&EPA
United States
Environmental Protection
Agency
EPA 620/K-09/011 | June 2009 | www.epa.gov/nanoscience
Nanomaterial Research Strategy
Office of Research and Development
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EPA620/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
4.1.2.2 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
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
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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
The Nanomaterial Research Strategy (NRS) guides
the nanotechnology research program within EPA's
Office of Research and Development.
Nanotechnology White Paper (EPA, 2007).
The purpose of EPA's nanotechnology research
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.
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Major Acronym List
AA
ADME
AML
BMPS
CAA
CEA
CERCLA
CR
CREM
CT
DAA
DOD
DOE
DSSTOX
HPG
IRIS
LCA
MOA
MOAS
MR-CAT
MYP
NAS
NCCT
NCEA
NCER
NCI
NCL
NEHIWG
NERL
NHEERL
NGO
NIEHS
NIOSH
NIST
NNCO
NNI
NPDS
NRC
NRMRL
NRS
NSET
NSF
NSTC
OECD
ORD
Assistant Administrator
Absorption, distribution, metabolism, elimination
Advanced Measurement Laboratory
Best management practices
Clean Air Act
Comprehensive environmental assessment
Comprehensive Environmental Response Compensation and Liability Act
Current Research
Council for Regulatory Environmental Modeling
Committee on Technology
Deputy Assistant Administrator
Department of Defense
Department of Energy
Distributed Structure-Searchable Toxicity
Hypothalamic-Pituitary-Gonadal
Integrated Risk Information System
Life cycle Analysis
Mechanism of action
Modes of Action
Materials Research Collaborative Access Team
Multi-year plan
National Academy of Science
National Center for Computational Toxicology
National Center for Environmental Assessment
National Center for Environmental Research
National Cancer Institute
Nanotechnology Characterization Laboratory
Nanotechnology Environmental and Health Implications Working Group
National Exposure Research Laboratory
National Health and Environmental Effects Laboratory
Non-Governmental Organization
National Institute of Environmental Health Sciences
National Institute for Occupational Safety and Health
National Institute of Standards and Technology
National Nanotechnology Coordination Office
National Nanotechnology Initiative
National Program Directors
National Research Council
National Risk Management Research Laboratory
Nanomaterial Research Strategy
Nanoscale Science Engineering and Technology
National Science Foundation
National Science and Technology Council
Organization for Economic Cooperation and Development
Office of Research Development
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1.0
Introduction
Purpose. The Nanomaterial Research Strategy
(NRS) describes the Environmental Protection
Agency's (EPA) strategy for conducting and
supporting research to understand the potential
human health and ecological (henceforth referred
to jointly as "environmental") implications from
exposure to manufactured nanomaterials, and
how nanotechnology can be used sustainably in
environmental protection applications. EPA has
written this document with three main purposes:
(1) to guide its own researchers and managers
as they conduct EPA's research program, (2) to
assist scientists in other organizations as they plan
research programs, and (3) to inform the public of
how EPA intends to generate scientific information
to guide environmental decisions related to
nanomaterials.
The purpose of EPA's research program is to
conduct focused research to address risk assessment
and risk management needs for nanomaterials
in support of the various environmental statutes
for which EPA is responsible. This program will
be coordinated with research conducted by other
federal agencies, where EPA will lead selected
research areas and coordinate and/or collaborate
with its federal research partners in other research
areas. 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.
Focus. The NRS focuses on developing scientific
information for nanomaterial decision support.
Because other entities also conduct research on
nanomaterial safety, EPA is focusing 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
In addressing these themes, EPA's research program
will focus on providing information that supports
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?
What particular NM properties
may raise toxicity concerns?
Are NMs with these properties
likely to be present in
environmental media or
biological systems at
concentrations of concern?
If "yes," can we change
properties or mitigate
exposure?
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Objectives. EPA believes that its research should
advance two key objectives: (1) the development
of approaches for identifying and addressing any
hazardous properties, while maintaining beneficial
properties, before a nanomaterial enters the
environment; and (2) identifying whether, once a
nanomaterial enters the environment, it presents
environmental risks. EPA will pursue these objectives
from a life cycle perspectivei.e., by understanding
where environmental impacts may occur and where
benefits may be attained throughout a nanomaterial's
existence; from its production, through its use in
products and as it is disposed of or recycled.
Approach. The NRS will be implemented in EPA's
Office of Research of Development (ORD), in two
main ways: by funding grants through the Science
to Achieve Results (STAR) and Small Business
Innovation Research (SBIR) programs, and by EPA
scientists within ORD's research laboratories and
centers. Expertise needs will determine how resources
are allocated between externally and internally
conducted research.
Organization. The NRS is organized around the
four research themes. Within each theme, research
activities are identified along critical paths toward
addressing science questions.
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2.0
Context
EPA's NRS is one component of an international
effort to generate information on nanomaterials and
the environment. Other US federal agencies, national
governments, industry, academic institutions, and
non-governmental organizations are also involved.
While the number of individuals and organizations
generating information on the environmental impacts
of nanomaterials is large and growing, for the
purposes of placing the NRS within a larger context
there are four major efforts underway:
Organization for Economic Cooperation
and Development (OECD) Working Party
on Manufactured Nanomaterials. The
OECD is coordinating a testing program on
nanomaterials deemed by the Working Party
to be representative of materials likely to enter
commerce. Test plans are to be completed in
mid-2009, with Phase 1 testing to be completed
in approximately three years.
National Nanotechnology Initiative (NNI)
Strategy For Nanotechnology-Related
Environmental, Health, and Safety Research.
This interagency research strategy outlines the
US federal research plans for approximately
the next ten years. Figure 2-1, taken from the
Strategy, illustrates the NEHI members' roles in
implementing the interagency strategy. While
coordinating agencies will play a leadership role
in advancing interagency implementation of the
NNI strategy, other agencies may play scientific
leadership roles in particular areas.
EPA NRS. The NRS was developed in concert
with the NNI strategy.
EPA Nanomaterial Stewardship Program
(NMSP). EPA's office of Pollution Prevention
and Toxic Substances has initiated a program
for the voluntary submission of nanomaterials
Figure 2-1. Roles of NEHI Working Group Member Agencies with Regard
to Nanotechnolosv -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.
Agency
NIH
NIST
EPA
FDA
NIOSH
NSF
DOD
DOE
USDA
DOT
OSHA
CPSC
uses
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*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.
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environmental, health, and safety information
from industry and others.
Collaboration for Decision Support. For the NRS
to provide maximum scientific value and guide
most efficient resource use, collaborating with and
leveraging the work of others is crucial. Figure
2-2 illustrates the breadth of information needed
to make decisions related to nanomaterials and
the environment, as well as the number of federal
entities involved in generating and using this
information.
EPA is using several approaches to link the NRS
to other efforts to develop scientific information in
support of decision making. They include:
Coordinating and collaborating with
other federal agencies. As shown in
Figure 2-1, EPA is the federal government's
coordinating agency for the "Nanomaterials
and the Environment" and "Risk
Management Methods" areas of the NNI
strategy. EPA also co-chairs the NEHI and
is leading efforts, such as planning state-
of-the-science workshops, to advance
implementation of the interagency strategy.
The NRS is also being implemented by EPA
issuing joint grant requests for applications
(RFA) with other federal agencies, including
the National Science Foundation (NSF),
the National Institute for Environmental
Health Sciences (NIEHS), and the National
Institute for Occupational Safety and
Health (NIOSH). EPA's laboratories are
also coordinating and collaborating with
other agencies, such as with the National
Toxicology Program and NIOSH on carbon
nanotubes. Also, EPA is co-sponsoring
with NSF new national Centers for the
Environmental Implications of Nanomaterial
Figure 2-2. Federal Sources to Inform EPA's Nanotechnology Activities
Understanding Nanotechnology
Characterization,
Properties
DOD
DOE
EPA
NASA
NIH
NIST
NSF
Pollution
Prevention
Green manufacturing
Green Engineering
Green Energy
EPA
DOD
DOE
Instrumentation,
Metrology,
Standards
DOD
DOE
NASA
NIH
NIST
NSF
EPA
Research
Risk assessment
Risk management
Sustainability
Stewaidship
Remediation
EPA
DHS
DOD
NASA
NSF
Applications
Sensors, Devices
DHS
DOD
DOE
EPA
NASA
NIH
NIOSH
NIST
NSF
USDA
USGS
Implications
Toxicity
DOD
EPA
FDA
NIH
NIOSH
NSF
Fate, Transport,
Transformation,
Release,
Treatment
DOD
DOE
EPA
NIH
NIOSH
NSF
Detection,
Monitoring
DOD
EPA
NIH
NIOSH
NSF
USGS
Note: NIH includes NIEHS , NCI (NCL), NTP
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Figure 2-3 EPA's NRS Within The Decision-Support Context
Decision-Support & Institutional Context:
EPA-centric View
Other Agencies
NEHI
Academic Research
"Bi-lateral"
EPA
OECD Testing Program
Industry-sponsored Testing
Health and Environmental
Decisions
(CEINT) to conduct fundamental research
and education on the implications of
nanotechnology for the environment and
living systems at all scales. The CEINTs will
address interactions of naturally derived,
incidental and manufactured nanomaterials
with the living world.
Participating in the OECD Testing
Program. In implementing the NRS,
EPA is co-sponsoring testing on a number
of nanomaterials. EPA researchers will
divide testing responsibilities and share
test materials with the co-sponsoring
organizations.
Nanomaterial Stewardship Program.
EPA believes that the NMSP will provide
material-specific and general information
that will be useful to advancing EPA's
research program. Also, ORD researchers
are collaborating with OPPT on identifying
information gaps that the NMSP can address.
Figure 2-2 depicts how EPA fits within the larger
information-gathering context to support decisions
related to nanomaterials and the environment.
Integration. Successfully implementing the NRS
within a larger scientific context will require EPA to
integrate into its research program information from
various sources. EPA is using the following means to
enable such integration:
Supporting and using the OECD's
international database on nanomaterial
environmental, health, and safety research.
Holding joint meetings with EPA researchers
and STAR grantees.
Convening state-of-the-science workshops
on each of the four NRS research themes.
Leading and participating in NNI-sponsored
workshops as part of implementing the
interagency strategy.
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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
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3.0
Key Considerations
This section outlines five key considerations that
ORD took into account as it developed the NRS.
These five considerationsselection of materials,
research themes and science questions, informing risk
assessment and risk management, setting priorities,
and implementationserve to bound the ORD
nanomaterials research program. Putting bounds around
the program is important, given resource limitations
and acknowledging that the NRS fits within and should
complement a larger national and international context
of nanomaterial EHS research.
3.1 Selection of Materials
ORD is focusing its research on seven manufactured
nanomaterial types: single-walled carbon nanotubes,
multi-walled carbon nanotubes, fullerenes, cerium
oxide, silver, titanium dioxide, zero-valent iron.
Ultimately, ORD has as a goal, the development of
predictive models and tools that will enable testing
across these material types, since testing the many
potential variations of materials within each of these
seven material types would be very resource intensive.
ORD selected these seven material types based on
the materials' current use in products, the near-term
needs of EPA's program and regional offices, research
underway at other federal agencies, and the materials
selected for testing in the OECD's Working Party on
Manufactured Nanomaterials. Overtime, ORD expects
to extend its efforts to other material types.
These materials are of interest to EPA either because of
their potential use in cleaning up pollution (zero-valent
iron) or because EPA may need to make safety
decisions on the materials under its regulatory
programs. EPA program offices that have already
given consideration to some of these specific
materials include the Office of Pollution Prevention
and Toxics, the Office of Pesticide Programs, and
the Office of Air and Radiation.
The United States, with EPA as a principal
participant, is sponsoring or co-sponsoring the
testing of all of the seven materials as part of
the OECD's nanomaterial testing program. In
particular, EPA is taking leadership roles in the
testing of cerium, C-60 fullerenes, nanotubes,
silver, and titanium dioxide. This program allows
the ORD to leverage the work of other nations
and organizations in advancing the Nanomaterial
Research Strategy. For example, for the carbon
materials Japan, Korea, and industry are conducting
mammalian toxicity testing, while EPA will do
environmental fate and ecological effects testing.
Thus, the partnership for these materials cover all
the endpoints under the OECD program.
There is no question that the types of, and
variations on, nanomaterials is large and growing,
and goes beyond the materials ORD has chosen
for near-term study. However, these seven material
types are a good starting point for the new ORD
program, which will evolve together with state of
nanoscience and as environmental decision-support
needs change.
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
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3.2 Strategic Direction of Research Themes and
Science Questions
EPA has identified four key research themes where it
can support the National Nanotechnology Initiative and
the science needs of EPA.
Key Science Questions. Under each of the four
research themes, the EPA research program will
address key science questions.
Theme 1. Sources, Fate, Transport, and Exposure
What technologies exist, can be modified,
or must be developed to detect and quantify
manufactured nanomaterials in environmental
media and biological samples?
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?
What are the exposures that will result from
releases of manufactured nanomaterials?
Theme 2. Human Health and Ecological Effects
Research to Inform Risk Assessment and Test Methods
* What are the health effects of manufactured
nanomaterials and their applications, and
how can these effects be best quantified and
predicted?
What are the ecological effects of
manufactured nanomaterials and their
applications, and how can these effects be best
quantified and predicted?
Theme 3. Risk Assessment Methods and Case
Studies. In what ways, if at all, do risk assessment
approaches need to be amended to incorporate special
characteristics of manufactured nanomaterials?
Figure 3-2 Relationship of Key Science Questions to Support Risk Assessment and Management Decisions; Based on
Comprehensive Environmental Assessment (Davis and Thomas, 2006)
Analytical Detection Method Development
Adaptation/
RevitalizatiorV
Restoration/
Remediation
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Theme 4. Preventing and Managing Risks
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?
How can manufactured nanomaterials be
applied in a sustainable manner for treatment
and remediation of contaminants?
3.3. Informing Risk Assessment and Risk
Management
Figure 3-2 illustrates the interrelationship of the
research activities and research products that inform
risk assessment and risk management issues. While
the basic paradigms of health and ecological risk
assessment are still relevant, they are expanded in
the comprehensive environmental assessment (CEA)
approach to encompass the product life cycle of
nanomaterials. By taking a broad view of the potential
for releases of both primary and secondary materials
to multiple environmental media, the evaluation of
the environmental and health risks of nanomaterials
is seen as an issue that cuts across EPA programmatic
domains and is not simply categorized as solely an
air, water, toxics, or solid waste issue. The CEA
approach (Davis and Thomas, 2006; Davis, 2007)
starts with a qualitative life cycle framework. It takes
into consideration multiple environmental pathways,
transport and transformation processes, cumulative
and aggregate exposure by various routes, and
ecological as well as human health effects. Depending
on the availability of data, both quantitative and
qualitative characterizations of risks may result.
However, given the limited information currently
available on nanomaterials, the CEA approach is being
used to identify where key data gaps exist with respect
to selected case studies of specific applications of
nanomaterials.
3.4 Prioritization of Research
ORD evaluated several key issues and activities to
identify priorities for its research program. Research
recommendations from the EPA Nanotechnology
White Paper and research coordination leadership
in the NNI Strategy (2008) were important
considerations. Defining questions for establishing
priorities were:
Does the research support EPA's mission to
protect human health and the environment?
Is the research important to support EPA
regulatory decisions on nanomaterials?
What role does EPA play in leading/
coordinating this research topic under the NNI
EHS strategy (2008)?
Is the research part of an international
agreement to collaborate and leverage
research activities?
What research is important to support Agency
risk assessment and management activities?
How do partnerships with federal, academic,
and industry researchers enhance research
activities?
Having considered these questions within the
context of resource constraints and research being
conducted by other organizations, ORD has focused
its nanotechnology research program on the areas
described in Section 4 of this strategy.
3.5 Implementation
The research described in this NRS will be
implemented through multi-year plans (MYP). The
Office of Research and Development's research
multi-year plans present the long-term strategic
vision of EPA's research programs. The MYPs serve
as a planning and communication tool to describe
the scope of research addressing EPA's priority
science questions. The MYPs are also used to help
(1) demonstrate how ORD's research programs
contribute to Agency outcomes and strategic goals; (2)
provide information to aid in and support decisions
during budget formulation; and (3) assist in managing
performance and accountability reporting.
ORD is forming a Nanomaterial Research
Coordination Team, which is a cross-EPA research
planning group, to communicate program office and
regional research needs to ORD and for ORD to
communicate its research activities and products under
the strategic research themes. This approach promotes
ORD's focus on the highest priority issues and
provides a roadmap to achieving long-term research
goals while allowing the flexibility for ORD to address
emerging nanotechnology issues that are affecting
specific programmatic areas.
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This section discusses the research themes and
associated key science questions. For each science
question, text addresses the topic background and
program relevance, describes the proposed research
activities, and discusses the anticipated outcomes.
Critical Paths. For each key science question, the
NRS presents a critical-path diagram for addressing
the question. The boxes within each diagram
represent the sequencing of key deliverables, and
the arrows indicate how one deliverable informs
another. The critical-path diagrams do not reflect
when specific research activities begin or end: in
general, work will be initiated far in advance of the
deliverable, and may continue in some form once a
deliverable has been completed.
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4.0
Research Themes
4.1 Research Theme: Sources, Fate, Transport, and
Exposure
4.1.1 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?
4.1.1.1 Background/ Program Relevance
The detection of manufactured nanomaterials in
various environmental media presents a significant
challenge. This is due in part to potential confounding
by the presence of anthropogenic and natural
nanomaterials. Challenges arise because many
different manufactured nanomaterials currently
exist and their numbers are increasing; for certain
types of nanomaterials, such as nanotubes, many
thousands of different structures are possible. In
addition, the fate, transformation, and mobility of
these materials are only beginning to be understood.
Consequently, scientific understanding of the
reactions these materials undergo, how they age in
various environmental media, how they interact with
other compounds present in the environment, and
whether and to what extent they form agglomerates
or aggregates is limited. These issues compound the
complexity of detecting and quantifying nanomaterials
in environmental media.
The development of effective methods for measuring
manufactured nanomaterials in environmental media at
concentrations relevant to potential exposure scenarios
is critical to understanding the environmental impacts
of these materials. Such methods would also enable
the more rapid achievement of the safe development
of nanotechnology-related products. ORD-sponsored
research will ultimately seek to develop remote, in
situ, and continuous monitoring devices that yield
real-time information and that can detect manufactured
nanomaterials at very low concentrations.
Risk assessments of nanomaterials will require the
ability to measure their environmental concentration in
the workplace, home, biota (including human tissues),
and ecosystems of interest. Analytical methods needed
to characterize and analyze nanomaterials will require
the modification of existing analytical tools and the
development of completely new tools and approaches
to meet these challenges. The same properties that
make nanomaterials a significant challenge to analyze
in any matrix (such as high binding capacities) may
also provide unique opportunities for developing new
analytical methods (e.g., tagging with fluorophores)
for their analysis in complex biological and
environmental systems. Obviously, studies will be
necessary to determine how such tagging techniques
will alter the physciochemical properties of the
nanomaterials. ORD will integrate fundamental
research on detection method development from NSF,
NIST, DoD, and others with its own focused methods
research effort to inform this research question.
4.1.1.2 Research Activities
Measurement science (based on analytical chemistry
and physical properties) will have multiple roles in
nanomaterials assessment and will require different
types of analytical methods. There are several major
areas of investigation with nanomaterials that require
the application of a wide array of measurement and
characterization techniques for characterization,
detection, identification, or quantification.
Characterization of nanomaterials: ORD will
undertake studies to characterize the physical and
chemical properties of bulk nanomaterials to assess
and quantify their unique features and characteristics
(e.g., surface-to-volume ratio, 3-dimensional structure,
size, size distribution, relative dimensions (aspect
ratio), chirality, electrical/magnetic properties, and
microstructure). Access to the equipment needed for
these studies will require the formation of partnerships
with other federal agencies, such as the National
Institute of Standards and Technology (NIST), the
National Cancer Institute (NCI) and the Department
of Energy (DOE). Each of these agencies has or is
in the process of establishing nanomaterial research
facilities, such as the Advanced Measurement
Laboratory (AML) at NIST and the Nanotechnology
Characterization Laboratory (NCL) at NCI. These
research facilities provide access to a wide variety of
measurement and characterization tools.
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Analytical methods supporting EF&T studies: ORD
will take advantage of existing analytical methods for
nanomaterials to support the initial focus on lab-based
studies. An ever increasing number of papers in the
literature have reported on the application of analytical
methods for the measurement of nanomaterials for
monitoring lab-based studies to model environmental
processes under controlled conditions (e.g., soil
leaching and subsurface transport) and concentrations.
Examples include the analysis of fullerenes by liquid
chromatography coupled to a photodiode array
detector, the tracking of 14C in radio-labeled carbon-
based nanotubes, and the analysis of quantum dots by
fluorescence spectroscopy.
Detection in environmental matrices: The published
literature on the use of existing analytical tools for
detecting or monitoring manufactured nanomaterials
in the environment (especially in matrices other than
the vapor phase) is very limited. Perhaps the first
publication that borders on being a review of this
literature is that of Nowack and Bucheli (2007). The
lack of methodologies for analyzing environmental
samples likely results from two major factors: (1)
only in the last couple of years has any need for
environmental analysis been contemplated, and (2) the
challenges facing the detection and quantification of
manufactured nanomaterials (especially those based
solely on carbon) in environmental samples far exceed
those associated with conventional pollutants, even
those pollutants that comprise complex mixtures of
many congeners (e.g., toxaphene).
To make unambiguous and quantitative determinations
of manufactured nanomaterials in environmental
samples, ORD will develop a combination of ensemble
techniques (e.g., hyphenated methods coupling
separation with spectroscopic detection, that measure
collectively a number of particles) and single-particle
techniques (e.g., methods, such as imaging, that
measure individual particles). The separation method
employed may be size exclusion chromatography,
sedimentation field flow fractionation, or capillary
electrophoresis. Determination could then be
made, 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.
To develop analytical methods suitable for
environmental monitoring, ORD will work
with NIST to contribute to the development of
standardized reference materials in a variety of
representative matrices. Methods for environmental
analysis or routine monitoring must account for the
extraordinarily wide array of potential parent materials
and transformation products. In contrast to methods
for the other roles described above, approaches to
environmental measurement must include non-target
analysis, where the type(s) of nanomaterials that
need to be detected are not known in advance (the
entire spectrum of parent materials must be amenable
to analysis). The problems that traditionally plague
environmental analysis, such as the wide array of
matrix interferences that limit detectability, make
environmental monitoring of nanomaterials even more
challenging. Examples of this type of application do
not yet exist, and are an additional research need. Once
suitable analytical methods have been developed in
the laboratory, sites will be selected for monitoring
of various media (i.e., air, water, soil, sediment and
sludge) where environmental concentrations would
be expected to be greatest, such as production sites
for nanomaterials and manufacturing sites of products
containing nanomaterials.
4.1.1.3 Anticipated Outcomes
Development of methods for characterizing
nanomaterials, through partnerships with
NIST, NCI and/or DOE
Development of analytical methods for the
detection of carbon-based nanomaterials in
environmental matrices
Development of analytical methods for the
detection of non-carbon-based nanomaterials
in environmental matrices
In cooperation with other federal agencies,
development of standardized test materials
for a variety of representative environmental
matrices
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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
and measurement in environmental media.
Develop methods for
measuring selected NM in
environmental matrices
Extend multimedia
modeling capabilities to
address NM exposure and
risk issues/applications
Evaluate physical and chemical
properties that influence exposure to
nanomaterials in environmental media.
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
2009
2010
4.1.2 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?
4.1.2.1 Background/Program Relevance
Given the current scientific uncertainty surrounding
fate, transport, detection and modeling of manufactured
nanomaterials, it is difficult to accurately assess the
environmental disposition of nanomaterials or the
potential exposure pathways to human and ecological
receptors. Ultimately predictive models for estimating
the environmental fate and transport of nanomaterials
are needed.
Nanotechnology research for fate, transport, detection
and modeling of manufactured nanomaterials is
needed to identify the most critical parameters and
uncertainties associated with these materials. This
research will characterize the environmental fate
and transport (EF&T) of nanomaterials from sources
to human and ecological receptors. The research
-------
will support risk assessments of manufactured
nanomaterials and ways to manage their potential
releases. Initially the research will provide a
fundamental understanding of the physical and
chemical properties of nanomaterials and their
impact on fate and transport pathways. In order to
address this fundamental understanding, research
to provide specific analytical detection techniques
for nanomaterials also will be necessary. Research
collaborations with agencies such as NIST,
academia, and industry are planned to advance the
understanding of the limitations and capabilities of
identified analytical techniques. Finally, existing
predictive models that may be used for nanomaterial
fate and transport will be modified, and if necessary,
new models will be developed. These efforts will
involve collaborations with other federal agencies,
consortiums, international partners and academia.
Because of the introduction and increased production
of nanomaterials, it is necessary to better understand
the fate, transport, detection and modeling of these
materials. Quantitative as well as qualitative research
is necessary to reduce the uncertainty surrounding
the introduction and existence of nanomaterials in the
environment and to identify the exposure pathways
of concern to receptors. Quantitative research such as
identifying the speciation of silver nano particles and
the impact of speciation on the mobility of the silver
particles in sediments as well as the bioavailability
to surrounding receptors is an example of one
ORD research project. Qualitative research such
as assessment of existing chemistry methods for
measuring nanometal oxides in ambient air is another
project. Research on these and other issues will assist
the Agency in risk assessment and risk management
of engineered nanomaterials. ORD will conduct the
following broad research activities as described below.
4.1.2.2 Research Activities
Understand the processes that govern the fate
and transport of manufactured nanomaterials
Understand the chemical and physical
properties of manufactured nanomaterials
and how they influence fate and transport
processes
Develop predictive models for transport of
manufactured nanomaterials
ORD has initiated a research program to study
nanotechnology fate and transport research;
the primary objectives will be to determine the
physciochemical properties controlling the mobility
of nanomaterials through ecosystems and develop
predictive models for estimating their mobility.
Research questions include the identification of system
parameters that alter the surface characteristics of
nanomaterials through aggregation (e.g., pH effects),
complexation (e.g., surface complexation by dissolved
organic carbon) or changes in oxidation state (e.g.,
chemical- or biological-mediated electron transfer).
This work will provide the basis for prioritizing
potential ecological exposure pathways that warrant
further exploration.
Understand the processes that govern the fate and
transport of manufactured nanomaterials
The potential for the occurrence of manufactured NMs
in sediments, soils, air and aqueous environments,
necessitates the understanding of the processes
controlling the fate and transport of these materials
in each of these environmental matrices. The
unique challenges to understanding the EF&T of
nanomaterials is based on knowledge that:
Nanomaterials exist as particles, and thus their
surface chemical and physical properties will
determine their environmental fate and transport
The chemical and surface properties of
nanomaterials will be modified by interaction
with naturally occurring constituents such as
dissolved organic matter, biota (e.g., bacteria, and
biomolecules (e.g., polysaccharides)
Changes in surface properties with naturally
occurring constituents will significantly alter the
mobility of nanomaterials in aquatic ecosystems
The wealth of information currently in the
environmental literature concerning the fate and
transport of chemical contaminants results from
the study of chemicals that are soluble to some
extent in aquatic ecosystems. Much of the existing
work will have little value for predicting the EF&T
of nanomaterials. The body of work concerning
the movement and stability of colloidal material,
which range in size from 1 nm to 1 (iM, in aquatic
ecosystems, however, is already providing insight
into the processes controlling the transport of
-------
nanomaterials in the environment (Loux and Savage,
2008). The EF&T processes most likely to control
the transport of nanomateials in the environment
will include dispersion, agglomeration, and surface
complexation with natural organic matter and
biological constituents.
ORD will conduct controlled laboratory studies to
understand these fate and transport processes and the
factors that control them. Initial work will focus on
understanding their transport in porous and compacted
media; the tendencies of nanomaterials to aggregate,
sorb or agglomerate in ecosystems; and the factors
that influence the mobility of the nanomaterials. ORD
has also identified research questions surrounding
the impact of nanomaterials in groundwater, surface
water, drinking water, wastewater and solid waste. In
addition to laboratory studies, ORD will collect data
from field systems to understand large-scale fate and
transport processes and the factors that influence them.
Understand the physical and chemical properties
of manufactured nanomaterials and how they
influence fate and transport processes
Processes that control movement (i.e., sorption,
dispersion, agglomeration, degradation) will be
strongly affected by the chemical and physical
properties of nanomaterials, such as surface charge,
pH, ionic strength, redox conditions, and ambient
air conditions such as temperature and humidity.
Consequently, typical chemical parameters for
predicting chemical fate and transport such as water
solubility, octanol-water partition coefficient and
vapor pressure will be substituted with parameters
such as particle size, surface charge and surface
potential. Obtaining information on the chemical
and physical properties of specific nanomaterials
and classes of materials is necessary to understand
their effect on fate and transport processes. For
example, a specific ORD research project is
characterizing the surface reactivity of silver, iron,
titanium dioxide and cerium oxide and determining
the impact of this reactivity on mobility and toxicity
of the nanomaterials. Another example is ORD's
investigation of processes controlling the mobility
of carbon-based nanomaterials in porous media. The
mobility of these materials largely depends on the
degree and type of functionalization (elements or other
functional groups at the surface of the nanostructures),
which affect solubility and surface charge.
Clearly, the determination of how transport of
nanomaterials through soils, the vadose zone, and
groundwater is affected by solution chemistry and
colloid surface properties is critical for understanding
the fate of nanomaterials. These are important
questions for understanding the fate of nanoiron
particles purposely placed in the ecosystem for source
control of DNAPL plumes. Previous metals research
has shown that chemical speciation of inorganic
engineered nanomaterials is an important factor to
understand for the fate and transport and ultimate
bioavailability of the materials. Initial research by
ORD on nanosilver particles impregnated in clothing
and washed indicates potential pathways for human
exposure and introduction of nanosilver to the
environment. Silver is impregnated in fabrics and
other materials as an anti-fungal/anti-microbial agent,
but little is known about how the properties of the
nanosilver particles impact their fate and transport
in the environment. Initial research indicates that the
presence of oxidants in the wash water likely limit
the bioavailability of the nanosilver particles. ORD
continues to assess the chemical transformation and
speciation of inorganics such as silver.
Develop predictive models for transport of
manufactured nanomaterials
The successful development of EF&T models for
nanomaterials will depend on understanding of
the processes controlling the EF&T of engineered
nanomaterials and the ability to determine the
chemical and physical properties needed to predict
such processes. ORD will study the applicability of
existing environmental fate and transport models
and to develop new predictive EF&T models that are
tailored specifically to nanomaterials. Early analysis
of the Estimation Programs Interface Suite (EPI
Suite) models, the primary set of predictive tools the
Agency uses for calculating the fate and transport of
soluble organic chemicals, indicates that they will
have little or no applicability to predicting the EF&T
of nanomaterials. Models do exist for predicting the
transport of natural colloidal materials and they are
being investigated for application to nanomaterials.
As such, traditional DLVO (Derjaguin. Landau.
Verwey and Overbeek) theory is already lending
insight into environmental fate and mobility trends
of nanomaterials (Loux and Savage, 2008). Basic
colloid models will have to be modified. Likiewise, a
modified version of EPA's MINTEQA2 model used
for calculating metal speciation could provide surface
-------
potentials for nanomaterials. Surface complexation
models are also finding use for determining the effect
of surface complexation on nanomaterial stability in
aquatic ecosystems (Fukushi and Sato, 2005).
4.1.2.3 Anticipated Outcomes
Results from this research will provide an improved
understanding of the EF&T of manufactured
nanomaterials in the environment. This will allow EPA
to develop a set of predictive tools.
Researchers will:
Develop a scientific understanding of the
processes that govern the fate and transport of
manufactured nanomaterials
Measure the chemical and physical properties
of manufactured nanomaterials and determine
how these properties influence and impact fate
and transport
Identify the exposure pathways associated
with production, end-use, and recycling or
disposal of manufactured nanomaterials in
different environmental matrices
Improve the scientific understanding of
detection methodologies for quantifying
manufactured nanomaterials
Develop multiple predictive models for
understanding and measuring the transport of
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?
Provide the underlying science
ontheF&TofNM
Assess the F&T of NM in
the aquatic environments
Determine the properties of NM that effect
F&T
Synthesis of physical/chemical properties
that influence exposure in environmental
media
Use F&T NM data to inform
multimedia transport and
deposition
Determine the major processes/properties that govern the
environmental fate of NM, and key physical/ chemical properties of
NM
2009
2010
2012
2014
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4.1.3 Key Science Question 3. What are the
exposures that will result from releases of
manufactured nanomaterials?
4.1.3.1 Background/ Program Relevance
Research is needed to provide insight into the type,
extent, and timing of exposures to nanomaterials in all
relevant environmental media and through all relevant
exposure pathways. Cumulative exposures, both with
other manufactured nanomaterials as well as with
bulk-scale pollutants, also need to be explored. The
information provided through this exposure research
can be linked with other exposure and biological
impact data to improve the scientific basis of risk
assessment for manufactured nanomaterials.
General population exposure may occur from
environmental releases from the production and use
of nanomaterials and from direct use of products (e.g.,
cosmetics) containing nanomaterials. The rapid growth
of products that contain nanomaterials could result
in their presence in soil and aquatic ecosystems. This
presence will result from effluents of manufacturing
plants, and the recycling or disposal of nano-based
consumer products into landfills and surface/ground
water. An exposure assessment attempts to answer
the following questions for a particular substance or
chemical:
Who or what is exposed (e.g., people,
ecosystems)?
What are the pathways for exposure (air,
water, land)?
How much exposure occurs?
How often and for how long does exposure
occur; that is, what is its frequency and
duration?
4.1.3.2 Research Activities
EPA uses a number of models to conduct chemical
exposure assessments. Descriptions and links to these
models can be found at the websites for the Council
for Regulatory Environmental Modeling (CREM:
http://cfpub.epa.gov/crem/) and the Center for
Exposure Assessment Modeling (CEAM: http://www.
epa.gov/ceampubl/). Table 4-1 provides a listing of
several of the models/tools used by the program offices
for exposure assessment and each model's general
application and applicability to nanomaterials in its
current form. With the exception of the EPI-Suite
calculators, all of the exposure assessment models
need the user to provide input data on the physical
and chemical properties for the chemical of interest.
The EPI Suite calculators are based on a single
input, a Simplified Molecular Identification and Line
Entry System (SMILES) string that is a typographical
method for representing unique chemical structures.
The other models in Table 1 were developed primarily
for exposure assessments of synthetic organic
chemicals, and thus require input such as water
solubility, octanol-water partition coefficients and
Henry's Law constants to predict fate and transport.
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
Acronym
E-FAST
EPI-
Suite
EXAMS
Trim Expo
Model Name
Assessment Screening
Tool Version 2.0
Estimation Programs
Interface Suite
Exposure Analysis
Modeling System
Total Risk Integrated
Methodology
Exposure-Event Module
Primary
Program
Office
OPPT
OPPT
OPP
OAQPS
Application
Estimates concentrations of
chemicals in multimedia from
multiple release activities
Estimates physical & chemical
properties for organic chemicals
Estimates fate, transport, and
exposure concentrations of
chemicals in aquatic ecosystems
Estimates human exposure to
criteria
and hazardous air pollutants
Applicability
toNMs
Modification
Required
Not Applicable
Modification
Required
Modification
Required
-------
Exposure models will require modification to allow
the input of molecular parameters and physical and
chemical data specific to nanomaterials (e.g., particle
size, surface charge, distribution or sticky coefficients,
and agglomeration tendencies). OPPT has recently
requested the assistance of ORD to review the E-FAST
model, which supports EPA's New Chemicals and
Existing Chemicals Programs, for its applicability to
nanomaterials. Specifically, ORD will:
Focus on the physical, chemical, and other
properties currently required as user provided/
default inputs
Determine whether these inputs are
appropriate for nanomaterials when assessing
exposures related to industrial releases to
surface water, air, and/or landfills
Identify other properties as potential inputs
that might be more appropriate for assessing
general population and environmental
exposure to nanomaterials
The challenges in identifying and measuring the
concentration of manufactured nanomaterials
in environmental and biological systems will
present significant obstacles to providing the data
necessary to conduct exposure assessments of these
materials for both ecological and human receptors.
Such assessments will require the development of
alternative methods for determining the source and
the environmental concentrations of nanomaterials
in aquatic and terrestrial ecosystems. The interest in
nanomaterials is driven by their unique properties and
activities at different scales; these same properties
provide the opportunity for developing indicators
of exposure by measuring changes in structures and
functions of biological organisms in contact with
nanomaterials. By identifying indicators of exposure
resulting from exposure to nanomaterials, it will
be possible to reconstruct the exposure pathway
and ultimately the source and the environmental
concentration of the nanomaterial of interest. This
ability to move from an internal biological response
to external environmental concentration represents
a growing area of exposure science referred to as
exposure reconstruction.
ORD's research in this area focuses on the linkage
of responses across endpoints at multiple biological
levels of organization, from molecular alterations
to populations. These linkages can serve as a basis
for identifying and validating mechanistic indicators
of exposure and effects, informing ecological risk
assessments of nanomaterials. Currently, a systems-
based approach is being used to assess exposures and
define toxicity pathways for model chemicals with
well-defined modes/mechanisms of action (MO A)
within the hypothalamic-pituitary-gonadal (HPG) axis.
These pathways serve as a basis for understanding
responses of small fish across biological levels of
organization, ranging from molecular responses to
adverse effects in individuals to, ultimately, changes in
population status. The studies employ a combination
of state-of-the-art molecular biology, bioinformatic,
and modeling approaches, in conjunction with whole
animal testing. As such, the project will enable a
unique opportunity to interface empirical toxicology
with computational biology in the exposure assessment
of nanomaterials.
The molecular biological tools for this research will
focus on the application of the 'omic'tools (i.e.,
genomics, proteomics and metabolomics) to identify
indicators of exposure. These tools provide the ability
to identify indicators of exposure by measuring gene
regulation, protein formation, and changes in an
organism's metabolome in response to exposure to a
chemical or mixture of chemicals. By elucidating the
kinetics of the marker's response, it is also possible to
provide an understanding of the temporal and spatial
aspects of exposure.
Currently, no information is available in the literature
concerning the identification of indicators of exposure
for nanomaterials. However, ongoing research
with pesticides exhibiting estrogenic activity is
demonstrating the feasibility of this approach. ORD
has developed molecular indicators of exposure
(based on genomic responses) of aquatic organisms
(water flea, Daphnia magna and fathead minnow,
Pimephales promelas) to estrogenic compounds
and is using advanced genomic methods to develop
androgenic indicators. The Nuclear Magnetic
Resonance (NMR)-based metabolomics research
program being conducted at ORD's NMR research
facility is demonstrating the use of high-resolution
NMR to identify changes in the profiles of endogenous
metabolites (i.e., the metabolome) in the serum and
urine of fathead minnows exposed to estrogenic
-------
compounds. The literature also provides examples of
the use of genomics to identify indicators of exposure
in humans. Microarray analysis of blood samples
taken from benzene-exposed workers has identified
peripheral blood mononuclear gene expression as an
indicator of exposure for benzene (Forest et. al, 2005).
Collaboration to further identify the exposure
pathways of manufactured nanomaterials
ORD will work in collaboration with other agencies
and academia to study and identify the most common
exposure pathways for manufactured nanomaterials.
ORD will seek to establish international collaborations
through the development of collaborative or
coordinated calls for proposals. These research
proposals will also engage ORD scientists in the
study of exposure routes and pathways, relevant
exposure doses, and critical exposure concentrations.
Research will also identify potential subpopulations of
organisms that are more susceptible to manufactured
nanomaterial exposure than others.
4.1.3.3 Anticipated Outcomes
Identification of the dominant exposure
pathways to ecological receptors of interest
Assessment of the applicability of EPA's
current exposure models to nanomaterials
Identification of the physical and chemical
properties required to inform exposure
Identification of indicators of exposure
through the application of genomics,
proteomics and metabolomics
Figure 4-3 Critical Path
'osure Pathways
Critical Path for Research on Exposure Pathways
Key Science Question 3: What are the exposures that will result from
releases of manufactured nanomaterials?
Provide the underlying science
on the exposure pathways of
NMs
An assessment of the
applicability of EPA's
current exposure models to
nanomaterials
Identify the exposure pathways associated
with production, end-use, and recycling or
disposal of manufactured nanomaterials in
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
Modification of current exposure model and development of new
exposure models to predict exposure pathways for nanomaterials in
environmental media
2009
2010
2012
2014
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4.2 Research Theme: Human Health and
Ecological Effects Research to Inform Risk
Assessments and Test Methods
4.2.1 Background and Program Relevance
As described in EPA's Nanotechnology White Paper,
nanomaterials could have health and ecological
implications arising from new routes of exposure
and/or toxicities associated with exposure to these
novel materials, by-products associated with their
applications, or their interactions with various
environmental media.
By characterizing nanomaterials' health and
ecological effects and identifying the physical and
chemical properties that regulate their toxicity and
biokinetics, ORD will address a lack of information
required for nanomaterials risk assessment.
ORD's research will provide EPA offices with
information on the health and ecological effects of
specific nanomaterials and applications impacting
EPA's mission, as well as guidance on best practices,
approaches and test methods for assessing/predicting
their health and ecological effects. ORD will also be
addressing key immediate priority effects research
needs identified in the US EPA Nanotechnology
White Paper, such as, adequacy of test methods,
characterization of the health and ecological
effects of nanomaterials (nanotoxicology), hazard
identification, dosimetry and biological fate.
ORD's nanomaterials health and ecological effects
research builds upon its ongoing risk assessment-
based research within the Air, Water, and Safe
Products/Safe Pesticides programs. These research
activities provide the facilities and expertise that
are directly applicable to addressing nanomaterial
health and ecological effects resulting from various
potential routes of exposure and environmental
interactions. ORD's research is conducted within
a risk assessment paradigm. ORD's nanomaterials
health and ecological effects program will conduct
re search to:
Evaluate current test methods to assess
their adequacy to determine the toxicity
of nanomaterials, and modify or develop
toxicity test methods, as required
Determine the acute and chronic health and
ecological effects of selected nanomaterials,
including their local and systemic toxicities
Determine the health and ecological effects
associated with nanomaterial applications
and their interactions with environmental
media
Determine the physical and chemical
properties responsible for nanomaterial
health and ecological toxicities, mode(s) of
action, and mechanism(s) of injury in order
to identify the appropriate exposure-response
metric(s), e.g., surface area, particle size, etc.
relative to traditional, concentration-based
metrics
Identify the physical and chemical properties
of nanomaterials that regulate their
deposition, uptake, and fate, as well as host
susceptibility and sensitivity factors (e.g.,
gender, age, life stage, disease conditions)
that may influence their toxicity and
biokinetics
Identify ecological systems that contain
especially susceptible organisms, life stages,
or populations
Identify and develop alternative testing
approaches, technologies, and models to
screen, rank, and predict the in vivo toxicity
of nanomaterials and their applications
4.2.2 Key Science Question 4. What are the health
effects of manufactured nanomaterials and their
applications, and how can these effects be best
quantified and predicted?
4.2.2.1 Human Health Effects Research Activities
ORD will examine the health effects of nanomaterials
that are relevant to EPA's mission and mandated
regulatory responsibilities by addressing the
health effects research needs identified in EPA's
Nanotechnology White Paper and the NNI's,
Environmental, Health and Safety Research Needs
for Engineered Nanoscale Materials. However,
there exist significant challenges associated with
addressing nanomaterials health effects; these
include:
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l)The significant diversity of manufactured
nanomaterials as well as their potential to
produce health effects due to their novel
properties, new routes of exposure associated
with their use, by-products associated with
their applications, or their interactions with
various environmental media
2) The need to provide nanomaterials health
effects information in a timely manner to
Agency offices to address their immediate
needs
3) The need to address the 3Rs of toxicity
testing (reduce, refine and replace the use of
animals) in research and regulatory programs
Opportunities do exist to address these challenges
associated with assessing nanomaterials health effects
and include:
1) Employing the vision and
recommendations of the National Academy
of Sciences, National Research Council
report, Toxicity Testing in the 21st Century:
A Vision and a Strategy that provides a
direction to identify alternative toxicity
testing approaches, assays, and methods
to ultimately predict in vivo health effects
of nanomaterials and their applications as
well as means to address the 3Rs of toxicity
testing
2) Leveraging ORD nanomaterials health
effects research with similar activities at the
national (NNI and other federal programs
including: NIOSH, National Toxicology
Program, etc.) and international levels
(Organization for Economic Cooperation and
Development, OECD)
3) The existence of validated alternative
testing methods and ORD's airborne
particulate matter health effects program
that has demonstrated the ability of in vitro
test methods to provide consistent results
reported for in vivo studies, including clinical
and epidemiology studies, associated with
examining the pulmonary toxicity of particles
Physicochemical
Characterization
Alternative Test
Methods
(Cellular and Non-
Cellular Based Assays)
/- Screen/Rank
-Design
I n Vivo Testing
-Identify and Validate
Alternative
Test Methods and Models
Predictive of
I n Vivo
Toxicity
In Vivo Toxicology
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An integrated multi-disciplinary testing strategy
for nanomaterials health effects research: ORD
will employ an integrated testing strategy as shown
in Figure 4-4 to address nanomaterials health effects
research described under Key Science Question
4. The strategy will integrate and coordinate the
expertise of toxicologists, material scientists, and
exposure assessment scientists to examine the health
effects of nanomaterials and their applications. An
integrated testing strategy to assess nanomaterials
health effects is consistent with numerous
nanomaterials health effects workshop reports (G.
Oberdorster et al, Particle and Fibre Toxicology 2:8,
2005; D.B. Warheit et al., Inhalation Toxicology
19(8):631-643, 2007; John Balbus, et al., Enviorn.
Health Perspect. 115:1664-1659, 2007; J.G. Ayres et
al, Inhalation Toxicology 20(l):75-99, 2008).
ORD's nanomaterials integrated testing approach
consists of three key components:
1. Nanomaterials Physical and Chemical
Characterization: Nanomaterials that are relevant
to EPA will undergo recommended physical
and chemical characterization. This will require
integrating the expertise of nanoscale material
scientists into ORD health effects research, since
physical and chemical information is critical to: 1)
ensure the purity and confirm/validate the properties
of nanomaterials before initiating research to assess
their health effects; 2) detect and quantifying
nanomaterials in cells and tissues in order to
determine nanomaterial biokinetic or ADME; and
3) provide information for the identification of
nanomaterials properties regulating their toxicity
(hazard identification) and exposure-response
metrics.
2. Alternative Test Methods: ORD will employ
cellular and non-cellular test methods to assess
the toxicity of nanomaterials that are relevant to
EPA. In vitro toxicity testing will use a variety of
cell types reflecting different routes of exposure
(dermal, inhalation, ingestion) and health effects
that may arise due to the ability of nanomaterials
to translocate from their initial site of deposition to
other organs within the body. Nanomaterials in vitro
toxicity testing will assess the mutagenic, intestinal,
pulmonary, dermal, immunological, neurological,
reproductive, cardiovascular, and developmental
toxicities using cellular models reflective of these
toxicities. Alternative testing methods will also
employ non-cellular assays to examine the surface
properties of nanomaterials by assessing their
reactivity and molecular interactions with proteins as
well as other biological constituents; e.g. antioxidants
and second messengers. Non-cellular interactions and
surface properties may play a key role in regulating
nanomaterial cellular uptake and toxicity.
Alternative toxicity testing methods provide a
means to: 1) rapidly screen and rank the relative
toxicities of various nanomaterials for in vivo toxicity
testing; 2) provide key information (e.g., exposure
dose and health endpoints) to assist in designing
in vivo toxicity testing that will potentially refine/
reduce the number of animals needed for in vivo
studies; 3) determine mechanism(s) of injury and
mode of action of nanomaterials; 4) rapidly perform
comparative toxicity studies between chemically
identical nano vs. micro-size materials; 5) perform
nanomaterials interactions, uptake, and distribution at
the biochemical, cellular, and intracellular levels; and
6) correlate nanoparticle surface properties with their
biological and cellular interactions, and toxicity.
ORD's ToxCast program (http://epa.gov/comptox/
toxcast/news.html) will assist in extending ORD's
efforts to develop alternative test methods to evaluate
nanomaterials toxicity. ToxCast offers an approach
to address the extreme diversity of nanomaterials
by applying high-throughput platforms and
computational approaches to screen a large number
of materials. The ToxCast program will assist in
ORD's efforts to rank the toxicity of nanomaterials
as well as develop models to identify physical and
chemical properties that determine the toxicity of
nanomaterials.
3. Nanomaterials In Vivo Toxicity Testing: ORD's
nanomaterial health effects research strategy will
assess the toxicity of nanomaterials in animals;
i.e., in vivo toxicity. These studies will examine
cancer, pulmonary, dermal, and gastrointestinal
toxicities associated with initial site of deposition of
nanomaterials by various routes of exposure (dermal,
inhalation, ingestion) as well as immunological,
neurological, reproductive, cardiovascular, and
developmental toxicities to assess their potential
systemic toxicities. In vivo toxicity studies will
examine the deposition and fate of nanomaterials
following various routes of exposure, as well as
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identify host susceptibility and sensitivity factors
(e.g., gender, age, life stage, and disease conditions)
that may influence their toxicity and biokinetics
Coordinating and Leveraging ORD's integrated
testing strategy to assess nanomaterials health
effects:
As depicted in Figure 4-4 and as previously
described, physical and chemical characterization of
nanomaterials will be conducted prior to assessing
their health effects. Also as depicted in Figure
4-4, it is anticipated that ORD's integrated testing
strategy to assess nanomaterials health effects will
be a coordinated, iterative process providing: 1) an
approach to rank nanomaterials for in vivo toxicity
testing; 2) assist in designing nanomaterial in vivo
toxicity testing studies; and 3) allow for shallow and
in-depth parallel toxicity testing in order to identify
those alternative approaches and in vitro assays/
responses that correlate with in vivo nanomaterial
toxicity. This information will be critical in order to
ultimately identify the physicochemical properties
of nanomaterials and alternative test methods that
predict their in vivo toxicity. Opportunities exist for
ORD's integrated nanomaterials health effects testing
strategy to progress at a rapid rate by leveraging its
efforts with similar activities at the national (other
federal programs under the NNI; for instance, those
of NIOSH and the National Toxicology Program) and
international levels (Organization for Economic Co-
operation and Development, OECD).
Figure 4-5 Critical Path for Conducting ORD 's Nanomaterial Human
Health Effects Research
Critical Path for Conducting ORD's Nanomaterial Human Health
Effects Research
Key Science Question 4: What are the health effects of manufactured
nanomaterials and their applications, and how can these effects be best
quantified and predicted?
Evaluate current test methods to assess their adequacy
to determine the toxicity of nanomaterials and modify
or develop test methods, as required
Determine the acute and chronic health effects
of selected nanomaterials including their local
and systemic toxicities
Determine the physical and chemical properties responsible
for nanomaterials mammalian: toxicity, mode(s) of action,
and mechanism(s) of injury in order to identify the
appropriate exposure-response metric(s), e.g. surface area,
particle size, etc. relative to traditional, concentration-based
metrics
Identify the physical and chemical properties of
nanomaterials regulating their deposition, uptake,
and fate, as well as host susceptibility and
sensitivity factors (e.g., gender, age, life stage,
disease conditions) that may influence their toxicity
Determine the health effects
nanomaterial applications and
interactions with environmental
media
Identify and develop approaches, technologies, and models to screen, rank,
and predict the in vivo toxicity of nanomaterials and their applications
2009
2010
2011
2012
2013
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4.2.3 Key Science Question 5. What are the
ecological effects of manufactured nanomaterials
and their applications, and how can these effects be
best quantified and predicted?
4.2.3.1 Ecological Effects Research Activities
ORD's nanomaterials ecological effects strategy will
address the ecological effects research needs identified
in EPA's Nanotechnology White Paper and the NNI's
Environmental, Health and Safety Research Needs
for Engineered Nanoscale Materials, and is intended
to be responsive to EPA's regulatory needs. The
ecological effects research strategy focuses on the
physical and chemical factors unique to nanomaterials
that may influence their toxicity, determine rates of
uptake and disposition in ecological matrices, and
require novel approaches for quantifying exposure-
response relationships. The strategy is organized
into chronological tasks, beginning with the need to
evaluate methods used in traditional toxicity for their
adequacy or applicability to nanomaterials. The tasks
are broadly defined and it is expected that research
will advance in an iterative manner; it is likely that
initial tasks will need to be revisited depending on
results of subsequent research efforts, and as new
nanomaterials are developed.
Task 1 - Evaluate the suitability of existing
test methods for assessing the hazards of manufactured
nanomaterials: nanomaterials, or products containing
nanomaterials, are already being submitted for
approval under Agency programs such as TSCA
and FIFRA. These and other Agency programs
have existing protocols for evaluating hazards to
ecological receptors in both aquatic and terrestrial
systems, but the appropriateness of these methods for
nanomaterials has yet to be evaluated. Key concerns
include how to expose organisms to nanomaterials in
ways that have relevance to exposures that may occur
in the environment, and whether these standardized
assays address the organisms, life stages, and
bioavailability considerations that are most important
for understanding the potential ecological risks of
nanomaterials. In addition to direct toxicity testing,
emphasis will be placed on measurements of exposure,
uptake, and dose.
Task 2 - Understand the mechanisms
underlying the ecological effects of nanomaterials
and identify potential gaps in hazard assessment
procedures: Building on results of exposures using
standard (or appropriately modified) test methods,
further research will explore the specific mechanisms
of nanomaterials toxicity and ecological effects.
Understanding the mechanisms of effects is key
to determining novel risks that may be created by
nanomaterials, denning the appropriate organisms
and endpoints for nanomaterials risk assessments,
and providing the basis for future predictive models.
Parameters that govern adsorption, distribution,
metabolism, and excretion (ADME) will be evaluated,
as will means of expressing toxicological dose. Other
studies will evaluate the interaction of nanomaterials
with physical, chemical, and biological components of
ecological systems to determine if there are effects of
nanomaterials not captured by single organism toxicity
testing, such as altering the relationships among
ecosystem components and thereby affecting overall
ecosystem function. Throughout Task 2, emphasis
will be given to determining whether nanomaterials
exert effects through mechanisms that would not be
well addressed by existing ecological hazard and risk
screening tools.
Task 3 - Develop methods and models to
predict the hazard or ecological risk of nanomaterials:
Due to the diversity of nanomaterials expected to
enter the marketplace in the coming years, EPA will
need predictive tools that can be used to prioritize
newly developed nanomaterials for testing and further
evaluation. For example, quantitative structure/
activity relationships (QSARs) may be developed
to predict the toxicity of untested materials based
on their chemical structure and an understanding
of the mechanisms underlying dose and toxicity.
Likewise, ecological effects models may be important
predictive tools if research in Task 2 indicates that
ecological processes above the organismal level are
being uniquely affected by nanomaterials. This work
will build directly from Tasks 1 and 2 and associated
research conducted by the Computational Toxicology
Program.
Leveraging research with ORD laboratories,
centers and other federal programs: ORD's
nanomaterials health and ecological risk assessment
research will leverage work with other federal
programs and international efforts where similar
nanomaterials are being monitored, studied, and
characterized. For example, ORD laboratories are
jointly addressing nano-cerium dioxide to assess
potential environmental exposures, and associated
-------
health effects. Research to examine the health and
ecological effects of nanomaterials following their
release into or interactions with environmental
media will require the combined expertise of ORD's
health and exposure scientists. ORD's nanomaterials
health effects multi-tier strategy allows a means to
interface with national and international nanomaterials
in vivo toxicity efforts as a means to allow for the
identification of alternative methods, approaches,
and biological responses that are consistent with
those generated in nanomaterials animal toxicity
testing studies. Finally, the physical and chemical
characterization of nanomaterials and their detection
in biological systems will require a multidisciplinary
approach with close interactions across ORD as well
as with other organizations such as the Department of
Energy's National Laboratories.
4.2.4 Anticipated Outcomes
ORD's human health and ecological effects research
programs will provide key information regarding the
health and ecological implications from exposures
to nanomaterials, and their applications, in order
to identify and manage potential adverse impacts
and inform program offices and regions regulatory
and other policy decisions. Specifically, ORD's
nanomaterials effects research will provide Agency
offices with information on the health and ecological
effects of specific nanomaterials and their applications,
as well as guidance on best practices and approaches/
test methods for assessing/predicting health and
ecological effects. ORD's nanotechnology health
and ecological effects research activities will provide
publications in peer-reviewed scientific journals on
the:
Characterization of nanomaterials health
and ecological effects; identification of
physical and chemical properties and host/
sensitivity factors that regulate nanomaterials
dosimetry, fate, and toxicity (information
for both risk assessment and development of
"greener" nanomaterials and a sustainable
nanotechnology)
Identification of testing methods/approaches
to predict in vivo toxicity of nanomaterials;
characterization of molecular expression
profiles that may provide biomarkers of
nanomaterial exposure and/or toxicity
(exposure assessment and predictive
nanotoxicology)
Provision of necessary counsel and guidance
that will assist in the review of premanufacture
notice applications and assess the adequacy
of harmonized nanomaterial test guidelines to
assist OPPTS and internationally, the OECD
(regulatory assistance/support and leveraging
nanomaterials effects research)
Addressing the gap in knowledge regarding
the toxicity of nanomaterials, which has
impeded the ability to conduct accurate life
cycle analysis
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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
will be necessary for the testing of nanomaterials for health
and ecological effects
Assess the hazard of selected
nanomaterials and identify especially
sensitive ecological receptors
Develop methods and approaches
for exposing whole organisms to
nanomaterials
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.
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
2009
2010
2011
2012
4.3 Research Theme: Developing Risk Assessment
Methods
4.3.1 Key Science Question 6. How may risk
assessment approaches need to be amended to
incorporate special characteristics of manufactured
nanomaterials?
4.3.2 Background/Program Relevance
Nanomaterials may have special properties that may
influence their environmental behavior and effects
on human health and ecosystems. These unusual
features introduce complications for basic aspects of
risk assessment such as characterization of exposure
and dose-response relationships. For example, is
particle count or one or more measures of surface
properties (area, charge, etc.) a better metric than
mass for describing dose-response relationships?
Although nanomaterials pose significant new and
possibly unique challenges for the practice of risk
assessment, features of the basic paradigm for risk
-------
assessment and risk management (NRC, 1983)
are presumed to apply to these materials. Hazard
identification determines qualitatively whether the
nanomaterial will cause an adverse health effect.
Dose-response assessments establish the quantitative
relationship between dose and incidence of health
effects. Exposure assessment is performed and the
incidence of an adverse effect (risk) in a particular
population is determined by combining exposure
and dose-response. The effects of nanomaterials
on the environment must also be assessed in order
to protect and restore ecosystem functions, goods,
and services. Ecological risk assessment entails
the evaluation of goals and selection of assessment
endpoints in a problem formulation step, followed by
analysis of exposure to stressors and determining the
relationship between stressor levels and ecological
effects. The next step is estimating risk through
the combination of exposure and stressor-response
profiles, description of risk by discussing lines of
evidence, and determination of ecological adversity
(U.S. EPA, 1998). Interfacing among risk assessors,
risk managers, and interested parties during the initial
planning of a risk assessment and communication of
risk at the end of the risk assessment are critical to
ensuring that the results of the assessment can be used
to support a management decision. The importance of
communication and stakeholder involvement in both
human health and ecological risk assessment and risk
management has also been noted by the Presidential/
Congressional Commission on Risk Assessment
and Risk Management (1997: (see Figure 2-1) and
recently affirmed in the National Academy of Sciences
"Science and Decisions: Advancing Risk Assessment"
(NAS, 2008).
While basic features of the health and ecological
risk assessment paradigms may still be relevant to
nanomaterials, this emerging technology nevertheless
warrants careful systematic evaluation such as that of
the comprehensive environmental assessment (CEA)
approach (Davis and Thomas, 2006; Davis, 2007),
which treats the evaluation of the environmental
and health risks of nanomaterials as an issue that
cuts across EPA programmatic domains and is not
simply categorized as solely an air, water, toxics, or
solid waste issue. The CEA approach starts with a
qualitative life cycle framework, as shown in Figure
4-7. It takes into consideration multiple environmental
pathways, transport and transformation processes,
cumulative and aggregate exposure by various
routes, and ecological as well as human health
effects. Depending on the availability of data, both
quantitative and qualitative characterizations of risks
may result. However, given the limited information
available on nanomaterials, the CEA approach is
currently being used to identify where key data gaps
exist with respect to selected case studies of specific
applications of nanomaterials.
Case studies are recommended in the EPA
Nanotechnology White Paper as a means to further
inform research supporting the risk assessment
process. The term "case study" is used to refer to
specific examples of nanomaterials and the types of
issues that would be need to be considered to assess
their respective environmental and health risks. By
focusing on specific examples of nanomaterials in
realistic applications, it is possible to identify and
prioritize research needs to assess the real world
impacts of these materials. Given the striking
differences in toxicological and physicochemical
properties of nanomaterials, generalizations across
nanomaterials need to be considered cautiously.
4.3.3 Research Activities
The role of ORD's nanomaterial risk assessment
research is (1) to help guide overall research efforts
toward generating the information needed to conduct
future comprehensive environmental assessments of
nanomaterials and (2) to carry out such assessments in
coordination with all of ORD and the program offices.
The research question ORD will address is, "How
may risk assessment approaches need to be amended
to incorporate special characteristics of manufactured
nanomaterials?" To address this question, ORD will
identify and prioritize information gaps by developing
a series of case studies and workshops to further
refine research needs for specific nanomaterials, as
recommended in the EPA Nanotechnology White
Paper.
In order to develop case studies of particular
nanomaterials and their specific applications,
appropriate nanomaterials must be selected. The
collective judgment of an internal workgroup
representing all relevant program offices was used for
this purpose. The workgroup was given a summary
of available information on the chemistry, human
health, toxicology, exposure, and release of various
-------
nanomaterials. Workgroup members were then asked
to select two nanomaterials based upon five criteria:
potential for biota/human exposure; apparent potential
for both health and ecological effects; a reasonable
amount of information with which to develop a case
study; relevance of the nanomaterial to programmatic
or regulatory needs; and "nanoness," e.g., having at
least one dimension less than 100 nm. Using these
criteria, nanoscale titanium dioxide and single walled
carbon nanotubes (SWCNTs) were initially selected;
subsequently, SWCNTs were replaced with nanoscale
silver (nano-Ag) due to difficulties in obtaining
adequate information on applications of SWCNTs
that had presumptive exposure potential for the
general population. Two applications of nanoscale
titanium dioxide are under development, for water
treatment and for sunscreen. The choice of a nano-
Ag application is currently under evaluation. These
selected classes of nanomaterials also serve as a
common focus and point of coordination for near-term
studies by the various ORD laboratories.
The case studies present available information for
specific nanomaterials using the CEA approach as an
organizing structure. These documents are intended to
be used as part of a process to systematically identify
and prioritize information gaps where additional
research is needed. Draft case studies will be the
focus for a series of workshops involving invited
technical experts and stakeholders. Workshops will be
conducted in a formal, structured manner using expert
judgment techniques (e.g., multi-criteria decision
analysis, expert elicitation). A detailed summary
of the discussions and views expressed during
the workshop will be used in refining the current
research strategy document. The workshop summary
will highlight areas of work that will be needed to
support comprehensive environmental assessments
of nanomaterials. This refined statement of research
priorities will provide longer-term guidance for both
ORD and the broader scientific community. This
approach is consistent with a recent NAS review of
the NNI's nanotechnology EHS research strategy
(National Academy of Sciences, 2008).
Concurrent with these longer range CEA-oriented
activities will be more immediate and more
narrowly focused assessment efforts in accordance
with programmatic needs and data availability.
Assessments of this type cannot be specified at
present but are anticipated, contingent on progress in
addressing scientific issues such as those identified
throughout this document.
4.3.4 Anticipated Outcomes
Note that the outcomes listed here and in the Critical
Path for Risk Assessment Research (see Figure
4-7) are intended to be representative of an iterative
process that will involve the creation of a series of
additional case studies and periodic reevaluation
of earlier case studies as new information becomes
available. The timeframe for the outcomes shown in
the Critical Path figure is conservatively estimated
but highly uncertain because of the many scientific
uncertainties currently associated with nanomaterials.
As indicated above, limited assessments (more
narrowly focused than a CEA) may be attempted as
data become more available, and such assessments
could occur at any point within the overall timeframe
shown in the Critical Path figure.
Initially, two draft case studies for different
applications of nano-titanium dioxide, to
be followed by additional case studies and
periodic iterative evaluation of earlier case
studies as new information becomes available
Workshop(s) for invited experts and
stakeholders and public observers, using
formal expert judgment methods to identify
and prioritize research needed to support
comprehensive environmental assessments of
nanomaterials
Using input from the workshop discussions,
a document that lays out long range research
directions for obtaining information needed
for nanomaterial CEAs
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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
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
Comprehensive Environmental Assessment (CEA) of
Selected NMs
Research Strategy for CEA of
Selected NMs, for use by ORD and
research community
Qualitative life cycle analysis for
selected NM(s)
Fate and transport assessment for
selected NM(s)
Exposure assessment for selected
NM(s)
Ecological effects assessment for
selected NM(s)
Health effects dose-response
assessment for selected NM(s)
CEA of selected NM(s), for use by OPPTS and other
program office
2009
2010
2014
4.4 Research Theme: Preventing and Managing
Risks
4.4.1 Key Science Question 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?
4.4.1.1 Background/Program Relevance
To understand the potential environmental
implications of nanomaterials and to identify potential
approaches to manage emissions/releases, it is critical
to understand potential entry points of nanomaterials
into the environment. Under this question, ORD will
conduct research to understand emissions/releases that
can occur either during production, use, recycling, or
disposal of nanomaterials. Examples of points of entry
into the environment include:
Manufacturing Waste Streams: During the
manufacture of nanomaterials, the inevitable
by-product and waste streams will need to be
evaluated. Pollution prevention (e.g., green
chemistry) research may be very helpful in
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the development of environmentally friendly
manufacturing processes for nanomaterials.
Air Treatment: Manufactured nanomaterials
can be emitted along with other conventional
pollutants during production processes.
In addition, there are products that use
manufactured nanomaterials where during
their use nanomaterials can be emitted to the
air, (e.g., brakes and fuel additives).
Water Treatment: Some nanomaterials are
intended to be biocides and may enter DW
treatment facilities. Personal care products
and Pharmaceuticals containing nanomaterials
will eventually be washed down the drain and
transported to wastewater treatment plants.
There they will either be removed from
the wastewater and end up in the biosolids
residuals or they will remain in the wastewater
and be discharged into surface water as part of
the treatment plant's effluent.
Disposal of Used Material: At the end of its
useful life, each of the consumer products and
equipment items created using nanomaterials
will enter the waste stream. It is critical to
understand where these products end up
(e.g., landfill, incinerator) in order to provide
guidance on possible emissions/releases of
nanomaterials.
Product Usage: As products incorporating
manufactured nanomaterials enter the
consumer market place, material release may
occur during the normal intended usage or
conversely during unintended usage. Releases
may occur through abrasion, adsorption/
absorption, or volatilization, among other
processes. For instance, if veterinary
Pharmaceuticals are administered using
nanomaterials, these materials may be excreted
and released into the environment when
manure is land applied as fertilizer.
In addition to human and ecological exposure, there
is a need to better understand how the manufacture,
use, and waste management of nanomaterials
will contribute to other environmental problems,
including climate changes due to global warming
and stratospheric ozone depletion; land use leading
to acidification, eutrophication, and photo-oxidation;
odor, noise, waste heat, radiation, and casualties. To
address these issues, researchers are implementing
more comprehensive assessment tools, such as
life- cycle assessment (LCA), that can establish
comparative impacts of products and processes in
terms of well-defined impact categories. Such an
assessment can be applied across the entire life cycle
[materials acquisition (cradle) to disposal (grave)] or
along any desired part there-of (gate-to-gate). Hence
within a single assessment, LCA for nanomaterials
has the potential to address both the toxicological
and environmental questions associated with these
materials.
LCA experts worldwide agree that existing LCA tools
are capable of supporting the development of decision
frameworks for nanomaterials and nanoproducts.1,2
A number of cradle-to-gate and gate-to-gate LCAs
have recently appeared in open literature, helping
researchers to identify the key concerns that must
be addressed if the goal of a full-scale LCA is to be
realized. The proper life cycle boundaries, particularly
the "grave," must be defined for a given material. This
can be confusing when considering nanomaterials
because they have the ability to permeate much smaller
regions, passing throughout the environment. Data
gaps concerning the transport, persistence, and toxicity
of nanomaterials must be filled. This is challenging,
because the diverse properties of nanomaterials (i.e.,
surface charge, size, shape, chemical composition)
that can be synthesized will strongly impact how these
materials disperse and react within the body and the
environment. Thus, either a large amount of research
or the development of accurate predictive models is
needed to acquire the missing data. Additionally, issues
such as the treatment of nanomaterials incorporated
into larger composite materials and the recycle of
nanomaterials must be addressed. The complexity of
choices associated with the use of nanomaterials that
can influence the LCA categories defined above is
summarized in Figure 4-8.
The value of any assessment is not only the data it
generates, but how the data are applied. Are there
acceptable tradeoffs associated with nanomaterials?
Is the large-scale production of an environmentally
taxing material justified if it has medical applications
1 Maynard, A.D., 2006. Nanotechnology: A Research Strategy
for Addressing Risk. Woodrow Wilson International Center for
Scholars,Washington, DC.
2 Kloepffer, W., M. A. Curran, et al. (2007). Nanotechnology and
Life Cycle Assessment: Synthesis of Results Obtained at a Work-
shop in Washington, DC, 2-3 October 2006.
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or can reduce costs or enhance performance?
Questions such as these illustrate the ultimate need for
a valuation system with suitable metrics. To this end,
research is needed to develop an easily applied, LCA-
based framework that can be used with other pertinent
factors such as cost and societal benefit to provide a
comprehensive evaluation of nanomaterials throughout
their life cycle.
Figure 4-8 Characterization of a Selected Nanotechnology for Life Cycle Assessment
Characterization ofnanotechnologiesfor 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
Surface
Functionalization/
Charge
Wet
Dry
Tube/Rod
Environmental
Medical
Manufactured Goods
Organic (Dendrimers, etc.)
Carbon (CNTs, Buckyballs)
Inorganic (Metals and/or
oxide/hydroxides)
4.4.1.2 Research Activities
ORD will identify industries, processes, and
products that have relatively high potential to
release manufactured nanomaterials into the
environment. Existing literature will be evaluated to
better understand the industries of importance and
identify where gaps in information preclude a full
assessment of emission/release points of concern.
ORD will perform a systematic assessment of the
production, use, and ultimate fate of nanomaterials
to understand the potential for emissions/releases
into the environment. A modified tool using life cycle
principles will be developed to better understand
which industries pose the greatest potential to emit/
release nanomaterials of concern and to inform
decision makers about the overall impact of
manufactured nanomaterials. This effort will also
include a series of assessments for the highest priority
industry categories. Results from ORD workshops will
be used to guide industry and nanomaterial selection
for assessment. Comparative assessments will be
produced to help inform decision-makers at what stage
in the lifecycle of nanomaterials interventions could
be used to avoid future environmental pollution. The
ORD effort will be closely coordinated with other
organizations, particularly EPA's Office of Pollution
Prevention and Toxics, which is also generating data
on nanotechnology industries.
This research can be used to inform EPA, industry,
and academia about potential proactive and "greener"
approaches for manufacturing nanomaterials that
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are designed to prevent nanomaterial release into
the environment. It could also be used as input
for future thorough LCAs. The development of a
robust assessment tool can support decisions in the
development of appropriate nanotechnologies. Such a
tool is highly needed and has yet to be fully developed.
In addition, the necessity for specific data will help
with the design of fate, transport, and toxicity studies
that are necessary to better understand the use and
release of nanomaterials. The goal is to develop a
decision-support framework available to stakeholders
that is easy to apply and can accommodate a wide
variety of nanomaterials and nanoproducts.
High-potential industries/processes
ORD will draw upon the latest literature, hold
workshops, and interact directly with industry
representatives to identify market trends for
nanotechnology industries that utilize the priority
manufactured nanomaterials indicated earlier in this
document. This research will attempt to quantify the
amounts of nanomaterials expected to be produced and
used by existing industries, identify key processes used
to manufacture these nanomaterials, and project future
industries where significant releases may occur.
Identification/characterization of potentially
released materials
Once we know where the manufactured nanomaterials
may be released, it will be important to understand
something about the characteristics of these materials
to inform future transport, transformation, exposure,
and health studies. The research will focus on whether
the nanomaterial emissions/releases have the same
characteristics (size, chemical composition) as the
original material or have been modified before release
to the environment. This area of research will be
highly dependent upon the availability of technology to
identify and characterize manufactured nanomaterials.
Unfortunately, the ability to make these measurements
is also highly uncertain and will require extensive
research. Efforts to identify, develop, test, and verify
detection technologies will be critical to the success of
this research activity.
Entry point into the environment
Given that during the manufacture, use, and recycling
or disposal of conventional products there are always
emissions/releases of pollutants, it is reasonable
to presume that some form of manufactured
nanomaterials will follow similar entry points into the
environment. One of the primary goals of this research
is to generate the data and tools needed to quantify
and project these points of entry, so they can evaluate
potential risks and possible approaches to manage
those risks. One of the key issues to investigate is
whether the nanomaterial compounds will be emitted/
released in their original form or whether they will be
physically or chemically bound with other compounds.
This will directly impact transport and transformation
and will influence potential exposures and health
risks. For instance nanomaterials that are introduced
to the environment in solution may be more likely
than other nanomaterials to remain in their original
form and become bioavailable. Nanomaterials that are
chemically cross-linked in a matrix are less likely to
be released in their original form and size, although
uncertainties remain. Because of their exceptional
properties and characteristics, some manufactured
nanomaterials are being intentionally released to
serve as catalytic agents for remediation or filtration
purposes or as instruments for detection of pollution.
This research will summarize the latest uses and
provide available information on the characteristics of
the materials released.
Materials modification to support green
manufacturing of nanomaterials
Research on greener synthesis approaches will
identify opportunities to reduce the environmental
implications of nanomaterial production. Since
basic nanotechnology production processes are still
under development, EPA is well placed to work with
others to design production processes that minimize
or eliminate any emissions/releases. One area of
research is producing nanomaterials using benign
agents such as phenolics from tea extract, vitamins
Bl, B2, and C, or even sugars and carbohydrates
which have been demonstrated to generate a wide
variety of nanomaterials for various applications.
These alternative synthesis methods use these benign
materials which act as capping agents (e.g., ensures
that nanoparticles do not agglomerate) creating and
allowing the nanomaterials to maintain their properties
and benefits. In addition to the addressing the key
science question above, this research will be designed
to answer the following question: how can energy
consumption be minimized and waste/pollution
prevented in the manufacturing of nanomaterials and
products? The general approach will be to develop a
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strategy that allows the greener preparation of these
materials. Three of the main green chemistry areas that
will be investigated include: 1) the choice of solvent,
2) the reducing agent employed, and 3) the capping or
dispersing agent. For example, ORD is using a flame
and furnace reactor combination to produce single-
walled and multi-walled carbon nanotubes. We are
using a common feed-stock (e.g., propane), as opposed
to mixtures of carbon monoxide and hydrogen, and a
metallic catalyst to initiate nanotube formation.
The goal of this research question is to perform the
key initial step to inform additional research on
transport, transformation, and subsequent exposure
and health studies. In addition, by identifying potential
release points, this research will provide key data
required to inform how best to manage any potential
risks.
Risk Management
ORD will conduct research on the feasibility of using
conventional technology to manage the emissions/
releases of manufactured nanomaterials or degradation
by-products to all media. This research will inform
regulatory officials and industry about the viability of
various risk management alternatives and potential
improvements to ensure the safe manufacturing,
use, and disposal of nanomaterials. This research
has the potential to influence decisions regarding
manufacturing, storage, handling, use, and disposal of
selected nanomaterials. The results of the research will
be provided in the form of reports and computer-based
systems that can be used to address the unique issues
associated with various industrial operations.
To support the research activities below, ORD
will conduct various workshops with industry,
academia, and other parts of EPA to discuss
potential environmental liabilities associated with
manufacturing, using, recycling, and disposing of
nanomaterials. The parties will exchange information
and ideas about where releases are more likely to pose
the greatest risks and what alternatives (e.g., preferred
manufacturing approaches via green chemistry) are
available that could minimize environmental liabilities.
These workshops will help all participants consider
how nanotechnology products can be designed in the
most environmentally sustainable manner possible.
ORD will conduct parametric studies to determine
if conventional operating conditions used to
incinerate traditional waste streams will effectively
destroy nanomaterials present in waste, interfere
with the effective destruction of traditional waste
material, and/or create new hazardous products of
incomplete combustion (PICs). In addition, since
nanomaterials are for the most part long-lasting and
not biodegradable, ORD will investigate their leaching
potential to water bodies. Also, nanomaterials could
serve as a means to concentrate other toxic pollutants
present in various types of landfills, making them more
bioavailable. This concern will also be investigated.
4.4.1.3 Anticipated Outcomes
Identification of industries, processes, and
products that have relatively high potential to
release manufactured nanomaterials into the
environment by working collaboratively with
other organizations to inform decision-makers
about the overall impact of manufactured
nanomaterials
Improved understanding of the industries
of importance and identification where
information gaps that preclude a full
assessment of emission/release points of
concern
A systematic assessment of the production,
use, and ultimate fate of nanomaterials that
will improve understanding of the potential for
emissions/releases into the environment
Development of a modified tool using life
cycle principles to: (a) better understand
which industries pose the greatest potential
to emit/release nanomaterials of concern and
(b) inform decision-makers about the overall
impact of manufactured nanomaterials
A series of assessments for the highest priority
industry categories, the results of which will
be used to guide industry and nanomaterial
selection for assessment
Development of comparative assessments to
help inform decision-makers at what stage in
the lifecycle of manufactured nanomaterials
interventions could be used to avoid future
environmental impacts
Design of production processes that minimize
or eliminate any emissions/releases and reduce
energy consumption during the manufacturing
of nanomaterials and products
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An evaluation of the efficacy of existing
pollution control approaches and technologies
to manage releases of manufactured
nanomaterials to all media during their
production
ORD will collaborate with others to report
on opportunities to reduce the environmental
implications of nanomaterial production by
employing greener synthesis approaches
Comprehensive evaluation of the impact
nanomaterials could have on conventional
thermal destruction and land disposal practices
ORD will identify design production processes
that minimize or eliminate any emissions/
releases and reduce energy consumption
during the manufacturing of nanomaterials and
products
4.4.2 Key Science Question 8. How can
manufactured nanomaterials be applied in a
sustainable manner for treatment and remediation of
contaminants?
While it is critical to understand the potential
environmental implications of nanotechnology,
it is also important to investigate how various
nanomaterials can be used to prevent, control or
remediate environmental contaminants that have up
to now been difficult to manage with conventional
technology.
Nanotechnology will be used to both create new
technologies and improve the performance of
conventional technologies. There are several avenues
to obtain environmental benefits from nanotechnology.
Use nanoscale materials in a synthesis process
as a substitute for more toxic components or
as a process mediator that reduces the mass
of potentially toxic materials employed in the
chemical process (e.g., catalysts)
Incorporate nanoscale materials into a part of
the production process used to treat noxious
chemicals prior to final discharge
Employ nanoscale materials to treat emissions/
releases from power production and industrial
processes waste streams
Treat contaminated environmental media (i.e.,
air, water, sediments, or soil)
ORD's initial emphasis will be to address key
pollutants of concern to EPA program and regional
offices that have historically been difficult to manage,
including sources that emit low concentrations of air
pollutants and remediation of hazardous materials in
complex heterogeneous environments.
In addition to supporting the recommendations of
outside experts, this research will be valuable to EPA
program and regional offices and outside stakeholders
such as industry and states who are constantly looking
for innovative solutions to address intractable pollution
problems. Many of these needs have already been
identified.
4.4.2.1 Research Activities
This area is primarily driven by the need to
address existing environmental problems through
the application of nanotechnologies. Only where
nanotechnologies potentially offer superior solutions
to high priority problems do they become viable
candidates for ORD environmental applications
research. Two key technical areas are identified below
where benefits can be anticipated either directly
through the development of nanotechnology-based
materials and processes and/or indirectly through the
development of technologies used to characterize
nanomaterials that may subsequently be applied in
support of environmental restoration efforts.
Waste/byproduct minimization
The use of nanotechnology in industrial processes
has many potential advantages. One potentially
significant environmental benefit is reducing the
amount of material sent to the waste stream. Under
this research area, ORD will work with its partners
in industry and academia to investigate advanced
approaches that have the potential to reduce waste
products in those industrial sectors with high
volumes of waste. Waste minimization benefits to be
realized through nanotechnology applications will
result either through the substitution of less-toxic
chemical components in the manufacturing process
or through the reduction in the required mass of
toxic chemical components via enhanced reaction
rates or efficiencies. An example of the first scenario
includes the use of nanomaterials to improve material
characteristics of bio-based, nanocomposite products.
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These products are being developed as substitutes for
more traditional petroleum-derived materials, resulting
in a reduction of the mass of toxic components that
could potentially be released into the environment.
There are also numerous examples of the development
of nanomaterials for use as catalysts in chemical
manufacturing processes. The use of nanoscale
catalysts results in an overall enhancement of process
efficiency, thus reducing the required mass of toxic
chemical components used in the manufacturing
process.
Application of nanomaterials to reduce
environmental risks
Under this research area, ORD will investigate the
potential for various nanomaterials to minimize the
release of toxic chemical constituents. Similar to
the use of nanoscale catalysts in the manufacturing
process, the use of nanomaterials to treat process
waste streams (gas, liquid, or solid phases) provides
enhancements in removal rates and/or efficiencies.
One key activity will include the application of
nano catalysis for the reduction of air pollutants
and a better understanding of how these catalysts
can be used in various environmental applications.
Inorganic nanoscale materials, including metallic iron
nanomaterials and aluminosilicate-based zeolites,
have been synthesized for removal or degradation of
metals and organic contaminants from air and water
effluents generated as a result of manufacturing and
power-generation operations. Similar to the case
described above for the manufacturing process, the use
of nanomaterials in end-of-pipe treatments affords the
opportunity for regeneration or controlled disposal of
treatment by-products. In addition, this research will
study the use of nano-scale iron particles to remediate
aqueous streams contaminated with chlorinated-
organics, pesticides, PCBs, heavy metals and such
inorganics like Cr+6, arsenates, perchlorates, and
nitrates. If these treatment and remediation processes
are successful, they can be incorporated into existing
treatment systems to further reduce contaminant
loading.
Another area of emphasis within this program
will be to investigate the ability to physically
and chemically tailor substances, surfaces, and
pores at the nano-scale to improve selectivity and
efficiency of membrane filtration, adsorption,
and catalysis. The objective is to identify and
evaluate innovative, high performance or lower
cost alternatives for treating critical contaminants.
Improvements for many different treatment
scenarios (e.g., matrices, contaminants, treatment
technologies, and treatment goals) may become
feasible. Examples of areas where such an
approach could provide significant improvements
in removal performance and cost savings is the
use of nanotechnology to produce advanced
sorbents for mercury control and water treatment.
In the mercury area, the ability to directly link
the physical and chemical nature of binding
sites in the materials with the performance of
those materials is the key to developing new
or improved adsorbents with properties that
exceed those that have conventionally been
used. In the water area, nanomaterials may
enable the manufacture of media that are more
selective, efficient, and economical for removal or
destruction of existing or emerging contaminants
from drinking water, wastewater, and storm
water. These improved media may arise from
better design and uniformity of pore size, particle
size, or composition made feasible by nano-scale
design and control of the manufacturing process.
Remediation of contaminated sites is another
area where ORD will explore the use of
nanomaterials. Examples of these research and
development efforts include the development
of nanoscale metallic solids or biopolymers
for the destruction of organic contaminants or
the extraction of inorganic contaminants from
ground water and soil. Ultimately, EPA can play
a significant role in advancing the development
and implementation of these technologies through
research and testing. Using past experience
implementing waste minimization, treatment,
and remediation technologies, EPA can fulfill
the much-needed role of a technical mediator
between the commercial entities actively pursuing
development of synthetic nanomaterials and those
who may be negatively affected by the large-scale
utilization of these materials.
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4.4.2.2 Anticipated Outcomes
Nanotechnology research will play a role in
providing environmental benefits to society
through the development of new materials or
technologies for waste minimization and treatment
of conventional pollutants. Through this research
ORD will report on the viability, performance,
and benefits of the use of nanotechnology for the
abatement and remediation of conventional toxic
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?
Characterize NM's with enhanced catalytic properties
Develop scientific foundation for the
use of NMs for environmental
remediation
Report on a Life Cycle Analysis
approach for evaluating future
nanotechnology applications
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
Develop preventive methods and nanomaterial technologies for risk
management of environmental contaminants
2009
2010
2011
2012
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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.
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For more about EPA research on nanotechnology, please visit:
www. epa. gov/nanoscience
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References
Ayres, J.G., et al, Inhalation Toxicology 20(l):75-99,
2008).
Balbus, John, et al., Enviorn. Health Perspect.
115:1664-1659, 2007; John Balbus, et al., Enviorn.
Health Perspect. 115:1664-1659, 2007.
D.B. Warheit et al., Inhalation Toxicology 19(8):631-
643, 2007.
Davis, J.M., "How to assess the risks of
nanotechnology: learning from past experience." J.
Nanosci. Nanotechnol. 7(2): 402-409, 2007.
Davis, J.M. and Thomas, V.M. (2006). "Systematic
approach to evaluating trade-offs among fuel options:
the lessons of MTBE," Ann. N.Y. Acad. Sci. 1076: 498-
515.
Dix et al., Toxicol Sci., 95(1):5-12, 2007
Environmental Defense - DuPont Nano Partnership
(2007), Nano Risk Framework. New York, NY:
Environmental Defense. Available at http://www.
environmentaldefense.org/go/nano.
Keisuke, F. and Sato, T. (2005) Using a surface
complexation model to predict the nature and stability
of nanoparticles. Envion. Sci. Technol. 39: 1250-1256.
Kloepffer, W., M. A. Curran, et al. (2007).
"Nanotechnology and Life Cycle Assessment:
Synthesis of Results Obtained at a Workshop in
Washington, DC," 2-3 October 2006.
Loux, N.T. and Savage, N. (2008). "An assessment of
the fate of metal oxide nanomaterials porous media."
Water Air SoilPollut In Press (Corrected proof
available online).
Maynard, A.D. (2006) Nanotechnology: A research
strategy for addressing risk. Woodrow Wilson
International Center for Scholars. PEN 3 July.
Washington, D.C.
Miyagawa, H., Mohanty, A.K., Drzal, L.T., and Misra,
M. (2005), "Nanocomposites from biobased epoxy
and single-wall carbon nanotubes: synthesis, and
mechanical and thermophysical properties evaluation."
Nanotechnology, 16: 118-124.
Morgan, K. (2005). "Development of a Preliminary
Framework for Informing the Risk Analysis and Risk
Management of Nanoparticles." Risk Analysis 25, No.
6, 1621-1635.
Nadagouda, M.N. and Varma, R.S., "Green Synthesis
of Silver and Palladium Nanoparticles at Room
Temperature Using Coffee and Tea Extract," Green
Chem., 10, 859(2008).
Nadagouda, M.N. and Varma, R.S.. "Green
and controlled Synthesis of Gold and Platinum
Nanomaterials Using Vitamin B2: Density-assisted
Self-assembly of Nanospheres, Wires and Rods."
Green Chem., 8, 516 (2006).
Nadagouda, M.N. and Varma, R.S., "Microwave-
assisted Shape-controlled Bulk Synthesis of Noble
Nanocrystals and their Catalytic Properties," Crystal
Growth and Design, 1, 686 (2007).
National Nanotechnology Initiative, Sept.2006.
(www.nano.gov/NNI_EHS_re search_needs.pdf)
National Research Council of the National Academy of
Sciences
(www.nap.edu/catalog/11970 .html#toc)
National Research Council (NRC, 1983). Risk
Assessment in the Federal Government: Managing the
Process. National Academy Press, Washington, DC.
Nowack, B. and Bucheli, T.D. (2007) "Occurrence,
behavior and effects of nanoparticles in the
environment." Environmental Pollution. In Press
(Corrected proof available online).
Nishioka, Y, Levy, J.I., Norris, G.A., etal. (2002),
"Integrating risk assessment and life cycle assessment:
a case study of insulation." Risk Analysis 22: 1003-
1017.
Oberdorster, G., et al, Particle and Fibre Toxicology
2:8,2005.
Ponder, S.M., Darab, J.G., and Mallouk, T.E. (2000).
"Remediation of Cr(VI) and Pb(II) aqueous solutions
using supported, nanoscale zero-valent iron."
Environmental Science and Technology, 34: 2564
-2569.
-------
Presidential/Congressional Commission on Risk
Assessment and Risk Management (1997). Framework
for Environmental Health Risk Management. Final
Report of the Commission. Volume 1
Schmidt, Karen F., Green Nanotechnology: It's easier
than you think. Woodrow Wilson International
Center for Scholars, April 2007
Shatkin, J.A. and Qian, A. (2004), "Classification
schemes for priority setting and decision making: a
selected review of expert judgment, rule-based, and
prototype methods." In Comparative Risk Assessment
and Environmental Decision Making. Linkov, I. & A.
Ramadan, Eds.: 213-244, Luewer, Amsterdam.
Shelley, S.A., and Ondrey, G., "Nanotechnology - The
Sky's the Limit," Chemical Engineering, December
2002, pp. 23-27.
Song, W., Li, G., Grassian, V.H., and Larsen, S.C.
(2005). "Development of improved materials for
environmental applications: Nanocrystalline NaY
zeolites." Environmental Science and Technology, 39:
1214-1220.
Sonneman, G., Castells, F., and Schumacher, M.
(2004). Integrated Life cycle and Risk Assessment for
Industrial Processes. Lewis Publishers. Boca Raton,
FL.
Surowiecki, J. (2004) The Wisdom of Crowds. Little
Brown, London
U.S. Environmental Protection Agency (1998).
Guidelines for Ecological Risk Assessment.
Washington, DC: Office of Research and
Development, U.S. Environmental Protection Agency.
EPA/63 0/R-95/002F.
U.S. Environmental Protection Agency (2007).
Nanotechnology White Paper. Washington, DC:
Science Policy Council, U.S. Environmental
Protection Agency. EPA 100/B-07/001.
(Endnotes)
1 Nadagouda, M.N. and Varma, R.S., "Green
Synthesis of Silver and Palladium Nanoparticles at
Room Temperature Using Coffee and Tea Extract,"
Green Chem., 10, 859 (2008).
2 Nadagouda, M.N. and Varma, R.S.. "Microwave-
assisted Shape-controlled Bulk Synthesis of Noble
Nanocrystals and their Catalytic Properties," Crystal
Growth and Design, 7, 686 (2007).
3 Nadagouda, M.N. and Varma, R.S.. A Greener
Synthesis of Core (Fe, Cu)-Shell (Au, Pt, Pd and
Ag) Nanocrystals Using Aqueous Vitamin C. Crystal
Growth and Design, 7, 2582 (2007).
4 Nadagouda, M.N. and Varma, R.S.. Green
and controlled Synthesis of Gold and Platinum
Nanomaterials Using Vitamin B2: Density-assisted
Self-assembly of Nanospheres, Wires and Rods.
Green Chem., 8, 516 (2006).
5 Miyagawa, H., Mohanty, A.K., Drzal, L.T., and
Misra, M. (2005), "Nanocomposites from biobased
epoxy and single-wall carbon nanotubes: synthesis,
and mechanical and thermophysical properties
evaluation." Nanotechnology, 16: 118-124.
6 Shelley, S.A., and Ondrey, G. "Nanotechnology
- The Sky's the Limit," Chemical Engineering,
December 2002, pp. 23-27.
7 Ponder, S.M., Darab, J.G., and Mallouk, T.E.
(2000) Remediation of Cr(VI) and Pb(II) aqueous
solutions using supported, nanoscale zero-valent iron.
Environmental Science and Technology, 34: 2564
-2569.
8 Song, W., Li, G., Grassian, V.H., and Larsen,
S.C. (2005) Development of improved materials for
environmental applications: Nanocrystalline NaY
zeolites. Environmental Science and Technology, 39:
1214-1220.
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