EPA 100/B-07/001 I February 2007
www.epa.gov/osa
United States
Environmental Protection
Agency
Nanotechnology White Paper
Office of the Science Advisor
Science Policy Council
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. ^ EPA 100/B-07/001
S. February 2007
3) in
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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
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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.
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EPA Nanotechnology White Paper
in
Nanotechnology White Paper
Workgroup Co-Chairs
Jeff Morris Jim Willis
Office of Research and Development 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 Seal era, OEI
Pollution Prevention
Walter Schoepf, Region 2
Physical-Chemical
Properties
Tracy Williamson, OPPTS
Environmental Detection and
Analysis
John Seal era, 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
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IV
EPA Nanotechnology White Paper
Workgroup Members
Suzanne Ackerman, OPA
Kent Anapolle, OPPTS
Fred Arnold, OPPTS
Ayaad Assaad, OPPTS
Dan Axelrad, OPEI
John Bartlett, OPPTS
Sarah Bauer, ORD
Norman Birchfield, OSA
John Blouin, OPPT
Jim Blough, Region 5
Pat Bonner, OPEI
William Boyes, ORD
Gordon Cash, OPPTS
Gilbert Castellanos, OIA
Tai-Ming Chang, Region 3
Paul Cough, OIA
Lynn Delpire, OPPTS
John Diamante, OIA
Christine Dibble, OPA
Jeremiah Duncan, AAAS fellow, OPPTS
Thomas Forbes, OEI
Conrad Flessner, OPPTS
Jack Fowle, ORD
Elisabeth Freed, OECA
Sarah Furtak, OW
Hend Galal-Gorchev, OW
David Giamporcaro, OPPTS
Michael Gill, ORD liaison for Region 9
Collette Hodes, OPPTS
Gene Jablonowski, Region 5
Lee Hofman, OSWER
Joe Jarvis, ORD
Y' Vonne Jones-Brown, OPPTS
Edna Kapust, OPPTS
Nagu Keshava, ORD
David Lai, OPPTS
Skip Laitner, OAR
Warren Layne, Region 5
Do Young Lee, OPPTS
Virginia Lee, OPPTS
Monique Lester, OARM, on detail to OIA
Michael Lewandowski, ORD
Bill Linak, ORD
David Lynch, OPPTS
Tanya Maslak, OSA intern
Paul Matthai, OPPT
Carl Mazza, OAR
Nhan Nguyen, OPPTS
Carlos Nunez, ORD
Onyemaechi Nweke, OPEI
Marti Otto, OSWER
Manisha Patel, OGC
Steve Potts, OW
Mary Reiley, OW
Mary Ross, OAR
Bill Russo, ORD
Mavis Sanders, OEI
Bernie Schorle, Region 5
Paul Solomon, ORD
Timothy Taylor, OSWER
Maggie Theroux-Fieldsteel, Region 1
Stephanie Thornton, OW
Alan Van Arsdale, Region 1
William Wallace, ORD
Barb Walton, ORD
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EPA Nanotechnology White Paper
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 IMPORT ANT 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 Ill
APPENDIX D: EPA STAR GRANTS FOR NANOTECHNOLOGY 113
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vi EPA Nanotechnology White Paper
APPENDIX E: LIST OF NANOTECHNOLOGY WHITE PAPER EXTERNAL PEER REVIEWERS AND
THEIR AFFILIATIONS 119
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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. NNINSET SUBCOMMITTEE STRUCTURE 16
FIGURE 13. NANOSCALE ZERO-VALENT IRON ENCAPSULATED IN AN EMULSION DROPLET 22
FIGURE 14. PlEZORESISTIVE 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
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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 co-
chairs 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
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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.
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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
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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
OS A 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
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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
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EPA Nanotechnology White Paper
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,
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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.
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EPA Nanotechnology White Paper
• 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.
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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/consumerprodocts). 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.
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EPA Nanotechnology White Paper
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).
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EPA Nanotechnology White Paper
Ant
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Figure 1. Diagram indicating relative scale of nanosized objects.
(From NNI website, courtesy Office of Basic Energy Sciences, U.S. Department of Energy.)
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EPA Nanotechnology White Paper
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," or
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 matter)
may aid in the understanding of intentionally produced
nanomaterials, this information will be discussed, but
the focus of this document is on intentionally produced
nanomaterials.
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.
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EPA Nanotechnology White Paper
Figure 3. Computer image of a
C-60 Fullerene. U.S. EPA
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Figure 5. "Forest" of aligned carbon nanotubes.
Figure 4. Computer images of various (Image courtesy David Carnahan of NanoLab, Inc.)
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.
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EPA Nanotechnology White Paper
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 three-
dimensional 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.
o-
Ok J9
e
/•' 1' Xo
"
la
r©
b
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.)
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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
^or^/44/cojisutnerjianotechnQlogy). 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)
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EPA Nanotechnology White Paper
11
Table 1. Examples of Products that Use Nanotechnology and Nanomaterials
Health and
Fitness
Wound dressing
Pregnancy test
Toothpaste
Golf club
Tennis Racket
Skis
Antibacterial
socks
Waste and stain
resistant pants
Cosmetics
Air filter
Sunscreen
Electronics and
Computers
Computer
displays
Games
Computer
hardware
Home and
Garden
Paint
Antimicrobial
pillows
Stain resistant
cushions
Food and
Beverage
Non-stick
coatings for pans
Antimicrobial
refrigerator
Canola oil
Other
Coatings
Lubricants
Source: Woodrow Wilson Center Consumer Products Inventory.
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
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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
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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.
Technological Complexity
increasing
O
First Generation ~2001: Passive nanostructures
Nano-structured coatings, nanoparticles, nanostructured metals, polymers, ceramics,
Catalysts, composites, displays
Second Generation ~Now: Active nanostructures
Transistors, amplifiers, targeted drugs and chemicals, actuators, adaptive
structures, sensors, diagnostic assays, fuel cells, solar cells, high performance
nanocomposites, ceramics, metals
Third Generation ~ 2010: 3-D nanosystems and systems of nanosystems
Various assembly techniques, networking at the nanoscale and new architectures,
Biomimetic materials, novel therapeutics/targeted drug delivery
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.
1.3 Why Nanotechnology Is Important to EPA
Nanotechnology holds great promise for creating new materials with enhanced properties
and attributes. These properties, such as greater catalytic efficiency, increased electrical
conductivity, and improved hardness and strength, are a result of nanomaterials' larger surface
area per unit of volume and quantum effects that occur at the nanometer scale ("nanoscale").
Nanomaterials are already being used or tested in a wide range of products such as sunscreens,
composites, medical and electronic devices, and chemical catalysts. Similar to nanotechnology's
success in consumer products and other sectors, nanomaterials have promising environmental
applications. For example, nanosized cerium oxide has been developed to decrease diesel
emissions, and iron nanoparticles can remove contaminants from soil and ground water.
Nanosized sensors hold promise for improved detection and tracking of contaminants. In these
and other ways, nanotechnology presents an opportunity to improve how we measure, monitor,
manage, and reduce contaminants in the environment.
Some of the same special properties that make nanomaterials useful are also properties
that may cause some nanomaterials to pose hazards to humans and the environment, under
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14 EPA Nanotechnology White Paper
specific conditions. Some nanomaterials that enter animal tissues may be able to pass through
cell membranes or cross the blood-brain barrier. This may be a beneficial characteristic for such
uses as targeted drug delivery and other disease treatments, but could result in unintended
impacts in other uses or applications. Inhaled nanoparticles may become lodged in the lung or
be translocated, and the high durability and reactivity of some nanomaterials raise issues of their
fate in the environment. It may be that in most cases nanomaterials will not be of human health
or ecological concern. However, at this point not enough information exists to assess
environmental exposure for most engineered nanomaterials. This information is important
because 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
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. Figure 11 lists examples of federal
sources of information and interaction to inform EPA's nanotechnology activities. Many sectors,
including U.S. federal and state agencies, academia, the private-sector, other national
governments, and international bodies, are considering potential environmental applications and
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.
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EPA Nanotechnology White Paper
15
Understanding Nanotechnology
Implications
Characterization,
Properties
DOD
DOE
EPA
NASA
NIH
NIST
NSF
Instrumentation,
Metrology,
Standards
DOD
DOE
NASA
NIH
NIST
NSF
EPA
Research
Risk assessment
Risk management
Sustainability
Stewardship
L
Sensors, Devices
Applications
NIEHS, NCI (NCL), NTP
Figure 11. Federal Sources to Inform EPA's Nanotechnology Activities.
(Based on information in the NNI Supplement to the 2006 and 2007 budget and other information.)
1.4.1 Federal Agencies - The National Nanotechnology Initiative
The National Nanotechnology Initiative (NNI) was launched in 2001 to coordinate
nanotechnology research and development across the federal government. Investments into
federally funded nanotechnology-related activities, coordinated through the NNI, have grown
from $464 million in 2001 to approximately $1.3 billion in 2006.
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 new nanoscale materials, and the development of nanotechnology-based devices
and systems. The NNI also supports research on instrumentation, metrology, standards, and
nanoscale manufacturing. Most important to EPA, the NNI has made responsible development
of this new technology a priority by supporting research on environmental health and safety
implications.
Twenty-five federal agencies currently participate in the NNI, thirteen of which have
budgets which include to nanotechnology research and development. The other twelve agencies
have made 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
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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
its Nanotechnology Environmental Health Implications workgroup (NEHI) (Figure 12). The
President's Council of Advisors on Science and Technology (PCAST) has been designated as the
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 provides
assessments and advice to the NNI.
Work under the NNI can be monitored through the website http://www.nano.gov.
National Research
Council
NNAP (PCAST)
International
Organizations
Press
Professional
Societies
Non-governmental
Organizations
Industry Sectors
24 in NNI
Working Groups
of
Subcommittee
Office of Science and
Technology Policy
Office of
and
NNCQ
of
Committee on Science
Committee on
Commerce, Science and
Transportation
Regional, State, Local
Nanotechnology Initiatives
NRC Review of (he NNI -August 25-26, 2005
ECTeague NNCO; NSET; NSTC
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 non-
federal 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).
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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
efforts toward environmental research. Other governments have also undertaken efforts to
identify research needs for nanomaterials (United Kingdom (UK) Department for Environment,
Food and Rural Affairs, 2005; European Union Scientific Committee on Emerging and Newly
Identified Health Risks (EU SCENIHR), 2005). International organizations such as the
International Standards Organization and the Organisation for Economic Co-operation and
Development (OECD) are engaged in nanotechnology issues. ISO has established a technical
committee to develop international standards for nanotechnologies. This technical committee,
ISO/TC 229 will develop standards for terminology and nomenclature, metrology and
instrumentation, including specifications for reference materials, test methodologies, modeling
and simulation, and science-based health, safety and environmental practices.
The OECD has engaged the topic of the implications of manufactured nanomaterials
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 the
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 international
harmonization and burden sharing. In a related activity, the OECD's Committee on Scientific
and Technology Policy is considering establishing a subsidiary body to address other issues
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, among
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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
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 well
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
EPA is actively participating in nanotechnology development and evaluation. Some of
the activities EPA has undertaken include: 1) actively participating in the National
Nanotechnology Initiative, which coordinates nanotechnology research and development across
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 the
development of a voluntary program for the evaluation of nanomaterials and reviewing
nanomaterial premanufacture notifications in the Office of Pollution Prevention and Toxics, 6)
reviewing nanomaterial registration applications in the Office of Air and Radiation/Office of
Transportation 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
Since 2001, EPA's ORD STAR grants program has funded 36 research grants nearly 12
million in the applications of nanotechnology to protect the environment, including the
development of: 1) low-cost, rapid, and simplified methods of removing toxic contaminants from
water, 2) new sensors that are more sensitive for measuring pollutants, 3) green manufacturing of
nanomaterials; and 4) more efficient, selective catalysts. Additional applications projects have
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
date in this area, totaling approximately $10 million. The most-recent research solicitations
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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.
Research areas of interest for this proposal include the toxicology, fate, release and treatment,
transport and transformation, bioavailability, human exposure, and life cycle assessment of
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 ultrafme particulate matter (e.g., Dreher, 2004). In addition, EPA scientists have
begun to gather information on various environmental applications currently under development.
ORD has also led development of an Agency Nanotechnology Research Framework for
conducting and coordinating intramural and extramural nanotechnology research (Appendix C).
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 effectiveness
in remediating volatile organic compounds. The study includes smaller pre-pilot studies and an
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
10) are also considering the use of zero-valent iron in site remediation.
1.5.3 Office of Pollution Prevention and Toxics Activities Related to Nanoscale Materials
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 Toxics
Advisory Committee (NPPTAC) to provide its views. NPPTAC established an Interim Ad Hoc
Work Group 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 is
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 Quality - Nanomaterials
Registration 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.
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20 EPA Nanotechnology White Paper
1.5.5 Office of Pesticide Programs to Regulate Nano-Pesticide Products
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 to support
licensing/registration or if the unique characteristics associated with nano-pesticides warrant
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 Workshop on
Nanotechnology for Site Remediation. The meeting summary and presentations from that
workshop are available at hj^/www.frtr.goy/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 cycle
of nanotechnology products. Information on the symposium will be posted on OSWER' s
website. OSWER' s Technology Innovation and Field Services Division (TIFSD) is compiling a
database of information on hazardous waste sites where project managers are considering using
nanoscale zero-valent iron to address groundwater contamination. TIFSD is also preparing a fact
sheet on the use of nanotechnology for site remediation that will be useful for site project
managers. In addition, TIFSD has a website with links to relevant information on
nanotechnology
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
regulatory frameworks to determine the enforcement issues associated with nanotechnology;
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 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
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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
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 approaches,
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 goal is
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 of nanotechnology and the increasing production of
nanomaterials and nanoproducts present both opportunities and challenges. Using nanomaterials
in applications that advance green chemistry and engineering and lead to the development of new
environmental sensors and remediation technologies may provide us with new tools for
preventing, identifying, and solving environmental problems. In addition, at this early juncture
in nanotechnology's development, we have the opportunity to develop approaches that will allow
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 regulatory agencies. To take advantage of these
opportunities and to meet the challenge of ensuring the environmentally safe and sustainable
development of nanotechnology, EPA must understand both the potential benefits and the
potential impacts of nanomaterials and nanoproducts. The following chapters of this document
discuss the science issues surrounding how EPA will gain and apply such understanding.
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22
EPA Nanotechnology White Paper
2.0 Environmental Benefits of Nanotechnology
2.1 Introduction
As applications of nanotechnology develop over time, they have the potential to help
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 pollution, and
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, nanotechnology
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.
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. lacqueline W. Quinn,
Kennedy Space Center, NASA)
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
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EPA Nanotechnology White Paper 23
(principally by abiotic means, with zero-valent iron serving as the bulk reducing agent),
including chlorinated methanes, ethanes, benzenes, and polychlorinated biphenyls (Elliot and
Zhang, 2001). Nanoscale zero-valent iron may not only treat aqueous dissolved chlorinated
solvents in situ, but also may remediate the dense nonaqueous phase liquid (DNAPL) sources of
these contaminants within aquifers (Quinn et al., 2005).
In addition to zero-valent iron, other nanosized materials such as metalloporphyrinogens
have been tested for degradation of tetrachlorethylene, trichloroethylene, and carbon
tetrachloride under anaerobic conditions (Dror, 2005). Titanium oxide based nanomaterials have
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 contaminants,
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 urethane
acrylate have been used to enhance the bioavailability of phenanthrene (Tungittiplakorn, 2005).
Metal remediation has also been proposed, using zero-valent iron and other classes of
nanomaterials. Nanoparticles such as poly(amidoamine) dendrimers can serve as chelating
agents, and can be further enhanced 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
hydroxymates (Diallo, 2005). Other research indicates that arsenite and arsenate may be
precipitated in the subsurface using zero-valent iron, making arsenic less mobile (Kanel, 2005).
Self-assembled monolayers on mesoporous supports (SAMMS) are nanoporous ceramic
materials that have been developed to remove mercury or radionuclides from wastewater
(Mattigod, 2003).
Nanomaterials have also been studied for their ability to remove metal contaminants from
air. Silica-titania nanocomposites can be used for elemental mercury removal from vapors such
as those coming from combustion sources, with silica serving to enhance adsorption and titania
to photocatalytically oxidize elemental mercury to the less volatile mercuric oxide (Pitoniak,
2005). Other authors have demonstrated nanostructured silica can sorb other metals generated in
combustion environments, such as lead and cadmium (Lee et al., 2005; Biswas and Zachariah,
1997). Certain nanostructured sorbent processes can be used to prevent emission of
nanoparticles and create byproducts that are useful nanomaterials (Biswas et al., 1998)
2.2.2 Sensors
Sensor development and application based on nanoscale science and technology is
growing rapidly due in part to the advancements in the microelectronics industry and the
increasing availability of nanoscale processing and manufacturing technologies. 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 category can eventually result
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24
EPA Nanotechnology White Paper
in lower material cost as well as reduced weight and power consumption of sensors, leading to
greater applicability and enhanced functionality.
Cantilever Specifications
Length ' 450 Mm
Resistor : 300 pm
Width : 70 pm
Thickness • 1.088 pm
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)
toxicants. Figure 14 shows an example of a nanoscale
One of the near-term research
products of nanotechnology for
environmental applications is the
development of new and enhanced
sensors to detect biological and
chemical contaminants.
Nanotechnology offers the potential to
improve exposure assessment by
facilitating collection of large numbers
of measurements at a lower cost and
improved specificity. It soon will be
possible to develop micro- and
nanoscale sensor arrays that can detect
specific sets of harmful agents in the
environment at very low concentrations.
Provided adequate informatics support,
these sensors could be used to monitor
agents in real time, and the resulting
data can be accessed remotely. The
potential also exists to extend these
small-scale monitoring systems to the
individual level to detect personal
exposures and in vivo distributions of
sensor.
In the environmental applications field, nanosensor research and development is a
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.
2.3 Benefits through Other Applications that Support Sustainability
Nanotechnology may be able to advance environmental protection by addressing the
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 process by
increasing materials and energy efficiency, reducing the need for solvents, and reducing waste
products.
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EPA Nanotechnology White Paper 25
Table 2. Outcomes for Sustainable Use of Major Resources and Resource Systems
Water sustain water resources of quality and availability for desired uses
Energy generate clean energy and use it efficiently
Materials use material carefully and shift to environmentally preferable materials
Ecosystems protect and restore ecosystem functions, goods, and services
Land support ecologically sensitive land management and development
Air sustain clean and healthy air
EPA Innovation Action Council, 2005
Many of the following applications can and should be supported by other agencies.
However, EPA has an interest in helping to guide the work in these areas.
2.3.1 Water
Nanotechnology has the potential to contribute to long-term water quality, availability,
and viability of water resources, such as through advanced filtration that enables more water re-
use, recycling, and desalinization. For example, nanotechnology-based flow-through capacitors
(FTC) have been designed that desalt seawater using one-tenth the energy of state-of-the art
reverse osmosis and one-hundredth of the energy of distillation systems. The projected capital
and operation costs of FTC-based systems are expected to be one-third less than conventional
osmosis systems (NNI, 2000).
Applications potentially extend even more broadly to ecological health. One long-term
challenge to water quality in the Gulf of Mexico, the Chesapeake Bay, and elsewhere is the build
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 contribute to
sustainability. These potential applications are still in the early research stage (USDA, 2003).
Applications involving dispersive uses of nanomaterials in water have the potential for wide
exposures to aquatic life and humans. Therefore, it is important to understand the toxicity and
environmental fate of these nanomaterials.
2.3.2 Energy
There is potential for nanotechnology to contribute to reductions in energy demand
through lighter materials for vehicles, materials and geometries that contribute to more effective
temperature control, technologies that improve manufacturing process efficiency, materials that
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 the manufacture of nanomaterials can be energy-intensive, it is important to consider the
entire product lifecycle in developing and analyzing these technologies
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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 result in national energy savings of about 14.5 quadrillion BTU's (British thermal units, a
standard unit of energy) per year, which is about 14.5% of total U.S. energy consumption per
year.
Table 3. Potential U.S. Energy Savings from Eight Nanotechnology Applications
(Adapted from Brown, 2005 a)
Estimated Percent
,T , , , . ,. ,. Reduction in Total
Nanotechnology Application . . TT „ _
&J FF Annual U.S. Energy
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
Smart roofs (temperature-dependent 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 BTUY Barrel conversion (corresponding to reformulated gasoline - from EIA monthly
energy review, October 2005, Appendix A)
**Based 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, one
of many examples of molecular-level control of industrial catalysis is a nanostructured catalytic
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 hydrocarbons at a significantly improved process
yield (NNI, 2000).
There are additional emerging innovative approaches to energy management that could
potentially reduce energy consumption. For example, nanomaterials arranged in superlattices
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).
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EPA Nanotechnology White Paper 27
In addition to increasing energy efficiency, nanotechnology also has the potential to
contribute to alternative energy technologies that are environmentally cleaner. For example,
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
implications for novel distributed wind power (Ball, 2004).
While nanotechnology has the potential to contribute broadly to energy efficiency and
cleaner sources of energy, it is important to consider energy use implications over the entire
product 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 technical and economic hurdles for these applications.
2.3.3 Materials
Nanotechnology may also lead to more efficient and effective use of materials. For
example, nanotechnology may improve the functionality of catalytic converters and reduce by up
to 95% the mass of platinum group metals required. This has overall product lifecycle benefits.
Because platinum group metals occur in low concentration in ore, this reduction in use may
reduce ecological impacts from mining (Lloyd et al., 2005). However, manufacturing precise
nanomaterials can be material-intensive.
With nanomaterials' increased material functionality, it may be possible in some cases to
replace toxic materials and still achieve the desired functionality (in terms of electrical
conductivity, material strength, heat transfer, etc.), often with other life-cycle benefits in terms of
material and energy use. One example is lead-free conductive adhesives formed from self-
assembled monolayers based on nanotechnology, which could eventually substitute for leaded
solder. Leaded solder is used broadly in the electronics industry; about 3900 tons lead are used
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). The OLED
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/ctns/pressreleases/PressRelease-12-03-
(34jxlf and htt]3^/wwwj3XCTiic^^ These manufacturers
also claim a more than 5- 10 % decrease in fuel consumption with an associated decrease in
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28 EPA Nanotechnology White Paper
vehicle emissions. Such a reduction in fuel consumption and decrease in emissions would result
in obvious environmental benefits. Limited published research and modeling have indicated that
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.
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EPA Nanotechnology White Paper
29
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).
Dose - Response
Assessment
Hazard
Identification
Risk
Characte rization
Exposure
Assessment
Figure 15. EPA's Risk Assessment Approach
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30
EPA Nanotechnology White Paper
Worker Exposure
Consumer Exposure
-----aif Ji
Raw Materia
Production
\ 4
•
\
s
1
.
Consumer
Manufacturing
\ 1
1
\
\
r
^ .
(ecycle
\
J
\
\
I
\
Fnrl nf 1 ife
\ ' \
'
Industrial emissions
Landfills
Incinerators
Human Population and Ecological Exposure
Figure 16. Life Cycle Perspective to Risk Assessment
The overall risk assessment approach used by EPA for conventional chemicals 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 properties relative to conventional
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 assessment of nanomaterials which identified 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
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EPA Nanotechnology White Paper 31
Kreyling, 2004). The European Union's Scientific Committee on Emerging and Newly
Identified Health Risks (SCENIHR, 2006) has also overviewed existing data on nanomaterials,
data 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
components needed to conduct a risk assessment on nanomaterials. The following key aspects of
risk assessment are addressed as they relate to nanomaterials: chemical identification and
physical properties characterization, environmental fate, environmental detection and analysis,
human exposure, human health effects, and ecological effects. Each of these aspects is discussed
by providing a synopsis of key existing information on each topic.
3.2 Chemical Identification and Characterization of Nanomaterials
The identification and characterization of chemical substances and materials is an
important first step in assessing their risk. Understanding the physical and chemical properties in
particular is necessary in the evaluation of hazard (both toxicological and ecological) and
exposure (all routes). Chemical properties that are important in the characterization of discrete
chemical substances include, but are not limited to, composition, structure, molecular weight,
melting point, boiling point, vapor pressure, octanol-water partition coefficient, water solubility,
reactivity, and stability. In addition, information on a substance's manufacture and formulation
is important in understanding purity, product variability, performance, and use.
The diversity and complexity of nanomaterials makes chemical identification and
characterization not only more important but also more difficult. A broader spectrum of
properties will be needed to sufficiently characterize a given nanomaterial for the purposes of
evaluating hazard and assessing risk. Chemical properties such as those listed above may be
important for some nanomaterials, but other properties such as particle size and size distribution,
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.
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32
EPA Nanotechnology White Paper
(A) (B)
Figure 17. Transmission Electron Microscope (TEM) image of aerosol-generated TiO2
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 important role
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 carbon nanotubes
can be produced by several different processes that can generate products with different
physical-chemical properties (e.g., size, shape, composition) and potentially different ecological
and toxicological properties (Thomas and Sayre, 2005; Oberdorster et al., 2005a). It is not clear
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 nomenclature 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
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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
into materials used to fabricate products for consumer use including pharmaceutical products,
and releases resulting from the use and disposal of consumer products containing nanoscale
materials (e.g., disposal of screen monitors, computer boards, automobile tires, clothing and
cosmetics). The fundamental properties concerning the environmental fate of nanomaterials are
not well understood (European Commission, 2004), as there are few available studies on the
environmental fate of nanomaterials. The following sections summarize what is known or can
be inferred about the fate of nanomaterials in the atmosphere, in soils, and in water. These
summaries are followed by sections discussing: 1) biodegradation, bioavailability, and
bioaccumulation of nanomaterials, 2) the potential for transformation of nanomaterials to more
toxic metabolites, 3) possible interactions between nanomaterials and other environmental
contaminants; and 4) the applicability of current environmental fate and transport models to
nanomaterials.
3.3.1 Fate of Nanomaterials in Air
Several processes and factors influence the fate of airborne particles in addition to their
initial dimensional and chemical characteristics: the length of time the particles remain airborne,
the nature of their interaction with other airborne particles or molecules, and the distance that
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 ultrafme particles and
may be applicable to nanomaterials as well (Wiesner et al., 2006). However, in some cases,
intentionally produced nanomaterials may behave quite differently from incidental ultrafme
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 aerodynamic
diameters in the nanoscale range (<100 nm) may follow the laws of gaseous diffusion when
released 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). Airborne
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-lived
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 in
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 Society, 2004; Dennenkamp et al., 2002). Note that these
generalizations apply to environmental conditions and do not preclude the possibility that
humans and other organisms may be exposed to large as well as smaller particles by inhalation.
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
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34 EPA Nanotechnology White Paper
priority. Current research is underway to produce carbon nanotubes that do not form clumps
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 characteristics of the nanomaterial. Nanomaterials released to soil can be strongly
sorbed to soil due to their high surface areas and therefore be immobile. On the other hand,
nanomaterials are small enough to fit into smaller spaces between soil particles, and might
therefore 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; Lecoanet et
al., 2004).
Additionally, the types and properties of the soil and environment (e.g., clay versus sand)
can affect nanomaterial mobility. For example, the mobility of mineral colloids in soils and
sediments is strongly affected by charge (Wiesner et al., 2006). Surface photoreactions provide a
pathway for nanomaterial transformation on soil surfaces. Humic substances, common
constituents 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 in
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-to-
mass ratios, nanosized particles have the potential to sorb to soil and sediment particles
(Oberdorster et al., 2005a). Where these soil and sediment particles are subject to sedimentation,
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
photocatalyzed 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 substances.
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EPA Nanotechnology White Paper
35
These reactions may alter the physical and chemical properties of nanomaterials and so alter their
behavior in aquatic environments. Certain organic and metallic nanomaterials may possibly be
transformed under anaerobic conditions, such as in aquatic (benthic) sediments. From past
studies, it is known that several types of organic compounds are generally susceptible to
reduction under such conditions. Complexation by natural organic materials such as humic
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 dispersed
insoluble nanoparticles can be stabilized in aquatic environments. For example, researchers at
Rice University have reported that although Ceofullerene is initially insoluble in water, it
spontaneously forms aqueous colloids containing nanocrystalline aggregates. The concentration
of nanomaterials 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; Former et al., 2005). Sea surface microlayers consisting of
lipid, carbohydrate and proteinaceous components along with naturally-occurring colloids made
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 metal
oxide surfaces are increasingly being used as a
method for drinking water, wastewater and
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, and
heterogeneous photocatalysis has been used for
water purification in treatment systems.
Nanoparticle photochemistry is being
studied with respect to its possible application in
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 al.,
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 plant is
a publicly owned treatment work or onsite industrial facility, etc. Broadly speaking, nanosized
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.)
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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 may
be removed from wastewater after biological treatment via settling in the secondary clarifier.
Normally the rate of gravitational settling of particles such as nanomaterials in water is
dependent on particle diameter, and smaller particles settle more slowly. However, settling of
nanomaterials could be enhanced by entrapment in the much larger sludge floes, 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, the
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 nonbiodegradable
inorganic chemicals, such as ceramics, metals and metal oxides, and are not expected to
biodegrade. However, a recent preliminary study found that Ceo and Cyo fullerenes were taken
up by wood decay fungi after 12 weeks, suggesting that the fullerene carbon had been
metabolized (Filley et al., 2005). For other nanomaterials biodegradability may be integral to the
material's design and function. This is the case for some biodegradable polymers being
investigated for use in drug transport (Madan et al., 1997; Brzoska et al., 2004), for which
biodegradability is mostly a function of chemical structure and not particle size.
Biodegradability in waste treatment and the environment may be influenced by a variety
of factors. Recent laboratory studies on Ceo fullerenes have indicated the development of stable
colloid structures in water that demonstrate toxicity to bacteria under aerobic and anaerobic
conditions (CBEN, 2005; Former et al., 2005). Further studies are needed to determine whether
fullerenes may be toxic to microorganisms under environmental conditions. One must also
consider the potential of photoreactions and other abiotic processes to alter the bioavailability
and thus biodegradation rates of nanomaterials. In summary, not enough is known to enable
meaningful predictions on the biodegradation of nanomaterials in the environment and much
further testing and research are needed.
3.3.5 Bioavailability and Bioaccumulation of Nanomaterials
Bacteria and living cells can take up nanosized particles, providing the basis for potential
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
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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 sediments in the
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 affected
by complexation. Complexation reduces biological availability by reducing free metal ion
concentrations and dissolved iron is quantitatively complexed by organic ligands. Solar UV
radiation can interact with these processes through photoreactions of the complexes. Further, iron
and iron oxides can participate in enzymatic redox reactions that change the oxidation state,
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 (Fe°)
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 also
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 compounds
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 degrade
under photolytic and oxidative conditions, and furthermore, compromise of quantum dot
coatings can reveal the metalloid core, which may be toxic (Hardman, 2006). Degradation
products from carbon nanomaterials (fullerenes and nanotubes) have not yet been reported.
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 demonstrated
to alter the partitioning behavior of chemicals between environmental compartments and
between the environment and living organisms. Furthermore, several nanomaterials are reactive
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.
It should be noted that the potential also exists for nanomaterials to effect unforseen changes, if
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
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(Christen, 2004), and solid support materials with coatings of nanoparticles (for example, see
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 nanoparticles.
No single overall effect can be described for the sorption of chemicals to nanomaterials
based on 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 Ceo or
nanotubes could either enhance or inhibit the mobility of organic pollutants (Cheng et al., 2004).
Stable colloids of hydrophobic nanomaterials in an aqueous environment could provide a
hydrophobic microenvironment that suspends hydrophobic contaminants and retards their rate of
deposition onto soils and sediments. Similar effects are known to happen with naturally
occurring colloids made up of humic acids and suspended sediment particles (Schwarzenbach et
al., 1993). Nanoparticles can be altered to optimize their affinities for particular pollutants by
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 Ceo 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 ultrafme aerosols of Ga2C>3 (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 of nanomaterials for the destruction of persistent
pollutants 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,
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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 Ceo have been shown to generate reactive oxygen species in water
under UV and polychromatic light. Similar colloids have been reported to degrade organic
contaminants and act as bacteriocides (Boyd et al., 2005). Fullerol (Ceo(OH)24) has also been
demonstrated to produce reactive oxygen species under similar conditions (Pickering and
Wiesner, 2005).
3.3.8 Applicability of Current Environmental Fate and Transport Models to Nanomaterials
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 inorganic nanomaterials. Many
models 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 as
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 provide
estimations for these materials; however, models cannot be developed without the experimental
data needed to design and validate them. Before the environmental fate, transport and
multimedia 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., PMio)
has been the subject of substantial research interest and is a principal regulatory focus of EPA's
Office 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
for exposure assessment of nanomaterials are likely to be found not in the area of environmental
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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 by
the extremely small size of the particles, but also by their unique physical structure and physico-
chemical characteristics. 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
nanomaterial. As noted above, the chemical properties of particles at the nanometer size can
significantly differ from the chemical properties of larger particles consisting of the same
chemical 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, or
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 some
quantum dots containing heavy metals, chemical characterization (qualitative and quantitative)
can play an important role in their detection and source identification.
The level of effort needed and costs to perform analysis for nanomaterials will depend on
which environmental compartment samples are being taken from, as well as the type of desired
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 also
depend on the degree of information being acquired. Analyzing samples for number
concentration (i.e., the number and size distribution of nanoparticles per unit volume) requires
significantly less effort than broadening such analyses to include characterization of particle
types (fullerenes, quantum dots, nanowires, etc.). The level of effort also increases for elemental
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 sized
particles, particles hundreds to a thousand times larger than nanoparticles, and are not effective
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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 analytical data
relevant to nanoparticles.
The information available from the bulk analysis of nanomaterials from environmental
samples has limitations when one is trying to identify a specific nanomaterial. As stated
previously, nanoscale particles generated by natural and other anthropogenic sources cannot be
separated from nanomaterials of interest using sampling methodologies based upon particle size.
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 the
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 the
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 subsequent analysis. These technologies provide nanoparticle
fraction separation based upon the aerodynamic mobility properties of the particles.
Aerodynamic 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 electrical
field to obtain particle size fractionation and collection. Instruments employing this technology
include differential mobility analyzers (DMAs) and scanning mobility particle sizers (SMPSs)
(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; Chen and Selegue, 2002).
On-line particle size analysis in liquid mediums can be done using various techniques including
dynamic 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., transmission electron
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 can be used to analyze nanomaterials. Atomic Force Microscopy, a
relatively new technology, can provide particle size and morphological information on single
nanoparticles in liquid, gas, and vacuum environments (Maynard, 2000)
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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 for human
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 the
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 minimizing worker exposure, describes potential tools and models that may be used
to estimate exposures, and identifies potential data sources for these models.
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 or
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 the
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, we
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 their
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predicted widespread applications in products. This section discusses some of the potential
sources and pathways by which humans may be exposed to nanomaterials.
3.5.2.1 Occupational Exposure
Workers may be exposed to nanoscale materials during manufacturing/synthesis of the
nanoscale materials, during formulation or end use of products containing the nanoscale material,
or during disposal or recycling of the products containing the nanoscale materials. Because
higher concentrations and amounts of nanoscale materials and higher frequencies and exposures
are more likely in workplace settings, occupational exposures warrant particular attention.
Table 4 presents the potential sources of occupational exposure during the common
methods for nanoscale material synthesis: gas phase synthesis, vapor deposition, colloidal, and
attrition methods.
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Table 4. Potential Sources of Occupational Exposure for Various Synthesis Methods
(adapted from Aitken, 2004)
Synthesis
Process
Gas Phase
Vapor Deposition
Colloidal/
Attrition
Particle
Formation
in air
on substrate
liquid
suspension
Exposure Source or Worker Activity
Direct leakage from reactor, especially if the reactor
is operated at positive pressure.
Product recovery from bag filters in reactors.
Processing and packaging of dry powder.
Equipment cleaning/maintenance (including reactor
evacuation and spent filters).
Product recovery from reactor/dry contamination of
workplace.
Processing and packaging of dry powder.
Equipment cleaning/maintenance (including 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.
Equipment cleaning/maintenance.
Primary Exposure Route
Inhalation
Inhalation / Dermal
Inhalation / Dermal
Dermal (and Inhalation during
reactor evacuation)
Inhalation
Inhalation / Dermal
Dermal (and Inhalation during
reactor evacuation)
Inhalation / Dermal
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
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45
could also occur during product machining (e.g., cutting, drilling and grinding), repair,
destruction and recycling [National Institute for Occupational Health and Safety (NIOSH),
2005a]. NIOSH (2004, 2005b) has issued additional documents on nanotechnology and
workplace safety and associated research needs.
3.5.2.2 Release and General Population Exposure
General population exposure may occur from environmental releases from the production
and use of nanomaterials and from direct use of products containing nanomaterials. During the
production of nanomaterials, there are several potential sources for environmental releases
including the evacuation of production chambers, filter residues, losses during spray drying,
emissions from filter or scrubber break-through, and wastes from equipment cleaning and
product handling. No data have been identified quantifying the releases of nanomaterials from
industrial processes or of the fate of nanomaterials after release into the environment. However,
due to the small size of nanomaterials, they will likely stay airborne for a substantially longer
time than other types of particulate. The most likely pathway for general population exposure
from releases from industrial processes is direct inhalation of materials released into the air
during manufacturing (UK Royal Society, 2004). Releases from industrial or transportation
accidents, natural disasters, or malevolent activity such as a terrorist attack may also lead to
exposure of workers or the general public.
Nanoscale materials have potential applications in many consumer products resulting in
potential general population exposure. Electronics, medicine, cosmetics, chemistry, and
catalysis are potential beneficiaries of nanotechnology. Widespread exposure via direct contact
with products from these sectors is expected. Table 5 presents several examples of potential
sources of general population and consumer exposure associates with the use of such products.
Table 5. Examples of Potential Sources of General Population and/or Consumer Exposure
for Several Product Types
Product Type
Sunscreen
containing
nanoscale
material
Metal catalysts in
gasoline for
reducing vehicle
exhaust*
Paints and
Coatings
Clothing
Release and/ or Exposure Source
Product application by consumer to skin
Release by consumer (e.g., washing with
soap and water) to water supply
Disposal of sunscreen container (with
residual sunscreen) after use (to landfill or
incineration)
Release from vehicle exhaust to air (then
deposition to surface water)
Weathering, disposal
Wear, washing, disposal
Exposed Population
Consumer
General population
General population
General population
Consumers, general
population,
Consumers, general
population
Potential Exposure Route
Dermal
Ingestion
Inhalation or Ingestion
Inhalation or Ingestion
Dermal, Inhalation or
Ingestion
Dermal, inhalation, ingestion
from surface or groundwater
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Product Type
Electronics
Sporting goods
Release and/ or Exposure Source
Release at end of life or recycling stage
Release at end of life or recycling stage
Exposed Population
Consumers, general
population
Consumers, general
population
Potential Exposure Route
Dermal, ingestion from
surface or groundwater
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 of
characteristics, such as size and dimensions, with other substances (e.g., ultrafine particles) for
which a large body of information exists on 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
airborne concentrations are agglomeration, deposition, and re-suspension. (UK Health and
Safety Executive, 2004) All of these issues, which are discussed in more detail in the reference,
are relevant for understanding, predicting, and controlling airborne concentrations of
nanomaterials.
One reference study was found to have investigated issues involved with aerosol release
of a single-walled carbon nanotube (SWCNT) material. This study noted that while laboratory
studies indicate that sufficient agitation can release fine particles into the air, aerosol
concentrations of SWCNT generated while handling unrefined material in the field at the work
loads and rates observed were very low on a mass basis (Maynard et al., 2004). The study
suggests that more research will be needed in this area.
3.5.3.2 Ingestion Exposure
Information on exposure to nanoscale environmental particles via oral exposure is
lacking. In addition to traditional ingestion of food, food additives, medicines and dietary
supplements, dust and soil (particularly in the case of children), ingestion of inhaled particles can
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also occur (such as through the activities of the mucocilliary escalator). The quantity ingested is
anticipated to be relatively small in terms of mass.
3.5.3.3 Dermal Exposure
Dermal exposure to nanomaterials has received much attention, perhaps due to concerns
with occupational exposure and the introduction of nanomaterials such as nanosized titanium
dioxide into cosmetic and drug products. One reference study was found to have investigated
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 SWCNT
may contribute to potential dermal exposure along with surface deposits due to material
handling. Surface deposits on gloves were estimated to be between 0.2 mg and 6 mg per hand.
(Maynard et al., 2004)
There is an ongoing debate over the potential for penetration through "healthy/intact"
versus damaged skin. Hart (2004) highlights physiological characteristics of the skin that may
permit 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 injected nanoscale
quantum dots were found to disperse into the surrounding viable subcutis and to draining lymph
nodes via subcutaneous lymphatics (Roberts, D.W. et al., 2005). 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). 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).
3.5.3.4 Ocular Exposure
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 and ultrafine particulates. Some
approaches such as engineering controls are applicable to the work place and may mitigate
environmental releases while others such as personal protective equipment (PPE) are primarily
applicable to the workplace. NIOSH suggests considering the range of control technologies and
personal protective equipment demonstrated to be effective with other fine and ultrafine particles
(NIOSH, 2005a). In the hierarchy of exposure reduction methods, engineering controls are
preferred over PPE.
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3.5.4.1 Engineering Controls
Engineering controls, and particularly those used for aerosol control, should generally be
effective for controlling exposures to airborne nanoscale materials (NIOSH, 2005a). Depending
on particle 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 well-
designed 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., enclosures,
local exhaust ventilation, fume hoods) used to control exposure to nanoparticles need to be of
similar quality and specification as those typically used for gases. However, the report also notes
that no 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
longest time. (Bidleman, 1988; Preining, 1998; Spurny, 1998; Atkinson, 2000; UK Royal
Society, 2004; Dennenkamp et al., 2002)
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 count
median diameter of 185 nm [42 CFR Part 84.181(g)], which have been found to be in the most
penetrating particle size range (Stevens and Moyer, 1989). However, as with all respirators, the
greatest factor in determining their effectiveness is not penetration through the filter, but rather
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). Only
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 jam polystyrene latex spheres) was
representative of vapor challenges such as sulfur hexafluoride (SF6) and isoamyl acetate (IAA)
(Gardner et al., 2004).
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EPA Nanotechnology White Paper 49
PPE may not be as effective at mitigating dermal exposure. PPE is likely to be less
effective against dermal exposure to nanomaterials than macro-sized particles from both human
causes (e.g., touching face with contaminated fingers) and PPE penetration (Aitken, 2004).
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 (Oberdorster et al., 2005a, b; NIOSH, 2005a, b). Many studies have indicated that
toxicity increases with decreased particle size and that particle surface area is a better metric for
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 particle weight and surface area can occur within a given batch. The average particle weight
and average particle surface area of the nanomaterials being assessed would also be required for
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
(Oberdorster et al., 2005b).
3.5.6 Tools for Exposure Assessment
Several tools exist for performing exposure assessments including monitoring data,
exposure models, and the use of analogous data from existing chemicals. The following sections
discuss these tools and their potential usefulness in assessing exposure to nanoscale materials.
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 sections.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 the
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 it is
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 current
limited knowledge on nanoscale materials in commerce, their uses, and their fate in the
environment and in the human body, it is difficult to identify or prioritize nanomaterials for
biomonitoring. Should biomonitoring become more feasible in the future, it presents an
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50 EPA Nanotechnology White Paper
opportunity to assess the spatial and temporal distribution of nanomaterials in workers and the
general population.
Personal Sampling
Personal sampling data provide an estimate of the exposure experienced by an individual,
and can be an important indicator of exposure in occupational settings. It is limited in that it
does not account for changes to the dose received by the target organ after the biological
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 measuring
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 exposure
concentrations of chemicals in populations when it is not feasible or practical to conduct personal
sampling for individuals in the populations. Typically, these data are used in models in addition
to other assumptions regarding exposure parameters, including population activities and
demographics such as age.
Challenges 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
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 and
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 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
properties 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 the
cumulative exposure project for air toxics recently completed for hazardous air toxics using the
Hazardous Air Pollutant Exposure Model (HAPEM)
This model predicts inhalation exposure
concentrations of air toxics from all outdoor sources, based on ambient concentrations from
modeling or monitor data for specific air toxics at the census tract level.
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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 potential dose rates for workers and environmental releases from workplaces. E-FAST
uses the 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 clear
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 predicting human exposure will depend on the parameters and assumptions of each model.
For models that are based on assumptions specific to the chemical such as the physical and
chemical properties, and interactions in humans and the environment based on these properties,
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
under statutory obligations, such as data collected for the Toxics Release Inventory (TRI) under
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 as
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 nanotubes
(Maynard et al., 2004). In the work environment, data on workplace exposure is frequently
collected under the purview of Occupational Safety and Health Administration (OSHA)-
mandated programs to assess worker exposure and assure compliance with workplace
regulations and worker protection. Employers, however, are not required to report these data. In
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 other
issues, nanoparticle exposure and ways of controlling exposure in the workplace (NIOSH, 2004).
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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 aid
in the understanding of intentionally produced nanomaterials.
3.6.1 Adequacy of Current Toxicological Database
The Agency's databases on the health effects of parti culate matter (PM), asbestos, silica,
or other 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 parti culate matter including ultrafme
ambient air (PM0.i), silica, carbon, and titanium dioxide particles (U.S. EPA, 2004). However, it
is important to note that ambient air ultrafme particles are distinct from intentionally produced
nanomaterials since they are not purposely engineered and represent a physicochemical and
dynamic 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 P articulate Matter document describe the toxicity of chemically defined ultrafme
particles, recently reviewed by Oberdorster 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 ultrafme 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 carbon-
particle 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 standard for
carbon nanotubes, since carbon nanotubes displayed very different mass-based dose-response
relationships and lung histopathology when directly compared with graphite.
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EPA Nanotechnology White Paper
53
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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.
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 carbon-
based 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.
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54 EPA Nanotechnology White Paper
3.6.2 Toxicity and Hazard Identification of Engineered/Manufactured Nanomaterials
Studies assessing the role of particle size on toxicity have generally found that ultrafme
or nanosize range (<100 nm) particles are more toxic on a mass-based exposure metric when
compared to larger particles of identical chemical composition (Oberdorster et al., 1994; Li et al.,
1999; Hohr 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
(Oberdorster et al., 1992; Driscoll, 1996; Lison et al., 1997; Donaldson et al., 1998; Iran 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
ultrafme 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 multi-
factorial, potentially being regulated by a variety of physicochemical properties such as size and
shape, as well as surface properties such as charge, area, and reactivity (Sayes et al., 2004; Cai et
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
(Donaldson et al., 2006).
Toxicological assessment of intentionally produced nanomaterials will require
information on the route (inhalation, oral, dermal) that carries the greatest risk for exposure to
these materials, as well as comprehensive physicochemical characterization of them in order to
provide information on size, shape, as well as surface properties such as charge, area, and
reactivity. Establishment of dose-response relationships linking physicochemical properties of
intentionally produced nanomaterials to their toxicities will identify the appropriate exposure
metrics that best correlate with adverse health effects.
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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
systemic 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 Oberdorster et al. (2004a, 2005a) Submicron particles have been
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 Ceo fullerenes bind to double and
single-stranded DNA and note that these simulations suggest that Ceo may negatively impact the
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 toxic
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 nanomaterials
is the wide diversity and complexity of the types of materials that are available commercially or
are under development. In many cases, the same type of nanomaterial can be produced by
several different processes, giving rise to a number of versions of the same type of nanomaterial.
For example, single-walled carbon nanotubes can be mass produced by four different processes,
each of which generates products of different size, shape, composition, and potentially different
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 by a different process. Manufactured materials may
also be treated with coatings, or other surface modifications, in order to generate mono-dispersed
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 criteria
for nanomaterial toxicity. Test methods that determine the toxicity and hazardous
physicochemical properties of intentionally produced nanomaterials in an accepted, timely and
cost effective manner are needed in order provide health risk assessment information for the
diversity of such nanomaterials that are currently available (Oberdorster 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 ultrafme metal oxide and carbon black studies (U.S. EPA,
2004; Oberdorster, 1996; Oberdorster et al., 2005a, b; Oberdorster et al., 2004a; Kreyling et al.,
2002). Ultrafme carbon black and metal oxide particles display differential deposition patterns
within the lung when compared to larger sized particles of identical chemical composition. For
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56 EPA Nanotechnology White Paper
example, 1 nm particles are preferentially deposited in the nasopharyngeal region while 5nm
particles are deposited throughout the lung and 20 nm particles are preferentially deposited in the
distal lung within the alveolar gas exchange region (Oberdorster 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 obstructive
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. EPA,
2004). Also, pulmonary deposited ultrafine particles can evade the normal pulmonary clearance
mechanisms and translocate by a variety of pathways to distal organs (Oberdorster 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 (Takenaka et al.,
2001; Oberdorster et al., 2002) and studies in humans (Brown et al., 2002; Chalupa et al., 2004).
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.
A significant amount of intradermally injected nanoscale quantum dots were found to
disperse into the surrounding viable subcutis and to draining lymph nodes via subcutaneous
lymphatics (Roberts, D.W. et al., 2005). Other studies (Tinkle et al., 2003) have shown
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 classes of
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 nanoparticle
physicochemical properties regulating their deposition and fate, is needed to determine exposure-
dose-response relationships associated with various routes of exposures. Information on the fate
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.
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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 or
approaches, such as the use of labeled or tagged nanomaterials, may have to be developed in
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
nanoparticles in the respiratory tract of asthmatics has been published (Chalupa et al., 2004).
More information is critically needed to understand the exposure-dose-response relationships of
intentionally produced nanomaterials in order to recommend safe exposure levels that protect the
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. Nanotechnology is
being employed to develop pollution control and remediation applications. Reactive zero-valent
iron nanoparticles are being used to treat soil and aquifers contaminated with halogenated
hydrocarbons, such as TCE (trichloroethylene) or DCE (dichloroethylene), and heavy metals
). However, the production of biphenyl and benzene associated with
nanoscale zero-valent iron degradation of more complex poly chlorinated 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-TiC>2 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
corresponding health effects is not known.
Cerium oxide nanoparticles are being employed in the United Kingdom as on- and off-
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 significantly
increase the ambient air levels of cerium (Health Effects Institute, 2001). The health impacts
associated with these alterations in diesel exhaust have not been examined and are currently not
known.
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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 variety
of environmental media such as soil, water, ambient air, and combustion emissions. The health
effects associated with these interactions are unknown. Research will be needed to assess the
health and environmental risks associated with environmental applications of nanotechnology.
3.7 Ecological Effects of Nanomaterials
Nanomaterials may affect aquatic or terrestrial organisms differently than larger particles
of the same materials. As noted above, assessing nanomaterial toxicity is extremely complex
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, use
of nanomaterials in the environment may result in novel byproducts or degradates that also may
pose risks. The following section summarizes available information and considerations
regarding the potential ecological effects of nanomaterials.
3.7.1 Uptake and Accumulation of Nanomaterials
Based on analogy to physical-chemical properties of larger molecules of the same
material, 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, this last
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 gill membranes of aquatic organisms or the GI tract of both
aquatic and terrestrial organisms. Uptake via passive diffusion of neutral particles is low, but
still measurable within a range of small molecular weights (600-900) (Zitko, 1981; Opperhuizen
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-C6o fullerene is about 720,
although the MW of a Cg4 carbon nanotube is greater than 1000. Passive diffusion through gill
membranes or the GI tract also depends on the cross sectional diameter of particles (Opperhuizen
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 suggests that
passive diffusion may be possible for nanomaterials within this range, but not for nanomaterials
with larger effective cross-sectional diameters.
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 several specific characteristics, including water chemistry (e.g., dissolved organic carbon
and particulate organic carbon) and biotic (lipid content and trophic level) characteristics, when
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EPA Nanotechnology White Paper 59
calculating 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
conduct studies that will provide a solid understanding of these phenomena with a range of
nanomaterials and species. Studies related to human health effects assessment will provide an
important foundation for understanding mammalian exposures and some cross-species processes
(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 in
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, and
phagocytosis).
3.7.2 Aquatic Ecosystem Effects
To date, very few ecotoxicity studies with nanomaterials have been conducted. Studies
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, Oberdorster (2004b) studied effects of fullerenes in the brain of juvenile
largemouth bass and concluded that Ceo fullerenes induce oxidative stress, based on their
observations that (a) there was a trend for reduced lipid peroxidation in the liver and gill, (b)
significant lipid peroxidation was found in brains, and (c) the metabolic enzyme glutathione-S-
transferease (GST) was marginally depleted in the gill. However, no concentration-response
relationship was evident as effects observed at a low dose were not observed at the single higher
dose and no changes in fish behavior were observed; effects could have been due to random
variation in individual fish.
Oberdorster (2004c) tested uncoated, water soluble, colloidal fullerenes (nCeo) and
estimated a Daphnid 48-hour LCso (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. Lovern
and Klaper (2006) tested titanium dioxide (TiO2) and uncoated Ceo 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 magnitude, with fullerene particle solutions
(particle clumps measured as 10-20 nm diameter) having an LC50 of 460 ppb and titanium
dioxide (10-20 nm) with an LC50 of 5.5 parts per million (ppm). Particle preparation impacted
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 toothpaste) did not cause toxicity. Figure 21
shows nanoparticles in the gut and lipid storage droplets of Daphnia magna following uptake
from water.
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EPA Nanotechnology White Paper
Additionally, in behavior tests
with filtered fullerenes, Daphnia
exhibited behavioral responses, with
juveniles 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 structure-
activity relationship predictions for
carbon black and suspended clay
particles, based on analyses by EPA's
OPPT, suggest that some suspended
natural nanosized particles in the aquatic
environment will have low toxicity to
aquatic organisms, with effects
thresholds ranging from tens to
thousands of parts per million. Limited
preliminary work with
engineered/manufactured nanomaterials
seems to substantiate this conclusion.
For example, Cheng and Cheng (2005)
reported that aggregates of single-walled
©Napier University
Figure 21. Fluorescent nanoparticles in water flea
(Daphnia magna).
Adult and neonate Daphnia were exposed to 20nm and
lOOOnm fluorescently tagged carboxylated nanospheres
for up to 24 hours. Nanoparticles were observed in gut
and fatty lipid storage droplets using laser scanning
confocal microscopy. (Image courtesy of Teresa
Fernandes and Philipp Rosenkranz, Copyright Napier
University. Research funded by CSL [DEFRA, UK])
carbon nanotubes (SWCNT) added to
zebrafish embryos reduced hatching rate at 72 hrs, but by 77 hrs post fertilization all embryos in
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 engineered or manufactured nanomaterials should be considered.
For example, as noted previously, SWCNTs displayed greater pulmonary toxicity than carbon
black nanoparticles (Lam et al., 2004). Shvedova et al. (2005) reported unusual inflammatory
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 against
both gram positive and negative bacteria in growth media (Former et al., 2005). The ability of
these "nano-Ceo" 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
nanomaterials to ecological terrestrial test species (plants, wildlife, soil invertebrates, or soil
microorganisms).
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EPA Nanotechnology White Paper 61
For terrestrial mammals, toxicity test data on rats and mice obtained for human health
risk assessments should be considered. For example, studies described above indicate that
ultrafine or nanosize range particles are more toxic on a mass-based exposure metric when
compared to larger particles of identical chemical composition in studies of lung toxicity
(Oberdorster et al., 1994; Li et al., 1999; Hohr et al., 2002), and some nanomaterials can display
unique toxicity that cannot be explained by differences in particle size alone (Lam et al., 2004;
Warheit et al., 2004). Toxicity to mammalian epidermal cell in culture has also been reported
(Shvedova et al., 2003).
The same properties of nanomaterials that regulate uptake in aquatic organisms may limit
uptake of nanoparticles by plant roots or transport through plant leaves and stomata (i.e.,
reducing passive transport at lower MW or size). Additionally, because many nanomaterials are
designed to have strongly reactive surfaces, it is quite possible that significant pathways for
toxicity may exist without uptake (e.g., disruption of respiratory epithelium structure/function or
other surface cell structure/function). In a recent study of nanomaterial effects on plants, Yang
and Watts (2005), reported that alumina nanoparticles (13 nm) slowed root growth in a soil-free
exposure medium. Species tested included commercially important species used in ecological
risk assessments of pesticides: corn (Zea mays), cucumber (Cucumis sativus), soybean (Glycine
max), cabbage (Brassica oleracea), and carrot (Daucus corota). The authors reported that coating
the alumina nanoparticles with an organic compound (phenanthrene), reduced the nanomaterial's
effect of root elongation inhibition. Larger alumina particles (200-300 nm) did not slow root
growth, indicating that the alumina itself was not causing the toxicity. The authors hypothesized
that the surface charge on the alumina nanoparticles may have played a role in the decreased
plant root growth. It should be noted that these studies were conducted in Petri dishes without
soil, so environmental relevance is uncertain. Further, Murashov (2006) noted some limitations
of this report including lack of discussion of known phytotoxicity of alumina, and that the
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 the
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 SARs for polycationic polymers, published in Boethling and
Nabholz (1997). Synthesis of radio-labeled nanomaterials (e.g., carbon-14 labeled nanotubes)
may be 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 often engineered to have very specific properties, it seems
reasonable to presume that they may end up having unusual toxicological effects. Experiences
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, initial
studies should include longer-term exposures measuring multiple, sub-lethal endpoints. They
should be conducted (using appropriate forms and routes of exposure) in a manner that will
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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. These
studies must also include careful tracking of uptake and disposition to understand toxicity as a
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 invertebrates, fish, amphibians, birds, and plants (including algae, rooted
macrophytes, and terrestrial plants) should be adaptable to nanomaterials. These tests are able to
examine 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 projecting
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.
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EPA Nanotechnology White Paper 63
4.0 Responsible Development
One of the stated goals of the National Nanotechnology Initiative is to support
responsible development of nanotechnology. EPA administers a statutory framework laid out in
this chapter that supports responsible development. EPA also funds and conducts research, and
identifies research needs within the context of its programmatic statutory mandates. The ways
that risks are characterized and decisions are made vary based on the program area (air, water,
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 EPA
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 categories
of research needs related to nanotechnology. As illustrated in Figure 22 and described in greater
detail in Chapter 5, an understanding of environmental applications, chemical identification,
potential 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.
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64
EPA Nanotechnology White Paper
Figure 22. EPA Office Roles, Statutory Authorities, and Categories of Research Needs Related to Nanotechnology.
Office of
Prevention,
Pesticides, and
Toxic
Substances
i
Toxic Substance
Control Act:
Review/Oversight of
Industrial Chemical
Federal
Insecticide,
Fungicide,
Rodenticide Act:
Registration of
Pesticides
D Chemical
Identification and
Analysis
D Environmental
Fate and
Treatment
D Releases and
Human Exposure
D Health and
Ecological Effects
D Risk Assessment
D Environmental
Detection and
Analysis
Pollution Prevention
Act: Incorporate P2
into all aspects of
chemical oversight
Chemical Identification •
and Analysis \
"1 Environmental Fate 1
and Treatment j
Office of Air and
Radiation
1
Clean Air Act:
Criteria air
pollutants,
— Hazardous air
pollutants,
Registration of fuels
and fuel additives
• D Chemical
! Identification and
1 Analysis
• D Environmental
! Fate
1 D Releases and
Human Exposure
! D Health and
j Ecological Effects
• D Risk Assessment
j D Environmental
j Detection and
Analysis
Office of Solid
Waste and
Emergency
Response
T
Comprehensive
Environmental
Compensation, and
Liability Act and
Resource Conservation
and Recovery Act:
Hazardous substances
or wastes,
Solid Waste
Chemical Identification
and Analysis
Environmental Fate
and Treatment
Releases and Human
Exposure
Health and Ecological
Effects
Risk Assessment
Environmental
Detection and
Analysis
Remediation
Applications
Chemical j
Identification
and Analysis I
Environmental j
Fate and
Treatment I
Key
Office of
Research and
Development
Office of
Enforcement
and Compliance
Assurance
Research
! Needs !
I I (
! D Evaluation :
I of existing !
• statutory/ |
! regulatory :
I framework !
— regarding |
! enforcement :
j issues !
• D Science to |
I support •
j enforcement \
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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
manufacturing processes and use. Human and environmental exposure information for these
particular substances likely would already be available to inform responsible development. For
some other nanoscale materials, there is less understanding of expected exposure and potential
hazard. The uncertainty may be greater where new industrial methods are employed.
EPA intends to review as appropriate new 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
EPA administers a wide range of environmental statutes, some of which may apply to
nanomaterials 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 review conventional hazard, exposure, and risk assessment tools for their applicability to
nanomaterials, 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
Generally, nanoscale 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
limits/controls, 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.
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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; require
development of test data; and/or require reporting of health and safety studies, categories of use,
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 subject to
some or all of these provisions and programs.
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. Pesticide registration decisions are based on a detailed assessment of the
potential effects of a product on human health and the environment, when used according to
label directions. FIFRA requires EPA and states to establish programs to protect workers, and 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 the
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 pollutants. As
amended in 1990, it also identified 190 Hazardous Air Pollutants (HAPs) for regulation (the list
currently includes 187 HAPs) and provides EPA with authority to identify additional HAPs. The
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 issued health effects testing requirements for fuels and fuel
additives. Gasoline and diesel fuels and their additives are subject to the regulations issued by
EPA. These fuels and additives for use in on-road applications may not be introduced into
commerce until they have been registered by EPA. As previously noted EPA has received and is
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
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EPA Nanotechnology White Paper 67
prevented or reduced at the source; (2) pollution that cannot be prevented should be recycled in
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 environment
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 Design for the Environment (DfE) Program and
the Green Chemistry Program. Under DfE, EPA works in partnership with industry sectors to
improve performance of commercial processes while reducing risks to human health and the
environment. The Green Chemistry Program promotes research to design chemical products and
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, and
biological integrity of the nation's waters as well as to ensure the health and welfare of the
environment, fish, shellfish, other aquatic organisms, wildlife, and humans that live in, recreate
on, or come in contact with waters of the United States. Depending on the toxicity of
nanomaterials to aquatic life, aquatic dependent wildlife, and human health, as well as the
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 waters.
The Safe Drinking Water Act (SDWA), as amended in 1996, is the main federal law that
protects 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 potential to contribute to better and more cost-effective removal of
drinking water contaminants, such as metals (e.g. arsenic or chromium), toxic halogenated
organic chemicals, suspended particulate matter and pathogenic microorganisms. If
nanoparticles enter drinking water, such as through their use in water treatment, then exposure to
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.
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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 EPA
the authority to respond to actual or threatened releases of hazardous substances to the
environment and to actual or threatened releases of pollutants or contaminants that may present
an imminent 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 Waste
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 municipal
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 regulations
and/or that exhibits a defining characteristic) potentially would be subject to subtitle C
regulations. Subtitle I covers underground storage tanks, and Subtitle J covers medical waste
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 Act
include response (cleanup/containment/prevention action) and enforcement actions related to
discharges and threatened discharges of oil or hazardous substances in the inland waters of the
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
certain other sectors, as well as federal facilities. Some producers of nanomaterials containing
materials 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 calendar
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 commonly
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 and others are supporting research into green nanotechnology, to
identify applications of nanotechnology that reduce pollution from industrial processes as well as
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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
industrial organizations and their suppliers have the opportunity at this early stage of technology
development and use to be leading environmental stewards.
At EPA, in addition to our support for green nanotechnology research, there are a number
of programs already in place that are based upon environmental stewardship principles. These
programs address processes, including inputs; waste streams; and the design, use, disposal, and
stewardship of products consistent with the goal of pollution prevention. Information on
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.
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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
nanomaterials. However, there are significant challenges to addressing research needs for
nanotechnology 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 we
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 research 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)?
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EPA Nanotechnology White Paper 71
• What is the life cycle of various types of nanomaterials and nanoproducts under a variety
of manufacturing and environmental conditions?
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?
• How can nanotechnology assist "green" energy production, distribution, and use?
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 site treatment methods. In addition, other
nanoremediation approaches can involve the methods of coating biological particles, determining
the effect on the particles (enzyme or bactedophage) following coating, and application
technologies. This is an area that has not been examined in any great detail. Therefore, research
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 nanoparticles
to decontaminate or prevent bacterial growth. In an age of antibiotic resistance and aversion to
chemical decontamination, enzyme and bacteriophage technologies offer an attractive option.
Remediation and treatment research questions include:
• Which nanomaterials are most effective for remediation and treatment?
• What are the fate and effects of nanomaterials used in remediation applications? When
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?
• How 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
toxic and what organisms are affected?
If toxic byproducts are produced, how can these be reduced?
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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 category can
eventually result in lower material cost as well as reduced weight and power consumption of
sensors, leading to greater applicability, and is the subject of this section. Research needs for
sensors to detect nanomaterials in the environment are discussed in the Environmental Detection
section below.
• How can 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
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) and
exposure (all routes). It is not clear whether existing physical-chemical property test methods
are adequate for sufficiently characterizing various nanomaterials. Alternative methods may be
needed. 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?
• To what extent will it be necessary to tailor research protocols to the specific type and use
pattern of each nanomaterial? Can properties and effects be extrapolated within a class of
nanomaterials?
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EPA Nanotechnology White Paper 73
• Are there 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?
• 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 intentionally produced nanomaterials are now on the market and what new types of
materials can be expected to be developed?
• How will manufacturing processes, formulations, and incorporations in end products alter
the characteristics of nanomaterials?
5.2.2 Environmental Fate and Treatment Research Needs
EPA needs to ascertain the fate of nanomaterials in the environment to understand the
availability of these materials for exposure to humans 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
increasingly in products. To support these investigations, existing methods should be evaluated
and if necessary, they should be modified or new methods should be developed. Research is
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?
• How are nanomaterials transported in the atmosphere? What nanomaterial properties and
atmospheric conditions control the atmospheric fate of nanomaterials?
• To what extent are nanomaterials mobile in soils and in groundwater? What is the
potential for these materials, if released to soil or landfills, to migrate to groundwater and
within aquifers, with potential exposure to general populations via groundwater
ingestion?
• What is the potential for these materials to be transported bound to particulate matter,
sediments, or sludge in surface waters?
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• 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 macro-
scale or bulk materials?
5.2.2.2 Transformation Research Questions
• How do nanoparticles react differently in the environment than their bulk counterparts?
• What are the physicochemical factors that affect the persistence of intentionally produced
nanomaterials in the environment? What data are available on the physicochemical
factors that affect the persistence of unintentionally produced nanomaterials (e.g., carbon-
based combustion products) that may provide information regarding intentionally
produced nanomaterials?
• Do particular nanomaterials persist in the environment, or undergo degradation via biotic
or abiotic processes? If they degrade, what are the byproducts and their characteristics?
Is the nanomaterial likely to be in the environment, and thus be available for
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 processes
influence environmental transformation of nanomaterials? To what extent are
nanomaterials photoreactive in the atmosphere, in water, or on environmental surfaces?
• How do the aggregation, sorption and agglomeration of nanoparticles affect
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, re-
use, and disposal.
5.2.2.3 Chemical Interaction Research Questions
• How do nanosized adsorbants and chemicals sorbed to them influence their respective
environmental interactions? Can these materials alter the mobility of other substances in
the environment? Can these materials alter the reactivity of other substances in the
environment?
5.2.2.4 Treatment Research Questions
• What is the potential for these materials to bind to soil, subsurface materials, sediment or
wastewater sludge, or binding agents in waste treatment facilities?
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• Are these materials effectively removed from wastewater using conventional wastewater
treatment methods and, if so, by what mechanism?
• Do these materials have an impact on the treatability of other substances in waste streams
(e.g., wastewater, hazardous and nonhazardous solid wastes), or on treatment facilities
performance?
• Are these materials effectively removed in drinking water treatment and, if so, by what
mechanism?
• 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) for treating nanomaterials?
5.2.2.5. Assessment Approaches and Tools Questions
• Can existing information on soil colloidal fate and transport, as well as atmospheric
ultrafme particulate fate and transport, inform our thinking? Do the current databases of
ultrafmes/fibers shed light on any of these questions?
• 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 relationships for
future materials?
• Should current fate and transport models be modified to incorporate the unique
characteristics of nanomaterials?
5.2.3 Environmental Detection and Analysis Research Needs
While there are a variety of methods currently available to measure nanoparticle
mass/mass concentrations, surface area, particle count, size, physical structure (morphology),
and chemical composition in the laboratory, the challenge remains to detect nanomaterials in the
environment. Research is needed to address the following high-priority questions:
5.2.3.1 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,
shape, surface properties (e.g., reactivity, charge, and area), etc.? Can they distinguish
between intentionally produced nanomaterials of interest and other ultrafme particles?
Can they distinguish between individual particles of interest and particles that may have
agglomerated or attached to larger particles?
• Are standard procedures available for both sample preparation and analysis?
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• Are quality assurance and control reference materials and procedures available?
• How would nanomaterials in waste media be measured and evaluated?
5.2.3.2 New Methods and Technologies Research Needs
• What low-cost, portable, and easy-to-use technologies can detect, characterize, and
quantify nanomaterials of interest in environmental media and for personal exposure
monitoring.
5.2.4 Human Exposures, Their Measurement and Control
Potential sources of human exposure to nanomaterials include workers exposed during
the production and use of nanomaterials, general population exposure from releases to the
environment during the production or use in the workplace, and direct general population
exposure during the use of commercially available products containing nanoscale materials.
Releases from industrial accidents, natural disasters, or malevolent activity such as a terrorist
attack should also be considered. Research is needed to identify potential sources, pathways, and
routes of exposure, potential tools and models that may be used to estimate exposures, and
potential data sources for these models, as well as approaches for measuring and mitigating
exposure. NIOSH has also examined research needs regarding risks to workers and developed a
strategic plan to address these needs (NIOSH 2005a, b). Research is needed to address the
following high-priority questions.
5.2.4.1. Risk and Exposure Assessment Research Questions
• 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 count, surface area) should be used to measure exposure?
Are sensitive populations' (e.g., endangered species, children, asthmatics, etc.) exposure
patterns included?
• How do physical and chemical properties of nanomaterials affect releases and exposures?
• How do variations in manufacturing and subsequent processing, and the use of particle
surface modifications affect exposure characteristics?
5.2.4.2 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 systems (e.g., TRI), measurement tools,
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models, etc)? Are these tools/resources adequate to measure, estimate, and assess releases
and exposures to nanomaterials? Is degradation of nanomaterials accounted for?
• What research is needed to develop sensors that can detect nanomaterials, including
personal exposure monitoring?
5.2.4.3 Release and Exposure Reduction and Mitigation Research Questions
• What tools/resources exist for limiting release and/or exposure during manufacture, use
or following release via waste streams? Are these tools/resources adequate for
nanomaterials?
• 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 non-
nanomaterials) be adapted to control nanomaterial spills?
• In the case of an unintentional spill, what are the appropriate emergency actions? How
are wastes from response actions disposed of properly?
• 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?
5.2.5 Human Health Effects Assessment Research Needs
Adverse health effects of intentionally produced nanomaterials may result from either
direct exposure resulting from inadvertent release of these novel materials or unintentional
byproducts produced by their intentional release into the environment. Very little data exist on
the toxicity, hazardous properties, deposition and fate, as well as susceptibility associated with
exposure to intentionally produced nanomaterials, their application byproducts, decomposition
products or production waste streams. Finally, it is uncertain whether standard test methods will
be capable of identifying toxicities associated with the unique physical chemical properties of
intentionally produced nanomaterials.
It will be important for nanomaterial health effects risk assessment research to also
establish whether current particle and fiber toxicological databases have the ability to predict or
assess the toxicity of intentionally produced nanomaterials displaying unique physicochemical
properties. The limited studies conducted to date indicate that the toxicological assessment of
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specific intentionally produced nanomaterials will be difficult to extrapolate from existing
databases. The toxic effects of nanoscale materials have not been fully characterized, but it is
generally believed that nanoparticles can have toxicological properties that differ from their bulk
material. A number of studies have demonstrated that nanoparticle toxicity is complex and
multifactorial, potentially being regulated by a variety of physiochemical properties such as size,
chemical composition, and shape, as well as surface properties such as charge, area and
reactivity. As the size of particles decreases, a resulting larger surface-to-volume ratio per unit
weight for nanoparticles correlates with increased toxicity as compared with bulk material
toxicity. Also as a result of their smaller size, nanoparticles may pass into cells directly through
cell membranes or penetrate the skin and distribute throughout the body once translocated to the
circulatory system. While the effects of shape on toxicity of nanoparticles appears unclear, the
results of a recent in vitro cytotoxicity study appear to suggest that single-wall carbon nanotubes
are more toxic than multi-wall carbon nanotubes. Therefore, with respect to nanoparticles, there
is concern for systemic effects (e.g., target organs, cardiovascular, and neurological toxicities) in
addition to portal-of-entry (e.g. lung, skin, intestine) toxicity.
Initially, it will be important to be specific with respect to the nature of the surface
material/coating, the application for which the material is used, the likely route of exposure, the
presence of other exposures which may affect toxicity (e.g., UV radiation) and not rely on
information derived from a study conducted under one set of conditions to predict outcomes that
may occur under another set of conditions. However, past experience with conventional
chemicals suggests that toxicology research on nanomaterials should be designed from the
beginning with an eye towards developing hypothesis-based predictive testing.
Research is also needed to examine health impacts of highly dispersive nanotechnologies
that are employed for site remediation, monitoring, and pollution control strategies. It will be
necessary to determine both the impacts these types of nanotechnologies have on regulated
pollutants in air, soil, or water, as well as their corresponding potential health effects. Research
should be conducted in the following areas:
A. Determining the adequacy of current testing schemes, hazard protocols, and dose
metrics.
B. Identifying the properties of nanomaterials that are most predictive of toxicity to
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 their byproducts, associated with those nanotechnology
applications that are most likely to have potential for exposure? (Addresses area C,
above)
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• Are there specific toxicological endpoints that are of higher concern for nanomaterials,
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 toxicity tests
(http://wivw.epa.gov/opptsfrs/OPPTSJiarmomzed/)? (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,
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 (local
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 intentionally produced nanomaterials? (Addresses area B,
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,
in a manner that links in vitro, in vivo, and in silico data?
5.2.6 Ecological Effects Research Needs
Ecosystems may be affected through inadvertent or intentional releases of intentionally
produced nanomaterials. Drug and gene delivery systems, for example, are not likely to be 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
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chemical modifications of soil or water. Nanoscale particles may affect aquatic or terrestrial
organisms differently than larger particles due to their extreme hydrophobicity, their ability to
cross and/or damage cell membranes, and differences in electrostatic charge. Furthermore, use
of nanomaterials in the environment may result in novel byproducts or degradates that also may
pose significant risks.
Important considerations for prioritizing and defining the scope of the research needs include
determining which nanomaterials are most used (volume), are likely to be used in the near future
(imminence of use), and/or have most potential to be released into the environment (dispersive
applications). Another consideration is the need to test representative materials from each of the
four classes of nanomaterials (carbon-based, metal-based, dendrimers, composites).
The same general research areas used for prioritizing human health effects research needs
were used to prioritize ecological research needs. Using these areas as a guide, the following
research questions were identified:
• Are current testing schemes and methods (organisms, endpoints, exposure regimes,
media, analytical methods) applicable to testing nanomaterials in standardized toxicity
tests? Both pilot testing protocols and definitive protocols should be evaluated with
respect to their applicability to nanomaterials.
• What is the distribution of nanomaterials in ecosystems? Research on model ecosystems
studies (micro, mesocosms) is needed to assist in determining the distribution of
nanomaterials in ecosystems and potentially affected compartments and species.
• What are the effects (local and systemic; acute and chronic) from either direct exposure
to nanomaterials, or to their byproducts, associated with those nanotechnology
applications that are most likely to have potential for exposure?
• What are the absorption, distribution, metabolism, elimination (ADME) parameters for
various nanomaterials for ecological receptors? This topic addresses the uptake, transport,
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?
• What research is needed to examine the interaction of nanomaterials with microbes in
sewage treatment plants, in sewage effluent, and in natural communities of microbes in
natural soil and natural water?
• 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?
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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'
special 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 to be
developed and applied to inform assessments of potential hazard and exposure.
Case studies could be conducted based on publicly available information on several
intentionally produced nanomaterials. Such case studies would be useful in further identifying
unique considerations that should be focused in conducting risk assessments for various types of
nanomaterials. From such case studies and other information, information gaps may be
identified, which can then be used to map areas of research that are directly affiliated with the
risk assessment process and the use of standard EPA tools such as tiered testing schemes. EPA
frequently uses tiered testing schemes for specific risk assessment applications. A series of
workshops involving a substantial number of experts from relevant disciplines could be held to
use case studies and other information for the identification of any unique considerations for
nanomaterials not previously identified, testing schemes, and associated research needs that will
have to be met to carry out exposure, hazard and risk assessments.
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6.0 Recommendations
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 been identified for
each recommendation. It may be appropriate for other EPA offices to collaborate with the
identified leads for specific recommendations. EPA should also collaborate with outside groups
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 promoting 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-
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6.1.5 Research Needs for Other Environmental Applications
• ORD should work with industrial partners to verify the performance of nanomaterials and
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 Analysis
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 application of
nanotechnology for exposure reduction; e.g., nano-enabled PPE, respirators containing
nanomaterials, and nanoscale end-of-life sensors, sensors that indicate when a product
has reached the end of its useful life.
6.2 Research Recommendations for Risk Assessment
A multidisciplinary approach is needed that involves physics, biology, and chemistry to
understand nanomaterials at a basic level and how they interact with the environment. This calls
for a cross-media approach and one that involves collaboration with other federal agencies, and
the private and non-profit sectors. This includes examining the implications (risks) of the
environmental applications of nanotechnology.
6.2.1 Research Recommendations for Chemical Identification and Characterization
• ORD should lead research on the unique chemical and physical characteristics of
nanomaterials and how these properties affect the material's reactivity, toxicity and other
attributes.
• ORD should lead research on how 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.
• 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 for Environmental Fate and Treatment
The following are recommendations, in order of priority, in support of the environmental
fate and treatment research needs identified as priorities in Chapter 5.
Fate, Treatment and Transport
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• 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
address the impacts of such nanomaterials on the fate of other contaminants at
remediation sites. These offices should collaborate with state environmental programs
and academia on this research. Based upon available field activities where nanomaterials
are being used for site remediation, this research could be conducted within the few
years.
• ORD and OAR should lead research on the stability of various types of intentionally
produced nanoparticles in the atmosphere. This effort should involve both theoretically
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 nanomaterials waters, soils and sediment that are relevant to
environmental conditions.
• ORD should lead research that defines the physical and chemical properties of
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 sewage
treatment plants, the efficiency of removing nanoparticles from the effluent, the fate of
nanomaterials after removal, methods for disposal of sludges containing nanomaterials,
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 should share the lead on research on the fate of nanomaterials used
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 processes; i.e., whether methods such as carbon
adsorption, filtration, and coagulation and settling are effective for treating
nanomaterials.
• ORD, OSW and OAR should lead research on the fate of nanomaterials in incineration
and other thermal treatment processes, including the efficiency of destroying
nanomaterials, the efficiency of various air pollution control devices (e.g., baghouses,
liquid scrubbers, and electrostatic precipitators) at removing entrained nanomaterials, the
fate of nanomaterials after removal, methods for disposal of ash containing
nanomaterials, and the impact nanomaterials may have on the removal 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
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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 other toxic
constituents in the waste stream. EPA should collaborate with treatment, storage, and
disposal facilities (TSDFs) and academia on this research.
• ORD and 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
scenarios (e.g., surface impoundments). Research would identify relevant waste streams,
the efficiency of current containment technologies (e.g., various cap and liner types,
leachate collection systems) at preventing the leaching of nanomaterials into
groundwater, the fate of nanomaterials after disposal, and the impact nanomaterials may
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.
6.2.3 Research Recommendations for Environmental Detection and Analysis
Where applicable, the initial focus of environmental detection and analysis related
research should be on nanomaterials or types of nanomaterials that have demonstrated potential
human or ecological toxicity. The following is a prioritized list of research needs for
environmental 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 manufacturers and
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 analysis
for nanomaterials of interest in various environmental media. ORD should collaborate
with NIOSH, DOD, industry, academia, the American Society for Testing Materials
(ASTM) and the American National Standards Institute (ANSI) in developing these
methods.
6.2.4 Research Recommendation Human Exposures, their Measurement and Control
The following is a prioritized list of research needs for human exposures, their
measurement and control.
• OPPT should conduct a literature search to evaluate the effects of nanomaterial
physical/chemical properties on releases and exposures.
• 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.
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• OPPT and ORD should evaluate sources of information for assessing chemical releases
and exposures for their applicability to nanomaterials. These sources, including release
and exposure tools and models, would be evaluated to determine whether they would be
applicable to assessing releases and exposures to nanomaterials. If found applicable, the
sources would be evaluated to determine whether additional data or methods would be
needed for assessing nanomaterials. Issues such as degradation would be considered
also.
• OSWER, ORD, and OPPT should evaluate the proper emergency response actions and
remediation in case of a nanomaterial spill, and the proper disposal of wastes from such
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 are
contingent upon completion of the risk and exposure assessment guidance documents noted
in the two paragraphs above. Until this contingency is met, many of the remaining research
needs 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 equipment
for controlling and reducing chemical exposures for their applicability to nanomaterials,
in collaboration with NIOSH and other external groups.
• ORD should lead development of sensors for monitoring personal exposures to
nanoparticles
6.2.5 Research Recommendations for Human Health Effects Assessment
The following is a prioritized list of health effects research needs:
Test Methods
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• ORD and OPPTS should determine the applicability of current testing methods
(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
analytical methods are capable of analyzing and quantifying intentionally produced
nanomaterials to generate dose-response relationships.
Nanotoxicology
• ORD should lead research to determine the health effects (local and systemic; acute and
chronic) resulting from either direct exposure to nanomaterials, or to their byproducts,
associated with dispersive nanotechnology applications such as remediation, pesticides,
and air pollution control technologies. Research should determine whether there are
specific toxicological endpoints that are of high concern for nanoparticles, such as
neurological, cardiovascular, respiratory, or immunological effects, etc. Research in this
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 also collaborate with stakeholders in catalyzing this research.
Hazard Identification andDosimetry & 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
and systemic; acute and chronic) of intentionally produced nanomaterials.
• ORD should lead research on the absorption, distribution, metabolism, and excretion
(ADME) of intentionally produced nanomaterials following various routes of exposure.
This research must also include determining what physicochemical properties regulate
intentionally produced nanomaterial ADME. ORD should collaborate with OPPTS on
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.
This is a need that cannot be established until information from earlier research needs
have been collected.
Computational Nanotoxicology
• ORD should lead research to determine what approaches are most effective to build
predictive toxicity assessment models (SAR, PBPK, "omics", etc.).
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Research into the human health effects assessment of intentionally produced
nanomaterials will be extremely challenging and the ability to interact with other federal,
international, academic, and private activities in this area would be most beneficial. A number of
organizations are engaged in health effects research. Collaboration with NASA, NIOSH, FDA,
NCI, NTP, DOD/MURI, NIST, NEHI, DOE, the European Union, EPA grantees, academic
institutions, and others will leverage resources in gaining knowledge on the potential health
effects of nanomaterials.
6.2.6 Ecological Exposure and Effects
It is critical that research be focused specifically upon the fate, and subsequent exposure
and effects, of nanomaterials on invertebrates, fish, and wildlife associated with ecosystems.
What is the behavior of nano materials in aquatic and terrestrial environments? How can
environmental exposures be simulated in the laboratory? What are the acute and chronic toxic
effects? There is a need for development and validation of analytical methodologies for
measuring nanoscale substances (both parent materials and metabolites/complexes) in
environmental matrices, including tissues of organisms. In terms of toxicity, a critical challenge
in the area of ecosystem effects lies in determining the impacts of materials whose cumulative
toxicity is likely to be a manifestation of both physical and chemical interactions with biological
systems. The following is a prioritized list of ecological research needs:
Test Methods
• ORD should collaborate with other EPA offices in research on the applicability of current
testing schemes and methods (organisms, endpoints, exposure regimes, media, analytical
methods) for testing nanomaterials in standardized toxicity tests. Both pilot testing
protocols and definitive protocols should be evaluated with respect to their applicability
to nanomaterials.
Environmental Fate/Distribution of Nanomaterials in Ecosystems
• ORD should lead on research on the distribution of nanomaterials in ecosystems.
Nanotoxicology and Dosimetry
• ORD should determine the effects of direct exposure to nanomaterials or their
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 the uptake, transport, and bioaccumulation of these materials.
• ORD, OW and OPPT should lead research on the interactions of nanomaterials with
microbes in sewage treatment plants in sewage effluent and natural communities of
microbes in natural soil and natural water.
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EPA Nanotechnology White Paper 89
• ORD should lead research aimed at developing structure-activity relationships (SARs) for
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 to Address Overarching Risk Assessment Needs - Case Study
One way to examine how a nanomaterial assessment would fit within EPA's overall risk
assessment paradigm is to conduct a case study based on publicly available information on one
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 reproduction,
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 areas of
research that are directly affiliated with the risk assessment process. This has been done in the
past with research on airborne paniculate matter.
Additionally, a series of workshops involving a substantial number of experts from
several disciplines should be held to use available information and principles in identifying data
gaps and research needs that will have to be met to carry out exposure, hazard and risk
assessments.
6.3 Recommendations for Pollution Prevention and Environmental
Stewardship
Opportunities exist to advance pollution prevention as nanotechnology industries form
and develop. EPA has the capability to support research into nanotechnology applications of
pollution prevention and environmental stewardship principles that have been developed for
green energy, green chemistry, green engineering, and environmentally benign manufacturing.
EPA is well-positioned to work with stakeholders on pollution prevention and product
stewardship approaches for producing nanomaterials in a green manner, as well as for identifying
areas where nanomaterials may be cleaner alternatives to exisiting industrial inputs. The
following are the primary recommendations for pollution prevention and environmental
stewardship:
• 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 for
the environment, green engineering and green chemistry principles and approaches to
nanomaterials and nanoproducts.
Other recommendations for pollution prevention and environmental stewardship:
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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
Network to identify nanotechnology sectors, supply chains, analytical and design tools,
and applications.
• OCIR and OCFO should encourage research within organizations such as the Ecological
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. These
collaborations will reduce resource burdens on EPA's science programs and will facilitate
communication with stakeholders.
• ORD should collaborate with other groups on research into the environmental
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 of
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 should lead efforts to investigate the possibilities for collaboration with and
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.
• OPEFs Small Business Omsbudsman should engage in information exchange with small
businesses, which comprise a large percentage of U.S. nanomaterial producers.
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EPA Nanotechnology White Paper 91
6.5 Recommendation to Convene an Intra-Agency Workgroup
The Agency should convene a standing intra-Agency group to foster information sharing
regarding risk assessment, and regulatory activities, as well as pollution prevention and
stewardship-oriented activities regarding nanomaterials across program offices and regions.
6.6 Recommendation for Training
EPA has begun educating itself about nanotechnology through seminars in the program
and regional offices, an internal cross-Agency workgroup (NanoMeeters) with an extensive
database, and a Millenium lecture series covering both the administrative and technical aspects
of nanotechnology. The SPC Nanotechnology Workgroup also held a "primer" session on
nanotechnology to help inform its members during the early stages of development of this paper.
While this white paper also provides information for Agency managers and scientists, there
should be ongoing education and training as well as expert support for EPA managers and staff
to assist in the understanding of nanotechnology, its potential applications, regulatory and
environmental implications, as well as unique considerations when conducting risk assessments
on nanomaterials relative to macro-sized materials.
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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
understands potential risks from human and environmental exposure to nanomaterials. Table 6
summarizes the staff recommendations identified above.
Table 6. Summary of Workgroup Recommendations Regarding Nanomaterials
6.1 Research for Environmental Applications. EPA should undertake, collaborate on, and
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.
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EPA Nanotechnology White Paper 93
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Appendix A: Glossary of Nanotechnology Terms
Aerosol: A cloud of solid or liquid particles in a gas.
Array: An arrangement of sensing elements in repeating or non-repeating units that are arranged
for increased sensitivity or selectivity.
Biomimetic: Imitating nature and applying those techniques to technology.
Buckyball/Ceo: see of which "buckyballs" is a subset. The term "buckyball" refers
only to the spherical fullerenes and is derived from the word "Buckminsterfullerene," which is
the geodesic dome / soccer ball-shaped Ceo molecule. Ceo was the first buckyball to be
discovered and remains the most common and easy to produce.
Catalyst: A substance, usually used in small amounts relative to the reactants, that modifies and
increases the rate of a reaction without being consumed or changed in the process..
Dendrimers: artificially engineered or manufactured molecules built up from branched units
called monomers. Technically, a dendrimer is a branched polymer, which is a large molecule
comprised of many smaller ones linked together.
Diamondoid: Nanometer-sizes structures derived from the diamond crystal structure.
Electron beam lithography: Lithographic patterning using an electron beam, usually to induce
a change in solubility in polymer films. The resulting patterns can be subsequently transferred to
other metallic, semiconductor, or insulating films.
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 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.
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 Ceo molecule and is named after Buckminster Fuller, an architect who described and made
famous the geodesic dome. Ceo and C?o are the most common and easy to produce fullerenes.
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Incidental nanosized materials: Nanomaterials that are the byproducts of human activity, such
as combustion, welding, or grinding.
Intentionally produced nanomaterials: See Engineered/manufactured nanoscale materials.
Manufacturing processes: General term used to identify the variety of processes used in the
production of the part. Processes may include plastic injection molding, vacuum forming,
milling, stamping, casting, extruding, die-cutting, sewing, printing, packaging, polishing,
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 nature works
on the nanometer scale, particularly how transport takes place in biological systems. The
interaction between the body and nanodevices are studied, for example, to develop processes for
the body to regenerate bone, skin, and other damaged tissues.
Nanochemistry: A discipline focusing on the unique properties associated with the assembly of
atoms or molecules on a nanometer scale. At this scale, new methods of carrying out chemical
reactions are possible. Alternatively, it is the development of new tools, technologies and
methodologies for doing chemistry in the nanolitre to femtolitre domains.
Nanoelectronics: Electronics on a nanometer scale, whether by current techniques or
nanotechnology; includes both molecular electronics and nanoscale devices resembling today's
semiconductor devices.
Nanomaterial: See Engineered/manufactured nanoscale materials
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 science devoted to the advancement of
nanotechnology.
Nanostructures: structures at the nanoscale; that is, structures of an intermediate size between
molecular and microscopic (micrometer-sized) structures.
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.
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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).
PMo.i: Particulate matter less than 0.1 micrometers in diameter
: Particulate matter less than 2.5 micrometers in diameter
PMi0: Particulate Matter less than 10 micrometers in diameter
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 hundred
nanometers. Changing the size of quantum dots changes their optical properties
Self-Assembled Monolayers on Mesoporous Supports (SAMMS): nanoporous ceramic
materials that have been developed to remove contaminants from environmental media.
Self-assembly: The ability of objects to assemble themselves into an orderly structure. Routinely
seen in living cells, this is a property that nanotechnology may extend to inanimate matter.
Self-replication: The ability of an entity such as a living cell to make a copy of itself.
Superlattice: nanomaterials composed of thin crystal layers. The properties (thickness,
composition) of these layers repeat periodically.
Unintentionally produced nanomaterials: See Incidental nanosized materials
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Appendix B: Principles of Environmental Stewardship Behavior
What does a good environmental steward do?
(based on statements by environmental stewards and others)
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
environmental steward considers and reduces the household, community, farm or company's
entire environmental footprint. A steward safeguards and restores nature at home and elsewhere.
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 resources
and conserves natural resources whenever possible. A steward reuses and recycles materials and
wastes and seeks sustainability.
Makes environment a key part of internal priorities, values and ethics, and leads by example.
Environmental stewards make decisions through their own volition that will prevent or minimize
environmental harm. They anticipate, plan for, and take responsibility for economic,
environmental and social consequences of actions. A steward approaches business strategies,
policy planning, and life as an integrated dynamic with the environment. A steward acts in
innovative ways, using all available tools and creating or adding value. A steward adopts
holistic, systems approaches.
Holds oneself accountable. An environmental steward measures the effects of behavior on the
environment and seeks progress. A steward applies an understanding of carrying capacity to
measure progress and update objectives to achieve continuous improvement, often using
indicators, environmental assessments, and environmental management systems.
Believes in shared responsibility. 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-of-
life). 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.
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EPA Nanotechnology White Paper 111
Appendix C: EPA's Nanotechnology Research Framework
Nanotechnology has the potential to provide benefits to society and to improve the environment,
both through direct applications to detect, prevent, and remove pollutants, the design of cleaner
industrial processes and the creation of environmentally friendly products. However, some of
the same unique properties that make manufactured nanoparticles beneficial also raise questions
about the potential impacts of nanoparticles on human health and the environment.
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 ecosystems, considering the entire life cycle. EPA also will conduct
research to identify approaches for detecting and measuring nanoparticles. This research
framework is based on the recommendations from the EPA Nanotechnology White Paper and is
consistent with the research needs identified by the Interagency Working Group on
Nanotechnology Environmental and Health Implications, one of the working groups of the
Nanoscale Science Engineering and Technology Subcommittee of the National Science and
Technology Council.
While some studies have been done to determine potential toxicity of certain nanoparticles to
humans and other organisms (both in vivo and in vitro), very little research has been performed
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 will vary
with size, surface charge, coating, state of agglomeration, etc. Therefore, in fiscal years 2007 and
2008, EPA will focus on the following high priority areas: environmental fate, transport,
transformation and exposure; and monitoring and detection methods. Resulting data will be used
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 measure
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
water
• 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 relevant
testing methods/protocols
Having laid a foundation for understanding possible material alterations under various
conditions, EPA will direct a greater share of fiscal year 2009 and 2010 resources to exploring
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the effects, specifically toxicity of the altered materials as identified in the first two years. This
approach will be informed and refined by case studies, initiating in fiscal year 2007, designed to
elicit information on how EPA can address high-exposure-potential nanoparticles/nanomaterials.
By 2011-2012, sufficient knowledge will result in the development of systematic and integrated
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 addition, the
Agency is collaborating with academia and industry to fill knowledge gaps in these areas.
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.
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EPA Nanotechnology White Paper
113
Appendix D: EPA STAR Grants for Nanotechnology
Through Science to Achieve Results (STAR) program in EPA's Office of Research and Development/National Center for
Environmental Research, a number of nanotechnology research grants have been awarded. The table below shows nanotechnology
grants funded though 2005. Additional grants focusing on implications of nanomaterials for the 2006 solicitation are in the process of
final selection and funding by EPA, the National Science Foundation (NSF), the National Institute for Occupational Safety and Health
(NIOSH), and the National Institute of Environmental Health Sciences (NIEHS). Information on funded grants, including abstracts
and progress reports is available online at www.epa.gov/ncer/nano.
Grant #
RD829621
RD829606
RD829603
RD829626
RD829599
RD829622
RD829600
RD829620
Principal
Investigator (PI)
Bhattacharyya,
Dibakar
Chen, Wilfred
Chumanov, George
Diallo, Mamadou
Gawley, Robert
Johnston, Murray
Larsen, Sarah
McMurry, Peter
Title
Membrane-Based Nanostructured Metals for
Reductive Degradation of Hazardous Organic
at Room Temperature
Nanoscale Biopolymers with Tunable
Properties for Improved Decontamination and
Recycling of Heavy Metals
Plasmon Sensitized TiO2 Nanoparticles as a
Novel Photocatalyst for Solar Applications
Dendritic Nanoscale Chelating Agents:
Synthesis, Characterization, Molecular
Modeling and Environmental Applications
Nanosensors for Detection of Aquatic Toxins
Elemental Composition of Freshly Nucleated
Particles
Development of Nanocrystalline Zeolite
Materials as Environmental Catalysts: From
Environmentally Benign Synthesis Emission
Abatement
Ion-Induced Nucleation of Atmospheric
Aerosols
Institution
University of
Kentucky
University of
California, Riverside
Clemson University
Howard University
University of
Arkansas
University of
Delaware
University of Iowa
University of
Minnesota
Year
2002
2002
2002
2002
2002
2002
2002
2002
Amount
$345,000
$390,000
$320,000
$400,000
$350,000
$390,000
$350,000
$400,000
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EPA Nanotechnology White Paper
Grant #
RD829624
RD829604
RD829602
RD829601
RD829623
RD829619
RD829605
RD829625
RD830907
RD830910
RD830904
RD830902
Principal
Investigator (PI)
Shah, S. Ismat
Shih, Wan
Sigmund, Wolfgang
Strongin, Daniel
Tao, Nongjian
Trogler, William
Velegol, Darrell
Zhang, Wei-xian
Anderson, Anne
Beaver, Earl
Drzal, Lawrence
Kan, Edwin
Title
Synthesis, Characterization and Catalytic
Studies of Transition Metal Carbide
Nanoparticles as Environmental Nanocatalysts
Ultrasensitive Pathogen Quantification in
Drinking Water Using Highly Piezoelectric
PMN-PT Microcantilevers
Simultaneous Environmental Monitoring and
Purification through Smart Particles
A Bioengineering Approach to Nanoparticle
Based Environmental Remediation
A Nanocontact Sensor for Heavy Metal Ion
Detection
Nanostructured Porous Silicon and
Luminescent Polysiloles as Chemical Sensors
for Carcinogenic Chromium (VI) and Arsenic
(V)
Green Engineering of Dispersed Nanoparticles:
Measuring and Modeling Nanoparticles Forces
Nanoscale Bimetallic Particles for In Situ
Remediation
Metal Biosensors: Development and
Environmental Testing
Implications of Nanomaterials Manufacture and
Use: Development of a Methodology for
Screening Sustainability
Sustainable Biodegradable Green
Nanocomposites from Bacterial Bioplastic for
Automotive Applications
Neuromorphic Approach to Molecular Sensing
with Chemoreceptive Neuron MOS Transistors
(CnMOS)
Institution
University of
Delaware
Drexel University
University of Florida
Temple University
Arizona State
University
University of
California, San Diego
Pennsylvania State
University
Lehigh University
Utah State University
BRIDGES to
Sustainability
Michigan State
University
Cornell University
Year
2002
2002
2002
2002
2002
2002
2002
2002
2003
2003
2003
2003
Amount
$350,000
$400,000
$390,000
$399,979
$375,000
$400,000
$370,000
$300,000
$336,000
$99,741
$369,000
$354,000
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EPA Nanotechnology White Paper
115
Grant #
RD830909
RD830905
RD83091 1
RD830898
RD830908
RD830901
RD830903
RD830906
RD830896
RD830899
RD830900
RD830897
Principal
Investigator (PI)
Kilduff, James
Lave, Lester
Lavine, Barry
Lowry, Gregory
Masten, Susan
Mitra, Somenath
Sabatini, David
Sadik, Omowunmi
Senkan, Selim
Subramanian,
Vivek
Wang, Joseph
Winter, William
Title
Graft Polymerization as a Route to Control
Nanofiltration Membrane Surface Properties to
Manage Risk of EPA Candidate Contaminants
and Reduce NOM Fouling
Environmental Implications of Nanotechnology
Compound Specific Imprinted Nanospheres for
Optical Sensing
Functional Fe(0)-Based Nanoparticles for In
Situ Degradation of DNAPL Chlorinated
Organic Solvents
Use of Ozonation in Combination with
Nanocomposite Ceramic Membranes for
Controlling Disinfection By-Products
Micro- Integrated Sensing System (u-ISS) by
Controlled Assembly of Carbon Nanotubes on
MEMS Structures
Nanostructured Microemulsions as Alternative
Solvents to VOCs in Cleaning Technologies
and Vegetable Oil Extraction
Advanced Nanosensors for Continuous
Monitoring of Heavy Metals
Nanostructured Catalytic Materials for NOx
Reduction Using Combinatorial Methodologies
Low Cost Organic Gas Sensors on Plastic for
Distributed Environmental Monitoring
Nanomaterial-Based Microchip Assays for
Continuous Environmental Monitoring
Ecocomposites Reinforced with Cellulose
Nanoparticles: An Alternative to Existing
Petroleum-Based Polymer Composites
Institution
Rensselaer
Polytechnic Institute
Carnegie Mellon
University
Oklahoma State
University
Carnegie Mellon
University
Michigan State
University
New Jersey Institute
of Technology
University of
Oklahoma, Norman
State University of
New York,
Binghamton
University of
California, Los
Angeles
University of
California, Berkeley
Arizona State
University
State University of
New York, Syracuse
Year
2003
2003
2003
2003
2003
2003
2003
2003
2003
2003
2003
2003
Amount
$349,000
$100,000
$323,000
$358,000
$353,959
$346,000
$315,000
$351,000
$356,000
$328,000
$341,000
$320,000
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EPA Nanotechnology White Paper
Grant #
RD831722
RD831716
RD831717
RD831712
RD831721
RD831719
RD831715
RD831714
RD831718
RD832531
RD831723
RD831713
GR832225\
RD832534
Principal
Investigator (PI)
Elder, Alison
Ferguson, P. Lee
Grassian, Vicki
Holden, Patricia
Huang, Chin-pao
Hurt, Robert
Monteiro-Riviere,
Nancy
Pinkerton, Kent
Tomson, Mason
Turco, Ronald
Veranth, John
Westerhoff, Paul
Zhang, Wei-xian
Alvarez, Pedro
Title
Iron Oxide Nanoparticle-lnduced Oxidative
Stress and Inflammation
Chemical and Biological Behavior of Carbon
Nanotubes in Estuarine Sedimentary Systems
A Focus on Nanoparticulate Aerosol and
Atmospherically Processed Nanoparticulate
Aerosol
Transformations of Biologically Conjugated
CdSe Quantum Dots Released Into Water and
Biofilms
Short-Term Chronic Toxicity of Photocatalytic
Nanoparticles to Bacteria, Algae, and
Zooplankton
Physical and Chemical Determinants of
Nanofiber/Nanotube Toxicity
Evaluated Nanoparticle Interactions with Skin
Health Effects of Inhaled Nanomaterials
Absorption and Release of Contaminants onto
Engineered Nanoparticles
Repercussion of Carbon Based Manufactured
Nanoparticles on Microbial Processes in
Environmental Systems
Responses of Lung Cells to Metals in
Manufactured Nanoparticles
The Fate, Transport, Transformation and
Toxicity of Manufactured Nanomaterials in
Drinking Water
Transformation of Halogenated PBTs with
Nanoscale Bimetallic Particles
Microbial Impacts of Engineered Nanoparticles
Institution
University of
Rochester
University of South
Carolina
University of Iowa
University of
California, Santa
Barbara
University of
Delaware
Brown University
North Carolina State
University
University of
California, Davis
Rice University
Purdue University
University of Utah
Arizona State
University
Lehigh University
William Marsh Rice
University
Year
2004
2004
2004
2004
2004
2004
2004
2004
2004
2004
2004
2004
2004
2005
Amount
$350,000
$349,740
$350,000
$343,853
$349,876
$350,000
$340,596
$349,998
$348,747
$350,000
$344,748
$349,881
$325,000
$375,000
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EPA Nanotechnology White Paper
117
Grant #
RD832531
RD832532
RD832530
RD832635
RD832536
RD832525
GR832382
RD832528
GR832371
RD832529
RD832526
GR832372
Principal
Investigator (PI)
Asgharian, Bahman
Bakshi, Bhavik
Barber, David
Bertsch, Paul
Bonzongo, Jean-
Claude
Colvin, Vicki
Cunningham, Mary
Jane
Diallo, Mamadou
Gawley, Robert
Gordon, Terry
Heiden, Patricia
Kibbey, Tohren
Kim, Jaehong
Kit, Kevin
Title
Mechanistic Dosimetry Models of Nanomaterial
Deposition in the Respiratory Tract
Evaluating the Impacts of Nanomanufacturing
via Thermodynamic and Life Cycle Analysis
Uptake and Toxicity of Metallic Nanoparticles in
Freshwater Fish
The Bioavailability, Toxicity, and Trophic
Transfer of Manufactured ZnO2 Nanoparticles:
A View from the Bottom
Assessment of the Environmental Impacts of
Nanotechnology on Organisms and
Ecosystems
Structure-Function Relationships in Engineered
Nanomaterial Toxicity
Gene Expression Profiling of Single-Walled
Carbon Nanotubes: A Unique Safety
Assessment Approach
Cellular Uptake and Toxicity of Dendritic
Nanomaterials: An Integrated Physicochemical
and Toxicogenomics Study
Nanosensors for Detection of Saxitoxin
Role of Particle Agglomeration in Nanoparticle
Toxicity
A Novel Approach to Prevent Biocide Leaching
Hysteretic Accumulation and Release of
Nanomaterials in the Vadose Zone
Fate and Transformation of C60 Nanoparticles
in Water Treatment Processes
Nanostructured Membranes for Filtration,
Disinfection and Remediation of Aqueous and
Gaseous Systems
Institution
CUT Centers for
Health Research
Ohio State University
University of Florida
University of Georgia
University of Florida
William Marsh Rice
Unibersity
Houston Advanced
Research Center
California Institute of
Technology
University of
Arkansas
New York University
School of Medicine
Michigan
Technological
University
University of
Oklahoma
Georgia Institute of
Technology
University of
Tennessee
Year
2005
2005
2005
2005
2005
2005
2005
2005
2005
2005
2005
2005
2005
2005
Amount
$375,000
$375,000
NSF
$363,680
$375,000
$375,000
NSF
$375,000
$340,000
$375,000
$333,130
$375,000
$375,000
$349,200
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EPA Nanotechnology White Paper
Grant #
GR832374
RD832527
GR832375
R01OH8806
RD832535
RD832537
RD832533
R010H8807
GR832373
Principal
Investigator (PI)
Lu, Yunfeng
Marr, Linsey
McDonald, Jacob
Mulchandani,
Ashok
O'Shaughnessy,
Patrick
Pennell, Kurt
Perrotta, Peter
Theodorakis, Chris
Xiong, Judy
Zhao, Dongye
Title
Novel Nanostructured Catalysts for
Environmental Remediation of Chlorinated
Compounds
Cross-Media Environmental Transport,
Transformation, and Fate of Manufactured
Carbonaceous Nanomaterials
Chemical Fate, Biopersistence, and Toxicology
of Inhaled Metal Oxide Nanoscale Materials
Conducting-Polymer Nanowire Immunosensor
Arrays for Microbial Pathogens
Assessment Methods for Nanoparticles in the
Workplace
Fate and Transport of C60 Nanomaterials in
Unsaturated and Saturated Soils
Effects of Nanomaterials on Human Blood
Coagulation
Acute and Developmental Toxicity of Metal
Oxide Nanoparticles to Fish and Frogs
Monitoring and Characterizing Airborne Carbon
Nanotube Particles
Synthesis and Application of a New Class of
Stabilized Nanoscale Iron Particles for Rapid
Destruction of Chlorinated Hydrocarbons in Soil
and Groundwater
Institution
Tulane University
Virginia Polytechnic
Institute and State
University
Lovelace Biomedical
& Environmental
Research Institute
University of
California, Riverside
University of Iowa
Georgia Institute of
Technology
West Virginia
University
Southern Illinois
University
New York University
School of Medicine
Auburn University
Year
2005
2005
2005
2005
2005
2005
2005
2005
2005
2005
Amount
$320,000
NSF
$375,000
$320,000
NIOSH
$375,000
$375,000
$375,000
NIOSH
$280,215
Total
EPA $22,613,343
70 TOTAL - 65 STAR, 3 NSF, 2 NIOSH
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EPA Nanotechnology White Paper 119
Appendix E: List of Nanotechnology White Paper External Peer
Reviewers and their Affiliations
Pratim Biswas, Ph.D.
Departments of Chemical and Civil Engineering
Environmental Engineering Science Program
Washington University in St. Louis
Richard A. Denison, Ph.D.
Senior Scientist
Environmental Defense
Rebecca D. Klaper, Ph.D.
Great Lakes WATER Institute
University of Wisconsin, Milwaukee
Igor Linkov, Ph.D.
Senior Scientist
Cambridge Environmental Inc
Current Affiliation: Managing Scientist, INTERTOX, Inc.
Andrew D. Maynard, Ph.D.
Chief Science Advisor
Project on Emerging Nanotechnologies
Woodrow Wilson International Center for Scholars
Vladamir V. Murashov, Ph.D.
Special Assistant to the Director
National Institute for Occupational Safety and Health
Stephen S. Olin, Ph.D.
Deputy Director
International Life Sciences Institute (ILSI) Research Foundation
Jennifer B. Sass, Ph.D.
Senior Scientist, Health and Environment
Natural Resources Defense Council
Donald A. Tomalia, Ph.D.
President & Chief Technical Officer
Dendritic Nanotechnologies, Inc.
Nigel J. Walker, Ph.D.
National Institute of Environmental Health Sciences
National Institutes of Health
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120 EPA Nanotechnology White Paper
David B. Warheit, Ph.D
Senior Research Toxicologist, Inhalation Toxicology
E.I. du Pont de Nemours & Co., Inc.
Haskell Laboratory
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