United States
Environmental Protection
Agency
EPA601K20001 March 2020www.epa.gov/research
Chemical Safety
for Sustainability
STRATEGIC RESEARCH ACTION PLAN
2019-2022
Office of Research and Development
Chemical Safety for Sustainability

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Chemical Safety for Sustainability
National Research Program
Strategic Research Action Plan
2019-2022
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Table of Contents
Executive Summary	5
Introduction	6
Research to Support EPA and ORD Strategic Plans	6
Statutory and Policy Context	7
Partner and Stakeholder Engagement	7
Environmental Problems and Program Objectives	9
Problem Statement	10
Program Vision	10
Program Objectives	11
Research Topics and Research Areas	12
Topic 1: Chemical Evaluation	12
Research Area 1: High-Throughput Toxicology	12
Research Area 2: Rapid Exposure Modeling and Dosimetry	14
Research Area 3: Emerging Materials and Technologies	15
Topic 2: Complex Systems Science	17
Research Area 4: Adverse Outcome Pathways	17
Research Area 5: Virtual Tissue Modeling	18
Research Area 6: Ecotoxicological Assessment and Modeling	19
Topic 3: Solutions-Driven Translation and Knowledge Delivery	21
Research Area 7: Chemical Safety Analytics	21
Research Area 8: Informatics, Synthesis, and Integration	23
Program Design	23
Solutions-Driven Research	24
Adapting to Changing Needs	24
Integration Among Research Programs	25
Intramural and Extramural Activities	26
Interagency and International Collaboration and Outreach	28
Anticipated Research Accomplishments and Projected Impacts	28
CSS Science Informs TSCA Implementation	28
CSS Science Enables EDSP Modernization	29
CSS Science Supports PFAS Decision Making	30
Conclusion	31
References	32
Appendix 1: CSS Partner and Stakeholder Needs, Research Areas, and Outputs	35
Appendix 2: Partner and Stakeholder Engagements to Inform CSS StRAP Development	46
Appendix 3: State Needs as Conveyed to EPA by the Environmental Council of the States (ECOS)	50
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List of Acronyms
AOP	Adverse Outcome Pathway
APCRA	Accelerating the Pace of Chemical Risk Assessment
CEC	Contaminants of Emerging Concern
CERCLA	Comprehensive Environmental Response, Compensation, and Liability Act
CompTox	Computational Toxicology
CSA	Chemical Safety Analytics
CSS	Chemical Safety for Sustainability
CWA	Clean Water Act
DMSO	Dimethyl Sulfoxide
DNT	Developmental Neurotoxicity
DOD	Department of Defense
ECHA	European Chemicals Agency
ECOS	Environmental Council of the States
ECOTOX	Ecotoxicology Knowledgebase
EDSP	Endocrine Disruptor Screening Program
EMT	Emerging Materials and Technologies
ENMs	Engineered Nanomaterials
EPA	U.S. Environmental Protection Agency
ESA	Endangered Species Act
ETAM	Ecotoxicological Assessment and Modeling
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
FIFRA SAP	Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel
FQPA	Food Quality Protection Act
FY	Fiscal Year
HERA	Health and Environmental Risk Assessment (formerly HHRA)
HHRA	Human Health Risk Assessment
HSRP	Homeland Security Research Program
HTT	High-Throughput Toxicology
HTTK	High-Throughput Toxicokinetics
ISI	Informatics, Synthesis, and Integration
IT	Information Technology
MCCs	Methodologically Challenging Chemicals
NaKnowBase Nanomaterials Relational Database
NAM	New Approach Methodology
NAS	National Academy of Sciences
NEHI	Nanotechnology Environmental and Health Implications Working Group
NIEHS	National Institute of Environmental Health Sciences
NIH	National Institutes of Health
NRP	National Research Program
NSTC	National Science and Technology Council
OCMs	Organotypic Culture Models
OCSPP	Office of Chemical Safety and Pollution Prevention
OLEM	Office of Land and Emergency Management
OPP	Office of Pesticide Programs
OPPT	Office of Pollution Prevention and Toxics
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ORD
Office of Research and Development
OSCP
Office of Science Coordination and Policy
OW
Office of Water
PCBs
Polychlorinated biphenyls
PFAS
Per- and Polyfluoroalkyl Substances
PFOA
Perfluorooctanoic acid
PFOS
Perfluorooctanesulfonic acid
PIP
Pathfinder Innovation Projects
PO
Program Office
QSAR
Quantitative Structure Activity Relationship
RARE
Regional Applied Research Effort
RCRA
Resource Conservation and Recovery Act
REMD
Rapid Exposure Modeling and Dosimetry
SAP
Science Advisory Panel
SDWA
Safe Drinking Water Act
SeqAPASS
Sequence Alignment to Predict Across Species Susceptibility
SHC
Sustainable and Healthy Communities
SSWR
Safe and Sustainable Water Resources
STAR
Science to Achieve Results
StRAP
Strategic Research Action Plan
Tox21
Toxicology Testing in the 21st Century
ToxCast
Toxicity Forecaster and Biological Materials
TSCA
Toxic Substances Control Act
USEPA
United States Environmental Protection Agency
UVCB
Chemical Substances of Unknown or Variable Composition, Complex Reaction Products,

and Biological Materials
VTM
Virtual Tissue Modeling
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Executive Summary
The Environmental Protection Agency's (EPA) Chemical Safety for Sustainability (CSS) National Research
Program (NRP) is transforming chemical risk-based decisions by conducting high-quality, innovative
scientific research. The results of this research support the Agency, states, tribes, and other stakeholders
in fulfilling their shared objectives to protect human health and the environment. CSS has a history of
conducting innovative science and is a hub of global scientific expertise and leadership in many areas,
such as computational toxicology and exposure, high-throughput toxicology, and complex systems
science.
The pressing environmental and health challenge in chemical safety evaluations has been, and continues
to be, a lack of sufficient information on most chemicals used in commerce, industry, and agriculture.
Traditional approaches for evaluating chemical safety have been unable to keep pace with innovations
in chemical design, synthesis, and use. Thus, many chemicals have little data available to make science-
based decisions. In addition, chemicals of emerging concern, such as per- and polyfluoroalkyl substances
(PFAS), heighten the need for rapid, scientifically-based approaches to evaluate chemical safety.
This CSS Strategic Research Action Plan (StRAP) reflects the priority needs of Agency program and
regional offices, states, tribes, and external stakeholders as determined through extensive, systematic
consultations and engagements. The CSS StRAP reflects the strategic plans of the Agency and the Office
of Research and Development and is firmly rooted in statutory authorities that authorize research to
fulfill the Agency's mission. The research and development work outlined in this StRAP is informed by
recent scientific advancements in the chemical safety field, many of which were developed by Agency
scientists.
CSS research will positively impact and advance chemical safety assessments through several anticipated
accomplishments, including:
•	A chemical safety informatics infrastructure to support decision makers;
•	High-throughput hazard and exposure approaches to fulfill data needs;
•	Complex systems science to inform interpretive frameworks and exploit the use of new
approach methodologies (NAMs);
•	Approaches to extrapolate data among chemicals, species, life stages, and biological levels of
organization to extend the applicability of existing data; and,
•	Consideration of sensitive populations and life stages in chemical safety evaluations.
CSS seeks to lead the development of new approach methodologies and take advantage of scientific and
technological developments that advance efficient evaluations of chemical safety. Through a robust
intramural research program, collaborations with partners and stakeholders (including academia and
other governmental organizations), and support from an innovative extramural grants program, CSS will
build a broader understanding of biology, chemical toxicity, and exposure while providing more rapid,
cost-effective approaches that protect human health and valued ecological resources and services.
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Introduction
The Environmental Protection Agency (EPA), along with other federal partners, states and tribes, plays a
central role in evaluating the potential impacts of chemicals on human health and the environment.
EPA's strives to provide efficient, transparent, and scientifically robust approaches to evaluating
chemical safety while continually improving these approaches in response to scientific and technological
advancements. To achieve this, EPA applies advanced toxicological and exposure methods, data, tools,
models, and information access to make better informed and more timely decisions about the safety of
chemicals, many of which have not been thoroughly evaluated for potential risks to human health and
the environment. EPA's Chemical Safety for Sustainability (CSS) National Research Program (NRP) is
designed to support the goal of reducing risks associated with exposure to chemicals in commerce,
consumer products, food, and the environment.
EPA's Office of Research and Development (ORD) developed
this Chemical Safety for Sustainability Strategic Research
Action Plan 2019-2022 (CSS StRAP) to articulate the
chemical safety research needs of ORD's partners, outline
outputs to address those needs, and guide development of
research implementation plans. The 2019-2022 CSS StRAP
builds upon previous CSS StRAPs (USEPA, 2012; USEPA,
2015) and continues a practice of conducting innovative
scientific research and development aimed at solving the
problems encountered by Agency partners and
stakeholders. The current CSS StRAP evolved through a
series of meetings, workshops, and consultations with
Agency partners, ORD scientists, and interactions with external stakeholders. It lays out a vision of
research and development that is focused on both near- and long-term needs and delivering scientific
products that inform implementation of environmental regulations and Agency rulemaking and
decisions.
The CSS StRAP is one of six research plans, one for each of EPA's national research programs in ORD1.
The six research programs are:
•	Air and Energy (A-E);
•	Chemical Safety for Sustainability (CSS);
•	Homeland Security Research Program (HSRP);
•	Health and Environmental Risk Assessment (HERA);
•	Safe and Sustainable Water Resources (SSWR); and,
•	Sustainable and Healthy Communities (SHC).
Research to Support EPA and ORD Strategic Plans
EPA's Strategic Plan for FY2018-2022 (USEPA, 2019b) outlines the need for chemical safety research.
Under Objective 1.4, Ensure Safety of Chemicals in the Marketplace, the Agency defines ambitious
goals to implement the Toxic Substances Control Act (TSCA), and the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA), "...to ensure new and existing chemicals and pesticides are reviewed for their
potential risks to human health and the environment and actions are taken when necessary." Further,
under Objective 3.3, Prioritize Robust Science, the Agency "will identify, assess, conduct, and apply the
1 https://www.epa.gov/research
ORD refers to EPA program and
regional offices, states, and tribes
(including organizations and
subsidiaries thereof) as partners.
ORD considers industry, professional
groups, and non-governmental
organizations that have interests in
chemical safety and management as
stakeholders.
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best available science to address current and future environmental hazards, develop new approaches,
and improve the scientific foundation for environmental protection decisions."
ORD's Strategic Plan (USEPA, 2018b) responds to and
builds upon the Agency's Strategic Plan by establishing the
goals of Advancing Environmental Science and Technology
(ORD Goal 1) and Informing and Supporting Federal, State,
Tribal, and Local Decision Making (ORD Goal 2). StRAPs for
ORD's six research programs respond to the ORD Strategic
Plan and outline specific research activities that address
objectives of both Agency and ORD strategic plans.
Further, ORD develops and maintains active partnerships
with our partners and stakeholders that inform ORD's
conduct of solutions-driven research.
CSS research will provide the scientific foundation that informs decisions about the use of chemicals and
the protection of human health and the environment. CSS research will also enable the Agency to
evaluate and predict impacts from chemical use and disposal and will provide the Agency, states, and
tribes with information, tools, and methods to make better informed and more timely decisions about
the thousands of chemicals used in commerce, industry, and agriculture.
Statutory and Policy Context
Managing chemical risks to protect human health and the environment, including the conduct of
supporting scientific research, is authorized and/or mandated in several statutes. The CSS research
portfolio is largely focused on requirements authorized under TSCA, FIFRA, the Food Quality Protection
Act (FQPA), the Federal Food, Drug, and Cosmetic Act (FFDCA), the Clean Water Act (CWA), Safe Drinking
Water Act (SDWA), the Resource Conservation and Recovery Act (RCRA), the Comprehensive
Environmental Response, Compensation, and Liability Act (CERCLA), and the Endangered Species Act
(ESA). Chemical assessment, regulation, and management associated with these statutes are
implemented by EPA's program offices, including the Office of Chemical Safety and Pollution Prevention
(OCSPP), the Office of Land and Emergency Management (OLEM), and the Office of Water (OW). CSS
works closely with each of these offices to ensure that research is designed to support current and
future needs. Furthermore, due to the fundamental nature of CSS's work, CSS data, tools, and models
are often used to inform decisions made under other authorities, both federal and state.
Partner and Stakeholder Engagement
Defining the problems and needs of partners and stakeholders is a necessary step to designing a
research portfolio that is both responsive and actionable. To achieve this, CSS has been engaging
partners and stakeholders since mid-2017 to assess their problems and needs (see Appendix 1 for
partner needs). CSS used several approaches to foster dialog, including: conducting topical workshops,
briefing partners on CSS StRAP development, conducting regularly scheduled consultations,
collaborating with partners on programmatic strategies and plans, participating in state and tribal
discussions, and providing opportunities for partners to review the CSS StRAP at different stages of
development (Appendix 2). These engagements will continue throughout the implementation of the
research outlined in this StRAP. CSS will measure its progress over the next four years by increasing the
percentage of research products that meet customer needs.
The Agency will produce innovative
tools that accelerate the pace of
data-driven evaluations, enable
knowledge-based decisions that
protect human health, and advance
the science required to anticipate
and solve problems.
FY 2018-2022 EPA Strategic Plan
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The highest priority needs are presented in Appendix 1. Most of the needs identified by Agency partners
were focused on toxicological considerations needed to support chemical risk assessment and risk
management decisions. Commonly identified themes were to provide: additional and/or better
information to fulfill data gaps identified through programmatic activities; quicker access to information
through user-friendly systems and formats; new approach methodologies for priority toxicological
pathways; and interpretive frameworks, approaches, and models to utilize new approach
methodologies in decision making.
The research needs presented in Appendix 1 are generally expressed in the context of specific
programmatic needs, with the research needs of TSCA, FIFRA, and FQPA driving much of the CSS
research portfolio. For example, OCSPP's Office of Pollution Prevention and Toxics (OPPT) expressed
several needs specific to supporting the implementation of TSCA, including:
•	Research towards the development of alternative, non-vertebrate chemical safety tests and
methods (TSCA, Section 4);
•	Improved approaches and guidance for the evaluation of new chemicals (TSCA, Section 5); and,
•	Development of rapid, reliable, and economical screening techniques and scientific procedures
supporting the review, prioritization, and risk evaluation of existing chemicals (TSCA, Section 6).
OCSPP's Office of Pesticide Programs (OPP) has similar scientific needs to OPPT, albeit in a different
programmatic context and with different timelines. These include supporting regular pesticide
registration processes, as well as re-registration activities to be completed in 2022 as required under
FIFRA. OCSPP's Office of Science Coordination and Policy (OSCP) has more specific needs associated with
the Endocrine Disruptor Screening Program (EDSP). These focus on completing certain estrogen- and
androgen-related aspects of the program in the near term, while refining the expectations and needs for
understanding effects of chemicals on steroidogenesis and thyroid hormone pathways.
Another driver for CSS research is the Agency's interest in understanding the potential role of
environmental chemicals on susceptible populations, such as children and the elderly. This requires
research to identify and quantify exposures at relevant life stages, to understand metabolic pathways
that are particularly important to susceptible populations, and to investigate the factors associated with
differential sensitivity, especially toxicokinetics and toxicodynamics. This type of information will inform
public health policy decisions as required under enacted federal environmental statutes (e.g., Executive
Order 13045, FQPA, SDWA, and most recently, the amended TSCA), and is of particular interest to the
Agency's Office of Children's Health Protection.
While the specific needs of Agency programs and regions are the primary drivers for ORD research,
there is renewed emphasis on addressing the needs of states and tribes. States and tribes are important
partners that work cooperatively with EPA and other federal partners, often with delegated authorities
to protect human health and the environment. CSS has further developed these relationships by
including states and tribes in consultations to identify their most important environmental problems.
For example, through these interactions, CSS has developed an increased awareness of the need to
address contaminants of emerging concern, such as per- and polyfluoroalkyl substances (PFAS), and for
improved access to integrated chemical safety information on exposure, toxicity, and persistence. A
summary of state needs reflected in ORD's research planning activities is presented in Appendix 3.
Evaluating chemical safety is challenging and depends on having available robust science for a wide
variety of disciplinary areas and chemical management contexts. Through extensive interactions with
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Agency, state, tribal, and external stakeholders, common themes emerge that reflect the current
problems and needs faced by decision makers. The common themes include:
•	The number of chemicals that need to be evaluated is large and is continually changing;
•	Environmental exposures most typically occur as complex chemical mixtures, not as individual
chemicals;
•	The timelines and expectations for rapid assessments are often difficult to meet;
•	The complexities associated with interpretation of information are often overwhelming;
•	Efficient and selective use of relevant information from vast and often disparate data
repositories is difficult;
•	There are continuing needs for generalizations, interpretive frameworks, and predictive models
to take advantage of modern data streams;
•	Requirements are high for new high-throughput and alternative test procedures to be
considered suitable substitutes for traditional toxicity-testing methods;
•	Approaches to extrapolation across chemical space, taxonomic groupings, organismal life stage,
and biological levels of organization are needed to inform data-poor situations;
•	There are increasing expectations to address sensitive populations and life stages; and,
•	There are legislative directives, Agency policy, and societal pressures to reduce, refine, and
replace the use of vertebrate animal testing.
These common themes are generally reflected throughout the CSS StRAP, specifically identified in the
outputs and will be addressed in the development of CSS Research Areas, which articulate specific and
responsive research products.
Environmental Problems and Program Objectives
Continuing innovation in chemical design, production, and use in commerce, industry, and agriculture is
a key feature of the economy. In addition to the inventories of existing chemicals, new chemicals and
new chemical uses are continually introduced to the marketplace to improve a wide variety of products
and processes. Because certain chemicals may have adverse impacts to humans and ecological species,
chemical manufacture, use, and disposition need to be managed to minimize potential effects to human
health and the environment. Efficient and effective management of chemical safety is a demanding
Agency priority. For example, the TSCA active inventory alone contains over 40,000 chemicals, and
hundreds more are introduced every year. However, the information for the majority of these 40,000
chemicals is incomplete to fully evaluate potential risks to human health and the environment,
especially for potentially vulnerable and sensitive populations. Traditional toxicity testing methods for
evaluating risks from exposures to individual chemicals are expensive, time consuming, and provide an
incomplete understanding of chemical interactions with biological systems. To address this critical
challenge, rapid, efficient, and cost-effective approaches are needed to prioritize, screen, and evaluate
chemicals for safety using scientifically-sound and transparent processes. Although the majority of
traditional toxicity testing has been done on individual chemicals, realistic environmental exposures
occur as mixtures. Thus, a significant challenge remains regarding approaches to evaluating chemical
mixtures.
The National Academy of Science (NAS) recognized the need to modernize the field of toxicology
through three seminal reports on toxicity testing, exposure science, and risk evaluation. The first report,
Toxicity Testing in the 21st Century: A Vision and a Strategy (National Research Council, 2007), provided
support for a paradigm shift in toxicology that favored the development and application of in vitro
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systems and computational modeling to replace expensive and time-consuming in vivo testing
approaches. This report supported the concept of conducting high-throughput toxicity testing for
thousands of chemicals with in vitro assays through efforts such as the interagency Tox21 Program
(Thomas et al. 2018) and EPA's ToxCast (Kavlock et al. 2012; Richard et al. 2016). Both efforts are
foundational to developing computational toxicology approaches. The second NAS report that guided
the development of the CSS Program, Science and Decisions: Advancing Risk Assessment (National
Research Council, 2009), provided practical recommendations to address the challenges of risk
assessment, including data gaps, uncertainties, and assessment complexities. The recommendations
focused on improving and accelerating risk-based decision making and are applicable to nearly all of
EPA's environmental legislation. The third report, Exposure Science in the 21s' Century: A Vision and a
Strategy (National Research Council, 2012b), supported complementary shifts for the exposure sciences,
introducing a vision for computational exposure science parallel to the computational toxicology
approaches introduced in the 2007 NAS report. The third report also supported expanding exposure
beyond the traditional external view to include the internal exposure, which provides the critical linkage
between external exposure and effects.
In addition, other NAS reports inform components of the CSS program, including work on engineered
nanomaterials (National Research Council, 2012a), design and use of safer chemical alternatives
(National Research Council, 2014a), evaluation of pesticide impacts on threatened and endangered
species (National Research Council, 2013), endocrine disruption by chemicals (National Research
Council, 2014b), and the use of new science in risk assessment (National Academies of Sciences,
Engineering, and Medicine, 2017a,b).
EPA's needs in assessing chemical safety are broad and varied according to the legislative authorities,
rules, and policies associated with different statutes. In response, CSS develops both fundamental
research products that can be applied to common needs among multiple Agency partners and
stakeholders, and targeted research products and outputs to meet specific programmatic and partner
needs.
Problem Statement
Tens of thousands of chemicals are currently in use and hundreds more are introduced to the market
every year. Currently available information provides an incomplete understanding of the potential risks
of chemicals to human health and the environment, which results in EPA programs and regions, states,
tribes, and others making many risk-based decisions with limited hazard and exposure data.
Additionally, traditional approaches to evaluate chemical toxicity and exposure are expensive and do
not fully reflect all biological responses and exposure pathways. Improved, scientifically-based
measurement and modeling approaches are needed to evaluate chemical toxicity and exposure. These
approaches need to be rapid, cost-effective, and accepted by regulatory and industry communities, non-
governmental organizations, and the public.
Program Vision
The CSS program is focused on addressing Agency needs while also being transformative, leading to
improved science-based approaches that build broader understanding of biology, chemical toxicity, and
exposure. Beyond the timeline of the current St RAP, the CSS long-term vision is broad and ambitious
and focuses on three main components. First, CSS will develop the science needed to reduce and
eliminate vertebrate animal testing to the extent that the replacement approaches are, at least, as
informative as in vivo tests. This effort is consistent with and supports the Administrator's memorandum
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regarding the elimination of in vivo mammalian testing by 2035 (USEPA, 2019a). The second component
of the long-term vision for CSS is accelerating the pace of chemical assessment to enable our partners
and stakeholders to make informed and timely decisions concerning the potential impacts of
environmental chemicals on human health and the environment. The third component of CSS's long-
term vision is to provide leadership to transform chemical testing, screening, prioritization, and risk
assessment practices. Realization of the CSS vision will require development of the computing
infrastructure, digital resources, computational models, new approach methodologies, and interpretive
frameworks needed to capture the complexity of toxicology on the organismal level, including the
effects of chemical mixtures. Additionally, CSS will need to develop ecological modeling frameworks and
approaches to extrapolate known or predicted effects on organisms to population and community level
effects. To achieve this vision, CSS will work with Agency, federal, and international partners, as well as
stakeholder experts from academia and professional societies. These efforts are outlined in the topics,
research areas, and outputs outlined in the sections that follow.
Program Objectives
CSS conducts high-quality chemical safety research to provide the fundamental data, knowledge
infrastructure, and complex systems understanding required to develop tools for rapid chemical
evaluation and to predict potential impacts from chemical use. CSS translates research results to provide
solutions and technical support to EPA partners and stakeholders.
CSS research is guided by the following four objectives:
•	Objective 1: Build Knowledge Infrastructure. CSS will use advanced information technology
tools to mine ever-expanding data sources for relevant information on chemical properties,
structure, toxicity, and exposure. CSS will focus efforts to annotate, curate, and efficiently serve
chemical information in formats usable to stakeholders and will generate high-quality, peer-
reviewed data to fill high-priority gaps in existing knowledge. CSS will address this objective by
integrating data across research activities. CSS intends to be the "first-stop-shop" for chemical
information needed by EPA partners, stakeholders, and the public and will incorporate user
feedback in designing the supporting information systems and user interfaces.
•	Objective 2: Develop Tools and Models for Chemical Evaluation. CSS will develop and apply
rapid, efficient, and effective tools and models to enhance and facilitate chemical safety
evaluations. CSS will combine different types of data in ways to characterize impacts of
chemicals to human health and the environment.
•	Objective 3: Promote Complex Systems Understanding. CSS research activities will investigate
the emergent properties of complex chemical-biological systems by probing how disturbances
and changes in one part affect the entire system. By forming a detailed understanding of
systems behavior, CSS research will expand predictive capabilities to anticipate and inform
future chemical safety challenges, including chemical and biological extrapolation, as well as
extrapolation across biological levels of organization.
•	Objective 4: Translate and Actively Deliver. Solutions-driven research is emphasized throughout
the CSS research portfolio. CSS will focus on the delivery, demonstration, and application of CSS
data, tools, and models through case studies and partner engagement to inform immediate,
high-priority needs. By engaging early and often, and with continued engagement after delivery
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of science products, CSS will promote the mutual understanding of needs and solutions, thereby
enhancing the impact of CSS research products.
Research Topics and Research Areas
CSS is organized around three broad research topics that include similar areas of disciplinary expertise
and capability relevant to the partner needs. Within each research topic are research areas that focus
expertise and capabilities on deliverable outputs and products originating in specific research and
development activities (Table 1). This section presents a description of each topic and research area and
introduces the outputs (Appendix 1) that will guide research implementation by ORD. Each output is led
by a research area team during research implementation. By design, CSS research is integrated across
research areas. Therefore, each of the 45 outputs in CSS may be supported by research efforts from one
or more research areas.
Table 1: CSS Research Topics and Researc
h Areas
Topic
Research Areas
1) Chemical Evaluation
High-Throughput Toxicology (HTT)
Rapid Exposure Modeling and Dosimetry (REMD)
Emerging Materials and Technologies (EMT)
2) Complex Systems Science
Adverse Outcome Pathways (AOP)
Virtual Tissue Modeling (VTM)
Ecotoxicological Assessment and Modeling (ETAM)
3) Solutions-Driven Translation
and Knowledge Delivery
Chemical Safety Analytics (CSA)
Informatics, Synthesis, and Integration (ISI)
Topic 1: Chemical Evaluation
Research under the Chemical Evaluation topic will provide rapid methods and high-throughput data for
risk-based evaluations of new and existing chemicals and emerging materials. This topic will emphasize
development and application of new approach methodologies to rapidly generate exposure and hazard
information for chemicals and emerging materials and technologies. The High-Throughput Toxicology
(HTT) Research Area focuses on hazard profiling of chemicals using rapid toxicity testing approaches.
The Rapid Exposure Modeling and Dosimetry (REMD) Research Area focuses on modeling and
forecasting chemical exposures across various scenarios relevant to human and ecological exposure
assessments. The third research area, Emerging Materials and Technologies (EMT), addresses hazard
and exposure data needs of engineered products that are often not amenable to the types of
approaches used to characterize conventional chemicals. The current focus of EMT is on engineered
nanomaterials.
Research Area 1: High-Throughput Toxicology
For most chemicals, the availability of data and information to assess the potential toxicity to humans
and other species is limited or incomplete. Existing chemical inventories and the introduction of new
chemicals have driven the need for rapid assessment approaches. The High-Throughput Toxicology
(HTT) Research Area is focused on addressing the limitations of current chemical testing methods and
fulfilling EPA's need to evaluate large numbers of chemicals for potential adverse human and ecological
effects. The HTT Research Area will design, develop, and apply new approach methodologies (NAMs) for
hazard testing of chemicals and chemical mixtures. These high-throughput approaches will rapidly
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generate chemical hazard data on specific endpoints of interest to partners and stakeholders and will
help prioritize, screen, and evaluate chemical safety for thousands of compounds while reducing
reliance on traditional toxicity tests.
Building on the successes of previous research efforts to
implement HTT approaches (e.g., ToxCast2, EDSP213, and
Tox214), the focus of these outputs will be methods
development and data generation for priority pathways of
toxicological relevance and for under-represented chemical
classes that are not amenable to current HTT testing methods
(see Appendix 1 for complete table of outputs). Scientific and
technological advances have paved the way for using
additional NAMs in the HTT Research Area. These represent
opportunities for HTT to adapt and evolve new high-
throughput approaches to meet the Agency's chemical safety
mission.
Outputs:
•	Develop assays, datasets, data analyses, and models to inform frameworks that support
rapid, cost-effective approaches for screening large inventories of chemicals for bioactivity
in the estrogen, androgen, thyroid, and steroidogenesis pathways. (HTT Output CSS.1.1)
•	Develop, evaluate, apply, and interpret a battery of assays for developmental neurotoxicity
(DNT) to reduce uncertainties in chemical safety evaluations. (HTT Output CSS.1.2)
•	Develop and apply medium- to high-throughput, transferrable methods to test and deliver
novel hazard data on methodologically challenging chemical classes, such as volatile and
non-dimethyl sulfoxide (DMSO)-soluble chemicals. (HTT Output CSS.1.3)
•	Develop and apply methods to advance a tiered, high-throughput toxicity testing strategy
including high-throughput and high-content methods (e.g., transcriptomics, phenotypic
profiling, and other methods) that address key information needs of assessments. (HTT
Output CSS.1.4)
In vitro assay limitations introduce uncertainty when using high-throughput data to inform chemical
safety decisions. For example, lack of endogenous metabolism/bioactivation in existing high-throughput
approaches could result in hazard mischaracterization for chemicals that undergo biotransformation.
Thus, there is an urgent need to develop approaches to address sensitivity and specificity concerns
resulting from the limitations of in vitro assays.
Output:
•	Develop and apply methods to incorporate endogenous and exogenous xenobiotic
metabolism into high-throughput in vitro assays. (HTT Output CSS.1.5)
In addition to accelerating risk-based evaluations of existing chemicals, HTT research has potential
applications for emerging materials and immediate environmental issues, such as contaminants of
emerging concern (CECs) in the environment. Examining the utility of high-throughput approaches for
2	https://www.epa.gov/comptox/toxcast
3	https://www.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-edsp-21st-centurv
4	https://tox21.gov
Research products from the HTT
Research Area will enable EPA
partners and stakeholders to
make better, more timely
decisions about chemicals by
increasing toxicological
information for more biological
endpoints and for more
chemicals while reducing the use
of vertebrates for testing.
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CECs requires collaboration with EPA partners and stakeholders in developing fit-for-purpose case
studies.
Output:
•	Develop the Per- and Polyfluoroalkyl Substances (PFAS) screening library and deliver
information from integrated exposure and effects studies. (HTT Output CSS.1.6)
The majority of existing HTT methods are based on human or other mammalian species, which results in
an underrepresentation of pathways that are relevant to some ecological species. Although advanced
extrapolation techniques can be used to infer activities across species where the toxicological target is
taxonomically conserved, determining potential ecological impacts of chemical exposure requires
alternative species approaches for high-throughput toxicity testing.
Output:
•	Develop, evaluate, and apply non-mammalian, high-throughput toxicity tests for priority
endpoints and pathways in ecological species. (HTT Output CSS.1.7)
Research Area 2: Rapid Exposure Modeling and Dosimetry
The Rapid Exposure Modeling and Dosimetry (REMD) Research Area addresses multiple EPA program
office needs for exposure and dosimetry information. REMD will develop data, tools, models, and
approaches to rapidly generate scientifically defensible exposure and dosimetry estimates for new and
existing chemicals and chemical mixtures found in consumer products and the environment. This
research will also include development of advanced chemical monitoring approaches, refinement of
exposure pathways and factors, and high-throughput toxicokinetics to support dosimetry estimates
associated with HTT hazard data. In concert with the toxicity information generated in the HTT Research
Area, estimates of human and ecological exposures developed in REMD represent critical inputs for
high-throughput, risk-based prioritization and screening of chemicals and chemical mixtures.
Experimental measurements and predictive modeling are
essential components in exposure assessment. While
collection of measured data is important to refine and
improve chemical exposure models, it is particularly
important to have confidence in exposure models when they
are the only means of estimating exposures for pathways with
limited source emissions data and data-poor parameters.
Currently, the collection of monitoring data and other model
inputs lag behind the data needs for model development. As a result, the focus of several REMD outputs
is to address the gaps in data collection and the curation of model inputs.
Outputs:
•	Collect and curate exposure factor-related data (behavior patterns, habits and practices,
product composition, and monitoring data) from publicly available sources for use as inputs
to models used in regulatory assessments of human or ecological risk. (REMD Output
CSS.2.1)
Products from the REMD Research
Area will provide chemical
exposure information supporting
risk assessments conducted by EPA
partners and stakeholders for both
new and existing chemicals.
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•	Develop consensus exposure models for various exposure pathways (e.g., consumer,
occupational, ambient, indoor environment, and ecological scenarios) that enable high-
throughput exposure predictions for chemicals. (REMD Output CSS.2.2)
•	Develop end-of-use models for tracking chemicals in waste streams and the subsequent
environmental releases and worker exposures, including novel end-of-life scenarios based
on chemical type and function. (REMD Output CSS.2.3)
•	Expand capabilities of generic scenario processes by minimizing development time and
increasing the number of available scenarios. This includes developing models and tools for
estimating common scenario needs, data, and methods for estimating new chemical
applications, life cycle releases, and occupational exposure support. (REMD Output CSS.2.4)
•	Develop methods, approaches, and frameworks to enable rapid exposure evaluations for
PFAS chemicals. (REMD Output CSS.2.5)
Uncertainties in relating in vitro assay doses to human environmental exposure concentrations limit
application of high-throughput data to chemical safety decisions. To address these uncertainties, rapid
toxicokinetic approaches are needed to convert the estimates of route-specific doses generated by the
exposure models to the corresponding measures of internal dose (i.e., concentrations at tissue and
organismal levels).
Output:
•	Further develop high-throughput toxicokinetic (HTTK) tools to support in vitro to in vivo
extrapolation. Tools to be developed include those needed to address current sources of
uncertainty, challenging chemistries, new exposure routes (e.g., inhalation), and the unique
exposures received by sensitive subpopulations. (REMD Output CSS.2.6)
Estimating chemical exposures requires accurate identification of chemicals occurring in the
environment. Current methods and tools characterize only a fraction of chemicals in the environment
and struggle to characterize certain materials. The REMD research area is developing models and tools
to address data needs for the composition and exposure potential of environmental media, including
consumer products.
Outputs:
•	Develop, evaluate, and apply next-generation monitoring methods, alongside traditional
monitoring methods, to identify critical sources and pathways of human and ecological
exposures. (REMD Output CSS.2.7)
•	Develop methods to characterize composition of and exposure to chemical substances of
unknown or variable composition, complex reaction products, and biological materials.
(REMD Output CSS.2.8)
Research Area 3: Emerging Materials and Technologies
Innovations in chemical and material design are rapidly changing the landscape of industrial and
consumer products. For example, novel materials, such as engineered nanomaterials (ENMs), are
incorporated into products to enhance their performance. Emerging materials and technologies often
have unique physicochemical properties, warranting specialized approaches for evaluating hazard and
exposure. The Emerging Materials and Technologies Research Area will develop, collate, mine, and apply
information on ENMs and potentially other emerging materials and technologies, such as biotechnology
products, to support risk-based decisions.
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Understanding the final disposition of ENMs is important to assessing their application-specific safety
and is challenging since the release of and exposure to ENMs through product use, aging, degradation,
decomposition, and recycling can be uncertain. For instance, previous research has shown that ENMs
released from consumer products are often altered from the ENMs used in the manufacturing of those
consumer products. Factors affecting the release and exposure to humans and ecological species vary
according to ENM type, product type, product use, environmental conditions, and receiving media type
The following output will evaluate exposure situations that capture a range of priority scenarios,
nanomaterials, and product types.
Output:
• Evaluate environmental release of ENMs and
assess and model human and ecological
exposures to ENMs, including data for nano-
enabled consumer products. (EMT Output
CSS.3.1)
To provide a centralized resource for Agency partners and
stakeholders, ORD developed NaKnowBase (Boyes et al.,
2017), a database that captures information from Agency
research on ENMs. The database was designed to be
consistent with the fields and format of external databases
yet needs to be integrated within the broader CSS research
portfolio to maximize utility. CSS intends to partner with
member agencies and departments of the National
Nanotechnology Initiative, and the Nanotechnology
Environmental and Health Implications (NEHI) Working
Group as we further develop NaKnowBase.
Output:
•	Develop a user interface for ORD's existing nanomaterials database: NaKnowBase. (EMT Output
CSS.3.2)
Recent advances in biotechnological approaches and methods have the potential to hasten the
development and use of novel biotechnology products that may need to be evaluated by the Agency.
Product submissions using emerging biotechnology are on the rise and EPA program offices may
encounter product types for which they have limited experience. Therefore, building on the
recommendations of the 2017 NAS report, Preparing for Future Products of Biotechnology (National
Academies of Sciences, Engineering, and Medicine, 2017a), it is prudent to anticipate future research
needs and build the scientific capabilities required to address the expected growth of diverse
biotechnology applications.
Output:
•	Evaluate the current regulatory approaches for products and processes involving emerging
biotechnology (synthetic biology, genome editing, and metabolic engineering) and determine
future research needs to support risk assessments. (EMT Output CSS.3.3)
The EMT Research Area will
deliver products that inform
Agency decisions related to
chemicals and chemical materials
manufactured using new
technologies or packaged in novel
forms. This research area
currently informs risk-based
decisions for nanomaterials. It
also includes work on
biotechnology to anticipate and
inform problem formulation for
this emerging technology.
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Topic 2: Complex Systems Science
Research conducted in the Complex Systems Science topic will build the scientific foundation to predict
adverse outcomes resulting from chemical exposures in various biological contexts. This topic will
develop interpretive frameworks and models to put complex information into biological, chemical, and
toxicological context. The Adverse Outcome Pathways (AOP) Research Area focuses on delineating
perturbations of specific biological pathways and applying that knowledge to predict apical outcomes
based on mechanistic effects. The Virtual Tissue Modeling (VTM) Research Area is bridging the gap
between molecular/cellular endpoints and apical outcomes by developing tissue-on-a-chip and in silico
models, with an emphasis on human developmental endpoints. The Ecotoxicological Assessment and
Modeling (ETAM) Research Area will develop integrated approaches to model ecological outcomes
across broad taxonomic and ecological scales.
Research Area 4: Adverse Outcome Pathways
Employing data from new approach methodologies in decision making, such as those being generated
by the HTT and REMD research areas, requires understanding the role of endpoint measurements in the
perturbation of one or more biological pathways. The Adverse Outcome Pathway (AOP) framework
provides a systematic and modular structure for organizing and communicating existing knowledge
concerning the linkage between chemical exposure (molecular initiating event), intermediate key events
along a toxicity pathway, and apical adverse outcomes considered relevant to risk assessment or
regulatory decision making. AOPs provide a scientifically-defensible foundation for extrapolating from
mechanistic data to predicted apical outcomes. AOP
networks can be assembled by evaluating shared nodes or
key events in individual AOPs, thereby providing insight into
the complex interactions among biological pathways.
Whether through individual pathways or pathway networks,
the interactions of multiple chemicals present in both simple
and complex mixtures will be assessed to facilitate analyses
of more realistic environmental exposure scenarios. The AOP
Research Area will continue to develop AOPs for high-
priority pathways and will emphasize the application of well-
developed and curated AOPs to address stakeholder needs
through case study examples.
Successful AOP development is based on having sufficient fundamental knowledge about biological
pathways to define and link the results of a perturbation to an adverse effect. Information generated
from the HTT, REMD, and VTM research areas will contribute to this knowledgebase to inform AOP
development. The outputs under this research area collectively address the need for developing priority
pathways, quantitative AOPs for well understood pathways, and novel pathways relevant to
underrepresented biological space.
Outputs:
• Coordinate with the scientific community to advance the AOP framework, grow the AOP
knowledgebase, and foster broader acceptance and use of AOPs in decision making. (AOP
Output CSS.4.1)
Products from the AOP Research
Area will provide partners and
stakeholders with a common,
integrated framework with which
to link chemical hazard and
exposure information from new
approach methodologies, and
better understand linkages
between molecular initiating
events and apical endpoints.
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•	Develop and conduct strategic in vitro and in vivo studies for high-priority AOPs to help
establish validity of NAMs approaches, support predictive model development, and reduce
vertebrate animal testing through in vivo testing refinements for decision-relevant
endpoints. (AOP Output CSS.4.2)
•	Conduct studies to elucidate and define biological points of departure and susceptibility
factors that need to be considered for quantitative application of AOPs. (AOP Output
CSS.4.3)
AOPs are intended to serve the needs of decision makers, in addition to identifying data gaps that can
be addressed to reduce uncertainty in chemical safety evaluations. Case studies provide critical
opportunities to facilitate the application of AOPs by decision makers, while at the same time informing
the science needed to support AOPs. The outputs below represent specific applications of AOPs in the
context of partner issues.
Outputs:
•	Develop rationale and case studies that apply AOPs and HTT data to inform test-order
decisions and establish scientific support for waiving testing requirements for pesticides as
part of the implementation of FIFRA. (AOP Output CSS.4.4)
•	Provide AOP knowledge along with conceptual frameworks and case study demonstrations
that support the use of high-throughput or other NAMS data in expedited risk assessments
for data poor chemicals. (AOP Output CSS.4.5)
•	Conduct case studies that demonstrate how pathway-based data from existing sources, or
from effects-based monitoring and surveillance approaches, can be used along with AOPs to
inform risks and associated management actions. (AOP Output CSS.4.6)
•	Develop AOPs relevant to human health and ecological impacts of perfluoroalkyl substances
(PFAS) and evaluate applicability across species, chemical groupings, and mixtures. (AOP
Output CSS.4.7)
Research Area 5: Virtual Tissue Modeling
To bridge the gap from molecular changes to endpoints relevant
for hazard assessment, models of biological systems are needed
that can be experimentally probed and computationally
simulated. Virtual tissue models connect in vitro and in vivo
observations with complex tissue- and organ-level changes. The
Virtual Tissue Modeling (VTM) Research Area will focus on
developing organotypic culture models and computational agent-
based models to test hypotheses regarding organ-specific toxicity
of priority chemicals, including pathways and endpoints relevant
to human developmental toxicity.
Agency partners and stakeholders support a tiered-testing
strategy for characterizing hazards associated with chemical
exposures. In tiered approaches, high-throughput data identify chemicals of potential concern.
Increasingly more specific secondary assays are then used to link molecular/cellular effects with an
apical outcome. To support tiered toxicity-testing approaches, the VTM Research Area will develop data
and methods to link high-throughput mechanistic toxicity data with apical outcomes at the organ or
tissue level.
The VTM Research Area will
provide physical models and
mathematical simulations of
specific organ systems and
developmental outcomes
informing risk-based assessments
of new and existing chemicals. This
research area expands
understanding of chemical effects
on developmental and
reproductive toxicology.
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Output:
•	Develop, characterize, and apply organotypic and complex tissue models that bridge the gap
between in vitro and organismal assays for decision-relevant endpoints. (VTM Output
CSS.5.1)
Chemical exposures on the developing embryo are important to understand, yet there are limited
developmental toxicity data available for most chemicals. Further, the ability to predict developmental
toxicants depends on understanding how developmental processes are impacted by chemical exposure.
To address these data gaps, VTM research will focus on applying organotypic and complex tissue models
to chemicals of programmatic importance. This will result in data from assay systems with increasing
levels of biological complexity that reflect morphological, functional, and behavioral impacts that are
relevant to the developing embryo.
Output:
•	Integrate and evaluate phenotypic responses in human cell-based in vitro- and virtual tissue-
model systems to predict chemical hazard during growth and development. (VTM Output
CSS.5.2)
Ultimately, effects of chemicals on human development must be modeled either through extrapolation
approaches, based on mammalian data, or through computational approaches. The focus here is the
latter, where sophisticated computational models are developed that recapitulate human
developmental processes and emulate their perturbations. These models are dependent on HTT and
AOP approaches and will be informed by relevant NAM data.
Output:
•	Develop and apply in silico agent-based and computational models to evaluate the effects of
chemicals on biological pathways critical for life stage endpoints. (VTM Output CSS.5.3)
Research Area 6: Ecotoxicological Assessment and Modeling
A tiered risk assessment approach is typically used to evaluate and regulate the potential impacts of
pesticides and other chemicals on ecological resources. Chemicals are first screened using rapid
assessment tools that require minimal data, followed by more detailed and complex assessments for
selected chemicals and scenarios. For most chemicals and ecological species, assessments must rely on
modeled estimates of exposure and effects. The Ecotoxicological Assessment and Modeling (ETAM)
Research Area will advance efficient and integrated
modeling approaches to improve risk assessments of
chemicals with limited data, as well as more complex,
refined approaches that can address data-rich applications.
The integrated models span the sequence of events typical
of ecological toxicity, including environmental release, fate
and transport, exposure, internal dosimetry, metabolism,
and toxicological responses relevant to organismal- and
population-level effects in species of interest to Agency
decisions.
Determining effects of chemicals on ecological species relies heavily on predictive models at scales that
are not readily testable, for species that cannot be tested directly, and for spatio-temporally complex
Products from the ETAM Research
Area inform understanding of
chemical impacts on ecological
species and include both
ecotoxicological- and exposure-
related measurement and modeling
activities to inform cumulative risk
assessment
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chemical exposure scenarios. Integrated environmental fate and transport, exposure, and ecotoxicity
models and tools will be developed and demonstrated through case study applications, including
probabilistic models for species and chemicals of interest.
Outputs:
•	Develop and apply models to translate data from submitted studies into input for models
that estimate population- and landscape-level impacts of pesticide use. (ETAM Output
CSS.6.1)
•	Develop methods and data to assess the impacts of pesticides on honey bees (Apis
mellifera) and non-Apis bees, apply species extrapolation techniques to determine
sensitivity differences across species, and further develop and apply honeybee colony
simulation models to support pesticide assessments. (ETAM Output CSS.6.2)
The ECOTOX Knowledgebase5 is a curated, interactive database of ecotoxicological information
developed by ORD. Outputs from the ECOTOX Knowledgebase are foundational for the majority of
Agency ecological assessments and are widely used by partners and stakeholders.
Output:
•	Improve efficiency, enhance analytical capabilities, and periodically update content of the
ECOTOX Knowledgebase, in general and for specific chemicals of interest. (ETAM Output
CSS.6.3)
Extrapolation across species is often a challenge in ecological assessments due to limited availability of
ecological toxicity data across broad taxonomic spaces of interest. The CSS outputs will include
extrapolation models for species sensitivity, use of surrogate species to fulfill data needs for untestable
species, differences in endpoint responses across taxa, and differential metabolic capabilities and
capacities between species.
Output:
•	Advance approaches for using surrogate species in ecological risk assessment, including
assessment of uncertainty of cross-species extrapolations in minimal data scenarios,
evaluation of species-response to high-priority pesticides, and extrapolation from
mammalian- to fish-metabolism pathways. (ETAM Output CSS.6.4)
Ecological toxicity assessments are necessary to evaluate the potential hazards of contaminants in the
environment. The outputs fill critical needs to conduct these assessments, which employ a broad range
of species and endpoints, including molecular biomarkers of exposure and effects, and will be evaluated
with field samples collected from impacted sites. Integrated exposure and effects models will be
developed for listed species and chemicals with demonstrated co-occurrence.
Output:
•	Develop improved approaches to protect threatened and endangered species from
cumulative exposures to pesticides released to the environment. (ETAM Output CSS.6.5)
Methodologically challenging chemicals (MCCs) are chemicals whose physicochemical properties and
behaviors are outside the domain ranges of existing predictive tools, methods, and models. Thus, new
5 https://cfpub.epa.gov/ecotox/
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approaches are needed to determine the toxicological effects and ecological impacts of the high-
priority MCC chemicals, including PFAS. Products associated with this output will use field and
laboratory approaches to address biotransformation, bioaccumulation, and effects of MCCs in non-
mammalian species.
Output:
• Improve ecological methods and models for predicting exposure, accumulation, and effects of
PFAS and other methodologically challenging compounds. (ETAM Output CSS.6.6)
Topic 3: Solutions-Driven Translation and Knowledge Delivery
Research in the Solutions-Driven Translation and Knowledge Delivery Topic will deliver data and
information resources relevant to chemical safety evaluations in a scientifically robust, transparent
manner. This work will aid the translation of these approaches by evaluating, establishing, and
demonstrating their effectiveness to EPA partners through program-specific applications. The intended
impact is for risk assessors and decision makers to have confidence that the new approaches, data, and
tools developed in CSS are scientifically sound and improve environmental decision making. The
Chemical Safety Analytics (CSA) Research Area will provide highly curated chemical information and
develop predictive approaches for chemical safety evaluations. The Informatics, Synthesis, and
Integration (ISI) Research Area will develop the online tools and platforms to integrate chemical
information to facilitate better access to that information by Agency partners and stakeholders. This
topic will make information accessible and usable through web-accessible applications, workflows, and
advanced modeling enabled through interoperable systems.
Research Area 7: Chemical Safety Analytics
Curated data and scientifically defensible, transparent, and
publicly accessible models are required for Agency chemical
safety decisions, yet many chemicals lack sufficient
information on hazard, exposure, and dosimetry,
particularly for susceptible populations. To address these
data gaps, the Chemical Safety Analytics (CSA) Research
Area will develop predictive models and tools to establish
common principles linking biological and chemical
properties to toxicity, environmental persistence, and
transformations in environmental and biological systems. In some cases, other CSS research areas (such
as HTT, REMD, and ETAM) will be a data source for the predictive models and tools produced by the CSA
Research Area. Case studies will be conducted with partners and stakeholders to evaluate fit-for-
purpose applications. The data, tools and models developed by the CSA Research Area will be available
through the CompTox Chemicals Dashboard6 (Williams et al. 2017).
CSS research products include an expanding array of datasets, models, and tools providing chemical,
hazard, exposure, pharmacokinetic, and environmental fate information. Efficiently assembling and
integrating these data and tools is essential to inform chemical safety decisions. To support Agency
partners and stakeholders, CSS outputs support data integration and interpretation in fit-for-purpose
applications.
The CSA Research Area provides
predictive tools to estimate hazard
and exposure information for data
poor chemicals supporting risk-
based decisions by Agency
partners and stakeholders.
6 https://comptox.epa.gov/dashboard
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Output:
•	Continued expansion of content and refinement of processes associated with curation and
quality assurance documentation for databases and lists of chemical substances, structures,
and samples. (CSA Output CSS.7.1)
Ecological risk assessments are required to make chemical safety decisions for a variety of species, yet
often toxicological data do not exist for species of interest. Approaches to extrapolate existing hazard
information across species are needed. To address this need, CSS developed the SeqAPASS tool7 using
biological conservation of protein targets to broadly assess potential species susceptibility differences to
chemical exposures. Expanding SeqAPASS tools and associated species extrapolation models is
necessary to support Agency partner and stakeholder needs for taxonomic relevance of AOPs and cross-
species extrapolation.
Output:
•	Develop data, tools, and models to inform the taxonomic relevance of AOPs and to support
cross-species extrapolation for human health and ecological assessments. (CSA Output
CSS.7.2)
Physical, chemical, and biological transformation of chemicals in the environment and endogenous
metabolism can contribute to uncertainties in estimating or predicting exposure and dosimetry. This
output focuses on tools to estimate transformation and metabolic products to predict the toxicity of
metabolites and environmental transformation products, and to reduce uncertainty in chemical
prioritization and risk assessment.
Output:
•	Expand modeling capabilities to predict potential metabolites and environmental
transformation products for priority chemicals, including emerging contaminants. (CSA
Output CSS.7.3)
In the absence of sufficient physicochemical or toxicological data, chemical safety assessments rely on
predictive approaches to estimate parameters. New Quantitative Structure Activity Relationship (QSAR)
models and read-across methods are needed to predict toxicity values and fill data gaps for ranking and
prioritizing chemicals. This output includes web tools for high-throughput prediction of toxicity and
physical properties and features to visualize toxicity data for multiple chemicals and toxicity categories.
Outputs:
•	Develop new and improve existing structure activity relationship models to support risk
assessment for industrial chemicals, pesticides, and emerging contaminants. (CSA Output
CSS.7.4)
•	Further develop and apply chemotype enrichment approaches and
categorization/classification schemes to support local chemical domain modeling and read-
across workflows for aiding the interpretation and prediction of bioassay/toxicity outcomes.
(CSA Output CSS.7.5)
7 https://www.epa.gov/chemical-research/sequence-alignment-predict-across-species-susceptibility
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Research Area 8: Informatics, Synthesis, and Integration
High-throughput NAMs, coupled with continually expanding
amounts of traditional toxicological and exposure data, enable
more informed chemical safety decisions, assuming data are
available and can be integrated. The Informatics, Synthesis,
and Integration (ISI) Research Area will develop approaches to
present, manage, and utilize the large data streams from CSS
research and relevant external data sources. ISI efforts will
include partnerships with Agency partners and stakeholders to
design systems and approaches to integrate these data into
existing assessment workflows and apply these data to
chemical safety decisions. The ISI Research Area is the
keystone for data dissemination and translation in the CSS research program.
CSS research has developed data, tools, and products to meet Agency partner and stakeholder needs.
These products were developed in multiple research projects, resulting in collections of data and tools
across online databases and websites. To increase efficiency in product development and deployment,
as well as meet the regulatory needs of our partners, it is necessary to formulate a comprehensive
Information Technology (IT) infrastructure. ISI outputs support development of this IT infrastructure and
advanced analytical models to address partner and stakeholder needs.
Outputs:
•	Develop unified and extensible software infrastructure to support all ISI data streams and
applications, integrating legacy and new applications, data streams and models. (ISI Output
CSS.8.1)
•	Develop and deliver rapid assessment workflows and applications for chemical evaluation
across a range of hazard and/or risk-based decision-contexts using multiple data streams,
models and visualizations. (ISI Output CSS.8.2)
•	Develop informatics to support rapid and seamless use of hazard, exposure, NAM and other
data streams in decision making, as applications advance beyond prioritization into higher
tier assessments. (ISI Output CSS.8.3)
•	Continued development and curation of databases to support chemical safety decision
making, including mammalian toxicity, exposure, and NAM data. (ISI Output CSS.8.4)
•	Develop, validate, and integrate models to fill data gaps and integrate NAM data to support
chemical safety decision making. (ISI Output CSS.8.5)
•	Develop risk-based approaches and computational tools to prioritize chemicals for program-
specific applications, integrating existing and new data on, for example, chemical properties,
hazard, exposure, persistence, and bioaccumulation. (ISI Output CSS.8.6)
Program Design
The structure of the CSS program for FY2019-FY2022 responds to the evolving needs and priorities of
partners while integrating areas of ORD scientific expertise and capacities that build on past
accomplishments. As such, most of the CSS program components have not changed dramatically from
the previous StRAP. The organizational and structural changes in the current CSS StRAP include:
•	The number of research areas was reduced from 11 to 8.
•	The previous research area, Partner Driven Research and Engagement and Outreach, was
eliminated. Given ORD's emphasis on translational research, which includes being
Products from the ISI Research
Area integrate and synthesize
chemical information in novel and
efficient ways to better inform
specific needs of Agency partners
and stakeholders. This research
area utilizes the mature data
outputs from other CSS research
areas.
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responsive to partners' needs, the objectives of those former projects, focusing on solution-
oriented research and engaging partners, are now embedded expectations across the entire
CSS program.
•	The previous research area, Life Cycle and Human Exposure Modeling, is now combined with
the former Rapid Exposure and Dosimetry research area to form the new research area,
Rapid Exposure Modeling and Dosimetry (REMD). This combination is largely driven by
convergence of the science and improves the integration of previously segregated efforts.
•	The former Sustainable Chemistry research area is refined and renamed Chemical Safety
Analytics (CSA). This change reflects an emphasis on developing analytical tools and
predictive models to inform Agency decisions.
In summary, the current CSS StRAP structure is revised to better meet the changing needs of CSS
partners and stakeholders, while responding to the evolution of chemical safety science. These changes
represent a more focused and efficient research program that is attentive to the priority needs of the
Agency partners and stakeholders.
Solutions-Driven Research
ORD is committed to producing research results that address real-world problems, inform
implementation of environmental regulations, and help EPA partners and stakeholders make timely
decisions based on sound science. This commitment includes improving our research processes through
application of a solutions-driven research framework that emphasizes:
•	Planned partner and stakeholder engagement throughout research planning,
implementation, and product delivery;
•	A focus on solutions-oriented outputs and products that are identified in collaboration with
partners and stakeholders through up-front problem formulation;
•	Coordination, communication, and collaboration among ORD researchers and partners to
develop highly valued, integrated research; and,
•	Cooperation with partners and stakeholders to apply research results to develop solutions
that are feasible and effective.
Consistent with EPA's Strategic Plan, ORD will work with partners to identify the most important
environmental problems they face. Through this engagement, ORD will provide the high-quality science
outputs needed to address their human health and environmental protection priorities for chemical
safety (USEPA, 2019b). Finally, ORD will work with partners and stakeholders to evaluate the usefulness
and effectiveness of the research products in attaining programmatic goals.
Adapting to Changing Needs
CSS has worked to understand the needs of the EPA partners and stakeholders and is responding to
those needs. However, CSS cannot anticipate all future needs. Unforeseen emerging issues arise that
need to be addressed rapidly. In such cases, CSS will provide the responsive scientific support needed to
address emerging issues in a timely manner. This may include redirection of resources and adjustments
to ongoing research and product commitments. CSS has the capability to provide scientific leadership
and technical expertise for a broad range of emerging chemical safety issues and stands ready to
respond accordingly.
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Integration Among Research Programs
ORD's six national research programs are coordinated to provide the science that informs Agency and
stakeholder decisions and actions. The primary focus of CSS is to support OCSPP in implementing the
chemical safety legislation represented in TSCA, FIFRA, and FQPA. Because EPA's programmatic
responsibilities for assessing chemical safety are distributed across the Agency, CSS also provides
support to other EPA program offices. The CSS research portfolio includes the development of data,
tools, and models that are fundamental to the evaluation of chemical safety and are, therefore, relevant
across statutes and their associated programs. CSS research efforts (and associated CSS research areas)
with broad applicability include:
•	Exposure and dosimetry data and models (REMD);
•	Hazard and effects data and models (HTT; AOP; ETAM);
•	Chemical and species extrapolation models (CSA);
•	Cheminformatics resources (ISI); and,
•	Predictive tools and analytical workflows (CSA, ISI).
One area of relevance across ORD's National Research Programs is the consideration of sensitive sub-
populations, such as children, in public health decision making. Although children, like adults, can be
exposed to contaminants in the air, water, soil, dust, food, and consumer products, they may respond
differently based on life stage-specific factors that enhance their sensitivity. CSS is developing and
applying advanced systems science, reflected in both AOP and VTM Research Areas, which are uniquely
positioned to address developmental toxicity in humans. Furthermore, the integration of diverse data
and life stage-specific knowledge of exposure, toxicology, and epidemiology will improve our
understanding of the role of early life stage chemical exposure on latent health impacts that could occur
at any point over the life course.
CSS research activities that complement and support research activities in ORD's other national research
programs are outlined below and are illustrative of program integration.
CSS and SSWR Integration
EPA's Office of Water (OW) is responsive to SDWA, the Clean Water Act (CWA), and other legislative
mandates, and is primarily supported by ORD's SSWR national research program. OW's priorities include
chemical safety issues in drinking water and surface water, notably the development of criteria values,
which establish safe concentrations of specific chemicals. Data, tools, and models originating in CSS are
routinely used by OW to support criteria development. For example, the ECOTOX Knowledgebase is
used in most ambient water quality criteria derivations (CWA, Section 304) conducted by OW and its
partners. Thus, integration and collaboration among CSS and SSWR is critical. Examples of integrative
activities among CSS and SSWR include:
•	Revision of the 1985 edition of Guidelines for Deriving Numerical National Water Quality
Criteria for the Protection of Aquatic Organisms and Their Uses through case studies with
data poor chemicals, including PFAS chemicals;
•	Characterization of PFAS chemical occurrences in surface and groundwater;
•	Evaluation of chemicals of emerging concern in the environment, as needed; and,
•	Characterization of microplastics of nanoparticle size.
CSS and SHC Integration
Programs within EPA's Office of Land and Emergency Management (OLEM) implement the Resource
Conservation and Recovery Act (RCRA) and the Comprehensive Environmental Response, Compensation,
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and Liability Act (CERCLA) and are primarily supported by ORD's SHC national research program. Both
RCRA and CERCLA address hazardous waste issues requiring robust, defensible chemical safety
information. Both OLEM and OCSPP have interest in the recycling of products and materials and how
these materials end up as waste. SHC and CSS are coordinating to better characterize chemical and
product life cycles to more effectively inform exposure scenarios. Through SHC, OLEM also has
programmatic requirements and activities that rely on the CSS ECOTOX Knowledgebase. Additionally,
OLEM has expressed interest in the following topics that are shared by the CSS and SHC research
portfolios:
•	Characterization of PFAS chemicals and transformation products in the environment and
their potential exposure and toxicity;
•	Determination of methodologically-challenging chemical behavior; and,
•	Development of a data informatics architecture and workflows (RapidTox) that support both
TSCA and RCRA activities.
CSS and HERA Integration
Both CSS and HERA national research programs inform Agency activities related to chemical safety. The
two research programs work in conjunction to improve chemical risk assessments, reduce uncertainties
associated with those assessments, and increase the speed of delivering chemical information to Agency
partners. Interactions between the two programs are helping HERA become "early adopters" of the in
vitro and in silico chemical data and the predictive tools being developed by CSS. For example, HERA is
using the EPA CompTox Chemicals Dashboard to inform chemical assessments and incorporate curated
data from HERA systematic review processes. It is anticipated that CSS and HERA will continue to
increase collaborative activities to provide the chemical information and scientifically robust chemical
assessments needed by the Agency. For example, the joint development of the RapidTox Dashboard by
both CSS and HERA allows decision makers to access and integrate available chemical-specific
information in fit-for-purpose applications such as scoping, screening, prioritization, and/or assessment.
CSS and HSRP Integration
Chemical risk assessors and the emergency response community both require access to reliable
chemical information. CSS and HSRP have begun to bring together the information supporting both
groups and are exploring the potential application of the EPA CompTox Chemicals Dashboard as a "first-
stop-shop" for both groups.
Intramural and Extramural Activities
CSS and Extramural Grants
Extramural research funded through grants and contracts complement and expand the reach of ORD's
intramural research program by engaging with external scientists and engineers from academic and
non-governmental organizations. Integral to ORD's efforts to address environmental research priorities,
extramural research engages the scientific community to strategically respond to current and emerging
environmental and public health challenges and help address important scientific knowledge gaps.
CSS uses EPA's Science to Achieve Results (STAR) Grant Program8 to engage with the academic
community through competitive assistance agreements (grants and cooperative agreements). These
grants have supported research that has contributed to significant advances in the field of chemical
safety, providing cutting-edge science that has enabled new avenues of investigation within CSS.
8 https://www.epa.gov/research-grants
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Examples of STAR-funded topics supported by CSS are provided in Table 2. CSS anticipates continuing to
engage with the academic community through STAR to inform and advance the objectives of the CSS
program.
Regional Applied Research Effort (RARE)
EPA's Regional Applied Research Effort (RARE)9 is an Agency program to engage EPA regions in
collaborative research with ORD experts. Topics are proposed by each EPA region that typically address
nearer-term issues of priority to the originating region. ORD resources are used to fund the work. CSS
scientists have been active participants in the RARE program and are currently engaged with EPA Region
8 in an FY2018 RARE project, entitled: Application of 21st Century Bioanalytical Tools to Identify Sources
and Effects of Bioactive Contaminants Associated with Select Municipal Wastewater Discharges to the
South Platte and Colorado River Watersheds.
Table 2. Examples of Recent STAR Grant Award Topics Supported by CSS	
Recent STAR Grant Award Topics Supported by CSS
Advancing Toxicokinetics for Efficient and Robust Chemical Evaluations
Advancing Actionable Alternatives to Vertebrate Animal Testing for Chemical Safety Assessment
Organotypic Culture Models for Predictive Toxicology Centers
Development and Use of Adverse Outcome Pathways that Predict Adverse Developmental
Neurotoxicity
Developing High-Throughput Assays for Predictive Modeling of Reproductive and Developmental
Toxicity Modulated Through the Endocrine System or Pertinent Pathways in Humans and Species
Relevant to Ecological Risk Assessment
Increasing Scientific Data on the Fate, Transport, and Behavior of Engineered Nanomaterials in
Selected Environmental and Biological Matrices
Systems-Based Research for Evaluating Ecological Impacts of Manufactured Chemicals
New Methods in 21st Century Exposure Science
Susceptibility and Variability in Human Response to Chemical Exposure
Innovative Proactive Research
Scientific innovation is the engine that enables pioneering research in CSS. Novel means of fostering
innovation include open innovation challenges, prizes, and award solicitations, both external to ORD and
EPA, and among ORD researchers. Many innovative approaches developed by CSS scientists were
initially supported by ORD's Pathfinder Innovation Project (PIP)10, an internal Agency competition that
challenges ORD's scientists to pursue high-risk, high-reward research ideas. Some previous successes
include, for example, development of novel bioassay approaches (such as "brain-on-a-chip" models) for
developmental neurotoxicity, application of non-targeted analytical methods to detect and measure
previously unknown chemicals in environmental media, and innovative approaches to evaluate
pollinator health. CSS supports the PIP approach and encourages PIP applications. As appropriate, CSS
incorporates the successful innovative developments into its research portfolio.
9	https://www.epa.gov/sites/production/files/2013-12/documents/rare-201304.pdf
10	https://www.epa.gov/innovation/pathfinder-innovation-projects
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Interagency and International Collaboration and Outreach
To meet the short- and long-term science needs of Agency partners, CSS actively collaborates with other
federal agencies and engages with the international scientific and chemical regulatory communities. For
example, the interagency collaboration for the Tox21 project (Thomas et al. 2018) leverages resources
to more efficiently deliver needed chemical information to Agency partners. CSS is actively coordinating
research activities with NIEHS to develop toxicological information for perfluorinated chemicals.
Additionally, CSS scientists are actively involved in interagency discussions focused on developing and
adopting new approach methodologies to toxicity testing.
Internationally, CSS is working with Health Canada and the European Chemicals Agency (ECHA) to
improve approaches for sharing chemical information and to develop improved approaches for
evaluation of environmental chemicals. Of particular note, is ORD's involvement with the initiative to
accelerate the pace of chemical risk assessment (APCRA - Kavlock et al. 2018). These international
efforts acknowledge that the regulation and management of chemicals is a global activity. Chemical
industries operate globally and have an interest in the regulatory community working together to
provide some level of consistency.
Anticipated Research Accomplishments and Projected Impacts
The CSS StRAP FY19-22 emphasizes the application of New Approach Methodologies (NAMs) to solve
problems faced by partners and stakeholders. Although the definition of NAMs varies according to the
different contexts in which it is used (European Chemicals Agency, 2016; ICCVAM, 2018; USEPA, 2018c),
NAMs are broadly defined here as new testing methods (e.g., in vitro, in vivo, in silico, and in chemico),
analytical tools (e.g., transcriptomics, proteomics, metabolomics), predictive computational toxicology
models (e.g., exposure and effects), and informatic and bioinformatic approaches. NAMs serve to inform
and accelerate the pace of chemical safety assessments and support the replacement, refinement, and
reduction of vertebrate animal testing. These include high-throughput and high-content methods, tiered
testing approaches, AOPs, and use of chemical categories for QSAR and read-across applications.
The use of NAMs has gained broad support and is now mandated, for example, by the Frank R.
Lautenberg Chemical Safety Act for the 21st Century. This Act directs EPA to reduce vertebrate animal
testing by using NAMs that "provide information of equivalent or better scientific quality and relevance"
compared to conventional approaches. It requires the Agency to "develop a strategic plan to promote
the development and implementation of alternative test methods." OCSPP and ORD scientists jointly
collaborated on the development of that strategy, which was released as final in June 2018 (USEPA,
2018c) and serves as one of the drivers for the research activities outlined in this StRAP. The
development and application of NAMs will play a central role in realizing substantive impacts across
several programmatic areas, including informing TSCA implementation, enabling EDSP modernization,
and supporting PFAS decisions.
CSS Science Informs TSCA Implementation
In June 2016, Congress passed the Frank R. Lautenberg Chemical Safety for the 21st Century Act, which
revised the 1976 Toxics Substances Control Act (TSCA). The revised TSCA includes much needed
improvements to protect American families from the potential health effects of chemicals, including:
• mandatory requirements for EPA to evaluate existing chemicals with clear and enforceable
deadlines;
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•	risk-based chemical assessments with consideration of potentially exposed or susceptible
subpopulations (such as infants, children, pregnant women, workers, or the elderly) as well
as inclusion of developmental life stages as part of study design;
•	increased public transparency for chemical information; and,
•	a consistent source of funding for EPA to carry out the responsibilities of the new law.
CSS research is actively supporting OPPT's implementation of the amended TSCA by providing chemical
data, information, models, tools, and approaches to improve understanding of chemical hazard and
exposure. Specifically, CSS is assisting with the implementation of the TSCA strategic plan (USEPA,
2018c) for developing and adopting new approach methodologies to reduce, refine, and replace the use
of vertebrates in toxicity testing and evaluation (TSCA Section 4). CSS scientists are also providing
information, tools, and approaches needed to improve and expedite the evaluation of new chemicals
(TSCA Section 5). Additionally, CSS activities are supporting the information, data, and approaches for
prioritizing existing chemicals (TSCA Section 6).
With the implementation of the activities outlined in this StRAP, CSS will provide additional bioassays
and other chemical evaluation approaches that will assist with the implementation of the TSCA
alternative toxicity testing strategy (TSCA Section 4). New and refined tests for developmental
neurotoxicity are planned, as are approaches for screening volatile organic compounds. Additionally,
CSS is moving forward with a proof-of-concept study to evaluate the performance of existing human
three-dimensional lung culture models to identify chemicals with portal-of-entry effects. Ultimately, the
goal of this 3D lung culture work is to develop a non-animal approach to replace the 28-day or 90-day
rodent inhalation toxicity study. Working with OPPT to improve and expedite the evaluation of new
chemicals will be an ongoing priority. Implementing StRAP activities will also improve approaches
currently used by OPPT to evaluate exposures resulting from the use of new chemicals (TSCA Section 6).
This has the potential to decrease the time needed by OPPT to evaluate new chemicals.
TSCA, as amended, requires the Agency to complete assessments of a defined number of chemicals
determined to be high-priority. Initially, OPPT will be turning to the TSCA 2014 Workplan to select high-
priority chemicals for assessment. Ultimately, OPPT would like to have an approach and data in place to
undertake prioritization evaluations of all chemicals actively produced or used in commerce (currently
about 40,000 chemicals). CSS activities are providing data that will inform this prioritization of existing
chemicals. For example, CSS scientists are conducting a proof-of-concept study that will inform further
development of the long-term chemical prioritization process outlined in an OCSPP document released
in September 2018 (USEPA, 2018a). That proof-of-concept study is scheduled to be completed in
FY2020. By the end of this StRAP implementation period, it is expected that OPPT will have the data to
inform prioritization of the TSCA active inventory list, not just those chemicals in the TSCA workplan.
CSS Science Enables EDSP Modernization
The Food Quality Protection Act (1996) contains provisions calling for the screening and testing of
chemicals for endocrine disrupting activity. In response, in 1998 EPA proposed the Endocrine Disrupter
Screening Program (EDSP)11, which was based on the concept of using a two-tiered empirical approach
to screening (Tier 1) and testing (Tier 2). The collection of tests for Tier 1 screening includes in vitro
assays and short-term in vivo assays as indicators of potential disruption of estrogen, androgen, and
thyroid pathways. If a chemical demonstrates potential endocrine disruption activity in Tier 1, then it
can be advanced to one or more Tier 2 tests, which are considered definitive dose-response approaches
11 https://www.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-edsp-overview
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that identify critical-effects concentrations. ORD has a long history of supporting EDSP assay
development, assay validation, and interpretation of test data obtained by the Agency. During the
twenty years of the program, major scientific advancements have been realized in numerous disciplines,
including molecular biology, analytical chemistry, and computational toxicology. In response to these
changes, the EDSP has evolved to take advantage of these developments by incorporating NAMs that
are more efficient, more informative, and reduce the need for vertebrate animal testing. CSS research
and development has been critical to this modernization effort by providing: 1) high-throughput toxicity
testing methods and data for estrogen receptor, androgen receptor, thyroid, and steroidogenesis
pathways; 2) computational models to predict estrogen receptor and androgen receptor activity; and, 3)
adverse outcome pathways to help interpret high-throughput toxicity testing data.
Research activities outlined in the current CSS StRAP will continue to support the evolution of the EDSP
through: 1) completion of computational models for estrogen receptor, androgen receptor activity, and
steroidogenesis; continued development of high-throughput thyroid assays and associated models; 2)
development of species extrapolation approaches; and, 3) development of interactive dashboard tools
for data interpretation, translation, and chemical prioritization.
CSS Science Supports PFAS Decision Making
Per- and poly-fluoroalkyl substances, collectively referred to as PFAS, are a large group of several
thousand man-made chemicals used in multiple consumer products and industrial applications.
Although specific PFAS chemicals, such as PFOA and PFOS, have been studied for over a decade, little
information exists for most PFAS chemicals. CSS is helping to expand information about PFAS chemicals
by:
•	Developing a curated library of PFAS chemicals;
•	Expanding the chemical breadth and biological depth of toxicity information for PFAS chemicals;
•	Improving exposure characterization of PFAS chemicals in the environment; and,
•	Sharing available and emerging PFAS information with EPA partners and stakeholders.
ORD has procured over 400 individual PFAS compounds and developed a curated screening library that
is already being used for high-throughput toxicity and pharmacokinetic testing. With the
implementation of the activities outlined in this StRAP, the library of PFAS compounds will be expanded
and made available to Agency partners, including federal partners (such as NIEHS) and state partners
involved in evaluating PFAS compounds. The library is a one-of-a-kind resource that ensures that EPA's
testing and evaluations are being performed on identically procured compounds.
CSS will expand the biological processes and phenotypic responses affected by PFAS exposure using
existing tiered toxicity testing approaches and by incorporating newer, high-throughput transcriptomic
studies combined with image-based phenotypic profiling. The results of these analyses will expand
ORD's ability to perform chemical read-across activities, identify PFAS categories with the greatest
potential for adverse health effects, inform prioritization for additional in vivo testing, and ultimately
inform risk-based decisions for PFAS chemicals.
In addition to expanding the breadth and depth of knowledge concerning the toxicity of PFAS chemicals,
CSS activities will also expand understanding of PFAS exposure. Already, CSS non-targeted analyses have
been instrumental in identifying PFAS chemicals in the environment and informing Agency enforcement
activities (Strynar et al. 2015). Similarly, non-targeted analysis approaches will continue under this StRAP
and will be used to further characterize the occurrence of PFAS chemicals in environmental media. CSS
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investments will also expand the capabilities of the Chemical Transformation Stimulator to better
predict PFAS degradates that may be detected using non-targeted analysis approaches.
CSS plans to make information about PFAS compounds available using the CompTox Chemicals
Dashboard. The CompTox Chemicals Dashboard is being designed to be the "first-stop shop" for
information about PFAS chemicals. Ultimately, Agency partners and stakeholders will be able to use the
information and tools produced by CSS to inform decisions about PFAS chemicals.
Conclusion
Chemicals are critical to a robust American economy. Thus, efficient, transparent, and scientifically-
sound approaches to chemical safety evaluations are essential. To achieve this, CSS is committed to
supporting partner and stakeholder needs by providing innovative science designed to solve their
priority problems.
CSS seeks to lead the development of new approach methodologies (NAMs) and take advantage of
scientific and technological developments that advance efficient evaluations of chemical safety. Through
a robust intramural research program, collaborations with partners and stakeholders including academia
and other governmental organizations, and through support from an innovative extramural grants
program, CSS will build a broader understanding of biology, chemical toxicity, and exposure while
providing more rapid, cost-effective approaches that protect human health and valued ecological
resources and services.
CSS is committed to translating its work through partner engagement and will maximize the benefits
and impacts of our work through outreach and training. This includes continually improving the
availability of curated information and executing case studies conducted with partners to demonstrate
and improve approaches under real-world circumstances.
CSS will strive to integrate its work within CSS and among other ORD national research programs to
bring added value to the science products that are developed and delivered by the EPA.
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USEPA (2019b). FY 2018-2022 EPA Strategic Plan. (Updated: September 2019). Washington, DC.
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9:61
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Appendix 1: CSS Partner and Stakeholder Needs, Research Areas, and Outputs.
Partner and Stakeholder Needs
Research
Area
Output
Topic 1: Chemical Evaluation
Research Area 1: High-Throughput Toxicology (HTT)
Endocrine Disruptor Screening Program (EDSP): The EDSP has relied
on conventional in vitro and in vivo assays limiting the number of
compounds that can be screened in a timely manner. The EDSP21
framework seeks to use New Approach Methodologies (NAMs) and
computational approaches to rapidly and more cost-efficiently
prioritize and screen chemicals for testing. An additional goal is to
reduce and/or replace the use of animals for testing. To reach these
goals, assays, models, data, tools, and interpretive frameworks are
needed that encompass the modes of action through which
estrogen, androgen, and thyroid signaling, and steroid biosynthesis,
can be disrupted. (OCSPP; OW; Regions; States)
HTT
CSS.1.1: Develop assays, datasets, data analyses, and models to
inform frameworks that support rapid, cost-effective approaches
for screening large inventories of chemicals for bioactivity in the
estrogen, androgen, thyroid, and/or steroidogenesis pathways.
(FY22)
Developmental neurotoxicity (DNT): DNT is an important risk
assessment endpoint for chemical assessments. However, currently
available in vivo methods are costly and do not fully represent
important mechanisms and pathways. Therefore, there is a need for
alternative approaches for evaluating DNT, including valid in vitro
methods and modeling approaches. (OCSPP; OLEM)
HTT
CSS.1.2: Develop, evaluate, apply, and interpret a developmental
neurotoxicity (DNT) battery of assays to reduce uncertainties in
chemical safety evaluations. (FY22)
Methodologically-challenging chemicals (MCCs): MCCs are
chemicals whose physicochemical, behavioral, and toxicological
properties are not well understood typically fall outside of the range
of current assays, models, and analytical methods. There is a need to
develop approaches to measure or model the toxicity and exposure
of these methodologically-challenging chemicals to inform
assessments and decision making. (OCSPP; OLEM; OW; Regions;
States)
HTT
CSS.1.3: Develop and apply medium- to high-throughput,
transferrable methods to test and deliver novel hazard data on
methodologically challenging chemical classes, such as volatile
and non-dimethyl sulfoxide (DMSO)-soluble chemicals. (FY22)
Tiered testing strategies: Tiered testing strategies are used to
evaluate chemical safety in an efficient, risk-based context. These
strategies typically use higher throughput approaches to prioritize
chemicals for subsequent testing and to screen chemicals for
HTT
CSS.1.4: Develop and apply methods to advance a tiered, high-
throughput toxicity testing strategy including high-throughput
and high-content methods (e.g., transcriptomics, phenotypic
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Partner and Stakeholder Needs
Research
Area
Output
potential hazards. There is a continuing need to develop,
demonstrate, and apply emerging technologies to provide actionable
information to support tiered decision making. (OCSPP; OLEM, OW,
Regions, States)

profiling, and other methods) that address key information needs
of assessments. (FY22)
Toxicokinetics: Acceptance and use of in vitro data for hazard
identification, prediction, and estimation is limited, in part, by
uncertainties associated with exposure characterization and
metabolism. Most in vitro systems lack the biotransformation
capabilities of intact in vivo systems, raising the possibility of over-
estimating the hazard of compounds that may be rapidly
metabolized in vivo or under-estimating the hazard of compounds
that may be transformed to more active metabolites. (OCSPP)
HTT
CSS.1.5: Develop and apply methods to incorporate endogenous
and exogenous xenobiotic metabolism into high-throughput in
vitro assays. (FY22)
Per- and polyfluoroalkyl substances (PFAS): PFAS chemicals are
frequently being detected in a variety of environmental media. As a
class, PFAS chemicals are structurally diverse and typically lack
adequate exposure and hazard information needed to support
decisions. (OCSPP; OLEM; OW; Regions; States; Tribes)
HTT
CSS.1.6: Develop the Per- and Polyfluoroalkyl Substances (PFAS)
screening library and deliver information from integrated
exposure and effects studies. (FY22)
High throughput toxicity approaches for ecological endpoints:
Ecological risk assessments address species across diverse taxonomic
groups, many of which have limited or no available data. The clear
majority of HTT methods are based on either human or mammalian
in vitro systems, which results in an under-representation of
pathways that are relevant and perhaps unique to non-mammalian
taxa. (OCSPP; OW)
HTT
CSS.1.7: Develop, evaluate, and apply non-mammalian high-
throughput toxicity tests for priority endpoints and pathways in
ecological species for ecological risk assessment. (FY22)
Research Area 2: Rapid Exposure Modeling and Dosimetry (REMD)
Chemical exposure from consumer products: Exposure models for
consumer products require use patterns and exposure factors to
develop exposure assessments for consumer pathways and specific
consumer users, including potentially exposed and sensitive
subpopulations (as defined in TSCA § 3(12) to include infants,
children, pregnant women, workers, or the elderly). For many
chemicals there are critical gaps in this information. (OCSPP; OCHP;
Regions)
REMD
CSS.2.1: Collect and curate exposure factor-related data (behavior
patterns, habits and practices, product composition, and
monitoring data) from publicly available sources for use as inputs
to models used in regulatory assessments of human or ecological
risk. (FY22)
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Partner and Stakeholder Needs
Research
Area
Output
Chemical exposure scenarios and pathways: Chemical exposure
evaluations require information to estimate exposure for a variety of
high-priority pathways, including scenario-specific data and models
particular to consumer products and materials in the indoor
environment, as well as occupational, ambient and ecological
pathways. (OCSPP; Regions)
REMD
CSS.2.2: Develop consensus exposure models for various exposure
pathways (e.g., consumer, occupational, ambient, indoor
environment, and ecological scenarios) that enable high
throughput exposure predictions for chemicals. (FY22)
REMD
CSS.2.3: Develop end-of-use models for tracking chemicals in
waste streams and the subsequent environmental releases and
worker exposures, including novel end-of-life scenarios based on
chemical type and function. (FY22)
REMD
CSS.2.4: Expand capabilities of generic scenario processes by
minimizing development time and increasing the number of
available scenarios. This includes development of models and
tools for estimating common scenario needs, data, and methods
for estimating new chemical applications, life cycle releases, and
occupational exposure support. (FY22)
Per- and polyfluoroalkyl substances (PFAS): PFAS chemicals are
frequently being detected in a variety of environmental media. As a
class, PFAS chemicals are structurally diverse and typically lack
adequate exposure and hazard information needed to support
decisions. (OCSPP; OLEM; OW; Regions; States; Tribes)
REMD
CSS.2.5: Develop methods, approaches, and frameworks to
enable rapid exposure evaluations for PFAS chemicals. (FY22)
Toxicokinetics: Acceptance and use of in vitro data for hazard
identification, prediction, and estimation is limited, in part, by
uncertainties associated with exposure characterization and
metabolism. Most in vitro systems lack the biotransformation
capabilities of intact in vivo systems, raising the possibility of over-
estimating the hazard of compounds that may be rapidly
metabolized in vivo or under-estimating the hazard of compounds
that may be transformed to more active metabolites. (OCSPP)
REMD
CSS.2.6: Further development of high-throughput toxicokinetic
(HTTK) tools to support in vitro to in vivo extrapolation. Tools to
be developed include those needed to address current sources of
uncertainty, challenging chemistries, new exposure routes (e.g.,
inhalation), and the unique exposures received by sensitive
subpopulations. (FY22)
Chemical exposure modeling: Chemical assessments under TSCA
consider exposure and conditions-of-use information which may be
reflected in monitoring data. Traditional monitoring, while
considered the gold-standard of exposure data, is resource and time
intensive. Therefore, methods and tools are necessary to bring next-
generation high-throughput monitoring data into agency decision
making. (OCSPP)
REMD
CSS.2.7: Develop, evaluate and apply next-generation monitoring
methods, alongside traditional monitoring methods, to identify
critical sources and pathways of human and ecological exposures.
(FY22)
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Partner and Stakeholder Needs
Research
Area
Output
Chemical information for UVCBs: Over half of the substances on the
TSCA inventory are classified as chemical substances of unknown or
variable composition (UVCB) with no definite molecular formula.
UVCB substances generally cannot be characterized using existing
chemical exposure estimation methods. Thus, new methods are
needed to further categorize and characterize UVCB exposure.
(OCSPP)
REMD
CSS.2.8: Develop methods to characterize composition of and
exposure to chemical substances of unknown or variable
composition, complex reaction products, and biological materials.
(FY22)
Research Area 3: Emerging Materials and Technologies (EMT)

EMT
CSS.3.1: Evaluate environmental release of ENMs and assess and
model human and ecological exposures to ENMs, including data
for nano-enabled consumer products. (FY22)
Engineered nanomaterials (ENMs): Safety assessments of ENMs
require information on human and ecological exposure to ENMs
from consumer products and environmental releases. Additional
data are needed to characterize potential release of and exposure to
ENMs. (OCSPP)


EMT
CSS.3.2: Develop a user interface for ORD's existing nanomaterials
database, NaKnowBase. (FY22)
EMT
CSS.3.3: Evaluate the current regulatory approaches for products
and processes involving emerging biotechnology (synthetic
biology, genome editing and metabolic engineering) and
determine future research needs to support risk assessments.
(FY21)
Topic 2: Complex Systems Science
Research Area 4: Adverse Outcome Pathways (AOP)
Pathway framework for New Approach Methodologies (NAMs):
Successful adoption and use of NAMs and pathway-based data in risk
assessments and regulatory decision making depends upon
developing confidence that these methods and approaches provide
equivalent or better scientific quality and relevance than existing
approaches. To achieve this confidence, integrated and synthesized
knowledge are needed to establish the scientific rationale that
support their use in evaluating the potential human health or
AOP
CSS.4.1: Coordinate with the scientific community to advance the
AOP framework, grow the AOP knowledgebase, and foster
broader acceptance and use of AOPs in decision making. (FY22)
AOP
CSS.4.2: Develop and conduct strategic in vitro and in vivo studies
for high-priority AOPs to help establish validity of NAMs
approaches, support predictive model development, and reduce
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Partner and Stakeholder Needs
Research
Area
Output
ecological consequences that are of management or regulatory
concern. (OCSPP: OLEM; OW; Regions; States).

vertebrate animal testing through in vivo testing refinements for
decision-relevant endpoints. (FY22)
AOP
CSS.4.3: Conduct studies to elucidate and define biological points
of departure and susceptibility factors that need to be considered
for quantitative application of AOPs. (FY22)
Pesticide risk assessment: Pesticide risk assessment practices
require data submissions that sometimes do not drive the final risk
assessment directly. In some cases, the data may not be targeted to
toxicological pathways of concern. In others, further analysis and
interpretation of the data are required to inform decision-relevant
endpoints. (OCSPP)
AOP
CSS.4.4: Develop rationale and case studies that apply AOPs and
HTT data to inform test-order decisions and establish scientific
support for waiving testing requirements for pesticides. (FY22)
Data poor chemicals: Chemical assessments and decisions for data-
poor chemicals are often constrained by a lack of ability to generate
or solicit additional toxicity data. Consequently, decision makers
need to both maximize the information they can extract from
available data and utilize predictive approaches and analytical
frameworks to evaluate chemicals. (OCSPP; OLEM; OW)
AOP
CSS.4.5: Provide AOP knowledge along with conceptual
frameworks and case study demonstrations that support the use
of high throughput or other NAMS data in expedited risk
assessments for data poor chemicals. (FY22)
Emerging contaminants and mixtures: Emerging contaminants are
frequently detected in surface waters and other environmental
media, but the toxicological information required to inform decision
making is often lacking. Assessments are further complicated
because these contaminants typically occur in complex mixtures.
Thus, it is difficult to prioritize, monitor, and manage potential risks.
(Regions; States; Tribes)
AOP
CSS.4.6: Conduct case studies that demonstrate how pathway-
based data from existing sources or from effects-based
monitoring and surveillance approaches can be used, along with
AOPs, to inform risks and associated management actions. (FY22)
Per- and polyfluoroalkyl substances (PFAS): PFAS chemicals are
frequently being detected in a variety of environmental media. As a
class, PFAS chemicals are structurally diverse and typically lack
adequate exposure and hazard information needed to support
decisions. (OCSPP; OLEM; OW; Regions; States; Tribes)
AOP
CSS.4.7: Develop AOPs relevant to human health and ecological
impacts of perfluoroalkyl substances (PFAS) and evaluate
applicability across species, chemical groupings, and mixtures.
(FY22)
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Partner and Stakeholder Needs
Research
Area
Output
Research Area 5: Virtual Tissue Modeling (VTM)
Tiered testing strategies: Tiered testing strategies are used to
evaluate chemical safety in an efficient, risk-based context. These
strategies typically use higher throughput approaches to prioritize
chemicals for subsequent testing and to screen chemicals for
potential hazards. There is a continuing need to develop,
demonstrate, and apply emerging technologies to provide actionable
information to support tiered decision making. (OCSPP; OLEM, OW,
Regions, States)
VTM
CSS.5.1: Develop, characterize, and apply organotypic and
complex tissue models that bridge between in vitro and
organismal assays for decision-relevant endpoints. (FY22)
Vulnerable and sensitive subpopulations: Chemical assessments
under TSCA include consideration of risks to vulnerable
subpopulations and life stages and to do so with less reliance on
traditional animal testing. Thus, new approach methodologies
(NAMs) are needed to address potential adverse developmental
outcomes that reflect the best available knowledge of human
developmental biology. (OCSPP)
VTM
CSS.5.2: Integrate and evaluate phenotypic responses in human
cell based in vitro and virtual tissue model systems to predict
chemical hazard during growth and development. (FY22)
VTM
CSS.5.3: Develop and apply in silico agent-based and
computational models to evaluate the effects of chemicals on
biological pathways critical for life stage endpoints. (FY22)
Research Area 6: Ecotoxicological Assessment and Modeling (ETAM)
Pesticide risk assessment: Pesticide risk assessment practices
require data submissions that sometimes do not drive the final risk
assessment directly. In some cases, the data may not be targeted to
toxicological pathways of concern. In others, further analysis and
interpretation of the data are required to inform decision-relevant
endpoints. (OCSPP)
ETAM
CSS.6.1: Develop and apply models to translate data from
submitted studies into input for models that estimate population-
and landscape-level impacts of pesticide use. (FY22)
Pollinators: Assessing the safety of pesticides to pollinators is an
Agency priority. However, methods and data to support evaluation
of effects in honey bees and other non-Apis bees are lacking.
Furthermore, honey bee colony simulation models are needed to
better inform pesticide safety assessments. (OCSPP)
ETAM
CSS.6.2: Develop methods and data to assess the impacts of
pesticides on honey bee (Apis mellifera) and non-Apis bees, apply
species extrapolation techniques to determine sensitivity
differences across species, and further develop and apply
honeybee colony simulation models to support pesticide
assessments. (FY22)
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Partner and Stakeholder Needs
Research
Area
Output
ECOTOX Knowledgebase: Virtually all major ecological risk
assessments and decisions depend on output from the ECOTOX
Knowledgebase. Users of ECOTOX need its content to be current,
reflecting the current state of knowledge. Furthermore, new,
enhanced analytical capabilities and improved data acquisition and
retrieval are needed to better support the varied activities of
numerous partners. (OCSPP: OLEM; OW; Regions; States; Tribes)
ETAM
CSS.6.3: Improve efficiency, enhance analytical capabilities, and
periodically update content of the ECOTOX Knowledgebase, in
general and for specific chemicals of interest. (FY22)
Ecological diversity and species extrapolation: Chemical safety
assessments are often conducted with limited or no toxicological
data for the animal or plant species of interest. Further, it is
frequently impractical to generate new data for those species.
Therefore, the sensitivity of species must be estimated based on
scientifically-based methods of cross-species extrapolation. The
problem is compounded for ecological assessments by the large
number of species in the wild and is particularly problematic for
species listed under the Endangered Species Act. (OCSPP; OLEM;
Regions)
ETAM
CSS.6.4: Advance approaches for using surrogate species in
ecological risk assessment, including assessment of uncertainty of
cross-species extrapolations in minimal data scenarios, evaluation
of species-response to high-priority pesticides, and extrapolation
from mammalian to fish metabolism pathways. (FY22)
Threatened and endangered species models: The Endangered
Species Act outlines requirements to consider potential impacts from
the cumulative exposure to multiple environmental chemicals,
including pesticides. Models are needed to estimate cumulative
exposures and impacts for threatened and endangered species.
(OCSPP; OLEM)
ETAM
CSS.6.5: Develop improved approaches to protect threatened and
endangered species from cumulative exposures to pesticides
released to the environment. (FY22)
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Partner and Stakeholder Needs
Research
Area
Output
PFAS and Other Methodologically-challenging chemicals (MCCs):
MCCs are chemicals whose physicochemical, behavioral, and
toxicological properties are not well understood typically fall outside
of the range of current assays, models, and analytical methods.
There is a need to develop approaches to measure or model the
toxicity and exposure of these methodologically-challenging
chemicals to inform assessments and decision making. (OCSPP;
OLEM; OW; Regions; States)
ETAM
CSS.6.6: Improve ecological methods and models for predicting
exposure, accumulation and effects of PFAS and other
methodologically challenging compounds. (FY22)
Topic 3: Solutions-Driven Translation and Knowledge Delivery
Research Area 7: Chemical Safety Analytics (CSA)
Chemical curation and informatics: Chemical safety decisions and
management can be hindered by the lack of ready-access to the
ever-expanding array of data, tools, and models that are relevant to
the analyses. Even though many chemical safety resources are
available, it may not be clear how the various sources of information
might be combined in targeted, efficient workflows to address their
specific questions. Furthermore, the use of information from
traditionally separate data sources is time-consuming and complex.
(OCSPP; OLEM; OW; Regions; States; Tribes)
CSA
CSS.7.1: Continued expansion of content and refinement of
processes associated with curation and quality assurance
documentation for databases and lists of chemical substances,
structures and samples. (FY22)
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Partner and Stakeholder Needs
Research
Area
Output
Ecological diversity and species extrapolation: Chemical safety
assessments are often conducted with limited or no toxicological
data for the animal or plant species of interest. Further, it is
frequently impractical to generate new data for those species.
Therefore, the sensitivity of species must be estimated based on
scientifically-based methods of cross-species extrapolation. The
problem is compounded for ecological assessments by the large
number of species in the wild and is particularly problematic for
species listed under the Endangered Species Act. (OCSPP; OLEM;
Regions)
CSA
CSS.7.2: Develop data, tools, and models to inform the taxonomic
relevance of AOPs and to support cross-species extrapolation for
human health and ecological assessments. (FY22)
Metabolism and environmental transformation: Regulatory and
management decisions for chemicals often consider
biotransformation and environmental transformation of the
chemical to one or more compounds that may present different
hazards than the parent chemical. Thus, tools are needed to identify
potential transformation products in biological and environmental
systems and to predict the physicochemical properties and toxicity
of these products. (OCSPP; OLEM; States)
CSA
CSS.7.3: Expand modeling capabilities to predict potential
metabolites and environmental transformation products for
priority chemicals, including emerging contaminants. (FY22)
ECOTOX Knowledgebase: Virtually all major ecological risk
assessments and decisions depend on output from the ECOTOX
Knowledgebase. Users of ECOTOX need its content to be current,
reflecting the current state of knowledge. Furthermore, new,
enhanced analytical capabilities and improved data acquisition and
retrieval are needed to better support the varied activities of
numerous partners. (OCSPP: OLEM; OW; Regions; States; Tribes)
CSA
CSS.7.4: Develop new and improve existing structure activity
relationship models to support risk assessment for industrial
chemicals, pesticides, and emerging contaminants. (FY22)
CSA
CSS.7.5: Further develop and apply chemotype enrichment
approaches and categorization/classification schemes to support
local chemical domain modeling and read-across workflows for
aiding the interpretation and prediction of bioassay/toxicity
outcomes. (FY22)
Research Area 8: Informatics, Synthesis, and Integration (ISI)
Chemical curation and informatics: Chemical safety decisions and
management can be hindered by the lack of ready-access to the
ever-expanding array of data, tools, and models that are relevant to
ISI
CSS.8.1: Develop unified and extensible software infrastructure to
support all ISI data streams and applications, integrating legacy
and new applications, data streams and models. (FY22)
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Partner and Stakeholder Needs
Research
Area
Output
the analyses. Even though many chemical safety resources are
available, it may not be clear how the various sources of information
might be combined in targeted, efficient workflows to address their
specific questions. Furthermore, the use of information from
traditionally separate data sources is time-consuming and complex.
(OCSPP; OLEM; OW; Regions; States; Tribes)
ISI
CSS.8.2: Develop and deliver rapid assessment workflows and
applications for chemical evaluation across a hazard and/or risk-
based decision-contexts using multiple data streams, models and
visualizations. (FY22)
ISI
CSS.8.3: Develop informatics to support rapid and seamless use of
hazard, exposure, NAM and other data streams in decision
making, as applications advance beyond prioritization into higher
tier assessments. (FY22)
Pathway framework for New Approach Methodologies (NAMs):
Successful adoption and use of NAMs and pathway-based data in risk
assessments and regulatory decision making depends upon
developing confidence that these methods and approaches provide
equivalent or better scientific quality and relevance than existing
approaches. To achieve this confidence, integrated and synthesized
knowledge are needed to establish the scientific rationale that
support their use in evaluating the potential human health or
ecological consequences that are of management or regulatory
concern. (OCSPP: OLEM; OW; Regions; States)
ISI
CSS.8.4: Continued development and curation of databases to
support chemical safety decision making, including mammalian
toxicity, exposure, and NAM data. (FY22)
Chemical prioritization: Several lists or inventories of chemicals that
may warrant assessment exist, originating in various Agency
programs. The chemicals on these lists typically have limited data to
inform decisions and may require additional studies. Thus, it is
important to prioritize chemicals to focus resources and attention on
those chemicals with the highest concern. The performance of
established prioritization approaches needs to be assessed and more
efficient approaches need to be developed to take advantage of
ISI
CSS.8.5: Develop, validate and integrate models to fill data gaps
and integrate NAM data to support chemical safety decision
making. (FY22)
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Partner and Stakeholder Needs
Research
Area
Output
recently developed predictive tools and models. (OCSPP; OLEM; OW;
Regions; Tribes; States)
ISI
CSS.8.6: Develop risk-based approaches and computational tools
to prioritize chemicals for program-specific applications,
integrating existing and new data on, for example, chemical
properties, hazard, exposure, persistence, and bioaccumulation.
(FY20)
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Appendix 2: Partner and Stakeholder Engagements to Inform CSS StRAP Development.
Meeting Title/Outreach Effort
Frequency/Date
Meeting Purpose
Individual Events
Stakeholder Engagement
Workshop
August 29-30, 2017
The Stakeholder Engagement Workshop was held to discuss how to better connect ORD
staff working on various stakeholder outreach activities, develop a more strategic
approach to ORD stakeholder outreach to maximize the impact of our efforts to be
more efficient with staff time and resources, and to better translate and package
research for stakeholders and partners.
Joint ORD-OPPT Exposure from
Consumer Products Workshop
September 13, 2017
ORD exposure scientists met with OPPT to discuss approaches to evaluate potential
chemical exposure from consumer products. The objective of this workshop was to
exchange information on existing tools and discuss future exposure science related
needs. The workshop helped to identify opportunities for additional collaboration
between ORD and OPPT for the successful implementation of TSCA and informed
development of specific research activities.
Joint ORD-OPPT Occupational
Exposure Workshop
October 12, 2017
The joint ORD-OPPT workshop focused on chemical exposure from consumer products.
CSS-OPPT Discussion of Improving
Exposure Information for TSCA
Chemical Prioritization and
Evaluation
October 20, 2017
As part of ongoing discussions to improve the set of exposure information and tools
available to support TSCA activities, CSS and OPPT scientists met to discuss joint
activities focused on chemical exposure from consumer products and occupational
exposure to chemicals.
Joint ORD-OPPT Ambient
Exposure Workshop
October 31, 2017
This workshop continued ORD-OPPT discussions on improving estimates of chemical
exposure estimates used for the evaluation of new and existing chemicals under TSCA.
The workshops strengthened and expanded working relationships between ORD and
OPPT and expanded the breadth of science that can be used for the implementation of
TSCA.
Translational Science Workshop
November 29-30,
2017
The Translational Science Workshop purpose was to introduce ORD scientists and
managers to the Translational Science for Environment and Public Health framework
and provide training and guidance for implementing the framework in designing,
implementing, and applying ORD research.
FIFRA Scientific Advisory Panel
November 28-30,
2017
The Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA
SAP) met on November 28-30 to discuss the topic of "Continuing Development of
Alternative High-Throughput Screens to Determine Endocrine Disruption, focusing on
Androgen Receptor, Steroidogenesis, and Thyroid Pathways." The SAP provided
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Meeting Title/Outreach Effort
Frequency/Date
Meeting Purpose


comment on a paper prepared by OCSPP and ORD scientists. Input from the SAP helped
inform the development of directions for research activities involving endocrine testing
and screening approaches.
Adverse Outcome Pathways
Workshop
January 17-18, 2018
CSS hosted a workshop involving program (OPPT, OPP, OSCP, OLEM, OW) and regional
office partners to discuss the development and use of adverse outcome pathways
(AOPs). The CSS team collected input on how research partners use AOPs in the
implementation of their programs, what pathways are of most interest and need further
development, and what are the barriers to the use of AOPs.
Federal Information Exchange on
PFAS
February 5-6, 2018
The Federal Information Exchange on PFAS meeting was sponsored by the Toxics & Risks
Subcommittee of the NSTC Committee on Environment, Natural Resources, and
Sustainability, co-chaired by the DoD, EPA, and NIH. This workshop established a
foundation of common knowledge across federal agencies, and facilitated future
information-sharing across federal agencies, from high-level officials to laboratory
researchers.
CSS-HHRA/ECOS Cross-Media
Team Meeting
May 3, 2018
As part of ongoing activities to identify specific research needs from states, CSS and
HHRA met with the Environmental Council of States (ECOS) Cross-Media Team.
3rd Annual STAR Organotypic
Culture Models (OCM) for
Predictive Toxicology Research
Centers Progress Review
May 22-23, 2018
The CSS funded STAR OCM Centers develop cell-based organoids and microscale tissue
systems that collect data on reactions to chemical exposure under normal physiological
conditions. Progress coming from the third year of the OCM Centers, their EPA
collaborators, and other colleagues were presented and discussed at this meeting.
ORD/OCSPP Discussion of
CSS StRAP Development
May 30, 2018
OCSPP senior management provided comments on the initial outline of the topics and
research areas to be included in the CSS StRAP.
National Academy of Science
Meeting
June 7, 2018
CSS staff met with representatives from the National Academy of Science. The purpose
of the meeting was to trade information concerning future directions for our programs
and outline potential research areas of mutual interest.
National Tribal Toxics Council
Meeting
July 17, 2018
CSS and HHRA provided an update on StRAP development for the monthly meeting of
the National Tribal Toxics Council. Presentations focused on the structure of the
revised StRAPs for the CSS and HHRA National Programs and specific research activities
that may be of interest to tribal communities.
Tribal Pesticide Program Council
Meeting
July 18, 2018
CSS provided an update on CSS StRAP development for the monthly meeting of the
Tribal Pesticide Program Council. The presentation focused on the structure of the
revised StRAP, highlighted specific research activities that may be of interest to tribal
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Meeting Title/Outreach Effort
Frequency/Date
Meeting Purpose


communities, and provided details for ongoing research activities for ecological risk
assessment.
National Tribal Science Council
Meeting
July 31-August 1,
2018
ORD National Program Directors provided an overview of StRAP development for the
National Tribal Science Council Meeting. NPDs highlighted specific research activities
relevant to tribal communities and to help address environmental concerns.
ORD/OCSPP Strategic Research
Plan discussion
October 18, 2018
OCSPP senior management provided feedback on the research areas, need statements
and outputs presented in an earlier version of the CSS StRAP. OCSPP ranked 84% of the
stated outputs as high or medium priority.
CSS Webinar for State
Stakeholder Community
March 5, 2019
CSS provided an update and summary of the proposed CSS StRAP and solicited input
concerning specific research topics.
BOSC Chemical Safety
Subcommittee Meeting
April 10-12, 2019
The EPA Board of Scientific Counselors, Chemical Safety Subcommittee were presented
with the draft StRAP for review and comment. BOSC members also had the opportunity
to meet with ORD investigators involved with the development of specific research
areas.
OPPT-ORD Partnership Meeting
April 16, 2019
ORD management meet with representatives from OPPT to discuss specific support for
the implementation of TSCA.
BOSC Executive Committee
Meeting
June 27-28, 2019
ORD National Program Directors received preliminary feedback on draft StRAPs from
the BOSC Executive Committee.
National Tribal Toxics Council
August 26, 2019
CSS briefed the NTTC concerning the structure and content of the CSS StRAP.
CSS Portfolio Discussion with
OCSPP
10/24/2019
CSS and ORD senior management outlined for OCSPP senior management the proposed
portfolio represented by the CSS StRAP. OCSPP senior management expressed support
and thanks for ORD's research planning efforts.
Ongoing Interactions
Developmental Neurotoxicity
(DNT) Work Group
Ongoing/Periodic
Interactions
A DNT Workgroup was formed to bring together researchers from ORD and Program
Office Partners to discuss research needs and approaches for the development of
alternative methods for Developmental Neurotoxicity Testing done in the ORD under
the auspices of the CSS National Research Program.
EDSP Workgroup
Ongoing Bi-
Monthly Interactions
The Endocrine Disruptor Screening Program (EDSP) uses a two-tiered approach to
screen pesticides, chemicals, and environmental contaminants for their potential effect
on estrogen, androgen and thyroid hormone systems. Participants in the EDSP
Workgroup provide expertise, answer questions, draft language, and review important
documents to further the program.
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Meeting Title/Outreach Effort
Frequency/Date
Meeting Purpose
Alternative Testing Strategies
Meetings
Ongoing Tri-monthly
Interactions
Regular meetings July 2017 through June 2018 with ORD and OCSPP to develop and
complete the TSCA Alternative Testing strategy document (USEPA, 2018e).
Quarterly meetings of OCSPP and ORD staff to guide the implementation of the strategy
document.
Children's Environmental Health
Partner Alliance Coordination
Team (CEH PACT)
Ongoing Monthly
Interactions
The Children's Environmental Health (CEH) Research PACT (Partner Alliance
Coordination Team) was formed to facilitate cross-ORD implementation of the CEH
Research Roadmap, enhance communication about CEH research among EPA
researchers, partners and stakeholders, and serve as a resource to EPA leadership on
CEH-related research. The PACT provides materials to Agency partners as needed,
develops CEH research web content, develops CEH relevant RFAs, provides input on CEH
webinar series; workshops, or conferences supported by ORD.
Accelerating the Pace of Chemical
Risk Assessment Meetings
(APCRA)
Ongoing/Periodic
Interactions
These meetings include ORD/PO and representatives from international chemical safety
management regulatory bodies and are focused on case studies leading to
transformational changes in chemical risk assessment.
AOPDD Webinar
Ongoing Monthly
Interactions
The purpose of this Adverse Outcome Pathway (AOP) webinar series is to strengthen
CSS AOP research efforts by facilitating communication and collaboration between CSS,
Program Offices, and Regions.
CSS Science Webinars
Ongoing Monthly
Interactions
The CSS monthly Science Webinars inform internal Agency partners and collaborators of
current and on-going CSS science and enhance communication and collaboration
between CSS, Program Offices, and Regions.
Biotechnology Community of
Practice
Ongoing/Periodic
Interactions
The Biotechnology Community of Practice is an agency-wide group of scientists
exchanging information about the application of biotechnology and the development of
synthetic biology with potential application to environmental problems.
Pollinators Community of
Practice
Ongoing/Periodic
Interactions
The Pollinators Community of Practice was formed to maintain communications among
ORD, Regional, and Program Offices on issues related to pollinator protection, ensure
that ORD's efforts in pollinator research align with Program Office needs.
Program Office Meetings
Ongoing/Periodic
Interactions
The CSS National Program Director and Deputy National Program Director routinely
meet with Agency Program Office Senior Management to discuss progress on ongoing
research activities, deliver completed products, and identify additional research
needs. These meetings occur biweekly, monthly and quarterly, depending upon the
program office.
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Appendix 3: State Needs as Conveyed to EPA by the Environmental Council of the States (ECOS).
Source
Identified State Need
CSS Research Area of Relevance
Water

Water Quality/Surface Water
Quality/GW Quality
New approaches to collecting and analyzing monitoring data (e.g., non-targeted and suspect
screening)
2016


Survey
More work on wastewater
treatment plants and landfills
(Michigan)
Effects-based monitoring and surveillance in conjunction with adverse outcome pathways
(AOPs) to understand risks and management decision associated with wastewater plant
discharges.
Emerging Contaminants

Manage new chemicals of
emerging concern and existing
chemicals
Assays, models, tools, data and interpretive frameworks to screen and prioritize chemicals for
exposure, toxicity, endocrine disruption, and risk; web-based infrastructure (i.e., dashboards)
2016
Survey
Improve and understand
process
Improved access to integrated chemical safety information on exposure, toxicity, and
persistence including information on methodologically challenging compounds
Adapt and respond to
emergencies
Methods, approaches and frameworks for rapid response to emerging high-profile chemicals
such as PFAS in water and PCBs in consumer products; Rapid Assessment workflows and
applications for hazard and/or risk-based decision contexts

More info for PFAS, surface
water standards, fish
consumption and biosolids
advisory levels
PFAS screening library for testing, method development and analyte confirmation; improved
understanding of PFAS uptake and bioavailability in ecological species
Cross-Media
2017-2018
Media
meeting
Help with/alternatives to
choosing emerging
contaminant surrogates for
regulation (Oklahoma)
Fundamental data, knowledge infrastructure, and complex systems understanding for rapid
chemical evaluation and to predict potential impacts
CSS FY2019-FY2022 StRAP
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Source
Identified State Need
CSS Research Area of Relevance

Nanomaterial measurement
(Washington)
Develop, collate, mine, and apply information on engineered nanomaterials to support risk-
based decisions
PFAS
•	Remediation techniques to
accompany EPA's work on
analysis/detection
(Oklahoma)
•	Health and environmental
impacts of PFAS
(Tennessee)
Developing a curated library of PFAS chemicals; expanding the chemical breadth and
biological depth of toxicity information for PFAS chemicals; developing tool to predict
transformation products of PFAS in the environment and improve exposure characterization
of PFAS chemicals
CSS FY2019-FY2022 StRAP
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