EPA/600/S-08/002
£EPA
United States
Environmental Protection
Agency
Draft Nanomaterial Research Strategy (MRS)
January 24, 2008
P
Office of Research and Development
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Writing Team
Nora Savage, Co-Lead
Randy Wentsel, Co-Lead
Michele Conlon, NERL Douglas McKinney, NRMRL
J. Michael Davis, NCEA Jeff Morris, OSP
Steve Diamond, NHEERL Dave Mount, NHEERL
Kevin Dreher, NHEERL Carlos Nunez, NRMRL
Maureen Gwinn, NCEA Chon Shoaf, NCEA
Thomas Holdsworth, NRMRL Barb Walton, NHEERL
Keith Houck, NCCT Eric Weber, NERL
Elaine Hubal, NCCT
Peer Review
ORD Science Council, August 2007
EPA Science Policy Council Steering Committee, September, 2007
External Peer Review April, 2008
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Table of Contents
MAJOR ACRONYM LIST VI
EXECUTIVE SUMMARY VII
1.0 INTRODUCTION 1
2.0 BACKGROUND 3
2.1 US NATIONALNANOTECHNOLOGY INITIATIVE 3
2.2 ENVIRONMENT, HEALTH, AND SAFETY Focus 4
2.3 EPA REGULATORY ROLE 6
2.4 ORD RESEARCH ACCOMPLISHMENTS 7
2.5 COLLABORATION/LEVERAGING 12
3.0 RESEARCH STRATEGY OVERVIEW 13
3.1 ORD SCIENTIFIC EXPERTISE APPLIED TO NANOMATERIALS 14
3.2 STRATEGIC DIRECTION OF RESEARCH THEMES AND SCIENCE QUESTIONS 17
Research Theme: Sources, Fate, Transport, and Exposure 18
Research Theme: Human Health and Ecological Research to Inform Risk Assessment and
Test Method 20
Research Theme: Risk Assessment 21
Research Theme: Preventing and Mitigating Risks 21
4.0 RESEARCH THEMES 22
4.1 RESEARCH THEME: SOURCES, FATE, TRANSPORT, AND EXPOSURE 22
4.1.1 KEY SCIENCE QUESTION 1: WHICH NANOMATERIALS HAVE A HIGH POTENTIAL FOR RELEASE
A LIFE-CYCLE PERSPECTIVE? 22
4.1.1.1 Background/Program Relevance 23
4.1.1.2 Research Activities 24
4.1.1.3 Anticipated Outcomes 26
4.1.2 KEY SCIENCE QUESTION 2: WHAT TECHNOLOGIES EXIST, CAN BE MODIFIED, OR MUST
BE DEVELOPED TO DETECT AND QUANTIFY ENGINEERED NANOMATERIALS IN ENVIRONMENTAL M EDIA
AND BIOLOGICAL SAMPLES? 27
4.1.2.1 Background/Program Relevance 27
4.1.2.2 Research Activities 28
4.1.2.3 Anticipated Outcomes 30
4.1.3 KEY SCIENCE QUESTION 3: WHAT ARE THE MAJOR PROCESSES/PROPERTIES THAT GOVERN THE
ENVIRONMENTAL FATE OF ENGINEERED NANOMATERIALS, AND HOW ARE THESE RELATED TO
PHYSIC ALAND CHEMICAL PROPERTIES OF THESE MATE RIALS? 31
4.1.3.1 Background/Program Relevance 31
4.1.3.2 Research Activities 32
4.1.3.3 Anticipated Outcomes 33
4.1.4 KEY SCIENCE QUESTION 4: WHAT ARE THE EXPOSURES THAT WILL RESULT FROM RELEASES OF
ENGINEERED NANOMATERIALS? 34
4.1.4.1 Background/ Program Relevance 34
4.1.4.2 Research Activities 35
4.1.4.3 Anticipated Results 37
4. 2 RESEARCH THEME: HUMAN HEALTH AND ECOLOGICAL EFFECTS RESEARCH
TO INFORM RISK ASSESSMENTS AND TEST METHODS 37
4.2.1 KEY SCIENCE QUESTION 5: WHAT ARE THE EFFECTS OF ENGINEERED NANOMATERIALS AND
THEIR APPLICATIONS ON HUMAN AND ECOLOGICAL RECEPTORS, AND HOW CAN THESE EFFECTS BEST BE
QUANTIFIED AND PREDICTED? 37
4.2.2 Background/Program Relevance 38
4.2.3 Research Activities 39
111
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4.2.4 Anticipated Outcomes 42
4.3 RESEARCH THEME: DEVELOPING RISK ASSESSMENT METHODS 43
4.3.1 KEY SCIENCE QUESTION 6: Do AGENCY RISK ASSESSSMENT APPROACHES NEED TO BE
AMENDEDTO INCORPORATE SPECIAL CHARACTERISTICS OFENGINEERED NANOMATERIALS 43
4.3.2 Background/Program Relevance 43
433 Research Activities 45
4.3.4 Anticipated Outcomes 46
4. 4 RESEARCH THEME: PREVENTING AND MANAGING RISKS 46
4.4.1 KEY SCIENCE QUESTION 7: WHAT TECHNOLOGIES OR PRACTICES CAN BE APPLIED TO MINIMIZE
RISKS OF ENGINEERED NANOMATERIALS THROUGHOUT THEIR LIFE CYCLE, AND HOW CAN
NANOMATERIALS' BENEFICIAL USES BE MAXIMIZED TO PROTECT THE ENVIRONM ENT? 46
4.4.2 Background/Program Relevance 46
4.4.3 Research Activities 48
4.4.4 Anticipated Outcomes 50
5.0 IMPLEMENTATION, RESEARCH LINKAGES, AND COMMUNICATION 51
6.0 REFERENCES 53
APPENDIX A RELATIONSHIP OF ORD RESEARCH STRATEGY TO EPA WHITE
PAPER RESEARCH NEEDS (CURRENT RESEARCH (CR), SHORT-TERM RESEARCH
(SR), AND LONG-TERM RESEARCH (LT)) 55
APPENDIX R DESCRIPTION OF EPA OFFICE OF RESEARCH AND DEVELOPMENT 65
List of Figures
Figure 2-1 Presidential/Congressional Commission on Risk Assessment and Risk
Management's Framework for Environmental Health Risk Management 6
Figure 2-2 EPA Office Roles, Statutory Authorities, and Categories of Research
Needs Related to Nanotechnology 8
Figure 2-3 STAR Grant Research Funding Areas 10
Figure 2-4 Federal Sources to Inform EPA's Nanotechnology Activities 12
Figure 3-1 Relative Priority of Research Themes 18
Figure 3-2 Relationship of Key Science Questions to Support Risk Assessment and
Management Decisions, Based on Comprehensive environmental
assessment (Davis and Thomas, 2006) 22
Figure 4-1 Relationship of Key Science Questions to Support Risk Assessment and
Management Decisions- Life Cycle Stages 23
Figure 4-2 Relationship of Key Science Questions to Support Risk Assessment and
Management Decisions- Analytical Detection 27
Figure 4-3 Relationships of Key Science Questions to Support Risk Assessment and
Management Decision - Pathways, Transport, and Transformation 31
Figure 4-4 Relationship of Key Science Questions to Support Risk Assessment and
Management Decisions-Exposure 34
Figure 4-5 Relationship of Key Questions to Support Risk Assessment and
Management Decisions- Effects 38
Figure 4-6 A multi-tier strategy for comparative and quantitive NMs/nanotechnology
health risk assessessment 40
IV
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Figure 4-7 Relationship of Key Science Questions to Support Risk Assessment and
Management Decisions-Risk Assessment 44
Figure 4-8 Relationships of Key Science Questions to Support Risk Assessment and
Management Decisions-Risk Management 46
Figure 5-1 Environmental and Health Research Theme Linkages 52
Figure B-1 Organization Chart for the Office of Research and Development 66
List of Tables
Table 2-1 STAR Grants for Nanotechnology Applications 9
Table 4-1 Several of the primary models/tools used by Program Offices for
Exposure assessment, general application and applicability to NMs in
their current form 35
v
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Major Acronym List
AA
ADME
AML
BMPs
CAA
CEA
CERCLA
CR
CREM
CT
DAA
DoD
DOE
DSSTox
HPG
IRIS
LCA
MOA
MOAs
MR-CAT
MYP
NAS
NCCT
NCEA
NCER
NCI
NCL
NEHI WG
NERL
NHEERL
NGO
NIEHS
NIOSH
NIST
NNCO
NNI
NPDs
NRC
NRMRL
NRS
NSET
NSF
NSTC
OECD
ORD
Assistant Administrator
absorption, distribution, metabolism, elimination
Advanced Measurement Laboratory
best management practices
Clean Air Act
comprehensive environmental assessment
Comprehensive Environmental Response Compensation and Liability Act
Current Research
Council for Regulatory Environmental Modeling
Committee on Technology
Deputy Assistant Administrator
Department of Defense
Department of Energy
Distributed Structure -Searchable Toxicity
Hypothalamic-Pituitary-Gonadal
Integrated Risk Information System
Life-Cycle Analysis
mechanism of action
Modes of Action
Materials Research Collaborative Access Team
multi-year plan
National Academy of Science
National Center for Computational Toxicology
National Center for Environmental Assessment
National Center for Environmental Research
National Cancer Institute
Nanotechnology Characterization Laboratory
Nanotechnology Environmental and Health Implications Working Group
National Exposure Research Laboratory
National Health and Environmental Effects Laboratory
Non-Governmental Organization
National Institute of Environmental Health Sciences
National Institute for Occupational Safety and Health
National Institute of Standards and Technology
National Nanotechnology Coordination Office
National Nanotechnology Initiative
National Program Directors
National Research Council
National Risk Management Research Laboratory
Nanomaterial Research Strategy
Nanoscale Science Engineering and Technology
National Science Foundation
National Science and Technology Council
Organization for Economic Cooperation and Development
Office of Research Development
VI
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The Nanomaterial Research Strategy (NRS) guides
the nanotechnology research program within EPA's
Office of Research and Development
Executive Summary
Research during the last two decades in science and engineering has resulted in the
fabrication of atomically precise structures. Nanotechnology is generally defined as the
ability to create and use materials, devices and systems with unique properties at the scale of
approximately 1 to 100 nm. At this particle size, quantum mechanical effects often dominate
and surface area per unit volume increases, resulting in materials that exhibit unique optical,
mechanical, magnetic, conductive and sorptive properties. The use of nanotechnology in the
consumer and industrial sectors is expected to increase significantly in the future.
Nanotechnology offers society the promise of major benefits, but also raises questions of
potential adverse effects.
The challenge for environmental protection is to ensure that, as nanomaterials are developed
and used, unintended consequences of exposures to humans and ecosystems are prevented or
minimized. In addition, knowledge concerning how best to apply nanotechnology to detect,
monitor, prevent, control, and cleanup pollution is needed.
The scope of this research
document is strategic in that it
discusses broad themes and
general approaches. The
purpose of this strategy is to
guide the EPA's Office of Research and Development (ORD) program in nanomaterial
research. The strategy builds on and is consistent with the foundation of scientific needs
identified in the report by the Nanotechnology Environmental and Health Implications
(NEHI) Working Group (NSTC, 2006), and on the EPA Nanotechnology White Paper (EPA,
2007). Special attention is given to EPA's role among federal agencies in addressing data
needs for hazard assessment, risk assessment, and risk management relevant to the EPA
mission and regulatory responsibilities. ORD will use the NRS and incorporate these
research activities into its multi-year planning process.
ORD has identified four key research themes and seven key scientific questions addressing
each of the research themes where we can provide leadership for the federal government
research program and support the science needs of the Agency.
• Sources, Fate, Transport, and Exposure
Which nanomaterials have a high potential for release from a life-cycle
perspective?
- What technologies exist, can be modified, or must be developed to detect and
quantify engineered nanomaterials in environmental media and biological
samples?
What are the major processes/properties that govern the environmental fate of
engineered nanomaterials, and how are these related to physical and chemical
properties of these materials?
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- What are the exposures that will result from releases of engineered
nanomaterials?
• Human Health and Ecological Research to Inform Risk Assessment and Test
Methods
- What are the effects of engineered nanomaterials and their applications on
human and ecological receptors, and how can these effects be best quantified
and predicted?
• Risk Assessment Methods and Case Studies
- Do Agency risk assessment approaches need to be amended to incorporate
special characteristics of engineered nanomaterials?
• Preventing and Mitigating Risks
- What technologies or practices can be applied to minimize risks of engineered
nanomaterials throughout their life cycle, and how can nanotechnologys'
beneficial uses be maximized to protect the environment?
The anticipated outcomes from this research program will be focused research products to
address risk assessment and management needs for nanomaterials in support of the various
environmental statutes for which the EPA is responsible.
Vlll
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IX
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1.0 Introduction
The purpose of this Nanomaterial Research Strategy (NRS) is to guide the nanotechnology
research program within the Environmental Protection Agency's (EPA's) Office of Research
and Development (ORD). The strategy builds on and is consistent with the foundation of
scientific needs identified in the report by the Nanotechnology Environmental and Health
Implications Working Group (NEHI) (NSTC, 2006), and on the EPA Nanotechnology White
Paper (EPA, 2007). Special attention is given to EPA's role among federal Agencies in
addressing data needs for hazard assessment, risk assessment, and risk management relevant
to the EPA mission and regulatory responsibilities. Key scientific questions of importance to
the Agency are identified and a research program is described to address those questions.
ORD will use the NRS to incorporate these research activities into its multi-year planning
process. As a living document, it is expected that this strategy will be further refined in
future years, based in part on the activities described herein and on other sources of new
knowledge about nanomaterials.
The NRS contains sections introducing the human health and environmental issues
associated with nanotechnology, provides background information on federal collaboration
and ORD research accomplishments to date, and discusses the development of the research
program. Since this emerging area of science is expanding at such a rapid pace, the NRS will
be a flexible document that is reviewed and modified as new scientific information is
published and as new issues arise for the EPA.
The use of nanotechnology in consumer and industrial sectors is expected to increase
significantly in the future. Nanotechnology is defined as the ability to create and use
materials, devices, and systems with unique properties at the scale of approximately 1 to 100
nanometers. Nanotechnology offers society \~T " " " ~. , ... ^
, • £• • , r- i i Nanotechnology is the ability to
the promise of major benefits, but also ^ , , • , . •
^ -11 rv- create and use materials, devices
raises questions or potential adverse effects. , , •,, .•
. , .M . , . F . , and systems with unique properties
At this particle size, quantum mechanical , ,, , f , , , ,
F 'M at the scale of approximately 1 to
100 nanometers.
effects often dominate and surface area per
mass is dramatically increased, resulting in
materials that exhibit unique physical, chemical, electrical, optical, mechanical and magnetic
properties. For example, gold is considered to be relatively inert, but depending on particle
size, nanoscale gold particles become very reactive and can be green, red, or other hues.
Beyond nanoscale versions of existing compounds, new structures such as the carbon-based
fullerenes and nanotubes can now be created using nanotechnology.
The challenge for environmental protection is to ensure that as nanomaterials are developed
and used, any unintended consequences of exposures to humans, ecosystems, and the
environment are prevented or minimized. In addition, knowledge concerning how best to
apply nanotechnology to detect, monitor, prevent, control, and cleanup pollution is needed.
The key to such understanding is a strong body of scientific information, and the sources of
such information are the numerous environmental research and development activities that
1 Use of the term nanomaterials refers to engineered nanomaterials and particles.
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are either currently underway or are pending within government agencies, academia, and the
private sector. Collaboration and communication in this field will undoubtedly play a pivotal
role in both how and when critical research questions are addressed.
Examples of the potential environmental benefits of nanotechnology and engineered
nanomaterials include: early environmental treatment and remediation; stronger and lighter
materials; and smaller, more accurate, and more sensitive sensing and monitoring devices.
Additional benefits include: cost-effective development and use of renewable energy sources;
development of processes with reduced material and energy requirements and minimal waste
generation; early detection and treatment of diseases; and improved systems to control,
prevent, and remediate pollution problems.
Revolutionary science and engineering advances applied to the existing infrastructure of
consumer goods, manufacturing methods, and materials usage could also have unintended
consequences on the environment. Members of the U.S. Congress, non-governmental
organizations (NGOs), and others have expressed concern that, while the field of
nanotechnology and the number of consumer products incorporating nanomaterials are
increasing dramatically, in many cases; the safety of these materials has not been
demonstrated.
EPA's mission is to protect human health and the environment. Therefore, understanding the
consequences of nanomaterials and how they may impact human health and ecosystems is of
critical importance to the Agency. This includes impacts associated with the manufacture,
processing, use, and disposal or recycling of engineered nanomaterials. These impacts can
occur as a result of exposure to and the toxicity of the materials themselves or altered
materials as these materials interact with other compounds or the environment as they age.
For instance, alterations in a materials' surface charge, morphology, coating stability,
functionalization, agglomeration, etc. will affect its fate, transport, and exposure to humans
and ecosystems. In fact, early toxicity studies have demonstrated changes in toxicity
potential with changes in surface charge, particle size, state of agglomeration and coating
type. In addition, exposure plays a pivotal role in the assessment of any potential harm from
these materials. Exposure can occur during production and/or manufacturing processes of
engineered nanomaterials, through their use, or when nanoproducts enter the waste stream
and are distributed throughout the environment.
ORD's mission in support of this broader Agency effort is comprised of, but not limited to,
the following actions.
• Performing research and development to identify, understand, and solve current and
future environmental problems
• Providing responsive technical support to EPA's mission
• Integrating the work of ORD' s science partners (other agencies, nations, private
sector organizations, academia, and international organizations)
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• Providing leadership in addressing emerging environmental issues and in
advancing the science and technology of risk assessment and risk management
The initial emphasis of the NRS will be to evaluate and assess the extent to which
nanomaterials and products impact the environment and human health. This focus is
consistent with EPA's primary statutory responsibilities to protect human health and the
environment and ORD's mission to address emerging environmental issues. Results from
this research will directly inform future policy decisions regarding how to address possible
adverse implications associated with the production, use, recycling or disposal of
nanomaterials and nanoproducts (i.e., products containing nanomaterials). Initially, a smaller
portion of the NRS proposed research will focus on beneficial environmental applications,
such as more effective control technologies and enhanced production processes that reduce
emissions and releases of conventional pollutants. As the program evolves over time, ORD
will augment its efforts in this area.
2.0 Background
2.1 US National Nanotechnology Initiative
The interest in research on the safety of nanomaterials extends beyond the EPA. The U.S.
National Nanotechnology Initiative (NNI) is a federal effort established to coordinate the
multiagency efforts in nanoscale science, engineering, and technology. The NNI is managed
within the framework of the National Science and Technology Council (NSTC), the Cabinet-
level council by which the President coordinates science, space, and technology policies
across the federal government. The Nanoscale Science Engineering and Technology (NSET)
Subcommittee of the NSTC coordinates
The U.S. National Nanotechnology
Initiative is a federal effort within the
planning, budgeting, program
U. S. established to responsibly develop implementation and review of the NNI to
nanotechnology. ensure a balanced and comprehensive
initiative. The NSET Subcommittee is
composed of representatives from the 26 agencies participating in the NNI. Interagency
management of the NNI occurs within the framework of the NSTC Committee on
Technology (CT).
As the active interagency coordinating body, the NSET Subcommittee establishes the goals
and priorities for the NNI and develops plans, including appropriate interagency activities,
aimed at achieving those goals. The NSET Subcommittee promotes a balanced investment
across all agencies, so as to address all of the critical elements that will support the
responsible development and utilization of nanotechnology. The NSET Subcommittee
exchanges information with academic, media, industry, and State and local government
groups. A number of working groups have been formed under the NSET Subcommittee to
improve the efficiency of its operations and focus interagency attention and activity. Current
working groups are focused on environmental and health implications of nanotechnology,
liaison with industries, nanomanufacturing, international and public engagement activities.
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The National Nanotechnology Coordination Office (NNCO) provides technical and
administrative support to the NSET Subcommittee, in the preparation of multi-agency
planning, budget, and assessment documents. The NNCO also serves as the point of contact
on federal nanotechnology activities for government organizations, academia, industry,
professional societies, foreign organizations, and others. Finally, the NNCO develops and
makes available printed and other materials concerning the NNI, and maintains the NNI
website, www.nano.gov.
2.2 Environment, Health, and Safety Focus
One of the priorities of the NNI is to support research and development that leads to a
detailed understanding of the environmental, health and safety impacts of nanomaterials and
nanoproducts and the potential environmental impacts of the application of nanotechnology.
The EPA Nanotechnology White Paper also indicates that research into the potential
implications of nanomaterials is critical. The following provides additional rationale to
support our initial focus on the implications of nanomaterials and nanoproducts:
• Studies of potential health risks of nanomaterials are supported by six federal
agencies: the National Institute of Environmental Health Sciences (NIEHS)
(including the National Toxicology Program); the National Institute for Occupational
Safety and Health (NIOSH); EPA; the Department of Defense (DoD); the Department
of Energy (DOE); and the National Science Foundation (NSF).
• The NSET interagency group was established to enable coordination among the
member agencies, to identify and prioritize research needed to support regulatory
decision-making, and to promote better communication among the federal
government, industry, and researchers. The Nanotechnology Environmental and
Health Implications (NEHI) working group established within NSET to focus on
coordination of environmental, health and safety research. ORD is a member NSET
and its various subgroups and also participates in international dialogue on
environmental, health, and other societal issues.
• In September 2006, the NEHI working group of the NSET released a report,
"Environmental, Health, and Safety Research Needs for Engineered Nanoscale
Materials," outlining the research needed for the federal government to understand
and adequately address the potential risks of nanomaterials. Areas of particular
interest to EPA in the NNI report include assessing exposure to nanomaterials,
determining the behavior and impact of nanomaterials on the environment,
understanding the fate, transport, and transformation of nanomaterials in biological
systems; the ecological effects on the environment; the health effects of
nanomaterials throughout living organisms; and development of sampling methods
for relevant nanomaterials to evaluate potential effects.
(http://nano.gov/NNI_EHS_research_needs.pdf)
• In 2004 EPA's Science Policy Council (SPC) created an Agency-wide workgroup to
examine nanotechnology from an environmental perspective. The workgroup
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developed aNanotechnology White Paper, which was issued in February, 2007
(EPA/100/B-07/001) http://www.epa.gov.OSA/nanotech.htm. The purpose of the
White Paper is to both inform EPA management of the science issues and needs
associated with nanotechnology and communicate nanotechnology science issues to
stakeholders and the public.
The Nanotechnology White Paper provides:
• A basic description of nanotechnology
• Information on why EPA is interested in nanotechnology
• Potential environmental benefits of nanotechnology
• Risk assessment issues specific to nanotechnology
• A discussion of responsible development of nanotechnology and the EPA's statutory
mandates
• An extensive review of research needs for health, ecological and environmental
applications and implications of nanotechnology
• Staff recommendations for addressing science issues and research needs, including
research needs within most risk assessment topic areas (e.g., human health and
ecological effects research, fate and transport research)
One of the Nanotechnology White Paper appendices describes EPA's framework for
nanotechnology research, which outlines the strategic focus of the research program. The
goal of EPA's nanotechnology research effort is to provide key information on
environmental implications and potential beneficial environmental applications to
complement other federal, academic, and private-sector research activities. Appendix A of
the NRS presents a side-by-side table that summarizes the research needs from the EPA
White Paper and a corresponding column that lists ORD current research (CR), short-term
research (SR) and long-term research (LR) activities. In addition, the Agency is actively
engaged in the pursuit of knowledge by:
• Supporting in-house and extramural research
• Organizing scientific workshops, symposia and conferences
Coordinating with stakeholders—including industry, academia, NGOs, other federal
agencies, and international organizations—to obtain information and enhance
coordination and collaboration
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• Coordinating within EPA to ensure that the right questions are asked and the right
data are obtained that will address the various statutory mandates for environmental
protection
In addition to the NEHI research needs document and the EPA Nanotechnology White Paper,
a number of national and international stakeholders have published articles and reports that
highlight the need for research related to the environmental, health, and safety aspects of
nanotechnology (Maynard, 2006). There is clearly global interest in understanding and
managing the risks of this emerging technology so that its many potential benefits, including
those for the environment, may be realized.
2.3 EPA Regulatory Role
Regulatory decision making in EPA requires risk managers to have sufficient information
on risk and the social and economic implications of various control options before
making decisions. Informing the risk manager of risk and options for controlling risk so
that wise decisions can be made has been further codified in the
Presidential/Congressional Commission on Risk Assessment and Risk Management
(Presidential/Congressional Commission, 1997). This Commission developed a general
framework for risk and risk management designed to work in a variety of situations, but
primarily intended for risk decisions related to setting standards, controlling pollution,
protecting health, and cleaning up the environment. The framework shown in Figure 2-1
puts health and environmental problems in their larger, real-world context. In this
framework, the process begins by defining the problem. Then the risks associated with
the problem are analyzed followed by an examination of the options for addressing the
risks. Decisions are made about which option to implement and actions to take to
implement the decisions. Measurement techniques are developed to allow determination
of the extent of the problem—both prior to, and after, the actions. Finally, an evaluation
of the action's results is conducted. All of this is carried out in collaboration with
stakeholders at every step possible.
Figure 2-1 - Presidential/Congressional Commission on Risk Assessment and Risk
Management's Framework for Environmental Health Risk Management
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Regulatory decisions regarding nanomaterials are covered under current statutes. EPA
intends to review nanomaterial products and processes, pursuant to its authorities under
the Toxic Substances Control Act (TSCA), the Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA), the Clean Air and Water Acts (CAA and CWA), the Safe
Drinking Water Act (SDWA) Comprehensive Environmental Response Compensation
and Liability Act (CERCLA) and Resource Conservation and Recovery Act (RCRA).
Under the Toxic Substances Control Act (TSCA), Premanufacture Notices must be
submitted to the EPA by an entity that wishes to manufacture or import new chemical
substances that are not currently on the TSCA Inventory of Chemical Substances. There
is some question as to whether nanomaterials are "new" compounds. Under FIFRA
nanomaterials added to an existing pesticide product may require reapproval, and the
EPA must determine whether the altered product might cause unreasonable adverse
effects on the environment including human health risks. The CAA allows for the
development of air quality criteria for pollutants anticipated to endanger public health and
welfare, mandates the identification of the sources and the issuance of technology-based
emissions standard for 189 pollutants, and requires that any mobile source fuel or
additive be registered. Risks from airborne nanomaterials may reasonably need assessing
in all of these areas. Wastewater streams containing nanomaterials might be controlled
through effluent limits in permits established under the CWA. If nanomaterials enter
drinking water they may be subject to regulation using Maximum Contaminant Level
Goals and Maximum Contaminant Levels under SDWA. Risks from nanomaterials in
waste sites would be evaluated and controlled under the authority of CERCLA and
RCRA Figure 2-2 highlights the information needs of the major statutes that EPA
administers.
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Figure 2-2 - EPA Office Roles, Statutory Authorities, and Categories of Research
Needs Related to Nanotechnology
Office of
Prevention,
Pesticides, and
Toxic
Substances
Toxic Substance
_ Control Act:
Review/Oversight of
Industrial Chemical
Federal
Insecticide ,
Fungicide,
RodenticideAct:
Registration of
Pesticides
Chemical
Identification and
Analysis
Environmental
Fate and
Treatment
Releases and
Human Exposure
Health and
Ecological Effects
Risk Assessment
Environmental
Detection and
Analysis
Pollution Prevention
_ Act: Incorporate P2
into all aspects of
chemical oversight
Chemical Identification •
and Analysis \
~! Environmental Fate 1
and Treatment j
Office of Air and
Radiation
Clean Air Act:
Criteria air
pollutants,
— Hazardous air
pollutants,
Registration of fuels
and fuel additives
1
: Chemical
! Identification and
1 Analysis
; Environmental
! Fate
1 Releases and
4 Human Exposure
! Health and
1 Ecological Effects
Risk Assessment
| Environmental
j Detection and
Analysis
Office of Water
Office of Sol id
Waste and
Emergency
Comprehensive
Environmental
Response,
Compensation, and
Liability Act and
Resource Conservation
and Recovery Act:
Hazardous substances
or wastes,
Solid Waste
Chemical Identification |
and Analysis •
Environmental Fate |
and Treatment j
Releases and Human •
Exposure I
Health and Ecological 1
Effects
Risk Assessment I
Environmental j
Detection and
Analysis I
Remediation i
Applications
Chemical |
Identification
and Analysis I
Environmental j
Fate and
Treatment I
-
-1
1
Office of
Research and
Development
1
Coordinate
Research
Strategy
Conduct
Research for
all of those
needs
Chemical
Identification
and Analysis
Environmental
Fate and
Treatment
Office of
Enforcement
and Compliance
Assurance
Evaluation :
of existing !
statutory/ I
regulatory j
framework !
regarding |
enforcement :
issues !
Science to |
support •
enforcement ]
Research
Needs
2.4 ORD Research Accomplishments
2.4.1 ORD Science to Achieve Results (STAR) Program
The extramural research program at EPA has taken a holistic approach to studying
nanotechnology, targeting research toward the identification of the beneficial applications of
nanotechnology and seeking to increase data and understanding of potential effects. Science
To Achieve Results (STAR) grants and Small Business Innovation Research (SBIR)
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contracts were designed to generate exposure, fate/transport, and human and eco-toxicity
data, pursue novel pollution prevention and environmentally benign manufacturing and
processing techniques, and assist in the development of novel treatment and remediation
technologies.
The objective of STAR is to meet the data needs of the various EPA offices as well as those
of other agencies, the scientific community, and the general public. This approach allows the
Agency to play an important role in supporting the development of new technologies that
could improve the environment, as well as in ensuring that new materials and compounds do
not pose unreasonable risks to humans or the environment. One of the ways that the Agency
supports research is through its STAR competitive grants program, managed by the National
Center for Environmental Research (NCER) in ORD. The objective of STAR is to meet the
data needs of the various EPA program offices, as well as those of other agencies, the
scientific community, and the general public. Grants funded through the STAR program
have focused on both the applications and implications of nanotechnology use.
The initial grants funded by STAR in 2002 were primarily on applications. Since 2002,
ORD has funded 35 grants focused on using nanotechnology to address environmental
challenges. The areas of research include green manufacturing, contamination remediation,
sensors for environmental pollutants, and waste treatment. Focus has shifted to implications
as interest in gathering data on the safety of nanomaterials have grown. By 2008, the STAR
program had funded more than $29 million for 86 research projects on the environmental
applications and implications of nanotechnology.
Table 2-1 - STAR Grants for Nanotechnology Applications
Research category
Green manufacturing
Remediation
Sensors
Treatment
TOTAL
Number of srants
7
10
13
5
35
Award totals
$2,393,000.00
$3,433,394.00
$4,564,000.00
$1,817,089.00
$12,207,483.00
Since 2004 STAR grants have been issued in collaboration with other federal agencies
including NSF, NIEHS, NIOSH, and DOE. ORD works with these agencies to identify and
issue calls for proposals in areas related to human and environmental health. EPA expects
that future calls for proposals will involve other federal agencies, as well as international
organizations, such as the European Commission. Future STAR research calls for proposals
that will seek to facilitate collaborations between ORD researchers and STAR researchers.
This will result in strengthening extramural research through the expertise of Agency
scientists and will also strengthen the Agency in-house nanotechnology research efforts,
which are in their initial stages.
Figure 2-3 shows STAR research funded to date in nanotechnology. Although it is apparent
from this figure that the bulk of the STAR research (up until the publication date of this
research strategy) falls within the categories of fate/transport and toxicity, the Agency's
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nanotechnology research strategy will focus on fate/transport and exposure. Furthermore,
this research will be conducted from a complete life cycle perspective to facilitate research
and improve understanding of the effects of nanomaterials, enabling appropriate risk
assessment and management strategies to be developed. These are focus areas where the
Agency can be most effective and have the most impact while also playing a key role in the
remaining areas by coordinating with other federal agencies.
$ Million
D Life Cycle • Aerosol D Exposure D Fate/Transport • Toxicity
Research Area
Figure 2-3 - STAR Grant Research Funding Areas
The number of grants related to the implications of nanotechnology use that have been
funded by the STAR program has increased significantly over the years. In 2002 there were
two grants funded for air research only, and in 2003 two were funded for life-cycle analysis
(LCA). In 2004, 2005, and 2006 EPA funded 12, 14, and 21 grants, respectively. The
Agency will continue to concentrate extramural support on implications research in the near
future. EPA expects that future calls for proposals will be done in collaboration with other
federal agencies, as well as international agencies, such as the European Commission. The
table below categorizes the nano implications studies into those that address the potential
human health and environmental effects, respectively. Each "x" in the table indicates that
the study includes a particular endpoint and material class as described in the research
protocol. A single study could be represented more than once in the table, and a single "x"
may represent a number of compounds in a particular materials class. For example, if a study
were to include several metal oxides in the research protocol, all of these compounds would
be represented by one "x. "
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Study Focus
Cytotoxicity
General toxicity
Dermal
Pulmonary
Translocati on/Disposition
Material Class
Carbon
Nanotubes
XXXX
X
XXXXX
X
Fullerenes
XX
XX
X
X
Metal-Based
XXXX
XX
XXXX
XXX
Other*
XXX
In addition to the STAR funded nanotechnology research grant program, EPA supports
nanotechnology research conducted by small businesses. EPA's Small Business Innovation
Research (SBIR) program has funded 49 projects for over $5 million in funding related to
nanotechnology development, nanomaterials, and clean technology. These projects range
from a nanocomposite-based filter for arsenic removal in drinking water to nanofibrous
manganese dioxide for emission control of volatile organic compounds (VOCs). The SBIR
program is also interested in technologies that utilize nanotechnology to detect conventional
pollutants in aqueous, air, and soil environments.
For a full list of nanotechnology projects funded under EPA's SBIR program, please visit:
http://es.epa.gov/ncer/nano/research/sbir_index.html
2.4.2 ORD's In-house Research Program
Within the in-house research program, ORD has to date engaged in limited research related
to nanotechnology including:
• Developing low-emitting coating formulations using nanopolymers: ORD researchers
developed a novel family of modified "hyperbranched" polymers, which were
successfully formulated with commercial resin for auto refmishing.
• Evaluating pollution prevention potential: ORD researchers have evaluated the
potential to reduce or eliminate waste from manufacturing processes and foster better
materials; allowing more efficient production, effective break down of hazardous
material, and providing alternatives to solvents or high temperature processes that can
damage the environment.
* Testing of nanotechnology membranes: ORD researchers used the Fyne Process
nanofiltration system (PCI Membrane Systems Inc.), to reduce total organic carbon
(TOC) concentration in source water by more than 95%.
• Studying iron-based permeable reactive barriers: ORD research in this area involves
in-situ remediation of contaminant plumes in ground-water systems. This work
improved the understanding of the dynamics of iron corrosion relative to the rates and
sustainability of beneficial reactions that effect contaminant removal or
transformation.
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• Researching health effects: Using various cellular models, ORD researchers have
examined the in vitro pulmonary toxicity of carbon nanotubes as well as the
neurological toxicity of nano TiO2. These studies have shown: 1) unique gene
expression patterns within airway cells exposed to carbon nanotubes versus
environmental particles; 2) surface modifications influenced carbon nanotube in vitro
pulmonary toxicity; and 3) cellular oxidative stress to be a mechanism of nano TiO2
induced toxicity in brain microglia cells.
2.5 Collaboration/ Leveraging
EPA is leveraging its research and development efforts by partnering with other federal
agencies such as NIH/NIEHS, NIOSH, NSF, and DOE, which are also conducting or
supporting research on the toxicity and human health effects of nanomaterials. The Agency
is also coordinating with the National Institute of Standards and Technology (NIST) and the
National Institutes of Health/Nanotechnology Characterization Laboratory (NIH/NCL),
which are conducting key research on nanomaterial metrology, characterization, and
detection devices. Seeking to continually broaden its collaborative efforts, EPA coordinates
its research activities with the Nanotechnology Environmental and Health Implications
working group of theNanoscale Science, Engineering, and Technology subcommittee of the
NSTC. Figure 2-4 illustrates the various federal sources of scientific information for use in
EPA decisions.
Figure 2-4: Federal Sources to Inform EPA's Nanotechnology Activities.
(Based on information in the NNI Supplement to the 2006 and 2007 budget and other information.)
Understanding Nanotechnology
Characterization,
Properties
DOD
DOE
EPA
NASA
N IH
NIST
NSF
Instrumentation,
Metrology,
Standards
DOD
DOE
NASA
NIH
NIST
NSF
EPA
Research
Risk assessment
Risk management
Sustainability
Stewardship
Applications
Implications
Fate, Transport,
Transformation,
Release,
Treatment
DOD
DOE
EPA
NIH
NIOSH
NSF
Detection,
Monitoring
DOD
EPA
NIH
NIOSH
NSF
USGS
Note: NIH includes NIEHS, NCI (NCL),NTP
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Internationally, EPA plays a leading role in the nanomaterial testing/test guidelines efforts of
the Organization for Economic Cooperation and Development (OECD). Future extramural
research efforts involve collaborating with the European Commission, Japan, China,
Singapore, and Taiwan, among others. Each of these entities has an important role to play in
meeting the considerable global research needs related to nanotechnology and the
environment. Because EPA's research and development program is focused on risk
assessment and management to support Agency decisions, as well as on research areas not
addressed by other agencies, the impact on the total federal research enterprise of the
scientific information generated by our laboratories and centers is disproportionately high
relative to the size of our program. This will enable the Agency to continue to provide strong
leadership in the area of nanotechnology EHS both nationally and internationally.
3.0 Research Strategy Overview
The purpose of ORD's research program in support of the National Nanotechnology
Initiative is to conduct focused research to address risk assessment and risk management
needs for nanomaterials in support of the various environmental statutes for which the EPA is
responsible. This program will be coordinated with research conducted by other federal
agencies, where the EPA will lead selected research areas and rely on research products
under the leadership of its federal research partners in other research areas. Collaboration is
encouraged among researchers across the government, industry, and the international
community.
ORD is uniquely positioned within the federal government to support the overall NNI
objectives while also supporting EPA's strategic goals.
• ORD's research laboratories and centers have the expertise to integrate human health
and ecological data to provide the Agency's program and regional offices with
scientific information most appropriate for risk assessment and decision support.
• ORD has extensive facilities to test nanomaterials in aquatic and terrestrial
ecosystems, as well as to measure and model the fate, transport, transformation, and
effects of nanomaterials in environmental media.
• ORD has unique and extensive historical laboratory expertise and capacity to identify
approaches to prevent and manage risks from environmental exposures to
nanomaterials, including the development and verification of technologies to detect,
measure, and remove nanomaterials from environmental media.
• ORD has the capability to leverage results from EPA STAR grant research, as well as
collaborating with grantees to address the many challenging research issues.
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3.1 OKD Scientific Expertise Applied to Nanomaterials2
3.1.1 Fate and Transport Expertise and Capabilities
ORD researchers have extensive expertise and experience in understanding and modeling the
fate, transport, retention, and release of chemicals in various environmental media.
Scientific knowledge concerning the fate and transport of compounds over a range of
conditions in air, aquatic systems, soils, and sediment has been a particular strength of ORD
science.
Examples of expertise in this area include:
• Residual soil contaminants at CERCLA waste sites have been evaluated by ORD
scientists to determine if the contaminants would eventually migrate to the underlying
aquifer.
• Assessments have been made by ORD researchers, based on considerations of the
phases in which a compound is likely to occur in the atmosphere, of the degree to
which the substance will respond to a group of factors that influence its fate in
atmospheric, surface, or subsurface environments.
• ORD researchers have estimated the approximate lifetime in the atmosphere, soil, or
water of a variety of compounds.
• ORD researchers have made accurate determinations concerning whether emitted or
released compounds can be detected in the environment.
• The ways and processes by which compounds are altered as they contact other
compounds, as they age, and as they enter and exit various environmental media have
been extensively studied by ORD researchers.
3.1.2 Human and Ecological Effects Expertise and Capabilities
ORD's health and ecological risk assessment research within the Air, Water, and Safe
Products/Safe Pesticides programs has established unique multi-disciplinary facilities and
expertise that are directly applicable to addressing the health and ecological implications of
nanomaterials, and their applications, resulting from various potential routes of exposure.
Facilities and scientific expertise established in ORD have been called upon by Congress
several times to assess the health effects of other types of particles including paniculate
matter in ambient air. These substantial health and ecological risk assessment-based research
activities have provided critical information for Agency and regional regulatory decisions
and guidance such as:
" A brief description of EPA Office of Research and Development is presented in Appendix B
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• ORD Particulate Matter (PM) (EPA/600/P-99/002af-bf) research program has
significantly contributed to the Air Quality Criteria Document for PM by elucidating
health and ecological effects of ultrafme, fine, and coarse ambient air, as well as
source specific primary combustion particle dosimetry, fate,
pulmonary/extrapulmonary effects, hazard identification, and susceptibility factors.
This research supports the CAA in setting ambient PM levels. In addition, research
on the health and ecological effects of Orimulsion® (EPA/600/R-01-056a, 2001) has
provided the Agency with risk assessment information on the use of alternative fossil
fuels.
• Research examining the health and ecological effects of pesticides, toxic substances,
as well as water borne pollutants such as arsenic has supported the FIFRA, TSCA,
and the CWA.
3.1.3 Computational Toxicology Expertise and Capabilities
The EPA program in computational toxicology applies mathematical and computer models
and molecular biological and chemical approaches to explore both qualitative and
quantitative relationships between sources of environmental pollutant exposure and adverse
health outcomes (http://www.epa.gov/comptox/index.htmn. This integration of modern
computing with molecular biology and chemistry is allowing scientists to better prioritize
data, inform decision makers on chemical risk assessments, and understand a chemical's
progression from the environment to the target tissue within an organism, and ultimately to
the key steps that trigger an adverse health effect. Unique capabilities that are currently
available and under development through ORD's National Center for Computational
Toxicology include DSSTox and ToxCast™
The Distributed Structure-Searchable Toxicity (DSSTox) database network is creating a
chemical data foundation for improved structure-activity and predictive toxicology
capabilities across and outside of EPA (http://www.epa.gov/ncct/dsstox/).
The ToxCast™ program for prioritizing toxicity testing of environmental chemicals
(http://www.epa.gov/comptox/toxcast/), is a new research effort in EPA to develop the ability
to forecast toxicity based on bioactivity profiling and, ultimately, to develop methods of
prioritizing chemicals for further screening and testing to assist EPA in the management and
regulation of environmental contaminants.
3.1.4 Risk Assessment Expertise and Capabilities
ORD has a risk assessment center that focuses on implementation of the risk assessment
paradigm as described by the National Academy of Sciences in its 1983 document, Risk
Assessment in the Federal Government. This is done by providing qualitative and
quantitative health hazard assessment of priority environmental contaminants for
incorporation into applied risk assessments, exemplified by the Integrated Risk Information
System (IRIS) toxicological reviews and summaries on reference doses, reference
15
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concentrations, oral cancer slope factors, and cancer inhalation unit risks. ORD also prepares
Integrated Science Assessments (formerly Air Quality Criteria Documents) for the six
criteria air pollutants. ORD has also used this capacity to respond to urgent agency priorities
such as Hurricane Katrina. In addition, developing models, methods, and guidance to
incorporate the latest scientific advances into EPA risk assessment practice is a continuing
function of ORD. ORD's National Center for Environmental Assessment identifies,
evaluates, and conveys to the scientific community key uncertainties and research needed to
improve health risk assessments through laboratory, field, and methods research. ORD also
provides program office support and consultation for assessments related to air, water, waste,
and pesticides. The application of risk assessment methods to nanomaterials is within the
scope of ORD's past performance and current capacity.
3.1.5 Source Characterization and Risk Management Expertise and Capabilities
ORD has extensive state-of-the-art facilities and equipment as well as significant expertise
that can be applied to characterize and manage releases of engineered nanomaterials.
ORD's nationally and internationally recognized scientists and engineers have developed the
following core engineering competencies/capabilities that can be applied to the
nanotechnology issue: 1) characterization of emissions to air and releases to water and land
and their subsequent movement through various media; 2) evaluation of devices and
procedures to detect and characterize nanomaterials in environmental media, including
identifying optimal operating conditions; 3) characterization of the effectiveness of
abatement technology for emissions or effluent control; 4) identification and characterization
of options to prevent pollution, including greener synthesis and manufacturing; 5) assessment
of the life cycle implications of industrial and commercial products and processes; 6)
verification of commercial-ready measurement and management technology; and 7)
modeling efforts to evaluate the effectiveness of potential risk management options.
This work is carried out in numerous facilities across various ORD sites. These facilities can
be readily deployed to address key nanotechnology science questions and perform needed
research. In the air area, combustion research facilities have been used to develop,
characterize, and optimize sorbents, catalysts, and other environmentally beneficial materials.
These facilities have also been used to understand the fundamental mechanisms of pollutant
capture and to determine the molecular scale structure-property relationships of these
environmental materials. In the water and land areas, ORD has multiple multi-purpose, high-
bay research facilities in Cincinnati, Ohio, which have the capacity to test and evaluate pilot
and bench-scale water, wastewater, and hazardous waste treatment technologies. These
facilities also have the capacity to evaluate the fate of nanomaterials in both anaerobic and
aerobic landfills. The groundwater research facility in Ada, Oklahoma has the capability to
evaluate nanomaterials in the subsurface soils and waters. Additionally, these facilities are a
RCRA permitted treatment, storage, and disposal facility. ORD also has access to other
state-of-the-art facilities and equipment through agreements with other organizations. For
example, ORD researchers are participating in the creation of a new laboratory facility at
Argonne National Laboratory dedicated to environmental research at the nanoscale. This
facility will provide a location for cutting-edge research using X-ray spectroscopy for studies
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on the characterization, speciation, and behavior of inorganic contaminants at the atomic
scale. It will also have the capability to examine engineered nanomaterials and assess their
physical properties (e.g. structure, bonding, and surface characteristics).
3.1.6 Exposure Expertise and Capabilities
In support of theNNI, the Agency will take the lead role to assess the environmental fate and
transport of nanomaterials through air, aquatic, and terrestrial ecosystems. ORD has both the
expertise and capability to play a significant role in this effort. ORD has a laboratory
dedicated to conducting human health and ecological exposure research that provides the
tools for EPA to conduct its mission. ORD also has the capability to provide cutting edge
research that addresses the most critical exposure uncertainties associated with EPA's policy
decisions and to provide international scientific leadership in the area of exposure research.
Exposure research is used to develop the methods, data, and models that describe our
understanding of those exposures that may lead to human and ecological health risks. ORD
is improving environmental quality through excellence in ecosystems and human exposure
research by discovering fundamental process knowledge (research) and integrating it into
state-of-the-science computational technologies and modeling systems (primarily
development).
3.2 Strategic Direction of Research Themes and Science Questions
EPA is developing a nanotechnology research strategy for fiscal years 2008-2012 that is
problem-driven and focused on addressing the Agency's needs. In developing this research
framework, ORD went through a prioritization process where it evaluated research
recommendations from the EPA Nanotechnology White Paper and the Nanotechnology
Environmental and Health Implications Interagency Working Group of the Nanoscale
Science, Engineering and Technology subcommittee on Nanotechnology (NNI, 2006). ORD
scientists prioritized research topics using several defining questions:
• What research themes are important to support Agency risk assessment and
management activities?
• Where can ORD expertise be applied to address and lead Federal government
research areas?
• How can partnerships with Federal, academic, and industry researchers enhance
research activities?
• What are the key scientific questions within each research theme that need to be
addressed?
ORD has identified four key research themes where it can provide leadership for the National
Nanotechnology Initiative and support the science needs of the Agency.
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ORD Research Themes:
Sources, Fate, Transport, and Exposure
Human Health and Ecological Research to Inform Risk Assessment
and Test Methods
Risk Assessment Methods and Case Studies
Preventing and Mitigating Risks
The current priority of these research themes follows the general directions described below.
* Sources, Fate, Transport, and Exposure will be high priority from PY07 - FY10 and
moderate priority in FY 11 — FY 12.
» Human Health and Ecological Research to Inform Risk Assessment and Test
Methods will be a moderate priority from FY07 - FY09 and a high priority in FY10-
FY12.
• Risk Assessment Methods and Case Studies will be a moderate priority in FY07 -
FY08, a high priority in FY09 - FY1 \, and a moderate priority in FY12.
• Preventing and Mitigating Risks will be a moderate priority in FY07 - FY10 and a
high priority in FY11 and FY12.
Preventing and Mitigating Risks
Human Health and Ecological Research
Sources, Fate, Transport, and Exposure
Risk Assessment Methods and Case Studies
2007
2012
Figure 3-1 - Relative Priority of Research Themes
The following section defines the research themes and the associated key science questions.
Research Theme: Sources, Fate, Transport, and Exposure
This research theme will focus on identifying potential sources of nanomaterials in the
environment, on understanding the fate and transport in environmental media, and on
characterizing exposure pathways. Activities under this research theme will address research
needs identified in the NEHI document (2006) and the EPA Nanotechnology White Paper.
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The primary objective of research conducted under this theme will be to determine the
release points of engineered nanomaterials into the environment and the physical and
chemical properties controlling the transport and transformation of nanomaterials in
environmental media. This work will provide the basis for prioritizing potential human
health and ecological exposure pathways that warrant further exploration.
Key Science Questions:
1. Which nanomaterials have a high potential for release from a life-cycle perspective?
-high-potential source characterization in industries/processes
-identification/characterization of potentially released materials
- characteristics and probability of byproducts
- entry point into the environment
-intentional "releases" such as cleanup or detection technology
-potential release during disposal/recycling
2. What technologies exist, can be modified, or must be developed to detect and quantify
engineered nanomaterials in environmental media and biological samples?
- adequacy of existing methods/technology
- new detection/quantification methods
- applications of nanomaterials in new analytical/monitoring techniques
-tools for personal or environmental monitoring
- performance evaluation/standardization
3. What are the major processes/properties that govern the environmental fate of engineered
nanomaterials, and how are these related to physical and chemical properties of those
materials?
- fate processes in air, water, soil, and biota
- environmental modification of released materials
- partitioning behavior
- chemical interactions
- environmental media interactions
-predictive environmental models
4. What are the exposures that will result from releases of engineered nanomaterials?
- adequacy of current exposure assessment approaches
- exposure variability for human subpopulations or specific eco receptors
- early identification of potential biomarkers
- longer term issues
- pathways for humans and ecological receptors
- specific routes of uptake
-frequency, duration, and magnitude as they relate to dose parameters
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Research Theme: Human Health and Ecological Research to Inform Risk Assessment
and Test Methods
The diversity of nanomaterials and their applications and their ability to translocate from
their initial site of deposition, represent significant challenges in assessing their human health
and ecological effects. Test methods that can determine the toxicity and hazardous physical
and chemical properties of nanomaterials in a validated, timely, and economic manner need
to be developed. ORD's human health and computational toxicology research programs will
contribute to the development of in vitro test methods predictive of in vivo toxicity,
quantitative structure-activity relationships, and other predictive models.
Similarly, for ecological testing, the EPA Nanotechnology White Paper points out that
because nanomaterials are often engineered to have very specific properties, it seems
reasonable to presume that they may end up having unusual toxicological effects. A number
of existing test procedures that assess long-term survival, growth, development, and
reproductive endpoints (both whole organism and physiological or biochemical) need to be
validated for their applicability to the testing of nanomaterials.
Evaluating the adequacy of existing test methods and the development of potential new test
methods to assess the toxicity of nanomaterials will complement the OECD's harmonized
international test guideline efforts.
Key Science Question:
5. What are the effects of engineered nanomaterials and their applications on human and
ecological receptors, and how can these effects be best quantified and predicted?
- evaluate current test methods to assess their adequacy to determine the toxicity
of nanomaterials and develop new toxicity test methods, as required
- determine the health and ecological effects of nanomaterials including acute and
chronic effects and local and systematic effects
- determine the health and ecological effects associated with nanomaterials
applications and/or interactions with environmental media, ecosystems, or other
stressors
- determine if toxicity, mode(s) of action, and mechanism(s) of injury are unique to
the novel physical and chemical properties of nanomaterials
- identify factors and properties regulating deposition, uptake, fate, and toxicity of
nanomaterials (including hazard identification; dose-response correlations; ADME;
and susceptibility/sensitivity host factors)
-identify ecological systems that have especially susceptible organisms, life stages,
or populations
- develop alternative approaches/technologies/models to screen, rank, and predict
the in vivo toxicity of nanomaterials and their applications
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Research Theme: Risk Assessment
Research conducted under this theme will focus on identifying and developing risk
assessment methodologies for use by Agency risk assessors that address the unique aspects
of engineered nanomaterials. The EPA Nanotechnology White Paper cited a number of
authors who have reviewed characterization, fate, and toxicological information for
nanomaterials and proposed research for risk evaluation of nanomaterials. These
publications are expected be important in developing nanomaterial risk assessment
procedures.
Key Science Question:
6. Do Agency risk assessment approaches need to be amended to incorporate special
characteristics of engineered nanomaterials?
- use case studies to inform the process and refine the current strategy
- integration of the other research areas
-focus on how "nanoness" affects risk assessment/regulatory programs
Research Theme: Preventing and Mitigating Risks
This research theme will focus on identifying technologies or practices that can be applied to
minimize exposure to engineered nanomaterials throughout their life cycle, and to investigate
how nanotechnology can be applied to prevent, control, and remediate pollution. This
includes studying the potential of conventional technologies to capture nanomaterials or
subsequent degradation by-products, materials modification to support green manufacturing
of engineered nanomaterials, waste and by-product minimization, and application of
nanomaterials to reduce existing environmental risks.
Key Science Question:
7. What technologies or practices can be applied to minimize risks of engineered
nanomaterials throughout their life cycle, and how can nanotechnologys' beneficial uses be
maximized to protect the environment?
-materials modification
- recycle/reuse
- waste/byproduct minimization
- application of nanomaterials to reduce other risks
Figure 3-2 illustrates the interrelationship of the research activities with research products
informing risk assessment and management issues. Initially, research activities on the left
side of the diagram will be emphasized. Because little is currently understood about the
potential implications of engineered nanomaterials and products containing these materials, a
life cycle perspective is proposed.
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The risks associated with exposure to nanomaterials arise not only from simple ambient air or
drinking water exposures. As with other production materials, engineered nanomaterials
have a life cycle that includes feedstocks3, the processing of feedstocks into manufactured
nanomaterials, the distribution of nanoproducts, the storage of those products, the use of
those products by consumers, and finally the recycle or disposal of the nanomaterials and
waste by-products. This is commonly known as the product life cycle framework and must
be considered when determining risks for nanomaterials. As shown in Figure 3-1, the
consideration of the product life cycle when doing risk assessment is part of a comprehensive
environmental assessment (CEA) (Davis and Thomas, 2006; Davis, 2007).
Adaptation/
Reuitafeation/
Restoration/
Remediation
Analytical Detection Method Development
Figure 3-2 - Relationship of Key Science Questions to Support Risk Assessment and Management
Decisions; Based on Comprehensive Environmental Assessment (Davis and Thomas, 2006)
4.0 Research Themes
This section discusses the research themes and associated key science questions. For each
science question, text addresses the topic background and program relevance, describes the
proposed research activities, and discusses the anticipated outcomes.
4.1 Research Theme: Sources, Fate, Transport, and Exposure
4.1.1 Key Science Question 1: Which nanomaterials have a high potential for release
from a life-cycle perspective?
5 A raw material required for an industrial process
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Feedstocks
Manufacture
\
Distribution—^
Storage/7
Use' /
Disposal
t
Primary
contaminants
V
Secondary /
contaminants
Ingestion
Dermal
^absorption
Ecosystems
Risk
Characterization
Quantitative
Qualitative
_Technology
Evaluation
Verification
Modelng
Cost
Process
Modifications
Adaptation/
Reuitalizatkm/
Restoration/
Remediation
Analytical Detection Method Development
Figure 4-1 - Relationship of Key Science Questions to Support Risk Assessment and Management
Decisions - Life Cycle Stages
4.1.1.1 Background/Program Relevance
Because they are so small, nanomaterials may be readily transported through the air, water
and soil, perhaps over much greater distances than conventional materials. Uncontrolled
release of these materials can occur during production, through spills, casual disposal,
recycling, wastewater, agricultural operations, or weathering (of paints containing
nanomaterials, for example) which may eventually lead to the presence of a large variety of
nanomaterials in the environment. It may be difficult, economically unfeasible, or even
impossible to remove nanomaterials from some media (e.g., surface waters or drinking
water), potentially resulting in exposures to large segments of the population to complex
mixtures of these materials. In order to understand the implications of nanomaterials and to
identify potential approaches to manage emissions/releases, it is critical to understand
potential entry points of nanomaterials into the environment. Under this question, ORD will
conduct research to understand emissions/releases that can occur either during production,
use, recycling, or disposal of nanomaterials. The transformation and transport of such
materials once they reach the environment is addressed under Key Scientific Question 3.
Examples of points of entry into the environment include:
• Manufacturing Waste Streams: During the manufacture of nanomaterials, the
inevitable by product and waste streams will need to be evaluated. Pollution
prevention (e.g. green chemistry) research may be very helpful in the development of
environmentally friendly manufacturing processes for nanomaterials.
• Air Treatment: Engineered nanomaterials can be emitted along with other
conventional pollutants during production processes. In addition, there are products
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that use engineered nanomaterials where during their use nanomaterials can be
emitted to the air, e.g., brakes, fuel additives.
• Water Treatment: Some nanomaterials are intended to be biocides and may disrupt
drinking water treatment facilities. Personal care products and pharmaceuticals
containing nanomaterials will eventually be washed down the drain and transported to
wastewater treatment plants. There they will either be removed from the wastewater
and end up in the biosolids residuals or they will remain in the wastewater and be
discharged into surface water as part of the treatment plant's effluent.
• Disposal of Used Material: At the end of its useful life, each of the consumer
products and equipment items created using nanomaterials will enter the waste
stream. It is critical to understand where these products end up (e.g., landfill,
incinerator) in order to provide guidance on possible emissions/releases of
nanomaterials.
• Product Usage: As products incorporating engineered nanomaterials enter the
consumer market place, material release may occur during the normal intended usage
or conversely during unintended usage. Releases may occur through abrasion,
adsorption/absorption, or volatilization, among other processes. For instance, if
veterinary pharmaceuticals are administered using nanomaterials, these materials may
be excreted and released into the environment when manure is land applied as
fertilizer. Additionally, the disposal of dead animals may result in the release of
nanomaterials present in the animal's body.
4.1.1.2 Research Activities
ORD will identify industries, processes, and products that have relatively high potential to
release engineered nanomaterials into the environment. Existing literature will be evaluated
to better understand the industries of importance and identify where gaps in information
preclude a full assessment of emission/release points of concern. ORD will perform a
systematic assessment of the production, use, and ultimate fate of nanomaterials to
understand the potential for emissions/releases into the environment. A modified tool using
life cycle principles will be developed to better understand which industries pose the greatest
potential to emit/release nanomaterials of concern and to inform decision-makers about the
overall impact of engineered nanomaterials. This effort will also include a series of
assessments for the highest priority industry categories. Results from ORD workshops will
be used to guide industry and nanomaterial selection for assessment. Comparative
assessments will be produced to help inform decision-makers at what stage in the lifecycle of
nanomaterials interventions could be used to avoid future environmental pollution. The
recent report from the Woodrow Wilson Institute entitled: Green Nanotechnology: Its Easier
than You Think, among other documents, indicates the need for life cycle research.
According to the Project on Emerging Technologies, "Nearly 400 company-identified
nanotechnology-based consumer products are on the market... This figure does not include
more than 600 raw material and intermediate components and industrial equipment items
used by nanotechnology manufacturers who participated in a survey by EmTech Research."
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(Green Nanotechnology: It's Easier than you Think, Woodrow Wilson International Center
for Scholars, p.6.) This effort will be closely coordinated with other organizations,
particularly OPPTS which is also generating data on nanotechnology industries.
This research can be used to inform the Agency, industry, and academia about potential
proactive and "greener" approaches for manufacturing nanomaterials that are designed to
prevent nanomaterial release into the environment. It could also be used as input for future
thorough LCAs.
High-potential industries/processes
ORD will draw upon the latest literature, hold workshops, and interact directly with industry
representatives to identify market trends for nanotechnology industries that utilize the
priority engineered nanomaterials indicated earlier in this document. This research will
attempt to quantify the amounts of nanomaterial expected to be produced and used by
existing industries, identify key processes used to manufacture these nanomaterials, and
project future industries where significant releases may occur.
Identification/characterization of potentially released materials
Once we know where the engineered nanomaterials may be released, it will be important to
understand something about the characteristics of these materials to inform future transport,
transformation, exposure, and health studies. The research will focus on whether the
nanomaterial emissions/releases have the same characteristics (size, chemical composition)
as the original material or have been modified before release to the environment. This area
of research will be highly dependent upon the availability of technology to identify and
characterize engineered nanomaterials. Unfortunately, the ability to make these
measurements is also highly uncertain and will require extensive research. Efforts to
identify, develop, test, and verify detection technologies will be critical to the success of this
research activity.
Entry point into the environment
Given that during the manufacture, use, and recycling or disposal of conventional products
there are always emissions/releases of pollutants, it is reasonable to presume that some form
of engineered nanomaterials will follow similar entry points into the environment. One of
the primary goals of this research is to generate the data and tools needed to quantify and
project these points of entry, so they can evaluate potential risks and possible approaches to
manage those risks. One of the key issues to investigate is whether the nanomaterial
compounds will be emitted/released in their original form or whether they will be physically
or chemically bound with other compounds. This will directly impact transport and
transformation and will influence potential exposures and health risks. Nanomaterials that
are introduced to the environment in solution are more likely to remain in their original form
and become bioavailable. Nanomaterials that are chemically cross-linked in a matrix are less
likely to be released in their original form and size, although uncertainties remain. Because
of their exceptional properties and characteristics, some engineered nanomaterials are being
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intentionally released to serve as catalytic agents for remediation or filtration purposes or as
instruments for detection of pollution. This research will summarize the latest uses and
provide available information on the characteristics of the materials released.
The goal of this research question is to perform the key initial step to inform additional
research on transport, transformation, and subsequent exposure and health studies. In
addition, by identifying potential release points, this research will provide key data required
to inform how best to manage any potential risks.
4.1.1.3 Anticipated Outcomes
• Identification of industries, processes, and products that have relatively high potential
to release engineered nanomaterials into the environment by working collaboratively
with other organizations to inform decision-makers about the overall impact of
engineered nanomaterials.
• Improved understanding of the industries of importance and identication where
information gaps that preclude a full assessment of emission/release points of concern
• A systematic assessment of the production, use, and ultimate fate of nanomaterials that
will improve our understanding of the potential for emissions/releases into the
environment.
• Development of a modified tool using life cycle principles to: (a) better understand
which industries pose the greatest potential to emit/release nanomaterials of concern
and (b) inform decision-makers about the overall impact of engineered nanomaterials
• A series of assessments for the highest priority industry categories, the results of which
will be used to guide industry and nanomaterial selection for assessment.
• Development of comparative assessments to help inform decision-makers at what stage
in the lifecycle of engineered nanomaterials interventions could be used to avoid future
environmental impacts.
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4.1.2 Key Science Question 2: What technologies exist, can be modified, or must be
developed to detect and quantify engineered nano materials in environmental media and
biological samples?
Analytical Detection Method Development
Figure 4-2 - Relationship of Key Science Questions to Support Risk Assessment and Management
Decisions - Analytical Detection
4.1.2.1 Background/Program Relevance
The detection of engineered nanomaterials in various environmental media presents a
significant challenge. This is due in part to potential confounding by the presence of
anthropogenic and natural nanomaterials. Challenges arise because many different
engineered nanomaterials currently exist and their numbers are increasing exponentially; for
certain types of nanomaterials, such as nanotubes, many thousands of different structures are
possible. In addition, the fate, transformation, and mobility of these materials are only
beginning to be understood. Consequently, scientific understanding of the reactions these
materials undergo, how they age in various environmental media, how they interact with
other compounds present in the environment, and whether and to what extent they form
agglomerates or aggregates is limited. These issues compound the complexity of detecting
and quantifying nanomaterials in environmental media.
The development of effective methods for measuring engineered nanomaterials in
environmental media at concentrations relevant to potential exposure scenarios is critical to
understanding the environmental impacts of these materials. Such methods would also
enable the more rapid achievement of the safe development of nanotechnology-related
products. ORD-sponsored research will ultimately seek to develop remote, in situ, and
continuous monitoring devices that yield real-time information and that can detect
engineered nanomaterials at very low concentrations.
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Risk assessments of nanomaterials will require the ability to measure their environmental
concentration in the workplace, home, biota (including human tissues), and ecosystems of
interest. Analytical methods needed to characterize and analyze nanomaterials will require
the modification of existing analytical tools and the development of completely new tools
and approaches to meet these challenges. The same properties that make nanomaterials a
significant challenge to analyze in any matrix (such as high binding capacities) may also
provide unique opportunities for developing new analytical methods (e.g., tagging with
fluorophores) for their analysis in complex biological and environmental systems. ORD will
integrate fundamental research on detection method development from NSF, National
Institute of Standards and Technology (NIST), DoD, and others with its own focused
methods research effort to inform this research question.
4.1.2.2 Research Activities
Measurement science (based on analytical chemistry and physical properties) will have
multiple roles in nanomaterials assessment and will require different types of analytical
methods. There are several major areas of investigation with nanomaterials that require the
application of a wide array of measurement and characterization techniques for
characterization, detection, identification, or quantification:
Bulk materials: ORD will undertake studies to characterize the physical and chemical
properties of bulk nanomaterials to assess and quantify their unique features and
characteristics (e.g., surface-to-volume ratio, 3-dimensional structure, size, size distribution,
relative dimensions (aspect ratio), chirality, electrical/magnetic properties, and
microstructure). Access to the equipment needed for these studies will require the formation
of partnerships with other federal agencies, such as NIST, the National Cancer Institute
(NCI) and the DOE. Each of these agencies has or is in the process of establishing
nanomaterial research facilities, such as the Advanced Measurement Laboratory (AML) at
NIST and the Nanotechnology Characterization Laboratory (NCL) at NCI. These research
facilities provide access to a wide variety of measurement and characterizations tools.
Lab-based studies: ORD will take advantage of existing analytical methods for
nanomaterials to support the initial focus on lab-based studies. An ever increasing number of
papers in the literature have reported on the application of analytical methods for the
measurement of nanomaterials for monitoring lab-based studies to model environmental
processes under controlled conditions (e.g., soil leaching and subsurface transport) and
concentrations. Examples include the analysis of fullerenes by liquid chromatography
coupled to a photodiode array detector, the tracking of 14C in radio-labeled carbon-based
nanotubes, and the analysis of quantum dots by fluorescence spectroscopy.
Trace environmental residues: The published literature on the use of existing analytical
tools for detecting or monitoring engineered nanomaterials in the environment (especially in
matrices other than the vapor phase) is very limited. Perhaps the first publication that
borders on being a "review" of this literature is that of Nowack and Bucheli (2007). The lack
of methodologies for analyzing environmental samples likely results from two major factors:
(1) only in the last couple of years has any need for environmental analysis been
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contemplated, and (2) the challenges facing the detection and quantification of engineered
nanomaterials (especially those based solely on carbon) in environmental samples far exceed
those associated with conventional pollutants, even those pollutants that comprise complex
mixtures of many congeners (e.g., toxaphene).
To address the challenges associated with directly measuring nanomaterials in the
environment, ORD will develop direct and indirect methods that capitalize on properties that
are unique to these substances. For example, creating opportunities for indirect detection
could capitalize on the extreme capacity of carbon-based nanomaterials to sorb certain
chemicals, especially those sorbates that would be amenable to fast and sensitive detection.
This could be done, for example, by equilibrating the sample unknown with an inorganic
substance with strong sorptive potential. This substance would act as a dopant, which would
be selected for its preferential sorption to carbon-based nanomaterials, its ready detectability,
and the fact that it should rarely occur in the environment (to minimize background
interference).
The complexities faced by analysis for nanomaterials in environmental matrices may prove
intractable to conventional instrumented approaches of analysis. The eventual solution may
well evolve from the development of new analytical approaches using arrays of standardized
assays based on biological/biochemical endpoints. A battery of suitable assays could
possibly be designed around a series of critical, evolutionarily conserved biological processes
that prove keys to significant biological effects known to be important for nanomaterials.
Two examples are: (1) the extent of physical penetration of a biological membrane (or
membrane model) by the substances in a given sample (this would possibly be relevant to
nanotubes), and (2) the generation of reactive oxygen species (as an indirect indicator of
surface-catalyzed reactions). These endpoint assays would need to be developed to cover the
entire spectrum of mechanisms of action for anthropogenic nanomaterials. Positive
responses from these assays could then be used to direct the use of instrumented detection
techniques to better target conventional analysis.
To make unambiguous and quantitative determinations of engineered nanomaterials in
environmental samples, ORD will develop a combination of ensemble techniques (e.g.,
hyphenated methods coupling separation with spectroscopic detection, that measure
collectively a number of particles) and single-particle techniques (e.g., methods, such as
imaging, that measure individual particles). The separation method employed may be size
exclusion chromatography, sedimentation field flow fractionation, or capillary
electrophoresis. Determination could then be made by the coupling of ICPMS or a
spectrofluorometer for fluorescent quantum dots. Ensemble methods can be developed for at
least some classes of nanomaterials that provide screening assays to confirm the absence of
detectable levels of nanomaterials or to provide an upper limit concentration estimate.
However, for most materials, non-specific, indirect detection techniques would have to be
combined with nanoscale imaging methods to confirm the presence of nanomaterials, and to
provide a more reliable concentration estimate.
To develop analytical methods suitable for environmental monitoring, ORD will develop
standardized reference materials in a variety of representative matrices. Methods for
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environmental analysis or routine monitoring must account for the extraordinarily wide array
of potential parent materials and transformation products. In contrast to methods for the
other roles described above, approaches to environmental measurement must include non-
target analysis, where the type(s) of nanomaterials that need to be detected are not known in
advance (the entire spectrum of parent materials must be amenable to analysis). The
problems that traditionally plague environmental analysis, such as the wide array of matrix
interferences that limit detectability, make environmental monitoring of nanomaterials even
more challenging. Examples of this type of application do not yet exist, and are an additional
research need.
4.1.2.3 Anticipated Outcomes
• Development of methods for characterizing nanomaterials, through partnerships with
NIST, NCI and/or DOE
• Development of analytical methods for the detection of carbon-based nanomaterials
in environmental matrices
• Development of analytical methods for the detection of non-carbon-based
nanomaterials in environmental matrices
• In cooperation with other federal agencies, development of standardized reference
materials for a variety of representative environmental matrices
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4.1.3 Key Science Question 3: What are the major processes/properties that govern the
environmental fate of engineered nanomaterials, and how are these related to physical
and chemical properties of those materials?
* * *
Analytical Detection Method Development
Figure 4-3 - Relationship of Key Science Questions to Support Risk Assessment and Management
Decisions - Pathways, Transport, and Transformation
4.1.3.1 Background/Program Relevance
Given the current scientific uncertainty surrounding fate, transport, detection and modeling
of engineered nanomaterials, it is difficult to accurately assess the environmental disposition
of nanomaterials or the potential exposure pathways to human and ecological receptors.
Ultimately predictive models for estimating the environmental fate and transport of
nanomaterials are needed.
Nanotechnology research for fate, transport, detection and modeling of engineered
nanomaterials is needed to identify the most critical parameters and uncertainties associated
with these materials. This research will characterize the fate and transport of nanomaterials
from sources to human and ecological receptors. The research will support risk assessments
of engineered nanomaterials and ways to manage their potential releases. It will also provide
a fundamental understanding of the physical and chemical properties of nanomaterials and
their impact on fate and transport pathways. In concert with the research questions above,
this research will also address detection issues of nanomaterials as it relates to fate and
transport questions. Finally, existing predictive models for nanomaterial fate and transport
will be modified, and if necessary, new models will be developed.
Because of the introduction and increased production of nanomaterials, it is necessary to
better understand the fate, transport, detection and modeling of these materials. Quantitative
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as well as qualitative research is necessary to reduce the uncertainty surrounding the
introduction and existence of nanomaterials in the environment and to identify the exposure
pathways of concern to receptors. Research on these issues will assist the Agency in both
risk assessment and risk management of engineered nanomaterials. ORD will conduct the
following research to meet the critical needs of the agency as described below.
4.1.3.2 Research Activities
• Understand the processes that govern the fate and transport of engineered
nanomaterials
• Understand the chemical and physical properties of engineered nanomaterials and
how they influence fate and transport processes
• Develop predictive models for transport of engineered nanomaterials
Understand the processes that govern the fate and transport of engineered
nanomaterials
ORD will work in collaboration with other agencies and academia to study the principles that
govern the transformation, transport, and longevity of engineered nanomaterials in the
environment. Since these materials could be present in sediments, soils, air and aqueous
environments, understanding their transport in porous and compacted media is important to
assess their migration through soils, the vadose zone, sediments, groundwater, surface water,
and the atmosphere to potential receptors, as well as to develop effective management
strategies. Studying the fate and transport of nanomaterials in all of these matrices is an
important research need. Processes that control movement, sorption, dispersion,
agglomeration, degradation, chemical and biological processes, and interactions between
nanomaterials and natural or anthropogenic chemicals need to be investigated. ORD will
conduct controlled laboratory studies to understand these fate and transport processes and the
factors that control them.
Understand the physical and chemical properties of engineered nanomaterials and how
they influence fate and transport processes
ORD will work in collaboration with other agencies and academia to study the chemical and
physical properties of engineered nanomaterials and how these properties affect the fate and
transport processes. Processes that control movement, sorption, dispersion, agglomeration,
degradation, chemical and biological processes, are strongly affected by the chemical and
physical properties of nanomaterials such as surface charge, pH, ionic strength, redox
conditions, and ambient air conditions such as temperature and humidity. Obtaining
information on the chemical and physical properties of specific nanomaterials and classes of
materials is necessary to understand their effect on fate and transport processes. For
example, in the case of carbon nanotubes, the mobility of these materials largely depends on
the degree and type of functionalization (elements or other functional groups at the surface of
the nanostructures), which affect solubility and surface charge. Research will focus on the
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understanding the impact solution chemistry and surface functionalization of multi-walled
carbon nanotubes have on mobility in porous media.
Determining how transport through soils, vadose zone, and groundwater is affected by
solution chemistry and colloid surface properties is critical for understanding the fate of
nanomaterials. In addition, previous metals research has shown that chemical speciation of
inorganic, engineered nanomaterials is an important factor to understand for the fate and
transport and ultimate bioavailability of the materials. ORD will assess the chemical
transformation and speciation of inorganics such as silver. (Silver is impregnated in fabrics
and washing machines as an anti-fungal/anti-microbial agent, but little is known about how
the properties of the nanosilver particles impact their fate and transport in the environment.)
Develop predictive models for transport of engineered nanomaterials
ORD will work in collaboration with other agencies and academia to study the applicability
of existing environmental fate and transport (EF&T) models and to develop new predictive
EF&T models that are tailored specifically to nanomaterials. Early analysis of the Estimation
Programs Interface Suite (EPI Suite) models, the primary set of predictive tools the Agency
uses for calculating the fate and transport of soluble organic chemicals and inorganics,
indicates that they will have little or no applicability to predicting the EF&T of
nanomaterials. Models do exist for predicting the transport of larger particle sized colloidal
materials and they are being investigated for application to nanomaterials. As such,
traditional DLVO (Derjaguin, Landau, Verwey and Overbeek) theory will likely lend insight
into environmental fate and mobility trends. The successful development of EF&T models
for nanomaterials will depend on our understanding of the processes controlling the EF&T of
engineered nanomaterials and our ability to determine the chemical and physical properties
needed to predict such processes.
4.1.3.3 Anticipated Outcomes
Results from this research will provide an improved understanding of the EF&T of
engineered nanomaterials in the environment. This will allow the Agency to develop a set of
predictive tools.
Researchers hope to:
• Develop a scientific understanding of the processes that govern the fate and transport
of engineered nanomaterials
• Measure the chemical and physical properties of engineered nanomaterials and
determine how these properties influence and impact fate and transport
• Identify the exposure pathways associated with production, end-use, and recycling or
disposal of engineered nanomaterials in different environmental matrices
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• Improve the scientific understanding of detection methodologies for quantifying
engineered nanomaterials
• Develop multiple predictive models for understanding and measuring the transport of
engineered nanomaterials
4.1.4 Key Science Question 4: What are the exposures that will result from releases of
engineered nanomaterials?
* * *
Analytical Detection Method Development
Figure 4-4 - Relationship of Key Science Questions to Support Risk Assessment and Management
Decisions - Exposure
4.1.4.1 Background/Program Relevance
Research is needed to provide insight into the type, extent, and timing of exposures to
nanomaterials in all relevant environmental media and through all relevant exposure
pathways. Cumulative exposures, both with other engineered nanomaterials as well as with
bulk-scale pollutants, also need to be explored. The information provided through this
exposure research can be linked with other exposure and biological impact data to improve
the scientific basis of risk assessment for engineered nanomaterials.
General population exposure may occur from environmental releases from the production
and use of nanomaterials and from direct use of products (e.g., cosmetics and medicines)
containing nanomaterials. The rapid growth of products that contain nanomaterials could
result in their presence in soil and aquatic ecosystems. This presence will result from
effluents of manufacturing plants, and the recycling or disposal of nano-based consumer
products into landfills and surface/ground water.
An exposure assessment attempts to answer the following questions for a particular substance
or chemical:
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• Who or what is exposed (e.g., people, aquatic ecosystems)?
• What are the pathways for exposure?
• How much exposure occurs?
• How often and for how long does exposure occur; that is, what is its frequency and
duration?
4.1.4.2 Research Activities
The Agency uses a number of models to conduct chemical exposure assessments.
Descriptions and links to these models can be found at the websites for the Council for
Regulatory Environmental Modeling (CREM: http://cfpub.epa.gov/crem/) and the Center for
Exposure Assessment Modeling (CEAM: http://www.epa.gov/ceampubl/). Table 4-1
provides a listing of several of the models/tools used by the program offices for exposure
assessment and each model's general application and applicability to nanomaterials in its
current form. With the exception of the EPI-Suite™ calculators, all of the exposure
assessment models need the user to provide input data on the physical and chemical
properties for the chemical of interest. The EPI Suite™ calculators are based on a single
input, a Simplified Molecular Identification and Line Entry System (SMILES) string that is a
typographical method for representing unique chemical structures. The other models in
Table 4-1 were developed primarily for exposure assessments of synthetic organic chemicals,
and thus require input such as water solubility, octanol-water partition coefficients and
Henry's Law constants to predict fate and transport.
Acronym
E-FAST
EPI-Suite™
EXAMS
Trim Expo
Model Name
Assessment Screening
Tool Version 2.0
Estimation Programs
Interface Suite
Exposure Analysis
Modeling System
Total Risk Integrated
Methodology
Exposure-Event Module
Primary Progran
Office
OPPT
OPPT
OPP
OAQPS
Application
Estimates concentrations of
chemicals in multimedia from
multiple release activities
Estimates physical & chemical
properties for organic chemicals
Estimates fate, transport, and
exposure concentrations of
chemicals in aquatic ecosystems
Estimates human exposure to criteria
and hazardous air pollutants
Applicability
toNMs
Modification
Required
Not Applicable
Modification
Required
Modification
Required
Table 4-1. Several of the primary models/tools used by the Program Offices for exposure
assessment and each model's general application and applicability to nanomaterials in their
current form
Exposure models will require modification to allow the input of molecular parameters and
physical and chemical data specific to nanomaterials (e.g., particle size, surface charge,
distribution or sticky coefficients, and agglomeration tendencies). OPPT has recently
requested the assistance of ORD to review the E-FAST model, which supports the New
Chemicals and Existing Chemicals Programs, for its applicability to nanomaterials.
Specifically, ORD will:
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• Focus on the physical, chemical, and other properties currently required as user
provided/default inputs
• Determine whether these inputs are appropriate for nanomaterials when assessing
exposures related to industrial releases to surface water, air, and/or landfills
• Identify other properties as potential inputs that might be more appropriate for
assessing general population and environmental exposure to nanomaterials
The challenges in identifying and measuring the concentration of engineered nanomaterials
in environmental and biological systems will present significant obstacles to providing the
data necessary to conduct exposure assessments of these materials for both ecological and
human receptors. Such assessments will require the development of alternative methods for
determining the source and the environmental concentrations of nanomaterials in aquatic and
terrestrial ecosystems. The interest in nanomaterials is driven by their unique properties and
activities at different scales; these same properties provide the opportunity for developing
indicators of exposure by measuring changes in structures and functions of biological
organisms in contact with nanomaterials. By identifying indicators of exposure resulting
from exposure to nanomaterials, it will be possible to reconstruct the exposure pathway and
ultimately the source and the environmental concentration of the nanomaterial of interest.
This ability to move from an internal biological response to external environmental
concentration represents a growing area of exposure science referred to as "Exposure
Reconstruction."
ORD's research in this area focuses on the linkage of responses across endpoints at multiple
biological levels of organization, from molecular alterations to populations. These linkages
can serve as a basis for identifying and validating mechanistic indicators of exposure and
effects, informing ecological risk assessments of nanomaterials. Currently, a systems-based
approach is being used to assess exposures and define toxicity pathways for model chemicals
with well-defined modes/mechanisms of action (MOA) within the hypothalamic-pituitary-
gonadal (HPG) axis. These pathways serve as a basis for understanding responses of small
fish across biological levels of organization, ranging from molecular responses to adverse
effects in individuals to, ultimately, changes in population status. The studies employ a
combination of state-of-the-art molecular biology, bioinformatic, and modeling approaches,
in conjunction with whole animal testing. As such the project will enable a unique
opportunity to interface empirical toxicology with computational biology in the exposure
assessment of nanomaterials.
The molecular biological tools for this research will focus on the application of the 'omic'
tools (i.e., genomics, proteomics and metabolomics) to identify indicators of exposure.
These tools provide the ability to identify indicators of exposure by measuring gene
regulation, protein formation, and changes in an organism's metabolome in response to
exposure to a chemical or mixture of chemicals. By elucidating the kinetics of the marker's
response, it is also possible to provide an understanding of the temporal and spatial aspects of
exposure.
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Currently, no information is available in the literature concerning the identification of
indicators of exposure for nanomaterials. On-going research with pesticides exhibiting
estrogenic activity, however, is demonstrating the feasibility of this approach. ORD has
developed molecular indicators of exposure (based on genomic responses) of aquatic
organisms (water flea, Daphnia magna and fathead minnow, Pimephalespromelas) to
estrogenic compounds and is using advanced genomic methods to develop androgenic
indicators. The Nuclear Magnetic Resonance (NMR) based metabolomics research program
being conducted at ORD's NMR research facility is demonstrating the use of high-resolution
NMR to identify changes in the profiles of endogenous metabolites (i.e., the metabolome) in
the serum and urine of fathead minnows exposed to estrogenic compounds. The literature
also provides examples of the use of genomics to identify indicators of exposure in humans.
Microarray analysis of blood samples taken from benzene-exposed workers has identified
peripheral blood mononuclear gene expression as an indicator of exposure for benzene
(Forest et. al, 2005).
Collaboration to further identify the exposure pathways of engineered nanomaterials
ORD will work in collaboration with other agencies and academia to study and identify the
most common exposure pathways for engineered nanomaterials. ORD will seek to establish
international collaborations through the development of collaborative or coordinated calls for
proposals. These research proposals will also engage ORD scientists in the study of
exposure routes and pathways, relevant exposure doses, and critical exposure concentrations.
Research will also identify potential subpopulations of organisms that are more susceptible to
engineered nanomaterial exposure than others.
4.1.4.3 Anticipated Outcomes
• Identification of the dominant exposure pathways to ecological receptors of interest
• An assessment of the applicability of the Agency's current exposure models to
nanomaterials
• Identification of the physical and chemical properties required to inform exposure
• Identification of indicators of exposure through the application of genomics,
proteomics and metabolomics
4.2 Research Theme: Human Health and Ecological Effects Research to Inform Risk
Assessments and Test Methods
4.2.1 Key Science Question 5: What are the effects of engineered nanomaterials and
their applications on human and ecological receptors, and how can these effects best be
quantified and predicted?
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Storaae/Y
Use/ /
Disposal
i * *
Analytical Detection Method Development
Figure 4-5 - Relationship of Key Science Questions to Support Risk Assessment and Management
Decisions - Effects
4.2.2 Background/Program Relevance
As described in EPA's Nanotechnology White Paper, nanomaterials could have health and
ecological implications arising from new routes of exposure and/or toxicities associated with
either direct exposure to these novel materials, by-products associated with their applications,
or their interactions with various environmental media.
By understanding nanomaterials biokinetics, characterizing their health and ecological
effects, and identifying the physical and chemical properties that regulate their toxicity, ORD
will address the critical lack of information required for nanomaterials risk assessment. The
results from ORD's nanomaterials health and ecological effects research will also inform risk
management strategies and decisions.
ORD's health and ecological effects research will provide EPA offices with information on
the health and ecological effects of specific nanomatierals and their applications, as well as
guidance on best practices and approaches/test methods for assessing/predicting health and
ecological effects. ORD will also be addressing key immediate priority effects research
needs identified in US EPA Nanotechnology White Paper, such as, adequacy of test methods,
characterization of the health effects of nanomaterials (nanotoxicology), hazard identification
and dosimetry and fate.
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4.2.3 Research Activities
To address this key science need, ORD will conduct research to:
• Evaluate current test methods to assess their adequacy to determine the toxicity of
nanomaterials, and develop new toxicity test methods, as required
• Determine the health and ecological effects of nanomaterials, including acute and
chronic effects and local and systemic effects
• Determine the health and ecological effects associated with nanomaterials
applications and/or interaction with environmental media, ecosystems, or other
stressors
• Determine if toxicity, mode(s) of action, and mechanism(s) of injury are unique to
the novel physical and chemical properties of nanomaterials
• Identify factors and properties regulating deposition, uptake, fate, and toxicity of
nanomaterials (including hazard identification; dose- response correlations; ADME;
and susceptibility/sensitivity host factors)
• Identify ecological systems that contain especially susceptible organisms, life stages,
or populations
• Develop alternative approaches/technologies/models to screen, rank, and predict the
in vivo toxicity of nanomaterials and their applications
Health effects: ORD's nanomaterial health and ecological implications research builds upon
its ongoing risk assessment research within the Air, Water, and Safe Products/Safe Pesticides
programs. These research activities provide the facilities and expertise that are directly
applicable to addressing the health and ecological implications of nanomaterials resulting
from various potential routes of exposure. ORD's research is conducted within a risk
assessment paradigm to address key research issues listed above.
A Multi-tiered strategy for assessing nanomaterial health effects: To address the
nanomaterial health and ecological research needs identified in EPA Nanotechnology White
Paper (1), Environmental, Health and Safety Research Needs for Engineered Nanoscale
Materials (2), and be consistent with recommendations of the National Academy of Sciences,
National Research Council report on Toxicity Testing in the 21s Century: A Vision and a
Strategy (3), ORD's research will employ a multi-tiered strategy, Figure 4-6.
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"Multi-Tiered Approach
-Rank NMs for Tier 2
-Design Tier 2 Studies
Tier 2
Zf? Vivo Toxicological
Studies
Tier 1
In Vitro Toxicology
Studies
Tier 3
Physicochemical Characterization
Acellular Tests: Reactivity; Protein
Interactions
Figure 4-6 - A multi-tier strategy for comparative and quantitative nanomaterials health risk assessment.
ORD's nanomaterials health effects multi-tiered strategy is driven by a number of additional
critical factors such as: the diversity of engineered/manufactured nanomaterials; the cost and
availability of nanomaterials; the need to identify alternative approaches, assays, and
methods that predict in vivo health effects resulting from direct exposure to nanomaterials or
following their interactions with environmental media resulting from inadvertent releases or
applications.
Tier I- In Vitro Toxicology of nanomaterials: Initially, studies will examine the in
vitro toxicity of various nanomaterials of interest to the Agency using a variety of cell types
reflecting different routes of exposure (inhalation, oral, dermal) to assess the health effects
that may arise due to the tendency of nanomaterials to translocate to other regions of the
body. This "virtual body" approach employed in Tier 1 studies will assess the in vitro
cancer, pulmonary, immunological, neurological, reproductive, cardiovascular, and
developmental toxicities of nanomateials. Tier 1 in vitro testing provides a means to: rapidly
screen and rank the relative toxi cities of various nanomaterials; determine mechanism(s) of
injury and mode of action; rapidly perform comparative toxicity studies between nano vs.
bulk size materials; conduct rapid screening to assess alterations in nanomaterials toxicity
following their interactions with environmental media; perform ADME at the cellular and
intracellular levels; and characterize nanomaterials-cellular interactions.
ORD's ToxCast program (http://epa.gov/comptox/toxcast/news.html) will assist
ORD's Tier 1 in vitro toxicological assessment of nanomaterials. ToxCast offers an
approach to deal with the extreme diversity of nanomaterials by applying high-throughput
platforms and computational approaches (physicochemical properties, biocomputational
models, biochemical assays, cellular assays, genomic studies, and model organisms) to
screen a large number of materials. The ToxCast program has the potential to rank the
toxicity of nanomaterials as well as develop models to identify physical and chemical
properties that determine the toxicity of nanomaterials.
Tier 2 - In Vivo Toxicology of Nanomaterials: Subsequent Tier 2 studies will
examine the animal or in vivo toxicity and biokinetics/ADME of nanomaterials. Tier 2
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studies will be guided by information generated in Tier 1 related to the prioritizing or ranking
of nanomaterials and designing appropriate nanomaterial exposure concentrations as well as
what health endpoints to monitor, Figure 4-6, solid red line. Tier 2 studies will examine
cancer, pulmonary, dermal, and gastrointestinal toxicities associated with initial deposition of
nanomaterials by various routes of exposure as well as immunological, neurological,
reproductive, cardiovascular, and developmental toxicities to assess their systemic toxicities.
Information generated from Tier 2 studies will provide a database from which to compare
Tier 1 studies in order to identify those in vitro assays that correlate with in vivo nanomaterial
toxicity or health effects, Figure 4-6, dashed red line.
Tier 3 - Nanomaterial Characterization and Surface Properties: Concurrent with
Tier 1 and 2 activities, Tier 3 research will relate the physical and chemical properties of
nanomaterials to their in vitro and in vivo toxicity (hazard identification), Figure 4-6, red
solid double-headed arrows. Tier 3 research will employ non-cellular or acellular methods
to assess nanomaterial surface reactivity as well as understand their interactions with
biological molecules/fluids in order to identify what surface properties and interactions
determine their in vitro and in vivo biokinetics/ADME. These studies will also investigate
nanomaterials effects in a variety of cell types and organ systems.
The multi-tier strategy will not only provide an approach to perform comparative and
quantitative nanomaterials health effects risk assessment for a number of different types of
nanomaterials of interest to Agency offices, but also offers an approach to assess alterations
in NM toxicity following their interactions with environmental media. Critical components
of Tiers 1, 2 and 3 are the use of high throughput screening assays and the application of
"omic-based" analyses and associated bioinformatics to characterize the health effects and
molecular response profiles. This research may lead to the identification of biomarkers of
exposure and/or effects as well as the identification/validation of in vitro toxicity and
acellular test methods that predict the in vivo toxicity of nanomaterials.
Ecological effects:
Tier 1 - Evaluate the suitability of existing test methods for assessing the hazards of
engineered nanomaterials: Nanomaterials, or products containing nanomaterials, are already
being submitted for approval under Agency programs such as TSCA and FIFRA These and
other Agency programs have existing protocols for evaluating hazards to ecological receptors
in both aquatic and terrestrial systems, but the appropriateness of these methods for
nanomaterials has yet to be evaluated. Key concerns include how to expose organisms to
nanomaterials in ways that have relevance to exposures that may occur in the environment,
and whether these standardized assays address the organisms, life stages, and bioavailability
considerations that are most important for understanding the potential ecological risks of
nanomaterials. In addition to direct toxicity testing, emphasis will be placed on
measurements of exposure, uptake, and dose.
Tier 2 - Understand the mechanisms underlying the ecological effects of
nanomaterials and identify potential gaps in hazard assessment procedures: Building on
results of exposures using standard (or appropriately modified) test methods, further research
will explore the specific mechanisms of nanomaterials toxicity and ecological effects.
Understanding the mechanisms of effects is key to determining novel risks that may be
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created by nanomaterials, defining the appropriate organisms and endpoints for
nanomaterials risk assessments, and providing the basis for future predictive models.
Parameters that govern adsorption, distribution, metabolism, and excretion (ADME) will be
evaluated, as will means of expressing toxicological dose. Other studies will evaluate the
interaction of nanomaterials with physical, chemical, and biological components of
ecological systems to determine if there are effects of nanomaterials not captured by single
organism toxicity testing, such as altering the relationships among ecosystem components
and thereby affecting overall ecosystem function. Throughout Tier 2, emphasis will be given
to determining whether nanomaterials exert effects through mechanisms that would not be
well addressed by existing ecological hazard and risk screening tools.
Tier 3 - Development of methods and models to predict the hazard or ecological risk
of nanomaterials: Due to the diversity of nanomaterials expected to enter the marketplace in
the coming years, the Agency will need predictive tools that can be used to prioritize newly
developed nanomaterials for testing and further evaluation. For example, quantitative
structure/activity relationships (QSARs) may be developed to predict the toxicity of untested
materials based on their chemical structure and an understanding of the mechanisms
underlying dose and toxicity. Likewise, ecological effects models may be important
predictive tools if research in Tier 2 indicates that ecological processes above the organismal
level are being uniquely affected by nanomaterials. This work will build directly from Tiers
1 and 2 and associated research conducted by the Computational Toxicology Program.
Leveraging research with OKD laboratories, centers and other federal programs:
ORD's nanomaterial health and ecological risk assessment research will leverage work with
other ORD Federal programs (NIOSH, NTP, DOE) where similar nanomaterials are being
monitored, studied, and characterized. For example, ORD laboratories are jointly addressing
nano-cerium dioxide assessing potential environmental exposures, and associated health
effects. Research to examine the health and ecological effects of nanomaterials following
their release into or interactions with environmental media will require the combined
expertise of ORD's health and exposure scientists. Finally, the physical and chemical
characterization of nanomaterials and their detection in biological systems will require a
multidisciplinary approach with close interactions across ORD as well as the DOE National
Laboratories.
4.2.4 Anticipated Outcomes
ORD's effects research will provide key information regarding the health and ecological
implications from exposures to nanomaterials, and their applications, in order to identify and
manage potential adverse impacts and inform program offices and regions regulatory and
other policy decisions. Specifically, ORD's nanomaterials effects research will provide
Agency offices with information on the health and ecological effects of specific
nanomaterials and their applications, as well as guidance on best practices and
approaches/test methods for assessing/predicting health and ecological effects. ORD's
nanotechnology health and ecological effects research activities will provide publications in
peer-reviewed scientific journals on the:
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• Characterization of nanomaterials health and ecological effects; identification of
physical and chemical properties and host/sensitivity factors that regulate
nanomaterials dosimetry, fate, and toxicity
• Identification of testing methods/approaches to predict in vivo toxicity of
nanomaterials; characterization of molecular expression profiles that may provide
biomarkers of nanomaterial exposure and/or toxicity
• Provision of necessary counsel and guidance that will assist in the review of
premanufacture notice applications and assess the adequacy of harmonized
nanomaterial test guidelines to assist OPPTS and internationally, the OECD
• Addressing the gap in our knowledge regarding the toxicity of nanomaterials which
has impeded the ability to conduct accurate life cycle analysis
4.3 Research Theme: Developing Risk Assessment Methods
4.3.1 Key Science Question 6: Do Agency risk assessment approaches need to be
amended to incorporate special characteristics of engineered nanomaterials?
4.3.2 Background/Program Relevance
Many data gaps exist in the areas of chemical and physical identification and
characterization, environmental fate, environmental detection and analysis, potential releases
and human exposures, human health effects, and ecological effects. Filling these data gaps
will aid in future risk assessments of nanomaterials when proven risk assessment methods are
available.
Although nanomaterials have special properties that may influence their environmental
behavior and effects on human health and ecosystems, the traditional paradigm for risk
assessment and risk management (NRC, 1983) is presumed to apply to these materials.
Hazard identification determines qualitatively whether the nanomaterial will cause an
adverse health effect. Dose-response assessments establish the quantitative relationship
between dose and incidence of health effects. Exposure assessment is performed and the
incidence of the adverse effect (risk) in a particular population is determined by combining
exposure and dose-response. The effects of nanomaterials on the environment must also be
assessed in order to protect and restore ecosystem functions, goods, and services. Ecological
risk assessment entails the evaluation of goals and selection of assessment endpoints in a
problem formulation step, followed by analysis of exposure to stressors and determining the
relationship between stressor levels and ecological effects. The next step is estimating risk
through the combination of exposure and stressor-response profiles, description of risk by
discussing lines of evidence, and determination of ecological adversity (U.S. EPA, 1998).
Interfacing among risk assessors, risk managers, and interested parties during the initial
planning of a risk assessment and communication of risk at the end of the risk assessment are
critical to ensuring that the results of the assessment can be used to support a management
decision. The importance of constant communication and stakeholder involvement in both
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human health and ecological risk assessment and risk management has also been noted by the
Presidential/Congressional Commission on Risk Assessment and Risk Management (see
Figure 2-1).
While the basic paradigms of health and ecological risk assessment are still relevant, they are
expanded in the comprehensive environmental assessment (CEA) approach to encompass the
product life cycle of nanomaterials. By taking a broad view of the potential for releases of
both primary and secondary materials to multiple environmental media, the evaluation of the
environmental and health risks of nanomaterials is seen as an issue that cuts across EPA
programmatic domains and is not simply categorized as solely an air, water, toxics, or solid
waste issue. The CEA approach (Davis and Thomas, 2006; Davis, 2007) starts with a
qualitative life cycle framework, as shown in Figure 4-7. It takes into consideration multiple
environmental pathways, transport and transformation processes, cumulative and aggregate
exposure by various routes, and ecological as well as human health effects. Depending on
the availability of data, both quantitative and qualitative characterizations of risks may result.
However, given the limited information currently available on nanomaterials, the CEA
approach is being used to identify where key data gaps exist with respect to selected case
studies of specific applications of nanomaterials.
Case studies are recommended in the EPA Nanotechnology White Paper as a means to
further inform research supporting the risk assessment process. The term "case study" is
used to refer to specific examples of nanomaterials and the types of issues that would be need
to be considered to assess their respective environmental and health risks. By focusing on
specific examples of nanomaterials in realistic applications, it is possible to identify and
prioritize research needs to assess the "real world" impacts of these materials. Given the
striking differences in toxicological and physicochemical properties of nanomaterials,
generalizations across nanomaterials need to be considered cautiously.
Adaptation/
Reuitafeation/
Restoration/
Remediation
Analytical Detection Method Development
Figure 4-7- Relationship of Key Science Questions to Support Risk Assessment and Management
Decisions - Risk Assessment
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4.3.3 Research Activities
The role of ORD's nanomaterial risk assessment research is (1) to help guide overall research
efforts toward generating the information needed to conduct future comprehensive
environmental assessments of nanomaterials and (2) to carry out such assessments in
coordination with all of ORD and the program offices. The research question ORD will
address is "Do Agency risk assessment approaches need to be amended to incorporate special
characteristics of engineered nanomaterials?" To answer this question, ORD will identify
and prioritize information gaps by conducting a series of case studies and workshops to
further refine research needs for specific nanomaterials, as recommended in the EPA
Nanotechnology White Paper.
In order to develop case studies of particular nanomaterials and their specific applications,
appropriate nanomaterials must be selected. The collective judgment of an internal
workgroup representing all relevant program offices was used for this purpose. The
workgroup was given a summary of available information on the chemistry, human health,
toxicology, exposure, and release of various nanomaterials. Workgroup members were then
asked to select two nanomaterials based upon five criteria: potential for biota/human
exposure; apparent potential for both health and ecological effects; a reasonable amount of
information with which to develop a case study; relevance of the nanomaterial to
programmatic or regulatory needs; and "nanoness," i.e., satisfying the NNI definition of
having at least one dimension less than 100 nm. Using these criteria, titanium dioxide and
single walled carbon nanotubes were selected. Two applications of nanotitanium dioxide are
under development, a water treatment agent and a sunscreen. The applications for the single
walled carbon nanotubes have not yet been determined. These selected classes of
nanomaterials also serve as a common focus and point of coordination for near-term studies
by the various ORD laboratories.
The intent of the case studies is to consider currently available information for nanomaterials
for the purpose of identifying gaps where additional information is needed. The draft case
studies will be internally reviewed, followed by distribution of each draft to selected
reviewers/contributors as part of a peer consultation process. After further development and
refinement through peer consultation, the case studies will be the subject of a workshop
(likely the first of a series of such meetings) involving invited technical experts and
stakeholders. The workshop will be conducted in a formal, structured manner using
experienced facilitators trained in expert judgment techniques (e.g., multi-criteria decision
analysis, expert elicitation). A detailed summary of the discussions and views expressed
during the workshop will be used in refining the current research strategy document. This
summary will highlight areas of work that will be needed to support comprehensive
environmental assessments of nanomaterials. This refined statement of research directions
will provide longer term guidance for both ORD and the broader scientific community.
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4.3.4 Anticipated Outcomes
• Development of 3-4 draft case studies for specific applications of nano-titanium
dioxide and single-wall carbon nanotubes. Each draft case study will undergo
internal workgroup review.
• Administration of external peer consultation review, elaboration, and refinement of
the draft case studies
• Scheduling of a workshop for invited experts and stakeholders and public observers,
using formal expert judgment methods to identify and prioritize research needed to
support comprehensive environmental assessments of nanomaterials
• Using input from the workshop discussions, a document that lays out long range
research directions for obtaining information needed for nanomaterial CEAs
4.4 Research Theme: Preventing and Managing Risks
4.4.1 Key Science Question 7: What technologies or practices can be applied to
minimize risks of engineered nanomaterials throughout their life cycle, and how can
nanotechnologys' beneficial uses be maximized to protect the environment?
Manufacture\
\\
Distribution-^-
Storage//
Use/ /
Wat>\
Soil— — -x*1
Food ^/
_Webx
Primary
contaijjinants
"y»
Secondary f
_contaminants
/
Disposal
Ingest ion
Dermal
-absorption
* * *
Analytical Detection Method Development
^Ecosystems
Figure 4-8 - Relationship of Key Questions to Support Risk Assessment and Management Decisions -
Risk management
4.4.2 Background/Program Relevance
While it is critical to understand the potential environmental implications of nanotechnology, it is
also important to investigate how various nanomaterials can be used to prevent, control or
remediate environmental contaminants that have up to now been difficult to manage with
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conventional technology (Figure 4-8). Nanotechnology will be used to both create new
technologies and improve the performance of conventional technologies. There are several
avenues to obtain environmental benefits from nanotechnology.
• Use nanoscale materials in a synthesis process as a substitute for more toxic
components or as a process mediator that reduces the mass of potentially toxic
materials employed in the chemical process (e.g., catalysts)
• Incorporate nanoscale materials into a part of the production process used to treat
noxious chemicals prior to final discharge
• Employ nanoscale materials to treat emissions/releases from power production and
industrial processes waste streams
• Treat contaminated environmental media (i.e., air, water, sediments, or soil)
ORD's initial emphasis will be to address key pollutants of concern to EPA program and
regional offices that have historically been difficult to manage, including sources that emit
low concentrations of air pollutants and remediation of hazardous materials in complex
heterogeneous environments. The Woodrow Wilson Center 2007 report, "Green
Nanotechnology: It's Easier than You Think," describes a variety of potential environmental
benefits associated with use of the nanotechnology for environmental improvement.
In addition to supporting the recommendations of outside experts, this research will be
valuable to EPA program and regional offices and outside stakeholders such as industry and
states who are constantly looking for innovative solutions to address intractable pollution
problems. Many of these needs (see Appendix A) have already been identified.
As the ORD research program progresses and identifies potential problems with specific
engineered nanomaterials and products, risk management research will be directed to respond
to study the impacts of these materials and products. This response could include process
change recommendations that reduce/prevent the amount of engineered nanomaterials
released/emitted or using the unique properties of nanomaterials to reduce potential risks.
A substantial increase in nanomaterial manufacturing is predicted in coming decades. When
these particles or their nano-sized manufacturing or degradation byproducts find their way
into water, land, and air, it will be necessary to effectively and efficiently remove or detoxify
these substances. As a result, another key component of this science question will be to
quantify how well technologies now in place reduce emissions/releases of potentially
hazardous engineered nanomaterials. While these systems were not originally designed to
capture such small materials or associated by-products, some technologies may be able to
reduce them particularly if they have become bound to larger particles which the systems
were designed to control.
ORD will conduct various workshops with industry, academia, and other parts of EPA to
discuss potential environmental liabilities associated with manufacturing, using, recycling,
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and disposing of nanomaterials. The parties will exchange information and ideas about
where releases are more likely to pose the greatest risks and what alternatives (e.g., preferred
manufacturing approaches via green chemistry) are available that could minimize
environmental liabilities. These workshops will help all participants consider how
nanotechnology products can be designed in the most environmentally sustainable manner
possible.
4.4.3 Research Activities
Research devoted to the capture of engineered nanomaterials or degradation by-products
using conventional technology will address the ability of these technologies to manage
releases of engineered nanomaterials to all media during their production. For nanomaterial s
that cannot be efficiently treated or controlled, this may indicate that production and use
should be strictly controlled. Example abatement technologies to be evaluated include:
primary, secondary and tertiary drinking water treatment plant technologies; best
management practices (BMPs) for contaminated storm water and combined sewer overflow;
wastewater treatment technologies; membrane technology; adsorption; and conventional
particulate control technologies. The data collected will indicate whether existing abatement
procedures or technologies are adequate or require substantial revisions to control
nanomaterials.
This research will inform regulatory officials and industry about whether there are potential
risks posed by the releases of engineered nanomaterials into the environment and what
potential controls might be available to limit potential risks. This research has the potential
to influence decisions regarding manufacturing, importing, storage, handling, and use of
selected nanomaterials. The results of the research will be provided in the form of reports
and computer-based systems that can be used to address the unique issues associated with
various industrial operations.
Materials modification to support green manufacturing of nanomaterials
Research on greener synthesis approaches will identify opportunities to reduce the
environmental implications of nanomaterial production. Since basic nanotechnology
production processes are still under development, EPA is well placed to work with others to
design production processes that minimize or eliminate any emissions/releases. The goal of
this research will be to answer the question: how can energy consumption be minimized and
waste/pollution prevented in the manufacturing of nanomaterials and products? The general
approach will be to develop a strategy that allows the greener preparation of these materials.
Three of the main green chemistry areas that will be investigated include: 1) the choice of
solvent, 2) the reducing agent employed, and 3) the capping agent (or dispersing agent). For
example, ORD is using a flame and furnace reactor combination to produce single-walled
and multi-walled carbon nanotubes. Researchers are using a common feed-stock (e.g.,
propane), as opposed to mixtures of carbon monoxide and hydrogen, and a metallic catalyst
to initiate nanotube formation. The challenges are to achieve high-quality and high-yield
carbon nanotubes, and to use them for adsorption and catalyst support to enhance control of
selectivity, activity, and stability.
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Waste/byproduct minimization
The use of nanotechnology in industrial processes has many potential advantages. One
potentially significant environmental benefit is reducing the amount of material sent to the
waste stream. Under this research area, ORD will work with its partners in industry and
academia to investigate advanced approaches that have the potential to reduce waste products
in those industrial sectors with high volumes of waste. Waste minimization benefits to be
realized through nanotechnology applications will result either through the substitution of
less-toxic chemical components in the manufacturing process or through the reduction in the
required mass of toxic chemical components via enhanced reaction rates or efficiencies. An
example of the first scenario includes the use of nanomaterials to improve material
characteristics of bio-based, nanocomposite products. These products are being developed as
substitutes for more traditional petroleum-derived materials, resulting in a reduction of the
mass of toxic components that could potentially be released into the environment. There are
also numerous examples of the development of nanomaterials for use as catalysts in chemical
manufacturing processes. The use of nanoscale catalysts results in an overall enhancement of
process efficiency, thus reducing the required mass of toxic chemical components used in the
manufacturing process.
Application of nanomaterials to reduce environmental risks
Under this research area, ORD will investigate the potential for various nanomaterials to
minimize the release of toxic chemical constituents. Similar to the use of nanoscale catalysts
in the manufacturing process, the use of nanomaterials to treat process waste streams (gas,
liquid, or solid phases) provides enhancements in removal rates and/or efficiencies. One key
activity will include the application of nano catalysis for the reduction of air pollutants and a
better understanding of how these catalysts can be used in various environmental
applications. Inorganic nanoscale materials, including metallic iron nanomaterials and
aluminosilicate-based zeolites, have been synthesized for removal or degradation of metals
and organic contaminants from air and water effluents generated as a result of manufacturing
and power-generation operations (Ponder 2000, Song 2005). Similar to the case described
above for the manufacturing process, the use of nanomaterials in end-of-pipe treatments
affords the opportunity for regeneration or controlled disposal of treatment by-products. In
addition, this research will study the use of nano-scale iron particles to remediate aqueous
streams contaminated with chlorinated- organics, pesticides, PCBs, heavy metals and such
inorganics like Cr+6, arsenates, perchlorates, and nitrates. If these treatment and remediation
processes are successful, they can be incorporated into existing treatment systems to further
reduce contaminant loading.
Another area of emphasis within this program will be to investigate the ability to physically
and chemically tailor substances, surfaces, and pores at the nano-scale to improve selectivity
and efficiency of membrane filtration, adsorption, and catalysis. The objective is to identify
and evaluate innovative, high performance or lower cost alternatives for treating critical
contaminants. Improvements for many different treatment scenarios (e.g., matrices,
contaminants, treatment technologies, and treatment goals) may become feasible. Examples
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of areas where such an approach could provide significant improvements in removal
performance and cost savings is the use of nanotechnology to produce advanced sorbents for
mercury control and water treatment. In the mercury area, the ability to directly link the
physical and chemical nature of binding sites in the materials with the performance of those
materials is the key to developing new or improved adsorbents with properties that exceed
those that have conventionally been used. In the water area, nanomaterials may enable the
manufacture of media that are more selective, efficient, and economical for removal or
destruction of existing or emerging contaminants from drinking water, wastewater, and storm
water. These improved media may arise from better design and uniformity of pore size,
particle size, or composition made feasible by nano-scale design and control of the
manufacturing process.
Remediation of contaminated sites is another area where ORD will explore the use of
nanomaterials. Examples of these research and development efforts include the development
of nanoscale metallic solids or biopolymers for the destruction of organic contaminants or the
extraction of inorganic contaminants from ground water and soil. Ultimately, EPA can play
a significant role in advancing the development and implementation of these technologies
through research and testing. Using past experience implementing waste minimization,
treatment, and remediation technologies, EPA can fulfill the much-needed role of a technical
mediator between the commercial entities actively pursuing development of synthetic
nanomaterials and those who may be negatively affected by the large-scale utilization of
these materials.
4.4.4 Anticipated Outcomes
Within this research theme, the near-term emphasis will be on addressing scientific questions
related to the first two outcomes listed below.
• An evaluation of the efficacy of existing pollution control approaches and
technologies to manage releases of engineered nanomaterials to all media during their
production
The results of this assessment will be provided in the form of reports and computer-
based systems that can be used to identify and address the unique issues associated
with various industrial operations. Ultimately, regulatory officials and industry could
be informed about whether there are potential risks posed by the releases of
engineered nanomaterials into the environment and what potential controls might be
available to limit potential risks. This has potential to influence decisions regarding
manufacturing, importing, storing, handling, and using of selected nanomaterials.
• ORD will collaborate with others to report on opportunities to reduce the
environmental implications of nanomaterial production by employing greener
synthesis approaches.
• ORD will identify design production processes that minimize or eliminate any
emissions/releases and reduce energy consumption during the manufacturing of
nanomaterials and products.
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• ORD will report on the viability, performance, and benefits of the use of
nanotechnology for the abatement and remediation of conventional toxic pollution.
5.0 Implementation, Research Linkages, and Communication
Implementation
The research described in this NRS will be implemented through the multi-year plan (MYP)
process. ORD uses MYPs to provide a link between the strategic plans and annual plans,
showing how we intend to meet our out year goals. The MYPs chart the direction of ORD's
research program in selected topic areas over a period of approximately five to ten years.
The MYPs also link to each other, showing how the different parts of ORD's research areas
are integrated. MYPs aid in the evaluation of research options and foster the integration of
strategic risk-based environmental protection and anticipation of future environmental issues.
They also allow for a more comprehensive understanding of any changes needed to
emphasize a new direction or accelerate an existing program. MYPs are updated periodically
to reflect changes in Agency strategic thinking, the realities of available resources, and the
current state-of-the-science.
ORD has formed a Nanomaterial Research Coordination Team, which is a cross-Agency
research planning group, to communicate program office and regional research needs to
ORD and for ORD to communicate its research activities and products under the strategic
research themes. This approach promotes ORD's focus on the highest priority issues and
provides a roadmap to achieving our long-term research goals while allowing the flexibility
for ORD to address emerging nanotechnology issues that are affecting specific programmatic
areas.
Selection of Primary Engineered Nanomaterials - Initial Focus for Study
The ORD NRS Team has decided to focus on five engineered nanomaterials for study. The
materials selected are: (1) titanium dioxide; (2) zero valent iron; (3) nanosilver; (4) carbon
nanotubes; and (5) cerium oxide. These materials were selected with the goal of developing
predictive models and tools that will enable representative classes of nanomaterials to be
tested in lieu of individual materials.
Linkages to Related Federal Research
Figure 5-1 displays the flow of the EPA research themes to support each other and to inform
decisions. EPA will rely on basic research conducted by other Federal agencies to support
EPA applied research. NSF and NIEHS will contribute much of the basic research on
biomedical, engineering, and material development and characterization. ORD and NTP
scientists are working to prioritize/evaluate toxicity testing and developing approaches to
predict toxicity, while NIST will provide nanomaterial characterization and analytical
standards to provide a common context for the Federal research programs. ORD's research
program is coordinated and leveraged with the other Federal agencies involved in
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nanotechnology environment, health, and safety research through various collaborative
activities. For example, NIOSH and NTP collaboration on the toxicology of carbon
nanotubes and will support ORD health effects research and assessment.
Primary Environment and Health Research Areas for the EPA
EPA Research Themes
Human and ecological effects
to Inform risk assessment
Risk assessment
methods, Case
studies
Inform
Regulatory
Decisions
, fate, transport and
exposure
Preventing and mitigating
risks
Figure 5-1 - Environmental and Health Research Theme Linkages
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6.0 References
Davis, J.M., How to assess the risks of nanotechnology: learning from past experience. J.
Nanosci. Nanotechnol. 7(2): 402-409, 2007.
Davis, J.M. and Thomas, V.M. (2006) Systematic approach to evaluating trade-offs among
fuel options: the lessons of MTBE, Ann. N.Y. Acad. Sci. 1076:498-515.
Morgan, K. (2005) Development of a Preliminary Framework for Informing the Risk
Analysis and Risk Management of Nanoparticles. Risk Analysis 2'5, No. 6, 1621-1635.
Dix et al, ToxicolSci., 95(1):5-12, 2007
Environmental Defense - DuPont Nano Partnership (2007) Nano risk framework. New York,
NY: Environmental Defense. Available at http://www.environmentaldefense.org/go/nano.
Maynard, AD. (2006) Nanotechnology: A research strategy for addressing risk. Woodrow
Wilson International Center for Scholars. PEN 3 July. Washington, D.C.
Morgan, K. (2005) Development of a Preliminary Framework for Informing the Risk
Analysis and Risk Management of Nanoparticles. Risk Analysis 25, No. 6, 1621-1635.
National Nanotechnology Initiative, Sept.2006.
(wwwnano.gov/NNI_EHS_research_needs.pdf)
National Research Council of the National Academy of Sciences
(www.nap.edu/catalog/ll 970.html#toc)
National Research Council (NRC, 1983). Risk Assessment in the Federal Government:
Managing the Process. National Academy Press, Washington, DC.
Nowack, B. and Bucheli, T.D. (2007) Occurrence, behavior and effects of nanoparticles in
the environment. Environmental Pollution. In Press (Corrected proof available online).
Nishioka, Y, Levy, J.I., Norris, G.A., et al. (2002) Integrating risk assessment and life cycle
assessment: a case study of insulation. Risk Analysis 22: 1003-1017.
Ponder, S.M., Darab, J.G., and Mallouk, I.E. (2000). Remediation of Cr(VI) and Pb(II)
aqueous solutions using supported, nanoscale zero-valent iron. Environmental Science and
Technology, 34: 2564 -2569.
Presidential/Congressional Commission on Risk Assessment and Risk Management (1997).
Framework for Environmental Health Risk Management. Final Report of the Commission.
Volume 1
Science Policy Council (SPC, 2007) U.S. Environmental Protection Agency Nanotechnology
White Paper EPA 100/B-07/001, February 2007
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Schmidt, Karen F., Green Nanotechnology: It's easier than you think. Woodrow Wilson
International Center for Scholars, April 2007
Shatkin, J.A. and Qian, A. (2004) Classification schemes for priority setting and decision
making: a selected review of expert judgment, rule-based, and prototype methods. In
Comparative Risk Assessment and Environmental Decision Making. Linkov, I. & A.
Ramadan, Eds.: 213-244, Luewer, Amsterdam.
Song, W., Li, G., Grassian, V.H., and Larsen, S.C. (2005). Development of improved
materials for environmental applications: Nanocrystalline NaY zeolites. Environmental
Science and Technology, 39: 1214-1220.
Sonneman, G., Castells, F., and Schumacher, M. (2004) Integrated Life-Cycle and Risk
Assessment for Industrial Processes. Lewis Publishers. Boca Raton, FL.
Surowiecki, J. (2004) The Wisdom of Crowds. Little Brown, London
U.S. Environmental Protection Agency (1998) Guidelines for ecological risk assessment.
Washington, DC: Office of Research and Development, U.S. Environmental Protection
Agency. EPA/630/R-95/002F.
U.S. Environmental Protection Agency (2007) U.S. Environmental Protection Agency
Nanotechnology White Paper. Washington, DC: Science Policy Council, U.S.
Environmental Protection Agency. EPA 100/B-07/001.
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APPENDIX A. Relationship of ORD Research Strategy to EPA White Paper Research
Needs (Current Research (CR), Short-term Research (SR), and Long-term Research
(LT))
The table below is only intended to link the activities described in this strategy with the
overall research need questions in the EPA White Paper. It is not designed to provide details
on implementation of the NRS.
Research Theme
Research Need Questions (from EPA
White Paper; EPA, 2007)
Relationship to ORD
Strategy
(CR,SR,LR)*
Research Needs for Risk
Assessment
Chemical Identification and
Characterization
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)?
SR
How do these properties affect the
material's reactivity, toxicity and other
attributes?
SR
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
class of nanomaterials?
SR
Are there adequate measurement
methods/technology available to fully
characterize nanomaterials, to distinguish
among different types of nanomaterials, and
distinguish intentionally produced
nanomaterials from ultrafine particles or
naturally occurring nanosized particles?
SR
Are current test methods for characterizing
nanomaterials adequate for the evaluation
hazard and exposure data?
SR
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?
SR
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What intentionally produced nanomaterials ;
now on the market and what new types
of materials can be expected to be
developed?
SR
How will manufacturing processes,
formulations, and incorporations in end
products alter the characteristics of
nanomaterials?
SR
Environmental Fate and
Treatment Research Needs
Transport Research
Questions
What are the physical and chemical 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 ultrafme
particulate fate and transport inform our
thinking?
SR
How are nanomaterials transported in the
atmosphere? What nanomaterials properties
and atmospheric conditions control the
atmospheric fate of nanomaterials?
SR
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
general populations via groundwater
ingestion?
CR
What is the potential for these materials to
be transported bound to particulate matter,
sediments, or sludge in surface waters?
SR
How do the aggregation, sorption and
agglomeration of nanoparticles affect their
transport?
SR
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?
SR
Transformation Research
Questions
How do nanoparticles react differently in
the environment than their bulk counterparts
SR
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What are the physical and chemical factors
that impact the persistence of intentionally
produced nanomaterials in the environment?
What data are available on the physical and
chemical factors that affect the persistence o
unintentionally produced nanomaterials
(e.g., carbon-based combustion products)
that may provide information regarding
intentionally produced nanomaterials?
SR
Do particular nanomaterials persist in the
environment, or undergo degradation via
biotic of abiotic processes? If they degrade,
what are the byproducts and their
characteristics? Is the nanomaterial likely tc
be in the environment, and thus be available
for bioaccumulation/biomagnification?
SR
How are the physical, chemical and biologic
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?
SR
How do the aggregation, sorption and
agglomeration of nanoparticles affect their
transport?
SR
In what amounts and in what forms may
nanoparticles be released from materials
that contain them, as a result of environmen
forces (rain, sunlight, etc.) or through use,
re-use, and recycle or disposal.
LR
Chemical Interaction
Research Questions
How do nanosized adsorbents and
chemicals sorbed to them in 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 environmental?
SR
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?
SR
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Are these materials effectively removed
from wastewater using conventional
wastewater treatment methods and, if so, by
what mechanism?
SR
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?
SR
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?
SR
Assessment Approaches anc
Tools Questions
Can existing information on soil colloidal
fate and transport, as well as atmospheric
ultrafine particulate fate and transport,
inform our thinking? Do the current
databases of ultrafines/fibers shed light
on any of these questions?
CR
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?
CR
Should current fate and transport models
be modified to incorporate the unique
characteristics of nanomaterials?
SR
Environmental Detection an
Analysis Research Needs
Existing Methods and
Technologies Research
Questions
Are existing methods and technologies
capable of detecting, characterizing, and
quantifying intentionally produced
nanomaterials by measuring particle numbei
size, shape, surface properties (e.g.,
reactivity, charge, and area), etc? Can they
distinguish between intentionally produced
nanomaterials of interest and other ultrafine
particles? Can they distinguish between
individual particles of interest and particles
that may have agglomerated or attached to
larger particles?
SR
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Are standard procedures available for both
sample preparation and analysis?
SR
Are quality assurance and control reference
materials and procedures available?
SR
How would nanomaterials in waste media
be measured and evaluated?
SR
New Methods and
Technologies Research Neet
What low-cost, portable, and easy-to-use
technologies can detect, characterize, and
quantify nanomaterials of interest in
environmental media and for personal
exposure
LR
Human Exposures, Their
Measurement and Control
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?
SR
How do physical and chemical properties
of nanomaterials affect releases and
exposures?
SR
How do variations in manufacturing and
subsequent processing, and the use of
particle surface modifications affect
exposure characteristics?
SR
Release and Exposure
Quantification Research
Questions
What information is available about unique
release and exposure patterns of
nanomaterials? What additional information
needed?
LR
What tools/resources currently exist for
assessing releases and exposures within
EPA (chemical release information/
monitoring systems (e.g., TRI),
measurement tools, models, etc)? Are these
tools/resources adequate to measure,
estimate, and assess releases and exposures
to nanomaterials? Is degradation of
nanomaterials accounted for?
SR
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What research is needed to develop sensors
that can detect nanomaterials, including
personal exposure monitoring?
SR
Release and Exposure
Reduction and Mitigation
Research Questions
What tools/resources exist for limiting
release and/or exposure during manufacture,
use of following release via waste streams?
Are these tools/resources adequate for
nanomaterials?
SR
Are current respirators, filters, gloves, and
other PPE capable of reducing or
eliminating exposure from nanomaterials?
LR
Are current engineering controls and pollutii
prevention devices capable of minimizing
releases and exposures to nanomaterials?
SR
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?
LR
In the case of an unintentional spill, what
are the appropriate emergency actions?
How are wastes from the response actions
disposed of properly?
LR
Do existing methods using vacuum
cleaners with HEPA filters work to clean up
spill of solid nanomaterials? If not, would a
wet vacuum system work?
LR
What PPEs would be suitable for use by
operators during spill mitigation?
LR
Human Health Effects
Assessment Research Needs
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?
CR
Are there specific toxicological endpoints
that are of higher concern for nanomaterials,
such as neurological, cardiovascular,
respiratory, or immunological effects, etc.?
SR
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Are current testing methods (organisms,
exposure regimes, media, analytical
methods, testing schemes) applicable to
testing nanomaterials in standardized
agency toxicity tests
(http://www.epa.gov/opptsfrs/OPPTS_
Harmonized/)?
SR
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?
SR
Are current analytical methods capable of
analyzing and quantifying intentionally
produced nanomaterials to generate dose-
response relationships?
SR
What physical and chemical properties
regulate nanomaterial absorption,
distribution, metabolism, and excretion
(ADME)?
SR
What physical and chemical properties and
dose metrics best correlate with the toxicity
(local and systemic; acute and chronic) of
intentionally produced nanomaterials
following various routes of exposure?
CR
How do variations in manufacturing and
subsequent processing, and the use of
particle surface modifications affect
nanomaterial hazard?
CR
Are there subpopulations that may be at
increased risk of adverse health effects
associated with exposure to intentionally
produced nanomaterials?
SR
What are the best approaches to build effecti
predictive models of toxicity
(SAR, PBPK, "omics", etc.)?
SR
Are there approaches to grouping particles ii
classes relative to their toxicity
potencies, in a manner that links in vitro, in
vivo, and in silico data?
LR
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Ecological Effects Research
Needs
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.
SR
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.
SR
What are the effects (local and systemic; aci
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?
SR
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).
SR
How do variations in manufacturing and
subsequent processing, and the use of partic
surface modifications affect nanomaterial
toxicity to ecological species?
SR
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?
LR
What research is needed to develop
structure activity relationships (SARs) for
nanomaterials for aquatic organisms?
SR
What are the modes of action (MOAs) for
various nanomaterials for ecological specie;
Are the MO As different or similar across
ecological species?
SR
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Risk Assessment Research -
Case Study
Which of the research needs identified in
the EPA Nanotechnology White Paper and
in the overarching and component questions
listed here are of the highest priority from
the standpoint of generating information
needed to support risk assessments of
nanomaterials selected as case studies?
SR
For selected case studies, using expert
judgment methods, what do we know and
what do we need to know (in priority
ranking) regarding the potential for
exposure (cumulative and aggregate) of
humans and biota to primary and secondary
materials via multi-media pathways?
SR
Which nanomaterials and applications
should ORD focus its efforts on first as case
studies? Which expert judgment method(s)
is (are) applicable to evaluating selected
case studies for identifying "what we know
and what we need to know" and for
prioritizing research needs?
CR
SR
For selected case studies, using expert
judgment methods, what do we know and
what do we need to know (in priority
ranking) regarding specific details of
product life cycle stages, including
feedstocks, manufacturing, distribution,
storage, use, and disposal/reuse?
SR
For selected case studies, using expert
judgment methods, what do we know and
what do we need to know (in priority
ranking) regarding likely primary
nanomaterials and secondary substances
(e.g., waste by-products) that may be
released/emitted at each stage of the product
life cycle?
SR
For selected case studies, using expert
judgment methods, what do we know and
what do we need to know (in priority
ranking) regarding likely environmental
SR
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Green Manufacturing
Research Needs
Green Energy Research Net
Environmental
Remediation/Treatment
Research Needs
media (air, water, soil, food web) to which
releases/emissions of primary and
secondary materials may occur, and about
potential transport and fate processes that
may be applicable?
How can nanotechnology be used to
reduce waste products during
manufacturing?
How can nanomaterials be made using beni^
starting materials?
How can nanotechnology be used to
reduce the resources needed for
manufacturing (both materials and energy)?
What is the life cycle of various types of
nanomaterials and nanoproducts under a
variety of manufacturing and environmental
conditions?
What research is needed for incentives to
encourage nanotechnology to enable green
energy?
How can nanotechnology assist "green"
energy production, distribution, and use?
Which nanomaterials are most effective for
remediation and treatment?
What are the fate and effects of nanomateria
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?
What is needed to enhance the efficiency am
cost-effectiveness of remediation and
treatment technology?
SR
CR
LR
SR
LR
LR
CR
CR
CR
SR
SR
LR
SR
64
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Sensors
How can nanomaterials be employed in
the development of sensors to detect
biological and chemical contaminants?
How can systems be developed to monitor
agents in real time and the resulting data
accessed remotely?
How these small-scale monitoring systems b
developed to detect personal exposures
and in vivo distributions of toxicants.
LR
LR
LR
Appendix B. Description of EPA Office of Research and Development
The Office of Research and Development (ORD) is the principal research arm of the
Environmental Protection Agency (EPA) (http://www.epa.gov/ord/). Its role is to provide the
critical science for the Agency's environmental decision-making. Unlike much of EPA,
ORD has no direct regulatory function; its responsibility is to inform the policymaking
process. Through the development of technical information and scientific tools, ORD's
research strengthens EPA's science base by providing its program offices and regional
offices with sound scientific advice and information for use in developing and implementing
scientifically defensible environmental policies, regulations, and practices.
As may be seen in Figure B-l, ORD is led by the Assistant Administrator (AA) for Research
and Development, who reports directly to the EPA Administrator. This position involves
providing leadership in establishing research priorities, ensuring the means for technical
evaluation and peer-review of ORD's products, and contributing scientific input into the
EPA's regulatory decisions.
The AA ORD is supported by a Deputy Assistant Administrator (DAA) for Management and
a DAA for Science. The Directors of ORD's Laboratories and Centers provide scientific
leadership relative to their respective organizations and report to the AA ORD. Recently,
ORD established National Program Directors (NPDs). The NPDs provide a strategic vision
of the stakeholder needs and overall coordination of research programs delineated in ORD
Multi-Year Plans (MYPs).
ORD is comprised of seven national Laboratories and Centers and two Offices. The
Laboratories and Centers, spread across the country, conduct research across the risk
assessment/risk management paradigm related to both the environment and human health.
ORD also has a National Homeland Security Research Center and a National Center for
Computational Toxicology. ORD's two offices are the Office of Science Policy (OSP) and
the Office of Resources Management and Administration (ORMA). OSP plays a vital role
by providing expert advice and evaluation on the use of scientific knowledge and science
policy to support sound science in the Agency. OSP accomplishes this mission by leading
efforts in science integration, coordination and communication across ORD, and between
ORD and the Agency's programs, regions, and external parties. ORMA manages a broad
65
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spectrum of issues and provides counsel/advice on all matters relating to the responsible
management of ORD's resources.
Immediate Office
of the Assistant Administrator
George Gray, Assistant Administrator & Agency Science Advisor
Kevin Teichman, Acting Deputy Assistant Administrator for
Science
Lek Kadeli, Deputy Assistant Administrator for Management
National Exposure
Research Laboratory
Larry Reiter
National Center for
Environmental
Assessment
Peter Preuss
National Program Directors
Air: Dan Costa
Drinking Water: Audrey Levine
Water Quality: Chuck Moss
Pesticides and Toxics/EDCs: Elaine Francis
Land: Randy Wenstel
Human Health: Salfy Darney
Ecosystem Protection: Rick Linthurst
Global Change/Mercury: Joel Scheraga
Sustasnability: Alan Hecht
Human Health Risk Assessment; John Vandenberg
National
Risk Management
Research Laboratory
Sally Gutierrez
National Center for
Environmental
Research
William Sanders
National Homeland
Security Research
Center
Jonathan Herrmann
Figure B-l - Organization Chart for the Office of Research and Development
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v>EPA
United States
Environmental Protection
Agency
PRESORTED STANDARD
POSTAGE & FEES PAID
EPA
PERMIT NO. G-3S
Office of Research and Development (81 OR)
Washington, DC 20460
Official Business
Penalty for Private Use
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