Nanotech Research Strategy Final

&EPA United States
EPA 620/K·09/011 I June 20091 www.epa.gov/nanoscience
Environmental Protection
Agency
_ Office of Research and Development
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EPA 620/K-09/011 | June 2009
Nanomaterial Research Strategy
Office of Research and Development

U.S. Environmental Protection Agency
Washington, D.C.
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Writing Team
Jeff Morris, Co-Lead
Randy Wentsel, Co-Lead
Michele Conlon, NERL Douglas McKinney, NRMRL

J. Michael Davis, NCEA Dave Mount, NHEERL
Steve Diamond, NHEERL Carlos Nunez, NRMRL
Kevin Dreher, NHEERL Nora Savage, NCER
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 March, 2008
External Letter Review, November 2008
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Contents
Executive Summary ........................................................................................................................ iii
Major acronym list........................................................................................................................... v
1.0 Introduction................................................................................................................................ 1
2.0 Context....................................................................................................................................... 3
3.0 Key Considerations.................................................................................................................... 7
3.1 Selection of Materials ................................................................................................................ 7
3.2 Strategic Direction of Research Themes and Science Questions .............................................. 8
4.0 Research Themes ......................................................................................................................11
4.1.1 Key Science Question 1 ..................................................................................................11
4.1.1.1 Background/ Program Relevance ..........................................................................11
4.1.1.2 Research Activities ................................................................................................11
4.1.1.3 Anticipated Outcomes ...........................................................................................12
4.1.2 Key Science Question 2...................................................................................................12
4.1.2.1 Background/Program Relevance ...........................................................................13
4.1.3.1 Background/ Program Relevance ..........................................................................17
4.2 Research Theme: Human Health and Ecological Effects Research
to Inform Risk Assessments and Test Methods ........................................................................20
4.2.1 Background and Program Relevance...............................................................................20
4.2.2.1 Human Health Effects Research Activities ...........................................................20
4.2.3.1 Ecological Effects Research Activities ..................................................................24
4.2.4 Anticipated Outcomes ......................................................................................................25
4.3 Research Theme: Developing Risk Assessment Methods ........................................................26
4.3.2 Background/Program Relevance .....................................................................................26
4.3.3 Research Activities ..........................................................................................................27
4.3.4 Anticipated Outcomes ......................................................................................................28
4.4 Research Theme: Preventing and Managing Risks.................................................................. 29
4.4.1.1 Background/Program Relevance ...........................................................................29
4.4.1.3 Anticipated Outcomes ............................................................................................33
4.4.2 Key Science Question 8 .........................................................................................................34
4.4.2.1 Reserach Activities ................................................................................................34
4.4.2.2 Anticipated Outcomes ............................................................................................36
5. Conclusion ..................................................................................................................................37
References.......................................................................................................................................39
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List of Figures
Figure 1-1 Nanomaterials and Environmental Decision Making: Key Decision-Support
Questions....................................................................................................................................1
Figure 2-1 Roles of NEHI Working Group Member Agencies with Regard to Nanotechnology –
Related EHS Research Needs ....................................................................................................3
Figure 2-2 Federal Sources to Inform EPA’s Nanotechnology Activities .........................................4
Figure 2-3 EPA’s NRS Within The Decision-Support Context.........................................................5
Figure 3-1 Relative Priority of Research Themes.............................................................................7
Figure 3-2 Relationship of Key Science Questions to Support Risk Assessment and Management
Decisions; Based on Comprehensive Environmental Assessment (Davis and Thomas, 2006) .8
Figure 4-1 Critical Path for Research on Detection – Key Science Question 1 .............................13
Figure 4-2 Critical Path for Research on Sources, Fate, and Transport–Key Science Question 2 .16
Figure 4-3 Critical Path for Research on Exposure Pathways – Key Science Question 3 .............19
Figure 4-4 An Integrated Testing Strategy for ORD’s Nanomaterials Health Effects
Research ...................................................................................................................................21
Figure 4-5 Critical Path for Conducting ORD’s Nanomaterial Human Health Effects Research –
Key Science Question 4 ...........................................................................................................23
Figure 4-6 Critical Path for Conducting ORD’s Nanomaterial Human Health Effects Research –
Key Science Question 5 ...........................................................................................................26
Figure 4-7 Critical Path for Risk Assessment Research – Key Science Question 6 .......................29
Figure 4-8 Characterization of a Selected Nanotechnology for Life Cycle Assessment ................31
Figure 4-9 Research Theme: Preventing and Mitigating Risk Methods –
Key Science Questions 7 & 8 ..................................................................................................36
List of Tables
Table 4-1 Models/Tools to Conduct Chemical Exposure Assessments .........................................17
ii
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Executive Summary
With the use of nanotechnology in the consumer and industrial sectors expected to increase
significantly in the future, nanotechnology offers society the promise of major benefits. 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 to sustainably apply nanotechnology to detect, monitor, prevent, control, and
clean up pollution is needed.
The purpose of the Nanomaterial Research Strategy is to guide the EPA’s Office of Research and
Development’s program in nanomaterial research. The strategy builds on and is consistent with the
foundation of scientific needs identified by the Nanotechnology Environmental and Health Implications
Working Group (NSTC, 2008), and in the EPA’s
Nanotechnology White Paper (EPA, 2007). The Nanomaterial Research Strategy (NRS) guides
the nanotechnology research program within EPA’s
The purpose of EPA’s nanotechnology research Office of Research and Development.
program is to conduct focused research to
inform nanomaterial safety decisions that may
be made under the various environmental statutes for which EPA is responsible. EPA recognizes that the
information generated through its research program
is also likely to have use in areas beyond the Agency’s purview. EPA will collaborate across the
government, industry, and the international community to implement this strategy. EPA’s in-house
research program will leverage results from EPA grant programs, as well as collaborate with grantees to
address the many challenging research issues outlined in this strategy.
EPA’s strategy focuses on four areas that take advantage of EPA’s scientific expertise as well as fill gaps
not addressed by other organizations. The four research themes are:
Identifying sources, fate, transport, and exposure
Understanding human health and ecological effects to inform risk assessments and test methods
Developing risk assessment approaches
Preventing and mitigating risks
EPA’s Nanomaterial Research Program is designed to provide information to support nanomaterial safety
decisions. The eight key science questions described in the strategy are intended to help decision makers
answer the following questions:
What nanomaterials, in what forms, are most likely to result in environmental exposure?
What particular nanomaterial properties may raise toxicity concerns?
Are nanomaterials with these properties likely to be present in environmental media or biological
systems at concentrations of concern, and what does this mean for risk?
If we think that the answer to the previous question is “yes,” can we change properties or mitigate
exposure?
Providing information to answer these questions will serve the public by enabling decisions that
minimize potential averse environmental impacts, and thereby maximize the net societal benefit from the
development and use of manufactured nanomaterials.
iii
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iv
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Major Acronym List
AA Assistant Administrator
ADME Absorption, distribution, metabolism, elimination
AML Advanced Measurement Laboratory
BMPS Best management practices
CAA Clean Air Act
CEA Comprehensive environmental assessment
CERCLA Comprehensive Environmental Response Compensation and Liability Act
CR Current Research
CREM Council for Regulatory Environmental Modeling
CT Committee on Technology
DAA Deputy Assistant Administrator
DOD Department of Defense
DOE Department of Energy
DSSTOX Distributed Structure-Searchable Toxicity
HPG Hypothalamic-Pituitary-Gonadal
IRIS Integrated Risk Information System
LCA Life cycle Analysis
MOA Mechanism of action
MOAS Modes of Action
MR-CAT Materials Research Collaborative Access Team
MYP Multi-year plan
NAS National Academy of Science
NCCT National Center for Computational Toxicology
NCEA National Center for Environmental Assessment
NCER National Center for Environmental Research
NCI National Cancer Institute
NCL Nanotechnology Characterization Laboratory
NEHIWG Nanotechnology Environmental and Health Implications Working Group
NERL National Exposure Research Laboratory
NHEERL National Health and Environmental Effects Laboratory
NGO Non-Governmental Organization
NIEHS National Institute of Environmental Health Sciences
NIOSH National Institute for Occupational Safety and Health
NIST National Institute of Standards and Technology
NNCO National Nanotechnology Coordination Office
NNI National Nanotechnology Initiative
NPDS National Program Directors
NRC National Research Council
NRMRL National Risk Management Research Laboratory
NRS Nanomaterial Research Strategy
NSET Nanoscale Science Engineering and Technology
NSF National Science Foundation
NSTC National Science and Technology Council
OECD Organization for Economic Cooperation and Development
v
ORD Office of Research Development
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vi
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1.0
Introduction
Purpose. The Nanomaterial Research Strategy with its federal research partners in other research
(NRS) describes the Environmental Protection areas. EPA’s in-house research program will
Agency’s (EPA) strategy for conducting and leverage results from EPA grant programs, as well
supporting research to understand the potential as collaborate with grantees to address the many
human health and ecological (henceforth referred challenging research issues outlined in this strategy.
to jointly as “environmental”) implications from
exposure to manufactured nanomaterials, and Focus. The NRS focuses on developing scientific
how nanotechnology can be used sustainably in information for nanomaterial decision support.
environmental protection applications. EPA has Because other entities also conduct research on
written this document with three main purposes: nanomaterial safety, EPA is focusing on four
(1) to guide its own researchers and managers areas that take advantage of EPA’s scientific
as they conduct EPA’s research program, (2) to expertise as well as fill gaps not addressed by other
assist scientists in other organizations as they plan organizations. The four research themes are:
research programs, and (3) to inform the public of
Identifying sources, fate, transport, and
how EPA intends to generate scientific information
exposure
to guide environmental decisions related to
nanomaterials. Understanding human health and ecological
effects to inform risk assessments and test
The purpose of EPA’s research program is to methods
conduct focused research to address risk assessment Developing risk assessment approaches
and risk management needs for nanomaterials
in support of the various environmental statutes Preventing and mitigating risks
for which EPA is responsible. This program will
be coordinated with research conducted by other In addressing these themes, EPA’s research program
federal agencies, where EPA will lead selected will focus on providing information that supports
research areas and coordinate and/or collaborate the type of decision logic outlined below in Figure
1-1.
Figure 1.1. Nanomaterials and Environmental Decision Making: Key Decision-Support Questions
What NMs, in what forms, are

most likely to result in
environmental exposure? Are NMs with these properties If “yes,” can we change
likely to be present in properties or mitigate
environmental media or
exposure?
biological systems at
What particular NM properties concentrations of concern?
may raise toxicity concerns?
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Objectives. EPA believes that its research should Approach. The NRS will be implemented in EPA’s
advance two key objectives: (1) the development Office of Research of Development (ORD), in two
of approaches for identifying and addressing any main ways: by funding grants through the Science
hazardous properties, while maintaining beneficial to Achieve Results (STAR) and Small Business
properties, before a nanomaterial enters the Innovation Research (SBIR) programs, and by EPA
environment; and (2) identifying whether, once a scientists within ORD’s research laboratories and
nanomaterial enters the environment, it presents centers. Expertise needs will determine how resources
environmental risks. EPA will pursue these objectives are allocated between externally and internally
from a life cycle perspective—i.e., by understanding conducted research.
where environmental impacts may occur and where
benefits may be attained throughout a nanomaterial’s Organization. The NRS is organized around the
existence; from its production, through its use in four research themes. Within each theme, research
products and as it is disposed of or recycled. activities are identified along critical paths toward
addressing science questions.

2.0
Context
EPA’s NRS is one component of an international National Nanotechnology Initiative (NNI)
effort to generate information on nanomaterials and Strategy For Nanotechnology-Related
the environment. Other US federal agencies, national Environmental, Health, and Safety Research.
governments, industry, academic institutions, and This interagency research strategy outlines the
non-governmental organizations are also involved. US federal research plans for approximately
While the number of individuals and organizations the next ten years. Figure 2-1, taken from the
generating information on the environmental impacts Strategy, illustrates the NEHI members’ roles in
of nanomaterials is large and growing, for the implementing the interagency strategy. While
purposes of placing the NRS within a larger context coordinating agencies will play a leadership role
there are four major efforts underway: in advancing interagency implementation of the
Organization for Economic Cooperation NNI strategy, other agencies may play scientific
and Development (OECD) Working Party leadership roles in particular areas.
on Manufactured Nanomaterials. The
EPA NRS. The NRS was developed in concert
OECD is coordinating a testing program on
with the NNI strategy.
nanomaterials deemed by the Working Party
to be representative of materials likely to enter EPA Nanomaterial Stewardship Program
commerce. Test plans are to be completed in (NMSP). EPA’s office of Pollution Prevention
mid-2009, with Phase 1 testing to be completed and Toxic Substances has initiated a program
in approximately three years. for the voluntary submission of nanomaterials
Figure 2-1. Roles of NEHI Working Group Member Agencies with Regard
to Nanotechnology –Related EHS Research Needs
Table 2. Roles of NEHI Working Group Member Agencies with Regard
to Nanotechnology-Related EHS Research Needs
- Coordinating agency - Contributor - User
All coordinating agencies have roles as contributors to and users of the research from the respective
categories, with the exception of FDA, which as the roles of coordinating agency and user.
Risk Management Methods
Instrumentation, Metrology,
Nanomaterials and Human

Research Need
Human & Environmental

and Analytical Methods
Nanomaterials and the
Exposure Assessment
Environment
Health
Agency
NIH
NIST
EPA
FDA
NIOSH
NSF * * * * *
DOD
DOE
USDA
DOT
OSHA
CPSC
USGS
*NSF is a contributor according to the mission of the agency covering the upstream, fundamental
research on utilization, implications, and risk mitigation of nanotechnology, infrastructure and education.
3

environmental, health, and safety information coordinating agency for the “Nanomaterials
from industry and others. and the Environment” and “Risk
Management Methods” areas of the NNI
Collaboration for Decision Support. For the NRS strategy. EPA also co-chairs the NEHI and
to provide maximum scientific value and guide is leading efforts, such as planning state-
most efficient resource use, collaborating with and of-the-science workshops, to advance
leveraging the work of others is crucial. Figure implementation of the interagency strategy.
The NRS is also being implemented by EPA
2-2 illustrates the breadth of information needed issuing joint grant requests for applications
to make decisions related to nanomaterials and (RFA) with other federal agencies, including
the environment, as well as the number of federal the National Science Foundation (NSF),
entities involved in generating and using this the National Institute for Environmental
information. Health Sciences (NIEHS), and the National
Institute for Occupational Safety and
EPA is using several approaches to link the NRS Health (NIOSH). EPA’s laboratories are
to other efforts to develop scientific information in also coordinating and collaborating with
support of decision making. They include: other agencies, such as with the National
Toxicology Program and NIOSH on carbon
Coordinating and collaborating with
nanotubes. Also, EPA is co-sponsoring
other federal agencies. As shown in
with NSF new national Centers for the
Figure 2-1, EPA is the federal government’s
Environmental Implications of Nanomaterial
Figure 2-2. Federal Sources to Inform EPA’s Nanotechnology Activities
Understanding Nanotechnology Implications

Characterization , Instrumentation , Toxicity
Properties Metrology,
DOD
Standards EPA
D OD FDA
D OE DOD NIH
EPA DOE NIOSH
N ASA
N IH
NASA
NIH
EPA NSF
N IST NIST
N SF Research Fate, Transport ,
NSF
Transformation,
Risk assessment Release,
Treatment
Risk management
D OD
Sustainability D OE
EPA
N IH
Stewardship N IOSH
N SF
Pollution Remediation Sensors, Devices Detection,

Prevention EPA DHS
Monitoring
Gre en ma nufacturing DHS DOD
Gree n En gine ering DOD DOE DOD
Green Energy EPA
NASA EPA
NSF NASA NIH
EPA NIOSH
D OD NIH
NIOSH NSF
D OE USGS
NIST
NSF
USDA
Applications USGS
Note: NIH includes NIEHS , NCI (NCL), NTP

Figure 2-3 EPA’s NRS Within The Decision-Support Context
Decision-Support & Institutional Context:

EPA-centric View
Other Agencies
NEHI “Bi-lateral”
Academic Research EPA OECD Testing Program
Industry-sponsored Testing
Health and Environmental

Decisions
(CEINT) to conduct fundamental research Figure 2-2 depicts how EPA fits within the larger
and education on the implications of information-gathering context to support decisions
nanotechnology for the environment and related to nanomaterials and the environment.
living systems at all scales. The CEINTs will
address interactions of naturally derived, Integration. Successfully implementing the NRS
incidental and manufactured nanomaterials within a larger scientific context will require EPA to
with the living world. integrate into its research program information from
various sources. EPA is using the following means to
Participating in the OECD Testing
enable such integration:
Program. In implementing the NRS,
EPA is co-sponsoring testing on a number Supporting and using the OECD’s
of nanomaterials. EPA researchers will international database on nanomaterial
divide testing responsibilities and share environmental, health, and safety research.
test materials with the co-sponsoring
Holding joint meetings with EPA researchers
organizations.
and STAR grantees.
Nanomaterial Stewardship Program.
Convening state-of-the-science workshops
EPA believes that the NMSP will provide
on each of the four NRS research themes.
material-specific and general information
that will be useful to advancing EPA’s Leading and participating in NNI-sponsored
research program. Also, ORD researchers workshops as part of implementing the
are collaborating with OPPT on identifying interagency strategy.
information gaps that the NMSP can address.

Periodically, EPA will issue a research progress assessments. Therefore, ORD will provide scientific
document describing EPA’s overall advance in expertise in applying existing methods, models, and
implementing the NRS. data to nanomaterial decision making, as well as
investigating alternative decision-support tools in
ORD also recognizes that it must provide decision the absence of risk assessment information.
support in the near term, even as data are generated
and methodologies developed for complete risk

3.0
Key Considerations
This section outlines five key considerations that iron) or because EPA may need to make safety
ORD took into account as it developed the NRS. decisions on the materials under its regulatory
These five considerations—selection of materials, programs. EPA program offices that have already
research themes and science questions, informing risk given consideration to some of these specific
assessment and risk management, setting priorities, materials include the Office of Pollution Prevention
and implementation—serve to bound the ORD and Toxics, the Office of Pesticide Programs, and
nanomaterials research program. Putting bounds around the Office of Air and Radiation.
the program is important, given resource limitations
and acknowledging that the NRS fits within and should The United States, with EPA as a principal
complement a larger national and international context participant, is sponsoring or co-sponsoring the
of nanomaterial EHS research. testing of all of the seven materials as part of
the OECD’s nanomaterial testing program. In
3.1 Selection of Materials particular, EPA is taking leadership roles in the
ORD is focusing its research on seven manufactured testing of cerium, C-60 fullerenes, nanotubes,
nanomaterial types: single-walled carbon nanotubes, silver, and titanium dioxide. This program allows
multi-walled carbon nanotubes, fullerenes, cerium the ORD to leverage the work of other nations
oxide, silver, titanium dioxide, zero-valent iron. and organizations in advancing the Nanomaterial
Ultimately, ORD has as a goal, the development of Research Strategy. For example, for the carbon
predictive models and tools that will enable testing materials Japan, Korea, and industry are conducting
across these material types, since testing the many mammalian toxicity testing, while EPA will do
potential variations of materials within each of these environmental fate and ecological effects testing.
seven material types would be very resource intensive. Thus, the partnership for these materials cover all
the endpoints under the OECD program.
ORD selected these seven material types based on
the materials’ current use in products, the near-term There is no question that the types of, and
needs of EPA’s program and regional offices, research variations on, nanomaterials is large and growing,
underway at other federal agencies, and the materials and goes beyond the materials ORD has chosen
selected for testing in the OECD’s Working Party on for near-term study. However, these seven material
Manufactured Nanomaterials. Over time, ORD expects types are a good starting point for the new ORD
to extend its efforts to other material types. program, which will evolve together with state of
nanoscience and as environmental decision-support
These materials are of interest to EPA either because of needs change.
their potential use in cleaning up pollution (zero-valent
Figure 3-1. Relative Priority of Research Themes
NRS Research Themes

Sources, Fate, Transport, and Exposure
Human Health and Ecological Effects Research to Inform Risk Assessment and Test Methods
Risk Assessment Methods and Case Studies
Preventing and Mitigating Risks

3.2 Strategic Direction of Research Themes and the physical and chemical properties of those
Science Questions materials?
EPA has identified four key research themes where it What are the exposures that will result from
can support the National Nanotechnology Initiative and releases of manufactured nanomaterials?
the science needs of EPA.
Theme 2. Human Health and Ecological Effects
Key Science Questions. Under each of the four Research to Inform Risk Assessment and Test Methods
research themes, the EPA research program will What are the health effects of manufactured
address key science questions. nanomaterials and their applications, and
how can these effects be best quantified and
Theme 1. Sources, Fate, Transport, and Exposure predicted?
What technologies exist, can be modified, What are the ecological effects of
or must be developed to detect and quantify manufactured nanomaterials and their
manufactured nanomaterials in environmental applications, and how can these effects be best
media and biological samples? quantified and predicted?
Theme 3. Risk Assessment Methods and Case
What are the major processes and/or Studies. In what ways, if at all, do risk assessment
properties that govern the environmental fate, approaches need to be amended to incorporate special
transport, and transformation of manufactured characteristics of manufactured nanomaterials?
nanomaterials, and how are these related to
Figure 3-2 Relationship of Key Science Questions to Support Risk Assessment and Management Decisions; Based on
Comprehensive Environmental Assessment (Davis and Thomas, 2006)
n
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ay
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t
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es hw
fo m en en
ag at ns Hu sm em
t lP a a/ ct
s
ag
e
S
ta Tr i ot fe es
l n (B f s an
yc e t& e E As M
C nm or ur sk sk
fe ro p s Ri Ri
Li vi a ns po
En Tr Ex
Technology
Feedstocks Evaluation
Verification
Air Primary Inhalation Ecosystems
Manufacture Risk Modeling
contaminants
Water Characterization
Distribtuion Cost
Ingestion Analyses
Soil
Storage Process
Secondary Quantitative Modifications
Food contaminants Dermal Health
Use Web Qualitative Adaptation/
absorption
Revitalization/
Disposal Restoration/
Remediation
Analytical Detection Method Development

Theme 4. Preventing and Managing Risks Does the research support EPA’s mission to
protect human health and the environment?
Which manufactured nanomaterials have a
high potential for release from a life cycle Is the research important to support EPA
perspective and what decision-making regulatory decisions on nanomaterials?
methods and practices can be applied
What role does EPA play in leading/
to minimize the risks of nanomaterials
coordinating this research topic under the NNI
throughout their life cycle?
EHS strategy (2008)?
How can manufactured nanomaterials be
Is the research part of an international
applied in a sustainable manner for treatment

agreement to collaborate and leverage
and remediation of contaminants?

research activities?
What research is important to support Agency

3.3. Informing Risk Assessment and Risk
risk assessment and management activities?
Management
Figure 3-2 illustrates the interrelationship of the How do partnerships with federal, academic,
research activities and research products that inform and industry researchers enhance research
risk assessment and risk management issues. While activities?
the basic paradigms of health and ecological risk Having considered these questions within the
assessment are still relevant, they are expanded in context of resource constraints and research being
the comprehensive environmental assessment (CEA) conducted by other organizations, ORD has focused
approach to encompass the product life cycle of its nanotechnology research program on the areas
nanomaterials. By taking a broad view of the potential described in Section 4 of this strategy.
for releases of both primary and secondary materials
to multiple environmental media, the evaluation of 3.5 Implementation
the environmental and health risks of nanomaterials The research described in this NRS will be
is seen as an issue that cuts across EPA programmatic implemented through multi-year plans (MYP). The
domains and is not simply categorized as solely an Office of Research and Development’s research
air, water, toxics, or solid waste issue. The CEA multi-year plans present the long-term strategic
approach (Davis and Thomas, 2006; Davis, 2007) vision of EPA’s research programs. The MYPs serve
starts with a qualitative life cycle framework. It takes as a planning and communication tool to describe
into consideration multiple environmental pathways, the scope of research addressing EPA’s priority
transport and transformation processes, cumulative science questions. The MYPs are also used to help
and aggregate exposure by various routes, and (1) demonstrate how ORD’s research programs
ecological as well as human health effects. Depending contribute to Agency outcomes and strategic goals; (2)
on the availability of data, both quantitative and provide information to aid in and support decisions
qualitative characterizations of risks may result. during budget formulation; and (3) assist in managing
However, given the limited information currently performance and accountability reporting.
available on nanomaterials, the CEA approach is being
used to identify where key data gaps exist with respect ORD is forming a Nanomaterial Research
to selected case studies of specific applications of Coordination Team, which is a cross-EPA research
nanomaterials. planning group, to communicate program office and
regional research needs to ORD and for ORD to
3.4 Prioritization of Research communicate its research activities and products under
ORD evaluated several key issues and activities to the strategic research themes. This approach promotes
identify priorities for its research program. Research ORD’s focus on the highest priority issues and
recommendations from the EPA Nanotechnology provides a roadmap to achieving long-term research
White Paper and research coordination leadership goals while allowing the flexibility for ORD to address
in the NNI Strategy (2008) were important emerging nanotechnology issues that are affecting
considerations. Defining questions for establishing specific programmatic areas.
priorities were:

This section discusses the research themes and represent the sequencing of key deliverables, and
associated key science questions. For each science the arrows indicate how one deliverable informs
question, text addresses the topic background and another. The critical-path diagrams do not reflect
program relevance, describes the proposed research when specific research activities begin or end: in
activities, and discusses the anticipated outcomes. general, work will be initiated far in advance of the
deliverable, and may continue in some form once a
Critical Paths. For each key science question, the
deliverable has been completed.
NRS presents a critical-path diagram for addressing
the question. The boxes within each diagram
10

4.0
Research Themes
4.1 Research Theme: Sources, Fate, Transport, and the modification of existing analytical tools and the
Exposure development of completely new tools and approaches
to meet these challenges. The same properties that
4.1.1 Key Science Question 1. What technologies make nanomaterials a significant challenge to analyze
exist, can be modified, or must be developed to in any matrix (such as high binding capacities) may
detect and quantify manufactured nanomaterials in also provide unique opportunities for developing new
environmental media and biological samples? analytical methods (e.g., tagging with fluorophores)
for their analysis in complex biological and
4.1.1.1 Background/ Program Relevance environmental systems. Obviously, studies will be
necessary to determine how such tagging techniques
The detection of manufactured nanomaterials in
will alter the physciochemical properties of the
various environmental media presents a significant
nanomaterials. ORD will integrate fundamental
challenge. This is due in part to potential confounding
research on detection method development from NSF,
by the presence of anthropogenic and natural
NIST, DoD, and others with its own focused methods
nanomaterials. Challenges arise because many
research effort to inform this research question.
different manufactured nanomaterials currently
exist and their numbers are increasing; for certain
4.1.1.2 Research Activities
types of nanomaterials, such as nanotubes, many
thousands of different structures are possible. In Measurement science (based on analytical chemistry
addition, the fate, transformation, and mobility of and physical properties) will have multiple roles in
these materials are only beginning to be understood. nanomaterials assessment and will require different
Consequently, scientific understanding of the types of analytical methods. There are several major
reactions these materials undergo, how they age in areas of investigation with nanomaterials that require
various environmental media, how they interact with the application of a wide array of measurement and
other compounds present in the environment, and characterization techniques for characterization,
whether and to what extent they form agglomerates detection, identification, or quantification.
or aggregates is limited. These issues compound the
complexity of detecting and quantifying nanomaterials Characterization of nanomaterials: ORD will
in environmental media. undertake studies to characterize the physical and
chemical properties of bulk nanomaterials to assess
The development of effective methods for measuring and quantify their unique features and characteristics
manufactured nanomaterials in environmental media at (e.g., surface-to-volume ratio, 3-dimensional structure,
concentrations relevant to potential exposure scenarios size, size distribution, relative dimensions (aspect
is critical to understanding the environmental impacts ratio), chirality, electrical/magnetic properties, and
of these materials. Such methods would also enable microstructure). Access to the equipment needed for
the more rapid achievement of the safe development these studies will require the formation of partnerships
of nanotechnology-related products. ORD-sponsored with other federal agencies, such as the National
research will ultimately seek to develop remote, in Institute of Standards and Technology (NIST), the
situ, and continuous monitoring devices that yield National Cancer Institute (NCI) and the Department
real-time information and that can detect manufactured of Energy (DOE). Each of these agencies has or is
nanomaterials at very low concentrations. in the process of establishing nanomaterial research
facilities, such as the Advanced Measurement
Risk assessments of nanomaterials will require the Laboratory (AML) at NIST and the Nanotechnology
ability to measure their environmental concentration in Characterization Laboratory (NCL) at NCI. These
the workplace, home, biota (including human tissues), research facilities provide access to a wide variety of
and ecosystems of interest. Analytical methods needed measurement and characterization tools.
to characterize and analyze nanomaterials will require
11

Analytical methods supporting EF&T studies: ORD To develop analytical methods suitable for
will take advantage of existing analytical methods for environmental monitoring, ORD will work
nanomaterials to support the initial focus on lab-based with NIST to contribute to the development of
studies. An ever increasing number of papers in the standardized reference materials in a variety of
literature have reported on the application of analytical representative matrices. Methods for environmental
methods for the measurement of nanomaterials for analysis or routine monitoring must account for the
monitoring lab-based studies to model environmental extraordinarily wide array of potential parent materials
processes under controlled conditions (e.g., soil and transformation products. In contrast to methods
leaching and subsurface transport) and concentrations. for the other roles described above, approaches to
Examples include the analysis of fullerenes by liquid environmental measurement must include non-target
chromatography coupled to a photodiode array analysis, where the type(s) of nanomaterials that
detector, the tracking of 14C in radio-labeled carbon- need to be detected are not known in advance (the
based nanotubes, and the analysis of quantum dots by entire spectrum of parent materials must be amenable
fluorescence spectroscopy. to analysis). The problems that traditionally plague
environmental analysis, such as the wide array of
Detection in environmental matrices: The published matrix interferences that limit detectability, make
literature on the use of existing analytical tools for environmental monitoring of nanomaterials even more
detecting or monitoring manufactured nanomaterials challenging. Examples of this type of application do
in the environment (especially in matrices other than not yet exist, and are an additional research need. Once
the vapor phase) is very limited. Perhaps the first suitable analytical methods have been developed in
publication that borders on being a review of this the laboratory, sites will be selected for monitoring
literature is that of Nowack and Bucheli (2007). The of various media (i.e., air, water, soil, sediment and
lack of methodologies for analyzing environmental sludge) where environmental concentrations would
samples likely results from two major factors: (1) be expected to be greatest, such as production sites
only in the last couple of years has any need for for nanomaterials and manufacturing sites of products
environmental analysis been contemplated, and (2) the containing nanomaterials.
challenges facing the detection and quantification of
manufactured nanomaterials (especially those based
solely on carbon) in environmental samples far exceed 4.1.1.3 Anticipated Outcomes
those associated with conventional pollutants, even Development of methods for characterizing
those pollutants that comprise complex mixtures of nanomaterials, through partnerships with
many congeners (e.g., toxaphene). NIST, NCI and/or DOE
To make unambiguous and quantitative determinations Development of analytical methods for the
of manufactured nanomaterials in environmental detection of carbon-based nanomaterials in
samples, ORD will develop a combination of ensemble environmental matrices
techniques (e.g., hyphenated methods coupling Development of analytical methods for the
separation with spectroscopic detection, that measure detection of non-carbon-based nanomaterials
collectively a number of particles) and single-particle in environmental matrices
techniques (e.g., methods, such as imaging, that
In cooperation with other federal agencies,
measure individual particles). The separation method
development of standardized test materials
employed may be size exclusion chromatography,
for a variety of representative environmental
sedimentation field flow fractionation, or capillary
matrices
electrophoresis. Determination could then be
made, for example, 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.
12

Figure 4-1 Critical Path for Research on Detection
Critical Path for Research on Detection
Key Science Question 1: What technologies exist, can be modified,

or must be developed to detect and quantify manufactured
nanomaterials in environmental media and biological samples?
Report on the state-of-the-science for sampling 2009

and measurement in environmental media.
Extend multimedia 2010

modeling capabilities to
Develop methods for address NM exposure and
measuring selected NM in risk issues/applications
environmental matrices
2011
Evaluate physical and chemical

properties that influence exposure to
nanomaterials in environmental media. 2013
Provide approaches for detection

of NM in the environmental
media
Modified or developed methodologies to detect and quantify NM in

environmental media and biological samples
4.1.2 Key Science Question 2. What are the potential exposure pathways to human and ecological
major processes and/or properties that govern the receptors. Ultimately predictive models for estimating
environmental fate, transport, and transformation the environmental fate and transport of nanomaterials
of manufactured nanomaterials, and how are these are needed.
related to the physical and chemical properties of
those materials? Nanotechnology research for fate, transport, detection
and modeling of manufactured nanomaterials is
4.1.2.1 Background/Program Relevance needed to identify the most critical parameters and
Given the current scientific uncertainty surrounding uncertainties associated with these materials. This
fate, transport, detection and modeling of manufactured research will characterize the environmental fate
nanomaterials, it is difficult to accurately assess the and transport (EF&T) of nanomaterials from sources
environmental disposition of nanomaterials or the to human and ecological receptors. The research
13

will support risk assessments of manufactured ORD has initiated a research program to study
nanomaterials and ways to manage their potential nanotechnology fate and transport research;
releases. Initially the research will provide a the primary objectives will be to determine the
fundamental understanding of the physical and physciochemical properties controlling the mobility
chemical properties of nanomaterials and their of nanomaterials through ecosystems and develop
impact on fate and transport pathways. In order to predictive models for estimating their mobility.
address this fundamental understanding, research Research questions include the identification of system
to provide specific analytical detection techniques parameters that alter the surface characteristics of
for nanomaterials also will be necessary. Research nanomaterials through aggregation (e.g., pH effects),
collaborations with agencies such as NIST, complexation (e.g., surface complexation by dissolved
academia, and industry are planned to advance the organic carbon) or changes in oxidation state (e.g.,
understanding of the limitations and capabilities of chemical- or biological-mediated electron transfer).
identified analytical techniques. Finally, existing This work will provide the basis for prioritizing
predictive models that may be used for nanomaterial potential ecological exposure pathways that warrant
fate and transport will be modified, and if necessary, further exploration.
new models will be developed. These efforts will
involve collaborations with other federal agencies, Understand the processes that govern the fate and
consortiums, international partners and academia. transport of manufactured nanomaterials
The potential for the occurrence of manufactured NMs
Because of the introduction and increased production in sediments, soils, air and aqueous environments,
of nanomaterials, it is necessary to better understand necessitates the understanding of the processes
the fate, transport, detection and modeling of these controlling the fate and transport of these materials
materials. Quantitative as well as qualitative research in each of these environmental matrices. The
is necessary to reduce the uncertainty surrounding unique challenges to understanding the EF&T of
the introduction and existence of nanomaterials in the nanomaterials is based on knowledge that:
environment and to identify the exposure pathways
of concern to receptors. Quantitative research such as Nanomaterials exist as particles, and thus their
identifying the speciation of silver nano particles and surface chemical and physical properties will
the impact of speciation on the mobility of the silver determine their environmental fate and transport
particles in sediments as well as the bioavailability
to surrounding receptors is an example of one The chemical and surface properties of
ORD research project. Qualitative research such nanomaterials will be modified by interaction
as assessment of existing chemistry methods for with naturally occurring constituents such as
measuring nanometal oxides in ambient air is another dissolved organic matter, biota (e.g., bacteria, and
project. Research on these and other issues will assist biomolecules (e.g., polysaccharides)
the Agency in risk assessment and risk management
of engineered nanomaterials. ORD will conduct the Changes in surface properties with naturally
following broad research activities as described below. occurring constituents will significantly alter the
mobility of nanomaterials in aquatic ecosystems
4.1.2.2 Research Activities The wealth of information currently in the

Understand the processes that govern the fate environmental literature concerning the fate and
and transport of manufactured nanomaterials transport of chemical contaminants results from
the study of chemicals that are soluble to some
Understand the chemical and physical extent in aquatic ecosystems. Much of the existing
properties of manufactured nanomaterials work will have little value for predicting the EF&T
and how they influence fate and transport of nanomaterials. The body of work concerning
processes the movement and stability of colloidal material,
Develop predictive models for transport of which range in size from 1 nm to 1 μM, in aquatic
manufactured nanomaterials ecosystems, however, is already providing insight
into the processes controlling the transport of
14

nanomaterials in the environment (Loux and Savage, Clearly, the determination of how transport of
2008). The EF&T processes most likely to control nanomaterials through soils, the vadose zone, and
the transport of nanomateials in the environment groundwater is affected by solution chemistry and
will include dispersion, agglomeration, and surface colloid surface properties is critical for understanding
complexation with natural organic matter and the fate of nanomaterials. These are important
biological constituents. questions for understanding the fate of nanoiron
particles purposely placed in the ecosystem for source
ORD will conduct controlled laboratory studies to control of DNAPL plumes. Previous metals research
understand these fate and transport processes and the has shown that chemical speciation of inorganic
factors that control them. Initial work will focus on engineered nanomaterials is an important factor to
understanding their transport in porous and compacted understand for the fate and transport and ultimate
media; the tendencies of nanomaterials to aggregate, bioavailability of the materials. Initial research by
sorb or agglomerate in ecosystems; and the factors ORD on nanosilver particles impregnated in clothing
that influence the mobility of the nanomaterials. ORD and washed indicates potential pathways for human
has also identified research questions surrounding exposure and introduction of nanosilver to the
the impact of nanomaterials in groundwater, surface environment. Silver is impregnated in fabrics and
water, drinking water, wastewater and solid waste. In other materials as an anti-fungal/anti-microbial agent,
addition to laboratory studies, ORD will collect data but little is known about how the properties of the
from field systems to understand large-scale fate and nanosilver particles impact their fate and transport
transport processes and the factors that influence them. in the environment. Initial research indicates that the
presence of oxidants in the wash water likely limit
Understand the physical and chemical properties the bioavailability of the nanosilver particles. ORD
of manufactured nanomaterials and how they continues to assess the chemical transformation and
influence fate and transport processes speciation of inorganics such as silver.
Processes that control movement (i.e., sorption,
dispersion, agglomeration, degradation) will be Develop predictive models for transport of
strongly affected by the chemical and physical manufactured nanomaterials
properties of nanomaterials, such as surface charge, The successful development of EF&T models for
pH, ionic strength, redox conditions, and ambient nanomaterials will depend on understanding of
air conditions such as temperature and humidity. the processes controlling the EF&T of engineered
Consequently, typical chemical parameters for nanomaterials and the ability to determine the
predicting chemical fate and transport such as water chemical and physical properties needed to predict
solubility, octanol-water partition coefficient and such processes. ORD will study the applicability of
vapor pressure will be substituted with parameters existing environmental fate and transport models
such as particle size, surface charge and surface and to develop new predictive EF&T models that are
potential. Obtaining information on the chemical tailored specifically to nanomaterials. Early analysis
and physical properties of specific nanomaterials of the Estimation Programs Interface Suite (EPI
and classes of materials is necessary to understand Suite) models, the primary set of predictive tools the
their effect on fate and transport processes. For Agency uses for calculating the fate and transport of
example, a specific ORD research project is soluble organic chemicals, indicates that they will
characterizing the surface reactivity of silver, iron, have little or no applicability to predicting the EF&T
titanium dioxide and cerium oxide and determining of nanomaterials. Models do exist for predicting the
the impact of this reactivity on mobility and toxicity transport of natural colloidal materials and they are
of the nanomaterials. Another example is ORD’s being investigated for application to nanomaterials.
investigation of processes controlling the mobility As such, traditional DLVO (Derjaguin, Landau,
of carbon-based nanomaterials in porous media. The Verwey and Overbeek) theory is already lending
mobility of these materials largely depends on the insight into environmental fate and mobility trends
degree and type of functionalization (elements or other of nanomaterials (Loux and Savage, 2008). Basic
functional groups at the surface of the nanostructures), colloid models will have to be modified. Likiewise, a
which affect solubility and surface charge. modified version of EPA’s MINTEQA2 model used
for calculating metal speciation could provide surface
15

potentials for nanomaterials. Surface complexation Measure the chemical and physical properties
models are also finding use for determining the effect of manufactured nanomaterials and determine
of surface complexation on nanomaterial stability in how these properties influence and impact fate
aquatic ecosystems (Fukushi and Sato, 2005). and transport
Identify the exposure pathways associated
4.1.2.3 Anticipated Outcomes
with production, end-use, and recycling or
Results from this research will provide an improved disposal of manufactured nanomaterials in
understanding of the EF&T of manufactured different environmental matrices
nanomaterials in the environment. This will allow EPA
to develop a set of predictive tools. Improve the scientific understanding of
detection methodologies for quantifying
Researchers will: manufactured nanomaterials
Develop a scientific understanding of the Develop multiple predictive models for
processes that govern the fate and transport of understanding and measuring the transport of
manufactured nanomaterials manufactured nanomaterials
Figure 4-2 Critical Path for Research on Sources, Fate, and Transport
Critical Path for Research on Sources, Fate, and Transport
Key Science Question 2: What are the major processes and/or

properties that govern the environmental fate, transport, and
transformation of manufactured nanomaterials, and how are these
related to the physical and chemical properties of those materials?
2009
Provide the underlying science Assess the F&T of NM in

the aquatic environments
2010
on the F&T of NM
Determine the properties of NM that effect 2012

F&T
Synthesis of physical/chemical properties

that influence exposure in environmental
media
Use F&T NM data to inform

multimedia transport and
deposition
2014
Determine the major processes/properties that govern the
environmental fate of NM, and key physical/ chemical properties of
NM
16

4.1.3 Key Science Question 3. What are the How much exposure occurs?
exposures that will result from releases of
How often and for how long does exposure
manufactured nanomaterials?
occur; that is, what is its frequency and
duration?
4.1.3.1 Background/ Program Relevance
Research is needed to provide insight into the type,
4.1.3.2 Research Activities
extent, and timing of exposures to nanomaterials in all
relevant environmental media and through all relevant EPA uses a number of models to conduct chemical
exposure pathways. Cumulative exposures, both with exposure assessments. Descriptions and links to these
other manufactured nanomaterials as well as with models can be found at the websites for the Council
bulk-scale pollutants, also need to be explored. The for Regulatory Environmental Modeling (CREM:
information provided through this exposure research http://cfpub.epa.gov/crem/) and the Center for
can be linked with other exposure and biological Exposure Assessment Modeling (CEAM: http://www.
impact data to improve the scientific basis of risk epa.gov/ceampubl/). Table 4-1 provides a listing of
assessment for manufactured nanomaterials. several of the models/tools used by the program offices
General population exposure may occur from for exposure assessment and each model’s general
environmental releases from the production and use application and applicability to nanomaterials in its
of nanomaterials and from direct use of products (e.g., current form. With the exception of the EPI-Suite™
cosmetics) containing nanomaterials. The rapid growth calculators, all of the exposure assessment models
of products that contain nanomaterials could result need the user to provide input data on the physical
in their presence in soil and aquatic ecosystems. This and chemical properties for the chemical of interest.
presence will result from effluents of manufacturing The EPI Suite™ calculators are based on a single
plants, and the recycling or disposal of nano-based input, a Simplified Molecular Identification and Line
consumer products into landfills and surface/ground Entry System (SMILES) string that is a typographical
water. An exposure assessment attempts to answer method for representing unique chemical structures.
the following questions for a particular substance or The other models in Table 1 were developed primarily
chemical: for exposure assessments of synthetic organic
chemicals, and thus require input such as water
Who or what is exposed (e.g., people,
solubility, octanol-water partition coefficients and
ecosystems)?
Henry’s Law constants to predict fate and transport.
What are the pathways for exposure (air,
water, land)?
Table 4-1 Models/Tools to Conduct Chemical Exposure
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
Primary
Applicability
Acronym Model Name Program Application
to NMs
Office
Estimates concentrations of
Assessment Screening Modification
E-FAST OPPT chemicals in multimedia from
Tool Version 2.0 Required
multiple release activities
EPI- Estimation Programs Estimates physical & chemical
OPPT Not Applicable
Suite™ Interface Suite properties for organic chemicals
Estimates fate, transport, and
Exposure Analysis Modification
EXAMS OPP exposure concentrations of
Modeling System Required
chemicals in aquatic ecosystems
Total Risk Integrated Estimates human exposure to
Modification
Trim Expo Methodology OAQPS criteria
Required
Exposure-Event Module and hazardous air pollutants
17

Exposure models will require modification to allow levels of organization, from molecular alterations
the input of molecular parameters and physical and to populations. These linkages can serve as a basis
chemical data specific to nanomaterials (e.g., particle for identifying and validating mechanistic indicators
size, surface charge, distribution or sticky coefficients, of exposure and effects, informing ecological risk
and agglomeration tendencies). OPPT has recently assessments of nanomaterials. Currently, a systems-
requested the assistance of ORD to review the E-FAST based approach is being used to assess exposures and
model, which supports EPA’s New Chemicals and define toxicity pathways for model chemicals with
Existing Chemicals Programs, for its applicability to well-defined modes/mechanisms of action (MOA)
nanomaterials. Specifically, ORD will: within the hypothalamic-pituitary-gonadal (HPG) axis.
These pathways serve as a basis for understanding
Focus on the physical, chemical, and other
responses of small fish across biological levels of
properties currently required as user provided/
organization, ranging from molecular responses to
default inputs
adverse effects in individuals to, ultimately, changes in
Determine whether these inputs are population status. The studies employ a combination
appropriate for nanomaterials when assessing of state-of-the-art molecular biology, bioinformatic,
exposures related to industrial releases to and modeling approaches, in conjunction with whole
surface water, air, and/or landfills animal testing. As such, the project will enable a
Identify other properties as potential inputs unique opportunity to interface empirical toxicology
that might be more appropriate for assessing with computational biology in the exposure assessment
general population and environmental of nanomaterials.
exposure to nanomaterials
The molecular biological tools for this research will
focus on the application of the ‘omic’ tools (i.e.,
The challenges in identifying and measuring the genomics, proteomics and metabolomics) to identify
concentration of manufactured nanomaterials indicators of exposure. These tools provide the ability
in environmental and biological systems will to identify indicators of exposure by measuring gene
present significant obstacles to providing the data regulation, protein formation, and changes in an
necessary to conduct exposure assessments of these organism’s metabolome in response to exposure to a
materials for both ecological and human receptors. chemical or mixture of chemicals. By elucidating the
Such assessments will require the development of kinetics of the marker’s response, it is also possible to
alternative methods for determining the source and provide an understanding of the temporal and spatial
the environmental concentrations of nanomaterials aspects of exposure.
in aquatic and terrestrial ecosystems. The interest in
nanomaterials is driven by their unique properties and Currently, no information is available in the literature
activities at different scales; these same properties concerning the identification of indicators of exposure
provide the opportunity for developing indicators for nanomaterials. However, ongoing research
of exposure by measuring changes in structures and with pesticides exhibiting estrogenic activity is
functions of biological organisms in contact with demonstrating the feasibility of this approach. ORD
nanomaterials. By identifying indicators of exposure has developed molecular indicators of exposure
resulting from exposure to nanomaterials, it will (based on genomic responses) of aquatic organisms
be possible to reconstruct the exposure pathway (water flea, Daphnia magna and fathead minnow,
and ultimately the source and the environmental Pimephales promelas) to estrogenic compounds
concentration of the nanomaterial of interest. This and is using advanced genomic methods to develop
ability to move from an internal biological response androgenic indicators. The Nuclear Magnetic
to external environmental concentration represents Resonance (NMR)-based metabolomics research
a growing area of exposure science referred to as program being conducted at ORD’s NMR research
exposure reconstruction. facility is demonstrating the use of high-resolution
NMR to identify changes in the profiles of endogenous
ORD’s research in this area focuses on the linkage metabolites (i.e., the metabolome) in the serum and
of responses across endpoints at multiple biological urine of fathead minnows exposed to estrogenic
18

compounds. The literature also provides examples of exposure doses, and critical exposure concentrations.
the use of genomics to identify indicators of exposure Research will also identify potential subpopulations of
in humans. Microarray analysis of blood samples organisms that are more susceptible to manufactured
taken from benzene-exposed workers has identified nanomaterial exposure than others.
peripheral blood mononuclear gene expression as an
indicator of exposure for benzene (Forest et. al, 2005). 4.1.3.3 Anticipated Outcomes
Identification of the dominant exposure
Collaboration to further identify the exposure
pathways to ecological receptors of interest
pathways of manufactured nanomaterials
ORD will work in collaboration with other agencies Assessment of the applicability of EPA’s
and academia to study and identify the most common current exposure models to nanomaterials
exposure pathways for manufactured nanomaterials. Identification of the physical and chemical
ORD will seek to establish international collaborations properties required to inform exposure
through the development of collaborative or
coordinated calls for proposals. These research Identification of indicators of exposure
proposals will also engage ORD scientists in the through the application of genomics,
study of exposure routes and pathways, relevant proteomics and metabolomics
Figure 4-3 Critical Path for Research on Exposure Pathways
Critical Path for Research on Exposure Pathways
Key Science Question 3: What are the exposures that will result from
releases of manufactured nanomaterials?
2009
Provide the underlying science An assessment of the

on the exposure pathways of applicability of EPA’s 2010
NMs current exposure models to
nanomaterials
Identify the exposure pathways associated

with production, end-use, and recycling or
disposal of manufactured nanomaterials in 2012
different environmental matrices
Synthesis of physical/chemical properties

that influence exposure in environmental
media
Identification of indicators of exposure

through the application of genomics,
proteomics and metabolomics
2014
Modification of current exposure model and development of new
exposure models to predict exposure pathways for nanomaterials in
environmental media
19

4.2 Research Theme: Human Health and ecological effects of selected nanomaterials,
Ecological Effects Research to Inform Risk including their local and systemic toxicities
Assessments and Test Methods
Determine the health and ecological effects
4.2.1 Background and Program Relevance associated with nanomaterial applications
As described in EPA’s Nanotechnology White Paper, and their interactions with environmental
nanomaterials could have health and ecological media
implications arising from new routes of exposure
and/or toxicities associated with exposure to these Determine the physical and chemical
novel materials, by-products associated with their properties responsible for nanomaterial
applications, or their interactions with various health and ecological toxicities, mode(s) of
environmental media. action, and mechanism(s) of injury in order
to identify the appropriate exposure-response
By characterizing nanomaterials’ health and metric(s), e.g., surface area, particle size, etc.
ecological effects and identifying the physical and relative to traditional, concentration-based
chemical properties that regulate their toxicity and metrics
biokinetics, ORD will address a lack of information
required for nanomaterials risk assessment. Identify the physical and chemical properties
of nanomaterials that regulate their
ORD’s research will provide EPA offices with deposition, uptake, and fate, as well as host
information on the health and ecological effects of susceptibility and sensitivity factors (e.g.,
specific nanomaterials and applications impacting gender, age, life stage, disease conditions)
EPA’s mission, as well as guidance on best practices, that may influence their toxicity and
approaches and test methods for assessing/predicting biokinetics
their health and ecological effects. ORD will also be
addressing key immediate priority effects research Identify ecological systems that contain
needs identified in the US EPA Nanotechnology especially susceptible organisms, life stages,
White Paper, such as, adequacy of test methods, or populations
characterization of the health and ecological
effects of nanomaterials (nanotoxicology), hazard Identify and develop alternative testing
identification, dosimetry and biological fate. approaches, technologies, and models to
screen, rank, and predict the in vivo toxicity
ORD’s nanomaterials health and ecological effects of nanomaterials and their applications
research builds upon its ongoing risk assessment-
based research within the Air, Water, and Safe 4.2.2 Key Science Question 4. What are the health
Products/Safe Pesticides programs. These research effects of manufactured nanomaterials and their
activities provide the facilities and expertise that applications, and how can these effects be best
are directly applicable to addressing nanomaterial quantified and predicted?
health and ecological effects resulting from various
potential routes of exposure and environmental 4.2.2.1 Human Health Effects Research Activities
interactions. ORD’s research is conducted within ORD will examine the health effects of nanomaterials
a risk assessment paradigm. ORD’s nanomaterials that are relevant to EPA’s mission and mandated
health and ecological effects program will conduct regulatory responsibilities by addressing the
research to: health effects research needs identified in EPA’s
Nanotechnology White Paper and the NNI’s,
Evaluate current test methods to assess Environmental, Health and Safety Research Needs
their adequacy to determine the toxicity for Engineered Nanoscale Materials. However,
of nanomaterials, and modify or develop there exist significant challenges associated with
toxicity test methods, as required addressing nanomaterials health effects; these
include:
Determine the acute and chronic health and
20

1)The significant diversity of manufactured A Vision and a Strategy that provides a
nanomaterials as well as their potential to direction to identify alternative toxicity
produce health effects due to their novel testing approaches, assays, and methods
properties, new routes of exposure associated to ultimately predict in vivo health effects
with their use, by-products associated with of nanomaterials and their applications as
their applications, or their interactions with well as means to address the 3Rs of toxicity
various environmental media testing
2) The need to provide nanomaterials health 2) Leveraging ORD nanomaterials health
effects information in a timely manner to effects research with similar activities at the
Agency offices to address their immediate national (NNI and other federal programs
needs including: NIOSH, National Toxicology
Program, etc.) and international levels
3) The need to address the 3Rs of toxicity
(Organization for Economic Cooperation and
testing (reduce, refine and replace the use of
Development, OECD)
animals) in research and regulatory programs
3) The existence of validated alternative
Opportunities do exist to address these challenges testing methods and ORD’s airborne
associated with assessing nanomaterials health effects particulate matter health effects program
and include: that has demonstrated the ability of in vitro
test methods to provide consistent results
1) Employing the vision and
reported for in vivo studies, including clinical
recommendations of the National Academy
and epidemiology studies, associated with
of Sciences, National Research Council
report, Toxicity Testing in the 21st Century: examining the pulmonary toxicity of particles
Figure 4-4 An Integrated Testing Strategy for ORD’s Nanomaterials Health Effects Research
21

An integrated multi-disciplinary testing strategy toxicities. Alternative testing methods will also
for nanomaterials health effects research: ORD employ non-cellular assays to examine the surface
will employ an integrated testing strategy as shown properties of nanomaterials by assessing their
in Figure 4-4 to address nanomaterials health effects reactivity and molecular interactions with proteins as
research described under Key Science Question well as other biological constituents; e.g. antioxidants
4. The strategy will integrate and coordinate the and second messengers. Non-cellular interactions and
expertise of toxicologists, material scientists, and surface properties may play a key role in regulating
exposure assessment scientists to examine the health nanomaterial cellular uptake and toxicity.
effects of nanomaterials and their applications. An
integrated testing strategy to assess nanomaterials Alternative toxicity testing methods provide a
health effects is consistent with numerous means to: 1) rapidly screen and rank the relative
nanomaterials health effects workshop reports (G. toxicities of various nanomaterials for in vivo toxicity
Oberdorster et al, Particle and Fibre Toxicology 2:8, testing; 2) provide key information (e.g., exposure
2005; D.B. Warheit et al., Inhalation Toxicology dose and health endpoints) to assist in designing
19(8):631-643, 2007; John Balbus, et al., Enviorn. in vivo toxicity testing that will potentially refine/
Health Perspect. 115:1664-1659, 2007; J.G. Ayres et reduce the number of animals needed for in vivo
al, Inhalation Toxicology 20(1):75-99, 2008). studies; 3) determine mechanism(s) of injury and
mode of action of nanomaterials; 4) rapidly perform
ORD’s nanomaterials integrated testing approach comparative toxicity studies between chemically
consists of three key components: identical nano vs. micro-size materials; 5) perform
nanomaterials interactions, uptake, and distribution at
1. Nanomaterials Physical and Chemical the biochemical, cellular, and intracellular levels; and
Characterization: Nanomaterials that are relevant 6) correlate nanoparticle surface properties with their
to EPA will undergo recommended physical biological and cellular interactions, and toxicity.
and chemical characterization. This will require
integrating the expertise of nanoscale material ORD’s ToxCast program (http://epa.gov/comptox/
scientists into ORD health effects research, since toxcast/news.html) will assist in extending ORD’s
physical and chemical information is critical to: 1) efforts to develop alternative test methods to evaluate
ensure the purity and confirm/validate the properties nanomaterials toxicity. ToxCast offers an approach
of nanomaterials before initiating research to assess to address the extreme diversity of nanomaterials
their health effects; 2) detect and quantifying by applying high-throughput platforms and
nanomaterials in cells and tissues in order to computational approaches to screen a large number
determine nanomaterial biokinetic or ADME; and of materials. The ToxCast program will assist in
3) provide information for the identification of ORD’s efforts to rank the toxicity of nanomaterials
nanomaterials properties regulating their toxicity as well as develop models to identify physical and
(hazard identification) and exposure-response chemical properties that determine the toxicity of
metrics. nanomaterials.
2. Alternative Test Methods: ORD will employ 3. Nanomaterials In Vivo Toxicity Testing: ORD’s
cellular and non-cellular test methods to assess nanomaterial health effects research strategy will
the toxicity of nanomaterials that are relevant to assess the toxicity of nanomaterials in animals;
EPA. In vitro toxicity testing will use a variety of i.e., in vivo toxicity. These studies will examine
cell types reflecting different routes of exposure cancer, pulmonary, dermal, and gastrointestinal
(dermal, inhalation, ingestion) and health effects toxicities associated with initial site of deposition of
that may arise due to the ability of nanomaterials nanomaterials by various routes of exposure (dermal,
to translocate from their initial site of deposition to inhalation, ingestion) as well as immunological,
other organs within the body. Nanomaterials in vitro neurological, reproductive, cardiovascular, and
toxicity testing will assess the mutagenic, intestinal, developmental toxicities to assess their potential
pulmonary, dermal, immunological, neurological, systemic toxicities. In vivo toxicity studies will
reproductive, cardiovascular, and developmental examine the deposition and fate of nanomaterials
toxicities using cellular models reflective of these following various routes of exposure, as well as
22

identify host susceptibility and sensitivity factors toxicity testing studies; and 3) allow for shallow and
(e.g., gender, age, life stage, and disease conditions) in-depth parallel toxicity testing in order to identify
that may influence their toxicity and biokinetics those alternative approaches and in vitro assays/
responses that correlate with in vivo nanomaterial
Coordinating and Leveraging ORD’s integrated toxicity. This information will be critical in order to
testing strategy to assess nanomaterials health ultimately identify the physicochemical properties
effects: of nanomaterials and alternative test methods that
As depicted in Figure 4-4 and as previously predict their in vivo toxicity. Opportunities exist for
described, physical and chemical characterization of ORD’s integrated nanomaterials health effects testing
nanomaterials will be conducted prior to assessing strategy to progress at a rapid rate by leveraging its
their health effects. Also as depicted in Figure efforts with similar activities at the national (other
4-4, it is anticipated that ORD’s integrated testing federal programs under the NNI; for instance, those
strategy to assess nanomaterials health effects will of NIOSH and the National Toxicology Program) and
be a coordinated, iterative process providing: 1) an international levels (Organization for Economic Co-
approach to rank nanomaterials for in vivo toxicity operation and Development, OECD).
testing; 2) assist in designing nanomaterial in vivo
Figure 4-5 Critical Path for Conducting ORD’s Nanomaterial Human

Health Effects Research
23

4.2.3 Key Science Question 5. What are the standard (or appropriately modified) test methods,
ecological effects of manufactured nanomaterials further research will explore the specific mechanisms
and their applications, and how can these effects be of nanomaterials toxicity and ecological effects.
best quantified and predicted? Understanding the mechanisms of effects is key
to determining novel risks that may be created by
4.2.3.1 Ecological Effects Research Activities nanomaterials, defining the appropriate organisms
ORD’s nanomaterials ecological effects strategy will and endpoints for nanomaterials risk assessments,
address the ecological effects research needs identified and providing the basis for future predictive models.
in EPA’s Nanotechnology White Paper and the NNI’s Parameters that govern adsorption, distribution,
Environmental, Health and Safety Research Needs metabolism, and excretion (ADME) will be evaluated,
for Engineered Nanoscale Materials, and is intended as will means of expressing toxicological dose. Other
to be responsive to EPA’s regulatory needs. The studies will evaluate the interaction of nanomaterials
ecological effects research strategy focuses on the with physical, chemical, and biological components of
physical and chemical factors unique to nanomaterials ecological systems to determine if there are effects of
that may influence their toxicity, determine rates of nanomaterials not captured by single organism toxicity
uptake and disposition in ecological matrices, and testing, such as altering the relationships among
require novel approaches for quantifying exposure- ecosystem components and thereby affecting overall
response relationships. The strategy is organized ecosystem function. Throughout Task 2, emphasis
into chronological tasks, beginning with the need to will be given to determining whether nanomaterials
evaluate methods used in traditional toxicity for their exert effects through mechanisms that would not be
adequacy or applicability to nanomaterials. The tasks well addressed by existing ecological hazard and risk
are broadly defined and it is expected that research screening tools.
will advance in an iterative manner; it is likely that
initial tasks will need to be revisited depending on Task 3 - Develop methods and models to
results of subsequent research efforts, and as new predict the hazard or ecological risk of nanomaterials:
nanomaterials are developed. Due to the diversity of nanomaterials expected to
enter the marketplace in the coming years, EPA will
Task 1 - Evaluate the suitability of existing need predictive tools that can be used to prioritize
test methods for assessing the hazards of manufactured newly developed nanomaterials for testing and further
nanomaterials: nanomaterials, or products containing evaluation. For example, quantitative structure/
nanomaterials, are already being submitted for activity relationships (QSARs) may be developed
approval under Agency programs such as TSCA to predict the toxicity of untested materials based
and FIFRA. These and other Agency programs on their chemical structure and an understanding
have existing protocols for evaluating hazards to of the mechanisms underlying dose and toxicity.
ecological receptors in both aquatic and terrestrial Likewise, ecological effects models may be important
systems, but the appropriateness of these methods for predictive tools if research in Task 2 indicates that
nanomaterials has yet to be evaluated. Key concerns ecological processes above the organismal level are
include how to expose organisms to nanomaterials in being uniquely affected by nanomaterials. This work
ways that have relevance to exposures that may occur will build directly from Tasks 1 and 2 and associated
in the environment, and whether these standardized research conducted by the Computational Toxicology
assays address the organisms, life stages, and Program.
bioavailability considerations that are most important
for understanding the potential ecological risks of Leveraging research with ORD laboratories,
nanomaterials. In addition to direct toxicity testing, centers and other federal programs: ORD’s
emphasis will be placed on measurements of exposure, nanomaterials health and ecological risk assessment
uptake, and dose. research will leverage work with other federal
programs and international efforts where similar
Task 2 - Understand the mechanisms nanomaterials are being monitored, studied, and
underlying the ecological effects of nanomaterials characterized. For example, ORD laboratories are
and identify potential gaps in hazard assessment jointly addressing nano-cerium dioxide to assess
procedures: Building on results of exposures using potential environmental exposures, and associated
24

health effects. Research to examine the health and Characterization of nanomaterials health
ecological effects of nanomaterials following their and ecological effects; identification of
release into or interactions with environmental physical and chemical properties and host/
media will require the combined expertise of ORD’s sensitivity factors that regulate nanomaterials
health and exposure scientists. ORD’s nanomaterials dosimetry, fate, and toxicity (information
health effects multi-tier strategy allows a means to for both risk assessment and development of
interface with national and international nanomaterials “greener” nanomaterials and a sustainable
in vivo toxicity efforts as a means to allow for the nanotechnology)
identification of alternative methods, approaches,
and biological responses that are consistent with Identification of testing methods/approaches
those generated in nanomaterials animal toxicity to predict in vivo toxicity of nanomaterials;
testing studies. Finally, the physical and chemical characterization of molecular expression
characterization of nanomaterials and their detection profiles that may provide biomarkers of
in biological systems will require a multidisciplinary nanomaterial exposure and/or toxicity
approach with close interactions across ORD as well (exposure assessment and predictive
as with other organizations such as the Department of nanotoxicology)
Energy’s National Laboratories.
Provision of necessary counsel and guidance
4.2.4 Anticipated Outcomes that will assist in the review of premanufacture
ORD’s human health and ecological effects research notice applications and assess the adequacy
programs will provide key information regarding the of harmonized nanomaterial test guidelines to
health and ecological implications from exposures assist OPPTS and internationally, the OECD
to nanomaterials, and their applications, in order (regulatory assistance/support and leveraging
to identify and manage potential adverse impacts nanomaterials effects research)
and inform program offices and regions regulatory
and other policy decisions. Specifically, ORD’s Addressing the gap in knowledge regarding
nanomaterials effects research will provide Agency the toxicity of nanomaterials, which has
offices with information on the health and ecological impeded the ability to conduct accurate life
effects of specific nanomaterials and their applications, cycle analysis
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:
25

Figure 4-6 Critical Path for Conducting ORD’s Nanomaterial Human Health Effects Research
Critical Path for Conducting ORD’s Nanomaterial Ecological Effects

Research
Key Science Question 5: What are the ecological effects of manufactured

nanomaterials and their applications, and how can these effects best be
quantified and predicted?
Evaluate standard test methods to identify modifications that 2009

will be necessary for the testing of nanomaterials for health
and ecological effects
2010
Assess the hazard of selected Develop methods and approaches
nanomaterials and identify especially for exposing whole organisms to
sensitive ecological receptors nanomaterials
2011
Identify appropriate metrics for quantifying exposure-
response relationships, e.g. potentially based on particle
size and number, surface area and charge, etc.
Where toxicity is detected, determine whether the

mode or mechanisms of toxicity are unique relative to
non-particulate contaminants
Identify factors and properties that

regulate adsorbtion, deposition,
metabolism, and elimination.
2012
Identify physical and chemical characteristics of nanomaterials that might be used in
predictive modeling (e.g. QSAR) to reduce the number of toxicity tests required for their
regulatation
4.3 Research Theme: Developing Risk Assessment influence their environmental behavior and effects
Methods on human health and ecosystems. These unusual
features introduce complications for basic aspects of
4.3.1 Key Science Question 6. How may risk risk assessment such as characterization of exposure
assessment approaches need to be amended to and dose-response relationships. For example, is
incorporate special characteristics of manufactured particle count or one or more measures of surface
nanomaterials? properties (area, charge, etc.) a better metric than
mass for describing dose-response relationships?
4.3.2 Background/Program Relevance Although nanomaterials pose significant new and
Nanomaterials may have special properties that may possibly unique challenges for the practice of risk
assessment, features of the basic paradigm for risk
26

assessment and risk management (NRC, 1983) routes, and ecological as well as human health
are presumed to apply to these materials. Hazard effects. Depending on the availability of data, both
identification determines qualitatively whether the quantitative and qualitative characterizations of risks
nanomaterial will cause an adverse health effect. may result. However, given the limited information
Dose-response assessments establish the quantitative available on nanomaterials, the CEA approach is
relationship between dose and incidence of health currently being used to identify where key data gaps
effects. Exposure assessment is performed and the exist with respect to selected case studies of specific
incidence of an adverse effect (risk) in a particular applications of nanomaterials.
population is determined by combining exposure
and dose-response. The effects of nanomaterials Case studies are recommended in the EPA
on the environment must also be assessed in order Nanotechnology White Paper as a means to further
to protect and restore ecosystem functions, goods, inform research supporting the risk assessment
and services. Ecological risk assessment entails process. The term “case study” is used to refer to
the evaluation of goals and selection of assessment specific examples of nanomaterials and the types of
endpoints in a problem formulation step, followed by issues that would be need to be considered to assess
analysis of exposure to stressors and determining the their respective environmental and health risks. By
relationship between stressor levels and ecological focusing on specific examples of nanomaterials in
effects. The next step is estimating risk through realistic applications, it is possible to identify and
the combination of exposure and stressor-response prioritize research needs to assess the real world
profiles, description of risk by discussing lines of impacts of these materials. Given the striking
evidence, and determination of ecological adversity differences in toxicological and physicochemical
(U.S. EPA, 1998). Interfacing among risk assessors, properties of nanomaterials, generalizations across
risk managers, and interested parties during the initial nanomaterials need to be considered cautiously.
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 4.3.3 Research Activities
to support a management decision. The importance of The role of ORD’s nanomaterial risk assessment
communication and stakeholder involvement in both research is (1) to help guide overall research efforts
human health and ecological risk assessment and risk toward generating the information needed to conduct
management has also been noted by the Presidential/ future comprehensive environmental assessments of
Congressional Commission on Risk Assessment nanomaterials and (2) to carry out such assessments in
and Risk Management (1997: (see Figure 2-1) and coordination with all of ORD and the program offices.
recently affirmed in the National Academy of Sciences The research question ORD will address is, “How
“Science and Decisions: Advancing Risk Assessment” may risk assessment approaches need to be amended
(NAS, 2008). to incorporate special characteristics of manufactured
nanomaterials?” To address this question, ORD will
While basic features of the health and ecological identify and prioritize information gaps by developing
risk assessment paradigms may still be relevant to a series of case studies and workshops to further
nanomaterials, this emerging technology nevertheless refine research needs for specific nanomaterials, as
warrants careful systematic evaluation such as that of recommended in the EPA Nanotechnology White
the comprehensive environmental assessment (CEA) Paper.
approach (Davis and Thomas, 2006; Davis, 2007),
which treats the evaluation of the environmental In order to develop case studies of particular
and health risks of nanomaterials as an issue that nanomaterials and their specific applications,
cuts across EPA programmatic domains and is not appropriate nanomaterials must be selected. The
simply categorized as solely an air, water, toxics, or collective judgment of an internal workgroup
solid waste issue. The CEA approach starts with a representing all relevant program offices was used for
qualitative life cycle framework, as shown in Figure this purpose. The workgroup was given a summary
4-7. It takes into consideration multiple environmental of available information on the chemistry, human
pathways, transport and transformation processes, health, toxicology, exposure, and release of various
cumulative and aggregate exposure by various
27

nanomaterials. Workgroup members were then asked Concurrent with these longer range CEA-oriented
to select two nanomaterials based upon five criteria: activities will be more immediate and more
potential for biota/human exposure; apparent potential narrowly focused assessment efforts in accordance
for both health and ecological effects; a reasonable with programmatic needs and data availability.
amount of information with which to develop a case Assessments of this type cannot be specified at
study; relevance of the nanomaterial to programmatic present but are anticipated, contingent on progress in
or regulatory needs; and “nanoness,” e.g., having at addressing scientific issues such as those identified
least one dimension less than 100 nm. Using these throughout this document.
criteria, nanoscale titanium dioxide and single walled
carbon nanotubes (SWCNTs) were initially selected;
subsequently, SWCNTs were replaced with nanoscale 4.3.4 Anticipated Outcomes
silver (nano-Ag) due to difficulties in obtaining Note that the outcomes listed here and in the Critical
adequate information on applications of SWCNTs Path for Risk Assessment Research (see Figure
that had presumptive exposure potential for the 4-7) are intended to be representative of an iterative
general population. Two applications of nanoscale process that will involve the creation of a series of
titanium dioxide are under development, for water additional case studies and periodic reevaluation
treatment and for sunscreen. The choice of a nano- of earlier case studies as new information becomes
Ag application is currently under evaluation. These available. The timeframe for the outcomes shown in
selected classes of nanomaterials also serve as a the Critical Path figure is conservatively estimated
common focus and point of coordination for near-term but highly uncertain because of the many scientific
studies by the various ORD laboratories. uncertainties currently associated with nanomaterials.
As indicated above, limited assessments (more
The case studies present available information for narrowly focused than a CEA) may be attempted as
specific nanomaterials using the CEA approach as an data become more available, and such assessments
organizing structure. These documents are intended to could occur at any point within the overall timeframe
be used as part of a process to systematically identify shown in the Critical Path figure.
and prioritize information gaps where additional
research is needed. Draft case studies will be the Initially, two draft case studies for different
focus for a series of workshops involving invited applications of nano-titanium dioxide, to
technical experts and stakeholders. Workshops will be be followed by additional case studies and
conducted in a formal, structured manner using expert periodic iterative evaluation of earlier case
judgment techniques (e.g., multi-criteria decision studies as new information becomes available
analysis, expert elicitation). A detailed summary
of the discussions and views expressed during Workshop(s) for invited experts and
the workshop will be used in refining the current stakeholders and public observers, using
research strategy document. The workshop summary formal expert judgment methods to identify
will highlight areas of work that will be needed to and prioritize research needed to support
support comprehensive environmental assessments comprehensive environmental assessments of
of nanomaterials. This refined statement of research nanomaterials
priorities will provide longer-term guidance for both Using input from the workshop discussions,
ORD and the broader scientific community. This a document that lays out long range research
approach is consistent with a recent NAS review of directions for obtaining information needed
the NNI’s nanotechnology EHS research strategy for nanomaterial CEAs
(National Academy of Sciences, 2008).
28

Figure 4-7 Critical Path for Risk Assessment Research
Critical Path for Risk Assessment Research
Key Science Question 6: How may risk assessment approaches need to

be amended to incorporate special characteristics of manufactured
nanomaterials?
Case Studies on selected nanomaterials (NM), incorporating 2009

Peer Consultation input, for use in NM Case Studies
Workshop (iterative)
Summary Report of NM Case Studies Workshop for

Identification and Prioritization of Research to Support 2010
Comprehensive Environmental Assessment (CEA) of
Selected NMs
Research Strategy for CEA of 2011

Qualitative life cycle analysis for
Selected NMs, for use by ORD and
selected NM(s)
research community
Fate and transport assessment for Exposure assessment for selected

selected NM(s) NM(s)
Ecological effects assessment for Health effects dose-response

selected NM(s) assessment for selected NM(s)
2014
CEA of selected NM(s), for use by OPPTS and other

program office
4.4 Research Theme: Preventing and Managing approaches to manage emissions/releases, it is critical
Risks to understand potential entry points of nanomaterials
into the environment. Under this question, ORD will
4.4.1 Key Science Question 7. Which manufactured conduct research to understand emissions/releases that
nanomaterials have a high potential for release from can occur either during production, use, recycling, or
a life cycle perspective, and what decision-making disposal of nanomaterials. Examples of points of entry
methods and practices can be applied to minimize the into the environment include:
risks of nanomaterials throughout their life cycle? Manufacturing Waste Streams: During the
manufacture of nanomaterials, the inevitable
4.4.1.1 Background/Program Relevance by-product and waste streams will need to be
To understand the potential environmental evaluated. Pollution prevention (e.g., green
implications of nanomaterials and to identify potential chemistry) research may be very helpful in
29

the development of environmentally friendly address these issues, researchers are implementing
manufacturing processes for nanomaterials. more comprehensive assessment tools, such as
lifecycle assessment (LCA), that can establish
Air Treatment: Manufactured nanomaterials
comparative impacts of products and processes in
can be emitted along with other conventional
terms of well-defined impact categories. Such an
pollutants during production processes.
assessment can be applied across the entire life cycle
In addition, there are products that use
[materials acquisition (cradle) to disposal (grave)] or
manufactured nanomaterials where during
along any desired part there-of (gate-to-gate). Hence
their use nanomaterials can be emitted to the
within a single assessment, LCA for nanomaterials
air, (e.g., brakes and fuel additives).
has the potential to address both the toxicological
Water Treatment: Some nanomaterials are and environmental questions associated with these
intended to be biocides and may enter DW materials.
treatment facilities. Personal care products
and pharmaceuticals containing nanomaterials LCA experts worldwide agree that existing LCA tools
will eventually be washed down the drain and are capable of supporting the development of decision
transported to wastewater treatment plants. frameworks for nanomaterials and nanoproducts.1,2
There they will either be removed from A number of cradle-to-gate and gate-to-gate LCAs
the wastewater and end up in the biosolids have recently appeared in open literature, helping
residuals or they will remain in the wastewater researchers to identify the key concerns that must
and be discharged into surface water as part of be addressed if the goal of a full-scale LCA is to be
the treatment plant’s effluent. realized. The proper life cycle boundaries, particularly
Disposal of Used Material: At the end of its the “grave,” must be defined for a given material. This
useful life, each of the consumer products and can be confusing when considering nanomaterials
equipment items created using nanomaterials because they have the ability to permeate much smaller
will enter the waste stream. It is critical to regions, passing throughout the environment. Data
understand where these products end up gaps concerning the transport, persistence, and toxicity
(e.g., landfill, incinerator) in order to provide of nanomaterials must be filled. This is challenging,
guidance on possible emissions/releases of because the diverse properties of nanomaterials (i.e.,
nanomaterials. surface charge, size, shape, chemical composition)
that can be synthesized will strongly impact how these
Product Usage: As products incorporating materials disperse and react within the body and the
manufactured nanomaterials enter the environment. Thus, either a large amount of research
consumer market place, material release may or the development of accurate predictive models is
occur during the normal intended usage or needed to acquire the missing data. Additionally, issues
conversely during unintended usage. Releases such as the treatment of nanomaterials incorporated
may occur through abrasion, adsorption/ into larger composite materials and the recycle of
absorption, or volatilization, among other nanomaterials must be addressed. The complexity of
processes. For instance, if veterinary choices associated with the use of nanomaterials that
pharmaceuticals are administered using can influence the LCA categories defined above is
nanomaterials, these materials may be excreted summarized in Figure 4-8.
and released into the environment when The value of any assessment is not only the data it
manure is land applied as fertilizer. generates, but how the data are applied. Are there
In addition to human and ecological exposure, there acceptable tradeoffs associated with nanomaterials?
is a need to better understand how the manufacture, Is the large-scale production of an environmentally
use, and waste management of nanomaterials taxing material justified if it has medical applications
will contribute to other environmental problems, 1 Maynard, A.D., 2006. Nanotechnology: A Research Strategy
including climate changes due to global warming for Addressing Risk. Woodrow Wilson International Center for
Scholars,Washington, DC.
and stratospheric ozone depletion; land use leading
to acidification, eutrophication, and photo-oxidation; 2 Kloepffer, W., M. A. Curran, et al. (2007). Nanotechnology and
odor, noise, waste heat, radiation, and casualties. To Life Cycle Assessment: Synthesis of Results Obtained at a Work-
shop in Washington, DC, 2-3 October 2006.
30

or can reduce costs or enhance performance? based framework that can be used with other pertinent
Questions such as these illustrate the ultimate need for factors such as cost and societal benefit to provide a
a valuation system with suitable metrics. To this end, comprehensive evaluation of nanomaterials throughout
research is needed to develop an easily applied, LCA- their life cycle.
Figure 4-8 Characterization of a Selected Nanotechnology for Life Cycle Assessment
Characterization of nanotechnologies for life cycle assessment is challenging because of

the various aspects of the material that can significantly influence the traditional impact
categories.
Characterization of a Selected Nanotechnology for Life Cycle Assessment
Recycle
Material Manufacturing Application Disposal

Selection
Landfill
Geometry
Dispersive
Composite
Chemistry
Top Down
Bottom Up
Incineration
Water
Treatment
Bio-
Accumulation
Shape
Size
Composition
“Spherical” Wet Environmental

Surface Particle
Functionalization/ Dry Medical
Charge Tube/Rod Manufactured Goods
Organic (Dendrimers, etc.)
Carbon (CNTs, Buckyballs)
Inorganic (Metals and/or

oxide/hydroxides)
4.4.1.2 Research Activities manufactured nanomaterials. This effort will also

ORD will identify industries, processes, and include a series of assessments for the highest priority
products that have relatively high potential to industry categories. Results from ORD workshops will
release manufactured nanomaterials into the be used to guide industry and nanomaterial selection
environment. Existing literature will be evaluated to for assessment. Comparative assessments will be
better understand the industries of importance and produced to help inform decision-makers at what stage
identify where gaps in information preclude a full in the lifecycle of nanomaterials interventions could
assessment of emission/release points of concern. be used to avoid future environmental pollution. The
ORD will perform a systematic assessment of the ORD effort will be closely coordinated with other
production, use, and ultimate fate of nanomaterials organizations, particularly EPA’s Office of Pollution
to understand the potential for emissions/releases Prevention and Toxics, which is also generating data
into the environment. A modified tool using life cycle on nanotechnology industries.
principles will be developed to better understand
which industries pose the greatest potential to emit/ This research can be used to inform EPA, industry,
release nanomaterials of concern and to inform and academia about potential proactive and “greener”
decision makers about the overall impact of approaches for manufacturing nanomaterials that
31

are designed to prevent nanomaterial release into nanomaterials will follow similar entry points into the
the environment. It could also be used as input environment. One of the primary goals of this research
for future thorough LCAs. The development of a is to generate the data and tools needed to quantify
robust assessment tool can support decisions in the and project these points of entry, so they can evaluate
development of appropriate nanotechnologies. Such a potential risks and possible approaches to manage
tool is highly needed and has yet to be fully developed. those risks. One of the key issues to investigate is
In addition, the necessity for specific data will help whether the nanomaterial compounds will be emitted/
with the design of fate, transport, and toxicity studies released in their original form or whether they will be
that are necessary to better understand the use and physically or chemically bound with other compounds.
release of nanomaterials. The goal is to develop a This will directly impact transport and transformation
decision-support framework available to stakeholders and will influence potential exposures and health
that is easy to apply and can accommodate a wide risks. For instance nanomaterials that are introduced
variety of nanomaterials and nanoproducts. to the environment in solution may be more likely
than other nanomaterials to remain in their original
High-potential industries/processes form and become bioavailable. Nanomaterials that are
ORD will draw upon the latest literature, hold chemically cross-linked in a matrix are less likely to
workshops, and interact directly with industry be released in their original form and size, although
representatives to identify market trends for uncertainties remain. Because of their exceptional
nanotechnology industries that utilize the priority properties and characteristics, some manufactured
manufactured nanomaterials indicated earlier in this nanomaterials are being intentionally released to
document. This research will attempt to quantify the serve as catalytic agents for remediation or filtration
amounts of nanomaterials expected to be produced and purposes or as instruments for detection of pollution.
used by existing industries, identify key processes used This research will summarize the latest uses and
to manufacture these nanomaterials, and project future provide available information on the characteristics of
industries where significant releases may occur. the materials released.
Identification/characterization of potentially Materials modification to support green

released materials manufacturing of nanomaterials
Once we know where the manufactured nanomaterials Research on greener synthesis approaches will
may be released, it will be important to understand identify opportunities to reduce the environmental
something about the characteristics of these materials implications of nanomaterial production. Since
to inform future transport, transformation, exposure, basic nanotechnology production processes are still
and health studies. The research will focus on whether under development, EPA is well placed to work with
the nanomaterial emissions/releases have the same others to design production processes that minimize
characteristics (size, chemical composition) as the or eliminate any emissions/releases. One area of
original material or have been modified before release research is producing nanomaterials using benign
to the environment. This area of research will be agents such as phenolics from tea extract, vitamins
highly dependent upon the availability of technology to B1, B2, and C, or even sugars and carbohydrates
identify and characterize manufactured nanomaterials. which have been demonstrated to generate a wide
Unfortunately, the ability to make these measurements variety of nanomaterials for various applications.
is also highly uncertain and will require extensive These alternative synthesis methods use these benign
research. Efforts to identify, develop, test, and verify materials which act as capping agents (e.g., ensures
detection technologies will be critical to the success of that nanoparticles do not agglomerate) creating and
this research activity. allowing the nanomaterials to maintain their properties
and benefits. In addition to the addressing the key
Entry point into the environment science question above, this research will be designed
Given that during the manufacture, use, and recycling to answer the following question: how can energy
or disposal of conventional products there are always consumption be minimized and waste/pollution
emissions/releases of pollutants, it is reasonable prevented in the manufacturing of nanomaterials and
to presume that some form of manufactured products? The general approach will be to develop a
32

strategy that allows the greener preparation of these incinerate traditional waste streams will effectively
materials. Three of the main green chemistry areas that destroy nanomaterials present in waste, interfere
will be investigated include: 1) the choice of solvent, with the effective destruction of traditional waste
2) the reducing agent employed, and 3) the capping or material, and/or create new hazardous products of
dispersing agent. For example, ORD is using a flame incomplete combustion (PICs). In addition, since
and furnace reactor combination to produce single- nanomaterials are for the most part long-lasting and
walled and multi-walled carbon nanotubes. We are not biodegradable, ORD will investigate their leaching
using a common feed-stock (e.g., propane), as opposed potential to water bodies. Also, nanomaterials could
to mixtures of carbon monoxide and hydrogen, and a serve as a means to concentrate other toxic pollutants
metallic catalyst to initiate nanotube formation. present in various types of landfills, making them more
bioavailable. This concern will also be investigated.
The goal of this research question is to perform the
key initial step to inform additional research on 4.4.1.3 Anticipated Outcomes
transport, transformation, and subsequent exposure
Identification of industries, processes, and
and health studies. In addition, by identifying potential
products that have relatively high potential to
release points, this research will provide key data
release manufactured nanomaterials into the
required to inform how best to manage any potential
environment by working collaboratively with
risks.
other organizations to inform decision-makers
about the overall impact of manufactured
Risk Management
nanomaterials
ORD will conduct research on the feasibility of using
conventional technology to manage the emissions/ Improved understanding of the industries
releases of manufactured nanomaterials or degradation of importance and identification where
by-products to all media. This research will inform information gaps that preclude a full
regulatory officials and industry about the viability of assessment of emission/release points of
various risk management alternatives and potential concern
improvements to ensure the safe manufacturing, A systematic assessment of the production,
use, and disposal of nanomaterials. This research use, and ultimate fate of nanomaterials that
has the potential to influence decisions regarding will improve understanding of the potential for
manufacturing, storage, handling, use, and disposal of emissions/releases into the environment
selected nanomaterials. The results of the research will
be provided in the form of reports and computer-based Development of a modified tool using life
systems that can be used to address the unique issues cycle principles to: (a) better understand
associated with various industrial operations. which industries pose the greatest potential
to emit/release nanomaterials of concern and
To support the research activities below, ORD (b) inform decision-makers about the overall
will conduct various workshops with industry, impact of manufactured nanomaterials
academia, and other parts of EPA to discuss A series of assessments for the highest priority
potential environmental liabilities associated with industry categories, the results of which will
manufacturing, using, recycling, and disposing of be used to guide industry and nanomaterial
nanomaterials. The parties will exchange information selection for assessment
and ideas about where releases are more likely to pose
the greatest risks and what alternatives (e.g., preferred Development of comparative assessments to
manufacturing approaches via green chemistry) are help inform decision-makers at what stage in
available that could minimize environmental liabilities. the lifecycle of manufactured nanomaterials
These workshops will help all participants consider interventions could be used to avoid future
how nanotechnology products can be designed in the environmental impacts
most environmentally sustainable manner possible. Design of production processes that minimize
or eliminate any emissions/releases and reduce
ORD will conduct parametric studies to determine energy consumption during the manufacturing
if conventional operating conditions used to of nanomaterials and products
33

An evaluation of the efficacy of existing Treat contaminated environmental media (i.e.,
pollution control approaches and technologies air, water, sediments, or soil)
to manage releases of manufactured
nanomaterials to all media during their ORD’s initial emphasis will be to address key
production pollutants of concern to EPA program and regional
offices that have historically been difficult to manage,
ORD will collaborate with others to report including sources that emit low concentrations of air
on opportunities to reduce the environmental pollutants and remediation of hazardous materials in
implications of nanomaterial production by complex heterogeneous environments.
employing greener synthesis approaches
Comprehensive evaluation of the impact In addition to supporting the recommendations of
nanomaterials could have on conventional outside experts, this research will be valuable to EPA
thermal destruction and land disposal practices program and regional offices and outside stakeholders
such as industry and states who are constantly looking
ORD will identify design production processes for innovative solutions to address intractable pollution
that minimize or eliminate any emissions/ problems. Many of these needs have already been
releases and reduce energy consumption identified.
during the manufacturing of nanomaterials and
products 4.4.2.1 Research Activities
This area is primarily driven by the need to
4.4.2 Key Science Question 8. How can address existing environmental problems through
manufactured nanomaterials be applied in a the application of nanotechnologies. Only where
sustainable manner for treatment and remediation of nanotechnologies potentially offer superior solutions
contaminants? to high priority problems do they become viable
While it is critical to understand the potential candidates for ORD environmental applications
environmental implications of nanotechnology, research. Two key technical areas are identified below
it is also important to investigate how various where benefits can be anticipated either directly
nanomaterials can be used to prevent, control or through the development of nanotechnology-based
remediate environmental contaminants that have up materials and processes and/or indirectly through the
to now been difficult to manage with conventional development of technologies used to characterize
technology. nanomaterials that may subsequently be applied in
support of environmental restoration efforts.
Nanotechnology will be used to both create new
technologies and improve the performance of Waste/byproduct minimization
conventional technologies. There are several avenues The use of nanotechnology in industrial processes
to obtain environmental benefits from nanotechnology. has many potential advantages. One potentially
significant environmental benefit is reducing the
Use nanoscale materials in a synthesis process amount of material sent to the waste stream. Under
as a substitute for more toxic components or this research area, ORD will work with its partners
as a process mediator that reduces the mass in industry and academia to investigate advanced
of potentially toxic materials employed in the approaches that have the potential to reduce waste
chemical process (e.g., catalysts) products in those industrial sectors with high
volumes of waste. Waste minimization benefits to be
Incorporate nanoscale materials into a part of realized through nanotechnology applications will
the production process used to treat noxious result either through the substitution of less-toxic
chemicals prior to final discharge chemical components in the manufacturing process
or through the reduction in the required mass of
Employ nanoscale materials to treat emissions/ toxic chemical components via enhanced reaction
releases from power production and industrial rates or efficiencies. An example of the first scenario
processes waste streams includes the use of nanomaterials to improve material
characteristics of bio-based, nanocomposite products.
34

These products are being developed as substitutes for evaluate innovative, high performance or lower
more traditional petroleum-derived materials, resulting cost alternatives for treating critical contaminants.
in a reduction of the mass of toxic components that Improvements for many different treatment
could potentially be released into the environment. scenarios (e.g., matrices, contaminants, treatment
There are also numerous examples of the development technologies, and treatment goals) may become
of nanomaterials for use as catalysts in chemical
feasible. Examples of areas where such an
manufacturing processes. The use of nanoscale
catalysts results in an overall enhancement of process approach could provide significant improvements
efficiency, thus reducing the required mass of toxic in removal performance and cost savings is the
chemical components used in the manufacturing use of nanotechnology to produce advanced
process. sorbents for mercury control and water treatment.
In the mercury area, the ability to directly link
Application of nanomaterials to reduce the physical and chemical nature of binding
environmental risks sites in the materials with the performance of
Under this research area, ORD will investigate the those materials is the key to developing new
potential for various nanomaterials to minimize the or improved adsorbents with properties that
release of toxic chemical constituents. Similar to exceed those that have conventionally been
the use of nanoscale catalysts in the manufacturing
used. In the water area, nanomaterials may
process, the use of nanomaterials to treat process
waste streams (gas, liquid, or solid phases) provides enable the manufacture of media that are more
enhancements in removal rates and/or efficiencies. selective, efficient, and economical for removal or
One key activity will include the application of destruction of existing or emerging contaminants
nano catalysis for the reduction of air pollutants from drinking water, wastewater, and storm
and a better understanding of how these catalysts water. These improved media may arise from
can be used in various environmental applications. better design and uniformity of pore size, particle
Inorganic nanoscale materials, including metallic iron size, or composition made feasible by nano-scale
nanomaterials and aluminosilicate-based zeolites, design and control of the manufacturing process.
have been synthesized for removal or degradation of
metals and organic contaminants from air and water Remediation of contaminated sites is another
effluents generated as a result of manufacturing and
area where ORD will explore the use of
power-generation operations. Similar to the case
described above for the manufacturing process, the use nanomaterials. Examples of these research and
of nanomaterials in end-of-pipe treatments affords the development efforts include the development
opportunity for regeneration or controlled disposal of of nanoscale metallic solids or biopolymers
treatment by-products. In addition, this research will for the destruction of organic contaminants or
study the use of nano-scale iron particles to remediate the extraction of inorganic contaminants from
aqueous streams contaminated with chlorinated- ground water and soil. Ultimately, EPA can play
organics, pesticides, PCBs, heavy metals and such a significant role in advancing the development
inorganics like Cr+6, arsenates, perchlorates, and and implementation of these technologies through
nitrates. If these treatment and remediation processes research and testing. Using past experience
are successful, they can be incorporated into existing implementing waste minimization, treatment,
treatment systems to further reduce contaminant and remediation technologies, EPA can fulfill
loading. the much-needed role of a technical mediator
between the commercial entities actively pursuing
Another area of emphasis within this program development of synthetic nanomaterials and those
will be to investigate the ability to physically who may be negatively affected by the large-scale
and chemically tailor substances, surfaces, and utilization of these materials.
pores at the nano-scale to improve selectivity and
efficiency of membrane filtration, adsorption,
and catalysis. The objective is to identify and
35

4.4.2.2 Anticipated Outcomes of conventional pollutants. Through this research
Nanotechnology research will play a role in ORD will report on the viability, performance,
providing environmental benefits to society and benefits of the use of nanotechnology for the
through the development of new materials or abatement and remediation of conventional toxic
technologies for waste minimization and treatment pollution.
Research Theme: Preventing and Mitigating Risks Methods
Key Science Questions:

7. Which manufactured nanomaterials have a high potential for release
from a life-cycle perspective, and what decision-making methods and
practices can be applied to minimize the risks of nanomaterials
throughout their life cycle?
8. How can manufactured nanomaterials be applied in a sustainable
manner for treatment and remediation of contaminants?
2009
Characterize NM’s with enhanced catalytic properties
2010
Develop scientific foundation for the Report on a Life Cycle Analysis
use of NMs for environmental approach for evaluating future
remediation nanotechnology applications
2011
Research brief to compare the life-cycle environmental
tradeoffs of different disposal options for engineered
nanomaterials
Research on what practices can be applied to

minimize the risks of nanomaterials throughout their
life cycle
.Field demonstrate NM treatment

technologies for ground water and
environmental contaminants
2012
Develop preventive methods and nanomaterial technologies for risk
management of environmental contaminants
36

5.0
Conclusion
The ORD Nanomaterial Research Program
is designed to provide information to support
nanomaterial environmental, health, and safety
decisions. The eight key science questions described
in the NRS are intended to help decision makers
answer the following questions:
What nanomaterials, in what forms, are most
likely to result in environmental exposure?
What particular nanomaterial properties may
raise toxicity concerns?
Are nanomaterials with these properties likely
to enter environmental media or biological
systems at concentrations of concern, and
what does this mean for risk?
If we think that the answer to the previous
question is “yes,” can we change properties
or mitigate exposure?
Providing information to answer these questions will
serve the public by enabling decisions that minimize
potential averse environmental impacts, and
thereby maximize the net societal benefit from the
development and use of manufactured nanomaterials.
37

For more about EPA research on nanotechnology, please visit:
www.epa.gov/nanoscience
38

References
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&EPA United States

EPA 620/K·09/011 I June 20091 www.epa.gov/nanoscience

_ Office of Research and Development

nanotechPublicationFINAL.indd 1 6/24/2009 10:10:07 AM

Nanomaterial Research Strategy

Ofﬁce of Research and Development

nanotechPublicationFINAL7-28-09.indd 3 7/29/2009 8:41:16 AM

Randy Wentsel, Co-Lead

Michele Conlon, NERL Douglas McKinney, NRMRL

ORD Science Council, August 2007

EPA Science Policy Council Steering Committee, September, 2007

External Peer Review March, 2008

External Letter Review, November 2008

nanotechPublicationFINAL7-28-09.indd 4 7/29/2009 8:41:16 AM

Executive Summary ........................................................................................................................ iii

Major acronym list........................................................................................................................... v

3.0 Key Considerations.................................................................................................................... 7

3.1 Selection of Materials ................................................................................................................ 7

3.2 Strategic Direction of Research Themes and Science Questions .............................................. 8

4.0 Research Themes ......................................................................................................................11

4.1.1 Key Science Question 1 ..................................................................................................11

4.1.1.1 Background/ Program Relevance ..........................................................................11

4.1.1.2 Research Activities ................................................................................................11

4.1.1.3 Anticipated Outcomes ...........................................................................................12

4.1.2 Key Science Question 2...................................................................................................12

4.1.2.1 Background/Program Relevance ...........................................................................13

4.1.2.2 Research Activities ................................................................................................13

4.1.2.3 Anticipated Outcomes ...........................................................................................16

4.1.3 Key Science Question 3...................................................................................................17

4.1.3.1 Background/ Program Relevance ..........................................................................17

4.1.3.2 Research Activities ................................................................................................17

4.1.3.3 Anticipated Outcomes ...........................................................................................19

4.2 Research Theme: Human Health and Ecological Effects Research

to Inform Risk Assessments and Test Methods ........................................................................20

4.2.1 Background and Program Relevance...............................................................................20

4.2.2 Key Science Question 4...................................................................................................20

4.2.2.1 Human Health Effects Research Activities ...........................................................20

4.2.3 Key Science Question 5...................................................................................................24

4.2.3.1 Ecological Effects Research Activities ..................................................................24

4.2.4 Anticipated Outcomes ......................................................................................................25

4.3 Research Theme: Developing Risk Assessment Methods ........................................................26

4.3.1 Key Science Question 6...................................................................................................26

4.3.2 Background/Program Relevance .....................................................................................26

4.3.3 Research Activities ..........................................................................................................27

4.3.4 Anticipated Outcomes ......................................................................................................28

4.4 Research Theme: Preventing and Managing Risks.................................................................. 29

4.4.1 Key Science Question 7...................................................................................................29

4.4.1.1 Background/Program Relevance ...........................................................................29

4.4.1.2 Research Activities ................................................................................................31

4.4.1.3 Anticipated Outcomes ............................................................................................33

4.4.2 Key Science Question 8 .........................................................................................................34

4.4.2.1 Reserach Activities ................................................................................................34

4.4.2.2 Anticipated Outcomes ............................................................................................36

nanotechPublicationFINAL7-28-09.indd Sec1:i 7/29/2009 8:41:19 AM

Related EHS Research Needs ....................................................................................................3

Figure 2-2 Federal Sources to Inform EPA’s Nanotechnology Activities .........................................4

Figure 2-3 EPA’s NRS Within The Decision-Support Context.........................................................5

What research is important to support Agency