EPA 100/B-07/001 

February 2007 

U.S. Environmental Protection Agency

Nanotechnology White Paper 

Prepared for the U.S. Environmental Protection Agency 

by members of the Nanotechnology Workgroup, 

a group of EPA’s Science Policy Council

Science Policy Council

U.S. Environmental Protection Agency

Washington, DC 20460
ii EPA Nanotechnology White Paper 

DISCLAIMER 

This document has been reviewed in accordance with U.S. Environmental Protection Agency 

policy and approved for publication and distribution. Mention of trade names or commercial 

products does not constitute endorsement of recommendation for use. Notwithstanding any use 

of mandatory language such as "must" and "require" in this document with regard to or to reflect 

scientific practices, this document does not and should not be construed to create any legal rights 

or requirements. 
EPA Nanotechnology White Paper iii

Nanotechnology White Paper 

Workgroup Co-Chairs 

Jeff Morris 

Office of Research and Development

Jim Willis 

Office of Prevention, Pesticides and 

Toxic Substances 

Science Policy Council Staff 

Kathryn Gallagher 

Office of the Science Advisor 

Subgroup Co-Chairs 

External Coordination 

Steve Lingle, ORD 

Dennis Utterback, ORD 

Ecological Effects 

Anne Fairbrother, ORD 

Tala Henry, OPPTS 

Vince Nabholz, OPPTS 

Risk Management 

Flora Chow, OPPT 

EPA Research Strategy 

Barbara Karn, ORD 

Nora Savage, ORD

Human Exposures 

Scott Prothero, OPPT

Converging Technologies 

Nora Savage, ORD

Risk Assessment 

Phil Sayre, OPPTS 

Environmental Fate 

Bob Boethling, OPPTS 

Laurence Libelo, OPPTS 

John Scalera, OEI 

Pollution Prevention 

Walter Schoepf, Region 2 

Physical-Chemical 

Properties 

Tracy Williamson, OPPTS 

Environmental Detection and 

Analysis 

John Scalera, OEI 

Richard Zepp, ORD 

Sustainability and Society 

Diana Bauer, ORD 

Michael Brody, OCFO 

Health Effects 

Deborah Burgin, OEI 

Kevin Dreher, ORD

Statutes, Regulations, and 

Policies 

Jim Alwood, OPPT

Public Communications 

and Outreach 

Anita Street, ORD
iv EPA Nanotechnology White Paper 

Workgroup Members 

Suzanne Ackerman, OPA Y’Vonne Jones-Brown, OPPTS 

Kent Anapolle, OPPTS Edna Kapust, OPPTS 

Fred Arnold, OPPTS Nagu Keshava, ORD 

Ayaad Assaad, OPPTS David Lai, OPPTS 

Dan Axelrad, OPEI Skip Laitner, OAR 

John Bartlett, OPPTS Warren Layne, Region 5 

Sarah Bauer, ORD Do Young Lee, OPPTS 

Norman Birchfield, OSA Virginia Lee, OPPTS 

John Blouin, OPPT Monique Lester, OARM, on detail to OIA 

Jim Blough, Region 5 Michael Lewandowski, ORD 

Pat Bonner, OPEI Bill Linak, ORD 

William Boyes, ORD David Lynch, OPPTS 

Gordon Cash, OPPTS Tanya Maslak, OSA intern 

Gilbert Castellanos, OIA Paul Matthai, OPPT 

Tai-Ming Chang, Region 3 Carl Mazza, OAR 

Paul Cough, OIA Nhan Nguyen, OPPTS 

Lynn Delpire, OPPTS Carlos Nunez, ORD 

John Diamante, OIA Onyemaechi Nweke, OPEI 

Christine Dibble, OPA Marti Otto, OSWER 

Jeremiah Duncan, AAAS fellow, OPPTS Manisha Patel, OGC 

Thomas Forbes, OEI Steve Potts, OW 

Conrad Flessner, OPPTS Mary Reiley, OW 

Jack Fowle, ORD Mary Ross, OAR 

Elisabeth Freed, OECA Bill Russo, ORD 

Sarah Furtak, OW Mavis Sanders, OEI 

Hend Galal-Gorchev, OW Bernie Schorle, Region 5 

David Giamporcaro, OPPTS Paul Solomon, ORD 

Michael Gill, ORD liaison for Region 9 Timothy Taylor, OSWER 

Collette Hodes, OPPTS Maggie Theroux-Fieldsteel, Region 1 

Gene Jablonowski, Region 5 Stephanie Thornton, OW 

Lee Hofman, OSWER Alan Van Arsdale, Region 1 

Joe Jarvis, ORD William Wallace, ORD 

Barb Walton, ORD 
EPA Nanotechnology White Paper v

Table of Contents 

FOREWORD ................................................................................................................................................... VIII

ACKNOWLEDGMENTS.................................................................................................................................. IX

ACRONYMS.........................................................................................................................................................X

EXECUTIVE SUMMARY ...................................................................................................................................1

1.0 INTRODUCTION ...........................................................................................................................................4

1.1 PURPOSE ........................................................................................................................................................4

1.2 NANOTECHNOLOGY DEFINED ........................................................................................................................5

1.3 WHY NANOTECHNOLOGY IS IMPORTANT TO EPA .......................................................................................13

1.4 NATIONAL AND INTERNATIONAL CONTEXT.................................................................................................14

1.5 WHAT EPA IS DOING WITH RESPECT TO NANOTECHNOLOGY .....................................................................18

1.6 OPPORTUNITIES AND CHALLENGES..............................................................................................................21

2.0 ENVIRONMENTAL BENEFITS OF NANOTECHNOLOGY ................................................................22

2.1 INTRODUCTION ............................................................................................................................................22

2.2 BENEFITS THROUGH ENVIRONMENTAL TECHNOLOGY APPLICATIONS.........................................................22

2.3 BENEFITS THROUGH OTHER APPLICATIONS THAT SUPPORT SUSTAINABILITY .............................................24

3.0 RISK ASSESSMENT OF NANOMATERIALS.........................................................................................29

3.1 INTRODUCTION ............................................................................................................................................29

3.2 CHEMICAL IDENTIFICATION AND CHARACTERIZATION OF NANOMATERIALS ..............................................31

3.3 ENVIRONMENTAL FATE OF NANOMATERIALS..............................................................................................32

3.4 ENVIRONMENTAL DETECTION AND ANALYSIS OF NANOMATERIALS ...........................................................40

3.5 HUMAN EXPOSURES AND THEIR MEASUREMENT AND CONTROL ................................................................42

3.6 HUMAN HEALTH EFFECTS OF NANOMATERIALS..........................................................................................52

3.7 ECOLOGICAL EFFECTS OF NANOMATERIALS................................................................................................58

4.0 RESPONSIBLE DEVELOPMENT.............................................................................................................63

4.1 RESPONSIBLE DEVELOPMENT OF NANOSCALE MATERIALS .........................................................................63

4.2 PROGRAM AREAS.........................................................................................................................................65

4.3 ENVIRONMENTAL STEWARDSHIP .................................................................................................................68

5.0 EPA’S RESEARCH NEEDS FOR NANOMATERIALS ..........................................................................70

5.1 RESEARCH NEEDS FOR ENVIRONMENTAL APPLICATIONS ............................................................................70

5.2 RESEARCH NEEDS FOR RISK ASSESSMENT...................................................................................................72

6.0 RECOMMENDATIONS ..............................................................................................................................82

6.1 RESEARCH RECOMMENDATIONS FOR ENVIRONMENTAL APPLICATIONS ......................................................82

6.2 RESEARCH RECOMMENDATIONS FOR RISK ASSESSMENT.............................................................................83

6.3 RECOMMENDATIONS FOR POLLUTION PREVENTION AND ENVIRONMENTAL STEWARDSHIP.........................89

6.4 RECOMMENDATIONS FOR COLLABORATIONS...............................................................................................90

6.5 RECOMMENDATION TO CONVENE AN INTRA-AGENCY WORKGROUP...........................................................91

6.6 RECOMMENDATION FOR TRAINING..............................................................................................................91

6.7 SUMMARY OF RECOMMENDATIONS .............................................................................................................92

7.0 REFERENCES ..............................................................................................................................................93

APPENDIX A: GLOSSARY OF NANOTECHNOLOGY TERMS .............................................................107

APPENDIX B: PRINCIPLES OF ENVIRONMENTAL STEWARDSHIP BEHAVIOR..........................110

APPENDIX C: EPA’S NANOTECHNOLOGY RESEARCH FRAMEWORK..........................................111

APPENDIX D: EPA STAR GRANTS FOR NANOTECHNOLOGY ..........................................................113
vi EPA Nanotechnology White Paper 

APPENDIX E: LIST OF NANOTECHNOLOGY WHITE PAPER EXTERNAL PEER REVIEWERS AND 

THEIR AFFILIATIONS ..................................................................................................................................119
EPA Nanotechnology White Paper vii

Table of Figures 

FIGURE 1. DIAGRAM INDICATING RELATIVE SCALE OF NANOSIZED OBJECTS......................................................6 

FIGURE 2. GALLIUM PHOSPHIDE (GAP) NANOTREES............................................................................................7 

FIGURE 3. COMPUTER IMAGE OF A C-60 FULLERENE...........................................................................................8 

FIGURE 4. COMPUTER IMAGES OF VARIOUS FORMS OF CARBON NANOTUBES. ....................................................8 

FIGURE 5. “FOREST” OF ALIGNED CARBON NANOTUBES.......................................................................................8 

FIGURE 6. ZINC OXIDE NANOSTRUCTURE SYNTHESIZED BY A VAPOR-SOLID PROCESS........................................9 

FIGURE 7. COMPUTER IMAGE OF AGALLIUM ARSENIDE QUANTUM DOT OF 465 ATOMS.....................................9 

FIGURE 8. COMPUTER IMAGE OF GENERATIONS OF A DENDRIMER......................................................................9 

FIGURE 9. COMPUTER IMAGE OF A NANO-BIO COMPOSITE. ...............................................................................10 

FIGURE 10. PROJECTED STAGES OF NANOTECHNOLOGY DEVELOPMENT..........................................................13 

FIGURE 11. FEDERAL SOURCES TO INFORM EPA’S NANOTECHNOLOGY ACTIVITIES.......................................15 

FIGURE 12. NNI NSET SUBCOMMITTEE STRUCTURE..........................................................................................16 

FIGURE 13. NANOSCALE ZERO-VALENT IRON ENCAPSULATED IN AN EMULSION DROPLET................................22 

FIGURE 14. PIEZORESISTIVE CANTILEVER SENSOR..............................................................................................24 

FIGURE 15. EPA’S RISK ASSESSMENT APPROACH...............................................................................................29 

FIGURE 16. LIFE CYCLE PERSPECTIVE TO RISK ASSESSMENT ...........................................................................30 

FIGURE 17. TRANSMISSION ELECTRON MICROSCOPE (TEM) IMAGE OF AEROSOL-GENERATED TIO2

NANOPARTICLES.....................................................................................................................................................32 

FIGURE 18. ZINC OXIDE NANOSTRUCTURES SYNTHESIZED BY A VAPOR-SOLID PROCESS...................................35 

FIGURE 19. SEM OF A SCANNING GATE PROBE.....................................................................................................42 

FIGURE 20. PARTICLE TOXICOLOGY CITATIONS..................................................................................................53 

FIGURE 21. FLUORESCENT NANOPARTICLES IN WATER FLEA (DAPHNIA MAGNA)..............................................60 

FIGURE 22. EPA OFFICE ROLES ...........................................................................................................................64 

Table of Tables

TABLE 1. EXAMPLES OF PRODUCTS THAT USE NANOTECHNOLOGY AND NANOMATERIALS ............................11 

TABLE 2. OUTCOMES FOR SUSTAINABLE USE OF MAJOR RESOURCES AND RESOURCE SYSTEMS ...................25 

TABLE 3. POTENTIAL U.S. ENERGY SAVINGS FROM EIGHT NANOTECHNOLOGY APPLICATIONS ....................26 

TABLE 4. POTENTIAL SOURCES OF OCCUPATIONAL EXPOSURE FOR VARIOUS SYNTHESIS METHODS ............44 

TABLE 5. EXAMPLES OF POTENTIAL SOURCES OF GENERAL POPULATION AND / OR CONSUMER EXPOSURE FOR 

SEVERAL PRODUCT TYPES ...................................................................................................................................45 

TABLE 6. SUMMARY OF WORKGROUP RECOMMENDATIONS REGARDING NANOMATERIALS...........................92 
viii EPA Nanotechnology White Paper 

FOREWORD 

 

 Nanotechnology presents opportunities to create new and better products. It also has the 

potential to improve assessment, management, and prevention of environmental risks. However, 

there are unanswered questions about the impacts of nanomaterials and nanoproducts on human 

health and the environment. 

 In December 2004, EPA’s Science Policy Council (SPC) formed a cross-Agency 

Nanotechnology Workgroup to develop a white paper examining potential environmental 

applications and implications of nanotechnology. This document describes the issues that EPA 

should consider to ensure that society benefits from advances in environmental protection that 

nanotechnology may offer, and to understand and address any potential risks from environmental 

exposure to nanomaterials. Nanotechnology will have an impact across EPA. Agency managers 

and staff are working together to develop an approach to nanotechnology that is forward thinking 

and informs the risk assessment and risk management activities in our program and regional 

offices. This document is intended to support that cross-Agency effort. 

 We would like to acknowledge and thank the Nanotechnology Workgroup subgroup cochairs and members and for their work in developing this document. We would especially like 

to acknowledge the Workgroup co-chairs Jim Willis and Jeff Morris for leading the workgroup 

and document development. We also thank SPC staff task lead Kathryn Gallagher, as well as 

Jim Alwood, Dennis Utterback, and Jeremiah Duncan for their efforts in assembling and refining 

the document. 

 It is with pleasure that we provide the EPA Nanotechnology White Paper to promote the 

use of this new, exciting technology in a manner that protects human health and the environment. 

William H. Benson Charles M. Auer 

Acting Chief Scientist Director, Office of Pollution 

Office of the Science Advisor Prevention and Toxics 
EPA Nanotechnology White Paper ix

ACKNOWLEDGMENTS 

 The Nanotechnology Workgroup would like to acknowledge the Science Policy Council 

and its Steering Committee for their recommendations and contributions to this document. We 

thank Paul Leslie of TSI Incorporated, and Laura Morlacci, Tom Webb and Peter McClure of 

Syracuse Research Corporation for their support in developing background information for the 

document. We also thank the external peer reviewers (listed in an appendix) for their comments 

and suggestions. Finally, the workgroup would like to thank Bill Farland and Charles Auer for 

their leadership and vision with respect to nanotechnology. 
x EPA Nanotechnology White Paper 

ACRONYMS 

ADME Absorption, Distribution, Metabolism, Elimination 

ANSI American National Standards Institute 

ASTM American Society for Testing and Materials 

CAA Clean Air Act 

CAAA Clean Air Act Amendments 

CAS Chemical Abstracts Service 

CDC Centers for Disease Control and Prevention 

CERCLA Comprehensive Environmental Response, Compensation and Liability Act 

CFCs Chlorofluorocarbons 

ChemSTEER Chemical Screening Tool for Exposures and Environmental Releases 

CNT Carbon nanotubes 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DfE Design for Environment 

DHHS Department of Health and Human Services 

DHS Department of Homeland Security 

DNA Deoxyribonucleic Acid 

DOC Department of Commerce 

DOE Department of Energy 

DOI Department of Interior 

DOJ Department of Justice 

DOS Department of State 

DOT Department of Transportation 

DOTreas Department of the Treasury 

E-FAST Exposure and Fate Assessment Screening Tool 

EPA Environmental Protection Agency 

EPCRA Emergency Planning and Community Right-to-Know Act 

FDA Food and Drug Administration 

FIFRA Federal Insecticide, Fungicide and Rodenticide Act 

GI Gastrointestinal 

GST Glutathione-S-Transferase 

HAPEM Hazardous Air Pollutant Exposure Model 

HAPs Hazardous Air Pollutants 

HEPA High Efficiency Particulate Air 

HPV High Production Volume 

IAC Innovation Action Council 

ISO International Organization for Standardization 

ITIC Intelligence Technology Information Center 

Kow Octanol-Water Partition Coefficient 

LCA Life Cycle Assessment 

LEDs Light Emitting Diodes 

MCLGs Maximum Contaminant Level Goals 
EPA Nanotechnology White Paper xi

MCLs Maximum Contaminant Levels 

MFA Material Flow Analysis 

MW Molecular Weight 

NAAQS National Ambient Air Quality Standards 

NASA National Aeronautics and Space Administration 

NCEI National Center for Environmental Innovation 

NCER National Center for Environmental Research 

NEIC National Enforcement Investigations Center 

NEHI Nanotechnology Environmental and Health Implications (NNI work group) 

NERL National Exposure Research Laboratory 

NHEERL National Health and Environmental Effects Research Laboratory 

NHEXAS National Human Exposure Assessment Survey 

NIH National Institutes of Health 

NIOSH National Institute for Occupational Safety and Health 

NNAP National Nanotechnology Advisory Panel 

NNCO National Nanotechnology Coordinating Office 

NNI National Nanotechnology Initiative 

NOx Nitrogen oxides 

NRC National Research Council 

NRML National Risk Management laboratory 

NSET NSTC Committee on Technology, Subcommittee on Nanoscale Science, 

 Engineering and Technology 

NSF National Science Foundation 

NSTC National Science and Technology Council 

NTP National Toxicology Program (DHHS) 

OAR Office of Air and Radiation 

OARM Office of Administration and Resource Management 

OCFO Office of the Chief Financial Officer 

OCIR Office of Congressional and Intergovernmental Relations 

OECA Office of Enforcement and Compliance Assurance 

OECD Organisation for Economic Co-operation and Development 

OEM Original Equipment Manufacturers 

OEI Office of Environmental Information 

OIA Office of International Affairs 

OLEDs Organic Light Emitting Diodes 

OPA Office of Public Affairs 

OPA Oil Pollution Act 

OPEI Office of Policy, Economics and Innovation 

OPPT Office of Pollution Prevention and Toxics 

OPPTS Office of Prevention, Pesticides and Toxic Substances 

ORD Office of Research and Development 

OSA Office of the Science Advisor 

OSHA Occupational Safety and Health Administration 

OSTP Office of Science and Technology Policy (Executive Office of the President) 

OSWER Office of Solid Waste and Emergency Response 

OW Office of Water 
xii EPA Nanotechnology White Paper 

PCAST President's Council of Advisors on Science and Technology 

PCBs Polychlorinated Biphenyls 

PM Particulate Matter 

PMN Premanufacture Notice 

PPE Personal Protective Equipment 

QSAR Quantitative Structure Activity Relationship 

RCRA Resource Conservation and Recovery Act 

SAMMS Self-Assembled Monolayers on Mesoporous Supports 

SAR Structure Activity Relationship 

SDWA Safe Drinking Water Act 

SDWIS Safe Drinking Water Information System 

SEM Scanning Electron Microscopy 

SFA Substance Flow Analysis 

SPC Science Policy Council 

STAR Science To Achieve Results 

STM Scanning Tunneling Microscope 

SWCNT Single-Walled Carbon Nanotubes 

TOC Total Organic Carbon 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

USDA US Department of Agriculture 

USPTO US Patent and Trade Office 

UST Underground Storage Tank 

ZVI Zero-Valent Iron 
EPA Nanotechnology White Paper 1

EXECUTIVE SUMMARY 

Nanotechnology has potential applications in many sectors of the American economy, 

including consumer products, health care, transportation, energy and agriculture. In addition, 

nanotechnology presents new opportunities to improve how we measure, monitor, manage, and 

minimize contaminants in the environment. While the U.S. Environmental Protection Agency 

(EPA, or “the Agency”) is interested in researching and developing the possible benefits of 

nanotechnology, EPA also has the obligation and mandate to protect human health and safeguard 

the environment by better understanding and addressing potential risks from exposure to 

nanoscale materials and products containing nanoscale materials (both referred to here as 

“nanomaterials”). 

Since 2001, EPA has played a leading role in funding research and setting research 

directions to develop environmental applications for, and understand the potential human health 

and environmental implications of, nanotechnology. That research has already borne fruit, 

particularly in the use of nanomaterials for environmental clean-up and in beginning to 

understand the disposition of nanomaterials in biological systems. Some environmental 

applications using nanotechnology have progressed beyond the research stage. Also, a number 

of specific nanomaterials have come to the Agency’s attention, whether as novel products 

intended to promote the reduction or remediation of pollution or because they have entered one 

of EPA’s regulatory review processes. For EPA, nanotechnology has evolved from a futuristic 

idea to watch, to a current issue to address. 

In December 2004, EPA’s Science Policy Council created a cross-Agency workgroup 

charged with describing key science issues EPA should consider to ensure that society accrues 

the important benefits to environmental protection that nanotechnology may offer, as well as to 

better understand any potential risks from exposure to nanomaterials in the environment. This 

paper is the product of that workgroup. 

The purpose of this paper is to inform EPA management of the science needs associated 

with nanotechnology, to support related EPA program office needs, and to communicate these 

nanotechnology science issues to stakeholders and the public. The paper begins with an 

introduction that describes what nanotechnology is, why EPA is interested in it, and what 

opportunities and challenges exist regarding nanotechnology and the environment. It then moves 

to a discussion of the potential environmental benefits of nanotechnology, describing 

environmental technologies as well as other applications that can foster sustainable use of 

resources. The paper next provides an overview of existing information on nanomaterials 

regarding components needed to conduct a risk assessment. Following that there is a brief 

section on responsible development and the Agency’s statutory mandates. The paper then 

provides an extensive review of research needs for both environmental applications and 

implications of nanotechnology. To help EPA focus on priorities for the near term, the paper 

concludes with staff recommendations for addressing science issues and research needs, and 

includes prioritized research needs within most risk assessment topic areas (e.g., human health 

effects research, fate and transport research). In a separate follow-up effort to this White Paper, 
2 EPA Nanotechnology White Paper 

EPA’s Nanotechnology Research Framework, attached in Appendix C of this paper, was 

developed by EPA's Office of Research and Development (ORD) Nanotechnology Research 

Strategy Team. This team is composed of representatives from across ORD. The 

Nanotechnology Research Framework outlines how EPA will strategically focus its own 

research program to provide key information on potential environmental impacts from human or 

ecological exposure to nanomaterials in a manner that complements other federal, academic, and 

private-sector research activities. Additional supplemental information is provided in a number 

of other appendices. 

Key Nanotechnology White Paper recommendations include: 

• Environmental Applications Research. The Agency should continue to undertake, 

collaborate on, and support research to better understand and apply information regarding 

environmental applications of nanomaterials. 

• Risk Assessment Research. The Agency should continue to undertake, collaborate on, 

and support research to better understand and apply information regarding 

nanomaterials’: 

o chemical and physical identification and characterization, 

o environmental fate, 

o environmental detection and analysis, 

o potential releases and human exposures, 

o human health effects assessment, and 

o ecological effects assessment. 

To ensure that research best supports Agency decision making, EPA should conduct 

case studies to further identify unique risk assessment considerations for 

nanomaterials. 

 

• Pollution Prevention, Stewardship, and Sustainability. The Agency should engage 

resources and expertise to encourage, support, and develop approaches that promote 

pollution prevention, sustainable resource use, and good product stewardship in the 

production, use and end of life management of nanomaterials. Additionally, the Agency 

should draw on new, “next generation” nanotechnologies to identify ways to support 

environmentally beneficial approaches such as green energy, green design, green 

chemistry, and green manufacturing.

• Collaboration and Leadership. The Agency should continue and expand its 

collaborations regarding nanomaterial applications and potential human health and 

environmental implications. 

• Intra-Agency Workgroup. The Agency should convene a standing intra-Agency group 

to foster information sharing on nanotechnology science and policy issues. 
EPA Nanotechnology White Paper 3

• Training. The Agency should continue and expand its nanotechnology training activities 

for scientists and managers. 

 Nanotechnology has emerged as a growing and rapidly changing field. New generations 

of nanomaterials will evolve, and with them new and possibly unforeseen environmental issues. 

It will be crucial that the Agency’s approaches to leveraging the benefits and assessing the 

impacts of nanomaterials continue to evolve in parallel with the expansion of and advances in 

these new technologies. 
4 EPA Nanotechnology White Paper 

1.0 Introduction 

1.1 Purpose 

 Nanotechnology presents potential opportunities to create better materials and products. 

Already, nanomaterial-containing products are available in U.S. markets including coatings, 

computers, clothing, cosmetics, sports equipment and medical devices. A survey by EmTech 

Research of companies working in the field of nanotechnology has identified approximately 80 

consumer products, and over 600 raw materials, intermediate components and industrial 

equipment items that are used by manufacturers (Small Times Media, 2005). A second survey 

by the Project on Emerging Nanotechnologies at the Woodrow Wilson International Center for 

Scholars lists over 300 consumer products (http://www.nanotechproject.org/index.php?id=44 or 

http://www.nanotechproject.org/consumerproducts). Our economy will be increasingly affected 

by nanotechnology as more products containing nanomaterials move from research and 

development into production and commerce. 

Nanotechnology also has the potential to improve the environment, both through direct 

applications of nanomaterials to detect, prevent, and remove pollutants, as well as indirectly by 

using nanotechnology to design cleaner industrial processes and create environmentally 

responsible products. However, there are unanswered questions about the impacts of 

nanomaterials and nanoproducts on human health and the environment, and the U.S. 

Environmental Protection Agency (EPA or “the Agency”) has the obligation to ensure that 

potential risks are adequately understood to protect human health and the environment. As 

products made from nanomaterials become more numerous and therefore more prevalent in the 

environment, EPA is thus considering how to best leverage advances in nanotechnology to 

enhance environmental protection, as well as how the introduction of nanomaterials into the 

environment will impact the Agency’s environmental programs, policies, research needs, and 

approaches to decision making. 

In December 2004, the Agency’s Science Policy Council convened an intra-Agency 

Nanotechnology Workgroup and charged the group with developing a white paper to examine 

the implications and applications of nanotechnology. This document describes key science 

issues EPA should consider to ensure that society accrues the benefits to environmental 

protection that nanotechnology may offer and that the Agency understands and addresses 

potential risks from environmental exposure to nanomaterials. 
EPA Nanotechnology White Paper 5

 The purpose of this paper is to inform EPA management of the science needs associated 

with nanotechnology, to support related EPA program office needs, and to communicate these 

nanotechnology science issues to stakeholders and the public. The paper begins with an 

introduction that describes what nanotechnology is, why EPA is interested in it, and what 

opportunities and challenges exist regarding nanotechnology and the environment. It then moves 

to a discussion of the potential environmental benefits of nanotechnology, describing 

environmental technologies as well as other applications that can foster sustainable use of 

resources. The paper next provides an overview of existing information on nanomaterials 

regarding components needed to conduct a risk assessment. Following that is a brief section on 

responsible development and the Agency’s statutory mandates. The paper then provides an 

extensive review of research needs for both environmental applications and implications of 

nanotechnology. To help EPA focus on priorities for the near term, the paper concludes with 

staff recommendations for addressing science issues and research needs, and includes prioritized 

research needs within most risk assessment topic areas (e.g., human health effects research, fate 

and transport research). In a separate follow-up effort to this White Paper, EPA’s 

Nanotechnology Research Framework, attached in Appendix C of this paper, was developed by 

EPA's Office of Research and Development (ORD) Nanotechnology Research Strategy Team. 

This team is composed of representatives from across ORD. The Nanotechnology Research 

Framework outlines how EPA will strategically focus its own research program to provide key 

information on potential environmental impacts from human or ecological exposure to 

nanomaterials in a manner that complements other federal, academic, and private-sector research 

activities. Additional supplemental information is provided in a number of additional 

appendices. 

A discussion of an entire technological process or series of processes, as is 

nanotechnology, could be wide ranging. However, because EPA operates through specific 

programmatic activities and mandates, this document confines its discussion of nanotechnology 

science issues within the bounds of EPA’s statutory responsibilities and authorities. In 

particular, the paper discusses what scientific information EPA will need to address 

nanotechnology in environmental decision making. 

1.2 Nanotechnology Defined 

 A nanometer is one billionth of a meter (10-9 m)—about one hundred thousand times 

smaller than the diameter of a human hair, a thousand times smaller than a red blood cell, or 

about half the size of the diameter of DNA. Figure 1 illustrates the scale of objects in the 

nanometer range. For the purpose of this document, nanotechnology is defined as: research and 

technology development at the atomic, molecular, or macromolecular levels using a length scale 

of approximately one to one hundred nanometers in any dimension; the creation and use of 

structures, devices and systems that have novel properties and functions because of their small 

size; and the ability to control or manipulate matter on an atomic scale. This definition is based 

on part on the definition of nanotechnology used by the National Nanotechnology Initiative 

(NNI), a U.S. government initiative launched in 2001 to coordinate nanotechnology research and 

development across the federal government (NNI, 2006a, b, c). 
6 EPA Nanotechnology White Paper 

Figure 1. Diagram indicating relative scale of nanosized objects. (From NNI website, courtesy Office of Basic Energy Sciences, U.S. Department of Energy.) 
EPA Nanotechnology White Paper 7

 Nanotechnology is the manipulation of matter for use in particular applications through 

certain chemical and / or physical processes to create materials with specific properties. There 

are both "bottom-up" processes (such as self-assembly) that create nanoscale materials from 

atoms and molecules, as well as "top-down" processes (such as milling) that create nanoscale 

materials from their macro-scale counterparts. Figure 2 shows an example of a nanomaterial 

assembled through “bottom-up” processes. Nanoscale materials that have macro-scale 

counterparts frequently display different or enhanced properties compared to the macro-scale 

form. For the remainder of this document such 

engineered or manufactured nanomaterials will be 

referred to as “intentionally produced nanomaterials,” o

simply “nanomaterials.” The definition of 

nanotechnology does not include unintentionally 

produced nanomaterials, such as diesel exhaust particles 

or other friction or airborne combustion byproducts, or 

nanosized materials that occur naturally in the 

environment, such as viruses or volcanic ash. Where 

information from incidentally formed or natural 

nanosized materials (such as ultrafine particulate m

may aid in the understanding of intentionally produced

nanomaterials, this information will be discussed, but 

the focus of this document is on intentionally pr

nanomaterials. 

r 

atter) 

oduced 

Figure 2. Gallium Phosphide (GaP) 

Nanotrees. 

Semiconductor nanowires produced by 

controlled seeding, vapor-liquid-solid 

self-assembly. Bottom-up processes used 

to produce materials such as these allow 

for control over size and morphology. 

(Image used by permission, Prof. Lars 

Samuelson, Lund University, Sweden. 

[Dick et al. 2004]) 

 There are many types of intentionally produced 

nanomaterials, and a variety of others are expected to 

appear in the future. For the purpose of this document, 

most current nanomaterials could be organized into four 

types: 

(1) Carbon-based materials. These nanomaterials are composed mostly of carbon, most 

commonly taking the form of a hollow spheres, ellipsoids, or tubes. Spherical and ellipsoidal 

carbon nanomaterials are referred to as fullerenes, while cylindrical ones are called nanotubes. 

These particles have many potential applications, including improved films and coatings, 

stronger and lighter materials, and applications in electronics. Figures 3, 4, and 5 show examples 

of carbon-based nanomaterials. 
8 EPA Nanotechnology White Paper 

Figure 5. “Forest” of aligned carbon nanotubes. 

(Image courtesy David Carnahan of NanoLab, Inc.) 

Figure 3. Computer image of a 

C-60 Fullerene. U.S. EPA.

Figure 4. Computer images of various 

forms of carbon nanotubes. 

(Images courtesy of Center for Nanoscale 

Materials, Argonne National Laboratory)

(2) Metal-based materials. These nanomaterials include quantum dots, nanogold, nanosilver 

and metal oxides, such as titanium dioxide. A quantum dot is a closely packed semiconductor 

crystal comprised of hundreds or thousands of atoms, and whose size is on the order of a few 

nanometers to a few hundred nanometers. Changing the size of quantum dots changes their 

optical properties. Figures 6 and 7 show examples of metal-based nanomaterials. 
EPA Nanotechnology White Paper 9

Figure 6. Zinc oxide nanostructure 

synthesized by a vapor-solid process. 

(Image courtesy of Prof. Zhong Lin Wang, 

Georgia Tech) 

Figure 7. Computer image of a Gallium 

arsenide quantum dot of 465 atoms. 

(Image courtesy of Lin-Wang Wang, 

Lawrence Berkeley National Laboratory) 

 (3) Dendrimers. These nanomaterials are nanosized polymers built from branched units. The 

surface of a dendrimer has numerous chain ends, which can be tailored to perform specific 

chemical functions. This property could also be useful for catalysis. Also, because threedimensional dendrimers contain interior cavities into which other molecules could be placed, 

they may be useful for drug delivery. Figure 8 shows an example a dendrimer. 

Figure 8. Computer image of generations of a dendrimer. 

Dendrimers are nanoscale branched polymers that are grown in a stepwise fashion, which 

allows for precise control of their size. (Image courtesy of Dendritic NanoTechnologies, 

Inc.) 
10 EPA Nanotechnology White Paper 

(4) Composites combine nanoparticles with other nanoparticles or 

with larger, bulk-type materials. Nanoparticles, such as nanosized 

clays, are already being added to products ranging from auto parts 

to packaging materials, to enhance mechanical, thermal, barrier, 

and flame-retardant properties. Figure 9 shows an example of a 

composite. 

 The unique properties of these various types of 

intentionally produced nanomaterials give them novel electrical, 

catalytic, magnetic, mechanical, thermal, or imaging features that 

are highly desirable for applications in commercial, medical, 

military, and environmental sectors. These materials may also 

find their way into more complex nanostructures and systems as 

described in Figure 10. As new uses for materials with these 

special properties are identified, the number of products 

containing such nanomaterials and their possible applications 

continues to grow. Table 1 lists some examples of 

nanotechnology products listed in the Woodrow Wilson Center 

Consumer Products Inventory 

(http://www.nanotechproject.org/44/consumer-nanotechnology). There are estimates that global 

sales of nanomaterials could exceed $1 trillion by 2015 (M.C. Roco, presentation to the National 

Research Council, 23 March 2005, presentation available at 

http://www.nsf.gov/crssprgm/nano/reports/nnipres.jsp). 

Figure 9. Computer image of a 

nano-biocomposite. 

Image of a titanium molecule 

(center) with DNA strands 

attached, a bio-inorganic 

composite. This kind of material 

has potential for new 

technologies to treat disease. 

(Image courtesy of Center for 

Nanoscale Materials, Argonne 

National Lab) 
EPA Nanotechnology White Paper 11

Table 1. Examples of Products that Use Nanotechnology and Nanomaterials 

Health and 

Fitness 

Electronics and 

Computers 

Home and 

Garden 

Food and 

Beverage 

Other 

Wound dressing 

Pregnancy test 

Toothpaste 

Golf club 

Tennis Racket 

Skis 

Antibacterial 

socks 

Waste and stain 

resistant pants 

Cosmetics 

Air filter 

Sunscreen 

Computer 

displays 

Games 

Computer 

hardware 

Paint 

Antimicrobial 

pillows 

Stain resistant 

cushions 

Non-stick 

coatings for pans 

Antimicrobial 

refrigerator 

Canola oil 

Coatings 

Lubricants 

Source: Woodrow Wilson Center Consumer Products Inventory. 

(http://www.nanotechproject.org/44/consumer-nanotechnology) 

1.2.1 Converging Technologies 

In the long-term, nanotechnology will likely be increasingly discussed within the context 

of the convergence, integration, and synergy of nanotechnology, biotechnology, information 

technology, and cognitive technology. Convergence involves the development of novel products 

with enhanced capabilities that incorporate bottom-up assembly of miniature components with 

accompanying biological, computational and cognitive capabilities. The convergence of 

nanotechnology and biotechnology, already rapidly progressing, will result in the production of 

novel nanoscale materials. The convergence of nanotechnology and biotechnology with 

information technology and cognitive science is expected to rapidly accelerate in the coming 

decades. The increased understanding of biological systems will provide valuable information 

towards the development of efficient and versatile biomimetic tools, systems, and architecture. 

Generally, biotechnology involves the use of microorganisms, or bacterial factories, 

which contain inherent “blueprints” encoded in the DNA, and a manufacturing process to 

produce molecules such as amino acids. Within these bacterial factories, the organization and 
12 EPA Nanotechnology White Paper 

self-assembly of complex molecules occurs routinely. Many “finished” complex cellular 

products are < 100 nanometers. For this reason, bacterial factories may serve as models for the 

organization, assembly and transformation for other nanoscale materials production. 

Bacterial factory blueprints are also flexible. They can be modified to produce novel 

nanobiotechnology products that have specific desired physical-chemical (performance) 

characteristics. Using this production method could be a more material and energy efficient way 

to make new and existing products, in addition to using more benign starting materials. In this 

way, the convergence of nano- and biotechnologies could improve environmental protection. As 

an example, researchers have extracted photosynthetic proteins from spinach chloroplasts and 

coated them with nanofilms that convert sunlight to electrical current, which one day may lead to 

energy generating films and coatings (Das et al., 2004). The addition of information and 

cognitive capabilities will provide additional features including programmability, 

miniaturization, increased power capacities, adaptability, and reactive, self-correcting capacities. 

 Another example of converging technologies is the development of nanometer-sized 

biological sensor devices that can detect specific compounds within the natural environment; 

store, tabulate, and process the accumulated data; and determine the import of the data, providing 

a specific response for the resolved conditions would enable rapid and effective human health 

and environmental protection. Responses could range from the release of a certain amount of 

biological or chemical compound, to the removal or transformation of a compound. 

The convergence of nanotechnology with biotechnology and with information and 

cognitive technologies may provide such dramatically different technology products that the 

manufacture, use and recycling/disposal of these novel products, as well as the development of 

policies and regulations to protect human health and the environment, may prove to be a 

daunting task. 

The Agency is committed to keeping abreast of emerging issues within the environmental 

arena, and continues to support critical research, formulate new policies, and adapt existing 

policies as needed to achieve its mission. However, the convergence of these technologies will 

demand a flexible, rapid and highly adaptable approach within EPA. As these technologies 

progress and as novel products emerge, increasingly the Agency will find that meeting constantly 

changing demands depends on taking proactive actions and planning. 

We may be nearing the end of basic research and development on the first generation of 

materials resulting from nanotechnologies that include coatings, polymers, more reactive 

catalysts, etc. (Figure 10). The second generation, which we are beginning to enter, involves 

targeted drug delivery systems, adaptive structures and actuators, and has already provided some 

interesting examples. The third generation, anticipated within the next 10-15 years, is predicted 

to bring novel robotic devices, three-dimensional networks and guided assemblies. The fourth 

stage is predicted to result in molecule-by-molecule design and self-assembly capabilities. 

Although it is not likely to happen for some time, this integration of these fourth-generation 

nanotechnologies with information, biological, and cognitive technologies will lead to products 

which can now only be imagined. While the Agency will not be able to predict the future, it 

needs to prepare for it. Towards that aim, understanding the unique challenges and opportunities 
EPA Nanotechnology White Paper 13

afforded by converging technologies before they occur will provide the Agency with the 

essential tools for the effective and appropriate response to emerging technology and science. 

.3 Why Nanotechnology Is Important to EPA 

Nanotechnology holds great promise for creating new materials with enhanced properties 

nd attributes. These properties, such as greater catalytic efficiency, increased electrical 

onductivity, and improved hardness and strength, are a result of nanomaterials’ larger surface 

rea per unit of volume and quantum effects that occur at the nanometer scale (“nanoscale”). 

anomaterials are already being used or tested in a wide range of products such as sunscreens, 

omposites, medical and electronic devices, and chemical catalysts. Similar to nanotechnology’s 

ccess in consumer products and other sectors, nanomaterials have promising environmental 

pplications. For example, nanosized cerium oxide has been developed to decrease diesel 

missions, and iron nanoparticles can remove contaminants from soil and ground water. 

anosized sensors hold promise for improved detection and tracking of contaminants. In these 

nd other ways, nanotechnology presents an opportunity to improve how we measure, monitor, 

anage, and reduce contaminants in the environment. 

Some of the same special properties that make nanomaterials useful are also properties 

at may cause some nanomaterials to pose hazards to humans and the environment, under 

Nano-structured coatings, nanoparticles, nanostructured metals, polymers, ceramics,

Catalysts, composites, displays

First Generation ~2001: Passive nanostructures

Transistors, amplifiers, targeted drugs and chemicals, actuators, adaptive 

structures, sensors, diagnostic assays, fuel cells, solar cells, high performance 

nanocomposites, ceramics, metals

Second Generation ~Now: Active nanostructures

Various assembly techniques, networking at the nanoscale and new architectures,

Biomimetic materials, novel therapeutics/targeted drug delivery

Third Generation ~ 2010: 3-D nanosystems and systems of nanosystems

Technological Complexity

increasing

Fourth Generation ~2015 Molecular Nanosystems

Molecular devices ”by design”, atomic design, emerging functions

Figure 10. Projected Stages of Nanotechnology Development. 

This analyis of the projected stages of nanotechnology development was first conceptualized by 

M.C. Roco. 

1

a

c

a

N

c

su

a

e

N

a

m

th
14 EPA Nanotechnology White Paper 

specific conditions. Some nanomaterials that enter animal tissues may be able to pass through 

ell membranes or cross the blood-brain barrier. This may be a beneficial characteristic for such 

ses as targeted drug delivery and other disease treatments, but could result in unintended 

pacts in other uses or applications. Inhaled nanoparticles may become lodged in the lung or 

e translocated, and the high durability and reactivity of some nanomaterials raise issues of their 

te in the environment. It may be that in most cases nanomaterials will not be of human health 

r ecological concern. However, at this point not enough information exists to assess 

nvironmental exposure for most engineered nanomaterials. This information is important 

ecause EPA will need a sound scientific basis for assessing and managing any unforeseen future 

impacts resulting from the introduction of nanoparticles and nanomaterials into the environment. 

 A challenge for environmental protection is to help fully realize the societal benefits of 

Figure 11 lists examples of federal 

ources of information and interaction to inform EPA’s nanotechnology activities. Many sectors, 

cludi

 and 

c

u

im

b

fa

o

e

b

nanotechnology while identifying and minimizing any adverse impacts to humans or ecosystems 

from exposure to nanomaterials. In addition, we need to understand how to best apply 

nanotechnology for pollution prevention in current manufacturing processes and in the 

manufacture of new nanomaterials and nanoproducts, as well as in environmental detection, 

monitoring, and clean-up. This understanding will come from scientific information generated 

by environmental research and development activities within government agencies, academia, 

and the private sector. 

1.4 National and International Context 

 EPA’s role in nanotechnology exists within a range of activities by federal agencies and 

other groups that have been ongoing for several years. 

s

in ng U.S. federal and state agencies, academia, the private-sector, other national 

governments, and international bodies, are considering potential environmental applications

implications of nanotechnology. This section describes some of the major players in this arena,

for two principal reasons: to describe EPA’s role regarding nanotechnology and the 

environment, and to identify opportunities for collaborative and complementary efforts. 
EPA Nanotechnology White Paper 15

Understanding Nanotechnology Implications

Applications

EPA

Research 

Risk assessment

Risk management

Sustainability

Stewardship

Toxicity

DOD

EPA

FDA

NIH

NIOSH

NSF

Fate, Transport, 

Transformation,

Release, 

Treatment

DOD

DOE

EPA

NIH

NIOSH

NSF

Detection, 

Monitoring

DOD

EPA

NIH

NIOSH

NSF

USGS

Pollution 

Prevention

Green manufacturing

Green Engineering

Green Energy

EPA

DOD

DOE

Remediation

EPA

DHS

DOD

NASA

NSF

Sensors, Devices

DHS

DOD

DOE

EPA

NASA

NIH

NIOSH

NIST

NSF

USDA

USGS

Characterization, 

Properties

DOD

DOE

EPA 

NASA

NIH

NIST

NSF

Instrumentation, 

Metrology, 

Standards

DOD

DOE

NASA

NIH

NIST

NSF

Note: NIH includes NIEHS, NCI (NCL), NTP

igure 11. Federal Sources to Inform EPA’s Nanotechnology Activities. 

ased on information in the NNI Supplement to the 2006 and 2007 budget and other information.) 

al Nanotechnology Initiative 

The National Nanotechnology Initiative (NNI) was launched in 2001 to coordinate 

anotechnology research and development across the federal government. Investments into 

derally funded nanotechnology-related activities, coordinated through the NNI, have grown 

rom $464 million in 2001 to approximately $1.3 billion in 2006. 

 new nanoscale materials, and the development of nanotechnology-based devices 

ology, standards, and 

nanoscale manufacturing. Most important to EPA, the NNI has made responsible development 

of this 

NI, thirteen of which have 

udgets which include to nanotechnology research and development. The other twelve agencies 

ave m

F

(B

1.4.1 Federal Agencies – The Nation

n

fe

f

 The NNI supports a broad range of research and development including fundamental 

research on the unique phenomena and processes that occur at the nano scale, the design and 

discovery of

and systems. The NNI also supports research on instrumentation, metr

new technology a priority by supporting research on environmental health and safety

implications. 

 Twenty-five federal agencies currently participate in the N

b

h ade nanotechnology relevant to their missions or regulatory roles. Only a small part of

this federal investment aims at researching the social and environmental implications of 

nanotechnology including its effects on human health, the environment, and society. Nine 
16 EPA Nanotechnology White Paper 

federal agencies are investing in implications research including the National Science 

Foundation, the National Institutes of Health, the National Institute for Occupational Health and 

Safety, and the Environmental Protection Agency. These agencies coordinate their efforts 

through the NNI’s Nanoscale Science, Engineering, and Technology Subcommittee (NSET) and 

s Nanotechnology Environmental Health Implications workgroup (NEHI) (Figure 12). The 

 the 

s 

Figure 12. NNI NSET Subcommittee Structure 

1.4.2 Efforts of Other Stakeholders 

About $2 billion in annual research and development investment are being spent by nonfederal U.S. sectors such as states, academia, and private industry. State governments 

collectively spent an estimated $400 million on facilities and research aimed at the development 

of local nanotechnology industries in 2004 (Lux Research, 2004). 

it

President’s Council of Advisors on Science and Technology (PCAST) has been designated as

national Nanotechnology Advisory Panel called for by the 21st Century Nanotechnology 

Research and Development Act of 2003. As such, PCAST is responsible for assessing and 

making recommendations for improving the NNI, including its activities to address 

environmental and other societal implications. The National Research Council also provide

assessments and advice to the NNI. 

 Work under the NNI can be monitored through the website http://www.nano.gov. 

NRC Review of the NNI – August 25-26, 2005 ECTeague NNCO/ NSET/ NSTC 

NSET Subcommittee Working Level Interactions NSET Subcommittee Working Level Interactions

NNCO

Office of Science and 

Technology Policy 24 Agencies Participating in NNI

Industry Sectors

House of Representatives 

Committee on Science 

Senate Committee on 

Commerce, Science and 

Transportation

Press 

National Research 

Council

Office of Management 

and Budget

NNAP (PCAST)

Professional 

Societies

International 

Organizations NSET 

Subcomm.

Working Groups and 

Task Forces of NSET 

Subcommittee

GIN 

WG

NEHI 

WG

Non-governmental 

Organizations NILI 

WG

NPEG 

WG

Regional, State, and Local 

Nanotechnology Initiatives 
EPA Nanotechnology White Paper 17

 Although the industry is relatively new, the private sector is leading a number of 

initiatives. Several U.S. nanotechnology trade associations have emerged, including the 

NanoBusiness Alliance. The American Chemistry Council also has a committee devoted to 

nanotechnology and is encouraging research into the environmental health and safety of 

nanomaterials. In addition, the Nanoparticle Occupational Safety and Health Consortium has 

been formed by industry to investigate occupational safety and health issues associated with 

aerosol nanoparticles and workplace exposure monitoring and protocols. A directory of 

nanotechnology industry-related organizations can be found at http://www.nanovip.com. 

 Environmental nongovernmental organizations (NGOs) such as Environmental Defense, 

Greenpeace UK, ETC Group, and the Natural Resources Defense Council are engaged in 

nanotechnology issues. Also, scientific organizations such as the National Academy of Sciences, 

the Royal Society of the United Kingdom, and the International Life Sciences Institute are 

providing important advice on issues related to nanotechnology and the environment. 

1.4.3 International Activities 

 Fully understanding the environmental applications and implications of nanotechnology 

will depend on the concerted efforts of scientists and policy makers across the globe. Europe 

and Asia match or exceed the U.S. federal nanotechnology research budget. Globally, 

nanotechnology research and development spending is estimated at around $9 billion (Lux 

Research, 2006). Thus, a great opportunity exists for internationally coordinated and integrated 

fforts toward environmental research. Other governments have also undertaken efforts to 

 (UK) Department for Environment, 

Food and Rural Affairs, 2005; European Union Scientific Committee on Emerging and Newly 

), 2005). International organizations such as the 

International Standards Organization and the Organisation for Economic Co-operation and 

Develo

mittee, 

st methodologies, modeling 

nd simulation, and science-based health, safety and environmental practices. 

als 

 the 

ational 

tific 

nd Technology Policy is considering establishing a subsidiary body to address other issues 

mong 

e

identify research needs for nanomaterials (United Kingdom

Identified Health Risks (EU SCENIHR

pment (OECD) are engaged in nanotechnology issues. ISO has established a technical 

committee to develop international standards for nanotechnologies. This technical com

ISO/TC 229 will develop standards for terminology and nomenclature, metrology and 

instrumentation, including specifications for reference materials, te

a

 The OECD has engaged the topic of the implications of manufactured nanomateri

among its members under the auspices of the Joint Meeting of the Chemicals Committee and

Working Party on Chemicals, Pesticides and Biotechnology (Chemicals Committee). On

basis of an international workshop hosted by EPA in Washington in December 2005, the Joint 

Meeting has agreed to establish a subsidiary body to work on the environmental health and 

safety implications of manufactured nanomaterials, with an eye towards enhancing intern

harmonization and burden sharing. In a related activity, the OECD’s Committee on Scien

a

related to realizing commercial and public benefits of advances in nanotechnology. 

Additionally, the United States and European Union Initiative to Enhance Transatlantic 

Economic Integration and Growth (June 2005) addresses nanotechnology. Specifically, the

Initiative states that the United States and the European Union will work together to, a
18 EPA Nanotechnology White Paper 

other things, “support an international dialogue and cooperative activities for the responsible 

development and use of the emerging field of nanotechnology.” EPA is also currently working 

l 

. 

EPA is actively participating in nanotechnology development and evaluation. Some of 

he ac

ss 

e 

 Toxics, 6) 

aterial registration applications in the Office of Air and Radiation/Office of 

Transp

ince 2001, EPA’s ORD STAR grants program has funded 36 research grants nearly 12 

million

m 

of 

 have 

date in this area, totaling approximately $10 million. The most-recent research solicitations 

with the U.S. State Department, the NNI, and the EU to bring about research partnerships in 

nanotechnology. Furthermore, in the context of environmental science, the EPA has worked 

with foreign research institutes and agencies (e.g., UK and Taiwan) to help inform 

nanotechnology and related environmental research programs. 

By continuing to actively participate in international scientific fora, EPA will be wel

positioned to inform both domestic and international environmental policy. This will provide 

essential support for U.S. policy makers who work to negotiate international treaties and trade 

regimes. As products made from nanomaterials become more common in domestic and 

international channels of trade, policy makers will then be able to rely on EPA for the high 

quality science necessary to make effective decisions that could have a significant impact, both

domestically and internationally, on human and environmental health, and economic well-being

1.5 What EPA is Doing with Respect to Nanotechnology 

t tivities EPA has undertaken include: 1) actively participating in the National 

Nanotechnology Initiative, which coordinates nanotechnology research and development acro

the federal government, 2) collaborating with scientists internationally in order to share the 

growing body of information on nanotechnology, 3) funding nanotechnology research through

EPA’s Science To Achieve Results (STAR) grant program and Small Business Innovative 

Research (SBIR) program and performing in-house research in the Office of Research and 

Development, 4) conducting regional nanotechnology research for remediation, 5) initiating th

development of a voluntary program for the evaluation of nanomaterials and reviewing 

nanomaterial premanufacture notifications in the Office of Pollution Prevention and

reviewing nanom

ortation and Air Quality, 7) reviewing potential nanoscale pesticides in the Office of 

Pesticide Programs, 8) investigating the use of nanoscale materials for environmental 

remediation in the Office of Solid Waste and Emergency Response; and 9) reviewing 

information and analyzing issues on nanotechnology in the Office of Enforcement and 

Compliance Assurance. 

. 

1.5.1 EPA’s Nanotechnology Research Activities 

S

 in the applications of nanotechnology to protect the environment, including the 

development of: 1) low-cost, rapid, and simplified methods of removing toxic contaminants fro

water, 2) new sensors that are more sensitive for measuring pollutants, 3) green manufacturing 

nanomaterials; and 4) more efficient, selective catalysts. Additional applications projects

been funded through the SBIR program. 

In addition, 14 recent STAR program projects focus on studying the possible harmful 

effects, or implications, of engineered nanomaterials. EPA has awarded or selected 30 grants to 
EPA Nanotechnology White Paper 19

include partnerships with the National Science Foundation, the National Institute for 

Occupational Safety and Health, and the National Institute of Environmental Health Sciences. 

esearc

ent of 

ve 

ent. 

dix C). 

ctiveness 

 and an 

R h areas of interest for this proposal include the toxicology, fate, release and treatment, 

transport and transformation, bioavailability, human exposure, and life cycle assessm

nanomaterials. Appendix D lists STAR grants funded through 2005. 

EPA’s own scientists have done research in areas related to nanotechnology, such as on 

the toxicity of ultrafine particulate matter (e.g., Dreher, 2004). In addition, EPA scientists ha

begun to gather information on various environmental applications currently under developm

ORD has also led development of an Agency Nanotechnology Research Framework for 

conducting and coordinating intramural and extramural nanotechnology research (Appen

1.5.2 Regional Nanotechnology Research Activities for Remediation 

 A pilot study is planned at an EPA Region 5 National Priorities List site in Ohio. The

pilot study will inject zero-valent iron nanoparticles into the groundwater to test its effe

in remediating volatile organic compounds. The study includes smaller pre-pilot studies

investigation of the ecological effects of the treatment method. Information on the pilot can be 

found at http://www.epa.gov/region5/sites/nease/index.htm. Other EPA Regions (2, 3, 4, 9, and 

ro-valent iron in site remediation. 

 Nanoscale Materials 

s 

s. NPPTAC established an Interim Ad Hoc 

Work G

s 

 Quality - Nanomaterials 

Registr

10) are also considering the use of ze

1.5.3 Office of Pollution Prevention and Toxics Activities Related to

 EPA’s Office of Pollution Prevention and Toxics (OPPT) convened a public meeting in 

June 2005 regarding a potential voluntary pilot program for nanoscale materials. (“Nanoscale 

Materials; Notice of Public Meeting,” 70 Fed. Reg. 24574, May 10, 2005). At the meeting EPA 

received comment from a broad spectrum of stakeholders concerning all aspects of a possible 

stewardship program. Subsequently, OPPT invited the National Pollution Prevention and Toxic

Advisory Committee (NPPTAC) to provide its view

roup on Nanoscale Materials which met in public to further discuss and receive 

additional public input on issues pertaining to the voluntary pilot program for nanoscale 

materials. The Interim Ad Hoc Work Group on Nanoscale Materials developed an overview 

document describing possible general parameters of a voluntary pilot program, which EPA i

considering as it moves forward to develop and implement such a program. OPPT is already 

reviewing premanufacture notifications for a number of nanomaterials that have been received 

under the Toxics Substances Control Act (TSCA). 

1.5.4 Office of Air and Radiation/Office of Transportation and Air

ation Applications 

 EPA’s Office of Air and Radiation/Office of Transportation and Air Quality has received 

and is reviewing an application for registration of a diesel additive containing cerium oxide. 

Cerium oxide nanoparticles are being marketed in Europe as on- and off-road diesel fuel 

additives to decrease emissions and some manufacturers are claiming fuel economy benefits. 
20 EPA Nanotechnology White Paper 

1.5.5 Office of Pesticide Programs to Regulate Nano-Pesticide Products 

o support 

licensing/registration or if the unique characteristics associated with nano-pesticides warrant 

shop on 

t 

 Recently, members of the pesticide industry have engaged the Office of Pesticide 

Programs (OPP) regarding licensing/registration requirements for pesticide products that make 

use of nanotechnology. In response to the rapid emergence of these products, OPP is forming a 

largely intra-office workgroup to consider potential exposure and risks to human health and the 

ecological environment that might be associated with the use of nano-pesticides. Specifically, 

the workgroup will consider whether or not existing data are sufficient t

additional yet undefined testing. The workgroup will consider the exposure and hazard profiles

associated with these new nano-pesticides on a case-by-case basis and ensure consistent review 

and regulation across the program. 

1.5.6 Office of Solid Waste and Emergency Response 

 The Office of Solid Waste and Emergency Response (OSWER) is investigating potential 

implications and applications of nanotechnology that may affect its programs. In October 2005, 

OSWER worked with EPA’s ORD and several other federal agencies to organize a Work

Nanotechnology for Site Remediation. The meeting summary and presentations from tha

workshop are available at http://www.frtr.gov/nano. In July 2006, OSWER held a symposium

entitled, “Nanotechnology and OSWER: New Opportunities and Challenges.” The symposium

featured national and international experts, researchers, and industry leaders who discussed 

issues relevant to nanotechnology and waste management practices and focused on the life cycl

of nanotechnology products. Information on the sy

e 

mposium will be posted on OSWER’s 

website. OSWER’s Technology Innovation and Field Services Division (TIFSD) is compiling a 

 address groundwater contamination. TIFSD is also preparing a fact 

anage

database of information on hazardous waste sites where project managers are considering using 

nanoscale zero-valent iron to

sheet on the use of nanotechnology for site remediation that will be useful for site project 

m rs. In addition, TIFSD has a website with links to relevant information on 

nanotechnology (http://clu-in.org/nano). 

1.5.7 Office of Enforcement and Compliance Assurance 

 The Office of Enforcement and Compliance Assurance (OECA) is reviewing Agency 

information on nanotechnology (e.g., studies, research); evaluating existing statutory and 

y; 

, 

encourage an open dialogue with all concerned parties about 

potential risks and benefits. EPA is committed to keeping the public informed of the potential 

environmental impacts associated with nanomaterial development and applications. As an initial 

regulatory frameworks to determine the enforcement issues associated with nanotechnolog

evaluating the science issues for regulation/enforcement that are associated with nanotechnology

and; considering what information OECA’s National Enforcement Investigations Center (NEIC) 

may need to consider to support the Agency. 

1.5.7 Communication and Outreach 

Gaining and maintaining public trust and support is important to fully realize the societal 

benefits and clearly communicate the impacts of nanotechnology. Responsible development of 

nanotechnology should involve and 
EPA Nanotechnology White Paper 21

step, EPA is developing a dedicated web site to provide comprehensive information and enable 

transparent dialogue concerning nanotechnology. In addition, EPA has been conducting 

hes, 

oal is 

f nanotechnology and the increasing production of 

nanomaterials and nanoproducts present both opportunities and challenges. Using nanomaterials 

 and lead to the development of new 

e 

low 

y agencies. To take advantage of these 

 of ensuring the environmentally safe and sustainable 

ust understand both the potential benefits and the 

potenti

outreach by organizing and sponsoring sessions at professional society meetings, speaking at 

industry, state, and international nanotechnology meetings. 

 EPA already has taken steps to obtain public feedback on issues, alternative approac

and decisions. For example, the previously noted OPPT public meetings were designed to 

discuss and receive public input. EPA will continue to work collaboratively with all 

stakeholders, including industry, other governmental entities, public interest groups, and the 

general public, to identify and assess potential environmental hazards and exposures resulting 

from nanotechnology, and to discuss EPA’s roles in addressing issues of concern. EPA's g

to earn and retain the public’s trust by providing information that is objective, balanced, accurate 

and timely in its presentation, and by using transparent public involvement processes. 

1.6 Opportunities and Challenges

 For EPA, the rapid development o

in applications that advance green chemistry and engineering

environmental sensors and remediation technologies may provide us with new tools for 

preventing, identifying, and solving environmental problems. In addition, at this early junctur

in nanotechnology’s development, we have the opportunity to develop approaches that will al

us to produce, use, recycle, and eventually dispose of nanomaterials in ways that protect human 

health and safeguard the natural environment. The integration and synergy of nanotechnology, 

biotechnology, information technology, and cognitive technology will present opportunities as 

well as challenges to EPA and other regulator

opportunities and to meet the challenge

development of nanotechnology, EPA m

al impacts of nanomaterials and nanoproducts. The following chapters of this document 

discuss the science issues surrounding how EPA will gain and apply such understanding. 
22 EPA Nanotechnology White Paper 

2.0 Environmental Benefits of Nanotechnology 

elp 

n, and 

 

ology 

may contribute to reducing pollution or energy intensity per unit of economic output, reducing 

the “volume effect” described by the OECD. 

2.2 Benefits Through Environmental Technology Applications 

2.2.1 Remediation/Treatment 

 Environmental remediation includes the 

degradation, sequestration, or other related approaches 

that result in reduced risks to human and environmental 

receptors posed by chemical and radiological 

contaminants such as those found at Comprehensive 

Environmental Response, Compensation and Liability 

Act (CERCLA), Resource Conservation and Recovery 

Act (RCRA), the Oil Pollution Act (OPA) or other state 

and local hazardous waste sites. The benefits from use 

of nanomaterials for remediation could include more 

rapid or cost-effective cleanup of wastes relative to 

current conventional approaches. Such benefits may 

derive from the enhanced reactivity, surface area, 

subsurface transport, and/or sequestration 

characteristics of nanomaterials. 

 Chloro-organics are a major class of 

contaminants at U.S. waste sites, and several 

nanomaterials have been applied to aid in their 

remediation. Zero-valent iron (Fig. 13) has been used 

successfully in the past to remediate groundwater by construction of a permeable reactive barrier 

(iron wall) of zero-valent iron to intercept and dechlorinate chlorinated hydrocarbons such as 

trichloroethylene in groundwater plumes. Laboratory studies indicate that a wider range of 

chlorinated hydrocarbons may be dechlorinated using various nanoscale iron particles 

2.1 Introduction 

 As applications of nanotechnology develop over time, they have the potential to h

shrink the human footprint on the environment. This is important, because over the next 50 

years the world’s population is expected to grow 50%, global economic activity is expected to 

grow 500%, and global energy and materials use is expected to grow 300% (World Resources 

Institute, 2000). So far, increased levels of production and consumption have offset our gains in

cleaner and more-efficient technologies. This has been true for municipal waste generation, as 

well as for environmental impacts associated with vehicle travel, groundwater pollutio

agricultural runoff (OECD, 2001). This chapter will describe how nanotechnology can create

materials and products that will not only directly advance our ability to detect, monitor, and

clean-up environmental contaminants, but also help us avoid creating pollution in the first place.

By more effectively using materials and energy throughout a product lifecycle, nanotechn

Figure 13. Nanoscale zero-valent iron 

encapsulated in an emulsion droplet. 

These nanoparticles have been used for 

remdiation of sites contaminated with 

variuos organic pollutants. (Image 

cortesy of Dr. Jacqueline W. Quinn, 

Kennedy Space Center, NASA) 
EPA Nanotechnology White Paper 23

(principally by abiotic means, with zero-valent iron serving as the bulk reducing agent), 

including chlor lliot and 

Zhang, 2001). Nanoscale zero-valent iron may not only treat aqueous dissolved chlorinated 

so may remediate the dense nonaqueous phase liquid (DNAPL) sources of 

these contaminants within aquifers (Quinn et al., 2005). 

ens 

e 

ts, 

e 

e (Tungittiplakorn, 2005). 

ther classes of 

nanomaterials. Nanoparticles such as poly(amidoamine) dendrimers can serve as chelating 

ced for ultrafiltration of a variety of metal ions (Cu (II), Ag(I), 

Fe(III), etc.) by attaching functional groups such as primary amines, carboxylates, and 

i

king arsenic less mobile (Kanel, 2005). 

MMS) are nanoporous ceramic 

mercury or radionuclides from wastewater 

bility to remove metal contaminants from 

tal mercury removal from vapors such 

rving to enhance adsorption and titania 

 less volatile mercuric oxide (Pitoniak, 

red silica can sorb other metals generated in 

an be us

e useful nanom

.2.2 Sensors 

sed on nano

 in the mi

uf ral, 

sult 

inated methanes, ethanes, benzenes, and polychlorinated biphenyls (E

solvents in situ, but al

 In addition to zero-valent iron, other nanosized materials such as metalloporphyrinog

have been tested for degradation of tetrachlorethylene, trichloroethylene, and carbon 

tetrachloride under anaerobic conditions (Dror, 2005). Titanium oxide based nanomaterials hav

also been developed for potential use in the photocatalytic degradation of various chlorinated 

compounds (Chen, 2005). 

 Enhanced retention or solubilization of a contaminant may be helpful in a remediation 

setting. Nanomaterials may be useful in decreasing sequestration of hydrophobic contaminan

such as polycyclic aromatic hydrocarbons (PAHs), bound to soils and sediments. The release of 

these contaminants from sediments and soils could make them more accessible to in situ

biodegradation. For example, nanomaterials made from poly(ethylene) glycol modified urethan

acrylate have been used to enhance the bioavailability of phenanthren

 Metal remediation has also been proposed, using zero-valent iron and o

agents, and can be further enhan

hydroxymates (Diallo, 2005). Other research ind

precipitated in the subsurface using zero-valent iron, ma

Self-assembled monolayers on mesoporous supports (SA

materials that have been developed to remove 

(Mattigod, 2003). 

 Nanomaterials have also been studied for their a

air. Silica-titania nanocomposites can be used for elemen

as those coming from combustion sources, with silica se

to photocatalytically oxidize elemental mercury to the

2005). Other authors have demonstrated nanostructu

combustion environments, such as lead and cadmium (Lee et al., 2005; Biswas and Zachariah, 

1997). Certain nanostructured sorbent processes c

nanoparticles and create byproducts that ar

cates that arsenite and arsenate may be 

ed to prevent emission of 

aterials (Biswas et al., 1998) 

2

 Sensor development and application ba

growing rapidly due in part to the advancements

increasing availability of nanoscale processing and man

nanosensors can be classified in two main categories: (1) sensors that are used to measure 

nanoscale properties (this category comprises most of the current market) and (2) sensors that are 

themselves nanoscale or have nanoscale components. The second category can eventually re

scale science and technology is 

croelectronics industry and the 

acturing technologies. In gene
24 EPA Nanotechnology White Paper 

in lower material cost as well as reduced weight and power consumption of sensors, lead

greater applicability and enhanced functionality. 

 One of the near-term research 

ing to 

products of nanotechnology for 

environmental applications is the 

nd 

o 

improve exposure assessment by 

facilitating collection of large numbers 

detect 

. 

Provided adequate informatics support, 

r 

g 

these 

o the 

ns of 

In the environmental applications field, nanosensor research and development is a 

2.3 Benefits through Other Applications that Support Sustainability 

 Nanotechnology may be able to advance environmental protection by addressing the 

ess by 

development of new and enhanced 

sensors to detect biological a

chemical contaminants. 

Nanotechnology offers the potential t

of measurements at a lower cost and 

improved specificity. It soon will be 

possible to develop micro- and 

nanoscale sensor arrays that can 

specific sets of harmful agents in the 

environment at very low concentrations

these sensors could be used to monito

agents in real time, and the resultin

data can be accessed remotely. The 

potential also exists to extend 

small-scale monitoring systems t

individual level to detect personal 

exposures and in vivo distributio

toxicants. Figure 14 shows an example of a nanoscale sensor. 

Figure 14. Piezoresistive cantilever sensor.

Devices such as these may be used to detect low levels of a 

wide range of substances, including pollutants, explosives, 

and biological or chemical warfare agents. (Image courtesy 

of Dr. Zhiyu Hu and Dr. Thomas Thundat, Nanoscale 

Science and Device Group, Oak Ridge National 

Laboratory) 

relatively uncharted territory. Much of the new generation nanoscale sensor development is 

driven by defense and biomedical fields. These areas possess high-need applications and the 

resources required to support exploratory sensor research. On the other hand, the environmental

measurement field is a cost sensitive arena with less available resources for leading-edge 

development. Therefore, environmental nanosensor technology likely will evolve by leveraging 

the investment in nanosensor research in related fields. 

long-term sustainability of resources and resource systems. Listed in Table 2 are examples

describing actual and potential applications relating to water, energy, and materials. Some

applications bridge between several resource outcomes. For example, green manufacturing 

using nanotechnology (both top down and bottom up) can improve the manufacturing proc

increasing materials and energy efficiency, reducing the need for solvents, and reducing waste 

products. 
EPA Nanotechnology White Paper 25

Table 2. Outcomes for Sustainable Use of Major Resources and Resource Systems 

 Many of the following applications can and should be supported by other agencies. 

However, EPA has an interest in helping to guide the wo

2.3.1 Water 

o

ce

c

ng one

rgy of disti

n costs of FTC-based systems are expected t

smosis systems (NNI, 2000). 

. One long-term 

hallenge to water quality in the Gulf of Mexico, the Chesapeake Bay, and elsewhere is the build 

bute to 

in water have the potential for wide 

xposures to aquatic life and humans. Therefore, it is important to understand the toxicity and 

2.3.2 Energy 

tive 

hat 

e manufacture of nanomaterials can be energy-intensive, it is important to consider the 

entire product lifecycle in developing and analyzing these technologies 

Water sustain water resources of quality and a

EPA Innovation Action Council, 2005 

rk in these areas. 

 long-term water quality, availability, 

d filtration that enables more water rehnology-based flow-through capacitors 

-tenth the energy of state-of-the art 

llation systems. The projected capital 

o be one-third less than conventional 

 Applications potentially extend even more broadly to ecological health

vailability for desired uses 

Energy generate clean energy and use it efficie

Materials use material carefully and shift to envir

Ecosystems protect and restore ecosystem functions

Land support ecologically sensitive land man

Air sustain clean and healthy air 

ntly 

onmentally preferable materials 

, goods, and services 

agement and development 

 Nanotechnology has the potential to contribute t

and viability of water resources, such as through advan

use, recycling, and desalinization. For example, nanote

(FTC) have been designed that desalt seawater usi

reverse osmosis and one-hundredth of the ene

and operatio

o

c

up of nutrients and toxic substances due to runoff from agriculture, lawns, and gardens. In

general with current practices, about 150% of nitrogen required for plant uptake is applied as 

fertilizer (Frink et al., 1996). Fertilizers and pesticides that incorporate nanotechnology may 

result in less agricultural and lawn/garden runoff of nitrogen, phosphorous, and toxic substances, 

which is potentially an important emerging application for nanotechnology that can contri

sustainability. These potential applications are still in the early research stage (USDA, 2003). 

Applications involving dispersive uses of nanomaterials 

e

environmental fate of these nanomaterials. 

 There is potential for nanotechnology to contribute to reductions in energy demand 

through lighter materials for vehicles, materials and geometries that contribute to more effec

temperature control, technologies that improve manufacturing process efficiency, materials t

increase the efficiency of electrical components and transmission lines, and materials that could 

contribute to a new generation of fuel cells and a potential hydrogen economy. However, 

because th
26 EPA Nanotechnology White Paper 

 Table 3 illustrates some potential future nanotechnology contributions to energy 

efficiency (adapted from Brown, 2005). Brown (2005a,b) estimates that the eight technologies 

could resu al units, a 

sta it of e

ye

Ta ia s 

 (A m 

Nanotechnology Application 

Estimated Percent 

Reduction in Total 

Annual U.S. Energy 

lt in national energy savings of about 14.5 quadrillion BTU’s (British therm

ndard un nergy) per year, which is about 14.5% of total U.S. energy consumption per 

ar. 

ble 3. Potent l U.S. Energy Savings from Eight Nanotechnology Application

dapted Brown, 2005 a) fro

Consumption** 

Strong, lightweight materials in transportation 6.2 * 

Solid state lighting (such as white light LED’s) 3.5 

Self-optimizing motor systems (smart sensors) 2.1 

S oofs (temperature-d mart r ependent reflectivity) 1.2 

Novel energy-efficient separation membranes 0.8 

Energy efficient distillation through supercomputing 0.3 

Molecular-level control of industrial catalysis 0.2 

Transmission line conductance 0.2 

Total 14.5 

*Assuming a 5.15 Million BTU/ Barr

gy re

el conversion (corresponding to reformulated gasoline – from EIA monthly 

*Based

ne 

ic 

 hydrocarbons at a significantly improved process 

yield (NNI, 2000). 

 There are additional emerging innovative approaches to energy management that could 

es 

ener view, October 2005, Appendix A) 

* on U.S. annual energy consumption from 2004 (99.74 Quadrillion Btu/year) from the Energy Information

Administration Annual Energy Review 2004 

 

 The items in Table 3 represent many different technology applications. For instance, o

of many examples of molecular-level control of industrial catalysis is a nanostructured catalyt

converter that is built from nanotubes and has been developed for the chemical process of 

styrene synthesis. This process revealed a potential of saving 50% of the energy at this process 

level. Estimated energy savings over the product life cycle for styrene were 8-9% (Steinfeldt et

al., 2004). Nanostructured catalysts can also increase yield (and therefore reduce energy and 

materials use) at the process level. For example, the petroleum industry now uses 

nanotechnology in zeolite catalysts to crack

potentially reduce energy consumption. For example, nanomaterials arranged in superlattic

could allow the generation of electricity from waste heat in consumer appliances, automobiles, 

and industrial processes. These thermoelectric materials could, for example, further extend the 

efficiencies of hybrid cars and power generation technologies (Ball, 2005). 
EPA Nanotechnology White Paper 27

In addition to increasing energy efficiency, nanotechnology also has the potential to 

ple, 

ations for novel distributed wind power (Ball, 2004). 

cy and 

plications over the entire 

roduct lifecycle, particularly in manufacturing nanomaterials. Many of the manufacturing 

processes currently used and being developed for nanotechnology are energy intensive (Zhang et 

al., 2006). In addition, many of the applications discussed here are projected applications. There 

are still some tech hese applications. 

2.3.3 Materials 

efficient and effective use of m For 

tionality of catalytic converters and reduce by up 

red. This has overall product lifecycle benefits. 

entration in ore, this reduction in use may 

t al., 2005). However, manufacturing precise 

eased material functionality, it may be possible in some cases to 

 toxic materials and still achieve the desired functionality (in terms of electrical 

of 

solder is used broadly in the electronics industry; about 3900 tons lead are used 

 The OLED 

/PressRelease-12-03-

contribute to alternative energy technologies that are environmentally cleaner. For exam

nanotechnology is forming the basis of a new type of highly efficient photovoltaic cell that 

consists of quantum dots connected by carbon nanotubes (NREL, 2005). Also, gases flowing 

over carbon nanotubes have been shown to convert to an electrical current, a discovery with 

implic

 While nanotechnology has the potential to contribute broadly to energy efficien

cleaner sources of energy, it is important to consider energy use im

p

nical and economic hurdles for t

 Nanotechnology may also lead to more aterials.

example, nanotechnology may improve the func

to 95% the mass of platinum group metals requi

Because platinum group metals occur in low conc

reduce ecological impacts from mining (Lloyd e

nanomaterials can be material-intensive. 

 With nanomaterials’ incr

replace

conductivity, material strength, heat transfer, etc.), often with other life-cycle benefits in terms 

material and energy use. One example is lead-free conductive adhesives formed from selfassembled monolayers based on nanotechnology, which could eventually substitute for leaded 

solder. Leaded 

per year in the United States alone. In addition to the benefits of reduced lead use, conductive 

adhesives could simplify electronics manufacture by eliminating several processing steps, 

including the need for acid flux and cleaning with detergent and water (Georgia Tech., 2005). 

 Nanotechnology is also used for Organic Light Emitting Diodes (OLEDs). OLEDs are a 

display technology substitute for Cathode Ray Tubes, which contain lead. OLEDs also do not

require mercury, which is used in conventional Flat Panel Displays (Frazer, 2003). 

displays have additional benefits of reduced energy use and overall material use through the 

lifecycle (Wang and Masciangioli, 2003). 

2.3.4 Fuel Additives 

 Nanomaterials also show potential as fuel additives and automotive catalysts and as 

catalysts for utility boilers and other energy-producing facilities. For example, cerium oxide 

nanoparticles are being employed in the United Kingdom as on- and off-road diesel fuel 

additives to decrease emissions (http://www.oxonica.com/cms/pressreleases

04.pdf and http://www.oxonica.com/cms/casestudies/CaseStudyV9SB.pdf). These manufacturers 

also claim a more than 5- 10 % decrease in fuel consumption with an associated decrease in 
28 EPA Nanotechnology White Paper 

vehicle emissions. Such a reduction in fuel consumption and decrease in emissions would re

in obvious environmental benefits. Limited published research and modeling have indicated t

the addition of cerium oxide to fuels may increase levels of specific organic chemicals in 

exhaust, and result in emission of cerium oxide (Health Effects Institute, 2001); the health 

impacts associated with such alterations in diesel exhaust were not examined. 

sult 

hat 
EPA Nanotechnology White Paper 29

Dose - Response

Assessment

Risk

Characterization

Hazard

Identification

Exposure

Assessment

3.0 Risk Assessment of Nanomaterials 

3.1 Introduction 

 Occupational and environmental exposures to a limited number of engineered 

nanomaterials have been reported (Baron et al., 2003; Maynard et al., 2004). Uncertainties in 

health and environmental effects associated with exposure to engineered nanomaterials raise 

questions about potential risks from such exposures (Dreher, 2004; Swiss Report Reinsurance 

Company, 2004; UK Royal Society Report, 2004; European Commission Report, 2004; 

European NanoSafe Report 2004; UK Health and Safety Executive, 2004) 

 EPA’s mission and mandates call for an understanding of the health and environmental 

implications of intentionally produced nanomaterials. A challenge in evaluating risk associated 

with the manufacture and use of nanomaterials is the diversity and complexity of the types of 

materials available and being developed, as well as the seemingly limitless potential uses of 

these materials. A risk assessment is the evaluation of scientific information on the hazardous 

properties of environmental agents, the dose-response relationship, and the extent of exposure of 

humans or environmental receptors to those agents. The product of the risk assessment is a 

statement regarding the probability that humans (populations or individuals) or other 

environmental receptors so exposed will be harmed and to what degree (risk characterization). 

 EPA generally follows the risk assessment paradigm described by the National Academy 

of Sciences (NRC, 1983 and 1994), which at this time EPA anticipates to be appropriate for the 

assessment of nanomaterials (Figure 15). In addition, nanomaterials should be assessed from a 

life cycle perspective (Figure 

16). 

Figure 15. EPA’s Risk Assessment Approach 
30 EPA Nanotechnology White Paper 

Raw Material 

Production

Consumer 

Product 

Manufacturing

Consumer Use End of Life

Worker Exposure Consumer Exposure 

Recycle

Landfills Incinerators

 Human Population and Ecological Exposure

Industrial emissions

Figure 16. Life Cycle Perspective to Risk Assessment 

by EPA for conventional chem als is thought 

to be generally applicable to nanomaterials. It is important to note that nanomaterials have large 

surface areas per unit of volume, as well as novel electronic prope ies relative to onventional 

chemicals. Some of the special properties that make nanomaterials useful are also properties that 

may cause some nanomaterials to pose hazards to humans and the environment, under specific 

conditions, as discussed below. Furthermore, numerous nanomaterial coatings are being 

developed to enhance performance for intended applications. These coatings may impact the 

behavior and effects of the materials, and may or may not be retained in the environment. It will 

be necessary to consider these unique properties and issues, and their potential impacts on fate, 

exposure, and toxicity, in developing risk assessments for nanomaterials. 

 A number of authors have reviewed characterization, fate, and toxicological information 

for nanomaterials and proposed research strategies for safety evaluation of nanomaterials 

(Morgan, 2005; Holsapple et al., 2005; Blashaw et al., 2005; Tsuji et al., 2006; Borm et al., 2006; 

Powers et al., 2006; Thomas and Sayre, 2005). Tsuji et al. (2006) proposed a general framework 

for risk a nanomaterial characteristics, such as 

particle size, structure/properties, coating, and particle behavior, that are expected be important 

in developing nanomaterial risk assessments. These issues are similar to those we note herein. 

Other governments have also undertaken efforts to identify research needs for nanomaterial risk 

assessment (UK Department for Environment, Food and Rural Affairs, 2005; Borm and 

 The overall risk assessment approach used ic

rt c

ssessment of nanomaterials which identified 
EPA Nanotechnology White Paper 31

Kreyl

entified Health Risks (SCENIHR, 2006) has also overviewed existing data on nanomaterials, 

ata gaps, and issues to be considered in conducting risk assessments on nanomaterials. 

The purpose of this chapter is to briefly review the state of knowledge regarding the 

omponents needed to conduct a risk assessment on nanomaterials. The following key aspects of 

sk assessment are addressed as they relate to nanomaterials: chemical identification and 

hysical properties characterization, environmental fate, environmental detection and analysis, 

uman exposure, human health effects, and ecological effects. Each of these aspects is discussed 

y providing a synopsis of key existing information on each topic. 

.2 Chemical Identification and Characterization of Nanomaterials

The identification and characterization of chemical substances and materials is an 

portant first step in assessing their risk. Understanding the physical and chemical properties in 

articular is necessary in the evaluation of hazard (both toxicological and ecological) and 

xposure (all routes). Chemical properties that are important in the characterization of discrete 

hemical substances include, but are not limited to, composition, structure, molecular weight, 

elting point, boiling point, vapor pressure, octanol-water partition coefficient, water solubility, 

activity, and stability. In addition, information on a substance’s manufacture and formulation 

 important in understanding purity, product variability, performance, and use. 

The diversity and complexity of nanomaterials makes chemical identification and 

haracterization not only more important but also more difficult. A broader spectrum of 

roperties will be needed to sufficiently characterize a given nanomaterial for the purposes of 

erties such as those listed above may be 

portant for some nanomaterials, but other properties such as particle size and size distribution, 

. 

ing, 2004). The European Union’s Scientific Committee on Emerging and Newly 

Id

d

c

ri

p

h

b

3

im

p

e

c

m

re

is

c

p

evaluating hazard and assessing risk. Chemical prop

im

surface/volume ratio, shape, electronic properties, surface characteristics, state of 

dispersion/agglomeration and conductivity are also expected to be important for the majority of 

nanoparticles. Figure 17 provides an illustration of different states of aggregation nanoparticles

Powers et al. (2006) provides a discussion of nanoparticle properties that may be important in 

understanding their effects and methods to measure them. 
32 EPA Nanotechnology White Paper 

20 nm 20 nm

Figure 17. Transmission Electron Microscope (TEM) image of aerosol-generated TiO2

t role 

rbon nanotubes 

gical 

r 

nclature conventions may not be 

adequate for some nanomaterials. Nomenclature conventions are important to eliminate 

ambiguity when communicating differences between nanomaterials and bulk materials and in 

reporting for regulatory purposes. EPA’s OPPT is participating in new and ongoing 

workgroup/panel deliberations with the American National Standards Institute (ANSI), the 

American Society for Testing and Materials (ASTM), and the International Organization for 

Standardization (ISO) concerning the development of terminology and chemical nomenclature 

for nanosized substances, and will also continue with its own nomenclature discussions with the 

Chemical Abstracts Service (CAS). 

3.3 Environmental Fate of Nanomaterials 

As more products containing nanomaterials are developed, there is greater potential for 

environmental exposure. Potential nanomaterial release sources include direct and/or indirect 

releases to the environment from the manufacture and processing of nanomaterials, releases from 

 (A) (B) 

nanoparticles. 

(A) Un-aggregated and (2-5 nm) (B) and aggregated (80-120 nm), used in exposure studies to determine 

the health impacts of manufactured nanoparticles. Nanoparticle aggregation may play an importan

in health and environmental impacts. (Images courtesy of Vicki Grassian, University of Iowa [Grassian,

et al., unpublished results]) 

 A given nanomaterial can be produced in many cases by several different processes 

yielding several derivatives of the same material. For example, single-walled ca

can be produced by several different processes that can generate products with different 

physical-chemical properties (e.g., size, shape, composition) and potentially different ecolo

and toxicological properties (Thomas and Sayre, 2005; Oberdörster et al., 2005a). It is not clea

whether existing physical-chemical property test methods are adequate for sufficiently 

characterizing various nanomaterials in order to evaluate their hazard and exposure and assess 

their risk. It is clear that chemical properties such as boiling point and vapor pressure are 

insufficient. Alternative methods for measuring properties of nanomaterials may need to be 

developed both quickly and cost effectively. 

 Because of the current state of development of chemical identification and 

characterization, current chemical representation and nome
EPA Nanotechnology White Paper 33

oil refining processes, chemical and material manufacturing processes, chemical clean up 

activities including the remediation of contaminated sites, releases of nanomaterials incorporated 

to materials used to fabricate products for consumer use including pharmaceutical products, 

nd releases resulting from the use and disposal of consumer products containing nanoscale 

aterials (e.g., disposal of screen monitors, computer boards, automobile tires, clothing and 

osmetics). The fundamental properties concerning the environmental fate of nanomaterials are 

ot well understood (European Commission, 2004), as there are few available studies on the 

nvironmental fate of nanomaterials. The following sections summarize what is known or can 

e inferred about the fate of nanomaterials in the atmosphere, in soils, and in water. These 

mmaries are followed by sections discussing: 1) biodegradation, bioavailability, and 

ioaccumulation of nanomaterials, 2) the potential for transformation of nanomaterials to more 

tes, 3) possible interactions between nan s and other environmental 

dels to 

and factors influence the fate of airborne particles in addition to their 

itial dimensional and chemical characteristics: the length of time the particles remain airborne, 

e nature of their interaction with other airborne particles or molecules, and the distance that 

es and 

ic 

ay follow the laws of gaseous diffusion when 

leased

irborne 

d 

 in 

ciety, 2004; Dennenkamp et al., 2002). Note that these 

 as well as smaller particles by inhalation. 

in

a

m

c

n

e

b

su

b

toxic metaboli omaterial

contaminants; and 4) the applicability of current environmental fate and transport mo

nanomaterials. 

3.3.1 Fate of Nanomaterials in Air 

Several processes 

in

th

they may travel prior to deposition. The processes important to understanding the potential 

atmospheric transport of particles are diffusion, agglomeration, wet and dry deposition, and 

gravitational settling. These processes are relatively well understood for ultrafine particl

may be applicable to nanomaterials as well (Wiesner et al., 2006). However, in some cases, 

intentionally produced nanomaterials may behave quite differently from incidental ultrafine 

particles, for example, nanoparticles that are surface coated to prevent agglomeration. In 

addition, there may be differences between freshly generated and aged nanomaterials. 

With respect to the length of time particles remain airborne, particles with aerodynam

diameters in the nanoscale range (<100 nm) m

re to air. The rate of diffusion is inversely proportional to particle diameter, while the rate 

of gravitational settling is proportional to particle diameter (Aitken et al., 2004). A

particles can be classified by size and behavior into three general groups: Small particles 

(diameters <80 nm) are described as being in the agglomeration mode; they are short-live

because they rapidly agglomerate to form larger particles. Large particles (>2000 nm, beyond 

the discussed <100 nm nanoscale range) are described as being in the coarse mode and are 

subject to gravitational settling. Intermediate-sized particles (>80 nm and < 2000 nm, which

includes particle sizes outside the discussed <100 nm nanoscale range) are described as being

the accumulation mode and can remain suspended in air for the longest time, days to weeks, and

can be removed from air via dry or wet deposition (Bidleman, 1988; Preining, 1998; Spurny, 

1998; Atkinson, 2000; UK Royal So

generalizations apply to environmental conditions and do not preclude the possibility that 

humans and other organisms may be exposed to large

Deposited nanoparticles are typically not easily resuspended in the air or re-aerosolized 

(Colvin 2003; Aitken et al., 2004). Because physical particle size is a critical property of 

nanomaterials, maintaining particle size during the handling and use of nanomaterials is a 
34 EPA Nanotechnology White Paper 

priority. Current research is underway to produce carbon nanotubes that do not form clum

either by functionalizing the tubes themselves, or by treatment with a coating or dispersing agent 

(UK Royal Society, 2004; Colvin, 2003), so future materials may be more easily dispersed. 

Many nanosized particles are reported to be photoactive (Colvin, 2003), but their 

susceptibility to photodegradation in the atmosphere has not been studied. Nanomaterials are 

also known to readily adsorb a variety of materials (Wiesner et al., 2006), and many act as 

catalysts. However, no studies are currently available that examine the interaction of nanosized

adsorbants and chemicals sorbed to them, and how this interaction might influence their 

respective atmospheric chemistries. 

3.3.2 Fate of Nanomaterials in Soil 

The fate of nanomaterials released to soil is likely to vary depending upon the physical 

and chemical characteris

ps 

tics of the nanomaterial. Nanomaterials released to soil can be strongly 

 areas and therefore be immobile. On the other hand, 

nanomaterials are small enough to fit into smaller spaces between soil particles, and might 

therefo

et et 

nd) 

d 

 provide a 

pathway for nanomaterial transformation on soil surfaces. Humic substances, common 

constitu

. 

 in 

ion, 

photoca

es. 

sorbed to soil due to their high surface

re travel farther than larger particles before becoming trapped in the soil matrix. The 

strength of the sorption of any intentionally produced nanoparticle to soil will be dependent on 

its size, chemistry, applied particle surface treatment, and the conditions under which it is 

applied. Studies have demonstrated the differences in mobility of a variety of insoluble 

nanosized materials in a porous medium (Zhang, 2003; Lecoanet and Wiesner, 2004; Lecoan

al., 2004). 

Additionally, the types and properties of the soil and environment (e.g., clay versus sa

can affect nanomaterial mobility. For example, the mobility of mineral colloids in soils an

sediments is strongly affected by charge (Wiesner et al., 2006). Surface photoreactions

ents of natural particles, are known to photosensitize a variety of organic photoreactions 

on soil and other natural surfaces that are exposed to sunlight. Studies of nanomaterial 

transformations in field situations are further complicated by the presence of naturally occurring 

nanomaterials of similar molecular structures and size ranges. Iron oxides are one example

3.3.3 Fate of Nanomaterials in Water 

Fate of nanomaterials in aqueous environments is controlled by aqueous solubility or 

dispersability, interactions between the nanomaterial and natural and anthropogenic chemicals

the system, and biological and abiotic processes. Waterborne nanoparticles generally settle more

slowly than larger particles of the same material. However, due to their high surface-area-tomass ratios, nanosized particles have the potential to sorb to soil and sediment particles 

(Oberdörster et al., 2005a). Where these soil and sediment particles are subject to sedimentat

the sorbed nanoparticles can be more readily removed from the water column. Some 

nanoparticles will be subject to biotic and abiotic degradation resulting in removal from the 

water column. Abiotic degradation processes that may occur include hydrolysis and 

talyzed reaction in surface waters. Particles in the upper layers of aquatic environments,

on soil surfaces, and in water droplets in the atmosphere are exposed to sunlight. Light-induced 

photoreactions often are important in determining environmental fate of chemical substanc
EPA Nanotechnology White Paper 35

These reactions may alter the physical and chemical properties of nanomaterials and so alter th

behavior in aquatic environments. Certain organic and metallic nanomaterials may possibly be 

transformed under anaerobic conditions, such as in aquatic (benthic) sediments. From past 

eir 

udies, it is known that several types of organic compounds are generally susceptible to 

reducti ic 

ispersed 

ed in aquatic environments. For example, researchers at 

Rice University have reported that although C60 fullerene is initially insoluble in water, it 

 containing nanocrystalline aggregates. The concentration 

of nanom

de 

 metal 

method for drinking water, wastewater and 

d 

Nanoparticle photochemistry is being 

 in 

l., 

nt is 

ed 

st

on under such conditions. Complexation by natural organic materials such as hum

colloids can facilitate reactions that transform metals in anaerobic sediments (see Nurmi et al., 

2005 and references therein). 

In contrast to processes that remove nanoparticles from the water column, some d

insoluble nanoparticles can be stabiliz

spontaneously forms aqueous colloids

aterials in the suspensions can be as high as 100 parts per million (ppm), but is more 

typically in the range of 10-50 ppm. The stability of the particles and suspensions is sensitive to 

pH and ionic strength (CBEN, 2005; Fortner et al., 2005). Sea surface microlayers consisting of 

lipid, carbohydrate and proteinaceous components along with naturally-occurring colloids ma

up of humic acids, may have the potential to sorb nanoparticles and transport them in aquatic

environments over long distances (Moore, 2006, Schwarzenbach et al., 1993). These 

interactions will also delay nanoparticle removal from the water column. 

Heterogeneous photoreactions on

oxide surfaces are increasingly being used as a 

groundwater treatment. Figure 18 shows an 

example of the surface of a synthesized metal 

oxide nanostructure, Semiconductors such as

titanium dioxide and zinc oxide as nanomaterials 

have been shown to effectively catalyze both the

reduction of halogenated chemicals and 

oxidation of various other pollutants, an

heterogeneous photocatalysis has been used for 

water purification in treatment systems. 

studied with respect to its possible application

water treatment. Processes that control transport 

and removal of nanoparticles in water and 

wastewater are being studied to understand 

nanoparticle fate (Moore, 2006; Wiesner et a

2006). The fate of nanosized particles in wastewater treatment plants is not well characterized. 

Wastewater may be subjected to many different types of treatment, including physical, chemical 

and biological processes, depending on the characteristics of the wastewater, whether the pla

a publicly owned treatment work or onsite industrial facility, etc. Broadly speaking, nanosiz

particles are most likely to be affected by sorption processes (for example in primary clarifiers) 

and chemical reaction. The ability of either of these processes to immobilize or destroy the 

particles will depend on the chemical and physical nature of the particle and the residence times 

Figure 18. Zinc oxide nanostructures 

synthesized by a vapor-solid process. 

 (Image courtesy of Prof. Zhong Win Lang of 

Georgia Tech.) 
36 EPA Nanotechnology White Paper 

in relevant compartments of the treatment plant. As noted above, sorption, agglomeration and 

mobility of mineral colloids are strongly affected by pH; thus pH is another variable that may 

affect sorption and settling of nanomaterials. Current research in this area includes the 

production of microbial granules that are claimed to remove nanoparticles from simulated

wastewater (Ivanov et al., 2004). Nanomaterials that escape sorption in primary treatment m

be removed from wastewater after biological treatment via settling in the secondary clarifier. 

Normally the rate of gravitatio

ay 

nal settling of particles such as nanomaterials in water is 

ependent on particle diameter, and smaller particles settle more slowly. However, settling of 

nanom

the 

degradable 

biodegrade. However, a recent preliminary study found

up by wood decay fungi after 12 weeks, suggest

metabolized (Filley et al., 2005). For other nano e 

material’s design and function. This is the case 

investigated for use in drug transport (Madan et 

biodegradability is mostly a function of chemica

 Biodegradability in waste treatment and 

of factors. Recent laboratory studies on C60 full

colloid structures in water that demonstrate toxicity to bacteria under aerobic and anaerobic 

conditions (CBEN, 2005; Fortner et al., 2005). 

fullerenes may be toxic to microorganisms unde

consider the potential of photoreactions and other abiotic processe

and thus biodegradation rates of nanomaterials. In summ not enough is known to enable 

radation of nanom

d. 

bility and Bioaccumulation of 

tial 

d

aterials could be enhanced by entrapment in the much larger sludge flocs, removal of 

which is the objective of secondary clarifiers. 

3.3.4 Biodegradation of Nanomaterials 

 Biodegradation of nanoparticles may result in their breakdown as typically seen in 

biodegradation of organic molecules, or may result in changes in the physical structure or surface

characteristics of the material. The potential for and possible mechanisms of biodegradation of 

nanosized particles have just begun to be investigated. As is the case for other fate processes, 

potential for biodegradation will depend strongly on the chemical and physical nature of the 

particle. Many of the nanomaterials in current use are composed of inherently nonbio

inorgan emicals, such as ceramics, metals ic ch and metal oxides, and are not expected to 

 that C60 and C70 fullerenes were taken 

ing that the fullerene carbon had been 

materials biodegradability may be integral to th

for some biodegradable polymers being 

al., 1997; Brzoska et al., 2004), for which 

l structure and not particle size. 

the environment may be influenced by a variety

erenes have indicated the development of stable

Further studies are needed to determine whether 

r environmental conditions. One must also 

s to alter the bioavailability 

ary,

meaningful predictions on the biodeg

further testing and research are neede

aterials in the environment and much 

Nanomaterials 

Bacteria and living cells can take up nanosized particles, providing the basis for poten

bioaccumulation in the food chain (Biswass and Wu, 2005). Aquatic and marine filter feeders

near the base of the food chain feed on small particles, even particles down to the nanometer size 

fraction. The bioavailability of specific nanomaterials in the environment will depend in part on 

the particle. Environmental fate processes may be too slow for effective removal of persistent 

nanomaterials before they can be taken up by an organism. In the previous section, it was noted 

that some physical removal processes, such as gravitational settling, are slower for nanosized 

particles than for microparticles. This would lead to an increased potential for inhalation 

3.3.5 Bioavaila
EPA Nanotechnology White Paper 37

exposure to terrestrial organisms and for increased exposure of aquatic organisms to aqueous 

colloids. Not enough information has been generated on rates of deposition of nanomaterials 

from the atmosphere and surface water, or of sorption to suspended soils and sedim

water column, to determine whether these processes could effectively sequester specific 

nanoparticles before they are taken up by organisms. 

Complexation of metallic nanomaterials may have important interactive effects on 

biological availability and photochemical reactivity. For example, the biological availability of 

iron depends on its free ion concentrations in water and the free ion concentrations are a

by complexation. Complexation reduces biological availability by reducing free metal ion 

concentrati

ents in the 

ffected 

ons and dissolved iron is quantitatively complexed by organic ligands. Solar UV 

radiation can interact with these processes through photoreactions of the complexes. Further, iron 

x reactions that change the oxidation state, 

so 

pounds 

degrade 

gradation 

roducts from carbon nanomaterials (fullerenes and nanotubes) have not yet been reported. 

ed 

e 

It should be noted that the potential also exists for nanomaterials to effect unforseen changes, if 

and iron oxides can participate in enzymatic redo

physical chemical properties and bioavailability of the metal (Reguera et al., 2005). 

3.3.6 Potential for Toxic Transformation Products from Nanomaterials 

 Certain nanomaterials are being designed for release as reactants in the environment, and 

therefore are expected to undergo chemical transformation. One example of this is iron (Fe0

) 

nanoparticles employed as reactants for the dechlorination of organic pollutants (Zhang, 2003). 

As the reaction progresses, the iron is oxidized to iron oxide. Other metal particles are al

converted to oxides in the presence of air and water. Whether the oxides are more or less toxic 

than the free metals depends on the metal. Under the right conditions, certain metal com

could be converted to more mobile compounds. In these cases, small particle size would most 

likely enhance this inherent reactivity. Some types of quantum dots have been shown to 

under photolytic and oxidative conditions, and furthermore, compromise of quantum dot 

coatings can reveal the metalloid core, which may be toxic (Hardman, 2006). De

p

3.3.7 Interactions Between Nanomaterials and Organic or Inorganic Contaminants: Effects

and the Potential for Practical Applications 

The examples cited in this section illustrate how nanomaterials have been demonstrat

to alter the partitioning behavior of chemicals between environmental compartments and 

between the environment and living organisms. Furthermore, several nanomaterials are reactiv

toward chemicals in the environment, generate reactive species, or catalyze reactions of other 

chemicals. These properties are currently under study for use in waste remediation operations. 

released to the environment in large quantities.

Two types of effects under study for possible exploitation are sorption and reaction. The 

high surface area of nanosized particles provides enhanced ability to sorb both organic and 

inorganic chemicals from environmental matrices compared to conventional forms of the same 

materials. This property can potentially be utilized to bind pollutants to enhance environmental 

remediation. Many examples of immobilized nanomaterials for use in pollution control or 

environmental remediation have been described in the literature. These include nanosponges or 

nanoporous ceramics, large particulate or bead materials with nanosized pores or crevasses 
38 EPA Nanotechnology White Paper 

(Christen, 2004), and solid support materials with coatings of nanoparticles (for example, 

Comparelli et al., 2004). This section will instead focus on releases of free nanoparticles and 

effects on chemicals in the environment. The remainder of this section will be organized into 

known changes in the mobility of chemicals caused by their sorption to nanoparticles, and 

known instances of reactivity and catalytic activity toward chemicals mediated by nanopa

see 

rticles. 

o single overall effect can be described for the sorption of chemicals to nanomaterials 

based o

4). 

e of 

ally 

occurring colloids made up of humic acids and suspended sediment particles (Schwarzenbach et 

lar pollutants by 

, 

 

 of nanomaterials for the destruction of persistent 

olluta

N

n their size or chemical makeup alone. In air, aerosolized nanoparticles can adsorb

gaseous or particulate pollutants. In soil or sediments, nanomaterials might increase the 

bioavailability of pollutants, thereby increasing the pollutant=s availability for biodegradation 

(UK Royal Society, 2004). Depending on the conditions, nanosized carbon such as C60 or 

nanotubes could either enhance or inhibit the mobility of organic pollutants (Cheng et al., 200

Stable colloids of hydrophobic nanomaterials in an aqueous environment could provide a 

hydrophobic microenvironment that suspends hydrophobic contaminants and retards their rat

deposition onto soils and sediments. Similar effects are known to happen with natur

al., 1993). Nanoparticles can be altered to optimize their affinities for particu

modifying the chemical identity of the polymer. 

Several studies investigating the sorption of organic pollutants and metals in air, soil, and

water to nanosized materials have recently been reported in the literature. The sorption of 

naphthalene to C60 from aqueous solution was compared to sorption to activated carbon (Cheng 

et al., 2004). The investigators observed a correlation between the surface area of the particles 

and the amount of naphthalene adsorbed from solution. In other studies, nanoparticles made of 

an amphiphilic polymer have been shown to mobilize phenanthrolene from contaminated sandy 

soil and increase its bioavailability (Tungittiplakorn et al., 2004, 2005). It has been reported that 

magnetite crystals adsorb arsenic and chromium (CrVI) from water (CBEN, 2005; Hu et al.

2004), suggesting potential purification techniques for metal-laden drinking water (CBEN, 

2005). The adsorption and desorption of volatile organic compounds from ambient air by 

fullerenes has been investigated (Chen et al., 2000). Inhalation exposures of benzo(a)pyrene 

sorbed to ultrafine aerosols of Ga2O3 (Sun et al., 1982) and diesel exhaust (140 nm) (Sun et al., 

1984) were studied in rats. The studies showed that when compared to inhalation of pure 

benzo(a)pyrene aerosols, material sorbed to the gallium oxide had increased retention in the 

respiratory tract, and increased exposure to the stomach, liver, and kidney. 

 Nanoscale materials are typically more reactive than larger particles of the same material. 

This is true especially for metals and certain metal oxides. In the environment, nanomaterials 

have the potential to react with a variety of chemicals; their increased or novel reactivity coupled

with their sorptive properties allows for accelerated removal of chemicals from the environment.

Many groups are currently investigating the use

p nts in the environment. 

Nanoscale iron particles have been demonstrated to be effective in the in situ remediation

of soil contaminated with tetrachloroethylene. A wide variety of additional pollutants are 

claimed to be transformed by iron nanoparticles in laboratory experiments, including 

halogenated (Cl, Br) methanes, chlorinated benzenes, certain pesticides, chlorinated ethanes, 
EPA Nanotechnology White Paper 39

polychlorinated hydrocarbons, TNT, dyes, and inorganic anions such as nitrate, perchlorate,

dichromate, and arsenate. Further investigations are underway with bimetallic nanoparticles 

(iron nanoparticles with Pt, Pd, Ag, Ni, Co, or Cu deposits) and metals deposited on nanoscale

support materials such as nanoscale carbon platelets and nanoscale polyacrylic acid (Zhang, 

2003). Nanosized clusters of C ater 

ontaminants and act as bacteriocides (Boyd et al., 2005). Fullerol (C60(OH)24) has also been 

demons

als 

nic nanomaterials. Many 

odels

s 

de 

ata needed to design and validate them. Before the environmental fate, transport and 

ultim

10

l research interest and is a principal regulatory focus of EPA=s 

Office 

for exposure assessment of nanomaterials are likely to be found not in the area of environmental 

60 have been shown to generate reactive oxygen species in w

under UV and polychromatic light. Similar colloids have been reported to degrade organic 

c

trated to produce reactive oxygen species under similar conditions (Pickering and 

Wiesner, 2005).

3.3.8 Applicability of Current Environmental Fate and Transport Models to Nanomateri

 When performing exposure assessments on materials for which there are no experimental 

data, models are often used to generate estimated data, which can provide a basis for making 

regulatory decisions. It would be advantageous if such models could be applied to provide 

estimated properties for nanomaterials, since there is very little experimental data available for 

these materials. The models used by EPA’s Office of Pollution Prevention and Toxics (OPPT) 

to assess environmental fate and exposure, are, for the most part, designed to provide estimates 

for organic molecules with defined and discrete structures. These models are not designed for 

use on inorganic materials; therefore, they cannot be applied to inorga

m derive their estimates from structural information and require that a precise structure of 

the material of interest be provided. Since many of the nanomaterials in current use, such a

quantum dots, ceramics and metals, are solids without discrete molecular structures, it is not 

possible to provide the precise chemical structures that these models need. While it is usually 

possible to determine distinct structures for fullerenes, the models cannot accept the complex 

fused-ring structures of the fullerenes. Also, the training sets of chemicals with which the 

quantitative structure-activity relationships (QSAR) in the models were developed do not include 

fullerene-type materials. Fullerenes are unique materials with unusual properties, and they 

cannot be reliably modeled by QSARs developed for other substantially different types of 

materials. 

 In general, models used to assess the environmental fate and exposure to chemicals are 

not applicable to intentionally produced nanomaterials. Depending on the relevance of the 

chemical property or transformation process, new models may have to be developed to provi

estimations for these materials; however, models cannot be developed without the experimental 

d

m edia partitioning of nanomaterials can be effectively modeled, reliable experimental data 

must be acquired for a variety of intentionally produced nanomaterials. 

 However, models are also used which focus on the fate and distribution of particulate 

matter (air models) and/or colloidal materials (soil, water, landfill leachates, ground water), 

rather than discrete organics. For example, fate of atmospheric particulate matter (e.g., PM ) 

has been the subject of substantia

of Air and Radiation. Since intentionally produced nanomaterials are expected to be 

released to and exist in the environment as particles in most cases, it is wise to investigate 

applicability of these other models. In fact it can be reasoned that the most useful modeling tools 
40 EPA Nanotechnology White Paper 

fate of specific organic compounds (more precisely, prediction of their transport and 

transformation), rather in fields in which the focus is on media-oriented pollution issues: air 

pollution, water quality, ground water contamination, etc. A survey of such tools should be 

made and their potential utility for nanomaterials assessed. 

3.4 Environmental Detection and Analysis of Nanomaterials 

 The challenge in detecting nanomaterials in the environment is compounded not only b

the extremely small size of the particles, but also by their unique physical structure and ph

chemical characte

y 

ysicoristics. The varying of physical and chemical properties can significantly 

impact the extraction and analytical techniques that can be used for the analysis of a specific 

significantly differ from the chemical properties of larger particles consisting of the same 

hemic

or 

me 

ive) 

 important role in their detection and source identification. 

n 

red 

lso 

unit volume) requires 

gnificantly less effort than broadening such analyses to include characterization of particle 

tal 

. 

zed 

nanomaterial. As noted above, the chemical properties of particles at the nanometer size can 

c al composition. Independent of the challenges brought on by the intrinsic chemical and 

physical characteristics of nanomaterials, the interactions of nanomaterials with and in the 

environment, including agglomeration, also provide significant analytical challenges. Some

nanomaterials are being developed with chemical surface treatments that maintain nanoparticle 

properties in various environments. These surface treatments can also complicate the detection 

and analysis of nanomaterials. 

In characterizing an environmental sample for intentionally produced nanomaterials, one 

must be able to distinguish between the nanoparticles of interest and other ultra-fine particles, 

such as nanoscale particles in the atmosphere generated from coal combustion or forest fires, 

nanoscale particles in aquatic environments derived from soil runoff, sewage treatment, or 

sediment resuspension. Information used to help characterize nanomaterials includes particle 

size, morphology, surface area and chemical composition. Other information taken into 

consideration in identifying the source of nanomaterials includes observed particle 

concentrations mapped over an area along with transport conditions (e.g., meteorology, currents) 

at the time of sampling. For nanomaterials with unique chemical composition as found in so

quantum dots containing heavy metals, chemical characterization (qualitative and quantitat

can play an

 The level of effort needed and costs to perform analysis for nanomaterials will depend o

which environmental compartment samples are being taken from, as well as the type of desi

analytical information. The analysis of nanomaterials from an air matrix requires significantly 

less (if any) “sample” preparation than samples taken from a soil matrix where it is necessary to 

employ greater efforts for sample extraction and/or particle isolation. Analytical costs a

depend on the degree of information being acquired. Analyzing samples for number 

concentration (i.e., the number and size distribution of nanoparticles per 

si

types (fullerenes, quantum dots, nanowires, etc.). The level of effort also increases for elemen

composition analyses.

Although significant advances in aerosol particle measurement technology have been 

made over the past two decades in response to National Ambient Air Quality Standards (U.S

EPA, 2004), many of these technologies were designed to effectively function on micron si

particles, particles hundreds to a thousand times larger than nanoparticles, and are not effective 
EPA Nanotechnology White Paper 41

in the separation or analysis of particles at the nanometer scale. However, some of these 

technologies have advanced so that they are effective in providing separation and anal

relevant to nanoparticles.

 The information available from the bulk analysis of n

ytical data 

anomaterials from environmental 

samples has limitations when one is trying to identify a specific nanomaterial. As stated 

 sources cannot be 

separated from nanomaterials of interest using sampling methodologies based upon particle size. 

, 

 the 

the 

ubsequent analysis. These technologies provide nanoparticle 

action separation based upon the aerodynamic mobility properties of the particles. 

Aerody

trical 

y 

PSs) 

n and Selegue, 2002). 

n-line particle size analysis in liquid mediums can be done using various techniques including 

ynam

on electron 

n be used to analyze nanomaterials. Atomic Force Microscopy, a 

latively new technology, can provide particle size and morphological information on single 

previously, nanoscale particles generated by natural and other anthropogenic

During analysis, detected signals generated by nanoscale particles that are not of interest can 

mask or augment the signals of nanomaterials of interest, resulting in inadequate or erroneous 

data. Where procedures are available for the selective extraction of nanomaterials of interest

one can avoid interfering signals from other nanoscale particles obtained during sampling. In

case of inseparable mixtures of natural and engineered/manufactured nanomaterials, the use of

single particle analysis methodologies may be necessary to provide definitive analysis for 

engineered/manufactured nanomaterials. 

 Even given all the challenges presented in analyzing for specific nanomaterials of 

interest, methods and technologies are available that have demonstrated success. For aerosols, 

multi-stage impactor samplers are available commercially that can separate and collect 

nanoparticle size fractions for s

fr

namic mobility-based instruments include micro-orifice uniform deposit impactors 

(MOUDIs), and electrical low-pressure impactors (ELPIs) (McMurry, 2000). There are also 

aerosol fractionation and collection technologies based upon the electrodynamic mobility of 

particles. These technologies use the mobility properties of charged nanoparticles in an elec

field to obtain particle size fractionation and collection. Instruments employing this technolog

include differential mobility analyzers (DMAs) and scanning mobility particle sizers (SM

(McMurry, 2000). 

 Available technologies for the size fractionation and collection of nanoparticle fractions 

in liquid mediums include size-exclusion chromatography, ultrafiltration and field flow 

fractionation (Powers et al., 2006; Rocha et al., 2000; Willis, 2002; Che

O

d ic light scattering (DLS) to obtain a particle size distribution (Biswas and Wu, 2005) and 

inductively-coupled mass spectrometry (ICP-MS), a technique that provides chemical 

characterization information (Chen and Beckett, 2001). For more definitive analytical data, 

single-particle analytical techniques can be employed. Single-particle laser microprobe mass 

spectrometry (LAMMS) can provide chemical composition data on single particles from a 

collected fraction (McMurry, 2000). Electron microscopy techniques [e.g., transmissi

microscopy (TEM), scanning electron microscopy (SEM)] can provide particle size, 

morphological and chemical composition information on collected single nanoparticles in a 

vacuum environment. Figure 19 shows an SEM of a scanning gate probe, which is an example 

of an instrument that ca

re

nanoparticles in liquid, gas, and vacuum environments (Maynard, 2000) 
42 EPA Nanotechnology White Paper 

Figure 19. SEM of a scanning gate probe. 

The large tip is the probe for a scanning tunneling 

microscope, and the smaller is a gate that allows 

sharper imaging of the sample. Instruments such 

as these can be used to analyze nanomaterials. 

(Image courtesy of Prof. Leo Kouwehnhoven, 

Delft University of Technology. Reprinted with 

permission from Gurevich, L., et al., 2000) 

(Copyright 2000, American Institute of Physics.)

3.5 Human Exposures and Their Measurement and Control

As the use of nanomaterials in society increases, it is reasonable to assume that their 

presence in environmental media will increase proportionately, with consequences fo

and environmental exposure. Potential human exposures to nanomaterials, or mixtures of 

nanomaterials, include workers exposed during the production, use, recycling and disposal of 

nanomaterials, general population exposure from releases to the environment as a result of th

production, use, recycling and disposal in the workplace, and direct general population exposure 

during the use of commercially available products containing nanomaterials. This section 

identifies potential sources, pathways, and routes of exposure, discusses potential means for 

mitigating or minimi

r human 

e 

zing worker exposure, describes potential tools and models that may be used 

 estimate exposures, and identifies potential data sources for these models. 

r 

he 

 we 

r 

to

3.5.1 Exposure to Nanomaterials 

The exposure paradigm accounts for a series of events beginning from when external 

mechanisms (e.g., releases or handling of chemicals) make a chemical available for absorption o

other mode of entry at the outer body boundary to when the chemical or its metabolite is 

delivered to the target organ. Between outer body contact with the chemical and delivery to t

target organ, a chemical is absorbed and distributed. Depending on the nature of the chemical 

and the route of exposure, the chemical may be metabolized. For the purposes of this section,

will limit the discussion to the types of resources that are needed (and available) to assess 

exposure up to the point where it is distributed to the target organ. 

3.5.2 Populations and Sources of Exposure 

 The potential for intentionally produced nanomaterials to be released into the 

environment or used in quantities that raise human exposure concerns are numerous given thei
EPA Nanotechnology White Paper 43

predicted widespread applications in products. This section discusses some of the potential 

urces and pathways by which humans may be exposed to nanomaterials. 

.5

so

3 .2.1 Occupational Exposure

Workers may be exposed to nanosca thesis of the 

anoscale materials, during formulation or material, 

r during disposal or recycling of the produ ecause 

igher concentrations and amounts of nanos osures 

re more likely in workplace settings, occup

Table 4 presents the potential source

ethods for nanoscale material synthesis: g and 

ttrition methods.

le materials during manufacturing/syn

end use of products containing the nanoscale

cts containing the nanoscale materials. B

cale materials and higher frequencies and exp

ational exposures warrant particular attention. 

s of occupational exposure during the common

as phase synthesis, vapor deposition, colloidal,

n

o

h

a

m

a
44 EPA Nanotechnology White Paper 

Table 4. Potential Sources of Occupational Exposure for Various Synthesis Methods 

(adapted from Aitken, 2004) 

Synthesis Particle 

Process Formation Exposure Source or Worker Activity Primary Exposure Route

Direct leakage from reactor, especially if the reactor 

is operated at positive pressure. 

Inhalation 

Product recovery from bag filters in reactors. Inhalation / Dermal 

Processing and packaging of dry powder. Inhalation / Dermal 

tion during 

Gas Phase in air 

Equipment cleaning/maintenance (including reactor 

evacuation and spent filters). 

Dermal (and Inhala

reactor evacuation) 

Product recovery from reactor/dry contamination of 

workplace. 

Inhalation 

Processing and packaging of dry powder. Inhalation / Dermal 

Vapor Deposition on substrate 

Equipment cleaning/maintenance (including reactor 

evacuation). 

Dermal (and Inhalation during 

reactor evacuation) 

If liquid suspension is processed into a powder, 

potential exposure during spray drying to create a 

powder, and the processing and packaging of the dry 

powder. 

Inhalation / Dermal 

Colloidal/ 

Attrition 

liquid 

suspension 

Equipment cleaning/maintenance. Dermal 

Note: Ingestion would be a secondary route of exposure from all sources/activities from deposition of nanomaterials 

on food or mucous that is subsequently swallowed (primary exposure route inhalation) and from hand-to-mouth 

contact (primary exposure route dermal). Ocular exposure would be an additional route of exposure from some 

sources/activities from deposition of airborne powders or mists in the eyes or from splashing of liquids. 

 While there are several potential exposure sources for each manufacturing process, 

packaging, transfer, and cleaning operations may provide the greatest potential for airborne 

levels of nanomaterials and resultant occupational exposures. “The risk of particle release during 

production seems to be low, because most production processes take place in closed systems 

with appropriate filtering systems. Contamination and exposure to workers is more likely to 

happen during handling and bagging of the material and also during cleaning operations.” 

(Luther, 2004). 

 During the formulation of the nanomaterials into products (e.g., coatings and composite 

materials), workplace releases and exposures may be most likely to occur during the 

transfer/unloading of nanoscale material from shipping containers and during cleaning of process 

equipment and vessels. During the use of some of these products in workplace settings, releases 

of and exposures to nanoscale material are highly dependent upon the application. For example, 

workers who manually apply spray coatings often have higher levels of occupational exposure. 

Alternately, components of composites are usually bound in the composite matrix, and workers 

handling the composites would generally have lower levels of occupational exposure. Exposure 
EPA Nanotechnology White Paper 45

could also occur during product machining (e.g., cutting, drilling and grinding), repair, 

destruction and recycling [Nationa ealth and Safety (NIOSH), 

2005a]. NIOSH (2004, 2005b) has issued additional documents on nanotechnology and 

work fety ted res

3 ease an neral P

l Institute for Occupational H

place sa and associa earch needs. 

.5.2.2 Rel d Ge opulation Exposure

 General population ex release tion 

and use of nanomaterials and from direct use of products containing nanomaterials. During the 

production of nanomaterials, r environm

including the evacuation of production cham ring spray drying, 

emissions from filter or scrub n

product handling. No data have been identified of nanom

i dustrial process s or of the v However, 

d m ey will likely stay airborne for a substantially longer 

tim ost likely pathway for general population exposure 

from releases from industrial rele

during manufacturing (UK Royal So

accidents, natural disasters, o

exposure of workers or the general public. 

 noscale ials h er products resulting in 

p eneral e emistry, and 

catalysis are potential beneficiaries of nanotechnology. Widespread exposure via direct contact 

with products from these sect ts several examples of potential 

sources of general population and co

e 

posure may occur from environmental s from the produc

there are several potential sources fo ental releases 

bers, filter residues, losses du

ber break-through, and wastes from equipme

quantifying the releases 

t cleaning and 

aterials from

n e fate of nanomaterials after release into the en

aterials, th

ironment.

ue to the small s

e than other types of particulate. The m

ize of nano

processes is direct inhalation of materials ased into the air 

ciety, 2004). Releases from industrial or transportation 

r malevolent activity such as a terrorist attack may also lead to 

Na

otential g

 mater

population

ave potential applications in many consum

xposure. Electronics, medicine, cosmetics, ch

ors is expected. Table 5 presen

nsumer exposure associates with the use of such products. 

Table 5. Examples of Potential Sources of General Population and/or Consumer Exposur

for Several Product Types 

Product Type Release and/ or Exposure Source Exposed Population Potential Exposure Route

Product application by consumer to skin Consumer Dermal 

Release by consumer (e.g., washing with 

soap and water) to water supply General population Ingestion 

Sunscreen 

containing 

nanoscale 

material 

Disposal of sunscreen container (with 

residual sunscreen) after use (to landfill or 

incineration) 

General population Inhalation or Ingestion 

Metal catalysts in 

gasoline for 

reducin

Release from vehicle exhaust to air (then 

deposition to surface water) General population Inhalation or Ingestion 

g vehicle 

exhaust*

Paints and 

Coatings 

Weathering, disposal Consumers, general 

population, 

Dermal, Inhalation or 

Ingestion 

Clothing Wear, washing, disposal Consumers, general 

population 

Dermal, inhalation, ingesti

from surface or groundwa

on 

ter 
46 EPA Nanotechnology White Paper 

Product Type Release and/ or Exposure Source Exposed Population Potential Exposure Route

Electronics Release at end of life or recycling stage Consumers, general 

population 

Dermal, ingestion fr

surface or groun

om 

dwater 

Sporting goods Release at end of life or recycling stage Consumers, general 

population 

Dermal, inhalation, ingestion 

from surface or groundwater 

NOTE: This is not an exhaustive list of consumer products or exposure scenarios. 

Ingestion would be a secondary route of exposure from some sources from deposition of nanomaterials on food or 

mucous that is subsequently swallowed (primary exposure route inhalation) and from hand-to-mouth contact 

(primary exposure route dermal). Ocular exposure would be an additional route of exposure from some 

sources/activities from deposition of airborne powders or mists in the eyes or from splashing of liquids.

* Metal catalysts are not currently being used in gasoline in the U.S. Cerium oxide nanoparticles are being 

marketed in Europe as on and off-road diesel fuel additives. 

3.5.3 Exposure Routes 

 Much remains to be scientifically demonstrated about the mechanisms by which human 

exposure to nanomaterials can occur. Intentionally produced nanomaterials share a number o

characteristics, such as size and dimensions, with other substances (e.g., ultrafine particles) f

hich a large body of information exists on

f 

or 

w how they access the human body to cause toxicity. 

The data from these other substances focus primarily on inhalation as the route of exposure. 

However, as the range of applications of nanomaterials expands, other routes of exposure, such 

as dermal, ocular, and oral, may also be found to be significant in humans. 

3.5.3.1 Inhalation Exposure

A UK Health and Safety Executive reference suggests that aerosol science would be 

applicable to airborne nanoparticle behavior. Aerosol behavior is primarily affected by particle 

size and the forces of inertia, gravity, and diffusion. Other factors affecting nanoparticle 

irborne concentrations are agglomeration, deposition, and re-suspension. (UK Health and 

Safety Executive, 2004) All of these issues, which are et

a t for u ll e concent f 

n ials. 

ed issues involved with aerosol release 

of a single-walled l d th

studies indicate th t agitation can release fine particles into the air, aerosol 

c un in t

loads and rates observed were very low on a mass basis (Maynard et al., 2004). The study 

s re research will be needed in this area.

3.5.3.2 Ingestion Exposure

a

discussed in more d ail in the reference, 

re relevan

anomater

One reference study was found to have investigat

nderstanding, predicting, and contro ing airborn rations o

 carbon nanotube (SWCNT) materia

at sufficien

. This study note at while laboratory 

oncentrations of

uggests that mo

 SWCNT generated while handling refined material he field at the work 

formation on exposure to nanoscale environm

lacking. In addition to traditional ingestion of food, fo cin

supplements, dust and soil (particularly in the case of children), ingestion o

In ental particles via oral exposure is 

od additives, medi es and dietary 

f inhaled particles can 
EPA Nanotechnology White Paper 47

also occur (such as through the activities of the mucocilliary escalator). The quantity ingested is 

a to be 

3.5.3.3 Dermal Exposure

nticipated relatively small in terms of mass. 

Dermal exposure to nanomaterials has received erh

with occupational exposure and the introduction of nanomaterials such as nanosized titanium 

und to have investigated 

T 

l 

and. 

al for penetration through “healthy/intact” 

rt (2004) highlights physiological characteristics of the skin that may 

ermit 

ed nanoscale 

isperse into the surrounding viable subcutis and to draining lymph 

et al., 2005). It has recently been reported 

d 

s 

rs 

 much attention, p aps due to concerns 

dioxide into cosmetic and drug products. One reference study was fo

issues involved with potential dermal exposure to a SWCNT material. The study suggests that 

more research will be needed in this area. This study noted that airborne particles of SWCN

may contribute to potential dermal exposure along with surface deposits due to materia

handling. Surface deposits on gloves were estimated to be between 0.2 mg and 6 mg per h

(Maynard et al., 2004) 

 There is an ongoing debate over the potenti

versus damaged skin. Ha

p the absorption of nanosized materials. In particular the review highlights a conceivable 

route for the absorption of nanoparticles as being through interstices formed by stacking and 

layering of the calloused cells of the top layer of skin (Hart, 2004). Movement through these 

interstices will subsequently lead to the skin beneath, from which substances can be absorbed 

into the blood stream. Nanomaterials also have a greater risk of being absorbed through the skin

than macro-sized particles (Tinkle, 2003). Reports of toxicity to human epidermal keratinocytes

in culture following exposure to carbon nanotubes have been made (Shvedova et al., 2003; 

Monteiro-Riviere et al., 2005). A significant amount of intradermally inject

quantum dots were found to d

nodes via subcutaneous lymphatics (Roberts, D.W. 

that quantum dots with different physicochemical properties (size, shapes, coatings) penetrate

the stratum corneum and localized within the epidermal and dermal layers of intact porcine skin 

within a maximum 24 hours of exposure (Ryman-Rasmussen et al., 2006). Drug delivery studie

using model wax nanoparticles have provided evidence that nanoparticle surface charge alte

blood-brain barrier integrity and permeability (Lockman et al., 2004). 

3.5.3.4 Ocular Exposure

d ultrafine particulates. Some 

ing controls are applicable to the work place and may mitigate 

rsonal protective equipment (PPE) are primarily 

s and 

rticles 

preferred over PPE. 

Ocular exposure to nanomaterials has received little attention. However, the potential for

ocular exposure to nanomaterials from deposition of airborne powders or mists in the eyes or 

from splashing of liquids must also be considered. 

3.5.4 Exposure Mitigation 

 Approaches exist to mitigate exposure to fine an

approaches such as engineer

environmental releases while others such as pe

applicable to the workplace. NIOSH suggests considering the range of control technologie

personal protective equipment demonstrated to be effective with other fine and ultrafine pa

(NIOSH, 2005a). In the hierarchy of exposure reduction methods, engineering controls are 
48 EPA Nanotechnology White Paper 

3.5.4.1 Engineering Controls

ls, and particularly those used for aerosol control, should generally be 

effective for controlling exposures

on part

res, 

ification as those typically used for gases. However, the report also notes 

at no 

 Engineering contro

 to airborne nanoscale materials (NIOSH, 2005a). Depending 

icle size, nanoparticles may diffuse rapidly and readily find leakage paths in engineering 

control systems in which containment is not complete (Aitken et al., 2004). However, a welldesigned exhaust ventilation system with a high efficiency particulate air (HEPA) filter should 

effectively remove nanoparticles (Hinds, 1999). As with all filters, the filter must be properly 

seated to prevent nanoparticles from bypassing the filter, decreasing the filter efficiency 

(NIOSH, 2003). Aitken et al. (2004) recommends that engineering controls (e.g., enclosu

local exhaust ventilation, fume hoods) used to control exposure to nanoparticles need to be of 

similar quality and spec

th research has been identified evaluating the effectiveness of engineering controls for 

nanoparticles. 

Efficient ultrafine particle control devices (e.g., soft x-ray enhanced electrostatic 

precipitation systems) may have applicability to nanoparticles control (Kulkarni et al., 2002). 

HEPA filters may be effective, and validation of their effectiveness is currently being studied 

(NIOSH, 2005a). Magnetic filter systems in welding processes have proven effective in 

capturing magnetic oxides and the use of nanostructured sorbents in smelter exhausts to prepare 

ferroelectric materials may also have applicability (Biswas et al., 1998). 

3.5.4.2 Personal Protective Equipment (PPE)

 Properly fitted respirators with a HEPA filter may be effective at removing 

nanomaterials. Contrary to intuition, fibrous filters trap smaller and larger particles more 

effectively than mid-sized particles. Small particles (<100 nm) tend to make random Brownian 

motions due to their interaction with gas molecules. The increased motion causes the particle to 

“zig-zag around” and have a greater chance of hitting and sticking to the fiber filter (Luther, 

2004). Intermediate-sized particles (>80 nm and < 2000 nm) can remain suspended in air for the 

ngest time. (Bidleman, 1988; Preining, 1998; Spurny, 1998; Atkinson, 2000; UK Royal 

p et al., 2002) 

t 

], which have been found to be in the most 

penetrating particle size range (Stevens and Moyer, 1989). However, as with all respirators, the 

 their effectiveness is not penetration through the filter, but rather 

nly 

lo

Society, 2004; Dennenkam

 NIOSH certifies particulate respirators by challenging them with sodium chloride (NaCl) 

aerosols with a count median diameter 75 nm or dioctyl phthalate (DOP) aerosols with a coun

median diameter of 185 nm [42 CFR Part 84.181(g)

greatest factor in determining

the face-seal leakage bypassing the device. Due to size and mobility of nanomaterials in the air, 

leakage may be more prevalent although no more than expected for a gas (Aitken, 2004). O

limited data on face-seal leakage has been identified. Work done by researchers at the U.S. 

Army RDECOM on a headform showed that mask leakage (i.e., simulated respirator fit factor) 

measured using submicron aerosol challenges (0.72 μm polystyrene latex spheres) was 

representative of vapor challenges such as sulfur hexafluoride (SF6) and isoamyl acetate (IAA) 

(Gardner et al., 2004). 

 
EPA Nanotechnology White Paper 49

PPE may not be as effective at mitigating dermal exposure. PPE is likely to be less 

ure to nanomaterials than macro-sized particles from both human 

auses (e.g., touching face with contaminated fingers) and PPE penetration (Aitken, 2004). 

at 

r 

 particle weight and surface area can occur within a given batch. The average particle weight 

and ave red for 

sure assessments including monitoring data, 

a from existing chemicals. The following sections 

materials. 

effective against dermal expos

c

However, no studies were identified that discuss the efficiency of PPE at preventing direct 

penetration of nanomaterials through PPE or from failure due to human causes. 

3.5.5 Quantifying Exposure to Nanomaterials 

 There is broad consensus that mass dose alone is insufficient to characterize exposure to

nanomaterials (Oberdörster et al., 2005a, b; NIOSH, 2005a, b). Many studies have indicated th

toxicity increases with decreased particle size and that particle surface area is a better metric fo

measuring exposures (Aitken, 2004). This is of particular concern for nanomaterials, which 

typically have very high surface-area-to-mass ratios. Additionally, there currently are no 

convenient methods for monitoring the surface area of particles in a worker’s breathing zone or 

ambient air. While there could be a correlation between mass and surface area, large variations 

in

rage particle surface area of the nanomaterials being assessed would also be requi

any assessments based on surface area. (Maynard and Kuempel, 2005). It has also been 

recommended that mass, surface area, and particle number all be measured for nanomaterials 

(Oberdörster et al., 2005b). 

3.5.6 Tools for Exposure Assessment 

 Several tools exist for performing expo

exposure models, and the use of analogous dat

discuss these tools and their potential usefulness in assessing exposure to nanoscale 

3.5.6.1 Monitoring Data

Types of monitoring data that can be used in exposure assessment include biological 

monitoring, personal sampling, ambient air monitoring, worker health monitoring and medical 

surveillance. Although monitoring and measurement are discussed earlier in section3.4, the 

discussion below includes coverage of some issues directly pertinent to exposure. 

Biological Monitoring

Biomonitoring data, when permitted and applied correctly, provides the best information

on the dose and levels of a chemical in the human body. Examples of bio-monitoring include th

Centers for Disease Control and Prevention (CDC) national monitoring program and smaller 

surveys such as the EPA’s National Human Exposure Assessment Survey (NHEXAS). 

Biomonitoring can be the best tool for understanding the degree and spread of exposure, 

information that cannot be captured through monitoring concentrations in ambient media. 

Biomonitoring, however, is potentially limited in its application to nanotechnology because i

a science that is much dependent on knowledge of biomarkers, and its benefits are highest when

there is background knowledge on what nanomaterials should be monitored. Given the c

limited knowledge on nanoscale materials in commerce, their uses, and their fate in the 

environment and in the

e 

t is 

urrent 

 human body, it is difficult to identify or prioritize nanomaterials for 

biomonitoring. Should biomonitoring become more feasible in the future, it presents an 
50 EPA Nanotechnology White Paper 

opportunity to assess the spatial and temporal distribution of nanomaterials in workers and th

general population. 

e 

Personal Sampling

Personal sampling data provide an estimate of the exposure experienced by an individual, 

 is limited in that it 

does not account for changes to the dose received by the target organ after the biological 

g 

and can be an important indicator of exposure in occupational settings. It

processes of absorption, distribution, metabolism and excretion. Generally, for cost and 

feasibility reasons, personal and biomonitoring data are not available for all chemicals on a scale 

that is meaningful to policymakers. Also, the applicability of personal sampling to 

nanomaterials is dependent on the development of tools for accurately detecting and measurin

such materials in ambient media. 

Ambient Monitoring 

Ambient media monitoring measures concentrations in larger spaces such as in 

workplaces, homes or the general environment. Ambient data are used as assumed expos

concentrations of chemicals in populations when it is not feasible or practical to conduct perso

sampling for individuals in the populations. Typically, these data are used in models in addition 

to other assumptions regarding exposure pa

ure 

nal 

rameters, including population activities and 

Cha

demographics such as age. 

llenges of Monitoring 

 As discussed in Section 3.4, there are many challenges to detecting and characterizing 

nanoscale materials, including the extremely small size of the analyte, as well as the need to 

distinguish the material of interest from other similarly-sized materials, the tendency for 

nanoparticles to agglomerate, and the cost of analysis. Additionally, as discussed in above, it is 

d 

be not only 

sensitive and specific, but also easy to use, durable, able to operate in a range of environments, 

and affordable. Additionally, data sometimes needs to be collected continuously and analyzed in 

real-time. Further, the nanomaterials may need to be measured in a variety of media and several 

propert

not always clear what the most appropriate metric is to measure. Mass may not be the most 

appropriate dose metric; therefore, techniques may be required for measuring particle counts an

surface area, or other parameters. These problems are compounded when there is a need for 

monitoring data to be used in exposure assessment. Monitoring equipment should 

ies may need to be measured in parallel. All of the current measuring methods and 

instruments individually fall short of adequately addressing all of these needs. 

3.5.6.2 Exposure Modeling

A recent use of ambient monitoring data to estimate the exposure of a population is 

cumulative exposure project for air toxics recently completed for hazardous air toxics using the 

Hazardous Air Pollutant Exposure Model (HAPEM) 

(

the 

http://www.epa.gov/ttn/fera/human_hapem.html). This model predicts inhalation exposure 

concentrations of air toxics from all outdoor sources, based on ambient concentrations fr

modeling or monitor data for specific air toxics at the census tract level. 

om 
EPA Nanotechnology White Paper 51

 Other EPA screening level models include the Chemical Screening Tool for Exposures 

and Environmental Releases (ChemSTEER) 

(http://www.epa.gov/oppt/exposure/docs/chemsteer.htm) and the Exposure and Fate Assessment 

Screening Tool (E-FAST) (http://www.epa.gov/oppt/exposure/docs/efast.htm). ChemSTEER 

estimates po

uses th

ar 

tential dose rates for workers and environmental releases from workplaces. E-FAST 

e workplace releases to estimate potential dose rates for the general population. E-FAST 

also estimates potential dose rates for consumers in the general public. However, whether 

ChemSTEER and E-FAST will be useful for assessments of nanoscale materials is not cle

because of the significantly different chemical and physical properties of nanomaterials. 

Challenges of Using Models with Nanoscale Materials

There are several models that span multiple levels of complexity and are designed to 

estimate exposure at several points in the exposure paradigm. The effectiveness of these models 

at p ure will depend on the parameters and assumptions of each model. 

odels that are based on assum

s, 

redicting human expos

For m ptions specific to the chemical such as the physical and 

chemical properties, and interactions in humans and the environment based on these propertie

much substance-specific data may be required. 

Data Sets for Modeling

The availability of ambient data is clearly critical to modeling exposure, and there are a 

number of resources within EPA for this type of data. In some cases such as for pesticides, the 

exposure can be anticipated based on the quantity of the substance that is proposed to be applied 

and the anticipated residue on a food item as an example. Sometimes there are data collected 

r 

 as 

es 

s frequently 

 Occupational Safety and Health Administration (OSHA)-

 worker exposure and assure compliance with workplace 

regulat n 

r 

04). 

under statutory obligations, such as data collected for the Toxics Release Inventory (TRI) unde

the Emergency Planning and Community Right to Know Act (EPCRA). For contaminants in

drinking water, the data may be reported to the Safe Drinking Water Information System 

(SDWIS). Generating data for nanomaterials necessitates the identification of nanomaterials as 

separate and different from other chemicals of identical nomenclature, and their classification

toxic substances, or in a manner that adds nanomaterials to the list of reportable 

releases/contaminants. 

 Though not fully representative of population exposure, workplace data have frequently 

provided the foundation for understanding exposure and toxicity for many chemicals in industrial 

production. A recent study in the United States, in which ambient air concentrations and glove 

deposit levels were measured, identified a concern for exposure during handling of nanotub

(Maynard et al., 2004). In the work environment, data on workplace exposure i

collected under the purview of

mandated programs to assess

ions and worker protection. Employers, however, are not required to report these data. I

addition, OSHA standards are typically airborne exposure levels that are based on health or 

economic criteria or both, and typically only defined exceedences of these standards are 

documented. To understand nanotechnology risks in the workplace, the National Institute of 

Occupational Safety and Health (NIOSH) is advancing initiatives to investigate amongst othe

issues, nanoparticle exposure and ways of controlling exposure in the workplace (NIOSH, 20
52 EPA Nanotechnology White Paper 

3.6 Human Health Effects of Nanomaterials

 There is a significant gap in our knowledge of the environmental, health, and ecological 

implications associated with nanotechnology (Dreher, 2004; Swiss Report, 2004; UK Royal 

Society, 2004; European NanoSafe, 2004; UK Health and Safety Executive, 2004). This section 

provides an overview of currently available information on the toxicity of nanoparticles; much of

the information is for natural or incidentally formed nanosized materials, and is presented to

in the understanding of intentionally produced nanomaterials. 

 aid 

3.6.1 Adequacy of Current Toxicological Database 

 The Agency’s databases on the health effects of particulate matter (PM), asbestos, silica, 

or othe

ioxide particles (U.S. EPA, 2004). However, it 

is important to note that ambient air ultrafine particles are distinct from intentionally produced 

nan not purposely engineered and represent a physicochemical and 

dynami

ndard for 

arbon nanotubes displayed very different mass-based dose-response 

lation

r toxicological databases of similar or larger sized particles of identical chemical 

composition (U.S. EPA, 1986, 1996, 2004) should be evaluated for their potential use in 

conducting toxicological assessments of intentionally produced nanomaterials. The toxicology

chapter of the recent Air Quality Criteria for Particulate Matter document cites hundreds of

references describing the health effects of ambient air particulate matter including ultrafine 

ambient air (PM0.1), silica, carbon, and titanium d

omaterials since they are

c complex mixture of particles derived from a variety of natural and combustion sources. 

In addition, only approximately five percent of the references cited in the current Air Quality 

Criteria for Particulate Matter document describe the toxicity of chemically defined ultrafine 

particles, recently reviewed by Oberdörster et al. (2005a) and Donaldson et al. (2006). 

A search of the literature on particle toxicity studies published up to 2005 confirms the 

paucity of data describing the toxicity of chemically defined ultrafine particles and, to an even

greater extent, that of intentionally produced nanomaterials (Figure 20). The ability to assess the

toxicity of intentionally produced carbon nanotubes by extrapolating from the current carbonparticle toxicological database was examined by Lam et al. (2004) and Warheit et al. (2004). 

Their findings demonstrate that graphite is not an appropriate safety reference sta

carbon nanotubes, since c

re ships and lung histopathology when directly compared with graphite. 
EPA Nanotechnology White Paper 53

These initial findings indicate a high degree of uncertainty in the ability of current 

particle toxicological databases to assess or predict the toxicity of intentionally produced carbonbased nanomaterials displaying novel physicochemical properties. Additional comparative 

toxicological studies are needed to assess the utility of the current particle toxicological 

databases in assessing the toxicity of other classes or types of intentionally produced 

nanomaterials, as well as to relate their health effects to natural or anthropogenic ultrafine 

particles. 

Figure 20. Particle Toxicology Citations. Results depict the number of toxicological 

publications for each type of particle obtained from a PubMed search of the literature up to 

2005 using the indicated descriptors and the term “toxicity.” Uf denotes ultrafine size (<100nm) 

particles. 
54 EPA Nanotechnology White Paper 

3.6.2 Toxicity and Hazard Identification of Engineered/Manufactured Nanomaterials 

multifactor e and 

shape t 

al., 1992; Sclafani and Herrmann, 1996; Nemmar et al., 2003; Derfus et al., 2004). The 

properties of carbon nanotubes in relation to pulmonary toxicology have recently been reviewed 

(Donal

re to 

 order to 

 Establishment of dose-response relationships linking physicochemical properties of 

tentionally produced nanomaterials to their toxicities will identify the appropriate exposure 

metrics that best correlate with adverse health effects. 

 Studies assessing the role of particle size on toxicity have generally found that ultrafine 

or nanosize range (<100 nm) particles are more toxic on a mass-based exposure metric when 

compared to larger particles of identical chemical composition (Oberdörster et al., 1994; Li et al., 

1999; Höhr et al., 2002). Other studies have shown that particle surface area dose is a better 

predictor of the toxic and pathologic responses to inhaled particles than is particle mass dose 

(Oberdörster et al., 1992; Driscoll, 1996; Lison et al., 1997; Donaldson et al., 1998; Tran et al., 

2000; Brown et al., 2001; Duffin et al., 2002). Studies examining the pulmonary toxicity of 

carbon nanotubes have provided evidence that intentionally produced nanomaterials can display 

unique toxicity that cannot be explained by differences in particle size alone (Lam et al., 2004; 

Warheit et al., 2004). For example, Lam reported single walled carbon nanotubes displayed 

greater pulmonary toxicity than carbon black nanoparticles. Similar results have been obtained 

from comparative in vitro cytotoxicity studies (Jia et al., 2005). Muller et al. (2005) reported 

multi-walled carbon nanotubes to be more proinflammatory and profibrogenic when compared to 

ultrafine carbon black particles on an equivalent mass dose metric. Shvedova et al. (2005) 

reported unusual inflammatory and fibrogenic pulmonary responses to specific nanomaterials, 

suggesting that they may injure the lung by new mechanisms. Exposure of human epidermal 

keratinocyte cells in culture to single-walled carbon nanotubes was reported to cause dermal 

toxicity, including oxidative stress and loss of cell viability (Shvedova et al., 2003). The 

combination of small particle size, large surface area, and ability to generate reactive oxygen 

species have been suggested as key factors in induction of lung injury following exposure to 

some incidentally produced nanomaterials (Nel et al., 2006). 

 Contrary to other reports, Uchino et al. (2002), Warheit et al. (2006) and Sayes et al. 

(2006) have reported nanoscale titanium dioxide toxicity was not found to be dependent on 

particle size and surface area. These authors reported that specific crystal structure and the 

ability to generate reactive oxygen species are important factors to consider in evaluating 

nanomaterial toxicity. Similar to other reports, Warheit demonstrated that nanomaterial coating

impacted toxicity (Warheit et al., 2005). 

Studies have demonstrated that nanoparticle toxicity is extremely complex and 

ial, potentially being regulated by a variety of physicochemical properties such as siz

, as well as surface properties such as charge, area, and reactivity (Sayes et al., 2004; Cai e

dson et al., 2006). 

 Toxicological assessment of intentionally produced nanomaterials will require 

information on the route (inhalation, oral, dermal) that carries the greatest risk for exposu

these materials, as well as comprehensive physicochemical characterization of them in

provide information on size, shape, as well as surface properties such as charge, area, and 

reactivity.

in
EPA Nanotechnology White Paper 55

 One of the most striking findings regarding particle health effects is the ability of 

particles to generate local toxic effects at the site of initial deposition as well as very significant 

ystem

en 

e 

oxic 

ls 

that are available commercially or 

re under development. In many cases, the same type of nanomaterial can be produced by 

ial. 

ses, 

ent 

 by a different process. Manufactured materials may 

lso be treated with coatings, or other surface modifications, in order to generate mono-dispersed 

 criteria 

s of intentionally produced nanomaterials in an accepted, timely and 

ost effective manner are needed in order provide health risk assessment information for the 

., 

 display differential deposition patterns 

rticles of identical chemical composition. For 

s ic toxic responses (U.S. EPA, 2004). Pulmonary deposition of polystyrene nanoparticles

was found to not only elicit pulmonary inflammation but also to induce vascular thrombosis 

(Nemmar et al., 2003). Pulmonary deposition of carbon black nanoparticles was found to 

decrease heart rate variability in rats and prolonged cardiac repolarization in young healthy 

individuals in recent toxicological and clinical studies (Harder et al., 2005; Frampton et al., 

2004). Extrapulmonary translocation following pulmonary deposition of carbon black 

nanoparticles was reported by Oberdörster et al. (2004a, 2005a) Submicron particles have be

shown to penetrate the stratum corneum of human skin following dermal application, suggesting 

a potential route by which the immune system may be affected by dermal exposure to 

nanoparticles (Tinkle et al., 2003; Ryman-Rasmussen et al., 2006). Zhao et al. (2005) have 

reported that in molecular dynamic computer simulations C60 fullerenes bind to double and 

single-stranded DNA and note that these simulations suggest that C60 may negatively impact th

structure, stability, and biological functions of DNA. It is clear that toxicological assessment of 

intentionally produced nanomaterials will require consideration of both local and systemic t

responses (e.g., immune, cardiovascular, neurological toxicities) in order to ensure that that we 

identify the health effects of concern from these materials. 

3.6.3 Adequacy of Toxicity Test Methods for Nanomaterials 

 A challenge facing the toxicological assessment of intentionally produced nanomateria

is the wide diversity and complexity of the types of materials 

a

several different processes, giving rise to a number of versions of the same type of nanomater

For example, single-walled carbon nanotubes can be mass produced by four different proces

each of which generates products of different size, shape, composition, and potentially differ

toxicological properties (Bekyarova, 2005). It is not known whether the toxicological 

assessment of one type and source of nanomaterial will be sufficient to assess the toxicity of the 

same class/type of nanomaterial produced

a

suspensions that extend and enhance their unique properties. The extent to which surface 

modifications of intentionally produced nanomaterials affect their toxicity is not known. Other 

testing issues include the possibility of physicochemical changes in the material before and after 

administration in a test system, presenting a challenge in identifying the characterization

for nanomaterial toxicity. Test methods that determine the toxicity and hazardous 

physicochemical propertie

c

diversity of such nanomaterials that are currently available (Oberdörster et al., 2005b). 

3.6.4 Dosimetry and Fate of Intentionally Produced Nanomaterials 

 Much of what is known regarding particle dosimetry and fate has been derived from 

pulmonary exposure studies using ultrafine metal oxide and carbon black studies (U.S. EPA, 

2004; Oberdörster, 1996; Oberdörster et al., 2005a, b; Oberdörster et al., 2004a; Kreyling et al

2002). Ultrafine carbon black and metal oxide particles

within the lung when compared to larger sized pa
56 EPA Nanotechnology White Paper 

e e, 1 nm particles are preferentially deposited in the nasopharyngeal region while 5n

particles are deposited throughout the lung and 20 nm particles are preferentially deposited in the

distal lung within the alveolar gas exchange region (Oberdörster et al., 2005a). Host 

susceptibility factors such as pre-existing lung disease significantly affect the amount and 

location of particles deposited within the lung. For example, individuals with chronic obstr

pulmonary disease have 4-fold higher levels of particles deposited in their upper bronchioles

when compared to health individuals exposed to the same concentration of particles (U.S. EP

2004). Also, pulmonary deposited ultrafine particles can evade the normal pulmonary c

mechanisms and translocate by a variety of pathways to distal organs (Oberdörster et al. 2004a, 

2005a; Kreyling et al., 2002; Renwick et al., 2001). Additional studies that provide information 

on the deposition and fate of inhaled nanomaterials include studies in animals (Takenak

2001; Oberdörster et al., 2002) and studies in humans (Brown et al., 2002; Chalupa et al., 20

 The deposition and fate of the class of nanomaterials called dendrimers have been 

examined to some degree due to their potential drug delivery applications (Malik et al 2000; 

Nigavekar et al., 2004.). Both studies demonstrated the critical role which surface charge and 

chemistry play in regulating the deposition and clearance of dendrimers in rodents. 

xampl m 

uctive 

A, 

learance 

a et al., 

04). 

 A significant amount of intradermally injected nanoscale quantum dots were found to 

h odes via subcutaneous 

lymphatics (Roberts, D.W. et al., 2005). Other studies (Tinkle et al., 2003) have shown 

es of 

le 

ine exposure-

 Information on the fate 

disperse into the surrounding viable subcutis and to draining lymp n

enhanced penetration of submicron fluorospheres into the stratum corneum of human skin 

following dermal application and mechanical stimulation. Drug delivery studies using model 

wax nanoparticles have provided evidence that nanoparticle surface charge alters blood-brain 

barrier integrity and permeability (Lockman et al., 2004). It has recently been reported that 

quantum dots with different physicochemical properties (size, shapes, coatings) penetrated the 

stratum corneum and localized within the epidermal and dermal layers of intact porcine skin 

within a maximum 24 hours of exposure (Ryman-Rasmussen et al., 2006). A recent review 

noted that quantum dots cannot be considered a uniform group of substances, and that size, 

charge, concentration, coating, and oxidative, photolytic, and mechanical stability are 

determining factors in quantum dot toxicity as well as their absorption, distribution, metabolism 

and excretion (Hardman, 2006). Toxicological studies have demonstrated the direct cellular 

uptake of multi-walled carbon nanotubes by human epidermal keratinocytes (Monteiro-Riviere et

al., 2005). 

 Very little is known regarding the deposition and fate of other types or class

intentionally produced nanomaterials following inhalation, ingestion, or dermal exposures. 

Knowledge of tissue and cell specific deposition, fate and persistence of engineered or 

manufactured nanomaterials, as well as factors such as host susceptibility and nanopartic

physicochemical properties regulating their deposition and fate, is needed to determ

dose-response relationships associated with various routes of exposures.

of nanomaterials is needed to assess their persistence in biological systems, a property that 

regulates accumulation of these particles to levels that may produce adverse health effects 

following long-term exposures to low concentrations of these particles. 
EPA Nanotechnology White Paper 57

 At a 2004 nanotoxicology workshop at the University of Florida (Roberts, S.M., 2005)

concerns were expressed about the ability of existing technologies to detect and quantify 

intentionally produced nanomaterials in biological systems. New detection methods o

approaches, such as the use of labeled or tagged nanomaterials, may have to be developed i

order to analyze and quantify nanomaterials within biological systems.

3.6.5 Susceptible Subpopulations 

 Particle toxicology research has shown that not all individuals in the population respond 

to particle exposures in the same way or to the same degree (U.S. EPA, 2004). Host 

susceptibility factors that influence the toxicity, deposition, fate and persistence of intentionally 

produced nanomaterials are largely unknown, although a study regarding the deposition of 

anoparticles in the respiratory tract of asthmatics has been published (Chalupa et al., 2004). 

, 

r 

n 

ps of 

 the 

-

y is 

alent 

n

More information is critically needed to understand the exposure-dose-response relationshi

intentionally produced nanomaterials in order to recommend safe exposure levels that protect

most susceptible subpopulations.

3.6.6 Health Effects of Environmental Technologies That Use Nanomaterials 

 The potential for adverse health effects may arise from direct exposure to intentionally

produced nanomaterials and/or byproducts associated with their applications. Nanotechnolog

being employed to develop pollution control and remediation applications. Reactive zero-v

iron nanoparticles are being used to treat soil and aquifers contaminated with halogenated 

hydrocarbons, such as TCE (trichloroethylene) or DCE (dichloroethylene), and heavy metals 

(www.bioxtech.com). However, the production of biphenyl and benzene associated with 

nanoscale zero-valent iron degradation of more complex polychlorinated hydrocarbons has been

reported (Elliott et al., 2005). 

 Photocatalytic titanium dioxide nanoparticles (nano-TiO2) are being incorporated into

building materials such as cement and surface coatings in order to reduce ambient air nitrogen 

oxides (NOx) levels. The European Union Photocatalytic Innovative Coverings Applications for

Depollution Assessment has evaluated the effectiveness of photocatalytic nano-TiO2 to decrease 

ambient air NOx levels and has concluded that this technology represents a viable approach to 

attain 21 ppb ambient air NOx levels in Europe by 2010 (www.picada-project.com). However, 

the extent to which nano-TiO2 reacts with other ambient air co-pollutants and alters their 

fantly 

ts 

d and are currently not 

nown. 

corresponding health effects is not known. 

 Cerium oxide nanoparticles are being employed in the United Kingdom as on- and of

road diesel fuel additives to decrease emissions and some manufacturers are claiming fuel 

economy benefits. However, one study employing a cerium additive with a particulate trap has 

shown cerium to significantly alter the physicochemistry of diesel exhaust emissions resulting in 

increased levels of air toxic chemicals such as benzene, 1,3-butadiene, and acetaldehyde. 

Modeling estimates have predicted that use of a cerium additive in diesel fuel would signific

increase the ambient air levels of cerium (Health Effects Institute, 2001). The health impac

associated with these alterations in diesel exhaust have not been examine

k
58 EPA Nanotechnology White Paper 

 Environmental technologies using nanotechnology lead to direct interactions of reactive,

intentionally produced nanomaterials with chemically complex mixtures present within a 

of environmental media such as soil, water, ambient air, and combustion emissions. The

effects associated with these interactions are unknown. Research will be needed to assess the 

health and environmental risks associated with environmental applicatio

variety 

 health 

ns of nanotechnology. 

materials 

omplex 

use 

y 

3.7.1 Uptake and Accumulation of Nanomaterials 

Based on analogy to physical-chemical properties of larger molecules of the same 

ateria

is last 

gill membranes of aquatic organisms or the GI tract of both 

quatic and terrestrial organisms. Uptake via passive diffusion of neutral particles is low, but 

till me n 

n 

sts that 

aterials within this range, but not for nanomaterials 

ith larger effective cross-sectional diameters. 

ral specific characteristics, including water chemistry (e.g., dissolved organic carbon 

nd particulate organic carbon) and biotic (lipid content and trophic level) characteristics, when 

3.7 Ecological Effects of Nano

 Nanomaterials may affect aquatic or terrestrial organisms differently than larger particles 

of the same materials. As noted above, assessing nanomaterial toxicity is extremely c

and multi-factorial, and is potentially influenced by a variety of physicochemical properties such

as size and shape, and surface properties such as charge, area, and reactivity. Furthermore, 

of nanomaterials in the environment may result in novel byproducts or degradates that also ma

pose risks. The following section summarizes available information and considerations 

regarding the potential ecological effects of nanomaterials. 

m l, it may be possible to estimate the tendency of nanomaterials to cross cell membranes 

and bioaccumulate. However, current studies have been limited to a very small number of 

nanomaterials and target organisms. Similarly, existing knowledge could lead us to predict a 

mitigating effect of natural materials in the environment (e.g., organic carbon); however, th

concept would need to be tested for a wide range of intentionally produced nanomaterials. 

Molecular weight (MW) and effective cross-sectional diameter are important factors in 

uptake of materials across the 

a

s asurable within a range of small molecular weights (600-900) (Zitko, 1981; Opperhuize

et al., 1985; Niimi and Oliver, 1988; McKim et al., 1985). The molecular weight of some 

nanomaterials falls within this range. For example, the MW of n-C60 fullerene is about 720, 

although the MW of a C84 carbon nanotube is greater than 1000. Passive diffusion through gill 

membranes or the GI tract also depends on the cross sectional diameter of particles (Opperhuize

et al., 1985; Zitko, 1981). Existing evidence indicates that the absolute limit for passive 

diffusion through gills is in the nanometer range (between 0. 95 and 1.5 nm), which sugge

passive diffusion may be possible for nanom

w

Charge is also an important characteristic to consider for nanomaterial uptake and 

distribution. For example, as noted above, drug delivery studies using model wax nanoparticles 

have provided evidence that nanoparticle surface charge alters blood-brain barrier integrity and 

permeability in mammals (Lockman et al., 2004). 

 Other chemical and biotic characteristics may need to be considered when predicting 

accumulation and toxicity of nanoparticles in aquatic systems. For example, the Office of Water

uses seve

a
EPA Nanotechnology White Paper 59

c ting national bioaccumulation factors for highly hydrophobic neutral organic compounds 

(U.S. EPA, 2003). 

Because the properties of some nanomaterials are likely to result in uptake and 

distribution phenomena different from many conventional chemicals, it is critically important to

alcula

conduct studies that will provide a solid understanding of these phenomena with a range of 

an health effects assessment will provide an 

important foundation for understanding mammalian exposures and some cross-species processes 

 in 

and 

dies 

observations that (a) there was a trend for reduced lipid peroxidation in the liver and gill, (b) 

signific

se 

er 

overn 

agnitude, with fullerene particle solutions 

(particle clumps measured as 10-20 nm diameter) having an LC50 of 460 ppb and titanium 

dioxide cted 

thpaste) did not cause toxicity. Figure 21 

hows nanoparticles in the gut and lipid storage droplets of Daphnia magna following uptake 

om w

nanomaterials and species. Studies related to hum

(e.g., ability to penetrate endothelium and move out of the gut and into the organism). However, 

other physiology differs among animal classes, most notably respiratory physiology (e.g., gills

aquatic organisms and air sacs and unidirectional air flow in birds), while plants and 

invertebrates (terrestrial and aquatic) have even greater physiological differences. Because of 

their size, the uptake and distribution of nanomaterials may follow pathways not normally 

considered in the context of conventional materials (e.g., pinocytosis, facilitated uptake, 

phagocytosis). 

3.7.2 Aquatic Ecosystem Effects 

To date, very few ecotoxicity studies with nanomaterials have been conducted. Stu

have been conducted on a limited number of nanoscale materials, and in a limited number of 

aquatic species. There have been no chronic or full life-cycle studies reported. 

For example, Oberdörster (2004b) studied effects of fullerenes in the brain of juvenile 

largemouth bass and concluded that C60 fullerenes induce oxidative stress, based on their 

ant lipid peroxidation was found in brains, and (c) the metabolic enzyme glutathione-Stransferease (GST) was marginally depleted in the gill. However, no concentration-respon

relationship was evident as effects observed at a low dose were not observed at the single high

dose and no changes in fish behavior were observed; effects could have been due to random 

variation in individual fish. 

Oberdörster (2004c) tested uncoated, water soluble, colloidal fullerenes (nC60) and 

estimated a Daphnid 48-hour LC50 (forty-eight-hour concentration that was lethal for 50 percent 

of the animals in the test) at 800 parts per billion (ppb), using standard EPA protocols. L

and Klaper (2006) tested titanium dioxide (TiO2) and uncoated C60 fullerenes in an EPA 

standard, 48-hour acute toxicity test using Daphnia magna. Toxicity of titanium dioxide 

particles and fullerenes differed by an order of m

 (10-20 nm) with an LC50 of 5.5 parts per million (ppm). Particle preparation impa

toxicity: filtering solutions to remove particles larger than 100 nm resulted in LC50 of 7.9 ppm, 

while larger titanium dioxide clumps yielded no measurable toxicity. Large particles of titanium

dioxide (the kind found in sunblock, paint, and too

s

fr ater. 
60 EPA Nanotechnology White Paper 

Additionally, in behavior tests 

with filtered fullerenes, Daphnia

xhibited behavioral responses, with 

juvenil

hat some suspended 

natural nanosized particles in the aquatic 

 to 

aquatic organisms, with effects 

ngineered/manufactured nanomaterials 

seems t

in 

 engineered or manufactured nanomaterials should be considered. 

For example, as noted previously, SWCNTs displayed greater pulmonary toxicity than carbon 

black n ry 

inst 

 of 

ls to ecological terrestrial test species (plants, wildlife, soil invertebrates, or soil 

microorganisms). 

e

es showing an apparent inability 

to swim down from the surface and 

adults demonstrating sporadic 

swimming and disorientation (Lovern 

and Klaper, 2005). Further research on 

ecological species is clearly needed. 

 Toxicity studies and structureactivity relationship predictions for 

carbon black and suspended clay 

particles, based on analyses by EPA’s 

OPPT, suggest t

environment will have low toxicity

thresholds ranging from tens to 

thousands of parts per million. Limited 

preliminary work with 

e

o substantiate this conclusion. 

For example, Cheng and Cheng (2005) 

reported that aggregates of single-walled 

carbon nanotubes (SWCNT) added to 

zebrafish embryos reduced hatching rate at 72 hrs, but by 77 hrs post fertilization all embryos 

the treated group had hatched. However, when evaluating a limited data set of nanoscale 

materials (i.e., carbon black and clay only), available information on differences in toxicity 

observed between natural and

Figure 21. Fluorescent nanoparticles in water flea 

(Daphnia magna). 

 observed in gut 

ser scanning 

Adult and neonate Daphnia were exposed to 20nm and 

1000nm fluorescently tagged carboxylated nanospheres 

for up to 24 hours. Nanoparticles were

and fatty lipid storage droplets using la

confocal microscopy. (Image courtesy of Teresa 

Fernandes and Philipp Rosenkranz, Copyright Napier 

University. Research funded by CSL [DEFRA, UK])

anoparticles (Lam et al., 2004). Shvedova et al. (2005) reported unusual inflammato

responses to specific nanomaterials in mammals, suggesting that some nanomaterials may injure 

organs by novel mechanisms. 

 Recent reports suggest that nanomaterials may be effective bactericidal agents aga

both gram positive and negative bacteria in growth media (Fortner et al., 2005). The ability

these “nano-C60” aggregates to inhibit the growth and respiration of microbes needs to be 

demonstrated under more realistic conditions. For example, effects on microbes in sewage 

sludge effluent and natural communities of bacteria in natural waters should be examined. 

3.7.3 Terrestrial Ecosystem Effects 

 To date, very few studies have successfully been conducted to assess potential toxicity of 

nanomateria
EPA Nanotechnology White Paper 61

y t

ered. For example, studies described above indicate that 

re more toxic on a mass-based exposure metric when 

chemical composition in studies of lung toxicity 

99; Höhr et al., 2002), and some nanomaterials can display 

xplained by differences in particle size alone (Lam et al., 2004; 

malian epidermal cell in culture has also been reported 

The same properties of nanomaterials that regulate uptake in aquatic organisms may limit 

r transport through plant leaves and stomata (i.e., 

W or size). Additionally, because many nanomaterials are 

 surfaces, it is quite possible that significant pathways for 

 disruption of respiratory epithelium structure/function or 

 In a recent study of nanomaterial effects on plants, Yang 

 root growth in a soil-free 

cluded 

(Zea ma

carr g 

c c s 

 inhibition. Larger 

wa ized 

anop

t th

in Further, Murashov (2006) noted some limitations 

on of known phytotoxicity of alumina, and that the 

 the 

ARs for polycationic polymers, published in Boethling and 

Nabholz (1997). Synthesis of radio-labeled nanomaterials (e.g., carbon-14 labeled nanotubes) 

ay be

n engineered to have very specific properties, it seems 

reasonable to presume that they may end up having unusual toxicological effects. Experiences 

tial 

de longer-term exposures measuring multiple, sub-lethal endpoints. They 

hould be conducted (using appropriate forms and routes of exposure) in a manner that will 

For terrestrial mammals, toxicit

risk assessments should be consid

ultrafine or nanosize range particles a

compared to larger particles of identical 

(Oberdörster et al., 1994; Li et al., 19

unique toxicity that cannot be e

Warheit et al., 2004). Toxicity to mam

(Shvedova et al., 2003). 

est data on rats and mice obtained for human health 

uptake of nanoparticles by plant roots o

reducing passive transport at lower M

designed to have strongly reactive

toxicity may exist without uptake (e.g.,

other surface cell structure/function). 

and Watts (2005), reported that alumina nanoparticles (13 nm) slowed

exposure medium. Species tested in

risk assessments of pesticides: corn 

max), cabbage (Brassica oleracea), and 

the alumina nanoparticles with an organi

effect of root elongation

growth, indicating that the alumina itself 

that the surface charge on the alumina n

plant root growth. It should be noted tha

soil, so environmental relevance is uncerta

of this report including lack of discussi

increased solubility of nanoscale alumina may have resulted in increased concentrations of 

alumina species, which may have contributed to the observed phytotoxicity, as opposed to

nanoscale properties of the alumina. 

Fundamentally, our ability to extrapolate toxicity information from conventional 

substances to nanomaterials will require knowledge about uptake, distribution, and excretion 

rates as well as modes of toxic action, and may be informed by existing structure-activity 

relationships (SARs), such as S

commercially important species used in ecological

ys), cucumber (Cucumis sativus), soybean (Glycine 

ot (Daucus corota). The authors reported that coatin

ompound (phenanthrene), reduced the nanomaterial’

alumina particles (200-300 nm) did not slow root 

s not causing the toxicity. The authors hypothes

articles may have played a role in the decreased 

ese studies were conducted in Petri dishes without 

.

m a useful tool, along with advanced microscopy (e.g., comparable to techniques used for

asbestos quantification) for developing information on sites of toxic action and metabolic 

distribution. 

3.7.4 Ecological Testing Issues 

 Because nanomaterials are ofte

with conventional chemicals suggest that in these cases, chronic effects of exposure are often a 

more important component of understanding ecological risk than acute lethality. As such, ini

studies should inclu

s
62 EPA Nanotechnology White Paper 

elucidate key taxonomic groups (i.e., highly sensitive organisms that may become indicator 

species) and endpoints that may be of greatest importance to determining ecological risk. Th

studies must also include careful tracking of uptake and disposition to understand toxicity as

function of dose at the site of action. 

 A number of existing test procedures that assess long-term survival, growth, 

development, and reproductive endpoints (both whole organism and physiological or 

biochemical) for inverteb

ese 

 a 

rates, fish, amphibians, birds, and plants (including algae, rooted 

acrophytes, and terrestrial plants) should be adaptable to nanomaterials. These tests are able to 

examin

jecting 

m

e a wide range of species and endpoints to help pinpoint the types of effects most 

significant to the evaluation of nanomaterials, and have a strong foundation relative to pro

likely ecological effects. Both pilot toxicity testing protocols and definitive protocols should be 

evaluated with respect to their applicability to nanomaterials. In addition, field studies or 

mesocosm studies might be conducted in systems known to be exposed to nanomaterials to 

screen for food chain bioaccumulation and unanticipated effects or endpoints. 
EPA Nanotechnology White Paper 63

4.0 Responsible Development

 One of the stated goals of the National Nanotechnology Initiative is to support 

sponsible development of nanotechnology. EPA administers a statutory framework laid out in 

earch, and 

e ways 

er, 

 EPA 

ories 

ater 

dentification, 

otential environmental release, environmental fate and transport, human exposure and 

mitigation, human and environmental effects, risk assessments, and pollution prevention is 

needed to provide sound scientific information that informs the responsible development of 

nanotechnology. 

4.1 Responsible Development of Nanoscale Materials 

 EPA recognizes the potential benefits of nanomaterials. To fully realize that potential, 

the responsible development of such products is in the interest of EPA, state environmental 

protection agencies, producers, their suppliers, as well as users of nanotechnology, and society as 

a whole. EPA believes that a proactive approach is appropriate in responsible development. 

EPA believes that partnerships with industrial sectors will ensure that responsible development is 

part of initial decision making. Working in partnership with producers, their suppliers, and users 

of nanomaterials to develop best practices and standards in the workplace, throughout the supply 

chain, as well as other environmental programs, would help ensure the responsible development 

of the production, use, and end of life management of nanomaterials. 

re

this chapter that supports responsible development. EPA also funds and conducts res

identifies research needs within the context of its programmatic statutory mandates. Th

that risks are characterized and decisions are made vary based on the program area (air, wat

chemical substances, etc.) and also the specific statute involved (for example, Clean Air Act, 

Clean Water Act, Toxic Substances Control Act). Supporting responsible development at

is informed by an understanding of the risk from exposure to potential hazard. Section 4 of this 

paper discusses the risk assessment process and the types of information that EPA could need to 

inform its decisions. Figure 22 identifies EPA office roles, statutory authorities, and categ

of research needs related to nanotechnology. As illustrated in Figure 22 and described in gre

detail in Chapter 5, an understanding of environmental applications, chemical i

p
64 EPA Nanotechnology White Paper 

Key

Office of 

Prevention, 

Pesticides, and 

Toxic 

Substances

Office of Air and 

Radiation Office of Water

Offic d 

Wa

Em

Res

e of Soli

ste and 

ergency 

ponse

Office of 

Environmental 

Information

Offi

Resea

Develo

Toxic Substance Control Act: Review/Oversight of Industrial Chemical

Federal Insecticide, Fungicide, Rodenticide Act: Registration of Pesticides

Pollution Prevention Act: Incorporate P2 into all aspects of chemical oversight

Clean Air Act: 

Criteria air 

pollutants,

Hazardous air 

pollutants, 

Registration of fuel

and fuel additives

s 

Clean Water Act: 

Effluent Guidelines, 

Water quality 

guidelines or 

standards

Safe Drinking 

Water Act: 

Contaminants in 

drinking water,

cleaning up 

contaminants

Comp e 

Envir l 

Re

Compe and 

Liabili nd 

source vation 

and Re Act: 

zardou nces 

or 

Soli

rehensiv

onmenta

sponse, 

nsation,

ty Act a

 Conser

covery 

s substa

wastes, 

d Waste

Re

Ha

Toxic Release Inventory: Reporting of chemical releases

 Coor

ReseStrat

 Cond

Reseall of need

Chemical Identification 

and Analysis

Environmental Fate 

and Treatment

 Chemical 

Identification anAnalysis

 Environmental 

Fate 

 Releases and 

Human Exposu

 Health and 

Ecological Effe

 Risk Assessme Environmental 

Detection and Analysis

d 

re

cts

nt

 Chemical 

Identification and Analysis

 Environmental 

Fate 

 Releases and 

Human Exposure

 Health and 

Ecological Effects

 Risk 

Assessment

 Environmental 

Detection and Analysis

 Remediation 

Applications



Chemi ificatioand AEnviroand Tr

Relea Human ExposHealth ologicaEffectsRisk As entEnviroDetectAnalysRemeApplic

cal Ident

nalysis

nmental Fate 

eatment

ses and 

ure

 and Ec

sessm

nmental 

ion and 

is

diation 

ations

n 

l 

Office

Statute

and Roles

Research 

Needs

 Chemical 

Identification and Analysis

 Environmental 

Fate and Treatment

 Releases and 

Human Exposure

 Health and 

Ecological Effects

 Risk Assessment Environmental 

Detection and Analysis

 Chemical 

Identification and Analysis

 Environmental 

Fate and Treatment

 Chem

Identand A

 Envi

Fate Trea

Figure 22. EPA Office Roles, Statutory Authorities, and Categorie R s of esearch Needs Related to Nano
EPA Nanotechnology White Paper 65

 Responsible development of nanomaterials may present issues that are not easily 

characterized because of the breadth of categories of such substances. Some nanoscale materials 

are produced under established industrial hygiene practices based on their history of 

ma

som her nanoscale materials, there is less understanding of expected exposure and potential 

hazard. The uncertainty may be greater where new industrial methods are employed. 

nanotechnology products and processes as they 

are introduced, under EPA’s product review authorities, such as TSCA, FIFRA, and the Clean 

Air Act. EPA intends to work with producers and users of nanomaterials to develop protocols 

and approaches that ensure responsible development. As new knowledge becomes incrementally 

available through the research needs identified in this white paper, refinement of approaches may 

be needed. 

4.2 Program Areas 

inisters a wide range of environmental statutes, some of which may apply to 

nan terials depending on the specific media of application or release, such as air or water. 

Other statutes may apply to certain nanomaterials depending on their specific uses, applications, 

and processes and may require EPA to evaluate the nanomaterials before they enter into 

commerce (such as pesticides, fuel additives, etc.). Some risk management activities carried out 

under these statutes could also utilize nanomaterials as products for environmental remediation 

or pollution prevention technologies. The statutes administered by EPA outlined below are a 

starting point for evaluating and managing risks and benefits from nanomaterials. Some current 

EPA policies and regulations may require modifications to address this new technology. 

 Nanoscale materials will present other novel risk assessment/management challenges. 

Standards that need to be developed include terminology/nomenclature, material 

characterization, metrology, testing procedures, and detection methodology. There is also a need 

to r w conventional hazard, exposure, and risk assessment tools for their applicability to 

nan terials, as well as development of risk mitigation options that are tailored to nanoscale 

materials. There may also be a need to review and modify reporting tools under various statutes 

to best cover nanoscale materials. 

4.2.1 Chemical Substances 

anoscale materials that meet the definition of “chemical substances” under 

the Toxic Substances Control Act (TSCA), but which are not on the TSCA Inventory, must be 

reported to EPA according to section 5(a) of the Act, which provides for pre-manufacture 

review. The premanufacture review process serves as a gatekeeper to identify concerns and 

exercise appropriate regulatory oversight. For example, use restrictions, occupational exposure 

lim ls, limits on releases to the environment and limits on manufacture may be required 

until toxicity and fate data are developed to better inform a risk assessment of the chemical. As 

previously noted EPA already is reviewing premanufacture notifications for some nanomaterials 

that have been received under TSCA. EPA also may review under section 5(a) of TSCA 

nanomaterials that represent significant new uses of chemicals already on the TSCA Inventory.

nufacturing processes and use. Human and environmental exposure information for these 

particular substances likely would already be available to inform responsible development. For 

e ot

EPA intends to review as appropriate new 

EPA adm

oma

evie

oma

Generally, n

its/contro
66 EPA Nanotechnology White Paper 

 Under TSCA, EPA has the authority, by rule, to prohibit or limit the manufacture, import, 

processing, distribution in commerce, use, or disposal of a chemical substance; requir

development of test data; and/or require reporting of health and safety studies, categories of us

production volume, byproducts, an estimate of the number of individuals potentially exposed, 

and duration of such exposures, if the necessary findings or determinations are made. 

Nanomaterials that meet the definition of a chemical substance under TSCA could be s

e 

e, 

ubject to 

me or all of these provisions and programs.

esticide registration decisions are based on a detailed assessment of the 

uct on human health and the environment, when used according to 

 establish programs to protect workers, and to 

the 

s. As 

mende t 

e 

sued health effects testing requirements for fuels and fuel 

l fuels and their additives are subject to the regulations issued by 

es for use in on-road applications may not be introduced into 

is 

so

4.2.2 Pesticides 

 Under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), EPA is 

responsible for registering pesticide products for distribution or sale in the United States. An 

application for registration under FIFRA must disclose to EPA the specific chemicals in the 

pesticide formulation. P

potential effects of a prod

label directions. FIFRA requires EPA and states to

provide training and certification for applicators. Pesticide products containing nanomaterials 

will be subject to FIFRA’s review and registration requirements. In addition, to the extent that

the use of pesticide products containing nanomaterials results in residues in food, the resulting 

residues require the establishment of a tolerance (maximum allowed residue limit) under 

Federal Food, Drug, and Cosmetic Act. 

4.2.3 Air 

 The Clean Air Act (CAA) governs, among other things, the establishment, review and 

revision of national ambient air quality standards and identification of criteria air pollutant

a d in 1990, it also identified 190 Hazardous Air Pollutants (HAPs) for regulation (the lis

currently includes 187 HAPs) and provides EPA with authority to identify additional HAPs. Th

CAA also contains requirements that address accidental releases of hazardous substances from 

stationary sources that potentially can have serious adverse effects to human health or the 

environment. Use or manufacture of nanomaterials could result in emissions of pollutants that 

are or possibly could be listed as criteria air pollutants or HAPs. 

 Under the CAA, EPA has is

additives. Gasoline and diese

EPA. These fuels and additiv

commerce until they have been registered by EPA. As previously noted EPA has received and 

reviewing an application for registration of a diesel additive containing cerium oxide. 

4.2.4 Pollution Prevention 

 The Pollution Prevention Act of 1990 was considered a turning point in how the nation 

looks at the control of pollution. Instead of focusing on waste management and pollution 

control, Congress declared a national policy for the United States to address pollution based on 

"source reduction." The policy established a hierarchy of measures to protect human health and 

the environment, where multi-media approaches would be anticipated: (1) pollution should be 
EPA Nanotechnology White Paper 67

prevented or reduced at the source; (2) pollution that cannot be prevented should be recycled in 

ironment 

esign for the Environment (DfE) Program and 

the Green Chemistry Program. Under DfE, EPA works in partnership with industry sectors to 

ance of commercial processes while reducing risks to human health and the 

environment. The Green Chemistry Program promotes research to design chemical products and 

. 

d 

c organisms, wildlife, and humans that live in, recreate 

on, or come in contact with waters of the United States. Depending on the toxicity of 

als to aquatic life, aquatic dependent wildlife, and human health, as well as the 

s. 

96, is the main federal law that 

rotects

ntial to contribute to better and more cost-effective removal of 

, such as metals (e.g. arsenic or chromium), toxic halogenated 

o 

an environmentally safe manner; (3) pollution that cannot be prevented or recycled should be 

treated in an environmentally safe manner; and (4) disposal or other release into the env

should be employed only as a last resort and should be conducted in an environmentally safe 

manner. 

 As a result of the Act, two programs were initiated, with two different approaches, to 

meet the spirit of the new national policy: the D

improve perform

processes that reduce or eliminate the use and generation of toxic chemical substances. 

In 1998, EPA complimented these two programs with the Green Engineering Program, which 

applies approaches and tools for evaluating and reducing the environmental impacts of processes

and products (see http://www.epa.gov/oppt/greenengineering). Nanotechnology offers an 

opportunity to implement pollution prevention principles into the design of a new technology

4.2.5 Water 

The stated goals of the Clean Water Act (CWA) are to protect the chemical, physical, an

biological integrity of the nation’s waters as well as to ensure the health and welfare of the 

environment, fish, shellfish, other aquati

nanomateri

potential for exposure, nanomaterials may be regulated under the CWA. A variety of approaches 

are available under the CWA to provide protection, including effluent limitation guidelines, 

water quality standards (aquatic life, human health, biological), best management practices, 

NPDES permits, and whole effluent toxicity testing. Simultaneously, nanomaterials may provide

an effective and efficient mechanism to resolve water quality contamination and its impacts on 

aquatic life, aquatic dependent wildlife, and human health. Both scenarios must be explored to 

determine how and when to regulate these potentially hazardous additions to the nation’s water

 The Safe Drinking Water Act (SDWA), as amended in 19

p public health by regulating hazardous contaminants in drinking water. SDWA authorizes 

the Agency to establish non-enforceable health-based Maximum Contaminant Level Goals 

(MCLGs) and enforceable Maximum Contaminant Levels (MCLs) or required treatment 

techniques, as close as feasible to the MCLGs, taking into consideration costs and available 

analytical and treatment technology. Nanotechnology has the potential to influence the setting of 

MCLs through improvements in analytical methodology or treatment techniques. 

Nanotechnology has the pote

drinking water contaminants

organic chemicals, suspended particulate matter and pathogenic microorganisms. If 

nanoparticles enter drinking water, such as through their use in water treatment, then exposure t

nanomaterials may occur through drinking water ingestion or inhalation (e.g. from showering). 

Based on their toxicity and occurrence in drinking water supplies, nanomaterials could be 

regulated under the SDWA. 
68 EPA Nanotechnology White Paper 

4.2.6 Solid Waste 

 The Comprehensive Environmental Response, Compensation, and Liability Act 

(CERCLA) addresses contamination at closed and abandoned waste sites. CERCLA gives EP

the author

A 

ity to respond to actual or threatened releases of hazardous substances to the 

nvironment and to actual or threatened releases of pollutants or contaminants that may present 

n imm

ste 

icipal 

s 

regulations. Subtitle I covers underground storage tanks, and Subtitle J covers medical waste 

ct 

s of the 

ertain other sectors, as well as federal facilities. Some producers of nanomaterials containing 

ateria

endar 

 commonly 

and others are supporting research into green nanotechnology, to 

hnology that reduce pollution from industrial processes as well as 

e

a inent and substantial danger to the public health or welfare. Nanomaterials that meet 

these criteria potentially would be subject to this authority. 

 The Resource Conservation and Recovery Act (RCRA), which amended the Solid Wa

Disposal Act, regulates, from the point of generation, the management of solid and hazardous 

wastes, underground storage tanks, and medical wastes. Subtitle D of RCRA covers mun

and other non-hazardous wastes. Subtitle C of RCRA covers the storage, transportation, 

treatment, disposal, and cleanup of hazardous wastes. Nanomaterials that meet one or more of 

the definitions of a hazardous waste (i.e., a waste that is specifically listed in the regulation

and/or that exhibits a defining characteristic) potentially would be subject to subtitle C 

incineration. 

 The 1990 Oil Pollution Act (OPA) amended the Clean Water Act (CWA) to address the 

harmful environmental impacts of oil spills. EPA responsibilities under the Oil Pollution A

include response (cleanup/containment/prevention action) and enforcement actions related to 

discharges and threatened discharges of oil or hazardous substances in the inland water

United States. 

4.2.7 Toxics Release Inventory Program 

 In 1986, Congress passed the Emergency Planning and Community Right to Know Act 

(EPCRA) and the Toxics Release Inventory (TRI) was established. The TRI is a publicly 

available database containing information on toxic chemical releases and other waste 

management activities that are reported annually by manufacturing facilities and facilities in 

c

m ls listed in the TRI may be subject to reporting under the TRI Program 

(www.epa.gov/tri/). Facilities required to report TRI chemical releases and other waste 

management quantities are those that met or exceeded the minimum criteria of number of 

employees and total mass of chemical manufactured, processed, or otherwise used in a cal

year. Of the nearly 650 toxic chemicals and chemical compounds on the TRI, a number are 

metals and compounds containing these metals, including cadmium, chromium, copper, cobalt 

and antimony. Such compounds may be produced as nanomaterials, and some are

used in quantum dots. 

4.3 Environmental Stewardship 

Nanotechnology provides an opportunity for EPA and other stakeholders to develop best 

practices for preventing pollution at its source and conserving natural resources whenever 

possible. For example, EPA 

identify applications of nanotec
EPA Nanotechnology White Paper 69

to develop manufacturing process that fabricate nanomaterials in an environmentally friendly 

manner. Appendix B provides a fuller discussion of stewardship principles. Many diverse 

nology 

r 

; and the design, use, disposal, and 

ewardship of products consistent with the goal of pollution prevention. Information on 

industrial organizations and their suppliers have the opportunity at this early stage of tech

development and use to be leading environmental stewards. 

At EPA, in addition to our support for green nanotechnology research, there are a numbe

of programs already in place that are based upon environmental stewardship principles. These

programs address processes, including inputs; waste streams

st

nanotechnologies and materials could be provided through existing information networks, and 

EPA could pursue additional voluntary initiatives or integrate nanotechnology and nanoscale 

materials into already existing voluntary programs to ensure responsible development. 
70 EPA Nanotechnology White Paper 

5.0 EPA’s Research Needs for Nanomaterials 

 Research is needed to inform EPA’s actions related to the benefits and impacts of 

anomaterials. However, there are significant challenges to addressing research needs for 

nanotec

e 

h will 

come from many sources, including academia, industry, EPA, and other agencies and 

organizations. Other government and international initiatives have also undertaken efforts to 

identify research needs for nanomaterials and have come to similar conclusions (UK Department 

for Environment, Food and Rural Affairs, 2005; NNI, 2006c ). 

 An overarching, guiding principle for all testing, both human health and ecological, is the 

determination of which nanomaterials are most used and/or have potential to be released to, and 

interact with, the environment. These nanomaterials should be selected from each of the broader 

classes of nanomaterials (carbon-based, metal-based, dendrimers, or composites) to serve as 

representative particles for testing/evaluation purposes. 

5.1 Research Needs for Environmental Applications 

 The Agency recognizes the benefits of using nanomaterials in environmental 

technologies. Research is needed to develop and test the efficacy of applications that detect, 

prevent and clean up contaminants. EPA also has the responsibility for determining the 

ecological and human health implications of these technologies. 

5.1.1 Green Manufacturing Research Needs 

 Nanotechnology offers the possibility of changing manufacturing processes in at least 

two ways: (1) by using less materials and (2) using nanomaterials for catalysts and separations to 

increase efficiency in current manufacturing processes. Nanomaterial and nanoproduct 

manufacturing offers the opportunity to employ the principles of green chemistry and 

engineering to prevent pollution from currently known harmful chemicals. Research enabling 

this bottom-up manufacturing of chemicals and materials is one of the most important areas in 

pollution prevention in the long term. Research questions regarding green manufacturing 

include: 

• How can nanotechnology be used to reduce waste products during manufacturing? 

• How can nanomaterials be made using benign starting materials? 

• How can nanotechnology be used to reduce the resources needed for manufacturing (both 

materials and energy)? 

n

hnology and the environment. The sheer variety of nanomaterials and nanoproducts adds 

to the difficulty of developing research needs. Each stage in their lifecycle, from extraction to 

manufacturing to use and then to ultimate disposal, will present separate research challenges. 

Nanomaterials also present a particular research challenge over their macro forms in that w

have a very limited understanding of nanoparticles’ physicochemical properties. Research 

should be designed from the beginning to identify beneficial applications and to inform risk 

assessment, pollution prevention, and potential risk management methods. Such researc
EPA Nanotechnology White Paper 71

• What is t nder a variety 

of manufacturing and environmental conditions? 

• How can nanotechnology assist “green” energy production, distribution, and use? 

te treatment methods. In addition, other 

iological particles, determining 

ating, and application 

e, research 

articles 

tic resistance and aversion to 

phage technologies offer an attractive option. 

Remediation and treatment research questions include: 

? When 

? 

ow can we improve methods for detecting and monitoring nanomaterials used in 

remediation and treatment? 

• To what extent are these materials and their byproducts persistent, bioaccumulative, and 

he life cycle of various types of nanomaterials and nanoproducts u

5.1.2 Green Energy Research Needs 

 Developing green energy approaches will involve research in many areas, including solar 

energy, hydrogen, power transmission, diesel, pollution control devices, and lighting. These 

areas have either direct or indirect impacts on environmental protection. In solar energy, 

nanomaterials may make solar cells more efficient and more affordable. In addition, 

nanocatalysts may efficiently create hydrogen from water using solar energy. Research 

questions for green energy include: 

• What research is needed for incentives to encourage nanotechnology to enable green 

energy? 

5.1.3 Environmental Remediation/Treatment Research Needs 

 The research questions in this area revolve around the effectiveness and risk parameters 

of nanomaterials to be used in site remediation. Materials such as zero-valent iron are expected 

to be useful in replacing current pump-and-treat or off si

nanoremediation approaches can involve the methods of coating b

the effect on the particles (enzyme or bacteriophage) following co

technologies. This is an area that has not been examined in any great detail. Therefor

is needed to develop technologies using nanocoated biological particles for environmental 

decontamination or prophylactic treatment to prevent contamination. The products of this 

research would be technologies utilizing innocuous biological entities treated with nanop

to decontaminate or prevent bacterial growth. In an age of antibio

chemical decontamination, enzyme and bacterio

• Which nanomaterials are most effective for remediation and treatment? 

• What are the fate and effects of nanomaterials used in remediation applications

nanomaterials are placed in groundwater treatment, how do they behave over time? Do

they move in groundwater? What is their potential for migrating to drinking water wells

• H

toxic and what organisms are affected? 

• If toxic byproducts are produced, how can these be reduced? 
72 EPA Nanotechnology White Paper 

• What is needed to enhance the efficiency and cost-effectiveness of remediation and 

treatment technology? 

5.1.4 Sensors 

 In general, nanosensors can be classified in two main categories: (1) sensors that are used 

to measure nanoscale properties (this category comprises most of the current market) and (2) 

sensors that are themselves nanoscale or have nanoscale components. The second categor

eventually result in lower material cost as well as reduced weight and power consump

sensors, leading to greater applicability, and is the subject of this section. Research need

sensors to detect nanomaterials in th

y can 

tion of 

s for 

e environment are discussed in the Environmental Detection 

ction below. 

• nanomaterials be employed in the development of sensors to detect biological 

and chemical contaminants? 

• How can sensor systems be developed to monitor agents in real time and the resulting 

d 

ysical-chemical property test methods 

re adequate for sufficiently characterizing various nanomaterials. Alternative methods may be 

nee

? 

To what extent will it be necessary to tailor research protocols to the specific type and use 

se

How can 

data accessed remotely? 

• How these small-scale monitoring systems be developed to detect personal exposures 

and in vivo distributions of toxicants. 

5.2 Research Needs for Risk Assessment 

5.2.1 Chemical Identification and Characterization 

 Research that can be replicated depends on agreement on the identification and 

characterization of nanomaterials. In addition, understanding the physical and chemical 

properties in particular is necessary in the evaluation of hazard (both human and ecological) an

exposure (all routes). It is not clear whether existing ph

a

ded. Research questions include: 

• What are the unique chemical and physical characteristics of nanomaterials? How do 

these characteristics vary among different classes of materials (e.g., carbon based, metal 

based) and among the individual members of a class (e.g., fullerenes, nanotubes)? 

• How do these properties affect the material’s reactivity, toxicity and other attributes

•

pattern of each nanomaterial? Can properties and effects be extrapolated within a class of

nanomaterials? 
EPA Nanotechnology White Paper 73

• Are there adequate measurement methods/technology available to fully characterize 

ish 

anomaterials from ultrafine particles or naturally occurring 

nanosized particles? 

•

entionally produced nanomaterials are now on the market and what new types of 

m

H sses, formulations, and incorporations in end products alter 

the characteristics of nanom

5.2.2 En reatment Research Needs 

 E

availabi ans and other life forms. Research on the 

transport and potential transformation of nanomaterials in soil, subsurface, surface waters, 

wastewater, drinking water, and the atmosphere is essential as nanomaterials are used 

ations, existing methods should be evaluated 

and if necessary, they should be modified or new methods should be developed. Research is 

. 

nanomaterials, to distinguish among different types of nanomaterials, and to distingu

intentionally produced n

Are current test methods for characterizing nanomaterials adequate for the evaluation 

hazard and exposure data? 

• Do nanomaterial characteristics vary from their pure form in the laboratory to their form 

as components of products and eventually to the form in which they occur in the 

environment? 

• What int

aterials can be expected to be developed? 

• ow will manufacturing proce

aterials? 

vironmental Fate and T

PA needs to ascertain the fate of nanomaterials in the environment to understand the 

lity of these materials for exposure to hum

increasingly in products. To support these investig

needed to address the following high-priority questions

5.2.2.1 Transport Research Questions

• What are the physicochemical factors that influence the transport and deposition of 

intentionally produced nanomaterials in the environment? How do nanomaterials move

through these media? Can existing information on soil colloidal fate and transport and 

atmospheric ultrafine particulate fate and transport inform our thinking? 

nd 

To what extent are nanomaterials mobile in soils and in groundwater? What is the 

nd 

within aquifers, with potential exposure to general populations via groundwater 

• ntial for these materials to be transported bound to particulate matter, 

sediments, or sludge in surface waters? 

• How are nanomaterials transported in the atmosphere? What nanomaterial properties a

atmospheric conditions control the atmospheric fate of nanomaterials? 

•

potential for these materials, if released to soil or landfills, to migrate to groundwater a

ingestion? 

What is the pote
74 EPA Nanotechnology White Paper 

• How do the aggregation, sorption and agglomeration of nanoparticles affect their 

transport? 

• How do nanomaterials bioaccumulate? Do their unique characteristics affect their 

bioavailability? Do nanomaterials bioaccumulate to a greater or lesser extent than macro5.2.2.2 Transformation Research Questions

scale or bulk materials? 

• parts? 

What are the physicochemical factors that affect the persistence of intentionally produced 

ionally produced nanomaterials (e.g., carbonmation regarding intentionally 

• Do particular nanomaterials persist in the environment, or undergo degradation via biotic 

roducts and their characteristics? 

Is the nanomaterial likely to be in the environment, and thus be available for 

esses 

? 

• How do the aggregation, sorption and agglomeration of nanoparticles affect 

5.2.2.3 Chemical Interaction Research Questions

How do nanoparticles react differently in the environment than their bulk counter

•

nanomaterials in the environment? What data are available on the physicochemical 

factors that affect the persistence of unintent

based combustion products) that may provide infor

produced nanomaterials? 

or abiotic processes? If they degrade, what are the byp

bioaccumulation/biomagnification? 

• How are the physicochemical and biological properties of nanomaterials altered in 

complex environmental media such as air, water, and soil? How do redox proc

influence environmental transformation of nanomaterials? To what extent are 

nanomaterials photoreactive in the atmosphere, in water, or on environmental surfaces

transformation? 

• In what amounts and in what forms may nanoparticles be released from materials that 

contain them, as a result of environmental forces (rain, sunlight, etc.) or through use, reuse, and disposal. 

• heir respective 

environmental interactions? Can these materials alter the mobility of other substances in 

5.2.2.4 Treatment Research Questions

How do nanosized adsorbants and chemicals sorbed to them influence t

the environment? Can these materials alter the reactivity of other substances in the 

environment? 

or 

aste treatment facilities? 

• What is the potential for these materials to bind to soil, subsurface materials, sediment 

wastewater sludge, or binding agents in w
EPA Nanotechnology White Paper 75

• Are these materials effectively removed from wastewater using conventional wast

treatment m

ewater 

ethods and, if so, by what mechanism? 

reams 

 in drinking water treatment and, if so, by what 

mechanism? 

•

) for treating nanomaterials? 

5.2

• Do these materials have an impact on the treatability of other substances in waste st

(e.g., wastewater, hazardous and nonhazardous solid wastes), or on treatment facilities 

performance? 

• Are these materials effectively removed

Do these materials have an impact on the removal of other substances during drinking 

water treatment, or on drinking water treatment facilities performance? 

How effective are existing treatment methods (e.g., carbon adsorption, filtration, 

coagulation and settling, or incineration/air pollution control system 

sequestration/stabilization

•

.2.5. Assessment Approaches and Tools Questions

Can existing information on soil colloidal fate and transport, as well as atmos

ultrafine particulate fate and transpor

• pheric 

t, inform our thinking? Do the current databases of 

ultrafines/fibers shed light on any of these questions? 

•

s for 

e 

 nanomaterials? 

5.2

ariety of methods currently available to measure nanoparticle 

mass/m , surface area, particle count, size, physical structure (morphology), 

enge remains to detect nanomaterials in the 

environment. Research is needed to address the following high-priority questions: 

5.2.3.1

Do the different nanomaterials act similarly enough to be able to create classes of like

compounds? Can these classes be used to predict structure-activity relationship

future materials? 

• Should current fate and transport models be modified to incorporate the uniqu

characteristics of

.3 Environmental Detection and Analysis Research Needs 

While there are a v

ass concentrations

and chemical composition in the laboratory, the chall

 Existing Methods and Technologies Research Questions

Are existing methods and technologies capable of detecting, characterizing, and 

quantifying intentionally

•

 produced nanomaterials by measuring particle number, size, 

ctivity, charge, and area), etc.? Can they distinguish 

between intentionally produced nanomaterials of interest and other ultrafine particles? 

• Are standard procedures available for both sample preparation and analysis? 

shape, surface properties (e.g., rea

Can they distinguish between individual particles of interest and particles that may have 

agglomerated or attached to larger particles? 
76 EPA Nanotechnology White Paper 

• s and procedures available? 

5.2.3.2 and Technologies Research Needs

Are quality assurance and control reference material

• How would nanomaterials in waste media be measured and evaluated? 

New Methods 

materials of interest in environmental media and for personal exposure 

monitoring. 

5.2.

the 

environ l population 

exposu taining nanoscale materials. 

alevolent activity such as a terrorist 

dentify potential sources, pathways, and 

rou 

pote i

exposu

trateg arch is needed to address the 

ll i

5.2.4.1

• What low-cost, portable, and easy-to-use technologies can detect, characterize, and 

quantify nano

4 Human Exposures, Their Measurement and Control 

Potential sources of human exposure to nanomaterials include workers exposed during 

production and use of nanomaterials, general population exposure from releases to the

ment during the production or use in the workplace, and direct genera

re during the use of commercially available products con

Releases from industrial accidents, natural disasters, or m

attack should also be considered. Research is needed to i

tes of exposure, potential tools and models that may be used to estimate exposures, and 

nt al data sources for these models, as well as approaches for measuring and mitigating 

re. NIOSH has also examined research needs regarding risks to workers and developed a 

s ic plan to address these needs (NIOSH 2005a, b). Rese

fo ow ng high-priority questions. 

. Risk and Exposure Assessment Research Questions

•

unt, surface area) should be used to measure exposure? 

atics, etc.) exposure 

s? 

5.2

Is the current exposure assessment process adequate for assessing exposures to 

nanomaterials? Is mass dose an effective metric for measuring exposure? What

alternative metric (e.g., particle co

Are sensitive populations’ (e.g., endangered species, children, asthm

patterns included? 

• How do physical and chemical properties of nanomaterials affect releases and exposure

• How do variations in manufacturing and subsequent processing, and the use of particle 

surface modifications affect exposure characteristics? 

.4.2 Release and Exposure Quantification Research Questions

What information is available about unique release and exposure patterns of 

nanomaterials? What additional information is needed? 

What tools/resources currently exist for assessing releases and exposures within EPA 

(chemical release information/monitoring system

•

•

s (e.g., TRI), measurement tools, 
EPA Nanotechnology White Paper 77

models, etc)? Are these tools/resources adequate to measure, estimate, and assess releases 

s, including 

personal exposure monitoring? 

5.2.4.3 Release and Exposure Reduction and Mitigation Research Questions

and exposures to nanomaterials? Is degradation of nanomaterials accounted for? 

• What research is needed to develop sensors that can detect nanomaterial

• se 

release via waste streams? Are these tools/resources adequate for 

nanomaterials? 

•

w 

tions disposed of properly? 

•

5.2.5 Human Health Effects Assessment Research Needs 

ire e

byp d

the toxi as susceptibility associated with 

exposure to intentionally produced nanomaterials, their application byproducts, decomposition 

 standard test methods will 

l chemical properties of 

inte o

ent research to also 

sta r 

ass l 

propert of 

What tools/resources exist for limiting release and/or exposure during manufacture, u

or following 

Are current respirators, filters, gloves, and other PPE capable of reducing or eliminating 

exposure from nanomaterials? 

• Are current engineering controls and pollution prevention devices capable of minimizing 

releases and exposures to nanomaterials? 

• Are technologies and procedures for controlling spills during manufacture and use 

adequate for nanomaterials? Can current conventional technologies (i.e., for nonnanomaterials) be adapted to control nanomaterial spills? 

• In the case of an unintentional spill, what are the appropriate emergency actions? Ho

are wastes from response ac

• Do existing methods using vacuum cleaners with HEPA filters work to clean up a spill of 

solid nanomaterials? If not, would a wet vacuum system work? 

What PPEs would be suitable for use by operators during spill mitigation? 

d

Adverse health effects of intentionally produced nanomaterials may result from either 

ct xposure resulting from inadvertent release of these novel materials or unintentional 

ro ucts produced by their intentional release into the environment. Very little data exist on 

city, hazardous properties, deposition and fate, as well 

products or production waste streams. Finally, it is uncertain whether

be capable of identifying toxicities associated with the unique physica

nti nally produced nanomaterials. 

It will be important for nanomaterial health effects risk assessm

e blish whether current particle and fiber toxicological databases have the ability to predict o

ess the toxicity of intentionally produced nanomaterials displaying unique physicochemica

ies. The limited studies conducted to date indicate that the toxicological assessment
78 EPA Nanotechnology White Paper 

specific

databas it is 

generally believed that nanoparticles can have toxicological properties that differ from their bulk 

mat a

multifa d by a variety of physiochemical properties such as size, 

chemical composition, and shape, as well as surface properties such as charge, area and 

ratio per unit 

weight for nanoparticles correlates with increased toxicity as compared with bulk material 

tox y

cell me ted to the 

circulat e the effects of shape on toxicity of nanoparticles appears unclear, the 

sults of a recent in vitro cytotoxicity study appear to suggest that single-wall carbon nanotubes 

are r

is conc get organs, cardiovascular, and neurological toxicities) in 

addition to portal-of-entry (e.g. lung, skin, intestine) toxicity. 

 with respect to the nature of the surface 

aterial/coating, the application for which the material is used, the likely route of exposure, the 

pre c

informa es that 

may oc nce with conventional 

chemicals suggests that toxicology research on nanomaterials should be designed from the 

beg i

Research is also needed to examine health impacts of highly dispersive nanotechnologies 

that e

necessa have on regulated 

ollutants in air, soil, or water, as well as their corresponding potential health effects. Research 

sho 

A. Determining the adequacy of current testing schemes, hazard protocols, and dose 

B. Identifying the properties of nanomaterials that are most predictive of toxicity to 

 their byproducts, associated with those nanotechnology 

applications that are most likely to have potential for exposure? (Addresses area C, 

 intentionally produced nanomaterials will be difficult to extrapolate from existing 

es. The toxic effects of nanoscale materials have not been fully characterized, but

eri l. A number of studies have demonstrated that nanoparticle toxicity is complex and 

ctorial, potentially being regulate

reactivity. As the size of particles decreases, a resulting larger surface-to-volume 

icit . Also as a result of their smaller size, nanoparticles may pass into cells directly through

mbranes or penetrate the skin and distribute throughout the body once transloca

ory system. Whil

re

mo e toxic than multi-wall carbon nanotubes. Therefore, with respect to nanoparticles, there

ern for systemic effects (e.g., tar

Initially, it will be important to be specific

m

sen e of other exposures which may affect toxicity (e.g., UV radiation) and not rely on 

tion derived from a study conducted under one set of conditions to predict outcom

cur under another set of conditions. However, past experie

inn ng with an eye towards developing hypothesis-based predictive testing. 

 ar employed for site remediation, monitoring, and pollution control strategies. It will be 

ry to determine both the impacts these types of nanotechnologies

p

uld be conducted in the following areas: 

metrics. 

receptors and their sensitive subpopulations. 

C. Identifying those nanomaterials with high commercial potential with dispersive 

applications, and their most probable exposure pathways. 

These areas lead to the following research questions: 

• What are the health effects (local and systemic; acute and chronic) from either direct 

exposure to nanomaterials, or to

above) 
EPA Nanotechnology White Paper 79

• Are there specific toxicological endpoints that are of higher concern for nanomateria

such as neurological, cardiovascular, respiratory, or immunological effects, etc.? 

(Addresses area C, above) 

• Are current testing methods (organisms, exposure regimes, media, analytical methods, 

testing schemes) applicable to testing nanomaterials in standardized agency toxic

(

ls, 

ity tests 

http://www.epa.gov/opptsfrs/OPPTS_Harmonized/)? (Addresses area A, above) 

• Are current test methods, for example OECD and EPA harmonized test guidelines, 

capable of determining the toxicity of the wide variety of intentionally produced 

nanomaterials and byproducts associated with their production and applications? 

 (Addresses area A, above) 

• Are current analytical methods capable of analyzing and quantifying intentionally 

produced nanomaterials to generate dose-response relationships? (Addresses area A, 

ocal 

lly produced nanomaterials? (Addresses area B, 

•

•

in a m

.2

produc used 

directly in the environment but may contaminate soils or surface waters through waste water 

treatment plants (from human use) or more directly as runoff from concentrated animal feeding 

operations (CAFOs) or from aquaculture. Direct applications may include nanoscale monitoring 

systems, control or clean-up systems for conventional pollutants, and desalination or other 

above) 

• What physicochemical properties regulate nanomaterial absorption, distribution, 

metabolism, and excretion (ADME)? (Addresses area A, above) 

• What physicochemical properties and dose metrics best correlate with the toxicity (l

and systemic; acute and chronic) of intentionally produced nanomaterials following 

various routes of exposure? (Addresses area A, above) 

• How do variations in manufacturing and subsequent processing, and the use of particle 

surface modifications affect nanomaterial hazard? (Addresses area B, above 

• Are there subpopulations that may be at increased risk of adverse health effects 

associated with exposure to intentiona

above) 

What are the best approaches to build effective predictive models of toxicity (SAR, 

PBPK, “omics”, etc.)? (Addresses areas A and B, above) 

Are there approaches to grouping particles into classes relative to their toxicity potencies, 

anner that links in vitro, in vivo, and in silico data? 

5 .6 Ecological Effects Research Needs 

Ecosystems may be affected through inadvertent or intentional releases of intentionally 

ed nanomaterials. Drug and gene delivery systems, for example, are not likely to be 
80 EPA Nanotechnology White Paper 

che c

organis ty to 

cross a es, and differences in electrostatic charge. Furthermore, use 

of nanomaterials in the environment may result in novel byproducts or degradates that also may 

pos i

Imp include 

determining which nanomaterials are most used (volume), are likely to be used in the near future 

(im n ive 

applica h of the 

four cla

he same general research areas used for prioritizing human health effects research needs 

we

researc

Are current testing schemes and methods (organisms, endpoints, exposure regimes, 

icity 

 be evaluated with 

• ems 

ining the distribution of 

partments and species. 

• t exposure 

to nanomaterials, or to their byproducts, associated with those nanotechnology 

• e the absorption, distribution, metabolism, elimination (ADME) parameters for 

various nanomaterials for ecological receptors? This topic addresses the uptake, transport, 

, 

What research is needed to examine the interaction of nanomaterials with microbes in 

effluent, and in natural communities of microbes in 

natural soil and natural water? 

mi al modifications of soil or water. Nanoscale particles may affect aquatic or terrestrial 

ms differently than larger particles due to their extreme hydrophobicity, their abili

nd/or damage cell membran

e s gnificant risks. 

ortant considerations for prioritizing and defining the scope of the research needs 

mi ence of use), and/or have most potential to be released into the environment (dispers

tions). Another consideration is the need to test representative materials from eac

sses of nanomaterials (carbon-based, metal-based, dendrimers, composites). 

T

re used to prioritize ecological research needs. Using these areas as a guide, the following 

h questions were identified: 

•

media, analytical methods) applicable to testing nanomaterials in standardized tox

tests? Both pilot testing protocols and definitive protocols should

respect to their applicability to nanomaterials. 

What is the distribution of nanomaterials in ecosystems? Research on model ecosyst

studies (micro, mesocosms) is needed to assist in determ

nanomaterials in ecosystems and potentially affected com

What are the effects (local and systemic; acute and chronic) from either direc

applications that are most likely to have potential for exposure? 

What ar

bioaccumulation relevant to a range of species (fish, invertebrates, birds, amphibians

reptiles, plants, microbes). 

• How do variations in manufacturing and subsequent processing, and the use of particle 

surface modifications affect nanomaterial toxicity to ecological species? 

•

sewage treatment plants, in sewage 

• What research is needed to develop structure activity relationships (SARs) for 

nanomaterials for aquatic organisms? 

• What are the modes of action (MOAs) for various nanomaterials for ecological species? 

Are the MOAs different or similar across ecological species? 
EPA Nanotechnology White Paper 81

5.2.7 Risk Assessment Research - Case Study 

 The overall risk assessment approach used by EPA for conventional chemicals is thought 

to be generally applicable to nanomaterials. It will be necessary to consider nanomaterials’ 

spe

o be 

developed and applied to inform assessments of potential hazard and exposure. 

unique considerations that should be focused in conducting risk assessments for various types of 

nanoma

identifi

risk ass

frequen

workshops involving a substantial num relevant disciplines could be held to 

use s

nanoma

have to

cial properties and their potential impacts on fate, exposure, and toxicity in developing risk 

assessments for nanomaterials. It may be useful to consider a tiered-testing scheme in the 

development of testing and risk assessment approaches to nanomaterials. Also, decisions will 

need to be made even as preliminary data are being generated, meaning that decision making will 

occur in an environment of significant uncertainty. Decision-support tools will need t

 Case studies could be conducted based on publicly available information on several 

intentionally produced nanomaterials. Such case studies would be useful in further identifying 

terials. From such case studies and other information, information gaps may be 

ed, which can then be used to map areas of research that are directly affiliated with the 

essment process and the use of standard EPA tools such as tiered testing schemes. EPA

tly uses tiered testing schemes for specific risk assessment applications. A series of 

ber of experts from

 ca e studies and other information for the identification of any unique considerations for 

terials not previously identified, testing schemes, and associated research needs that will 

 be met to carry out exposure, hazard and risk assessments. 
82 EPA Nanotechnology White Paper 

6.0 Recommendations 

en identified for 

ach re

s 

moting ways to apply 

nanotechnology to reduce waste products generated, and energy used, during 

manufacturing of conventional materials as well as nanomaterials. 

6.1.2 Research Recommendations for Green Energy 

• ORD and OPPT should promote research into applications of nanomaterials green energy 

approaches, including solar energy, hydrogen, power transmission, diesel, pollution 

control devices, and lighting. 

6.1.3 Environmental Remediation/Treatment Research Needs 

• ORD should support research on improving pollutant capture or destruction by exploiting 

novel nanoscale structure-property relations for nanomaterials used in environmental 

control and remediation applications. 

6.1.4 Research Needs for Sensors 

• ORD should support development of nanotechnology-enabled devices for measuring and 

monitoring contaminants and other compounds of interest, including nanomaterials. For 

example, ORD should lead development of new nanoscale sensors for the rapid detection 

of virulent bacteria, viruses, and protozoa in aquatic environments

 This section provides staff recommendations for Agency actions related to 

nanotechnology. These staff recommendations are based on the discussion of nanotechnology 

environmental applications and implications discussed in this paper, and are presented to the 

Agency as proposals for EPA actions for science and regulatory policy, research and 

development, collaboration and communication, and other Agency initiatives. Included below

are staff recommendations for research that EPA should conduct or otherwise fund to address the 

Agency’s decision-making needs. When possible, relative priorities have been given to these 

needs. Clearly, the ability of EPA to address these research needs will depend on available

resources and competing priorities. Potential lead offices in the Agency have be

e commendation. It may be appropriate for other EPA offices to collaborate with the 

identified leads for specific recommendations. EPA should also collaborate with outside group

to avoid duplication and leverage research by others. Identified research recommendations were 

used as a point of departure for Agency discussion and development of the EPA Nanotechnology 

Research Framework, attached as Appendix C. 

6.1 Research Recommendations for Environmental Applications 

6.1.1 Research Recommendations for Green Manufacturing 

• ORD and OPPT should take the lead in investigating and pro
EPA Nanotechnology White Paper 83

6.1.5 Research Needs for Other Environmental Applications 

• ORD should work with industrial partners to ance of nanomaterials and 

alysis 

n of 

ct 

k Assessment 

 A multidisciplinary approach is needed that involves physics, biology, and chemistry to 

ent. This calls 

for a cross-media approach and one that involves collaboration with other federal agencies, and 

plications (risks) of the 

environmental applications of nanotechnology. 

6.2.1 R ion 

• ORD should lead research on the unique chemical and physical characteristics of 

 material’s reactivity, toxicity and other 

attributes. 

• orm 

s components of products, and eventually to the form in 

for Environmental Fate and Treatment 

fate and

Fat

verify the perform

nanoproducts used for environmental applications. 

• ORD should develop rapid screening methods that keep pace with rapid technological 

change for nanomaterials and nanoproducts building on existing Life Cycle An

methods. OPPTS, OW and OAR should collaborate with stakeholders developing rapid 

screening methods. 

• ORD and OPPT should collaborate with NIOSH and others to evaluate the applicatio

nanotechnology for exposure reduction; e.g., nano-enabled PPE, respirators containing 

nanomaterials, and nanoscale end-of-life sensors, sensors that indicate when a produ

has reached the end of its useful life. 

6.2 Research Recommendations for Ris

understand nanomaterials at a basic level and how they interact with the environm

the private and non-profit sectors. This includes examining the im

esearch Recommendations for Chemical Identification and Characterizat

nanomaterials and how these properties affect the

ORD should lead research on how nanomaterial characteristics vary from their pure f

in the laboratory to their form a

which they occur in the environment. 

• ORD should determine if there are adequate measurement methods/technology available 

to fully characterize nanomaterials, to distinguish among different types of nanomaterials, 

and to distinguish intentionally produced nanomaterials from ultrafine particles or 

naturally occurring nanosized particles.

6.2.2 Research Recommendations 

The following are recommendations, in order of priority, in support of the environmental 

 treatment research needs identified as priorities in Chapter 5. 

e,Treatment and Transport
84 EPA Nanotechnology White Paper 

• OSWER and ORD should lead research on the fate of nanomaterials, such as zero-valent 

iron, used in the remediation of chemically contaminated sites. This research should also 

with state environmental programs 

and academia on this research. Based upon available field activities where nanomaterials 

• ld lead research on the stability of various types of intentionally 

produced nanoparticles in the atmosphere. This effort should involve both theoretically 

•

rials waters, soils and sediment that are relevant to 

environmental conditions. 

mical properties of 

e 

ing nanoparticles from the effluent, the fate of 

rials, 

• should share the lead on research on the fate of nanomaterials used 

es; i.e., whether methods such as carbon 

• tion 

cluding the efficiency of destroying 

., baghouses, 

aterials, the 

emoval or degradation of 

other substances during the treatment process. 

• ORD and OSW should lead research on the fate of nanomaterials in other waste treatment 

processes (e.g. chemical oxidation, stabilization). Research would identify relevant waste 

address the impacts of such nanomaterials on the fate of other contaminants at 

remediation sites. These offices should collaborate 

are being used for site remediation, this research could be conducted within the few 

years. 

ORD and OAR shou

derived information as well as some laboratory testing. 

ORD, OPPT, OPP, OSWER and OW should lead research on the biotic and abiotic 

transport and degradation of nanomate

• ORD should lead research that defines the physical and che

nanomaterials that impact their environmental fate. 

• ORD, OSW and OW should collaboratively lead research on treatment methods used for 

removing nanomaterials from wastewater. Research should include analysis of the 

specific types of nanomaterials that are likely to end up in large quantities in sewag

treatment plants, the efficiency of remov

nanomaterials after removal, methods for disposal of sludges containing nanomate

and the impact nanomaterials may have on the removal or degradation of other 

substances in sewage during the treatment process. EPA should collaborate with 

municipal sewage treatment facilities and academia on this research. 

ORD, OPPT and OW

in the purification of drinking water. Research would be based on actual field and/or 

laboratory findings and recommendations would be provided on how to improve the 

nanomaterial removal process where human health issues are a concern. This research 

should also evaluate individual process

adsorption, filtration, and coagulation and settling are effective for treating 

nanomaterials. 

ORD, OSW and OAR should lead research on the fate of nanomaterials in incinera

and other thermal treatment processes, in

nanomaterials, the efficiency of various air pollution control devices (e.g

liquid scrubbers, and electrostatic precipitators) at removing entrained nanom

fate of nanomaterials after removal, methods for disposal of ash containing 

nanomaterials, and the impact nanomaterials may have on the r
EPA Nanotechnology White Paper 85

streams, the efficiency of current treatment regimes at addressing nanomaterials, the fate 

of nanomaterials after treatment, methods for disposal of treatment output containing 

nanomaterials, and the impact nanomaterials may have on the treatment of othe

constituents in the waste stream. EPA should collaborate with treatment, storage, and 

disposal facilities (TSDFs) and academia on this research. 

ORD a

r toxic 

• nd OSW should lead research on the fate of nanomaterials in municipal, industrial, 

and hazardous waste (i.e., Subtitle C) landfills, and other land-based waste management 

ms, 

 nanomaterials into 

groundwater, the fate of nanomaterials after disposal, and the impact nanomaterials may 

.2.3 R s for Environmental Detection and Analysis 

ed 

esearc ls that have demonstrated potential 

um

env n

•

• nufacturers and 

• is 

rials 

g these 

6.2

measur

•

posures. 

scenarios (e.g., surface impoundments). Research would identify relevant waste strea

the efficiency of current containment technologies (e.g., various cap and liner types, 

leachate collection systems) at preventing the leaching of

have on the containment of other toxic constituents in the waste stream. EPA should

collaborate with municipal and industrial stakeholders, and academia on this research. 

6 esearch Recommendation

Where applicable, the initial focus of environmental detection and analysis relat

r h should be on nanomaterials or types of nanomateria

h an or ecological toxicity. The following is a prioritized list of research needs for 

iro mental detection and analysis. 

ORD should lead the development of a report on the assessment of available 

environmental detection methods and technologies for nanomaterials in environmental 

media and for personal exposure monitoring. ORD could collaborate with NIOSH, 

DOD, industry and academia in developing this report. 

ORD should collaborate with NIST, NIOSH, DOD, nanomaterial ma

government and private sector organizations in the development of quality control 

reference materials for analytical methods for nanomaterials. 

ORD should lead development of a set of standard methods for the sampling and analys

for nanomaterials of interest in various environmental media. ORD should collaborate 

with NIOSH, DOD, industry, academia, the American Society for Testing Mate

(ASTM) and the American National Standards Institute (ANSI) in developin

methods. 

.4 Research Recommendation Human Exposures, their Measurement and Control 

The following is a prioritized list of research needs for human exposures, their 

ement and control. 

OPPT should conduct a literature search to evaluate the effects of nanomaterial 

physical/chemical properties on releases and ex

• ORD and OPPT should lead research to determine what dose metrics (e.g. mass, surface 

area, particle count, etc.) are appropriate for measuring exposure to nanomaterials. 
86 EPA Nanotechnology White Paper 

• s 

e 

rials. If found applicable, the 

sources would be evaluated to determine whether additional data or methods would be 

• d 

from such 

•

•

re 

in t

nee

• ent 

als, 

tion with NIOSH and other external groups. 

dations for Human Health Effects Assessment 

The l

OPPT and ORD should evaluate sources of information for assessing chemical release

and exposures for their applicability to nanomaterials. These sources, including release

and exposure tools and models, would be evaluated to determine whether they would b

applicable to assessing releases and exposures to nanomate

needed for assessing nanomaterials. Issues such as degradation would be considered 

also. 

OSWER, ORD, and OPPT should evaluate the proper emergency response actions an

remediation in case of a nanomaterial spill, and the proper disposal of wastes 

response actions. 

OPPT should define risk assessment needs for various types of nanomaterials in 

consultation with other stakeholders. 

OPPT should consider approaches for performing exposure assessments for 

nanomaterials for human and environmental species, including sensitive populations 

(e.g., endangered species, children, asthmatics, etc.), in consultation with other offices 

and stakeholders. 

 Some parts of the remaining exposure and release research initiatives below a

contingent upon completion of the risk and exposure assessment guidance documents noted 

he two paragraphs above. Until this contingency is met, many of the remaining research

ds cannot be fully completed. 

• OPPT should lead development of exposure and release scenarios for nanomaterials in 

manufacturing and use operations. This effort should be conducted by OPPT in 

consultation with industry, NIOSH, and ORD, as appropriate. 

• OPPT and ORD should evaluate and test equipment for controlling and reducing 

chemical releases and exposures for their applicability to nanomaterials. 

OPPT, ORD, OSWER, and OPP should evaluate and test personal protective equipm

for controlling and reducing chemical exposures for their applicability to nanomateri

in collabora

• ORD should lead development of sensors for monitoring personal exposures to 

nanoparticles 

6.2.5 Research Recommen

 fo lowing is a prioritized list of health effects research needs: 

Test Methods
EPA Nanotechnology White Paper 87

• ORD and OPPTS should determine the applicability of current testing methods 

ical methods are capable of analyzing and quantifying intentionally produced 

nanomaterials to generate dose-response relationships. 

Nan

(organisms, exposure regimes, media, analytical methods, testing schemes) 

(http://www.epa.gov/opptsfrs/home/testmeth.htm) for evaluating nanoparticles in 

standardized agency toxicity tests. These offices should consider whether OECD and 

EPA harmonized test guidelines are capable of determining the toxicity of the wide 

variety of intentionally produced nanomaterials and waste byproducts associated with 

their production. In this effort ORD should lead research evaluating whether current 

analyt

otoxicology

• ORD should lead research to determine the health effects (local and systemic; acute and 

ucts, 

ine whether there are 

ch as 

his 

 also collaborate with stakeholders in catalyzing this research. 

chronic) resulting from either direct exposure to nanomaterials, or to their byprod

associated with dispersive nanotechnology applications such as remediation, pesticides, 

and air pollution control technologies. Research should determ

specific toxicological endpoints that are of high concern for nanoparticles, su

neurological, cardiovascular, respiratory, or immunological effects, etc. Research in t

area should also provide information as to the adequacy of existing toxicological 

databases to predict or extrapolate the toxicity of intentionally produced nanomaterials. 

The Agency should

Hazard Identification and Dosimetry & Fate 

• ORD should lead research to determine what physicochemical properties and dose 

metrics (mass, surface area, particle number, etc.) best correlate with the toxicity (local 

• tion 

ious routes of exposure. 

S on 

and systemic; acute and chronic) of intentionally produced nanomaterials.

ORD should lead research on the absorption, distribution, metabolism, and excre

(ADME) of intentionally produced nanomaterials following var

This research must also include determining what physicochemical properties regulate 

intentionally produced nanomaterial ADME. ORD should collaborate with OPPT

this research. 

Susceptibility

• ORD should lead research to identify subpopulations that may be at increased risk for 

adverse health effects associated with exposure to intentionally produced nanomaterials. 

eeds 

ected. 

This is a need that cannot be established until information from earlier research n

have been coll

Computational Nanotoxicology

• ORD should lead research to determine what approaches are most effective to build 

predictive toxicity assessment models (SAR, PBPK, “omics”, etc.). 
88 EPA Nanotechnology White Paper 

nanoma al, 

interna ber of 

organiz , 

NCI, N

institut

effects 

6.2.6 E

at research be focused specifically upon the fate, and subsequent exposure 

and effects, of nanomaterials on invertebrates, fish, and wildlife associated with ecosystems. 

Wh i

environ

effects?

measur

environ lenge 

in the a

toxicity logical 

system

Test Methods

Research into the human health effects assessment of intentionally produced 

terials will be extremely challenging and the ability to interact with other feder

tional, academic, and private activities in this area would be most beneficial. A num

ations are engaged in health effects research. Collaboration with NASA, NIOSH, FDA

TP, DOD/MURI, NIST, NEHI, DOE, the European Union, EPA grantees, academic 

ions, and others will leverage resources in gaining knowledge on the potential health 

of nanomaterials.

cological Exposure and Effects 

It is critical th

at s the behavior of nano materials in aquatic and terrestrial environments? How can 

mental exposures be simulated in the laboratory? What are the acute and chronic toxic 

 There is a need for development and validation of analytical methodologies for 

ing nanoscale substances (both parent materials and metabolites/complexes) in 

mental matrices, including tissues of organisms. In terms of toxicity, a critical chal

rea of ecosystem effects lies in determining the impacts of materials whose cumulative 

 is likely to be a manifestation of both physical and chemical interactions with bio

s. The following is a prioritized list of ecological research needs: 

• ORD should collaborate with other EPA offices in research on the applicability of current 

ytical 

applicability 

to nanomaterials. 

v

testing schemes and methods (organisms, endpoints, exposure regimes, media, anal

methods) for testing nanomaterials in standardized toxicity tests. Both pilot testing 

protocols and definitive protocols should be evaluated with respect to their 

En ironmental Fate/Distribution of Nanomaterials in Ecosystems

• ORD should lead on research on the distribution of nanomaterials in ecosystems. 

Nanotoxicology and Dosimetry

ld determine the effects of direct exposure to nanomaterials or their 

e uptake, transport, and bioaccumulation of these materials. 

ORD, OW and OPPT should lead research on the interactions of nanomaterials with 

• ORD shou

byproducts, associated with dispersive nanotechnology uses, on a range of ecological 

species (fish, inverts, birds, amphibians, reptiles, plants, microbes). This research should 

be focused on organisms residing in ecological compartments that the nanomaterials in 

question preferentially distribute to, if any, as identified above. This research should 

include evaluation of th

•

microbes in sewage treatment plants in sewage effluent and natural communities of 

microbes in natural soil and natural water. 
EPA Nanotechnology White Paper 89

• s (SARs) for 

to Address Overarching Risk Assessment Needs - Case Study 

aterial assessment would fit within EPA’s overall risk 

assessment paradigm is to conduct a case study based on publicly available information on one 

ion, 

as of 

e in the 

les in identifying data 

gaps and research needs that will have to be met to carry out exposure, hazard and risk 

asse

6.3 e

Stewa

and develop. EPA has the capability to support research into nanotechnology applications of 

pol e been developed for 

gre benign manufacturing. 

EPA s

stew d tifying 

area leaner alternatives to exisiting industrial inputs. The 

following are the prim for pollution prevention and environmental 

stew d

•

• or 

the environment, green engineering and green chemistry principles and approaches to 

Other r d environmental stewardship: 

ORD should lead research aimed at developing structure-activity relationship

nanomaterials for aquatic organisms. 

• ORD should lead research on the modes of action for various nanomaterials for a range 

of ecological species. 

6.2.7 Recommendations 

One way to examine how a nanom

or several intentionally produced nanomaterials. In the past, such case studies have proven 

useful to the Agency in adjusting the chemical risk assessment process for stressors such as 

bacteria. For example, assessments of recombinant bacteria need to account for reproduct

and other factors not considered with chemical risk assessments. From such case studies and 

other information, information gaps may be identified, which can then be used to map are

research that are directly affiliated with the risk assessment process. This has been don

past with research on airborne particulate matter. 

 Additionally, a series of workshops involving a substantial number of experts from 

several disciplines should be held to use available information and princip

ssments. 

 R commendations for Pollution Prevention and Environmental 

rdship 

Opportunities exist to advance pollution prevention as nanotechnology industries form 

lution prevention and environmental stewardship principles that hav

en energy, green chemistry, green engineering, and environmentally

 i well-positioned to work with stakeholders on pollution prevention and product 

ar ship approaches for producing nanomaterials in a green manner, as well as for iden

s where nanomaterials may be c

ary recommendations 

ar ship: 

EPA should support research into approaches that encourage environmental stewardship 

throughout the complete life cycle of nanomaterials and products. 

OPPT, ORD, and other stakeholders should encourage product stewardship, design f

nanomaterials and nanoproducts. 

ecommendations for pollution prevention an
90 EPA Nanotechnology White Paper 

• NCEI and OECA should research nanotechnology sectors, supply chains, analytical and 

design tools, and applications in order to inform pollution prevention approaches. OECA 

should collaborate with other Agency programs, such as OPPT’s Green Supply Chain 

ical 

se 

educe resource burdens on EPA’s science programs and will facilitate 

uld collaborate with other groups on research into the environmental 

f 

should lead efforts to investigate the possibilities for collaboration with and 

• an should engage in information exchange with small 

Network to identify nanotechnology sectors, supply chains, analytical and design tools, 

and applications. 

• OCIR and OCFO should encourage research within organizations such as the Ecolog

Council of the States (ECOS), state technology assistance organizations, and other 

technology transfer groups to further the understanding of how to integrate environmental

stewardship for nanotechnology into their ongoing assistance efforts. 

• OPEI, OPPT, and ORD should support research on economic incentives for 

environmental stewardship behavior associated with nanomaterials and nanoproducts. 

• ORD should continue to support research to promote clean production of nanomaterials 

and nanoproducts.. 

6.4 Recommendations for Collaborations 

 In addition to the Agency’s current collaborations on nanotechnology issues and our 

ongoing communication activities, we recommend the following additional actions. The

collaborations will r

communication with stakeholders. 

• ORD sho

applications and implications of nanotechnology. ORD’s laboratories should put a 

special emphasis on establishing Cooperative Research and Development Agreements 

(CRADAs) to leverage non-federal resources to develop environmental applications o

nanotechnology (CRADAs are established between the EPA and research partners to 

leverage personnel, equipment, services, and expertise for a specific research project.) 

• EPA should collaborate with other countries (e.g., through the OECD) on research on 

potential human health and environmental impacts of nanotechnology. 

• OCIR 

through state and local government economic development, environmental and public 

health officials and organizations. 

• OPA and program offices, as appropriate, should lead an Agency effort to implement the 

communication strategy for nanotechnology. 

OPEI’s Small Business Omsbudsm

businesses, which comprise a large percentage of U.S. nanomaterial producers. 
EPA Nanotechnology White Paper 91

6.5 e

g 

regardi

steward ities regarding nanomaterials across program offices and regions. 

6.6 e

and reg an extensive 

atabase, and a Millenium lecture series covering both the administrative and technical aspects 

of n o ion on 

nano ec r. 

hile this white paper also provides information for Agency managers and scientists, there 

sho 

to assist in the understanding of nanotechnol

environm nsiderations when conducting risk assessments 

 R commendation to Convene an Intra-Agency Workgroup 

The Agency should convene a standing intra-Agency group to foster information sharin

ng risk assessment, and regulatory activities, as well as pollution prevention and 

ship-oriented activ

 R commendation for Training 

EPA has begun educating itself about nanotechnology through seminars in the program 

ional offices, an internal cross-Agency workgroup (NanoMeeters) with

d

an technology. The SPC Nanotechnology Workgroup also held a “primer” sess

t hnology to help inform its members during the early stages of development of this pape

W

uld be ongoing education and training as well as expert support for EPA managers and staff 

ogy, its potential applications, regulatory and 

ental implications, as well as unique co

on nanomaterials relative to macro-sized materials. 
92 EPA Nanotechnology White Paper 

6.7 Summary of Recommendations 

EPA should begin taking steps to help ensure both that society accrues the important 

benefits to environmental protection that nanotechnology may offer and that the Agency 

 environmental exposure to nanomaterials. Table 6 

summarizes the staff recommendations identified above. 

d 

understands potential risks from human and

Table 6. Summary of Workgroup Recommendations Regarding Nanomaterials 

6.1 Research for Environmental Applications. EPA should undertake, collaborate on, an

support research on the various types of nanomaterials to better understand and apply 

information regarding their environmental applications. Specific research recommendations

for each area are identified in the text. 

6.2 Research for Risk Assessment. EPA should undertake, collaborate on, and support 

research on the various types of nanomaterials and nanotechnologies to better understand and 

apply information regarding: 

i) chemical identification and characterization, 

ii) environmental fate and treatment methods, 

iii) environmental detection and analysis, 

iv) potential human exposures, their measurement and control, 

v) human health effects assessment, 

vi) ecological effects assessment, and 

vii) conducting case studies to further identify unique risk assessment 

considerations for nanomaterials. 

Specific research recommendations for each area are identified in the text.

6.3 Pollution Prevention, Stewardship and Sustainability. EPA should engage resources 

and expertise as nanotechnology industries form and develop to encourage, develop and 

support nanomaterial pollution prevention at its source and an approach of stewardship. 

Detailed pollution prevention recommendations are identified in the text. Additionally, the 

Agency should draw on the “next generation” nanotechnologies for applications that support 

environmental stewardship and sustainability, such as green energy and green manufacturing.

6.4 Collaboration. EPA should continue and expand its collaborations regarding 

nanomaterial applications and potential human and environmental health implications.

6.5 Intra-Agency Workgroup. EPA should convene a standing intra-Agency group to foster 

information sharing regarding risk assessment or regulatory activities for nanomaterials across 

program offices and regions.

6.6 Training. EPA should continue and expand its activities aimed at training Agency 

scientists and managers regarding potential environmental applications and environmental 

implications of nanotechnology.
EPA Nanotechnology White Paper 93

7.0 References 

Aitken, . 

nd 

Atkinson, R. 2000. Atmospheric Oxidation (Chapter 14), in Boethling, R.S.; Mackay, D. (eds.), 

 Sciences, 

ewis Publishers, CRC Press, Boca Raton, FL. 

 March 

ember 

Balshaw, D ategies for Safety Evaluation of 

Nanomateri ing and Improving Public Health. 

Toxicol. Sc

Baron, P.A.

Handling of tube Material. NIOSH-DART-02-191 Rev. 

1.1, April 2

ddon, R. C., Parpura, 

l 

ds 

nage. Assoc. 

0. 

 Phase Silica Sorbent Precursors. Environ. Sci. Technol. 31(9): 

455-2463. 

Boethling, R.S., Nabholz, J.V. 1997. Environmental Assessment of Polymers Under the U.S. 

Toxic Substances Control Act, Chapter 10. pp. 187-234. in Hamilton, J. D. and R. Sutcliffe 

 R.J., Creely, K.S., Tran, C.L. 2004. Nanoparticles: An Occupational Hygiene Review

Research Report 274. Prepared by the Institute of Occupational Medicine for the Health a

Safety Executive, North Riccarton, Edinburgh, England. 

Handbook of Property Estimation Methods for Chemicals, Environmental and Health

L

Ball, P. 2005. Nanomaterials Draw Electricity from Heat. Nature Materials Update. 24

2005. 

Ball, P. 2004. Nanotubes Show the Way to Wind Power. Nature Materials Update. 2 Sept

2004. 

.M., Philbert, M., Suk, W.A.. 2005. Research Str

als, Part III: Nanoscale Technologies for Assess

i. 88(2): 298-306. 

, Maynard, A.D., Foley, M. 2003. Evaluation of Aerosol Release During the 

 Unrefined Single Walled Carbon Nano

003. 

Bekyarova, E., Ni, Y., Malarkey, E. B., Montana, V., McWilliams, J. L., Ha

V. 2005. Applications of Carbon Nanotubes in Biotechnology and Biomedicine. J. Biomedica

Nanotechnology 1:3-17. 

Bidleman, T.F. 1988. Atmospheric Processes, Wet and Dry Deposition of Organic Compoun

are Controlled by their Vapor-Particle Partitioning. Environ. Sci. Technol. 22(4), 361-367. 

Biswas P., Wu, C-Y. 2005. Nanoparticles and the Environment. J. Air & Waste Ma

55:708-746. 

Biswas, P., Yang, G., and Zachariah, M.R 1998. In Situ Processing of Ferroelectric Materials 

from Lead Waste Streams by Injection of Gas Phase Titanium Precursors: Laser Induced 

Fluorescence and X-Ray Diffraction Measurements. Combust. Sci. Technol.134: 183-20

Biswas, P., Zachariah, M.R. 1997. In Situ Immobilization of Lead Species in Combustion 

Environments by Injection of Gas

2
94 EPA Nanotechnology White Paper 

(eds.), Ecological Assessment of Polymers: Strategies for Product Stewardship and Regulatory 

Programs. Van Nostrand Reinhold, Ne

orm, P., Klaessig, F.C., Landry, T.D., Moudgil, B., Pauluhn, J., Thomas, K., Trottier, R., 

-

onsumer Protection Directorate General of the 

uropean Commission. http://europa.eu.int/comm/health/ph_risk/events_risk_en.htm

w York. 345 p. 

B

Wood, S. 2006. Research Strategies for Safety Evaluation of Nanomaterials, Part V: Role of 

Dissolution in Biological Fate and Effects of Nanoscale Particles. Toxicol. Sciences 90(1): 23

32. 

Borm, P.J.A., Hreyling, W. 2004. A Need for Integrated Testing of Products in Nanotechnology, 

in Nanotechnologies: A Preliminary Risk Analysis on the Basis of a Workshop, Organized in 

Brussels on 1-2 March 2004 by the Health and C

E . 

A.M., Lyon, D., Velasquez, V., Sayes, D.Y., Fortner, J., Colvin, V.L. 2005. Photocatalytic 

egradation of Organic Contaminants by Water-Soluble Nanocrystalline C60. ACS Meeting 

rown, M. 2005a. Nano-Bio-Info Pathways to Extreme Efficiency. Presentation to the AAAS 

Boyd, 

D

Abstracts, 229th ACS National Meeting, San Diego, CA, March 13-17, 2005. 

B

Annual Meeting, Washington, DC. http://www.ornl.gov/sci/eere/aaas/abstracts.htm. 

Brown, M., Laitner, J.A. 2005b. Emerging Industrial Innovations to Create New Energyfficient Technologies, in Proceedings of the American Council for an Energy-Efficient 

er, K., Coester, C., Loitsch, S., Wagner, T.O., Mallinckrodt, C. 2004. 

corporation of Biodegradable Nanoparticles into Human Airway Epithelium Cells-In vitro 

ai R. et al. 1992. Increment of Photocatalytic Killing of Cancer Cells Using TiO2 with the Aid 

BEN. 2005. Center for Biological and Environmental Nanotechnology, Rice University. 

n.rice.edu/centersandinst/cben/

E

Economy (ACEE) Summer Study on Energy Efficiency in Industry, pp. 4-70 to 4-83. 

Brzoska, M., Lang

In

Study of the Suitability as a Vehicle for Drug or Gene Delivery in Pulmonary Diseases. 

Biochem. Biophys. Res. Commun. 318(2): 562-570. 

C

of Superoxide Dismutase. The Chemical Society of Japan, Chemistry Letters: 427-430. 

C

Information about the center and current research summaries are available online: 

http://cohesio .

Chen, B., Beckett, R. 2001. Development of SdFFF-ETASS for Characterizing Soil and Sed. 

Colloids Analyst 126:1588-1593. 

Chen, B., Selegue, J. 2002. Separation and Characterization of Single-Walled and Multiwalled 

80. 

eng, G., Wang, X., Fu, J., Chen, J., Liu, S. 2000. Adsorption Characteristics of 

ullerenes and Their Application for Collecting VOCs in Ambient Air. Juanjing Juaxue, 19(2), 

Carbon Nanotubes by Using Flow Field-Flow Fractionation. Anal. Chem. 74 (18): 4774-47

Chen, C., Sh

F

165-169. [The original report is published in Chinese. The abstract published in Chemical 

Abstracts does not specify if the fullerenes used are free particles or immobilized.] 
EPA Nanotechnology White Paper 95

Chen, Y., Crittenden, J.C., Hackney, S., Sutter, L., Hand, D.W. 2005. Preparation of a Novel 

iO2-Based p-n Junction Nanotube Photocatalyst. Environ. Sci. Technol. 39(5): 1201-1208 

h 

heng, X., Kan, A.T., Tomson, M.B. 2004. Naphthalene Adsorption and Desorption from 

omparelli, R., Cozzoli, P.D., Curri, M.L., Agostiano, A., Mascolo, G., Lovecchio, G. 2004. 

 L.E., 

 

evices. 

ano Letters: 4(6): 1079-1083. 

 1): 

s Using 

 Core and Terminal NH2 Groups. Environ. Sci. 

echnol. 39(5): 1366-1377 

.W., Mårtensson, T. Seifert,W., Wallenberg, L.R. 

amuelson, L. 2004. Synthesis of branched 'nanotrees' by controlled seeding of multiple 

onaldson, K., Aitken, R., Tran, L., Stone, R., Duffin, R., Forrest, G., and Alexander, A. 2006. 

T

Cheng, S.H., Cheng, J. 2005. Carbon Nanotubes Delay Slightly the Hatching Time of Zebrafis

Embryos. 229th American Chemical Society Meeting, San Diego, CA March 2005. 

C

Aqueous C60 Fullerene. J. Chem. Eng. Data 49: 675-683. 

Christen, K. 2004. Novel Nanomaterial Strips Contaminants from Waste Streams. Environ. Sci. 

Technol. 38(23): 453A-454A. 

Colvin, V. 2003. The Potential Environmental Impact of Engineered Nanoparticles. Nature 

Biotechnol. 21(10), 1166-1170. 

C

Photocatalytic Degradation of Methyl-red by Immobilized Nanoparticles of TiO2 and ZnO. 

Water Sci. Technol. 49(4): 183-188. 

Das R., Kiley, P.J., Segal, M., Norville, J., Yu, A.A., Wang, L., Trammell, S.A., Reddick,

Kumar, R., Stellacci, F., Lebedev, N., Schnur, J., Bruce, B.D, Zhang, S., Baldo, M. 2004.

Integration of Photosynthetic Protein Molecular Complexes in Solid-State Electronic D

N

Dennekamp, M., Mehenni, O.H., Cherrie, J., Seaton, A. 2002. Exposure to Ultrafine Particles

and PM2.5 in Different Micro-Environments. Annals of Occupational Hygiene 46 (suppl.

412–414. 

Derfus, A.M., Chan, W.C.W., Bhatia, S.N. 2004. Probing the Cytotoxicity of Semiconductor 

Quantum Dots. Nano Letters 4(1):11-18. 

Diallo, M.S., Christie, S., Swaminathan, P., Johnson, J.H., Jr., Goddard, W.A., III. 2005. 

Dendrimer Enhanced Ultrafiltration. 1. Recovery of Cu (II) from Aqueous Solution

PAMAM Dendrimers with Ethylene Diamine

T

Dick, K.A., Deppert, K., Larsson, M

S

branching events. Nature Materials 3: 380–384. 

D

Carbon Nanotubes: A review of Their Properties in Relation to Pulmonary Toxicology and 

Workplace Safety. Toxicol. Science 92:5-22. 
96 EPA Nanotechnology White Paper 

Dreher, K.L 2004. Health and Environmental Impact of Nanotechnology: Toxicological 

ror, I., Baram, D., Berkowitz, B. 2005. Use of Nanosized Catalysts for Transformation of 

lliott et al. 2005. Novel Products From the Degradation of Lindane by Nanoscale Zero Valent 

uropean Commission Scientific Committee on Emerging and Newly Identified Health Risks 

 Adventitious Products of Nanotechnologies. Document number 

CENIHR/002/05. 

ropean Commission, Community Health and Consumer 

rotection. Nanotechnologies: A Preliminary Risk Analysis on the Basis of a Workshop 

isk/events_risk_en.htm

Assessment of Manufactured Nanoparticles. Toxicological Sciences 77:3-5. 

D

Chloro-Organic Pollutants. Environ. Sci. Technol. 39(5): 1283-1290. 

E

Iron. American Chemical Society Annual Meeting, San Diego, CA, Abstract. 

E

(SCENIHR). 2006. The Appropriateness of Exisiting Methodolgies to Assess the Potential Risks

Associated with Engineered and

S

European Commission. 2004. Eu

P

Organized in Brussels on 1-2 March 2004 by the Health and Consumer Protection Directorate

General of the European Commission. 

http://europa.eu.int/comm/health/ph_r . 

European NanoSafe Report. 2004. Technical Analysis: Industrial Application of Nanomaterials 

Chances and Risks. www.nano.uts.edu.au/nanohouse/nanomaterials%20risks.pdf. 

Filley, T.R., Ahn, M., Held, B.W., Blanchette, R.A. 2005. Investigations of Fungal Mediated 

C60-C70) Fullerene Decomposition. Preprints of Extended Abstracts Presented at the ACS 

ortner, J.D., Lyon, D.Y., Sayes, C.M., Boyd, A.M, Falkner, J.C., Hotze, E.M., Alemany, L.B, 

ponse. Environ. Sci. Technol. 39:4307-4316. 

, P.E., 

d 

: 1-47. 

 Perspect. 

rink, C.R., Waggoner, P.E., Asubel, J.H. 1996. Nitrogen Fertilizer: Retrospect and Prospect. 

. Comparison of Simulated Respirator Fit Factors 

sing Aerosol and Vapor Challenges. J. Occupat. Environ. Hygiene 1: 29–38. 

(

National Meeting, American Chemical Society, Division of Environmental Chemistry 45(1), 

446-450. 

F

Tao, Y.J., Guo, W., Ausman, K.D., Colvin, V.L. and J.B. Hughes. 2005. C60 in water: 

Nanocrystal Formation and Microbial Res

Frampton, M. W., Utell, M.J., Zareba, W., Oberdörster, G., Cox, C., Huang, L-S., Morrow

Lee, F.E-H., Chalupa, D., Frasier, L.M., Speers, D.M., Stewart. J. 2004. Effects of Controlle

Exposure to Ultrafine Carbon Particles in Healthy Subjects and Subjects with Asthma. Health

Effects Institute. Report 126

Frazer, L. 2003. Organic Electronics: A Cleaner Substitute for Silicon. Environ. Health

111:5. 

F

Proc. Natl. Acad. Sci., p. 1175-1180. 

Gardner, P., Hofacre, K., Richardson, W. 2004

U
EPA Nanotechnology White Paper 97

Georgia Tech. 2005. March 2005 press release 

http://gtresearchnews.gatech.edu/newsrelease/adhesive.htm; Abstract posted at: 

ttp://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.abstractDetail/abstract/6352/rep

rassian, V.H., O’Shaughness, P.T, Adamcakova-Dodd, A., Pettibone, J.M., and Thorne, P.S. 

urevich, L., Canali, L., Kouwenhoven, L.P. 2000. Scanning gate spectroscopy on nanoclusters. 

 Environmental Factors. Environ. Health Perspect. 114(2): 165-172. 

h

ort/0 

G

2006. unpublished results 

G

Applied Physics Letters 76(3):384. 

Hardman, R. 2006. A Toxicological Review of Quantum Dots: Toxicity Depends on 

Physicochemical and

Health Effects Institute, Communication 9, August 2001. www.healtheffects.org/pubscomm.htm. 

Hinds, W.C. 1999. Aerosol Technology

Airborne Particles. 2

: Properties, Behavior, and Measurement of 

k.

lammatory 

esponse After Instillation of Fine and Ultrafine TiO2 in the Rat. Int. J. Hyg. Environ. Health 

 U., Heyder, J., Schulz, H. 2005. Cardiovascular Responses in Unrestrained WKY 

ats to Inhaled Ultrafine Carbon Particles. Inhal. Toxicol. 17:29-42. 

alker 

art II: 

oxicological and Safety Evaluation of Nanomaterials, Current Challenges and Data Needs. 

erization of Atmospheric Ultrafine Particles in the Los Angeles Area. Environ. Sci. 

echnol. 32(9):1153-1161. 

, H.L. 2004. Removal of Micro-Particles by Microbial 

ranules used for Aerobic Wastewater Treatment. Water Sci. Technol. 50(12): 147-154. 

Cytotoxicity of 

arbon Nanomaterials. Environ. Sci. Technol. 39:1378-1383. 

nd ed. John Wiley and Sons, Inc., New Yor

Höhr, D., Steinfartz, Y., Schins, R.P.F., Knaapen, A.M., Martra, G., Fubini , B.,. Borm, P.J.A. 

2002. The Surface Area Rather Than the Surface Coating Determines the Acute Inf

R

205:239-244. 

Harder, V., Gilmour, P., Lentner, B., Karg, E., Takenaka, S., Ziesenis, A., Stampfl, A., 

Kodavanti,

R

Holsapple, M.P., Farland, W.H., Landry, T.D., Monteiro-Riviere, N.A., Carter, J.M., W

N.J., Thomas, K.V. 2005. Research Strategies for Safety Evaluation of Nanomaterials, P

T

Toxicol. Sci. 88(1): 12-17. 

Hu, J., Lo, I.M., Chen, G. 2004. Removal of Cr(VI) by Magnetite Nanoparticle. Water Sci. 

Technol. 50(12):139-46. 

Hughes L.S., Cass, G.R., Gone, J., Ames, M., Olmez, I. 1998. Physical and Chemical 

Charact

T

Ivanov, V., Tay, J.H., Tay, S.T., Jiang

G

Jia, G., Wang, H.,Yan, L., Wang, X., Pei, R., Yan, T., Zhao, Y., Guo, X. 2005. 

C
98 EPA Nanotechnology White Paper 

Kanel, S.R., Manning, B., Charlet, L., Choi, H. 2005. Removal of Arsenic (III) fr

Groundwater by Nanoscale Zero-Valent Iron. Environ. Sci. Technol. 39(5):1291-1298. 

om 

reyling, W.G., Semmler, M., Erbe, F., Mayer, P., Takenaka, S., Schulz, H., Oberdörster., G, 

is Size Dependent But Very Low. J. Toxicol. Environ. Health A 

5:1513-1530. 

swas P. 2002 Charging of particles in unipolar coronas 

radiated by in-situ soft X-rays: Enhancement of Capture Efficiency of Ultrafine Particles. J. 

am, C.W., James, J.T., McCluskey, R., Hunter, R.L. 2004. Pulmonary Toxicity of Singlel. Sci. 

bility of 

169. 

o, K., Shah, A.P., Biswas, P. 2005. Nanostructured Sorbents for Capture of 

admium Species in Combustion Environments. Environ. Sci. Technol. 39(21):8481-8489. 

arbon Black in Rats. Inhal. 

oxicol. 11:709-731. 

es 

Integrity and Permeability. J. Drug Targeting 12 (9-10):635-641. 

 dioxide 

uther, W., ed. 2004. Technological Analysis, Industrial Application of Nanomaterials - Chances 

K

Ziesenis, A. 2002. Translocation of Ultrafine Insoluble Iridium Particles From Lung Epithelium

to Extrapulmonary Organs 

6

Kulkarni P., Namiki N., Otani Y., Bi

ir

Aerosol Sci. 33 (9), 1279-1298 

L

Walled Carbon Nanotubes in Mice 7 and 90 Days after Intratracheal Instillation. Toxico

77:126-134. 

Lecoanet, H.F., Bottero, J.Y., Wiesner, M.R. 2004. Laboratory Assessment of the Mo

Nanomaterials in Porous Media. Environ. Sci. Technol. 38:5164-5

Lecoanet, H.F., Wiesner, M.R. 2004. Velocity Effects on Fullerene and Oxide Nanoparticle 

Deposition in Porous Media. Environ. Sci. Technol. 38:4377-4382. 

Lee, M.-H., Ch

C

Li, X.Y., Brown, D., Smith S., MacNee, W., Donaldson, K. 1999. Short Term Inflammatory 

Responses Following Intratracheal Instillation of Fine and Ultrafine C

T

Lloyd, S.M., Lave, L.B., Matthews, H.S. 2005. Life Cycle Benefits of Using Nanotechnology to

Stabilize Platinum-Group Metal Particles in Automotive Catalysts. Environ. Sci. Technol. 

39:1384-1392. 

Lockman P.R., Kozaria, J.M., Mumper, R.J., Allen, D.D. 2004. Nanoparticle Surface Charg

Alter Blood-Brain Barrier 

Lovern, S.B. and Klaper, R. 2006 Daphnia magna mortality when exposed to titanium

and fullerene (C60) nanoparticles. Environ. Toxicol. Chem. 25(4):1132-1137. 

L

and Risks. Future Technologies Division, VDI Technologiezentrum GmbH, Düsseldorf, 

Germany. 

Lux Research. 2006. http://www.luxresearchinc.com/TNR4_TOC.pdf

http://www.luxresearchinc.com/press/RELEASE_TNR4.pdf. 
EPA Nanotechnology White Paper 99

Lux Research. 2004. www.luxresearchinc.com/press/RELEASE_econ.pdf

Madan, T., Munshi, N., De, T.K., Usha Sarma, P., Aggarwal, S.S. 1997. Biodegradable 

attanapatapee, R., Klopsch, R., Lorenz, K., Frey, H., Weener, J.W., Meijer, E.W., 

aulus, W., Duncan, R. 2000. Dendrimers: Relationship Between Structure and Biocompatibility 

ang, W.-X. Masciangioli, T., 2003. Environmental Technologies at the Nanoscale. Environ. 

., Kuempel, E.D. 2005. Airborne Nanostructured Particles and Occupational 

ealth. J. Nanoparticle Res. 7(6): 587-624. 

 Castranova, V. 2004. 

xposure to Carbon Nanotube Material: Aerosol Release During the Handling of Unrefined 

aynard, A. D. 2000. Overview of Methods for Analysing Single Ultafine Particles. Phil. Trans. 

cKim, J., Schmieder, P., Veith, G. 1985. Adsorption Dynamics of Organic Chemical Transport 

cMurry, P. H. 2000. A Review of Atmospheric Aerosol Measurements. Atmospheric Environ. 

e, N.A., Nemanich, R.J., Inman, A.O., Yunyu, Y.W., Riviere, J.E. 2005. Multialled carbon nanotubes interactions with human epidermal keratinocytes. Toxicol. Lett. 155(3): 

oore, M.N. 2006. Do Nanoparticles Present Ecotoxicological Risks for the Health of the 

organ, K. 2005. Development of a Preliminary Framework for Informing the Risk Analysis 

uaux, F., Moreau, N., Misson, P., Heilier, J-F., Delos, J., Arras, M., Fonseca, A., 

agy, J. B., Lison, D. 2005. Respiratory toxicity of multi-wall carbon nanotubes. Toxicol. Appl. 

Nanoparticles as a Sustained Release System for the Antigens/Allergens of Aspergillus 

fumigatus: Preparation and Characterization. Int. J. Pharm. 159, 135-147. 

Malik, N., Wiw

P

In Vitro, and Preliminary Studies on the Biodistribution of 125I-Labeled Polyamidoamine 

Dendrimers In Vivo. J. Control. Release 65:133-148. 

W

Sci. Technol. A-Pages. 37(5):102A-108A. 

Maynard, A.D

H

Maynard, A.D., Baron, P.A., Foley, M., Shvedova, A.A., Kisin, E.R., and

E

Single-Walled Carbon Nanotube Material. J. Toxicol. Environ. Health A 67: 87-107. 

M

R. Soc. Lond. A 358: 2593-2610. 

M

Across Trout Gills as Related to Octanol-Water Partition Coefficient. Government Reports 

Announcements and Index, Issue 17, NTIS report number PB85-198315, 12 p. 

M

34(12-14):1959-1999. 

Monteiro-Rivier

w

377-384. 

M

Aquatic Environment? Environ. Int. 32(8): 967-976. 

M

and Risk Management of Nanoparticles. Risk Anal. 25:1-15. 

Muller, J., H

N

Pharmacol. 207: 221-231. 
100 EPA Nanotechnology White Paper 

Murashov. V. 2006. Letter to the Editor:Comments on Particle Surface Characteristics May 

, L., Watts, D.J., 

oxicology Letters, 2005, 158, 122-132. Toxicol. Lett 164 185-187. 

ttp:www.cdc.gov/niosh/topics/nanotech/nano_exchnge.html.

Play an Important Role in Phytotoxicity of Alumina Nanoparticles by Yang

T

National Institute for Occupational Health and Safety. 2005a. Approaches to Safe 

nanotechnology: An Information Exchage with NIOSH. 

h

National Institute for Occupational Health and Safety. 2005b. Strategic Plan for NIOSH 

Nanotechnology Research Program. http:www.cdc.gov/niosh/topics/nanotech/strat_plan.html.

National Institute for Occupational Health and Safety. 2004. Nanotechnology Workplace Safety 

and Health. http://www.cdc.gov/niosh/topics/nanotech/default.html. 

National Institute for Occupational Health and Safety. 2003. Filtration and Air-Cleaning Systems 

Disease Control and Prevention, National Institute 

r Occupational Safety and Health, DHHS (NIOSH) Publication No. 2003–136.

e 

to Protect Building Environments. Cincinnati, OH: U.S. Department of Health and Human 

Services, Public Health Service, Centers for 

fo

National Research Council. 1983. Risk Assessment in the Federal Government: Managing th

Process. National Academy of Sciences, Washington, D.C. 192 pp. 

National Research Council. 1994. Science and Judgment in Risk Assessment, National Academy 

of Sciences, Washington, D.C. 

National Nanotechnology Initiative. 2006a. What is Nanotechnology? 

http://www.nano.gov/html/facts/home_facts.html

National Nanotechnology Initiative. 2006b. About the NNI. 

http://www.nano.gov/html/about/home_about.html

National Nanotechnology Initiative. 2006c. Environmental, Health and Safety Research Needs 

for Engineered Nanoscale Materials. http://www.nano.gov. 

National Nanotechnology Initiative. 2004. National Nanotechnology Initiative Strategic Plan, 

Goal 4: Support Responsible Development of Nanotechnology. 

http://www.nano.gov/NNI_Strategic_Plan_2004.pdf. 

National Nanotechnology Initiative. 2000. The Initiative and Its Implementation Plan. 

http://www.nano.gov/html/facts/whatIsNano.html. 

Nagaveni, K., Sivalingam, G., Hegde, M.S., Madras, G. 2004. Photocatalytic Degradation of 

Organic Compounds over Combustion-Synthesized Nano-TiO2. Environ. Sci. Technol. 38, 1600-

1604. 
EPA Nanotechnology White Paper 101

Nel, A., Xia, T., Madler, L., Li, N. 2006. Toxic Potential of Materials at the Nanolevel. Scienc

311: 622-627. 

e 

emmar A., Hoylaerts, M.F., Hoet, P.H.M., Vermylen, J., Nemery, B. 2003. Size Effect of of 

xicol. Appl. 

igavekar, S.S., Sung, L.Y., Llanes, M., El-Jawahri, A., Lawrence, T.S., Becker, C.W., Blaogh, 

. 21 

ci. 45(2):222-227. 

ang, C., 

inehan, J.C., Matson, D.W., Penn, R.L., Driessen, M.D. 2005. Characterization and Properties 

 bass. Environ. Health Perspect. 12(10):1058-1062 

es: Daphnia and 

naheim, CA, March 27-April 2004. Abstract 

C21 

05a. Nanotoxicology: An Emerging 

iscipline Evolving from Studies of Ultrafine Particles. Environ. Health Perspect. 113(7): 823-

berdörster, G., Maynard, A., Donaldson, K., Castranova, V., Fitzpatrick, J., Ausman, K., 

. 

ffects from exposure to 

ort from the ILSI Research 

oundation/Risk Science Institute Nanomaterial Toxicity Screening Working Group. 

berdörster, G., Sharp, Z., Atudorei, V., Elder, A., Gelein, R., Kreyling, W., Cox, C. 2004a. 

rster, G., Sharp, Z., Atudorei, V., Elder, A., Gelein, R., Lunts, A., Kreyling, W., Cox, C., 

002. Extrapulmonary translocation of ultrafine carbon particles following whole-body 

inhalation exposure of rats. J. Toxicol. Environ. Health A 65:1531-1543. 

N

Intratracheally Instilled Particles on Pulmonary Unflammation and Thrombosis. To

Pharmacol. 186: 38-45. 

N

L., Khan, M.K. 2004. 3H Dendrimer Nanoparticle Organ/Tumor Distribution. Pharm. Res

(3):476-483. 

Niimi, A., Oliver, B. 1988. Influence of Molecular Weight and Molecular Volume on Dietary 

Adsorption Efficiency of Chemicals by Fishes. Can. J. Fish. Aquat. S

NREL. 2005. National Renewable Energy Laboratory Nanoscience & Nanotechnology: Meeting 

21st Century Energy Challenges. 

Nurmi, J.T., Tratnyek, P.G., Sarathy, V., Baer, D.R., Amonette, J.E., Pecher, K., W

L

of Metallic Iron Nanoparticles: Spectroscopy, Electrochemistry, and Kinetics. Environ. Sci. 

Technol. 39(5):1221-1230. 

Oberdörster, E. 2004b. Manufactured nanomaterial (fullerenes, C60) induce oxidative stress in 

the brain of juvenile largemouth

Oberdörster E. 2004c. Toxicity of nC60 Fullerenes to Two Aquatic Speci

Largemouth bass. American Chemical Society, A

IE

Oberdörster, G., Oberdörster, E., Oberdörster, J. 20

D

839. 

O

Carter, J., Karn, B., Kreyling, W., Lai, D., Olin, S., Monteiro-Riviere, N., Warheit, D., Yang, H

2005b. Principles for characterizing the potential human health e

nanomaterials: elements of a screening strategy. A rep

F

Part. Fibre Toxicol.: 2:8. 

O

Translocation of inhaled ultrafine particles to the brain. Inhal. Toxicol. 16:437-445. 

Oberdö

2
102 EPA Nanotechnology White Paper 

Oberdörster, G. 1996. Significance of Particle Parameters in the Evaluation of Exposure-Doseesponse Relationships of Inhaled Particles. Inhal. Toxicol. 8 (Suppl. 8):73-89. 

jury. Environ. Health Perspect. 102(Suppl 5):173-179. 

. 

cd.org/dataoecd/33/40/1863539.pdf

R

Oberdörster G., Ferin, J., Lehnert, B.E. 1994. Correlation Between Particle Size, In Vivo Particle

Persistence, and Lung In

Organisation for Economic Co-operation and Development. 2001. Environmental Strategy for 

the First Decade of the 21st Century. Adopted by OECD Environment Ministers. 16 May 2001

http://www.oe . 

4(11/12):1871-1896. 

ciency Promotional Literature. 

ttp://www.oxonica.com/cms/promotional/Fuel-Efficiency.pdf

Opperhuizen, A., Velde, E., Gobas, F., Llem, D., Steen, J. 1985. Relationship between 

bioconcentration in fish and steric factors of hydrophobic chemicals. Chemosphere 

1

Oxonica, 2005. Envirox Fuel Effi

h . 

itoniak, E., Wu, C.-Y., Mazyck, D.W., Powers, K. W., Sigmund, W. 2005. Adsorption 

l. 

6. 

ale Particles for Toxicological Evaluation. Toxicol. Sci. 90(2): 296-303. 

Their 

uinn, J., Geiger, C., Clausen, C., Brooks, K., Coon, C., O’Hara, S., Krug, T., Major, D., Yoon, 

. 2005. 

enwick, L.C., Donaldson, K, Clouter, A. 2001. Impairment of Alveolar Macrophage 

oberts, D.W. et al. 2005. Localization of Intradermally Injected Quantum Dot Nanoparticles in 

Pickering, K.D., Wiesner, M.R. 2005. Fullerol-Sensitized Production of Reactive Oxygen 

Species in Aqueous Solution. Environ. Sci. Technol. 39(5):1359-1365. 

P

enhancement mechanisms of silica-titania nanocomposites for elemental mercury vapor remova

Environ. Sci. Technol. 39(5):1269-1274. 

Powers, K.W., Brown, S.C, Krishna, V.B., Wasdo, S.C., Moudgil, B.M., Robert, S.M 200

Research Strategies for Safety Evaluation of Nanomaterials, Part VI: Characterization of 

Nanosc

Preining, O. 1998. The Physical Nature of Very, Very Small Particles and its Impact on 

Behaviour. J. Aerosol Sci. 29(5/6):481-495. 

Q

W-S., Gavsakar, A., Holdsworth, T. 2005. Field Demonstration of DNAPL Dehalogenation

Using Emulsified Zero-Valent Iron. Environ. Sci. Technol. 39(5):1309-1318. 

Reguera, G., McCarthy, K.D., Mehta, T., Nicoll, J.S., Tuominen, M.T., Lovley, D.R

Extracellular Electron Transfer Via Microbial Nanowires. Nature 453(23):1098-1101. 

R

Phagocytosis by Ultrafine Particles. Toxicol. Appl. Pharmacol. 172:119-127. 

R

Regional Lymph Nodes. Society of Toxicology Annual Meeting, New Orleans, LO, 2005, 

Abstract. 
EPA Nanotechnology White Paper 103

Roberts, S. M. 2005. Developing Experimental Approaches for the Evaluation of Toxicological 

, 

ttp://www.nanotoxicology.ufl.edu/workshop/index.html. 

tic Humus from 

n Unpolluted Brazillian Dark-Brown Stream: General Characterization and Size Fractionation 

es 7000 Source Particulate Monitor. Web 

ite May 2005. http://www.rpco.com/products/cemprod/cem7000/index.htm.

Interactions of Nanoscale Materials. Workshop proceedings, University of Florida, Gainesville

FL. Nov. 3-4, 2004. http://ntp.niehs.nih.gov/files/NanoToxWorkshop.pdf, 

h

Rocha J.C., de Sen, J.J., dos Santos, A., Tosacano, I.A.S., Zara, L.F. 2000. Aqua

a

of Bound Heavy Metals. J. Env. Monit. 2:39-44. 

Rupprecht & Patashnick Co., Inc. 2005. TEOM Seri

s

Intact Skin 

Diverse Physicochemical Properties. Toxicol. Sci. 91(1):159-165. 

, K.D., Warheit, D.B., Colvin, 

: A Cytotoxicity Inflammatory 

eponse Study with Human Dermal Fibroblasts and Human Lung Epithelial Cells. Toxicol. Sci. 

ayes, C. M., Fortner, J. D., Guo, W., Lyon, D., Boyd, A. M., Ausman, K. D., Tao, Y. J., 

tial 

chwarzenbach, R.P., Gshwend, P.M., Imboden, D.M., (eds.) 1993. Sorption: Solid-Aqueous 

w 

clafani, A. and Herrmann, J. M. 1996. Comparison of the Photoelectronic and Photocatalytic 

3661. 

u, 

 Unusual 

flammatory and Fibrogenic Pulmonary Responses to Single Walled Carbon Nanotubes in 

hvedova, A.A., Castranova, V., Kisin, E.R., Scwegler, B-D., Murray, A.R., Gandelsman, V.Z., 

anotube 

6(20): 1909-1926. 

mall Times Media, LLC, Nanotechnology Products Report, August 2005. 

ric Aerosols (UAAA): New Advances. Toxicol. Lett. 96-97: 253-261. 

Ryman-Rasmussen, J.P., Riviere, J.E., Monteiro-Riviere, N.A. 2006. Penetration of 

by Quantum Dots with 

Sayes, C.M., Wahi, R., Kurian, P.A., Liu, Y., West, J.L., Ausman

V.L. 2006. Correlating Nanoscale Titania Structure with Toxicity

R

92(1):174-185. 

S

Sitharaman, B., Wilson, L. J., Hughes, J. B., West, J. L., Colvin, V. L. 2004. The Differen

Cytotoxicity of Water Soluble Fullerenes. Nano Letters 4(10):1881-1887, 2004 

S

Solution Exchange (Chapter 11) in Environmental Organic Chemistry, Wiley-Interscience, Ne

York. 

S

Activities of Various Anatase and Rutile Forms of Titania in Pure Liquid Organic and in 

Aqueous Phases. J. Phys. Chem. 100:13655-1

Shvedova, A.A., Kisin, E.R., Mercer, R., Murray, A.R., Johnson, V.J., Potapovich, A.I., Tyurina,

Y.Y., Gorelik, O., Arepalli, S., Schwegler-Berry, D., Hubbs, A.F., Antonini, J., Evans, D.E., K

B-K., Ramsey, D., Maynard, A., Kagan, V.E., Castranova, V., Baron, P. 2005.

In

Mice. Am. J. Physiol. Lung Cell Mol. Physiol. 289:L698-L708. 

S

Maynard, A., Baron, P. 2003. Exposure to Carbon Nanotube Material: Assessment of N

Cytotoxicity using Human Keratinocyte Cells. J. Toxicol. Environ. Health A. 6

S

Spurny, K.R. 1998. On the Physics, Chemistry and Toxiology of Ultrafine Anthropogenic, 

Atmosphe
104 EPA Nanotechnology White Paper 

Stevens, G., Moyer, E. 1989. ‘Worst case’ aerosol testing parameters: I. Sodium chloride and 

dioctyl phthalate aerosol filter efficiency as a function of particle size and flow rate. Am. Indust. 

Hygiene Assoc. J. 50(5):257-64. 

Steinfeldt, M., Petschow, U., Haum, R. Gleich, A.V. 2004. Nanotechnology and Sustainability. 

Discussion Paper #65/04. Institute for Ecological Economy Research. Berlin. www.ioew.de. 

Sun, J.D., Wolff, R.K., Kanapilly, G.M. 1982. Deposition, Retention and Biological Fate of 

haled Benzo(a)pyrene Adsorbed onto Ultrafine Particles and as a Pure Aerosol. Toxicol. Appl. 

un, J.D., Wolff, R.K., Kanapilly, G.M., McClellan, R.O. 1984. Lung Retention and Metabolic 

In

Pharmacol. 65(2): 231-244. 

S

Fate of Inhaled Benzo(a)pyrene Associated with Diesel Exhaust Particles. Toxicol. Appl. 

Pharmacol. 73(1): 48-59. 

Swiss Report Reinsurance Company. 2004. Nanotechnology: Small Matter, Many Unknowns. 

www.swissre.com. 

Thomas, K., Sayre, P. 2005. Research Strategies for Safety Evaluation of Nanomaterials, Part I: 

valuating Human Health Implications for Exposure to Nanomaterials. Toxicol.Sci. 87(2): 316-

dkijns, E.J. 

003. Skin as a Route of Exposure and Sensitization in Chronic Beryllium Disease. Environ. 

.S., Maynard, A.D., Howard, P.C., James, J.T., Lam, C-W., Warheit, D.B., Santamaria, 

.B. 2006. Research Strategies for Safety Evaluation of Nanomaterials, Part IV: Risk 

gineered Polymeric Nanoparticles for the 

ioremediation of Hydrophobic Contaminants. Environ. Sci. Technol. 39:1354-1358. 

e Determination of OH 

adical Generation and its Cytotoxicity Induced by TiO2-UVA Treatment. Toxicol. In Vitro 

h Report. Available 

t: www.defra.gov.uk/environment/nanotech/nrcg/pdf/nanoparticles-riskreport.pdf

E

321. 

Tinkle, S.S, Antonini, J.M., Rich, B.A., Roberts, J.R., Salmen, R., DePree, K., A

2

Health Perspect. 111:1202-1208. 

Tsuji, J

A

Assessment of Nanoparticles. Toxicol. Sci. 88(1):12-17. 

Tungittiplakorn, W., Cohen, C., Lion, L.W. 2005. En

B

Tungittiplakorn, W., Lion, L.W., Cohen, C., Kim, J.Y. 2004. Engineered Polymeric 

Nanoparticles for Soil Remediation. Environ. Sci. Technol. 38: 1605-1610. 

Uchino, T., Tokunaga, H., Ando, M., Utsuni, H. 2002. Quantitativ

R

16:629-635. 

UK Department for Environment, Food and Rural Affairs. 2005 Characterising the Potential 

Risks Posed by Engineered Nanoparticles: A First UK Government Researc

a . 

 Review. 

esearch Report 274. http://www.hse.gov.uk/research/rrhtm/rr274.htm

UK Health and Safety Executive. 2004. Nanoparticles: An Occupational Hygiene

R . 
EPA Nanotechnology White Paper 105

UK Royal Society. 2004. The Royal Society and the Royal Academy of Engineering. 

Nanoscience and Nanotechnologies: Opportunities and Uncertainties. 

http://www.nanotec.org.uk/finalreport.htm. 

ood Systems. Report Submitted to Cooperative State Research, Education, and Extension 

 Agency. Innovation Action Council. 2005. Presentation by Jay 

enforado. June 30, 2005. 

2 

http://www.epa.gov/greenchemistry/principles.html

U.S. Department of Agriculture. 2003. Nanoscale Science and Engineering for Agriculture and 

F

Service. Norman Scott (Cornell University) and Hongda Chen (CSREES/USDA) Co-chairs. 

U.S. Environmental Protection

B

U.S. Environmental Protection Agency. 2005. Office of Pollution Prevention and Toxics. 1

Principles of Green Chemistry. . 

y 

te Matter. Report Number EPA/600/P-99/002a,bF. October. 

ttp://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=87903

U.S. Environmental Protection Agency. 2004. Office of Research and Development. Air Qualit

Criteria for Particula

h . 

nt Water Quality Criteria for the Protection of Human Health (2000) Technical Support 

ocument Volume 2: Development of National Bioaccumulation Factors. 

49. NTIS PB86134608. 

U.S. Environmental Protection Agency. 2003. Office of Water. Methodology for Deriving 

Ambie

D

U.S. Environmental Protection Agency. 1986. Health Effects Assessment for Asbestos. 

Washington, D.C. EPA/540/1-86/0

U.S. Environmental Protection Agency. 1998. Guidelines for Ecological Risk Assessment. 

EPA/630/R095/002F. http://cfpub.epa.gov/ncea/raf/recordisplay.cfm?deid=12460. 

U.S. Environmental Protection Agency. 1996. Health Effects of Inhaled Crystalline and 

arheit, D.B., Webb, T.R., Sayes, C.M., Colvin, V.L., Reed K.L. 2006. Pulmonary Instillation 

le Size and 

nary 

 of 

ment on Particle Toxicity. Toxicol. Sci. 88(2): 514-524. 

. 

isks 

Amorphous Silica. EPA/600/R-95/115. 

W

Studies with Nanoscale TiO2 Rods and Dots: Toxicity Is Not Dependent Upon Partic

Surface Area. Toxicol. Sci. 91(1): 227-236. 

Warheit, D.B. , Brock, W.J., Lee, K.P., Webb, T.R., Reed, K.L. 2005. Comparative Pulmo

Toxicity Instillation and Inhalation Studies with Different TiO2 particle Formulaitons: Impact

Surface Treat

Warheit, D.B, Laurence, B.R., Reed, K.L., Roach, D.H., Reynolds, G.A., Webb, T.R. 2004. 

Comparative Pulmonary Toxicity Assessment of Single-wall Carbon Nanotubes in Rats. Toxicol

Sciences 77:117-125. 

Wiesner, M.R., Lowry, G.V., Alvarez, P., Dionysiou, D., Bisawas, P. 2006. Assessing the R

of Manufactured Nanomaterials. Environ. Sci. Tech. 40(14):4336-4345. 
106 EPA Nanotechnology White Paper 

Willis, R.S. 2002. When Size Matters. Today’s Chemist at Work, American Chemical S

July 2002, p. 21-24. 

ociety, 

oodrow Wilson Center Project on Emerging Nanotechnologies, Inventory of Consumer 

conomies. 

 Particle surface characteristics may play an important role in 

hytotoxicity of alumina nanoparticles. Toxicol. Lett. 158:122-132. 

le 

anufacturing. Proceedings of the 2006 IEEE International Symposium on Electronics and the 

mediation: An Overview. J. 

anoparticle Res. 5: 323-332. 

kes PM 

 Press. 

W

Products. 2006. http://www.nanotechproject.org/44. 

 

World Resources Institute. 2000. The Weight of Nations: Material Outflows from Industrial 

E

Yang, L., Watts, D.J. 2005.

p

Zhang, T.W., Boyd,S.,Vijayaraghavan, A., Dornfeld, D. 2006. Energy Use in Nanosca

M

Environment, pp. 266-271. 

Zhang, W. 2003. Nanoscale Iron Particles for Environmental Re

N

Zhao, X., Striolo, A., Cummings, P.T. 2005. C60 Binds to and Deforms Nulceotides. 

Biophysical J. 89:3856-3862. 

Zitko V. 1981. Uptake and excretion of chemicals by aquatic fauna. pages 67 to 78 in Sto

(ed.) Ecotoxicology and the Aquatic Environment, Pergamon

Conversation with Hongda Chen. May, 2005. 
EPA Nanotechnology White Paper 107

Appendix A: Glossary of Nanotechnology Terms 

Aerosol: A cloud of solid or liquid particles in a gas. 

ting or non-repeating units that are arranged 

r increased sensitivity or selectivity. 

itating nature and applying those techniques to technology. 

Array: An arrangement of sensing elements in repea

fo

Biomimetic: Im

Buckyball/C60:see Fullerenes, of which “buckyballs” is a subset. The term “buckyball” 

only to the spherical fullerenes and is derived from the word “Buckm

refers 

insterfullerene,” which is 

e geodesic dome / soccer ball-shaped C molecule. C was the first buckyball to be 

lly used in small amounts relative to the reactants, that modifies and 

ered or manufactured molecules built up from branched units 

olecule 

on beam, usually to induce 

atterns can be subsequently transferred to 

s. 

Engineered/manufactured nanomaterials: Nanosized materials are purposefully made. These 

are in contrast to incidental and naturally occurring nanosized materials. 

Engineering/manufacturing may be done through certain chemical and / or physical processes to 

create materials with specific properties. There are both "bottom-up" processes (such as selfassembly) that create nanoscale materials from atoms and molecules, as well as "top-down" 

processes (such as milling) that create nanoscale materials from their macro-scale counterparts. 

Nanoscale materials that have macro-scale counterparts frequently display different or enhanced 

properties compared to the macro-scale form. 

Exposure assessment: The determination or estimation (qualitative or quantitative) of the 

magnitude, frequency, duration, route, and extent (number of people) of exposure to a chemical, 

material, or microorganism. 

Fullerenes: Pure carbon, cage-like molecules composed of at least 20 atoms of carbon. The 

word ‘fullerene’ is derived from the word “Buckminsterfullerene,” which refers specifically to 

the C60 molecule and is named after Buckminster Fuller, an architect who described and made 

famous the geodesic dome. C60 and C70 are the most common and easy to produce fullerenes. 

th 60 60

discovered and remains the most common and easy to produce. 

Catalyst: A substance, usua

increases the rate of a reaction without being consumed or changed in the process.. 

Dendrimers: artificially engine

called monomers. Technically, a dendrimer is a branched polymer, which is a large m

comprised of many smaller ones linked together. 

Diamondoid: Nanometer-sizes structures derived from the diamond crystal structure. 

Electron beam lithography: Lithographic patterning using an electr

a change in solubility in polymer films. The resulting p

other metallic, semiconductor, or insulating film
108 EPA Nanotechnology White Paper 

Incidental nanosized materials: Nanomaterials that are the byproducts of human activity, such 

as combustion

red/manufactured nanoscale materials. 

clude plastic injection molding, vacuum forming, 

milling, stamping, casting, extruding, die-cutting, sewing, printing, packaging, polishing, 

e works 

 biological systems. The 

interaction between the body and nanodevices are studied, for example, to develop processes for 

Nanochemistry: A discipline focusing on the unique properties associated with the assembly of 

l 

 to femtolitre domains. 

nanotechnology; includes both molecular electronics and nanoscale devices resembling today's 

noscale materials 

nce devoted to the advancement of 

nanotechnology. 

icrometer-sized) structures. 

. 

, welding, or grinding.

Intentionally produced nanomaterials: See Enginee

Manufacturing processes: General term used to identify the variety of processes used in the 

production of the part. Processes may in

grinding, metal spinning, welding, and so forth. 

Nano-: a prefix meaning one billionth. 

Nanobiology: A field of study combining biology and physics which looks at how natur

on the nanometer scale, particularly how transport takes place in

the body to regenerate bone, skin, and other damaged tissues. 

atoms or molecules on a nanometer scale. At this scale, new methods of carrying out chemica

reactions are possible. Alternatively, it is the development of new tools, technologies and 

methodologies for doing chemistry in the nanolitre

Nanoelectronics: Electronics on a nanometer scale, whether by current techniques or 

semiconductor devices. 

Nanomaterial: See Engineered/manufactured na

Nanometer: one billionth of a meter. 

Nanoparticle: Free standing nanosized material, consisting of between tens to thousands of 

atoms. 

Nanoscale: having dimensions measured in nanometers. 

Nanoscience: the interdisciplinary field of scie

Nanostructures: structures at the nanoscale; that is, structures of an intermediate size between 

molecular and microscopic (m

Nanotechnology: Research and technology development at the atomic, molecular or 

macromolecular levels, in the length scale of approximately 1 - 100 nanometer range; creating 

and using structures, devices and systems that have novel properties and functions because of 

their small and/or intermediate size; and the ability to control or manipulate on the atomic scale
EPA Nanotechnology White Paper 109

Nanotube: Tubular structure, carbon and non-carbon based, with dimensions in nanometer 

regime. 

Nanowire: High aspect ratio structures with nanometer diameters that can be filled (nanorods) or 

hollow (nanotubes). 

rs in diameter 

icrometers in diameter 

PM0.1: Particulate matter less than 0.1 micrometers in diameter 

PM2.5: Particulate matter less than 2.5 micromete

PM10: Particulate Matter less than 10 m

Quantum dot: A quantum dot is a closely packed semiconductor crystal comprised of hundreds 

or thousands of atoms, and whose size is on the order of a few nanometers to a few hundre

nanometers. Changing the size of quantum dots changes their optical properties 

d 

Self-Assembled Monolayers on Mesoporous Supports (SAMMS): nanoporous ceramic 

tinely 

animate matter. 

als composed of thin crystal layers. The properties (thickness, 

composition) of these layers repeat periodically. 

Unintentionally produced nanomaterials: See Incidental nanosized materials

materials that have been developed to remove contaminants from environmental media. 

Self-assembly: The ability of objects to assemble themselves into an orderly structure. Rou

seen in living cells, this is a property that nanotechnology may extend to in

Self-replication: The ability of an entity such as a living cell to make a copy of itself. 

Superlattice: nanomateri
110 EPA Nanotechnology White Paper 

Appendix B: Principles of Environmental Stewardship Behavior 

sed on statements by environmental stewards and others) 

What does a good environmental steward do? 

(ba

Exceeds required compliance. An environmental steward views environmental regulations only 

as a floor, not a target. 

Protects natural systems and uses natural resources effectively and efficiently. An 

mmunity, farm or company’s 

entire environmental footprint. A steward safeguards and restores nature at home and elsewhere. 

es 

s materials and 

wastes and seeks sustainability. 

ple.

environmental steward considers and reduces the household, co

A steward follows the pollution prevention hierarchy of acting first to prevent pollution at its 

source. A steward uses less toxic, more environmentally benign materials, uses local resourc

and conserves natural resources whenever possible. A steward reuses and recycle

Makes environment a key part of internal priorities, values and ethics, and leads by exam 

Environmental stewards make decisions through their own volition that will prevent or minimize 

, 

policy planning, and life as an integrated dynamic with the environment. A steward acts in 

ts 

holistic, systems approaches. 

environmental harm. They anticipate, plan for, and take responsibility for economic, 

environmental and social consequences of actions. A steward approaches business strategies

innovative ways, using all available tools and creating or adding value. A steward adop

Holds oneself accountable. An environmental steward measures the effects of behavior on the 

nvironment and seeks progress. A steward applies an understanding of carrying capacity to 

sing 

indicators, environmental assessments, and environmental management systems. 

Believes in shared responsibility.

e

measure progress and update objectives to achieve continuous improvement, often u

 An environmental steward recognizes obligations and 

connections to all stakeholders- shareholders, customers, communities at home and elsewhere. 

For a company, this means being concerned with the full life cycle of products and services, 

beyond company boundaries, up and down the supply chain (including consumers and end-oflife). For a community, this means to protect the environment for all members and takes 

responsibility for effects on downstream air pollution, and effects of wastes disposed elsewhere. 

A steward operates with transparency. They encourage others to be collaborative stewards. 

Invests in the future. An environmental steward anticipates the needs of future generations 

while serving the needs of the present generation. Their actions reflect possible changes in 

population, the economy and technology. A steward guides the development of technology to 

minimize negative environmental implications and maximize potential environmental 

stewardship applications. A steward values and protects natural and social capital. They seek 

preventative and long-term solutions in community development, business strategy, agricultural 

strategy, and household plans. 
EPA Nanotechnology White Paper 111

Appendix C: EPA’s Nanotechnology Research Framework 

Nanotechnology h he environment, 

oth through direct applications to detect, prevent, and remove pollutants, the design of cleaner 

ies that make manufactured nanoparticles beneficial also raise questions 

bout the potential impacts of nanoparticles on human health and the environment. 

ms, considering the entire life cycle. EPA also will conduct 

search to identify approaches for detecting and measuring nanoparticles. This research 

s 

f the 

done to determine potential toxicity of certain nanoparticles to 

umans and other organisms (both in vivo and in vitro), very little research has been performed 

ill vary 

ears 2007 and 

008, EPA will focus on the following high priority areas: environmental fate, transport, 

e used 

e 

water 

levant 

derstanding possible material alterations under various 

conditions, EPA will direct a greater share of fiscal year 2009 and 2010 resources to exploring 

as the potential to provide benefits to society and to improve t

b

industrial processes and the creation of environmentally friendly products. However, some of 

the same unique propert

a

Based on the fiscal year 2007 President’s budget request of $8.6 million, EPA is developing a

nanotechnology research strategy for fiscal years 2007-2012 that is problem-driven, focused on 

addressing the Agency's needs. The framework for this strategy, as outlined here, involves 

conducting research to understand whether nanoparticles, in particular those with the greatest 

potential to be released into the environment and/or trigger a hazard concern, pose significant 

risks to human health or ecosyste

re

framework is based on the recommendations from the EPA Nanotechnology White Paper and i

consistent with the research needs identified by the Interagency Working Group on 

Nanotechnology Environmental and Health Implications, one of the working groups o

Nanoscale Science Engineering and Technology Subcommittee of the National Science and 

Technology Council. 

While some studies have been 

h

on environmental fate and transport, transformation, and exposure potential. Research also is 

lacking on technologies and methods to detect and quantify nanomaterials in various 

environmental media. In addition, studies indicate that the toxicity of the nanomaterial w

with size, surface charge, coating, state of agglomeration, etc. Therefore, in fiscal y

2

transformation and exposure; and monitoring and detection methods. Resulting data will b

to inform and develop effects and exposure assessment methods and identify important points of

releases for potential management. Specific activities will include: 

 Identifying, adapting, and, where necessary, developing methods and techniques to measur

nanomaterials from sources and in the environment 

 Enhancing the understanding of the physical, chemical, and biological reactions 

nanomaterials undergo and the resulting transformations and persistence in air, soil and 

 Characterizing nanomaterials through their life cycle in the environment 

 Providing the capability to predict significant exposure pathway scenarios 

 Providing data to inform human health and ecological toxicity studies, as well as 

computational toxicological approaches, and aid in the development of the most re

testing methods/protocols 

Having laid a foundation for un
112 EPA Nanotechnology White Paper 

the effects, specifically toxicity of the altered materials as identified in the first two years. This 

approa d to 

elicit information on how EPA can address high-exposure-potential nanoparticles/nanomaterials. 

y 2011-2012, sufficient knowledge will result in the development of systematic and integrated 

ddition, the 

gency is collaborating with academia and industry to fill knowledge gaps in these areas. 

ch will be informed and refined by case studies, initiating in fiscal year 2007, designe

B

approaches to assess, manage and communicate risks associated with engineered nanomaterials 

in the environment. 

To complement its own research program, EPA is working with other federal agencies to 

develop research portfolios that address environmental and human health needs. In a

A

Finally, the Agency is working internationally and is part of the Organization of Economic 

Cooperation and Development’s efforts on the topic of the implications of manufactured 

nanomaterials. 
EPA Nanotechnology White Paper 

Appendix D: EPA STAR Grants for Nanotechn

Through Science to Achieve Results (STAR) program in EPA’s Office of Research and Develop 

Environmental Research, a number of nanotechnology research grants have been awarded. The t 

grants funded though 2005. Additional grants focusing on implications of nanomaterials for the 20 final selection and funding by EPA, the National Science Foundation (NSF), the National Institute f(NIOSH), and the National Institute of Environmental Health Sciences (NIEHS). Information on fu and progress reports is available online at www.epa.gov/ncer/nano

ology 

ment/National C

able below show

06 solicitation 

or Occupatio

nded grants, 

.

Grant # 

Principal 

Investigator (PI) Title Institution 

Year 

RD829621 

Bhattacharyya, Dibakar 

Membrane-Based Nanostructured Metals for Reductive Degradation of Hazardous Organic at Room Temperature 

University of Kentucky 2002 

RD829606 Chen, Wilfred 

Nanoscale Biopolymers with Tunable Properties for Improved Decontamination and Recycling of Heavy Metals 

University of California, Riverside 2002 

RD829603 Chumanov, George 

Plasmon Sensitized TiO2 Nanoparticles as a Novel Photocatalyst for Solar Applications Clemson University 2002 

RD829626 Diallo, Mamadou 

Dendritic Nanoscale Chelating Agents: Synthesis, Characterization, Molecular Modeling and Environmental Applications 

Howard University 

2002 

RD829599 Gawley, Robert Nanosensors for Detection of Aquatic Toxins University of Arkansas 2002 RD829622 Johnston, Murray 

Elemental Composition of Freshly Nucleated Particles 

University of Delaware 2002 

RD829600 Larsen, Sarah 

Development of Nanocrystalline Zeolite Materials as Environmental Catalysts: From Environmentally Benign Synthesis Emission Abatement 

University of Iowa 

2002 

RD829620 McMurry, Peter 

Ion-Induced Nucleation of Atmospheric Aerosols 

University of Minnesota 2002 
114 EPA Nanotechnology White Paper 

Grant # 

Principal 

Investigator (PI) Title Institution Year 

RD829624 Shah, S. Ismat Nanoparticles as Environmental Nanocatalysts 2002 

Synthesis, Characterization and Catalytic Studies of Transition Metal Carbide University of Delaware 

RD829604 Shih, Wan 

Ultrasensitive Pathogen Quantification in Drinking Water Using Highly Piezoelectric PMN-PT Microcantilevers 

Drexel University 

2002 

RD829602 Sigmund, Wolfgang 

Simultaneous Environmental Monitoring and Purification through Smart Particles University of Florida 2002 

RD829601 Strongin, Daniel 

oparticle Temple University 2002 

A Bioengineering Approach to Nan Based Environmental Remediation 

RD829623 Tao, 

A Nanocontact Sens Heavy Metal Ion Detection 

ArizoUniv Nongjian 2002 

or for na State 

ersity 

RD829619 Trogler, William 

s as Chemical Sensors 

rsenic California, San Diego 

2002 

Nanostructured Porous Silicon and Luminescent Polysilolefor Carcinogenic Chromium (VI) and A(V) 

University of 

RD829605 Velegol, Darrell 

rsed Nanoparticles: 

s University 2002 

Green Engineering of DispeMeasuring and Modeling Nanoparticles Force

Pennsylvania State 

RD829625 Zhang, Wei-xian Lehigh University 2002 

Nanoscale Bimetallic Particles for In Situ Remediation 

RD830907 Anderson, Anne Utah State University 

Metal Biosensors: Development and Environmental Testing 2003 

RD830910 Beaver, Earl 

d 

 2003 

Implications of Nanomaterials Manufacture anUse: Development of a Methodology for Screening Sustainability 

BRIDGES to Sustainability

RD830904 Drzal, Lawrence 

ble Biodegradable Green 

c for Michigan State 

2003 

SustainaNanocomposites from Bacterial BioplastiAutomotive Applications University 

RD830902

ng 

sistors 

Kan, Edwin rsity 

Neuromorphic Approach to Molecular Sensiwith Chemoreceptive Neuron MOS Tran(CnMOS) Cornell Unive 2003 
EPA Nanotechnology White Paper 

Grant # 

Principal 

Investigator (PI) Title Institution Year 

RD830909 Kilduff, 

erties to 

James Polytechnic Institute 

Graft Polymerization as a Route to ControlNanofiltration Membrane Surface PropManage Risk of EPA Candidate Contaminants and Reduce NOM Fouling 

Rensselaer 

2003 

RD830905 Lave, Lester Environmental Implications of Nanotechnology 

Carnegie Mellon University 2003 

RD830911

or Oklahoma State 

Lavine, Barry 

Compound Specific Imprinted Nanospheres fOptical Sensing University 2003 

RD830898 Lowry, Gregory University 

Functional Fe(0)-Based Nanoparticles for In Situ Degradation of DNAPL Chlorinated Organic Solvents 

Carnegie Mellon 

2003 

RD830908 Masten, Susan 

te Ceramic Membranes for an State 

University 2003 

Use of Ozonation in Combination with NanocomposiControlling Disinfection By-Products 

Michig

RD830901 Mitra, Somenath MEMS Structures of Technology 

Micro-Integrated Sensing System (μ-ISS) by Controlled Assembly of Carbon Nanotubes on New Jersey Institute 

2003 

RD830903 Sabatini, David n 2003 

Nanostructured Microemulsions as Alternative Solvents to VOCs in Cleaning Technologies and Vegetable Oil Extraction 

University of Oklahoma, Norma

RD830906 i 

us 

tals 

New York, 

Sadik, Omowunm

Advanced Nanosensors for ContinuoMonitoring of Heavy Me

State University of Binghamton 2003 

RD830896 m logies 

University of 

s 

Senkan, Seli

Nanostructured Catalytic Materials for NOx Reduction Using Combinatorial Methodo

California, LoAngeles 2003 

RD830899 

Subramanian, Vivek 

Plastic for University of 

eley 2003 

Low Cost Organic Gas Sensors on Distributed Environmental Monitoring California, Berk

RD830900 Wang, Joseph 

ochip Assays for te 

University 2003 

Nanomaterial-Based MicrContinuous Environmental Monitoring 

Arizona Sta

RD830897 Winter, William 

les: An Alternative to Existing 

Petroleum-Based Polymer Composites New York, Syracuse 2003 Ecocomposites Reinforced with Cellulose Nanopartic State University of 
116 EPA Nanotechnology White Paper 

Grant # 

Principal 

Investigator (PI) Title Institution Year 

RD831722 Elder, Alison 

University of Rochester 2004 

Iron Oxide Nanoparticle-Induced Oxidative Stress and Inflammation 

RD831716 Ferguson, P. Lee 

Chemical and Biological Behavior of Carbon South Nanotubes in Estuarine Sedimentary Systems 

University ofCarolina 2004 

RD831717 Grassian, Vicki 

A Focus on Nanoparticulate Aerosol and 

 2004 

Atmospherically Processed Nanoparticulate Aerosol University of Iowa

RD831712 Holden, Patricia 

d nta 

 2004 

Transformations of Biologically Conjugated CdSe Quantum Dots Released Into Water anBiofilms 

University of California, SaBarbara

RD831721 Huang, Chin-pao 

s to Bacteria, Algae, and 

Delaware 2004 

Short-Term Chronic Toxicity of Photocatalytic NanoparticleZooplankton 

University of 

RD831719 Hurt, Robert ersity 

Physical and Chemical Determinants of Nanofiber/Nanotube Toxicity Brown Univ 2004 

RD831715 

Monteiro-Riviere, Nancy 

North Carolina State 

Evaluated Nanoparticle Interactions with Skin University 2004 

RD831714 Pinkerton, Kent Health Effects of Inhaled Nanomaterials California, Davis 2004 

University of 

RD831718 Tomson, Mason 

ntaminants onto 

Engineered Nanoparticles 2004 Absorption and Release of Co

Rice University 

RD832531 Turco, Ronald 

tured 

Processes in 

ity 2004 

Repercussion of Carbon Based ManufacNanoparticles on Microbial Environmental Systems Purdue Univers

RD831723 Veranth, John y of Utah 

Responses of Lung Cells to Metals in Manufactured Nanoparticles Universit 2004 

RD831713 Westerhoff, Paul 

s in 

 2004 

The Fate, Transport, Transformation and Toxicity of Manufactured NanomaterialDrinking Water 

Arizona State University

GR832225\ Zhang, Wei-xian 

with 

Lehigh University 2004 

Transformation of Halogenated PBTs Nanoscale Bimetallic Particles 

RD832534 Alvarez, Pedro Microbial Impacts of Engineered Nanoparticles 

William Marsh RiceUniversity 2005 
EPA Nanotechnology White Paper 

Grant # 

Principal 

Investigator (PI) Title Institution Year 

RD832531 hman

rial for 

Asgharian, Ba rch 

Mechanistic Dosimetry Models of NanomateDeposition in the Respiratory Tract 

CIIT Centers Health Resea 2005 

RD832532

g 

Bakshi, Bhavik y 

Evaluating the Impacts of Nanomanufacturinvia Thermodynamic and Life Cycle Analysis Ohio State Universit 2005 

Barber, David University of Florida 2005 

Uptake and Toxicity of Metallic Nanoparticles in Freshwater Fish 

RD832530 Bertsch, Paul 

es: 

rgia 2005 

The Bioavailability, Toxicity, and Trophic Transfer of Manufactured ZnO2 NanoparticlA View from the Bottom University of Geo

RD832635 Claude Florida 2005 

Bonzongo, JeanAssessment of the Environmental Impacts of Nanotechnology on Organisms and 

Ecosystems University of 

RD832536 Colvin, Vicki 

Structure-Function Relationships in EngiNanomaterial Toxic

neered h Rice 

ity 

William MarsUnibersity 2005 

 Mary 

ed 

ue Safety 

Assessment Approach 2005 

Cunningham,Jane 

Gene Expression Profiling of Single-WallCarbon Nanotubes: A Uniq Houston Advanced 

Research Center 

RD832525 Diallo, Mamadou 

Nanomaterials: An Integrated Physicochemical itute of 

Cellular Uptake and Toxicity of Dendritic and Toxicogenomics Study 

California InstTechnology 2005 

GR832382 Gawley, Robert 

University of 

Nanosensors for Detection of Saxitoxin Arkansas 2005 

RD832528 Gordon, Terry 

ion in Nanoparticle rsity 

School of Medicine 2005 

Role of Particle AgglomeratToxicity 

New York Unive

GR832371 Heiden, Patricia eaching 

Michigan 

A Novel Approach to Prevent Biocide L 2005 

Technological University 

RD832529 Kibbey, Tohren 

Hysteretic Accumulation and Release of Nanomaterials in the Vadose Zone homa 2005 

University of Okla 

RD832526

les 

ent Processes 

te of 

Kim, Jaehong y 

Fate and Transformation of C60 Nanoparticin Water Treatm

Georgia InstituTechnolog 2005 

GR832372 Kit, Kevin 

f Aqueous and 

Gaseous Systems 2005 Nanostructured Membranes for Filtration, Disinfection and Remediation o University of 

Tennessee 
118 EPA Nanotechnology White Paper 

Grant # 

Principal 

Investigator (PI) Title Institution Year 

GR832374 Lu, Yunfeng 

Novel Nanostructured Catalysts for Environmental Remediation of Chlorinated Compounds Tulane University 

2005 

Marr, Linsey University 2005 

Cross-Media Environmental Transport, Transformation, and Fate of Manufactured Carbonaceous Nanomaterials 

Virginia Polytechnic Institute and State 

RD832527 McDonald, Jacob 

gy & Environmental 

Research Institute 2005 

Chemical Fate, Biopersistence, and Toxicoloof Inhaled Metal Oxide Nanoscale Materials 

Lovelace Biomedical 

GR832375 California, Riverside 2005 

Mulchandani, Ashok 

Conducting-Polymer Nanowire ImmunosensorArrays for Microbial Pathogens 

University of 

R01OH8806 

O'Shaughnessy, s in the Patrick 

Assessment Methods for NanoparticleWorkplace University of Iowa 2005 

RD832535 Pennell, Kurt 

Fate and Transport of C60 Nanomaterials in Unsaturated and Saturated Soils 

Georgia Institute of Technology 2005 

RD832 Peter 

lood 

537 Perrotta, 

Effects of Nanomaterials on Human BCoagulation 

West Virginia University 2005 

RD832533 Theodorakis, Chris 

al Southern Illinois 

2005 

Acute and Developmental Toxicity of MetOxide Nanoparticles to Fish and Frogs University 

R01OH8807 Xiong, Judy 

g Airborne Carbon 

Nanotube Particles 

iversity 

dicine 2005 

Monitoring and Characterizin New York Un

School of Me

GR832373 Zhao, Dongye 

ss of 

ion of Chlorinated Hydrocarbons in Soil 

and Groundwater University 2005 

Synthesis and Application of a New ClaStabilized Nanoscale Iron Particles for Rapid Destruct

Auburn 

Total 

EPA 

70 TOTAL - 65 STAR, 3 NSF, 2 NIOSH 
EPA Nanotechnology White Paper 119

Appendix E: List of Nanotechnology White Paper External Peer 

Reviewers and their Affiliations 

Pratim Biswas, Ph.D. 

Departme of Chemical C l in n

Environmental Engineering Science Program 

Washington University in St. Louis 

Richard A enis Ph.D

Senior Scientist 

Environmen efen

Rebecca D , P

Great Lak

Universit ee

Igor Link

Senior Scientist 

Cambridge Environmen In

Current Affilia : Ma ci st T O In

Andrew D. Maynard, P

Chief Science Advisor 

Proje E N s

Woodrow W er r ar

Vlad . v

Special Assi he

National Ins O fe ea

Stephen S. Olin, Ph.D. 

Depu

Inter en

Jennifer B. Sass, Ph.D. 

Senior Scientist, Health a nvir ent 

Natural R urce fens c

Donald A mal h.D

President hie chni

Dendritic Nanotechnologies, Inc. 

Nigel J. W er, Ph.D. 

National te of Environm s 

National tes of Hea

nts and ivi Eng eeri g 

. D on, . 

tal D

laper

WATER

 Wiscon

Ph.D. 

se 

h.D. 

 Institute 

sin, Mil

. K

es 

y of

ov, 

wauk

tal 

nagin

h.D. 

anotec

nation

, Ph.D

 Direc

ccupa

ces In

c 

g S

hnolo

al Ce

. 

tor 

tiona

stitut

tion

merging 

ilson Int

 Murasho

stant to t

titute for 

tor 

 Life Sci

enti

gie

nte

l Sa

e (ILS

, IN

 

for Sc

ty and

I) Re

ERT

hol

 H

searc

X,

s 

lth 

h Fou

c. 

ndati

ct on 

amir V

ty Direc

national on 

nd E

e C

. 

cal 

onm

il 

er 

eso

. To

 & C

s De

ia, P

f Te

oun

Offic

alk

Institu

Institu

ental Health Science

lth 
120 EPA Nanotechnology White Paper 

David B. Warheit, Ph.D 

Senior Research Toxicolo

.I. du Pont de Nemours & Co., Inc. 

gist, Inhalation Toxicology 

E

Haskell Laboratory