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DHHS (NIOSH) Publication No. 2013–101

safer • healthier • peopleTM

Delivering on the Nation’s promise: 

safety and health at work for all people 

through research and prevention
On the cover: A graphical representation of the reach of a highly cited NIOSH journal article specific to nanomaterials. The scatter plot illustrates the initial publication (red dot) surrounded by the 

number of times it was directly cited in other papers (primary citations are yellow dots) and then 

the number of times the primary citation papers were cited by other papers (secondary citations 

are white dots). This diagram was developed using Cytoscape, an open source platform for complex 

network analysis and visualization.  
Filling the Knowledge Gaps for Safe

Nanotechnology in the Workplace

A Progress Report from the NIOSH Nanotechnology Research Center, 2004–2011

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention 

National Institute for Occupational Safety and Health
ii Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

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 websites 

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 websites. 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:

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

TTY: 1–888–232–6348 

E-mail: cdcinfo@cdc.gov

or visit the NIOSH website 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. 2013–101

November 2012

Safer • Healthier • PeopleTM
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace iii

2 Qualitative Assessment on Meeting NTRC Goals

Foreword

With any new or emerging technology, the greatest period of uncertainty about 

hazards and associated risks generally occurs in the early stages of development. This is 

true for engineered nanomaterials, where exposures to the pure and most concentrated 

form are most likely to occur in the workplace during the research, manufacture, or 

use of these materials. In 2004, the National Institute for Occupational Safety and 

Health (NIOSH) established the Nanotechnology Research Center (NTRC) to address 

the occupational safety and health concerns that might be associated with this new 

technology. Through the NTRC, NIOSH forged partnerships with other government 

agencies, countries, academia, industry, labor, and nongovernmental organizations to 

conduct research on the potential workplace implications and the beneficial applications of nanotechnology. A critical element of the research program is to conduct 

research on the potential health effects of worker exposure to engineered nanomaterials and to develop guidance in preventing exposure. 

In 2007 and 2009, NIOSH published progress reports detailing the accomplishments 

of the NTRC, including the results of ongoing laboratory and field research and the 

publication of technical and other guidance documents on the safe handling of engineered nanomaterials (see Progress Toward Safe Nanotechnology in the Workplace, 

www.cdc.gov/niosh/topics/nanotech/pubs.html). This 2012 update presents the program accomplishments of the NTRC from its inception in 2004 through 2011. It includes an analysis of the progress made toward accomplishing the goals and objectives 

of the NIOSH Strategic Plan for Nanotechnology Research and toward addressing the 

goals and research needs identified in the U.S. National Nanotechnology Initiative 

(NNI) Environmental, Health, and Safety (EHS) research strategy. The NTRC continues to support and promote the responsible development of nanotechnology through 

its ongoing research program and its contributions to the development of guidelines 

for hazard identification, exposure assessment, and risk characterization that can be 

used to develop and implement effective risk management practices. 

John Howard, M.D. 

Director, National Institute for Occupational 

 Safety and Health 

Centers for Disease Control and Prevention 
iv Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

Executive Summary 

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

develop, coordinate, and deliver an organized program of research to identify, investigate, and develop science-based solutions to workplace health and safety knowledge 

gaps in nanotechnology. The NTRC provides overall strategic direction and coordination of the NIOSH nanotechnology cross-sector research program (http://www.

cdc.gov/niosh/topics/nanotech/). The responsibilities of the NTRC are in accordance 

with the legislative mandate issued to NIOSH in Section 20(a) (4) of the Occupational 

Safety and Health Act of 1970, which states: 

“...conduct special research, experiments, and demonstrations relating to occupational safety and health as are necessary to explore new problems, including those 

created by new technology in occupational safety and health, which may require 

ameliorative action beyond that which is otherwise provided for in the operating 

provisions of this Act.”

Nanotechnology is a rapidly emerging material science technology that has been identified as a critical U.S. scientific and commercial enterprise with global economic benefits. 

Concern over the lack of knowledge about the potential health risks associated with the 

handling of pure, unbound engineered nanomaterials has been expressed by investors, entrepreneurs, government agencies, and public health advocacy groups. Such 

concerns create potential barriers to the growth of nanotechnology and the commercialization of products and devices that could help address serious global problems 

concerning energy, transportation, pollution, health, and food. Issues that have been 

raised about worker health and safety must be addressed to ensure responsible development, societal benefit, and associated economic growth. 

Vision Statement 

The NTRC facilitates responsible development of nanotechnology by identifying 

and addressing gaps in occupational safety and health knowledge. This vision is accomplished by creating a strategic plan of research, coordinating and facilitating the 

delivery of results, developing and disseminating science-based risk management 

recommendations, and providing national and world leadership.

Strategic Plan

In 2005, NIOSH developed a strategic research plan for the NTRC to address critical issues of health and safety associated with nanotechnology. The plan was revised 

in 2009, and a final report was published following review by the NIOSH Board of 

Scientific Counselors with input from a work group of subject matter experts. The strategic plan recommended four overarching goals (www.cdc.gov/niosh/docs/2010-105) 

[NIOSH 2009a]:
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace v

Executive Summary

NIOSH NTRC Strategic Goals

1. Determine whether nanoparticles and nanomaterials pose risks for 

work-related injuries and illnesses.

2. Conduct research on applying nanotechnology to the prevention of 

work-related injuries and illnesses.

3. Promote healthy workplaces through interventions, recommendations, 

and capacity building.

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

Within these four goals, 10 critical areas of research and communication were identified to serve as the foundation for a comprehensive plan of action: 

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 (PPE)

7. Fire and explosion safety

8. Recommendations and guidance

9. Communication and information

10. Applications of nanotechnology for occupational safety and health 
vi Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

Executive Summary

By initiating a plan to conduct concurrent and integrated research in each of these 

10 critical areas, NIOSH has undertaken the challenge of addressing the information and knowledge gaps necessary to protect workers so that the ultimate societal 

benefits of nanotechnology can be realized.

In 2012, the activities and outputs of the NTRC from 2004 through 2011 (and some projects that carried over into 2012) were evaluated to determine the extent of accomplishing 

the NTRC Strategic goals. Measurable outputs of the NTRC generally consisted of: 

 ■ NIOSH guidance documents, scientific journal publications, and presentations at conferences and workshops

 ■ the development of new technologies, including sampling and analytical methods

 ■ results from NIOSH collaborations and research (toxicology, workplace exposure measurements, engineering control, and epidemiology) used to develop 

risk management recommendations for the safe handling of nanomaterials

 ■ creation of strategic collaborations and partnerships. 

Summary of NTRC Program Outputs and Impacts

Among the many program outputs and impacts, the NTRC researchers:

 ■ Developed some of the earliest guidance on the design and conduct of nanotoxicology studies.

 ■ Identified pulmonary and cardiovascular hazards of some types of carbon nanotubes in animals.

 ■ Determined that the dispersion of ultrafine carbon black nanoparticles in the 

lungs of rats following intratracheal instillation results in an inflammatory 

response that is greater than agglomerated ultrafine carbon black.

 ■ Determined that ultrafine TiO2 or carbon black is more inflammogenic than 

fine TiO2 or carbon black on a mass-dose basis.

 ■ Developed a system to generate nanoparticle aerosols for inhalation toxicologic studies.

 ■ Conducted over 40 field assessments in nanomaterial manufacturer and 

user facilities.

 ■ Produced more than 400 peer-reviewed scientific publications, resulting in over 

5,000 primary and 82,000 secondary citations.

 ■ Provided over 650 invited presentations.

 ■ Published a framework for conducting workplace emission testing.

 ■ Developed innovative sampling methods for engineered nanomaterials.

 ■ Contributed to the development of a bio-mathematical model in rats to 

describe clearance, retention, and translocation of inhaled nanoparticles 

throughout the body.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace vii

Executive Summary

 ■ Developed recommended exposure limits (RELs) for TiO2 and carbon nanotubes (CNTs) and carbon nanofibers (CNFs).

 ■ Developed interim guidance for medical screening and hazard surveillance.

 ■ Identified what research will be needed to ensure the health of workers handling nanomaterials.

 ■ Established formal partnerships and collaborations with private, governmental and academic centers in the U.S. and globally.

 ■ Co-chaired the NNI Nanotechnology Environmental and Health Implications 

(NEHI) Working Group and contributed significantly to the development of 

the 2011 NEHI environmental health and safety (EHS) strategy.

 ■ Chaired the Organization for Economic Cooperation and Development (OECD) 

Working Party on Manufactured Nanomaterials Steering Group 8 on exposure 

measurement and exposure mitigation for manufactured nanomaterials.

 ■ Provided widely used guidance on responsible development of nanotechnology.

 ■ Helped to establish the U.S. and international position that a precautionary 

approach to controlling exposures to engineered nanoparticles is warranted. 

 ■ Have shown how responsible nanotechnology development and worker safety 

and health can be achieved. 

Responsible development of nanotechnology must include worker 

safety and health. NIOSH has been a leader in identifying hazards 

of nanomaterials, exposures, and risks to workers and has provided 

extensive guidance to protect workers in the face of broad uncertainties in these areas. NIOSH hazard identification has vastly increased 

scientific knowledge about potential hazards of nanomaterials. This 

increase in scientific knowledge has moved scientists to develop further research and more effectively address knowledge gaps. NIOSH 

efforts laid the groundwork for generating nanomaterial aerosols so 

that realistic animal studies could be developed. The investment of 

$42.6 million over seven years has served to drive scientific research, 

as illustrated by the large number of citations of NIOSH publications. Moreover, the pioneering toxicological work served to focus 

exposure assessment so that the actual exposure of workers could 

be characterized. Building on the hazard and exposure information, 

NIOSH developed a broad range of risk management guidance that 

became a cornerstone in the national and global response to nanotechnology. NIOSH has helped define the world’s precautionary 

approach to nanotechnology and provided the technical, scientific, and health information to protect workers and develop the 

technology responsibly. 
viii Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

Executive Summary

NTRC Programmatic Reviews

The NTRC will continue to evaluate its research progress in nanotechnology through 

a series of programmatic internal and external reviews. For example, past program 

evaluations have included a review by the National Academies (nanomaterial section 

of the NIOSH Respiratory Disease program) and a review of the NTRC strategic plan 

by the NIOSH Board of Scientific Counselors with input from a work group of subject 

matter experts. One result of these programmatic reviews was the creation of a more 

focused set of research priorities for 2009–2012. The NIOSH research strategy is consistent with the recommendations of the President’s Council of Advisors on Science 

and Technology (PCAST) report to the President on the third and fourth assessment 

of the NNI (http://nano.gov/node/786). Internally, the NTRC will continue to conduct 

annual program reviews, conduct regular project reviews, and publish a biannual or 

triannual Progress Report. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace ix

Contents

Forward............................................................... iii

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

Abbreviations.......................................................... xiii

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

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

2 Qualitative Assessment on Meeting the NTRC Goals ...................... 3

3 Alignment with the NNI EHS Strategy .................................. 53

4 NIOSH Extramural Nanotechnology Research Activities ................... 55

5 The Next Steps ....................................................... 57

6 References ........................................................... 59

Appendix A: Project Specific Progress Reports.............................. 63

Project 1: Nanotechnology Research Center Coordination................. 71

Project 2: Nanotechnology Safety and Health Research 

Coordination (Nanotoxicology) ........................... 92

Project 3: Development of New Research in Occupational Health 

(Nanotoxicology) ........................................ 96

Project 4: Systemic Microvascular Dysfunction: Effects

of Ultrafine vs. Fine Particles ............................. 102

Project 5: Particle Surface Area as a Dose Metric ......................... 105

Project 6: Role of Carbon Nanotubes in Cardiovascular

and COPD-Related Diseases ............................. 108

Project 7: Investigations of Multi-walled Carbon Nanotube Toxicity ........ 112

Project 8: Toxicological Effects of Aerosolized MWCNT .................. 116

Project 9: Pulmonary Toxicity of Metal Oxide Nanospheres and Nanowires. . 118

Project 10: WC-Co Nanoparticles in Initiating Angiogenesis by 

Reactive Oxygen Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

Project 11: Evaluation of the Pulmonary Deposition and Translocation 

of Nanomaterials........................................ 123

Project 12: Occupational Exposures and Potential Neurological Risks ....... 127

Project 13: Lung Effects of Resistance Spot Welding with Adhesives......... 132

Project 14: Neurotoxicity after Pulmonary Exposure to Welding Fumes ..... 133

Project 15: Welding Fumes and Cardiovascular Dysfunction............... 138

Project 16: Potential Aneuploidy Following Exposure to Carbon Nanotubes... 139

Project 17: Nanoparticle Properties and Mechanisms Causing 

Lung Fibrosis........................................... 144

Project 18: Pulmonary Toxicity of Carbon Nanotube Particles.............. 148
x Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

Contents

Project 19: Assessment of Engineered Nanomaterials of 

Respiratory Immunity ................................... 154

Project 20: Dermal Toxicity of Nanotube Particles........................ 159

Project 21: Bioassay Screen of Lung Toxicity of Silver Nanoparticles ........ 164

Project 22: Specific Biomarkers for Unusual Toxicity of Nanomaterials ...... 166

Project 23: Pulmonary Toxicity of Diesel Exhaust Particles ................ 168

Project 24: Induction of Lung Fibrosis by Cerium Oxide in Diesel Exhaust... 170

Project 25: Potential Effects of Silicon-based Nanowires on Lung Toxicity.... 173

Project 26: Workplace Exposure, Inflammation, and Cardiovascular Toxicity . . 177

Project 27: Cardiovascular Toxicity Assessment of Subchronic 

Inhalation Exposure to Fullerene C60....................... 180

Project 28: Cell-Based Assessment for Iron Nanoparticle–Induced Health Risks 181

Project 29: Assessment of Carbonaceous Materials on Mutagenicity ........ 183

Project 30: Durability of Nanoscale Cellulose Fibers in Artificial 

Human Lung Fluids ..................................... 185

Project 31: Osteopontin and Carbon Nanotubes ......................... 186

Project 32: Determination of Diameter Distribution for Carbon 

Nanotubes by Raman Spectroscopy......................... 187

Project 33: Inhalation Facility Support .................................. 188

Project 34: Generation and Characterization of Nanoparticles . . . . . . . . . . . . . 196

Project 35: Dustiness of Nanomaterials ................................. 200

Project 36: Measurement of Nanoscale Carbonaceous Aerosols ............ 202

Project 37: Nanoaerosol Monitoring Methods (formerly Automotive 

Ultrafine Intervention) ................................... 204

Project 38: Workplace Monitoring of Carbon Nanofibers/Nanotubes........ 210

Project 39: Real-time Instrument for Nanoaerosol Exposure Measurement ... 215

Project 40: Nanoparticle Reference Materials for Health Protection . . . . . . . . . 218

Project 41: International Coordination of Nanoscale Reference Materials.... 220

Project 42: A Standard Method for Determining Airborne 

Nanoparticle Size ....................................... 222

Project 43: Calm Air Chamber and Wind Tunnel Evaluation of Personal 

Aerosol Samplers for Nanoparticle Exposure Assessment ...... 223

Project 44: Efficacy of NIOSH Method 0600 for Fine and Ultrafine 

Titanium Dioxide ........................................ 224

Project 45: Ultrafine TiO2

 Surface and Mass Concentration 

Sampling Method ....................................... 225

Project 46: Development and Evaluation of Nanoaerosol Surface Area 

Measurement Methods ................................... 227
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace xi

Contents

Project 47: Respiratory Deposition of Airborne Carbon Nanotubes ......... 230

Project 48: Exposure Potential From Use of Nanomaterial-Enabled 

Consumer Products ..................................... 232

Project 49: Ultrafine Aerosols from Diesel-Powered Equipment ............ 233

Project 50: Titanium Dioxide and Other Metal Oxides Exposure 

Assessment Study ........................................ 237

Project 51: Field Research Team ....................................... 239

Project 52: Factors Affecting Exposure to Engineered Nanomaterials........ 244

Project 53: Assessing the Feasibility of Industrywide Exposure and 

Epidemiology Studies of Workers Exposed to Engineered 

Nanomaterials—Phase I .................................. 247

Project 54: Engineered Carbon Nanomaterials Workforce: Feasibility of 

Industrywide Exposure Assessment and Epidemiology Studies 

on Carbon Nanotubes and Nanofibers—Phase II ............. 249

Project 55: Nanoparticles—Dosimetry and Risk Assessment ............... 252

Project 56: Titanium Dioxide Quantitative Risk Assessment ............... 259

Project 57: Engineering Controls for Nanomaterial Handling .............. 261

Project 58: Applying PtD to the Safe Handling of Engineered Nanomaterials .. 264

Project 59: Penetration of Nanoparticles Through Respirators/Development 

of Respirator Filtration Test Methods ....................... 265

Project 60: Nanoparticle Penetration through Protective Clothing .......... 270

Project 61: Respirator Performance Against Engineered Nanoparticles 

Under Laboratory and Workplace Settings................... 271

Project 62: Development of Personal Protective Equipment Ensemble 

Test Methods ........................................... 274

Project 63: Explosibility and Flammability of Carbon Nanotubes ........... 277

Project 64: Current Intelligence Bulletin: Carbon Nanotubes and 

Carbon Nanofibers....................................... 279

Project 65: Assessing the Utility of Control Banding in the U.S.............. 281

Project 66: Web-based Nanoparticle Information Library Implementation ... 283

Project 67: Nanoparticles in the Workplace and Metrics for Field and 

Toxicity Studies.......................................... 286

Project 68: Global Harmonization of Exposure Measurement and Exposure 

Mitigation Approaches for Nanomaterials ................... 297

Project 69: New Sensor Technology Development for Filter Respirator 

Cartridge End-of-Service Life Indicators (ESLI) .............. 305

Appendix B: NTRC Projects in the 10 Critical Areas for 2004–2011 ........... 309

Appendix C: NIOSH Extramural Research................................. 317

Appendix D: NIOSH Logic Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
xii Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting NTRC Goals

Appendix E: Progress Toward Meeting the NTRC Performance Measures ...... 377

Appendix F: Summary of the Citation Analysis.............................. 395
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace xiii

Abbreviations 

AIHA American Industrial Hygiene Association 

AIHce American Industrial Hygiene conference and exposition

ACGIH American Conference of Governmental Industrial Hygienists

AM alveolar macrophage

ANSI American National Standards Institute

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 

CD-ROM compact disc, read only memory

CIB Current Intelligence Bulletin

CMPND Center for Multifunctional Polymer Nanomaterial and Devices 

CNF carbon nanofiber

CNSE College of Nanoscale Science and Engineering

CNT carbon nanotube 

CO carbon monoxide

COIN Center of Innovation for Nanobiotechnology 

COPD chronic obstructive pulmonary disease 

CPC condensation particle counter

CPSC Consumer Product Safety Commission

DDT dichlorodiphenyltrichloroethane

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

DOD U.S. Department of Defense
xiv Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

Abbreviations

DOE U.S. Department of Energy

DPF diesel particulate filter

EC–SOD extracellular superoxide dismutase

EHS environmental, health, and safety

ELSI ethical, legal, and societal implications

EPA U.S. Environmental Protection Agency

ERC Education and Research Center

ESLI end of service-life indicator 

ESP electrostatic precipitator

ESR erythrocyte sedimentation rate

EU European Union

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

FY fiscal year

GAO U.S. Government Accountability Office

GMA–MS gas metal arc–mild steel

HEI Health Effects Institute

HEPA high-efficiency particulate air filter 

HHE Health Hazard Evaluation

HPS Health Physics Society

IANH International Alliance for NanoEHS Harmonization

ICOH International Commission on Occupational Health

ICON International Council on Nanotechnology

IDLH immediately dangerous to life and health

IEC International Electrotechnical Commission

IOHA International Occupational Hygiene Association

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

JOEH Journal of Occupational and Environmental Hygiene

JOEM Journal of Occupational and Environmental Medicine

kW kilowatt
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace xv

Abbreviations

LDH lactate dehydrogenase

LEV local exhaust ventilation

LLC limited liability company

LM Listeria monocytogenes

LNW long nanowire

MAPKs mitogen-activated protein kinase

MINChar Minimum Information Needed for Characterization of Nanomaterials

MMA–HS manual metal arc–hard surfacing

MOU Memorandum of Understanding

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

NCER National Center for Environmental Research 

NEAT nanoparticle emission assessment technique

NEHI Nanotechnology Environmental and Health Implications 

NFkB nuclear factor kappa beta 

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 

nm nanometer(s) 

NNI National Nanotechnology Initiative 

NO nitric oxide

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

NTP National Toxicology Program

NTRC Nanotechnology Research Center
xvi Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

Abbreviations

OEP Office of Extramural Programs 

OECD Organization for Economic Cooperation and Development

OEP Office of Extramural Programs

OH&S occupational health and safety

ONAMI Oregon Nanoscience and Microtechnologies Institute

OPC optical particle counter

OPN osteoponin

OSHA U.S. Occupational Safety and Health Administration 

PAMS portable aerosol mobility spectrometer 

PEL permissible exposure limit

PEROSH Partnership for European Research in Occupational Safety and Health

PMN polymorphonuclear neutrophil

PNS personal nanoaerosol sizer

POSS polyhedral oligomeric silsesquioxane

PPE personal protective equipment 

r2p Research to Practice

RELs recommended exposure limits

RFA request for application

RMs reference materials

RNS reactive nitrogen species

ROI return on investment

ROS reactive oxygen species

SBIR small business innovation research

SEMATECH semiconductor manufacturing technology consortium

SG steering group

SMPS scanning mobility particle sizer

SNW short nanowire

SRM standard reference material

STEL short-term exposure limit

SWCNT single-walled carbon nanotube 

TAPPI Technical Association of the Pulp and Paper Industry

TC technical committee

TEM transmission electron microscopy 

TGF-ß transforming growth factor–beta

TiO2 titanium dioxide 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace xvii

Abbreviations

TNO Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek (Netherlands Organization for Applied 

Scientific Research)

TR technical report

μg/m3 microgram per cubic meter

UK United Kingdom

UN United Nations

UNITAR United Nations Institute for Training and Research

USAF U.S. Air Force

VEGF vascular endothelial growth factor

Wc–Co tungsten carbide

WHO World Health Organization 

WT wild type
xviii Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

Acknowledgments

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

Nanotechnology Research Center (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 for 

writing and organizing the report. Others who contributed substantially to this progress 

report include James Antonini, Eileen Birch, Vincent Castranova, Teh-hsun Chen, Brian 

Curwin, Matt Dahm, Min Ding, Kevin Dunn, Aaron Erdely, Douglas Evans, Larry Foster, Pengfei Gao, Mark Hoover, Bon-Ki Ku, Eileen Kuempel, Pramod Kulkarni, Stephen 

Leonard, Li Ming Lo, Jane Ma, Ken Martinez, Robert Mercer, Mark Methner, Vladimir 

Murashov, Terri Pearce, Dale Porter, Viji Potula, Yong Qian, Appavoo Rengasamy, Jennifer Roberts, Liying Wang Rojanasakul, Linda Sargent, Mary Schubauer-Berigan, Ronald 

Shaffer, Anna Shvedova, Jay Snyder, Krishnan Sriram, Aleksandr Stefaniak, Jennifer 

Topmiller, Douglas Trout, Leonid Turkevich, and Ralph Zumwalde. 

The NIOSH NTRC also acknowledges the contributions of Vanessa Williams, Gino 

Fazio, Eric Gentry, and Rachel Thieman for the publication design and production 

and Seleen Collins for editing. Photographs are courtesy of Catherine Beaucham, 

Teh-hsun Chen, Matt Dahm, Doug Evans, Mark Hoover, Robert Mercer, Ken Martinez, Mark Methner, and Leonid Turkevich.

Thanks are extended to Cathy Sarli and Kristi Holmes, Washington University in St. 

Louis School of Medicine, for their advice in developing the progress report. 

External Peer Reviewers 

Jay West 

Senior Director, Regulatory and Technical Affairs 

American Chemistry Council 

William Kojola

Industrial Hygienist 

The American Federation of Labor–Congress of 

 Industrial Organizations (AFL-CIO) 

Janet Carter 

Industrial Hygienist 

U.S. Occupational Safety and Health Administration
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 1

1 Introduction 

Historically, the commercial development and application of some potentially useful 

substances have turned out to have negative health consequences among producers and 

users if those potential impacts are not identified and investigated early. For example, 

asbestos was commercially used because of its good insulating and fireproofing properties, but later it was determined to cause significant health problems 20 to 40 years after 

exposure. Other useful chemicals such as DDT (for eradicating mosquitoes and reducing the incidence of malaria) and lead (for antimicrobial uses and paint formulations) 

were also determined to be detrimental to human health and the environment, years 

after they were put into commerce. Mass production of chemicals before investigating 

potential health concerns and societal impacts has significant human burden and financial repercussions because of the high cost of remedial actions to remove these hazardous materials (e.g., asbestos, lead) and because of the medical and liability costs incurred 

for compensating individuals with an exposure-related disease or injury. 

Nanotechnology and the commercialization of nanoenabled products and devices could 

help address serious global problems concerning energy, transportation, pollution, health, 

medicine, and food. The potential benefits of nanotechnology are huge; however, these benefits may not be realized unless a concerted effort is made to evaluate the safety and health 

concerns regarding these new nanomaterials and to develop effective methods for their 

responsible introduction. This concern is supported by an industry survey in which nanotechnology business leaders identified health and safety issues as a key barrier to commercialization of their products [Lekus et al. 2006; U.S. Department of Commerce 2007]. 

NIOSH is committed to promoting the responsible development and advancement of 

nanotechnology through its research and communication efforts to protect workers. 

It is difficult to estimate how many workers are involved in this field. Nanotechnology 

is not one specific type of chemical or industry but more of a scientific understanding and capability that can be used to improve nearly every material in commerce 

and to make a wide variety of new types of chemicals, materials, and products. By one 

estimate, there are 400,000 workers worldwide in the field of nanotechnology, with an 

estimated 150,000 of those in the United States [Roco et al. 2010]. The National Science Foundation has estimated that approximately 6 million workers will be employed 

in nanotechnology industries worldwide by 2020 (http://nano.gov/node/622).

The total NIOSH Nanotechnology Research Center (NTRC) intramural investment 

from FY 2004 to FY 2011 was $42.7 million (Figure 1). In that same timeframe there 

was an additional $12 million*

 investment in the funding of extramural research 

through grants from the NIOSH Office of Extramural Programs (OEP). This total 

investment included research (e.g., toxicology, field studies) on ultrafine particulates 

(i.e., nanoscale particles), during 2004 to 2006, and a portfolio of projects focused 

specifically on engineered nanomaterials, from 2006 to 2011. The majority of the NIOSH 

investment in nanotechnology research involved reprogrammed funds, with no additional 

funds received through or as a part of the National Nanotechnology Initiative (NNI). 

*

This represents all extramural projects that in any way include nanomaterials. Projects may not 

necessarily be 100% nanotechnology, but rather a portion of the research includes nanomaterials.
2 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

1 IntroductionFigure 1. NTRC Intramural funding by fiscal year (FY) and critical research area.

Research AreaToxicologyMeasurement MethodsExposure AssessmentEpidemiology and SurveillanceRisk AssessmentEngineering Controls and PersonalProtective EquipmentFire and ExplosivityRecommendationsCommunications

$9,000,000$1,000,000

Dollars

FY

2004

FY

2005

FY

2006

FY

2007

FY

2008

FY

2009

FY

2010

FY

2011

$8,000,000$7,000,000$6,000,000$5,000,000$4,000,000$3,000,000$2,000,000

ToxicologyMeasurement MethodsExposure AssessmentEpidemiology and SurveillanceRisk AssessmentEngineering Controls and PersonalProtective EquipmentFire and ExplosivityRecommendationsCommunicationsApplications Applications
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 3

1 Introduction

2 Qualitative Assessment on Meeting

the NTRC Goals

In 2005, NIOSH developed a strategic research plan for the NTRC to address critical issues of health and safety associated with nanotechnology. The plan was updated 

in 2009 (Figure 2), and a final report was published following review by the NIOSH 

Board of Scientific Counselors with input from a work group of subject matter experts. The strategic plan recommended four overarching goals [www.cdc.gov/niosh/

docs/2010-105] [NIOSH 2009a]:

NIOSH NTRC Strategic Goals

1. Determine whether nanoparticles and nanomaterials pose risks for workrelated injuries and illnesses.

2. Conduct research on applying nanotechnology to the prevention of workrelated injuries and illnesses.

3. Promote healthy workplaces through interventions, recommendations, and 

capacity building.

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

Within these four goals, 10 critical areas of research and communication were identified to serve as the foundation for a comprehensive plan of action: 

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 (PPE)

7. Fire and explosion safety

8. Recommendations and guidance

9. Communication and information

10. Applications of nanotechnology for occupational safety and health 

To ensure an effective nanotechnology research program, projects were initiated to 

address each element of the risk management process (Figure 3). Areas of research 

were chosen that support and compliment the portfolio of projects within the NTRC 

research program, and activity was started in each risk management area. For example, 

concurrent with the generation of nanoparticle exposures for toxicology research were 

development and assessment of sampling and analytical methods that could be used for 

quantifying worker exposures so that comparisons could be made with toxicology study 
4 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

results. Parallel research efforts have also been undertaken to determine 1) the strengths 

and weaknesses of different risk management strategies for controlling worker exposure to airborne nanoparticles and 2) the types of personal protective equipment (PPE) 

that might be required to protect exposed workers. As findings of field investigations 

and laboratory research become available, the information will be used to develop and 

update guidance for evaluating and managing potential risk from nanomaterials. 

Program Evaluation Strategy 

The success of a research program is frequently determined by how the results (or 

outputs) from research activities meet the intended program objectives and advance 

Figure 2. Cover of the Strategic Plan for NIOSH Nanotechnology Research 

and Guidance, 2009.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 5

2 Qualitative Assessment on Meeting the NTRC Goals

Hazard Identification

“Is there reason to believe 

this could be harmful?”

Risk Management

“Develop procedures to 

minimize exposures”

Hazard Characterization

“How and under what 

conditions could it be harmful?”

Exposure Assessment

“Will there be exposure in 

real-world conditions?”

Risk Characterization

“Is substance hazardous 

and will there be exposure?”

• Toxicologic research

• Health effects assessment

• Safety research

• Toxicologic research

• Field assessment

• Epidemiologic and hazard

surveillance research

• Metrology research

• Field assessment

• Control technology research

• Personal protective equipment

(PPE) research

• Risk assessment

• Dose modeling

• Exposure characterization

• Epidemiologic research

• Risk communication

• Guidance development for

controls, exposure limits, PPE,

and medical surveillance

• Information dissemination

• Adherence investigation

Gaps in the

Protection of Workers NIOSH Focus

Adapted from Gibbs, 2006

Figure 3. Gaps that need to be filled to protect nanomaterial workers.
6 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

knowledge and ultimately stakeholder needs [Sarli et al. 2010]. The NTRC has identified the following outputs as a means of measuring the success of its research program: 1) scientific journal publications, publication and dissemination of NIOSH 

guidance documents, and communication of research through presentations at scientific (technical) and business conferences and workshops; 2) the development and dissemination of new technologies, including sampling and analytical methods; and 3) 

results from NTRC research (toxicology and workplace exposure measurements) used 

to develop risk assessment, characterization, and management strategies. Research 

outputs for each of the 10 critical research areas follow. 

2.1 Nanotoxicology and Internal Dose

In the early 2000s, little was known about the potential hazards of engineered nanomaterials, but there was concern that smaller particles with increased surface-to-mass 

ratios could be highly reactive and cause adverse effects. NTRC nanotoxicologic 

research is critical to understanding the potential health risks to workers exposed to 

engineered nanomaterials. Results from experimental animal studies with engineered 

nanomaterials have provided evidence that some nanoparticle exposures can result in 

serious health effects involving pulmonary and cardiovascular systems and possibly 

other organ systems. NTRC researchers have conducted or participated in the following research activities:

 ■ Determined that asbestos and carbon nanotubes (CNTs) affect similar molecular signaling pathways in cultured lung cells, with asbestos exhibiting 

greater potency

 ■ Determined that nano or ultrafine titanium dioxide (TiO2) causes pulmonary 

inflammation and neuroimmune responses

 ■ Determined that ultrafine TiO2 or carbon black is more inflammogenic than 

fine TiO2 or carbon black on a mass-dose basis

 ■ Developed a method to improve dispersion of nanoparticles in biologically 

compatible suspension media for use in in vitro studies and in vivo exposures 

employing intratracheal instillation or aspiration of nanoparticle suspensions

 ■ Determined that the dispersion of ultrafine carbon black nanoparticles in the 

lungs of rats following intratracheal instillation results in an inflammatory 

response that is greater than with agglomerated ultrafine carbon black

 ■ Determined that pulmonary exposure to single-walled carbon nanotubes 

(SWCNTs) and multi-walled carbon nanotubes (MWCNTs) in mice 

causes acute and chronic systemic responses associated with adverse 

cardiovascular effects 

 ■ Determined that SWCNTs, MWCNTs, and carbon nanofibers (CNFs) have 

equal or greater potency in causing adverse health effects in laboratory animals, 

including pulmonary inflammation and fibrosis, in comparison with other 

inhaled particles (ultrafine TiO2, carbon black, crystalline silica, and asbestos)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 7

2 Qualitative Assessment on Meeting the NTRC Goals

 ■ Determined that CNTs are genotoxic and can transform lung epithelial cells 

after long-term, low-dose in vitro exposure 

 ■ Developed methods for labeling CNTs so that their potential translocation 

from the lungs to other organs can be studied

 ■ Developed some of the earliest guidance on the design and conduct of nanotoxicology studies

 ■ Co-sponsored a number of nanotoxicology conferences to promote dissemination and growth of scientific information 

By conducting some of the world’s leading animal and cellular laboratory studies, 

NTRC researchers have identified a broad range of potential health effects associated with exposure to engineered nanoparticles as well as the physical and chemical 

characteristics of these nanomaterials that potentially contribute to their biologic 

activity. The significance of this research is evidenced by the number of times the 

results of NTRC research have been cited by other researchers. To date, the most 

highly cited NTRC paper is a sentinel toxicologic study report authored by Anna 

Shvedova and colleagues, Exposure to Carbon Nanotube Material: Assessment of 

Nanotube Cytotoxicity using Human Keratinocyte Cells. This report has generated 

505 primary and 16,482 secondary publication citations (Figure 4) [Shvedova et al. 

2003]. This sentinel paper was also cited in 14 patents (or patent applications) from 

three patent offices [World Intellectual Property Organizations, European Patent 

Office, and US Patent and Trademark Office] as well as in university theses and dissertations from the US, Germany, United Kingdom, Hong Kong, Switzerland, and 

France [Elsevier SciVerse Scopus database]. The paper was published in 2003 prior 

to the official formation of the NIOSH NTRC but after NIOSH began conducting 

nanotoxicology research. 

Other frequently cited NTRC research results include those reported by Maynard et 

al. [2004] (Exposure to Carbon Nanotube Material during the Handling of Unrefined 

Single Walled Carbon Nanotube Material), with 363 primary and 14,587 secondary 

publication citations (Figure 5) and cited in 8 patent applications, and those reported 

by Shvedova et al. [2005] (Unusual Inflammatory and Fibrogenic Pulmonary Responses 

to Single Walled Carbon Nanotubes in Mice), with 449 primary and 9,777 secondary publication citations and cited in 1 patent. Citation data were compiled by using 

Google Scholar, Thomson Reuters Web of Knowledge, and Elsevier SciVerse Scopus 

database. 

The research published by Li et al. [2007] entitled Cardiovascular Effects of Pulmonary Exposure to Single-Wall Carbon Nanotubes was nominated for the Charles C. 

Shepard Science Award (given by the Centers for Disease Control and Prevention 

[CDC], Department of Health and Human Services). This research was also highlighted as the “Hot-off-the-Presses Peer-Reviewed Research Article” in the EH&S 

Nano News [www.ehsnanonews.com/] as one of the first investigations on the potential cardiovascular effects of pulmonary exposure to SWCNTs. 
8 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Figure 4. A graphical representation of the 505 primary and 16,482 secondary citations of the 2003 article Exposure to Carbon Nanotube Material: Assessment of Nanotube Cytotoxicity using Human Keratinocyte Cells. The scatter plot illustrates the initial 

publication (red dot) surrounded by the number of times it was directly cited in other 

papers (primary citations are yellow dots) and then the number of times the primary 

citation papers were cited by other papers (secondary citations are white dots). This 

diagram was developed with Cytoscape, an open source platform for complex network 

analysis and visualization. 

Figure 5. A graphical representation of the 363 primary and 14,587 secondary citations of the 2004 article Exposure to Carbon Nanotube Material during the Handling 

of Unrefined Single Walled Carbon Nanotube Material. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 9

2 Qualitative Assessment on Meeting the NTRC Goals

2.1.1 Development of Innovative Technologies

To conduct experimental animal studies with nanoparticles, NTRC researchers 

designed an innovative aerosol exposure system to generate particles of specific size 

for animal inhalation studies [McKinney et al. 2009] (Figures 6 and 7). This system 

has allowed NTRC researchers to generate airborne exposures to various nanoscale 

materials (e.g., CNT, crystalline silica, TiO2) for toxicological studies. The results from 

these studies have provided the scientific evidence necessary to make workplace risk 

management recommendations. The scientific community has expressed interest in 

the design of this technology, and groups from Japan, England, and Germany have 

requested information. Researchers from Fraunhofer-Institut, Germany, also visited 

the NIOSH facilities to learn how to construct their own inhalation exposure system 

for generating nanofiber exposures.

2.2 Measurement Methods

Accurate exposure measurement methods are important for assessing the potential health risk to workers and for validating the effectiveness of exposure controls. 

Since 2004, NTRC researchers have set the precedent for characterizing occupational 

exposures to engineered nanoparticles by using both standardized and nonstandardized sampling and analytical techniques. Experience gained from this research has 

led to the publication of the Nanomaterial Emission Assessment Technique (NEAT), 

which established the initial framework for NTRC researchers and others in evaluating workplace nanomaterial emissions [Methner et al. 2010]. This stratified (or tiered) 

exposure emission strategy recommended the assessment of workplace exposures using both commonly applied measurement techniques (e.g., determination of particle 

count and elemental mass) and more sophisticated nanoparticle analysis (e.g., characterization by electron microscopy). Information gained from the evaluation of workplace exposures was incorporated in the NIOSH 2009 document Approaches to Safe 

Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered 

Nanomaterials [http://www.cdc.gov/niosh/docs/2009-125/]. 

NTRC researchers were the first to utilize elemental carbon as a selective marker for 

quantifying CNF and CNT worker exposure [Mether et al. 2007, Birch et al. 2011]. 

From a direct reading instrument perspective, NTRC researchers observed that respirable particle mass was a more practical monitoring metric than particle number, 

because the latter metric may be dominated by other particle sources in the workplace 

[Evans et al. 2010]. As a result, NIOSH field investigations routinely include continuous monitoring of respirable particle mass in addition to other particle metrics (Figure 8). The Evans et al. [2010] publication received the NIOSH 2011 Alice Hamilton 

Award in the category of Engineering and Physical Sciences. 

NTRC researchers continue to refine nanomaterial exposure characterization strategies, 

using data gathered from ongoing workplace exposure measurement studies and from 

participation in the global dialogue on this topic. The results from workplace studies on 

CNT and CNF during 2010–2011 have contributed to the development and advancement of measurement techniques for these carbonaceous nanomaterials [Evans et al. 
10 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Figure 6. The multi-walled carbon nanotube aerosol generator.

Figure 7. The nanomaterial exposure system interface.

Power Amp.

Dryer Charcoal Filter HEPA

MFC

MFC

HEPA MFC House

Vacuum

Pressure

Regulator (30 psi)

House

Air

Box Air 

relief port

Used for generator

Trans-diaphragm

pressure control

Used for 

exposure air

flow control

Acoustical

Generator

P

P

Used for exposure

chamber pressure

control

Temp / %RH

sensor

Exposure

Chamber

DataRAM

exposure

concentration

Secondary

sample lines

Computer

Used for exposure

concentration control

Gravimetric Analysis

Moudi/Nano-moudi

(10 nm-10um)

TEM,SEM (imaging)

Chemical analysis

Characterization

Measurements

Trans-diaphragm

pressure

Chamber Pressure

MFC = Mass Flow Controller

Damp Sponges

HEPA
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 11

2 Qualitative Assessment on Meeting the NTRC Goals

2010; Birch et al. 2011; Birch 2011]. For example, in the draft 2010 NIOSH Current 

Intelligence Bulletin (CIB) Occupational Exposure to Carbon Nanotubes and Nanofibers, 

a modified NIOSH sampling and analytical method (NMAM 5040 for CNTs/CNFs) was 

recommended to provide the means for quantifying occupational exposures to CNTs 

and CNFs. This modified method is currently in use for an ongoing NIOSH industrywide study of workers exposed to CNTs and CNFs [Dahm et al. 2011]. 

NTRC researchers are also collaborating with the National Institute of Standards and 

Technology (NIST) and National Research Council Canada to identify and develop 

nanoscale reference materials (RMs) for use in calibrating and evaluating measurement instruments and for toxicology studies. NIOSH provided technical input and 

aided in the organization of the interlaboratory study for a titanium dioxide RM, 

NIST SRM 1898: Titanium Dioxide Nanopowder. Current efforts focus on qualifying 

nanocrystalline cellulose (powder and suspension) and SWCNTs as RMs. 

2.2.1 Development of Innovative Technologies 

NTRC researchers have pioneered the development of new sampling equipment to 

measure nanomaterials. NTRC researchers developed a hand-held electrostatic precipitator (ESP) particle sampler that permits the collection of airborne nanoparticles onto a 

sample grid that can be directly used for electron microscopy (EM) analysis. The handheld ESP eliminates the need for a conventional pump-and-filter to collect airborne 

nanoparticle samples and provides the ability to quickly assess multiple processes and 

Figure 8. Particle instrument array and time series of particle metrics used in the Evans 

et al. [2010] CNF workplace study. 
12 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Figures 9 and 10. Hand-held electrostatic precipitator developed by NIOSH researchers 

and licensed to Dash Connector Technology, Inc.

areas. This sample collection method also reduces the time needed to prepare samples 

for EM analysis. The prototype (developed by NIOSH in 2004–2007) was subsequently 

licensed to a commercial supplier, Dash Connector Technology, Inc., which is marketing the instrument for aerosol and industrial hygiene sampling (Figures 9 and 10). 

Two additional nanomaterial sampling instruments have been developed by NTRC 

researchers: a Portable Aerosol Mobility Spectrometer (PAMS) and a Personal Nanoaerosol Sizer (PNS). Both instruments can continuously measure and record (in nearreal-time) particle number, surface area, and mass concentrations of nanoparticle and 

ultrafine aerosols in the workplace. PAMS is a handheld instrument that uses a condensation particle counter as a detector and allows reliable measurement of aerosols 

over a wide nanoparticle size range. PNS is a low-cost, robust personal sampler that 

allows the measurement of personal exposures to nanoaerosols. These instruments are 

expected to be valuable tools for workplace nanoaerosol exposure measurements. A 

prototype of PAMS has been successfully developed in collaboration with Kanomax, 

USA, Inc. (Figure 11). A prototype of PNS has been designed and fabricated, and its 

performance is being evaluated.

NTRC researchers are continuing to evaluate measurement methods and technologies and 

conducting research to link the measurements to toxicologic data and health end points. 

2.3 Exposure Assessment

Workplace exposure assessments are vital to developing accurate risk characterizations of exposure of workers to engineered nanomaterials. The NTRC has direct 

responsibility for conducting exposure assessments at nanomaterial production and 

user facilities to support epidemiologic and control research, as well as the development of comprehensive risk management guidance. Since 2006, NTRC researchers 

have conducted over 40 workplace investigations at research facilities, pilot plants, 

and manufacturing sites that are actively making or using engineered nanomaterials. This research effort has been one of the most productive activities of the NTRC 

Particle Characterization
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 13

2 Qualitative Assessment on Meeting the NTRC Goals

because of the success of engaging the private sector as partners. From these efforts, 

NIOSH has developed partnerships with large and small nanomaterial manufacturing companies and has gained invaluable insight on how nanomaterials are being 

handled. This activity has also resulted in formal agreements with other government 

agencies and several major nanotechnology research centers and business consortia for 

conducting workplace exposure assessments. Three companies that have voluntarily 

received site evaluations from NTRC researchers were interviewed by Nanowerk, LLC, 

for its August/September 2007 issue of Nanorisk (www.nanorisk.org/). Overall, the 

companies described the collaborations as beneficial and encouraged other companies 

to take advantage of NIOSH’s expertise, services, instrumentation, and objective assessments. At the 2010 Nanomanufacturing Summit, sponsored by the NanoBusiness 

Commercialization Association, four companies publically described their experience 

with NTRC researchers as being extremely helpful in providing guidance on the safe 

handling of engineered nanomaterials. One of those companies, NanoComp Technologies, Inc., listed NIOSH as a key partner in developing an effective environmental 

health and safety (EHS) program that supported the growth of its company (M. Banash, 

2010 presentation: Managing NanoEHS: Moving from the Lab to the Plant). 

Figure 11. Portable Aerosol Mobility Spectrometer (PAMS) developed in collaboration with 

Kanomax, USA, Inc. 
14 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Usefulness of collaborative EHS research or related activities with NNI member agencies, 

according to GAO questionnaire respondents

Note: Excludes respondents who selected “No basis to judge” and those who did not check a response. 

Figure 12. Summary of the GAO questionnaire on the usefulness of collaborative studies 

with select Federal agencies working on EHS [GAO 2012]. 

The most recent demonstration of the effectiveness of NIOSH partnerships comes in 

a study of NNI EHS by the Government Accountability Office [GAO 2012]. The GAO 

made inquiries of seven select NNI agencies engaged in EHS research on the extent 

to which they collaborate with each other and with external partners. The intent of 

the inquiry was to evaluate the effectiveness of the collaborations. GAO surveyed 100 

private sector stakeholders and found that the stakeholders placed greatest value in 

partnerships with NIOSH, over other NNI agencies (Figure 12). In the same inquiry, 

the GAO asked how often these same stakeholders went to one of the NNI agencies 

for information, and which agency. Among those who indicated they went to agency 

sources “often," NIOSH was identified as the lead agency. 

Workplace exposure assessment studies conducted by NTRC researchers have provided 1) identification of the types of nanomaterials being considered for commercialization, 2) information on the potential for worker exposure associated with the 

processes that manufacture or use those materials, and 3) the basis for risk management guidance. Early investigations have identified nanomaterial processes and tasks 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 15

2 Qualitative Assessment on Meeting the NTRC Goals

that were good candidates for detailed follow-up studies to evaluate the effectiveness 

of in-place exposure control measures (e.g., engineering controls). Recommendations 

by NTRC researchers on the effective use of exposure controls have resulted in companies adopting improved engineering controls, including local exhaust ventilation 

(LEV) [Methner and Old (Ed.) 2008, Methner 2010, Evans et al. 2010]. For example:

1. Recommendations from NTRC researchers to a graphene manufacturer resulted in the company taking the following steps to reduce exposures: 

 ■ running the spray dryer ventilation system while scraping out the inside of 

the spray dryer during equipment cleaning.

 ■ delaying the product harvest of graphene for at least 15 minutes after process 

completion to reduce the potential for emissions and worker exposure. 

2. Birch et al. [2011] reported respirable elemental carbon concentrations (area 

samples) inside a nanofiber manufacturing facility that were about 6–68 times 

higher than outdoors, whereas personal breathing zone samples were up to 170 

times higher. Elevated particle number concentrations and high concentrations 

of carbon monoxide (CO) were also identified at the same facility [Evans et 

al. 2010]. The report to these companies included recommended engineering 

control measures for reducing the exposures. 

3. In the industrywide exposure assessment study of primary and secondary 

manufacturers of CNT and CNF, Dahm et al. [2011] identified short-term 

peak exposures to CNTs and CNFs at various job tasks and processes. Various 

risk management practices (e.g., engineering controls) were recommended to 

assist in preventing worker exposure. 

By 2011, findings from the NTRC exposure investigations at various workplaces handling 

engineered nanomaterials (Figures 13–16) had yielded the knowledge and experience 

needed to conduct more comprehensive exposure assessment studies to quantitate workers’ 

exposure. The findings from these studies supported the initiation of a health effects study 

of workers exposed to carbonaceous nanomaterials (primarily CNTs and CNFs) and the 

initiation of studies to evaluate the effectiveness of engineering controls to reduce worker 

exposure. These research activities will build upon existing partnerships and forge new 

partnerships to accomplish objectives. Outcomes from this research are expected to provide 

additional guidance on the safe handling of these materials during commercial application. 

2.4 Epidemiology and Surveillance

In 2009, NIOSH published the CIB 60: Interim Guidance for Medical Screening and Hazard Surveillance for Workers Potentially Exposed to Engineered Nanoparticles [www.cdc.gov/

niosh/docs/2009-116/], which provided the first (interim) guidance on medical surveillance 

and medical screening for workers potentially exposed to engineered nanoparticles [NIOSH 

2009c]. To address gaps in information needed to implement an effective occupational 

health surveillance program for nanotechnology workers, NIOSH and the University of 

Colorado Mountain and Plains Education and Research Center (ERC) organized the 2010 

workshop Nanomaterials and Worker Health: Medical Surveillance, Exposure Registries, and 
16 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Epidemiologic Research. The workshop was convened to catalyze the thinking behind the 

research necessary to support human health studies needed to more completely characterize 

potential health risks. The proceedings from this workshop were subsequently published in 

a June 2011 supplemental issue of the Journal of Occupational and Environmental Medicine

[Schulte, Trout, and Hodson 2011] (Figure 17). In 2010, NIOSH drafted the CIB Occupational 

Exposure to Carbon Nanotubes and Nanofibers, which includes recommendations for medical 

surveillance and screening specific for workers potentially exposed to these materials.

In 2008, NTRC researchers undertook a pilot study to determine whether the conduct 

of an epidemiological or other health study of workers exposed to carbonaceous nanomaterials was feasible [Schubauer-Bergian et al. 2011]. The initial steps of the study 

involved identifying potentially eligible U.S. companies producing engineered carbonaceous materials, to determine workforce size, location, and estimated growth. Companies were contacted by telephone and a questionnaire was administered to confirm the 

use of carbonaceous materials and their interest in participating in the study. A total of 

35 U.S. manufacturers and users of carbonaceous nanomaterials completed the survey. 

Follow-up site visits to 16 of the facilities was conducted to confirm workforce size, location, characteristics of the nanomaterials produced, and whether the reported use of 

engineering controls and personal protective equipment was accurate (Table 1). 

Figures 13–16. Nanomaterial workers participating in the NTRC field research efforts. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 17

2 Qualitative Assessment on Meeting the NTRC Goals

Figure 17. The 2010 Nanomaterials and Worker Health conference resulted in a 2011 supplemental issue of the Journal of Occupational and Environmental Medicine dedicated to nanomaterials and worker health, medical surveillance, exposure registries, and epidemiologic health. 

Table 1. Statistics on use of administrative and engineering controls, as well as personal 

protective equipment, in the carbonaceous nanomaterials industry in the United States

 Variable 

NIOSH survey result 

(2008–2011)*

Concordance of field observations 

with survey reports

Observed exactly 

as reported

Observed as 

reported or better

Total N 35 16 16

Wet-wipe cleanup methods 22 (63%) 69% 94%

Use of HEPA vacuum for cleanup 18 (51%) 94% 94%

Lab coats/Tyvek suits 29 (83%) 88% 94%

Gloves 33 (94%) 94% 100%

Respirators 28 (80%) 81% 100%

Local exhaust ventilation 25 (71%) 88% 88%

Chemical fume hoods 29 (83%) 75% 75%

Ventilated enclosures 14 (40%) 75% 88%

Glove boxes 14 (40%) 81% 88%

Enclosed production 12 (34%) 63% 88%

*Among sites surveyed by NTRC researchers. Includes producers and users of engineered 

carbonaceous nanomaterials.
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2 Qualitative Assessment on Meeting the NTRC Goals

The follow-up site visits also included assessments of exposure to CNTs and CNFs, as 

described in Section 2.3 and reported by Dahm et al. [2011]. These assessments led 

to the recognition that the conduct of an epidemiologic study of workers potentially 

exposed to CNTs and CNFs was feasible. Therefore, NIOSH researchers in FY12 developed a draft protocol to conduct a cross-sectional epidemiologic study among 100 

workers at facilities manufacturing or using CNTs or CNFs. This protocol focuses on 

identifying early markers of pulmonary or cardiovascular health effects, together with 

the collection of worker CNT and CNF personal exposure data.

The NIOSH survey of companies handling CNT and CNFs found that 70% reported 

having a health and safety program for the use of nanomaterials [Dahm et al. 2011]. 

The supplemented survey data (n = 35) show that 83% of the companies reported using 

chemical fume hoods, 71% reported using local exhaust ventilation, 40% reported using 

ventilated enclosures or gloveboxes, 34% were using enclosed production processes, and 

more than 80% were using each type of PPE (Table 1). NIOSH subsequently visited 16 

of the 35 companies responding to the survey. On-site evaluation confirmed that nearly 

all companies visited used administrative and engineering controls and PPE as reported 

or more stringently than reported (Table 1). More than 90% of the CNT and CNF companies used all PPE types, wet-wipe cleanup methods, and HEPA vacuums, as reported 

in the survey or better. At least 75% were using engineering controls as reported in the 

survey or better. 

NIOSH also conducted field investigations between 2006 and 2012 in 46 facilities 

(including the 16 handling CNT and CNFs) handling other types of nanomaterials. These field evaluation reports and field notes were evaluated to assess the level 

of adherence with risk management principles within the participating companies. 

Since 16 of the ECN facilities participating in the survey were also part of the 46 

field evaluations, this created the opportunity to assess the accuracy of self-reported 

administrative and engineering control and PPE use. Of the 46 companies visited for 

a field evaluation, PPE use was observed somewhat more frequently than administrative and engineering control use: 89% used some form of PPE and 83% used a hood 

or other enclosure for at least some processes. Of the 46 companies evaluated, 54% 

used chemical fume hoods, 59% used local exhaust ventilation, 50% used ventilated 

enclosures or gloveboxes, 48% used enclosed production processes, and 78% used 

respiratory protection (Figure 18).

2.5 Risk Assessment

NTRC researchers continue to investigate how exposure-response data (human or 

animal) for fine and ultrafine particles can be used to quantitate the risk of exposure 

for workers. NTRC researchers conducted a risk assessment on the pulmonary effects 

seen in experimental animal studies following exposure to fine and ultrafine TiO2, 

CNTs, and CNFs. The results of these assessments supported the development of 

NIOSH recommended exposure limits (RELs) for ultrafine TiO2, CNTs, and CNFs. 

These are the first occupational exposure limits for these classes of nanomaterials issued by a U.S. government agency. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 19

2 Qualitative Assessment on Meeting the NTRC Goals

NTRC risk assessors continue to collaborate with the following researchers in the development of particle dosimetry models and risk assessment techniques for nanomaterials:

 ■ Institute of Occupational Medicine (IOM), Edinburgh, UK, and EU 7th Framework Program on Risk Assessment of Engineered Nanoparticles (ENPRA) 

 ■ Toxicology Excellence for Risk Assessment (TERA)

 ■ Applied Research Associates (ARA), Raleigh, NC

 ■ Lovelace Respiratory Research Institute (LRRI), Albuquerque, NM

 ■ The Hamner Institutes for Health Sciences, Research Triangle Park, NC 

These collaborations have resulted in 1) the completion of an olfactory deposition 

model of spherical nanoparticles in humans and in rats (Hamner Institute/NIOSH 

research collaboration), 2) modeling methods to predict human respiratory tract 

deposition for carbon nanofiber/nanotube structures, based on fiber aerosol theory 

(Hamner Institute and ARA/NIOSH research collaboration), and 3) experiments to 

characterize deposition of airborne CNTs in a human respiratory tract replica. Data 

from this later study are being used in the human lung deposition model for carbon 

nanotubes/nanofibers that is being developed by ARA (LRRI/NIOSH collaboration). 

Figure 18. A summary of the use of engineering controls and PPE use in 46 nanomaterial 

facilities visited by NTRC researchers. 

Chemical fume...

Local exhaust...

Percent of Companies

Using Controls
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2 Qualitative Assessment on Meeting the NTRC Goals

Figure 19. Steps to developing occupational exposure limits or control bands, according 

to availability of toxicologic data. 

Develop and Issue Guidance: Impact of the Level of Information

Control

Banding

Adequate Suggestive Minimal

Available Toxicity &

Physical-Chemical Data

Quantitative Risk

Assessment

Derive Health-Based

OEL

Hazard

Banding

Structure-Activity

Relationship

Comparative

Potency

Reason by

Analogy

Benchmark

Particles

[Adapted from Schulte et al. 2010 and Kuempel et al. 2011]

Because of the lack of hazard data on each type of engineered nanomaterial, NTRC 

researchers are investigating the utility of risk assessment methods that can be applied 

to categories of nanomaterials (Figure 19). 

NTRC researchers also participate in the Organization for Economic Cooperation and 

Development (OECD) Steering Group 6 (SG6) to develop guidance on critical issues 

in nanotechnology risk assessment. 

2.6 Engineering Controls and Personal Protective Equipment 

Given the uncertainty about the hazard potential of many nanomaterials, there remains 

the need for information on engineering controls and PPE. NTRC researchers are investigating the effectiveness of various engineering control techniques and PPE in preventing worker exposure to engineered nanoparticles (Figure 20). Results from NTRC field 

activities (described in 2.3 Exposure Assessment) conducted to assess engineering control measures have been published in the following NIOSH workplace survey reports 

and peer-reviewed literature:
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 21

2 Qualitative Assessment on Meeting the NTRC Goals

 ■ Methner MM, 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–D69.

 ■ Methner MM [2010]. Effectiveness of a custom-fitted flange and LEV system 

in controlling the release of nano-scale metal oxide particulate. Intl J Occup 

Environ Health 16:475–487.

 ■ Evans DE, Ku Ki B, Birch ME, Dunn KH [2010]. Aerosol monitoring during 

carbon nanofiber production: mobile direct-reading sampling. Ann Occup 

Hyg 54(5):514–531.

■ Lo LM, Dunn KH, Hammond D, Almaguer D, Bartholomew I, Topmiller J, 

Tsai CSJ, Ellenbecker M, Huang CC [2011]. Evaluation of engineering controls for manufacturing nanofiber sheets and yarns. Cincinnati, OH: U.S. 

Department of Health and Human Services, Centers for Disease Control and 

Prevention, National Institute for Occupational Safety and Health, DHHS 

(NIOSH) Report No. EPHB 356–11a.

Figure 20. Local exhaust ventilation and PPE used during reactor cleanout.
22 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

 ■ NIOSH [2012]. General safe practices for working with engineered nanomaterials in research laboratories. Cincinnati, Ohio: U.S. Department of Health 

and Human Services, Centers for Disease Control and Prevention, National 

Institute for Occupational Safety and Health, Publication No. 2012–147 

(Figure 21).

 ■ A NIOSH draft document on engineering control guidance for nanomaterial 

manufacturers and users, entitled Current Strategies for Engineering Controls in 

Nanomaterial Handling Processes, is scheduled for publication in late 2012. 

NTRC researchers have evaluated and published the results on the effectiveness of respiratory protection for capturing nanoparticles, as well as created an information blog on the 

NIOSH Web page [http://blogs.cdc.gov/niosh-science-blog/category/respiratory-health/]. 

Figure 21. The cover of the NIOSH guidance document detailing best practices for working with engineered nanomaterials in research laboratories. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 23

2 Qualitative Assessment on Meeting the NTRC Goals

Respirator performance studies conducted by NTRC researchers have shown that 

NIOSH-approved respirators should provide levels of performance consistent with their 

assigned protection factors [Rengasamy et al. 2008; Shaffer and Rengasamy 2009; Rengasamy and Eimer 2011; Rengasamy and Eimer 2012]. 

Research with other types of PPE (gloves and clothing) is ongoing (Figure 22). NTRC 

researchers developed and evaluated a multidomain magnetic passive aerosol sampler 

for measuring particulate penetration through protective ensembles. The design of 

this sampler was submitted as an employee invention to the CDC Technology Transfer Office (Ref. #I-007-08). This new sampler significantly enhances collection of magnetically susceptible particles, better simulates the user’s real situation in the workplace than alternative filtration-based approaches, and improves the capability for 

determining particle penetration through protective clothing materials. Results from 

a study evaluating the penetration of nanoparticle and submicron particle penetration 

through different fabrics show that particle penetration increased with increasing face 

velocity and also increased with increasing particle size up to about 300 to 500 nm 

[Gao et al. 2011]. Penetrations measured by the wind-driven method were lower than 

those obtained with the filtration method for most of the fabrics selected, and the relative penetration performances were very different because of the vastly different pore 

structures of the fabric. 

2.7 Fire and Explosion Safety

Research is ongoing into the physical and chemical properties that contribute to dustiness, combustibility, flammability, and conductivity of nanomaterials. Explosion testing 

was performed on 20 types of carbonaceous particles, including SWCNTs, MWCNTs, 

CNFs, graphene, diamonds, fullerene, and carbon black graphite. The typical overpressure and deflagration indexes were observed to be similar to those of cotton or wood 

dust. The explosion parameters did not appear to correlate with particle size. For selected materials, explosion testing was conducted at scans of dust concentration, which 

Figure 22. (Left) An improperly connected glove and garment. (Right) A properly connected 

glove and coverall do not permit the nanomaterials to touch (reach) the skin. 
24 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

yielded low minimum explosive concentrations (at the low end of the range typically observed for coals) which could be of concern for workers. Scans of ignition energy proved 

inconclusive due to electrical shorting of the equipment by the conductive powders. 

Research results on dustiness, flammability, and explosibility of nanomaterials have 

been presented at numerous meetings and conferences. A publication on the dustiness 

of 27 fine and nanoscale powders, tested with a device developed for pharmaceutical 

application, is in progress. 

2.8 Recommendations and Guidance 

While in the early stages of understanding the health risks associated with exposure to 

engineered nanoparticles, NTRC researchers developed the first comprehensive compendium of guidance to inform employers of the potential hazards of nanomaterials and the 

steps that could be taken to help minimize the health risks from exposure. The document 

Approaches to Safe Nanotechnology: An Information Exchange with NIOSH was first posted 

on the NIOSH Web site in 2005 and became one of the most widely utilized nanomaterial occupational safety and health guidance documents throughout the world. Recommendations given in the document have provided the rationale and basis for guidance 

documents developed by the Organization for Economic Cooperation and Development 

(OECD), the International Standards Organization (ISO), National Institute of Occupational Safety and Health Japan, and Safe Work Australia. The OECD recommendations on 

exposure measurement and mitigation were tailored after the NIOSH recommendations 

provided in Approaches to Safe Nanotechnology. This OECD guidance document is used by 

nearly every industrialized country in the world. ISO Standard 12885, entitled Nanotechnologies: Health and Safety Practices in Occupational Settings Relevant to Nanotechnologies, 

also was based on the NIOSH compendium. In 2009, the NIOSH document was updated 

and released as Approaches to Safe Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered Nanomaterials [www.cdc.gov/niosh/docs/2009-125/] 

[NIOSH 2009b]. This document continues to be one of the most widely used and cited 

occupational risk management frameworks for nanomaterials in the United States. The 

document has been downloaded from the NIOSH Web site over 11,000 times (Table 2). 

An abbreviated companion brochure, Safe Nanotechnology in the Workplace: An 

Introduction for Employers, Managers, and Safety and Health Professionals, was developed to highlight the uncertainty about the health risks of nanomaterials and the need 

to take precautionary actions to control workplace exposures. Approximately 45,000 

copies of the brochure have been distributed in both English and Spanish. Other 

countries have translated the brochure into Italian, Portuguese, and Japanese. 

In 2005, NIOSH posted on the Web for public comment a draft of the world’s first recommended exposure limit (REL) specifically for a nanomaterial, by issuing guidance 

for nanosized TiO2 in addition to micrometer-sized TiO2 (bulk fine pigment). Even 

as a draft, this pioneering document was widely cited. CIB 63: Occupational Exposure 

to Titanium Dioxide [www.cdc.gov/niosh/docs/2011-160/] was finalized and disseminated in early 2011 [NIOSH 2011]. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 25

2 Qualitative Assessment on Meeting the NTRC Goals

In 2010, NIOSH drafted another CIB, Occupational Exposure to Carbon Nanotubes

and Nanofibers. This CIB includes a REL for CNTs and CNFs, as well as comprehensive risk management recommendations for medical surveillance and monitoring, 

exposure monitoring, and procedures for controlling workplace exposure. Many of 

the risk management recommendations are derived from field and laboratory findings 

of NTRC researchers. 

NTRC researchers have provided a broad range of guidance on topics ranging from medical surveillance, epidemiologic research, precautionary approaches, occupational exposure 

limits, active nanomaterials, and governance [Schulte and Salamanca-Buentello 2007; Murashov and Howard 2008; Schulte et al. 2008; Schulte et al. 2009; Howard and Murashov 

2009; Schulte et al. 2010; Schulte, Trout, and Hodson 2011; Schulte et al. 2012]. 

Table 2. Dissemination of NIOSH NTRC nanotechnology

guidance documents between 2004 and 2011

Publication Number printed

Number 

disseminated 

Number of Web 

site downloads

NIOSH Pub No. 2004–175 

Nanotechnology Workplace Safety and Health

1,099 1,099 1,750

NIOSH Pub No. 2008–112 

Safe Nanotechnology in the Workplace: An 

Introduction for Employers, Managers, and 

Safety and Health Professionals (English)

36,000 29,055 1,987

NIOSH Pub No. 2008–112 

Safe Nanotechnology in the Workplace: An 

Introduction for Employers, Managers, and 

Safety and Health Professionals (Spanish)

17,000 15,485 N/A

NIOSH Pub No. 2008–121 

NIOSH Field Research Effort Fact Sheet

5,000 2,067 556

NIOSH Pub No. 2009–116 

CIB 60. Interim Guidelines for Medical Screening and Hazard Surveillance for Workers Potentially Exposed to Engineered Nanoparticles

3,000 1,338 2,551

NIOSH Pub No. 2009–125 

Approaches to Safe Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered Nanomaterials

7,850 2,528 11,487
26 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Highlights of NIOSH Recommendation Activities

1. Approaches to Safe Nanotechnology: Managing the Health and Safety 

Concerns Associated with Engineered Nanomaterials continues to be one 

of the most widely used and cited occupational risk management frameworks for nanomaterials. 

2. NIOSH is the first agency globally to conduct the scientific research and 

assessments necessary to issue recommended exposure limits specifically 

for an engineered nanomaterial (titanium dioxide). Even as a draft, this 

pioneering document was widely cited. It was published in 2011.

3. NIOSH issued a draft CIB Occupational Exposure to Carbon Nanotubes and 

Carbon Nanofibers in 2010.

2.9 Communications and Information

Communicating the results of ongoing research activities is an important objective of the 

NTRC. Since the inception of the nanotechnology research program in 2004, researchers have delivered over 650 invited presentations, including over 100 internationally, at 

scientific meetings, symposia, and workshops (Figure 23). NTRC staff members have also 

conducted workshops and training sessions on effective risk management practices for 

handling nanomaterials in the workplace (Appendix A). The dissemination of research 

findings and risk management recommendations resulted in early recognition for NIOSH 

as a key contributor in the development of the national environmental health and safety 

research strategy prepared by the U.S. National Nanotechnology Initiative (NNI). Clayton 

Teague, director of the National Nanotechnology Coordination Office (NNCO), recognized NIOSH at the June 25, 2008, TAPPI International Conference on Nanotechnology 

for the Forest Products Industry for its initiative in recommending a national occupational 

1 2 3
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 27

2 Qualitative Assessment on Meeting the NTRC Goals

health and safety research strategy. The NNCO also cited NIOSH’s success in developing 

partnerships with private companies to assist with responsible development of nanotechnology. This acknowledgement is noteworthy because the NNCO serves as a central point 

of contact for Federal nanotechnology R&D activities and provides public outreach on 

behalf of the NNI. The NNCO coordinates the preparation and publication of NNI interagency planning, budget, and assessment documents, such as the annual NNI supplement 

to the President’s budget. In addition, the NNCO coordinates development of information 

for the NNI and its activities for Congress when requested. 

NIOSH has sponsored and co-sponsored many nanomaterial workshops at which representatives from academia, labor, industry, and health and safety have collaborated. 

The substantive input by NTRC researchers on the interpretation of research results, 

identification of research gaps (toxicology, exposure characterization), and recommendations on good risk-management practices are frequently used in developing the 

conclusions and recommendations contained in the workshop proceedings. 

Figure 23. Distribution of presentations by critical research area. 

NTRC Presentations by Critical Research Area 2004–2011

Toxicology and Internal Dose

Communications and Information

Measurement Methods

Exposure Assessment

Recommendations and Guidance

Engineering Controls and PPE

Risk Assessment

Epidemiology and Surveillance

Flammability and Explosivity

Applications

206

164

77

66

60

47

32

18

9

8

206

164

77

66

60

47

32

18 9 8 # Research Area
28 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

NIOSH–Sponsored or –Co-Sponsored Workshops and Conferences 

on Engineered Nanomaterials

 ■ First Symposium on Occupational Health Implications of Nanomaterials, Buxton, 

United Kingdom (2004)

 ■ Second Symposium on Occupational Health Implications of Nanomaterials, 

Minneapolis, MN (2005)

 ■ International Conference on Nanotechnology Occupational and Environmental 

Health and Safety: Research to Practice; Cincinnati, OH (2006) 

 ■ First International Conference on Nanotoxicology, Miami, FL (2006)

 ■ In collaboration with the International Aerosol Research Assembly and the 

American Association for Aerosol Research: Second International Symposium 

on Nanotechnology and Occupational Health, in conjunction with International 

Aerosol Conference, St. Paul, MN (2007)

 ■ Third Symposium on Occupational Health Implications of Nanomaterials, Taipei, 

Taiwan (2007) 

 ■ In collaboration with government, academia, labor, and industry, workshop to 

review a draft document developed by NIOSH and a cross-agency workgroup, 

Interim Guidelines on Medical Screening of Workers Potentially Exposed to 

Engineered Nanoparticles, in Washington, DC (2008) 

 ■ In collaboration with the National Institute of Standards and Technology, 

Enabling Standards for Nanomaterial Characterization (workshop), in 

Gaithersburg, MD (2009)

 ■ Second International Conference on Nanotechnology, Zurich, Switzerland (2009)

 ■ In collaboration with OECD, Exposure Assessment and Exposure Mitigation 

workshop, Frankfurt (2009) and Karlsruhe (2010), Germany 

 ■ As lead organizer, NNI Workshop on Human and Environmental Exposure, 

Bethesda, MD (2009)

 ■ Fourth International Conference on Nanotechnology—Occupational and 

Environmental Health, Helsinki, Finland (2009)

 ■ As lead organizer, Nanomaterials and Worker Health: Exposure Registries, 

Medical Surveillance and Epidemiologic Research, Keystone, CO (2010)

 ■ Fifth International Conference on Nanotechnology—Occupational and 

Environmental Health, Boston, MA (2011)

 ■ Workshop on Global Harmonization of Exposure Measurements, Boston, MA (2011)

 ■ Safe Nano Design: Molecule » Manufacturing » Market: Applying Prevention 

through Design to Nanomaterials, with the College of Nanoscale Science & 

Engineering (CNSE), University at Albany, State University of New York, Albany, 

NY (2012) 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 29

2 Qualitative Assessment on Meeting the NTRC Goals

2.9.1 NIOSH Nanotechnology Web Site 

In 2005, NIOSH created the first nanotechnology topic page on the NIOSH Web site 

devoted to providing information on the potential hazards of engineered nanomaterials 

in the workplace (Figure 24). The Web site provides a one-stop source of scientific 

and technical information intended to help guide the public and safety and health 

professionals in making good risk management decisions. Since its inception in 2005, 

the topic page on the NIOSH Web site has evolved into a comprehensive source that 

contains links to all of the NIOSH nanotechnology guidance documents, abstracts of 

published articles, nanotechnology health and safety news updates, and links to other 

sources of nanotechnology information. In 2011, individuals from 139 countries visited 

the NIOSH nanotechnology topic page on the Web site; the United States accounted for 

61% of the total visits, and other countries accounted for the remaining 39% (Table 3). 

The topic page on the Web site receives over 2,000 visits each month (Figure 25).

2.9.2 Bibliometric Analysis

When NIOSH published its first progress report, Progress Toward Safe Nanotechnology 

in the Workplace in 2007, NTRC researchers had already published more than 70 articles in the peer-reviewed scientific literature (Figure 26). This number had increased 

to over 170 with the publication of the second progress report in 2009. These publications included results from some of the first scientific studies demonstrating that 

Figure 24. Screen shot of the NIOSH Nanotechnology Topic Page. 
30 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

0

2000

4000

6000

8000

10000

Jan-09

Mar-09

May-09

Jul-09

Sep-09

Nov-09

Jan-10

Mar-10

May-10

Jul-10

Sep-10

Nov-10

Jan-11

Mar-11

May-11

Jul-11

Sep-11

Nov-11

Number

Month

Number of visitors to the NIOSH 

Nanotechnology Topic Page (2009–2011)

Table 3. The top 20 countries accounting for visitors to the NIOSH 

Nanotechnology Topic Page in 2011.

Countries Page views

1. United States 23,437 60.8%

2. Canada 1,432 3.7%

3. United Kingdom 1,084 2.8%

4. France 937 2.4%

5. India 821 2.1%

6. Japan 745 1.9%

7. Australia 674 1.7%

8. Italy 621 1.6%

9. Spain 534 1.4%

10. Iran (Islamic Republic of) 528 1.4%

11. Brazil 487 1.3%

12. Germany 479 1.2%

13. Malaysia 401 1.0%

14. Korea-South 371 1.0%

15. China 305 0.8%

16. Singapore 271 0.7%

17. Netherlands 256 0.7%

18. Switzerland 241 0.6%

19. Taiwan 241 0.6%

20. Belgium 237 0.6%

Figure 25. Average number of visits to NIOSH Nanotechnology Topic Page. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 31

2 Qualitative Assessment on Meeting the NTRC Goals

exposure to CNT causes harmful pulmonary effects (such as acute fibrosis) in mice 

at relatively low doses. To date, more than 400 articles have been published by the 

NIOSH nanotechnology program (Appendix A, Figure 27). Publications in the areas 

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

and risk management have provided important needed information and a framework 

for others in addressing potential hazards and risks from engineered nanoparticles. 

Because the value of information is determined by those who use it, one measure of the 

value or outcome of a publication is the number of times it has been cited [Burdorf and 

Viikara-Juntura 2007; Kostoff et al. 2009]. A diagram of the citation process, with initial 

citations spawning clusters of secondary citations, is shown in Figure 28. 

As of December 31, 2011, more than 400 NTRC-authored publications pertaining 

to engineered nanomaterials have been cited over 5,000 times in the peer-reviewed 

scientific literature. These primary citations have resulted in over 82,000 secondary citations, thus illustrating the impact and reach of NTRC research results in 

the field of nanotechnology. As seen in Figure 29, a large number of NTRC-authored 

journal articles have been much more commonly cited than the average citation value of 

5 calculated from 11 journals that NTRC researchers published in. The same holds true 

even when using a higher value of 20 as an average number of times that publications 

in biomedical sciences are cited over their lifetime [MacRoberts and MacRoberts 1989]. 

Citation data were compiled with both Google Scholar and Thomson Reuters Web 

of Knowledge. 

Figure 26. The previously published NTRC Progress Reports.
32 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Figure 27. Distribution of journal publications, by critical research area. 

Figure 28. A graphical representation of the Shvedova et al. 2008 paper, Inhalation Versus Aspiration of Single-Walled Carbon Nanotubes in C57bl/6 Mice: Inflammation, Fibrosis, Oxidative 

Stress and Mutagenesis. The scatter plot illustrates the initial publication (red dot) surrounded 

by the number of times (101) it was directly cited in other papers (primary citations are yellow 

dots) and then the number of times (738) the primary citation papers were cited by other 

papers (secondary citations are white dots). This diagram was developed using Cytoscape, an 

open source platform for complex network analysis and visualization. The paper was one of 

the first to demonstrate that inhalation of carbon nanotubes would cause pulmonary fibrosis. 

NTRC Publications by Critical Research Area 2004–2011

Toxicology and Internal Dose

Measurement Methods

Exposure Assessment

Communications and Information

Recommendations and Guidance

Engineering Controls and PPE

Risk Assessment

Epidemiology and Surveillance

Applications

258

48

31

30

26

21

19

6

3

# Research Area

258

48

31

30

26

21

19 6 3
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 33

2 Qualitative Assessment on Meeting the NTRC Goals

1

10

100

1000

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Number of

citations

Log 10 scale

Publication Year Numberof Published Papers

Citations of NIOSH authored papers 2003-2011

n=5 average 

citations in 11

journals

Figure 29. Citations of NIOSH NTRC-authored publications compared to the average number of citations in 11 biomedical and occupational safety and health journals containing 

NIOSH publications.*

*

Scandinavian Journal of Public Health, International Archives of Occupational and Environmental Health, Journal of Toxicology and Environmental Health–Part A–Current Issues, 

Inhalation Toxicology, Journal of Nanoparticle Research, Journal of Occupational and 

Environmental Hygiene, Particle and Fibre Toxicology, Annals of Occupational Hygiene, 

Toxicology Letters, Nature Nanotechnology, and Journal of Aerosol Science. 
34 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

While citation analysis illustrates the extent to which scientists use and reflect on 

NRTC research, these citations are influenced by the time since publication. Many 

of the papers have only been published within the last 2 or 3 years of the time period 

(2003–2011) and they have not had much opportunity to be cited. The cited halflife (i.e., the number of years going back from the current year) generally is close to 

7 years (range, 4.8 to 8.4 years) [Gehanno et al. 2007, Smith 2008]. Consequently, a 

large number of NIOSH published papers have not been in the literature long enough 

to reach the average cited half-life, and further citations are anticipated. 

2.9.2.1 Perspective

To put into perspective the impact of some of the NTRC papers, it is possible to 

compare the number of times they are cited with other papers that are widely cited. 

For example, Gehanno et al. [2007] found that among 15,553 articles published in 

five major occupational medicine journals since 1949, only 85 (0.55%) had been cited 

more than 100 times. In comparison, the 2003 and 2005 NTRC papers by Shvedova 

et al. were cited 505 and 449 times, respectively. A review by Kostoff et al. [2009] of 

the seminal research literature of nanotechnology listed the most highly cited papers going back to 1991. The review focused on physical phenomenon and construct 

structures rather than on health-impact-related papers in nanotechnology, but if it had 

focused on the latter, then the papers by Shvedova et al. [2003 and 2005] would have 

been the fourth and sixth most cited papers on that seminal list. Clearly, some key 

NTRC papers identified in this progress report have achieved citation rates comparable to several of the papers that Kostoff et al. assessed as seminal in nanotechnology. 

Figures 30–37 show the number of citations in eight of the NTRC research areas.

Six articles published by NTRC researchers from 2008 through 2010 were included 

in the top-10 most cited articles (as of June 2012), from the Journal of Occupational 

and Environmental Hygiene (JOEH) [http://www.tandf.co.uk/journals/cited/UOEH.

pdf] (Table 4). This journal has a readership of over 10,000 industrial hygienists and 

occupational safety and health professionals. 

In addition to citations of NIOSH research, NIOSH guidance was also widely cited 

(Figure 38), as demonstrated by the 80 primary and 661 secondary citations of Occupational Risk Management of Nanoparticles [Schulte et al. 2008]. 

Three articles published by NTRC researchers from 2009 through 2011 were included 

in the top-5 most cited articles from the Journal of Toxicology and Environmental Health, 

Part A [http://www.tandfonline.com/toc/uteh20/current#cited] (Table 5).

In addition, the Scandinavian Journal of Work, Environment & Health reported that the 

2008 article Sharpening the Focus on Occupational Safety and Health in Nanotechnology, 

by NTRC researchers (Schulte PA, Geraci CL, Zumwalde R, Hoover M, Castranova V, 

Kuempel E, Murashov V, Vainio H, and Savolainen K; 34:471–478) was one of the top–

10 most viewed articles in 2009 [http://www.sjweh.fi/list_top_viewed.php?year=2009]. 

This journal is distributed to 34 countries on 6 continents and has, according to the 

journal website, a 5-year impact factor of 3.83. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 35

2 Qualitative Assessment on Meeting the NTRC Goals

Figures 30–37. Citations by NTRC research area. Recommendations and Guidance and 

Communications have been combined and there were no publications in the research 

area of fire and explosion safety. The red line at n=5 is the average number 

of citations for 11 journals in which the NTRC published. 
36 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Figures 30–37 (Continued). Citations by NTRC research area. Recommendations and 

Guidance and Communications have been combined and there were no publications in 

the research area of fire and explosion safety. The red line at n=5 is the average number 

of citations for 11 journals in which the NTRC published. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 37

2 Qualitative Assessment on Meeting the NTRC Goals

Figures 30–37 (Continued). Citations by NTRC research area. Recommendations and 

Guidance and Communications have been combined and there were no publications in 

the research area of fire and explosion safety. The red line at n=5 is the average number 

of citations for 11 journals in which the NTRC published. 
38 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Figures 30–37 (Continued). Citations by NTRC research area. Recommendations and 

Guidance and Communications have been combined and there were no publications in 

the research area of fire and explosion safety. The red line at n=5 is the average number 

of citations for 11 journals in which the NTRC published. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 39

2 Qualitative Assessment on Meeting the NTRC Goals

Table 4. Six of the top 10 cited JOEH articles for 2008 through 2010 had 

NIOSH authorship

Schulte P, Geraci C, Zumwalde R, et al. [2008]. Occupational Risk Management of Engineered 

Nanoparticles (Figure 38), 5(4):239–249.

Methner MM, Old L [2008]. Effectiveness of Local Exhaust Ventilation (LEV) in Controlling 

Engineered Nanomaterial Emissions during Reactor Cleanout Operations, 5(6):D63–D69. 

Methner M, Hodson L, Geraci C [2010]. Nanoparticle Emission Assessment Technique (NEAT) for 

the Identification and Measurement of Potential Inhalation Exposure to Engineered Nanomaterials—

Part A, 7(3):127–132. 

Rengasamy S, King WP, Eimer BC, et al. [2008]. Filtration Performance of NIOSH-Approved 

N95 and P100 Filtering Facepiece Respirators against 4 to 30 Nanometer-Size Nanoparticles,

5(9):556–564. 

Methner M, Hodson L, Dames A, et al. [2010]. Nanoparticle Emission Assessment Technique 

(NEAT) for the Identification and Measurement of Potential Inhalation Exposure to Engineered 

Nanomaterials—Part B: Results from 12 Field Studies, 7(3):163–176. 

Heitbrink WA, Evans DE, Ku BK, et al. [2009]. Relationships Among Particle Number, Surface 

Area, and Respirable Mass Concentrations in Automotive Engine Manufacturing, 6(1):19–31.

Figure 38. A graphical representation of the 80 primary and 661 secondary citations of 

the 2008 article Occupational Risk Management of Nanoparticles.
40 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Many of the NTRC journal publications have been nominated for the Alice Hamilton 

Awards (NIOSH’s highest scientific award). A few of the winning publications are 

listed here.

2006 Biological Sciences Category

Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina 

YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku 

BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P [2005]. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes 

in mice. Am J Physiol Lung Cell Mol Physiol 289(5):L698–L708.

2009 Biological Sciences Category

Shvedova AA, Kisin E, Murray AR, Johnson VJ, 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 [2008]. Inhalation vs. aspiration of singlewalled carbon nanotubes in c57bl/6 mice: inflammation, fibrosis, oxidative stress, and 

mutagenesis. Am J Physiol Lung Cell Mol Physiol 295:L552–L565.

2010 Biological Sciences Category

Porter DW, Hubbs AF, Mercer RR, Wu N, Wolfarth MG, Sriram K, Leonard S, Battelli L, Schwegler-Berry D, Friend S, Andrew M, Chen BT, Shuji Tsuruoka S, Endo M, 

Castranova V [2010]. Mouse pulmonary dose- and time course-responses induced by 

exposure to multi-walled carbon nanotubes. Toxicology 269(2–3):136–147. 

Table 5. Three of the top 5 cited articles for Journal of Toxicology and Environmental 

Health, Part A, 2009 through 2011, had NIOSH authorship

Wang L, Mercer R, Rojanasakul Y, Qiua A, Lub Y, Scabillonia J, Wuc N, Castranova V [2010]. Direct 

Fibrogenic Effects of Dispersed Single-Walled Carbon Nanotubes on Human Lung Fibroblasts. 

73(5–6):410–422. 

Rushton EK, Jiang J, Leonard SS, Eberly S, Castranova V, Biswas P, Elder A, Han X, Gelein R, Finkelstein J, Oberdörster G, et al. [2010]. Concept of Assessing Nanoparticle Hazards Considering 

Nanoparticle Dosemetric and Chemical/Biological Response Metrics. 73(5–6):445–461.

Pacurari M, Castranova V, Vallyathan V [2010]. Single- and Multi-Wall Carbon Nanotubes Versus 

Asbestos: Are the Carbon Nanotubes a New Health Risk to Humans? 73(5–6):378–395.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 41

2 Qualitative Assessment on Meeting the NTRC Goals

2011 Engineering and Physical Sciences Category

Evans DE, Ku BK, Birch ME, Dunn KH [2010]. Aerosol monitoring during carbon 

nanofiber production: mobile direct-reading sampling. Ann Occup Hyg 54(5):514–531. 

2011 Bullard Sherwood Award, Research2Practice Knowledge Category 

Hodson L, Geraci C, Zumwalde, R, Castranova V, Keumpel, E, Schulte P, Birch E, 

Curwin B, Evans D, Gao P, Hoover M, Ku B, Mercer R, Methner M, Murashov V, Pearce 

T, Rengasamy A, Schubauer-Berigan M, Shaffer R, Shvedova A, Stefaniak A, Trout D, 

Turkevich L, Williams V, and Fazio G. Approaches to Safe Nanotechnology: Managing the 

Health and Safety Concerns Assoicated with Engineered Nanomaterials.

2.9.3 Collaborations and Partnerships

The fourth goal of the NTRC is to enhance global workplace safety and health 

through national and international collaborations on nanotechnology research and 

guidance. NIOSH continues to be an active contributor to the NNI by providing the 

occupational health and safety expertise in support of the U.S. Government’s Strategic Plan for Nanotechnology Health and Safety Research. NIOSH co-chairs the NNI 

Nanotechnology Environmental and Health Implications (NEHI) Working Group. 

NTRC researchers made significant contribution to the development of the 2011 

NEHI environmental health and safety (EHS) strategy and had primary responsibility 

for the chapters on human exposure assessment and human health. This EHS research 

strategy provides guidance to Federal agencies on what research is needed to support 

the development of risk management policies, regulatory decision-making, product 

use, research planning, and public outreach. The core research areas in the NNI 2011 

EHS Research Strategy are (1) Nanomaterial Measurement Infrastructure, (2) Human 

Exposure Assessment, (3) Human Health, (4) Environment, (5) Risk Assessment and 

Risk Management Methods, and (6) Informatics and Modeling. 

The NTRC is also conducting several types of research under formal interagency 

agreements with the National Toxicology Program (NTP), Occupational Safety and 

Health Administration (OSHA), and Consumer Products Safety Commission (CPSC) 

and collaborating through a Framework Memorandum with the Department of Defense (DOD). NTRC researchers have informal collaborations with the Environmental Protection Agency (EPA), National Institute of Standards and Technology (NIST), 

Department of Energy (DOE), and National Aeronautics and Space Administration 

(NASA). NTRC researchers also 1) serve on the American Society for Testing and 

Materials (ASTM) standards committees and contribute to ASTM E-56 (Nanotechnology) and 2) chair the ANSI U.S. Technical Advisory Group to ISO Technical Committee 229 Working Group 3 on Nanotechnology Health, Safety, and Environment. 

NIOSH has formal partnerships with two research centers under Memoranda of Understanding (MOU). One MOU is with the National Science Foundation (NSF)–funded 

Center for High-Rate Nanomanufacturing (CHN) at Northeastern University. This 

MOU provides collaboration with the Nano EHS program at the University of 
42 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

Massachusetts–Lowell and has provided the opportunity for joint research. A second 

MOU was developed with the College of Nanoscale Science and Engineering (CNSE), 

at the State University of New York–Albany. The CNSE partnership provides direct access to the SEMATECH semiconductor industry consortium. Under this partnership 

NTRC researchers have access to conducting exposure assessments at the CNSE, and 

NIOSH partnered with CNSE to host a conference in Albany, NY, in summer 2012: 

Safe Nano Design: Molecule » Manufacturing » Market: Applying Prevention through 

Design to Nanomaterials [http://www.cdc.gov/niosh/topics/ptd/nanoworkshop/default.html]). This first-of-its kind workshop brought together experts in molecular 

design, toxicology, facility design, exposure assessment, and engineering controls 

to develop guidance on the application of Prevention through Design principles to 

nanotechnology. 

NIOSH has ongoing collaborations with the International Council on Nanotechnology (ICON) and provides direct support to the GoodNanoGuide at Rice University. 

NTRC researchers collaborate with the states of California and Massachusetts and 

have been invited to contribute to several nanobusiness consortia, including the 

NanoBusiness Commercialization Association, the Nano Panel of the American 

Chemistry Council, the NanoAlliance of the Society of Chemical Manufacturers and 

Affiliates, Center of Innovation for Nanobiotechnology (COIN) in North Carolina, 

and the Consortium for Multifunctional Polymers and Nanodevices (CMPND). 

NIOSH maintains several private sector partnerships, including close to 40 companies who have sponsored NTRC field research activities. NIOSH maintains working 

relationships with West Virginia University Nanotechnology Center, West Virginia 

University Medical School, University of Wisconsin, Madison, University of Iowa, 

University of Pittsburgh, University of Cincinnati, Birck Center for Nanotechnology 

at Purdue University, and the University of Dayton Research Institute.

NTRC researchers participate with several health and safety organizations and expert 

groups, including the American Industrial Hygiene Association (AIHA), American Conference of Governmental Industrial Hygienists (ACGIH), American Society of Safety Engineers 

(ASSE), Hamner Institutes for Health Sciences, Health Physics Society (HPS), International 

Safety Equipment Association, International Alliance for Nanotoxicology Harmonization 

(IAHN), International Life Sciences Institute (ILSI)–based NanoRelease Initiative, Technical Association of the Pulp and Paper Industry’s International Nanotechnology Standards 

Coordination Committee (INSCC), National Safety Council (NSC), and the initiative on 

Minimum Information Needed for Characterization of Nanomaterials (MINChar).

NTRC reseachers participated with experts from 45 other national and international organizations in creating the community-based Nanoinformatics 2020 Roadmap published by 

the National Nanomanufacturing Network (www.internano.org/nanoinformatics). Building on experience and input of NTRC researchers, the Roadmap defines nanoinformatics as the science and practice of determining which information is relevant to the 

nanoscale science and engineering community, and then developing and implementing 

effective mechanisms for collecting, validating, storing, sharing, analyzing, modeling, 

and applying that information. The Roadmap provides a framework for the emergence 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 43

2 Qualitative Assessment on Meeting the NTRC Goals

of nanotechnology in broad sectors of research, development, and commerce, and enables researchers to recognize its potential hazards as well as benefits; evaluate specific 

applications and exposure situations for nanomaterials; develop controls to prevent or 

minimize exposure; and confirm the effectiveness of those controls by workplace measurements and epidemiological studies of worker populations. Since its publication in 

the spring of 2011, the Roadmap has been downloaded more than 1000 times by more 

than 700 users. The www.InterNano.org online resource of the National Nanomanufacturing Network provides monthly newsletters and weekly mailers that are distributed to 4,500 subscribers, and it supports the information needs of the nanomanufacturing community by reporting on advances in applications, devices, metrology, and 

materials that will facilitate the commercial development and marketable application 

of nanotechnology. Links to NIOSH resources are provided on InterNano.org. 

NTRC researchers have actively shared with health and safety professionals the knowledge 

and expertise gained from the assessment of exposures in workplaces where various types of 

engineered nanomaterials are manufactured and used. This sharing of knowledge often includes hands-on training at national, state, and local meetings, workshops, and conferences. 

The American Industrial Hygiene Association also recorded the training course “Nanoparticles in the Workplace: Assessing and Managing Risks” conducted by NTRC researchers in 

2009 and has made the course available on CD-ROM for distance learning. In December 

2011, NTRC researchers provided direct assistance to the State of California, Division of 

Toxic Substances Control, by conducting a day-long training class on nanomaterial exposure 

assessment techniques. The training class was followed the next day by having the California 

State staff accompany NTRC researchers on a site visit to a local nano-metal oxide manufacturer to gain hands-on experience for assessing workplace exposures. 

On the international level, NIOSH is collaborating with World Health Organization 

(WHO), United Nations Institute for Training and Research (UNITAR), International 

Labor Organization (ILO), Organization for Economic Cooperation and Development (OECD), International Organization for Standardization (ISO), International 

Commission on Occupational Health (ICOH), the NanoImpactNet consortium in 

the European Union (EU), Japan NIOSH, Safe Work Australia, Institute of Occupational Medicine (IOM), ANSES (Administración Nacional de la Seguridad Social in 

Argentina), Fundracentro (Brazil), and several European Commission 7th Framework 

Projects (Figure 39). A member of the NTRC chairs the ICOH Scientific Committee on nanotechnology, and a member of the NTRC chairs the OECD Working Party 

on Manufactured Nanomaterials steering group (SG) on exposure measurement and 

exposure mitigation for manufactured nanomaterials (SG8). The OECD publication 

Emission Assessment for Identification of Sources and Release of Airborne Manufactured 

Nanomaterials in the Workplace: Compilation of Existing Guidance is based on the 

NIOSH Nanomaterials Emission Assessment Technique described in Appendix A of 

the NIOSH document Approaches to Safe Nanotechnology: Managing the Health and 

Safety Concerns Associated with Engineered Nanomaterials.

In 2008, NIOSH signed an agreement with ILO to collaborate on several projects 

specific to nanotechnology, including the development of content for the 5th edition 

of the ILO Encyclopedia. 
44 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting the NTRC Goals

NIOSH leads the development of a nanotechnology topic page for the World Health 

Organization (http://www.who.int/occupational_health/topics/nanotechnologies/en/). 

Most recently NIOSH also expanded its leadership in developing global nanotechnology workplace guidance documents for WHO and the Inter-organizational Program 

for Sound Management of Chemicals.

NTRC reseachers are coordinating efforts with the Netherlands Organization for Applied 

Scientific Research (TNO), Partnership for European Research in Occupational Safety and 

Health (PEROSH), and NanoImpactNet to develop a global exposure registry database. 

They are also leading the development of a health surveillance project incorporating exposure registries in the International Occupational Hygiene Association (IOHA). 

NIOSH, through its collaborations with ISO, OECD, and WHO, fosters the translation of NIOSH nanotechnology guidance documents into other languages. For 

example, China Occupational Safety and Health Association is translating Approaches 

to Safe Nanotechnology into Mandarin. NTRC reseachers worked with the Italian 

National Institute for Occupational Safety and Prevention to translate and publish the 

NIOSH nanotechnology brochure into Italian. 

Figure 39. NIOSH global collaborations.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 45

2 Qualitative Assessment on Meeting the NTRC Goals

Highlights of NIOSH Collaboration Activities and Outcomes

NIOSH led the development of WHO Guidelines on Protecting Workers from Potential 

Risks of Manufactured Nanomaterials (http://www.who.int/occupational_health/topics/

nanotechnologies/en/). 

NIOSH’s international partnership with the Organisation for Economic Co-operation 

and Development (OECD) to examine potential occupational health and safety risks 

from nanoparticles is reflected in the OECD Report of the Workshop on Risk Assessment of 

Manufactured Nanomaterials in a Regulatory Context. NIOSH representatives participated 

in the workshop and contributed to the report. The workshop provided input for an SG6 

document on issues relating to risk assessment methods for engineered nanoparticles. For 

more information, see http://www.oecd.org/LongAbstract/ 

0,3425,en_2649_37015404_45020877_1_1_1_1,00.html. 

NIOSH research provided the Consumer Product Safety Commission (CPSC) with valuable 

information on the nature of a TiO2 product (aerosol characterization); the potential for consumer exposure (simulated use); and the health hazard potential (animal toxicology testing of 

the product). This work provided CPSC with important data needed to conduct a consumerbased risk assessment on a spray aerosol product containing nanoparticles and support the 

development of a policy on this class of products. CPSC is extending its collaboration with 

NIOSH to include the testing of nano-silver–containing products. 

NIOSH is recognized as one of the leading agency participants in the U.S. National Nanotechnology Initiative (NNI) because of its expertise in nanotechnology and development 

of guidance on the safe handling of engineered nanomaterials.

2.10 Applications

NTRC researchers have developed nano-enabled sensors used as end-of-life service 

indicators for respiratory protection devices. The first application integrated them into 

air-purifying respirator (APR) and powered air-purifying respirator (PAPR) cartridges 

for evaluation. Research findings are now being used to update NIOSH PAPR respirator standards related to the useful service life of air-purifying cartridges. 

NTRC researchers collaborated in the development of new nanomaterials for chemical sensing. This research resulted in a patent assigned to the Regent of the University 

of California: Sailor, Ruminski, King, and Snyder, “Optical fiber-mounted porous 

photonic crystals and sensors,” U.S. Patent #7,889,954, issued Feb. 15, 2011. Improved 

sensitivity and specificity in chemical sensing will have beneficial applications in 

monitoring exposures to toxic materials in the workplace and will have broad utility 

in emergency response. 

2.11 Summary of NIOSH NTRC Progress Through 2011

Nanotechnology, a rapidly emerging application of multiple technologies to materials 

at the nanoscale, has been identified as an important U.S. commercial enterprise that 
46 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting NTRC Goals

has global scientific and economic benefits. Workers are the first people in society exposed to a new technology and the resulting new or transformed materials. Concerns 

about nanomaterial worker health and safety must be addressed to ensure the responsible development and associated economic growth. This responsible development is 

built on addressing worker safety and health (Figure 40). 

The emerging nanomaterial manufacturing community has repeatedly stated that 

it cannot operate effectively in an environment of uncertainty created by a lack of 

authoritative recommendations from government agencies (Lekus et al. 2006; U.S. 

Department of Commerce 2007). The availability of recommendations has been 

identified as necessary for the implementation of effective risk management programs. 

NIOSH is meeting this mandate by conducting research and disseminating information on preventive and precautionary practices that protect the workforce and promote the responsible development of nanotechnology in the U.S. and globally. 

NIOSH was one of the earliest occupational safety and health agencies globally to develop 

guidance on the identification, measurement, and control of occupational exposures 

to engineered nanoparticles, in the 2005 report Approaches to Safe Nanotechnology: An 

Information Exchange with NIOSH. Researchers with the NIOSH NTRC were also the 

first to conduct the scientific research and comprehensive scientific data assessment 

necessary to develop recommended exposure limits (RELs) for TiO2 and CNTs/CNFs. 

CIB 63: Occupational Exposure to Titanium Dioxide, was published in May 2011, and the 

Significant

benefits to 

society

Responsible 

development of

the technology

Nanomaterial 

worker safety 

and health

Figure 40. Nanomaterial worker safety and health: critical for responsible development of 

the technology and societal benefit
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 47

2 Qualitative Assessment on Meeting NTRC Goals

CIB Occupational Exposure to Carbon Nanotubes and Carbon Nanofibers was released 

for public review in November 2010; both documents provide risk management recommendations based on results from NTRC research and from the partnerships with the 

private sector. 

Nanotoxicologic research conducted by the NTRC is considered instrumental in the 

initial determination in laboratory animal studies that exposure to certain types of 

engineered nanoparticles have the potential to result in serious health effects involving pulmonary, cardiovascular, and possibly other organ systems. NTRC researchers 

have identified a broad range of potential health effects and nanoparticle physical and 

chemical parameters of importance in toxicity. 

NIOSH helped to establish the U.S. and international position that a precautionary approach to controlling exposures to engineered nanoparticles is warranted [Schulte and 

Salamanca-Buentello 2007; Schulte et al. 2008; Murashov and Howard 2008; Howard and 

Murshov 2009]. Workplace exposure characterization and engineering control evaluation 

studies have also shown that a range of NIOSH-recommended control strategies are 

being used. In addition, recommendations from these reports have resulted in companies’ 

adopting process changes and implementation of improved engineering controls [Dahm 

et al. 2011; Methner 2010; Methner 2011; Lo 2011; Evans et al. 2010]. 

When NIOSH published its first progress report in 2007, NTRC researchers had 

already published more than 70 articles in the peer-reviewed scientific literature. The 

number of publications increased to over 170 in the 2009 Progress report, and as of 

the end of 2011 more than 400 articles had been published in support of the NIOSH 

NTRC nanotechnology program since its inception. Some of the highlights of the 

NIOSH NTRC program and publications are listed in Table 6. 

The NTRC will continue to evaluate its research progress in nanotechnology through a 

series of internal and external reviews. For example, past evaluations have included external peer review by the National Academies, as well as a peer review of the NTRC strategic plan by the NIOSH Board of Scientific Counselors with input from a work group of 

subject matter experts. The review of the last NTRC strategic plan led the NIOSH NTRC 

to coalesce its priorities to complete the CIBs for TiO2 and CNTs/CNFs. The NTRC will 

continue to conduct annual program reviews and regular project reviews and to publish 

progress reports. 

Progress toward meeting the NIOSH NTRC strategic goals is described in Appendices 

A, B, and C, which contain project summaries, a list of NTRC projects by critical area, 

and a report of funded extramural activities. Appendix D describes the NIOSH logic 

and operational models that govern all NIOSH research. Appendix E summarizes how 

the performance measures of the NTRC Strategic Plan have been met. Appendix F 

contains the list of citation numbers.

2.12 Summary of the Impact of NIOSH Investment in Nanotechnology

Achieving responsible development of nanotechnology requires that the critical elements of worker safety and health be addressed early in the life cycle of 
48 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting NTRC Goals

Table 6. Highlights of the NTRC program and publication activities for 2003–2011

Year Highlights

2003 Toxicologic studies on CNT begun

2004 NTRC established

2004 Co-sponsored the First Symposium on Occupational Health Implications of Nanomaterials

2005 First Health Hazard Evaluation at a facility handling carbon nanofibers

2005 Nanotechnology Topic Web Page created

2005 Approaches to Safe Nanotechnology: An Information Exchange posted on the Web

2006 NTRC Field team established 

2006 Co-sponsored the NanOEHS conference in Cincinnati, OH

2006 First Progress Report published

2007 70+ NTRC Publications

2008 Safe Nanotechnology in the Workplace an Introduction for Employers, Managers and 

Safety and Health Professionals published

2009 170+ NTRC Publications

2009 CIB 60: Interim Guidelines for Medical Screening and Hazard Surveillance for Workers 

Potentially Exposed to Engineered Nanomaterials published

2009 Approaches to Safe Nanotechnology, Managing the Health and Safety Concerns Associated with Engineered Nanomaterials published

2009 Strategic Plan for NTRC 2009–2012 published

2010 Draft CIB, Occupational Exposure to Carbon Nanotubes and Carbon Nanofibers published on Web 

2011 CIB 63: Occupational Exposure to Titanium Dioxide published

2011 40+ Field Assessments completed

2011 400+ NTRC Publications

2011 Co-sponsor of the Fifth International Conference on Nanotechnology–Occupational and 

Environmental Health
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 49

2 Qualitative Assessment on Meeting NTRC Goals

any application. NIOSH has been a leader in identifying hazards of nanomaterials, 

evaluating exposures, and characterizing risks to workers, and has provided extensive 

guidance to protect workers in the face of broad uncertainties in these areas (Table 7). 

NIOSH toxicology-based hazard identification has vastly increased scientific knowledge about potential hazards of nanomaterials. This increase in scientific knowledge 

has moved scientists to develop further research and more effectively address knowledge gaps. NIOSH efforts laid the groundwork for developing reliable procedures for 

generating nanomaterial aerosols so that realistic animal studies could be conducted. 

The investment of $42.6 million over seven years has served to drive scientific research, as illustrated by the large number of citations of NIOSH publications. Moreover, the pioneering toxicological work served to focus exposure assessment efforts on 

high priority materials so that the actual exposure of workers could be characterized. 

Building on the hazard and exposure information, NIOSH developed a broad range 

of risk management guidance that became a cornerstone in the national and global 

response to nanotechnology. NIOSH has helped define the world’s precautionary approach to nanotechnology and provided the technical, scientific, and health information to protect workers and develop the technology responsibly. 
50 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting NTRC Goals

Gaps in the protection of workers 

and critical research area

Approximate investment 

2004–2011 Outputs Outcomes

Hazard IdentificationIs there reason to believe this material could be harmful? 

• Toxicology• Fire and explosibility• Metrology

$12.3 million 258 nanotoxicology journal publications that included 

findings of genotoxicity, cytotoxicity, neurotoxicity, and cardiovascular and respiratory disease in association with various types of nanoparticles (e.g., CNT). Completed 30 nanotoxicology research projects. Over 200 presentations at national and international meetings and conferences pertinent to the toxicity of engineered nanoparticles. 9 presentations pertinent to dustiness and flammability of engineered nanoparticles. 

Over 5,000 primary and 83,000 secondary citations of NIOSH research papers. Toxicity studies with CNT helped to establish an understanding of possible mechanisms for causing adverse health effects, which may be useful for estimating the potential toxicity of other nanoparticles of similar physical/chemical characteristics. Hazard findings of CNT and CNF toxicity have resulted in the adoption of workplace risk management practices to prevent worker exposure. Awareness was raised of possible flammability of carbonaceous nanomaterials. Most toxicological research drove the assessment of exposure and the development of guidance to protect workers and develop the technology responsibly.

Hazard CharacterizationHow and under what conditions could it be harmful? 

• Toxicology• Metrology• Field exposure 

assessments

• Epidemiologic and 

hazard surveillance

$13.7 million 258 nanotoxicology journal publications that included 

findings of genotoxicity, cytotoxicity, neurotoxicity, and cardiovascular and respiratory disease in association with various types of nanoparticles (e.g., CNT). 40+ field team assessments and reports, 31 nanomaterial exposure assessment journal articles, and 

48 nanomaterial measurement journal articles that 1) described techniques and exposure assessment strategies used for characterizing workplace exposures and 2) exposure measurement data. Completed feasibility study and published results on epidemiology study of workers exposed to carbonaceous nanomaterials.

Data used to complete risk assessments of TiO2, 

CNT, and CNF. Raised awareness among nanomaterial producers on the potential hazards of engineered nanomaterials and steps that can be taken to minimize workplace exposures. Engaged the occupational health community in medical surveillance, exposure registries, and epidemiologic studies through presentations and workshops. Partnerships with the private sector accelerated the dissemination and adoption of NIOSH recommendations.

Table 7. Impact of NIOSH investment in nanotechnology

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 51

2 Qualitative Assessment on Meeting NTRC Goals Gaps in the protection of workers and critical research area Approximate investment 2004–2011 Outputs Outcomes Exposure Assessment Will there be exposures in real-world conditions? • Field exposure assessments • Metrology • Engineering controls and PPE $11.8 million 40+ field team assessments and reports, 31 nanomaterial exposure assessment journal articles, and 48 nanomaterial measurement journal articles that 1) described techniques and exposure assessment strategies used for characterizing workplace exposures, and 2) exposure measurement data. Developed innovative applications of measurement strategies, including methods for sampling different types of engineering nanoparticles. Collaborated with the National Institute of Standards and Technology (NIST) and National Research Council (NRC) Canada to identify and develop nanoscale reference materials (RMs) for use in calibrating and evaluating measurement instruments and for toxicology studies. A titanium 

dioxide nanopowder was qualified as a RM, and current efforts focus on qualifying nanocrystalline cellulose (powder and suspension) and SWCNTs as RMs.

Research institutions and companies manufacturing or using engineered nanoparticles adopted 

many of the techniques recommended by NIOSH scientists on the collection and analysis of engineered nanoparticles. 

Exposure assessment studies conducted by NIOSH scientists resulted in recommendations for controlling exposure, which were frequently adopted by health and safety professionals. NIST and NRC will be providing nanoscale reference materials.

Risk CharacterizationIs substance hazardous and will there be exposure?

• Risk assessment• Epidemiologic research• Medical surveillance

$1.4 million NIOSH scientists conducted novel risk assessments on 

TiO2 and carbon nanotubes (CNT) that were published 

in the documents: 

1. CIB 63: Occupational Exposure to TiO2 (NIOSH Pub 

No. 2011–160). 

2. CIB, Occupational Exposure to Carbon Nanotubes 

and Nanofibers (draft Dec 2010).

NIOSH sponsored a workshop on issues related to epidemiology studies, medical surveillance, and worker exposure registries; the findings of that workshop were published in the Journal of Occupational and Environmental Medicine, “Nanomaterials and Worker Health” 2011:53 (6S).

NIOSH published recommended exposure limits for TiO2 and CNT and CNF based on risk assessments 

conducted by NIOSH scientists. Engaged the occupational health community in medical surveillance, exposure registries, and epidemiologic studies by presentations, conferences, and workshops. Foundation for hazard banding shared among global partners as a means for identifying workplace exposures to engineered nanomaterials when information on the potential toxicity is limited. 

Table 7 (Continued). Impact of NIOSH investment in nanotechnology

(continued)
52 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting NTRC Goals

Gaps in the protection of workers 

and critical research area

Approximate investment 

2004–2011 Outputs Outcomes

Risk ManagementDevelop procedures to minimize exposures

• Risk communication• Guidance development

$3.4 million Co-sponsored 16 conferences on issues pertinent to 

the potential health risks of engineering nanomaterials and the implementation of appropriate risk management practices. 

NIOSH developed guidance documents: 

1. Approaches to Safe Nanotechnology (NIOSH Pub No. 

2009–125).

2. CIB: Occupational Exposure to Carbon Nanotubes 

and Nanofibers (draft published 2010).

3. CIB 63: Occupational Exposure to Titanium Dioxide 

(NIOSH Pub No. 2011–160). 

4. General Safe Practices for Working with Engineered 

Nanomaterials in Research Laboratories (NIOSH Pub No. 2012–147). 

Created NIOSH Topic Page Provided over 220 presentations at local, national, and international venues pertinent to health and safety information and recommendations. Contributed to international collaborations on the development of risk management practices.

Raised awareness among nanomaterial producers and users on the potential hazards of engineered nanomaterials and steps that can be taken to minimize workplace exposures. Approaches to Safe Nanotechnology downloaded over 11,000 times from the NIOSH web site. Approaches to Safe Nanotechnology translated into Mandarin, Japanese, and Spanish. Approaches to Safe Nanotechnology brochure translated into Japanese, Italian, Spanish, and Portuguese. GoodNanoGuide co-sponsored by NIOSH Recommendations by NIOSH were used in the development of: 

1. ISO Standard published, ISO/TR 12885:2008 

Health and Safety Practices in Occupational Settings Relevant to Nanotechnologies 

2. Development of WHO’s nanotechnology topic 

page 

3. OECD sponsored workshops on nanomaterial 

exposure measurement and exposure mitigation. 

Preliminary indication of the wide use of risk management strategies.

Table 7 (Continued). Impact of NIOSH investment in nanotechnology
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 53

3 Alignment with the NNI EHS Strategy 

NIOSH uses the National Nanotechnology Initiative (NNI) Environmental, Health 

and Safety (EHS) Research Strategy to help establish and align the objectives of the 

NTRC program and to identify research projects that provide direct support to specific EHS research needs. The 2008 NNI strategy confirmed that the research priorities 

and goals established by the NTRC were aligned with the broader EHS issues identified by the NNI (Table 8). 

NIOSH continues to be an active participant and contributor to the NNI by providing 

the occupational health and safety expertise in support of the U.S. Government’s Strategic Plan for Nanotechnology Health and Safety Research. NIOSH co-chairs the NNI 

Nanotechnology Environmental and Health Implications (NEHI) Working Group 

(Section 2.9.3). NTRC researchers contributed significantly to the development of the 

2011 NEHI EHS research strategy, and had primary responsibility for the chapters on 

human exposure assessment and human health. 

The NNI EHS research strategy focuses on the use of science-based risk analysis and 

risk management to protect the public health and the environment while fostering the 

technological advancements that benefit society. This strategy is consistent with the 

NTRC nanotechnology strategic plan, which includes research activities in nanomaterial measurement; human exposure; human health; risk assessment and risk management; and informatics and modeling. 

In addition to the NEHI Working Group, NIOSH also has agency level representation 

on the Nanoscale Science, Engineering and Technology (NSET) Sub-Committee. NSET 

coordinates the overall U.S. government effort in nanotechnology. Meeting key challenges of health and safety is recognized by NSET as a critical element in promoting the 

technology. NIOSH provides expert technical support to NSET to meet that challenge. 

NTRC research objectives will continue to align with the 2011 NNI EHS research 

strategy in the development of the FY2013–FY2016 NTRC Strategic Plan (Section 5).
54 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

3 Alignment with the NNI EHS Strategy

Table 8. Alignment of critical research areas with the four strategic goals of the NIOSH NTRC (2009–2012) and the 2008 NNI EHS priority environmental health and safety areas

NIOSH NTRC 

strategic goals

Toxicity and 

internal 

dose

Measurement 

methods

Exposure 

assessment2

Epidemiology 

and surveillance

Risk 

assessment

Engineering 

controls and 

PPE

Fire and 

explosion 

safety

Recommendations and 

guidance

Communication and 

information Applications

1. Determine if 

nanoparticles and nanomaterials pose risks for work-related injuries and illnesses

3

A24

B1B2B3B4B5



A1A2A3A4A5

B2



A1A2

D1D4D5

E1E2



D1D2D3D4

E4



A2

B1B2

D4

E3



D5



A2

2.Research application of 

nanotechnology to prevent workrelated injuries and illnesses1







3. Promote healthy 

workplaces through interventions, recommendations, and capacity building



E1



E2



E4



E3E5



E1



E1E5



E1E5

4. Enhance global 

workplace safety and health1







    





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 identifies 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 2008 NNI priority research needs.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 55

2 Qualitative Assessment on Meeting NTRC Goals

4 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, cross-sector, or coordinated 

emphasis areas of the NIOSH Program Portfolio (http://www.cdc.gov/niosh/programs). 

From FY–01 to FY–04, OEP funded three R43/44 projects. 

In FY–05, NIOSH funded two nanotechnology research grants through the R01 Program 

Announcement. OEP also began participating in requests for applications (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 

of these 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–06, 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 

of these were in the competitive range for funding consideration. NIOSH was able to 

fund one application. EPA funded 21 projects, NSF funded 4, and NIEHS funded 3 

under this RFA. NIOSH also funded two SBIR grants on nanotechnology in FY–06. 

In FY–07, NIOSH funded a three-year career development (mentored scientist) grant 

involving research at the University of Iowa on personal exposure to nanoparticles. 

In addition, a two-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. 

In FY–08, NIOSH funded a major research grant (R01) from the joint RFA on Manufactured 

Nanomaterials (Physico-chemical Principles of Biocompatibility and Toxicity). This project 

was 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–09 and FY–10, nanotechnology-related research proposals submitted to standing program announcements were 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 NTRC regarding needs and future 

directions for nanotechnology research. 

Summaries of the extramural projects funded by NIOSH/OEP are included in Appendix C as part of this portfolio project summary update. Contact information for the 

principal investigators of the projects is provided in Table C–2.
56 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

2 Qualitative Assessment on Meeting NTRC Goals
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 57

2 Qualitative Assessment on Meeting NTRC Goals

5 The Next Steps 

The NTRC will follow the successes established in its first seven years by continuing 

to work concurrently in all of the major areas of research needed to close knowledge 

gaps in the the safety and health implications of engineered nanomaterials. Specifically, the NTRC will continue to generate toxicologic data for hazard identification; 

conduct dose/response risk assessments; evaluate worker exposures and characterize 

risk; develop, disseminate and assist employers in implementing risk management 

practices; and continue to develop and disseminate effective communication products 

and authoritative recommendations. Figure 3 (Gaps that need to be filled to protect 

nanomaterial workers) provides a visual representation of the critical areas of research. 

For the period 2013–2016, NIOSH will continue to fill information and knowledge 

gaps by focusing on priority research areas to protect the nanotechnology workforce 

as shown in Figure 41. 

In meeting the NIOSH NTRC Strategic Goals for FY2013– FY2016, the NTRC will 

accomplish the following:

1. Increase understanding of potential hazards and related health risks to nanomaterial workers

2. Expand understanding of the initial hazard findings of engineered nanomaterials

3. Support the creation of guidance materials to inform nanomaterial workers, 

employers, health professionals, regulatory agencies and decision makers 

about hazards, risks, and risk management approaches

4. Support epidemiologic studies for nanomaterial workers, including medical 

and exposure studies 

5. Assess and promote national adherence with risk management guidance, particularly on exposure assessment, control technology, PPE, and occupational 

exposure limits.
58 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

5 The Next Steps

Critical Next Steps

Assess National

Adherence To Guidelines

Develop and

Update Guidance

Clarify Initial

Hazard Findings

Identify New

Hazards

Conduct

Epidemiologic Studies

Informatics

Control Technology

and PPE

Risk

Assessment

Medical

Surveillance

Exposure

Assessment

Develop Exposure

Registries

Address

Hotspots

Protecting the

Nanotechnology Workforce

Develop Categorical and

Specific Exposure Limits

Risk Management

Figure 41. Anticipated focus of NIOSH NTRC nanomaterial research, FY2013–FY2016.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 59

6 References 

Birch ME, Ku B-K, Evans DE, Ruda-Eberenz [2011]. Exposure and emissions monitoring during carbon nanofiber production. Part I: elemental carbon and iron-soot 

aerosols. Ann Occup Hyg 55(9):1016–1036.

Birch ME [2011]. Exposure and emissions monitoring during carbon nanofiber production—part II: polycyclic aromatic hydrocarbons. Ann Occup Hyg 

55(9):1037–1047.

Burdorf A, Viikari-Juntura E [2007]. Bibliometric analysis of the Scandanavian 

Journal of Work, Environment & Health—results from the past 10 years. Scan J Work 

Environ Health 33(4):318–319.

Dahm MM, Evans DE, Schubauer-Berigan MK, Birch ME, Fernback JE [2011]. Exposure assessment in carbon nanotube and nanofiber primary and secondary manufacturers. Ann Occup Hyg [doi:10.1093/annhyg/mer110].

Evans DE, Ku BK, Birch ME, Dunn KH [2010]. Aerosol monitoring during carbon 

nanofiber production: mobile direct-reading sampling. Ann Occup Hyg 54(5):514–531.

Evans DE, Turkevich LA, Roettgers CT, Deye GJ, Baron PA [ 2012]. Dustiness of fine 

and nanoscale powders. Ann Occup Hyg [in press].

Gao P, Jaques PA, Hsiao T-C, Shepherd A, Eimer BC, Yang M, Miller A, Gupta B, 

Ronald Shaffer R [2011]. Evaluation of nano- and submicron particle penetration 

through ten nonwoven fabrics using a wind-driven approach. J Occup Environ Hyg 

8(1):13–22.

Gehanno JF, Takahashi K, Darmoni S, Weber J [2007]. Citation classics in occupational 

medicine journals. Scand J Work Environ Health 33(4):245–251.

Howard J, Murashov V [2009]. National nanotechnology partnership to protect workers. J Nanopart Res 11(7):1673–1683.

Kagan VE, Tyurina YY, Tyurin VA, Konduru NV, Potapovich AI, Osipov AN, Kisin 

ER, Schwegler-Berry D, Mercer RR, Castranova V, Shvedova AA [2006]. Direct and 

indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role 

of iron. Toxicol Lett 165:88–100.

Kostoff RN, Murday JS, Lau CGY, TollesWM [2009]. Seminal nanotechnology literature: A review. Journal of Nanoscience and Nanotechnology 9(11):6239–6270.

Lekus D, Lifset R, Rejeski D [2006]. Nanotechnology startup concerns, information needs, 

and opportunities to proactively address environmental, health and social issues: focus on 
60 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

6 References

firms in Connecticut and New York. Masters Degree Project, Yale University, July [http://

www.nanotechproject.org/process/files/2717/87_nanotech_startup_study_ct_and_ny.pdf]. 

Li Z, Hulderman T, Salmen R, Chapman R, Leonard S, Young S, Shvedova A, Luster 

M, Simeonova P [2007]. Cardiovascular effects of pulmonary exposure to single-wall 

carbon nanotubes. Environ Health Perspect 115(3):77–82.

Lo LM, Dunn KH, Hammond D, Almaguer D, Bartholomew I, Topmiller J, Tsai CSJ, 

Ellenbecker M, Huang CC [2011]. Evaluation of engineering controls for manufacturing nanofiber sheets and yarns. Cincinnati, OH: U.S. Department of Health and 

Human Services, Centers for Disease Control and Prevention, National Institute for 

Occupational Safety and Health, DHHS (NIOSH) Report No. EPHB 356–11a.

MacRoberts MH, MacRoberts BR [1988]. Problems of citation analysis: a critical 

review. J Am Soc Inf Sci 40:342–349.

Maynard AD, Baron PA, Foley M, Shvedova AA, Kisin ER, Castranova V [2004]. 

Exposure to carbon nanotube material during the handling of unrefined single walled 

carbon nanotube material. J Toxicol Environ Health Part A 67:87–107.

McKinney W, Chen B, Frazer D [2009]. Computer controlled multi-walled carbon 

nanotube inhalation exposure system. Inhal Toxicol 21(12):1053–1061.

Methner, MM, Birch E, Evans DE, Ku B-K, Crouch K, Hoover M, Mazzuckelli L (Ed) 

[2007]. 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.

Methner MM, 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–D69.

Methner MM, Hodson L, Geraci C [2010]. Nanoparticle emission assessment technique (NEAT) for the identification and measurement of potential exposure to engineered nanomaterials: Part A. J Occup Environ Hyg 7:127–132.

Methner MM [2010]. Effectiveness of a custom-fitted flange and LEV system in 

controlling the release of nano-scale metal oxide particulate. Int J Occup Environ 

Health 16:475–487.

Murashov V, Howard J [2008]. The U.S. must help set international standards for 

nanotechnology. Nature Nanotechnol 3:635–636.

NIOSH [2009a]. Strategic plan for NIOSH nanotechnology research and guidance. 

Cincinnati, Ohio: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, 

Publication No. 2010–105.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 61

6 References

NIOSH [2009b]. Approaches to safe nanotechnology: managing the safety and health 

concerns associated 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, Publication No. 2010–125.

NIOSH [2009c]. Current intelligence bulletin 60: interim guidance for medical 

screening and hazard surveillance for workers potentially exposed to 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, Publication No. 2009–116.

NIOSH [2011]. Current intelligence bulletin 63: occupational exposure to titanium 

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

for Disease Control and Prevention, National Institute for Occupational Safety and 

Health, Publication No. 2011–160.

NIOSH [2012]. General safe practices for working with engineered nanomaterials in 

research laboratories. Cincinnati, Ohio: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational 

Safety and Health, Publication No. 2012–147.

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 [2011]. Total inward leakage of nanoparticles through filtering 

facepiece respirators. Ann Occup Hyg 55:253–263.

Rengasamy S, Eimer B [2012]. Nanoparticle filtration performance of NIOSH certified 

particulate air purifying filtering facepiece respirators: evaluation by light scattering 

photometric and particle number-based test methods. J Occup Environ Hyg 9(2):99–

109 [DOI: 10.1080/18459624.2011.642703].

Rengasamy S, Eimer B [2012]. Nanoparticle penetration through filter media and 

leakage through face seal interface of N95 filtering facepiece respirators. Ann Occup 

Hyg, Jan 31 [DOI:10.1093/annhyg/mer122].

Roco MC, Mirkin CA, Hersam MC [2010] Nanotechnology research directions for 

societal needs in 2020: retrospective and outlook. Arlington, VA: National Science 

Foundation [http://wtec.org/nano2/].

Sarli CG, Dubinsky EK, Holmes KL [2010]. Beyond citation analysis: a model for assessment of research impact. J Med Libr Assoc 98(1):17–23.

Schubauer-Berigan MK, Dahm MM, Yencken MS [2011]. Engineered carbonaceous 

nanomaterials manufacturers in the United States: workforce size, characteristics and 

feasibility of epidemiologic studies. J Occup Environ Med 53(6 Suppl):S62–S67.
62 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

6 References

Schulte PA, Salamanca-Buentello F [2007]. Ethical and scientific issues of nanotechnology in the workplace. Environ Health Perspect 115:512.

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.

Schulte PA, Schubauer-Berigan MK, Mayweather C, Geraci Cl, Zumwalde R, McKernan JL [2009]. Issues in the development of epidemiologic studies of workers exposed 

to engineered nanomaterials. J Occup Env Med 51:323–335.

Schulte PA, Murashov M, Zumwalde R, Kuempel E, Geraci CL [2010]. Occupational 

exposure limits for nanomaterials: state of the art. J Nanopart Res 12:1971–1987.

Schulte PA, Trout D, Hodson L [2011]. Introduction to nanomaterials and worker health: 

medical surveillance, exposure registries, and epidemiologic research. JOEM 53(6S):1.

Schulte PA, Kuempel E, Zumwalde R, Geraci CL, Schubauer-Berigan M, Castranova 

V, Hodson L, Murashov V, Dahm MM, Ellenbecker M [2012]. Focused actions to 

protect carbon nanotube workers. Am J Ind Med [DOI10.1002/ajim.22028].

Shaffer R, Rengasamy S [2009]. Respiratory protection against nanoparticles: a review. 

J Nanopart Res 11:1661–1672.

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

Maynard A, Baron P [2003]. Exposure to carbon nanotube material: assessment of nanotube 

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

Shvedova A, Kisin E, Mercer R, Murray A, Johnson VJ, Potapovich A, Tyurina Y, 

Gorelic O, Arepalli S, Schwegler-Berry D, Antonini J, Evans DE, Ku B-K, Ramsey D, 

Maynard A, Kagan VE, Castranova V, Baron P [2005]. Unusual inflammatory and 

fibrogenic pulmonary responses to single walled carbon nanotubes in mice. Am J 

Physiol: Lung Cell Mol Physiol 289:L698–L708.

Shvedova AA, Potapovich AL, Osipov AN, Tyurina YY, Kisin E, Schwegler-Berry D, 

Mercer RR, Castranova V, Kagan VE [2006]. Oxidative interactions of single walled 

carbon nanotubes with RAW 264.7 macrophages: role of iron. Toxicology 90(1):A1557.

Smith DR [2007]. Historical development of journal impact factors and its relevence 

for occupational health. Ind Health 45:730–742.

U.S. Department of Commerce [2007]. Barriers to nanotechnology commercialization: 

final report. September. [http://www.ntis.gov/pdf/Report-BarriersNanotechnology

Commercialization.pdf].

U.S. Government Accountability Office [2012]. Nanotechnology improved performance 

information needed for environmental, health, and safety research GAO-12-427, May 21, 

2012 [http://www.gao.gov/products/GAO-12-427].
APPENDIX A

Project-Specific 

Progress Reports
64 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project number Project title Principle investigator Project duration

1 Nanotechnology Research 

Center Coordination

Charles Geraci, PhD FY2005–2012

2 Nanotechnology Safety and 

Health Research Coordination 

(Nanotoxicology)

Vincent Castranova, PhD FY2004–2008

3 Development of New Research 

in Occupational Health 

(Nanotoxicology)

Vincent Castranova, PhD FY2009–2012

4 Systemic Microvascular 

Dysfunction: Effects of 

Ultrafine vs. Fine Particles

Vincent Castranova, PhD FY2006–2010

5 Particle Surface Area as a 

Dose Metric

Vincent Castranova, PhD FY2004–2008

6 Role of Carbon Nanotubes 

in Cardiovascular and COPDRelated Diseases

Aaron Erdely, PhD FY2004–2010

7 Investigations of Multi-Walled 

Carbon Nanotube Toxicity

Dale Porter, PhD FY2007–2011

8 Toxicological Effects of 

Aerosolized MWCNT

Dale Porter, PhD FY2010–2012

9 Pulmonary Toxicity of Metal 

Oxide Nanospheres and 

Nanowires

Dale Porter, PhD FY2007–2011

10 WC-Co Nanoparticles in 

Initiating Angiogenesis by 

Reactive Oxygen Species

Min Ding, PhD FY2008–2011

11 Evaluation of the Pulmonary 

Deposition and Translocation 

of Nanomaterials

Robert Mercer, PhD FY2006–2011

Summary of 69 NIOSH Nanotechnology Research Projects, 2004–2011

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 65

APPENDIX A | A Summary of 69 NIOSH Research Projects

Summary of 69 NIOSH Nanotechnology Research Projects, 2004–2011 (Continued)

Project number Project title Principle investigator Project duration

12 Occupational Exposures and 

Potential Neurological Risks

Krishan Sriram, PhD FY2008–2012

13 Lung Effects of Resistance 

Spot Welding Using Adhesives 

James Antonini, PhD FY2007–2010

14 Neurotoxicity after Pulmonary 

Exposure to Welding Fumes

James Antonini, PhD FY2007–2010

15 Welding Fume and 

Cardiovascular Dysfunction

Hong Kan FY2010–2013

16 Potential Aneuploidy Following 

Exposure to Carbon Nanotubes

Linda Sargent, PhD FY2007–2010

17 Nanoparticle Properties and 

Mechanisms Causing Lung 

Fibrosis

Liying Wang Rojanasakul, PhD FY2008–2012

18 Pulmonary Toxicity of Carbon 

Nanotube Particles

 Anna Shvedova, PhD FY2004–2008

19 Assessment of Engineered 

Nanomaterials on Respiratory 

Immunity

Anna Shvedova, PhD FY2009–2012

20 Dermal Toxicity of Nanotube 

Particles

Anna Shvedova, PhD FY2005–2010

21 Bioassay Screen of Lung 

Toxicity of Silver Nanoparticles

Jenny Roberts, PhD FY2010–2012

22 Specific Biomarkers 

for Unusual Toxicity of 

Nanomaterials

Liying Wang Rojanasakul, PhD FY2007–2009

23 Pulmonary Toxicity of Diesel 

Exhaust Particles

Jane Ma, PhD FY2003–2008

(continued)
66 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project number Project title Principle investigator Project duration

24 Induction of Lung Fibrosis by 

Cerium Oxide in Diesel Exhaust

Jane Ma, PhD FY2009–2012

25 Potential Effects of Siliconbased Nanowires on Lung 

Toxicity

Stephen Leonard, PhD FY2008–2012

26 Workplace Exposure, 

Inflammation and 

Cardiovascular Toxicity

Aaron Erdely, PhD FY2010–2014

27 Cardiovascular Toxicity 

Assessment of Subchronic 

Inhalation Exposure to 

Fullerene C60

Aaron Erdely, PhD FY2009–2010

28 Cell-based Assessment for Iron 

Nanoparticle-Induced Health 

Risks

Yong Qian, PhD FY2008–2011

29 Assessment of Carbonaceous 

Materials on Mutagenicity

Anna Shvedova, PhD FY2008–2009

30 Durability of Nanoscale 

Cellulose Fibers in Artificial 

Human Lung Fluids

Aleksandr Stefaniak, PhD FY2011–2012

31 Osteopontin and Carbon 

Nanotubes

Petia Simeonova, PhD 

(deceased) 

FY2004–2009

32 Determination of Diameter 

Distribution for Carbon 

Nanotubes by Raman 

Spectroscopy

Madalina Chirila, PhD FY2007–2009

33 Inhalation Facility Support Teh-Hsun B. Chen, PhD FY2000–2015

34 Generation and 

Characterization of 

Nanoparticles

Bon-Ki Ku, PhD FY2004–2008

Summary of 69 NIOSH Nanotechnology Research Projects, 2004–2011 (Continued)

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 67

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project number Project title Principle investigator Project duration

35 Dustiness of Nanomaterials Douglas Evans, PhD FY2007–2010

36 Measurement of Nanoscale 

Carbonaceous Aerosols

M. Eileen Birch, PhD FY2007–2008

37 Nanoaerosol Monitoring 

Methods

M. Eileen Birch, PhD FY2006–2012

38 Workplace Monitoring of 

Carbon Nanofibers/Nanotubes

M. Eileen Birch, PhD FY2009–2012

39 Real time Instrument for 

Nanoaerosol Exposure 

Measurement

Pramod Kulkarni, DSc FY2008–2011

40 Nanoparticle Reference 

Materials for Health Protection

Aleksandr Stefaniak, PhD FY2007–2009

41 International Coordination 

of Nanoscale Reference 

Materials

Aleksandr Stefaniak, PhD FY2010–2012

42 A Standard Method for 

Determining Airborne 

Nanoparticle Size

Aleksandr Stefaniak, PhD FY2009–2011

43 Calm Air Chamber and 

Wind Tunnel Evaluation of 

Personal Aerosol Samplers 

for Nanoparticle Exposure 

Assessment

Terri Pearce, PhD FY2008–2010

44 Efficacy of NIOSH Method 

0600 for Fine and Ultrafine 

Titanium Dioxide

Terri Pearce, PhD FY2010–2011

45 Ultrafine TiO2 Surface and 

Mass Concentration Sampling 

Method

Aleksandr Stefaniak, PhD FY2007–2011

Summary of 69 NIOSH Nanotechnology Research Projects, 2004–2011 (Continued)

(continued)
68 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project number Project title Principle investigator Project duration

46 Development and Evaluation 

of Nanoaerosol Surface Area 

Measurement Methods

Bon-Ki Ku, PhD FY2009–2010

47 Respiratory Deposition of 

Airborne Carbon Nanotubes

Pramod Kulkarni, PhD FY2010–2012

48 Exposure Potential from Use 

of Nanomaterial-Enabled 

Consumer Products

Aleksandr Stefaniak, PhD FY2009–2012

49 Ultrafine Aerosols from DieselPowered EquipmentAleksandar Bugarski, PhD FY2004–2008

50 Titanium Dioxide and Other 

Metal Oxides Exposure 

Assessment Study

Brian Curwin, PhD FY2006–2010

51 Field Research Team Charles Geraci, PhD FY2006–2012

52 Factors Affecting Exposure to 

Engineered Nanomaterials

M. Abbas Virji, PhD FY2010–2012

53 Assessing the Feasibility 

of Industrywide Exposure 

and Epidemiology Studies 

of Workers Exposed to 

Engineered Nanomaterials–

Phase I

Mary Schubauer-Berigan, PhD FY2008–2009

54 Assessing the Feasibility 

of Industrywide Exposure 

and Epidemiology Studies 

of Workers Exposed to 

Engineered Nanomaterials–

Phase II

Matthew Dahm, MPH FY2010–2011

55 Nanoparticles—Dosimetry and 

Risk Assessment

Eileen Kuempel, PhD FY2005–2012

56 Titanium Dioxide Quantitative 

Risk Assessment

David Dankovic, PhD FY2005–2011

Summary of 69 NIOSH Nanotechnology Research Projects, 2004–2011 (Continued)

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 69

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project number Project title Principle investigator Project duration

57 Engineering Controls for 

Nanomaterial Handling

Li-Ming Lo, PhD FY2010–2012

58 Applying PtD to the Safe 

Handling of Engineered 

Nanomaterials

Donna Heidel, CIH FY2009–2013

59 Penetration of Nanoparticles 

through Respirators/

Development of Respirator 

Filtration Test Methods

Samy Rengasamy, PhD FY2005–2011

60 Nanoparticle Penetration 

through Protective Clothing

Pengfei Gao, PhD FY2009–2010

61 Respirator Performance 

Against Engineered 

Nanoparticles Under 

Laboratory and Workplace 

Settings

Ziqing Zhuang, PhD FY2011–2015

62 Development of Personal 

Protective Equipment 

Ensemble Test Methods

Pengfei Gao, PhD FY2005–2012

63 Explosibility and Flammability 

of Carbon Nanotubes

Leonid Turkevich, PhD FY2010–2013

64 Current Intelligence Bulletin: 

Carbon Nanotubes and Carbon 

Nanofibers

Eileen Kuempel, PhD FY2009–2014

65 Assessing the Utility of Control 

Banding in the U.S.

T.J. Lentz, PhD FY2004–2012

66 Web-Based Nanoparticle 

Information Library 

Implementation

Arthur Miller, PhD FY2004–2008

67 Nanoparticles in the 

Workplace and Metrics for 

Field and Toxicity Studies 

Mark Hoover, PhD FY2004–2011

Summary of 69 NIOSH Nanotechnology Research Projects, 2004–2011 (Continued)

(continued)
70 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project number Project title Principle investigator Project duration

68 Global Harmonization of 

Exposure Measurement 

and Exposure Mitigation 

Approaches for Nanomaterials

Vladimir Murashov, PhD FY2006–2011

69 New Sensor Technology 

Development for Filter 

Respirator Cartridge End-ofService Life Indicators (ESLI)

Jay Snyder, MS FY2002–2010

Summary of 69 NIOSH Nanotechnology Research Projects, 2004–2011 (Continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 71

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 1: Nanotechnology Research

Center Coordination

Principal Investigator: Charles Geraci, PhD

Project Duration: FY 2005–2012 

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 to 

identify and prioritize nanotechnology research.

 ■ Sponsored and provided strategic direction to the Nanotechnology Field Research Team, which conducted 31 site visits to 26 sites in the reporting period.

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

Metal oxide reactor cleanout
72 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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

 — International Alliance for NanoEHS Harmonization

 — University of Massachusetts, Lowell

 — The Ohio State University

 — University of Dayton Research Institute

 — SUNY, Albany College of Nanoscale Science Engineering (CNSE)

 ■ 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: Springer-Verlag, pp.119–145.

 ■ Murashov V, Howard [2007]. Occupational health and nanotechnology. J Applied Biosafety 12(3):43–56. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 73

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Schulte PA, Salamanca-Buentello F [2007]. Ethical and scientific issues of 

nanotechnology in the workplace. Environ Health Perspect 115:5–12. 

 ■ NIOSH [2008]. Safe nanotechnology in the workplace: an introduction for 

employers, managers, and safety and health professionals. Cincinnati, OH: 

U.S. Department of Health and Human Services, Centers for Disease Control, 

National Institute for Occupational Safety and Health, National Institute for 

Occupational Safety and Health, DHHS (NIOSH) Publication No. 2008–112.

 ■ NIOSH [2008]. The nanotechnology field research team update. Cincinnati, 

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

Control, National Institute for Occupational Safety and Health, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 

2008–120.

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

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

for Disease Control, National Institute for Occupational Safety and Health, 

DHHS (NIOSH) Publication No. 2008–121.

 ■ NIOSH [2008]. NIOSH nanotechnology metal oxide particle exposure assessment study. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control, National Institute for Occupational Safety 

and Health, National Institute for Occupational Safety and Health, DHHS 

(NIOSH) Publication No. 2008–122. 

 ■ NIOSH [2008]. Draft strategic plan for NIOSH nanotechnology research: 

filling the knowledge gaps. Cincinnati, OH: U.S. Department of Health and 

Human Services, Centers for Disease Control, National Institute for Occupational Safety and Health, National Institute for Occupational Safety and 

Health, February 2008.

 ■ 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 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 

34:471–478.

 ■ Murashov V, Howard J [2008]. The U.S. must help set international standards 

for nanotechnology. Nature Nanotech 3:635–636.

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

for workers potentially exposed to engineered nanoparticles. Cincinnati, OH: 
74 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

U.S. Department of Health and Human Services, Centers for Disease Control, 

National Institute for Occupational Safety and Health, National Institute for 

Occupational Safety and Health, DHHS (NIOSH) Publication No. 2009–116.

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

safety concerns with engineered nanomaterials. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control, National 

Institute for Occupational Safety and Health, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2009–125. 

 ■ NIOSH [2009]. Strategic plan for NIOSH nanotechnology research and guidance. Cincinnati, OH: U.S. Department of Health and Human Services, Centers 

for Disease Control, National Institute for Occupational Safety and Health, National Institute for Occupational Safety and Health, Publication No. 2010–105.

 ■ Schulte PA, Schubauer-Berigan MK, Mayweather C, Geraci CL, Zumwalde 

R, McKernan JL [2009]. Issues in the development of epidemiologic studies of workers exposed to engineered nanoparticles. J Occup Environ Med 

51(3):323–335.

 ■ Murashov V, Howard J [2009]. Letter to the editor. Nature Nanotech 4:205–206.

 ■ Murashov V, Howard J [2009]. Essential features for proactive risk management of nanotechnology. Nature Nanotech 4(8):467–470.

 ■ Howard J, Murashov V [2009]. National Nanotechnology Partnership to Protect Workers. J Nanoparticle Res 11(7):1673–1683. 

 ■ Schulte PA, Schubauer-Berigan MK, Mayweather C, Geraci CL, Zumwalde 

R, McKernan JL [2009]. Issues in the development of epidemiologic studies of workers exposed to engineered nanoparticles. J Occup Environ Med 

51:323–335.

 ■ Schulte PA [2010]. Nanoparticles. In: Identification of research needs to resolve the carcinogenicity of high-priority IARC carcinogens. IARC Technical 

Publication No. 42. Lyon, France: IARC.

 ■ Trout DB, Schulte PA [2010]. Medical surveillance, exposure registries, and 

epidemiologic research for workers exposed to nanomaterials. Toxicology 

269:128–135.

NTRC Researchers at 2012 bi-annual meeting
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 75

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Schulte PA, Murashov V, Zumwalde R, Kuempel ED, Geraci CL [2010]. Occupational exposure limits for nanomaterials: state of the art. J Nanoparticle 

Res 12(6):1971–1987. 

 ■ Geraci CL, Castranova V [2010]. Challenges in assessing nanomaterial toxicology: a personal perspective. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2(6):569–577. 

 ■ Ramachandran G, Ostraat M, Evans DE, Methner MM, O’Shaughnessy P, 

D’Arcy J, Geraci CL, Stevenson E, Maynard A, Rickabaugh K [2011]. A strategy for assessing workplace exposures to nanomaterials. J Occup Environ Hyg 

8(11):673–685.

 ■ Murashov V, Schulte P, Geraci C, Howard J [2011]. Regulatory approaches 

to worker protection in nanotechnology industry in the USA and European 

Union. Ind Health 49(3):280–296.

 ■ Dankovic D, Kuempel E, Geraci C, Gilbert S, Rice F, Schulte P, Smith R, Sofge 

C, Wheeler M, Lentz TJ, Zumwalde R, Maynard A, Attfield M, Pinheiro G, 

Ruder A, Hubbs A, Ahlers H, Lynch D, Toraason M, Vallyathan V [2011]. 

Current intelligence bulletin 63: occupational exposure to titanium dioxide. 

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

Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 

2011–160.

 ■ Brouwer D, Berges M, Fransman W, Virji A, Bello D, Hodson L, Gabriel S, 

Tielemans E [2011]. Harmonization of measurement strategies for the assessment of exposure to manufactured nano object: report of a workshop. Ann 

Occup Hyg 56(1):1–9.

 ■ Schulte PA, Trout DB, Hodson LL [2011]. Nanomaterials and worker 

health: medical surveillance, exposure registries, and epidemiologic 

research [introduction to supplement]. J Occup Environ Med 53(6)

(Suppl):S1–S2. 

 ■ Methner M, Beaucham C, Crawford C, Hodson L, Geraci C [2012]. Field 

application of the Nanoparticle Emission Assessment Technique (NEAT): 

task-based air monitoring during the processing of engineered nanomaterials 

(ENMs) at four facilities. J Occup Environ Hyg 9(9):543–555.

 ■ Howard J [2011]. Dynamic oversight: implementation gaps and challenges. J 

Nanoparticle Res 13:1427–1434 (DOI 10.1007/s11051-011-0225-2).

 ■ Eastlake A, Hodson L, Geraci C, Crawford C [2012]. A critical evaluation of 

material safety data sheets (MSDS) for engineered nanomaterials. J Chem 

Health Safety 19(5):1–8. (DOI 10.1016/j.jchas.2012.02.002).
76 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Invited Presentations

 ■ Schulte PA [2005]. NIOSH Nanotechnology Research. Nanoparticle Occupational Health and Safety Workshop sponsored by the Massachusetts Toxics 

Use Reduction Institute and the Center for High-Rate Nonmanufacturing. 

Westborough, Massachusetts, December 2.

 ■ Schulte PA [2005]. Panel member. Ethical and legal aspects of nanomaterials and environmental regulation. Materials Research Society Fall Meeting. 

Boston, Massachusetts, December 1.

 ■ Kuempel E, Geraci C, Schulte P [2006]. Risk assessment approach, and 

research need for nanoparticles. NATO Advanced Research Workshop on 

Nanotechnology. Varna, Bulgaria, August 18.

 ■ Schulte PA [2006]. Overview of conference. International Conference on 

Nanotechnology Occupational and Environmental Health and Safety: Research to Practice. Cincinnati, Ohio, December 5.

 ■ Schulte PA [2007]. NIOSH Nanotechnology Program. Meeting of the NanoBusiness Alliance. Washington, DC, January 30.

 ■ Schulte PA [2007]. Nanotechnology: A progress report on understanding occupational safety and health issues. Woodrow Wilson International Center for 

Scholars. Washington DC, February 28.

 ■ Schulte PA, Mundt D, Mundt K [2007]. Medical Surveillance and Nanotechnology Overview. Workshop on Occupational Health Surveillance and Nanotechnology Workers. Arlington, Virginia, April 17–18.

 ■ Schulte PA [2007]. Occupational Safety and Health Issues in Nanotechnology. 

International Commission on Occupational Health. Milan, Italy, June 12.

 ■ Schulte PA [2007]. Progress in addressing gaps in the occupational safety and 

health of nanotechnology. 3rd International Symposium on Nanotechnology 

and Environmental Health. Taipei, Taiwan, August 30.

 ■ Schulte PA [2007]. Analysis of ethical issues of nanotechnology in the workplace. (Invited Presentation) 3rd International Symposium on Nanotechnology and Environmental Health. Taipei, Taiwan, August 31.

 ■ Schulte PA [2007]. Interim guidance on medical monitoring of workers 

potentially exposed to engineered nanoparticles. US Nanotechnology Policy 

Coordinating Group on the NIOSH Current Intelligence Bulletin. Washington, DC, September 17.

 ■ Schulte PA [2007]. Occupational Safety and Health Issues of Nanotechnology 

in the Workplace. Keynote address 2007 E&S Loss Control Executive Forum. 

Orlando, Florida, November 7.

 ■ Schulte PA [2007]. Occupational Safety and Health Issues of Nanotechnology in the Workplace. Nanotechnology and Occupational Health and Safety 

Conference. Santa Barbara, California, November 15.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 77

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Schulte PA [2007]. Current occupational safety and health issues of nanotechnology in the USA. European NanOSH Conference. Helsinki, Finland. 

December 3.

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

Implications and applications. Ohio Safety Congress and Expo, Columbus, 

Ohio, March 20.

 ■ Geraci CL [2007]. The NIOSH Nanotechnology Research Program: occupational implications and applications. General Electric nanotechnology summit, Miskayuna, New York, April 18.

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

address difficult questions. Society for Chemical Hazard Communication 

Spring Meeting, San Antonio, Texas, April 25.

 ■ Geraci CL [2007]. The NIOSH Nanotechnology Research Program: occupational implications and applications. Northeastern University panel on 

nanotechnology and policy, Boston, Massachusetts, 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, Pennsylvania, 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, Pennsylvania, 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, Florida, 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.
78 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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. NanoTexas’07, Dallas, Texas, October 3.

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

implications. Professional Conference on Industrial Hygiene, Louisville, Kentucky, October 17. 

 ■ Geraci CL [2007]. Nanotechnology: the new workplace. Nano 101 for the industrial hygienist. Professional Conference on Industrial Hygiene, Louisville, 

Kentucky, October 23. 

 ■ Geraci CL [2007]. The NIOSH Nanotechnology Research Program. Professional Conference on Industrial Hygiene, Louisville, Kentucky, October 23.

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

assessment challenges. American College of Occupational Medicine State-ofthe-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, Massachusetts, 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.

 ■ Hodson LL [2007]. Nanoparticles: NIOSH Nanoparticles Research Program. 

The Insurance Loss Control Association, Lexington, Kentucky, October 31.

 ■ 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.

 ■ Geraci CL [2008]. Occupational safety and health issues and nanotechnology. 

Education Resource Committee program directors meeting, Galveston, Texas, 

February 10.

 ■ Schulte PA [2008]. Occupational safety and health issues and nanotechnology. 

Food and Drug Law meeting, Washington, DC, February 18 and 19.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 79

APPENDIX A | A Summary of 69 NIOSH Research Projects

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

concerns of nanotechnology. Meeting with Lockheed Martin, Baltimore, 

Maryland, 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, New Jersey, March 4.

 ■ Geraci CL, Methner MM, Pearce TA, Hodson LL [2008]. Nanotechnology 

for industrial hygienists. American Industrial Hygiene Association—Central 

Ohio section meeting, Columbus, Ohio, April 22. 

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

do we know? SESHA Annual High Technology Environmental Health and 

Safety Symposium, Portland, Oregon, March 27.

 ■ 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, 

Minnesota, 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, Minnesota, 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, Maryland, 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, Missouri, June 25.

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

summary and update of activities. DOE nanoscale science research centers 

symposium: safe handling of engineered nanoscale materials, teleseminar to 

Argonne, 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, Florida, 

November 11. 
80 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

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

hygienist. California Industrial Hygiene Council, San Diego, California, 

December 8.

 ■ Methner MM, Hodson LL, Geraci CL [2008]. Nanotechnology Emission Assessment Technique (NEAT) used by NIOSH for Identifying Sources and Releases of Engineered Nanoparticles. Ohio Valley American Industrial Hygiene 

Association section, West Chester, Ohio, December 16.

 ■ Hodson LL [2008]. Workplace exposure assessment and risk management 

practices for nanomaterials. The Ohio Safety Congress and Expo, Columbus, 

Ohio, April 3.

 ■ 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, Ohio, June 24.

 ■ Hodson LL [2008]. NIOSH Nanotechnology Research Program. American 

Industrial Hygiene Association, Indiana section meeting, Indianapolis, Indiana, July 9. 

 ■ Hodson LL [2008]. Nanoparticles—NIOSH Nanoparticle Research Program. 

The Edison Electric Institute spring occupational health and safety conference, Louisville, Kentucky, April 29. 

 ■ Schulte PA [2008]. Occupational Safety and Health Issues and Nanotechnology (Keynote Address). Institute of Environmental Sciences and Technology. 

Bloomingdale, Illinois, May 6.

 ■ Schulte PA [2008]. Occupational Safety and Health Issues and Nanotechnology 1st Annual Conference on Nanotechnology Law, Regulation and Policy. 

Washington, DC, February 29.

 ■ Schulte PA [2008]. Prevention through Design National Initiative. ORC 

Worldwide quarterly occupational safety and health meeting. Washington, 

DC, February 7.

 ■ Schulte PA [2008]. Occupational Safety and Health Issues in Nanotechnology (Keynote Address). Northwest Occupational Health Conference. Seattle, 

Washington, October 15.

 ■ Schulte PA, Kuempel E, Castranova V, Trout D [2008]. Assessing the toxicologic evidence base for medical surveillance of workers exposed to engineered 

nanoparticles (poster presentation). Second International Nanotechnology 

Conference—Nanotox 2008. Zurich, Switzerland, September 9.

 ■ Schulte PA [2009]. Medical surveillance, exposure registries, and epidemiologic research. Presentation at the 4th International Conference on Nanotechnology—Occupational and Environmental Health. Helsinki, Finland, August 28.

 ■ Schulte PA [2009]. Risk identification and evaluation of nanomaterials. Meeting on the nanotechnologies for members of the WHO Collaborating Center 

in Occupational Health. Helsinki, Finland, August 26.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 81

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Schulte PA [2009]. Issues in epidemiological studies of workers exposed to 

engineered nanomaterials. 29th International Congress on Occupational 

Health. Capetown, South Africa, March 23.

 ■ Schulte PA [2009]. Nanoparticles: challenges and solutions. 29th International 

Congress on Occupational Health. Capetown, South Africa, March 22–27.

 ■ Geraci CL [2009]. Nanotechnology: is your (process) safety management 

system ready? Executive Conference Workshop on Handling Potent Pharmaceutical Compounds, Philadelphia, Pennsylvania, January 15.

 ■ Geraci CL [2009]. Reapplication of potent compound handling containment 

practices to engineered nanoparticles. Executive Conference Workshop on 

Handling Potent Pharmaceutical Compounds, Philadelphia, Pennsylvania, 

January 15.

 ■ Geraci CL [2009]. Good current practices for managing nanomaterials. 2nd 

Annual Massachusetts Nanotechnology Workshop, Massachusetts Department of Environmental Protection, Boston, Massachusetts, January 29.

 ■ Geraci CL [2009]. Nanotechnology: the new workplace. Human health and 

exposure issues. NanoImpact Net Coordination Meeting, Lausanne, Switzerland, March 25.

 ■ Geraci CL [2009]. Nanotechnology: the new workplace. NIOSH research 

to meet the challenge. Howard Hughes Medical Institute—Janelia Farm 

Research Campus, Environmental Health and Safety Conference, Loudon, 

Maryland, April 13–15.

 ■ Geraci CL [2009]. Nanotechnology: the new workplace. NIOSH research to 

meet the challenge. INNO 09, IRSST Symposium, Montreal, Canada, April 24.

 ■ Geraci CL [2009]. The role of NIOSH in responsible development of nanotechnology. NSTI Nanotech2009, Houston, Texas, May 4.

 ■ Geraci CL [2009]. Working with nanomaterials: NIOSH research to meet the 

challenge. SOCMA-AIU Holdings, Inc., Webinar, April 21.

 ■ Geraci CL [2009]. Evaluating exposure to engineered nanoparticles: progress 

in support of risk characterization. Toxicology and Risk Assessment Conference (TRAC), West Chester, Ohio, April 27.

 ■ Geraci CL [2009]. An update of the NIOSH nanotechnology research program. American Industrial Hygiene Conference and Expo, Toronto, Canada, 

May 31.

 ■ Geraci CL [2009]. The NIOSH Nanotechnology Research Program: update 

on carbon nanotube activity. California DTSC Carbon Nanotube Panel, San 

Francisco, California, June 22.

 ■ Geraci CL [2009]. Nanotechnology: the new workplace. NIOSH research to 

meet the challenge. NPE International Plastics Expo, Chicago, Illinois, June 26.
82 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Geraci CL [2009]. An update of the NIOSH Nanotechnology Research Program. University of California, School of Public Health Nanoparticle Safety 

Symposium, Webinar, July 29.

 ■ Geraci CL [2009]. Evaluating nanoparticle emissions in the workplace: a 

description of the approach used by NIOSH and a summary of findings from 

12 site visits. 4th International Conference on Nanotechnology Occupational 

and Environmental Health, Helsinki, Finland, August 26.

 ■ Geraci CL [2009]. Nanotechnology: the new workplace. Awareness to meet 

the challenge. Greater St. Louis Safety and Health Conference, St. Louis, MO, 

October 15.

 ■ Geraci CL [2009]. Working with nanomaterials—addressing HS&E concerns 

in the workplace through successful collaborations. California DTSC Nanotechnology Initiative Symposium V: An Industry Perspective, Sacramento, 

California, November 16.

 ■ Geraci CL [2009]. Nanomaterial exposure measurements: challenges and experiences. NNI Workshop: Nanomaterials and Human Health & Instrumentation, Metrology, and Analytical Methods, Washington, DC, November 18. 

 ■ Geraci CL [2009]. Nanotechnology: the new workplace. Meeting the challenge. 2nd USAF ASC/AFRL ESOH Nanomaterials Workshop, Dayton, Ohio, 

November 3.

 ■ Hodson LL [2009]. Demonstration of the NIOSH nanoparticle emission assessment technique and facilitator of a breakout session on paint with silver 

nanoparticles. The Safe Development of Nanotechnology in Massachusetts. 

Boston, Massachusetts, January 29.

 ■ Hodson LL [2009]. Nanotechnology–potential exposures and emission monitoring of engineered nanoparticles. 48th Annual Navy and Marine Corps 

Public Health Conference, Hampton, Virginia, March 25.

 ■ Hodson LL [2009]. NIOSH nanotechnology research program and the 

nanoparticle emission assessment technique. University of SW Texas ERC, 

Health and Safety Conference on Nanotechnology. Austin, Texas, April 26.

 ■ Hodson LL [2009]. Evaluating nanoparticle emissions in the workplace: a 

description of the approach used by NIOSH and a summary of findings from 

12 site visits. Nanotech 2009, Houston, Texas, May 4.

 ■ Crawford C, Hodson LL [2009]. Guidance for preparing good material safety 

data sheets (MSDSs) for engineered nanomaterials. Poster presentation at 

AIHce 2009, Toronto, Canada, June 1–4.

 ■ Hodson LL [2009]. Update of the NIOSH nanotechnology field research 

team. AIHce 2009, Toronto, Canada, June 3.

 ■ Hodson LL [2009]. Nanotechnology: a “tiny” primer on future and current 

issues. FL Workers Compensation Educational Conference, Orlando, FL 

August 17.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 83

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Geraci CL, Hodson LL [2009]. Nanotechnology: demonstration of the emission assessment technique. Greater St. Louis Safety and Health Conference, 

St. Louis, MO, October 15.

 ■ Hodson LL [2009]. Nanotechnology: role today and EHS implications. 

California Industrial Hygiene Council Conference, San Francisco, California, 

December 16.

 ■ Schulte PA [2010]. NIOSH nanotechnology research program. Committee to 

Develop a Research Strategy for Environmental Health Aspects of Engineered 

Nanoparticles, National Academy of Science. Washington, DC, February 3.

 ■ Geraci CL [2010]. Nanotechnology: risk management challenges. Yuma Pacific—

Southwest Section, AIHA, Annual Meeting, Irvine, California, January 15.

 ■ Geraci CL [2010]. The U.S. NIOSH nanotechnology research program. Keynote address to a special workshop of science and labor ministries in Japan, 

Tokyo, Japan, January 27–29.

 ■ Geraci CL [2010]. The NIOSH nanotechnology research program: meeting 

the challenge for a safer workplace. Keynote address at a special symposium 

on worker education at the 2010 International Conference on Nanoscience 

and Nanotechnology, Sydney, Australia, February 23–25.

 ■ Geraci CL [2010]. Nanotechnology: an opportunity to shape good policy by 

effectively converting research to practice. Keynote address at the 2nd Coordinating Meeting of NanoImpactNet, Lausanne, Switzerland, March 12.

 ■ Geraci CL [2010]. Nanotechnology: collaboration opportunities for workplace safety. NanoBusiness Alliance Annual Policy Meeting, Washington, DC, 

March 16.

 ■ Geraci CL [2010]. Risk management & the workplace. NNI Capstone Workshop: Risk Management Methods & Ethical, Legal, and Societal Implications 

of Nanotechnology, Washington, DC, March 30–31.

 ■ Geraci CL [2010]. Update: NIOSH nanotechnology activities: what’s new, and 

will it impact your research labs? Howard Hughes Medical Institute—

Environmental Health and Safety Conference, Janelia Farm Research Campus, Ashburn, Virginia, April 7.

 ■ Geraci CL [2010]. Working with nanomaterials: NIOSH research to meet the 

challenge. Chubb Insurance Company Loss Control Cornerstone Webinar, 

April 8.

 ■ Geraci CL [2010]. Progress review: NTRC coordination. Scientific Symposium and NIOSH NTRC 2010 Update, Wheeling, West Virginia, April 20–21.

 ■ Geraci CL [2010]. NIOSH nanotechnology activities: what’s new, and will it 

apply to your research labs? Webinar for NASA Goddard Space Flight Center, 

Safety Campaign, April 26.
84 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Geraci CL [2010]. Prevention through design, nanotechnology, and green 

chemistry: facilitating a green economy. Green Chemistry Council, Houston, 

Texas, April 28.

 ■ Geraci CL [2010]. Making green jobs safe: using prevention through design 

and green chemistry in nanotechnology. Good Jobs, Green Jobs Conference, 

Washington, DC, May 5.

 ■ Geraci CL [2010]. Exposure to nanomaterials: challenges and lessons from 

the workplace. Toward Regulation of Nanomaterials. University of Notre 

Dame, May 10–12.

 ■ Geraci CL [2010]. Overview of nanotechnology: NIOSH research to meet the 

challenge. Webinar presented to the Florida Office of the Judges of Compensation Claims, May 14.

 ■ Geraci CL [2010]. Ask the experts: an update on NIOSH nanotechnology 

research. American Industrial Hygiene Conference, Denver, Colorado, May 

25–27.

 ■ Geraci CL [2010]. An overview of key health, safety and environmental issues. NanoTech 2011, Anaheim, California, June 21.

 ■ Geraci CL [2010]. Exposure assessment: current exposure data. Nanomaterials and Worker Health: Medical Surveillance, Exposure Registries, and Epidemiologic Research, Key Stone, Colorado, July 21–22.

 ■ Geraci CL [2010]. Responsible development of nanotechnology: NIOSH 

research to meet the challenge. Destination Nano Scientific Symposium, 

UMass-Lowell, Lowell, Massachusetts, September 22.

 ■ Geraci CL [2010]. Nanotechnology: an opportunity for partnership, good science and good policy. Nanotechnology and Society: Emerging Organizations, 

Oversight, and Public Policy Systems, UMass-Amherst, Amherst, Massachusetts, September 24.

 ■ Geraci CL [2010]. The NIOSH nanotechnology program: strategic research 

supporting responsible development. Smalley Institute Year of Nano, Occupational EH&S Symposium, Rice University, Houston, Texas, October 12.

 ■ Geraci CL [2010]. Nanotechnology in the workplace: NIOSH research to 

meet the challenge. 2010 Technical Conference of the Association of Industrial Metalizers, Coaters and Laminators, Myrtle Beach, South Carolina, 

October 20.

 ■ Geraci CL [2010]. Nanoinformatics and field investigations: customer and 

supplier. Nanoinformatics 2010, Arlington, Virginia, November 3–5.

 ■ Geraci CL [2010]. Nanotechnology: challenges and opportunities for the industrial hygienist. Keynote address at the 2010 Northeast Regional Industrial 

Hygiene Conference and Exposition, Brunswick, NJ, December 3.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 85

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Geraci CL [2010]. Nanotechnology: this century’s biggest challenge. 20th Annual California Industrial Hygiene Council Conference, San Diego, California, December 6.

 ■ Geraci CL [2010]. NIOSH nanotechnology research: promoting responsible 

development and partnerships. NNI Innovation Summit, Washington, DC, 

December 8–10.

 ■ Schulte PA [2010]. Nanotechnologies and nanomaterials in the occupational 

setting. National Nanotechnology Initiative at Ten: Nanotechnology Innovation Summit, National Harbour, MD, December 8–10.

 ■ Schulte PA [2010]. NIOSH nanotechnology efforts: progress report on protecting H & S of nanotech workers, Nanoinformatics 2010, Arlington, Virginia, November 3.

 ■ Schulte PA [2010]. Nanotechnology Symposium VI: Progress in Protection, 

Department of Toxic Substance Control and California NanoSystems Institute. Los Angeles, California, October 13.

 ■ Schulte PA [2010]. Nanotechnologies and nanomaterials in the workplace. 

Invited keynote presentation at the 8th International Scientific Conference, 

International Occupational Hygiene Association. Rome, Italy, September 29.

 ■ Schulte PA [2010]. Occupational safety and health aspects of nanotechnology. 

Wisconsin Legislative Special Committee on Nanotechnology. Madison, WI, 

September 16.

 ■ Schulte PA [2010]. Exposure Registries, Nanomaterials, and Worker Health 

Conference. Keystone, Colorado, July 22.

 ■ Schulte PA [2010]. Overview of conference and issues. Opening presentation 

at the Conference on Nanomaterials and Worker Health: Medical Surveillance, Exposure Registries, and Epidemiologic Research. Keystone, Colorado, 

July 21.

 ■ Schulte PA, Geraci CL [2010]. Protecting the health and safety of workers: 

a progress report. New England Nanomanufacturing Summit 2010. Lowell, 

Massachusetts, June 22.

 ■ Schulte PA [2010]. Health surveillance of workers involved with nanomaterials. Invited presentation via SKYPE at the 1st Symposium on Impact of Nanotechnology in Workers Health and Safety and the Environment. Sao Paulo, 

Brazil, May 25.

 ■ Schulte PA [2010]. Nanotechnology: the 3rd industrial revolution in preventing adverse health effects from nanotechnology. Public Health Grand Rounds: 

Centers for Disease Control and Prevention, Atlanta, Georgia, April 15.

 ■ Schulte PA [2010]. NIOSH nanotechnology research program. Committee to 

Develop a Research Strategy for Environmental Health Aspects of Engineered 

Nanoparticles: National Academy of Science. Washington, DC, February 3.
86 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Hodson LL [2010]. Occupational health aspects of engineered nanomaterials: 

the NIOSH perspective. Northwestern University Town Hall Meeting, Evanston, Illinois, January 12. 

 ■ Hodson LL [2010]. Application of control banding to engineered nanomaterials. One section of an AIHA teleweb training class on hazard banding. 

February 25. 

 ■ Hodson LL [2010]. Risk management of nanomaterials. 2010 Indiana Safety 

and Health Conference, Indianapolis, Indiana, March 2. 

 ■ Hodson LL [2010]. Occupational health aspects of polymer nanocomposites. 

Polymer Nanocomposites 2010, Lehigh University, Bethlehem, Pennsylvania, 

March 8. 

 ■ Hodson LL, Methner MM, Geraci CL [2010]. Lessons learned from the field: 

how to protect yourself from occupational exposure to engineered nanomaterials. Nanotech 2010, Anaheim, California, June 24. 

 ■ Methner MM, Hodson LL, Geraci CL, Crawford C [2010]. Findings from 

the nanotechnology field research team: a photodocumentary. Poster at the 

Nanomaterials and Worker Health Conference, Keystone, Colorado, July 

21–23.

 ■ Hodson LL, Methner MM, Geraci CL, Crawford C [2010]. Findings from the 

nanotechnology field research team. Poster at the Nanomaterials and Worker 

Health Conference, Keystone, Colorado, July 21–23.

 ■ Hodson LL [2010]. Imaging challenges. NanoImpact Net, Dublin, Ireland, 

September 9.

 ■ Hodson LL [2010]. Advantages of the nanoparticle emission assessment technique and challenges of data interpretation. NanoImpact Net, Dublin, Ireland, 

September 9.

 ■ Hodson LL [2010]. Engineering case control studies: nanomaterials. Professional Conference on Industrial Hygiene (PCIH), Fort Worth, Texas, October 12.

 ■ Hodson LL [2010]. The NIOSH nanotechnology research program: meeting 

the challenge for a safer workplace. American Institute of Chemical Engineers 

(AIChE), Salt Lake City, Utah, November 9.

 ■ Hodson LL [2010]. Minimizing potential exposure to nanomaterials in the 

workplace through process design. American Institute of Chemical Engineers 

(AIChE), Salt Lake City, Utah, November 9,

 ■ Hodson LL [2010]. Exposure to nanomaterials: lessons learned from the 

workplace. American Institute of Chemical Engineers (AIChE), Salt Lake 

City, Utah, November 9.

 ■ Hodson LL [2010]. Nanomaterial workplace sampling. Workshop on Nano 

Measurement Strategy and Database, TNO, Zeist, the Netherlands, December 

16–17.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 87

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Trout D [2010]. Medical surveillance and screening overview. NTRC 2010 

Update, Wheeling, West Virginia, April 20. 

 ■ Trout D [2010]. Medical surveillance for workers potentially exposed to nanomaterials. Nanomaterials and Worker Health: Medical Surveillance, Exposure 

Registries, and Epidemiologic Research Conference, Keystone, Colorado, July 21.

 ■ Schulte PA, Trout D, Hodson L [2011]. Critical issues in medical surveillance 

and epidemiologic investigation of workers exposed to nanomaterials. Presentation at the 5th International Symposium on Nanotechnology, Occupational, 

and Environmental Health, Boston, Massachusetts, August 11.

 ■ Geraci CL [2011]. Workplace exposure to nanomaterials: current state of 

understanding. American Insurance Association Issues Briefing, Washington, 

DC, January 20.

 ■ Schulte PA [2011]. Overview of the draft NIOSH current intelligence bulletin 

(CIB): occupational exposure to carbon nanotubes and nanofibers. Presentation to the Nanotechnology Environmental Health Implications Working 

Group Meeting, Washington, DC, January 20, 2011.

 ■ Geraci CL [2011]. Overview of the NIOSH current intelligence bulletin: occupational exposure to carbon nanotubes/nanofibers. Public Meeting, Cincinnati, Ohio, February 3.

 ■ Schulte PA [2011]. Proposal for the constitution of a new working group on 

occupational safety and health and exposure to nanomaterials. Mid-term 

Meeting of the International Commission on Occupational Health, Milan, 

Italy, February 3.

 ■ Geraci CL [2011]. How relevant are model nanoparticles to understanding 

exposure in the workplace? How relevant are they to recommending industrial hygiene practices? US-EU Workshop on Bridging Nano EHS Research 

Efforts, National Nanotechnology Initiative, Washington, DC, March 10.

 ■ Schulte PA [2011]. Critical issues in the identification and control of occupational hazards of nanomaterials. The NANODEVICE Annual Forum for 

Nanosafety workshop. Berlin, Germany, March 18.

 ■ Geraci CL [2011]. Regulation and risk management of nanotechnology: the 

NIOSH perspective. Arizona State University Workshop: The Biggest Issues 

for the Smallest Stuff. Phoenix, Arizona, March 21.

 ■ Geraci CL [2011]. Building a risk management program: where to start for 

nanomaterials. Annual Scientific Symposium, Pittsburgh Section AIHA, Pittsburgh, Pennsylvania, April 6.

 ■ Geraci CL [2011]. NIEHS/NIOSH concept: nanomaterials exposure assessment. NIEHS/NTP Board of Scientific Counselors Meeting, Research Triangle Park, North Carolina, April 13.

 ■ Geraci CL [2011]. Recent significant activities specific to carbon nanotubes 

and nanofibers. Ohio Innovation Summit, Toledo, Ohio, April 20.
88 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Geraci CL [2011]. The NIOSH nanotechnology strategic plan for research and 

guidance. Mercer—ORC EHS Law Network, Washington, DC, May 3.

 ■ Geraci CL [2011]. Recent actions on specific nanomaterials: impact on risk 

management? University of Cincinnati Symposium on Nanotechnology, Cincinnati, Ohio, May 10.

 ■ Geraci CL [2011]. An update of the NIOSH nanotechnology research program: ask the experts. American Industrial Hygiene Conference and Exposition, Portland, Oregon, May 17.

 ■ Geraci CL [2011]. Nanomaterial exposure assessment: current knowledge and 

challenges. American Industrial Hygiene Conference and Exposition, Portland, Oregon, May 17.

 ■ Geraci CL [2011]. Roundtable 234. Risk assessment applied to engineered 

nanomaterials: managing risk with limited data. American Industrial Hygiene 

Conference and Exposition, Portland, Oregon, May 17.

 ■ Geraci CL [2011]. The NIOSH nanotechnology research program: responsible 

development and commercialization. 2011 TAPPI International Conference 

on Nanotechnology for Renewable Materials, Washington, DC, June 6.

 ■ Geraci CL [2011]. Update to the NNI on NIOSH research activities. US NNI 

Nanotechnology Environmental and Health Implications Workgroup, Washington, DC, June 25.

 ■ Geraci CL, Schulte PA, Zumwalde R, Kuempel E, Castranova V [2011]. The 

NIOSH current intelligence bulletin for carbon nanotubes and nanofibers. 

5th International Symposium on Nanotechnology Occupational and Environmental Health, Boston, Massachusetts, August 10–12.

 ■ Geraci CL [2011]. The U.S. National Nanotechnology Initiative: safety and 

health research & development coordination and strategy development. 5th 

International Symposium on Nanotechnology Occupational and Environmental Health, Boston, Massachusetts, August 10–12.

 ■ Geraci CL [2011]. Nanotechnology: opportunities and challenges in manufacturing. National Occupational Research Agenda: Manufacturing Sector 

Symposium, Cincinnati, Ohio, September 7.

 ■ Geraci CL [2011]. The NIOSH approach to supporting nanomaterial commercialization. Nanomanufacturing Summit 2011 & 10th Annual NanoBusiness Conference, Boston, Massachusetts, September 26.

 ■ Geraci CL [2011]. Nanotechnology: preparing for new workplace challenges–

hazards, risks and regulations. National Safety Council Webinar, September 27.

 ■ Geraci CL [2011]. Meeting the challenge of sustainable use of nanomaterials in construction. American Concrete Institute, Fall Technical Conference, 

Cincinnati, Ohio, October 17.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 89

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Geraci CL [2011]. Nanotechnology research at NIOSH: ensuring responsible 

nanomaterial development and commercialization. Nanotechnology for Defense Conference, Department of Defense, Seattle, WA, October 27.

■ Geraci CL [2011]. Nanomaterials: applying risk assessment/management 

approaches in the face of uncertainty. Professional Conference on Industrial 

Hygiene, Risk Assessment Symposium, Baltimore, Maryland, November 3.

 ■ Geraci CL, Schulte PA [2011]. ETIPC update: key NIOSH activities. Emerging Technologies Interagency Policy Committee, US Office of Science and 

Technology Policy, Washington, DC, November 7.

 ■ Geraci CL [2011]. The NIOSH nanotechnology research program: promoting best practices in research and development. University of Alberta, Science 

Symposium, Edmonton, Alberta, Canada, November 16.

 ■ Geraci CL [2011]. Research to practice to policy: the information needs for 

safe and responsible development of nanotechnology. NSF Workshop on 

Nanotechnology Infrastructure Safety, University of Central Florida, Orlando, 

Florida, December 9.

 ■ Hodson L, Geraci C, Crawford C [2011]. A critical evaluation of past and 

present safety data sheets for engineered nanomaterials. AIHce 2011, Portland, Oregon, June 6–9. 

■ Hodson L [2011]. Use of model nanoparticles to understand exposures in the 

workplace. Bridging US-EU Nano EHS Research Efforts, Washington, DC, 

March 11.

 ■ Hodson L, Geraci C [2011]. Significant NIOSH activities specific to carbon nanotubes and nanofibers. Presented at Nanotech 2011, Boston, Massachusetts, June 16. 

 ■ Berges M, Brouwer D, Fransman W, Bello D, Hodson L, et al. [2011]. Towards 

a harmonized assessment of the exposure to manufactured nano objects: 

common approaches in measurement strategy and obstacles. Report of a 

workshop. NanoImpactNet Meeting, Nancy, France, April 5–7.

 ■ Hodson L, Schulte P, Geraci C [2011]. The NIOSH Nanotechnology Research 

Center strategic plan for FY 13–15. 5th International Symposium on Nanotechnology–Occupational and Environmental Health, Boston, Massachusetts, 

August 10–12.

 ■ Schulte P, Kuempel E, Zumwalde R, Geraci C, Schubauer‐Berigan M, Castranova 

V, Hodson L, Murashov V, Ellenbecker M [2011]. Focused actions to protect 

carbon nanotube workers. 5th International Symposium on Nanotechnology–

Occupational and Environmental Health, Boston, Massachusetts, August 10–12.

■ Schulte P, Trout D, Hodson L [2011]. Critical issues in medical surveillance 

and epidemiologic investigation of workers exposed to nanomaterials. 5th 

International Symposium on Nanotechnology–Occupational and Environmental Health, Boston, Massachusetts, August 10–12.
90 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Schulte P, Kuempel E, Castranova V, Geraci C, Hoover M, Stefaniak A, Hodson L, Zumwalde R, Murashov V [2011]. Issues in establishing categorical 

occupational exposure limits for nanomaterials. 5th International Symposium 

on Nanotechnology Occupational and Environmental Health. Boston, Massachusetts, August 10–12.

 ■ Beaucham C, Geraci C, Hodson L, Tsai S, Ellenbecker M [2011]. Safe practices for working with engineered nanomaterials in research laboratories. Poster 

presentation, PS 404-6. American Industrial Hygiene Conference and Exposition, Portland, Oregon, May 16–19.

 ■ McKernan J, Geraci C, Ellenbecker M, Dunn K, Tsai S [2011]. Engineering 

control recommendations for nanomaterials. Poster presentation, PS 404-8. 

American Industrial Hygiene Conference and Exposition. Portland, Oregon, 

May 16–19.

 ■ Beaucham C, Dahm M, Evans D, Geraci C, Hodson L [2011]. Refining the 

nanoparticle emission assessment technique. Poster presentation, PA-02. 5th 

International Symposium on Nanotechnology Occupational and Environmental Health, Boston, Massachusetts, August 10–12.

 ■ Ramachandran G, D’Arcy J, O’Shaughnessy P, Geraci C, Ostraat M, Evans 

D, Methner M, Stevenson E, Maynard A, Rickabaugh K [2011]. A research‐

to‐practice approach to promote nanotechnology health and safety. Poster 

presentation, PA-03. 5th International Symposium on Nanotechnology Occupational and Environmental Health, Boston, Massachusetts, Aug 10–12. 

 ■ Kuempel E, Geraci C, Castranova V, Schulte P [2011]. Development of risk‐

based nanoparticle groups for occupational exposure control. 5th International 

Symposium on Nanotechnology Occupational and Environmental Health, 

Boston, Massachusetts, August 10–12. 

 ■ Ostraat M, Ramachandran G, D’Arcy J, O’Shaughnessy P, Geraci C, Olson 

G, Evans D, Methner M, Stevenson E, Maynard A, Rickabaugh K [2011]. An 

expert working group to promote nanotechnology health and safety. 5th International Symposium on Nanotechnology Occupational and Environmental 

Health, Boston, Massachusetts, August 10–12.

NIOSH Nanotechnology Exhibits 

 ■ International Conference on Nanotechnology, Occupational and Environmental Health and Safety: Research to Practice, Cincinnati, Ohio, December 

4–7, 2006

 ■ Ohio Innovation Summit, Mason, Ohio, April 15–16, 2008 

 ■ Ohio Innovation Summit, Dayton, Ohio, April 20–22, 2009

 ■ Nanotech 2009, Houston, Texas, May 4–7, 2009

■ AIHce 2009, June 1–3, 2009
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 91

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ National Plastics Exhibition (NPE 2009), June 22–24, 2009

 ■ Florida’s Workers Compensation Educational Conference, August 17–18, 2009

 ■ Greater St. Louis Safety and Health Conference, St. Louis, Missouri, October 

15, 2009

 ■ RIMS 2010, Boston, Massachusetts, April 21–23, 2010

 ■ Nanotech 2010, Anaheim, California, June 22–24, 2010 

 ■ NNI at 10, National Harbor, Maryland, December 8–9, 2010

 ■ Ohio Innovation Summit, Toledo, Ohio, April 18–20, 2011

 ■ Nanotech 2011, Boston, Massachusetts, June 13–16, 2011

 ■ 5th International Symposium on Nanotechnology–Occupational and Environmental Health, Boston, Massachusetts, August 19–21, 2011
92 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 2: Nanotechnology Safety and 

Health Research Coordination 

(Nanotoxicology) 

Principal Investigator: Vincent Castranova, PhD

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

 — 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 93

APPENDIX A | A Summary of 69 NIOSH Research Projects

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

C, Gaughan D [2007]. Particle size dependent generation from wildland fire 

smoke. Toxicology 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 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.
94 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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 toxicologic pathway of inhaled multi-walled carbon 

nanotubes. Vet Pathol 45:A 220. 

 ■ 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 

34:471–478.

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, Ohio, May 8.

 ■ Castranova V [2007]. Nanotoxicology research in NIOSH. NASA Glenn Research Center, Cleveland, Ohio, May 8.

 ■ Castranova V [2007]. Nanotoxicology research in NIOSH. American Industrial Hygiene Association conference and exposition, Philadelphia, Pennsylvania, June 2–7.

 ■ Castranova V [2007]. Nanotoxicology research in NIOSH. West Virginia 

University Cancer Center, NTRC meeting in Morgantown, West Virginia, 

February 21.

 ■ Castranova V [2007]. Critical toxicity parameters for nanoparticles vs. conventional particles. Presentation for the Department of Occupational Medicine, West Virginia University, Morgantown West Virginia, August 28.

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

conventional particles. Department of Physiology, West Virginia University, 

Morgantown, West Virginia, August 30.

 ■ 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, Kentucky, October 18.

 ■ Castranova V [2007]. Biological effects of nanoparticles. State-of-the-Art 

Conference/ International Conference on Health Care Worker Health, Vancouver, Canada, October 26–28.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 95

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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, California, 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, Maryland, 

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, California, May 14.

 ■ Castranova V [2008]. NIOSH nanotoxicology program. American Industrial 

Hygiene Association Conference and Exposition, Minneapolis, Minnesota, 

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, Minnesota, May 31–June 5.
96 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 3: Development of New Research in 

Occupational Health (Nanotoxicology)

Principal Investigator: Vincent Castranova, PhD

Project Duration: FY 2009–2015 

Critical Topic Area: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Evaluated the role of various physicochemical properties of nanoparticles, 

such as generation of oxidants and particle surface area, on their bioactivity.

 ■ Determined that improved dispersion enhances the bioactivity of 

nanoparticles.

 ■ Determined that the pulmonary toxicity and systemic translocation of ZnO 

nanoparticles is determined by their dissolution rate.

 ■ Determined that asbestos and CNT affect similar molecular signaling pathways in cultured lung cells, with asbestos exhibiting greater potency.

 ■ Determined the effects of TiO2

 nanoparticles on pulmonary inflammation 

and neuroimmune responses in developing airways.

 ■ Determined that in vitro exposure of endothelial cells alters the cytoskeleton, 

making tight junctions leaky.

Penetration of visceral pleura by multi-walled carbon nanotube
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 97

APPENDIX A | A Summary of 69 NIOSH Research Projects

Publications and Abstracts

 ■ Nel A, Madler L, Velegol D, Xia T, Hoek E, Somasundaran S, Klaessig F, Castranova V, Thompson M [2009]. Understanding bio-physicochemical interactions at the nano-bio interface. Nature Nanomaterials 8:543–557.

 ■ Apopa PL, Qian Y, Guo NL, Schwegler-Berry D, Pacurari M, Porter D, Shi 

X, Vallyathan V, Castranova V, Flynn DC [2009]. Iron nanoparticles induce 

human microvascular endothelial cell permeability through reactive oxygen 

species production and microtubule remodeling. Particle Fibre Toxicol 6:1.

 ■ Sager TM, Castranova V [2009]. Surface area of particle administered versus mass in determining the pulmonary toxicity of ultrafine and fine carbon 

black: comparison to ultrafine titanium dioxide. Particle Fibre Toxicol 6:15.

 ■ Borm P, Castranova V [2009]. Toxicology of nanomaterials: permanent interactive learning. Particle Fibre Toxicol 6:28.

 ■ Donaldson K, Borm PJA, Castranova V, Gulumian M [2009]. The limits of 

testing particle-mediated oxidative stress in vitro in predicting diverse pathologies; relevance for testing of nanoparticles. Particle Fibre Toxicol 6:13.

 ■ Moon C, Park H-J, Choi Y-H, Park E-M, Castranova V, Kang J-HL [2010]. 

Pulmonary inflammation after intra peritoneal administration of ultrafine 

titanium dioxide (TiO2

) at rest or in lungs primed with lipopolysaccharide. J 

Toxicol Environ Health Part A 73:396–409.

 ■ Pacurari M, Castranova V, Vallyathan V [2010]. Single- and multi-walled 

carbon nanotubes vs asbestos: are the carbon nanotubes a new health risk to 

humans? J Toxicol Environ Health Part A 73:378–395.

 ■ Geraci CL, Castranova V [2010]. Challenges in assessing nanoparticle toxicology: a personal perspective. Wiley Interdisciplinary Reviews: Nanomedicine 

and Nanobiotechnology, doi:10.1002/wnan.108.

 ■ Rushton EK, Jiang J, Leonard SS, Eberly S, Castranova V, Biswas P, Elder A, 

Han X, Gelein R, Finkelstein J, Oberdorster G [2010]. Concepts of assessing 

nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response-metrics. J Toxicol Environ Health Part A 73:445–461.

 ■ Sager TM, Molina R, Donaghey T, Brian J, Castranova V [2010]. Effects of 

particle size and route of exposure on the bioavailability of zinc from nanosized zinc oxide particles. Toxicologist 114:1, A278.

 ■ Scuri M, Chen BT, Castranova V, Reynolds JS, Johnson VJ, Samsell L, Walton 

C, Piedimonte G [2010]. Effects of titanium dioxide nanoparticle exposure 

on neuroimmune responses in rat airways. J Toxicol Environ Health Part A 

73:1353–1369.

 ■ Castranova V [2011]. Factors governing pulmonary response to inhaled 

particulate matter. In: Kulkarni P, Baron PA, Willeke K, eds. Aerosol measurement: principles, techniques, and applications. 3rd ed. New York: John Wiley 

& Sons, Inc., pp. 793–803.
98 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Xia T, Zhao Y, Sager T, George S, Pokhrel S, Li N, Schoenfield D, Meng H, 

Lin S, Wang X, Wang M, Ji Z, Zink JL, Madler L, Castranova V, Lin S, Nel AE 

[2011]. Decreased dissolution of ZnO by iron doping yields nanoparticles 

with reduced toxicity in the rodent lung and zebrafish embryos. ACS Nano 

5:1223–1235.

 ■ Hubbs AF, Mercer RR, Benkovic SA, Harkema J, Sriram K, Schwegler-Berry 

D, Goravanahally MP, Nurkiewicz TR, Castranova V, Sargent LM [2011]. 

Nanotoxicology: a pathologist’s perspective. Toxicol Pathol 39(2):301–324.

 ■ Kuempel E, Castranova V [2011]. Hazard and risk assessment of workplace 

exposure to engineered nanoparticles: Methods, issues, and carbon nanotubes 

case study. In: Ramachandran G, ed. Assessing nanoparticle risks to human 

health. New York: Elsevier, pp. 65–97.

 ■ Schulte PA, Geraci CL, Zumwalde R, Castranova V, Kuempel E, Methner 

MM, Hoover M, Murashov V [2010]. Nanotechnologies and nanomaterials in 

the occupational setting. Ital J Occup Environ Hyg 1(2) 63–68.

 ■ Knuckles TL, Yi L, Frazer D, Cumpston J, Chen B, Castranova V, Nurkiewicz 

TR [2011]. Nanoparticles alter cyclooxygenase activity in microvascular dysfunction. Toxicologist 120:316, A1471.

 ■ Stapleton PG, Minarchick VC, Cumpston A, McKinney W, Chen BT, Frazer 

D, Castranova V, Nurkiewicz TR [2011]. Time-course of impaired coronary 

arteriolar endothelium-dependent dilation after multi-walled carbon nanotube inhalation. Toxicologist 120:41, A194. 

 ■ Zhao J, Castranova V [2011]. Toxicology of nanomaterials used in nanomedicine. J Toxicol Environ Health Part B 14:593–632.

 ■ Pacurari M, Schwegler-Berry D, Friend S, Leonard SS, Mercer RR, Vallyathan 

V, Castranova V [2011]. Raw single wall carbon nanotube-induced cytotoxic 

effects in human bronchial epithelial cells: comparison to asbestos. Toxicol 

Environ Chem 93:1045–1072.

 ■ Pacurari M, Qian Y, Porter DW, Wolfarth M, Wan Y, Luo D, Ding M, Castranova V, Guo NL [2011]. Multi-walled carbon nanotube–induced gene 

expression in the mouse lung: association with lung pathology. Toxicol Appl 

Pharmacol 255:18–31.

Invited Presentations

 ■ Castranova V [2009]. Comparison of in vitro, pharyngeal aspiration and 

inhalation results for single-walled carbon nanotubes. American Industrial 

Hygiene Association Distance Learning Program, Toxicology of Engineered 

and Incidential Nanoparticles. Jan. 27.

 ■ Castranova V [2009]. The nanotoxicology research program in NIOSH. 

Nanotoxicology Specialty Section, SOT, Baltimore, Maryland, March 22.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 99

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Castranova V [2009]. The nanotoxicology research program in NIOSH. EPA, 

Washington, DC, May 27.

 ■ Castranova V [2009]. Critical toxicity parameters for nanoparticles vs. conventional particles. Ceramics Meeting, Cleveland, Ohio, May 21.

 ■ Castranova V [2009]. Elongated nanoparticles–how they resemble and differ 

from asbestos. Interagency Asbestos Working Group, Atlanta, Georgia, April 22.

 ■ Castranova V [2009]. Elongated nanoparticles–how they resemble and differ 

from asbestos. Nanofiber 2009, Tokyo, Japan, June 19.

 ■ Castranova V [2009]. Pulmonary response to MWCNT exposure. Nanofiber 

Extended Workshop, Nagano, Japan, June 22.

 ■ Castranova V [2009]. NIOSH nanotoxicology research: biological activity of 

single-walled carbon nanotubes. toxicology forum, Aspen, Colorado, July 16.

 ■ Castranova V [2009]. Potential pulmonary effects of single-walled carbon 

nanotube (SWCNT) exposure: in vitro genotoxic effects. 10th International 

Conference on Environmental Mutagens, Florence, Italy, Aug. 20.

 ■ Castranova V [2009]. Pulmonary response to pharyngeal aspiration of multiwalled carbon nanotubes in mice. 4th International Conference on Nanotechnology: Occupational and Environmental Health, Helsinki, Finland, Aug. 28.

 ■ Castranova V [2009]. Possible health implications of nanotechnology. Catholic Academy of Science in the United States, Sept. 26.

 ■ Chen BT, McKinney WD, Schwegler-Berry, Castranova V, Frazer DG [2009]. 

Aerosolization and characterization of multi-walled carbon nanotubes for 

inhalation studies. AAAR 28th Annual Conference, October 26–30.

 ■ Castranova V [2009]. Pulmonary responses to MWCNT exposure. Department of Environmental and Occupational Health, University of Pittsburgh, 

Pennsylvania, Nov. 22.

 ■ Castranova V [2010]. Pulmonary responses to MWCNT exposure. UCLA, 

Los Angeles, California, Feb. 9.

 ■ Castranova V [2010]. Developing risk characterization information to determine and classify nanomaterials based on physical and chemical properties. 

NNI Capstone Workshop, Arlington, Virginia, March 30.

 ■ Castranova V [2010]. Hazard assessment of nanomaterials: why is it so challenging? CDC Public Health Grand Rounds, Atlanta, Georgia, April 15.

 ■ Castranova V [2010]. Pulmonary response to pharyngeal aspiration of multiwalled carbon nanotubes in mice. American Association for Cancer Research 

Conference, Washington, DC, April 17.

 ■ Castranova V [2010]. Risk assessment strategy for nanoparticles: multi-walled 

carbon nanotubes as a test case. Conference on workplace aerosols. Karlsruhe, 

Germany, July 2.
100 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Castranova V [2010]. Pulmonary response to pharyngeal aspiration of multiwalled carbon nanotubes in mice. NIST, Boulder, Colorado, July 20.

 ■ Castranova V [2010]. Overview of current toxicological knowledge of engineered nanoparticles, nanomaterials and worker health: Medical Surveillance, 

Exposure Registries, and Epidemiologic Research Conference, Keystone, 

Colorado, July 21.

 ■ Castranova V [2010]. Risk assessment strategy for nanoparticles: multi-walled 

carbon nanotubes as a test case, ORC WORLDWIDE Occupational Safety 

and Health Group and Corporate Health Directors Network Meeting, Washington, DC, August 4.

 ■ Castranova V [2010]. Overview of current toxicological knowledge of engineered nanoparticles, 5th International Conference on the Environmental 

Effects of Nanoparticles and Nanomaterials: 2010, Clemson, South Carolina, 

August 23.

 ■ Castranova V [2010]. Elongated nanoparticles: how they resemble and differ 

from asbestos. Columbia University, New York, New York, November 4.

 ■ Castranova V [2010]. Pulmonary response to pharyngeal aspiration of multiwalled carbon nanotubes in mice. SUNY-Stony Brook, Stony Brook, New 

York, November 9. 

 ■ Castranova V [2011]. Pulmonary and systemic responses to carbon nanotubes. SOT Meeting, Washington, DC, March 9.

 ■ Castranova V [2011]. The effect of agglomerate structure size on the bioactivity of nanoparticles. SOT Meeting, Washington, DC, March 9.

 ■ Castranova V [2011]. Nanotechnology research in NIOSH. US-EU Nanotoxicology Workshop, Washington, DC, March 10.

 ■ Castranova V [2011]. Risk assessment and development of a recommended 

exposure limit for carbon nanotubes by NIOSH. Harvard School of Public 

Health, Boston, Massachusetts, April 7.

 ■ Castranova V [2011]. Overview of current toxicological knowledge of engineered nanoparticles. NPPTL/NIOSH, Bruceton, Pennsylvania, April 21. 

 ■ Castranova V [2011]. Responses of pulmonary exposure to nanoparticles. 

nanoparticles: tools for toxicology, The Toxicology Forum and the Regulatory 

Governance Initiative, Ottawa, Canada, May 2.

 ■ Castranova V [2011]. Risk assessment and development of a recommended 

exposure limit for carbon nanotubes by NIOSH. Health Canada, Ottawa, 

Canada, May 2.

 ■ Castranova V [2011]. Responses to pulmonary exposure to nanoparticles 

in NIOSH animal studies. Medichem: Occupational Health in a Changing 

World, Heidelberg, Germany, June 4.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 101

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Castranova V [2011]. Cardiovascular effects of pulmonary exposure to nano 

or fine particles. 7th International Symposium on Modern Principles of Air 

Monitoring and Biomonitoring, Loen, Norway, June 20.

 ■ Castranova V [2011]. Overview of current toxicological knowledge of engineered nanoparticles. 5th International Symposium on Nanotechnology, 

Occupational and Environmental Health. Boston, Massachusetts, August 9.

 ■ Castranova V [2011]. Potential pulmonary effects of single-walled carbon 

nanotube (SWCNT) exposure: in vitro genotoxic effects. 5th International 

Symposium on Nanotechnology, Occupational and Environmental Health. 

Boston, Massachusetts, August 10.

 ■ Castranova V [2011]. Responses to pulmonary exposure to nanoparticles in 

niosh animal studies. ESF Symposium: Nanocarbons 2011. Acquafredda di 

Maratea, Italy, September 6–11.
102 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 4: Systemic Microvascular Dysfunction: 

Effects of Ultrafine vs. Fine Particles

Principal Investigator: Vincent Castranova, PhD

Project Duration: FY 2006–2010

Critical Topic Area: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Determined that pulmonary exposure to nano TiO2 inhibits the responsiveness of coronary arterioles to dilators.

 ■ Evaluated mechanisms by which generation of reactive species inhibits the 

ability of systemic and coronary microvessels to respond normally to dilators 

after inhalation of nano TiO2

. 

 ■ Evaluating neurogenic mechanisms by which inhalation of nano TiO2

 alters 

the normal response of systemic microvessels to dilators and sympathetic 

constriction.

 ■ Evaluating the effect of inhalation of MWCNT on the ability of coronary arterioles to respond normally to dilatory inputs.

 ■ Evaluating the cardiovascular response to inhalation of an antimicrobial spray 

containing TiO2

 particles.

Publications and Abstracts 

 ■ Nurkiewicz TR, Porter DW, Barger M, Millecchia L, Rao KM, Marvar PJ, 

Hubbs AF, Castranova V, Boegehold MA [2007]. Systemic microvascular 

dysfunction and inflammation after pulmonary particulate matter exposure. 

Environ Health Perspect 114:412–419.

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

D, Castranova V, Boegehold M [2007]. Inhalation of ultrafine titanium dioxide 

augments particle-dependent microvascular dysfunction. FASEB J 21(6):A 846.

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

Castranova V [2008]. Nanoparticle inhalation augments particle-dependent 

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 Eur Soc Microcir Conf Budapest, Hungary, 

August 26–29, pp. 13–17.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 103

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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.

 ■ Nurkiewicz TR, Porter DW, Hubbs AF, Tone S, Chen BT, Frazer DG, Boegehold MA, Castranova V [2009]. Pulmonary nanoparticle exposure disrupts 

systemic microvascular nitric oxide signaling. Toxicol Sci 110(1):191–203.

 ■ LeBlanc AJ, Cumpston JL, Chen BT, Frazer D, Castranova V, Nurkiewicz 

TR [2009]. Nanoparticle inhalation impairs endothelium-dependent vasodilatation in subepicardial arterioles. J Toxicol Environ Health Part A 

72:1576–1584.

 ■ LeBlanc AL, Moseley AM, Chen BT, Frazer D, Castranova V, Nurkiewicz TR 

[2010]. Nanoparticle inhalation impairs coronary microvascular reactivity 

via a local reactive oxygen species-dependent mechanism. Cardiovas Toxicol 

10:27–36.

 ■ Knuckles TL, Frazer DG, Cumpston JL, Chen BT, Castranova V, Nurkiewicz 

TR [2010]. Nanoparticle inhalation modulates arteriolar sympathetic constriction: role of nitric oxide, prostanoids, and α-adrenergic receptors. Toxicologist 114:1, A1728.

 ■ Chen BT, Afshari A, Stone S, Jackson M, Schwegler-Berry D, Frazer D, Castranova V, Thomas TA [2010]. Nanoparticles-containing spray can aerosol: 

characterization, exposure assessment, and generator design. Inhal Toxicol 

22:1072–1082.

Invited Presentations

 ■ Nurkiewicz TR, Porter DW, Barger M, Hubbs AF, Millecchia L, Rao K, Chen 

BT, Frazer D, Castranova V, Boegehold MA [2006]. Peripheral microvascular 

dysfunction follows ultrafine titanium dioxide inhalation. Health Effects Institute Annual Conference, San Francisco, California, April 9–11.

 ■ 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, Wisconsin, 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, Ohio, 

April 25.

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

particle-dependent microvascular dysfunction. Center for Environmental 

Health, University of Montana, Missoula, Montana, September 21.
104 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

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

fine vs. ultrafine particles. University of Connecticut, Storrs, Connecticut, April 7.

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

to fine vs. ultrafine particles. Meeting held at John Hopkins University, Baltimore, Maryland, June 10.

 ■ Castranova V [2008]. Ambient particulates and/or nanoparticles: cardiovascular and pulmonary toxic and morphologic manifestations. International 

Conference on Particles: Risks and Opportunities, Cape Town, South Africa, 

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, Florida, October 20–24.

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

to particles. Presentation at the Harvard School of Public Health, Cambridge, 

Massachusetts, October 24. 

 ■ LeBlanc AF, Hu Y, Miller-Delp J, Chen D, Frazer BT, Castranova V, Nurkiewicz TR [2008]. Nanoparticle inhalation impairs endothelium-dependent 

vasoreactivity in coronary arterioles. American Heart Association Conference, Washington DC, November 8–12.

 ■ Castranova V [2009]. Systemic microvascular dysfunction following pulmonary exposure to fine vs. ultrafine TiO2

. EPA, Washington, DC, May 27.

 ■ Castranova V [2009]. Systemic microvascular dysfunction following pulmonary exposure to fine vs. ultrafine TiO2

. WV Nano 2009, Morgantown, West 

Virginia, May 11.

 ■ Castranova V [2009]. Systemic microvascular dysfunction following pulmonary exposure to fine vs. ultrafine TiO2

. American Industrial Hygiene Conference and Expo, Toronto, Canada, June 4.

 ■ Castranova V [2009]. Effect of pulmonary exposure to particles on systemic 

microvascular response. University of Roma, Rome, Italy, August 24.

 ■ Castranova V [2009]. Systemic microvascular response to pulmonary exposure to particles. NASA, Houston, Texas, December 8.

 ■ Chen BT, JL Cumpston, AM Moseley, S Stone, D Schwegler-Berry, D Porter, AF Hubbs, Frazer D, Castranova V, Nurkiewicz TR [2009]. Particleassociated systemic microvascular dysfunction. 28th Annual Conference of the 

American Association for Aerosol Research, Minneapolis, MN, October 26–30.

 ■ Chen BT, Afshar A, Stone S, Jackson M, McKinney M, Schwegler-Berry D, 

Frazer DG, Castranova V, Thomas T [2010]. Nanoparticle-containing spray 

can aerosol: characterization, exposure assessment, and inhalation chamber 

design. 29th Annual Conference of the American Association for Aerosol 

Research. Portland, OR, October 25–29.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 105

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 5: Particle Surface Area as a

Dose Metric

Principal Investigator: Vincent Castranova, PhD

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

 ■ Castranova V [2007]. Comparison of pulmonary responses to single-walled 

vs. multi-walled carbon nanotubes. Toxicologist 96(1):8.

 ■ Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monterio-Riviere N, 

Warheit D, Yang H [2005]. Principles for characterizing the potential human 

effects from exposure to nanomaterials: elements of screening strategy. Particle Fibre Toxicol 2:8.

 ■ Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monterio-Riviere N, 

Warheit D, Yang H [2005]. Principles for characterizing the potential human 

effects from exposure to nanomaterials: elements of a screening strategy. Toxicology 90:A2333.
106 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Sager T, Robinson VA, Porter DW, Schwegler-Berry DE, Lindsley W, Castranova V [2007]. An improved method to prepare suspensions of nanoparticles 

for treatment of lung cells in culture or in vivo exposure by pharyngeal aspiration or intratracheal instillation. Toxicologist 96(1):232.

 ■ Sager T, Porter DW, Robinson VA, Lindsley WG, Schwegler-Berry DE, Castranova V [2007]. Improved method to disperse nanoparticles for in vitro and 

in vivo investigation of toxicity. Nanotoxicity 1(2):118–129.

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

of possible adverse pulmonary effects resulting from airborne nanoparticles. 

In: Monteiro-Riviere N, Tran L, eds. Nanotechnology: characterization, dosing and health effects. New York: Taylor and Francis.

 ■ Sriram K, Porter DW, Tsuruoka S, Endo M, Jefferson AM, Wolfarth MG, 

Rogers GM, Castranova V, Luster MI [2007]. Neuroinflammatory responses 

following exposure to engineered nanomaterials. Toxicologist 96(1):288.

 ■ 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.

 ■ 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 107

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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 Presentation

 ■ 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.
108 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 6: Role of Carbon Nanotubes in 

Cardiovascular and COPD-Related 

Diseases

Principal Investigator: Aaron Erdely, PhD (Petia Simeonova, PhD, 

deceased)

Project Duration: FY 2004–2010

Critical Topic Area: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Evaluated cardiovascular effects resulting from respiratory exposure to purified and MWCNT. 

 ■ A single exposure resulted in distressed mitochondrial homeostasis, an effect 

that was dose-dependent. Oxidative alterations of mitochondria can trigger 

endothelial dysfunction, a leading mechanism in atherosclerosis progression. 

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

 ■ Respiratory exposure to SWCNTS and MWCNT resulted in acute and chronic systemic responses related to potential adverse cardiovascular effects. 

 ■ SWCNTS and MWCNT deposited in the lung induced acute systemic inflammatory and prothrombotic responses. These effects were portrayed by a 

complex pattern of gene expression and protein blood analyses indicating a 

close cross-talk between the lung and systemic circulation following pulmonary exposure.

 ■ 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 on the basis of their physiochemical characteristics and potential to induce 

oxidative stress, inflammation, and specific pulmonary and systemic toxicity. 

Study results demonstrated that the evaluation of systemic effects in parallel 

with pulmonary toxicity studies provide a more complete toxicological assessment that can be used in predicting risk. 

 ■ Osteopontin (OPN) is involved in granulomatous lung disease, of which CNT 

exposure is included. Immunohistochemistry showed markedly increased 

levels of OPN and the binding receptor CD44 following MWCNT exposure. 

Mice lacking the OPN gene were protected from some of the histological 

abnormalities caused by MWCNT. Increased circulating levels of OPN, a suggested biomarker for asbestos exposure, proved to be inconclusive.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 109

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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 SWCNTS or MWCNT. These effects were 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.

 ■ In vitro studies were conducted to explore the interaction between OPN and 

CD44. The exposure of RAW 264.7 cells, a murine macrophage cell line, to 

MWCNT or asbestos increased gene expression levels of OPN and CD44, 

protein release of OPN and modifications of the interactions between CD44 

and OPN at cellular and extracellular levels in both a time- and dose-dependent manner.

Publications and Abstracts

 ■ Li Z, Salmen R, Hulderman T, Kisin E, Shvedova A, Luster M, Simeonova P 

[2004]. Pulmonary carbon nanotube exposure and oxidative status in vascular 

system. Free Radical Biol Med 37(1):S142.

 ■ Li Z, Salmen R, Hulderman T, Kisin E, Shvedova AA, Luster MI [2005]. Pulmonary exposure to carbon nanotubes induces vascular toxicity. Toxicologist 

84:A1045.

 ■ Li ZJ, Chapman R, Hulerman T, Salmen R, Shvedova, A, Luster MI, Simeonova PP [2006]. Relationship of pulmonary exposure to multiple doses of single 

wall carbon nanotubes and atherosclerosis in apoE-/-mouse model. Toxicologist 90(1):A1555.

 ■ 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. 

***Nominated for Charles C. Shepard Science Award, 2008, and was highlighted and discussed in the section Hot-off-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 SWCNTs.

 ■ Simeonava PP, 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.

 ■ 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. 
110 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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.

 ■ 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.

 ■ 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 cardiovascular disease. 

Allegheny-Erie Chapter meeting, Society of Toxicology. April 18. *** Awarded 

best overall poster.

 ■ Erdely A, Hulderman T, Salmen R, Liston A, Zeidler-Erdely PC, Simeonova 

PP [2009]. Time course of systemic effects following a single exposure to carbon nanotubes. Toxicologist 108(1):279.

 ■ Erdely A, Hulderman T, Salmen R, Liston A, Zeidler-Erdely P, SchweglerBerry, Castranova V, Koyama, S, Kim Y-A, Endo M, Simeonova PP [2009]. 

Cross-talk between the lung and systemic circulation during carbon nanotube 

respiratory exposure. Potential biomarkers. Nano Lett 9(1):36–43. ***Nominated for Charles C. Shepard Science Award and the American Chemical 

Society Office of Public Affairs highlighted the paper in its weekly PressPac.

 ■ Simeonova PP [2009]. Update on carbon nanotube toxicity. Nanomedicine 

4(4):373–375.

 ■ Simeonova PP, Erdely A [2009]. Engineered nanoparticle respiratory exposure and potential risks for cardiovascular toxicity: predictive tests and 

biomarkers. Inhal Toxicol 21(S1):68–73.

 ■ Walker VG, Li Z, Hulderman T, Schwegler-Berry D, Kashon M, Simeonova 

PP [2009]. Potential in vitro effects of carbon nanotubes on human aortic 

endothelial cells. Tox Appl Pharm 236(3):319–328.

 ■ Walker VG, Hulderman T, Simeonova PP [2009]. Carbon nanotube exposure 

induces cytotoxicity in human bronchial epithelial cells. Toxicologist 108(1):461.

 ■ Walker VG, Hulderman T, Simeonova PP [2009]. Mechanism of multiwalled 

carbon nanotube-and asbestos-induced osteopontin/CD44 in raw 264 macrophages. Mol Biol Cell 20:2689.

Invited Presentations

 ■ Simeonova P, Li J, Luster MI, Shvedova A, Salmen R [2005]. Carbon nanotube 

exposure and cardiovascular outcomes. 2nd International Symposium on Nanotechnology and Occupational Health, Minneapolis, Minnesota, October 3–6.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 111

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Simeonova PP [2006]. Nanomaterial exposure and risk for systemic effects. 

Toxicology and Risk Assessment Meeting, Cincinnati, Ohio, April 19.

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

systemic effects. Society of Toxicology, Charlotte, North Carolina, March 

25–29.

 ■ Simeonova PP [2007]. Carbon nanotubes—toxicological evaluation. International meeting of nanotechnology, San Francisco, California, November 5–7.

 ■ 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, California, 

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, Massachusetts, 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, Massachusetts, 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, West Virginia, March 2008).

 ■ Erdely A [2009]. Systemic effects following exposure to carbon nanotubes. 

Society of Toxicology, Baltimore, Maryland, March 15–19.
112 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 7: Investigations of Multi-walled Carbon 

Nanotube Toxicity 

Principal Investigator: Dale W. Porter, PhD

Project Duration: FY 2007–2011

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 contaminants and endotoxin levels present 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 MWCNTinduced toxicity after exposure by pharyngeal aspiration.

Multi-walled carbon nanotubes in lungs 1 hour post aspiration
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 113

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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. 

 ■ 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.

 ■ A dose-response and time course study in mice exposed to MWCNT by pharyngeal aspiration was conducted. 

 ■ MWCNT caused pulmonary inflammation and damage which peaked at 7 

days post-exposure and returned to control levels by 56 days post-exposure 

 ■ Histopathological studies determined that MWCNT exposure caused rapid 

development of pulmonary fibrosis, by 7 days post-exposure, and granulomatous inflammation persisted through 56 days post-exposure.

 ■ MWCNT exposure caused lymphangiectasia, which is dilation of the pulmonary lymphatics.

 ■ A morphometry study determined that MWCNT penetration of alveolar 

macrophages, the alveolar wall, and visceral pleura are both frequent and 

sustained, indicating a need to investigate the chronic toxicity of MWCNT at 

these sites.

 ■ Pulmonary exposure to MWCNT increased hippocampal beta-amyloid 

(Abeta) protein content and caused hyper-phosphorylation of hippocampal 

Tau protein, indicative of Alzheimer’s disease–like neuronal abnormality. 

 ■ Pulmonary exposure to MWCNT altered the mRNA expression of several 

blood-brain barrier (BBB) and glial-related markers, suggestive of BBB 

dysfunction. 

 ■ Pulmonary exposure to MWCNT altered the mRNA expression of several 

AD-related genes in the hippocampus, consistent with the increased expression of Abeta and hyper-phosphorylated Tau in this region.

 ■ Gene expression profiling studies have been conducted on mRNA isolated 

from lung samples obtained from this study.

 ■ Partner in the International Alliance for NanoEHS Harmonization. 

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.
114 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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 multi-walled carbon nanotubes. Vet Pathol 45:786.

 ■ Wolfarth M, Porter DW, Hubbs AF, Leonard SS, Battelli LA, Andrew ME, 

Castranova V [2009]. Pulmonary toxicity of multi-walled carbon nanotubes. 

Toxicologist 108:457.

 ■ Sriram K, Porter DW, Jefferson AM, Lin GX, Wolfarth M, Chen, McKinney W, 

Frazer DG, Castranova V [2009]. Neuroinflammation and blood-brain barrier 

changes following exposure to engineered nanomaterials. Toxicologist 108:458.

 ■ Hubbs AF, Mercer RR, Coad JE, Battelli LA, Willard P, Sriram K, Wolfarth M, 

Castranova V, Porter DW [2009]. Persistent pulmonary inflammation, airway 

mucous metaplasia and migration of multi-walled carbon nanotubes from the 

lung after subchronic exposure. Toxicologist 108:457.

 ■ Mercer RR, Hubbs AF, Scabilloni J, Wang L, Castranova V, Porter DW [2010]. 

Distribution and persistence of pleural penetrations by multi-walled carbon 

nanotubes. Am J Respir Crit Care Med 181(1):A3102.

 ■ Porter DW, Hubbs AF, Mercer RR, Wu N, Wolfarth MG, Sriram K, Leonard 

S, Battelli L, Schwegler-Berry D, Friend S, Andrew M, Chen BT, Tsuruoka 

S, Endo M, Castranova V [2010]. Mouse pulmonary dose- and time-course 

responses induced by exposure to multi-walled carbon nanotubes. Toxicology 

269:136–147.

 ■ Mercer RR, Hubbs AF, Scabilloni JF, Wang L, Battelli LA, Schwegler-Berry 

D, Castranova V, Porter DW [2010]. Distribution and persistence of pleural 

penetrations by multi-walled carbon nanotubes. Particle Fibre Toxicol 7:28.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 115

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Pacurari M, Qian Y, Hubbs A, Porter D, Wolfarth M, Luo D, Wan Y, Castranova V, Guo N [2011]. Multi-wall carbon nanotube (MWCNT)–induced gene 

expression in the mouse lung: implication of carcinogenesis risk. Toxicologist 

120:253–254.

 ■ Pacurari M, Qian Y, Porter DW, Wolfarth M, Wan Y, Luo D, Ding M, Castranova V, Guo NL [2011]. Multi-walled carbon nanotube-induced gene expression in the mouse lung: association with lung pathology. Toxicol Applied 

Pharmacol 255:18–31.

 ■ Mercer RR, Hubbs AF, Scabilloni JF, Wang L, Battelli LA, Friend S, Castranova V, Porter DW [2011]. Pulmonary fibrotic response to aspiration of multiwalled carbon nanotubes. Particle Fibre Toxicol 8:21.

 ■ Mercer R, Hubbs AF, Scabilloni JF, Rojanasakul L, Battelli LA, Castranova V, 

Porter DW [2011]. Pulmonary fibrotic response to sub-chronic multi-walled 

carbon nanotube exposure. Toxicologist 120:11.

 ■ Sager TM, Wolfarth M, Porter D, Castranova V, Wu N, Holian A [2011]. Effect of surface modification on the bioavailability and inflammatory potential 

of multi-walled carbon nanotubes. Toxicologist 120:252.

 ■ Battelli LA, Castranova V, Porter DW, Friend S, Schwegler-Berry D, Willard P, 

Hubbs AF [2011]. The use of E-cadherin immunofluorescence in pulmonary 

toxicologic pathology studies. Toxicologist 120:123.

Invited Presentations

 ■ 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, Florida, October 20–24. 

 ■ Porter DW [2009]. MWCNT toxicity in the lung. NIOSH (Morgantown, West 

Virginia), for the visiting Japanese METI Delegation, February 29.

 ■ Porter DW [2009]. Pulmonary dose- and time course responses induced by 

exposure to multi-walled carbon nanotubes. US EPA, Washington, DC, November 9–10.

 ■ Sriram K [2010]. Central nervous system effects of pulmonary exposure to 

nanoparticles. NTRC 2010 Update, Wheeling, West Virginia, April 20. 

 ■ Sriram K [2010]. Neurological risks of exposure to incidental and engineered 

nanoparticles. West Virginia University Center for Neuroscience, Morgantown, West Virginia, September 29. 

 ■ Porter WD [2011]. Introduction to nanotoxicology: an emerging field. Pittsburgh AIHA Local Section, Pittsburgh, Pennsylvania, April 6.
116 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 8: Toxicological Effects of

Aerosolized MWCNT

Principle Investigator: Dale W. Porter, PhD

Project Duration: FY 2010–2012 

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Developmental Engineering Research Team (DERT) designed and tested an 

exposure chamber necessary for the studies in this project. 

 ■ Methodology to measure MWCNT lung burden was developed.

 ■ A dose-response study to aerosolized MWCNT has been done and determined that pulmonary inflammation and damage are dose dependent at one 

day post-exposure.

 ■ Inhalation exposure to MWCNT also elicited neuroinflammation in the olfactory bulb and hippocampus at one day post-exposure.

 ■ A time course study (up to 48 weeks post-exposure) of pulmonary and central 

nervous system responses to inhalation of MWCNT is currently being conducted.

 ■ For the time course study, pulmonary toxicity studies will examine MWCNTinduced pulmonary inflammation, damage, and fibrosis. 

 ■ For the time course study, neurotoxicity studies will evaluate the integrity of 

the blood-brain barrier (BBB), as well as neuroinflammatory and oxidative 

stress responses, and assess neuronal damage by biochemical and histological techniques to determine progressive neurodegenerative changes related to 

Alzheimer’s-like pathology.

 ■ A study to determine if exposure to aerosolized MWCNT induces lung cancer 

began in 2011.

 ■ For the MWCNT cancer study, gross lung tumor counts and tumor size will 

be evaluated, and some tumors will be excised for comparative genomic hybridization (CGH) and expression analysis.

 ■ A study to determine if exposure to aerosolized MWCNT induces mesothelioma is tentatively scheduled to begin in 2011.

Publications and Abstracts 

 ■ Porter DW, Wolfarth M, Chen TB, McKinney W, Hubbs AF, Battelli LA, 

Andrew ME, Frazer DG, Castranova V [2009]. Pulmonary toxicity of inhaled 

multi-walled carbon nanotubes. Toxicologist 108:457.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 117

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Sriram K, Porter DW, Jefferson AM, Lin GX, Wolfarth M, Chen TB, McKinney W, Frazer DG, Castranova V [2009]. Neuroinflammation and blood-brain 

barrier changes following exposure to engineered nanomaterials. Toxicologist 

108:458.

 ■ Wolfarth M, McKinney W, Chen TB, Castranova V, Porter DW [2011]. Acute 

pulmonary responses to MWCNT inhalation. Toxicologist 120:10.

 ■ Hubbs AM, Castranova V, Chen TB, Frazer DG, McKinney W, Mercer RR, 

Kashon ML, Battelli LA, Willard P, Porter DW [2011]. Pulmonary inflammation, epithelial hyperplasia, and lymph node translocation after multi-walled 

carbon nanotube inhalation. Toxicologist 120:11.

Invited Presentations

 ■ Sriram K [2010]. Central nervous system effects of pulmonary exposure to 

nanoparticles. NTRC 2010 Update, Wheeling, West Virginia, April 20.

 ■ Sriram K [2010]. Neurological risks of exposure to incidental and engineered 

nanoparticles. Presented at West Virginia University Center for Neuroscience, 

Morgantown, West Virginia, September 29. 

 ■ Porter DW [2011]. Introduction to nanotoxicology: an emerging field. Pittsburgh AIHA Local Section, Pittsburgh, Pennsylvania, April 6.

 ■ Hubbs AF, Mercer R, Sargent L, Castranova V, Sriram K, Battelli LA, Porter 

DW [2011]. Nanoparticulate pathology. The American College of Veterinary 

Pathologists 62nd Annual Meeting, Nashville, TN, December 3–7.
118 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 9: Pulmonary Toxicity of Metal Oxide 

Nanospheres and Nanowires

Principal Investigator: Dale W. Porter, PhD

Project Duration: FY 2007–2011

Critical Topic Area: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Developed and validated a biocompatible dispersion medium for use in nanotoxicology studies.

 ■ TiO2

 nanospheres (NS), short nanobelts (NB1), and long nanobelts (NB2) 

were synthesized and used in these studies.

 ■ Characterized physical (diameter, length, width) and crystal structure of the 

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.

 ■ In vitro, NB2 induced inflammasome activation and release of inflammatory 

cytokines through a cathepsin B-mediated mechanism.

 ■ Alveolar macrophages from MARCO null mice indicate that the MARCO 

receptor is involved in the binding and uptake of the NS but not NB1 or NB2.

 ■ All three TiO2

 nanoparticles caused some degree of lipid peroxidation and, in 

comparison with controls, caused significant increases in intracellular reactive 

oxygen species.

 ■ The in vitro studies indicate that relative toxicity of NS < NB1 < NB2.

 ■ In vivo studies were conducted in mice exposed by pharyngeal aspiration to 

0–30 μg/mouse to evaluate the effect of exposure to NS, NB1, and NB2 on the 

pulmonary and central nervous systems.

 ■ NB1 and NB2 induced dose- and time-dependent increases in pulmonary 

inflammation and damage.

 ■ By 28 days post-exposure, markers of pulmonary inflammation and damage 

had returned to control levels. 

 ■ Clearance of NS was greater than that of NB2 at 112 days post-exposure.

■ Histopathology studies determined that NB2 caused pulmonary fibrosis.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 119

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ The data also suggest that NB2, but not NS, activates the NALP3 

inflammasome.

 ■ Overall, in vivo studies indicated relative pulmonary toxicity of NS < NB1 < 

NB2. 

 ■ Elemental analyses of titanium in brain following pulmonary exposure to NS 

or NB2 determined that NB2, in particular, resulted in a transient translocation of elemental titanium to the brain.

 ■ NS, NB1, and NB2 (30-μg dose) induced subtle neuroinflammation in the 

striatum and hippocampus regions of the brain at 1 day post-exposure, as 

determined by the expression of inflammatory cytokine (IL1b) and chemokine (Cxcl2). No significant differences in the relative toxicities of the three 

nanoparticles were observed.

 ■ NS, NB1, and NB2 (30-μg dose) caused downregulation of endothelin 2 

(Edn2) at 1 day post-exposure that persisted through 112 days post-exposure, 

suggesting alterations in cerebral blood flow. 

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.

 ■ 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. Nanotoxicology 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.

 ■ Hamilton RF Jr, Wu N, Porter D, Buford M, Wolfarth M, Holian A [2009]. 

Particle length-dependent titanium dioxide nanomaterials’ toxicity and bioactivity. Particle Fibre Toxicol 6:35.

 ■ Sriram K, Porter DW, Jefferson AM, Lin GX, Wolfarth M, Chen TB, McKinney M, Frazer DG, Castranova V [2009]. Neuroinflammation and bloodbrain barrier changes following exposure to engineered nanomaterials. 

Toxicologist 108: 458.

 ■ Yang RS, Porter DW [2011]. Efficient design of biological experiments for 

dose-response modeling in toxicology studies. Toxicologist 120:102.
120 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Porter DW, Wolfarth MG, Wu N, Holian A, Hubbs A, Funk KA, Castranova 

V [2011]. Effect of engineered titanium dioxide nanoparticle shape on toxicity 

in vivo. Toxicologist 120:312.

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. 

 ■ Sriram K [2010]. Central nervous system effects of pulmonary exposure to 

nanoparticles. NTRC 2010 Update, Wheeling, West Virginia, April 20. 

 ■ Sriram K [2010]. Neurological risks of exposure to incidental and engineered 

nanoparticles. West Virginia University Center for Neuroscience, Morgantown, West Virginia, September 29. 

 ■ Porter DW [2011]. Introduction to nanotoxicology: an emerging field. Pittsburgh AIHA Local Section, Pittsburgh, Pennsylvania, April 6.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 121

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 10: WC-Co Nanoparticles in Initiating 

Angiogenesis by Reactive Oxygen 

Species

Principal Investigator: Min Ding, PhD

Project Duration: FY 2008–2011

Critical Topic Area: Toxicology and internal dose

Accomplishments and Research Findings

 ■ This project investigated the potential pulmonary carcinogenesis in response 

to tungsten carbide–cobalt (WC-Co) particles exposure, with cell culture and 

an animal model.

 ■ CEM assay showed that both fine particles and nanoparticles of WC-Co 

stimulate angiogenesis. 

 ■ 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-kB, and 

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

in nanoscale WC-Co, in comparison with fine-sized WC-Co at the same 

concentration.

Publications and Abstracts

 ■ Ding M, Kisin ER, Zhao J, Bowman L, Lu Y, Jiang B, Leonard S, Vallyathan 

V, Castranova V, Murray AR, Fadeel B, Shvedova AA [2009]. Size-dependent 

effects of tungsten carbide–cobalt particles on oxygen radical production and 

activation of cell signaling pathways in murine epidermal cells. Toxicol Appl 

Pharmacol 241(3):260–268. 

 ■ Zhang XD, Zhao J, Bowman L, Shi X, Castranova V, Ding M [2010]. Tungsten 

carbide–cobalt particles activate Nrf2 and its downstream target genes in JB6 

cells possibly by ROS generation. J Environ Pathol Toxicol Oncol 29(1):31–40. 

 ■ Shvedova AA, Kisin E, Murray A, Zhao J, Bowman LL, Lu Y, Jiang B, Leonard 

SS, Vallyathan V, Castranova V, Fadeel B, Ding M [2010]. Size-dependent effects of tungsten carbide–cobalt particles on induction of oxidative stress and 

activation of cell signaling pathways in vitro. Toxicologist 114(1):59.
122 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Invited Presentations

 ■ Ding M, Zhao JS, Bowman L, Leonard S, Lu YJ, Vallyathan V, Castranova V, 

Shvedova A [2008]. Induction of AP-1-MAPKs and NF-kB signal pathways 

by tungsten carbide–cobalt particles. Poster presentation at Society of Toxicology’s 47th Annual Meeting, Seattle, Washington, March 16–20.

 ■ Zhang X, Zhao J, Bowman L, Shi X, Castranova V, Ding M [2008]. Nano-sized 

tungsten carbide–cobalt particles induced Nrf2 signaling and phase ii enzyme 

activity. Poster presentation at 5th Conference on Molecular Mechanisms of 

Metal Toxicity and Carcinogenesis, Morgantown, West Virginia, September 

20–22.

 ■ Ding M, Zhang X-D, Zhao J-S, Bowman L, Shi X, Castranova V [2009]. 

Tungsten carbide–cobalt particles activate Nrf2 signaling pathway in JB6 cells. 

Presented at 4th International Conference on Oxidative/Nitrosative Stress and 

Disease, New York, New York, October 27–30.

 ■ Zhao J, Bowman L, Leonard S, Shi X, Castranova V, Ding M [2009]. Tungsten 

carbide–cobalt (WC-Co) induces apoptosis in JB6 cells by generation of ROS 

and FAS-FADD/mitochondrial signal pathways. 4th International Conference 

on Oxidative/Nitrosative Stress and Disease, New York, New York, October 

27–30.

 ■ Ding M, Zhao J, Bowman L, Castranova V, Jiang B-H [2010]. Tungsten carbide–cobalt nanoparticles induce angiogenesis through reactive oxygen species, AKT, ERK, and VEGF signal pathways. NTRC meeting, Olgebay, West 

Virginia, April 19–21.

 ■ Ding M, Liu L-Z, Castranova V, Shi X, Flynn D, Biang B-H [2010]. Tungsten 

carbide–cobalt nanoparticles induce AKT, ERK, AP-1, NF-kB, VEGF, and 

angiogenesis. 2010 Experimental Biology (EB) Meeting, Anaheim, California, 

April 23–28.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 123

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 11: Evaluation of the Pulmonary 

Deposition and Translocation

of Nanomaterials

Principal Investigator: Robert R. Mercer, PhD

Project Duration: FY 2006–2011

Critical Topic Area: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Found that aggregates of SWCNTS disperse when deposited in the lungs.

 ■ Demonstrated that diffuse interstitial fibrosis following exposure to SWCNTS 

is due to a dispersed submicron form of SWCNTS that had not yet been 

identified.

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

the inhalation of SWCNTS is similar to that produced by the aspiration of 

SWCNTS, a less costly and more feasible delivery method.

Lung tissue of the MWCNT-exposed mouse
124 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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 and identification of CNTs and other 

nanoparticles so that their potential translocation from the lungs to other 

organs can be studied. 

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

the inhalation of SWCNTS is similar to that produced by the aspiration of 

SWCNTS, a less costly and more feasible delivery method.

 ■ 2008 paper “Inhalation vs. Aspiration of Single-Walled Carbon Nanotubes in 

C57BL/6 Mice: Inflammation, Fibrosis, Oxidative Stress, and Mutagenesis” 

won the 2009 Alice Hamilton Award for Outstanding Scientific Paper

 ■ Demonstrated that MWCNT are transported to the pleura surface and subsequently determined the time course and persistence of MWCNT transport to 

the pleura. 

Publications and Abstracts

 ■ Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, 

Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini 

J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron 

P [2005]. Unusual inflammatory and fibrogenic pulmonary responses to 

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

289:698–708.

 ■ Kagan VE, Tyurina YY, Tyurin VA, Konduru NV, Potapovich AI, Osipov AN, 

Kisin ER, Schwegler-Berry D, Mercer RR, Castranova V, Shvedova AA [2006]. 

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

macrophages: role of Iron. Toxicol Lett 165:88–100.

 ■ Mercer RR, Scabilloni JF, Wang L, Schwegler-Berry D, Shvedova A, Castranova V [2007]. Dispersion significantly enhances the pulmonary toxicity of 

single walled carbon nanotubes. Toxicologist 96(1):231.

 ■ 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. Toxicologist 96(1):230.

 ■ 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 125

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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–L97.

 ■ 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.

 ■ Wang L, Rojanasakul Y, Castranova V, Qiu A, Lu Y, Scabilloni JF, Wu N, 

Mercer RR [2010]. Direct fibrogenic effects of dispersed single-walled carbon 

nanotubes on human lung fibroblasts. J Toxicol Environ Health A 73:410–422.

 ■ Porter DW, Hubbs AF, Mercer RR, Wu N, Wolfarth MG, Sriram K, Leonard 

SS, Battelli L, Schwegler-Berry D, Friend S, Andrew M, Chen BT, Tsuroka 

S, Endo M, Castranova V [2010]. Mouse pulmonary dose and time course 

responses induced by exposure to multi-walled carbon nanotubes. Toxicology 

269:136–147.

 ■ Ma JY, Zhao H, Mercer RR, Barger M, Murali R, Meighan T, Schwegler-Berry 

D, Castranova V, Ma JK [2011]. Cerium oxide nanoparticles–induced pulmonary inflammation and alveolar macrophage functional change in rats. 

Nanotechnology 5(3):312–325.

 ■ Wang L, Castranova V, Mishra A, Chen B, Mercer RR, Schwegler-Berry B, 

Rojanasakul Y [2010]. Dispersion of single-walled carbon nanotubes by a 

natural lung surfactant for pulmonary in vitro and in vivo toxicity studies. 

Part Fibre Toxicol (Epub) 7:31.

 ■ Mercer RR, Hubbs AF, Scabilloni JF, Wang LY, Battelli LA, Schwegler-Berry D, 

Castranova V, Porter D [2010]. Distribution and persistence of pleural penetrations by multi-walled carbon nanotubes. Part Fibre Toxicol (Epub) 7:28.

 ■ Hubbs AF, Mercer R, Benkovic S, Harkema J, Sriram K, Schwegler-Berry DE, 

Goravanahally M, Nurkiewicz T, Castranova V, Sargent L [2011]. Nanotoxicology, a pathologist‘s perspective. Toxicol Pathol 39(2):301–324.

 ■ Pacurari M, Schwegler-Berry D, Friend S, Leonard SS, Mercer RR, Vallyathan V, Castranova V [2011]. Raw single-walled carbon nanotube–induced 

cytotoxic effects in human bronchial epithelial cells: comparison to asbestos. 

Toxicological Environ Chem 93:1045–1072.
126 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Mercer RR, Hubbs AF, Scabilloni JF, Wang LY, Battelli LA, Friend S, Castranova 

V, Porter DW [2011]. Pulmonary fibrotic response to aspiration of multiwalled carbon nanotubes. Part Fibre Toxicol (Epub) 8:21.

 ■ Castranova V, Mercer RR [2011]. Responses to pulmonary exposure to carbon nanotubes. In: Donaldson, Duffin, Bonner, Poland, eds. The toxicology of 

carbon nanotubes. New York, NY: Cambridge University Press, pp. 1–22.

Invited Presentations

 ■ Mercer RR [2007]. Inhalation toxicology of SWCNTS. 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.

 ■ Mercer RR, Scabilloni JF, Wang L, Battelli LA, Castranova V [2009]. Use 

of labeled single walled carbon nanotubes to study translocation from the 

lungs. Society of Toxicology, Baltimore, Maryland, March 16. Toxicologist 

108(S-1):A2192. 

 ■ Mercer RR, Hubbs AF, Scabilloni JF, Wang L, Castranova V, Porter D [2010]. 

Distribution and persistence of pleural penetrations by multi-walled carbon 

nanotubes. American Thoracic Society, New Orleans, Louisiana, May 16. Am 

J Respir Crit Care Med 181:A3102.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 127

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 12: Occupational Exposures and 

Potential Neurological Risks

Principal Investigator: Krishnan Sriram, PhD 

Project Duration: FY 2008–2012

Critical Topic Area: Toxicology and internal dose

Accomplishments and Research Findings

1. Welding fumes study

 ■ Repeated-dose (1/week x 28 weeks) pulmonary exposures to fumes generated 

by gas metal arc–mild steel (GMA-MS) and manual metal arc–hardsurfacing 

(MMA-HS) welding have been completed. 

 ■ Demonstrated that repeated pulmonary exposure to GMA-MS or MMA-HS 

welding fumes caused loss of tyrosine hydroxylase protein, a marker of dopaminergic neurons.

 ■ Demonstrated that repeated pulmonary exposure to GMA-MS or MMA-HS 

welding fumes altered the expression of specific Parkinson’s disease (PD)–related (Park) proteins, loss-of-function mutations of which have been linked to 

familial forms of PD. As there is a concern that welding fume exposure may 

accelerate the onset of Parkinsonism among welders, the current findings may 

provide early clues to the pathogenesis of the disease. Further, as the loss of 

these Park proteins preceded any observable neurobehavioral or neuropathological abnormalities, their utility as early predictors (biomarkers) of welding 

fume–associated dopaminergic dysfunction is promising.

 ■ The study demonstrating the role of Park genes in the neurological effects of 

welding fumes won the 2011 Alice Hamilton Award in the Biological Sciences 

Category and was also nominated for the 2011 Charles Shepard Award.

 ■ The work on the role of Park genes in the neurological effects of welding 

fumes was highlighted in Science News magazine’s feature article, entitled 

Destination Brain: Inhaled Pollutants May Inflame More Than the Lungs (May 

22, 2010;177(11):16), and in a feature article entitled Dirty Minds, published 

by the Australian science magazine COSMOS (March 2011:37) http://www.

cosmosmagazine.com/features/print/4268/dirty-minds. 

 ■ Demonstrated that following repeated pulmonary exposure to welding fumes, 

Mn levels in the nails appeared to specifically reflect the pattern of accumulation in the brain but not the lung, liver, heart, or kidney. These findings suggest that nail Mn has the potential to be a sensitive and reliable biomarker for 

WF-related manganese intoxication and neurotoxicity. 
128 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Short-term inhalation exposure (5d/week x 2 weeks) to gas metal arc–Stainless Steel (GMA-SS) under regular voltage (RVSS; 25V) and high voltage 

(HVSS; 30V) conditions has been studied.

 ■ Demonstrated that short-term inhalation exposure to GMA-SS fumes generated at high voltage (HVSS) fails to elicit a neurotoxic response compared to 

that generated at regular voltage (RVSS). The lack of neurotoxicity was linked 

to the reduced solubility of Mn in the HVSS fumes.

 ■ Three important findings have emerged from ongoing neurotoxicology 

studies conducted with the welding fumes. First, our findings of the involvement of Park genes in the neurotoxicity of welding fumes provides scope 

for evaluating these factors as potential biomarkers of adverse welding fume 

exposures. Second, our findings of the lack of neurotoxicity of GMA-SS fumes 

upon altering process conditions, i.e., high voltage, suggest that simple modifications of process parameters may alter the fume profile and thereby its toxicological properties. As welding process conditions can be easily controlled at 

the workplace, such efforts may contribute to prevention of adverse exposures 

and associated neurological risks. Third, our findings that accumulation of 

Mn in nails selectively reflects the pattern of brain Mn accumulation, but not 

Mn accumulation in other organs, suggest that nail can serve as a reliable surrogate to monitor WF-related manganese intoxication and neurotoxicity.

2. Carbon nanotubes study

 ■ Single-dose pulmonary exposure (pharyngeal aspiration) to MWCNT has been 

completed. Dose-response and time-course studies have been completed. 

 ■ Pulmonary exposure to MWCNT altered the expression of several bloodbrain barrier (BBB) and glial-related markers suggestive of BBB dysfunction. 

 ■ Pulmonary exposure to MWCNT increased hippocampal beta-amyloid 

(Abeta) protein content and caused hyper-phosphorylation of hippocampal 

Tau protein, indicative of Alzheimer’s disease–like neuronal abnormality. 

 ■ Pulmonary exposure to MWCNT altered the expression of several AD-related 

genes in the hippocampus, consistent with the increased expression of Abeta 

and hyper-phosphorylation of Tau in this region.

 ■ Short-term whole-body inhalation exposures (2, 4, 8, and 12 days) to MWCNT aerosol have been completed.

 ■ Demonstrated that short-term whole-body inhalation exposure to MWCNT 

elicited neuroinflammation in the olfactory bulb and hippocampus, findings 

consistent with observations following pulmonary (pharyngeal aspiration) 

exposure. 

 ■ Post-exposure recovery studies (up to 48 weeks post-exposure) to determine the persistence or progression of MWCNT-mediated neurotoxicity 

is ongoing.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 129

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ An important finding that has emerged is that exposure to multi-walled 

carbon nanotubes (MWCNT) may pose a neurological risk, causing Alzheimer’slike cellular/molecular aberrations that could potentially culminate in neurodegeneration. These findings call for extensive safety evaluation of carbonbased engineered nanomaterials to avert adverse human health effects.

3. Titanium dioxide study

 ■ Single-dose pulmonary exposures (pharyngeal aspiration) to nanosphere 

titanium dioxide and nanowire titanium dioxide have been completed. Brain 

samples from dose-response (7.5–30 μg) and time-course (1–112 days postexposure) studies have been collected.

 ■ Elemental analyses of titanium in lung and brain following pulmonary exposure to nanosphere titanium dioxide and nanowire titanium dioxide have 

been completed.

 ■ Determined that pulmonary exposure to nanowire titanium dioxide, in particular, resulted in a transient translocation of elemental titanium to the brain.

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, North Carolina, 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 profiles. Society of 

Toxicology Annual Meeting, Seattle, Washington, 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, Washington, 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 multi-walled carbon nanotubes. Vet Pathol 45:786.

 ■ Antonini JM, Sriram K, Benkovic SA, Roberts JR, Stone S, Chen BT, 

Schwegler-Berry D, Jefferson AM, Billig BK, Felton CM, Hammer MA, Ma 

F, Frazer DG, O’Callaghan JP, Miller DB [2009]. Mild steel welding fume 
130 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

causes manganese accumulation and subtle neuroinflammatory changes but 

not overt neuronal damage in discrete brain regions of rats after short-term 

inhalation exposure. Neurotoxicology 30:915–925.

 ■ Hubbs A, Mercer RR, Coad JE, Battelli LA, Willard PA, Sriram K, Wolfarth 

M, Castranova V, Porter DW [2009]. Persistent pulmonary inflammation, airway mucous metaplasia and migration of multiwalled carbon nanotubes from 

the lung after subchronic exposure. Toxicologist 108(1):457. 

 ■ Sriram K, Porter DW, Jefferson AM, Lin GX, Wolfarth MG, Chen BT, McKinney 

W, Frazer DG, Castranova V [2009]. Neuroinflammation and blood-brain barrier 

changes following exposure to engineered nanomaterials. Toxicologist 108(1):458. 

 ■ Sriram K, Lin GX, Jefferson AM, Wirth O, Hayashi Y, Roberts JR, Chapman 

RS, Krajnak KM, Antonini JM [2009]. Welding fume–related dopaminergic 

neurotoxicity. Parkinsonism & Related Disorders 15(2):S162.

 ■ Sriram K, Lin GX, Jefferson AM, Roberts JR, Stone S, Chen BT, Frazer DG, 

Soukup JM, Ghio AJ, Antonini JM [2009]. Dopaminergic neurotoxicity 

following exposure to manganese-containing welding fumes. Program No. 

154.26. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience (Online). 

 ■ Sriram K, Lin GX, Jefferson AM, Roberts JR, Chapman RS, Chen BT, Soukup 

JM, Ghio AJ, Antonini JM [2010]. Dopaminergic neurotoxicity following 

pulmonary exposure to manganese-containing welding fumes. Arch Toxicol 

84(7):521–540.

 ■ Sriram K, Lin GX, Jefferson AM, Roberts JR, Wirth O, Hayashi Y, Krajnak 

KM, Soukup JM, Ghio AJ, Reynolds SH, Castranova V, Munson AE, Antonini 

JM [2010]. Mitochondrial dysfunction and loss of Parkinson’s disease-linked 

proteins contribute to neurotoxicity of manganese-containing welding fumes. 

FASEB J 24:4989–5002.

 ■ Antonini JM, Roberts JR, Chapman R, Soukup JM, Ghio AJ, Sriram K [2010]. 

Pulmonary toxicity and extrapulmonary tissue distribution of metals after 

repeated exposure to different welding fumes. Inhal Toxicol 22(10):805–816.

 ■ Porter DW, Hubbs AF, Wu N, Wolfarth MG, Mercer R, Sriram K, Leonard 

S, Battelli L, Schwegler-Berry D, Friend S, Andrew M, Castranova V [2010]. 

Mouse pulmonary dose- and time-course responses induced by exposure to 

multi-walled carbon nanotubes. Toxicology 269:136–147.

 ■ Antonini JM, Chen BT, Stone S, Roberts JR, Schwegler-Berry D, Chapman R, 

Moseley A, Cumpston JL, Leonard H, Keane M, Frazer DG, Sriram K [2010]. 

Alterations in welding process parameters change particle characteristics and 

influence lung responses. Am J Respir Crit Care Med 181:A1746.

 ■ Antonini JM, Roberts JR, Sriram K. Nail manganese as a biomarker of welding fume exposure [2011]. 50th Annual Meeting of the Society of Toxicologists, Washington DC, March 7–12. Toxicologist 120(Suppl 2):499.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 131

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Antonini JM, Keane M, Chen BT, Stone S, Roberts JR, Schwegler-Berry D, 

Andrews RN, Frazer DG, Sriram K [2011]. Alterations in welding process 

voltage affect the generation of ultrafine particles, fume composition, and 

pulmonary toxicity. Nanotoxicology 5(4):700–710.

 ■ Sriram K, Lin GX, Jefferson AM, Roberts JR, Andrews RN, Kashon ML, Antonini JM [2012].  Manganese accumulation in nail clippings as a biomarker 

of welding fume exposure and neurotoxicity. Toxicology 291(1–3):73–82.

Invited Presentations 

 ■ Sriram K [2010]. Dopaminergic neurotoxicity following exposure to manganese-containing welding fumes. Neurological responses after exposure to 

inhaled metal particles [symposium], 49th Annual Meeting of the Society of 

Toxicology, Salt Lake City, Utah, March 08. 

 ■ Sriram K [2010]. Central nervous system effects of pulmonary exposure to 

nanoparticles. Invited talk at the NIOSH NTRC 2010 Update, Wheeling, West 

Virginia, April 20.

 ■ Sriram K [2010]. Neurological risks of exposure to incidental and engineered 

nanoparticles. Invited talk at the Center for Neuroscience, West Virginia University, Morgantown, West Virginia, September 29. 
132 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 13: Lung Effects of Resistance Spot 

Welding with Adhesives

Principal Investigator: James Antonini, PhD

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.

 ■ Completed construction of the resistance spot welding generator.

 ■ Characterized the physical and chemical properties of aerosols generated 

after heating.

 ■ Completed short-term animal exposure study.

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, Washington, March 16–20. Toxicologist 102:226.

 ■ Afshari AA, Chen BT, Schwegler-Berry D, Cumpston MJ, Cumpston A, Leonard D, Friend S, Zeidler-Erdely PC, Frazer DG, Antonini JM [2011]. Characterization of welding aerosols generated by resistance spot welding. Society 

of Toxicology Annual Meeting, Washington, DC, March 8–10. Toxicologist 

120:120–121.

 ■ Zeidler-Erdely PC, Afshari AA, Meighan TG, McKinney W, Chen BT, Schwegler-Berry D, Jackson M, Cumpston A, Cumpston JL, Leonard HD, Erdely 

A, Frazer DG, Antonini JM [2012]. Pulmonary responses after inhalation of 

resistance spot welding fume using adhesives. Society of Toxicology Annual 

Meeting, San Francisco, California, March 2012. Toxicologist 126(1):226–227.

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, Nevada, September 24.

 ■ Antonini J [2009]. Health effects of welding. American Industrial Hygiene Association Annual Meeting: AIHce 2009, Toronto, Ontario, June 2. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 133

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 14: Neurotoxicity after Pulmonary 

Exposure to Welding Fumes

Principal Investigator: James Antonini, PhD

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 fumes (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 regions.

 ■ Observed molecular alterations in inflammatory mediators, impairment of 

mitochondrial function, loss of tyrosine hydroxylase, and altered expression 

of different Parkin (Park2, Park5, and Park7) genes in dopaminergic brain 

areas after repeated exposure to welding fumes.

 ■ Recognized by CDC Charles C. Shepard Science Award, 2011; Honorable 

Mention, Laboratory and Methods Category: Sriram K, Lin GX, Jefferson 

AM, Roberts JR, Wirth O, Hayashi Y, Krajnak KM, Soukup JM, Ghio AJ, 

Reynolds SH, Castranova V, Munson AE, Antonini JM [2010]. Mitochondrial 

dysfunction and loss of Parkinson’s disease–linked proteins contribute to neurotoxicity of manganese-containing welding fumes. FASEB J 24:4989–5002.

 ■ Received the NIOSH Alice Hamilton Award, 2011; Best Paper, Biological Science Category: Sriram K, Lin GX, Jefferson AM, Roberts JR, Wirth O, Hayashi Y, Krajnak KM, Soukup JM, Ghio AJ, Reynolds SH, Castranova V, Munson 

AE, Antonini JM [2010]. Mitochondrial dysfunction and loss of Parkinson’s 

disease–linked proteins contribute to neurotoxicity of manganese-containing 

welding fumes. FASEB J 24:4989–5002.

 ■ Received the NIOSH Alice Hamilton Award, 2011; Honorable Mention, 

Best Paper, Biological Science Category: Leonard SS, Chen BT, Stone SG, 

Schwegler-Berry D, Kenyon AJ, Frazer, DG, Antonini JM [2010]. Comparison 

of stainless and mild steel welding fumes in generation of reactive oxygen species. Particle Fibre Toxicol 7:32.
134 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Publications and Abstracts

 ■ Antonini JM, Taylor MD, Zimmer AT, Robert JR [2004]. Pulmonary responses to welding fumes: role of metal constituents. J Toxicol Environ Health 

67:233–249.

 ■ Antonini JM, Taylor MD, Millecchia L, Ebeling AR, Robert JR [2004]. Suppression in lung defense responses after bacterial infection in rats pretreated 

with different welding fumes. Toxicol Appl Pharmacol 200:206–218.

 ■ Antonini JM, Leonard SS, Robert JR, Solano-Lopez C, Young S-H, Shi X, 

Taylor MD [2005]. Effect of stainless steel manual metal arc welding fume 

on free radical production, DNA damage, and apoptosis induction. Mol Cell 

Biochem 279:17–23.

 ■ Antonini JM, Afshari AAA, Stone S, Chen B, Schwegler-Berry D, Fletcher 

WG, Goldsmith WT, Vandestouwe KH, McKinney W, Castranova, V, Frazer 

DG [2006]. Design, construction, and characterization of a novel robotic 

welding fume generation and inhalation exposure system for laboratory animals. J Occup Environ Hyg 3:194–203.

 ■ Antonini JM, Santamaria A, Jenkins NT, Albini E, Lucchini R [2006]. Fate of 

manganese associated with the inhalation of welding fumes: potential neurological effects. Neurotoxicology 27:304–310.

 ■ Antonini JM, O’Callaghan JP, Miller DB, Miller DB [2006]. Development of 

an animal model to study potential neurotoxic effects associated with welding 

fume inhalation. Neurotoxicology 27(5):745–751.

 ■ Santamaria AB, Cushing CA, Antonini JM, Finley BL, Mowat FS [2007]. Potential neurological effects of manganese exposure during welding: a state-ofthe-science analysis. J Toxicol Environ Health 10(6):417–465.

 ■ Solano-Lopez C, Zeidler-Erdely PC, Hubbs AF, Reynolds SH, Roberts JR, 

Taylor MD, Young S-H, Castranova V, Antonini JM [2006]. Welding fume 

exposure and associated inflammatory and hyperplastic changes in the lungs 

of tumor susceptible A/J Mice. Toxicol Pathol 34(4):364–372.

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

welding processes. Toxicologist 91(1):216. 

 ■ Zeidler-Erdely PC, Young S-H, Roberts JR, Antonini JM [2007]. Acute lung 

inflammatory response following pharyngeal aspiration of stainless steel 

welding fume or soluble chromium in A/J and C57Bl/6J mice. Toxicologist 

96(1):224. 

 ■ Santamaria AB, Cushing CA, Antonini JM, Finley BL, Mowat FS [2007]. Potential neurological effects of manganese exposure during welding: a state-ofthe-science analysis. J Toxicol Environ Health 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 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 135

APPENDIX A | A Summary of 69 NIOSH Research Projects

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 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, Washington, 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.

 ■ Antonini JM, Schwegler-Berry D, Stone S, Chen TB, Zeidler-Erdely PC, 

Frazer DG, Roberts JR [2009]. Comparison of the persistence of deposited 

particles and the inflammatory potential of stainless steel versus mild steel 

welding fume in rat lungs after inhalation. Society of Toxicology Annual 

Meeting, Baltimore, Maryland, March 15. Toxicologist 108:329.

 ■ Zeidler-Erdely PC, Kashon ML, Li S, Antonini JM [2009]. Microarray analysis 

of the pulmonary effects of stainless and mild steel welding fumes in A/J and 

C57BL/6J mice. Society of Toxicology Annual Meeting, Baltimore, Maryland, 

March 15. Toxicologist 108:325.

 ■ Sriram K, Lin GX, Jefferson AM, Roberts JR, Stone S, Chen TB, Frazer DG, 

Soukup JM, Ghio AJ, Antonini JM [2009]. Dopaminergic neurotoxicity following exposure to manganese-containing welding fumes. Program No. 154.26. 

Society for Neuroscience Annual Meeting, Chicago, Illinois, October 20. 

 ■ Sriram K, Lin GX, Jefferson AM, Wirth O, Hayashi Y, Roberts JR, Chapman 

RS, Krajnak KM, Antonini JM [2009]. Welding fume–related dopaminergic neurotoxicity. XVIII WFN World Congress on Parkinson’s Disease and 

Related Disorders, Miami, Florida, December 13. Parkinsonism & Related 

Disorders 15(2):S162.
136 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Antonini JM, Roberts JR, Stone S, Chen BT, Schwegler-Berry D, Frazer DG 

[2009]. Short-term inhalation exposure to mild steel welding fume had no 

effect on lung inflammation and injury but did alter defense responses to 

bacteria in rats. Inhal Toxicol 21:182–192.

 ■ Keane M, Stone S, Chen BT, Slaven J, Schwegler-Berry D, Antonini JM [2009]. 

Hexavalent chromium content in stainless steel welding fumes is dependent 

on the welding process and shield gas type. J Environ Monitoring 11:418–424.

 ■ Antonini JM, Sriram K, Benkovic SA, Roberts JR, Stone S, Chen BT, Schwegler-Berry D, Jefferson AM, Billig BK, Felton CM, Hammer MA, Ma F, Frazer 

DG, O’Callaghan JP, Miller DB [2009]. Mild steel welding fume causes manganese accumulation and subtle neuroinflammatory changes but not overt 

neuronal damage in discrete brain regions of rats after short-term inhalation 

exposure. Neurotoxicology 30:915–925.

 ■ Erdely A, Zeidler-Erdely PC, Liston A, Salmen-Muniz R, Hulderman T, 

Antonini JM, Simeonova PP [2010]. Acute systemic inflammation to welding 

fume: comparison of various types. Society of Toxicology Annual Meeting, 

Salt Lake City, Utah, March 15. Toxicologist 114:463.

 ■ Antonini JM, Chen BT, Stone S, Roberts JR, Schwegler-Berry D, Chapman R, 

Moseley A, Cumpston JL, Leonard H, Frazer DG, Keane M, Sriram K [2010]. 

Alterations in welding process parameters change particle characteristics and 

influence lung responses. American Thoracic Society International Conference, New Orleans, LA, May 14. Am J Respir Crit Care Med 181:A1746.

 ■ Erdely A, Hulderman T, Zeidler-Erdely PC, Liston A, Salmen-Muniz R, Stone 

S, Chen BT, Frazer DG, Antonini JM, Simeonova PP [2010]. Effects of inhalation of gas metal arc–stainless steel welding fume on systemic inflammation 

and atherosclerosis. American Thoracic Society International Conference, 

New Orleans, LA, May 14. Am J Respir Crit Care Med 181:A1754.

 ■ Zeidler-Erdely PC, Li S, Kashon ML, Antonini JM [2010]. Response of the 

mouse lung transcriptome to welding fume: effects of stainless and mild steel 

fumes on lung gene expression in A/J and C57 BL/6J mice. Resp Res 11:70.

 ■ Sriram K, Lin, GX, Jefferson AM, Roberts JR, Chapman RS, Soukup JM, Ghio 

AJ, Chen BT, Antonini JM [2010]. Dopaminergic neurotoxicity following 

pulmonary exposure to manganese-containing welding fumes. Arch Toxicol 

84:521–540.

 ■ Antonini JM, Roberts JR, Chapman R, Soukup JM, Ghio AJ, Sriram K [2010]. 

Pulmonary toxicity and extrapulmonary tissue distribution of metals after 

repeated exposure to different welding fumes. Inhal Toxicol 22:805–816.

 ■ Sriram K, Lin GX, Jefferson AM, Roberts JR, Wirth O, Hayashi Y, Krajnak 

KM, Soukup JM, Ghio AJ, Reynolds SH, Castranova V, Munson AE, Antonini 

JM [2010]. Mitochondrial dysfunction and loss of Parkinson’s disease–linked 

proteins contribute to neurotoxicity of manganese-containing welding fumes. 

FASEB J 24:4989–5002.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 137

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Leonard SS, Chen BT, Stone SG, Schwegler-Berry D, Kenyon AJ, Frazer, DG, 

Antonini JM [2010]. Comparison of stainless and mild steel welding fumes in 

generation of reactive oxygen species. Particle Fibre Toxicol 7:32.

 ■ Antonini JM, Roberts JR, Stone S, Chen BT, Schwegler-Berry D, Chapman R, 

Zeidler-Erdely PC, Andrews RN, Frazer DG [2011]. Persistence of deposited 

metals in the lungs after stainless steel and mild steel welding fume inhalation 

in rats. Arch Toxicol 85:487–498.

 ■ Antonini JM, Keane M, Chen BT, Stone S, Roberts JR, Schwegler-Berry D, 

Andrews RN, Frazer DG, Sriram K [2011]. Alterations in welding process 

voltage affect the generation of ultrafine particles, fume composition, and 

pulmonary toxicity. Nanotoxicology 5:700–710.

Invited Presentations

 ■ Antonini J [2008]. Manganese exposure during welding. Institute of Occupational and Environmental Health, West Virginia University, Morgantown, 

West Virginia, Occupational Medicine Grand Rounds Seminar, March 4. 

 ■ Antonini J [2008]. Health effects of welding. American Industrial Hygiene 

Association conference and exposition AIHce 2008, Minneapolis, Minnesota, 

May 31–June 5. 

 ■ Antonini J [2009]. Hexavalent chromium carcinogenesis, welding exposure 

assessments, and epidemiology studies. American Industrial Hygiene Association Annual Meeting: AIHce 2009, Toronto, Ontario, May 30–June 4.

 ■ Antonini J [2010]. Neurological responses after exposure to inhaled metal particles 49th Society of Toxicology Annual Meeting, Salt Lake City, Utah, March 15.

 ■ Antonini J [2011]. Health effects of welders. American Industrial Hygiene Association Annual Meeting: AIHce 2011, Portland, Oregon, May 15–19.
138 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 15: Welding Fumes and

Cardiovascular Dysfunction

Principle Investigator: Hong Kan

Project Duration: FY 2010–2013

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings 

Our laboratory utilized novel animal and in vitro models to assess the short- and 

long-term effects of pulmonary exposure to nano-sized particles produced from industrial and occupational settings. 

Pulmonary exposure to ultrafine titanium dioxide (UFTiO2

) or intratracheal instillation of welding fumes can cause either biological or functional changes in rat hearts, 

which include the following: 

 ■ Alteration in cytokine gene expressions in the heart (welding fumes).

 ■ Change in phosphorylation status of cardiac regulatory proteins (UFTiO2

 and 

welding fumes).

 ■ More prone to heart arrhythmias under stress condition (UFTiO2

 and welding fumes).

 ■ Reduction in contractile function of the heart (welding fumes).

 ■ Increase in synthesis of neurotransmitter substance P in nodose ganglia, 

which is involved in the integration and control of lung and heart function 

(UFTiO2

).

UFTiO2

- and welding fume–induced biological and functional changes in the heart 

that we observed in our study are often associated with heart failure or other cardiovascular dysfunctions. Our findings suggest that workers exposed to nanoparticles 

might have a higher risk of developing cardiovascular disease. 

Publications and Abstracts 

 ■ Hong K [2011]. Nanoparticle inhalation enhances cardiac protein phosphorylation and neurotransmitter synthesis in the nodose ganglia of rats (Abstract 

submitted to SOT 2012).
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 139

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 16: Potential Aneuploidy Following 

Exposure to Carbon Nanotubes

Principal Investigator: Linda Sargent, PhD

Project Duration: FY 2007–2011

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 single-walled carbon nanotubes (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 with fluorescent and confocal laser scanning microscopy. The chromosome number was examined by fluorescent in situ hybridization (FISH).

 ■ Binucleate cells, large polyploid appearing nuclei, bundled tubulin, and fragmented centrosomes were observed following 24 hours of exposure to either 

SWCNTs or vanadium pentoxide.

 ■ The SWCNT-treated cells were further examined by FISH, with 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), SWCNTs were observed to be inside the cells. DIC 

combined with fluorescent confocal laser imaging showed that many of the 

cells had SWCNTs in the nucleus and within the cellular and mitotic tubulin. 

Some of the binucleate cells appeared to be connected by SWCNTs. CNTs in 

the mitotic spindle appear to distort the mitotic spindle apparatus. This damage was seen even at the lowest dose (24 μg/cm3

). 

 ■ In vitro genotoxicity of SWCNTs:

 — Exposure to multi-walled carbon nanotubes (MWCNTs) and SWCNTs has 

been shown to result in hypertrophied epithelial cells, macrophages without nuclei, and mutations in K-ras, indicating potential genotoxicity. 

A study by Sargent et al. in 2009 showed that SWCNT exposure resulted in fragmenting of the mitotic spindle pole (centrosome) as well as gross errors in chromosome 

number. The study further demonstrated a close association of SWCNTs with the 

centrosome, the DNA, and the microtubules of the mitotic spindle. The nanosized 

particles appeared to be incorporated into the mitotic spindle, resulting in a dramatic 
140 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

disruption of the spindle apparatus and aneuploidy. This research proposed a new 

mechanism of genotoxicity. 

 ■ Received the 2010 Charles C. Shepard Science Award nomination for outstanding scientific paper, Induction of Aneuploidy by Single-Walled Carbon 

Nanotubes.

 ■ In vitro dose response and time course:

 — Demonstrated that SWCNT exposure results in multipolar mitotic spindles 

at realistic occupational exposure levels. The nanotubes were incorporated 

into the DNA, the microtubules, and the centrosome. Cell cycle analysis demonstrated a block in the G2 phase of the cell cycle. Analysis of the 

chromosome changes (either loss or gain of chromosome 1 or 4) demonstrated that the aneuploidy was randomly distributed between alterations of 

chromosome 1 or chromosome 4. The aneuploid population was attributed 

to both losses and gains of chromosome 1 and 4. The SWCNT-treated cells 

exhibit a statistically significant higher percentage of the G2/M population 

than in the PBS-treated control cells, indicating a G2 block in the cell cycle.

 ■ Comparison of in vitro genotoxicity of MWCNTs and SWCNTs:

 — The MWCNT exposure results in predominantly monopolar mitotic spindles. 

The MWCNTs associate with the microtubules and the DNA and fragment the 

centrosomes similar to SWCNTs. By contrast, however, the MWCNT-exposed, 

fragmented centrosomes cluster to organize a single pole. These data indicate 

that both nanotubes associate with mitotic structures; however, the difference in 

the spindle morphology following exposure suggests a difference in the inhibition of the cell motors. 

Multi-walled carbon nanotubes in cells and tissue
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APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ In vivo dose response of genotoxicity:

 — BALB/c X C57Bl/6 hybrid mice have been bred to BALB/c mice for 5 generations. The GFP-centrin BALB-c mice are intermediate in their proliferative response, which is a distinct advantage for cytogenetic studies requiring proliferating cells.

GFP-centrin/Balb/c mice have been exposed to SWCNTs (40 mg/mouse) and the 

positive control vanadium pentoxide. The lungs have been perfused, the Type II cells 

have been separated and cultured, and the proliferating cells have been prepared for 

analysis of the mitotic spindle and the chromosome number. The advantage of the 

GFP-centrin transgenic mouse is that the centrosome damage can be seen without 

staining. It is a rapid in vivo test of the integrity of the centrosome.

Publications and Abstracts

 ■ Sargent L, Shvedova AA, Hubbs AF, Lowry DT, Kashon ML, Murray AR, 

Kisin E, Benkovic S, Miller D, McKinstry KA, Reynolds SH [2009]. Induction of aneuploidy by single walled carbon nanotubes [abstract]. Toxicologist 

108(1):411, A1979. 

 ■ Sargent LM, Shvedova AA, Hubbs AF, Kashon ML, Salisbury JL, Lowry DT, 

Murray A, Kisin E, Friend S, Benkovic S, McKinstry KA, Battelli LA, Reynolds S [2009]. Induction of aneuploidy by single walled carbon nanotubes. 

Environ Mol Mutagen 50(8):708–717. 

 ■ Dinu CZ , Mohanraj B, Schiele NR, Sargent LM, Corr DT, Chrisey DB [2010]. 

Real-time detection of carbon nanotube cytoxicity using electric cell-impedance sensing [abstract]. Presented (by collaborator) at the European Materials 

Research Society 2010 Meeting on Functional Biointerfaces in Strasbourg, 

France, June 7–11. 

 ■ Sargent LM, Hubbs AF, Shvedova AA, Kashon ML, Salisbury JL, Lowry DT, 

Murray A, Kisin E, Benkovic S, McKinstry KA, Reynolds SH [2010]. Induction of mitotic spindle aberrations by occupationally relevant doses of single 

walled carbon nanotubes [abstract]. Toxicologist 114(1):170, A799. 

 ■ Sargent L, Reynolds S, Castranova V [2010]. Potential pulmonary effects of 

engineered carbon nanotubes: In vitro genotoxic effects. Nanotoxicology 

4:396–408. 

 ■ Hubbs AF, Mercer R, Benkovic S, Harkema J, Sriram K, Schwegler-Berry DE, 

Gorvavanahally M, Nurkiewicz T, Castranvoa V, Sargent LM [2011]. Nanotoxicology, a pathologist’s perspective. Toxicol Patholog 39(2):301–324.

 ■ Kisin E, Murray AR, Sargent L, Lowry DT, Siegrist KJ, Chirila M, SchweglerBerry DE, Leonard SS, Castranova V, Fadeel B, Kagan VE, Shvedova AA 

[2011]. Comparative genotoxicity of fibrous particles: carbon nanofibers, 

single-walled carbon nanotubes and asbestos [abstract]. Toxicologist 120(2):2.
142 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Kisin ER, Murray, AR, Sargent L, Lowry D, Chirila M, Siegrist KJ, Schewegler-Berry D, Leonard S, Castranova V, Fadeel B, Kagan VE and Shvedova 

AA [2011]. Genotoxicity of carbon nanofibers: are they potentially more or 

less dangerous than carbon nanotubes or asbestos? Toxicol Appl Pharmacol 

252(April 1):1–10.

 ■ Sargent LM , Reynolds SH, Benkovic SA, Lowry DT, Kashon ML, Hubbs AF, 

Mastovich J, Siegrist KJ, Chrisey DB, Dinu DZ [2011]. Understanding carbon 

nanotube genotoxicity. Toxicologist 120(2):11–12. 

 ■ Archer-Hartmann SA, Sargent LM, Lowry D, Holland LA [2011]. Microscale 

enzymatic and lectin classification of glycans with phospholipid assisted capillary electrophoresis separations. Analytical Chem 83(7):2740–2747. 

 ■ Sargent LM, Young S-H, Hubbs AF, Benkovic SA, Shvedova AA, Salisbury JL , 

Kashon ML, Lowry DT, Murray AR, Kisin ER, Mckinstry KT, Batelli L, Steven 

H Reynolds [2011]. Multi-polar mitotic spindle disruption and aneuploidy at 

occupationally relevant doses of single-walled-carbon nanotubes. Mutation 

Res (in press). 

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, Ohio, 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 on Cancer, February 12.

 ■ Sargent LM [2009]. Induction of aneuploidy by single walled carbon nanotubes. 

Society of Toxicology Annual Meeting, Baltimore, Maryland, March 15–19. 

 ■ Dinu CZ, Lowry DT, Chrisey DB, Sargent LM [2010]. Understanding nanomaterial cytotoxicity through functional biohybrids [abstract]. European 

Materials Research Society 2010 Meeting on Functional Biointerfaces, Strasbourg, France, June 7–11.

 ■ Dinu CZ, Mohanraj B, Schiele NR, Sargent L, Corr DT, Chrisey DB [2010]. 

Real-time detection of carbon nanotube cytoxicity using electric cell–impedance 

sensing [abstract]. Presented (by collaborator) at the European Materials Research Society 2010 Meeting on Functional Biointerfaces, Strasbourg, France, 

June 7–11. 

 ■ Sargent LM, Dinu C, Hubbs AF, Benkovic S, Shvedova AA, Lowry DT, 

Kashon ML, Salisbury J, Murray A, Kisin E, Reynolds S [2010]. Induction of 

mitotic spindle aberrations by occupationally relevant doses of single walled 

carbon nanotubes and multi-walled carbon nanotubes. NTRC 2010 Update, 

Wheeling, West Virginia, April 19–21.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 143

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Sargent LM, Dinu C, Hubbs AF, Benkovic S, Shvedova AA, Lowry DT, 

Kashon ML, Salisbury J, Murray A, Kisin E, Reynolds S [2010]. Induction of 

mitotic spindle aberrations by occupationally relevant doses of single walled 

carbon nanotubes and multiwalled carbon nanotubes [abstract]. NTRC Update, Wheeling, West Virginia, April 19–21. 

 ■ Dinu Z, Lowry DT, Chrisey DB, Sargent L [2010]. Understanding nanomaterial cytotoxicity through functional biohybrids [abstract]. Presented (by 

collaborator) at the European Materials Research Society 2010 Meeting on 

Functional Biointerfaces. Strasbourg, France, June 7–11. 

 ■ Dinu C, Reynolds S, Lowry DT, Kashon ML, Chrisey D, Sargent L [2010]. 

Understanding carbon nanotube genotoxicity [abstract]. Presentation at European Materials Research Society 2010 Meeting on Functional Biointerfaces. 

Strasbourg, France, June 7–11.
144 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 17: Nanoparticle Properties and 

Mechanisms Causing Lung Fibrosis

Principle Investigator: Liying Wang Rojanasakul, PhD

Project Duration: FY 2008–2012

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings 

 ■ Dispersed single-walled carbon nanotubes (SWCNTs) exhibited a biphasic 

effect on cells, inducing proliferation at low doses and causing toxicity at high 

doses, whereas non-dispersed SWCNTs had no significant effects.

 ■ Dispersed SWCNTs upregulated collagen expression from cultured lung 

fibroblasts and lung tissue in a mouse model, whereas non-dispersed SWCNTs 

had a lesser effect. The data supported our proposed hypothesis that the 

dispersion status of CNTs is a key factor in determining their bioactivities. 

Direct stimulation of fibroblasts by dispersed SWCNTs translocated into the 

interstitium could be a novel mechanism of unique nanoparticle-induced 

lung fibrosis.

 ■ Survanta, a natural lung surfactant, effectively disperses SWCNT agglomerate into a small structure that is similar to aerosolized SWCNTs in size. In 

addition, at the concentration of Survanta used for the dispersion, it showed 

no toxic or mask effect, which makes it an almost ideal dispersion agent for 

nanoparticle suspension.

 ■ SWCNTs or MWCNTs induce well-known fibrogenic mediators from cultured human lung cells, i.e., transformation growth factor (TGF-b1) and 

matrix metalloproteinase 9 (MMP 9).

 ■ These data show that in vitro cell culture models using human lung fibroblasts 

and epithelial cells may be used as rapid screening tools for fibrogenicity and 

cytotoxicity testing of nanomaterials.

Publications and Abstracts 

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

Y [2009]. Nanoparticle dispersion method using natural lung surfactant. 

Toxicologist 108:A2198.

 ■ Mercer RR, Scabilloni F, Wang L, Battelli L, Castranova V [2009]. Use of 

labeled single walled carbon nanotubes to study translocation from the lungs. 

Toxicologist 108:A2192.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 145

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Wang L, Castranova V, Mishra A, Chen B, Mercer R.R, Schwegler-Berry D, 

Rojanasakul Y [2010]. Dispersion of single-walled carbon nanotubes by a 

natural lung surfactant for pulmonary in vitro and in vivo toxicity studies. 

Particle Fibre Toxicol 7:31.

 ■ Mercer RR, Hubbs A, Scabilloni J, Wang L, Battelli L, Schwegler-Berry D, 

Castranova V, Porter P [2010]. Distribution and persistence of pleural penetrations by multi-walled carbon nanotubes. Particle Fibre Toxicol 7:28.

 ■ Wang L, Mercer RR, Rojanasakul Y, Qiu A, Lu Y, Scabilloni JF, Wu N, Castranova V [2010]. Direct fibrogenic effects of dispersed single-walled carbon 

nanotubes on human lung fibroblasts. J Toxicol Environ Health A73:410–422.

 ■ Mercer RR, Hubbs AF, Scabilloni JF, Wang L Castranova V, Porter D [2010]. 

Distribution and persistence of pleural penetrations by multi-walled carbon 

nanotubes. Am J Respir Crit Care Med 181:A3102.

 ■ Lu Y, Azad N, Wang L, Iyer AKV, Castranova V, Jiang BH, Rojanasakul Y 

[2010]. Phosphatidylinositol-3-kinase/AKT regulates fibrogenesis in human 

lung fibroblasts. Am J Respir Cell Mol Biol 42(4):432–441 (Epub 2009 Jun 11).

 ■ Wang L, Mishra A, Castranova V, Schwegler-Berry D, Chen B, Mercer R, 

Rojanasakul Y [2010]. Dispersion status of single walled carbon nanotubes is 

a key determinant of their biological activities. Toxicologist 114:1, A797.

 ■ Mishra A, Castranova V, Rojanasakul Y, Hall J, Wang L [2010]. Pulmonary 

toxicity assessment of multi-wall carbon nanotubes in vitro. Toxicologist 

114:1, A798.

 ■ Wang L, Luanpitpong S, Castranova V, Lu Y, Pongrakhananon V, Rojanasakul 

Y [2011]. Carbon nanotubes induce malignant transformation and tumorigenesis of human lung epithelial cells. Nano Letters 13;11(7):2796–2803.

 ■ Song Y, Li X, Wang L, Rojanasakul Y, Castranova V, Li H, Ma J [2011]. Nanomaterials in humans: identification, characteristics, and potential damage. 

Toxicol Pathol 39:841.

 ■ Yao S, Wang L, Chen Z, Xu Y, Bai Y, Chen G, Zhang X, Zhang C, Yu Y, Shen 

F, Yuan J, Chen J, He Q [2011]. Fas/FasL pathway–mediated alveolar macrophage apoptosis involved in human silicosis. Apoptosis 16:1195–1204.

 ■ Iyer A, Azad N, Talbott S, Stehlik C, Lu B, Wang L, Rojanasakul Y [2011]. 

Antioxidant C- flip regulates fas ligand–induced NF-kB activation in a PI3K/

AKT-dependent manner. J Immunol 15;187(6):3256–3266.

 ■ Mercer RR, Hubbs A, Scabilloni J, Wang L, Battelli L, Castranova V, Porter 

D [2011]. Pulmonary fibrotic response to aspiration of multi-walled carbon 

nanotubes. Particle Fibre Toxicol 8:21.

 ■ Pongrakhananon V, Lu Y, Wang L, Stueckle T, Luanpitpong S, Rojanasakul Y 

[2011]. Carbon nanotubes induce apoptosis resistance through flice-inhibitory 

protein. Toxicologist 253:1187.
146 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Wang L, Lu Y, Castranova V, Luanpitpong S, Pongrakhananon V, Rojanasakul Y [2011]. Potential carcinogenicity of carbon nanotubes. Toxicologist 

253:1188.

 ■ Derk R, Mishra A, Stueckle T, Rojanasakul Y, Castranova V, Wang L [2011]. 

Elucidation of factors determining carbon nanotubes’ ability to penetrate 

alveolar epithelial barrier and interact with lung fibroblasts in vitro. Toxicologist 253:1181. 

 ■ Mercer RR, Hubbs AF, Scabilloni J, Wang L, Battelli L, Castranova V, Porter 

D [2011]. Pulmonary fibrotic response to sub-chronic multi-walled carbon 

nanotube exposure. Toxicologist 253:56.

 ■ Stueckle T, Mishra A, Derk R, Rojanasakul Y, Castranova V, Wang L [2011]. 

In vitro assessment of potential tumorgenicity of chronic SWCNT and 

MWCNT exposure to lung epithelium. Toxicologist 253:1182.

 ■ Mishra A, Rojanasakul Y, Castranova V, Mercer RR, Wang L [2011]. Assessment of fibrogenic biomarkers induced by multi wall carbon nanotubes. 

Toxicologist 253:1183.

Invited Presentations

 ■ Wang L, Chanvorachote P, Lu Y, Talbott S, Rojanasakul Y [2009]. Nitric oxide 

regulates lung carcinoma cell anoikis through s-nitrosylation and inhibition of 

proteasomal degradation of caveolin-1. The 4th International Conference on 

Oxidative/Nitrosative Stress and Disease, New York, New York, October 30.

 ■ Mishra A, Hall J, Wang L [2009]. Assessment of pulmonary toxicity of dispersed carbon nanotubes. WVU-Van-Liere Convocation and Research Day, 

Morgantown, West Virginia, April 27. 

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

Y [2009]. Nanoparticle dispersion method using natural lung surfactant. Society of Toxicology Annual Meeting, Baltimore, MD, March 17. 

 ■ Mishra A, Rojanasakul Y, Wang L [2009]. Evaluation of unique pulmonary 

toxicity of surfactant-dispersed carbon nanotubes using in-vitro methods. 

WVNano Research Symposium, Morgantown, West Virginia, May 11. 

 ■ Wang L, Castranova V, Lu Y, Rojanasakul Y [2010]. Development of an in 

vitro model with predictive potential for carcinogenicity of carbon nanotubes. 

Nanotoxicology International Conference, Scotland, UK, June 2–4. 

 ■ Mercer RR, Hubbs A, Scabilloni JF, Wang L, Castranova V, Porter D [2010]. 

Distribution and persistence of pleural penetrations by multi-walled carbon 

nanotubes. American Thoracic Society, New Orleans, LA, May 14–19. 

 ■ Wang L [2010]. Physicochemical properties of carbon nanotubes affecting 

their bio-activities. Inaugural School of Pharmacy Research Day, West Virginia University, Morgantown, West Virginia, February 19. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 147

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Wang L, Rojanasakul Y, Mishra A, Chen B, Schwegler-Berry D, Mercer RR 

and Castranova V [2010]. Dispersion status of single walled carbon nanotubes is a key determinant of their biological activities. NIOSH NTRC 2010 

Update , Wheeling, West Virginia, April 20.

 ■ Wang L, Rojanasakul Y, Castranova V [2010]. Properties of carbon nanotubes 

influencing their bio-activities. NIOSH Intramural Science Conference, Salt 

Fork, Ohio, August 10.

 ■ Stueckle T, Wang L, Mishra A, Castronova V, Rojanasakul Y [2010]. Properties and dispersion status of single and multi walled carbon nanotubes influence their bioactivities in rapid in vitro and in vivo assays. Clemson Meeting, 

Atlanta, August 23. 

 ■ Wang L, Mishra A, Castranova V, Schwegler-Berry D, Chen B, Mercer R, 

Rojanasakul Y [2010]. Dispersion status of single walled carbon nanotubes is 

a key determinant of their biological activities. Society of Toxicology Annual 

Meeting, Salt Lake City, Utah, March 9. 

 ■ Mishra A, Castranova V, Rojanasakul Y, Hall J, Wang L [2010]. Pulmonary 

toxicity assessment of multi-wall carbon nanotubes in vitro. Society of Toxicology Annual Meeting, Salt Lake City, Utah, March 9. 

 ■ Iyer A, Azad N, Wang L, Rojanasakul Y [2010]. Tumorigenic potential of 

single-walled carbon nanotubes. Towards Personalized Cancer Medicine: 

New York Academic Science Conference, Barcelona, Spain, May 20. 

 ■ Mishra A, Castranova V, Rojanasakul Y, Qiu L, Wang L [2010]. Assessment of 

fibrogenic potential of carbon nanotubes in vitro. Van-Liere Convocation and 

Research Day, West Virginia University, Morgantown, West Virginia, April 21.

 ■ Liying W, Rojanasakul Y [2010]. Direct fibrogenic effects of single-walled carbon nanotubes on human lung fibroblasts. WVNano Initiative, West Virginia 

University, Morgantown, West Virginia, April 5.

 ■ Liying W, Rojanasakul Y [2010]. Physicochemical Properties of Carbon Nanotubes Affecting their Bio-activities. Inaugural School of Pharmacy Research 

Day, West Virginia University. Morgantown, West Virginia. February 19.

 ■ Wang L [2011]. Potential carcinogenicity of carbon nanotubes. Beijing University, Beijing, China, September 14. 

 ■ Wang L [2011]. Micron sized particle and nano-sized particle (carbon nanotubes): different ways to cause lung fibrosis. Hebei United University, Hebei, 

China, September 13.

 ■ Wang L [2011]. General introduction of carbon nanotubes and nano-toxicology. 

Harbin Medical University, 4th affiliated hospital. Harbin, China, August 31.

 ■ Wang L, Mishra A, Stueckle T, Derk R, Rojanasakul Y, Castranova V [2011]. Development of in vitro vs. in vivo models to evaluate fibrogenic and carcinogenic 

potential of carbon nanotubes. NORA Symposium, Cincinnati, Ohio, July 12.
148 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 18: Pulmonary Toxicity of Carbon 

Nanotube Particles

Principal Investigator: Anna Shvedova, PhD

Project Duration: FY 2004–2008

Critical Topic Area: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Found that low levels of antioxidants in vitamin E–deficient mice were 

associated with a higher sensitivity to single-walled carbon nanotube (SWCNT)- induced acute inflammation, released LDH, total protein content, 

levels of proinflammatory cytokines, and enhanced profibrotic responses and 

collagen deposition. 

 ■ Found that exposure to SWCNTs markedly shifted the ratio of cleaved to 

full-length 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 was observed to enhance 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.

 ■ An increased accumulation of neutrophils and decreased fibrosis were 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 TGF-beta, and reduced levels of 

collagen deposition. 

 ■ Found NADPH oxidase to be an important regulator of the transition from 

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

 ■ Developed a generation system that aerosolizes SWCNTs for an inhalation 

study. The resulting aerosol was size-separated with 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%.
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APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Completed inhalation study of SWCNT in C57BL/6 mice (http://www.

ncbi.nlm.nih.gov/pubmed/18658273?ordinalpos=2&itool=EntrezSystem2.

PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.

Pubmed_RVDocSum). 

 ■ The inhalation of nonpurified SWCNTs (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 μg per mouse) of the same SWCNTs. 

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

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

material: assessment of nanotube cytotoxicity using human keratinocyte cells. 

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

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

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

bronchial epithelial cells to carbon nanotubes caused oxidative stress and 

cytotoxicity. Proceedings of the Society for Free Radical Research Meeting, 

European Section, Ioannina, Greece, June 26–29, 2003, pp. 91–103.

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

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

pulmonary toxicity of carbon nanotubes. Free Radical Biol Med 37(1).

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

N, Schwegler-Berry D, Gandelsman V, Gorelik O, Aperalli S, Kagan V, Castranova V [2004]. Assessment of carbon nanotube cytotoxicity using human 

cells and animal models. Proceedings of The Toxicology Forum’s 29th Toxicology Annual Winter Meeting, Washington, DC, February 2–4.

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

Y, Gorelic O, Arepalli S, Schwegler-Berry D, Antonini J, Evans DE, Ku B-K, 

Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P [2005]. Unusual 

inflammatory and fibrogenic pulmonary responses to single walled carbon 

nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289:L698–L708.

 ■ Heck DE, Kagan VE, Shvedova AA, Laskin JD [2005]. An epigrammatic 

(abridged) recounting of the myriad tales of astonishing deeds and dire 

consequences pertaining to nitric oxide and reactive oxygen species in 
150 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

mitochondria with an ancillary missive concerning origin of apoptosis. Toxicology 208(2):259–271.

 ■ Kagan VE, Bayir H, Shvedova AA [2005]. Nanomedicine and nanotoxicology: 

two sides of the same coin. J Nanomed Nanotechnol Biol Med 1(4):313–316.

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

Hubbs AF, Mercer RR, Baron P, Kagan VE, Castranova V, Shvedova AA 

[2005]. Pulmonary toxicity of carbon nanotubes. Toxicologist 84:A1041.

 ■ Mercer RR, Scabilloni J, Kisin E, Gorelik O, Arepalli S, Murray AR, Castranova V, Shvedova AA [2005]. Responses of lung parenchyma to carbon nanotubes. Toxicologist 84:A1042.

 ■ Shvedova AA, Potapovich AL, Osipov AN, Tyurina YY, Kisin E, SchweglerBerry D, Mercer RR, Castranova V, Kagan VE [2006]. Oxidative interactions 

of single walled carbon nanotubes with RAW 264.7 macrophages: role of iron. 

Toxicology 90(1):A1557.

 ■ Kisin E, Murray AR, Castranova V, Kagan VE, Shvedova AA [2006]. Singlewall carbon nanotubes induce oxidative stress, acute inflammation, and 

progressive pulmonary fibrosis. Toxicology 90(1):A1556.

 ■ Kagan VE, Potapovich AN, Osipov YY, Tyurina ER, Kisin E, Schwegler-Berry 

D, Mercer R, Castranova V, Shvedova AA [2006]. Direct and indirect effects 

of single-walled carbon nanotubes on RAW 264.7 macrophages: role in iron. 

Toxicol Lett 165:88–100.

 ■ Feng WH, Tyurina YY, Bayir H, Shvedova AA, Kagan VE [2007]. Phosphatidylserine enhances recognition and uptake of single-walled carbon nanotubes 

by rat microglial cells. Toxicologist 96(1):289.

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

Fadeel B, Shvedova A [2007]. Targeted delivery of phosphatidylserine-coated 

single-walled carbon nanotubes to macrophages. Toxicologist 96(1):233.

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

Young S-H, Gao F, Tyurina YY, Oury T, Kagan VE [2007]. Vitamin E deficiency enhances pulmonary inflammatory response and oxidative stress induced 

by single-walled carbon nanotubes in C57B6/L mice. Toxicologist 96(1):37.

 ■ 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, Opopol N, Luster MI, eds. 
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APPENDIX A | A Summary of 69 NIOSH Research Projects

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]. 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.

 ■ 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]. Singlewalled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast V79 

cells. J Tox Environ Health A 70(24):2071–2079.

 ■ 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.

 ■ 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]. 
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APPENDIX A | A Summary of 69 NIOSH Research Projects

Combined exposure to carbon nanotubes and bacteria-enhanced 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.

Invited Presentations

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

229th American Chemical Society Meeting, San Diego, California, March 12–16.

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

low density fibrous carbon powders (single-walled carbon nanotubes and 

Pyrograf III). In: Proceedings of the 24th Annual AAAR Conference, Austin, 

Texas, October 17–21, p. 214.

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

very low density fibrous carbon powders (single-walled carbon nanotubes 

and Pyrograf III). In: Proceedings of the 2nd International Symposium 

on Nanotechnology and Occupational Health, Minneapolis, Minnesota, 

October 3–6, p. 40.

 ■ Shvedova AA [2007]. Pulmonary toxicity of singled-walled nanotubes. International conference on nanotoxicology, Venice, Italy, April 19–21.

 ■ 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, 

Maryland, 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, West Virginia, 

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. 
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 ■ 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.
154 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 19: Assessment of Engineered 

Nanomaterials of Respiratory 

Immunity

Principle Investigator: Anna A. Shvedova, PhD

Project Duration: FY 2009–2012

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Found that exposure of SWCNTs with low content of metal impurities to primary human monocyte–derived macrophages (HMDMs) did not exert direct 

cytotoxicity. 

 ■ In vitro exposure indicated that SWCNTs are not chemotactic for human 

monocyte–derived macrophages. SWCNT suppressed chemotaxis of primary 

human monocytes. 

 ■ Macrophage engulfment of apoptotic target cells was significantly impaired 

following pre-incubation of HMDMs with SWCNTs at non-cytotoxic 

concentrations. 

 ■ New data are in line with previous results showing that ultrafine carbon 

particles and SWCNTs impaired alveolar macrophage ingestion of microorganisms, thus suggesting that tissue homeostasis may be compromised by 

SWCNTs because of their suppressive effects on macrophages. 

Bulk multi-walled carbon nanotubes observed as an agglomerated “bird’s nest” 

and as a loose bundle
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 ■ Pharyngeal aspiration of pristine (C60) and functionalized fullerenes (C60-

TRIS) and SWCNTs causes inflammation and pulmonary damage, demonstrated by accumulation of PMNs, changes in lung permeability, lung cell damage, 

and cytokine release. Toxicity to the lung: SWCNT> C60-TRIS> C60.

 ■ Pulmonary exposure to fullerenes and SWCNTs causes the release of both 

proinflammatory (i.e., TNF-a) and regulatory (i.e., IL-10) cytokines. 

 ■ Pulmonary exposure to SWCNTs facilitated the recruitment of dendritic cells to 

the lung, followed by their subsequent migration to the draining lymph nodes.

 ■ Pulmonary exposure to fullerenes and SWCNTs suppresses systemic immunity. Splenic T cells from mice exposed to NP demonstrated suppressed 

response after stimulation by dendritic cells (up to 20% lower for control). 

 ■ Mechanisms of altered systemic immunity in treated mice may be, at least in 

part, due to the direct effects of SWCNTs on dendritic cells, as evidenced by 

the impaired T cell responsiveness to re-stimulation following pre-incubation 

with SWCNT-exposed dendritic cells (in vitro).

Publications and Abstracts 

 ■ Kisin E, Murray AR, Hubbs AF, Mercer RR, Keohavong P, Sussman N, Chen 

BT, Deye G, Castranova V, Baron PA, Kagan VE, Shvedova AA [2009]. Pulmonary effects of single walled carbon nanotubes: inhalation vs aspiration. 

Toxicologist 108(1):2202.

 ■ Kisin E, Murray AR, Schwegler-Berry D, Scabilloni J, Mercer RR, Chirila 

M, Young S, Leonard S, Keohavong P, Fadeel B, Kagan VE, Castranova V, 

Shvedova AA [2010]. Pulmonary response, oxidative stress and genotoxicity 

induced by carbon nanofibers. Toxicologist 114(1):169.

 ■ Tyurin VA, Tyurina YY, Jung Mi-Y, Tungekar MA, Wasserloos KJ, Bayır H, 

Greenberger JS, Kochanek PM, Shvedova AA, Pitt B, Kagan VE [2009]. Massspectrometric analysis of hydroperoxy- and hydroxy-derivatives of cardiolipin 

and phosphatidylserine in cells and tissues. J Chromatogr B Analyt Technol 

Biomed Life Sci 877(26):2863–2872.

 ■ Shvedova AA, Kisin ER, Porter D, Schulte P, Kagan VE, Fadeel B, Castranova 

V [2009]. Mechanisms of pulmonary toxicity and medical applications of 

carbon nanotubes: two faces of Janus? Pharm Ther 121(2):192–204.

 ■ Konduru NV, Tyurina YY, Feng W, Basova LV, Belikova NA, Bayir H, Clark K, 

Rubin M, Stolz D, Vallhov H, Scheynius A, Witasp E, Fadeel B, Kichambare 

PD, Star A, Kisin ER, Murray AR, Shvedova AA, Kagan VE [2009]. Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes 

in vitro and in vivo. PLoS One 4(2):e4398.

 ■ Witasp E, Shvedova AA, Kagan VE, Fadeel B [2009]. Single-walled carbon 

nanotubes impair human macrophage engulfment of apoptotic cell corpses. 

Inhal Toxicol 21(S1):131–136. 
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APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Shvedova AA, Kagan VE, Fadeel B [2010]. Close encounters of the small kind: 

adverse effects of man-made materials interfacing with the nano-cosmos of 

biological systems. Ann Rev Pharmacol Toxicol 50:63–88.

 ■ Shvedova AA, Kagan VE [2010].The role of nanotoxicology in realizing 

the ‘helping without harm’ paradigm of nanomedicine: lessons from studies of pulmonary effects of single-walled carbon nanotubes. J Intern Med 

267(1):106–118.

 ■ Kagan VE, Konduru NV, Feng W, Allen BL, Conroy J, Volkov Y, Vlasova II, 

Belikova NA, Yanamala N, Kapralov A, Tyurina YY, Shi J, Kisin ER, Murray 

AR, Franks J, Stolz D, Gou P, Klein-Seetharaman J, Fadeel B, Star A, Shvedova AA [2010]. Carbon nanotubes degraded by neutrophil myeloperoxidase 

induce less pulmonary inflammation. Nat Nanotechnol 5(5):354–359.

 ■ Kagan VE, Shi J, Feng W, Shvedova AA, Fadeel B [2010]. Fantastic voyage and 

opportunities of engineered nanomaterials: what are the potential risks of occupational exposures? J Occup Environ Med 52(9):943–946.

 ■ Kisin ER, Murray AR, Sargent L, Lowry D, Chirila M, Siegrist KJ, SchweglerBerry D, Leonard S, Castranova V, Fadeel B, Kagan VE, Shvedova AA [2011]. 

Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos? Toxicol Appl Pharmacol 252(1):1–10.

 ■ Teeguarden JG, Webb-Robertson BJ, Waters KM, Murray AR, Kisin ER, 

Varnum SM, Jacobs JM, Pounds JG, Zanger RC, Shvedova AA [2011]. Comparative proteomics and pulmonary toxicity of instilled single-walled carbon 

nanotubes, crocidolite asbestos, and ultrafine carbon black in mice. Toxicol 

Sci 120(1):123–135.

 ■ Tkach A, Shurin M, Shurin G, Kisin, Murray, AR, Yang, Houng S, Star A, 

Bengt F, Kagan VE, Shvedova AA [2011]. Direct effects of carbon nanotubes 

on dendritic cells induce immune suppression upon pulmonary exposure. 

ACS Nano 5(7):5755–5762.

 ■ Tyurina YY, Kisin ER, Murray A, Tyurin VA, Kapralova VI, Sparvero LJ, 

Amoscato AA, Samhan-Arias AK, Swedin L, Lahesmaa R, Fadeel B, Shvedova 

AA, Kagan VE [2011]. Global phospholipidomics analysis reveals selective 

pulmonary peroxidation profiles upon inhalation of single-walled carbon 

nanotubes. ACS Nano 5(9):7342–7353.

 ■ Mohamed BM, Verma NK, Davies AM, McGowan A, Staunton KC, PrinaMello A, Kelleher D, Botting CH, Causey CP, Thompson PR, Pruijn GJM, 

Kisin ER, Tkach AV, Shvedova AA, Volkov Y [2012]. Citrullination of proteins: a common post-translational modification pathway induced by different 

nanoparticles in vitro and in vivo. Nanomedicine 7(8)1181–1195.

 ■ Murray AR, Kisin ER, Tkach AV, Yanamala N, Mercer R, Young S-H, Fadeel 

B, Kagan VE, Shvedova AA [2012]. Factoring-in agglomeration of carbon 

nanotubes and nanofibers for better prediction of their toxicity versus asbestos. Particles Fibre Toxicol J 9:10.
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APPENDIX A | A Summary of 69 NIOSH Research Projects

Invited Presentations 

 ■ Kisin E, Murray AR, Mercer RR, Keohavong P, Fadeel B, Kagan VE, Shvedova 

AA [2009]. Pulmonary and genotoxic effects of nanofibers. 6th International 

Key Symposium on Nanomedicine, Stockholm, Sweden, September 9–11.

 ■ Shvedova AA [2009]. Nanotoxicology in vivo: Pulmonary effects of carbon 

nanotubes. 6th Symposium on Nanomedicine, Royal Swedish Academy of 

Sciences, Stockholm, Sweden, September 9–11.

 ■ Shvedova AA [2009]. Unsolicited pulmonary effects of carbon nanotubes: 

genetic, nutritional and microbial factors. 4th Oxygen/Nitrogen Radicals 

and Cellular Injury Meeting, NY Academy of Sciences, New York, New York, 

October 28–30.

 ■ Shvedova AA [2010]. Toxicity of carbon nanotubes: from mechanisms to 

regulatory consequences. Nanoscience and Technology in Chemistry, Health, 

Environment and Energy, International Conference, Agra, India, January 6–9.

 ■ Shvedova AA [2010]. Oxidative stress, pulmonary toxicity of single walled 

carbon nanotubes in vivo: relevance to occupational exposures. International 

Conference on Advances in Free Radicals Research, Natural Products, Antioxidants and Radio-protectors in Health/9th Annual Meeting of Society for 

Free Radical Research, Hyderabad, India, January 11–13.

 ■ Shvedova AA [2010]. Toxicity of carbon nanotubes: acute, long-term effects and 

mechanisms. 3rd Nanotoxicology Conference, Edinburgh, Scotland, June 2–4.

 ■ Shvedova AA [2010]. Pulmonary toxicity of single-walled carbon nanotubes: 

inflammation, fibrosis, mutagenic effects. 2nd Nobel Forum, Understanding 

the Interactions of Engineered Nanomaterials with Biological Systems, Stockholm, Sweden, October 23.

 ■ Kisin E, Murray AR, Schwegler-Berry D, Scabilloni J, Mercer RR, Chirila 

M, Young S, Leonard S, Keohavong P, Fadeel B, Kagan VE, Castranova V, 

Shvedova AA [2010]. Pulmonary response, oxidative stress and genotoxicity 

induced by carbon nanofibers. NTRC 2010 Update, Wheeling, West Virginia, 

April 19–21.

 ■ Kisin E, Murray AR, Schwegler-Berry D, Mercer RR, Keohavong P, Fadeel 

B, Castranova V, Kagan VE, Shvedova AA [2010]. Assessment of pulmonary 

outcomes following exposure to fibrous nanomaterials. Nanotoxicology 2010, 

Edinburgh, UK, June 2–4, p. 105.

 ■ Tkach A, Shurin GV, Shurin MR, Star A, Kisin E, Murray AR, Fadeel B, 

Kagan VE, Shvedova AA [2010]. Study of immunomodulating properties of 

pristine and functionalized fullerenes. A-E 24th SOT meeting, Pittsburgh, 

Pennsylvania, April 30.

 ■ Shvedova AA [2011]. Pulmonary toxicity of single-walled carbon nanotubes: 

inflammation, fibrosis, and mutagenic effects. Nanocomposite and Nanotube 

European Meeting, Brussels, Belgium, April 6–7.
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 ■ Shvedova AA [2011]. Assessment of quantitative changes in biomarkers of 

immune, inflammatory, and oxidative stress. 4th Annual Consortium Meeting, Karolinska Institutet, Contract Agreement: NMP4-SL-2008-214281; 

Stockholm, Sweden, June 16.

 ■ Shvedova AA [2011]. FP7-NANOMMUNE Workshop: understanding nanoimmuno-interactions; Pulmonary Toxicity of Carbonaceous Nanomaterials 

versus Asbestos Fibers, Stockholm, Sweden, June 17.

 ■ Shvedova AA [2011]. Nanoparticles as an emerging environmental and occupational hazard: does oxidative stress matter? Environmental stresses in 

biology and medicine. 2nd International Meeting, Siena, Italy, October 5–7.

 ■ Shvedova AA [2011]. Carbon nanotubes: from safety assessment to biomedical applications. Workshop: in vivo studies. Carbon Nanomaterials versus 

Asbestos: Immune Effects, 7th FP, EU Commission, Brussels, Belgium, November 29.
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APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 20: Dermal Toxicity of Nanotube 

Particles

Principal Investigator: Anna Shvedova, PhD

Project Duration: FY 2005–2010

Critical Topic Area: Toxicology and internal dose

Accomplishments and Research Findings

 ■ SWCNTs induced genotoxic 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 SWCNTs 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 SWCNTs (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 

SWCNTs (0.23% iron) were introduced to JB6 P+ cells.

Nanomaterial worker
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APPENDIX A | A Summary of 69 NIOSH Research Projects

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

generation, oxidative stress, and inflammation, thus causing dermal toxicity.

Exposure to Single-Wall Carbon Nanotubes (SWCNTs):

 ■ Topical exposure of SWCNTs to skin caused dermal toxicity. Found toxicity is dependent upon the metal (particularly iron) content of SWCNTs as 

well as its ability to penetrate the skin and induce oxidative stress/leading 

inflammation. 

 ■ Topical exposure of SKH-1 mice to SWCNT exposure (2 mg/kg, 4 mg/kg, or 

8 mg/kg, 5 days) caused oxidative stress and skin inflammation assessed by 

increased myeloperoxidase activity, accumulation of PMNs and elevated skin 

thickness/edema. 

 ■ Exposure of human keratinocytes (HaCaT) cells revealed less cytotoxicity in 

cells exposed to partially purified SWCNTs (2.5% weight iron) compared to 

unpurified SWCNT (0.23%; 40% iron). 

 ■ Murine epidermal cells (JB6 P+) revealed a significant dose-dependent activation of AP-1 following exposure to unpurified SWCNTs, whereas partially 

purified SWCNTs did not activate AP-1. On the contrary, activation of NFkB 

was dose-dependent by both unpurified and partially purified SWCNTs. 

 ■ These data indicate that dermal exposure to SWCNTs, particularly unpurified SWCNTs, could result in inflammation, accelerated oxidative stress, 

and dermal toxicity during direct contact of SWCNTS with occupationally 

unprotected skin.

Tungsten carbide–cobalt (WC-Co) Exposure:

 ■ Demonstrated size-dependent effects of tungsten carbide–cobalt (WC-Co) 

nano/micro sized particles on oxygen radical production and activation of 

cell signaling pathways in murine epidermal cells. 

 ■ Found adverse effects of nano-WC-Co generated a higher level of hydroxyl 

radicals, greater oxidative stress, and caused accelerated JB6 P(+) cell growth/

proliferation. In addition, nano-WC-Co activated AP-1 and NF-kappaB more 

efficiently in JB6(+/+) cells as compared to micronized WC-Co. 

 ■ In AP-1-luciferase reporter transgenic mice was found the activation of AP-1 

by nano-WC-Co but not micronized NP. 

 ■ Nano- and fine-sized WC-Co particles also stimulated MAPKs, including 

ERKs, p38, and JNKs with significantly higher potency of nano-WC-Co. 

 ■ Co-incubation of the JB6(+/+) cells with N-acetyl-cysteine–antioxidant decreased AP-1 activation and phosphorylation of ERKs, p38 kinase, and JNKs, 

thus suggesting that oxidative stress is intimately involved in WC-Co-induced 

toxicity and AP-1 activation.
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APPENDIX A | A Summary of 69 NIOSH Research Projects

Superparamagnetic Iron Oxide Nanoparticles (SPION) Exposure:

 ■ Found that exposure of SPION to Human Epidermal Keratinocytes caused 

cytotoxic effects. 

 ■ Exposure of JB6 mouse epidermal cells to SPION resulted in activation of AP-1.

 ■ Exposure to SPION alone was not sufficient to induce NFkB activation; however, co-exposure with UVB resulted in significant NFkB induction in cells 

exposed to SPION particles. 

 ■ Co-exposure of mouse epidermal cells to UVB and NPs significantly accelerated depletion of glutathione, release of cytokines, and cell damage as assessed 

by release of lactate dehydrogenase. 

 ■ Demonstrated that exposure of iron oxide nanoparticles (SPION) to dermal 

cells caused size-dependent dermal toxicity via induction of cell damage, 

oxidative stress, activation of signal transduction pathways and subsequent 

release of inflammatory mediators. 

Publications and Abstracts

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

[2007]. Single-walled carbon nanotubes induce oxidative stress and inflammation in skin. Toxicologist 96(1):291.

 ■ 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]. Singlewalled carbon nanotubes: geno- and cytotoxic effects in fibroblast V79 cells. J 

Tox Environ Health, Part A, 70(24):2071–2079.

 ■ 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. 

 ■ 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 
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APPENDIX A | A Summary of 69 NIOSH Research Projects

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.

 ■ Elder A, Lynch I, Grieger K, Chan-Remillard S, Gatti A, Gnewuch H, Kenawy 

E-R, Korensten R, Kuhlbusch T, Linker F, Matias S, Monteiro-Riviere N, pinto 

V, Rudnitsky R, Savolainen K, Shvedova A [2009]. Disposition of Nanoparticles as a Function of their Interactions with Bio-molecules. In Nanomaterials Risks and Benefits, Eds. Linkov & Steevens, Springer, the Netherland, 

Proceedings of the NATO Advanced Research Workshop on Nanomaterials: 

Environmental Risks and Benefits Faro, Portugal 27–30 April, 2008, pp 3–29.

 ■ Ding M, Kisin ER, Zhao J, Bowman L, Lu Y, Jiang B, Leonard S, Vallyathan 

V, Castranova V, Murray AR, Fadeel B, Shvedova AA [2009]. Size-dependent 

effects of tungsten carbide–cobalt particles on oxygen radical production and 

activation of cell signaling pathways in murine epidermal cells Toxicol Appl 

Pharmacol 241(3):260–8.

 ■ Murray AR, Kisin E, Leonard SS, Young SH, Kommineni C, Kagan VE, Castranova V, Shvedova AA [2009]. Oxidative stress and inflammatory response 

in dermal toxicity of single-walled carbon nanotubes. Toxicology 29; 257

(3):161–71.

 ■ Murray AR, Kisin E, Leonard SS, Young SH, Kommineni C, Kagan VE, 

Castranova V, Shvedova AA [2009]. Single-Walled carbon nanotubes: skin 

exposures. Toxicologist 108(1):2201.

 ■ Konduru NV, Tyurina YY, Feng W, Basova LV, Belikova NA, Bayir H, Clark K, 

Rubin M, Stolz D, Vallhov H, Scheynius A, Witasp E, Fadeel B, Kichambare 

PD, Star A, Kisin ER, Murray AR, Shvedova AA, Kagan VE [2009]. Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes 

in vitro and in vivo. PLoS One 4(2):e4398.

 ■ Murray AR, Kisin E, Leonard SS, Young SH, Schwegler-Berry D, Castranova 

V, Fadeel B, Kagan VE, Shvedova AA [2010]. Toxic effects of metal/metal 

oxide nanoparticles in skin model. Toxicologist 114(1):270.

 ■ Murray AR, Kisin E, Inman A, Young SH, Muhammed M, Burks T, Uheida 

A, Tkach A, Waltz M, Castranova V, Fadeel B, Kagan VE, Riviere JE, Monteiro-Riviere N, Shvedova AA [2011]. Oxidative stress and dermal toxicity of 

iron oxide nanoparticles in vitro. Cell biochem and biophys [in press].

Invited Presentations 

 ■ Ding M, Lu Y, Bowman L, Leonard S, Castranova V, Vallyathan V [2006]. 

Titanium nanoparticles induces AP-1 activation through ROS and MAPKS 
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APPENDIX A | A Summary of 69 NIOSH Research Projects

pathways. 1st International Toxicology of Nanomaterial: Biomedical Aspects 

Meeting, Miami Beach, Florida, January 29–February 1.

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

[2006]. Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes. 1st International Toxicology of Nanomaterial: 

Biomedical Aspects Meeting, Miami Beach, Florida, January 29–February 1.

 ■ 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, West Virginia, 

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.

 ■ Murray AR, Kisin E, Leonard SS, Young S, Schwegler-Berry D, Castranova V, 

Fadeel B, Kagan VE, Shvedova AA [2010]. Metal/Metal Oxide Nanoparticle 

Induced Toxicity in Skin Model. Nanotoxicology 2010, Edinburgh, UK, June 

2–4.

 ■ Murray AR, Kisin E, Leonard SS, Castranova V, Kagan VE, Shvedova AA 

[2009]. Assessment of Toxic Outcomes of metal/metal oxide nanoparticles in 

skin model in vitro and in situ. 6th Key Symposium on Nanomedicine, Stockholm, Sweden, September 9–11.

 ■ Murray AR, Kisin E, Leonard SS, Castranova V, Kagan VE, Shvedova AA 

[2010]. Toxic Effects of Metal/Metal Oxide Nanoparticles in Skin Model. 

NTRC 2010 Update, Wheeling, West Virginia, April 19–21.
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APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 21: Bioassay Screen of Lung Toxicity of 

Silver Nanoparticles

Principle Investigator: Jenny R. Roberts, PhD

Project Duration: FY 2010–2012

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings 

 ■ Established collaboration with researchers at NIST and DRDS/NIOSH to 

conduct a physical characterization of a battery of silver nanoparticles (Ag 

NPs) to be employed in the study, including uncoated particles, particles with 

a polyvinylpovidone (PVP) coating, and citrate-suspended particles. Surface 

area measurements on the dry powder form of the Ag NPs, hydrodynamic 

particle sizing in dispersion medium, and size evaluation of the particle suspension in dispersion medium by electron microscopy have been evaluated 

for the uncoated Ag NPs and the PVP–coated particles. Based on the characterization and OECD recommendations, the emphasis of the project will be 

on Ag NPs with PVP and citrate-suspended Ag NPs.

 ■ Established collaboration with nanoComposix and Air Force Research Laboratory to investigate pulmonary toxicity associated with an additional form 

of silver nanomaterial, silver nanowires of different lengths. NanoComposix 

has generated, characterized, and supplied us with nanowires of two different 

lengths. The Air Force Research Lab has begun in vitro analysis of toxicity using a variety of pulmonary cell types.

 ■ Conducted a pilot study in vivo to determine if the PVP coating itself possessed any toxic properties related to the bioassay screen that may interfere 

with evaluation of the pulmonary toxicity of Ag NPs. PVP, at the concentration that it exists in the highest proposed dose of Ag NPs, did not produce any 

inflammation, injury, or alteration in immune parameters in the lung.

 ■ Completed an in vivo dose-response time course study evaluating pulmonary 

toxicity of PVP-coated Ag NPs after a single acute exposure in rats. Ag NPs 

caused a dose-dependent increase in pulmonary injury and inflammation. In 

addition, Ag NPs induced alterations in immune parameters in the lung and 

in lung-associated lymph nodes. Increases in lung injury and inflammation, 

and alterations in immune parameters, persisted for at least one month postexposure in a dose-dependent manner.

 ■ Completed an in vivo dose-response time course study evaluating toxicity 

of PVP-coated Ag NPs after repeated exposures (1x per week for 8 weeks) to 

doses in the lower range of the single acute dose-response time course study. 

Repeated exposure to the lowest dose in this study caused no significant lung 
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APPENDIX A | A Summary of 69 NIOSH Research Projects

injury or inflammation. Exposure to the higher dose in this study caused 

significant inflammation and injury up to one month after the last exposure, 

with resolution over time.

 ■ Characterized two silver nanowire samples that differ in length and evaluated pulmonary toxicity associated with them in vivo based on lung lavage 

cell and fluid analysis. Both samples cause a dose-dependent increase in lung 

injury and inflammation, with a more severe response at days one and seven 

post-exposure with the long wire sample, while the short wire sample caused 

a more persistent response at the later time points post-exposure.

Publications and Abstracts 

 ■ Roberts JR, Chapman RS, Young S-H, Kenyon A, Schwegler-Berry D, Stefaniak AB, Chen BT, Antonini JM [2011]. Pulmonary Toxicity Following 

Intratracheal Instillation of Dispersed Silver Nanoparticles in Rats. Society of 

Toxicology Annual Meeting, Washington, DC, March 6–10th, 2011. Toxicologist 120(Suppl 2): A1759, 377–378.

 ■ Schaeblin NM, Estep CA, Roberts JR, Hussain SM [2011]. Silver Nanowires 

Incduced Inflammation in an In vitro Human Alveolar Lung Model. Society 

of Toxicology Annual Meeting, Washington, DC, March 6–10th, 2011. Toxicologist 120(Suppl 2): A2181, 468.

 ■ Roberts JR, Kenyon A, Young SH, Schwegler-Berry D, Hackley VA, MacCuspie RI, Stefaniak AB, Kashon ML, Chen BT, Antonini JM [2012]. Pulmonary 

Toxicity Following Repeated Intratracheal Instillation of Dispersed Silver 

Nanoparticles in Rats. Society of Toxicology Annual Meeting, San Francisco, 

California, March 11–15th, 2012. Toxicologist, In Press.

 ■ Kenyon A, Antonini JM, Mercer RR, Schwegler-Berry D, Schaeublin NM, 

Hussain SM, Oldenburg SJ, Roberts JR [2012]. Pulmonary Toxicity Associated 

with Different Aspect Ratio Silver Nanowires after Intratracheal Instillation in 

Rats. Society of Toxicology Annual Meeting, San Francisco, California, March 

11–15th, 2012. Toxicologist, In Press.
166 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 22: Specific Biomarkers for Unusual 

Toxicity of Nanomaterials

Principal Investigator: Liying Wang Rojanasakul, PhD

Project Duration: FY 2007–2009

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. 

 ■ Mercer RR, Scabilloni JF, 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(1):L87–97.

 ■ Lu Y, Azad N, Wang L, Iyer AKV, Castranova V, Jiang BH, Rojanasakul Y 

[2009]. Phosphatidylinositol-3-Kinase/Akt Regulates Fibrogenesis in Human 

Lung Fibroblasts. Am J Respir Cell Mol Biol 42(4):432–41.

 ■ Wang L, Rojanasakul Y, Castranova V, Qiu A, Lu Y, Scabilloni J, Wu N, Mercer 

RR [2010]. Direct fibrogenic effects of dispersed single-walled carbon nanotubes on human lung fibroblasts. J Toxicol Environ Health A 73(5):410–22.

Invited Presentations

 ■ Wang L [2007]. Carbon nanotubes exhibit tumorigenic and fibrogenic potential in vitro. West Virginia University research meeting, Morgantown, West 

Virginia, September 1.

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

and Poison Control on nanotoxicology research, Beijing, China, November 16 

and 17.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 167

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Castranova V [2008]. The ability of in vitro tests to predict pulmonary responses to SWCNT. John Hopkins University, Baltimore, Maryland, June 11.

 ■ Wang L, Castranova V, Mercer RR, Wu N, Tiao Li T, Li S, Hall J, Li M, Rojanasakul Y [2009]. Nanoparticle dispersion method using natural lung surfactant. Society of Toxicology Annual Meeting, Baltimore, Maryland, March 

15–19.

 ■ Mishra A, Hall J, Wang L [2009]. Assessment of pulmonary toxicity of dispersed carbon nanotubes. WVU-Van-Liere Convocation and Research Day, 

Morgantown, West Virginia, April 27.
168 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 23: Pulmonary Toxicity of Diesel

Exhaust Particles

Principal Investigator: Jane Ma, PhD

Project Duration: FY 2003–2008

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Studies have shown that diesel-exhaust-particle (DEP) exposure induces lung 

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

 ■ 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. 

 ■ Exposure to carbon black but not to DEPE 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 carbonblack-induced infiltration of polymorphonuclear neutrophils (PMNs), air/

capillary damage, and cytotoxicity. 

 ■ Carbon-black-exposed AMs 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 AMs, which was not markedly affected by the NO deficiency. In 

contrast, DEPE did not significantly induce ROS generation or mitochondrial 

function in AMs.

 ■ Carbon black and DEPE did not significantly affect adenosine triphosphate (ATP) 

levels in either WT or iNOS KO mice. This is due to the fact that mitochondrial 

oxidative phosphorylation pathway is not the major energy source for AMs. 

 ■ Transmission electron microscopy analysis has shown that animals exposed 

to DEPs or carbon black, but not DEPE, were heavily laden with particlefilled vacuoles in the lung.

 ■ Found that vacuoles containing DEPs 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 169

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ DEP and carbon black both induced DNA damage in AMs, according to 

comet assay findings. 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(S-1):A183.

 ■ Yin XJ, Dong CC, Ma JYC, Roberts JR, Antonini 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 A 

70(10):820–822.

 ■ Hongwen Z, Ma JK, Mercer R, Millecchia1 L, Barger MW, Castranova V, Ma 

JY [2009]. Reactive oxygen/nitrogen species-mediated lung inflammation and 

mitochondrial dysfunction in wild type and iNOS deficient mice exposed to 

diesel exhaust particles. J Toxicol Environ Health A 72(8):560–570.

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, New York, April 8.
170 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 24: Induction of Lung Fibrosis by Cerium 

Oxide in Diesel Exhaust

Principal Investigator: Jane Ma, PhD

Project Duration: FY 2009–2012 

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings

In vitro studies

 ■ Cerium oxide did not induce intracellular oxidant generation or alter mitochondrial function of alveolar macrophages (AMs) 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 co-exposure, may elicit new 

cellular toxicity in addition to DEP-induced toxicity and that cerium oxide 

suppresses cellular defense capability.

In vivo studies

 ■ Found that 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. 

 ■ Cerium oxide exposure increased reactive oxygen species production in 

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

 ■ Cerium oxide exposure significantly reduced AM production of NO in response to ex vivo LPS challenge but further increased IL-12 production at 1 

day post-exposure. 

 ■ Exposure of rats to cerium oxide induced Arg-1 at 28 days, but not 1 day, 

post-exposure. The induced OPN mRNA expression was increased at 1 day 

and sustained though 28 days of exposure, suggesting that these particle 

exposures play a direct role in skewing AM development away from M1 

towards M2.

 ■ Cerium oxide exposure significantly increased the phospholipid content in 

the BAL fluid in a dose-dependent manner. TEM showed a significant number of lamellar bodies in AM.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 171

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Cerium oxide induced lung fibrosis in a dose-dependent manner. The fibrosis 

is measured via increased hydroxyproline content in the lung tissues.

 ■ Cerium oxide induced fibrotic cytokine OPN and TGF-β1 production and 

phospholipidosis.

 ■ Cerium oxide induced MMP-2, -9, and TIMP-1, resulting in imbalance of the 

MMP-9/ TIMP-1 ratio that favors fibrosis.

 ■ Cerium oxide–induced lung fibrosis was evident by morphometric analysis 

of the lung tissues, which detected significantly increased localized collagen 

formation via Sirius Red staining.

 ■ Cerium oxide particles were detected in lung tissue, AMs, and fibroblasts.

 ■ Intratracheal instillation of cerium oxide nanoparticles also resulted in liver 

damage, which occurred through extrapulmonary translocation of the particles into the systemic circulation.

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, Hongwen Z, Barger M, Rao M, Meighan T, Castranova V, Ma JK 

[2009]. Pulmonary responses to diesel fuel catalyst cerium oxide nanoparticles. Toxicologist 108(S-1):49.

 ■ Hongwen Z, Ma JK, Mercer R,Millecchia L, Barger MW, Castranova V, Ma JY 

[2009]. Reactive oxygen/nitrogen species-mediated lung inflammation and 

mitochondrial dysfunction in wild type and iNOS deficient mice exposed to 

diesel exhaust particles. J Toxicol Environ Health A 72(8):560–570.

 ■ Ma JY, Zhao H, Mercer RR, Barger M, Rao M, Meighan T, Schwegler-Berry D, 

Castranova V, Ma JK [2011]. Cerium oxide nanoparticle–induced pulmonary 

inflammation and alveolar macrophage functional change in rats. Nanotoxicology 5:312–325. Epub 2010 October 6.

 ■ Ma JY, Mercer RR, Rao M, Barger M, Meighan T, Castranova V, Ma JK 

[2010]. Cerium oxide, a diesel fuel catalyst, induces pulmonary fibrosis. Toxicologist 114(S-1):55–56. 

 ■ Ma JY, Mercer RR, Rao M, Barger M, Meighan T, Ma JK, Castranova V 

[2011]. Matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 in cerium oxide induced pulmonary fibrosis. Toxicologist 

120(S-2):446.

 ■ Nalabotu SK, Kolli MB, Triest WE, Ma JY, Manne ND, Katta A, Addagarla 

HS, Rice KM, Blough ER [2011]. Intratracheal instillation of cerium oxide 

nanoparticles induces hepatic toxicity in male Sprague-Dawley rats. Int J 

Nanomedicine 6:2327–2335.
172 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Ma JY, Mercer RR, Barger M, Ma JK, Castranova V [2011]. Effects of cerium 

oxide nanoparticles on diesel exhaust particles–induced pulmonary responses. 2012 SOT Annual Meeting [accepted]. 

 ■ Dolash BD, Barger MW, Castranova V, Ma JY [2011]. Effects of combined 

exposure to diesel exhaust particles and cerium oxide nanoparticles on the 

response to endotoxin in rats. 2012 SOT Annual Meeting [accepted].

 ■ Nalabotu SK, Manne N, Kolli MB, Nandyala G, Para RK, Valentovic M, Rice 

K, Ma JY, Blough ER [2011]. Evaluation of oxidative stress and apoptosis in 

the liver following a single intratracheal instillation of cerium oxide nanoparticles in male Sprague Dawley rats. 2012 SOT Annual Meeting [accepted].
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 173

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 25: Potential Effects of Silicon-based 

Nanowires on Lung Toxicity

Principle Investigators: Stephen S. Leonard, PhD, and

Jenny R. Roberts, PhD

Project Duration: FY 2008–2012

Critical Topic Areas: 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 nanowire-induced 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 titanium nanowires were found to induce 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 

over time.

 ■ Evaluated a potential fluorescent marker, quantum dots, for tracking distribution of nanomaterials in the lung.

 ■ Completed an in vivo dose-response time course study evaluating pulmonary 

toxicity of silicon nanowires for up to 3 months after exposure in rats. Silicon 

nanowires caused a dose-dependent increase in lung injury, inflammation, 

and immune parameters that was transient, resolving approximately one week 

after exposure.

 ■ Evaluated distribution and clearance of silicon nanowires after intratracheal instillation in rats, using morphometric analyses. At a dose that 

induced inflammation early after exposure, the clearance half-life was 

calculated to be approximately 19 days, and 80% of the deposited material 

was cleared after 3 months. All of the nanowires were located within the 

alveolar region by day 1 post-exposure. By 1 week post-exposure the bulk 

of the material had been phagocytized by alveolar macrophages, and by 

3 months post-exposure the 20% of instillate that remained was contained 

entirely in alveolar macrophages.
174 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Conducted histological and morphological analysis of lung tissue following pulmonary exposure to silicon nanowires to assess the potential of the 

nanowires to induce fibrotic disease. Histological analysis revealed no overt 

signs of fibrosis throughout the 3-month time course; however, at 1 and 3 

months post-exposure, morphometric analysis indicated a slight thickening 

of connective tissue at doses that induced inflammation at earlier time points.

 ■ Evaluated alterations in lung immune responses in rats following pulmonary 

exposure to silicon nanowires. A dose-dependent increase in lymphocytes 

and eosinophils in the lungs was found to persist for up to 1 week postexposure, and rats challenged with a pulmonary bacterial infection following exposure to nanowires had a heightened immune response, resulting in 

increased clearance of the bacteria from the lungs.

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. Toxicology 236:103–113.

 ■ 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.

 ■ Murray AR, Kisin E, Leonard SS, Young S, Kommineni CV, Kagan CE, 

Castranova V, Shvedova AA [2009]. Oxidative stress and inflammatory 

response in dermal toxicity of single-walled carbon nnotubes. Toxicology 

257(3):161–171.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 175

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Pacurari M, Yin XJ, Ding M, Leonard S, Schwegler-Berry D, Ducatman BS, 

Endo M, Castranova V, Vallyathan V [2008]. Oxidative and molecular interactions of multi-wall carbon nanotubes (MWCNT) in normal and malignant 

human mesothelial cells. Nanotoxicology 2(3):155–170.

 ■ Roberts JR, Schwegler-Berry D, Chapman R, Antonini JM, Scabilloni JF, 

Castranova V, Mercer RR [2009]. Biodistribution of quantum dots after pulmonary exposure in rats. Society of Toxicology Annual Meeting, Baltimore, 

Maryland, March 16–18. Toxicologist 108:49, A240.

 ■ Chapman R, Roberts JR, Castranova V, Leonard SS [2009]. Generation of 

reactive oxygen species by silicon nanowires. Society of Toxicology Annual 

Meeting, Baltimore, Maryland, March 16–18. Toxicologist 108:184, A888.

 ■ Roberts JR, Chapman RS, Cohen GM, Bangsaruntip S, Schwegler-Berry D, 

Antonini JM, Leonard SS [2010]. Assessment of pulmonary toxicity following intratracheal exposure to silicon nanowires. Society of Toxicology Annual 

Meeting, Salt Lake City, Utah, March 7–11. Toxicologist 114:297, A1400.

 ■ Leonard SS, Chen TB, Stone S, Schwegler-Berry DE, Kenyon A, Frazer DG, 

Antonini JM [2010]. Comparison of stainless and mild steel welding fumes in 

generation of reactive oxygen species. Part Fibre Toxicol 7:32.

 ■ Rushton EK, Jiang J, Leonard SS, Eberly S, Castranova V, Biswas P, Elder A, 

Gelein R, Finkelstein J, Oberdorster G [2010]. Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological 

response-metric. J Toxicol Environ Health 73(5):445–461.

 ■ Kisin E, Murray A, Schwegler-Berry DE, Scabilloni JF, Mercer R, Chirila 

M, Young S, Leonard SS, Keohavong P, Fadeel B, Kagan VE, Castranova V, 

Shvedova AA [2010]. Pulmonary response, oxidative stress and genotoxicity 

induced by carbon nanofibers [abstract]. Toxicol Sci 114(1):176.

 ■ Murray A, Kisin E, Leonard SS, Young S, Schwegler-Berry DE, Castranova V, 

Fadeel B, Kagan VE, Shvedova AA [2010]. Toxic effects of metal/metal oxide 

nanoparticles in skin model [abstract]. Toxicologist 114(1):58.

 ■ Roberts JR, Chapman RS, Leonard SS, Cohen GM, Bangsaruntip S, Scabilloni 

JF, Antonini JM, Mercer RR [2010]. Analysis of distribution and clearance 

of silicon nanowires after pulmonary exposure in rats. American Thoracic 

Society International Conference, New Orleans, LA, May 14–19. Am J Respir 

Crit Care Med 181:A3092.

 ■ Porter DW, Hubbs AF, Mercer R, Wu N, Wolfarth M, Sriram K, Leonard SS, 

Battelli LA, Schwegler-Berry DE, Friend S, Andrew ME, Chen TB, Tsuruoka 

S, Endo M, Castranova V [2010]. Mouse pulmonary dose- and time courseresponses induced by exposure to multi-walled carbon nanotubes. Toxicology 

269(2–3):136–147.
176 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Wang J, Tafen D, Zheng J, Lewis JP, Leonard SS, Manivannan A, Wu N [2010]. 

Shape-enhanced photocatalytic activity of anatase TiO2 (101) nanobelts. J 

Am Chem Soc 132(19):6679–6685.

 ■ Roberts JR, Chapman RS, Tirumala VR, Karim A, Chen BT, Schwegler-Berry 

D, Stefaniak AB, Leonard SS, Antonini JM [2011]. Toxicological evaluation of 

lung responses after intratracheal exposure to non-dispersed titanium dioxide 

nanorods. J Toxicol Environ Health 74(12):790–810.

 ■ Roberts JR, Mercer RR, Chapman RS. Guy GM, Bangsaruntip S, SchweglerBerry D, Scabilloni JF, Castranova V, Antonini JM, Leonard SS [2012]. Pulmonary toxicity, distribution, and clearance of intratracheally-instilled silicon 

nanowires in rats. J Nanomaterials [submitted].

Invited Presentations 

 ■ Leonard SS, Kenyon AJ, Chapman R, Schwegler-Berry D, Cohen G, Roberts J 

[2010]. Generation of reactive oxygen species from silicon nanowires [poster]. NIOSH NTRC 2010 Update, Wheeling, West Virginia, April 19–21.

 ■ Leonard SS [2010]. Generation of reactive oxygen species from silicon 

nanowires. PPRB Seminar, NIOSH, Morgantown, West Virginia, July 6.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 177

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 26: Workplace Exposure, Inflammation, 

and Cardiovascular Toxicity

Principal Investigator: Aaron Erdely, PhD

Project Duration: FY 2010–2014

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings

 ■ These studies continue the exploration into the systemic effects following an 

occupational pulmonary exposure.

 ■ Low-dose inhalation exposure to gas metal arc–stainless steel (GMA-SS) 

welding fume showed an immunomodulatory response in C57BL/6J mice. 

Microarray analysis indicated a specific immune-mediated signature evident in the blood and aorta. The pathway was also a top network in the lung 

analysis, supporting the concept of a systemic signature reflecting the ongoing 

pulmonary response.

Nanomaterial worker
178 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ This study utilized a unique approach by simultaneously exploring molecular 

signaling in multiple compartments (lung, circulation, and vasculature). This 

approach has the utility to identify consistent, prominent, and/or novel pathways induced by a toxicant exposure. 

 ■ Low-dose inhalation exposure to GMA-SS welding fume showed a lowgrade systemic inflammatory and oxidative response in atherosclerotic 

prone apoE-/- mice. Inhalation of GMA-SS welding fume increased progression of atherosclerosis.

 ■ Studies using various types of welding fume provided findings regarding 

pulmonary and systemic markers of exposure. The measurable stress response 

in the vasculature was related to the initial cytotoxicity resulting from particle exposure. Systemic inflammation was related to the temporal increase in 

pulmonary inflammatory gene expression.

 ■ Studies to evaluate circulating markers after carbon nanotube (CNT) 

exposure showed increased systemic inflammatory mediators, a consistent 

eosinophilic response, and elevated acute-phase proteins related to immune activation.

Publications and Abstracts

 ■ Erdely A, Zeidler-Erdely PC, Liston A, Salmen-Muniz R, Hulderman T, 

Antonini JM, Simeonova PP [2010]. Acute systemic inflammation to welding 

fume: comparison of various types. Toxicologist 114(1):463.

 ■ Erdely A, Hulderman T, Zeidler-Erdely PC, Liston A, Salmen-Muniz R, Stone 

S, Chen BT, Frazer DG, Antonini JM, Simeonova PP [2010]. Effects of inhalation of gas metal arc–stainless steel welding fume on systemic inflammation 

and atherosclerosis. Am J Respir Crit Care Med 181:A1754.

 ■ Zeidler-Erdely, Erdely A, Stone S, Kashon ML, Li S, Antonini JM [2011]. Molecular pathways of pulmonary inflammation following aspiration and inhalation of stainless steel welding fume in mice. Toxicologist 120(S-2):2322.

 ■ Hulderman T, Liston AL, Salmen-Muniz R, Young S-H, Zeidler-Erdely PC, 

Castranova V, Simeonova PP, Erdely A [2011]. Identification of systemic markers from a pulmonary carbon nanotube exposure. Toxicologist 120(S-2):1492.

 ■ Erdely A, Hulderman T, Liston AL, Salmen-Muniz R, Stone S, Chen BT, 

Frazer DG, Li S, Kashon ML, Antonini JM, Simeonova PP, Zeidler-Erdely PC 

[2011]. Interferon signaling, systemic inflammation and atherosclerosis following welding fume inhalation exposure: from the lung to the blood to the 

vasculature. Toxicologist 120(S-2):185.

 ■ Erdely A, Hulderman T, Salmen-Muniz R, Liston A, Zeidler-Erdely PC, Chen 

BT, Stone S, Frazer DG, Antonini JM, Simeonova PP [2011]. Inhalation exposure of gas-metal arc stainless steel welding fume increased atherosclerotic 

lesions in apolipoprotein E knockout mice. Toxicol Lett 204(1):12–16.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 179

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Erdely A, Liston A, Salmen-Muniz R, Hulderman T, Young S-H, ZeidlerErdely PC, Castranova V, Simeonova PP [2011]. Identification of systemic 

markers from a pulmonary carbon nanotube exposure. J Occup Environ Med 

53(6 Suppl):S80– S86.

 ■ Erdely A, Salmen-Muniz R, Liston A, Hulderman T, Zeidler-Erdely PC, 

Antonini JM, Simeonova PP [2011]. Relationship between pulmonary and 

systemic markers of exposure to multiple types of welding particulate matter. 

Toxicology 287(1–3):153–159.

Invited Presentations

 ■ Erdely A [2010]. Systemic markers of pulmonary exposure to nanoparticles. 

Nanomaterials and Worker Health Conference, Keystone, Colorado, July 

21–23.
180 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 27: Cardiovascular Toxicity Assessment 

of Subchronic Inhalation Exposure 

to Fullerene C60

Principal Investigator: Aaron Erdely, PhD (and Petia Simeonova, 

PhD, deceased)

Project Duration: FY 2009–2010

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Evaluated cardiovascular effects of subchronic inhalation exposure to fullerene C60 particles (1 and 0.05 μm in diameter) in the mouse and rat (in collaboration with the National Institute of Environmental Health and Safety).

 ■ The initial screening for cardiovascular toxicity demonstrated changes in the 

expression of several genes related to a stress response, including c-fos and 

heat shock proteins 25, 70, and 90 in the aortas of the exposed mice. A select 

panel specific for heat shock and associated genes showed an increase in 

multiple related genes. Further evaluation also showed effects in the heart as 

well as female and male mice. A dose-dependent effect was evident, and the 

smaller of the two fullerenes had a greater effect. 

 ■ Heat shock proteins are involved in regulating 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.

 ■ Interestingly, inhalation exposure to fullerene C60 in rats did not have the 

same pronounced effect on heat shock protein changes as in the mouse. Instead, inhalation exposure resulted in a significant inflammatory response in 

the heart and vasculature. Mediators included Il6, Il10, Ptgs2 and Serpine1. 

 ■ These combined results indicate differential effects by species. Despite the 

differences, the changes overall indicate that prolonged inhalation exposure 

results in significant alterations in cardiovascular tissue expression profiles, 

absent of any observable pulmonary effect. 

Publications and Abstracts

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

NJ [2009]. Potential cardiovascular effects of fullerene C60 inhalation exposure. Toxicologist 108(1):50.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 181

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 28: Cell-Based Assessment for Iron 

Nanoparticle–Induced Health Risks

Principal Investigator: Yong Qian, PhD

Project Duration: FY 2008–2011

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings 

 ■ Developed a cell-based model for assessing iron nanoparticle–induced potential health risks.

 ■ Trained two post-PhD fellows and one PhD graduate student. 

 ■ 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.

 ■ Developed a cell-based model for assessing iron nanoparticle–induced potential health risks.

 ■ Identified a possible association between exposure to multi-walled carbon 

nanotubes (MWCNTs) and lung cancer proliferation and progression. This 

study indicates that MWCNT exposure may induce the alteration of several 

key carcinogenesis-related signaling transduction pathways. Taken together, 

the results obtained from this study suggest potentially carcinogenic effects of 

MWCNT exposure on human lungs. 

Publications and abstracts

 ■ Apopa PL, Qian Y, Guo NL, Schwegler-Berry D, Pacurari M, Porter D, Shi 

X,Vallyathan V, Castranova V, Flynn DC [2009]. Iron oxide nanoparticles 

induce human microvascular endothelial cell permeability through reactive 

oxygen species production and microtubule remodeling. Particle Fibre Toxicol 6:1–14.

 ■ Pacurari M, Qian Y, Porter DW, Wolfarth M, Wan Y, Luo D, Castranova V, 

Guo NL [2011]. Multi-walled carbon nanotube–induced gene expression 

in the mouse lung: implication of carcinogenesis risk. Particle Fibre Toxicol 

[submitted].

Invited Presentations

 ■ Qian Y, Apopa PL, Guo NL, Schwegler-Berry D, Pacurari M, Porter D, Shi 

X, Vallyathan V, Castranova V, Flynn DC [2010]. Iron oxide nanoparticles 

induce human microvascular endothelial cell permeability through reactive 
182 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

oxygen species production and microtubule remodeling. 6th Conference on 

Molecular Mechanisms of Metal Toxicity and Carcinogenesis, Lexington, 

Kentucky, November 12–16.

 ■ Apopa PL, Guo NL, Schwegler-Berry D, Pacurari M, Porter D, Shi X, Vallyathan V, Castranova V, Flynn DC, Qian Y [2010]. Iron oxide nanoparticles 

induce human microvascular endothelial cell permeability through reactive 

oxygen species production and microtubule remodeling. Annual Society of 

Toxicology Meeting, Salt Lake City, Utah, March 7–11.

 ■ Pacurari M, Qian Y, Porter DW, Wolfarth M, Wan Y, Luo D, Castranova V, 

Guo NL [2011]. Multi-walled carbon nanotube–induced gene expression in 

the mouse lung: implication of carcinogenesis risk. Abstract for 2011 Annual 

Society of Toxicology Meeting Washington, DC, March 6–10.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 183

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 29: Assessment of Carbonaceous 

Materials on Mutagenicity

Principal Investigator: Anna A. Shvedova, PhD, DSc

Project Duration: FY 2008–2009

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings

 ■ Inhalation exposure of C57BL/6 mice (5 mg/m3, 5 hours a day, for 4 days) to 

respirable single-walled carbon nanotubes (SWCNTs) caused formation of 

anuclear macrophages with fibrillar cytoplasm, along with mitotic changes, 

in the lung interstitial cells. A pattern of anaphase bridges in macrophages 

was clearly detected at 7 and 28 days post-inhalation. Therefore, such mitotic changes within macrophages with anaphase bridges indicated feasible 

spindle aberrations.

 ■ Post-exposure findings at 7 days revealed observable foci of bronchiolar 

epithelial cell hypertrophy in all exposed mice. Post-exposure findings at 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 

SWCNTs 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 

DNA damage. 

 ■ K-ras mutations were observed in the lung of C57BL/6 mice after inhalation 

exposure to SWCNTs. 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 mice exposed to SWCNTs 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 to 

SWCNT exposure.

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, 
184 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

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– L565.

 ■ Elder A, Lynch I, Grieger K, Chan-Remillard S, Gatti A, Gnewuch H, Kenawy E-R, Korensten R, Kuhlbusch T, Linker F, Matias S, Monteiro-Riviere 

N, Pinto V, Rudnitsky R, Savolainen K, Shvedova A [2008]. Deposition of 

nanoparticles as a function of their interactions with biomolecules. In: Linkov 

& Steevens, eds. Nanomaterials: risks and benefits. Proceedings of the NATO 

Advanced Research Workshop on Nanomaterials: Environmental Risks and 

Benefits, Faro, Portugal, April 27–30. Amsterdam, The Netherlands: Springer, 

pp. 3–29.

 ■ 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 Dec 6, PMID: 19103221. 

Invited Presentations

 ■ 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 on Cancer, Morgantown, West Virginia, February 12.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 185

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 30: Durability of Nanoscale Cellulose 

Fibers in Artificial Human Lung Fluids 

Principle Investigators: Aleksandr B. Stefaniak, PhD

 and Elizabeth Shogren

Project Duration: FY 2011–2012

Critical Topic Areas: Toxicology and internal dose; exposure assessment

Accomplishments and Research Findings 

 ■ Obtained funding from the National Toxicology Program.

 ■ Recruited four private and public sector organizations in the United States 

and Canada that donated five materials for planned studies.

 ■ Developed analytical protocols for material characterization and biodurability testing.

 ■ Characterized material physicochemical properties, including hydrodynamic 

diameter (photon correlation spectroscopy), zeta potential (light scattering), 

specific surface area (gas adsorption), density (pycnometry), crystallinity (xray diffraction), endotoxin and glucan content (LAL assay), and free radical 

generation (electron spin resonance).

 ■ Attended the TAPPI Workshop on International Standards for Nanocellulose, 

Arlington, Virginia.

 ■ Member of ISO TC229–Cellulose Task Group, which is drafting the United 

States’ position on terminology for nanocellulose through TAPPI.

Publications and Abstracts 

 ■ None

Invited Presentations 

 ■ None
186 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 31: Osteopontin and Carbon Nanotubes

Principal Investigator: Petia Simeonova, PhD

Project Duration: FY 2004–2009

Critical Topic Areas: Toxicology and Internal Dose

Accomplishments and Research Findings 

Respiratory exposure to engineered nanoparticles carries a potential risk for systemic 

effects including cardiovascular. We demonstrated that respiratory exposure to carbon 

nanotubes (CNT) induces blood and vascular alterations related to potential adverse 

cardiovascular outcomes. An interesting finding was that CNT accumulation in the 

lung after a single exposure is associated with a chronic and persistent release of 

osteopontin (OPN) into the systemic circulation. The blood release was accompanied 

by the expression of OPN and several closely related genes in the lung. Our hypothesis 

is that CNT-exposure induces persistent macrophage activation in the lung which is 

associated with expression and secretion of OPN. OPN may play a role in the CNT—

induced local and cardiovascular responses and represent a biomarker of response. 

Publications and Abstracts

 ■ Erdely A, Hulderman T, Salmen R, Liston A, Zeidler-Erdely P, Simeonova P 

[2009]. Time course of systemic effects following a single exposure to carbon 

nanotubes. Toxicologist 108(1):279

 ■ Walker V, Hulderman T, Simeonova P [2009]. Mechanism of multiwalled 

carbon nanotube- and asbestos-induced osteopontin/CD44 in Raw 264 macrophages. Mol Biol Cell 12(20 Suppl):2689

Invited Presentations

None
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 187

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 32: Determination of Diameter

Distribution for Carbon Nanotubes

by Raman Spectroscopy

Principal Investigator: Madalina Chirila, PhD

Project Duration: FY 2007–2009

Critical Topic Areas: Measurement methods

Accomplishments and Research Findings 

 ■ Installed digital camera on the microscope of the Raman system. 

 ■ Developed procedures for Raman and photoluminescence (PL) analysis of 

airborne CNT samples deposited on stainless steel grids. 

 ■ Performed Raman analyses on a set of 6 CNT samples, using 785 nm excitation to quantify fiber dimensions. 

 ■ Performed scanning electron microscopy (SEM) analysis on airborne CNT 

samples from NYU to quantify dimensions. 

Publications and Abstracts

 ■ Pacurari M, Yin X, Ding M, Leonard S, Schwegler-Berry D, Ducatman 

B, Chirila M, Endo M, Castranova V, Vallyathan V [2008]. Oxidative and 

molecular interactions of multi-wall carbon nanotubes (MWCNT) in normal 

and malignant human mesothelial cells. Nanotoxicology 2(3):155–170.

 ■ Stefaniak A, Chirila M [2008]. Tungsten oxide fiber dissolution and persistence in artificial human lung fluids. Proceedings of the inhalable particles 

2009. J Phys Conf Ser 151 012013 doi:10.1088/1742-6596/151/1/012013

 ■ Kisin E, Murray A, Schwegler-Berry D, Scabilloni J, Mercer R, Chirila M, 

Young S, Leonard S, Keohavong P, Fadeel B, Kagan V, Castranova V, Shvedova 

A [2010]. Pulmonary response, oxidative stress and genotoxicity induced by 

carbon nanofibers. Toxicologist 114(1):169.

 ■ Chirila M, Chisholm WP, Harper M [2006]. Raman spectroscopy: A powerful tool for characterizing physical properties and dispersion of single wall 

carbon nanotubes. Internat Aerosol Conf pp:170–171.

Invited Presentations

 ■ Chirila M [2007]. Assessment of metallic to semiconducting single wall carbon 

nanotubes ratio from Raman spectroscopy. Pittcon, Chicago, IL, February 26. 
188 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 33: Inhalation Facility Support

Principle Investigator: Teh-Hsun B. Chen, PhD

Project Duration: FY 2000–2015

Critical Topic Areas: Toxicology and internal dose

Accomplishments and Research Findings

MWCNT

 ■ Designed and fabricated an exposure chamber for multi-walled carbon nanotube (MWCNT) studies.

 ■ Characterized the MWCNT aerosol in the chamber, including the concentration, particle size distribution, and particle morphology.

 ■ Designed the inhalation exposure, based on the estimation of deposited lung 

burden of MWCNT aerosol from its size distribution and mass concentration.

 ■ Providing exposed animals for evaluation of cardiovascular effects of MWCNTs.

 ■ Successfully completed a dose-response study.

 ■ Successfully conducted 6 inhalation exposures (each involving 5 hours of 

exposure per day for 12 days) in the 1-year time-course study. Endpoints 

to be evaluated include pulmonary, central nervous system, and tumor 

development.

TiO2 Spray 

 ■ Characterized the aerosol resulting from the application of a commercial TiO2

spray. Results demonstrated the presence of nano-sized TiO2

 particles in 

the aerosol, with a concentration of 105 particles/cm3

 as the worst-case 

exposure scenario.

 ■ Designed and fabricated a generation/exposure system for a spray can study. 

This system uses a computer-controlled solenoid finger aided with an innovative can-shaking device to provide desirable aerosols in a custom-built wholebody chamber. Seven exposures were successfully conducted by exposing 

Sprague-Dawley rats to different combinations of concentrations (2–4 mg/m3

) 

and times (2–16 hours).

Welding Fumes

 ■ Fabricated a cone-shaped welding chamber according to physical dimensions 

recommended by the American Welding Society. This chamber is being used 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 189

APPENDIX A | A Summary of 69 NIOSH Research Projects

to evaluate the influence of welding process parameters on fume emission 

factors, profiles of the individual metals, and biological responses of ultrafine 

fume particles.

 ■ Observed that modest changes in welding process parameters (e.g., voltage) 

affected particle size and elemental composition and altered the temporal 

lung toxicity profile. Results indicated that although welding fume generated at a high voltage (30 kV) produced more nanoparticles, it did not elicit a 

neurotoxic response, compared to that generated at regular voltage (25 kV). 

The lack of neurotoxicity may be linked to the reduced solubility of Mn in the 

high-voltage fumes.

 ■ Constructed an automated resistance spot-welding generation and 

exposure system.

 ■ Generated fume aerosols of consistent concentrations (1–15 mg/m3

) in the 

animal exposure chamber during spot welding. The generated fumes have 

been characterized in terms of particle size, composition, and morphology. 

With or without an adhesive, the aerosol consists of both a metal particle and 

a volatile substance. The metal particle is composed of Fe, Mn, Cr, Zn, and Si. 

Samples of the volatile chemical have been sent for analyses.

Inhalation Exposure System

Power Amp.

Dryer Charcoal Filter HEPA

MFC

MFC

HEPA MFC House

Vacuum

Pressure

Regulator (30 psi)

House

Air

Box Air 

relief port

Used for generator

Trans-diaphragm

pressure control

Used for 

exposure air

flow control

Acoustical

Generator

P

P

Used for exposure

chamber pressure

control

Temp / %RH

sensor

Exposure

Chamber

DataRAM

exposure

concentration

Secondary

sample lines

Computer

Used for exposure

concentration control

Gravimetric Analysis

Moudi/Nano-moudi

(10 nm-10um)

TEM,SEM (imaging)

Chemical analysis

Characterization

Measurements

Trans-diaphragm

pressure

Chamber Pressure

MFC = Mass Flow Controller

Damp Sponges

HEPA
190 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Publications and Abstracts

 ■ Antonini JM, Afshari AA, Stone S, Chen BT, Schwegler-Berry D, Fletcher 

WG, Goldsmith WT, Vandestouwe KH, McKinney W, Castranova V, Frazer 

DG [2006]. Design, construction, and characterization of a novel robotic 

welding fume generation and inhalation exposure system for laboratory animals. J Occup Environ Hyg 3:194–203.

 ■ Nurkiewicz TR, Porter DW, Barger M, Hubbs AF, Millecchia L, Rao K, Chen 

BT, Frazer D, Castranova V, Boegehold MA [2006]. Ultrafine particulate matter inhalation induces remote microvascular dysfunction. FASEB J 20(5)(Part 

2):A1150.

 ■ Antonini JM, Stone S, Roberts JR, Chen BT, 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.

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

Frazer D, Castranova V [2007]. Nanoparticle inhalation attenuates systemic 

microvascular endothelium-dependent nitric oxide production. Microcirculation 14(4–5): IA-20, 470.

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

Castranova V [2008]. Nanoparticle inhalation augments particle-dependent 

systemic microvascular dysfunction. Particle Fibre Toxicol 5:1.

 ■ Baron PA, Deye GJ, Chen BT, Schwegler-Berry D, Shvedova AA, Castranova 

V [2008]. Aerosolization of single-walled carbon nanotubes for an inhalation 

study. Inhal Toxicol 8:751–760.

 ■ 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 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:L552–L565.

 ■ Antonini JM, Roberts JR, Stone S, Chen BT, Schwegler-Berry D, Frazer DG 

[2009]. Short-term inhalation exposure to mild steel welding fume had no 

effect on lung inflammation and injury but did alter defense responses to 

bacteria in rats. Inhal Toxicol 21:182–192.

 ■ Keane M, Stone S, Chen B, Slaven J, Schwegler-Berry D, Antonini J [2009]. 

Hexavalent chromium content in stainless steel welding fumes is dependent 

on the welding process and shield gas type. J Environ Monit 11:418–424.

 ■ Nurkiewicz TR, Porter DW, Hubbs AF, Stone S, Chen BT, Frazer DG, Boegehold MA, Castranova V [2009]. Pulmonary nanoparticle exposure disrupts 

systemic microvascular nitric oxide signaling. Toxicol Sci 110(1):191–203.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 191

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ McKinney W, Chen BT, Frazer D [2009]. Computer controlled multiwalled carbon nanotube inhalation exposure system. Inhal Toxicol 

21(12):1053–1061.

 ■ LeBlanc AJ, Cumpston JL, Chen BT, Frazer D, Castranova V, Nurkiewicz TR 

[2009]. Nanoparticle inhalation impairs endothelium-dependent vasodilation 

in subepicardial arterioles. J Toxicol Environ Health A 72:1576–1584.

 ■ Antonini JM, Sriram K, Benkovic SA, Roberts JR, Stone S, Chen BT, Schwegler-Berry D, Jefferson AM, Billig BK, Felton DM, Frazer DG, O’Callaghan JP, 

Miller DB [2009]. Mild steel welding fume causes manganese accumulation 

and subtle neuroinflammatory changes but not overt neuronal damage in 

discrete brain regions of rats after short-term inhalation exposure. Neurotoxicology 30:915–925.

 ■ Porter DW, Hubbs AF, Mercer RR, Wu N, Wolfarth MG, Sriram K, Leonard 

S, Battelli L, Schwegler-Berry D, Friend S, Andrew M, Chen BT, Tsuruoka 

S, Endo M, Castranova V [2010]. Mouse pulmonary dose- and time courseresponses induced by exposure to multi-walled carbon nanotubes. Toxicology 

269:136–147.

 ■ Keane M, Stone S, Chen BT [2010]. Welding fumes from stainless steel gas 

metal arc processes contain multiple manganese chemical species. J Environ 

Monit 12:1133–1140.

 ■ LeBlanc AJ, Moseley AM, Chen BT, Frazer D, Castranova V, Nurkiewicz TR 

[2010]. Nanoparticle inhalation impairs coronary microvascular reactivity 

via a local reactive oxygen species-dependent mechanism. Cardiovascular 

Toxicol 10:27–36.

 ■ Sriram K, Lin GX, Jefferson AM, Roberts JR, Chapman RS, Chen BT, Soukup 

JM, Ghio AJ, Antonini JM [2010]. Dopaminergic neurotoxicity following 

pulmonary exposure to manganese-containing welding fumes. Arch Toxicol 

84:521–540.

 ■ Scuri M, Chen BT, Castranova V, Reynolds JS, Johnson VJ, Samsell L, Walton 

C, Piedimonte G [2010]. Effects of titanium dioxide nanoparticles exposure 

on neuroimmune responses in rat airways. J Toxicol Environ Health Part A 

73:1353–1369.

 ■ Chen BT, Afshari A, Stone S, Jackson M, Schwegler-Berry D, Frazer DG, Castranova V, Thomas TA [2010]. Nanoparticles-containing, spray can aerosol: 

characterization, exposure assessment, and generator design. Inhal Toxicol 

22:1072–1082.

 ■ Wang L, Castranova V, Mishra A, Chen B, Mercer R, Schwegler-Berry D, 

Rojanasakul Y [2010]. Dispersion of single-walled carbon nanotubes by a 

natural lung surfactant for pulmonary in vitro and in vivo toxicity studies. 

Particle Fibre Toxicol 7:31.
192 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Leonard SS, Chen BT, Stone SG, Schwegler-Berry D, Kenyon AJ, Frazer D, 

Antonini JM [2010]. Comparison of stainless and mild steel welding fumes in 

generation of reactive oxygen species. Particle Fibre Toxicol 7:32.

 ■ Zeidler-Erdely PC, Battelli LA, Stone S, Chen BT, Frazer DG, Young S, Erdely 

A, Kashon ML, Andrews R,, Antonini JM [2011]. Short-term inhalation of 

stainless steel welding fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible A/J mice. Inhal Toxicol 23:112–120.

 ■ Roberts JR, Chapman RS, Tirumala V, Karim A, Chen BT, Schwegler-Berry 

D, Stefaniak AB, Leonard SS, Antonini JM [2011]. Toxicological evaluation of 

lung responses after intratracheal exposure to non-dispersed titanium dioxide 

nanorods, J Toxicol Environ Health Part A 74:790–810.

 ■ Antonini JM, Roberts JR, Stone S, Chen BT, Schwegler-Berry D, Chapman R, 

Zeidler-Erdely PC, Andrews RN, Sriram K, Frazer DG [2011]. Persistence of 

deposited metals in the lungs after stainless steel and mild steel welding fume 

inhalation in rats. Arch Toxicol 85:487–498.

 ■ Erdely AD, Hulderman T, Salmen R, Liston A, Zeidler-Erdely PC, Chen BT, 

Stone S, Frazer DG, Antonini JM, Simeonova PP [2011]. Inhalation exposure 

of gas–metal arc stainless steel welding fume increased atherosclerotic lesions 

in apolipoprotein E knockout mice. Toxicol Lett 204:12–16.

 ■ Antonini JM, Keane M, Chen BT, Stone S, Roberts JR, Schwegler-Berry D, 

Andrews RN, Frazer DG, Sriram K [2011]. Alterations in welding process 

voltage affect the generation of ultrafine particles, fume composition, and 

pulmonary toxicity. Nanotoxicology 5:700–710.

 ■ LeBouf RF, Stefaniak AB, Chen BT, Frazer DG, Virji MA [2011]. Measurement of airborne nanoparticle surface area using a filter-based gas adsorption 

method for inhalation toxicology experiments. Nanotoxicology 5:687–699.

 ■ Nurkiewicz TR, Porter DW, Hubbs AF, Stone S, Moseley AM, Cumpston JL, 

Goodwill AG, Frisbee SJ, Perrotta PL, Frisbee JC, Boegehold MA, Frazer DG, 

Chen BT, Castranova V [2011]. Pulmonary particulate matter and systemic 

microvascular dysfunction. HEI Research Report No. 164, Boston, MA, 

December.

 ■ Knuckles TL, Yi J, Frazer DG, Leonard HD, Chen BT, Castranova V, Nurkiewicz TR [2011]. Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways. Nanotoxicology. Online doi:10.3109/17435390.2011.606926.

 ■ Sellamuthu R, Umbright C, Roberts J+, Chapman R, Young S, Richardson D, 

Leonard D, McKinney W, Chen B, Frazer D, Li S, Kashon M, Joseph P [2011]. 

Blood gene expression profiling detects silica exposure and toxicity. Toxicol 

Sci 122(2):253–264.

 ■ Kan H, Wu ZX, Young SH, Chen BT, Cumpston JL, Chen F, Kashon ML, Castranova V [2011]. Pulmonary exposure of rats to ultrafine titanium dioxide enhances 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 193

APPENDIX A | A Summary of 69 NIOSH Research Projects

cardiac protein phosphorylation and substance P synthesis in nodose ganglia. 

Nanotoxicology. Online doi:10.3109/17435390.2011.611915

 ■ LeBouf RF, Ku BK, Chen BT, Frazer DG, Cumpston JL, Stefaniak AB [2011]. 

Measuring surface area of airborne titanium dioxide powder agglomerates: 

relationships between gas adsorption, diffusion and mobility-based methods. 

J Nanoparticle Res 13(12):7029–7039.

 ■ Sellamuthu R, Umbright C, Roberts J, Cumpston A, McKinney W, Chen 

BT, Frazer D, Li S, Kashon M, Joseph P [2012]. Molecular insights into the 

progression of crystalline silica–induced pulmonary toxicity in rats. J Appl 

Toxicol [http://dx.doi.org/10.1002/jat2733].

 ■ Mishra A, Rojanasakul Y, Chen BT, Castranova V, Mercer R, Wang L [2012]. 

Assessment of pulmonary fibrogenic potential of multi-walled carbon nanotubes in human lung cells. J Nanomater 3:930931.

 ■ Erdely AD, Antonini JM, Salmen-Muniz R, Liston A, Hulderman T, Simeonova PP, Kashon M, Li S, Stone S, Chen BT, Frazer DG, Zeidler-Erdely PC 

[2011]. Type I interferon and pattern recognition receptor signaling following 

particulate matter inhalation. Particle Fibre Toxicol [submitted].

 ■ McKinney W, Jackson M, Sager TM, Reynolds JS, Chen BT, Afshari A, Krajnak K,Waugh S, Johnson C, Mercer RR, Frazer DG, Thomas TA, Castranova 

V [2012]. Pulmonary and cardiovascular responses of rats to inhalation of a 

commercial antimicrobial spray containing titanium dioxide nanoparticles. 

Inhal Toxicol 24(7):447–457.

 ■ Chen BT, Schwegler-Berry D, Mckinney W, Stone S, Cumpston JL, Friend 

S, Porter DW, Castranova V, Frazer DG [2011]. Multi-walled carbon nanotubes aerosols: physical characterization and health relevance. Inhal Toxicol 

[submitted].

Invited Presentations

 ■ Chen BT, Cumpston JL, Moseley AM, Stone S, Schwegler-Berry D, Porter 

DW, Hubbs AF, Frazer DG, Castranova V, Nurkiewicz TR [2009]. Particleassociated systemic microvascular dysfunction [abstract #7I.27]. Annual 

Conference of the American Association for Aerosol Research. Minneapolis, 

Minnesota, October 26–30.

 ■ Antonini JM, Chen BT, Stone S, Roberts JR, Schwegler-Berry D, Chapman R, 

Moseley A, Cumpston JL, Leonard H, Frazer DG, Keane M, Sriram K [2010]. 

Alterations in welding process parameters change particle characteristics and 

influence lung responses [abstract]. American Thoracic Society International 

Conference, New Orleans, Louisiana, May 14–19. Am J Respir Crit Care Med 

181:A1746.

 ■ Chen BT, Afshari A, Stone S, Jackson M, McKinney W, Schwegler-Berry D, 

Frazer DG, Castranova V, Thomas TA [2010]. Nanoparticle-containing, spray 
194 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

can aerosol: characterization, exposure assessment, and inhalation chamber 

design [abstract #2J1]. The 29th Annual Conference of the American Association for Aerosol Research, Portland, Oregon, October 25–29.

 ■ McKinney W, Afshari A, Chen BT, Frazer DG [2010]. Automated aerosolization, dispersion, and concentration control of silica powder for use in inhalation exposure studies [abstract]. Society of Toxicology Annual Meeting, Salt 

Lake City, Utah, March 7–11. Toxicologist 114(1):317.

 ■ Afshari A, Chen BT, Schwegler-Berry D, Cumpston JL, Cumpston A, Leonard 

HD, Friend S, Zeidler-Erdely PC, Frazer DG, Antonini JM [2011]. Characterization of welding aerosols generated by resistance spot welding. Society of 

Toxicology Annual Meeting, Washington, DC, March 6–10.

 ■ Erdely A, Hulderman T, Liston AL, Salmen-Muniz R, Stone S, Chen BT, 

Frazer DG, Li S, Kashon ML, Antonini JM, Simeonova PP, Zeidler-Erdely 

PC [2011]. Interferon signaling, systemic inflammation and atherosclerosis 

following welding fume inhalation exposure–from the lung to the blood to 

the vasculature. Society of Toxicology Annual Meeting, Washington, DC, 

March 6–10.

 ■ Hubbs AF, Castranova V, Chen BT, Frazer DG, McKinney W, Mercer RR, 

Kashon ML, Battelli LA, Willard P, Porter DW [2011]. Pulmonary inflammation, epithelial hyperplasia, and lymph node translocation after multi-walled 

carbon nanotube inhalation. Society of Toxicology Annual Meeting, Washington, DC, March 6–10.

 ■ Kan H, Wu Z, Young S, Chen TB, Cumpston JL, Chen F, Castranova V [2011]. 

Nanoparticle inhalation enhances cardiac protein phosphorylation and neurotransmitter synthesis in the nodose ganglia of rats. Society of Toxicology 

Annual Meeting, Washington, DC, March 6–10.

 ■ Knuckles TL, Yi J, Frazer DG, Cumpston JL, Chen BT, Castranova V, 

Nurkiewicz TR [2011]. Nanoparticles alter cyclooxygenase activity in microvascular dysfunction. Society of Toxicology Annual Meeting, Washington, DC, March 6–10.

 ■ LeBouf RF, Ku BK, Chen BT, Cumpston JL, Stefaniak AB [2011]. Measurement of surface area of airborne titanium dioxide powder agglomerates: 

relationships between real-time diffusion charging-based and gas adsorption 

filter-based methods. 5th International Symposium on Nanotechnology, Occupational and Environmental Health, Boston, Massachusetts, August 11–12.

 ■ Roberts JR, Chapman RS, Young SH, Kenyon A, Schwegler-Berry D, Stefaniak 

AB, Chen BT, Antonini JM [2011]. Pulmonary toxicity following intratracheal 

instillation of dispersed silver nanoparticles in rats. Society of Toxicology Annual Meeting, Washington, DC, March 6–10.

 ■ Sellamuthu R, Umbright C, Roberts J, Chapman R, Young S, Leonard D, 

McKinney W, Chen B, Frazer D, Li S, Kashon M, Joseph P [2011]. Peripheral 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 195

APPENDIX A | A Summary of 69 NIOSH Research Projects

blood gene expression profiling reveals silica-induced pulmonary toxicity. 

Society of Toxicology Annual Meeting, Washington, DC, March 6–10.

 ■ Stapleton PA, Minarchick V, Cumpston A, McKinney W, Chen BT, Frazer D, 

Castranova V, Nurkiewicz TR [2011]. Time-course of impaired coronary 

arteriolar endothelium-dependent dilation after multi-walled carbon nanotube inhalation. Society of Toxicology Annual Meeting, Washington, DC, 

March 6–10.

 ■ Wolfarth M, McKinney W, Chen TB, Castranova V, Porter DW [2011]. Acute 

pulmonary responses to MWCNT inhalation. Society of Toxicology Annual 

Meeting, Washington, DC, March 6–10.
196 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 34: Generation and Characterization

of Nanoparticles 

Principal Investigator: Bon-Ki Ku, PhD

Project Duration: FY 2004–2008

Critical Topic Area: Measurement methods

Accomplishments and Research Findings

 ■ Developed an electrospray generation system to produce single-walled carbon 

nanotube (SWCNT) aerosols with well-defined morphology for the purpose 

of evaluation of 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 relationships 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.

 ■ Investigated 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 monitoring 

methods and new/improved instrument designs that are needed for accurate 

characterization of worker exposures.

 ■ In conjunction with Yale University, contributed a large number 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 197

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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 [2004]. Nanotechnology—a new occupational health challenge 

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

 ■ Maynard AD [2004]. Responsible nanotech at work. Nanotechnology: A Materials Today Supplement, p. 56.

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

[2004]. Exposure to carbon nanotube material during the handling of unrefined single walled carbon nanotube material. J Toxicol Environ Health Part A 

67:87–107.

 ■ Ku BK, Maynard AD [2005]. Comparing aerosol surface-area measurement of 

monodisperse ultrafine silver agglomerates using mobility analysis, transmission electron microscopy and diffusion charging. J Aerosol Sci 36:1108–1124.

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

84:A649.

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

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

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

nanoparticles with specific size and morphology by homogeneous nucleation, 

coagulation, and sintering. J Aerosol Sci 37:452–470.

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

situ structure characterization of airborne carbon nanofibers by a tandem 

mobility-mass analysis. Nanotechnology 17:3613–3621.

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

mapping of fine and ultrafine particle concentrations in an engine machining 

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

 ■ 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 [in Korean]. Indust 

Health 2:44–49. 

 ■ 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. 
198 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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 [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–L565.

 ■ Ku B-K, Kulkarni P [2009]. Morphology of single-wall carbon nanotube aggregates generated by electrospray of aqueous suspensions. J Nanopart Res 

11(6):1393–1403. 

Invited Presentations

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

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

Symposium on Neurobehavioral Methods and Effects in Occupational and 

Environmental Health, Gyeongju, South Korea, September 26–29.

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

surface area in the automotive industry. 24th Annual AAAR Conference, 

Austin, Texas, October 17–21.

 ■ Ku BK, Maynard AD [2005]. Physical characterization of airborne carbon 

nanofibers. In: Proceedings of the 2nd International Symposium on Nanotechnology and Occupational Health, Minneapolis, Minnesota, October 3–6, p. 119.

 ■ Ku BK, Maynard AD, Baron PA, Deye G [2005]. Anomalous responses (arcing, electrical discharge) in a differential mobility analyzer caused by ultrafine 

fibrous carbon aerosols. In: Proceedings of the 24th Annual AAAR Conference, Austin, Texas, October 17–21, p. 43.

 ■ Ramsey D, Ku BK, Maynard AD, Evans DE, Bennett J [2005]. Evaluation 

of nanoparticle de-agglomeration by disc centrifuge. In: Proceedings of the 

2nd International Symposium on Nanotechnology and Occupational Health, 

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

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

Obtaining dispersion of an intensive particle property from a tandem-sizing 

experiment. 7th International Aerosol Conference, Minneapolis, Minnesota, 

September 10–15.

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

Measurement of airborne carbon nanofiber structure using a tandem mobility-mass analysis. 7th International Aerosol Conference, Minneapolis, Minnesota, September 10–15.

 ■ 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 199

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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, Nevada, September 24–28.

 ■ Ku B-K [2007]. Nanoparticles and Occupational Health: Toward Safe Nanotechnology Conference. University of Kentucky, Lexington, Kentucky, 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, Florida, 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, Florida, October 20–24. 
200 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 35: Dustiness of Nanomaterials

Principle Investigator: Douglas E. Evans, PhD

Project Duration: FY 2007–2010

Critical Topic Areas: Measurement methods; exposure assessment; fire and 

explosion safety

Accomplishments and Research Findings

 ■ Completed pilot phase of the research.

 ■ Evaluated novel method/device for testing pharmaceutical powders and 

found it to be suitable for testing nanomaterials. Advantages of the method 

include

 — Only small powder samples required (mg quantities), allowing for a potentially greater number of powdered 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

 — Simple (gravimetric) size selective sampling of dispersed powders

Dustiness testing
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 201

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Tested 27 fine and nanoscale materials—consisting of at least five replicate 

tests—for total and respirable mass. Dustiness values span two orders of magnitude on both a respirable and total mass basis.

 ■ Strong positive correlation between respirable and total mass observed for 

powders tested.

 ■ Size distribution measurements of powders conducted.

 ■ Other metrics considered, such as particle number.

 ■ Interest in method/research expressed by U.S. EPA.

Publications and Abstracts 

 ■ Evans DE, Turkevich LA, Roettgers CT, Deye GJ, Baron PA [2012]. Dustiness 

of fine and nanoscale powders. Ann Occup Hyg, doi 10.1093/annhyg/mes060.

Invited Presentations 

 ■ Evans DE [2007]. Working at the nanoscale: the occupational health and 

safety perspective. NANOMIST final meeting, Birmingham, United Kingdom, February 19.

 ■ 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.

 ■ Evans DE [2010]. Workplace monitoring during CNF production. Ask the 

Expert: An Update on the NIOSH Nanotechnology Program. The American 

Industrial Hygiene Conference and Exposition, Denver, Colorado, May 25.

 ■ Evans DE, Turkevich LA, Roettgers C, Deye GJ, Baron PA [2011]. Dustiness 

of nanomaterials. AIHce, Portland, Oregon, May 14–19.

 ■ Evans DE, Turkevich LA, Roettgers C, Deye GJ, Baron PA [2011]. Dustiness of 

nanomaterials. 5th International Symposium on Nanotechnology–Occupational 

and Environmental Health, Boston, Massachusetts, August 10–12.

 ■ Evans DE, Turkevich LA, Roettgers C, Deye GJ, Baron PA [2011]. Dustiness 

of nanomaterials. American Association for Aerosol Research Annual Conference, Orlando, Florida, October 3–7.
202 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 36: Measurement of Nanoscale 

Carbonaceous Aerosols

Principle Investigator: M. Eileen Birch, PhD 

Project Duration: FY 2007–2008 (Continued in FY09

 as project 37)

Critical Topic Areas: Measurement methods, exposure assessment 

Accomplishments and Research Findings

 ■ 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 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 FY2007 and FY2008) at 

a major CNF manufacturer. Found CNF dispersion within the facility. Identified production byproducts and informed company regarding air quality. Also 

provided recommendations to improve air quality. 

 ■ Began work on generation of a carbon black aerosol and its collection on filter 

sets (FY08). Work continued in FY2009 under project 37. 

 ■ 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.

 ■ 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 203

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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, Nevada, 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, Florida, 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, Ohio, June 10–14. 
204 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 37: Nanoaerosol Monitoring Methods 

(formerly Automotive Ultrafine 

Intervention)

Principle Investigators: M. Eileen Birch, PhD, and

 Douglas E. Evans, PhD

Project Duration: FY 2006–2012 

Critical Topic Areas: Measurement methods, exposure assessment

Accomplishments and Research Findings 

This project was initiated as an umbrella project of the aerosol research team in the 

NIOSH Division of Applied Research and Technology (DART). It has supported multiple pilot investigations on fine/ultrafine and nanomaterial aerosols. Project objectives are to evaluate monitoring methods for nanoscale aerosols and to characterize 

aerosol properties. Filter-based methods and state-of-the-art instruments have been 

applied. Metrics include particle mass, surface area, number, size distribution, composition, and morphology. Significant activities included the following: 

 ■ Conducted first Institute study (FY06) at a carbon nanofiber (CNF) composite facility (University of Dayton Research Institute [UDRI]). This first 

Institute study on engineered nanomaterials inspired creation of a NIOSH 

nanotechnology field team for screening surveys.

 ■ Collaborated on collection and analysis of diesel particulate samples from mines.

 ■ Contributed technical input to multiple other nano surveys (e.g., quantum 

dots, filter manufacturer).

 ■ Completed walk-through and screening surveys at a major CNF producer. 

Provided summary of results and submitted report to company.

 ■ Completed survey on ultrafine aerosol sources at diesel engine manufacturing plant. 

 ■ Provided direct-reading instrument data collected at titanium dioxide manufacturing facility to an environmental health and safety facilitator. 

 ■ Completed construction of a novel instrument for fast measurement of 

nanoparticle size distribution (instrument has been developed as a commercial prototype under a new project). 

 ■ Conducted initial survey of firefighters’ exposures during vehicle fire suppression training exercises (three engine and three cabin fires) (July 2009). 

Coauthored HHE report (2010). 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 205

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Monitored fine/ultrafine particles during structural fire training exercise at 

the Illinois Fire Service Institute, with the Chicago Fire Department (three 

structural fires in 08/10 and three structural fires in 08/11). 

 ■ Co-authored (Evans) small NORA proposal (with DSHEFS) on exposures to 

firefighters during structural fire suppression. Proposal was funded. Preliminary findings suggest that self-contained breathing apparatus (SCBA) should 

be worn throughout all stages of fire suppression.

 ■ Completed pilot studies on direct-reading instrument for determining the 

elemental composition of aerosols. 

 ■ Submitted new NORA proposal on development of a direct-reading instrument for elemental composition of aerosol; proposal was approved (2QFY12) 

for funding. 

 ■ Established partnerships for research translation (e.g., Photon Machines, Inc., 

BGI Inc. are partners on a new FY12 NORA project; Kanomax, Inc. is a partner on commercialization of a portable aerosol monitor).

 ■ Collaborated on rail yard study of worker exposure to diesel emissions. 

Publications and Abstracts

 ■ Liang F, Lu M, Birch ME, Keener TC, Liu Z [2006]. Determination of polycyclic aromatic sulfur heterocycles in diesel particulate matter and diesel fuel 

by gas chromatography with atomic emission detection. J Chromatogr A 

1114(1):145–153. 

 ■ Methner M, Birch ME, Evans D, Hoover M [2006]. NIOSH Health Hazard 

Evaluation (HHE) on workplace assessment of potential exposure to carbonaceous nanomaterials, HETA Report #2005-0291-3025.

 ■ 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.

 ■ 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].
206 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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. 

Toxicologist 102(1):307. 

 ■ Baron PA, Deye GJ, Chen B, Schwegler-Berry DE, Shvedova AA, Castranova 

V [2008]. Aerosolization of single-walled carbon nanotubes for an inhalation 

study. Inhal Toxicol 20(8):751–760. 

 ■ 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 [2008]. Inhalation versus 

aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, 

fibrosis, oxidative stress, and mutagenesis. Am J Physiol 95(4):L552–L565.

 ■ Heitbrink WA, Evans DE, Ku B-K, Maynard AD, Slavin TJ, Peters TM [2009]. 

Relationships between particle number, surface area, and respirable mass 

concentration in automotive engine manufacturing. J Occup Environ Hyg 

6(1):19–32. 

 ■ Kulkarni PK, Deye GJ, Baron PA [2009]. Bipolar diffusion charging characteristics of single-walled carbon nanotube aerosols. J Aerosol Sci 40(2):164–179.

 ■ Fent KW, Evans DE [2011]. Assessing the risk to firefighters from chemical vapors and gases during vehicle fire suppression. J Environ Monit 

13(3):536–543.

 ■ Fent KW, Evans DE, Couch J [2010]. Evaluation of chemical and particle 

exposures during vehicle fire suppression training: Health Hazard Evaluation 

Report, HETA 2008-0241-3113, Miami Township Fire and Rescue, Yellow 

Springs, Ohio (July 2010).

 ■ Fent KW, Evans DE, Couch J, Niemeier M [2012]. Evaluating vehicle fire 

training inhalation hazards. Fire Engineering 165(2): 63–68.

 ■ Diwakar PK, Kulkarni PS, Birch ME [2012]. New approach for near-real-time 

measurement of elemental composition of aerosols using laser induced breakdown spectroscopy. Aerosol Science and Technology 46:316–332.

 ■ Diwakar PK, Kulkarni PS [2012]. Measurement of elemental concentration 

of aerosols using spark emission spectroscopy. Journal of Analytical Atomic 

Spectrometry, doi: 10.1039/C2JA30025G 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 207

APPENDIX A | A Summary of 69 NIOSH Research Projects

Invited Presentations

 ■ Evans DE [2006]. Field measurement of aerosols at the nanoscale. International Conference for Nanotechnology. Occupational and Environmental 

Health and Safety; Research to Practice. Cincinnati, Ohio, December 7th.

 ■ Dunn KH [2006]. Nanotech exposure controls and best practices. International Conference for Nanotechnology. Occupational and Environmental 

Health and Safety; Research to Practice. Cincinnati, Ohio, December 7th. 

 ■ Birch ME, Evans DE, Methner M, McCleery RE, Crouch KG, Ku B-K, Hoover 

MD [2006]. Workplace assessment of potential exposure to carbonaceous 

nanomaterials, International Conference for Nanotechnology. Occupational 

and Environmental Health and Safety; Research to Practice, Cincinnati, Ohio, 

December 7th.

 ■ Kulkarni P, Wang J [2006]. High-time rsolution measurement of nanoaerosol size distribution using fast integrated mobility spectrometer (FIMS) 

[2006]. International Conference for Nanotechnology. Occupational and 

Environmental Health and Safety; Research to Practice. Cincinnati, Ohio, 

December 7th.

 ■ Liang F, Birch ME, Lu M [2006]. Load dependent composition of diesel particulate emissions from a non-road diesel generator, International Conference 

for Nanotechnology. Occupational and Environmental Health and Safety; 

Research to Practice. Cincinnati, Ohio, December 7th.

 ■ Baron PA [2006]. Description of an aerosol calculator. 7th International Aerosol Conference, Minneapolis, Minnesota, September 10–15.

 ■ Birch ME, Evans DE, Methner MM, McCleery RE, Crouch KG, Ku B-K, 

Hoover MD [2006]. Workplace assessment of potential exposure to carbonaceous nanomaterials. International Aerosol Conference, St. Paul, Minnesota, 

September 10–15.

 ■ 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 PK, Deye GJ, Baron PA [2007]. Bipolar diffusion charging characteristics of airborne, single-walled carbon nanotubes. American Association for 

Aerosol Research Annual Conference, Reno, Nevada, September 24–28.

 ■ Evans DE [2007]. Working at the nanoscale: the occupational health and 

safety perspective. NANOMIST Meeting, Birmingham, United Kingdom, 

February 19. 
208 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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, Ohio, April 29.

 ■ Diwakar P, Kulkarni PS, Birch ME [2010]. Matrix effect in substrate based laser-induced breakdown spectroscopy. 6th International Conference on LaserInduced Breakdown Spectroscopy (LIBS 2010), Memphis, TN, Sep 13–17.

 ■ Diwakar P, Kulkarni PS, Birch ME [2010]. Novel approach for analysis of fine 

and ultra-fine aerosol particles using laser induced breakdown spectroscopy. 

6th International Conference on Laser-Induced Breakdown Spectroscopy 

2010 (LIBS 2010), Memphis, TN, Sep 13–17.

 ■ Diwakar P, Kulkarni PS, Birch ME [2010]. Matrix effects in laser-induced 

breakdown spectroscopy. 29th American Association for Aerosol Research 

Annual Conference, Portland, OR, October 25–29.

 ■ Diwakar P, Kulkarni PS, Birch ME [2010]. Semi-continuous measurement of 

elemental composition of aerosol particles using laser induced breakdown 

spectroscopy. 29th American Association for Aerosol Research Annual Conference, Portland, OR, October 25–29.

 ■ Lu M, Hu JC, Birch ME, Yang J, Keener T, Wei H [2011]. Measurement of 

near-road black carbon exposure from traffic sources in a midwestern urban 

area, NORA Symposium 2011: Achieving Impact through Research and Partnerships. Cincinnati, OH, July 12–13.

 ■ Diwakar P, Kulkarni P, Birch E [2011]. Novel approach for analysis of fine 

and ultra-fine aerosol particles using laser induced breakdown spectroscopy. 

NORA Symposium 2011: Achieving Impact through Research and Partnerships, Cincinnati, OH, July 12–13

 ■ Diwakar P, Kulkarni P [2011]. Spark-induced breakdown spectroscopy for 

near real-time elemental analysis of aerosols. 3rd North American Symposium on Laser-Induced Breakdown Spectroscopy, (NASLIBS), Clearwater 

Beach, FL, July 18–20.

 ■ Diwakar P, Kulkarni P, Efthimion P [2011]. Corona-assisted microwave 

plasma spectroscopy (CAMPS) for aerosol analysis. 3rd North American 

Symposium on Laser Induced Breakdown Spectroscopy (NASLIBS 2011), 

Clearwater Beach, FL, July 18–20.

 ■ Cauda E, Miller A, Ku BK, Barone T [2011]. Surface area of diesel particulate 

matter nanoparticles in underground mines. 5th International Conference 

on Nanotechnology—Occupational and Environmental Health, Boston, MA, 

August 9–12.

 ■ Diwakar P., Kulkarni PS [2011]. Near real-time elemental analysis of aerosols 

using spark-induced breakdown spectroscopy. AAAR 30th Annual Conference, Orlando, FL, October 3–7.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 209

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Diwakar P, Hahn DW, Niemax K, Groh S [2011]. Role of analyte diffusion in 

laser-induced plasmas. FACSS 2011, Reno, NV, Oct 2–7.

 ■ Diwakar P, Kulkarni PS [2011]. Near real-time elemental analysis of aerosols 

using laser and spark-induced breakdown spectroscopy. FACSS 2011, Reno, 

NV, October 2–7.
210 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 38: Workplace Monitoring of Carbon 

Nanofibers/Nanotubes

Principle Investigators: M. Eileen Birch, PhD, and

 Douglas E. Evans, PhD

Project Duration: FY 2009–2012

Critical Topic Areas: Measurement methods, exposure assessment 

Accomplishments and Research Findings 

Field/Laboratory Research 

 ■ Conducted follow-up survey at CNF manufacturer and submitted report to 

company (FY09).

 ■ Conducted two surveys with the Division of Surveillance and Hazard Evaluations collaborators: at a multi-walled CNT [MWCNT] and SWCNT manufacturer and at a SWCNT and fullerene manufacturer (FY10) 

 — Completed sample analyses (NIOSH 5040). Performed direct-reading 

monitoring, analyzed data, and co-authored two company reports. Provided recommendations to companies to reduce potential exposures. 

 ■ Conducted survey at single-walled CNT (SWCNT) manufacturer in OK 

(FY10).

 — Found surface contamination by SWCNTs and catalyst precursor. Completed sample analyses (NIOSH 5040) and reported to manufacturer.

 ■ Developed aerosol generation method to collect matched filter sets with 

known organic and elemental carbon (OC and EC).

 ■ Completed international round robin on OC-EC filter sets; completed journal 

paper on results.

 ■ Characterized over 20 CNF/CNT materials chemically and physically. Properties were quite variable—e.g., specific surface areas ranged from 22 to 662 

m2

/g, with a material (Mitsui) tested in an inhalation study by NIOSH Health 

Effects Research Division (HELD) being the lowest (manuscript submitted). 

 ■ Designed modified air sampler to improve NIOSH 5040 LOD for respirable 

aerosol. 

 ■ Completed sampler comparison (FY11–FY12).

 ■ Began investigation of a method for determining the metal content of 

CNTs/CNFs. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 211

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Completed additional surface area (BET) measurements on CNF/CNT 

materials. 

 ■ Completed TGA analyses of CNF/CNT materials (FY11). 

 ■ Initiated research on a TEM-based method for counting CNT/CNF 

structures.

 ■ Collaborated on field studies with IWSB colleagues. 

 — Doug Evans participated in two exposure assessment surveys with 

DSHEFS/IWSB colleagues. Assessments consisted of personal breathing zone and area monitoring with time-integrated and direct-reading 

methods. 

 — Dr. Birch reviewed TEM and NIOSH 5040 results for six field surveys by 

IWSB (and others) to assist with data interpretation and quality.

Other

 ■ Reviewed and responded to public and peer reviewers’ comments on draft 

CNT/CNF CIB.

 ■ Established MOA with University of Cincinnati (UC) regarding sharing of the 

NIOSH TEM facility in exchange for technical assistance with TEM analyses 

and UC contribution to the instrument maintenance contract. 

Nanoparticle sampling equipment
212 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Reviewed multiple Laboratory Information Management System (LIMS) 

reports on TEM results (FY11–12). 

 ■ Established IA on carbonaceous aerosols with U.S. EPA.

 ■ Established MOA with University of Cincinnati (UC) regarding NIOSH 

transmission electron microscopy (TEM) facility. (FY11–12) 

 ■ Coauthored NTP proposal on CNF/CNT exposure assessment with DSHEFS 

colleagues (funded in FY12–FY13). Evans et al. [2010] journal article on workplace monitoring of CNFs by direct reading intruments won the NIOSH 2011 

Alice Hamilton Award in the Engineering and Physical Sciences category.

Publications and Abstracts 

 ■ Evans DE, Ku BK, Birch ME, Dunn KH [2010]. Aerosol monitoring during 

carbon nanofiber production: mobile direct-reading sampling. Ann Occup 

Hyg 54(5):514–531.

 ■ Birch ME [2010]. Appendix C: NIOSH method 5040, and exposure monitoring section. NIOSH current intelligence bulletin: occupational exposure to 

carbon nanotubes and nanofibers (draft). NIOSH docket number: NIOSH 

161-A [www.cdc.gov/niosh/docket/review/docket161A/]. 

 ■ Birch ME, Ku BK, Evans DE, Ruda-Eberenz T [2011]. Exposure and emissions monitoring during carbon nanofiber production. Part I: elemental 

carbon and iron-soot aerosols. Ann Occup Hyg 55(9):1016–1036.

 ■ Birch ME [2011]. Exposure and emissions monitoring during carbon nanofiber production. Part II: polycyclic aromatic hydrocarbons. Ann Occup Hyg 

55(9):1037–47. 

 ■ Gurumurthy R, Ostraat M, Evans DE, Methner MM, O’Shaughnessy P, D’Arcy 

J, Geraci C, Stevenson E, Maynard A [2011]. A strategy for assessing workplace exposures to nanomaterials. J Occup Environ Hyg 8:673–685.

 ■ He X, Young S-H, Berry DS, Chisholm WP, Fernback JE, Ma Q [2011]. 

Multiwalled carbon nanotubes induce a fibrogenic response by stimulating 

reactive oxygen species production, activating NF-κB signaling, and promoting fibroblast-to-myofibroblast transformation. Chem Res Toxicol dx.doi.

org/10.1021/tx200351d.

 ■ He X, Young S-H, Fernback JE, Ma Q [2012]. Single-walled carbon nanotubes 

induce fibrogenic effect by disturbing mitochondrial oxidative stress and activating NF-B signaling. J Clin Toxic doi:10.4172/2161-0495.S5-005.

 ■ Chai M, Birch ME, Deye G [2012]. Organic and elemental carbon filter sets: 

preparation method and interlaboratory results. Ann Occup Hyg Hyg doi: 

10.1093/annhyg/mes029. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 213

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Dahm MM, Evans DE, Schubauer-Berigan MK, Birch ME, Fernback JE 

[2012]. Occupational exposure assessment in carbon nanotube and nanofiber 

primary and secondary manufacturers. Ann Occup Hyg 56(5):542–556.

 ■ Ruda-Eberenz TA, Birch ME [2012]. Specific surface areas of commercially 

produced carbon manomaterials. Ann Occup Hyg (submitted).

Invited Presentations 

 ■ Evans DE, Ku B-K, Birch ME, Dunn KH [2009]. Airborne contaminants in 

a carbon nanofiber manufacturing facility: direct reading monitoring. Poster 

presentation at the American Association for Aerosol Research (AAAR) 28th 

Annual Conference, Minneapolis, Minnesota, October 26–30.

 ■ Birch ME, Evans DE, Ku B-K, Ruda-Eberenz T [2009]. Air contaminants in a 

carbon nanofiber manufacturing facility. Poster presentation at the American 

Association for Aerosol Research (AAAR) 28th Annual Conference, Minneapolis, Minnesota, October 26–30.

 ■ Birch ME, Evans DE, Ku B-K, Ruda-Eberenz T [2009]. Air contaminants in a 

carbon nanofiber manufacturing facility. The 4th International Conference on 

Nanotechnology–Occupational and Environmental Health (NanOEH2009), 

Helsinki, Finland, August 26–29. 

 ■ Evans DE, Ku B-K, Birch ME, Dunn KH [2009]. Direct reading monitoring 

of contaminants in a carbon nanofiber manufacturing facility. The 4th International Conference on Nanotechnology–Occupational and Environmental 

Health (NanOEH2009), Helsinki, Finland, August 26–29.

 ■ Evans DE [2010]. Workplace monitoring during CNF production. Ask the expert: an update on the niosh nanotechnology program. The American Industrial Hygiene Conference and Exposition, Denver, Colorado, May 25.

 ■ Birch ME [2010]. Overview of aerosol research on engineered nanomaterials. Invited seminar sponsored by the Center for Sustainable Urban Environments, University of Cincinnati, Cincinnati, Ohio, February 26. 

 ■ Evans DE, Birch ME, Ku B-K, Dunn K, Ruda-Eberenz T [2010]. Emissions 

and exposure monitoring during carbon nanofiber production. The American 

Industrial Hygiene Conference and Exposition, Denver, Colorado, May 22–27. 

 ■ Agnew RA, Lu M, Birch ME [2010]. Investigation of health relevant physical 

and chemical properties of select engineered carbon nanotubes. Presented 

at the American Chemical Society (ACS) National Meeting and Exposition, 

Boston, Massachusetts, August 22–26. 

 ■ Birch ME, Ku B-K, Evans DE, Ruda-Eberenz T [2010]. Exposure and emissions monitoring during carbon nanofiber production. NIOSH Intramural 

Science Conference (Salt Fork), Cambridge, Ohio, August 9–11.
214 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Evans DE, Birch ME, Ku B-K, Dunn K, Turkevich L [2010]. Differentiating 

workplace aerosol emissions by direct-reading instrumentation. International 

Conference on Workplace Aerosols, Karlsruhe, Germany, June 28–July 2. 

 ■ Agnew RA, Lu, M, Birch ME, Hu J [2010]. Characterization and size distribution of engineered carbon nanomaterials. 2010 OIS Conference, Materials 

and Energy: Building Blocks for Ohio’s Economic Future, Columbus, Ohio, 

April 20–21.

 ■ Evans DE, Turkevich LA, Roettgers C, Deye GJ, Baron PA [2011]. Dustiness 

of nanomaterials. AIHce, Portland, Oregon, May 14–19.

 ■ Birch ME, Ku BK, Evans DE [2011]. Monitoring mixed exposure during carbon nanofiber production. 5th International Conference on Nanotechnology– 

Occupational and Environmental Health, Boston, Massachusetts, August 

10–12.

 ■ Chai M, Birch ME, Deye G [2011]. Organic and elemental carbon filter sets: 

preparation method and interlaboratory results. 5th International Conference on Nanotechnology–Occupational and Environmental Health, Boston, 

Massachusetts, August 10–12.

 ■ Lu M, Hu J, Birch ME, Yang J, Keener T, Wei H [2011]. Measurement of nearroad black carbon exposure from traffic sources in a midwestern urban area. 

NORA Symposium 2011: Achieving Impact through Research and Partnerships, Cincinnati, Ohio, July 12–13.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 215

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 39: Real-time Instrument for 

Nanoaerosol Exposure Measurement 

Principle Investigator: Pramod Kulkarni, DSc

Project Duration: FY 2008–2011

Critical Topic Areas: Measurement methods, exposure assessment 

Accomplishments and Research Findings 

 ■ Development of first prototype of Portable Aerosol Mobility Spectrometer 

(PAMS).

 ■ Design and testing of miniature bipolar charger.

 ■ Design of miniature differential mobility analyzer with extended size range 

and improved resolution.

 ■ Design of miniature condensation particle counter.

 ■ Development of second prototype of PAMS in collaboration with Kanomax Inc. 

 ■ Design and testing of prototype of personal nanoaerosol sizer (PNS).

Publications and Abstracts 

 ■ Lin L, Chen DR, Qi C, Kulkarni P [2009]. A miniature disk electrostatic aerosol classifier for personal nanoparticle sizers. J Aerosol Sci 40:982–992.

 ■ Qi C, Kulkarni P [2012]. Unipolar charging based hand-held mobility spectrometer for aerosol size distribution measurement. J Aerosol Science 49

(0):32–47. doi:10.1016/j.jaerosci.2012.02.005

 ■ Diwakar P, Kulkarni P, Birch ME [2011]. New approach for near-real- time 

measurement of elemental composition of aerosol using laser-induced breakdown spectroscopy. Aerosol Science and Technology 46:316–332.

 ■ Diwakar P, Kulkarni P [2012]. Measurement of Elemental Concentration of 

Aerosols Using Spark Emission Spectroscopy, J Analytical and Atomic Spectrometry, DOI: 10.1039/C2JA30025G.

Patents and Inventions

 ■ Kulkarni P, Diwakar P, “Method for focused electrostatic collection of aerosol 

particles for chemical analysis by spectroscopic techniques”, US Patent application #13315372.

 ■ Kulkarni P, Qi C, “Non-radioactive, Miniature Bipolar Charger for Aerosols”, 

US Patent application #13315344.
216 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Kulkarni P, Efthimion P, Diwakar P. Method for spectrochemical analysis of 

aerosols using microwave plasma spectroscopy, CDC Employee Invention 

Report #I-013-12, patent application pending. 

 ■ Kulkarni P, Qi C. Low-flow, wide-range differential mobility analyzer for personal mobility instrumentaion, CDC Employee Invention Report #I-010-12.

Invited Presentations

 ■ Qi C, Kulkarni P, Chen DR [2009]. Development of a portable aerosol spectrometer (PAS) for nanoaerosol exposure measurement. 28th AAAR Conference, Minneapolis, Minnesota, October 26–30.

 ■ Qi C, Kulkarni P [2009]. New miniature unipolar corona charger for personal 

aerosol instrumentation. 28th AAAR Conference, Minneapolis, Minnesota, 

October 26–30.

 ■ Lin L, Chen DR, Qi C, Kulkarni P [2009]. A miniature disk electrostatic aerosol classifier for personal nanoparticle sizers. 28th AAAR Conference, Minneapolis, Minnesota, October 26–30.

 ■ Ku BK, Kulkarni P [2010]. Comparison of different approaches for measuring 

aerosol surface area in the submicrometer size range. NIOSH Intramural Science Conference (Salt Fork), Cambridge, OH, August 10–11.

 ■ Ku BK, Kulkarni P [2010]. Comparison of different approaches for measurement of surface area of nanoaerosols. The AAAR Conference, Portland, OR, 

October 25–29.

 ■ Diwakar P, Kulkarni P, Birch ME [2010]. Semi-continuous measurement of 

elemental composition of aerosol particles using laser induced breakdown 

spectroscopy. 29th Annual AAAR Conference, Portland, OR, October 25–29.

 ■ Diwakar P, Kulkarni P, Birch ME [2010]. Matrix effects in laser-induced 

breakdown spectroscopy. 29th Annual AAAR Conference, Portland, OR, 

October 25–29.

 ■ Qi C, Kulkarni P [2010] Personal nanoparticle spectrometer for nanoaerosol exposure measurement. 29th AAAR Annual Conference, Portland, OR, 

October 25–29.

 ■ Diwakar P, Kulkarni P, Birch ME [2010]. Novel approach for analysis of fine 

and ultra-fine aerosol particles using laser induced breakdown spectroscopy. 

6th International Conference on Laser-Induced Breakdown Spectroscopy, 

Memphis, TN, September 13–17.

 ■ Diwakar P, Kulkarni P, Birch ME [2010]. Matrix effect in substrate based 

laser-induced breakdown spectroscopy. 6th International Conference on 

Laser-Induced Breakdown Spectroscopy, Memphis, TN, September 13–17.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 217

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Diwakar P, Kulkarni P, [2011]. Near Real-time Elemental Analysis of Aerosols 

Using Laser and Spark-induced Breakdown Spectroscopy. FACSS 2011, Reno, 

NV, October 2–6. 

 ■ Diwakar P, Kulkarni P, [2011]. Near Real-time Elemental Analysis of Aerosols 

Using Spark-induced Breakdown Spectroscopy. 30th Annual AAAR Conference, Orlando, FL, October 3–7. 

 ■ Diwakar P, Kulkarni P, Efthimion P, [2011]. Corona-Assisted Microwave 

Plasma Spectroscopy [CAMPS) for Aerosol Analysis. 3rd North American 

Symposium on LIBS, Clearwater, FL, July 18–20.

 ■ Diwakar P, Kulkarni P, [2011]. Spark-Induced Breakdown Spectroscopy for 

Near Real-Time Elemental Analysis of Aerosols. 3rd North American Symposium on LIBS, Clearwater, FL, July 18–20.

 ■ Qi C, Kulkarni P, [2011]. A Miniature, Non-radioactive Bipolar Charger for 

Electrical Charging of Aerosols. [2011) 30th AAAR Annual Conference, Orlando, FL, October 3–7.

 ■ Qi C, Kulkarni P, Kato T, Fukushima N, [2011]. Development of Portable 

Aerosol Electrical Mobility Spectrometer (PAEMS) for Aerosol Exposure 

Measurement. 30th AAAR Annual Conference, Orlando, FL, October 3–7.

 ■ Qi C, Kulkarni P, [2011]. Development of a Portable Aerosol Mobility Spectrometer (PAMS) for Nanoaerosol Exposure Measurement. Symposium on 

Nanotechnology—Health and Safety Issues, Cincinnati, OH, May 10.
218 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 40: Nanoparticle Reference Materials 

for Health Protection

Principle Investigator: Aleksandr B. Stefaniak, PhD

Project Duration: FY 2007–2009

Critical Topic Area: Measurement methods

Accomplishments and Research Findings

 ■ Participated in NIST-sponsored Workshop on Nanomaterial Manufacturing 

in Gaithersburg, Maryland, May 2008.

 — 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, Arlington, Virginia, June 2008.

 ■ Co-sponsored with American National Standards Institute, National Cancer 

Institute, and NIST the Workshop on Enabling Standards for Nanomaterial 

Characterization, Gaithersburg, Maryland, October 2008.

 — Co-leader of breakout session—Reference and test materials, media and 

sample preparation.

 ■ Expanded project to become an international collaborative effort and obtained 

funding for the new project through the NIOSH NTRC (see Project 39).

Publications and Abstracts

 ■ None

Invited Presentations

 ■ 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 31.

 ■ 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 11–15.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 219

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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, Florida, February 19–21.

 ■ 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, Tennessee, October 19.

 ■ Stefaniak AB (presented by Hoover MD) [2008]. Minimal material characterization of nanomaterials. Workshop on Ensuring Appropriate Material 

Characterization in Nanotoxicity Studies, Washington, DC, October 10.
220 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 41: International Coordination of 

Nanoscale Reference Materials

Principle Investigator: Aleksandr B. Stefaniak, PhD

Project Duration: FY 2010–2012

Critical Topic Area: Measurement methods

Accomplishments and Research Findings 

 ■ Successfully developed Division-funded project (project 40) into competitively funded project through NIOSH NTRC.

 ■ Traveled to Cincinnati, OH, for the NTRC Nano Exposure Assessment Working Group meeting and presented data and concepts related to nanoparticle 

measurement and participated in strategy development.

 ■ Participated as a NIOSH representative to U.S. Technical Advisory 

Group to International Organization for Standardization Committee 229: 

Nanotechnologies.

 — Participated in teleconferences and contributed to development of new 

U.S. work items presented at meeting in Johannesburg, South Africa.

 — Use of electron microscopy to determine primary particle size

 — Measurement methods matrix

 ■ Organization for Economic Cooperation and Development (OECD)

 — Provided expert input and content to revision of Guide 24: Preliminary 

Guidance Note on Sample Preparation and Dosimetry for the Safety Testing of Manufactured Nanomaterials.

 — Provided expert review of the report Techniques and Sampling Protocols for 

Determining the Concentrations of Manufactured Nanomaterials in Air.

 ■ Recruited an international working group consisting of health and safety professionals and metrology experts from North America, Asia, and Europe.

 ■ Reviewed existing literature and identified lists of nanoscale materials and 

characteristics of interest for developing into reference materials. Manuscript 

undergoing Institutional review.

 ■ Collaborated with the U.S. National Institute of Standards and Technology on 

development of Standard Reference Material 1898: TiO2

 nanopowder. Manuscript in preparation.

 — Co-developed protocol and helped to organize inter-laboratory studies 

(ILS) of nanopowder specific surface area.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 221

APPENDIX A | A Summary of 69 NIOSH Research Projects

 — Recruited 17 laboratories to participate in ILS.

 — Measured powder surface area and density for reference material

 ■ Collaborated with the National Research Council Canada on development of 

Reference Material NCC-1: NanoCrystalline Cellulose and Reference Material NCCS-1: 6% Aqueous Suspension of NanoCrystalline Cellulose.

 — Contributed measurements of:

 — Hydrodynamic diameter (photon correlation spectroscopy)

 — Zeta potential (light scattering)

 — Specific surface area (gas adsorption)

 — Density (pycnometry)

 — Crystallinity (x-ray diffraction)

 — Endotoxin and glucan content (LAL assay)

 ■ Collaborating with the National Research Council Canada on development of 

Reference Material 2LV-BIO-SWCNTS: Single-walled carbon nanotubes.

Publications and Abstracts

 ■ None

Invited Presentations 

 ■ Stefaniak AB, Hackley VA, Patri A, Postek MT [2009]. Nanoscale reference 

materials for environmental, health and safety applications. 4th International 

Conference on Nanotechnology–Occupational and Environmental Health, 

Helsinki, Finland, August 26–28.

 ■ Stefaniak AB, Lawrence RB [2009]. Morphology specifications for dimensional analysis of engineered nano-objects. 4th International Conference on 

Nanotechnology–Occupational and Environmental Health, Helsinki, Finland, 

August 26–28.

 ■ Stefaniak AB [2009]. Approaches to measurement of airborne engineered 

nano-objects. Nanoparticle Air Monitoring Workshop, Research Triangle 

Park, North Carolina, March 2.

 ■ Stefaniak AB [2010]. International coordination of nanoscale reference materials for environmental health and safety measurement applications. Pacifichem 2010, Honolulu, Hawaii, December 16.

 ■ Stefaniak AB [2011]. What materials and properties are needed for nanoscale 

reference materials for environmental, health, and safety measurements? 5th 

International Conference on Nanotechnology—Occupational and Environmental Health, Boston, Massachusetts, August 10–12. 
222 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 42: A Standard Method for Determining 

Airborne Nanoparticle Size

Principle Investigator: Aleksandr B. Stefaniak, PhD

Project Duration: FY 2009–2011 

Critical Topic Areas: Measurement methods, exposure assessment

Accomplishments and Research Findings 

 ■ Formed collaboration with a microscopy supply company and developed a 

protocol for an inter-laboratory study of a sample preparation method using 

functionalized grids and NIST nanoparticle reference materials 8011, 8012, 

and 8013: Gold Nanoparticles.

 ■ Recruited six laboratories (academic, private sector, government) to participate in a series of inter-laboratory studies to evaluate the sample preparation 

and analysis protocols.

 ■ Piloted sample preparation and analysis protocols with four laboratories.

 ■ Study materials sent out for first inter-laboratory study (to be completed in 2012).

 ■ Developing ASTM International standard on sample preparation for transmission electron microscopy through committee E56: Nanotechnology.

Publications and Abstracts 

 ■ None

Invited Presentations 

 ■ None 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 223

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 43: Calm Air Chamber and Wind Tunnel 

Evaluation of Personal Aerosol 

Samplers for Nanoparticle

Exposure Assessment

Principal Investigator: Terri Pearce, PhD

Project Duration: FY 2008–2010

Critical Topic Area: Measurement methods

Accomplishments and Research Findings

 ■ Developed study protocol.

 ■ Obtained external peer-review for protocol.

Publications and Abstracts 

 ■ None

Invited Presentation

 ■ Pearce T [2008]. Direct-reading nanoaerosol instrument comparison. Abstract and poster for the American Association for Aerosol Research Annual 

Conference, Orlando, Florida, October 20–24. 

Chamber evaluating direct reading instruments
224 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 44: Efficacy of NIOSH Method 0600 for 

Fine and Ultrafine Titanium Dioxide

Principle Investigator: Terri Pearce, PhD

Project Duration: FY 2010–2011

Critical Topic Area: Measurement methods

Accomplishments and Research Findings

 ■ Completed collection efficiency evaluations for six different types of personal 

samplers using surrogate nanoaerosol (sodium fluorescein particles with 

count mean diameter of 40 nanometers).

 ■ Designed a feedback-controlled aerosol generation system for fine and ultrafine titanium dioxide aerosols.

 ■ Utilized the results from the preliminary testing to choose three sampler types 

for further collection efficiency evaluations using titanium dioxide aerosols.

Publications and Abstracts 

 ■ None

Invited Presentations 

 ■ None 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 225

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 45: Ultrafine TiO2 Surface and Mass 

Concentration Sampling Method

Principle Investigators: Aleksandr B. Stefaniak, PhD,

 and Ryan F. LeBouf, PhD

Project Duration: FY 2007–2011

Critical Topic Area: Measurement methods

Accomplishments and Research Findings

 ■ Characterized bulk powder physicochemical properties (density, morphology, 

primary particle size, particle cluster size, total surface area by gas adsorption, 

purity, and crystallinity).

 ■ Developed a protocol for determining background surface area of blank filter 

media using krypton gas isotherms.

 ■ Developed protocol for measuring TiO2

 mass and surface area in animal 

inhalation chambers.

 ■ Performed collaborative chamber studies using TiO2 powder.

 ■ Successfully balloted an ASTM International draft standard through subcommittee E56.02–‘Standard Test Method for Measurement of Airborne Metal 

and Metal Oxide Nanoparticle Surface Area in Inhalation Exposure Chambers using Gas Adsorption.’ Standard scheduled for committee and society 

level balloting in 2012.

Publications and Abstracts 

 ■ LeBouf RF, Stefaniak AB, Chen BT, Frazer DG, Virji MA [2011]. Measurement of airborne nanoparticle surface area using a filter-based gas adsorption method following inhalation toxicology experiments. Nanotoxicology 

5:687–699.

 ■ Roberts JR, Chapman RS, Tirumala V, Karim A, Chen BT, Schwegler-Berry 

D, Stefaniak AB, Leonard SS, Antonini JM [2011]. Toxicological evaluation of 

lung responses after intratracheal exposure to non-dispersed titanium dioxide 

nanorods. J Toxicol Environ Health A 74:790–810.

 ■ LeBouf RF, Ku BK, Chen BT, Stefaniak AB [2011]. Measuring surface area 

of airborne titanium dioxide powder agglomerates: relationships between 

gas adsorption, diffusion and mobility-based methods. J Nanoparticle Res 

13:7029–7039.
226 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Invited Presentations

 ■ Stefaniak AB, Sbarra DC, Duling MG, LeBouf RF, Virji MA [2009]. Measurement of airborne ultrafine TiO2

 mass and surface area from a single filter 

sample. 4th International Conference on Nanotechnology–Occupational and 

Environmental Health, Helsinki, Finland, August 26–29.

 ■ Stefaniak AB [2011]. Measuring nanomaterials in the real world. ILSI 

NanoRelease Steering Committee Workshop, Arlington, Virginia, May 10–11.

 ■ LeBouf RF, Ku BK, Chen BT, Cumpston JL, Stefaniak AB [2011]. Measurement of surface area of airborne titanium dioxide powder agglomerates: relationships among total, active and mobility-based methods. 5th International 

Conference on Nanotechnology–Occupational and Environmental Health, 

Boston, Massachusetts, August 10–12.

 ■ Roberts JR, Chapman RS, Young SH, Kenyon A, Schwegler-Berry D, Stefaniak 

AB, Chen BT, Antonini JM [2011]. Pulmonary toxicity following intratracheal 

instillation of dispersed silver nanoparticles in rats. Society of Toxicology, 

Washington, DC, March 6–10.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 227

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 46: Development and Evaluation 

of Nanoaerosol Surface Area 

Measurement Methods

Principal Investigator: Bon-Ki Ku, PhD

Project Duration: FY 2009–2010

Critical Topic Areas: Measurement methods, exposure assessment 

Accomplishments and Research Findings 

 ■ Characterized aerosol surface area measurement methods in the submicron 

size range.

 ■ Compared different diffusion charging-based sensors using different types of 

agglomerates such as silver, PSL, and wax. LQ1-DC (Matter Eng), DC2000CE 

(EcoChem), and NSAM (TSI Inc) were tested. The diffusion charger responses were also compared with the following methods for estimating aerosol 

surface area.

 — Surface area estimation from agglomerate particle mass and primary particle size

 — Surface area estimation based on particle mobility diameter

 — Surface area estimation based on mobility diameter of a chain aggregate 

with uniform primary particle size

 ■ The response of the three diffusion charging-based sensors to silver agglomerates were similar but substantially underestimated the geometric surface area 

by a factor of 3–10 in the size range studied.

 ■ Surface area estimated by the mobility-based approach decreases compared 

to the true geometric surface area as particle structure becomes compact, 

indicating that the mobility-based surface area strongly depends on the 

particle structure.

 ■ Caution should be exercised in the interpretation of measurements from diffusion charging-based semi-empirical instruments.

 ■ The mobility diameter-based surface area measurements may be relatively 

accurate for open and moderate agglomerates compared to the diffusion chargers, but they may not be accurate for highly compact agglomerates. 

 ■ Investigated aerosol surface area estimated from number and mass concentration measurements (referred to as Maynard estimation method) to quantitatively investigate the effect of actual particle density on the Maynard’s estimation method.
228 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ The methods developed and evaluated for measuring aerosol surface area 

have been used by other researchers from inside and outside NIOSH for exposure assessment of nanoaerosols.

 — University of Iowa for surface area measurement of incidental nanoparticles

 — NIOSH Pittsburgh Research Laboratory (PRL) for surface area measurement of diesel particulate matter (DPM)

 — NIOSH Morgantown Division of Respiratory Disease Studies (DRDS) for 

surface area measurement of airborne fine and ultrafine TiO2

 ■ Collaborated with University of Iowa, NIOSH Pittsburgh Research Laboratory, and NIOSH Morgantown Division of Respiratory Disease Studies.

Publications and Abstracts 

 ■ Ku BK [2010]. Determination of the ratio of diffusion charging-based surface area to geometric surface area for spherical particles in the size range of 

100–900 nm. J Aerosol Sci 41:835–847.

 ■ Ku BK, Deye GJ, Kulkarni P, Baron PA [2011]. Bipolar diffusion charging of 

high-aspect ratio aerosols. J Electrostat 69(6):641–647.

 ■ Ku BK, Kulkarni P [2012]. Comparison of diffusion charging and mobilitybased methods for measurement of aerosol agglomerate surface area. J Aerosol Sci DOI: 10.1016/j.jaerosci.2012.01.002.

 ■ Ku BK, Evans DE [2012]. Investigation of aerosol surface area estimation 

from number and mass concentration measurements: particle density effect. 

Aerosol Sci Technol 46(4):473–484. 

 ■ Cena LG, Ku BK, Peters TM [2012]. Particle collection efficiency for nylon 

mesh screens. Aerosol Sci Technol 46(2):214–221. 

Invited Presentations

 ■ Ku BK [2009]. Diffusion charger-based aerosol surface-area monitor response 

to airborne spherical particles 100–800 nm in diameter. The 4th International 

Conference on Nanotechnology–Occupational and Environmental Health 

(NanOEH2009), Helsinki, Finland, August 26–29. 

 ■ Ku BK, Maynard AD, Evans DE [2009]. Surface-area estimation of polydisperse nanoparticles with controlled morphologies: diffusion charging method 

and estimates from number and mass concentrations. The 4th International 

Conference on Nanotechnology–Occupational and Environmental Health 

(NanOEH2009), Helsinki, Finland, August 26–29.

 ■ Ku BK, Kulkarni P [2010]. Comparison of different approaches for measurement of surface area of nanoaerosols. The AAAR Conference, Portland, 

Oregon, October 25–29.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 229

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Ku BK, Evans DE [2011]. The effect of particle density on aerosol surface area 

estimation from number and mass concentration measurements. The 5th 

International Conference on Nanotechnology–Occupational and Environmental Health, Boston, Massachusetts, August 10–12. 
230 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 47: Respiratory Deposition of Airborne 

Carbon Nanotubes

Principle Investigators: Pramod Kulkarni, PhD, and Bon-Ki Ku, PhD

Project Duration: FY 2010–2012

Critical Topic Areas: Measurement methods, risk assessment 

Accomplishments and Research Findings 

This project has made progress in meeting the original objectives and has been extended to include different types of nanomaterials such as silver nanowire, graphene, 

and fullerene (C60), which are of many interests in nanotechnology. The following 

objectives were stated in the project proposal:

 — Generate SWCNTS and MWCNT aerosols, using a variety of methods to 

span a range of morphologies of workplace aerosols (FY10–11).

 — Perform laboratory measurements on these CNT aerosols to characterize 

their diffusional and aerodynamic diameter, effective density, and dynamic 

shape factor (FY11).

 — Develop an approach that uses these measurements to estimate size-dependent 

lung deposition fraction of SWCNTS and MWCNT aerosol particles, using a Multiple Path Particle Dosimetry (MPPD) model (FY11–12).

 ■ Generated SWCNTS and MWCNT aerosols, using a variety of methods to 

span a range of morphologies of workplace aerosols.

 ■ Designed a laboratory setup on these CNT aerosols to characterize their diffusional and aerodynamic diameter, effective density, and dynamic shape factor.

 ■ Laboratory experiments have been conducted to measure diffusion and 

aerodynamic diameters of airborne nanotube and nanomaterial aerosols that 

were generated using different techniques. Tandem mobility-mass measurements were made on nanomaterial aerosols generated by liquid atomization, 

electrospray, and dry dispersion techniques. The nanomaterials studied in the 

project are as follows:

 — Single-walled carbon nanotubes 

 — Multi-walled carbon nanotubes (MWCNTs-OH with short length)

 — Gas-phase MWCNTs (10–20 nm in tube diameter)

 — Liquid-phase MWCNTs (10–20 nm in tube diameter)

 — Gas-phase MWCNTs (60–100 nm in tube diameter)

— Silver nanowires
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 231

APPENDIX A | A Summary of 69 NIOSH Research Projects

 — Graphene nanoparticles

 — Fullerene (C60)

 ■ Measured aerodynamic and diffusion diameters of SWCNT aerosols.

 ■ Measured aerodynamic and diffusion diameters of different types of engineered nanomaterials mentioned above.

 ■ Characterized particle morphology for different nanomaterials using Transmission Electron Microscopy (TEM). 

 ■ Correlations from these measurements were used as an input to spherical particle dosimetry model to probe relative difference in SWCNT and MWCNT 

aerosol deposition with respect to spherical particle deposition.

 ■ Collaborators on this project include Eileen Kuempel (NIOSH/EID) and 

Lovelace Respiratory Research Institute, Albuquerque, NM.

Publications and Abstracts

 ■ Ku BK, Deye GJ, Kulkarni P, Baron PA [2011]. Bipolar diffusion charging of 

high-aspect ratio aerosols. J Electrostat 69(6):641–647.

Invited Presentations 

 ■ None
232 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 48: Exposure Potential From Use of 

Nanomaterial-Enabled Consumer 

Products

Principle Investigator: Aleksandr B. Stefaniak, PhD

Project Duration: FY 2009–2012

Critical Topic Areas: Measurement methods, exposure assessment

Accomplishments and Research Findings 

 ■ Obtained 18 commercially available products (textiles, cleaning products, 

medical products, paints, personal hygiene, electronics, and sporting goods) 

that claim to contain nanosilver.

 ■ Coordinated with U.S. Environmental Protection Agency and National Institute of Standards and Technology to devise analytical approaches to determine whether the products contain silver and, if so, whether it is nanoscale.

 ■ Characterized the amount and form of silver in 10 products, using ICP, UV-Vis, 

and electron microscopy.

 ■ Performing release studies for textiles in contact with artificial skin fluids 

(sweat, sebum)

Publications and Abstracts 

 ■ None

Invited Presentations 

 ■ None
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 233

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 49: Ultrafine Aerosols from DieselPowered Equipment

Principal Investigator: Aleksandar Bugarski, PhD

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 a sintered metal DPF system and to assess the effects of 

DPF regeneration strategy (fuel-borne catalyst) on concentrations of aerosols 

and gases in mine air.

 ■ Evaluated potential of biodiesel fuels to reduce concentrations of aerosols in 

mine air. 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 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 (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 by 

means of biosamplers and a versatile aerosol concentration enrichment system developed in cooperation with University of Southern California. 

 ■ Developed the novel methodology for preparing and analyzing samples collected by 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, 
234 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

nanoparticle surface area monitor, PAS2000, and filter-sampling methodologies for measurement and sampling of diesel aerosols.

 ■ Completed the new engine/dynamometer system with a Mercedes-Benz engine and 400 kW dynamometer. 

Publications

 ■ Bugarski AD, Schnakenberg GH Jr., Hummer JA, Cauda E, Janisko SJ, Patts 

LD [2009]. Effects of diesel exhaust aftertreatment devices on concentrations 

and size distribution of aerosols in underground mine air. Environmental Science and Technology 43:6737–6743.

 ■ Shi X-C, Keane MJ, Ong T, Li S-Q, Bugarski AD [2010]. Mutagenicity of diesel exhaust particles from an engine with differing exhaust after treatments. J 

Toxicol Environ Health, Part A 73(19):1314–1324.

 ■ Shi X-C, Keane MJ, Ong TM, Bugarski AD, Gautam M, Wallace WE [2009]. 

Diesel exhaust particulate material expression of in vitro genotoxic activities 

when dispersed into a phospholipid component of lung surfactant. Journal of 

Physics: Conference Series 151:1–10.

 ■ Cauda EG, Bugarski A, Mischler SE [2010]. A review of the effects of exhaust 

aftertreatment on nitrogen dioxide emissions from underground mining 

equipment. Mining Engineering November:60–64.

 ■ Bugarski AD, Cauda E, Janisko SJ, Hummer JA, Patts LD [2010]. Aerosols 

emitted in underground mine air by diesel engine fueled with biodiesel. Journal of Air and Waste Management Association 60:237–244.

 ■ Bugarski AD, Schnakenberg GH Jr., Hummer JA, Cauda E, Janisko SJ, Patts 

LD [2011]. Evaluation of high-temperature disposable filter elements in an 

experimental underground mine. Society for Mining, Metallurgy, and Exploration Transactions 330:373–382.

Invited Presentations

 ■ 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 on CombustionGenerated 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 235

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ 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, Nevada, 

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, California, November 12–14.

 ■ C Bugarski A, Schnakenberg GH, Cauda E [2008]. Effects Of Sintered Metal 

Diesel Particulate Filter System On Diesel Aerosols and Nitric Oxides In Mine 

Air. Proceeding of 12th United States/North American Mine Ventilation Symposium, Reno, NV, June 9–11.

 ■ 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, UK, September 23–25.

 ■ Cauda E, Bugarski AD, Mischler SE [2008]. NO2 Emissions from Diesel 

Engine Powered Vehicles, 14th Annual Mining Diesel Emissions Conference 

(MDEC), 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. 14th Annual Mining Diesel 

Emissions Conference (MDEC), Richmond Hill/Toronto, Ontario, Canada, 

October 5–10.

 ■ Bugarski AD, Cauda E, Janisko S, Patts LD, Hummer JA, Mischler SE [2008]. 

Biodiesel and nano and ultrafine aerosols in underground mine. 14th Annual Mining Diesel Emissions Conference (MDEC), Richmond Hill/Toronto, 

Ontario, Canada, October 5–10.

 ■ Bugarski AD, Hoover M [2009]. Metric for Exposure Monitoring, Hazard Assessment, and Risk Management for Diesel Aerosols in Underground Mines. 

Poster at 13th ETH Conference on Combustion Generated Nanoparticles, 

Zürich, Switzerland, June 22–24, ISBN 978-3-033-01994-2. 
236 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Bugarski AD, Shi X-C [2009]. Controlling exposure to dpm: diesel particulate filters vs. biodiesel. 15th Annual Mining Diesel Emissions Conference 

(MDEC), Richmond Hill/Toronto, Ontario, Canada, October 5–9.

 ■ Bugarski AD [2010]. The role of DPM loading on the filtration process in 

DFEs and DPFs. 16th Annual Mining Diesel Emissions Council (MDEC) 

Conference, North Toronto, Ontario, Canada, October 4–8. 

 ■ Cauda E, Bugarski A, Patts L [2010]. Diesel aftertreatment control technologies 

in underground mines: the NO2 issue. Proceeding of 13th United States/North 

American Mine Ventilation Symposium, Sudbury, ON, June 13–17. 

 ■ Bugarski AD, Schnakenberg GH Jr., Hummer JA, Cauda E, Janisko SJ, Patts 

LD [2011]. Evaluation of high-temperature disposable filter elements in an 

experimental underground mine. 140th SME Annual Meeting and Exhibit, 

Denver CO, February 27–March 2.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 237

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 50: Titanium Dioxide and Other Metal 

Oxides Exposure Assessment Study

Principle Investigator: Brian Curwin, PhD

Project Duration: FY 2006–2010

Critical Topic Areas: Measurement methods, exposure assessment 

Accomplishments and Research Findings

 ■ Protocol for titanium dioxide study was written and underwent peer review.

 ■ Critical exposure assessment equipment was purchased, including a TSI 3007 

condensation particle counter, an Ecochem DC2000 CE portable diffusion 

charger, and a MOUDI impactor.

 ■ A contract was awarded for support in company recruitment. Recruitment 

was completed in June 2008. 

 ■ Of the 189 companies contacted for recruitment, 10 initially agreed to participate and 7 companies were sampled. 

 ■ Company reports were sent to all participating companies.

 — Workers in large facilities and performing handling tasks had the highest 

mass concentrations for all analytes. 

 — Medium size facilities had higher particle number concentrations in the 

air, followed by small facilities for all particle sizes measured. 

 — Production processes generally had the highest particle number concentrations, particularly for the smaller particles. 

 — Similar to particle number, the medium sized facilities and production 

process had the highest particle surface area concentration. 

 — The TEM analysis confirmed the presence of the specific metal oxide particles of interest, and the majority of the particles were agglomerated, with 

the predominant particle size being between 0.1 and 1 μm. 

 — The greatest potential for exposure to workers occurred during handling 

process. However, the exposure is occurring at levels that are well below 

established and proposed limits.

Publications and Abstracts

 ■ Curwin B, Bertke S [2011]. Exposure characterization of metal oxide 

nanoparticles in the workplace. J Occup Environ Hyg 8(10):580–587.
238 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Invited Presentations

 ■ Curwin B [2009]. Ask the Experts, an Update of the Metal Oxide Exposure 

Assessment Study. AIHce 2009, Toronto, Canada, May 30–June 4.

 ■ Curwin B [2011]. Exposure Characterization of Metal Oxide Nanoparticles 

in the Workplace. International Soceity for Exposure Science (ISES) 2011, 

Baltimore, Maryland, October 23–27.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 239

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 51: Field Research Team

Principle Investigators: Charles Geraci, PhD, CIH; Mark Methner, 

PhD, CIH; and Ken Martinez, MS, CIH

Project Duration: FY 2006–2012

Critical Topic Area: Exposure assessment

Accomplishments and Research Findings:

Field Surveys

 ■ Developed and published a method to evaluate potential emissions to engineered nanomaterials (nanomaterial emission assessment technique, or 

NEAT) that utilizes direct reading portable aerosol sampling equipment 

including optical particle counters and condensation particle counters, as well 

as filter-based sampling for electron microscopy and elemental analysis.

 ■ The field team used the NEAT to evaluate potential emissions and to gain 

an understanding of nanomaterial research, manufacture, uses, and controls 

applied in the workplace. Knowledge gained led to creation of the sentinel 

document Approaches to Safe Nanotechnology. 

Nanomaterial workers
240 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Completed a survey as part of a health hazard evaluation at a research and 

development laboratory in 2005. This facility was incorporating CNF into 

polymers. Report issued in 2006.

 ■ Completed three surveys during 2006, at a commercial nanoscale metal oxide 

powder production facility, a research and development laboratory engaged 

in the development of optical products with Quantum Dot (QD) coatings, 

and a facility spinning a nylon 6 nanofiber. 

 ■ Completed eight surveys during 2007, involving the following: a multi-walled 

carbon nanotube manufacturer; a metal oxide manufacturer (two site visits); a 

research and development laboratory that handles and compounds nanoscale 

polyhedral oligomeric silsesquioxanes (POSS); a manufacturer of nanoenhanced, silica-iron absorbent media; a pilot-scale research and development 

facility that creates nanoscale alumina via radiofrequency plasma torch reaction (two trips to evaluate chamber ventilation role in controlling releases 

during cleanout operations); and an environmental toxicology laboratory that 

conducts MWCNT and fullerene toxicology studies on invertebrates. 

 ■ Completed seven surveys during 2008, involving the following: a manufacturer that compounds/blends MWCNTs and boron carbide; a pilot-scale 

research and development laboratory that handles/processes MWCNTs for 

use in composite material production; a research and development laboratory 

that handles a variety of engineered nanomaterials (MWCNTs, metal oxides); 

a pilot-scale research and development facility that synthesizes and handles 

MWCNTs for inclusion in composite materials; a repeat visit to the development facility that creates nanoscale alumina; a research and development 

laboratory creating SWCNTs; and a Department of Defense Applied Toxicology Laboratory that handles engineered nanomaterials (elemental metals and 

oxides) for use in animal toxicological studies. 

 ■ Completed six surveys during 2009. Studied materials included MWCNT 

mats and yarns, SWCNT and MWCNTs, CNF, CaPO4

, CaF2, and various 

metal oxides.

 ■ Completed nine surveys during 2010. Studied materials include singleand multi-walled carbon nanotubes, sheets and yarns manufactured from 

SWCNTs and MWCNTs, various metal oxides, carbon nanofibers, and plastic 

composite material containing carbon nanofibers.

 ■ Designed local exhaust ventilation flange for use during metal oxide reactor 

cleanout operations; evaluated effectiveness of different engineering controls 

(e.g., local exhaust ventilation, ventilated enclosures).

 ■ Developed a Framework Memorandum of Understanding between Department of Defense (DoD) and NIOSH regarding initial assessments at various 

DoD installations that create or handle nanomaterials.

 ■ The NEAT was revised to reflect more focus on integrated sampling to 

conduct exposure assessment with supplementation from direct reading 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 241

APPENDIX A | A Summary of 69 NIOSH Research Projects

instruments to characterize engineering control deficiencies and work 

practice problems.

 ■ Revised the field study report format in response to more complex studies 

and the presentation of occupational safety and health criteria to create context for better communication of results to customers.

 ■ Created a sample archival system that included the identification and use of 

appropriate storage space and the development of a database to track samples 

and site investigations.

 ■ Completed nine surveys during 2011. Nanomaterials studied include CNT 

threads, CNF composites, silica, aluminum oxide, quantum dots, silver 

nanowires, and metal oxides (silver oxide, nickel oxide, iron oxide, and palladium oxide).

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 during polymer 

composite laboratory operations. J Occup Environ Hyg 4(12):D125–D130.

A graphical representation of the primary and secondary citations 

of the 2010 article Nanoparticle Emission Assessment Technique 

(NEAT) for the identification and measurement of potential inhalation 

exposure to engineered nanomaterials–part A
242 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Methner MM, 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.

 ■ Methner MM [2010]. Effectiveness of a custom-fitted flange and LEV system 

in controlling the release of nano-scale metal oxide particulate. Intl J Occup 

Environ Health 16:475–487.

 ■ Johnson D, Methner M, Kennedy A, Steevens J [ 2010]. Potential for occupational exposure to engineered carbon-based nanomaterials in environmental 

laboratory studies. Environ Health Perspect 118(1):49–54.

 ■ Methner MM, Hodson L, Geraci C [2010]. Nanoparticle Emission Assessment Technique (NEAT) for the identification and measurement of potential exposure to engineered nanomaterials–part A. J Occup Environ Hyg 

7:127–132.

 ■ Methner MM, Hodson L, Dames A, Geraci C [2010]. Nanoparticle Emission 

Assessment Technique (NEAT) for the identification and measurement of 

potential exposure to engineered nanomaterials–part B: results from 12 field 

studies. J Occup Environ Hyg 7:163–176.

 ■ Methner M [2010]. Effectiveness of a custom-fitted flange and local exhaust 

ventilation (LEV) system in controlling the release of nanoscale metal oxide 

particulates during reactor cleanout operations. Int J Occup Environ Health 

16(4):475–487.

 ■ Gurumurthy R, Ostraat M, Evans DE, Methner M, O’Shaughnessy P, D’Arcy J, 

Geraci C, Stevenson E, Maynard A [2011]. A strategy for assessing workplace 

exposures to nanomaterials. J Occup Environ Hyg 8(11):673–685.

Invited Presentations 

 ■ 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, Ohio, April 22. 

 ■ 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, Minnesota, 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, 

Minnesota, 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 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 243

APPENDIX A | A Summary of 69 NIOSH Research Projects

exposure to engineered nanoparticles. International Inhalation Symposium, 

Hanover, Germany June 11–14.

 ■ 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, 

Ohio, December 16. 

 ■ Methner MM, Hodson LL, Geraci CL [2009]. Evaluating nanoparticle emissions in the workplace: a description of the approach used by NIOSH and 

a summary of findings from 12 site visits. NSTI–Nanotech 2009, Houston, 

Texas, May 3–7. ISBN 978-1-4398-1783-4 Vol. 2.

 ■ Methner MM [2010].What’s going on out there? The NIOSH field experience. 

Center for the Environmental Implications of Nanotechnology, University of 

California Los Angeles, October 13.

 ■ Hodson LL, Methner MM, Geraci CL, Crawford C [2010]. Findings from 

the NIOSH nanotechnology field research team. Nanomaterials and Worker 

Health: Medical Surveillance, Exposure Registries and Epidemiologic Research, Keystone, Colorado, July 21–23.

 ■ Methner MM, Hodson LL, Geraci CL, Crawford C [2010]. Findings from the 

NIOSH nanotechnology field research team: a photo documentary. Nanomaterials and Worker Health: Medical Surveillance, Exposure Registries and 

Epidemiologic Research, Keystone, Colorado, July 21–23.

 ■ Methner MM [2010]. Overview of experiences from the field. Ask the expert 

session: an update of the NIOSH nanotechnology program. American Industrial Hygiene Conference, Exposition (AIHce), Denver, Colorado, May 22–27.

 ■ Johnson DR, Methner MM, Kennedy AJ, Stevens JA [2010]. Potential for occupational exposure to carbon-based nanomaterials using common laboratory processes. Nanotechnology for Defense Conference, Atlanta, Georgia, 

May 3–6.

 ■ Beaucham CC, Dahm M, Evans D, Geraci C, Hodson L [2011]. Refining the 

nanoparticle emission assessment technique. 5th International NanOEH 

Meeting, Boston, Massachusetts, August 10–12.

 ■ Beaucham C [2011]. GestiÓn del riesgo ocupacional de la utilizaciÓn de 

nanomaterials, Caracas, Venezuela, November 8.

 ■ Martinez KF [2011]. Nano-Materials: NIOSH’s Current Approach to Exposure Assessment, San Francisco, California, December 5.

 ■ Martinez KF, Beaucham C, Sparks C [2011]. Occupational exposure assessment in the nanotechnology industry, a full day course. Irvine, California, 

December 7.
244 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 52: Factors Affecting Exposure to 

Engineered Nanomaterials

Principle Investigator: M. Abbas Virji, PhD 

Project Duration: FY 2010–2011

Critical Topic Areas: Exposure assessment; epidemiology and surveillence

Accomplishments and Research Findings

 ■ Established collaborations with researchers at University of Massachusetts 

Lowell and Seoul National University to develop a model of nanoparticle 

exposure data analysis.

 ■ Developed a conceptual model for collecting macro-, mid-, and micro-level 

exposure factors (contextual information) during exposure monitoring for 

multipurpose application. 

 ■ Developed a database for nanomaterial exposure data along with paper and 

electronic versions of sampling forms to collect contextual information during sampling. 

Macro Level Factors

Explain differences in exposures between different ENM production 

sectors or product/ENM types

Mid Level Factors

Explain differences in exposures between organizations within 

the same ENM production sector or product/ENM type

Micro Level Factors

Explain differences in exposures between operations 

using the same ENM or between ENM’s during 

the same task

A multi-tiered model of Potential Exposure Determinants
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 245

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Conducted analysis of various nanomaterial exposures during a number 

of processes, using time series analysis in conjunction with mixed models 

analyses to investigate the fixed effects of workplace factors on exposure levels 

while accounting for correlation due to repeated measurements of the continuous exposures.

 ■ Hosted researchers from TNO, the Netherlands, and University of Massachusetts, along with the NTRC (via envision) to discuss the harmonization of 

sampling strategy, data analyses and reporting, and database development of 

engineered nanomaterials. 

 ■ Member of the organizing committee and participant in the first international 

workshop on Nano Measurement Strategy and Database hosted by the TNO 

in Zeist, the Netherlands (Dec 16–17, 2010). Presented a position paper on 

data summarization and reporting. Participants agreed on the need to develop a harmonized strategy for monitoring, summarizing, reporting, and 

storing nano exposure data. 

 ■ Conducted comprehensive exposure assessment at a nano wire manufacturing facility for titanium dioxide and aluminum oxide, using time-integrated 

and real-time instruments, including assessment of the ventilation system and 

observations of tasks and activities. 

Publications and Abstracts 

 ■ Pfefferkorn FE, Bello D, Haddad G, Park J-Y, Powell M, McCarthy J, Bunker 

KL, Fehrenbacher A, Jeon Y M, Virji MA, Gruetzmacher G, Hoover MD 

[2010]. Characterization of exposures to airborne nanoscale particles during 

friction stir welding of aluminum. Ann Occup Hyg 54(5):486–503.

 ■ Woskie SR, Bello D, Virji MA, Stefaniak AB [2010]. Understanding workplace 

processes and factors that determine exposure to nanomaterials. Intl J Occup 

Environ Health 16(4):365–377.

 ■ Bello D, Wardle BL, Zhang J, Yamamoto N, Santeufemio C, Hallock M, Virji 

MA [2010]. Exposure to nanoscale particles and fibers during machining of 

hybrid CNT advanced composites II: abrasive drilling. Intl J Occup Environ 

Health 16(4):434–450. 

 ■ Brower D, Berges M, Virji MA, Fransman W, Bello D, Hodson L, Gabriel S, 

Tielemans E [2012]. Harmonization of measurement strategies for the assessment of exposure to manufactured nano object: report of a workshop. Ann 

Occup Hyg 56(1):1–9. Epub 2011 Dec 8.

Invited Presentations

 ■ Virji MA, Bello D [2010]. Nanomaterial data summarization and reporting. 

Workshop on Nano Measurement Strategy and Database, TNO, Zeist, The 

Netherlands, December 16–17.
246 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Ewert D, Geraci C, Virji MA, Hoover MD, Gilkey D, Kosnett M, Petroka G 

[2010]. A comprehensive occupational health program for emerging nanotechnology processes in a pharmaceutical facility. NIOSH Workshop on 

Nanomaterials and Worker Health: Medical Surveillance, Exposure Registries, 

and Epidemiologic Research, Keystone, Colorado, July 21–23.

 ■ Park JY, Virji MA, Kim SW, Ramachandran G, Raynor PC [2011]. Field 

evaluation of a nanoparticle surface area monitor in workplaces generating 

incidental nanoparticles. 5th International NanoEHS Conference, Boston, 

Massachusetts, August 10–12.

 ■ Brouwer D, Fransman W, Berges M, Virji MA, Bello D, Hodson L, Gabriel S, 

Tielemans E [2011]. Harmonization of measurement strategies for the assessment of exposure to manufactured nano object: report of a workshop. 5th 

International NanoEHS Conference, Boston, Massachusetts, August 10–12.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 247

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 53: Assessing the Feasibility of 

Industrywide Exposure and 

Epidemiology Studies of 

Workers Exposed to Engineered 

Nanomaterials—Phase I

Principle Investigator: Mary Schubauer-Berigan, PhD

Project Duration: FY 2008–2009

Critical Topic Areas: 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 manufacturers of engineered carbonaceous nanomaterials 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 and two journal articles on the feasibility of conducting industrywide exposure surveys and epidemiological studies among 

this workforce.

 ■ Made presentations describing results at conference on Medical Surveillance 

and Epidemiology for Nanomaterials (Keystone, Colorado, July 2010).

Publications and Abstracts 

 ■ Schubauer-Berigan M, Dahm M, Yencken M [2011]. Engineered carbonaceous nanomaterials manufacturers in the United States: workforce size, 
248 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

characteristics and feasibility of epidemiologic studies. J Occup Environ Med 

53(6S):S62–S67.

 ■ Dahm M, Yencken M, Schubauer-Berigan M [2011]. Exposure control 

strategies in the carbonaceous nanomaterial industry. J Occup Environ Med 

53(6S):S68–S73.

Invited Presentations

 ■ Schubauer-Berigan MK, Dahm MM [2010]. Engineered carbon nanomaterials workers: Is it time to conduct epidemiology studies? Nanomaterials & 

Worker Health: Medical Surveillance, Exposure Registries, & Epidemiologic 

Research, Keystone, CO, July 21–23.

 ■ Schubauer-Berigan MK, Dahm MM [2010]. Engineered carbon nanomaterials workforce: Feasibility of industrywide exposure assessment and epidemiology studies. Presented at the 2010 American Industrial Hygiene Conference 

and Exposition, Denver, CO, May 25.

 ■ Schubauer-Berigan MK, Trout DB, Schulte PA [2011]. Medical Surveillance 

among nanomaterials workers: Recommendations from the NIOSH Keystone 

Conference. Presented at “Nanomaterials: Risk Perception & Early Warning 

Systems” International Workshop, Berlin, May 25–26.

 ■ Schubauer-Berigan MK, Dahm MM [2011]. Feasibility of epidemiologic 

studies among engineered carbon nanomaterials workers. Sigma Xi Scientific 

Research Society, Cincinnati chapter, February 2. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 249

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 54: Engineered Carbon Nanomaterials 

Workforce: Feasibility of 

Industrywide Exposure Assessment 

and Epidemiology Studies on Carbon 

Nanotubes and Nanofibers—Phase II

Principle Investigators: Matthew Dahm, MPH; Mary SchubauerBerigan, PhD

Project Duration: FY 2010–2011

Critical Topic Areas: Epidemiology and surveillance; exposure assessment

Accomplishments and Research Findings

 ■ Recruited companies to participate in phase II of the feasibility study (for 

industrywide exposure assessment and epidemiology studies of the CNT & 

CNF workforce).

Nanomaterial workers
250 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Conducted 6 exposure assessment site visits at 3 primary manufacturers (producers), as well as 3 secondary manufacturers (users) of SWCNTs, MWCNTs, 

and CNFs for FY 2010.

 ■ Six additional exposure assessment site visits were conducted at one primary 

manufacturer and five secondary manufacturers of MWCNTs and SWCNTs 

during FY 2011. 

 ■ Developed a consistent sampling approach for CNTs and CNFs. 

 ■ Was able to observe typical forms of production and uses of the material(s). 

 ■ Personal and area samples collected, using both real-time instruments and 

filter-based sampling, to study several different exposure metrics.

 — Real-time instrument metrics: surface area, respirable mass, particle counts.

 — Filter-based: respirable and inhalable mass of elemental carbon (NMAM 

5040) and CNT structure counts by TEM (NMAM 7402).

 ■ Concluded that detectable levels of exposure are occurring in workplaces and 

that gradients of exposure can be determined with current exposure assessment methods. 

 ■ Made important contacts with companies and explained the future goals 

of the IWSB epidemiological/biomarker study (phase III) to company 

officials/workers. 

 ■ Sent detailed reports describing site visit and analytical results, along with recommendations to improve material handling processes at all surveyed companies.

 ■ Drafted a protocol for industrywide exposure assessment and epidemiologic study.

Publications and Abstracts 

 ■ Dahm M, Evans D, Schubauer-Berigan M, Birch ME, Fernback J [2012]. 

Occupational exposure assessment in carbon nanotube and nanofiber 

primary and secondary manufacturers. Ann Occup Hyg 56(5):542–556. 

DOI:10.1093/annhyg/mer110.

Invited Presentations 

 ■ Schubauer-Berigan M, Dahm M, Geraci C [2010]. Engineered carbon nanomaterials workforce: Feasibility of industrywide exposure assessment and epidemiology studies. Presented at AIHce roundtable, Ask the expert: an update on the 

NIOSH nanotechnology research program. AIHce: Denver, Colorado, May 25. 

 ■ Dahm M, Yencken M, Schubauer-Berigan M [2010]. Exposure control strategies in the carbonaceous nanomaterial industry. Nanomaterials and Worker 

Health: Medical Surveillance, Exposure Registries, and Epidemiologic Research Conference, Keystone, Colorado, July 21–23.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 251

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Schubauer-Berigan M, Dahm M [2010]. Engineered carbon nanomaterials 

workforce: feasibility of industrywide exposure assessment and epidemiology studies. Nanomaterials and Worker Health: Medical Surveillance, 

Exposure Registries, and Epidemiologic Research Conference, Keystone, 

Colorado, July 21–23. 

 ■ Dahm M, Schubauer-Berigan M [2011]. Industrywide studies: evaluating and 

addressing workplace exposures to carbon nanotubes and nanofibers. Ohio 

Innovation Summit, Toledo, Ohio, April 19–20. 

 ■ Dahm M, Schubauer-Berigan M [2011]. Nanomaterials exposure assessment: 

status of the NIOSH carbon nanotube and nanofiber industrywide study. 

Ask the expert: an update on the NIOSH nanotechnology research program. 

AIHce, Portland, Oregon, May 14–19.

 ■ Schubauer-Berigan M, Trout D, Schulte P [2011]. Medical surveillance among 

nanomaterials workers: recommendations from the NIOSH Keystone Conference. Nanomaterials: Risk Perception & Early Warning Systems International 

Workshop: Berlin, Germany, May 26. 

 ■ Dahm M, Evans D, Schubauer-Berigan M, Birch ME, Fernback J [2011]. 

Occupational exposure assessment in carbon nanotube and nanofiber 

primary and secondary manufacturers. 5th International Symposium on 

Nanotechnology, Occupational and Environmental Health, Boston, Massachusetts, August 10–12.
252 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 55: Nanoparticles—Dosimetry and

Risk Assessment

Principle Investigator: Eileen D. Kuempel, PhD

Project Duration: FY 2005–2012

Critical Topic Area: Risk assessment

Accomplishments and Research Findings

 ■ Coordinated the NTRC Critical Research Area in Risk Assessment. 

 ■ Developed research collaborations in dosimetry and risk assessment of nanomaterials, including with the following:

 — Institute of Occupational Medicine (IOM), Edinburgh, UK, and EU 

7th Framework Program on Risk Assessment of Engineered Nanoparticles (ENPRA) 

 — Toxicology Excellence for Risk Assessment (TERA)

 — Applied Research Associates (ARA), Raleigh, NC

 — Lovelace Respiratory Research Institute, Albuquerque, NM

 — The Hamner Institutes for Health Sciences, Research Triangle Park, NC

 — Provided presentations and contributed to publications pertaining to 

dosimetry, risk assessment, and occupational exposure limits (OELs) 

for nanoparticles.

 ■ Represented NIOSH in the Organization for Economic Cooperation and 

Development (OECD) Study Group 6 (SG6) to develop guidance on critical 

issues in nanotechnology risk assessment. 

 ■ Contributed to quantitative risk assessments used in developing draft NIOSH 

recommended exposure limits (RELs) for titanium dioxide and for carbon 

nanotubes/fibers. 

 ■ Developed and published risk assessment methods for inhaled poorly soluble 

particles, including nanoparticles.

 ■ 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 humans 

and in rats. Revised multipath particle deposition (MPPD) model to include 

site-specific deposition efficiency in nasal-pharyngeal region. Published rat 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 253

APPENDIX A | A Summary of 69 NIOSH Research Projects

model and prepared manuscript of human model (Hamner Institute/NIOSH 

research collaboration). 

 ■ Developing modeling methods to predict human respiratory tract deposition model for carbon nanofiber/nanotube structures based on fiber aerosol 

theory (Hamner Institute and ARA/NIOSH research collaborations). 

 ■ Completed experiments to characterize deposition of airborne carbon nanotubes in a human respiratory tract replica. Data are being used in the human 

lung deposition model for carbon nanofibers/nanotubes being developed by 

ARA (LRRI/NIOSH collaboration). 

 ■ Presented research and risk assessment findings at several scientific conferences and a public review meeting.

 ■ Published scientific articles on inhalation dosimetry and risk assessment 

methods for occupational exposure to nanomaterials and contributed to 

NIOSH guidance documents.

Publications and Abstracts 

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

occupational health. J Nanoparticle Res 7(6):587–614.

 ■ Kuempel ED, Wheeler M, Smith R, Bailer AJ [2005]. Quantitative risk assessment in workers using rodent dose-response data of fine and ultrafine 

titanium dioxide [abstract]. In: Nanomaterials: a risk to health at work? First 

A graphical representation of the 210 primary and 2,449 secondary citations of 

Airborne nanostructured particles and occupational health
254 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

International Symposium on Occupational Health Implications of Nanomaterials,12–14 October 2004, Buxton, Derbyshire, UK, Report of Presentations 

at Plenary and Workshop Sessions and Summary of Conclusions. Buxton: 

Health and Safety Executive, UK, p. 111.

 ■ Kuempel ED, Aitken RJ [2005]. Regulatory implications of nanotechnology: summary of discussion and recommendations from Workshop G. In: 

Nanomaterials: a risk to health at work? First International Symposium on 

Occupational Health Implications of Nanomaterials,12–14 October 2004, 

Buxton, Derbyshire, UK, Report of Presentations at Plenary and Workshop 

Sessions and Summary of Conclusions. Buxton: Health and Safety Executive, UK, pp. 142–143.

 ■ Kuempel ED, Tran CL, Castranova V, Bailer AJ [2006]. Lung dosimetry and 

risk assessment of nanoparticles: evaluating and extending current models in 

rats and humans. Inhal Toxicol 18(10):717–724.

 ■ Maynard AM, Kuempel ED [2006]. Addressing the potential environmental 

and human health impact of engineered nanomaterials. In: The Symposium 

Q. Proceedings of the 3rd International Conference on Materials for Advanced Technologies (ICMAT), Singapore, July 3–8. 

 ■ Kuempel ED [2007]. Estimating nanoparticle dose in humans: issues 

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

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

USA Inc., pp. 141–152. 

 ■ 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 assessment 

for TiO2. Inhal Toxicol 19(Suppl 1):205–212.

 ■ Tran CL, Kuempel ED [2007]. Biologically based lung dosimetry and exposuredose-response models for poorly soluble, inhaled particles. In: Donaldson K, 

Borm P, eds. Particle toxicology. Boca Raton, FL: 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; 

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. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 255

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Schulte P, Geraci C, Zumwalde R, Hoover M, Kuempel E [2008]. Occupational risk management of engineered nanoparticles. J Occup Environ Hyg 

5(4):239–249.

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

Mundt DJ, Mundt KA, Halperin WE [2008]. Options for occupational health 

surveillance of workers potentially exposed to engineered nanoparticles: state 

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

 ■ Schulte P, Geraci C, Zumwalde R, Hoover M, Castranova V, 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.

 ■ Dankovic DA, Kuempel ED, Wheeler MW [2009]. Your results may vary: exploring the sensitivity of titanium dioxide risk estimates to different modeling 

assumptions. Toxicologist 108(1):305.

 ■ Kuempel ED, Smith RJ, Dankovic DA, Stayner LT [2009]. Rat- and humanbased risk estimates of lung cancer from occupational exposure to poorlysoluble particles: a quantitative evaluation. J Phys Conf Ser 151(1):012011.

 ■ MacCalman L, Tran CL, Kuempel E [2009]. Development of a bio-mathematical 

model in rats to describe clearance, retention and translocation of inhaled 

nano particles throughout the body. J Phys Conf Ser 151(1):012028.

 ■ Garcia GJ, Kimbell JS [2009]. Deposition of inhaled nanoparticles in the rat 

nasal passages: dose to the olfactory region. Inhal Toxicol 21(14):1165–1175.

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

safety concerns associated with engineered nanomaterials. Cincinnati, OH: 

U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational 

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

 ■ Schulte PA, Murashov V, Zumwalde R, Kuempel ED, Geraci CL [2010]. Occupational exposure limits for nanomaterials: state of the art. J Nanoparticle 

Res 12(6):1971–1987.

 ■ Schulte PA, Geraci CL, Zumwalde R, Castranova V, Kuempel E, Methner 

MM, Hoover M, Murashov V [2010]. Nanotechnologies and nanomaterials 

in the occupational setting. Ital J Occup Environ Hyg 1(2):63–68.

 ■ OECD [2010]. Report of the workshop on risk assessment of manufactured 

nanomaterials in a regulatory context. Organization for Economic Cooperation and Development. OECD Environment, Health, and Safety Publications. Series on the Safety of Manufactured Nanomaterial, No. 21. ENV/JM/

MOMO(2010)10, 16 Apr. 

 ■ Kuempel ED [2011]. Carbon nanotube risk assessment: implications for exposure and medical monitoring. J Occup Environ Med 53(6)(Suppl):S91–S97.
256 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Dankovic D, Kuempel E, Geraci C, Gilbert S, Rice F, Schulte P, Smith R, 

Sofge C, Wheeler M, Lentz TJ, Zumwalde R, Maynard A, Attfield M, Pinheiro G, Ruder A, Hubbs A, Ahlers H, Lynch D, Toraason M, Vallyathan V 

[2011]. Current intelligence bulletin 63: occupational exposure to titanium 

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

Public Health Service, Centers for Disease Control and Prevention, National 

Institute for Occupational Safety and Health, DHHS (NIOSH) Publication 

No. 2011–160.

 ■ Kuempel E, Castranova V [2011]. Hazard and risk assessment of workplace 

exposure to engineered nanoparticles: methods, issues, and carbon nanotube 

case study. In: Ramachandran G, ed. Assessing nanoparticle risks to human 

health. Micro & Nano Technologies Series. Boston: William Andrew Publishing, pp. 65–97.

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 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 humanbased 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 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 257

APPENDIX A | A Summary of 69 NIOSH Research Projects

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.

 ■ Kuempel E [2009]. Nanotoxicology and risk assessment: current trends and 

NIOSH research. Kick-off Meeting for the Engineered Nanoparticles Risk Assessment (ENPRA) Collaborative Research Program in the EU and US, Paris, 

France, May 14.

 ■ Kuempel E [2009]. Risk assessment of nanomaterials: current trends and 

NIOSH research. Meeting between NIOSH and the U.K. House of Lords Science and Technology Committee on Nanoparticles in Food, Washington, DC, 

June 23.

 ■ Kuempel E [2009]. Risk assessment case study: carbon nanotubes. Organization for Economic Cooperation and Development (OECD) Workshop on 

Risk Assessment of Manufactured Nanomaterials in a Regulatory Context, 

Washington, DC, September 17.

 ■ Kuempel E, Zumwalde R [2010]. Risk assessment of carbon nanotubes and 

status of NIOSH current intelligence bulletin. NTRC 2010 Update, Wheeling, 

West Virginia, April 20.

 ■ Kuempel E [2010]. Carbon nanotube risk assessment: implications for medical screening. Nanomaterials and Worker Health: Medical Surveillance, 

Exposure Registries, and Epidemiological Research, Keystone, Colorado, 

July 21–23.

 ■ Kuempel E [2010]. Carbon nanotube risk assessment: using toxicology data 

to develop RELs. NIOSH Intramural Science Conference, Salt Fork, Ohio, 

August 10–11.

 ■ Kuempel E [2010]. Nanoparticles: lung dosimetry and risk assessment. NTRC 

Program Review, Cincinnati, Ohio, October 4. 

 ■ Kuempel E [2010]. Assessing occupational health risk of nanofibers: lessons 

learned from asbestos. National Institute of Occupational Health, Webster 

Day Event, Johannesburg, South Africa, November 10.

 ■ Kuempel E [2011]. Risk assessment of carbon nanotubes. NIOSH Public 

Review Meeting on the Draft Current Intelligence Bulletin on Occupational 

Exposure to Carbon Nanotubes and Nanofibers, Cincinnati, Ohio, February 3. 

 ■ Kuempel E [2011]. Occupational health risk assessment and CNT case study. 

Guest lecture in a graduate course at the University of Michigan, Ann Arbor, 

Michigan, March 24.

 ■ Kuempel E, Geraci C, Schulte P [2011]. Risk assessment and risk management 

of nanomaterials in the workplace: what we know and what we still need to 

know. The Institut National de Recherche et de Sécurité (INRS) Occupational 
258 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Health Research Conference: Risks Associated to Nanoparticles and Nanomaterials, Nancy, France, April 5 [Keynote presentation]. 

 ■ Kuempel E [2011]. Risk assessment of nanomaterials. American Industrial 

Hygiene Asssociation, in Roundtable 215: Ask the Expert: Update on NIOSH 

Nanotechnology Research Program, Portland, Oregon, May 17.

 ■ Kuempel ED, Geraci CL, Castranova V, Schulte PA [2011]. Development of 

risk-based nanoparticle groups for occupational exposure control. The 5th 

International Conference on Nanotechnology–Occupational and Environmental Health (NanOEH), Boston, Massachusetts, August 10–12.

 ■ Schulte P, Kuempel E, Zumwalde R, Geraci C, Schubauer‐Berigan M, Castranova V, Hodson L, Murashov V, Ellenbecker M [2011]. Focused actions 

to protect carbon nanotube workers. The 5th International Symposium on 

Nanotechnology Occupational and Environmental Health, Boston, Massachusetts, August 10–12.

 ■ Schulte PA, Kuempel ED, Castranova V, Geraci C, Hoover MD, Stefaniak A, 

Hodson L, Zumwalde R, Murashov V [2011]. Issues in establishing categorical occupational exposure limits for nanomaterials. The 5th International 

Conference on Nanotechnology–Occupational and Environmental Health 

(NanOEH), Boston, Massachusetts, August 10–12.

 ■ Kuempel ED, Geraci CL [2011]. NIOSH draft current intelligence bulletin: 

occupational exposure to carbon nanotubes and nanofibers. Society for 

Chemical Hazard Communication (SCHC) Fall Meeting, Arlington, Virginia, 

October 4. 

 ■ Su W-C, Cheng YS [2011]. A new experimental method to measure the 

deposition of carbon nanotubes in the human airway replica. The American 

Association for Aerosol Research (AAAR), Orlando, Florida, October 4.

 ■ Kuempel ED [2011]. Methods and uncertainties in carbon nanotube risk 

assessment. Society for Risk Analysis Annual Meeting, Charleston, South 

Carolina, December 5.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 259

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 56: Titanium Dioxide Quantitative

Risk Assessment

Principle Investigators: David Dankovic, PhD; Eileen Kuempel,

 PhD; Faye Rice, MS; Christine Sofge, PhD

Project Duration: FY 2005–2011

Critical Topic Areas: Risk assessment, recommendations, and guidance

Accomplishments and Research Findings 

 ■ Responded to external review, public, and stakeholder comments on a draft 

Current Intelligence Bulletin (CIB) on titanium dioxide.

 ■ The CIB was published in 2011. The CIB describes the risk of potential 

adverse respiratory effects from exposure to either fine (pigment-grade) or ultrafine (nano-size) titanium dioxide, including recommended exposure limits 

(RELs) for both fine and ultrafine particles.

Cover of the Current Intelligence Bulletin 63: Occupational Exposure to 

Titanium Dioxide
260 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Publications and Abstracts 

 ■ Dankovic D, Kuempel E, Wheeler M [2006]. An approach to risk assessment 

for TiO2. In: Proceedings of the 10th International Inhalation Symposium on 

Airborne Particulate Matter: Relevance of Particle Components and Size for 

Health Effects and Risk Assessment, Hannover, Germany, May 31–June 3. 

 ■ Dankovic D, Kuempel E, Wheeler M [2007]. An approach to risk assessment 

for TiO2. Inhal Toxicol 19(Suppl 1):205–212.

 ■ Dankovic DA, Kuempel ED, Wheeler MW [2009]. Your results may vary: exploring the sensitivity of titanium dioxide risk estimates to different modeling 

assumptions. Toxicologist 108(1):305. 

 ■ Dankovic D, Kuempel E, Geraci C, Gilbert S, Rice F, Schulte P, Smith R, Sofge 

C, Wheeler M, Lentz TJ, Zumwalde R, Maynard A, Attfield M, Pinheiro G, 

Ruder A, Hubbs A, Ahlers H, Lynch D, Toraason M, Vallyathan V [2011]. 

Current intelligence bulletin 63: occupational exposure to titanium dioxide. 

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

Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 

2011–160.

Invited Presentations

 ■ Dankovic DA, Kuempel ED, Wheeler MW [2009]. Your results may vary: exploring the sensitivity of titanium dioxide risk estimates to different modeling 

assumptions. Poster presented at the Society of Toxicology Annual Meeting, 

Baltimore, Maryland, March 18. Recognized by the Risk Assessment Specialty 

Section of the Society of Toxicology as outstanding presentation.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 261

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 57: Engineering Controls for 

Nanomaterial Handling

Principle Investigators: Li-Ming Lo, PhD; Kevin H. Dunn, MS, CIH; 

Jennifer Topmiller, MS

Project Duration: FY 2010–2012 

Critical Topic Areas: Engineering controls, recommendations, and guidance

Accomplishments and Research Findings 

 ■ The draft of the guidance document titled Current Strategies for Engineering 

Controls in Nanomaterial Handling Processes (EPHB report 356–14a) completed internal review in 2011 and is being prepared for external review. The 

topics covered include a summary of exposure control strategies, an overview 

of engineering controls for nanotechnology processes, and strategies for 

evaluating engineering control effectiveness. 

 ■ Two in-depth site surveys were conducted in 2010 to assess the performance 

of ventilated enclosures, at a manufacturing facility for carbon nanotubes 

(CNTs) and at another for nanographene platelets (NGPs). Process and 

task-based exposures were evaluated by direct-reading instruments. Enclosure design and operation factors were assessed with thermal anemometry 

and airflow visualization techniques. Recommendations were discussed and 

included improved enclosure design and containment of contamination in 

production areas through general ventilation pressurization schemes. Both 

survey reports have been finalized.

 ■ Two in-depth site surveys were conducted in 2011 to evaluate the control effectiveness of engineering controls at nanocomposite companies. The controls 

evaluated at these plants included a laboratory fume hood, canopy hood, 

downdraft table, and downflow room. Task-based exposure assessments included tasks such as weigh-out of nanomaterials, mixing, and post-processing 

of composite goods (such as manual and powered cutting). Good containment was seen with the laboratory fume hood when the unit was operated 

properly. The use of a HEPA-filtered downflow room also maintained low 

contaminant concentrations during nanomaterial manufacturing and handling. Some controls were ineffective, and recommendations were made to 

improve their design or operation. Both draft reports are being reviewed. 

 ■ One case study was completed in 2011 to evaluate process change and ventilation in reducing exposure during product harvesting and equipment cleaning 

at a nanographene production facility. The study showed that increasing wait 

times prior to product harvesting (allowing airborne products to settle into 

the collection containers) can significantly lower nanomaterial emissions. In 
262 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

addition, the use of available process exhaust ventilation helped the facility 

eliminate particle emissions during maintenance of the process tank and save 

the nanomaterials for reuse. The study report is being prepared. 

 ■ A laboratory study was conducted to assess the performance of an enclosure 

used to handle nanomaterials. Initial tests of nanomaterial handling have 

shown that nanopowders can easily migrate to the breathing zone of a worker 

without the use of proper controls. A test rig has been constructed to produce 

nanomaterial aerosols (including salts, multi-walled CNTs, TiO2, SiO2, and 

Al2O3) for assessing enclosure containment effectiveness. A sampling probe 

array is being designed to provide better detection of enclosure leakage during tests with trace gas and nanomaterials.

Publications

 ■ Evans DE, Ku BK, Birch ME, Dunn KH [2010]. Aerosol monitoring during 

carbon nanofiber production: mobile direct-reading sampling Ann Occup 

Hyg 54(5):514–531.

 ■ Lo LM, Dunn KH, Hammond D, Almaguer D, Bartholomew I, Topmiller J, 

Tsai CSJ, Ellenbecker M, Huang CC [2011]. Evaluation of engineering controls for manufacturing nanofiber sheets and yarns. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for 

Disease Control and Prevention, National Institute for Occupational Safety 

and Health, DHHS (NIOSH) Report No. EPHB 356–11a.

 ■ Lo LM, Hammond D, Bartholomew I, Almaguer D, Heitbrink W, Topmiller J 

[2012]. Engineering controls for nano-scale graphene platelets during manufacturing and handling processes. Cincinnati, OH: U.S. Department of Health 

and Human Services, Public Health Service, Centers for Disease Control and 

Prevention, National Institute for Occupational Safety and Health, DHHS 

(NIOSH) Report No. EPHB 356–12a. 

 ■ Topmiller J, Dunn KH, Earnest S, Lo LM, Gressel M, Echt A, Hall R [2012]. 

Current strategies for engineering controls in nanomaterial handling processes. Cincinnati, OH: U.S. Department of Health and Human Services, Public 

Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Report No. EPHB 

356–14a [being prepared for external review].

 ■ Lo LM, Hammond D, Dunn KH, Marlow D, Topmiller J, Tsai CSJ, Ellenbecker M, Huang CC [2012]. Evaluation of engineering controls in a manufacturing facility producing carbon nanotube-based products. Cincinnati, 

OH: U.S. Department of Health and Human Services, Public Health Service, 

Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Report No. EPHB 356–13a [draft 

in reviewed].
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APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Heitbrink WA, Lo LM, Farwick DF [2012]. Evaluation of enclosing hood and 

downflow room for nanocomposite manufacturing. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for 

Disease Control and Prevention, National Institute for Occupational Safety 

and Health, DHHS (NIOSH) Report No. EPHB 356–16a [draft in review]. 

Invited Presentations 

 ■ Dunn KH, Lo LM, Heitbrink W, Garcia A, Topmiller J [2010]. Engineering 

Control Strategies for Nanomaterials: Current State of Knowledge and Future 

Research Needs. NIOSH NTRC Science Meeting, Oglebay Resort & Conference Center, Wheeling, West Virginia, April 19–21.

 ■ Lo LM, Dunn KH, Heitbrink W, Garcia A, Topmiller J [2010]. Field Evaluation of Engineering Controls for Nanomaterial Manufacturing. Poster presentation at NIOSH NTRC Science Meeting, Oglebay Resort & Conference 

Center, Wheeling, West Virginia, April 19–21.

 ■ Tsai C, Huang CC, Ellenbecker M, Dunn KH [2011]. The optimum approach to control nanoparticle exposure using local exhaust ventilation. 

American Industrial Hygiene Conference and Exposition, Portland, Oregon, May 14–19.

 ■ McKernan JL, Geraci C, Dunn KH, Tsai S-J, Ellenbecker MJ [2011]. Engineering control recommendations for nanomaterials. Poster presentation at the 

American Industrial Hygiene Conference and Exposition, Portland, Oregon, 

May 14–19.

 ■ Lo LM, Dunn KH, Hammond D, Almaguer D, Bartholomew I, Topmiller 

J, Tsai C, Ellenbecker M, Huang CC [2011]. Assessing control measures for 

mitigating exposures during the production of carbon nanotubes. Poster presentation at 2011 National Occupational Research Agenda (NORA) Symposium. Cincinnati, Ohio, July 12–13.

 ■ Dunn KH, Tsai C, Huang CC, Ellenbecker M [2011]. Evaluation of nanoparticle dispersion and leakage from fume hoods using computational fluid dynamics. 5th International Symposium on Nanotechnology, Occupational and 

Environmental Health (NanOEH), Boston, Massachusetts, August 9–12.

 ■ Lo LM, Bartholomew I, Almaguer D, Heitbrink W, Hammond D, Topmiller 

J [2011]. Field evaluation of emission controls for the processing of nanographene materials. Poster presentation at the 5th International Symposium 

on Nanotechnology–Occupational and Environmental Health (NanOEH), 

Boston, Massachusetts, August 9–12.

 ■ Lo LM, Hammond D, Bartholomew I, Almaguer D, Topmiller J [2011]. Evaluation of engineering controls for occupational exposure to airborne nanomaterials. Poster presentation at 2011 National Occupational Research Agenda 

(NORA) Manufacturing Sector Conference, Cincinnati, Ohio, September 7–8.
264 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 58: Applying PtD to the Safe Handling of 

Engineered Nanomaterials

Principle Investigators: Donna Heidel, CIH, and Charles Geraci,

 PhD, CIH

Project Duration: FY 2009–2013

Critical Topic Areas: Engineering controls, recommendations, and guidance

Accomplishments and Research Findings 

 ■ Statement of work developed to support drafting the Nanotechnology Prevention through Design (PtD) workshop agenda and expected outcomes. Workshop to be held in 2012.

 ■ Contract awarded.

 ■ Contractor has developed stakeholder questionnaire to provide information 

for agenda development.

Publications

 ■ None

Invited Presentations

 ■ None
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 265

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 59: Penetration of Nanoparticles 

Through Respirators/Development 

of Respirator Filtration Test Methods 

Principle Investigator: Samy Rengasamy, PhD

Project Duration: FY 2005–2011

Critical Topic Areas: Engineering controls and personal protective equipment

Accomplishments and Research Findings

 ■ Developed and constructed novel test systems and methods to measure filter 

penetration and face seal leakage with a breathing manikin system.

 ■ Conducted studies to measure nanoparticle penetration through filter materials and face seal leakage, and evaluated particle number-based and photometric test methods to measure filter penetrations through the following types of 

devices/materials:

 — NIOSH-approved N, R, and P series filtering facepiece respirators (FFRs) 

of classes 95, 99, and 100

 — FDA-cleared surgical masks

 — Dust masks available in home improvement/hardware stores

 — Cloth masks available in beauty and personal care stores

 — Commonly used clothing materials

 ■ Key findings from these studies included the following:

 — N95 FFR penetrations measured by a particle number-based (countbased) method were two to six times greater than the levels measured 

by a photometric method (TSI 8130),when tested with the same aerosols 

employed in the NIOSH respirator certification method. Filtration test 

methods using photometric detection lack sensitivity for particles <100 

nm in size.

 — As expected, NIOSH-approved N95 and P100 air-purifying respirators 

have more consistent levels of filtration performance against nanoparticles 

than dust masks, FDA-cleared surgical masks, or cloth masks/commonly 

used clothing materials. NIOSH-approved N95 and P100 FFRs had similar 

levels of nanoparticle filtration performance as their CE-marked counterparts (FFP2 and FFP3). 

 — Respirator total inward leakage (TIL) increased with increasing leak sizes, 

demonstrating the need for using a good-fitting respirator. However, with 
266 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

relatively small leaks, TIL measured for 50-nm-size particles was about 

two-fold higher than the values for 8- and 400-nm-size particles.

 — NIOSH-approved respirators should provide levels of performance consistent with their OSHA-assigned protection factors (APF). Thus, current 

NIOSH tools for respirator selection can be used. However, employers 

may wish to factor in particle size during the respirator selection process. 

This could be accomplished by choosing a different type of respirator, 

offering higher levels of protection (i.e., higher APF), or by choosing a 

particulate respirator with a higher filtration rating (e.g., switching from 

N95 to N100 series).

 — Collaborated with IRSST, Canada, and Lovelace Respiratory Research 

Institute, NM, on nanoparticle filtration research projects.

 — Research findings from the work have been cited in nanotechnology 

documents, including those of NIOSH, IOM, IRSST, EU-OSHA, Edinburgh Napier University Report, Safe Work Australia, and ISO-TC. CDC 

highlighted one of the publications in the Science Clips in This Week’s top 

scientific articles.

Nanomaterial worker 

wearing a half face 

elastomeric respirator 

with p100 cartridges
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 267

APPENDIX A | A Summary of 69 NIOSH Research Projects

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. JOEH 5:556–564.

 ■ Shaffer R, Rengasamy S [2009]. Respiratory protection against nanoparticles: 

a review. J Nanopart Res 11:1661–1672.

 ■ Rengasamy S, Eimer B, Shaffer R [2009]. Comparison of nanoparticle filtration performance of NIOSH-approved and CE-marked particulate filtering 

facepiece respirators. Ann Occup Hyg 53:117–128. 

 ■ Shaffer R, Rengasamy S [2009]. Respiratory protection against nanoparticles: 

a review. J Nanopart Res 11:1661–1672.

 ■ Rengasamy S, Eimer B, Shaffer R [2009]. Filtration performance of FDAcleared surgical masks. J Int Soc Res Prot 26:54–70.

 ■ Rengasamy S, Zhuang Z, Roberge R, Shaffer R [2010]. Particulate respiratory 

protection: overview, emerging issues and research needs. In: Argosyan VE, 

ed. Protective devices: types, uses and safety. Hauppauge, New York: Nova 

Science Publishers, Inc., pp. 131–160.

 ■ Rengasamy S, Eimer B, Shaffer R [2010]. Simple respiratory protection: evaluation of the filtration performance of cloth masks and common fabric materials against 20–1000 nm size particles. Ann Occup Hyg 54:789–798. 

 ■ Rengasamy S, Eimer B, Miller A [2010]. Effects of organic solvents on the 

laboratory filtration performance of N95 and P100 filtering facepiece respirators. J Int Soc Res Prot 27:53–64.

 ■ Rengasamy S, Miller A, Eimer B [2011]. Evaluation of the filtration performance of NIOSH-approved N95 filtering facepiece respirators by photometric 

and number-based test methods. J Occup Environ Hyg 8:23–30.

 ■ Rengasamy S, Eimer B [2011]. Total inward leakage of nanoparticles through 

filtering facepiece respirators. Ann Occup Hyg 55:253–263.

 ■ Rengasamy S, Eimer B [2012]. Nanoparticle filtration performance of NIOSH 

certified particulate air purifying filtering facepiece respirators: evaluation by 

light scattering photometric and particle number-based test methods. J Occup Environ Hyg 9(2):99–109, DOI: 10.1080/18459624.2011.642703. 

 ■ Rengasamy S, Eimer B [2012]. Nanoparticle penetration through filter media 

and leakage through face seal interface of N95 filtering facepiece respirators. 

Ann Occup Hyg Jan 31, DOI:10.1093/annhyg/mer122.
268 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

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, Pennsylvania, November 11–13.

 ■ Rengasamy S, Eimer B, Shaffer R [2008]. Filtration performance of NIOSHapproved N95 and P100 filtering facepiece respirators against nanoparticles. 

American Industrial Hygiene Association Conference, Minneapolis, Minnesota, 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, Florida, October 20–24.

 ■ Rengasamy S, Shaffer R [2007]. Respiratory protection against nanoparticles. 

Chesapeake Area Biological Association Scientific Symposium, Columbia, 

Maryland, June 14.

 ■ Shaffer R [2008]. Effectiveness of personal protective equipment and engineering controls. Safe Handling of Engineered Nanoscale Materials Symposium, Argonne, Illinois, 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, California, 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. 

 ■ 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.

 ■ Rengasamy S, Eimer B [2009]. Nanoparticles leakage around face/mask interface of filtering facepiece respirators. American Industrial Hygiene Conference and Exposition, Toronto, Canada. May 30–June 5.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 269

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Shaffer RE, Hoover M [2009]. Effectiveness of personal protective equipment 

(PPE) and engineering controls for nanomaterials. American Chemical Society National Meeting and Exposition, Salt Lake City, Utah, March 22–26. 

 ■ Shaffer RE [2009]. Personal protective equipment and filtration [2009]. EH&S 

Challenges of the Nanotechnology Revolution Workshop, The Molecular 

Foundry, Lawrence Berkeley National Laboratory, Berkeley, California, July 29.

 ■ Shaffer RE [2009]. Respiratory protection against emerging hazards. Keynote 

speaker for the ERC Pilot Symposium at the University of Cincinnati, Cincinnati, Ohio, October 1–2.

 ■ Rengasamy S, Eimer B [2010]. Total inward leakage of nanoparticles through 

filtering facepiece respirators. International Society for Respiratory Protection, Hong Kong, China, September 26–30.

 ■ Shaffer RE [2010]. Towards improved personal protective equipment: possible applications for nanofibers? Nanofibers for the 3rd Millennium–Nano 

for LifeTM—2010 Conference, Raleigh Marriott City Center, Raleigh, North 

Carolina, August 30.

 ■ Rengasamy S, Eimer B [2011]. Evaluation of filtration performance of 

NIOSH-approved particulate air purifying filtering facepiece respirators. 

American Industrial Hygiene Conference and Exposition, Portland, Oregon, 

May 14–19.

 ■ Rengasamy S, Eimer B [2011]. Advances in respiratory protection and personal protective equipment. American Industrial Hygiene Conference and 

Exposition, Portland, Oregon, May 14–19.

 ■ Rengasamy S, Eimer B, Shaffer R [2011]. Respiratory protection against 

nanoparticles. NSF Nano Workshop, University of Massachusetts, Lowell, 

Massachusetts, August 10–12.

 ■ Rengasamy S [2011]. Respiratory protection against nanoparticles. NSF Nano 

Workshop. University of Central Florida, Orlando, Florida, December 9–10.
270 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 60: Nanoparticle Penetration through 

Protective Clothing

Principle Investigator: Pengfei Gao, PhD, CIH

Project Duration: FY 2009–2010

Critical Topic Areas: Engineering controls and personal protective equipment

Accomplishments and Research Findings 

 ■ The project was focused on the design and characterization of a method simulating typical wind-driven conditions for evaluating the performance of materials used in the construction of protective clothing. Ten nonwoven fabrics were 

selected, and physical properties including fiber diameter, fabric thickness, air 

permeability, porosity, pore volume, and pore size were determined. Particle 

penetration levels were measured under different face velocities and compared 

with a filtration-based method using the TSI 3160 automated filter tester. 

 ■ Our research findings show that particle penetration increased with increasing face velocity, and penetration also increased with increasing particle 

size up to about 300 to 500 nm. Penetrations measured by the wind-driven 

method were lower than those obtained with the filtration method for most 

of the fabrics selected, and the relative penetration performances of the fabrics were very different due to the vastly different pore structures. 

 ■ Particle penetration data from this study can be used to improve NIOSH 

guidance on the penetration of nanoparticles through protective clothing 

and ensembles.

 ■ The research findings could be used by government agencies, standards 

development organizations, and professional organizations to improve and/

or develop scientifically appropriate guidance documents, protective clothing 

performance requirements, and test methods.

Publications and Abstracts 

 ■ Gao P, Jaques PA, Hsiao TH, Shepherd A, Eimer B, Yang M, Miller A, Gupta 

B, Shaffer R [2011]. Evaluation of nano- and sub-micron particle penetration 

through ten nonwoven fabrics using a wind-driven approach. J Occup Environ Hyg 8(1):13–22.

Invited Presentations 

 ■ Gao P, Jaques PA, Shaffer R, Yang M, Shepherd A [2010]. A wind-driven 

method to assessing nano- and sub-micron particle penetration through fabrics. Presented at the American Industrial Hygiene Conference & Exposition, 

Denver, Colorado, May 22–27, 2010. Received Best Poster of the Section Award.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 271

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 61: Respirator Performance Against 

Engineered Nanoparticles Under 

Laboratory and Workplace Settings

Principle Investigator: Ziqing Zhuang, PhD

Project Duration: FY 2011–2015

Critical Topic Areas: Engineering controls and personal protective equipment; 

exposure assessment

Accomplishments and Research Findings

 ■ A NIOSH Science Blog on Respiratory Protection and Nanoparticles was 

developed and posted in December 2011 (http://blogs.cdc.gov/niosh-scienceblog/category/respiratory-health/). This science blog summarizes the science 

and rationale behind NIOSH’s recommendations for the use and selection of 

respirators against engineered nanoparticles.

 ■ A study protocol, titled Respirator Performance Against Engineered Nanoparticles Under Laboratory and Workplace Settings, has been developed and 

peer-reviewed. The protocol has been approved by the NIOSH human subject 

review board and data collection will begin in 2012.

 ■ Pilot laboratory studies were initiated while the full protocol was being 

drafted, reviewed, and approved. These pilot studies investigated the leak 

behavior of nanoparticles, analyzed previously collected human subject data 

on respirator fit, and measured the filtration performance of NIOSH approved 

respirators against carbon nanotubes. Key findings from these pilot studies 

include the following:

 — Nanoparticle penetration through manufactured leaks in electret media may be significantly reduced when compared to mechanical media 

and theory. The theoretical model was modified to achieve good 

agreement with experimental results for electret media. Future studies 

done under breathing conditions using manikins are needed to validate the revised model with fitting parameters to better understand 

nanoparticle leak behavior.

 — Nanoparticle fit factors obtained from N95 filtering facepiece respirators (FFRs) donned by human subjects were the same or higher than 

fit factors obtained from human subjects tested using to a more diverse 

particle size range. This preliminary data suggests than respirator leakage 

for nanoparticles should be similar to leakage levels found during typical 

respirator fit testing.
272 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 — With use of a custom-designed carbon nanotube aerosol respirator testing system, the filtration performance of NIOSH-approved N95, N99, 

and P100 series FFRs was measured. The results indicated that different 

FFR models yielded different levels penetrations. As expected, P100 FFRs 

had the highest levels of filtration performance, followed by N99 series 

and N95 series FFRs.

Personal protective equipment and controls used by 

nanomaterial workers
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 273

APPENDIX A | A Summary of 69 NIOSH Research Projects

Publications

 ■ None

Invited Presentations 

 ■ Zhuang Z, Bergman M, Eimer B, Shaffer R, BerryAnn R [2011]. Laboratory 

fit evaluation of N95 filtering facepiece respirators against nanoparticles and 

“all size” particles. Poster presentation at the 5th International Symposium on 

Nanotechnology, Occupational and Environmental Health, Boston, Massachusetts, August 9–12.

 ■ Zhuang Z, Bergman M, Eimer BC, Shaffer RE [2011]. Laboratory fit evaluation of N95 filtering facepiece respirators against nanoparticles and “all size” 

particles. Oral presentation at the ISRP Americas Section Annual General 

Meeting, St. Paul, Minnesota, September 11–12.

 ■ Pearce T, Fries M, Zhuang Z [2012]. Behavior of nanoparticle penetration 

through simulated filtering facepiece respirator faceseal leaks: experiment and 

theory. Abstract accepted for an oral presentation at the American Industrial 

Hygiene Association Conference & Expo, Indianapolis, Indiana, June 17–21.
274 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 62: Development of Personal Protective 

Equipment Ensemble Test Methods 

Principle Investigator: Pengfei Gao, PhD, CIH

Project Duration: FY 2005–2012

Critical Topic Areas: Engineering controls and personal protective equipment 

Accomplishments and Research Findings

 ■ Developed and evaluated 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]). The new sampler significantly enhances collection of magnetically susceptible particles, simulates the user’s real situation in the workplace 

better than alternative filtration-based approaches, and is promising for determining particle penetration through protective clothing materials. 

 ■ Developed and constructed a recirculation aerosol wind tunnel (RAWT) for 

evaluating aerosol samplers and measuring particle penetration through protective clothing materials. The RAWT is able to maintain relatively constant 

aerosol concentrations within a wide range of wind velocities and minimizes 

costs associated with conventional single-pass tunnels for our research needs.

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.

 ■ Jaques PA, Hsiao TH, Gao P [2011]. A recirculation aerosol wind tunnel for 

evaluating aerosol samplers and measuring particle penetration through protective clothing materials. Ann Occup Hyg 55(7):784–796. 

 ■ Gao P, Jaques PA, Hsiao TH, Shepherd A, Eimer B, Yang M, Miller A, Gupta 

B, Shaffer R [2011]. Evaluation of nano- and sub-micron particle penetration 

through ten nonwoven fabrics using a wind-driven approach. J Occup Environ Hyg 8(1):13–22.

 ■ Jaques PA, Hopke PH, Gao P [2012]. Quantitative analysis of uniquely distributed submicron paramagnetic Fe3O4 particles using computer controlled 

scanning electron microscopy. Aerosol Sci Technol 46(8):905–912.

 ■ Gao P, Jeffrey LB, Shaffer R [2011]. Considerations for selection of PPE to 

protect against nanoparticle exposure. In: Anna D, ed. Chemical protective 

clothing. 3rd ed. Fairfax, Virginia: AIHA [in press].
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 275

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Hsiao TH, Jaques PA, Gao P [2011]. Multi-domain magnetic passive 

aerosol sampler, part I: design and principle of operation. Aerosol Sci 

Technol [submitted].

 ■ Hsiao TH, Jaques PA, Li L, Lee CN, Gao P [2011]. Multi-domain magnetic 

passive aerosol sampler, part II: experimental evaluation of the performance. 

Aerosol Sci Technol [submitted].

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, Nevada, 

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, Pennsylvania, 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, California, May 14.

 ■ Shaffer R [2008]. Effectiveness of PPE and engineering controls. Safe Handling of Engineered Nanoscale Materials Symposium, Argonne, Illinois, 

July 7 and 8.

 ■ Jaques PA, Gao P [2008]. Effect of wind velocity on particle collection using 

a multi-domain magnetic passive aerosol sampler. Presented at the American 

Association for Aerosol Research (AAAR) 27th Annual Conference, Orlando, 

Florida, October 20–24. 

 ■ Hsiao TC, Jaques PA, Gao P [2010]. Development of a multi-domain magnetic passive aerosol sampler for measuring particle penetration through 

personal protective ensembles. Presented at the American Association for 

Aerosol Research (AAAR) 29th Annual Conference, Portland, Oregon, 

October 25–29.

 ■ Gao P, Jaques PA, Shaffer R, Yang M, Shepherd A [2010]. A wind-driven 

method to assessing nano- and sub-micron particle penetration through fabrics. Presented at the American Industrial Hygiene Conference & Exposition, 

Denver, Colorado, May 22–27.

 ■ Gao P, Jaques PA [2011]. Investigation of Fe3O4 particle deposition pattern on 

an individual magnet of a multi-domain magnetic passive aerosol sampler. 

Presented at the 5th International Symposium on Nanotechnology: Occupational and Environmental Health, Boston, Massachusetts, August 9–12.
276 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Gao P, Jaques PA, Hopke PH [2011].Quantitative analysis of uniquely distributed submicron paramagnetic Fe3O4 particles using computer controlled 

scanning electron microscopy. Presented at the American Industrial Hygiene 

Conference & Exposition, Portland, Oregon, May 14–19.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 277

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 63: Explosibility and Flammability of 

Carbon Nanotubes

Principle Investigator: Leonid A. Turkevich, ScD

Project Duration: FY 2010–2013

Critical Topic Areas: Fire and explosion

Accomplishments and Research Findings 

 ■ Explosion testing performed on 20 codes of carbonaceous particles (including 

single-walled and multi-walled carbon nanotubes, carbon nanofibers, graphene, diamond, fullerene, carbon blacks, graphites).

 — Typical overpressure p ~ 5–7 bar, deflagration index KSt ~ 10–80 bar-m/s 

(i.e., St-1, similar to cotton and wood dust).

 — Explosive parameters uncorrelated with particle size.

 ■ Selected additional analyses identified minimum explosive concentration 

(MEC) ~ 101–102 g/m3

 (order of magnitude lower than coals).

 ■ Concentration scans yielded higher over-pressures and deflagration indices; 

e.g., fullerene is borderline St-1/St-2. 

 ■ Powder conductivity (which shorted out the electrical ignition) raised additional 

safety concern of using these materials in the presence of electrical equipment.

 ■ Investigated dustiness of many fine and nanoscale powders (including singlewalled and multi-walled carbon nanotubes, carbon nanofibers, carbon blacks).

 — Respirable and total dustiness spanned two orders of magnitude.

Publications

 ■ Evans DE, Turkevich LA, Roettgers CT, Deye GJ, Baron PA [2012]. Dustiness 

of fine, nanoscale powders. Ann Occup Hyg doi 10.1093/annhyg/mes060.

Invited Presentations

 ■ Evans DE, Ku BK, Birch ME, Dunn KH, Turkevich LA [2010], Differentiating 

workplace aerosol emissions by direct-reading instrumentation. International 

Conference on Workplace Aerosols, Karlsruhe, Germany, June 28–July 2. 

 ■ Turkovich LA [2010]. Explosibility of carbonaceous nanoparticles. NIOSH 

Nanotechnology Research Center (NTRC) Review Meeting, Oglebay, Wheeling, West Virginia, April 19–21.
278 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Turkevich LA [2010]. Potential explosive hazard of carbonaceous nanoparticles. NIOSH Intramural Science Conference, Salt Fork, Ohio, August 10.

 ■ Evans DE, Turkevich LA, Roettgers CT, Deye GJ, Baron PA [2011]. Dustiness of nanomaterials. American Industrial Hygiene Conference, Portland, 

Oregon, May 14–19.

 ■ Turkevich LA, Dastidar A, Fernback J [2011]. Potential explosive hazard of carbonaceous nanoparticles. 5th International Conference on Nanotechnology Occupational and Environmental Health, Boston, Massachusetts, August 10–12.

 ■ Evans DE,Turkevich LA, Roettgers CT, Deye GJ, Baron PA [2011]. Dustiness 

of nanomaterials. 5th International Conference on Nanotechnology Occupational and Environmental Health, Boston, Massachusetts, August 10–12.

 ■ Turkevich LA, Fernback JE, Dastidar AG [2011]. Potential explosive hazard of 

carbonaceous nanoparticles. 2011 NORA Manufacturing Sector Conference, 

Cincinnati, Ohio, September 7–8.

 ■ Evans DE, Turkevich LA, Roettgers CT, Deye GJ, Baron PA [2011]. Dustiness of 

nanomaterials. 30th AAAR Annual Conference, Orlando, Florida, October 3–7.

 ■ Turkevich LA [2011]. Potential explosive hazard of carbonaceous nanoparticles. Technical seminar, NIOSH/DART Exposure Sciences Research (EXPSR) 

Program Science Exposition, Cincinnati, Ohio, September 21.

Explosion testing of carbon nanotubes
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 279

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 64: Current Intelligence Bulletin: 

Carbon Nanotubes and Carbon 

Nanofibers

Principle Investigators: Eileen Kuempel, PhD; Vincent Castranova, 

PhD; Douglas Trout, MD; and Eileen Birch, PhD

Project Duration: FY 2009–2014

Critical Topic Area: Recommendations and guidance

Accomplishments and Research Findings 

 ■ A draft Current Intelligence Bulletin (CIB) was prepared, describing the risk of 

potential adverse respiratory effects from exposure to carbon nanotubes and 

nanofibers. Risk management strategies were provided to minimize health risks 

to exposed workers, including a recommended exposure limit (REL). 

 ■ A NIOSH Nanotechnology Research Center (NTRC) review of the CIB was 

conducted, and a revised draft of the CIB was prepared for external review.

 ■ A Federal Register Notice was prepared and published in December 2010, announcing the release of the draft CIB for public and stakeholder review. 

Publications

 ■ Kuempel ED [2011]. Carbon nanotube risk assessment: implications for exposure and medical monitoring. J Occup Environ Med 53(6)(Suppl):S91–S97.

 ■ Kuempel E, Castranova V [2011]. Hazard and risk assessment of workplace exposure to engineered nanoparticles: methods, issues, and carbon nanotube case study. 

In: Ramachandran G, ed. Assessing nanoparticle risks to human health. Micro & 

Nano Technologies Series. Boston: William Andrew Publishing, pp. 65–97.

Invited Presentations

 ■ Kuempel E [2009]. Risk assessment case study: carbon nanotubes. Organization for Economic Cooperation and Development (OECD) Workshop on 

Risk Assessment of Manufactured Nanomaterials in a Regulatory Context, 

Washington, DC, September 17.

 ■ Kuempel E [2010]. Carbon nanotube risk assessment: implications for 

medical screening. Nanomaterials and Worker Health: Medical Surveillance, 

Exposure Registries, and Epidemiological Research, Keystone, Colorado, 

July 21–23.
280 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Kuempel E [2010]. Carbon nanotube risk assessment: using toxicology data 

to develop RELs. NIOSH Intramural Science Conference, Salt Fork, Ohio, 

August 10–11.

 ■ Kuempel E, Zumwalde R [2010]. Risk assessment of carbon nanotubes and 

status of NIOSH current intelligence bulletin. NTRC 2010 Update, Wheeling, 

West Virginia, April 20.

 ■ Kuempel E [2011]. Risk assessment of carbon nanotubes. NIOSH Public 

Review Meeting on the Draft Current Intelligence Bulletin on Occupational 

Exposure to Carbon Nanotubes and Nanofibers, Cincinnati, Ohio, February 3. 

 ■ Kuempel E [2011]. Occupational health risk assessment and CNT case study. 

Guest lecture in a graduate course at the University of Michigan, Ann Arbor, 

Michigan, March 24.

 ■ Kuempel ED [2011]. Methods and uncertainties in carbon nanotube risk 

assessment. Society for Risk Analysis Annual Meeting, Charleston, South 

Carolina, December 5.

 ■ Kuempel ED, Geraci CL [2011]. NIOSH draft current intelligence bulletin: occupational exposure to carbon nanotubes and nanofibers. Society for Chemical 

Hazard Communication (SCHC) Fall Meeting, Arlington, Virginia, October 4. 

 ■ Schulte PA [2011]. Overview of the draft NIOSH current intelligence bulletin: occupational exposure to carbon nanotubes and nanofibers. Nanotechnology Environmental Health Implications Working Group, Washington, 

D.C., January 20.

 ■ Schulte P, Kuempel E, Zumwalde R, Geraci C, Schubauer‐Berigan M, Castranova V, Hodson L, Murashov V, Ellenbecker M [2011]. Focused actions 

to protect carbon nanotube workers. The 5th International Symposium on 

Nanotechnology Occupational and Environmental Health, Boston, Massachusetts, August 10–12.
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Project 65: Assessing the Utility of Control 

Banding in the U.S.

Principal Investigator: T.J. Lentz, PhD

Project Duration: FY 2004–2012

Critical Topic Areas: Recommendations and Guidance

Accomplishments and Research Findings 

 ■ Coordinated a conference on Control Banding in the United States: This 

conference/workshop assembled national experts and stakeholders to discuss 

a national control banding plan and agenda (Washington, DC, March 2005)

 ■ Coordinated Intercontinental Workshop on the Occupational Safety and 

Health Toolkit. This event demonstrated the opportunities for international 

linkages to promote control banding strategies in developing and developed 

nations alike. This program promoted acceptance of the Global Implementation Strategy for control banding with effective demonstration of controlfocused solutions observed simultaneously at two international scientific 

venues on different continents (Johannesburg, South Africa and Orlando, FL, 

September 2005). 

 ■ Completed NIOSH Control Banding Topic Page—The topic page provides a 

focal point for the Institute’s control banding effort, conveying information 

and resources to and from multiple global sources. 

 ■ Control Banding Letter of Agreement—This component leveraged resources 

of NIOSH, U.K. HSE, and OSHA in coordinating efforts to develop and promote control banding solutions to occupational safety and health challenges 

and shared priorities.

 ■ Outreach in training efforts in FY07 and FY08 included workshops in 

Chile and India coordinated by NIOSH and the World Health Organization 

(WHO) to present concepts and control-focused solutions for exposures to 

silica and other hazards in the workplace.

Publications and Abstracts

 ■ Qualitative Risk Characterization and Management of Occupational Hazards: 

Control Banding (CB). DHHS (NIOSH) Publication No. 2009–152. 

Invited Presentations

 ■ Lentz TJ, Beaucham C [2009]. Chemical control banding. Ohio Safety Congress, Columbus, OH, April 1.
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 ■ Lentz TJ [2009]. Practical use of control banding for qualitative risk assessment and management of occupational hazards. ORC Worldwide Joint Conference of Occupational Physicians and Safety and Health Groups, Washington, DC, February 3–4.

 ■ Lentz TJ [2008]. Control banding: Qualitative risk assessment and management approaches for chemical exposures. Joint EFCOG/DOE Chemical Safety 

and Lifecycle Management Workshop, Washington, DC, March 4–6.

 ■ Lentz TJ [2007]. Control banding (bandas de controles): Qualitative occupational risk assessment and management using control-focused solutions and 

guidance. Control Banding Workshop, Chilean Institute of Public Health, 

Santiago, Chile, South America, July 17–19.

 ■ Lentz TJ [2007]. Control banding (bandas de controles): Applications for 

silica and silicosis prevention. Control Banding Workshop, Chilean Institute 

of Public Health, Santiago, Chile, South America, July 17–19.

 ■ Lentz TJ [2007]. Investigating the merits of control banding for workplace 

chemical hazards. Panel session at the Second Control Banding Workshop, 

University of Connecticut Health Center, Hartford, CT, February 1.

 ■ Lentz TJ (arranger), Miller J, Hildreth Watts C [2006]. Introduction to control 

banding—The GTZ Chemical Risk Management Guide and Training. Kentucky Governor’s Safety and Health Conference, Louisville, KY, May 9–12.

 ■ Lentz TJ [2009]. National efforts to explore control-focused solutions and 

their application. 48th Navy and Marine Corps Public Health Conference, 

Hampton, VA, March 25.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 283

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 66: Web-based Nanoparticle 

Information Library Implementation

Principal Investigator: Arthur Miller, PhD, and Mark Hoover, PhD

Project Duration: FY 2004–2008

Critical Topic Areas: 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 analysis of workplace nanoaerosol samples, using 

transmission electron microscopy/energy dispersive spectroscopy.

 ■ Developed a protocol for nanoaerosol characterization fieldwork, including quasireal 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.

 ■ Developed online newsletters and disseminated them to persons on the 

Nanoparticle Information Library mailing list.

 ■ Applied content of the Nanoparticle Information Library in development of a 

course 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, 
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APPENDIX A | A Summary of 69 NIOSH Research Projects

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.

 ■ During FY2009–FY2010, activities on the Nanoparticle Information Library 

(NIL) initiated in this project were advanced though work in the NTRC 

project on Nanoparticles in the Workplace and Metrics for Field and Toxicity 

Studies. The NIL can be accessed at www.nanoparticlelibrary.net.

Publications and Abstracts

 ■ 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. 

 ■ 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 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. In: American Conference of Governmental Industrial Hygienists Handbook. Air Sampling Technologies: Principles 

and Applications. Cincinnati, OH: American Conference of Governmental 

Industrial Hygienists.

 ■ Park K, Kim J-S, Miller AL [2008]. A study on effects of size and structure on 

hygroscopicity of nanoparticles using a tandem differential mobility analyzer 

and transmission electron microscopy. J Nanopart Res 11(1):175–183. 

 ■ 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):1–37.
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APPENDIX A | A Summary of 69 NIOSH Research Projects

Invited Presentations

 ■ Hoover MD, Miller AL, Lowe NT, Stefaniak AB, Day GA, Linch KD [2004]. 

Information management for nanotechnology safety and health. 1st International Symposium on Nanotechnology and Occupational Health, Buxton, 

UK, October 11–14.

 ■ Hoover MD [2005]. NIOSH nanotechnology informatics overview. NIOSH–

Altair Nanotechnologies, Inc., Information Exchange Meeting, Reno, Nevada, 

April 19.

 ■ Hoover MD [2005]. Informatics for nanotechnology safety and health: round 

table on the role of the occupational safety and health professional in the 

emerging nanotechnology industry. American Industrial Hygiene Conference 

and Exposition, Anaheim, California, May 24.

 ■ Miller AL, Hoover MD [2006]. Building a nanoparticle information library. 

National Occupational Research Agenda Symposium, Washington, DC, 

April 18–20.

 ■ 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, Oregon, 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, Minnesota, 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, Washington, 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, Oregon, September 8–10.
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Project 67: Nanoparticles in the Workplace and 

Metrics for Field and Toxicity Studies

Principle Investigator: Mark D. Hoover, PhD

Project Duration: FY 2004–2011

Critical Topic Areas: Communication and information; exposure assessment 

and measurement 

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 document on guidance for conducting control banding analyses. Provided leadership in activities of the American Industrial Hygiene Association 

control banding working group and the American Industrial Hygiene Association 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 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. Round-robin evaluations of analytical methods for beryllium 

detection in air filtration samples spiked with SRM 1877 are under way, under 

the auspices of the Beryllium Health and Safety Committee. Results of the 

evaluations are expected to have relevance for digestion and detection efficiencies of other ultrafine metal oxide particles. 

 ■ Provided leadership in a multi-organizational group of experts to develop an 

improved industrial hygiene decision-making framework (Anticipate, Recognize, Evaluate, Control, and Confirm) to provide a stronger basis for guidance 

for conducting control banding analyses by ensuring that measurements and 

epidemiology are conducted to confirm the efficacy of control.

 ■ Conducted filtration performance tests and comparisons with field experience for filtration behavior of ultrafine particles and incorporated the results 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 287

APPENDIX A | A Summary of 69 NIOSH Research Projects

into scientific presentations and in a book chapter on filtration. The chapter 

includes exposure assessment guidance for characterizing and managing 

particles of all sizes.

 ■ Led national experts in development of new ANSI consensus standards for 

calibration of air monitoring instruments used for airborne particles, including those in the nanometer size range.

 ■ Collaborated in conducting and publishing the results of experimental investigations into the production and characteristics of aerosol releases from a number of scenarios, including disruption of uranium in high-energy environments 

and melting and vaporization of metals in advanced welding techniques.

 ■ Helped organize and worked with a group of national experts on development 

of a standard file format for data submission and exchange on nanomaterials 

and characterizations.

 ■ Worked in conjunction with Oregon State University’s Knowledgebase of 

Nanomaterial-Biological Interactions to reestablish open web-based access 

to NIOSH Nanoparticle Information Library (NIL) and collaborated with the 

National Institute for Biomedical Imaging and Bioengineering to establish a 

Nanomaterials Registry at Research Triangle Institute. An initial focus of the 

new registry was the incorporation of data from the NIL.

 ■ Helped organize and conduct the Nanoinformatics Workshop series, which resulted in development of terminology, community goals, and pilot projects that 

are now incorporated into a comprehensive Nanoinformatics 2020 Roadmap.

 ■ 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 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-based initiative on minimum information for nanomaterial characterization and through development of the nanotechnology 

community-based Nanoinformatics 2020 Roadmap.

Publications and Abstracts

 ■ Castranova V, Hoover MD, Maynard A [2005]. NIOSH nanotechnology safety 

and health research program. In: Mark D, ed. Nanoparticles: a risk to health 

at work? Final Report of the First International Symposium on Occupational 

Health Implications of Nanomaterials, June, p. 117.

 ■ Hoover MD [2005]. Mixed exposure issues for nanotechnology safety. In: 

Mark D, ed. Nanoparticles: a risk to health at work? Final Report of the First 
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International Symposium on Occupational Health Implications of Nanomaterials, June, p. 115. 

 ■ Hoover MD, Miller AL, Lowe NT, Stefaniak AB, Day GA, Linch KD [2005]. 

Information management for nanotechnology safety and health. In: Mark D, 

ed. Nanoparticles: a risk to health at work? Final Report of the First International Symposium on Occupational Health Implications of Nanomaterials, 

June, p. 110.

 ■ Northage C, Hoover MD [2005]. Report of workshop Group F on regulatory 

implications. In: Mark D, ed. Nanoparticles: a risk to health at work? Final 

Report of the First International Symposium on Occupational Health Implications of Nanomaterials, June, pp. 145–147.

 ■ Stefaniak AB, Day GA, Scripsick RC, Hoover MD [2005]. Comprehensive 

characterization strategies for ultrafine particles: lessons from beryllium 

health and safety studies. In: Mark D, ed. Nanoparticles: a risk to health at 

work? Final Report of the First International Symposium on Occupational 

Health Implications of Nanomaterials, June, p. 118.

 ■ Stefaniak AB, Hoover MD, Day GA, Ekechukwu AA, Whitney G, Brink 

CA, Scripsick RC [2005]. Characteristics of beryllium oxide and beryllium metal powders for use as reference materials. J ASTM Intl 2(10):DOI 

10.1520/JAl13174.

 ■ Phalen RF, Hoover MD [2006]. Aerosol dosimetry research needs. Inhal Toxicol 18(7–10):841–843.

 ■ Watters RL, Hoover MD, Day GA, Stefaniak AB [2006]. Opportunities for 

development of reference materials for beryllium. J ASTM Intl 3(1):DOI 

10.1520/JAl13171.

 ■ 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, Virginia: American Industrial Hygiene Association. Document 9–2007. 

 ■ Hoover MD, Poster D [2008]. Environmental, health, and safety cross-cut 

issues for nanomanufacturing. In: Postek MT, Lyons KW, Ouimette MS, 

Holdridge GM, eds. Instrumentation, Metrology, and Standards for Nanomanufacturing Workshop final report. Washington, DC: National Science and 

Technology Council Interagency Working Group on Manufacturing Research 

and Development.
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APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Winchester MR, Turk GC, Butler TA, Oatts TJ, Coleman C, Nadratowski D, 

Sud R, Hoover MD, Stefaniak AB [2009]. Certification of beryllium mass 

fraction in SRM1877 beryllium oxide powder, using high-performance 

inductively-coupled plasma optical emission spectrometry with exact matching. Anal Chem 81(6):2208–2217.

 ■ Holmes TD, Guilmette RA, Cheng YS, Parkhurst MA, Hoover MD [2009], 

Aerosol sampling system for collection of capstone depleted uranium particles in a high-energy environment. Health Phys 96(3):221–237.

 ■ Hoover MD [2009]. Radiation research needs for direct-reading exposure 

assessment methods: update from the 2008 NIOSH workshop. Health Phys 

97(1):S97.

 ■ Hoover MD, Baltz D, Eimer BC, Rengasamy S [2009]. Evaluation of filter 

media for alpha continuous air monitoring in the ultrafine particle size range. 

Health Phys 97(1):S97.

 ■ Ekechukwu A, Hendricks W, White KT, Liabastre A, Archuleta M, Hoover 

MD [2009]. Validation of analytical methods and instrumentation for beryllium measurement: review and summary of available guides, procedures, and 

protocols. J Occup Environ Hyg 6:766–774.

 ■ Hoover MD, Johnson ML [2009]. American national standard for radiation 

protection instrumentation test and calibration–air monitoring instruments, 

ANSI N323C. New York: American National Standards Institute.

 ■ Pfefferkorn FE, Bello D, Haddad G, Park J-Y, Powell M, McCarthy J, Bunker 

KL, Fehrenbacher A, Jeon Y, Gruetzmacher G, Virji MA, Hoover MD [2010]. 

Characterization of exposures to airborne nanoscale particles during friction 

stir welding of aluminum. Ann Occup Hyg 54(5):486–503.

 ■ Decker JA, DeBord G, Weston A, Hoover MD [2010]. Exploring the exposome: a focus on totality of exposures could mean new opportunities for 

industrial hygienists. The Synergist 21(6):32–33.

 ■ Hoover MD, Cox M [2011]. A life-cycle approach to development and application of air sampling methods and instrumentation. In: Maiello ML, Hoover 

MD, eds. Radioactive air sampling methods. Boca Raton, Florida: CRC Press, 

pp. 43–52.

 ■ Hoover MD [2011]. Behavior of radioactive aerosols and gases. In: Maiello ML, Hoover MD, eds. Radioactive air sampling methods. Boca Raton, 

Florida: CRC Press, pp.135–155.

 ■ Hoover MD [2011]. Filtration. In: Maiello ML, Hoover MD, eds. Radioactive 

air sampling methods. Boca Raton, Florida: CRC Press, pp. 157–180.

 ■ Hoover MD [2011]. Methods for comprehensive characterization of radioactive aerosols: a graded approach. In: Maiello ML, Hoover MD, eds. Radioactive air sampling methods. Boca Raton, Florida: CRC Press, pp. 341–353.
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 ■ Hoover MD, Armstrong T, Blodgett T, Fleeger AK, Logan PW, McArthur B, 

Middendorf PJ [2011]. Confirming our industrial hygiene decision-making 

framework. The Synergist 22(1):10.

 ■ de la Iglesia D, Harper S, Hoover MD, Klaessig F, Lippell P, Maddux B, Morse 

J, Nel A, Rajan K, Reznik-Zellen R, Tuominen MT [2011]. Nanoinformatics 

2020 roadmap. Available at http://eprints.internano.org/607/.

 ■ Thomas DG, Klaessig F, Harper SL, Fritts M, Hoover MD, Gaheen S, Stokes 

TH, Reznik-Zellen R, Freund ET, Klemm JD, Paik DS, Baker NA [2011]. Informatics and standards for nanomedicine technology. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 3(5):511–532.

 ■ Schulte PA, Geraci CL, Hodson L, Zumwalde R, Castranova V, Kuempel E, 

Methner MM, Hoover MD, Murashov V [2011]. Nanotechnologies and nanomaterials in the occupational setting. Ital J Occup Environ Hyg 1(2):63–68.

 ■ Hoover MD [2011]. Nanotechnology: risk management challenges and opportunities. In: Knief RA, Prelas MA, eds. Risk management for tomorrow’s 

challenges. LaGrange Park, Illinois: American Nuclear Society, pp. 16–26. 

Invited Presentations

 ■ Hoover MD [2004]. Mixed exposure issues for nanotechnology safety. 1st 

International Symposium on Nanotechnology and Occupational Health, Buxton, UK, October 11–14.

 ■ Hoover MD, Miller AL, Lowe NT, Stefaniak AB, Day GA, Linch KD [2004].

Information management for nanotechnology safety and health. 1st International Symposium on Nanotechnology and Occupational Health, Buxton, 

UK, October 11–14.

 ■ Hoover MD, Hearl FA [2005]. NORA mixed exposures research agenda. 

Society of Toxicology Workshop on Contemporary Concepts in Toxicology—

Charting the Future: Building the Scientific Foundation for Mixtures Joint 

Toxicity and Risk Assessment, Atlanta, GA, February 16–17.

 ■ Hoover MD [2005]. An introduction to nanotechnology and the possible 

hazards. Institute of Occupational and Environmental Health Lecture, West 

Virginia University, March 1.

 ■ Hoover MD [2005]. Lung dosimetry of boundary fire smoke samples. Wildfire Symposium, Morgantown, West Virginia, March 31.

 ■ Hoover MD [2005]. NIOSH nanotechnology informatics overview. NIOSH—

Altair Nanotechnologies, Inc. Information Exchange Meeting, Reno, NV, 

April 19.

 ■ Hoover MD [2005]. Informatics for nanotechnology safety and health. Round 

table on the role of the occupational safety and health professional in the 

emerging nanotechnology industry. American Industrial Hygiene Conference 

and Exposition, Anaheim, California, May 24.
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 ■ Hoover MD [2005]. Nanotechnology: addressing potential health impact. Council of State and Territorial Epidemiologists, Albuquerque, New 

Mexico, June 6.

 ■ Hoover MD [2005]. Planning for the next decade of NORA: opportunities to translate research into practice through the National Occupational 

Research Agenda. Annual Meeting of the Health Physics Society, Spokane, 

Washington, July 13.

 ■ Hoover MD [2005]. Nanotechnology: understanding and addressing potential health impacts. National Association of Scientific Materials Managers, 

Reno, Nevada, July 25.

 ■ Hoover MD [2005]. Nanoparticles in the workplace. NIOSH NanoAerosols 

2005 Workshop, Oglebay, Wheeling, West Virginia, August 24.

 ■ Hoover MD, Murashov V [2005]. National and international standards activities related to nanotechnologies. NIOSH NanoAerosols 2005 Workshop, 

Oglebay, Wheeling, West Virginia, August 25.

 ■ Hoover MD, Murashov V [2005]. Overview of national and international 

standards activities related to nanotechnologies and draft ideas for discussion. 

U.S. Technical Advisory Group Meeting for ISO TC 229 Nanotechnologies, 

National Institute for Standards and Technology, Gaithersburg, Maryland, 

September 8.

 ■ Hoover MD [2005]. Nanotechnology: understanding and addressing potential health impacts. Southern California Environmental Safety, Hygiene, and 

Health Joint Technical Symposium, Long Beach, California, October 27.

 ■ Miller AL, Hoover MD [2006]. Building a nanoparticle information library. 

National Occupational Research Agenda Symposium, Washington, DC, 

April 18–20.

 ■ Eshelman JC, Hoover MD, Petsonk EL, Antao VC, Trout DB, Schulte PA 

[2006]. Occupational medicine issues for nanotechnology. American Occupational Health Conference, Los Angeles, California, May 10.

 ■ Hoover MD [2006]. Exposure assessment for nanotechnology. American 

Industrial Hygiene Conference, Chicago, Illinois, May 13–18.

 ■ Hoover MD [2006]. Characterization of nanoparticles in the workplace. Ask 

the Expert session on the NIOSH Nanotechnology Research Program, American Industrial Hygiene Conference, Chicago, Illinois, May 13–18.

 ■ Schulte P, Geraci C, Zumwalde R, Hoover M, Castranova V, Murashov V, 

Howard J [2006]. Occupational safety and health issues in nanotechnology. 

28th International Congress on Occupational Health, Milan, Italy, June 8–16.

 ■ Hoover MD [2006]. NIOSH approaches to safe nanotechnology. NIST Safety 

Day Symposium, National Institute for Standards and Technology, Gaithersburg, Maryland, June 15.
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 ■ 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, 

Florida, April 17.

 ■ Hoover MD [2007]. NIOSH experience in assessing practical measurement 

and control practices for nanoparticles. Midwest Nanotechnology Safety 

Workshop, Madison, Wisconsin, May 21.

 ■ 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, Pennsylvania, June 2.

 ■ Hoover MD [2007]. Nanotechnology health and safety issues. U.S. Department of Energy Industrial Hygiene and Occupational Safety Special Interest 

Group, Philadelphia, Pennsylvania, June 8.

 ■ 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, Pennsylvania, June 27.

 ■ 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, Maryland, June 14.

 ■ Hoover MD [2007]. Nanoparticle Information Library. National Nanomanufacturing Network Workshop on Nanoinformatics Strategies, Arlington, 

Virginia, June 12.

 ■ 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, California, 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, Maryland, 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, Maryland, 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, California, January 29.
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 ■ Hoover MD [2008]. NIOSH nanotechnology initiative: remarks on exposure 

assessment and control and informatics opportunities. NIOSH Education and 

Research Centers Industrial Hygiene Program Directors’ Meeting, Galveston, 

Texas, 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, California, 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, 

Minnesota, 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, Pennsylvania, July 16.

 ■ Hoover MD [2008]. Update on the NIOSH direct-reading methods initiative. 

Annual Meeting of the Health Physics Society, Pittsburgh, Pennsylvania, July 16.

 ■ Hoover MD [2008]. Demonstration of the NIOSH prototype Web-based 

Nanoparticle Information Library. Workshop on International Collaboration 

for nanoEHS Informatics, National Institute of Standards and Technology, 

Gaithersburg, Maryland, 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, Pennsylvania, December 10.

 ■ Shaffer R, Hoover MD [2009]. Effectiveness of PPE and engineering controls 

for nanomaterials. 237th National Meeting of the American Chemical Society, 

Salt Lake City, Utah, March 23.

 ■ Hoover MD [2009]. Applying principles of control banding to engineered 

nanoparticles. Teleweb Update on Control Banding: Fundamentals, Issues, 

Applications and Strategies for Implementation, American Industrial Hygiene 

Association, Distance Learning Program, March 26.

 ■ Kulinowski KM, Hankin SM, Hoover MD, Jaffe M, Riediker M, Stockmeier 

BC [2009]. Promoting good practices for handling nanomaterials: an international wiki project. NanoImpactNet Conference for a Healthy Environment in 

a Future with Nanotechnology, Lausanne, Switzerland, March 26.

 ■ Hoover MD [2009]. Nanotechnology exposure assessment, control, and 

informatics. Nanotechnology Health and Safety Conference, Austin, Texas, 

April 28.
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 ■ Hoover MD [2009]. Radiation research needs for direct-reading exposure 

assessment methods: update from the 2008 NIOSH workshop. 54th Annual 

Meeting of the Health Physics Society, Minneapolis, Minnesota, July 15.

 ■ Hoover MD, Baltz D, Eimer BC, Rengasamy S [2009]. Evaluation of filter media 

for alpha continuous air monitoring in the ultrafine particle size range. 54th 

Annual Meeting of the Health Physics Society, Minneapolis, Minnesota, July 15.

 ■ Gaheen S, Hoover MD [2009]. Informatics to support the health implications 

and applications of nanotechnology. CDC Public Health Informatics Conference, Atlanta, Georgia, August 30.

 ■ Hoover MD [2009]. Nanotechnology: risk management challenges and opportunities. American Nuclear Society Embedded Topical Meeting on Risk 

Management for Tomorrow’s Challenges, Washington, DC, November 16.

 ■ Hoover MD [2010]. A graded approach to safe nanotechnology in the workplace. Teleweb Introduction to Nanotechnology and Occupational Health, 

American Industrial Hygiene Association, Distance Learning Program, 

March 23.

 ■ Hoover MD [2010]. Public health applications of nanotechnology. CDC Public Health Grand Rounds Session on Preventing Adverse Health Effects from 

Nanotechnology, Atlanta, Georgia, April 15.

 ■ Hoover MD [2010]. Nanoinformatics. NIOSH Nanotechnology Research 

Center Face-to-Face Workshop, Wheeling, West Virginia, April 21.

 ■ Hoover MD [2010]. Exploring the exposome. American Industrial Hygiene 

Conference and Exposition, Denver, Colorado, May 25.

 ■ Hoover MD [2010]. Informatics in relation to nanomaterials and worker 

health. Workshop on Nanomaterials and Worker Health: Medical Surveillance, Exposure Registries, and Epidemiologic Research, Keystone, Colorado, 

July 21–23.

 ■ Ewert D, Geraci CL, Virji MD, Hoover MD, Gilkey D, Kosnett M, Petroka G 

[2010]. A comprehensive occupational health program for emerging nanotechnology processes in a pharmaceutical facility. Workshop on Nanomaterials and Worker Health: Medical Surveillance, Exposure Registries, and 

Epidemiologic Research, Keystone, Colorado, July 21–23.

 ■ Baker N, Cachau R, Collins B, Freund D, Fritts M, Gaheen S, Harper S, 

Hoover MD, Klaessig F, Klemm J, Malghan S, Paik D, Pan S, Thomas D, Stafford G [2010]. Identifying the common informatics needs of nanomedicine 

characterization methodology. caBIG Annual Meeting, Washington, DC, 

September 6–8.

 ■ Klemm J, Baker N, Thomas D, Harper S, Hoover MD, Fritts M, Cachau R, 

Gaheen S, Pan S, Stafford G, Paik D, Collins B, Freund E [2010]. nano-TAB: A 

standard file format for data submission and exchange on nanomaterials and 

characterizations. caBIG Annual Meeting, Washington, DC, September 6–8.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 295

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Hoover MD [2010]. Welcome and charge to the group. NIOSH Exploring the 

Exposome Workshop, Cincinnati, Ohio, September 22–23.

 ■ Hoover MD [2010]. Nanoparticle information library. Nanoinformatics 2010, 

Arlington, Virginia, November 3–5.

 ■ Baker N, Cachau R, Collins B, Freund D, Fritts M, Gaheen S, Harper S, 

Hoover MD, Klaessig F, Klemm J, Malghan S, Paik D, Pan S, Thomas D, Stafford G [2010]. Identifying the common informatics needs of nanomedicine 

characterization methodology. Nanoinformatics 2010, Arlington, Virginia, 

November 3–5.

 ■ Klemm J, Baker N, Thomas D, Harper S, Hoover MD, Fritts M, Cachau R, 

Gaheen S, Pan S, Stafford G, Paik D, Collins B, Freund E [2010]. nano-TAB: A 

standard file format for data submission and exchange on nanomaterials and 

characterizations. Nanoinformatics 2010, Arlington, Virginia, November 3–5.

 ■ Hoover MD [2010]. Safe nanotechnology in the workplace. Atlanta Health 

Physics Society Chapter Meeting, Atlanta, Georgia, November 9.

 ■ Hoover MD [2010]. Informatics resources and opportunities in relation to 

nanomaterials and worker health. Grand Rounds Lecture, Institute of Occupational and Environmental Health, West Virginia University, Morgantown, 

West Virginia, November 12.

 ■ Hoover MD [2011]. Filtration and flow control fundamentals for sampling 

airborne nanoparticles. Professional Enrichment Program—PEP 3B, Health 

Physics Society Mid-Year Meeting, Charleston, South Carolina, February 6.

 ■ Hoover MD [2011]. Some key elements for nanomaterial exposure assessment and management to advance sustainable manufacturing. EH&S 

Panel II Discussion, National Institute of Standards and Technology 

Workshop on Enabling the Carbon Nanomaterials Revolution, Gaithersburg, Maryland, March 1.

 ■ Hoover MD [2011]. NIOSH exposure assessment strategy. AIHA–Pittsburgh 

Local Section Workshop on Putting Safe Nanotechnology into Practice, Nevillewood, Pennsylvania, April 6.

 ■ Hoover MD [2011]. Emergency preparedness and response to nanoparticle 

incidents. AIHA–Pittsburgh Local Section Workshop on Putting Safe Nanotechnology into Practice, Nevillewood, Pennsylvania, April 6.

 ■ Hoover MD, Stefaniak AB [2011]. Chronic beryllium disease and current 

research on solubility of exposure materials. Beryllium Health and Safety 

Committee Meeting, Edgewood, Maryland, April 7.

 ■ Hoover MD [2011]. Case studies for anticipating, recognizing, evaluating, 

controlling, and confirming safe nanotechnology. Professional Development 

Course 503 on Applied Concepts of Nanotechnology for the EHS Professional, American Industrial Hygiene Conference and Exposition, Portland, 

Oregon, May 15.
296 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Hoover MD [2011]. Confirming the critical issues for advancing the exposure sciences. Special Session on The Exposome: The Future of Exposure 

Science? American Industrial Hygiene Conference and Exposition, Portland, Oregon, May 17.

 ■ Hoover MD [2011]. ANSI/HPS N13.8 update: an opportunity to advance 

radioactive air sampling for radiation protection in uranium mines. 56th 

Annual Meeting of the Health Physics Society, West Palm Beach, Florida, 

June 28.

 ■ Hoover MD [2011]. Nanoparticle characterization and control fundamentals: a 

graded approach. Professional Enrichment Program Course W3, 56th Annual 

Meeting of the Health Physics Society, West Palm Beach, Florida, June 29.

 ■ Day LM, Walker LS, Hoover MD [2011]. Panel discussion on emerging 

radiation-related health and safety issues for nanotechnology. 56th Annual 

Meeting of the Health Physics Society, West Palm Beach, Florida, June 30.

 ■ Hoover MD [2011]. Nanoinformatics tools. Continuing Education Course 

C2, 5th International Symposium on Nanotechnology, Occupational and 

Environmental Health, Boston, Massachusetts, August 9.

 ■ Hoover MD [2011]. Radioactive nanoparticles: working at the frontier of 

interdisciplinary science. Los Alamos National Laboratory, Los Alamos, NM, 

September 20.

 ■ Hoover MD [2011]. Case study: emergency preparedness and response for 

nanoparticle incidents. Putting Safe Nanotechnology into Practice, TVSAIHA Local Section Workshop, Knoxville, Tennessee, October 19.

 ■ Hoover MD [2011]. NIOSH exposure assessment strategies: a work in progress. Putting Safe Nanotechnology into Practice, TVS-AIHA Local Section 

Workshop, Knoxville, Tennessee, October 19.

 ■ Hoover MD, Stefaniak AB [2011]. Physicochemical characterization of beryllium. Beryllium Summit 2011: 4th International Conference on Beryllium 

Disease, Cleveland, Ohio, October 21.

 ■ Hoover MD [2011]. Lung deposition model for beryllium. Beryllium Summit 

2011: 4th International Conference on Beryllium Disease, Cleveland, Ohio, 

October 21.

 ■ Hoover MD [2011]. Confirming approaches to nanosafety and characterization through field and toxicity studies. 3rd Annual Conference of the American Society for Nanomedicine, Gaithersburg, Maryland, November 9.

 ■ Hoover MD [2011]. Anticipating, recognizing, evaluating, controlling, and confirming an effective nanoinformatics roadmap. 3rd Annual Conference of the 

American Society for Nanomedicine, Gaithersburg, Maryland, November 10.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 297

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 68: Global Harmonization of Exposure 

Measurement and Exposure 

Mitigation Approaches for 

Nanomaterials

Principal Investigator: Vladimir Murashov, PhD

Project Duration: FY 2006–2011 

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.

 ■ Chaired the Organization for Economic Cooperation and Development 

Working Party for Manufactured Nanomaterials Steering Group 8, Exposure 

Measurement and Exposure Mitigation.

 ■ Organized two OECD workshops on nanomaterial exposure measurement 

and mitigation.

 ■ Chaired the development of WHO Guidelines on Protecting Workers from 

Potential Risks of Nanomaterials and developed WHO topic page on nanomaterial safety.

 ■ Co-led a WHO project on best practices for safe handling of nanomaterials.

 ■ Developed content for UNITAR training material on occupational safety and 

health for nanotechnology for low and medium income countries and made 

presentations at UNITAR workshops.

 ■ Developed occupational safety and health content for United Nations Environmental Program’s report on nanotechnology safety and health.

 ■ Led the development and publication of ISO TR/12885:2008 Health and 

Safety Practices in Occupational Settings Relevant to Nanotechnologies. 

 ■ Chaired ANSI U.S. Technical Advisory Group to ISO TC229 Working Group 

3 on Nanotechnology Safety and Health.

 ■ Provided technical expertise for several ISO TC229 standards projects.

 ■ Represented NIOSH on several national and international working groups 

and committees on nanotechnology safety and health.
298 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Represented NIOSH on the National Nanotechnology Initiative interagency 

subcommittee and its working groups.

 ■ Presented overviews of the NIOSH Nanotechnology Research Program to 

outside stakeholders.

 ■ Edited a Special Issue on Exposure Assessment for Nanomaterials in the International Journal of Occupational and Environmental Health.

 ■ Led the development of WHO Guidelines on Protecting Workers from Potential Risks of Manufactured Nanomaterials and of WHO topic page on nanomaterial safety.

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, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, NIOSH Science 

Blog, May.

 ■ NIOSH [2009]. Nanotechnology: Human and Environmental Exposure Assessment for Nanomaterials Workshop. Cincinnati, OH: U.S. Department of 

Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, 

NIOSH Science Blog, March.

 ■ Howard J, Murashov V [2009]. National nanotechnology partnership to protect workers. J Nanopart Res 11(7):1673–1683.

 ■ Murashov V, Engel S, Savolainen K, Fullam B, Lee M, Kearns P [2009].Occupational safety and health in nanotechnology and Organisation for Economic 

Co-operation and Development. J Nanopart Res 11(7):1587–1591. 

 ■ Murashov V, Howard J [2009]. Essential features of proactive risk management. Nature Nanotech 4(8):467–470.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 299

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Murashov V, Howard J [2009]. International standards for risk management 

in nanotechnology. Nature Nanotech 4:205–206.

 ■ Murashov V [2009]. Occupational exposure to nanomedical applications. 

Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 

1(2):203–213. 

 ■ OECD [2009]. Comparison of guidance on selection of skin protective equipment and respirators for use in the workplace: manufactured nanomaterials. Organization for Economic Cooperation and Development, ENV/JM/

MONO(2009)17. 

 ■ OECD [2009]. Emission assessment for identification of sources and release 

of airborne manufactured nanomaterials in the workplace: compilation of existing guidance. Organization for Economic Cooperation and Development, 

ENV/JM/MONO(2009)16.

 ■ OECD [2009]. Preliminary analysis of exposure measurement and exposure 

mitigation in occupational settings: manufactured nanomaterials. Organization for Economic Cooperation and Development, ENV/JM/MONO(2009)6. 

 ■ Schulte PA, Geraci CL, Hodson L, Zumwalde R, Castranova V, Kuempel E, 

Methner MM, Hoover M, Murashov V [2010]. Nanotechnologies and nanomaterials in the occupational setting. Ital J Occup Environ Hyg 1(2):63–68.

 ■ Murashov [2010]. Human and environmental exposure assessment for 

nanomaterials: an introduction to this issue. Int J Occup Environ Health 

16(4):363–364. 

 ■ Schulte P, Murashov V, Kuempel E, Zumwalde R, Geraci C [2010]. Occupational exposure limits for nanomaterials: state of the art. J Nanopart Res 

12(6):1971–1987.

 ■ Murashov V, Schulte P, Geraci C, Howard J [2011]. Regulatory approaches 

to worker protection in nanotechnology industry in the USA and European 

Union. Ind Health 49(3):280–296.

 ■ NIOSH [2011]. Titanium dioxide: a changing paradigm in occupational risk 

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

Public Health Service, Centers for Disease Control and Prevention, National 

Institute for Occupational Safety and Health, NIOSH Science Blog, May.

 ■ NIOSH [2011]. Pleuropulmonary disease in a polyacrylate facility: a reminder 

of the need to protect workers from hazardous dust. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for 

Disease Control and Prevention, National Institute for Occupational Safety 

and Health, NIOSH Science Blog, July.

 ■ Murashov V, Howard J, eds [2011]. Nanotechnology standards. New York, 

NY: Springer Science+Business Media, ISBN: 978-1-4419-7852-3.

 ■ Murashov V, Howard J [2011]. Introduction. In: Murashov V, Howard J, eds. 

Nanotechnology standards. New York, NY: Springer, pp. 1–20.
300 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Murashov V, Howard J [2011]. Health and safety standards. In: Murashov V, 

Howard J, eds. Nanotechnology standards. New York, NY: Springer, pp. 209–238.

 ■ SAICM [2011]. Report on nanotechnologies and manufactured nanomaterials [SAICM/OEWG.1/INF/8]. Strategic approach to international chemicals 

management. Geneva, Switzerland: United Nations.

Government Publications

 ■ NSTC [2007]. The national nanotechnology initiative strategic plan. By Nanoscale Science, Engineering, and Technology Subcommittee, Committee on 

Technology. Arlington, VA: National Science and Technology Council.

 ■ 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. Arlington, VA: National Science and Technology Council.

 ■ NSTC [2008]. Strategy for nanotechnology-related environmental health and 

safety research. By Nanoscale Science, Engineering, and Technology Subcommittee, Committee on Technology. Arlington, VA: National Science and 

Technology Council. 

 ■ NSTC [2010]. Draft National Nanotechnology Initiative 2011: Environmental, Health, and Safety Strategy. Available at http://strategy.nano.gov/wp/wpcontent/uploads/2010/12/DraftEHSstrategy-17Dec2010-to-post.pdf.

 ■ NSTC [2010]. Human and environmental exposure assessment. Available at http://

www.nano.gov/html/society/ExposureAssessmentWorkshopReportforWeb.pdf.

 ■ EPA [2010]. A set of scientific issues being considered by the environmental 

protection agency regarding: evaluation of the hazard and exposure associated with nanosilver and other nanometal pesticide products. By Barber D, Hu 

Z, Filon FL, Linkov I, Murashov V, Philbert M, Roberts J, Sayes C, Westerhoff 

P, Yu IJ. EPA SAP Minutes No. 2010-01, February 2010.

 ■ NSTC [2011]. National Nanotechnology Initiative 2011: Environmental, 

Health, and Safety (EHS) Research Strategy. Nanoscale Science, Engineering, 

and Technology Subcommittee, Committee on Technology, National Science 

and Technology Council, October 2011. Available at http://www.nano.gov/

node/681.

Invited Presentations

 ■ Murashov V [2007]. Nanotechnology: occupational safety and health. Stateof-the-Art Conference/International Conference on Health Care Worker 

Health, Vancouver, British Columbia, Canada, October 26.

 ■ Murashov V [2007]. Nanotechnology: occupational safety and health. Nano 

Applications Summit—CleanTech Day, Cleveland, Ohio, October 24.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 301

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Murashov V [2007]. Nanotechnology: occupational health and safety. MidAtlantic Regional Conference on Occupational Medicine, Baltimore, Maryland, October 13.

 ■ Murashov V [2007]. Nanotechnology health and safety concerns. American 

Society of Safety Engineers, Region VI PDC, Myrtle Beach, South Carolina, 

September 20.

 ■ 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, Maryland, September 12.

 ■ Murashov V [2007]. NIOSH nanotechnology research program. Interagency 

Workshop on the Environmental Implications of Nanotechnology, Washington, DC, September 5.

 ■ Murashov V [2007]. NIOSH nanotechnology research program. Annual Environmental Health and Exposure Assessment Workshop, Washington, DC, 

August 17.

 ■ Murashov V [2007]. Social studies at NIOSH. The Joint Wharton-CHF 

Symposium on Social Studies of Nanotechnology, Philadelphia, Pennsylvania, 

June 8.

 ■ Murashov V [2007]. Nanotechnology: occupational health and safety. Conference on Risk Assessment for Nanomaterials, Cambridge, Massachusetts, 

May 29.

 ■ Murashov V [2007]. NIOSH nanotechnology research program. Conference 

on Nanotech 2007, Santa Clara, California, May 21.

 ■ Murashov V [2007]. Nanotechnology health and safety concerns. Meeting of 

National Aeronautics and Space Administration Code 500 Safety Awareness 

Campaign, Greenbelt, Maryland, April 18.

 ■ Murashov V [2007]. NIOSH nanotechnology research program. Navy Occupational Health and Safety Preventive Medicine Conference, Hampton, 

Virginia, 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—NIOSH 

nanotechnology research program. Intertech-PIRA Workshop, Washington, 

DC, February 8.

 ■ Murashov V [2008]. Nanotechnology and risk. Metro Washington College 

of Occupational and Environmental Medicine Meeting, Bethesda, Maryland, December 3.
302 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Murashov V [2008]. NIOSH nanotechnology research program. Meeting of 

National Center for Nanoscience and Technology of China, Beijing, China, 

November 14. 

 ■ 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. Conference 

on Sustainable Nanotechnology Innovations, Products, and Toxicology, Fayetteville, Arkansas, August 14.

 ■ Murashov V [2008]. NIOSH nanotechnology research program. Nanoscale 

Science, Engineering and Technology Subcommittee Meeting, Arlington, 

Virginia, July 15.

 ■ Murashov V [2008]. Nanotechnology: occupational safety and health. Workshop on Biological Interaction of Engineered Nanomaterials: Environmental, 

Safety, and Health Issues of Military Concern, Wright Patterson Air Force 

Base, Dayton, Ohio, June 25.

 ■ Murashov V [2008]. Nano health, safety and environment and worker protection. Second Jisso International Forum, Atlanta, Georgia, May 22.

 ■ Murashov V [2008]. Nanotechnology: exposure assessment. International 

Symposium on Risk Assessment of Manufactured Nanomaterials, Tokyo, 

Japan, April 23.

 ■ Murashov V [2008]. Nanotechnology and risk. 2008 Controlled Environment 

Testing Association Conference, San Antonio, Texas, April 14.

 ■ Murashov V [2008]. Nanotechnology and risk. Joint BIONET/BSAF Symposium on Current Topics in Biosafety, La Jolla, California, March 7.

 ■ Murashov V [2008]. Exposure assessment and control practices for nanoparticles. University of California, San Diego, Forum, San Diego, California, 

March 6.

 ■ Murashov V [2008]. International Organization for Standardization TC146/

SC2. International Organization for Standardization Workshop on Documentary Standards for Measurement and Characterization in Nanotechnologies, 

Gaithersburg, Maryland, 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, Maryland, February 26.

 ■ Murashov V [2008]. Nanotechnology and risk. California State University in 

Northridge, Environmental and Occupational Health Nanotech Symposium, 

Northridge, California, February 20.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 303

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Murashov V [2008]. NIOSH Nanotechnology Research Program. State-ofthe-Art Conference/International Conference on Health Care Worker Health, 

Vancouver, British Columbia, Canada, October 27.

 ■ Murashov V [2009]. Exposure mitigation in the workplace. UNITAR Workshop on Nanotechnology Safety and Health, Lodz, Poland, December 11.

 ■ Murashov V [2009]. Nanomaterial exposure assessment. Institute for Safety 

and Health at Work, Lausanne, Switzerland, October 2.

 ■ Murashov V [2009]. NIOSH nanotechnology program. UK House of Lords 

Science and Technology Committee visit, Washington, June 23.

 ■ Murashov V [2009]. NIOSH nanotechnology program. Nanotechnology 

Health and Safety Forum, Seattle, Washington, June 8.

 ■ Murashov V [2009]. Nanotechnology: occupational safety and health. Fifth 

International Conference on Collaboration in Nanotechnology, Los Angeles, 

California, May 18. 

 ■ Murashov V [2009]. Nanotechnology risk and potential for health surveillance. DOE Spring EFCOG Occupational Medicine Subgroup Meeting, 

Argonne, Illinois, April 20.

 ■ Murashov V [2009]. Carbon nanotube data call-in from NIOSH. Nanomaterial Data Call-Ins and Their Regulatory and Enforcement Implications, 

Washington, DC, April 15.

 ■ Murashov V [2009]. Overview of nanotechnology environmental and health 

implications workgroup. NNI Human and Environmental Exposure Assessment Workshop, Bethesda, Maryland, February 24–25.

 ■ Murashov V [2010]. NIOSH current intelligence bulletin on carbon 

nanotubes and nanofibers. ISO TC229 Meeting, Kuala Lumpur, Malaysia, 

December 6.

 ■ Murashov V [2010]. Advances and interventions related to occupational 

health risks of nanomaterials. 1st International Congress on Environmental 

Health, Guadalajara, Mexico, October 20.

 ■ Murashov V [2010]. Exposure mitigation in the workplace. UNITAR Workshop on Nanotechnology Safety and Health, Kingston, Jamaica, March 12.

 ■ Murashov V [2010]. Regulatory approaches to nanotechnology OSH. 4th 

JNIOSH International Workshop for Occupational Safety and Health Promotion, Tokyo, Japan, January 28.

 ■ Murashov V [2011]. ISO TC229/WG3: strategy considerations. ISO TC229 

Meeting, Johannesburg, South Africa, November 14.

 ■ Murashov V [2011]. WHO guidelines on protecting workers from potential 

risks of manufactured nanomaterials. ISO TC229 Meeting, Johannesburg, 

South Africa, November 14.
304 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Murashov V [2011]. Nanotechnology Occupational Safety and Health: global 

standards development. 5th International Conference on Nanotechnology 

Occupational and Environmental Health, Boston, USA, August 10–12.

 ■ Murashov V [2011]. Nanotechnology occupational safety and health: global 

standards development. INRS 2011, Nancy, France, April 7.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 305

APPENDIX A | A Summary of 69 NIOSH Research Projects

Project 69: New Sensor Technology Development 

for Filter Respirator Cartridge Endof-Service-Life Indicators (ESLI)

Principle Investigator: Jay Snyder, MS

Project Duration: FY 2002–2010

Critical Topic Area: Applications

Accomplishments and Research Findings

 ■ Developed sensors and integrated them into APR cartridges for evaluation.

 ■ Developed sensors and integrated them into PAPR cartridges for evaluation.

 ■ Developed new nanomaterials for chemical sensing.

 ■ Research findings are now being used in the update of NIOSH PAPR respirator standards.

 ■ Obtained a patent: Sailor, Ruminski, King, Snyder. Optical fiber–mounted 

porous photonic crystals and sensors. U.S. Patent #7,889,954, issued Feb. 15, 

2011. Patent assigned to the Regent of the University of California.

Publications and Abstracts

 ■ McCullough RD, Sauvé G, Li B, Jeffries ELM, Santhanam S, Schultz L, Zhang 

R, Iovu MC, Cooper J, Sreedharan P, Revelli JC, Kusner AG, Kowalewski T, 

Snyder JL, Weiss LE, Lambeth DN, Fedder GK [2005]. Regioregular polythiophene nanowires and sensors. In: Proceedings of SPIE, Vol. 5940. Organic 

Field-Effect Transistors IV. Bellingham, WA: International Society for Optical 

Engineering, pp. 28–34.

 ■ Li B, Santhanam S, Schultz L, Jeffries ELM, Iovu MC, Sauvé G, Cooper J, 

Zhang R, Revelli JC, Kusne AG, Snyder J, Kowalewski T, Weiss LE, McCullough RD, Fedder GK, Lambeth DN [2007]. Inkjet printed chemical sensor array based on polythiophene conductive polymers. Sensors Actuators B 

123(2):651–660.

 ■ Fedder GK, Bedair SS, Garg N, Greenblatt J, Jin R, Lambeth DN, Lazarus N, 

Santhanam S, Schultz L, Snyder JL, Weiss LE, Wu J [2008]. Jetted nanoparticle 

chemical sensor circuits for respirator end-of-service-life detection. In: Proceedings of the 12th International Meeting on Chemical Sensors 2008 (IMCS 

08), Columbus, Ohio, July 13–16. 

 ■ Qian H, Jin R [2009]. Controlling nanoparticles with atomic precision: the 

case of Au144(SCH2CH2Ph)60. Nano Lett 9:4083–4087.
306 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Bedair SS, Fedder GK [2009]. Picogram material dosing of microstructures. J 

Appl Phys 106(10):4913–4917.

 ■ Lazarus N, Bedair SS, Lo C-C, Fedder GK [2010]. CMOS-MEMS capacitive 

humidity sensor. J Microelectromech Syst 19(1):183–191.

 ■ Garg N, Mohanty A, Lazarus N, Schultz L, Rozzi TR, Santhanam S, Weiss 

L, Snyder JL, Fedder GK, Jin R [2010]. Robust gold nanoparticles stabilized by trithiol for application in chemiresistive sensors. Nanotechnology 

21(40):405–501.

 ■ King BH, Ruminski AM, Snyder JL, Sailor MJ [2007]. Optical-fiber-mounted 

porous silicon photonic crystals for sensing organic vapor breakthrough in 

activated carbon. Adv Mater 19:4530–4534.

 ■ Ruminski AM, King BH, Salonen J, Snyder JL, Sailor MJ [2010]. Porous siliconbased optical microsensors for volatile organic analytes: effect of surface 

chemistry on stability and specificity. Adv Funct Mater 20:2874–2883.

 ■ Sailor, Ruminski, King, Snyder. Optical fiber-mounted porous photonic crystals and sensors. U.S. Patent #7,889,954, issued Feb. 15, 2011. Patent assigned 

to the Regent of the University of California.

Invited Presentations 

 ■ Snyder JL [2005]. Volatile organic compound discrimination using nanostructured polythiophene sensors. Presented at the IEEE 2005 Sensors Conference, Irvine, California, October 30–November 3.

 ■ Snyder J [2007]. End-of-service-life sensor systems for personal protective 

equipment. Scientific Conference on Chemical and Biological Defense Research, Timonium, Maryland, November 13–15.

 ■ Snyder J [2007]. End-of-service life sensors and models. Technical Support 

Working Group, Personal Protective Equipment Conference, Fort Lauderdale, 

Florida, November 27–29.

 ■ Snyder J [2008]. Jetted nanoparticle chemical sensor circuits for respirator 

end-of-service-life detection. 12th International Meeting on Chemical Sensors, Columbus, Ohio, July 13–16.

 ■ Snyder J [2008]. Chemically modified porous silicon for optical sensing of 

organic vapor breakthrough in activated carbon filters. Nanomaterials for 

Defense Conference, Arlington, Virginia, April 21–24. 

 ■ Snyder J [2008]. End-of-service life sensor development. International Isocyanate Institute (III) America Analytical Subcommittee Meeting, Boulder, 

Colorado, June 9.

 ■ 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 307

APPENDIX A | A Summary of 69 NIOSH Research Projects

 ■ Snyder J [2010]. Application of chemistry to end-of service life determination 

of personal protective equipment. 240th American Chemical Society Meeting, 

Boston, Massachusetts, August 25.

 ■ Snyder J [2011]. Sensor development for personal protective equipment. 

NPPTL III Meeting, Pittsburgh, Pennsylvania, June 9.

APPENDIX B

NTRC Projects

in the 10 Critical 

Areas for 2004–2011
310 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX B | NTRC Projects in the 10 Criticall Areas for 2004–2011

Project 

number

Toxicology 

and 

internal 

dose

Measurement 

methods

Exposure 

assessment

Epidemiology 

and 

surveillance

Risk 

assessment

Engineering 

controls and 

PPE*

Fire 

and 

explosion

Recommendation 

and guidance

Communication 

and information Applications

1 X X X X X X X X X X2 X3 X4 X5 X6 X7 X8 X9 X

10 X

11 X

Table B1. NTRC projects in the 10 critical topic areas for 2004–2011

See footnote at end of table. (continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 311

APPENDIX B | NTRC Projects in the 10 Criticall Areas for 2004–2011 Project number Toxicology and internal dose Measure- ment methods Exposure assessment Epidemiology and surveillance Risk assessment Engineering controls and PPE* Fire and explosion Recommendation and guidance Communication and information Applications 12 X 13 X 14 X 15 X 16 X 17 X 18 X

19 X

20 X

21 X

22 X

Table B1 (Continued). NTRC projects in the 10 critical topic areas for 2004–2011

See footnote at end of table. (continued)
312 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX B | NTRC Projects in the 10 Criticall Areas for 2004–2011

Project 

number

Toxicology 

and 

internal 

dose

Measurement 

methods

Exposure 

assessment

Epidemiology 

and 

surveillance

Risk 

assessment

Engineering 

controls and 

PPE*

Fire 

and 

explosion

Recommendation 

and guidance

Communication 

and information Applications

23 X

24 X

25 X26 X

27 X

28 X29 X30 X X

31 X

32 X X

33 X

See footnote at end of table. (continued)

Table B1 (Continued). NTRC projects in the 10 critical topic areas for 2004–2011
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 313

APPENDIX B | NTRC Projects in the 10 Criticall Areas for 2004–2011 Project number Toxicology and internal dose Measure- ment methods Exposure assessment Epidemiology and surveillance Risk assessment Engineering controls and PPE* Fire and explosion Recommendation and guidance Communication and information Applications 34 X 35 X X X 36 X X 37 X X 38 X X 39 X X 40 X

41 X X

42 X X43 X

44 X

See footnote at end of table. (continued)

Table B1 (Continued). NTRC projects in the 10 critical topic areas for 2004–2011
314 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX B | NTRC Projects in the 10 Criticall Areas for 2004–2011

Project 

number

Toxicology 

and 

internal 

dose

Measurement 

methods

Exposure 

assessment

Epidemiology 

and 

surveillance

Risk 

assessment

Engineering 

controls and 

PPE*

Fire 

and 

explosion

Recommendation 

and guidance

Communication 

and information Applications

45 X46 X X

47 X X X

48 X X49 X50 X X

51 X X X X X X

52 X X

53 X X

54 X X

55 X

See footnote at end of table. (continued)

Table B1 (Continued). NTRC projects in the 10 critical topic areas for 2004–2011
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 315

APPENDIX B | NTRC Projects in the 10 Criticall Areas for 2004–2011 Project number Toxicology and internal dose Measure- ment methods Exposure assessment Epidemiology and surveillance Risk assessment Engineering controls and PPE* Fire and explosion Recommendation and guidance Communication and information Applications 56 X 57 X X 58 X X 59 X 60 X 61 X X 62 X

63 X

64 X X

65 X X

66 X

Table B1 (Continued). NTRC projects in the 10 critical topic areas for 2004–2011

See footnote at end of table. (continued)
316 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX B | NTRC Projects in the 10 Criticall Areas for 2004–2011

Project 

number

Toxicology 

and 

internal 

dose

Measurement 

methods

Exposure 

assessment

Epidemiology 

and 

surveillance

Risk 

assessment

Engineering 

controls and 

PPE*

Fire 

and 

explosion

Recommendation 

and guidance

Communication 

and information Applications

67 X X X68 X X X X

69 X

Table B1 (Continued). NTRC projects in the 10 critical topic areas for 2004–2011

*PPE: Personal Protective Equipment 
APPENDIX C

NIOSH Extramural 

Research

Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 319

APPENDIX C | NIOSH Extramural Research

Nanotechnology Portfolio Summary

2001–2011

Prepared by

W. Allen Robison, Ph.D. and Viji Potula, Ph.D.

National Institute for Occupational Safety and Health

Office of Extramural Programs

Atlanta, GA

December 31, 2011
320 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

Background

The mission of NIOSH is to generate new knowledge in the field of occupational 

safety and health and to transfer that knowledge into practice for the betterment of 

workers. To accomplish this mission, NIOSH conducts scientific research, develops 

guidance and authoritative recommendations, disseminates information, and responds to requests for workplace health hazard evaluations. NIOSH provides national 

and world leadership to prevent work-related illness, injury, disability, and death by 

gathering information, conducting scientific research, and translating the knowledge 

gained into products and services, including scientific information products, training 

videos, and recommendations for improving safety and health in the workplace.

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) Program, congressional mandates, and the 

NIOSH Program Portfolio.

A variety of occupational safety and health-related research grants, 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.

What is Nanotechnology?

Nanotechnology involves engineering and manipulation of materials at the molecular 

level. This technology creates materials with dimensions from 1 to 100 nanometers (1 

nanometer is 1 billionth of a meter). Particles created at the nanoscale have different 

chemical and physical properties than larger particles of the same material. Scientists 

and manufacturers can use nanoparticles to create new products that would be impossible with larger particles (http://www.cdc.gov/niosh/docs/2008-112).

Purpose

Extramural funding of nanotechnology-related research has been undertaken to help 

increase the knowledge of nanotechnology and manufactured nanomaterials as they 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 321

APPENDIX C | NIOSH Extramural Research

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 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 2001–2011, NIOSH/OEP has committed $12 million (M) to extramural nanotechnology research. Ongoing projects currently funded through FY-2014 account 

for another $3.6M (Figure 1), which brings the total to about $15.6M. This has been 

accomplished by 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 specific funds 

for nanotechnology research.

Figure 1. NIOSH/OEP funding for nanotechnology research, 2001–2011.

Funding Partnerships

OEP has partnered 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-05. The National Institute of Environmental Health Sciences (NIEHS) joined in FY-06. Funding 
322 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

was available to support Research (R01) grants for three years and Exploratory (R21) 

grants for two 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.

Figure 2. NIOSH extramural projects (2001–2011) in nanotechnology, 

by grant mechanism.

Extramural Research Projects and NIOSH 

Nanotechnology Goals

Major NIOSH goals for nanotechnology research are:

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. 

For more information on NIOSH nanotechnology goals, please visit the following 

website: http://www.cdc.gov/niosh/topics/nanotech/strat_planINTRO.html.

Mentored Scientist (KO1)

Developmental (R21)

Small Research (RO3)

Research program (RO1)

SBIR (R33/R44)

8

9

1

3

1
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 323

APPENDIX C | NIOSH Extramural Research

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 US 

and other countries.

Figure 3. NIOSH extramural nanotechnology projects by strategic goals.

Additional Information on Extramural Portfolio

From FY-01 to FY-04, OEP funded three R43/44 projects for a total funding commitment of about $950K (Table 1).

In FY-05, 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 of these 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-06, 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 of 

these 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-06.

In FY-07, NIOSH funded a three-year career development (mentored scientist) grant 

involving research on personal exposure to nanoparticles at the University of Iowa. 

In addition, a two-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.

Goal 1: Health Effects Research

Goal 2: Nanotech Products-Prevention

Goal 3: Engineering Controls

Goal 4: Global Collaborations (no projects)

6 7

9
324 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

In FY-08, 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-09 and FY-10, nanotechnology-related research proposals submitted to standing program announcements were 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.html

 ■ http://www2a.cdc.gov/niosh-nil/

NIOSH has identified 10 critical topic areas to guide in addressing knowledge gaps, 

developing strategies, and providing recommendations. NIOSH’s key role in conducting and partnering in research on occupational exposures to nanomaterials is noted in 

a new strategic plan under the National Nanotechnology Initiative.

Information on the NIOSH goal to transfer research findings, technologies and information into prevention practices and products in the workplace is provided at the 

website: 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 on the diverse activities of 

NIOSH can be found at the NIOSH home page (http://www.cdc.gov/niosh/homepage.

html) and the program portfolio website (http://www.cdc.gov/niosh/programs/).
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 325

APPENDIX C | NIOSH Extramural Research

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.
326 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

Grant number Investigator Institution Project title Start End

1st year 

funding Total funding

Prior to FY-04 NIOSH SBIR

1R43OH 007471–01

Hooker Nanomaterials 

Research LLC, Longmont, CO

Novel Hydrogen Sulfide Sensors for Portable Monitors 9/30/2001 3/31/2002 — —

2R44OH 007471–02

Williams Synkera Technologies Inc., 

Longmont, CO

Novel Hydrogen Sulfide Sensors for Portable Monitors 9/16/2003 9/15/2006 — —

Pre-FY-04 Total $473,400 $849,995

FY-04 NIOSH SBIR

1R43OH 007963–01A1

Rajagopalan Nanoscale 

Materials, Inc., Manhattan, KS

From Nanoparticles to Novel Protective Garments

9/1/2004 5/15/2005 — —FY-04 Total $100,000 $100,000

FY-05 NIOSH R01 Program Announcement

1R01OH0 08282–01A

Kagan University of 

Pittsburgh

Lung Oxidative Stress/Inflammation by Carbon Nanotubes

7/1/2005 6/30/2009 — —

Table 1. Extramural nanotechnology research funded by NIOSH, 2001–2011

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 327

APPENDIX C | NIOSH Extramural Research Table 1 (Continued). Extramural nanotechnology research funded by NIOSH, 2001–2011 Grant number Investigator Institution Project title Start End 1st year funding Total funding FY-05 Co-sponsored RFA (EPA STAR-2005-B1) 1R01OH 008806–01 O'Shaughnessy University of Iowa Assessment Methods for Nanoparticles in the Workplace 7/1/2005 6/30/2008 — — 1R01OH 

008807–01

Xiong New York University School of 

Medicine

Monitoring and Characterizing Airborne Carbon Nanotube Particles 8/1/2005 7/31/2008 — —

FY-06 NIOSH SBIR

1R43OH 008739–01

Thompson Eltron Research 

Boulder, CO

Antistatic Paint with Silent Discharge

8/30/2006 8/30/2007 — —

1R43OH 008939–01

Deininger Synkera Technologies Inc., 

Longmont, CO

New Nanostructured Sensor Arrays for Hydride Detection

8/1/2006 2/28/2007 — —

FY-06 Co-sponsored RFA (EPA G2006-STAR F1 to F7)

1R01OH 009141–01

Dutta Ohio State 

University

Role of Surface Chemistry in the Toxicological Properties of Manufactured Nanoparticles

9/1/2006 8/31/2009 — —

(continued)
328 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

Grant number Investigator Institution Project title Start End

1st year 

funding Total funding

5R01OH 008173–05

Timchalk Battelle Pacific Northwest 

Laboratories

Non-Invasive Biomonitoring of Pesticides

9/1/2006 8/31/2011 — —FY-06 Total $1,144,713 $1,553,935 

FY-07 NIOSH Exploratory/Developmental Research (R21) Program Announcement

1R21OH 009114–01

Volckens Colorado State 

University

A High-Flow Personal Sampler for Inhalable Aerosol 8/1/2007 7/31/2009 — —

FY-07 Career Development Grants (K01) Program Announcement

1K01OH 009255–01

Peters University of Iowa Personal Exposure to Engineered Nanoparticles 9/1/2007 8/31/2010 — —

FY-07 Total $314,138 $741,945 

FY-08 Co-sponsored RFA (NIEHS RFA-ES-06-008)

1R01OH 009448–01

Grassian University of Iowa An Integrated Approach 

Toward Understanding the Toxicity of Inhaled Nanomaterials

4/1/2008 3/31/2012 — —

Table 1 (Continued). Extramural nanotechnology research funded by NIOSH, 2001–2011

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 329

APPENDIX C | NIOSH Extramural Research Table 1 (Continued). Extramural nanotechnology research funded by NIOSH, 2001–2011 Grant number Investigator Institution Project title Start End 1st year funding Total funding FY-08 NIOSH Small Research Grant (PAR-06-551) Program Announcement 1R03OH 009381 Volckens Colorado State University A Personal Sampler for Assessing Inhaled Nanopar- ticle Exposures 7/1/2008 6/30/2010 — — FY-08 NIOSH SBIR

2R44OH0 07963–02

Rajagopalan Nanoscale 

Materials, Inc., Manhattan, KS

From Nanoparticles to Novel Protective Garments

7/1/2008 6/30/2010 — —FY-08 Total $796,841 $2,115,644 

FY-09 NIOSH SBIR

5R44OH0 08939–03

Deininger Synkera Technologies Inc. New Nanostructured Sensing Arrays for Hydride 

Detection

9/1/2009 8/31/2011 — —

5R44OH 009026–03

Routkevitch Synkera Technologies Inc. Phase II: Advanced Personal Gas Detection for Mining 

Applications

9/1/2009 8/31/2011 — —FY-09 Total $368,661 $750,000 

(continued)
330 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

Table 1 (Continued). Extramural nanotechnology research funded by NIOSH, 2001–2011 (Continued)

Grant number Investigator Institution Project title Start End

1st year 

funding Total funding

FY-10 NIOSH Research Grant

2R01OH 008282–05

Kagan University of 

Pittsburgh

Carbon nanotube biodegradation by neutrophil myeloperoxidase 

7/1/2010 6/30/2015 — —

1R21OH 009920–01

Peters University of Iowa Methods to Assess Personal 

Exposures to Airborne Metallic Nanoparticles

9/1/2010 8/30/2012 — —

1R01OH 009801–01A1

Cheng Lovelace Biomedical and 

Envir. Res. Inst.

Development of a personal sampler for nanoparticles

9/1/2010 8/31/2013 — —

5R01OH 09644–02

Mason Michigan State 

University

Autonomous electrochemical gas detection microsystem for mine safety 9/1/2010 8/31/2014 — —

FY-10 Total $2,497,499 $5,118,191 

FY-11 NIOSH Research Grant

1R21OH 009970–01

Delouise University of 

Rochester

Reagents to Enhance Detection of Raw and Biologically Transformed Nanomaterials

9/1/2011 8/31/2013 — —

FY-11 Total $185,108 $402,956 

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 331

APPENDIX C | NIOSH Extramural Research Table 1 (Continued). Extramural nanotechnology research funded by NIOSH, 2001–2011 Grant number Investigator Institution Project title Start End 1st year funding Total funding Total NIOSH Extramural Nanotech- nology Funding — $13, 870, 574
332 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

Extramural Nanotechnology Research Project Summaries

The project summaries included here were either publicly available information from 

the NIH RePORTER database (http://projectreporter.nih.gov/) or obtained by the 

principal investigator. For projects that have ended, abstracts from the Final Reports 

are included. 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) Novel Hydrogen Sulfide Sensors for Portable Monitors

Final Report Abstract

During this SBIR Phase I project, Nanomaterials Research (NRLLC) successfully 

demonstrated a new type of sensor device for detecting hydrogen sulfide (H2S). This 

gas is extremely toxic at low concentrations, and workplace exposure is common in 

a number of industries. Improved sensors and gas detection instruments are sorely 

needed to ensure protection of these exposed workers and to reduce H2S emissions 

into the atmosphere, thereby affecting public health.

NRLLC’s new sensor device combines recent advances in both semiconductor materials and alternative sensor fabrication approaches. These novel components were produced using processes and architectures that are similar to those used in the manufacture of multilayer ceramic capacitors. The sensors had a footprint of only 0.45 cm 

× 0.30 cm and exhibited the requisite mechanical strength needed for handling and 

integration into traditional electronic packages.

The sensors responded well to H2S at concentrations ranging from 5 to 50 ppm. These 

levels are commensurate with the monitoring requirements for workplace exposures, 

in which the personal exposure limit, or PEL, is 10 ppm and the short-term exposure 

limit, or STEL, is 15 ppm. The sensors exhibited a large decrease in resistance when 

the toxic gas was present, which is characteristic of n-type semiconductor behavior. 

This response was found to be linear with concentration and repeatable during multiple exposures. Response times (t50) were on the order of 20 seconds.

Several variables were investigated to determine their effect on the sensor response 

and recovery. These included the composition of the sensor material, the operating 

temperature of the device, the particle size of the raw materials, the design of the multilayer structure, and the degree of porosity retained in the final device. While a more 

extensive study is required, the Phase I results suggest that the processing and operation of the devices can be optimized by controlling such variables, thereby ensuring reliable gas detection. In addition, such devices can be designed to meet specific 

instrumentation requirements.

The small size and tailorability of NRLLC’s sensor devices are important features 

for implementation of the sensors in gas detection instruments. NRLLC envisions 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 333

APPENDIX C | NIOSH Extramural Research

a number of different application scenarios for these sensors including their use in 

stationary industrial monitoring systems, hand-held detection equipment, and revolutionary new personal monitors based on smart card technology. During the Phase 

II program, NRLLC plans to explore all three application areas, while building on the 

Phase I results to optimize sensor performance.

WILLIAMS 7471 (R44) Novel Hydrogen Sulfide Sensors for Portable Monitors

Final Report Abstract

Synkera’s primary objective for this SBIR project was the design, development, and 

demonstration of a better sensor technology for the detection of hydrogen sulfide. 

Hydrogen sulfide is a colorless, flammable gas that is highly toxic. It reacts with the 

enzymes in the blood that inhibit cell respiration. At high concentrations, it can 

literally shut off the lungs, while lower levels can burn the respiratory tract and cause 

eye irritation This gas is encountered in a wide range of industries, and a number of 

standards have been established for occupational exposure. The OSHA Permissible 

Exposure Limit (PEL) is 10 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, there are several potential spin-off opportunities in leak detection, emission 

monitoring, and process control. Synkera’s approach is to utilize alternative ceramic 

oxide materials, and a unique multilayer fabrication process to accomplish the objectives of this project. The work plan includes optimization of the sensor materials, sensor element fabrication, sensor element packaging, in-house and external evaluation 

of the sensors, and establishing the foundation for new instrument development. The 

ultimate aim is a low-cost, low-power sensor that can be used in a new type of personal monitor The envisioned monitor is a low profile, credit card sized “smart-card” that 

can not only alert the wearer when unsafe concentrations have been encountered but 

also track cumulative individual worker exposure to a particular toxic gas species. 

RAJAGOPALAN 7963 (R43) From Nanoparticles to Novel Protective Garments 

The goal of this project is to develop breathable, lightweight and disposable chemical protective clothing for use by personnel associated with law enforcement agencies, 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, having a limited number of distinct layers, which in turn can be assembled 

into a breathable, protective garment wherein the particular 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 
334 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

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 that protects the sorbent from contact 

with and contamination by liquids and that 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 broad-spectrum 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 by 

means of 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. Public Health 

Relevance: A 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® materials offer promise of 

protection and comfort.

KAGAN 8282 (R01) 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.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 335

APPENDIX C | NIOSH Extramural Research

Peer-reviewed publications specifically credited to this project:

The role of nanotoxicology in realizing the ‘helping without harm’ paradigm of nanomedicine: lessons from studies of pulmonary effects of single-walled carbon nanotubes. Shvedova AA, Kagan VE. J Intern Med. 2010; 267(1):106–18.

Abstract: Nano-sized materials and nano-scaled processes are widely used in many industries. They are being actively introduced as diagnostic and therapeutic in biomedicine and they are found in numerous consumer products. The small size of nanoparticles, comparable with molecular machinery of cells, may affect normal physiological 

functions of cells and cause cytotoxicity. Their toxic potential cannot be extrapolated 

from studies of larger particles due to unique physicochemical properties of nanomaterials. Therefore, the use of nanomaterials may pose unknown risks to human 

health and the environment. This review discusses several important issues relevant to 

pulmonary toxicity of nanoparticles, especially single-walled carbon nanotubes (SWCNT), their direct cytotoxic effects, their ability to cause an inflammatory response, 

and induce oxidative stress upon pharyngeal aspiration or inhalation. Further, recognition and engulfment of nanotubes by macrophages as they relate to phagocytosis 

and bio-distribution of nanotubes in tissues and circulation are discussed. The immunosuppressive effects of CNT and their significance in increased sensitivity of exposed 

individuals to microbial infections are summarized. Finally, data on biodegradation 

of SWCNT by oxidative enzymes of inflammatory cells are presented in lieu of their 

persistence and distribution in the body.

Lipid accumulation and dendritic cell dysfunction in cancer. Herber DL, Cao W, 

Nefedova Y, Novitskiy SV, Nagaraj S, Tyurin VA, Corzo A, Cho HI, Celis E, Lennox B, 

Knight SC, Padhya T, McCaffrey TV, McCaffrey JC, Antonia S, Fishman M, Ferris RL, 

Kagan VE, Gabrilovich DI. Nat Med. 2010;16(8):880–6.

Abstract: Dendritic cells (DCs), a type of professional antigen-presenting cells, are 

responsible for initiation and maintenance of immune responses. Here we report 

that a substantial proportion of DCs in tumor-bearing mice and people with cancer 

have high amounts of triglycerides as compared with DCs from tumor-free mice 

and healthy individuals. In our studies, lipid accumulation in DCs was caused by 

increased uptake of extracellular lipids due to upregulation of scavenger receptor A. 

DCs with high lipid content were not able to effectively stimulate allogeneic T cells or 

present tumor-associated antigens. DCs with high and normal lipid levels did not differ in expression of major histocompatibility complex and co-stimulatory molecules. 

However, lipid-laden DCs had a reduced capacity to process antigens. Pharmacological normalization of lipid abundance in DCs with an inhibitor of acetyl-CoA carboxylase restored the functional activity of DCs and substantially enhanced the effects 

of cancer vaccines. These findings suggest that immune responses in cancer can be 

improved by manipulating the lipid levels in DCs.

Close encounters of the small kind: adverse effects of man-made materials interfacing 

with the nano-cosmos of biological systems. Shvedova AA, Kagan VE, Fadeel B. Annu 

Rev Pharmacol Toxicol., 2010; 50:63–88. 
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Abstract: Engineered nanomaterials have unique physico-chemical properties that 

make them promising for many technological and biomedical applications, including tissue regeneration, drug and gene delivery, and in vivo monitoring of disease 

processes. However, with the burgeoning capabilities to manipulate structures at the 

nano-scale, intentional as well as unintentional human exposures to engineered nanomaterials are set to increase. Nanotoxicology is an emerging discipline focused on 

understanding the properties of engineered nanomaterials and their interactions with 

biological systems, and may be viewed as the study of the undesirable interference between man-made nanomaterials and cellular nanostructures or nanomachines. In this 

review, we discuss recognition of engineered nanomaterials by the immune system, 

our primary defense system against foreign invasion. Moreover, as oxidative stress is 

believed to be one of the major deleterious consequences of exposure to nanomaterials, we explore triggering of pro- and antioxidant pathways as well as biomarkers of 

oxidative stress. Finally, we highlight in vivo studies of the toxicological outcomes of 

engineered nanomaterials, including carbon nanotubes, with an emphasis on inflammation and genotoxic responses.

Mechanistic investigations of horseradish peroxidase-catalyzed degradation of 

single-walled carbon nanotubes. Allen BL, Kotchey GP, Chen Y, Yanamala NV, KleinSeetharaman J, Kagan VE, Star A. J Am Chem Soc. 2009;131(47):17194–205.

Abstract: Single-walled carbon nanotubes (SWNTs) have been investigated for a 

variety of applications including composite materials, electronics, and drug delivery. 

However, these applications may be compromised depending on the negative effects 

of SWNTs to living systems. While reports of toxicity induced by SWNTs vary, means 

to alleviate or quell these effects are in small abundance. We have reported recently 

the degradation of carboxylated SWNTs through enzymatic catalysis with horseradish 

peroxidase (HRP). In this full Article, we investigated the degradation of both carboxylated and pristine SWNTs with HRP and compared these results with chemical 

degradation by hemin and FeCl3. The interaction between pristine and carboxylated 

SWNTs with HRP was further studied by computer modeling, and the products of the 

enzymatic degradation were identified. By examining these factors with both pristine and carboxylated SWNTs through a variety of techniques including atomic force 

microscopy (AFM), transmission electron microscopy (TEM), Raman spectroscopy, 

ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy, gas chromatographymass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), and 

liquid chromatography-mass spectrometry (LC-MS), degradation pathways were elucidated. It was observed that pristine SWNTs demonstrate no degradation with HRP 

incubation but display significant degradation when incubated with either hemin or 

FeCl3. Such data signify a heterolytic cleavage of H2O2 with HRP as pristine nanotubes 

do not degrade, whereas Fenton catalysis results in the homolytic cleavage of H2O2

producing free radicals that oxidize pristine SWNTs. Product analysis shows complete 

degradation produces CO2 gas. Conversely, incomplete degradation results in the 

formation of different oxidized aromatic hydrocarbons.
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Mass-spectrometric analysis of hydroperoxy- and hydroxy-derivatives of cardiolipin and 

phosphatidylserine in cells and tissues induced by pro-apoptotic and pro-inflammatory 

stimuli. Tyurin VA, Tyurina YY, Jung MY, Tungekar MA, Wasserloos KJ, Bayir H, 

Greenberger JS, Kochanek PM, Shvedova AA, Pitt B, Kagan VE. J Chromatogr B Analyt 

Technol Biomed Life Sci. 2009;877(26):2863–72.

Abstract: Oxidation of two anionic phospholipids—cardiolipin (CL) in mitochondria 

and phosphatidylserine (PS) in extramitochondrial compartments—is important 

signaling event, particularly during the execution of programmed cell death and 

clearance of apoptotic cells. Quantitative analysis of CL and PS oxidation products 

is central to understanding their molecular mechanisms of action. We combined the 

identification of diverse phospholipid molecular species by ESI-MS with quantitative assessments of lipid hydroperoxides using a fluorescence HPLC-based protocol. 

We characterized CL and PS oxidation products formed in a model system (cyt c/

H2O2), in apoptotic cells (neurons, pulmonary artery endothelial cells) and mouse 

lung under inflammatory/oxidative stress conditions (hyperoxia, inhalation of single 

walled carbon nanotubes). Our results demonstrate the usefulness of this approach for 

quantitative assessments, identification of individual molecular species and structural 

characterization of anionic phospholipids that are involved in oxidative modification 

in cells and tissues.

Recognition of live phosphatidylserine-labeled tumor cells by dendritic cells: a novel 

approach to immunotherapy of skin cancer. Shurin MR, Potapovich AI, Tyurina YY, 

Tourkova IL, Shurin GV, Kagan VE. Cancer Res. 2009; 69(6):2487–96.

Abstract: Dendritic cells (DC) loaded with tumor antigens from apoptotic/necrotic 

tumor cells are commonly used as vaccines for cancer therapy. However, the use of 

dead tumor cells may cause both tolerance and immunity, making the effect of vaccination unpredictable. To deliver live tumor “cargoes” into DC, we developed a new 

approach based on the “labeling” of tumors with a phospholipid “eat-me” signal, phosphatidylserine. Expression of phosphatidylserine on live tumor cells mediated their 

recognition and endocytosis by DC resulting in the presentation of tumor antigens to 

antigen-specific T cells. In mice, topical application of phosphatidylserine-containing 

ointment over melanoma induced tumor-specific CTL, local and systemic antitumor 

immunity, and inhibited tumor growth. Thus, labeling of tumors with phosphatidylserine is a promising strategy for cancer immunotherapy.

Single-walled carbon nanotubes impair human macrophage engulfment of apoptotic 

cell corpses. Witasp E, Shvedova AA, Kagan VE, Fadeel B. Inhal Toxicol. 2009; 21 

Suppl 1:131–6.

Abstract: Single-walled carbon nanotubes (SWCNT) are being produced in increasing quantities and the application of these materials in a large number of new technologies and consumer products necessitates studies of their potential impact on 

human health and the environment. To determine whether SWCNT affect viability 

or function of macrophages, important components of the innate immune system, 
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we performed in vitro studies using primary human monocyte-derived macrophages 

(HMDM). Our findings show that SWCNT with a low content of metal impurities do not exert direct cytotoxic effects on HMDM. However, SWCNT suppressed 

chemotaxis of primary human monocytes in a standard chemotaxis assay. Moreover, 

macrophage engulfment of apoptotic target cells was significantly impaired following pre-incubation of HMDM with SWCNT at non-cytotoxic concentrations. These 

results are in line with previous studies showing that ultrafine carbon particles and 

carbon nanotubes may impair alveolar macrophage ingestion of microorganisms, and 

suggest that tissue homeostasis may be compromised by SWCNT due to suppressive 

effects on macrophages.

Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo. Konduru NV, Tyurina YY, Feng W, Basova LV, Belikova 

NA, Bayir H, Clark K, Rubin M, Stolz D, Vallhov H, Scheynius A, Witasp E, Fadeel 

B, Kichambare PD, Star A, Kisin ER, Murray AR, Shvedova AA, Kagan VE. PLoS 

One. 2009;4(2):e4398. Epub 2009 Feb 9. Erratum in: PLoS One. 2009; 4(5):10.1371/

annotation/1801d3b3-2082-4eb7-913b-b93e1fe4c219.

Abstract: Broad applications of single-walled carbon nanotubes (SWCNT) dictate 

the necessity to better understand their health effects. Poor recognition of nonfunctionalized SWCNT by phagocytes is prohibitive towards controlling their biological action. We report that SWCNT coating with a phospholipid “eat-me” signal, 

phosphatidylserine (PS), makes them recognizable in vitro by different phagocytic 

cells-murine RAW264.7 macrophages, primary monocyte-derived human macrophages, dendritic cells, and rat brain microglia. Macrophage uptake of PS-coated 

nanotubes was suppressed by the PS-binding protein, Annexin V, and endocytosis 

inhibitors, and changed the pattern of pro- and anti-inflammatory cytokine secretion. Loading of PS-coated SWCNT with pro-apoptotic cargo (cytochrome c) allowed 

for the targeted killing of RAW264.7 macrophages. In vivo aspiration of PS-coated 

SWCNT stimulated their uptake by lung alveolar macrophages in mice. Thus, PScoating can be utilized for targeted delivery of SWCNT with specified cargoes into 

professional phagocytes, hence for therapeutic regulation of specific populations of 

immune-competent cells.

Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon 

nanotubes. Murray AR, Kisin E, Leonard SS, Young SH, Kommineni C, Kagan VE, 

Castranova V, Shvedova AA. Toxicology. 2009;257(3):161–71.

Abstract: Single-walled carbon nanotubes (SWCNT) represent a novel material 

with unique electronic and mechanical properties. The extremely small size ( approximately 1 nm diameter) renders their chemical and physical properties unique. 

A variety of different techniques are available for the production of SWCNT; however, the most common is via the disproportionation of gaseous carbon molecules 

supported on catalytic iron particles (high-pressure CO conversion, HiPCO). The 

physical nature of SWCNT may lead to dermal penetration following deposition on 

exposed skin. This dermal deposition provides a route of exposure which is important 
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APPENDIX C | NIOSH Extramural Research

to consider when evaluating SWCNT toxicity. The dermal effects of SWCNT are 

largely unknown. We hypothesize that SWCNT may be toxic to the skin. We further 

hypothesize that SWCNT toxicity may be dependent upon the metal (particularly 

iron) content of SWCNT via the metal’s ability to interact with the skin, initiate oxidative stress, and induce redox-sensitive transcription factors thereby affecting/leading 

to inflammation. To test this hypothesis, the effects of SWCNT were assessed both in 

vitro and in vivo using EpiDerm FT engineered skin, murine epidermal cells (JB6 P+), 

and immune-competent hairless SKH-1 mice. Engineered skin exposed to SWCNT 

showed increased epidermal thickness and accumulation and activation of dermal 

fibroblasts which resulted in increased collagen as well as release of pro-inflammatory 

cytokines. Exposure of JB6 P+ cells to unpurified SWCNT (30% iron) resulted in 

the production of ESR detectable hydroxyl radicals and caused a significant dosedependent activation of AP-1. No significant changes in AP-1 activation were detected 

when partially purified SWCNT (0.23% iron) were introduced to the cells. However, 

NFkappaB was activated in a dose-dependent fashion by exposure to both unpurified 

and partially purified SWCNT. Topical exposure of SKH-1 mice (5 days, with daily 

doses of 40 microg/mouse, 80 microg/mouse, or 160 microug/mouse) to unpurified 

SWCNT caused oxidative stress, depletion of glutathione, oxidation of protein thiols 

and carbonyls, elevated myeloperoxidase activity, an increase of dermal cell numbers, 

and skin thickening resulting from the accumulation of polymorphonuclear leukocytes (PMNs) and mast cells. Altogether, these data indicated that topical exposure to 

unpurified SWCNT, induced free radical generation, oxidative stress, and inflammation, thus causing dermal toxicity.

Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: 

Two faces of Janus? Shvedova AA, Kisin ER, Porter D, Schulte P, Kagan VE, Fadeel B, 

Castranova V. Pharmacol Ther. 2009 Feb;121(2):192–204. 

Abstract: Nanotechnology is an emerging science involving manipulation of materials 

at the nanometer scale. There are several exciting prospects for the application of engineered nanomaterials in medicine. However, concerns over adverse and unanticipated 

effects on human health have also been raised. In fact, the same properties that make 

engineered nanomaterials attractive from a technological and biomedical perspective 

could also make these novel materials harmful to human health and the environment. 

Carbon nanotubes are cylinders of one or several coaxial graphite layer(s) with a 

diameter in the order of nanometers, and serve as an instructive example of the Januslike properties of nanomaterials. Numerous in vitro and in vivo studies have shown 

that carbon nanotubes and/or associated contaminants or catalytic materials that arise 

during the production process may induce oxidative stress and prominent pulmonary 

inflammation. Recent studies also suggest some similarities between the pathogenic 

properties of multi-walled carbon nanotubes and those of asbestos fibers. On the 

other hand, carbon nanotubes can be readily functionalized and several studies on 

the use of carbon nanotubes as versatile excipients for drug delivery and imaging of 

disease processes have been reported, suggesting that carbon nanotubes may have a 

place in the armamentarium for treatment and monitoring of cancer, infection, and 

other disease conditions. Nanomedicine is an emerging field that holds great promise; 
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APPENDIX C | NIOSH Extramural Research

however, close attention to safety issues is required to ensure that the opportunities 

that carbon nanotubes and other engineered nanoparticles offer can be translated into 

feasible and safe constructs for the treatment of human disease.

Mitochondria-targeted disruptors and inhibitors of cytochrome c/cardiolipin peroxidase complexes: a new strategy in anti-apoptotic drug discovery. Kagan VE, Bayir A, 

Bayir H, Stoyanovsky D, Borisenko GG, Tyurina YY, Wipf P, Atkinson J, Greenberger 

JS, Chapkin RS, Belikova NA. Mol Nutr Food Res. 2009;53(1):104–14.

Abstract: The critical role of mitochondria in programmed cell death leads to the 

design of mitochondriotropic agents as a strategy in regulating apoptosis. For anticancer therapy, stimulation of proapoptotic mitochondrial events in tumor cells and their 

suppression in surrounding normal cells represents a promising paradigm for new 

therapies. Different approaches targeting regulation of components of mitochondrial 

antioxidant system such as Mn-SOD demonstrated significant antitumor efficiency, 

particularly in combination therapy. This review is focused on a newly discovered early 

stage of mitochondria-dependent apoptosis-oxidative lipid signaling involving a mitochondria-specific phospholipid cardiolipin (CL). Cytochrome c (cyt c) acts as a CL-specific peroxidase very early in apoptosis. At this stage, the hostile events are still secluded 

within the mitochondria and do not reach the cytosolic targets. CL oxidation process is 

required for the release of pro-apoptotic factors into the cytosol. Manipulation of cyt c 

interactions with CL, inhibition of peroxidase activity, and prevention of CL peroxidation are prime targets for the discovery of anti-apoptotic drugs acting before the “pointof-no-return” in the fulfillment of the cell death program. Therefore, mitochondriatargeted disruptors and inhibitors of cyt c/CL peroxidase complexes and suppression of 

CL peroxidation represent new strategies in anti-apoptotic drug discovery.

Biodegradation of single-walled carbon nanotubes through enzymatic catalysis. Allen 

BL, Kichambare PD, Gou P, Vlasova II, Kapralov AA, Konduru N, Kagan VE, Star A. 

Nano Lett. 2008; 8(11):3899–903.

Abstract: We show here the biodegradation of single-walled carbon nanotubes through 

natural, enzymatic catalysis. By incubating nanotubes with a natural horseradish peroxidase (HRP) and low concentrations of H2O2 (approximately 40 microM) at 4 degrees C 

over 12 weeks under static conditions, we show the increased degradation of nanotube 

structure. This reaction was monitored via multiple characterization methods, including 

transmission electron microscopy (TEM), dynamic light scattering (DLS), gel electrophoresis, mass spectrometry, and ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy. These results mark a promising possibility for carbon nanotubes to be degraded by 

HRP in environmentally relevant settings. This is also tempting for future studies involving biotechnological and natural (plant peroxidases) ways for degradation of carbon 

nanotubes in the environment.

Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Shvedova AA, Kisin E, Murray AR, 

Johnson VJ, Gorelik O, Arepalli S, Hubbs AF, Mercer RR, Keohavong P, Sussman N, 
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APPENDIX C | NIOSH Extramural Research

Jin J, Yin J, Stone S, Chen BT, Deye G, Maynard A, Castranova V, Baron PA, Kagan 

VE. Am J Physiol Lung Cell Mol Physiol. 2008; 295(4):L552–65.

Abstract: Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and 

thermal properties, single-walled carbon nanotubes (SWCNT) are finding numerous 

applications in electronics, aerospace devices, computers, and chemical, polymer, 

and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. 

Previously, we (47) have reported that pharyngeal aspiration of purified SWCNT by 

C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, 

acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated 

with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT 

dispersions obtained by a newly developed aerosolization technique (2). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m3

, 5 h/day for 

4 days was compared with pharyngeal aspiration of varying doses (5–20 microg 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.

Increased accumulation of neutrophils and decreased fibrosis in the lung of NADPH 

oxidase-deficient C57BL/6 mice exposed to carbon nanotubes. Shvedova AA, Kisin 

ER, Murray AR, Kommineni C, Castranova V, Fadeel B, Kagan VE. Toxicol Appl 

Pharmacol. 2008; 231(2):235–40.

Abstract: Single-walled carbon nanotubes (SWCNT) have been introduced into a 

large number of new technologies and consumer products. The combination of their 

exceptional features with very broad applications raised concerns regarding their 

potential health effects. The prime target for SWCNT toxicity is believed to be the 

lung where exposure may occur through inhalation, particularly in occupational settings. Our previous work has demonstrated that SWCNT cause robust inflammatory 

responses in rodents with very early termination of the acute phase and rapid onset 

of chronic fibrosis. Timely elimination of polymorphonuclear neutrophils (PMNs) 

through apoptosis and their subsequent clearance by macrophages is a necessary stage 

in the resolution of pulmonary inflammation whereby NADPH oxidase contributes 

to control of apoptotic cell death and clearance of PMNs. Thus, we hypothesized 

that NADPH oxidase may be an important regulator of the transition from the acute 

inflammation to the chronic fibrotic stage in response to SWCNT. To experimentally 

address the hypothesis, we employed NADPH oxidase-deficient mice which lack the 

gp91(phox) subunit of the enzymatic complex. We found that NADPH oxidase null 

mice responded to SWCNT exposure with a marked accumulation of PMNs and elevated levels of apoptotic cells in the lungs, production of pro-inflammatory cytokines, 
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APPENDIX C | NIOSH Extramural Research

decreased production of the anti-inflammatory and pro-fibrotic cytokine, TGF-beta, 

and significantly lower levels of collagen deposition, as compared to C57BL/6 control 

mice. These results demonstrate a role for NADPH oxidase-derived reactive oxygen 

species in determining course of pulmonary response to SWCNT.

Sequential exposure to carbon nanotubes and bacteria enhances pulmonary inflammation and infectivity. 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. Am J Respir Cell Mol Biol. 2008; 38(5):579–90.

Abstract: Carbon nanotubes (CNT), with their applications in industry and medicine, 

may lead to new risks to human health. CNT induce a robust pulmonary inflammation and oxidative stress in rodents. Realistic exposures to CNT may occur in conjunction with other pathogenic impacts (microbial infections) and trigger enhanced 

responses. We evaluated interactions between pharyngeal aspiration of single-walled 

CNT (SWCNT) and bacterial pulmonary infection of C57BL/6 mice with Listeria 

monocytogenes (LM). Mice were given SWCNT (0, 10, and 40 mug/mouse) and 3 

days later were exposed to LM (103

 bacteria/mouse). 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-exposed mice measured 3 to 7 days after microbial infection versus 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 naïve alveolar macrophages with SWCNT in vitro also resulted in decreased nitric oxide generation and 

suppressed phagocytizing activity toward 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, bronchoalveolar lavage neutrophils, alveolar macrophages, and lymphocytes, as well as lactate 

dehydrogenase level, were increased compared with 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.

The hierarchy of structural transitions induced in cytochrome c by anionic phospholipids determines its peroxidase activation and selective peroxidation during apoptosis in cells. Kapralov AA, Kurnikov IV, Vlasova II, Belikova NA, Tyurin VA, Basova 

LV, Zhao Q, Tyurina YY, Jiang J, Bayir H, Vladimirov YA, Kagan VE. Biochemistry. 

2007;46(49):14232–44.

Abstract: Activation of peroxidase catalytic function of cytochrome c (cyt c) by anionic lipids is associated with destabilization of its tertiary structure. We studied effects of 

several anionic phospholipids on the protein structure by monitoring (1) Trp59 fluorescence, (2) Fe-S(Met80) absorbance at 695 nm, and (3) EPR of heme nitrosylation. 

Peroxidase activity was probed using several substrates and protein- derived radicals. 

Peroxidase activation of cyt c did not require complete protein unfolding or breakage 
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APPENDIX C | NIOSH Extramural Research

of the Fe-S(Met80) bond. The activation energy of cyt c peroxidase changed in parallel 

with stability energies of structural regions of the protein probed spectroscopically. 

Cardiolipin (CL) and phosphatidic acid (PA) were most effective in inducing cyt c 

peroxidase activity. Phosphatidylserine (PS) and phosphatidylinositol bisphosphate 

(PIP2) displayed a significant but much weaker capacity to destabilize the protein and 

induce peroxidase activity. Phosphatidylinositol trisphosphate (PIP3) appeared to be a 

stronger inducer of cyt c structural changes than PIP2, indicating a role for the negatively charged extra phosphate group. Comparison of cyt c-deficient HeLa cells and 

mouse embryonic cells with those expressing a full complement of cyt c demonstrated 

the involvement of cyt c peroxidase activity in selective catalysis of peroxidation of 

CL, PS, and PI, which corresponded to the potency of these lipids in inducing cyt c’s 

structural destabilization.

Single-walled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast V79 

cells. Kisin ER, Murray AR, Keane MJ, Shi XC, Schwegler-Berry D, Gorelik O, Arepalli S, Castranova V, Wallace WE, Kagan VE, Shvedova AA. J Toxicol Environ Health 

A. 2007;70(24):2071–9.

Abstract: With the development of nanotechnology, there is a tremendous growth 

of the application of nanomaterials, which increases the risk of human exposure 

to these nanomaterials through inhalation, ingestion, and dermal penetration. 

Among different types of nanoparticles, single-walled carbon nanotubes (SWCNT) 

with extremely small size (1 nm in diameter) exhibit extraordinary properties and 

offer possibilities to create materials with astounding features. Since the release of 

nanoparticles in an enclosed environment is of great concern, a study of possible 

genotoxic effects is important. Our previous data showed that pharyngeal aspiration of SWCNT elicited pulmonary effects in C57BL/6 mice that was promoted by 

a robust, acute inflammatory reaction with early onset resulting in progressive interstitial fibrogenic response and the formation of granulomas. In the present study, 

the genotoxic potential of SWCNT was evaluated in vitro. The genotoxic effects of 

nanoparticles were examined using three different test systems: the comet assay 

and micronucleus (MN) test in a lung fibroblast (V79) cell line, and the Salmonella 

gene mutation assay in strains YG1024/YG1029. Cytotoxicity tests showed loss of 

viability in a concentration- and time-dependent manner after exposure of cells to 

SWCNT. Results from the comet assay demonstrated the induction of DNA damage 

after only 3 h of incubation with 96 microg/cm2

 of SWCNT. The MN test indicated 

some but not significant micronucleus induction by SWCNT in the V79 cell line at 

the highest concentrations tested. With two different strains of Salmonella typhimurium, no mutations were found following SWCNT exposure.

Sequential Exposure to Carbon Nanotubes and Bacteria Enhances Pulmonary Inflammation and Infectivity. Am J Respir Cell Mol Biol. 2007 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.
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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 single walled CNT (SWCNT) and bacterial pulmonary infection of C57BL/6 mice with Listeria monocytogenes (LM). Mice were given SWCNT (0, 10 and 40 microg/mouse) and 3 days later 

exposed to LM (103

 bacteria/mouse). 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.

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, 2007 Shvedova AA, Kisin ER, Murray AR, Gorelik O, 

Arepalli S, Castranova V, Young SH, Gao F, Tyurina YY, Oury TD, Kagan VE.

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 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 to 

aspired SWCNTs. The vitamin E-deficient diet caused a 90-fold depletion of alphatocopherol 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 as compared to 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 pro-inflammatory cytokines, TNFalpha and IL-6) and enhanced profibrotic responses (elevation of TGF-beta and collagen deposition). Exposure to SWCNTs markedly shifted the ratio of cleaved to fulllength extracellular superoxide dismutase (EC-SOD). Given that pulmonary levels of 

vitamin E can be manipulated through diet, its effects on SWCNT-induced inflammation may be of practical importance in optimizing protective strategies.
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Nitrosative stress inhibits the aminophospholipid translocase resulting in phosphatidylserine externalization and macrophage engulfment: implications for the resolution 

of inflammation. Tyurina YY, Basova LV, Konduru NV, Tyurin VA, Potapovich AI, Cai 

P, Bayir H, Stoyanovsky D, Pitt BR, Shvedova AA, Fadeel B, Kagan VE. J Biol Chem. 

2007; 282(11):8498–509.

Abstract: Macrophage recognition of apoptotic cells depends on externalization of 

phosphatidylserine (PS), which is normally maintained within the cytosolic leaflet of 

the plasma membrane by aminophospholipid translocase (APLT). APLT is sensitive 

to redox modifications of its -SH groups. Because activated macrophages produce 

reactive oxygen and nitrogen species, we hypothesized that macrophages can directly 

participate in apoptotic cell clearance by S-nitrosylation/oxidation and inhibition of 

APLT causing PS externalization. Here we report that exposure of target HL-60 cells 

to nitrosative stress inhibited APLT, induced PS externalization, and enhanced recognition and elimination of “nitrosatively” modified cells by RAW 264.7 macrophages. 

Using S-nitroso-L-cysteine-ethyl ester (SNCEE) and S-nitrosoglutathione (GSNO) 

that cause intracellular and extracellular trans-nitrosylation of proteins, respectively, 

we found that SNCEE (but not GSNO) caused significant S-nitrosylation/oxidation 

of thiols in HL-60 cells. SNCEE also strongly inhibited APLT, activated scramblase, 

and caused PS externalization. However, SNCEE did not induce caspase activation or 

nuclear condensation/fragmentation suggesting that PS externalization was dissociated from the common apoptotic pathway. Dithiothreitol reversed SNCEE-induced 

S-nitrosylation, APLT inhibition, and PS externalization. SNCEE but not GSNO 

stimulated phagocytosis of HL-60 cells. Moreover, phagocytosis of target cells by 

lipopolysaccharide-stimulated macrophages was significantly suppressed by an NO. 

scavenger, DAF-2. Thus, macrophage-induced nitrosylation/oxidation plays an important role in cell clearance, and hence in the resolution of inflammation.

Interactions of cardiolipin and lyso-cardiolipins with cytochrome c and tBid: conflict 

or assistance in apoptosis. Tyurin VA, Tyurina YY, Osipov AN, Belikova NA, Basova 

LV, Kapralov AA, Bayir H, Kagan VE. Cell Death Differ. 2007;14(4):872–5. 

Abstract: This is a brief communication explaining essential roles that two mityochondrial phospholipids—cardiolipin and lyso-cardilipin—play in the execution of apoptotic program. 

Cardiolipin switch in mitochondria: shutting off the reduction of cytochrome c and 

turning on the peroxidase activity. Basova LV, Kurnikov IV, Wang L, Ritov VB, Belikova NA, Vlasova II, Pacheco AA, Winnica DE, Peterson J, Bayir H, Waldeck DH, 

Kagan VE. Biochemistry. 2007; 46(11):3423–34.

Abstract: Upon interaction with anionic phospholipids, particularly mitochondriaspecific cardiolipin (CL), cytochrome c (cyt c) loses its tertiary structure and its 

peroxidase activity dramatically increases. CL-induced peroxidase activity of cyt 

c has been found to be important for selective CL oxidation in cells undergoing 

programmed death. During apoptosis, the peroxidase activity and the fraction of 
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CL-bound cyt c markedly increase, suggesting that CL may act as a switch to regulate 

cyt c’s mitochondrial functions. Using cyclic voltammetry and equilibrium redox 

titrations, we show that the redox potential of cyt c shifts negatively by 350–400 mV 

upon binding to CL-containing membranes. Consequently, functions of cyt c as an 

electron transporter and cyt c reduction by Complex III are strongly inhibited. Further, CL/cyt c complexes are not effective in scavenging superoxide anions and are not 

effectively reduced by ascorbate. Thus, both redox properties and functions of cyt c 

change upon interaction with CL in the mitochondrial membrane, diminishing cyt c’s 

electron donor/acceptor role and stimulating its peroxidase activity.

Peroxidase activity and structural transitions of cytochrome c bound to cardiolipincontaining membranes. Belikova NA, Vladimirov YA, Osipov AN, Kapralov AA, 

Tyurin VA, Potapovich MV, Basova LV, Peterson J, Kurnikov IV, Kagan VE. Biochemistry. 2006; 45(15):4998–5009.

Abstract: During apoptosis, cytochrome c (cyt c) is released from intermembrane 

space of mitochondria into the cytosol where it triggers the caspase-dependent machinery. We discovered that cyt c plays another critical role in early apoptosis as a cardiolipin (CL)-specific oxygenase to produce CL hydroperoxides required for release 

of pro-apoptotic factors [Kagan, V. E., et al. (2005) Nat. Chem. Biol. 1, 223–232]. We 

quantitatively characterized the activation of peroxidase activity of cyt c by CL and 

hydrogen peroxide. At low ionic strength and high CL/cyt c ratios, peroxidase activity of the CL/cyt c complex was increased >50 times. This catalytic activity correlated 

with partial unfolding of cyt c monitored by Trp(59) fluorescence and absorbance at 

695 nm (Fe-S(Met(80)) band). The peroxidase activity increase preceded the loss of 

protein tertiary structure. Monounsaturated tetraoleoyl-CL (TOCL) induced peroxidase activity and unfolding of cyt c more effectively than saturated tetramyristoylCL (TMCL). TOCL/cyt c complex was found more resistant to dissociation by high 

salt concentration. These findings suggest that electrostatic CL/cyt c interactions are 

central to the initiation of the peroxidase activity, while hydrophobic interactions are 

involved when cyt c’s tertiary structure is lost. In the presence of CL, cyt c peroxidase 

activity is activated at lower H2O2 concentrations than for isolated cyt c molecules. 

This suggests that redistribution of CL in the mitochondrial membranes combined 

with increased production of H2O2 can switch on the peroxidase activity of cyt c and 

CL oxidation in mitochondria-a required step in execution of apoptosis.

Apoptotic interactions of cytochrome c: redox flirting with anionic phospholipids within and outside of mitochondria. Bayir H, Fadeel B, Palladino MJ, Witasp 

E, Kurnikov IV, Tyurina YY, Tyurin VA, Amoscato AA, Jiang J, Kochanek PM, 

DeKosky ST, Greenberger JS, Shvedova AA, Kagan VE. Biochim Biophys Acta. 2006 

May-Jun;1757(5–6):648–59.

Abstract: Since the (re)discovery of cytochrome c (cyt c) in the early 1920s and subsequent detailed characterization of its structure and function in mitochondrial electron 

transport, it took over 70 years to realize that cyt c plays a different, not less universal 

role in programmed cell death, apoptosis, by interacting with several proteins and 
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forming apoptosomes. Recently, two additional essential functions of cyt c in apoptosis have been discovered that are carried out via its interactions with anionic phospholipids: a mitochondria specific phospholipid, cardiolipin (CL), and plasma membrane 

phosphatidylserine (PS). Execution of apoptotic program in cells is accompanied by 

substantial and early mitochondrial production of reactive oxygen species (ROS). 

Because antioxidant enhancements protect cells against apoptosis, ROS production 

was viewed not as a meaningless side effect of mitochondrial disintegration but rather 

playing some-as yet unidentified-role in apoptosis. This conundrum has been resolved 

by establishing that mitochondria contain a pool of cyt c, which interacts with CL and 

acts as a CL oxygenase. The oxygenase is activated during apoptosis, utilizes generated 

ROS and causes selective oxidation of CL. The oxidized CL is required for the release 

of pro-apoptotic factors from mitochondria into the cytosol. This redox mechanism 

of cyt c is realized earlier than its other well-recognized functions in the formation 

of apoptosomes and caspase activation. In the cytosol, released cyt c interacts with 

another anionic phospholipid, PS, and catalyzes its oxidation in a similar oxygenase 

reaction. Peroxidized PS facilitates its externalization essential for the recognition and 

clearance of apoptotic cells by macrophages. Redox catalysis of plasma membrane 

PS oxidation constitutes an important redox-dependent function of cyt c in apoptosis and phagocytosis. Thus, cyt c acts as an anionic phospholipid specific oxygenase 

activated and required for the execution of essential stages of apoptosis. This review 

is focused on newly discovered redox mechanisms of complexes of cyt c with anionic 

phospholipids and their role in apoptotic pathways in health and disease.

Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. Kagan VE, Tyurina YY, Tyurin VA, Konduru NV, Potapovich AI, 

Osipov AN, Kisin ER, Schwegler-Berry D, Mercer R, Castranova V, Shvedova AA. 

Toxicol Lett. 2006; 165(1):88–100.

Abstract: Single-walled carbon nanotubes (SWCNT), nano-cylinders with an 

extremely small diameter (1–2 nm) and high aspect ratio, have unique physicochemical, electronic and mechanical properties and may exhibit unusual interactions 

with cells and tissues, thus necessitating studies of their toxicity and health effects. 

Manufactured SWCNT usually contain significant amounts of iron that may act as a 

catalyst of oxidative stress. Because macrophages are the primary responders to different particles that initiate and propagate inflammatory reactions and oxidative stress, 

we utilized two types of SWCNT: (1) iron-rich (non-purified) SWCNT (26 wt.% 

of iron) and (2) iron-stripped (purified) SWCNT (0.23 wt.% of iron) to study their 

interactions with RAW 264.7 macrophages. Ultrasonication resulted in predominantly 

well-dispersed and separated SWCNT strands as evidenced by scanning electron 

microscopy. Neither purified nor non-purified SWCNT were able to generate intracellular production of superoxide radicals or nitric oxide in RAW 264.7 macrophages as 

documented by flow-cytometry and fluorescence microscopy. SWCNT with different 

iron content displayed different redox activity in a cell-free model system as revealed 

by EPR-detectable formation of ascorbate radicals resulting from ascorbate oxidation. In the presence of zymosan-stimulated RAW 264.7 macrophages, non-purified 

iron-rich SWCNT were more effective in generating hydroxyl radicals (documented 
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by EPR spin-trapping with 5,5-dimethyl-1-pyrroline-N-oxide, DMPO) than purified SWCNT. Similarly, EPR spin-trapping experiments in the presence of zymosanstimulated RAW 264.7 macrophages showed that non-purified SWCNT more effectively converted superoxide radicals generated by xanthine oxidase/xanthine into 

hydroxyl radicals as compared to purified SWCNT. Iron-rich SWCNT caused significant loss of intracellular low molecular weight thiols (GSH) and accumulation of lipid 

hydroperoxides in both zymosan-and PMA-stimulated RAW 264.7 macrophages. 

Catalase was able to partially protect macrophages against SWCNT induced elevation 

of biomarkers of oxidative stress (enhancement of lipid peroxidation and GSH depletion). Thus, the presence of iron in SWCNT may be important in determining redoxdependent responses of macrophages.

Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon 

nanotubes in mice. Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini 

J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P. Am J 

Physiol Lung Cell Mol Physiol. 2005; 289(5):L698–708.

Abstract: Single-walled carbon nanotubes (SWCNT) are new materials of emerging 

technological importance. As SWCNT are introduced into the life cycle of commercial products, their effects on human health and environment should be addressed. 

We demonstrated that pharyngeal aspiration of SWCNT elicited unusual pulmonary 

effects in C57BL/6 mice that combined a robust but acute inflammation with early 

onset yet progressive fibrosis and granulomas. A dose-dependent increase in the 

protein, LDH, and gamma-glutamyl transferase activities in bronchoalveolar lavage 

were found along with accumulation of 4-hydroxynonenal (oxidative biomarker) and 

depletion of glutathione in lungs. An early neutrophils accumulation (day 1), followed 

by lymphocyte (day 3) and macrophage (day 7) influx, was accompanied by early elevation of proinflammatory cytokines (TNF-alpha, IL-1beta; day 1) followed by fibrogenic transforming growth factor (TGF)-beta1 (peaked on day 7). A rapid progressive 

fibrosis found in mice exhibited two distinct morphologies: 1) SWCNT-induced granulomas mainly associated with hypertrophied epithelial cells surrounding SWCNT 

aggregates and 2) diffuse interstitial fibrosis and alveolar wall thickening likely associated with dispersed SWCNT. In vitro exposure of murine RAW 264.7 macrophages 

to SWCNT triggered TGF-beta1 production similarly to zymosan but generated less 

TNF-alpha and IL-1beta. SWCNT did not cause superoxide or NO.production, active 

SWCNT engulfment, or apoptosis in RAW 264.7 macrophages. Functional respiratory 

deficiencies and decreased bacterial clearance (Listeria monocytogenes) were found in 

mice treated with SWCNT. Equal doses of ultrafine carbon black particles or fine crystalline silica (SiO2) did not induce granulomas or alveolar wall thickening and caused 

a significantly weaker pulmonary inflammation and damage.

Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Kagan VE, Tyurin VA, Jiang J, Tyurina YY, Ritov VB, Amoscato AA, Osipov AN, 

Belikova NA, Kapralov AA, Kini V, Vlasova II, Zhao Q, Zou M, Di P, Svistunenko DA, 

Kurnikov IV, Borisenko GG. Nat Chem Biol. 2005;1(4):223–32.
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Abstract: Programmed death (apoptosis) is turned on in damaged or unwanted cells 

to secure their clean and safe self-elimination. The initial apoptotic events are coordinated in mitochondria, whereby several proapoptotic factors, including cytochrome c, 

are released into the cytosol to trigger caspase cascades. The release mechanisms include interactions of B-cell/lymphoma 2 family proteins with a mitochondria- specific 

phospholipid, cardiolipin, to cause permeabilization of the outer mitochondrial 

membrane. Using oxidative lipidomics, we showed that cardiolipin is the only phospholipid in mitochondria that undergoes early oxidation during apoptosis. The oxidation is catalyzed by a cardiolipin-specific peroxidase activity of cardiolipin-bound 

cytochrome c. In a previously undescribed step in apoptosis, we showed that oxidized 

cardiolipin is required for the release of proapoptotic factors. These results provide 

insight into the role of reactive oxygen species in triggering the cell-death pathway 

and describe an early role for cytochrome c before caspase activation.

Nanomedicine and nanotoxicology: two sides of the same coin. Kagan VE, Bayir H, 

Shvedova AA. Nanomedicine. 2005;1(4):313–6. 

Abstract: Current advances in nanotechnology have led to the development of the 

new field of nanomedicine, which includes many applications of nanomaterials and 

nanodevices for diagnostic and therapeutic purposes. The same unique physical and 

chemical properties that make nanomaterials so attractive may be associated with 

their potentially calamitous effects on cells and tissues. Our recent study demonstrated that aspiration of single-walled carbon nanotubes elicited an unusual inflammatory 

response in the lungs of exposed mice with a very early switch from the acute inflammatory phase to fibrogenic events resulting in pulmonary deposition of collagen and 

elastin. This was accompanied by a characteristic change in the production and release 

of proinflammatory to anti-inflammatory profibrogenic cytokines, decline in pulmonary function, and enhanced susceptibility to infection. Chemically unmodified 

(nonfunctionalized) carbon nanotubes are not effectively recognized by macrophages. 

Functionalization of nanotubes results in their increased recognition by macrophages 

and is thus used for the delivery of nanoparticles to macrophages and other immune cells to improve the quality of diagnostic and imaging techniques as well as for 

enhancement of the therapeutic effectiveness of drugs. These observations on differences in recognition of nanoparticles by macrophages have important implications in 

the relationship between the potentially toxic health effects of nanomaterials and their 

applications in the field of nanomedicine.

O’SHAUGHNESSY 8806 (R01) Assessment Methods for Nanoparticles in 

the Workplace

Final Report Abstract:

The aims of this research were to: Identify and evaluate methods to measure airborne 

nanoparticle concentrations; characterize nanoparticles using a complementary 

suite of techniques to assess their surface and bulk physical and chemical properties; 

and determine the collection efficiency of commonly-used respirator filters when 
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challenged with nanoparticles. Aim 1 findings have led to practical proposals for the 

use of instrumentation by industrial hygienists when evaluating a workplace for the 

presence, and amount, of nanoparticle aerosols. Our laboratory findings have led to a 

method for using two hand-held instruments to reproduce the size distribution of an 

aerosol from the sub-micrometer to micrometer range in order to obtain an understanding of the nanoparticle count and distribution. This is significant because the 

only alternative methods require very expensive, bench-top instruments. Our field 

component of Aim I led to the development of a method which utilizes the same two 

hand-held instruments, in conjunction with transmission electron microscopy, to 

also physically and chemically characterize the nanoparticles counter; therefore, their 

potential source can be identified. Aim 2 findings centered on the best of use of sophisticated analytical instruments to best determine the nature of a nanopowder from 

a bulk sample. A suite of surface and bulk powder analytical techniques was found to 

provide the most information including. The findings obtained from these analyses 

allowed us to distinguish specific characteristics of the nanopowders used from the 

many possible for each powder type. This result was especially apparent when analyzing carbon nanotubes which can have a wide variety, and concentration, of contaminant compounds that can potentially change its physical properties and toxicological 

effects. Work associated with Aim 3 involved testing two respirator filter types, and 

N95 and P100, when challenged with a variety of nanoparticle types. In general, the 

filters performed within their expected efficiency requirements except when challenged with carbon nanotubes.

The principle aspect of our research that can be translated into practice is the development and assessment of a nanoparticle exposure methodology that can be employed 

by industrial hygienists in the field. This method utilizes field-capable instruments 

to both enumerate nanoparticles and characterize their morphology and elemental 

composition. Given that the instruments associated with this method are currently 

available, the method can be presently utilized by industrial hygienists. The relevance 

of this work is related to the current need for a method to assess workplaces for 

nanoparticle exposures. The field of nanotechnology, and the related development of 

nanopowders in particular, has advanced more rapidly than the steps needed to offer 

guidance to these industries in terms of both threshold limit values (TLVs) and proper 

assessment methods. Both the TLVs and related assessment methods for most occupational dust types are based on a mass measurement. These are clearly inadequate 

when dealing with particles in the submicrometer range, which necessarily constitute 

a very low percentage of the total mass of an aerosol (given a wide distribution) or 

are undetectable on a mass-basis (given a narrow distribution). The results from this 

study will aid in the important work needed to develop both TLVs and associated 

sampling methods for nanoparticle exposures.

Recent Publications

O’Shaughnessy PT. (2008) Occupational Health Hazards of Nanoparticles. In: Nanoscience and Nanotechnology: Environmental and Health Impacts. VH Grassian Ed. 

New York: John Wiley & Sons. 
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Pettibone J, Elzey S, Grassian VH. (2008) An integrated Approach Toward Understanding the Environmental Fate, Transport, Toxicity and Health Hazards of Nanomaterials. In: Nanoscience and Nanotechnology: Environmental and Health Impacts. VH 

Grassian Ed. New York: John Wiley & Sons. 

Peters, Thomas M., Elzey, Sherrie, Johnson, Ronald, Park, Heaweon, Grassian, Vicki 

H, Maher, Tabitha and O’Shaughnessy, Patrick (2009). Airborne Monitoring to Distinguish Engineered Nanomaterials from Incidental Particles for Environmental Health 

and Safety. Journal of Occupational and Environmental Hygiene, 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 200nm. 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 (<300nm), 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 airborne nanoparticles in this facility are dominated by “incidental” sources (e.g., welding or grinding), and that 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.

XIONG 8807 (R01) 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 
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air. This method will be capable of 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 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 utilize 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 potential 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.

THOMPSON 8739 (R43) Antistatic Paint with Silent Discharge

For the variety of organizations that process, store, and handle flammable materials, static electricity can present a serious danger. This is demonstrated when a static 

discharge releases more energy than the minimum ignition energy of the flammable 

material in the presence of the right oxidation source (i.e., air). This leads to ignition 

of the material and under the right pressure constraints can lead to a violent explosion. Statistics from the National Fire Prevention Association show that, on average, 

static electricity is implicated in 280 structure fires reported to US fire departments 

annually.’ These organizations can include fuel refineries, service stations, and coal 

mining operations that handle volatile chemicals. In addition, facilities that generate 

fine particulates whose increased surface area enhances their flammability such as 

grain elevators, mining operations, food processing, or sawmills are also in peril from 

static discharge. Aside from the millions of dollars in lost property, ESD-initiated fires 

and explosions have been implicated in numerous injuries and fatalities.

Proposed is the development of paint that relies on an alternative grounding mechanism. Nano-sized “emitter” particles will be added to the paint that will expose nanosized ridges and tips. Because charge is proportional to area, in the nano-region around 

the particle tips, there will be a tremendous buildup of charge leading to nano-voltages 

that are well above the breakdown voltage of air. Consequently, the charge would leak off 

in corona discharges until safe voltage is reached. Because the points where these events 

take place is so small, the regional voltage and charge density will stay at “safe” levels.

DEININGER 8939 (R43) New Nanostructured Sensor Arrays for Hydride Detection

DESCRIPTION (provided by applicant): Development of improved detectors for the 

detection of hydrides (including arsine, phosphine and diborane) will provide an 
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APPENDIX C | NIOSH Extramural Research

increase in the protection of worker health and safety. This Phase II proposal aims to 

develop and demonstrate a prototype gas detection system capable of affordably and 

reliably detecting toxic gases at low ppb levels. Drawing upon advances in nanotechnology, micromachining and materials chemistry, the Phase I proposal demonstrated 

the feasibility of creating electronic sensors that are substantially better than current 

state of the art for hydrides detection. These improved sensors will be the basis for 

improved personal and permanent monitors for increased protection of workers in 

the semiconductor industry and other applications. Furthermore, the development of 

these highly innovative, sensitive and selective sensors will lay the groundwork for the 

development of additional sensors for detecting a wide range of chemical hazards that 

exist in the workplace today. Public Health Relevance: Hydrides are dangerous gases 

that are widely used in the semiconductor and other industries. The proposed project 

will develop advanced sensors that can be used in personal protective devices to warn 

users about the presence of these highly toxic gases.

Synkera’s Hydride Microsensor

DUTTA 9141 (R01) 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 as compared to 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 is dependent on their surface reactivity. The basis of these 

hypotheses is that nanoparticles contain significantly higher number 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, 
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APPENDIX C | NIOSH Extramural Research

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, 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.

TIMCHALK 8173(R01) Non-Invasive Biomonitoring of Pesticides

This research project will establish a non-invasive biomonitoring capability to evaluate 

exposure to organophosphorus (OP) insecticides utilizing a sensitive, non-invasive, 

micro-analytical instrument for realtime analysis of biomarkers of exposure and 

response in saliva. This project will create a miniaturized nanobioelectronic biosensor 

that is highly selective and sensitive for the target analyte(s). In addition, a physiologically based pharmacokinetic and pharmacodynamic model (PBPK/PD) for the OP 

insecticide chlorpyrifos will be modified to incorporate a salivary gland compartment 

that will be used to quantitatively predict blood chlorpyrifos concentration and saliva 

cholinesterase (ChE) inhibition to estimate exposure based on a saliva specimen. The 

utilization of saliva for biomonitoring, coupled to real-time monitoring and modeling 

is a novel approach with broad application for evaluating occupational exposures to 

insecticides. An OP sensor will be developed based on a new biosensing principle of 

antigen-induced formation of nanoparticle-immuno complex nanostructure. A ChE 

sensor will also be developed based on the electrodetection of the ChE hydrolyzed 

reaction products choline and hydrogen peroxide. Subsequently, the sensors will be 

transformed to a “lab-on-a-chip”, and the biochip performance will be characterized, 

optimized and validated. To validate this approach the pharmacokinetics of chlorpyrifos excretion and ChE inhibition in saliva under various physiological conditions 

and dose levels will be assessed to ensure that these endpoints are accurate predictors 

of internal dose. The development of a real-time saliva analysis coupled to a predictive 

pharmacokinetic model represents a significant advancement over current biomonitoring strategies. Once this model system has been adequately validated it can readily 

be employed to assess worker exposure to insecticides under a wide range of occupational situations.

Executive Highlight

In articulating a vision for Toxicity Testing in the 21st Century, the National Research 

Council (NRC) noted that exposure science will play a critical role in a new risk-based 
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APPENDIX C | NIOSH Extramural Research

framework. In this context, biomonitoring is a key component that quantitatively 

associates an internal dose with a measurable effect. It has also been suggested that 

epidemiology studies which accurately assess chemical exposures along with biological effects will have the most meaningful interpretation and thus maximal impact. 

However, a major impediment in conducting quantitative biomonitoring within 

epidemiology studies is the lack of rapid, field deployable, quantitative technologies that measure chemical exposure/response biomarkers using minimally invasive 

biological fluids (i.e. saliva). Due to the complex nature of environmental exposures 

and biological systems, measurement of a single biomarker may not provide adequate 

quantitative assessment of exposure. Hence, this project has undertaken development, 

validation, and refinement of novel sensor platforms capable of quantifying multiple 

biomarkers associated with pesticide exposures (dose), utilizing saliva as a readily obtainable biological fluid. In addition, pharmacokinetic evaluations have been 

exploited to facilitate quantifying dosimetry. Our ongoing research has focused on the 

development of a number of organophosphorus specific pesticide sensor platforms. 

These include a quantum dot-based immunochromatographic fluorescent biosensor 

for quantifying the chlorpyrifos metabolite trichloropyridinol (TCPy), and a carbon 

nanotube-enhanced flow-injection amperometric detection system for quantifying 

cholinesterase activity. This technology innovation makes the proposed multiplex sensor strategy substantially more compelling for use in detecting anticipated low level 

biomarker concentrations. A key focus of the current project has been to develop and 

validate the sensors in experimental animal (in vitro & in vivo) and human (in vitro) 

systems. This novel platform will enable a more accurate prediction of exposures and 

once validated, can readily be employed to assess dosimetry to pesticides in support of 

biomonitoring and epidemiology studies.

Peer-reviewed publications (credited to this project).

1. Timchalk, C., Campbell, J. A., Liu, G., Lin, Y. and Kousba, A. A. (2007). Development of a non-invasive biomonitoring approach to determine exposure 

to the organophophorus insecticide chlorpyrifos in saliva of rats. Toxicol. 

Appl. Pharmacol., 219: 217–225, PMID: 17118418.

2. Timchalk, C., Busby, A., Campbell, J. A., Needham, L. L., and Barr, D. B. 

(2007). Comparative pharmacokinetics of the organophsophorus insecticide 

chlorpyrifos and its major metabolites diethylphospate, diethylthiophospate 

and 3,5,6-trichloro-2-pyridinol in the rat. Toxicol., 237: 145–157, PMID: 

17590257.

3. Timchalk, C., Kousba, A. A., and Poet, T. S. (2007). An age-dependent physiologically based pharmacokinetic/pharmacodynamic model for the organophosphosphorus insecticide chlorpyrifos in the preweanling rat. Toxicol. Sci., 

98(2): 348–365, PMID: 17504771.

4. Marty, M. S., Domoradzki, J. Y., Hansen, S. C., Timchalk, C., Bartels, M. 

J., Mattsson, J. L. (2007). The effect of route, vehicle, and divided doses on 

the pharmacokinetics of chlorpyrifos and its metabolite trichloropyridinol 
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in neonatal Sprague-Dawley rats. Toxicol. Sci., 100(2): 360–373, PMID: 

17928393.

5. Liu G, and Y Lin. (2007). Nanomaterial Labels in Electrochemical Immunosensors and Immunoassays. Talanta 74(3): 308–317.

6. Liu G, YY Lin, J Wang, H Wu, CM Wai, and Y Lin. (2007). Disposable Electrochemical Immunosensor Diagnosis Device Based on Nanoparticle Probe 

and Immunochromatographic Strip. Analytical Chemistry 79(20): 7644–7653

7. Timchalk, C. and Poet, T. S. (2008) Development of a physiologically based 

pharmacokinetic and pharmacodynamic model to determine dosimetry and 

cholinesterase inhibition for a binary mixture of chlorpyrifos and diazinon in 

the rat. NeuroTox. 29: 428–443.

8. Wang, J., Timchalk, C., and Lin, Y. (2008) Carbon nanotube-based electrochemical sensor for assay of salivary cholinesterase enzyme activity: an exposure biomarker of organophosphate pesticides and nerve agents. Environ. Sci. 

Tech. 42(7): 2688–2693.

9. Liu G, J Wang, RC Barry, CE Petersen, C Timchalk, PL Gassman, and Y Lin. 

(2008). Nanoparticle-Based Electrochemical Immunosensor for Detection of 

Phosphorylated Acetylcholinesterase Adduct: An Exposure Biomarker of Organophosphate Pesticides and Nerve Agents. Chemistry-a European Journal 

14(32): 9951–9959. 

10. Wang J, and Y Lin. (2008). Functionalized carbon nanotubes and nanofibers 

for biosensing applications. Trends in Analytical Chemistry. 27(7): 619–626. 

11. Wang H, J Wang, C Timchalk, and Y Lin. (2008). Magnetic Electrochemical 

Immunoassays with Quantum Dot Labels for Detection of Phosphorylated 

Acetylcholinesterase in Plasma. Analytical Chemistry 80(22): 8477–8484.

12. Du, D., Wang, J., Smith, J. N., Timchalk, C. and Lin, Y. (2009). Biomonitoring 

of organophosphorus pesticide inhibition by reactivation of saliva cholinesterase enzyme based on carbon nanotube-enhanced flow-injection amperometric detection. Anal. Chem. 81: 9341–9320 PMID: 19839597.

13. Smith, J. N., Campbell, J. A., Busby, A. L., Lee, S., Poet, T. S., Barr, D. B. and 

Timchalk, C. (2009). Comparative chlorpyrifos pharmacokinetics via multiple 

routes of exposure and vehicles of administration in the adult rat. Toxicol. 

261: 47–58 PMID: 19397948.

14. Lowe, E. R., Poet, T. S., Rick, D. L., Marty, M. S., Mattson, J. L., Timchalk C., 

and Bartels, M. J. (2009). The effect of lipid changes on the tissue partitioning 

of chlorpyrifos and the impact on perinatal dosimetry using a late gestational 

PBPK/PD model. Toxicol. Sci., 108(2): 258–272 PMID: 19223661. 
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15. Lee, S., Busby, A. L., Timchalk, C. and Poet, T. S. (2009). Effects of nicotine 

exposure on in vitro CYP450-mediated metabolism of chlorpyrifos in SpragueDawley male rats. J. Toxicol. Environ. Health A., 72: 74–82 PMID: 19034796.

16.Barry, R. C., Lin, Y., Wang, J., Liu, G., and Timchalk, C. (2009). Nanotechnology-based electrochemical sensors for biomonitoring chemical exposures. J. Exp. 

Sci. and Environ. Epidemiol. 19(1): 1-18 Invited Review PMID: 19018275.

17. Garabrant, D. H., Aylward, L. L., Berent, S., Chen, Q., Timchalk, C., Burns, C. 

J., Hays, S. M., and Albers, J. W. (2009). Cholinesterase inhibition in chlorpyrifos workers: characterization of biomarkers of exposure and response 

in relation to urinary TCP. J. Exp. Sci. and Environ. Epidemiol. 19: 634–642 

PMID: 18716607.

18. Lee, S., Poet, T. S., Smith, J. N., Busby-Hjerpe, A. L. and Timchalk C. (2010). 

Effects of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and 

pharmacodynamics in the rat. Chemico-Biological Interaction. 184 (3): 449-

457 PMID: 20097188. 

19. Smith, J. N., Wang, J., Lin, Y. and Timchalk, C. (2010). Pharmacokinetics of 

the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol (TCPy) in rat saliva. 

Toxicol. Sci., 113(2): 315-32 PMID: 19920072.

20. Hjerpe-Busby, A. L., Campbell, J. A., Smith, J. N., Lee, S., Poet, T. S., Barr, D. 

B. and Timchalk, C. (2010). Comparative pharmacokinetics of chlorpyrifos 

versus its major metabolites following oral administration in the rat. Toxicol. 

268 (1-2): 55-63 PMID: 19963030.

Book Chapters & Non-Peer Reviewed Presentation (credited to this project): 

1. Wang J, G Liu, and Y Lin (2007). Nanotubes, Nanowires, and Nanocantilevers in Biosensor Development. Chapter 3 In: Nanomaterials for Biosensors, Nanotechnologies for Life Sciences, vol. 8, ed. Challa S.S.R. Kumar, pp. 

56–100. Wiley-VCH, Weinheim, Germany. 

2. Poet, T. S. and Timchalk, C. (2008). PBPK/PD model simulations of the effects of changes in enzyme levels on plasma esterase inhibition and urinary 

TCPy elimination following chlorpyrifos exposure. Public Comments (EPAHQ-OPP-2008-0274-0002.1), EPA, FIFRA Science Advisory Panel.

3. Lin, Y., Wang, J, and Timchalk C. (2009). Portable Analytical Systems for 

On-Site Diagnosis of Exposure to Pesticides and Nerve Agents. In: Nanoscience and Nanotechnology for Chemical and Biological Defense, Invited Book 

Chapter ACS Symposium Series. 

4. Timchalk, C. (2010) Organophosphorus insecticide pharmacokinetics, Chapter 66 In: Hayes’ Handbook of Pesticide Toxicology, Third Edition, (Ed. R. 

Krieger), Academic Press, San Diego, CA.
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5. Timchalk, C. (2010). Biomonitoring of pesticides: pharmacokinetics of 

organophosphorus and carbamate insecticides. In: Anticholinesterase pesticides: metabolism, neurotoxicity and epidemiology. (eds. T. Satoh and R. C. 

Gupta), John Wiley (In Press).

6. Timchalk, C., Hinderliter P. M. and Poet, T. S. (2010). Cholinesterase Inhibition. In: Quantitative Modeling in Toxicology. (Eds. M. Andersen and K. 

Krishnan). John Wiley, West Sussex, UK., pp. 137–165.

Presentations (credited to this project):

1. Timchalk, C., Kousba, A, Busby, A. and Poet, T. (2007). Development of 

physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) 

models to determine dosimetry and cholinesterase inhibition following exposure to binary mixtures of organophosphorus insecticides. (Invited Symposium), ToxSci (Toxicologist), 96(1): 1324.

2. Liu, G., Lin, Y., Campbell, J. A and Timchalk, C. (2007). Development of a 

magnetic immunosensor to biomonitor for the chlorpyrifos metabolite trichloropyridinol. Tox Sci (Toxicologist), 96(1): 414.

3. Lin, Y., Liu, G., Wang, J., Timchalk, C., Gassman, P. L., Barry, R. C., Busby, A. 

L. and Wang, H. (2008). Nanoparticle-based electrochemical immunosensor 

for detection of phosphorylated acetylcholinesterase adduct: an exposure biomarker of organophosphate pesticides and nerve agents. SOT Annual Meeting, March 16–20th, Seattle WA.

4. Liu, G., Riechers, S. L., Timchalk, C., and Lin, Y. (2008). Quantum-dots-based 

electrochemical immunoassay for the chlorpyrifos and trichlopyr metabolite 

trichloropyridinol. SOT Annual Meeting, March 16–20th, Seattle WA.

5. Timchalk, C., Busby, A. L., and Poet, T. S. (2008). PBPK modeling of the 

major chlorpyrifos metabolite trichloropyridinol: a potential biomonitoring 

strategy. SOT Annual Meeting, March 16–20th, Seattle WA.

6. Wang, L., Liu, G., Timchalk, C., and Lin, Y. (2008). Carbon nanotube-based 

electrochemical sensor for cholinesterase enzyme activity: an organophosphorus insecticide and nerve agent exposure monitor. SOT Annual Meeting, 

March 16–20th, Seattle WA.

7. Wang. J., Lin, Y., Campbell, J. A., and Timchalk, C. Nanoparticle label-based 

immunosensor for biomonitoring of trichlorpyridinol. 47th Annual Meeting 

of SOT, Seattle, WA. March 17–19, 2008.

8. Lin, Y., Wang, J., Liu, G. D., Timchalk, C., Nanoparticle-based electrochemcial 

immunosensor for detection of phosphorylated acetylcholinesterase adduct: 

an exposure biomarker of organophosphate pesticides and nerve agents. 47th 

Annual Meeting of SOT, Seattle, WA. March 17–19, 2008.
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9. Poet, T. S., Campbell, J. A., Busby, A. L. and Timchalk, C. (2008). PBPK/PD 

modeling of chlorpyrifos in sensitive populations: Implications for biomonitoring of exposure. NIOSH, Health and Safety in Western Agriculture Conference, Nov 11–13th, Cle Elum, WA.

10. Smith, J. N., Poet, T. S., Campbell, J. A. and Timchalk, C. (2008). Pharmacokinetics of chlorpyrifos metabolites in saliva. NIOSH,Health and Safety in 

Western Agriculture Conference, Nov 11–13th, Cle Elum, WA.

11. Timchalk, C. (2008). Nanotechnology-based electrochemical sensors for 

biomonitoring chemical exposure. CDC/NIOSH, Direct-Reading Exposure 

Assessment Methods (DREAM Workshop). Nov. 13–14th, Washington, DC. 

(Invited Speaker).

12. Fox RM, Smith JN, Busby AL, and Timchalk C. (2008). Effects of chlorpyrifos and chlorpyrifos-oxon on cholinesterase in lungs of the rat. Micro Nano 

Breakthrough Conference (Vancouver, WA, USA).

13. Smith JN, Wang J, Lin Y, Campbell JA, Timchalk C. (2008). Development of 

Non-invasive Sensors to Detect Pesticides in Saliva. Center for Disease Control/

National Institute for Occupational Safety and Health (CDC/NIOSH) National 

Occupational Research Agenda Symposium (NORA) (Denver, CO, USA).

14. Busby AL, Smith JN, Campbell JA, Timchalk C, Poet TS, Needham LL, Barr 

D. (2008). Use of C-13 Labeled Chlorpyrifos to Quantify Oral Bioavailability 

in the Rat. American Society for Mass Spectrometry Conference (ASMS) 

(Denver, CO, USA).

15. Timchalk, C., Fox, R. M., Meyer, K. M., Lee, S., Smith, J. N., Busby, A. L. and 

Poet, T. S. (2009). Metabolism and cholinesterase inhibition in lungs of rats 

following in vitro chlorpyrifos exposure. Society of Toxicology Annual Meeting, March, Baltimore MD.

16. Smith, J. N., Campbell, J. A., Busby, A. L., Poet, T. S., Barr, D. B. and Timchalk, 

C. (2009). Comparative chlorpyrifos pharmacokinetics via multiple routes of 

exposure and vehicles of administration. Society of Toxicology Annual Meeting, March, Baltimore MD.

17. Klohe, E. M., Smith, J. N., Lee, S., and Timchalk, C. (2010). Characterization 

and normalization of cholinesterase activity in rat saliva. Society of Toxicology Annual Meeting, March 7–11th, Salt Lake City, UT.

18. Timchalk, C., Campbell, J. A., Busby, A. L., Smith, J. N., Lee, S., Poet, T. S., 

and Barr, D. B. (2010). Comparative pharmacokinetics of chlorpyrifos versus 

its major metabolites following oral administration in the rat. Society of Toxicology Annual Meeting, March 7–11th, Salt Lake City, UT.
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19. Smith, J. N., Wang, J. Lin, Y., Timchalk, C. (2010). Pharmacokinetics of 

3,5,6-trichloro-2-pyridinol (TCPy), a chlorpyrifos metabolite, in rat saliva. 

Society of Toxicology Annual Meeting, March 7–11th, Salt Lake City, UT.

20.Du, D., Wang, J., Timchalk, C. and Lin, Y. (2009). Carbon nanotube-based 

electrochemical sensor for assay of saliva cholinesterase enzyme activity: an exposure biomarker of organophosphorus pesticides. American Chemical Society 

64th Northwest Regional Meeting (NORM 2009), June 30th, Tacoma, WA.

21. Zhang, U., Lin, C. T., Wang, J., Hong, W., Pinwatana, K., Tang, Z., Timchalk, 

C. and Lin, Y. (2009). Immunoassays of phosphorylated cholinesterase as biomarkers for rapid diagnosis of exposure to organophosphorus agents. American Chemical Society 64th Northwest Regional Meeting (NORM 2009), June 

30th, Tacoma, WA.

VOLCKENS 9114 (R21) A High-Flow Personal Sampler for Inhalable Aerosol

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 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. There 

are 3 specific aims for this project. First, 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. Second, to evaluate sampler performance using computational fluid dynamic modeling and to refine the prototype design based on results 

from these tests. Third, to validate the refined design through laboratory tests in a 

wind tunnel and field tests in actual occupational environments.

PETERS 9255 (K01) Personal Exposure Monitoring to Engineered Nanoparticles

Final Report Abstract:

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 
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APPENDIX C | NIOSH Extramural Research

have shown some nanoparticles to be toxic, methods to assess exposure do not exist. 

However, knowledge of personal exposure may be particularly important for such 

small particles because their concentration tends to decay rapidly with distance from a 

source. The immediate objective of this K01 Career Development Award was to allow 

Dr. Thomas Peters to make a successful transition to an independent investigator in 

the field of occupational and environmental health, with emphasis on protecting the 

health of workers from exposure to aerosols. 

In the research component of this Award, laboratory studies were conducted under 

Aim 1 to develop and evaluate methods to assess personal exposure to nanoparticles. 

We developed a method to assess rapid fluctuations in nanoparticle concentrations 

with direct-read instruments and a filter-based method to quantitatively collect 

nanoparticles for subsequent analysis by electron microscopy. Under Aim 2 field studies, we used these methods to investigate the extent to which workers are exposed to 

engineered nanoparticles in facilities that produce and handle them. We found that 

workplace exposure to engineered nanomaterials can be highly variable by worker, by 

activity and/or by area of a facility. Handling nanomaterials was found to be associated 

with particles that were respirable but not nano-sized. Further, incidental nanoparticles 

were generated by hot processes and unrelated to nanomaterial handling. Samples of 

particles collected from workplaces were analyzed by electron microscopy with energy 

dispersive X-ray detection under Aim 3. These analyses allowed us to classify particles 

within the workplace by size, composition, and morphology. These data are critical in 

evaluating hazards of working with nanomaterials and controlling sources. 

Our field measurements have shown the inherent complexity of assessing nanoparticles in the workplace. We have identified new processes required to produce and 

handle engineered nanomaterials that pose a significant challenge to environmental 

health and safety. These processes represent a small number of many that will be 

required in the burgeoning field of nanotechnology. We have shown that substantial 

exposures to nanoparticles may occur in environments where respirable mass concentrations are low. Consequently, the industrial hygiene sampling paradigm of comparing mass measurements with mass-based OELs has severe limitations when applied to 

engineered nanomaterials.

This research component was complemented by a vigorous career development plan, 

which included: (1) formal training in; (2) regular meetings with the sponsors of this 

award; (3) participation 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 has played an active and critical role in both the 

research and career development components of this K01 Award.

GRASSIAN 9448 (R01) An Integrated Approach Toward Understanding the 

Toxicity of Inhaled Nanomaterials

Manufactured nanomaterials are found in cosmetics, lotions, coatings, and used in 

environmental remediation applications. There exists a large opportunity for exposure 

through many different routes making it necessary to study the health implications 
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APPENDIX C | NIOSH Extramural Research

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 those 

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 if pulmonary clearance is impaired by inhaled nanoparticles and if 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.

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).

 ■ Pettibone JM, Adamcakova-Dodd A, Thorne PS, O’Shaughnessy PT, Weydert 

JA, Grassian VH. 2008. Inflammatory response of mice following inhalation 

exposure to iron and copper nanoparticles. Nanotoxicology (1): 1–16.

 ■ Pettibone J.B.; Elzey, S.; Grassian, V. H. “An Integrated Approach Toward 

Understanding the Environmental Fate, Transport, Toxicity and Health Hazards of Nanomaterials” a book chapter in Nanoscience and Nanotechnology: 

Environmental and Health Impacts, Ed. Vicki H. Grassian 2008, 43–68.

 ■ Elzey, S.; Larsen, R.G.; Howe, C.; Grassian, V.H. “Nanoscience and Nanotechnology: Environmental and Health Impacts” in Nanoscale Materials in Chemistry, 2nd Edition, Editors K.J. Klabunde and R. M. Richards, John Wiley and 

Sons, Hoboken, NJ 2009, 676–721.

 ■ Park, H.; Grassian, V.H. 2010. “Commercially Manufactured Engineered 

Nanomaterials for Environmental and Health Studies: Important Insights 
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Provided by Independent Characterization” Environmental Toxicology and 

Chemistry (29):715–721.

 ■ Adamcakova-Dodd, A.; Thorne, P.S.; Grassian, V.H. “In Vivo Toxicity Studies 

of Metal and Metal Oxide Nanoparticles” in Handbook of Systems Toxicology, John Wiley and Sons 2010.

 ■ Peters, T.M.; Grassian, V.H. “Engineered Nanomaterials” in Patty’s Industrial 

Hygiene, Sixth Edition, Eds. Vernon Rose and Barbara Cohrssen, John Wiley 

and Sons, 2010.

 ■ Stebounova, L. V.; Adamcakova-Dodd, A.; Kim, J.-S.; Park, H.; 

O’Shaughnessy, P. T.; Grassian, V.H.; Thorne, P.S. “Nanosilver Induces Minimal Lung Toxicity or Inflammation in a Subacute Murine Inhalation Model”, 

Particle and Fibre Toxicology 2011, 8:5.

 ■ Adamcakova-Dodd, A.; Kim, J.-S.; Stebounova, L. V.;’Shaughnessy, P. T.; 

Grassian, V.H.; Thorne, P.S. “Murine Pulmonary Responses after Sub-chronic 

Exposure to Aluminum Oxide Nanowhiskers”, Particle and Fibre Toxicology 

2012, 9:22.

 ■ Kim, J.-S.; Adamcakova-Dodd, A.; Park, H.; O’Shaughnessy, P. T.; Grassian, 

V.H.; Thorne, P.S. “Effects of Copper Nanoparticle Exposure on Host Defense in a Murine Pulmonary Infection Model”, Particle and Fibre Toxicology 2011, 8:29.

 ■ Stebounova, L. V.; Morgan, H.; Brenner, S.; Grassian, V. H.Larissa [2012] 

“Health and and Safety Implications of Exposure to Engineered Nanomaterials”, Nanomedicine and Nanobiotechnology 4(3):310–321.

VOLCKENS 9381 (R03) A Personal Sampler for Assessing Inhaled 

Nanoparticle Exposures

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 
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APPENDIX C | NIOSH Extramural Research

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

Integration of nanocrystalline metal oxide formulations with lightweight fabric layers 

has been investigated and established as a plausible approach towards the development and use of reactive liners as inserts for CPC. A series of mixed metal oxide formulations were initially developed and tested for their ability to destructively absorb 

various TICs and CWA simulants. In addition to chemical reactivity, other properties 

such as granulation size and hardness were optimized for the down selected formulation. Generally, the sorbent was embedded between layers of non woven fabric 

to produce a laminate suitable for use as reactive liners. All the test swatches were 

prepared using a bench top laminator. Issues related to laminate weight and shedding 

of granules were addressed and resolved during the first stage of fabric lamination 

experiments. Comfort and chemical destruction properties were further refined during the second stage lamination experiments. Overall, the liner was optimized for the 

following properties: moisture vapor transfer, air permeability, chemical decontamination property, and reduced weight. As attested by industry standard test methods, 

these liners performed as a Class II Protective Garment for 2-CEES, HCN, NH3, and 

DMMP. IR and GC-MS analyses of the extracted sorbent and swatch material confirmed the degradation of DMMP and 2-CEES to less toxic by-products. Longer yardage of the down selected fabric swatch was produced by a commercial entity as well as 

a bench top laminator. As a proof-of-concept, a military jacket insert liner prototype 

was sewn from the manufactured fabric liner.

DEININGER 8939-03 (R44) New Nanostructured Sensing Arrays for 

Hydride Detection 

DESCRIPTION (provided by applicant): Development of improved detectors for the 

detection of hydrides (including arsine, phosphine and diborane) will provide an 

increase in the protection of worker health and safety. This Phase II proposal aims to 

develop and demonstrate a prototype gas detection system capable of affordably and 

reliably detecting toxic gases at low ppb levels. Drawing upon advances in nanotechnology, micromachining and materials chemistry, the Phase I proposal demonstrated 

the feasibility of creating electronic sensors that are substantially better than current 

state of the art for hydrides detection. These improved sensors will be the basis for 

improved personal and permanent monitors for increased protection of workers in 

the semiconductor industry and other applications. Furthermore, the development of 

these highly innovative, sensitive and selective sensors will lay the groundwork for the 
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development of additional sensors for detecting a wide range of chemical hazards that 

exist in the workplace today. Public Health Relevance: Hydrides are dangerous gases 

that are widely used in the semiconductor and other industries. The proposed project 

will develop advanced sensors that can be used in personal protective devices to warn 

users about the presence of these highly toxic gases.

ROUTKEVITCH 902602A1 (R44) Phase II: Advanced Personal Gas Detectors 

for Mining Applications

The risk of explosions in underground mines due to the presence of combustible gases 

is severe. The overall long-term objective of the proposed project is to develop and 

commercialize a new generation of affordable, reliable and portable hazardous gas 

detector in a Smart Gas Card format for use as a personal safety tool. The development of such an easy to use and wear personal monitor for the detection of combustible gases (e.g. methane) would be a substantial benefit to worker health and safety. 

In Phase I Synkera successfully demonstrated the feasibility of the critical element of 

such monitor, namely a low power, high performance reliable gas microsensor for detection of combustible gases. Now the objective of the Phase II effort is to advance the 

sensor technology to the maturity level required for portable detectors and to develop 

prototypes of Smart Combustible Gas Cardj. It will also facilitate the development of 

a Smart Multigas Card (methane, oxygen and carbon monoxide) required for each 

group of underground miners and for each miner who works alone. Portable combustible gas detectors on the market today typically catalytic bead sensors, or in the case 

of permanent installations, also infrared (IR) sensor technology. These are not suitable for personal monitoring due either bulk and cost (IR) or high power consumption (catalytic bead). Additionally, the stability and reliability of existing combustible 

gas sensors must be improved in order to enable fail-safe operation. Proposed new 

and improved catalytic combustible gas microsensors are based on a new microsensor platform technology, integrating precision-engineered nanostructured sensing 

elements with high surface area into a robust monolithic ceramic platform. In order 

to achieve the project objectives, in Phase II Synkera will (1) complete the sensor 

development and realize targeted performance; (2) develop and validate applicationspecific sensors, (3) identify and validate scale-up approaches, (4) develop low power 

electronics for portable Smart Card monitors, (5) fabricate Smart Combustible Gas 

Cardj prototypes and (6) develop partnerships for commercialization of microsensors and Smart Gas Card products. The proposed project is an opportunity to develop 

highly competitive products that address industry needs for personal safety tools, 

eliminate current cost and performance barriers, and provide a substantial benefit to 

worker health and safety, empowering individuals to make life-saving decisions in 

hazardous conditions as well during and in the aftermath of accidents. Public Health 

Relevance: The mining industry is one of the more challenging occupational sectors 

that involve adverse workers conditions, including the presence of hazardous and 

combustible gases. Current gas monitoring is accomplished via both fixed systems 

and portable instruments; however, the size and cost of current portable instruments 

has been a barrier to their use by all mining employees. Proposed sensor will support a new type of dramatically improved and inexpensive portable combustible gas 
366 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

monitors for individual use, thus enabling a new approach to alleviating intrinsic 

hazards of this occupation.

KAGAN 8282-05 (R01) Carbon Nanotube Biodegradation by 

Neutrophil Myeloperoxidase 

Background:

PI: Valerian E. Kagan, PhD, DSc. Widespread applications of engineered nanomaterials, particularly carbon nanotubes (CNT), in different spheres of industry, 

consumer products, and medicine raise concerns about their possible adverse 

effects on human health in occupational settings and in the environment. The 

unique physico-chemical characteristics combined with the vast surface area 

make the biological effects of CNT largely unpredictable. Our in vivo studies 

have demonstrated robust and unusual pulmonary inflammatory/oxidative stress 

responses to single walled CNT (SWCNT) upon exposure of mice via aspiration 

or inhalation. To date, no demonstration of biodegradation of carbon nanotubes 

in a physiologically relevant setting has been provided. Our preliminary results 

demonstrate that strong oxidants such as hypochlorous acid and oxoferryl species 

generated as reactive products of the myeloperoxidase reaction may be effective in 

biodegrading SWCNT. Therefore, we hypothesized that myeloperoxidase in neutrophils has the ability to catalyze the biodegradation of SWCNT and inactivate 

them inducers of inflammatory responses. To determine the extent to which enzymatic catalysis by human neutrophil myeloperoxidase (hMPO) represents a novel 

route of biodegradation of SWCNT, we designed experiments formulated in three 

Specific Aims of the proposal as follows: Specific Aim 1 will determine molecular 

mechanisms, products and reaction pathways through which hMPO catalyzes 

biodegradation of SWCNT. Specific Aim 2 will define the conditions maximizing 

biodegradation of SWCNT in human neutrophils and determine possible contribution and role of neutrophil interactions with macrophages in the biodegradation process through the formation of redox phagocytic synapse. Specific Aim 3 

will elucidate hMPO-catalyzed biodegradation of single-walled carbon nanotubes 

by neutrophils in vivo and quantitatively assess the contribution of the biodegradation process in mitigation of the SWCNT induced inflammatory responses 

in mouse lung. Discovery of a novel enzymatic pathway for “green” biochemical 

biodegradation of carbon nanotubes may revolutionize the ways to regulate their 

distribution in the body and contribute to a roadmap to new effective approaches 

to decrease their toxicity. 

Public Health Relevance:

Widespread applications of engineered nanomaterials, particularly carbon nanotubes (CNT), in different spheres of industry, consumer products, and medicine 

raise concerns about their possible adverse effects on human health in occupational 

settings and in the environment. Based on known robust and unusual pulmonary proinflammatory effects of CNT, identification of their biodegradation pathways becomes 
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APPENDIX C | NIOSH Extramural Research

a necessity. We demonstrate that an enzyme of neutrophils- myeloperoxidase-has the 

ability to catalyze biodegradation of SWCNT and inactivate them as inducers of pulmonary inflammation thus indicating new ways to regulate their distribution in the 

body and reduce the toxicity.

Peer-reviewed publications specifically credited to this project:

Fantastic voyage and opportunities of engineered nanomaterials: what are the potential risks of occupational exposures? Kagan VE, Shi J, Feng W, Shvedova AA, Fadeel B. 

J Occup Environ Med. 2010; 52(9):943–6.

PETERS 9920 (R21) Methods to Assess Personal Exposures to Airborne 

Metallic Nanoparticles

When inhaled, nanoparticles can elicit adverse cardiopulmonary health outcomes and 

their toxicity, particularly for metals and metal oxides, can be substantially greater than 

that of larger particles of the same composition. No standard measurement methods 

are available to quantitatively assess personal exposures to engineered nanoparticles, 

and without such methods, the extent to which workers are at risk from inhalation of 

nanoparticles is unknown. The laboratory work proposed in this research plan will 

standardize and validate measurement methods needed to quantify personal exposure 

to a range of metallic nanoparticles that are commonly incorporated into commercial 

products. We will develop an innovative nanoparticle deposition (NPD) sampler to 

collect nanoparticles specifically (separate from the larger particles in workplace air) 

and in a manner that reflects their deposition in the respiratory tract (Aim 1). We will 

also develop and validate a method to analyze the content of metal in the nanoparticles 

collected with the NPD sampler (Aim 2). These sampling and analysis methods will 

be easily adaptable by industrial hygiene practitioners to provide the system needed to 

assess worker exposure to metal nanoparticles. They will also represent enabling tools 

to study potential epidemiological relationships among metallic nanoparticle exposures and adverse acute health effects. Public Health Relevance: This work will result 

in methodologies to measure personal exposure to airborne metal and metal-oxide 

nanoparticles. As such it is applicable to assessing worker exposures to engineered 

nanomaterials in the burgeoning field of nanotechnology.

MASON 9644 Autonomous Electromechanical Gas Detection Microsystem 

for Mine Safety

Despite continued safety improvements and increased regulations, underground 

mines remain a very dangerous work environment, as evident from recent disasters 

at the Sago (2006), Darby (2006), and Crandall Canyon (2007) mines. As recommended by the Mine Safety Technology and Training Commission, new, cost effective 

technologies are needed to enhance monitoring within mines. We propose to develop 

key sensor, instrumentation and data analysis technologies that will be integrated to 

form a miniaturized intelligent electrochemical gas analysis system (iEGAS) tailored 

to the needs and challenges of mine safety applications. Major innovations in diverse 

technical areas will be synergistically combined within the following specific aims: 1) 
368 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

Develop and characterize a miniaturized electrochemical sensor array for detection 

and quantification of multiple mine gases, 2) Design and optimize compact electrochemical instrumentation electronics and intelligent algorithms for autonomous operation, 3) Integrate and characterize a model multigas electrochemical microsystem for 

mine safety monitoring and hazardous condition prediction. Through an innovative 

electrochemical sensor array approach, room-temperature ionic liquids and conductive polymer membranes will be developed for detection of multiple mine gases. An 

innovative instrumentation chip will implement multiple electrochemical measurement techniques to enable a very compact, low power microsystem implementation 

of the iEGAS system. New, highly efficient sensor array data analysis algorithms will 

enable concentrations of specific gases to be accurately measured within a mixedgas Environment and provide pattern recognition to generate information critical to 

mine safety decision making. The proposed microsystem offers significant advantages 

over existing gas sensors. It will measure all gases linked to fires and explosions (CH4, 

CO, CO2, O2) as well as hazardous exhaust gases (NO, NO2, SO2). It will intelligently 

analyze sensor data to predict hazardous conditions, report alerts and aid escape 

route planning. The autonomous iEGAS system can be deployed with miners or at 

fixed locations within a mine for long-term monitoring without user input or training. It will be inexpensive, ultra compact and lightweight, easily carried by miners 

and rescue teams. It will utilize a standard interface to communicate with existing 

mine infrastructure or with wireless mine communication handsets to realize a highly 

distributed, mobile, multi-gas monitoring network. The robust sensor platform is 

inherently resistant to vibration, smoke, moisture, and other common mine interferents, and sensors will be internally calibrated for variable environmental conditions 

(temperature, humidity). An operational model of the proposed iEGAS system will be 

implemented and characterized in a laboratory where gas concentrations and environmental parameters can be accurately controlled to mimic the range of conditions 

within underground mines. The multidisciplinary team of investigators will consult 

with mine safety experts throughout the project to ensure the developed technologies 

meet mining industry needs.

CHENG 9801(R01) Development of a personal sampler for nanomaterials

Production of nanomaterials has increased continuously because of their unique 

physicochemical characteristics and extensive applications. There are great concerns 

for the potential health effects of exposure to these nanoparticles. Because of nanomaterials’ small sizes and large surface areas, many studies have shown that the biological 

effects of nanomaterials are greater than bulk material of the same chemical composition. In 2005, the NIOSH recommended exposure limits of 1.5 mg/m3

 for fine TiO2

and 0.1 mg/m3

 for ultrafine TiO2, as time-weighted average concentrations (TWA) for 

up to 10 hr/day during a 40-hr work week. However, there are no suitable personal 

samplers capable of assessing the exposure level of ultrafine or nanoparticles. The 

overall objective of this study is to develop a personal sampler capable of collecting 

the ultrafine particles (nanoparticles) in the occupational environment. This sampler consists of a cyclone for respirable particle classification, a polycarbonate tracketched (PCTE) membrane filter with an acceleration nozzle to achieve nanoparticle 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 369

APPENDIX C | NIOSH Extramural Research

classification, and a backup filter to collect nanoparticles. By applying high and 

localized filtration velocity in the nozzle, diffusion deposition of nanoparticles can be 

avoided in the classifying PCTE filter, and nanoparticles can be collected in the downstream backup filter. This research will lead to the development of a unique personal 

sampling device capable of classifying the nanoparticle fraction (< 100 nm) from the 

aerosol stream and collecting this fraction for gravimetric, chemical, and other analyses. This device can be used to accurately assess personal exposure to nanoparticles 

in terms of mass concentration and physicochemical characteristics. Public Health 

Relevance: The overall objective is to develop a personal sampler capable of collecting 

the ultrafine particle (nanoparticle) fraction of the aerosol in an occupation environment. It can be used to assess personal exposure to nanoparticles in terms of mass 

concentration and physicochemical characteristics.

DELOUISE 9970 (R21) Reagents to Enhance Detection of Raw and Biologically 

Transformed Nanomaterials

Abstract (Official) DESCRIPTION (provided by applicant): The increasing use of 

engineered nanomaterials in industrial and consumer applications has raised serious 

concerns about their environment health safety (EH&S). A particular concern is for 

occupational exposure to raw materials in the form of highly dispersed spherical and 

fiber- like shapes. Researchers seek to quantify nanomaterial interactions with biological systems and to develop predictive models of nanoparticle EH&S risk. However, 

limitations imposed by the model systems employed, the lack of NP standards, the 

failure of researchers to quantify or report the physiochemical properties of the NP 

investigated, and the inadequate availability of sensitive analytical instrumentation, 

have collectively hampered progress in attaining these EH&S goals. In the proposed 

project we seek to overcome limitations in detecting nanoparticles by developing a set 

of reagents (NProbes) that will enhance their presence in biological tissues that due 

to their size may be obscured from detection by other means. NProbe reagents will 

function in a similar fashion to those used to detect and quantify proteins in standard immunohistological analysis. NProbes with high binding affinity to both raw 

NP and transformed nanomaterials will be generated using protein-based (antibody 

and fibronectin) phage display technology. Nanomaterials of interest include carbon 

nanotubes, metal oxides, metals, and semiconductors. We will validate the binding of 

NProbes to raw nanomaterials and test their cross reactivity to samples of related and 

dissimilar composition. NProbe binding to nanomaterials transformed by penetration through skin will be also be demonstrated. We believe that NProbe reagents will 

be useful to researchers assessing nanoparticles tissue interactions in all mammalian, 

vertebrate, invertebrates systems as well as detection of nanoparticles in the environment. Successfully development of NProbe reagents will have a transformative effect 

on nanoparticle risk assessment research. Public Health Relevance: Over the past few 

years the use of engineered nanomaterials in industrial and consumer applications has 

accelerated, raising serious concerns about the environment health safety (EH&S) risk 

from nanoparticle exposure. Limitations imposed by inadequate availability of sensitive analytical instrumentation have contributed to gaps in our ability to quantify the 

fate and transport of engineered nanomaterials. In this proposed project we address 
370 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

this issue by developing a set of reagents (NProbes) that will enable detection of 

nanoparticles skin and in other biological or environmental systems. NProbe reagents 

will function in a similar fashion to those used to detect and quantify proteins in standard immunohistological analysis. NProbes with high binding affinity to both raw NP 

and transformed nanomaterials will be generated using protein-based (antibody and 

fibronectin) phage display technology. 

Specific Aims: The goal of this project is to develop high affinity reagents (NProbes) 

that can bind nanomaterials with high specificity, both in the raw and transformed 

state, using phage display technology. These reagents will enable researchers to 

amplify presence of nanomaterials that have penetrated biological tissues that due to 

their size may be obscured from detection by other means. This technology will help 

fill gaps in our ability to understand and quantify parameters that influence nanomaterial penetration into biological systems. This knowledge is essential for accurately 

evaluating nanomaterial environmental health and safety risk. The specific aims 

are as follows: Aim 1 Develop Reagents with Binding Specificity to Technologically 

Important Nanomaterials 1.1 Hypothesis-phage display technology employing scFv 

and fibronectin library can be used to develop reagents (NProbes) with high binding 

specificity to nanomaterials Aim2 Validate Reagent Binding to Raw Nanomaterials 

2.1 Hypothesis-NProbes will bind raw nanomaterials 2.2 Hypothesis-NProbe binding 

specificity to carbon-based NP will have cross- reactivity due to common graphene 

structural element 2.3 Hypothesis-NProbe binding affinity will depend on NP size 

and shape Aim3 Validate Reagent Binding Biologically Transformed Nanomaterials 

3.1 Hypothesis-NProbes will bind nanomaterials transformed by penetration through 

skin 3.2 Hypothesis-NProbes will resolve discrepancy in QD skin penetration levels 

between TEM and visible fluorescence microscopy.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 371

APPENDIX C | NIOSH Extramural Research

Table 2. Nanotechnology principal investigators 

funded by NIOSH/OEP, 2001–2011

Yung-Sung Cheng 

Lovelace Biomed/Environ Res Inst 

Department of Toxicology 

2425 Ridgecrest Drive SE 

Albuquerque, NM 87108 

(505) 348–9410 (t)/ (505) 348–8567 (f) 

ycheng@lrri.org 

1R01OH009801-01A1 (2010)

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) 

5R44OH008939-03 (2009)

Lisa A. Delouise, PhD, MPH 

University of Rochester Medical Center 

School of Medicine and Dentistry 

601 Elmwood Ave, Box 697 

Rochester, NY 14642 

(585) 275–1810 (t)/(585) 273–1346 (f) 

lisa_delouise@urmc.rochester 

1R21OH009970-01 (2011)

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)

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) 

2R01OH008282-05 (2010)

Andrew Mason, PhD 

Michigan State University 

Department of Electrical & 

 Computer Engineering 

2120 Engineering Bldg. 

East Lansing, MI 488241226 

(517) 355–6502 

MASON@EGR.MSU.EDU 

5R01OH09644-02 (2010)

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)

(continued)
372 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX C | NIOSH Extramural Research

Table 2 (Continued). Nanotechnology principal investigators 

funded by NIOSH/OEP, 2001–2011 

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 

1K01OH009255–01 (2007) 

1R21OH009920–01 (2010)

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) 

2R44OH007963–02 (2008)

Dmitri Routkevitch 

Synkera Technologies Inc 

2021 Miller Drive, Suite B 

Longmont, CO 80501 

droutkevitch@synkera.com 

(720) 494–8401 x102 

5R44OH009026–03 (2009)

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)

Charles Timchalk 

Battelle Memorial Institute 

Health Effects & Risk Scis 

Pacific NW Division, Box 999

RICHLAND, WA 99352 

(509) 376–0434 (t)/(509) 376–9064 (f) 

charles.timchalk@pnl.gov 

5R01OH008173–05 (2006)

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 (2008) 

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)
APPENDIX D

NIOSH Logic Model
374 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX D | NIOSH Logic Model

NIOSH Logic Model

Like other scientific organizations, NIOSH can be described by a model of the way it functions to 

solve identified problems under various conditions. The overall NIOSH logic model is presented in 

Figure D–1. It has a conventional horseshoe shape with the operational upper branch proceeding 

from inputs to outcomes and with the strategic lower branch proceeding from strategic goals to 

management objectives. Both branches are correlated vertically and are subject to external factors. 

Inputs Activities Outputs Customers

Management

Objectives

Annual

Goals

External factors

Intermediate

Goals

Strategic

Goals

Outcomes

Operations

Strategy and design

Mission

Figure D–1. Schematic of the overall NIOSH logic model. 

The NIOSH research program begins with an analysis of production and planning inputs and follows 

the NIOSH operational model (Figure D–2). This analysis determines what can and should be done and 

thereby identifies research priorities. Intramural and extramural researchers present their project proposals, which receive appropriate internal and external review and are funded on the basis of proposal 

merits. Research activities produce outputs such as published materials, oral presentations, training and 

educational materials, tools, methods, and technologies. NIOSH research outputs are transferred directly 

to the final customers and partners (who implement improvements in workplace safety and health) or to 

intermediate customers (who transform further NIOSH outputs and produce intermediate outcomes). 

These intermediate outcomes such as training programs, regulations and standards are forwarded to the 

final customers. Since NIOSH is not a regulatory agency, it relies heavily on efforts by intermediate and 

final customers to achieve ultimate outcomes in the form of workplace safety and health improvements. 

Effectiveness in achieving these ultimate outcomes is influenced at all stages of program operation 

by both external factors (such as economic and social conditions) and the regulatory environment. 

Results of NIOSH-funded research and customer feedback (intermediate and final) contribute to 

the subsequent rounds of program planning. 
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 375

APPENDIX D | NIOSH Logic Model Research*: Surveillance, epidemiological 

and behavioral 

studies, intervention 

studies, laboratory 

and field studies, 

exposure and 

measurements and 

risk assessment, 

control studies 

and development, 

PPE studies and 

development

*intramural and 

extramural, including 

domestic and 

international efforts, 

such as work 

conducted at ERCs, 

AFCs, and WHO 

Global Network of 

Collaborating Centers

Mission: To Provide National and World Leadership to Prevent Work-Related Illness and Injuries

End 

 Outcomes

Production 

Inputs:

budget, staff, 

facilities, 

managerial, 

infrastructure

Planning 

Inputs:

customer/

stakeholder 

inputs, 

surveillance 

and 

intervention 

effectiveness 

data, HHE’s, 

earmarks, risk 

assessments

OSHA, MSHA, 

other federal 

agencies; NIOSH 

programs; 

Congress; 

State and 

local agencies; 

standards 

bodies; labor, 

trade and 

professional 

associations; 

technology 

developers and 

manufacturers; 

other 

researchers; SH 

practitioners

Employees, 

employers, 

industry, 

educators, 

regulators 

who reduce 

or prevent 

hazardous 

exposures or 

conditions

Improvements 

in safety and 

health in 

workplaces

Pilot and/or 

market ready 

technologies, 

training and 

education 

programs, 

guidance, 

regulations, 

standards, 

trade and major 

media releases; 

websites

Transfer:

•	Translation of 

research into practice, products and technologies

•	Information 

dissemination

•	Capacity building 

through technical assistance (HHE’s), training and education

•	Recommendations, 

reports, publications, workshops, databases, conferences

•	Training and 

education materials and demonstration programs, trained professionals

•	Tools and methods, 

best practices, developmental technologies, licenses, patents

External Factors:

Economic and social 

conditions and regulator 

envoronment

Conduct surveillance and evaluate intervention effectiveness

Research Partners Feedback

Transfer

Inputs Activities Outputs Intermediate Outcomes

Figure D–2. Schematic of the NIOSH operational model.

APPENDIX E

Progress Toward 

Meeting the NTRC 

Performance 

Measures
378 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures(continued)

NTRC critical research area

2009 Strategic plan performance measure 

(Measure numbers are from the Strategic Plan, 

NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011

Toxicity and internal dose 1.1.1 Elucidate toxicological mechanisms over the 

next five years (2009–2013)

Determined the pulmonary response (dose dependence and time course) to single-walled carbon nanotubes (SWCNT) and testing continues with multi-walled carbon nanotubes (MWCNT). Cardiovascular response to pulmonary exposure to SWCNT and ultrafine titanium dioxide completed. Determination of the pulmonary deposition and fate of SWCNT, MWCNT and ultrafine TiO2 continues. The in vitro effects of SWCNT and metal 

oxide nanoparticles on skin cells is ongoing. Genotoxic and carcinogenic effects of SWCNT are being studied. Central nervous system effects of pulmonary exposure to nanoparticles is ongoing.

Toxicity and internal dose 1.1.2 Address the development of predictive algorithms for toxicity over the next five years Testing continues to determine the role of oxidant- generating potential, shape (nanospheres vs. nanowires), diameter and length in bioactivity of metal oxide 

nanoparticles and carbon nanotubes. In vitro assays for oxidant generation, fibrogenic potential, and ability to cause endothelial dysfunction are ongoing.

Toxicity and internal dose 1.1.3 Address issues of most appropriate dose 

metric over the next three years.

Determined the pulmonary response to exposure to fine vs. ultrafine particles using both mass and surface area as the dose metric. Continuing to coordinate dose metrics with the field sampling capabilities.

Table E1. Progress toward meeting the NTRC performance measures
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 379

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures Table E1 (Continued). Progress toward meeting the NTRC performance measures NTRC critical research area 2009 Strategic plan performance measure (Measure numbers are from the Strategic Plan, NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011 Toxicity and internal dose 1.1.4 Address issues of internal dose over the next five years Developing methods to label carbon nanotubes and track their pulmonary deposition and fate (i.e., clear- ance, interstitialization, and translocation) with time post-exposure. Using chemical analysis to track the deposition and fate of metal oxide nanoparticles. Measurement methods 1.2.1-1 Within three years evaluate the correla- tion between particle number, surface area, mass, and particle size distribution airborne measurement results and pro- vide guidance for sampler selection based on the nanomaterial of interest. Evaluating current methods for measuring airborne mass concentrations of respirable particles in the workplace and investigating whether these mass- based methods can be used as an interim approach for measuring nanomaterials in the workplace. Recom- mended a quantitative selective mass based approach (elemental carbon) for the CNT REL based on previous published work [Birch et al. 2011]. Results of chamber studies comparing various methods for determination of aerosol surface area have been published. Particle number, active surface area and respirable mass were compared in a published CNF workplace study [Evans et al. 2010]. Particle size distributions were also 

monitored. Respirable mass was found to be the most useful and practical metric for monitoring CNFs and likely other nanoscale powders. Use of a photometer (response proportional to mass) was recommended.

(continued)
380 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures

Table E1 (Continued). Progress toward meeting the NTRC performance measures

NTRC critical research area

2009 Strategic plan performance measure 

(Measure numbers are from the Strategic Plan, 

NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011

Measurement Methods 1.2.1-2 Continue to conduct measurement studies of nanoparticles in the workplace over 

the next five years and establish a suite of instruments and protocols for nanoparticle measurement in the workplace.

The Nanomaterial Emission Assessment Technique was developed and refinement continues with the collection of exposure samples, use of data logging and additional instrumentation and mass based sampling in the field (Methner et al 2010). Following published workplace study findings with CNFs (Evans et al. 2010, Birch et al. 2011), time integrated sampling and direct reading instruments are being applied to an industrywide study on CNT/CNF exposures (Dahm et al. 2012).

Measurement Methods 1.2.1-3 Continue with refining NIOSH Method 

5040 specifications for the collection of elemental and organic carbon for application to the collection of carbon nanotubes and nanofibers.

An Appendix was added to the draft 2010 CIB on CNT/CNF describing modifications to Method 5040 for CNT/CNF. Quantitative worker exposures have been and continue to be determined using NIOSH 5040 (Birch et al. 2011, Dahm et al. 2012).

Measurement Methods 1.2.2 Within five years develop a handheld fastresponse nanoparticle monitor and software for spatial mapping of nanoparticles A prototype hand held electrostatic precipitator was developed and licensed to a vendor. A Portable Aerosol Mobility Spectrometer (PAMS) has been fully developed 

and validated, and a Personal Nanoaerosol Sizer (PNS) prototype has been completed and its performance is being evaluated. No progress on software for spatial mapping. For nanomaterial handling, spatial concentration mapping may not be the most efficient tool for workplace evaluations.

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 381

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures

(continued)

NTRC critical research area

2009 Strategic plan performance measure 

(Measure numbers are from the Strategic Plan, 

NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011

Measurement Methods 1.2.3 Within three years publish procedures for 

validation of nanoparticle sampling instruments and methods.

Developing testing and evaluation systems for comparison and validation of nanoparticle sampling instruments and methods. A workplace aerosol sampling platform was developed for simultaneous monitoring and comparison of an array of aerosol instruments and metrics [Evans et al. 2010]. Laboratory and field work continues.

Measurement Methods 1.2.4 Within three years strengthen interactions 

with the National Institute of Standards and Technology to identify commercially available nanomaterials and perform coherent research to develop and qualify nanoscale reference materials (RMs) and benchmark materials for evaluating measurement tools, instruments, and methods

Collaborating with NIST to identify and qualify scientifically credible, nanoscale certified reference materials (RMs) with assigned physical and/or chemical values for use in evaluating measurement tools, instruments, and methods. Collaboration has resulted in production of a certified reference material for specific surface area. Using NIST RM for particle size to evaluate TEM analysis. Additionally, the NTRC is collaborating with National Research Council—Canada on qualification of three high-aspect ratio nanoparticle reference materials.

Exposure Assessment 1.3.1 Support at least 12 research projects (field 

trips) over the next three years (2009–2011) to assess the fate of nanomaterials in the work environment.

Between 2009–2011 a total of 27 field trips were completed by members of the various NTRC field research teams. The increase in the amount of field studies is because the initial goal of 12 visits did not include the industrywide study to evaluate exposures in the carbonaceous nanomaterial facilities nor additional studies to evaluate method development and engineering controls.

Table E1 (Continued). Progress toward meeting the NTRC performance measures
382 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures

NTRC critical research area

2009 Strategic plan performance measure 

(Measure numbers are from the Strategic Plan, 

NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011

Exposure Assessment 1.3.2 Within three years (2009–2011) develop a 

baseline worker exposure assessment that identifies how exposures differ by work task or process.

Quantitatively assessing exposures to nanomaterials in the workplace including inhalation and dermal exposure. Determining how exposures differ by work task or process. Baseline database not created.

Epidemiology and Surveillance 1.4.1 Over the next three years, seek input from 

a collaborative working group made up of representatives from industry, government, academia, and labor concerning the value and utility of establishing exposure registries for workers potentially exposed to engineered nanoparticles.

(1) Co-sponsored a Keystone conference in Keystone, Colorado in 2010, [Nanomaterials and Worker Health: Medical Surveillance, Exposure Registries, and Epidemiologic Research] attended by a diverse group of national and international stakeholders. Working group findings from this conference were published in a Journal of Occupational and Environmental Medicine (JOEM) Supplement; (2) Participating in European working groups to ensure consistency between US and EU exposure databases. 

Epidemiology and Surveillance 1.4.2 Over the next three years assess the feasibility of industry-wide exposure and epidemiological studies of workers exposed to 

engineered nanomaterials.

Evaluated the need for and feasibility of initiating epidemiological or other health studies in workers exposed to carbonaceous nanomaterials. Completed the feasibility study.

(continued)

Table E1 (Continued). Progress toward meeting the NTRC performance measures
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 383

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures NTRC critical research area 2009 Strategic plan performance measure (Measure numbers are from the Strategic Plan, NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011 Epidemiology and Surveillance 1.4.3 Finalize the “Interim Guidance for the Medi- cal Screening and Hazard Surveillance of Workers Potentially Exposed to Engineered Nanoparticles” by 2009, followed by an update within the following three years. Investigate the feasibility of establishing a registry of workers exposed to engineered nanoparticles. The CIB 60: Interim Guidance for the Medical Screen- ing and Hazard Surveillance of Workers Potentially Exposed to Engineered Nanoparticles was published in 2009 (NIOSH Pub No. 2009–116). Updates of medical screening and hazard surveillance guidance are being provided in an “agent-specific” manner; guidance has been prepared for titanium dioxide and is in review status for carbon nanotubes and nanofibers. Initial investigations into the feasibility of nanotechnol- ogy worker registries have been conducted at 2010 Keystone, CO, conference: Nanomaterials and Worker Health: Exposure Registries, Medical Surveillance and Epidemiologic Research. Those efforts were summa- rized in a Supplement of JOEM dedicated to the confer- ence. Feasibility of such registries is a continuing topic of investigation and discussion in various forums with stakeholders.

Epidemiology and Surveillance 1.4.4 By 2012, create a GIS infrastructure populated with nanotechnology exposure data. Minimal progress. Collection of exposure data is ongoing.

(continued)

Table E1 (Continued). Progress toward meeting the NTRC performance measures
384 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures

NTRC critical research area

2009 Strategic plan performance measure 

(Measure numbers are from the Strategic Plan, 

NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011

Risk Assessment 1.5.1 Within three years complete a quantitative 

risk assessment (QRA) on ultrafine and fine materials from existing studies. Evaluate QRA methods for nanomaterials. Start QRA for nanoparticles using new NIOSH data. Use NIOSH nanoparticle data to calibrate and validate dosimetry models for nanoparticles. 

QRAs on airborne exposure to ultrafine and fine TiO2

were completed, using dose-response data from subchronic and chronic inhalation studies in animals. This QRA provided the health basis for the NIOSH recommended exposure limits (RELs) for airborne exposure to nanometer-diameter(ultrafine) and micrometer-diameter (fine) respirable TIO2 (NIOSH Pub No. 2011–160). 

QRA methods were evaluated in that document and in peer reviewed publications (e.g., Kuempel et al. 2009; Kuempel 2011). A QRA on carbon nanotubes (CNT) and carbon nanofibers (CNF) was completed, which provided the health basis for the NIOSH draft REL for CNT and CNF (NIOSH 2010). New NIOSH data from toxicology and aerosol research studies were used for those QRAs. Dosimetry model calibration, evaluation, and validation have been completed through collaboration with NIOSH partners (MacCalman et al. 2009; Sweeney et al. in preparation). New research was initiated in 2011 to develop a human respiratory tract deposition model of airborne CNT.

Risk Assessment 1.5.2 Within five years develop a risk assessment 

framework to rank hazard and estimate risk from exposure to selected nanoparticles in the workplace.

Began development of a risk assessment framework for evaluating the hazard and predicting the risk of exposure to nanoparticles. New data from in vitro and in vivo toxicology tests of several types of nanomaterials from NIOSH and external partners are being utilized in these hazard and risk assessments.

(continued)

Table E1 (Continued). Progress toward meeting the NTRC performance measures
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 385

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures NTRC critical research area 2009 Strategic plan performance measure (Measure numbers are from the Strategic Plan, NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011 Engineering Controls and Personal Protective Equipment 3.1.1 Conduct field investigations of workplaces where nanoparticles are manufactured and used and evaluate existing engineering controls. Within three years publish updated engineering control guidance. Four field investigations have been conducted and one engineering control survey report released to the spon- soring facility. Drafts of the reports for the remaining three facilities along with two case study reports are in progress. Engineering control evaluations are ongoing and a draft engineering control guidance document has been created. External review and completion of the document on target for late 2012. Engineering Controls and Personal Protective Equipment 3.1.2 Within five years publish updated guidance on the effectiveness of PPE for reducing worker exposures to nanoparticles Researchers have evaluated respiratory protection and other types of PPE for use with nanomaterials and published journal articles and a NIOSH Science Blog. http://blogs.cdc.gov/niosh-science-blog/2011/12/ resp-nano/ Research is ongoing. Expanding respirator research from bench to human subject studies and to the field. Work on gloves has not been done, but still remains a 

need. There are still some data gaps relevant to protective clothing materials that need addressed.

Engineering Controls and Personal Protective Equipment

3.1.3 Within five years publish updated respiratory protection guidance. Ongoing. Journal publications pertaining to nanomate- rial leakage and filtration published. Updated respiratory protection guidance in the CIB on TiO2, in the 2010 

Approaches to Safe Nanotechnology, DHHS (NIOSH) Pub No. 2010–125, the CIB on CNT/CNF, and in the Science Blog.

(continued)

Table E1 (Continued). Progress toward meeting the NTRC performance measures
386 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures

Table E1 (Continued). Progress toward meeting the NTRC performance measures

NTRC critical research area

2009 Strategic plan performance measure 

(Measure numbers are from the Strategic Plan, 

NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011

Engineering Controls and Personal Protective Equipment

3.1.4 Within five years publish updated work practice and administrative control guidance. Ongoing. Approaches to Safe Nanotechnology DHHS (NIOSH) Pub No. 2010–125 was published in 2010 and 

will be updated as new information becomes available. General Safe Practices for Working with Engineered Nanomaterials in Research Laboratories, DHHS (NIOSH) Pub No. 2012–147 was published in 2012. An Engineering Control document is scheduled to be published late in 2012.

Engineering Controls and Personal Protective Equipment

3.1.5 Within three years publish a document on 

the suitability of control banding approaches for nanomaterials.

Document delayed due to need for hazard banding prior to control banding. Investigating the ability to hazard group nanomaterials by physico chemical or other relevant properties.

Engineering Controls and Personal Protective Equipment

3.1.6 Support at least three projects over the next 

five years to evaluate substitute and modified nanoparticles with toxicological studies.

Prevention through design (PtD) work is ongoing. Conference to address safe nano design, molecule-> manufacturing -> market held in August 2012.Researchers evaluated the toxicity of functionalized versus pristine MWCNT.

Fire and Explosion Safety 3.2.1 Support at least two projects to evaluate explosion and fire hazards. Within three years 

publish guidance to eliminate or reduce explosion and fire hazards.

Physical and chemical properties that contribute to dustiness, combustibility, flammability, and conductivity of nanomaterials is ongoing. Recommendation of appropriate work practices to eliminate or reduce the risk to explosions and fire not yet begun. 

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 387

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures NTRC critical research area 2009 Strategic plan performance measure (Measure numbers are from the Strategic Plan, NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011 Recommendations and Guidance 3.3.1 Update and finalize the document, Ap- proaches to Safe Nanotechnology, Manag- ing the Health and Safety Concerns Associ- ated with Engineered Nanomaterials by 2009. Within two years, produce brochures and fact sheets to provide guidance to work- ers and laboratory staff. Continue to look for opportunities to translate research from the critical research areas into practice. Approaches to Safe Nanotechnology was updated and published; DHHS (NIOSH) Pub No. 2010–125. General Safe Practices for Working with Engineered Nanomate- rials in Research Laboratories; DHHS (NIOSH) Pub No. 2012–147 published. An Engineering Control docu- ment is scheduled to be published late in 2012. Recommendations and Guidance 3.3.2 By 2009, complete the CIB, Evaluation of Health Hazard and Recommendations for Occupational Exposure to Titanium Dioxide, with the OEL for ultrafine titanium dioxide. Support a project over the next three years to evaluate other ultrafine or nanoparticle OELs. Develop a CIB on carbon nanotubes by 2011. The CIB on titanium dioxide was finalized in early 2011, DHHS (NIOSH Pub No. 2011–160). The draft CIB on CNT/CNF was published on the NIOSH web page for public review in December 2010; a final document is scheduled for completion in 2012.

Recommendations and Guidance 3.3.3. Initiate a project that will develop a classification scheme based on chemical and 

physical properties. Release this classification scheme within the next three years.

Risk assessment project to classify nanomaterials based on toxicologic relevance is ongoing. Began development of a risk assessment framework for evaluating the hazard and predicting the risk of exposure to nanoparticles. New data from in vitro and in vivo

toxicology tests of several types of nanomaterials from NIOSH and external partners are being utilized in these hazard and risk assessments. May need to extend target completion date.

(continued)

Table E1 (Continued). Progress toward meeting the NTRC performance measures
388 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures

Table E1 (Continued). Progress toward meeting the NTRC performance measures

NTRC critical research area

2009 Strategic plan performance measure 

(Measure numbers are from the Strategic Plan, 

NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011

Recommendations and Guidance 3.3.4 Support a project to evaluate the existing 

toxicity information of high production volume nanoscale materials.

Nanotoxicology projects investigated the high volume materials SWCNT and MWCNT. Fullerenes and silver are scheduled to be evaluated.

Recommendations and Guidance 3.3.5 Within three years, increase awareness of 

the need for specific nanomaterial information on MSDS among the target audience by 

33% over baseline.

Two posters presented at AIHce 2009 and 2011 demonstrated that there has been little progress in the improvement of nanomaterial safety data sheets. A critical evaluation of material safety data sheets (MSDSs) for engineered nanomaterials (Eastlake et al. 2012) published in the Journal of Chemical Health and Safety to 

reach a broader audience so that nano manufacturers understand the need to identify the nano material and conduct annual literature searches for recent toxicologic info to include on the MSDSs. 

Communications and Information 4.1.1. Creation of a roadmap that aligns new 

nanoinformatics with the NIOSH Nanoparticle Information Library (NIL) within the next 

three years (2009-2011).

The NIL was migrated to Oregon State, ONAMI, as a solution to open access and maintenance issues. Specific nanoinformatics project areas were identified through NIOSH participation in the NanoInformatics 2011 workshops held in November 2010 and December 2011, and through creation of the Nanoinformatics 2020 Roadmap (available at http://eprints.internano.org/607/1/Roadmap_FINAL041311.pdf).

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 389

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures NTRC critical research area 2009 Strategic plan performance measure (Measure numbers are from the Strategic Plan, NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011 Communications and Information 4.1.2 Within one year, identify and initiate/es- tablish contact with at least one potential partner from each of the following areas: government, industry, academia, and labor. Many new contacts were made between 2009–2011 including formal MOUs with the National Science Foundation Center for High-rate Nanomanufacturing, in collaboration with the University of Massachusetts Low- ell, Northeastern University, and the University of New Hampshire; and with the College of Nanoscale Science and Engineering, State University of New York-Albany (CNSE). Communications and Information 4.1.3 Within one year, develop at least one informational document tailored to a target audience nanotechnology workers and employers, occupational safety and health professionals, policy-makers, or decision- makers. Evaluate/assess the reach and effectiveness of the above tailored informa- tional piece within two years. Approaches to Safe Nanotechnology: Managing the Health and Safety Concerns Associated with Engi- neered Nanomaterials was updated in 2010; DHHS (NIOSH) Publication No. 2010–125, and General Safe Practices for Working with Engineered Nanomateri- als in Research Laboratories; DHHS (NIOSH) Pub No. 2012–147 was published in 2012. An Impact card was created by the Office of Health Communications to high- light the Approaches to Safe Nanotechnology document 

DHHS (NIOSH) Publication No. 2011–206.The effectiveness of the guidance was evaluated as part of an epidemiology feasibility project and a journal article summarizing adherence was drafted. 

(continued)

Table E1 (Continued). Progress toward meeting the NTRC performance measures
390 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures

Table E1 (Continued). Progress toward meeting the NTRC performance measures

NTRC critical research area

2009 Strategic plan performance measure 

(Measure numbers are from the Strategic Plan, 

NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011

Communications and Information 4.1.3 Update progress report on the NIOSH 

nanotechnology research and communication efforts within two years. Continue to update the document, Approaches to Safe Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered Nanomaterials as new information becomes available.

2012 update of the Progress Report completed herein. It includes updating all NIOSH nanotechnology research from 2004–2011. Approaches to Safe Nanotechnology [NIOSH Publication 2010–125] is being evaluated for an update involving an updated appendix on exposure assessment.

Applications for Occupational Safety and Health

2.1.1 Support at least three projects over the 

next three years to evaluate the application of nanotechnology in the manufacture of filters, respirators, and respirator cartridge end-of-service indicator.

NTRC researchers have developed nano enabled sensors (end of life service indicators) and integrated them into air purifying respirator (APR) and powered air purifying respirator (PAPR) cartridges for evaluation. Research findings are now being used in the update of NIOSH PAPR respirator standards. NTRC researchers also collaborated and developed new nanomaterials for chemical sensing (see performance measure 2.1.2).

Applications for Occupational Safety and Health

2.1.2 Within five years publish application findings 

and disseminate findings to workers, employers, and occupational safety and health professionals.

NTRC researchers collaborated and developed new nanomaterials for chemical sensing. This research resulted in a patent assigned to the Regent of the University of California: Sailor, Ruminski, King, and Snyder, “Optical fiber-mounted porous photonic crystals and sensors,” U.S. Patent #7,889,954, issued Feb. 15, 2011. 

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 391

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures NTRC critical research area 2009 Strategic plan performance measure (Measure numbers are from the Strategic Plan, NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011 International Activities 4.2.1-1 Strengthen coordination of research through government-level organizations (OECD and WHO). Additional NTRC researchers were asked to partici- pate on global nanotechnology OH&S programs. NTRC researchers participated in several joint EU/US confer- ences. NTRC researchers initiated development of WHO Guidelines on Protecting Workers from Potential Risks of Manufactured Nanomaterials (http://www.who.int/ occupational_health/topics/nanotechnologies/en/) International Activities 4.2.1-2 Expand collaborations to developing na- tions and emerging powers (Asia-Pacific, Eastern Europe). NTRC researchers participated in meetings held in Australia, Japan, and India during 2009–2011. Many of the EU workshops attended by NTRC researchers also included attendees from Poland and the Czech Repub- lic. NTRC researchers established collaborations with research labs in Russia. International Activities 4.2.2-1 Develop global portal for information on nanomaterials relevant to occupational 

safety and health.

NIOSH nanotechnology topic page has been widely used by the international community. NIOSH sponsors the GoodNanoGuide portal bringing together health and safety professionals to exchange experiences and good practices in the workplace. NTRC researcher leads the development of nanotechnology topic page in World Health Organization (http://www.who.int/occupational_health/topics/nanotechnologies/en/)

(continued)

Table E1 (Continued). Progress toward meeting the NTRC performance measures
392 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures

Table E1 (Continued). Progress toward meeting the NTRC performance measures

NTRC critical research area

2009 Strategic plan performance measure 

(Measure numbers are from the Strategic Plan, 

NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011

International Activities 4.2.2-2 Develop global exposure registry database: European countries, ECHA, Asian 

countries, OECD.

Coordinating efforts between NIOSH, the TNO, PEROSH, and NanoImpactNet for a global exposure registry database. Discussions underway but no database yet. Leading development of a health surveillance project incorporating exposure registries in IOHA. The nano proposal to IOHA was ‘received favorably’ in 2011.

International Activities 4.2.2.3 Participate in OECD Nanomaterial Safety 

Testing Program by sponsoring nanomaterial testing and by data exchange.

NIOSH conducts research and acts as contributor for OECD for several nanomaterials: silver, single and multiwall carbon nanotubes, and fullerenes.

International Activities 4.2.3-1 Facilitate development of government-level exposure mitigation guidance (OECD). NTRC researcher leads the OECD steering group developing guidance on exposure mitigation. Most 

recently this steering group published a compilation of occupational guidance for nanotechnology laboratories. Presently this steering group is developing guidance on measuring exposures to airborne nanomaterials.

International Activities 4.2.3-2 Increase utilization of web-based tools for 

document development (such as wikibased platforms

NIOSH sponsors the GoodNanoGuide portal, based on wiki, bringing together health and safety professionals to exchange experiences and develop best practice guidance for nanotechnology workplaces.

(continued)
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 393

APPENDIX E | Progress Toward Meeting the NTRC Performance Measures NTRC critical research area 2009 Strategic plan performance measure (Measure numbers are from the Strategic Plan, NIOSH Pub No. 2010–105) Progress as of Dec 31, 2011 International Activities 4.2.4-1 Increase utilization of emerging informa- tion technology mechanisms (e.g., NIOSH science blog, web-based social networks, virtual reality). NTRC nanotechnology team actively utilizes emerging information technology mechanisms to dissemination NIOSH products. For example, NIOSH nanotechnology topic page is regularly updated, and NTRC researchers post blogs on critical topics related to nanotechnology OH&S. International Activities 4.2.4-2 Establish partnerships for translation of NIOSH publications to other languages. US NIOSH worked with Italian NIOSH to translate and publish the US NIOSH nanotechnology brochure into Italian. NIOSH through its engagement with ISO, OECD and WHO pushes translation of its leading nanotech- nology guidance documents into other languages. For example, Chinese NIOSH is translating NIOSH “Ap- proaches to Safe Nanotechnology” into Mandarin. International Activities 4.2.5-1 Strengthen participation in globally recog- nized organizations. NTRC researcher leads projects in ISO and OECD. Most recently NIOSH also expanded its leadership in developing global nanotechnology workplace guidance documents in WHO and Inter-organizational Program for 

Sound Management of Chemicals.

International Activities 4.2.5-2 Expand partnerships to international bodies with economic instruments to implement OSH measures such as financial 

institutions (Inter-American Development Bank, World Bank) and insurance companies (Swiss Re, Munich Re, Lloyds)

No formal projects in place.

Table E1 (Continued). Progress toward meeting the NTRC performance measures

APPENDIX F

Summary of the 

Citation Analysis
396 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

 Appendix F | Summary of the Citation Analysis

A Summary of the citation analysis as of December 31, 2011. Note that publications 

with no citations and those in Toxicologist are not included, as these are published 

as Society of Toxicology annual conference proceedings and are not searchable via 

Google Scholar or Web of Knowledge. NIOSH numbered publications are also not 

available for the citation analysis.
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 397

Appendix F | Summary of the Citation Analysis Table F–1. Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling

Apopa, Qian, Guo, Schwegler-Berry, Pacurari, Porter, Shi, Vallyathan, Castranova, Flynn 

2009 32 96

Evaluating the toxicity of airborne particulate matter and nanoparticles by measuring oxidative stress potential—a workshop report and consensus statement

Ayres, Borm, Cassee, Castranova, Donaldson, Ghio, Harrison, Hider, Kelly, Kooter, Marano, Maynard, Mudway, Nel, Sioutas, Smith, Baeza-Squiban, Cho, Duggan, Froines 

2008 51 459

Meeting report: hazard assessment for nanoparticles Balbus, Maynard, Colvin, Castranova, Daston, 

Denison, Dreher, Goering, Goldberg, Kulinowski, Monteiro-Riviere, Oberdörster, Omenn, Pinkerton, Ramos, Rest, Sass, Silbergeld, Wong 

2007 79 450

Aerosolization of single-walled carbon nanotubes for an inhalation study

Baron, Deye, Chen, Schwegler-Berry, Shvedova, Castranova 

2008 15 191

Size shifts in measurements of droplets with the aerodynamic particle sizer and the aerosizer Baron, Deye, Martinez, Jones, Bennett 2008 2 1

Toxicology of nanomaterials: permanent interactive learning

Borm, Castranova 2009 2 1

Overview of current toxicological knowledge of engineered nanoparticles Castranova 2011 1 0

Nanoparticles-containing spray can aerosol: characterization, exposure assessment, and generator design Chen, Afshari, Stone, Jackson, Schwegler-Berry, Frazer, Castranova, Thomas 2010 1 0
398 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX F | Summary of the Citation Analysis

Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Exposure control strategies in the carbonaceous nanomaterial industry Dahm, Yencken, Schubauer-Berigan 2011 3 0

An approach to risk assessment for TiO2 Dankovic, Kuempel, Wheeler 2007 18 88

The limits of testing particle-mediated oxidative stress in vitro in predicting diverse pathologies; relevance for testing of nanoparticles

Donaldson, Borm, Castranova, Gulumian 2009 19 61

Cross-talk between lung and systemic circulation during carbon nanotube respiratory exposure—potential biomarkers

Erdely, Hulderman, Salmen, Liston, Erdely, Schwegler-Berry, Castranova, Koyama, Kim Endo, Simeonova 

2009 29 95

Ultrafine and respirable particles in an automotive grey iron foundry

Evans, Heitbrink, Slavin, Peters 2008 24 93

Aerosol characterization during carbon nanofiber production: mobile direct-reading sampling Evans, Ku, Birch, Dunn 2010 3 2

There’s plenty of room at the forum: potential risks and safety assessment of engineered nanomaterials

Fadeel, Kagan, Krug, Shvedova, Svartengren, Tran, Wiklund 

2007 19 228

Deposition of inhaled nanoparticles in the rat nasal passages: dose to the olfactory region

Garcia, Kimbell 2009 2 0

Challenges in assessing nanoparticle toxicology: a personal perspective

Geraci, Castranova 2010 1 0

Particle length-dependent titanium dioxide nanomaterials’ toxicity and bioactivity Hamilton Jr., Wu, Porter, Buford, Wolfarth, Holian 2009 12 5
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 399

APPENDIX F | Summary of the Citation Analysis Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Relationships between particle number, surface area, and respirable mass concentration in automotive engine manufacturing

Heitbrink, Evans, Ku, Maynard, Slavin, Peters 2009 14 22

Characterization and mapping of very fine particles in an engine machining and assembly facility

Heitbrink, Evans, Peters, Slavin 2007 13 95

Exposure assessment considerations for nanoparticles in the workplace

Hoover, Stefaniak, Day, Geraci 2007 3 1

National nanotechnolgy partnership to protect workers Howard, Murashov 2009 7 13

Persistent pulmonary inflammation, airway mucous metaplasia and migration of multi-walled carbon nanotubes from the lung after subchronic exposure

Hubbs, Mercer, Coad, Battelli, Willard, Sriram, Wolfarth, Castranova, Porter 

2009 9 38

Potential for occupational exposure to engineered carbon-based nanomaterials in environmental laboratory studies

Johnson, Methner, Kennedy, Steevens 2010 16 12

Nanomedicine and nanotoxicology: two sides of the same coin

Kagan, Bayir, Shvedova 2005 88 558

Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation Kagan, Konduru, Feng, Allen, Conroy, Volkov, Vlasova, Belikova, Yanamala, Kapralov, Tyurina, 

Shi, Kisin, Murray, Franks, Stolz, Gou, KleinSeetharaman, Fadeel, Star, Shvedova 

2010 38 36

Direct and indirect effects of single-walled carbon nanotubes on RAW 264.7 macrophages: role in iron

Kagan, Potapovich, Osipov, Tyurina, Kisin, Schwegler-Berry, Mercer, Castranova, Shvedova 

2006 189 3865
400 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX F | Summary of the Citation Analysis

Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

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

Kang, Moon, Lee, Park, Kim, Castranova 2008 17 142

Optical-fiber-mounted porous silicon photonic crystals for sensing organic vapor breakthrough in activated carbon

King, Ruminski, Snyder, Sailor 2007 7 18

Pulmonary response, oxidative stress and genotoxicity Induced by carbon nanofibers

Kisin, Murray, Schwegler-Berry, Scabilloni, Mercer, Chirila, Young, Leonard, Keohavong, Fadeel, Kagan, Castranova, Shvedova 

2010 2 3

Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo Konduru, Tyurina, Feng, Basova, Belikova, Bayir, Clark, Rubin, Stolz, Vallhov, Scheynius, Witasp, 

Fadeel, Kichambare, Star, Kisin, Murray, Shvedova, Kagan 

2009 14 115

In situ structure characterization of airborne carbon nanofibers by a tandem mobility-mass analysis

Ku, Emery, Maynard, Stolzenburg, McMurry 2006 17 184

Measurement of airborne carbon nanofiber structure using a tandem mobility-mass analysis

Ku, Emery, Maynard, Stolzenburg, McMurry 2006 17 184

Relation between electrical mobility, mass, and size for nanodrops 1–6.5 nm in diameter in air

Ku, Fern ez de la Mora 2009 24 162

Morphology of single-wall carbon nanotube aggregates generated by electrospray of aqueous suspensions

Ku, Kulkarni 2009 2 2
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 401

APPENDIX F | Summary of the Citation Analysis Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Comparing aerosol surface-area measurement of monodisperse ultrafine silver agglomerates using mobility analysis, transmission electron microscopy and diffusion charging

Ku, Maynard 2005 53 1324

Generation and investigation of airborne silver nanoparticles with specific size and morphology by homogeneous nucleation, coagulation, and sintering

Ku, Maynard 2006 27 292

Anomalous responses (arcing, electrical discharge) in a differential mobility analyzer caused by ultrafine fibrous carbon aerosols

Ku, Maynard, Baron, Deye 2005 10 33

Observation and measurement of anomalous responses in a differential mobility analyzer by ultrafine fibrous carbon aerosols

Ku, Maynard, Baron, Deye 2007 10 33

Risk assessment approaches and research needs for nanomaterials: an examination of data and information from current studies

Kuempel, Geraci, Schulte 2007 5 78

Rat- and human-based risk estimates of lung cancer from occupational exposure to poorly-soluble particles: a quantitative evaluation

Kuempel, Smith, Dankovic, Stayner 2009 2 0

Lung dosimetry and risk assessment of nanoparticles: evaluating and extending current models in rats and humans

Kuempel, Tran, Castranova, Bailer 2006 24 246
402 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX F | Summary of the Citation Analysis

Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Quantitative risk assessment in workers using rodent dose-response data of fine and ultrafine titanium dioxide

Kuempel, Wheeler, Smith, Bailer 2005 5 44

Bipolar diffusion charging characteristics of airborne carbon nanotube aerosols

Kulkarni, Deye, Baron 2009 1 0

Nanoparticle inhalation impairs endothelium-dependent vasodilatation in subepicardial arterioles LeBlanc , Cumpston, Chen, Frazer, Castranova, Nurkiewicz 2009 11 17

Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism LeBlanc, Moseley, Chen, Frazer, Castranova, Nurkiewicz 2010 10 7

Relationship of pulmonary exposure to multiple doses of single-wall carbon nanotubes and atherosclerosis in APOE-/-mouse model

Li, Chapman, Hulerman, Salmen, Shvedova, Luster, Simeonova 

2006 2 65

Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes

Li, Hulderman, Salmen, Chapman, Leonard, Shvedova, Luster, Simeonova 

2007 116 887

Pulmonary exposure to carbon nanotubes induces vascular toxicity

Li, Salmen, Hulderman, Kisin, Shvedova, Luster 2005 12 608

Pulmonary carbon nanotube exposure and oxidative status in vascular system

Li, Salmen, Hulderman, Kisin, Shvedova, Luster, Simeonova 

2004 3 31

Cerium oxide, a diesel fuel catalyst, induces pulmonary fibrosis Ma, Mercer, Rao, Barger, Meighan, Castranova, Ma 2010 2 0
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 403

APPENDIX F | Summary of the Citation Analysis Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Development of a bio-mathematical model in rats to describe clearance, retention and translocation of inhaled nano particles throughout the body

MacCalman, Tran, Kuempel 2009 2 6

Exposure to carbon nanotube material during the handling of unrefined single-walled carbon nanotube material

Maynard, Baron, Foley, Shvedova, Kisin, Castranova 2004 363 14587

Airborne nanostructured particles and occupational health

Maynard, Kuempel 2005 210 2449

Addressing the potential environmental and human health impact of engineered nanomaterials

Maynard, Kuempel 2006 1 2

Distribution and persistence of pleural penetrations by multi-walled carbon nanotubes

Mercer, Hubbs, Scabilloni, Wang, Castranova, Porter 

2010 9 2

Use of labeled single-walled carbon nanotubes to study translocation from the lungs

Mercer, Scabilloni, Wang, Battelli, Castranova 2009 3 3

Alteration of deposition pattern and pulmonary response as a result of improved dispersion of aspirated single-walled carbon nanotubes in a mouse model

Mercer, Scabilloni, Wang, Kisin, Murray, SchweglerBerry, Shvedova, Castranova 2008 74 893

Nanoparticle emission assessment technique (NEAT) for the identification and measurement of potential exposure to engineered nanomaterials—part B: results from 12 field studies

Methner, Hodson, Dames, Geraci 2010 17 8
404 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX F | Summary of the Citation Analysis

Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Nanoparticle emission assessment technique (NEAT) for the identification and measurement of potential exposure to engineered nanomaterials—part A

Methner, Hodson, Geraci 2010 21 17

The fate of metal (Fe) during diesel combustion: morphology, chemistry, and formation pathways of nanoparticles

Miller, Ahlstr, Kittelson, Zachariah 2007 18 44

Real-time estimation of elemental carbon emitted from a diesel engine

Miller, Habjan, Park 2007 1 1

The nanoparticle information library (NIL): a prototype for linking and sharing emerging data

Miller, Hoover, Mitchell, Stapleton 2007 2 1

Role of lubrication oil in particulate emissions from a hydrogen-powered internal combustion engine

Miller, Stipe, Habjan, Ahlstr 2007 10 12

Pulmonary inflammation after intra peritoneal administration of ultrafine titanium dioxide (TiO2) at rest or in 

lungs primed with lipopolysaccharide

Moon, Park, Choi, Park, Castranova, Kang 2010 1 2

Mechanisms of action of inhaled fibers, particles, and nanoparticles in lung and cardiovascular diseases

Mossman, Borm, Castranova, Costa, Donaldson, Kleeberger 

2007 47 217

Occupational exposure to nanomedical applications Murashov 2009 2 0

Occupational safety and health in nanotechnology and organisation for economic co-operation and development

Murashov, Engel , Savolainen, Fullam, Lee, Kearns 2009 10 3
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 405

APPENDIX F | Summary of the Citation Analysis Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Biosafety, occupational health, and nanotechnology Murashov, Howard 2007 1 0

Essential features of proactive risk management Murashov, Howard 2009 12 0

International standards for risk management in nanotechnology

Murashov, Howard 2009 1 5

Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes

Murray, Kisin, Leonard, Young, Kommineni, Kagan, Castranova, Shvedova 

2009 51 179

Effects of sampling artifacts on occupational samples of diesel particulate matter

Noll, Birch 2008 4 6

Systemic microvascular dysfunction and inflammation after pulmonary particulate matter exposure

Nurkiewicz, Porter, Barger, Millecchia, Rao, Marvar, Hubbs, Castranova, Boegehold 

2007 67 677

Nanoparticle inhalation augments particle-dependent systemic microvascular dysfunction

Nurkiewicz, Porter, Hubbs, Cumpston, Chen, Frazer, Castranova 

2008 31 131

Inhalation of ultrafine titanium dioxide augments particle-dependent microvascular dysfunction

Nurkiewicz, Porter, Hubbs, Millecchia, Stone, Chen, Frazer, Castranova, Boegehold 

2007 2 52

Pulmonary nanoparticle exposure distrupts systemic microvascular nitric oxide signaling

Nurkiewicz, Porter, Hubbs, Tone, Chen, Frazer, Boegehold, Castranova 

2009 17 37

Principles for characterizing the potential human effects from exposure to nanomaterials: elements of screening strategy

Oberdorster, Maynard, Donaldson, Castranova, Fitzpatrick, Ausman, Carter, Karn, Kreyling, Lai, Olin, Monterio-Riviere, Warheit, Yang 

2005 417 6462

Rapid measurements of aerosol size distributions using a fast integrated mobility spectrometer Olfert, Kulkarni, Wang 2008 10 18
406 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX F | Summary of the Citation Analysis

Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Oxidative and molecular interactions of multi-wall carbon nanotubes (MWCNT) in normal and malignant human mesothelial cells

Pacurari, Yin, Ding, Leonard, Schwegler-Berry, Ducatman, Endo, Castranova, Vallyathan 

2008 8 21

Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kB, and Akt in normal and malignant human mesothelial cells

Pacurari, Yin, Zhao, Ding, Leonard, SchweglerBerry, Ducatman, Sbarra, Hoover, Castranova, Vallyathan 

2008 62 353

Human health implications of nanomaterial exposure Papp, Schiffmann, Weiss, Castranova, Vallyathan, 

Rahman 

2008 14 82

A study on effects of size and structure on hygroscopicity of nanoparticles using a tandem differential mobility analyzer and transmission electron microscopy Park, Kim, Miller 2008 6 18

The mapping of fine and ultrafine particle concentrations in an engine machining and assembly facility Peters, Heitbrink, Evans, Slavin, Maynard 2006 47 462

Characterization of exposures to airborne nanoscale particles during friction stir welding of aluminum

Pfefferkorn, Bello, Haddad, Park Powell, McCarthy, Bunker, Fehrenbacher, Jeon, Gruetzmacher, Virji, Hoover 

2010 1 0

Aerosol dosimetry research needs Phalen, Hoover 2006 2 14

Engineered titanium dioxide nanowire toxicity in vitroand in vivo

Porter, Holian, Sriram, Wu, Wolfarth, Hamilton, Buford 

2008 5 39

Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes

Porter, Hubbs, Mercer, Wu, Wolfarth, Sriram, Leonard, Battelli, Schwegler-Berry, Friend, Andrew, Chen, Tsuruoka, Endo, Castranova 

2010 33 46
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 407

APPENDIX F | Summary of the Citation Analysis Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

A biocompatible medium for nanoparticle dispersion Porter, Sriram, Wolfarth, Jefferson, SchweglerBerry, Andrew, Castranova 2008 31 201

Total inward leakage of nanoparticles through filtering facepiece respirators

Rengasamy, Eimer 2011 1 0

Nanoparticle filtration performance of commercially available dust masks

Rengasamy, Eimer, Shaffer 2008 8 29

Comparison of nanoparticle filtration performance of NIOSH-approved and CE-marked particulate filtering facepiece respirators

Rengasamy, Eimer, Shaffer 2009 14 16

Filtration performance of NIOSH-approved N95 and P100 filtering facepiece respirators against 4–30 nanometer-size nanoparticles

Rengasamy, King, Eimer, Shaffer 2008 23 81

Evaluation of the filtration performance of NIOSHapproved N95 filtering facepiece respirators by photometric and number-based test methods Rengasamy, Miller, Eimer 2011 1 0

Nanoparticle penetration through NIOSH-approved N95 filtering facepiece respirators

Rengasamy, Verfobsky, King, Shaffer 2007 18 138

Concepts of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response-metrics

Rushton, Jiang, Leonard, Eberly, Castranova, Biswas, Elder, Han, Gelein, Finkelstein, Oberdorster 

2010 18 26
408 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX F | Summary of the Citation Analysis

Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Surface area of particle administered versus mass in determining the pulmonary toxicity of ultrafine and fine carbon black: comparison to ultrafine titanium dioxide

Sager, Castranova 2009 27 62

Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of surface area

Sager, Kommineni, Castranova 2008 37 159

An improved method to disperse nanoparticles for in vitro and in vivo investigation of toxicity

Sager, Porter, Robinson, Lindsley, Schwegler-Berry, Castranova 

2007 74 1023

Potential pulmonary effects of engineered carbon nanotubes: In vitro genotoxic effects

Sargent, Reynolds, Castranova 2010 2 0

Induction of aneuploidy by single-walled carbon nanotubes

Sargent, Shvedova, Hubbs, Kashon, Salisbury, Lowry, Murray, Kisin, Friend, Benkovic, McKinstry, Battelli, Reynolds 

2009 18 85

Engineered carbonaceous nanomaterials manufacturers in the United States: workforce size, characteristics and feasibility of epidemiologic studies

Schubauer-Berigan, Dahm, Yencken 2011 2 4

Nanotechnologies and nanomaterials in the occupational setting Schulte, Geraci, Hodson, Zumwalde, Castranova, Kuempel, Methner, Hoover, Murashov 2010 1 1

Sharpening the focus on occupational safety and health of nanotechnology

Schulte, Geraci, Zumwalde, Hoover, Castranova, Kuempel, Murashov, Vainio, Savolainen 

2008 5 17

Occupational risk management of engineered nanoparticles 

Schulte, Geraci, Zumwalde, Hoover, Kuempel 2008 50 286
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 409

APPENDIX F | Summary of the Citation Analysis Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Occupational exposure limits for nanomaterials: state of the art 

Schulte, Murashov, Zumwalde, Kuempel, Geraci 2010 11 5

Ethical and scientific issues of nanotechnology in the workplace

Schulte, Salamanca-Buentello 2007 60 136

Options for occupational health surveillance of workers potentially exposed to engineered nanoparticles: state of the science

Schulte, Trout, Zumwalde, Kuempel, Geraci, Castranova, Mundt, Mundt, Halperin 

2008 19 41

Effects of titanium dioxide nanoparticle exposure on neuroimmune responses in rat airways

Scuri, Chen, Castranova, Reynolds, Samsell, Walton, Piedimonte. 

2011 1 0

Respiratory protection against nanoparticles: A review Shaffer, Rengasamy 2009 9 6

Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells

Shvedova, Castranova, Kisin, Schwegler-Berry, Murray, Gandelsman, Maynard, Baron 

2003 505 16482

Sequential exposure to carbon nanotubes and bacteria enhances pulmonary inflammation and infectivity Shvedova, Fabisiak, Kisin, Murray, Roberts, Tyurina, Antonini, Feng, Kommineni, Reynolds, Barchowsky, 

Castranova, Kagan 

2008 42 331

The role of nanotoxicology in realizing the ‘helping without harm’ paradigm of nanomedicine: lessons from studies of pulmonary effects of single-walled carbon nanotubes

Shvedova, Kagan 2010 14 16
410 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX F | Summary of the Citation Analysis

Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Close encounters of the small kind: adverse effects of man-made materials interfacing with the nano-cosmos of biological systems

Shvedova, Kagan, Fadeel 2010 19 41

Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice Shvedova, Kisin, Mercer, Murray, Johnson, Potapovich, Tyurina, Gorelik, Arepalli, SchweglerBerry, Hubbs, Antonini, Evans, Ku, Ramsey, 

Maynard, Kagan, Castranova, Baron 

2005 449 9777

Vitamin-E deficiency enhances pulmonary inflammatory response and oxidative stress induced by singlewalled carbon nanotubes in C57BL/6 mice Shvedova, Kisin, Murray, Gorelik, Arepalli, Castranova, Young, Gao, Tyurina, Oury, Kagan 2007 55 396Inhalation versus aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis

Shvedova, Kisin, Murray, Johnson, Gorelik, Arepalli, Hubbs, Mercer, Keohavong, Sussman, Jin, Yin, Stone, Chen, Deye, Maynard, Castranova, Baron, Kagan 

2008 101 738

Inhalation of carbon nanotubes induces oxidative stress and cytokine response causing respiratory impairment and pulmonary fibrosis in mice

Shvedova, Kisin, Murray, Johnson, Gorelik, Arepalli, Hubbs, Mercer, Stone, Frazer, Chen, Deye, Maynard, Baron, Mason, Kadiiska, Stadler, Mouithys-Mickalad, Castranova, Kagan 

2008 2 2

Accumulation of neutrophils and decreased fibrosis in NADPH oxidase-deficient C57BL/6 mice exposed to carbon nanotubes

Shvedova, Kisin, Murray, Kommineni, Castranova, Fadeel, Kagan 

2008 21 115
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 411

APPENDIX F | Summary of the Citation Analysis Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: two faces of janus? Shvedova, Kisin, Porter, Schulte, Kagan, Fadeel, Castranova 2009 58 249

Oxidative interactions of single-walled carbon nanotubes with RAW 264.7 macrophages: role of iron Shvedova, Potapovich, Osipov, Tyurina, Kisin, Schwegler-Berry, Mercer, Castranova, Kagan 2006 189 3865

Critical issues in the evaluation of possible adverse pulmonary effects resulting from airborne nanoparticles

Shvedova, Sager, Murray, Kisin, Porter, Leonard, Schwegler-Berry, Robinson, Castranova 

2007 14 338

Update on carbon nanotube toxicity Simeonova 2009 6 5

Engineered nanoparticle respiratory exposure and potential risks for cardiovascular toxicity: predictive tests and biomarkers

Simeonova, Erdely 2009 9 23

Carbon nanotube exposure and risk for cardiovascular effects

Simeonova, Erdely, Li 2007 4 39

Carbon nanotube respiratory exposure and risk from systemic effects

Simeonova, Li, Erdely 2007 4 39

Nanotechnology: toxicological issues and environmental safety, NATO security through science series book Simeonova, Luster 2007 3 16

Neuroinflammation and blood-brain barrier changes following exposure to engineered nanomaterials

Sriram, Porter, Jefferson, Lin, Wolfarth, Chen, McKinney, Frazer, Castranova 

2009 3 3
412 Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace

APPENDIX F | Summary of the Citation Analysis

Table F–1 (Continued). Summary of the citation analysis.

(continued)

Title Authors

Year 

published

Citations 

(Google)

Secondary 

citations 

Neuroinflammatory responses following exposure to engineered nanomaterials

Sriram, Porter, Tsuruoka, Endo, Jefferson, Wolfarth, Rogers, Castranova, Luster 

2007 6 3

Medical surveillance, exposure registries, and epidemiologic research for workers exposed to nanomaterials

Trout, Schulte 2010 16 9

Potential in vitro effects of carbon nanotubes on human aortic endothelial cells Walker, Li, Hulderman, Schwegler-Berry, Kashon, Simeonova 2009 13 65

Dispersion of single-walled carbon nanotubes by a natural lung surfactant for pulmonary in vitro and in vivo toxicity studies

Wang, Castranova, Mishra, Chen, Mercer, Schwegler-Berry, Rojanasakul 

2010 3 0

Fibrous particle deposition in human and nasal passage: the influence of particle length, flow rate, and geometry of nasal airway

Wang, Hopke, Ahamadi, Cheng, Baron 2008 3 16

Direct fibrogenic effects of dispersed single-walled carbon nanotubes on human lung fibroblasts

Wang, Mercer, Rojanasakul, Qiu, Lu, Scabilloni, Wu, Castranova 

2010 13 48

Shape-enhanced photocatalytic activity of anatase TiO2 (101) nanobelts

Wang, Tafen, Zheng, Lewis, Leonard, Manivannan, Wu 

2010 28 10

Single-walled carbon nanotubes impair human macrophage engulfment of apoptotic cell corpses Witasp, Shvedova, Kagan, Fadeel 2009 6 53Understanding workplace processes and factors that determine exposure to nanomaterials

Woskie, Bello, Virji, Stefaniak 2010 2 1
Filling the Knowledge Gaps for Safe Nanotechnology in the Workplace 413

APPENDIX F | Summary of the Citation Analysis Table F–1 (Continued). Summary of the citation analysis. Title Authors Year published Citations (Google) Secondary citations Decreased dissolution of ZnO by iron doping yields nanoparticles with reduced toxicity in the rodent lung and zebrafish embryos Xia, Zhao, Sager, George, Pokhrel, Li, Schoenfield, Meng, Lin, Wang, Wang, Ji, Zink, Madler, Castranova, Lin, Nel 2011 3 5 SUMMARY 5,135 82,512
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