specificity using bulk powder and perylene diimide dye adsorbed to 

particle surfaces.
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NIOSH Nanotechnology Research Center

Project 29: Standard Determination of 

Nanoparticle Size

Principle Investigator: Aleksandr B. Stefaniak, Ph.D.

Project Duration: FY 2009–2010

Critical Topic Area: measurement methods

Accomplishments and Research Findings

■ Obtained external peer-review of study protocol.

■ Procured three different sizes of spherical gold nanoparticle reference 

materials from the National Institute of Standards and Technology 

(NIST).

■ Developed a protocol for depositing each size of gold nanoparticle reference material onto functionalized electron microscopy grids.

■ Determined particle diameter for each size of gold reference material 

on an electron microscopy grids.

■ Evaluated data to compare measurement results with certified size values. Communicated with NIST statisticians on comparison statistics.

■ Cosponsored with American National Standards Institute, National 

Cancer Institute, and NIST a workshop on enabling standards for 

nanomaterial characterization, Oct 8 and 9, 2008 in Gaithersburg, 

Maryland. Acted as co-discussion leader of breakout session—

Reference and test materials, media and sample preparation.
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Project 30: Development and Evaluation 

of Nanoaerosol Surface Area 

Measurement Methods

Principal Investigator: Bon-Ki Ku, Ph.D.

Project Duration: FY 2009

Critical Topic Area: measurement methods

Planned Research:

■ The objectives of this project are to (1) generate well characterized 

nanoaerosols with different physical and chemical properties to be used 

as test aerosols and (2) completely characterize diffusion charging and 

mobility analysis methods for nanoaerosol particles in the size range up 

to several microns.

■ Conduct a preliminary study on diffusion charger responses to spherical particles in the range from 100 nm up to 600 nm to assess whether 

the diffusion charger response decreases with increasing mobility 

diameter. 
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Project 31: Workplace Monitoring of Carbon 

Nanofibers/Nanotubes

Principle Investigator: M. Eileen Birch, Ph.D. 

Project Duration: FY 2009

Critical Topic Areas: measurement methods, exposure assessment 

Accomplishments and Research Findings

■ Contacted carbon nanotube manufacturer to discuss production processes and tentative date for field survey in FY 2009. 

■ Generation methods for carbon black aerosol are being investigated. 

The objective is collection of a matched filter set for interlaboratory 

comparisons. 

■ Initiated collaboration with NIST on an analytical reference material 

for carbon nanotubes. 

Electron micrograph of carbon nanofibers at 15,000x
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NIOSH Nanotechnology Research Center

Project 32: Ultrafine Aerosols from DieselPowered Equipment

Principal Investigator: Aleksandar Bugarski, Ph.D.

Project Duration: FY 2004–2008

Critical Topic Area: measurement methods

Accomplishments and Research Findings

■ Evaluated the effects of a fuel-borne, catalyst-regenerated, sintered 

metal, diesel-particulate-filter (DPF) system from Mann-Hummel on 

size distribution and concentration of nano and ultrafine aerosols in 

mine air. This study conducted at NIOSH Diesel Laboratory at Lake 

Lynn Laboratory was used to characterize physical and chemical properties of aerosols emitted from an engine equipped with sintered metal 

DPF system and to assess the effects of DPF regeneration strategy (fuelborne catalyst) on concentrations of aerosols and gases in mine air.

■ Evaluated the potential of biodiesel fuels to reduce concentrations of 

aerosols in mine air. This study was conducted at the NIOSH Diesel 

Laboratory at Lake Lynn Laboratory. Compared neat and blended 

biodiesel fuels with ultra low sulfur petroleum diesel relating to their 

effects on the concentrations and size distributions of diesel aerosols in 

underground mine conditions. The physical and chemical properties 

and toxicity of diesel and biodiesel aerosols in mine air were studied. 

■ Evaluated the effects of an electrically regenerated, sintered metal DPF 

system from Rypos on size distribution and concentration of nano- and 

ultrafine aerosols in mine air. This study, conducted at NIOSH Diesel 

Laboratory at Lake Lynn Laboratory, was used to characterize physical 

and chemical properties of aerosols emitted from an engine equipped 

with sintered metal DPF system and to assess the effects of DPFregeneration strategy (electrical current) on concentrations of aerosols 

and gases in mine air.

■ Developed novel methodology for collection of diesel particulates for 

genotoxicity analysis. The samples are collected directly on lung surfactant using biosamplers and versatile aerosol concentration enrichment 

system developed in cooperation with University of Southern California. 
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■ Developed the novel methodology for preparing and analyzing samples 

collected using aforementioned sampling system.

■ Using the salmonella reversion assays, assessed genotoxic potential of 

the solvent extracted diesel aerosols samples collected during DPF and 

biodiesel studies.

■ Evaluated suitability of various aerosol instrumentation, such as fast 

mobility particle sizer, scanning mobility particle sizer, electrical low 

pressure impactor, nanoparticle surface area monitor, PAS2000, and 

filter-sampling methodologies for measurement and sampling of diesel 

aerosols.

■ Completed the new engine/dynamometer system with a MercedesBenz engine and 400 kW dynamometer. It is awaiting deployment to 

NIOSH Diesel Laboratory at Lake Lynn Laboratory.

■ The Lake Lynn Laboratory mine has been under reconstruction since 

July 2008. For safety reasons, the experimental work is postponed 

probably until spring 2009.

■ Disseminated findings in peer-review papers and at 13th and 14th 

Mining Diesel Emissions Council conference, 13th Diesel EngineEfficiency and Emissions Research (DEER) conference, 12th United 

States/North American mine ventilation symposium. 

Invited Presentations

■ Bugarski AD, Schnakenberg GH Jr., Hummer JA, Cauda E, Janisko 

SJ, Patts LD [2007]. Examination of diesel after-treatment systems at 

NIOSH Lake Lynn Laboratory. Annual mining diesel emissions conference, Richmond Hill/Toronto, Ontario, Canada, October 1–5.

■ Shi XC, Keane M, Ong T, Harrison J, Gautam M, Li S-Q, Bugarski A, 

Wallace W [2007]. Preserving diesel exhaust ultrafine (nano-) particulate structure in genotoxicity studies to support engineering development of emissions controls. Diesel engine-efficiency and emissions 

research (DEER) conference, Detroit, MI, August 13–16.

■ Bugarski A, Schnakenberg GH Jr., Mischler S, Cauda E [2007]. Characterization of the physical and chemical properties of diesel aerosols in 

an underground mine diesel laboratory. ETH conference on combustion generated nanoparticles, Zurich, Switzerland, August 13–15.

■ Gautam M, Wilt G, Carder D, Bugarski A [2007]. Evaluation of diesel 

exhaust particulate matter in a ventilated mine tunnel. ETH conference 
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on combustion generated nanoparticles, Zurich, Switzerland, August 

13–15.

■ Bugarski AD, Cauda E, Janisko S, Patts LD, Hummer JA, Mischler SE 

[2008]. Effects of biodiesel on aerosols in underground mine. Annual 

mining diesel emissions conference, Richmond Hill/Toronto, Ontario, 

Canada, October 5–10.

■ Bugarski AD, Cauda E, Janisko S, Patts LD, Hummer JA, Mischler SE 

[2008]. Evaluation of an electrically regenerated sintered metal diesel particulate filter system in underground mine laboratory. Annual 

mining diesel emissions conference, Richmond Hill/Toronto, Ontario, 

Canada, October 5–10.

■ Shi X-C, Keane MJ, Ong T-M, Bugarski AD, Gautam M, Wallace WE 

[2008]. Diesel exhaust particulate material expression of in vitro genotoxic activities when dispersed into a phospholipid component of lung 

surfactant. Inhaled Particles X conference, Sheffield, United Kingdom, 

September 23–25.

■ Bugarski AD, Schnakenberg GH Jr., Cauda E [2008]. Effects of sintered 

metal diesel particulate filter system on diesel aerosols and nitric oxides 

in mine air. United States/North American mine ventilation symposium, Reno, NV, June 9–11.

■ Bugarski A [2008]. Diesel particulate filtration technology in underground mines. California Air Resource Board (CARB)/Southern California Air Quality Management District, course on ultrafine particles 

and retrofit technologies for diesel engines, Diamond Bar, CA, 

November 12–14.
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Project 33: Titanium Dioxide and Other Metal 

Oxides Exposure Assessment 

Study

Principle Investigator: Brian Curwin, Ph.D.

Project Duration: FY 2006–2009

Critical Topic Areas: measurement methods, exposure assessment 

Accomplishments and Research Findings

■ Wrote protocol for titanium dioxide study, which underwent peer 

review.

■ Purchased critical exposure assessment equipment, including a TSI 

3007 condensation particle counter, an Ecochem DC2000 CE portable 

diffusion charger, and a MOUDI impactor.

■ Awarded a contract for support in company recruitment. Recruitment 

was completed in June 2008. 

■ Contacted 189 companies for recruitment; 10 initially agreed to participate and surveys were conducted at 7 companies. Three more companies waiting to be scheduled.

■ Sent survey reports to three companies.
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Project 34: Field Research Team

Principle Investigators: Mark Methner, Ph.D., and Charles 

Geraci, Ph.D.

Project Duration: FY 2006–2012

Critical Topic Area: exposure assessment

Accomplishments and Research Findings (field surveys)

■ Performed sampling at a multi-walled carbon nanotubes manufacturer. 

Report issued in 2007.

■ Completed two site visits at a metal oxide manufacturer to evaluate 

engineering controls (2007, 2008). Reports issued in 2008. Engineering 

case study published in the Journal of Occupational and Environmental 

Health in 2008.

■ Conducted an observational walkthrough at a research and development laboratory that handles and compounds nanoscale polyhedral 

oligomeric silsesquioxanes (POSS). Subsequent air sampling was performed by facility. Future collaborations on additional air sampling and 

possible engineering controls are expected.

Cleaning of metal oxide reactor. Note 

local exhaust ventilation is in use. Image 

courtesy of Mark Methner, NIOSH.
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■ Performed sampling at a manufacturer of nanoenhanced, silica-iron, 

absorbent media. Evaluated a spray deposition of nanomaterial onto 

cellulose substrate inside ventilated chamber. Report issued in 2008.

■ Completed two trips to evaluate chamber ventilation role in controlling releases during cleanout operations at a pilot-scale research and 

development facility that creates nanoscale alumina via radiofrequency 

plasma torch reaction. Issued two reports (2007, 2008). Future collaboration to evaluate alternative engineering controls expected.

■ Performed sampling at an environmental toxicology laboratory. Facility 

conducts toxicology studies on invertebrates. Evaluated handling procedures during MWCNT- and fullerene-solution preparation. Report 

issued in 2008.

■ Performed sampling at a manufacturer that compounds/blends MWCNTs and boron carbide. Company ships product to manufacturer 

that uses material to create body armor. Report issued in 2009. Expect 

future collaborations to include engineering control evaluation and 

potential exposure to end-user of material.

■ Performed sampling at a pilot-scale, research-and-development laboratory that handles/processes MWCNTs for use in composite material production. Facility installed HEPA-filtered downdraft ventilated 

enclosure for use during handling operations. Air sampling conducted 

with and without ventilation system operating. Report issued in 2009.

■ Performed sampling at a research and development laboratory that 

handles a variety of engineered nanomaterials (MWCNTs, metal oxides). Report issued in 2009.

■ Performed sampling at a pilot-scale, research-and-development facility that synthesizes and handles MWCNTs for inclusion in composite 

materials. Report issued in 2009.

■ Performed sampling at a Department of Defense Applied Toxicology 

laboratory that handles engineered nanomaterials (elemental metals and 

oxides) for use in animal toxicological studies. Report issued in 2009.

■ Performed sampling at a research laboratory producing carbon nanotube infused fiber composites. Report issued in 2009.

Publications and Abstracts

■ Methner MM, Birch ME, Evans DE, Ku B-K, Crouch K, Hoover MD, 

Mazzukelli LF (Ed) [2007]. Case study: identification and characterization of potential sources of worker exposure to carbon nanofibers 
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during polymer composite laboratory operations. J Occup Environ Hyg 

4(12):D125–D130.

■ Methner MM and Old L (Ed.) [2008]. Engineering case study: effectiveness of local exhaust ventilation in controlling engineered nanomaterial emissions during reactor cleanout operations. J Occup Environ 

Hyg 5(6):D63–69.

Invited Presentations

■ Hodson LL [2007]. Nanoparticles-NIOSH Nanoparticles Research Program. The Insurance Loss Control Association, Oct 31.

■ Hodson, LL [2008]. Workplace exposure assessment and risk management practices for nanomaterials. The Ohio Safety Congress and Expo, 

Columbus, OH, April 3.

■ Methner MM, Hodson LL, Geraci CL [2008]. One day workshop: 

Nanoparticles in the Workplace: Demonstration of the instruments 

used when using the nanoparticle emission assessment technique 

(NEAT). American Industrial Hygiene Association, Central Ohio Section, Columbus, OH, April 22. 

■ Hodson LL [2008]. Nanoparticles—NIOSH Nanoparticle Research 

Program. The Edison Electric Institute spring occupational health and 

safety conference, Louisville, KY, April 29. 

■ Methner MM [2008]. Nanotechnology: ask the expert panel discussion: 

results pertaining to the field use of the nanoparticle emission assessment technique (NEAT). American Industrial Hygiene Association 

conference and exposition, Minneapolis, MN, May 31–June 5.

■ Methner MM, Hodson LL [2008]. Professional Development Course: 

Nanoparticles in the Workplace: Demonstration of the instruments 

used when using the nanoparticle emission assessment technique 

(NEAT). American Industrial Hygiene Association conference and 

exposition, Minneapolis, MN, May 31–June 5.

■ Mark D, Bard D, Wake D, Hoover MD, Stefaniak AB, Methner MM, 

Evans DE, Geraci CL [2008]. Problems and experiences of measuring 

worker exposure to engineered nanoparticles. International Inhalation 

Symposium, Hanover, Germany, June 11–14.

■ Hodson LL [2008]. The NIOSH field research team—a brief summary 

and update of activities. U.S. Air Force (USAF) workshop on biological 

interaction of engineered nanoparticles, Wright Patterson AFB, Dayton, OH, June 24.
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■ Hodson LL [2008]. NIOSH Nanotechnology Research Program. American Industrial Hygiene Association, Indiana section meeting, Indianapolis, IN, July 9.

■ Methner MM, Hodson LL, Geraci CL [2008]. Professional Development Course: Nanoparticles in the Workplace: Demonstration of the 

instruments used when using the nanoparticle emission assessment 

technique (NEAT). American Industrial Hygiene Association, Ohio 

Valley Section, West Chester, OH, December 16.

Weighing CNF in an exhausted 

enclosure. Image courtesy of 

Mark Methner, NIOSH.

Crumbling carbon nanofiber paper. Image courtesy of Mark Methner, 

NIOSH.
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NIOSH Nanotechnology Research Center

Project 35: Assessing the Feasibility of 

Industrywide Exposure and 

Epidemiology Studies of 

Workers Exposed to Engineered 

Nanomaterials

Principle Investigator: Mary Schubauer-Berigan, Ph.D.

Project Duration: FY 2008–2009

Critical Topic Area: epidemiology and surveillance

Accomplishments and Research Findings

■ Developed and funded a statement of work to collect and compile 

information on the size, characteristics, and future trends of the U.S. 

workforce involved in the manufacture of engineered carbonaceous 

nanomaterials.

■ Attended the 2008 Micro Nano Breakthrough conference in Vancouver, 

Washington, to learn about the latest applications of engineered carbonaceous nanomaterials as well as possible timeframes and barriers for 

transition from startup to full-scale production for the most promising 

applications.

■ Reviewed and compiled information on companies identified as engineered carbonaceous nanomaterials manufacturers in the Lux Report 

(fourth and fifth editions), supplemented with information collected 

from Dun and Bradstreet. 

■ Contacted and conducted interviews with health and safety managers 

at each identified company to confirm the information collected on 

workforce size, location, characteristics of the nanomaterials produced, 

and use of engineering controls and personal protective equipment.

■ Developed a report on the feasibility of conducting industrywide exposure surveys and epidemiological studies among this workforce.
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Project 36: Nanoparticles—Dosimetry and 

Risk Assessment

Principle Investigator: Eileen D. Kuempel, Ph.D.

Project Duration: FY 2005–2012

Critical Topic Area: risk assessment

Accomplishments and Research Findings

■ Developed and published risk assessment methods for inhaled poorly 

soluble nanoparticles, including quantitative dose-response analysis 

in rodents, dosimetry modeling, and extrapolation of risk estimates to 

humans.

■ Completed nanoparticle dosimetry model in rats. Dosimetry model 

describes clearance, retention, and translocation from lungs to systemic circulation, and early biological responses. Model calibration 

used dose-response data from NIOSH animal studies (IOM/NIOSH 

research collaboration).

■ Completed olfactory deposition model of spherical nanoparticles in 

rats. Revised multipath particle deposition (MPPD) model to include 

site-specific deposition efficiency in nasal-pharyngeal region (Hamner 

Institute/NIOSH research collaboration). 

■ Initiated research with Hamner Institute to develop human olfactory 

deposition model of spherical nanoparticles. Will use estimates of 

olfactory deposition proportion in estimating dose and assessing risk of 

nanoaerosols. 

■ Developed modeling methods to predict human respiratory tract deposition model for carbon nanofibers/nanotubes structures based on fiber 

aerosol theory. Additional methods are being evaluated to account for 

diffusion diameter and to model deposition of heterogeneous nanoaerosol structures. (Hamner Institute/NIOSH research collaboration). 

Publications and Abstracts

■ Kuempel ED [2007]. Estimating nanoparticle dose in humans: issues 

and challenges. Chapter 10. In: Monteiro-Riviere NA, Tran CL, eds. 

Nanotoxicology: characterization, dosing, and health effects. New York: 

Informa Healthcare USA Inc., pp. 141–152. 
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■ Kuempel ED, Geraci CL, Schulte PA [2007]. Risk assessment approaches and research needs for nanoparticles: An examination of 

data and information from current studies. In: Simeonova PP, Opopol 

N, Luster MI, eds. Nanotechnology: toxicological issues and environmental safety, NATO security through science series book. New York: 

Springer-Verlag, pp. 119–145. 

■ Dankovic D, Kuempel E, Wheeler M [2007]. An approach to risk as An approach to risk assessment for TiO2

. Inhal Toxicol 19(Suppl 1):205–212.

■ Tran CL, Kuempel ED [2007]. Biologically based lung dosimetry and 

exposure-dose-response models for poorly soluble, inhaled particles. 

In: Donaldson K, Borm P, eds. Particle Toxicology. Boca Raton, Florida: 

CRC Press, Taylor and Francis Group, Chapter 20. 

■ Kuempel ED, Tran CL, Castranova V, Bailer AJ [2007]. Response to 

letter to the editor from Dr. Peter Morfeld [re: Lung dosimetry and risk 

assessment of nanoparticles: evaluating and extending current models in rats and humans. Inhal Toxicol 18(10):717–24]. Inhal Toxicol 

19(2):197–198. 

■ Garcia GJM, Nazridoust K, Kimbell JS [2008]. Nanoparticle deposition 

in the rat nasal cavity: prediction of dose to the olfactory epithelium. 

Toxicologist 102(1):204. 

■ MacCalman L, Tran CL, Kuempel E [in press]. Development of a biomathematical model in rats to describe particle size-specific clearance 

and translocation of inhaled nano particles. J Physics.

■ Kuempel ED, Smith RJ, Dankovic DA, Stayner LT [in press]. Rat- and 

human-based risk estimates of lung cancer from occupational exposure 

to poorly soluble particles: a quantitative evaluation. J Physics.

Invited Presentations

■ Kuempel ED [2007]. Review of hazard information on nanoparticles: as 

relates to occupational health surveillance. Workshop on occupational 

health surveillance and nanotechnology workers. Washington, DC, 

April 17.

■ Geraci CL, Schulte PA, Zumwalde R, Kuempel E, Hoover M [2007]. 

Occupational risk management for nanomaterials along the product 

life cycle. International symposium on nanotechnology, occupational, 

and environmental health. Taipei, Taiwan, August 29–September 1.

■ Schulte PA, Murashov VV, Geraci CL, Zumwalde RD, Hoover MD, 

Castranova V, Kuempel ED [2007]. Current occupational safety and 
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health issues of nanotechnology in the USA. European NanOSH conference—Nanotechnologies: a critical area in occupational safety and 

health, Helsinki, Finland, December 3–5.

■ MacCalman L, Tran CL, Kuempel E [2008]. Development of a biomathematical model in rats to describe the retention, clearance, and 

translocation of nanoparticles from the lungs. Inhaled Particles X conference, Sheffield, United Kingdom, September 23–25.

■ Kuempel ED, Smith RJ, Dankovic DA, Stayner LT [2008]. Rat- and 

human-based risk estimates of lung cancer from occupational exposure 

to poorly soluble particles: a quantitative evaluation. Inhaled Particles 

X conference, Sheffield, United Kingdom, September 23–25.

■ MacCalman L, Tran L, Kuempel E [2008]. Developing and testing a 

biomathematical model to describe particle size-specific clearance and 

translocation of nanoparticles in rats. Nanotoxicology—Second international nanotoxicology conference, Zurich, Switzerland, September 

7–10.

■ Schulte PA, Kuempel E, Castranova V, Trout D [2008]. Assessing the 

toxicological evidence base for medical surveillance of workers potentially exposed to engineered nanoparticles. Second international nanotoxicology conference, Zurich, Switzerland, September 7–10.

■ Kuempel ED [2008]. Should engineered nanoparticles be considered 

“new chemicals”? NTRC annual meeting, Morgantown, West Virginia, 

January 23.
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NIOSH Nanotechnology Research Center

Project 37: Penetration of Nanoparticles 

through Respirators

Principle Investigator: Samy Rengasamy, Ph.D.

Project Duration: FY 2005–2009

Critical Topic Area: engineering controls and personal protective equipment

Accomplishments and Research Findings

■ Conducted studies to measure nanoparticle penetration through the 

following:

1. NIOSH-approved N95 and P100 and European-certified CE 

marked filtering facepiece respirators

2. Dust masks that are available in home improvement/hardware 

stores

3. FDA-approved surgical masks

Publications and Abstracts

■ Rengasamy S, Verfobsky R, King W, Shaffer R [2007]. Nanoparticle 

penetration through NIOSH-approved N95 filtering facepiece respirators. JISRP 24:49–59. 

■ Rengasamy S, Eimer B, Shaffer R [2008]. Nanoparticle filtration performance of commercially available dust masks. JISRP 25:27–41.

■ Rengasamy S, King W, Eimer B, Shaffer R [2008]. Filtration performance of NIOSH-approved N95 and P100 filtering facepiece respirators against 4–30 nanometer-size nanoparticles. J Occup Environ Hyg 

5:556–564.

■ Rengasamy S, Eimer B, Shaffer R [in press]. Comparison of nanoparticle filtration performance of NIOSH-approved and CE-marked filtering facepiece respirators. Annals of Occ Hyg. 

■ Shaffer R, Rengasamy S [in press]. Respiratory protection against 

nanoparticles: A review. J Nanopart Res. Special issue on “Exposure assessment and exposure mitigation for nanomaterials in the workplace”. 

■ Fisher E, Rengasamy S, Viscusi D, Vo E, Shaffer R [in press]. Development of a test system of apply virus containing particles to filtering 
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facepiece respirators for the evaluation of decontamination procedures. 

App Environ Microbiol.

Invited Presentations

■ Shaffer R [2007]. Air purifying respirators for the nanotechnology 

industry. National Response Team-Worker Safety and Health Conference, Washington, DC, August 7.

■ Shaffer R [2007]. An overview of NIOSH nanotechnology research and 

an update on the efficacy of personal protective equipment for reducing 

worker exposure to nanoparticles. Commercialization of nanomaterials 

meeting, Pittsburgh, PA, November 11–13.

■ Rengasamy S, Eimer B, Shaffer R [2008]. Filtration performance of 

NIOSH-approved N95 and P100 filtering facepiece respirators against 

nanoparticles. American Industrial Hygiene Association conference, 

Minneapolis, MN, May 31–June 5.

■ Rengasamy S, Eimer B, Shaffer R [2008]. Comparison of nanoparticle 

filtration performance of NIOSH-approved and European-certified 

filtering facepiece respirators. ISRP international conference, Dublin, 

Ireland, September 14–18.

■ Rengasamy S, Eimer B, Shaffer R [2008]. Comparison of nanoparticle 

filtration performance of NIOSH-approved and European-certified 

filtering facepiece respirators. American Association for Aerosol Research annual conference, Orlando, FL, October 20–24.

■ Rengasamy S, Shaffer R [2007]. Respiratory protection against 

nanoparticles. Chesapeake Area Biological Association scientific symposium, Columbia, MD, June 14.

■ Shaffer R [2008]. Effectiveness of personal protective equipment and 

engineering controls. Safe handling of engineered nanoscale materials 

symposium, Argonne, IL, July 7 and 8.

■ Shaffer R [2008]. Control and filtration of nanomaterials. Occupational 

health aspects of nanotechnology symposium. Northern California 

Section of the American Industrial Hygiene Association, Menlo Park, 

CA, May 14.

■ Rengasamy S [2008]. Respiratory protection against biological and 

inert particles. International Society for Respiratory Protection meeting 

on respiratory protection issues in emergency response and healthcare, 

Montreal, Canada, October 6. 
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■ Rengasamy S [2008]. Respiratory protection against nanoparticles. Institut de recherche en sante et en securite du travail, colloquium on respiratory protection: research priorities, Montreal, Canada, October 7.
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NIOSH Nanotechnology Research Center

Project 38: Nanoparticle Penetration through 

Protective Clothing

Principle Investigator: Pengfei Gao, Ph.D.

Project Duration: FY 2009–2009

Critical Topic Area: engineering controls and personal protective clothing 

Planned Research

■ Development of a model based on single-fiber theory to predict 

nanoparticle penetration through clothing materials.

■ Development of a bench-scale particulate penetration test method 

based on a wind-driven approach.

■ Measurement of particle penetration levels through various fabrics 

used in protective clothing ensembles.
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Project 39: Development of Personal 

Protective Equipment Ensemble 

Test Methods 

Principle Investigator: Pengfei Gao, Ph.D.

Project Duration: FY 2005–2009

Critical Topic Area: engineering controls and personal protective equipment 

Accomplishments and Research Findings

■ Developed a multidomain, magnetic passive aerosol sampler for measuring particulate penetration through protective ensembles. Submitted an employee invention report to CDC Technology Transfer Office: 

Ref. I–007–08 (Gao P [2007]). 

Publications and Abstracts

■ Gao P, King WP, Shaffer R [2007]. Review of chamber design requirements for testing of personal protective clothing ensembles. J Occup 

Environ Hyg 4(8):562–571.

■ Gao P, Jeffrey LB, Shaffer R [in press]. Considerations for selection of 

PPE to protect against nanoparticle exposure. In: Anna D, ed. Chemical protective clothing, 3rd edition. Fairfax, VA: AIHA.

Invited Presentations

■ Wang ZM, Gao P [2007]. A study on magnetic passive aerosol sampler 

for measuring aerosol particle penetration through protective ensembles. American Association for Aerosol Research annual conference, 

Reno, NV, September 24–28. 

■ Shaffer R [2007]. An overview of NIOSH nanotechnology research and 

an update on the efficacy of personal protective equipment for reducing 

worker exposure to nanoparticles. Commercialization of nanomaterials 

meeting, Pittsburgh, PA, November 12.

■ Shaffer R [2008]. Control and filtration of nanomaterials. Occupational 

health aspects of nanotechnology symposium, Northern California 

Section of the American Industrial Hygiene Association, Menlo Park, 

CA, May 14.
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■ Shaffer R [2008]. Effectiveness of PPE and engineering controls. Safe 

handling of engineered nanoscale materials symposium, Argonne, IL, 

July 7 and 8.

■ Jaques PA, Gao P [2008]. Effect of wind velocity on particle collection 

using a multidomain magnetic passive aerosol sampler. American Association for Aerosol Research annual conference, Orlando, FL, October 20–24.
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NIOSH Nanotechnology Research Center

Project 40: Web-based Nanoparticle 

Information Library 

Implementation

Principal Investigator: Arthur Miller, Ph.D.

Project Duration: FY 2004–2008

Critical Topic Area: communication and information

Accomplishments and Research Findings

■ Collaborated with Oregon State University and a Health Effects Institute (HEI) consortium toward the development of an informational 

hub for nanotechnology and health effects.

■ Developed Web links for the NIOSH Nanoparticle Information Library 

to online resources at the Wilson International Center for International 

Scholars, the International Council on Nanotechnology bibliography 

on nanotechnology safety and health at Rice University and the National Science Foundation’s Nanomanufacturing Network at the University of Massachusetts at Lowell. 

■ Continued input for redesigning the nanotechnology topic page on the 

NIOSH Web site.

■ Developed a prototype, portable, hand-held electrostatic precipitator that 

would enhance development of new information for the Nanoparticle 

Information Library by enabling nanoparticle sampling and subsequent 

electron microscopy analysis.

■ Developed protocols for analyzing workplace nanoaerosol samples using transmission electron microscopy/energy dispersive spectroscopy.

■ Developed a protocol for nanoaerosol characterization fieldwork, including quasi-real time spatial mapping of nanoparticle concentrations 

in the workplace.

■ Updated Nanoparticle Information Library software to meet new CDC 

security requirements.

■ Incorporated a mailing interface and a newsletter interface in the design of the Nanoparticle Information Library.
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■ Developed online newsletters and disseminated them to persons on the 

Nanoparticle Information Library mailing list.

■ Developed course curriculum entitled Nanotechnology Science and 

Engineering for the mechanical engineering department at Gonzaga 

University. The course covers the basic chemical, physical, and engineering principles governing nanomaterials, highlighting their differences from classic materials, as well as the science required to use them 

in nanotechnologies for real-world problem solving.

■ Led a team of students in the design, building, and testing of a rapid 

mobility particle sizer, which has application for the Nanoparticle Information Library and nanotechnology science in general and won first 

place in the 2008 American Society of Mechanical Engineers (ASME) 

national design contest.

Publications and Abstracts

■ Miller AL, Stipe C, Habjan MC, Ahlstrand G [2007]. Role of lubrication oil in particulate emissions from a hydrogen-powered internal 

combustion engine. Environ Sci Technol 41:6828–6835.

■ Miller AL, Hoover M D, Mitchell DM, Stapleton BP [2007]. The 

nanoparticle information library (NIL): a prototype for linking and 

sharing emerging data. J Occup Environ Hyg 4(12):D131–D134. 

■ Miller A, Ahlstrand G, Kittelson DB, Zachariah MR [2007]. The fate 

of metal (Fe) during diesel combustion: morphology, chemistry, and 

formation pathways of nanoparticles. Combust Flame 149:129–143.

■ Miller AL, Habjan MC, Park K [2007]. Real-time estimation of elemental carbon emitted from a diesel engine. Environ Sci Technol 41:5783–

5788.

■ Ng A, Miller A, Ma H, Kittelson DB [2007]. Comparing measurements 

of carbon in diesel exhaust aerosols using the aethalometer, NIOSH 

method 5040 and SMPS. SAE tech paper series 2007–01–0334. 

■ Miller AL, Habjan M, Beers-Green A, Ahlstrand G [2008]. Microscopic 

analysis of airborne particles and fibers, a chapter for the new American Conference of Governmental Industrial Hygienists handbook, Air 

sampling technologies: principles and applications [www.acgih.org/

store/ProductDetail.cfm?id=2015]. 

■ Park K, Kim J-S, Miller AL [2008]. A study on effects of size and struc A study on eff ects of size and structure on hygroscopicity of nanoparticles using a tandem differential 
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mobility analyzer and transmission electron microscopy. J Nanopart 

Res [http://dx.doi.org/10.1007/s11051-008-9462-4]. 

■ Choo S-W, Lee D, Lee K-S, Miller AL, Park K, Zachariah M, Zhou L 

[2008]. Understanding nanoscale phenomena using single particle 

mass spectrometry and improvement of its performance—a review. 

Chem Physics Res J 2(1/2):17.

Invited Presentations

■ Miller A [2007]. Occupational safety and health challenges of nanotechnology: What we know and what we don’t know. Oregon governor’s occupational health and safety conference, Portland, OR, March 

13. 

■ Miller A [2007]. Characterization of hazardous pollutants in the workplace. IERC workshop for sound management of hazardous chemicals 

and sustainable energy, sponsored by the Gwangju Institute of Science 

and Technology, Gwangju, Korea, October 30–November 3.

■ Miller A [2008]. Spatial mapping of industrial hygiene data in the 

workplace. American Industrial Hygiene Association conference and 

exhibition, Minneapolis, MN, May 31–June 5.

■ Miller A, Geraci CL, Maynard A [2008]. NIOSH’s role in improving 

health and safety in nanotechnology workplaces. Special Libraries Association annual meeting, Seattle, WA, June 15–17.

■ Miller A [2008]. NIOSH’s role in improving health and safety in nanotechnology workplaces: knowledge management of nanotechnology 

information. Micro-nano breakthrough conference, Portland, OR, 

September 8–10.
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Project 41: Nanoparticles in the Workplace

Principle Investigator: Mark D. Hoover, Ph.D.

Project Duration: FY 2004–2009

Critical Topic Areas: exposure assessment, communication and 

information

Accomplishments and Research Findings

■ Summarized and published issues and approaches for exposure assessment of nanoparticles in the workplace as a chapter in a book on 

nanotoxicology that involved a spectrum of international contributors. 

The exposure assessment chapter included a comprehensive formulaic 

method for assessing and managing determinants of workplace exposure such as material at risk, damage ratio, airborne release fraction, 

respirable fraction, and control factors.

■ Contributed to the development of an American Industrial Hygiene 

Association (AIHA) document on guidance for conducting control 

banding analyses. Provided leadership in activities of the AIHA control 

banding working group and the AIHA nanotechnology working group 

to develop potential nanotechnology applications of control banding 

approaches from pharmaceutical and other historical experiences.

■ Developed a new ultrafine beryllium oxide standard reference material 

(SRM) through the collaborations with the National Institute of Standards and Technology (NIST), and U.S. Department of Energy (DOE). 

SRM 1877 was formally approved and issued for distribution and use 

in August 2008. This is one of the first reference materials issued in the 

ultrafine particle size range and will improve calibration and development of sampling and analytical methods and toxicity testing. Roundrobin evaluations of analytical methods for beryllium detection in 

air filtration samples spiked with SRM 1877 are underway under the 

auspices of the Beryllium Health and Safety Committee. Results of the 

evaluatons are expected to have relevance for digestion and detection 

effeciencies of other ultrafine metal oxide particles. 

■ Developed partnerships with nanotechnology industries, academia, 

government agencies, labor, and voluntary consensus standard committees to conduct joint research and develop guidelines on working 

safely with nanomaterials. This included involvement in activities of the 
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American National Standards Institute, ASTM International, the International Standards Organization, and the International Electrotechnical Commission. This included collaboration on development of a new 

Web site, wiki, and other informatics and knowledge-management 

capabilities for sharing information, including through the NIOSH 

Nanoparticle Information Library and through a nanotechnology community initiative on minimum information for nanomaterial characterization.

Publications and Abstracts

■ Hoover MD, Stefaniak AB, Day GA, Geraci CL [2007]. Exposure 

assessment considerations for nanoparticles in the workplace. In: 

Monteiro-Riviere NA, Tran CL, eds. Nanotoxicology: characterization, 

dosing, and health effects. New York: Informa Healthcare USA Inc., pp. 

71–83.

■ Miller AL, Hoover MD, Mitchell DM, Stapleton BP [2007]. The 

Nanoparticle Information Library (NIL): a prototype for linking and 

sharing emerging data. J Occup Environ Hyg 4(12):D131–D134. 

■ American Industrial Hygiene Association [2007]. Guidance for conducting control banding analyses. Fairfax, VA: American Industrial 

Hygiene Association, Document 9–2007. 

■ Hoover MD, Poster D [2008]. Environmental, health, and safety crosscut issues for nanomanufacturing. In: Instrumentation, metrology, and 

standards for nanomanufacturing workshop final report. Postek MT, 

Lyons KW, Ouimette MS, Holdridge GM eds. National Science and 

Technology Council Interagency Working Group on Manufacturing 

Research and Development, Washington, DC 

Invited Presentations

■ Hoover MD [2007]. NIOSH research on applications, safety hazards, and 

environmental issues for nanotechnology. CSHEMA-PRIZIM regional 

Environmental Health and Safety seminar, University of Central Florida, 

Orlando, FL, April 17.

■ Hoover MD [2007]. NIOSH experience in assessing practical measurement and control practices for nanoparticles. Midwest Nanotechnology 

Safety workshop, Madison, WI, May 21.
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NIOSH Nanotechnology Research Center

■ Hoover MD [2007]. Case studies in assessing practical measurement 

and control practices for nanoparticles. American Industrial Hygiene 

Association aerosol technology committee symposium on nanotechnology: wonders and worries, Philadelphia, PA, June 2.

■ Hoover MD [2007]. Nanotechnology health and safety issues. U.S. Department of Energy industrial hygiene and occupational safety special 

interest group, Philadelphia, PA, June 8.

■ Hoover MD [2007]. Nanoparticle Information Library. National Nanomanufacturing Network workshop on nanoinformatics strategies, 

Arlington, VA, June 12.

■ Hoover MD [2007]. Reference material updates and insights from the 

NIOSH nanotechnology and exposure assessment research programs. 

NIOSH-NIST information exchange meeting, National Institute of 

Standards and Technology, Gaithersburg, MD, June 14.

■ Hoover MD [2007]. Overview of NIOSH research on environmental health and safety issues for nanotechnology session on health and 

safety issues associated with nanomaterials. Air and Waste Management Association annual meeting, Pittsburgh, PA, June 27.

■ Hoover MD [2007]. Environmental Health and Safety overview—

exposure assessment and control for nanoparticles in the workplace: insights from the NIOSH Nanotechnology Research Program. 

NanoScience+Engineering SPIE Optics+Photonics conference, San 

Diego, CA, August 30.

■ Hoover MD [2007]. Materials necessary for health and occupational 

exposure studies, workshop on standards for environmental health and 

safety research needs for engineered nanoscale materials. National Institute of Standards and Technology, Gaithersburg, MD, September 12.

■ Hoover MD [2008]. NanoMetrology research at NIOSH, National 

Institute of Standards and Technology—NIOSH scientific information 

exchange, National Institute of Standards and Technology, Gaithersburg, MD, January 28.

■ Hoover MD [2008]. Insights from the NIOSH Nanotechnology Research Program, panel discussion on accelerators and nanoparticles, 

Health Physics Society midyear meeting on radiation-generating devices, Oakland, CA, January 29.

■ Hoover MD [2008]. NIOSH nanotechnology initiative: remarks on exposure assessment and control and informatics opportunities. NIOSH 
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NIOSH Nanotechnology Research Center

education and research centers industrial hygiene program directors’ 

meeting, Galveston, TX, February 10.

■ Hoover MD [2008]. The collection and characterization of nanomaterials for exposure assessment. American Industrial Hygiene Association—Northern California section technical symposium on the occupational health aspects of nanomaterials, Menlo Park, CA, May 14.

■ Hoover MD [2008]. Exposure assessment data needs for emerging issues: a case study for nanotechnology risk assessment and risk management. American Industrial Hygiene Association conference and exposition, Minneapolis, MN, May 31–June 5.

■ Hoover MD [2008]. Nanoparticle issues for the health physicist: insights from the NIOSH Nanotechnology Research Program. Annual 

meeting of the Health Physics Society, Pittsburgh, PA, July 16.

■ Hoover MD [2008]. Update on the NIOSH direct-reading methods 

initiative. Annual meeting of the Health Physics Society, Pittsburgh, 

PA, July 16.

■ Hoover, MD [2008]. Demonstration of the NIOSH prototype Webbased Nanoparticle Information Library. Workshop on international 

collaboration for nanoEHS informatics, National Institute of Standards 

and Technology, Gaithersburg, MD, October 10.

■ Hoover MD [2008]. Nanotechnology safety issues for radioactive materials: insights from the NIOSH Nanotechnology Research Program, 

regional inspector counterpart seminar. U.S. Nuclear Regulatory Commission, Region 1, King of Prussia, PA, December 10.
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NIOSH Nanotechnology Research Center

Project 42: New Sensor Technology 

Development for ESLI

Principle Investigator: Jay Snyder

Project Duration: FY 2002–2010

Critical Topic Area: applications

Accomplishments and Research Findings

■ Developed sensors and integrated them into APR cartridges for evaluation.

■ Developed new nanomaterials for chemical sensing.

Publications and Abstracts

■ King BH, Ruminski AM, Snyder JL, Sailor MJ [2007]. Optical-fibermounted porous silicon photonic crystals for sensing organic vapor 

breakthrough in activated carbon. Adv Mater 19:4530–44.

Invited Presentations 

■ Snyder J [2007]. End-of-service-life sensor systems for personal protective equipment. Scientific conference on chem bio defense research, 

Timonium, MD, November 13–15.

■ Snyder J [2007]. End-of-service life sensors and models. Technical Support Working Group, Personal Protective Equipment Conference, Fort 

Lauderdale, FL, November 27–29.

■ Snyder J [2008]. Chemically modified porous silicon for optical sensing 

of organic vapor breakthrough in activated carbon filters. Nanomaterials for Defense conference, Arlington, VA, April 21–24. 

■ Snyder J [2008]. End-of-service life sensor development. International 

Isocyanate Institute (III) America analytical subcommittee meeting, 

Boulder, CO, June 9.

■ Snyder J [2008]. Jetted nanoparticle chemical sensor circuits for respirator end-of-service-life detection. 12th International meeting on 

Chemical Sensors, Columbus, OH, July 13–16.
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■ Snyder J [2008]. A cartridge simulator for testing end-of-service life 

indicators. International Society for Respiratory Protection, 14th International Conference, Dublin, Ireland, September 14–18.
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NIOSH Nanotechnology Research Center

Project 43: Global Harmonization of 

Exposure Measurement and 

Exposure Mitigation Approaches 

for Nanomaterials

Principal Investigator: Vladimir Murashov, Ph.D.

Project Duration: FY 2006–2008 

Critical Topic Areas: international activities in safety and health, including exposure assessment, risk assessment, recommendations and guidance, 

and communication and information.

Accomplishments and Research Findings

■ Coordinated the international and interagency activities of the NIOSH 

Nanotechnology Research Program.

■ Led the development and publication of ISO TR/12885:2008 Health 

and safety practices in occupational settings relevant to nanotechnologies. 

■ Provided technical expertise for several ISO TC229 projects.

■ Chaired the Organization for Economic Cooperation and Development Working Party for Manufactured Nanomaterials Steering Group 

8, exposure measurement and exposure mitigation.

■ Co-led the WHO project on best practices for safe handling of nanomaterials.

■ Fostered collaboration in nanotechnology research with the following:

— EPA 

— Consumer Products Safety Commission 

— NASA

— National Institute of Standards and Technology 

— European Comission

— Australia

■ Represented NIOSH on several national and international working 

groups on nanotechnology safety and health.
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NIOSH Nanotechnology Research Center

■ Represented NIOSH on the National Nanotechnology Initiative interagency subcommittee and its working groups.

■ Presented overviews of the NIOSH Nanotechnology Research Program 

to outside stakeholders.

Publications and Abstracts

■ Murashov VV, Howard J [2007]. Biosafety, occupational health, and 

nanotechnology. Appl Biosafety 12(3):158–167

■ Murashov V, Howard J [2008]. The U.S. must help set international 

standards for nanotechnology. Nature Nanotechnol 3:635–636.

■ Schulte PA, Geraci CL, Zumwalde R, Hoover M, Castranova V, Kuempel E, Murashov V, Vainio H, Savolainen K [2008]. Sharpening the 

focus on occupational safety and health of nanotechnology in the 

workplace. Scand J Work Environ Health 34(6):471–478.

■ ISO [2008]. Health and safety practices in occupational settings relevant to nanotechnologies. Geneva, Switzerland: International Organization for Standardization, ISO/TR–12885.

■ NIOSH [2008]. Nanotechnology: should carbon nanotubes be handled 

in the workplace like asbestos? Cincinnati, Ohio: U.S. Department of 

Health and Human Services, Centers for Disease Control, National 

Institute for Occupational Safety and Health, NIOSH Science Blog May. 

[www.cdc.gov/niosh/blog/nsb052008_nano.html].

■ Murashov VV [in press]. Occupational exposure to nanomedical applications. Wiley Interdisciplinary Reviews: nanomedicine.

Government Publications

■ NSTC [2007]. The national nanotechnology initiative strategic plan. 

By Nanoscale science, engineering, and technology subcommittee, 

committee on technology. National Science and Technology Council, 

Arlington, VA. [http://www.nano.gov/NNI_Strategic_Plan_2007.pdf].

■ NSTC [2007]. Prioritization of environmental, health, and safety research needs for engineered nanoscale materials. An interim document 

for public comment. By Nanoscale science, engineering, and technology subcommittee, committee on technology. National Science and 

Technology Council, Arlington, VA.

■ NSTC [2008].Strategy for nanotechnology-related environmental health and safety research. Nanoscale science, engineering, and 
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NIOSH Nanotechnology Research Center

technology subcommittee, committee on technology. National Science 

and Technology Council, Arlington, VA. [http://www.nano.gov/NNI_

EHS_Research_Strategy.pdf].

Invited Presentations

■ Murashov V [2007]. Nanotechnology health and safety concerns—

NIOSH Nanotechnology Research Program. Intertech-PIRA workshop, 

Washington, DC, February 8.

■ Murashov V [2007]. NIOSH Nanotechnology Research Program. Navy 

occupational health and safety preventive medicine conference, Hampton, VA, March 20.

■ Murashov V [2007]. Safe handling of nanotechnology. OSHA/NIOSH 

Journal Club, Washington, DC, March 29.

■ Murashov V [2007]. Nanotechnology health and safety concerns. Meeting of National Aeronautics and Space Administration Code 500 safety 

awareness campaign, Greenbelt, MD, April 18.

■ Murashov V [2007]. NIOSH Nanotechnology Research Program. Conference on Nanotech 2007, Santa Clara, CA, May 21.

■ Murashov V [2007]. Nanotechnology: occupational health and safety. 

Conference on risk assessment for nanomaterials, Cambridge, MA, 

May 29.

■ Murashov V [2007]. Social studies at NIOSH. The Joint Wharton-CHF 

symposium on social studies of nanotechnology, Philadelphia, PA, June 8.

■ Murashov V [2007]. NIOSH Nanotechnology Research Program. Annual environmental health and exposure assessment workshop, Washington, DC, August 17.

■ Murashov V [2007]. NIOSH Nanotechnology Research Program. Interagency workshop on the environmental implications of nanotechnology, Washington, DC, September 5.

■ Murashov V [2007]. Considerations for selecting standard materials for 

occupational safety and health. Interagency workshop on standards for 

environmental health and safety research needs for engineered nanoscale materials, Gaithersburg, MD, September 12.

■ Murashov V [2007]. Nanotechnology health and safety concerns. American Society of Safety Engineers, Region VI PDC, Myrtle Beach, SC, 

September 20.
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■ Murashov V [2007]. Nanotechnology: occupational health and safety. 

Mid-Atlantic Regional conference on occupational medicine, Baltimore, 

MD, October 13.

■ Murashov V [2007]. Nanotechnology: occupational safety and health. 

NanoApplications summit—CleanTech Day, Cleveland, OH, October 24.

■ Murashov V [2007]. Nanotechnology: occupational safety and health. 

State-of-the-Art Conference/International Conference on Health Care 

Worker Health, Vancouver, British Columbia, Canada, October 26.

■ Murashov V [2008]. Nanotechnology and risk. California State University in Northridge, Environmental and Occupational Health Nanotech 

symposium, Northridge, CA, February 20.

■ Murashov V [2008]. International Organization for Standardization 

TC146/SC2. International Organization for Standardization workshop 

on documentary standards for measurement and characterization in 

nanotechnologies, Gaithersburg, MD, February 26.

■ Murashov V [2008]. OECD WPMN SG8 Cooperation on exposure measurement and exposure mitigation. International Organization for Standardization workshop on documentary standards for measurement and 

characterization in nanotechnologies, Gaithersburg, MD, February 26.

■ Murashov V [2008]. Exposure assessment and control practices for 

nanoparticles. University of California, San Diego, forum, San Diego, 

CA, March 6.

■ Murashov V [2008]. Nanotechnology and risk. Joint BIONET/BSAF 

symposium on current topics in biosafety, La Jolla, CA, March 7.

■ Murashov V [2008]. Nanotechnology and risk. 2008 Controlled Environment Testing Association conference, San Antonio, TX, April 14.

■ Murashov V [2008]. Nanotechnology: exposure assessment. International symposium on risk assessment of manufactured nanomaterials, 

Tokyo, Japan, April 23.

■ Murashov V [2008]. Nano health, safety and environment and worker 

protection. Second Jisso international forum, Atlanta, GA, May 22.

■ Murashov V [2008]. Nanotechnology: occupational safety and health. 

Workshop on biological interaction of engineered nanomaterials: 

environmental, safety, and health issues of military concern, WPAFB, 

Dayton, OH, June 25.
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■ Murashov V [2008]. NIOSH Nanotechnology Research Program. Nanoscale Science, Engineering and Technology subcommittee meeting, 

Arlington, VA, July 15.

■ Murashov V [2008]. NIOSH Nanotechnology Research Program. 

Conference on sustainable nanotechnology innovations, products, and 

toxicology, Fayetteville, AR, August 14.

■ Murashov V [2008]. NIOSH Nanotechnology Research Program. 

State-of-the-Art Conference/International Conference on Health Care 

Worker Health, Vancouver, British Columbia, Canada, October 27.

■ Murashov V [2008]. NIOSH Nanotechnology Research Program. 

Meeting of Chinese National Institute of Occupational Health and Poison Control, Beijing, China, November 13.

■ Murashov V [2008]. NIOSH Nanotechnology Research Program. 

Meeting of National Center for Nanoscience and Technology of China, 

Beijing, China, November 14. 

■ Murashov V [2008]. Nanotechnology and risk. Metro Washington College of Occupational and Environmental Medicine Meeting, Bethesda, 

MD, December 3.

■
Appendices

119

Appendix A Projects by Critical Topic Area

A. Toxicology and Internal Dose

Project 1: Nanotechnology Research Center Coordination 

Project 2: Nanotechnology Safety and Health Research Coordination 

Project 3: Systemic Microvascular Dysfunction: Effects of Ultrafine vs. Fine Particles 

Project 4: Particle Surface Area as a Dose Metric 

Project 5: Role of Carbon Nanotubes in Cardiovascular and COPD-Related Diseases 

Project 6: Investigations of Multi-Walled Carbon Nanotube Toxicity 

Project 7: Pulmonary Toxicity of Metal Oxide Nanospheres and Nanowires 

Project 8: WC-Co Nanoparticles in Initiating Angiogenesis by Reactive Oxygen 

Species 

Project 9: Evaluation of the Pulmonary Deposition and Translocation of 

Nanomaterials 

Project 10: Occupational Exposures and Potential Neurological Risks 

Project 11: Lung Effects of Resistance Spot Welding Using Adhesives 

Project 12: Neurotoxicity after Pulmonary Exposure to Welding Fumes 

Project 13: Potential Aneuploidy Following Exposure to Carbon Nanotubes 

Project 14: Pulmonary Toxicity of Carbon Nanotube Particles 

Project 15: Dermal Toxicity of Nanotube Particles 

Project 16: Specific Biomarkers for Unusual Toxicity of Nanomaterials 

Project 17: Pulmonary Toxicity of Diesel Exhaust Particles 

Project 18: Induction of Lung Fibrosis by Cerium Oxide in Diesel Exhaust 

Project 19: Potential Effects of Silicon-based Nanowires on Lung Toxicity

Project 20: Cell-based Assessment for Iron Nanoparticle-Induced Health Risks

Project 21: Assessment of Carbonaceous Materials on Magenicity

B. Measurement Methods

Project 1: Nanotechnology Research Center Coordination 

Project 22: Generation and Characterization of Nanoparticles 

Project 23: Dustiness of Nanomaterials 
120

NIOSH Nanotechnology Research Center

120

Project 24: Nanoaerosol Monitoring Methods 

Project 25: Measurement of Nanoscale Carbonaceous Aerosols 

Project 26: Nanoparticle Reference Materials for Health Protection 

Project 27: Calm Air Chamber and Wind Tunnel Evaluation of Personal Aerosol 

Samplers for Nanoparticle Exposure Assessment 

Project 28: Ultrafine TiO2 Surface and Mass Concentration Sampling Method

Project 29: Standard Determination of Nanoparticle Size

Project 30: Development and Evaluation of Nanoaerosol Surface Area Measurement 

Methods

Project 31: Workplace Monitoring of Carbon Nanofibers/Nanotubes

Project 32: Ultrafine Aerosols from Diesel-Powered Equipment

Project 33: Titanium Dioxide and Other Metal Oxides Exposure Assessment Study 

C. Exposure Assessment

Project 1: Nanotechnology Research Center Coordination

Project 23: Dustiness of Nanomaterials 

Project 24: Nanoaerosol Monitoring Methods 

Project 25: Measurement of Nanoscale Carbonaceous Aerosols 

Project 31: Workplace Monitoring of Carbon Nanofibers/Nanotubes

Project 33: Titanium Dioxide and Other Metal Oxides Exposure Assessment Study 

Project 34: Field Research Team

Project 41: Nanoparticles in the Workplace

Project 43: Global Harmonization of Exposure Measurement and Exposure Mitigation 

Approaches for Nanomaterials

D. Epidemiology and Surveillance

Project 1: Nanotechnology Research Center Coordination 

Project 35: Assessing the Feasibility of Industrywide Exposure and Epidemiology 

Studies of Workers Exposed to Engineered Nanomaterials 

E. Risk Assessment

Project 1: Nanotechnology Research Center Coordination 

Project 36: Nanoparticles—Dosimetry and Risk Assessment
121

Appendix A| Projects by Critical Topic Area

121 121

Appendix A| Projects by Critical Topic Area

121

Project 43: Global Harmonization of Exposure Measurement and Exposure Mitigation 

Approaches for Nanomaterials 

F. Engineering Controls and Personal Protective Equipment

Project 1: Nanotechnology Research Center Coordination 

Project 37: Penetration of Nanoparticles through Respirators 

Project 38: Nanoparticle Penetration through Protective Clothing

Project 39: Development of Personal Protective Equipment Ensemble Test Methods 

G. Fire and Explosion

Project 1: Nanotechnology Research Center Coordination

Project 23: Dustiness of Nanomaterials 

H. Recommendations and Guidance

Project 1: Nanotechnology Research Center Coordination 

Project 43: Global Harmonization of Exposure Measurement and Exposure Mitigation 

Approaches for Nanomaterials 

I. Communication and Information 

Project 1: Nanotechnology Research Center Coordination 

Project 40: Web-based Nanoparticle Information Library Implementation

Project 41: Nanoparticles in the Workplace 

Project 43: Global Harmonization of Exposure Measurement and Exposure Mitigation 

Approaches for Nanomaterials

J. Applications

Project 1: Nanotechnology Research Center Coordination

Project 42: New Sensor Technology Development for ESLI
122

Appendix B NIOSH Extramural Nanotechnology

Research Activities

Background

NIOSH sponsors research and training outside the Institute through the Office of Extramural Programs (OEP). The creativity and special resources available in the extramural 

community make these programs an important component in achieving a national goal to 

have safe jobs and healthy workers. The office also serves to help NIOSH address priorities 

from the National Occupational Research Agenda (NORA), the NIOSH Research to Practice (r2p) initiative, congressional mandates, and the NIOSH Program Portfolio (http://

www.cdc.gov/niosh/programs).

A variety of occupational safety and health-related research grants and cooperative agreements, training grants, and conference grants outside the Institute are managed by OEP. 

The competitive process for soliciting applications, conducting peer reviews, and for making awards is managed by OEP.

The extramural office works closely with public and private academic institutions, State 

and Federal agencies, and with small private businesses. Extramural program scientists 

also consult with intramural scientists. Extramural applicants are encouraged to collaborate with NIOSH scientists when possible; however, extramural projects are managed 

separately from intramural programs to ensure fair competition, maintain research integrity, and to eliminate financial and intellectual conflicts of interest.

Purpose

Extramural 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. Extramural 

nanotechnology research adds to the overall development of new information and complements efforts undertaken within the Institute.

Overall NIOSH Extramural Nanotechnology Research Program

From 2001–2008, NIOSH/OEP has committed $5.2 million (M) to extramural nanotechnology research. Ongoing projects currently funded through 2011 account for another 

$1.4M (Figure 1), which brings the total to about $6.6M. This has been accomplished by 
123 123

Appendix B| NIOSH Extramural Nanotechnology Research Activities

the use of non-earmarked research funds, NIOSH program announcements, joint requests 

for applications with other Federal agencies, and Small Business Innovation Research 

(SBIR) funds. The office has not received additional funds for nanotechnology research.

Figure 1. New and ongoing NIOSH/OEP funding in nanotechnology (Pre-2004–2008)

Funding Partnerships

OEP has partnered in two joint Requests for Applications (RFAs) for Nanotechnology 

Research Grants Investigating Environmental and Human Health Issues. The U.S. Environmental Protection Agency’s National Center for Environmental Research (NCER) and 

the National Science Foundation (NSF) participated in FY 2005. The National Institute of 

Environmental Health Sciences (NIEHS) joined in FY 2006. Funding was available to support Research (R01) grants for 3 years and Exploratory (R21) grants for 2 years.

Funding Mechanisms

Figure 2 summarizes the five types of funding mechanisms used by NIOSH for extramural 

nanotechnology research. SBIR (R43/44) and major research projects (R01) represent the 

major categories.
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NIOSH Nanotechnology Research Center

Figure 2. NIOSH/OEP funding (2001–2008) in nanotechnology by Grant Mechanism

Extramural Research Projects and NIOSH Nanotechnology Goals

The major NIOSH goals for nanotechnology research are as follows:

1. Determine if nanoparticles and nanomaterials pose risks for work-related injuries 

and illnesses.

2. Conduct research to prevent work-related injuries and illnesses by applying nanotechnology products.

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.

Extramural NIOSH funding for nanotechnology research has primarily been related to 

goals 1–3 (Figure 3). NIOSH/OEP continues to pursue partnerships in sponsoring funding opportunities that involve global collaborations between scientists in the United States 

and other countries. 

n=5

n=6

n=1

n=1

n=1 Mentored scientist (KO1)

Developmental (R21)

Small research (RO3)

Research program (RO1)

SBIR (R33/R44) n=5

n=6

n=1

n=1

n=1 Mentored scientist (KO1)

Developmental (R21)

Small research (RO3)

Research program (RO1)

SBIR (R33/R44)
125

Appendix B Appendix B|| NIOSH Extramural Nanotechnology Research Activities NIOSH Extramural Nanotechnology Research Activities

Figure 3. NIOSH/OEP nanotechnology funding by Strategic Goals

Additional Information about Extramural Portfolio

From FY 2001 to FY 2004, OEP funded three R43/44 projects for a total funding commitment of about $950K (Table 1).

In FY 2005, NIOSH funded two nanotechnology research grants through the R01 Program Announcement (Table 1). OEP also began participating in RFAs for Nanotechnology Research Grants Investigating Environmental and Human Health Issues. For the first 

RFA, 83 applications were received and 19 were recommended for funding. Fourteen of 

these met NIOSH criteria for relevance to occupational safety and health. Five were in the 

competitive range for funding consideration and one was funded by NIOSH. EPA funded 

14 projects and NSF funded two projects under this RFA. 

In FY 2006, 81 applications were received in response to the joint RFA on environmental 

and human health issues. Six of these met NIOSH criteria for relevance and three were in 

the competitive range for funding consideration. NIOSH was able to fund one application 

(Table 1). EPA funded 21 projects, NSF funded four, and NIEHS funded three projects under this RFA. NIOSH also funded two SBIR grants on nanotechnology in FY 2006.

In FY 2007, NIOSH funded a 3-year career development (mentored scientist) grant 

involving research on personal exposure to nanoparticles at the University of Iowa. In addition, a 2-year exploratory/developmental research project was funded at Colorado State 

University. NIOSH also participated in RFA-ES-06-008 Manufactured Nanomaterials: 

Physico-chemical Principles of Biocompatibility and Toxicity, which was jointly sponsored 

by NIEHS, EPA, and NIOSH.

n=4, 29%

n=0, 0%

n=4, 29%

n=6, 42%

Goal 1: Health effects research

Goal 3: Engineering controls

Goal 4: Global collaboration

Goal 2: Nanotechnology products

 prevention

n=4, 29%

n=0, 0%

n=4, 29%

n=6, 42%

Goal 1: Health effects research

Goal 3: Engineering controls

Goal 4: Global collaboration

Goal 2: Nanotechnology products

 prevention
126

NIOSH Nanotechnology Research Center Table 1. Extramural nanotechnology research funded by NIOSH, 2001–2008 Grant Number Investigator Institution Project title Start End 1st year funding Total funding Prior to FY-04 NIOSH SBIR 1R43OH007471-01 Hooker Nanomaterials Research LLC, Longmont, CO Novel Hydrogen Sulfide Sensors for Portable Monitors 9/30/2001 3/31/2002 $100,000 $100,000 2R44OH007471-02 Hooker Synkera Technologies Inc., Longmont, CO Novel Hydrogen Sulfide Sensors for Portable Monitors 9/16/2003 9/15/2006 $373,400 $750,000 Pre-FY-04 Total $473,400 $850,000 FY-04 NIOSH SBIR

1R43OH007963-01A1 Rajagopalan Nanoscale Materials, 

Inc., Manhattan, KS

From Nanoparticles to Novel Protective Garments

9/1/2004 5/15/2005 $100, 000 $100,000

FY-04 Total $100,000 $100,000FY-05 NIOSH R01 Program Announcement1R01OH008282-01A Kagan University of Pittsburgh Lung Oxidative 

Stress/Inflammation by Carbon Nanotubes

7/1/2005 6/30/2009 $364,000 $1,451,500

FY-05 Co-sponsored RFA (EPA STAR-2005-B1)1R01OH008806-01 O’Shaughnessy University of Iowa Assessment 

Methods for Nanoparticles in the Workplace

7/1/2005 6/30/2008 $133,000 $391,200

1R01OH008807-01 Xiong New York University

School of Medicine

Monitoring and Characterizing Airborne Carbon Nanotube Particles

8/1/2005 7/31/2008 $158,000 $395,200

FY-05 Total $655,000 $2,237,900FY-06 NIOSH SBIR1R43OH008739-01 Thompson Eltron Research

Boulder, CO

Antistatic Paint with Silent Discharge

8/30/2006 8/30/2007 $100,000 $100,000

(Continued)
127

Appendix B Appendix B|| NIOSH Extramural Nanotechnology Research Activities NIOSH Extramural Nanotechnology Research Activities

Grant Number Investigator Institution Project title Start End

1st year

 funding

Total

funding

1R43OH008939-01 Deininger Synkera Technologies 

Inc., Longmont, CO

New Nanostructured Sensor Arrays for Hydride Detection

8/1/2006 2/28/2007 $100,000 $100,000

FY-06 Co-sponsored RFA (EPA G2006-STAR F1 to F7)1R01OH009141-01 Dutta Ohio State University Role of Surface 

Chemistry in the Toxicological Properties of Manufactured Nanoparticles

9/1/2006 8/31/2009 $120,000 $360,200

FY-06 Total $320,000 $560,200FY-07 NIOSH Exploratory/Developmental Research (R21) Program Announcement 1R21OH009114-01 Volckens

Colorado State University A High-Flow Personal Sampler for 

Inhalable Aerosol

8/1/2007 7/31/2009

$207,200 $421,000

FY-07 Career Development Grants (K01) Program Announcement1K01OH009255-01 Peters University of Iowa Personal Exposure 

to Engineered Nanoparticles

9/1/2007 8/31/2010 $106,900 $321,000

 FY-07 Total $314,100 $742,000 FY-08 Co-sponsored RFA (NIEHS RFA-ES-06-008)1R01OH009448-01 Grassian University of Iowa An Integrated 

Approach Toward Understanding the Toxicity of Inhaled Nanomaterials

4/1/2008 3/31/2012 $337,600 $1,222,600

FY-08 NIOSH Small Research Grant (PAR-06-551) Program Announcement

Table 1. Extramural Nanotechnology research funded by NIOSH, 2001–2008
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NIOSH Nanotechnology Research Center Grant Number Investigator Institution Project title Start End 1st year funding Total funding 1R03OH009381 Volckens Colorado State University A Personal Sam- pler for Assessing Inhaled Nanopar- ticle Exposures 7/1/2008 6/30/2010 $71,500 $143,000 FY-08 NIOSH SBIR 2R44OH007963-02 Rajagopalan Nanoscale Materials, Inc., Manhattan, KS From Nanoparticles to Novel Protective 

Garments

7/1/2008 6/30/2010 $387,700 $750,000

FY-08 Total $796,800 $2,115,600 Grand Total $6.6M

Table 1. Extramural nanotechnology research funded by NIOSH, 2001–2008
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In FY 2008, NIOSH funded a major research grant (R01) from the joint RFA on Manufactured Nanomaterials (Physico-chemical Principles of Biocompatibility and Toxicity). This 

project is being conducted at the University of Iowa. NIOSH also funded a small research 

grant (R03) at Colorado State University and an SBIR grant at Nanoscale Materials, Inc. in 

Kansas.

In FY 2009, nanotechnology related research proposals submitted to standing program 

announcements will be considered for funding. NIOSH plans to 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 continue to consult with the NIOSH Nanotechnology Research Center regarding needs and 

future directions for nanotechnology research.

Extramural Project Descriptions

Summaries of the extramural projects funded by NIOSH/OEP are included as part of this 

portfolio update. Contact information for the principal investigators of the projects is provided in Table 2 to encourage collaborative scientific efforts among researchers.

Current NIOSH Nanotechnology Related Information

Extramural investigators interested in pursuing nanotechnology studies related to occupational health and safety 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/research.htm

NIOSH has identified 10 critical topic areas to guide in addressing knowledge gaps, developing strategies, and providing recommendations. The key role for NIOSH in conducting 

and partnering in research on occupational exposures to nanomaterials is noted in a new 

strategic plan under the National Nanotechnology Initiative.

Information about the NIOSH goal to transfer research findings, technologies, and information into prevention practices and products in the workplace is provided at the Web 

site http://www.cdc.gov/niosh/r2p/. This emphasis on Research to Practice (r2p) is intended to reduce occupationally-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 on the NIOSH home page (http://www.cdc.gov/niosh/homepage.html) and 

the program portfolio Web site (http://www.cdc.gov/niosh/programs/).
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The Nanoscale Science, Engineering, and Technology (NSET) Subcommittee of the National Science and Technology Council’s Committee on Technology, with support from 

the National Nanotechnology Coordination Office, has released a new NNI Strategic Plan 

as called for in the 21st Century Nanotechnology Research and Development Act (Public 

Law 108-153) of 2003. This plan updates and replaces the NNI Strategic Plan of December 2004 and is available at http://www.nano.gov/NNI_Strategic_Plan_2007.pdf . NIOSH 

participates as a member organization on this subcommittee.

Extramural Nanotechnology Research Project Summaries

The project summaries included here contain the publicly available information from the 

NIH CRISP database (http://crisp.cit.nih.gov/). For additional information, please contact 

the Office of Extramural Programs. Investigator contact information is provided in Table 

2 to encourage collaborative scientific efforts between researchers. Contact information 

for Dr. Hooker was not available. Project summaries are listed in the order they appear in 

Table 1.

HOOKER 7471 (R43, R44)

Novel Hydrogen Sulfide Sensors for Portable Monitors

Background

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 shut off the lungs, while lower concentrations 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 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 

health and safety field. In addition, several potential spin-off opportunities are available in 

leak detection, emission monitoring, and process control. We will use alternative ceramic 

oxide materials and a unique multi-layer fabrication process to accomplish the objectives of this project. The work plan includes optimization of the sensor materials, sensor 
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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 not only alerts 

the wearer when unsafe concentrations have been encountered but also tracks cumulative 

individual worker exposure to a particular toxic gas species.

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 using 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-R43) 

From Nanoparticles to Novel Protective Garments

Background

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 hazardous materials are released, 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 (a) establish the feasibility of incorporating highly adsorbent and reactive nanoparticles into lightweight, permeable textiles and (b) evaluate the utility of the resultant fabric as protective clothing using standard industry testing procedures. These novel 

protective garments will be tailored 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 

sorptive capacity. Based on the outcome of this research, a single reactive nanoparticle 
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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.

KAGAN (8282) 

Lung Oxidative Stress/Inflammation by Carbon Nanotubes

Background

Specific Aim 1 is to establish the extent to which SWCNT 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 is to determine the potential for SWCNT and microbial stimuli to synergistically interact to promote macrophage activation, oxidative stress, and lung inflammation.

Specific Aim 3 is to reveal the extent to which SWCNT 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/biochemistry, cell and molecular 

biology of inflammation and its interactions with microbial agents, and pulmonary toxicology of nanoparticles.

Progress

Two types of single walled carbon nanotubes were used (iron-rich and iron-stripped) to 

study their interactions with RAW 264.7 macrophages. Following ultrasonication of the 

SWCNT to separate strands, neither types were able to generate intracellular production of superoxide radicals or nitric oxide macrophages observed by flow-cytometry and 

fluorescence microscopy. SWCNT with different iron content displayed different redox 

activity in a cell-free model system. In the presence of microbial (zymosan)-stimulated 

macrophages, non-purified, iron-rich SWCNT were more effective in generating hydroxyl 

radicals than purified SWCNT. The presence of iron in SWCNT may be important in determining redox-dependent responses of macrophages. Dose and time-dependence studies of inflammatory responses in mice using pharyngeal aspiration of SWCNT demonstrated that SWCNT 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 affects of SWCNT may 

exert toxic effects in the lung of exposed animals in vivo. SWCNT induced inflamma-
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tion, and exposure caused altered pulmonary function and microbial stimulation. Clearance from the lungs of SWCNT exposed mice was compromised. An unusual and robust 

inflammatory and fibrogenic response was correlated with the progression of oxidative 

stress and apoptotic signaling. Not only are toxic effects of SWCNT important to consider 

but also the role of transitional metals, particularly iron should be investigated.

Recent Publications

Shvedova AA, Fabisiak JP, Kisin ER, Murray AR, Roberts JR, Tyurina YY, Antonini JM, 

Feng WH, Kommineni C, Reynolds J, Barchowsky A, Castranova V, Kagan VE [2007].Sequential Exposure to carbon nanotubes and bacteria enhances pulmonary inflammation 

and infectivity. Am J Respir Cell Mol Biol. 

Abstract

Realistic exposures to carbon nanotubes (CNT) may occur in conjunction with other 

pathogenic impacts (microbial infections) and trigger enhanced responses. We evaluated 

interactions between pharyngeal aspiration of SWCNT and bacterial pulmonary infection 

of C57BL/6 mice with Listeria monocytogenes (LM). Mice were given SWCNT (0, 10, 

and 40 microg/mouse) and exposed to LM (10(3) bacteria/mouse) 3 days later. Sequential 

exposure to SWCNT/LM amplified lung inflammation and collagen formation. Despite 

this robust inflammatory response, SWCNT pre-exposure significantly decreased the pulmonary clearance of LM measured 3–7 days after microbial infection vs PBS/LM treated 

mice. Decreased bacterial clearance in SWCNT pre-exposed mice was associated with 

decreased phagocytosis of bacteria by macrophages and a decrease in nitric oxide production by these phagocytes. Pre-incubation of naive alveolar macrophages with SWCNT 

in vitro also resulted in decreased nitric oxide generation and suppressed phagocytizing 

activity towards LM. Failure of SWCNT-exposed mice to clear LM led to a continued 

elevation in nearly all major chemokines and acute phase cytokines into the later course 

of infection. In SWCNT/LM exposed mice, BAL PMNs, AMs, and lymphocytes as well as 

LDH level were increased compared to mice exposed to SWCNT or LM alone. In conclusion, enhanced acute inflammation and pulmonary injury with delayed bacterial clearance 

after SWCNT exposure may lead to increased susceptibility to lung infection in exposed 

populations.

Shvedova AA, Kisin ER, Murray AR, Gorelik O, Arepalli S, Castranova V, Young SH, Gao 

F, Tyurina YY, Oury TD, Kagan VE [2007].Vitamin E deficiency enhances pulmonary 

inflammatory response and oxidative stress induced by single-walled carbon nanotubes in 

C57BL/6 mice. Toxicol Appl Pharmacol 221(3):339–348

Abstract

Exposure of mice to single-walled carbon nanotubes (SWCNTs) induces an unusually 

robust pulmonary inflammatory response with an early onset of fibrosis, which is 
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accompanied by oxidative stress and antioxidant depletion. The role of specific components of the antioxidant protective system (specifically vitamin E, the major lipid-soluble 

antioxidant) in the SWCNT-induced reactions has not been characterized. We used 

C57BL/6 mice, maintained on vitamin E-sufficient or vitamin E-deficient diets, to explore 

and compare the pulmonary inflammatory reactions with aspired SWCNTs. The vitamin 

E-deficient diet caused a 90-fold depletion of alpha-tocopherol in the lung tissue and 

resulted in a significant decline of other antioxidants (GSH, ascorbate) as well as accumulation of lipid peroxidation products. A greater decrease of pulmonary antioxidants was 

detected in SWCNT-treated vitamin E-deficient mice compared with controls. Lowered 

levels of antioxidants in vitamin E-deficient mice were associated with a higher sensitivity 

to SWCNT-induced acute inflammation (total number of inflammatory cells, number of 

polymorphonuclear leukocytes, released LDH, total protein content and levels of proinflammatory cytokines, TNF-alpha and IL-6) and enhanced profibrotic responses (elevation of TGF-beta and collagen deposition). Exposure to SWCNTs markedly shifted the 

ratio of cleaved to full-length extracellular superoxide dismutase (EC-SOD). Given that 

pulmonary levels of vitamin E can be manipulated through diet, its effects on SWCNTinduced inflammation may be of practical importance in optimizing protective strategies.

O’SHAUGHNESSY (8806) 

Assessment Methods for Nanoparticles in the Workplace

Background

The primary objectives are to provide the scientific community and practicing industrial 

hygienists with verified instruments and methods for accurately accessing airborne concentrations of nanoparticles, and to assess the efficacy of respirator use for controlling 

nanoparticle exposures.

We will satisfy these objectives through a combination of laboratory and field-based studies centered on the following specific aims: (1) identify and evaluate methods to measure 

airborne nanoparticle concentrations, (2) characterize nanoparticles using a complementary suite of techniques to assess their surface and bulk physical and chemical properties, 

and (3) determine the collection efficiency of commonly-used 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. Although the primary particle size of these powders average 
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20nm, an aerosol with a median size of 120 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 levels in two facilities, one in 

MN and one in TX.

Recent Publication

Peters TM, Elzey S, Johnson R, Park H, Grassian VH, Maher T, O’Shaughnessy P [2009]. 

Airborne monitoring to distinguish engineered nanomaterials from incidental particles 

for environmental health and safety. J Occup Environ Hyg 6:2,73–81.

Abstract

Two methods were used to distinguish airborne engineered nanomaterials from other 

airborne particles in a facility that produces nano-structured lithium titanate metal oxide 

powder. The first method involved off-line analysis of filter samples collected with conventional respirable samplers at each of seven locations (six near production processes and 

one outdoors). Throughout most of the facility and outdoors, respirable mass concentrations were low (<0.050 mg/m3

) and were attributed to particles other than the nanomaterial (<10% by mass titanium determined with inductively coupled plasma atomic emission 

spectrometry). In contrast, in a single area with extensive material handling, mass concentrations were greatest (0.118 mg/m3

) and contained up to 39% ± 11% lithium titanium, indicating the presence of airborne nanomaterial. Analysis of the filter samples collected in 

this area by transmission electron microscope and scanning electron microscope revealed 

that the airborne nanomaterial was associated only with spherical aggregates (clusters of 

fused 10–80 nm nanoparticles) that were larger than 200 nm. This analysis also showed 

that nanoparticles in this area were the smallest particles of a larger distribution of submicrometer chain agglomerates likely from welding in an adjacent area of the facility. The 

second method used two hand-held, direct-reading, battery-operated instruments to obtain a time series of very fine particle number (<300 nm), respirable mass, and total mass 

concentration, which were then related to activities within the area of extensive material 

handling. This activity-based monitoring showed that very fine particle number concentrations (<300 nm) had no apparent correlation to worker activities, but that sharp peaks 

in the respirable and total mass concentration coincided with loading a hopper and replacing nanomaterial collection bags. These findings were consistent with those from the 

filter-based method in that they demonstrate that (1) airborne nanoparticles in this facility 

are dominated by “incidental” sources (e.g., welding or grinding), and (2) the airborne 

“engineered” product is predominately composed of particles larger than several hundred 

nanometers. The methods presented here are applicable to any occupational or environmental 

setting in which one needs to distinguish incidental sources from engineered product.
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XIONG (8807) 

Monitoring and Characterizing Airborne Carbon Nanotube Particles

Background

The proposed research will develop a comprehensive yet practical method for sampling, 

quantification, and characterization of carbon nanotube (CNT) particles in air. This 

method will be capable of (1) classifying sampled particles into three categories: tubes, 

ropes (bundles of single-walled CNTs bounded by Van der Waals attraction force), and 

non-tubular particles (soot, metal catalysts, and dust, etc.) and (2) measuring the number 

concentrations and size distributions for each type, and the shape characters (diameter, 

length, aspect ratio and curvature) of CNTs. 

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 a validated method for sampling airborne. 

CNTs in workplaces; and a practical method using atomic force microscopy image analysis technology to classify sampled CNT particles by type, and quantifying and characterizing each type separately. These methods are needed to determine health risks that may 

result from worker exposure to the various types: CNTs, nanoropes, and non-tubular 

nanoparticles. The results will also provide a foundation for field and personal sampling 

devices for CNTs.

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.

THOMPSON (8739) 

Antistatic Paint with Silent Discharge

Background

Proposed is an anti-static paint that can be used to alleviate danger from fires and explosions initiated by static discharge. The innovation for the proposed paint lies in its discharge mechanism, which doesn’t require grounding or hydration like other products that 

are currently on the market. Paint can be sprayed onto surfaces of clothing or equipment, 

resulting in a lower capacitance or ability to build up charge on the material.
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Research Design

A series of formulations will be synthesized and tested on both metallic and plastic substrates.

Relevance to Public Health

Development of the antistatic paint will lead to immediate safety improvements for persons that work with volatile solvents in the fuel, coatings, and plastic industries as well as 

emergency responders in haz-mat situations. The paint could be useful for protecting the 

general public from electrostatic initiated explosions at the gas-pump or from uncomfortable static shock. In addition, this paint could lead to substantial savings in the electronics industry, where electrostatic discharge (ESD) events cost millions of dollars each year 

because of lost products.

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 protecting 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 better sensors. These improved sensors will be the basis 

for improved personal and permanent monitors for increased protection of workers in the 

semiconductor industry.

Progress

Phase I feasibility studies have shown a significant enhancement in the sensitivity of hydride sensors fabricated from tailored nanostructured materials grown via a templated 

deposition process inside the pores of anodic alumina. Detection limits of less than 10 

ppb were achieved, allowing application of this rugged, low-cost sensor technology to the 

detection of highly toxic gases (e.g. hydrides) that heretofore were not amenable to reliable 

detection via this sensor technology.
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DUTTA (9141) 

Role of Surface Chemistry in the Toxicological Properties of Manufactured 

Nanoparticles

Background

The objectives of this program are to verify two hypotheses. First, the quantifiable differences in surface reactivity of nanoparticles (as measured by acidity, redox chemistry, 

metal ion binding and Fenton chemistry) compared with micron-sized particles of similar 

composition cannot be explained by the increase in surface area alone. Second, the oxidative stress and inflammatory response induced by nanoparticles upon interaction with 

macrophages and epithelial cells depend on their surface reactivity. The basis of these 

hypotheses is that nanoparticles contain significantly higher numbers of “broken” bonds 

on the surface that provide different reactivity as compared to larger particles.

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 carbon nanotubes 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.

VOLCKENS (9114) 

A High-Flow Personal Sampler for Inhalable Aerosol

Background

While occupational respiratory diseases inflict a severe toll on our national workforce, 

existing exposure assessment methods for many respiratory hazards lack sufficient detection sensitivity, preventing the practicing industrial hygienist from determining whether 

a hazard even exists. The goal of this research is to design a high-flow sampling device engineered to assess inhalable aerosol hazards in the workplace in a physiologically relevant 
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fashion. This device will extend overall method detection limits by considerably increasing 

sampler flow rate. The design will be inexpensive and readily integrated into the commonly used 37-mm filter cassette. Because of its low cost, accuracy, ease-of-use, and adaptability, this device will have widespread application, especially in developing countries 

where exposure assessment resources and budgets are limited. Such widespread use was a 

major design goal for this technology, as increased use of an accurate exposure assessment 

technology will ultimately result in increased protection of worker health on a national 

and global scale. This project has three specific aims: (1) To design an inexpensive, modular sampling head that (a) interfaces with a standard 37-mm cassette, (b) operates at a 

high rate of airflow, 10 Lpm, and (c) meets the criteria for inhalable sampling set by the 

American Conference of Governmental Industrial Hygienists/International Standards 

Organization. This high-flow design will proceed from a wide body of research on existing 

low-flow inhalable devices. (2) Evaluate sampler performance using computational fluid 

dynamic modeling and to refine the prototype design based on results from these tests. (3) 

To validate the refined design through laboratory tests in a wind tunnel and field tests in 

actual occupational environments.

PETERS (9255) 

Personal Exposure Monitoring to Engineered Nanoparticles

Background

Worldwide production of engineered nanoparticles is expected to grow from 2,000 metric 

tons to 50,000 metric tons over the next decade. New industrial processes must be introduced into the workplace to accommodate this growth. Although studies have shown 

some nanoparticles to be toxic, methods to assess personal exposure do not exist. Knowledge of personal exposure may be particularly important for such small particles because 

their concentration tends to decay rapidly with distance from a source.

Dr. Peters will conduct laboratory studies to evaluate the precision and accuracy of 

methods developed by his research group to assess personal exposure to nanoparticles. 

These methods will then be used to investigate the extent to which workers are exposed 

to engineered nanoparticles in a facility that produces and handles them. Mixed models 

will be used to identify the determinants of exposure while controlling for the betweenworker (spatial) and within-worker (temporal) variability. Computer-controlled electron 

microscopy with energy dispersive X-ray detection will be used to further characterize the 

samples collected in the field study by size, composition, and morphology. These data will 

be used to apportion exposures to sources. The research proposed in this application is 

significant, because it will enable direct assessment of personal exposure to nanoparticles 

on time scales relevant to potential acute and chronic adverse health outcomes. As an 

outcome of these studies, an understanding of exposures will help to prioritize studies in 

toxicology, epidemiology, and engineering controls to better protect workers.
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The research component will be complemented by a vigorous career development plan 

that will include the following: (1) formal training in responsible conduct of research, epidemiology, and electron microscopy; (2) regular meetings with the sponsors of this award; 

(3) participating in group meetings and departmental seminars; (4) presenting results at 

scientific meetings; and (5) publishing results in peer-reviewed journals. The multidisciplinary team of sponsors will play an active roll in both the research and career development component of this award.

GRASSIAN (9448) 

An Integrated Approach Toward Understanding the Toxicity of Inhaled 

Nanomaterials

Background

Manufactured nanomaterials are found in cosmetics, lotions, and coatings, and are used 

in environmental remediation applications. An opportunity exists for exposure through 

many different routes, making it necessary to study the health implications of these materials. The primary objective of this research is to fully integrate studies of the physical and 

chemical properties of commercially manufactured nanoparticles with inhalation toxicological studies of these same nanoparticles to determine properties that most significantly 

affect nanoparticle toxicity. Our central hypothesis is that nanoparticle physico-chemical 

properties differ widely among particle types, and certain properties induce adverse health 

outcomes. Furthermore, we hypothesize that nanoparticle toxicity is influenced by the 

susceptibility of the individual as well as the presence of other inflammatory substances. 

We will address these hypotheses through a series of specific study aims designed to establish a relationship between nanoparticle physicochemical properties and health outcomes.

Specific Aim 1: Evaluate nanoparticle chemical composition (bulk and surface) on 

nanoparticle toxicity in acute and sub-acute exposure studies. Experiments will be designed to investigate nanoparticle composition (bulk and surface) before, during, and after 

inhalation exposure studies.

Specific Aim 2: Determine the impact of nanoparticle physical morphology (agglomeration size, agglomeration state, and nanoparticle shape) on nanoparticle toxicity. This study 

will incorporate animal inhalation studies to determine the relationship between nanoparticle agglomerate size and nanoparticle shape on toxicity.

Specific Aim 3: Determine whether (1) pulmonary clearance is impaired by inhaled 

nanoparticles and (2) impaired clearance increases the risk of pulmonary infection. The 

pulmonary clearance mechanism, especially the ability of alveolar macrophages to clear 

microbes or foreign particles, can be impaired by inhaled particulates. We will compare 

lung clearance rates after inhalation of nanoparticles of different composition.
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Specific Aim 4: Compare lung inflammation produced by co-exposure of nanoparticles 

with other inflammatory substances and relative to the nanoparticles alone. We plan to 

evaluate synergistic effects with other common aerosols present in the indoor and outdoor 

environments including endotoxins and sulfate aerosols (e.g. ammonium sulfate).

VOLCKENS (9381) 

A Personal Sampler for Assessing Inhaled Nanoparticle Exposures

Background

Elucidation of potential nanoparticle exposure-disease relationships requires the development of an adequate exposure assessment method, as exposure assessment provides key 

input into subsequent epidemiologic and toxicological investigation. The absence of a 

personal exposure assessment method for nanoparticle aerosols prevents progress towards 

understanding potential nanoparticle exposure-disease relationships. The goal of this 

work is to develop an accurate, sensitive, and specific method to assess personal exposures 

to engineered nanoparticles. The method will assess the inhalation route of exposure, and 

hence, the measurement of nanoparticle concentrations in air.

To quantify concentrations of airborne nanoparticles, a measurement must be able to 

segregate the aerosol by size (to capture only particles smaller than 100 nm) and count 

these particles following size segregation. Also, because inhaled nanoparticles enter 

strictly through the oral/nasal route, the method should be oriented to measure breathing zone concentrations within the vicinity of the upper torso. Finally, and perhaps most 

importantly, the method must be able to distinguish engineered nanoparticles from other 

incidental nanoparticles (i.e., ultrafine particles) that are ubiquitous in workplace and 

ambient air.

Successful completion of this research will establish a method to estimate human exposures to engineered nanoparticles in workplace environments. Such a method is critical 

to the establishment of nanoparticle dose-response relationships, as current methods lack 

both specificity and sensitivity. Results from this research can also be translated to the 

larger realm of health-related air pollution outside of the workplace (e.g., indoor air, ambient air pollution), both nationally and internationally.

RAJAGOPALAN (7963-R44) 

From Nanoparticles to Novel Protective Garments

Background

The goal of this project is to develop breathable, lightweight, and disposable chemical protective clothing for use by personnel associated with law enforcement agencies, 
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emergency medical services, medical/triage facilities, and other Federal, State, or local 

emergency agencies as well as by fire fighters and civilian first responders. This goal will 

be accomplished by producing a lightweight, chemical protective garment material. The 

material will have a limited number of distinct layers, that can be assembled into a breathable, protective garment. The layers impart at least one key property to the composite 

material. Non-breathable materials retard the human body’s process of heat dissipation 

normally achieved through the evaporation of perspiration. Without significant transmission of water vapor or breathability, prolonged use of non-breathable materials can 

result in intolerable discomfort and even death to a person wearing garments made from 

these materials. The novelty of the proposed approach is the development of granulated 

reactive NanoActive(r) sorbents containing composite layered textile material. The material protects the sorbent from contact with and contamination by liquids and has good 

vapor permeability, thus providing for passage of air and water vapor as well as sorption 

of harmful and noxious vapors and gases. Based on the outcome of Phase I research, it 

is clear that granulated mixed metal oxide nano-formulations are required for a broadspectrum reactivity. As a result, this Phase II project will begin by developing methodologies for granulation of mixed metal oxides based on NanoActive materials. This will be 

followed by performance screening of formulations against toxic industrial chemicals and 

chemical warfare agent simulants by a breakthrough testing procedure. The down selected 

formulations will then be incorporated into down selected textile materials with optimum 

air and water vapor permeable properties. Next, these composite fabric test swatches will 

be evaluated for a number of criteria using industry-recognized ASTM test methods. The 

top four granulated nanoparticles embedded fabrics will be tested for chemical resistance against four toxic chemicals using a standard ASTM procedure. The project will 

conclude by pilot studies involving scale-up of granulated nanoparticles and composite 

textile preparation followed by production of prototype chemical protective clothing. 

Relevance major deficiency of the available chemical protective garments is the failure to 

provide desired levels of toxic vapor sorption and still maintain sufficient transfer of heat 

and moisture to keep a wearer cool and comfortable. Permeable textiles containing highly 

reactive NanoActive(r) materials offer promise of protection and comfort. Public health 

relevance: major deficiency of the available chemical protective garments is the failure to 

provide desired levels of toxic vapor sorption and still maintain sufficient transfer of heat 

and moisture to keep a wearer cool and comfortable. Permeable textiles containing highly 

reactive NanoActive(r) materials offer promise of protection and comfort.
143

Appendix B Appendix B|| NIOSH Extramural Nanotechnology Research Activities NIOSH Extramural Nanotechnology Research Activities

Table 2. Nanotechnology Principal Investigators Funded by NIOSH/

OEP, 2001–2008

Thomas M. Peters

University of Iowa

Department of Occupational and

 Environmental Health

100 Oakdale Campus, 102 IREH

Iowa City, IA 52242–5000

(319) 335–4436 (t)/ (319)335–4225 (f)

thomas-m-peters@uiowa.edu

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)

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)

Joel S. Thompson

Eltron Research

4600 Nautilus Court South

Boulder, CO 80301–3241

(303) 530–0263 Ext. 118 (t); (303) 530–0264 (f)

eltron@eltronresearch.com

1R43OH008739-01 (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)

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)

Vicki H. Grassian

Professor and Institute Director

Nanoscience & Nanotechnology Institute

University of Iowa

The University of Iowa

Iowa City, IA 52242

(319) 384–3292 (t)/(319) 353–1115 (f)

vicki-grassian@uiowa.edu

1R01OH009448-01 (2008)

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)

(Continued)
144

NIOSH Nanotechnology Research Center

Dr. John Volckens

153 Environmental Health Building

Colorado State University

Fort Collins, CO 80523–1681

(970) 491–6341 (t); (970) 491–2940 (f)

John.Volckens@colostate.edu

1R03OH009381

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)

Table 2 (Continued). Nanotechnology Principal Investigators Funded 

by NIOSH/OEP, 2001–2008

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