Research Strategy 2015-2019 June 2014
Research Strategy
2015-2019
June 2014
LRI Research Strategy 2015-2019
Contents
Executive Summary ....................................................................................................... i
I. The LRI - Addressing Challenges to the Chemical Industry .................................. 1
II. LRI Research Strategy 2015-2019: Research to Support Advocacy Success ..... 2
A. Advance Understanding of Consumer Exposures: Predictive Models for
Generating Exposure Estimates ........................................................................... 3
B. Integrate Hazard and Exposure to Assess Risks from Chemicals: New Tools for
Linking the Data .................................................................................................... 4
C. Improve Chemical Safety Testing Technologies: Design Fit-for-Purpose Assays
and Advance Data Interpretation .......................................................................... 5
III. Building on a Foundation of Success .................................................................... 6
IV. Defining Future Success for the LRI Program ...................................................... 8
V. LRI Research Portfolio 2015-2019 ........................................................................... 9
Figure 1. Evolution of the LRI Research Program ...................................................... 6
Figure 2. Elements for LRI Success ............................................................................ 8
Figure 3. LRI Research Portfolio 2015-2019: Timeline and Milestones .................. 15
Table 1. LRI Research Portfolio – Addressing Challenges to the Chemical Industry
...................................................................................................................................... 10
LRI Research Strategy 2015-2019
i
Executive Summary
The American Chemistry Council’s Long-Range Research Initiative (LRI) is designed to address
the challenges facing the industry in chemical safety assessment. The LRI Research Strategy
2015-2019 outlines an agenda that complements ACC’s advocacy priorities by advancing the
analytical and scientific tools necessary for success in three crucial areas:
Many chemicals in commerce lack exposure data, jeopardizing the industry’s ability to
argue effectively for approaches that integrate hazard and exposure information to
calculate risk. The overwhelming focus of the LRI Research Strategy 2015-2019 is on
developing the tools necessary to quickly and reliably provide exposure information to
assess risks from chemicals and avoid unwarranted product characterization and de-
selection by customers.
The American public and the chemical value chain are increasingly demanding safe
products. The chemical value chain, non-governmental organizations, and even
governments have found that use of hazard data alone to support decision-making is
significantly less costly and burdensome than the efforts required to develop risk
estimations. The LRI Research Strategy 2015-2019 addresses this challenge with a
focus on improving predictive exposure models to establish a basis for safe use of
substances and enhance public confidence.
A considerable amount of research activity and media reports focus on epidemiological
studies that link detection of chemicals in the human body to a variety of adverse health
effects, such as heart disease, obesity, and diabetes. The LRI has funded research in
innovative tools that link exposure and hazard, particularly tools based on
physiologically-based pharmacokinetic (PBPK) models that consider how chemicals are
metabolized by the body and then result in the concentrations measured in humans. The
LRI Research Strategy 2015-2019 continues this effort to evaluate the scientific basis for
associations between chemical exposures and health outcomes.
The LRI-developed methodologies can help meet the requirements for chemical safety
assessments under the proposed reforms of the Toxic Substances Control Act (TSCA) under
consideration in the Congress. They can also serve as a resource for American Chemistry
Council members to address their own product issues regarding hazard, exposure, and risk
assessments; they can support company product-defense efforts, new product development,
and sustainable design of new materials.
LRI research has laid an important foundation for success. Collaborations between LRI
investigators and scientists from federal governmental agencies during the past five years have
been an essential contribution of the LRI program. These collaborations have facilitated
acceptance of LRI outcomes in the broader scientific community and are influencing chemical
safety assessments today.
The LRI is the chemical industry’s investment in research that affirms its commitment to product
safety and stewardship. Through the LRI, the industry is actively engaged in scientific research
that addresses current advocacy challenges and influences the transformation of chemical
safety assessment. The LRI program, in short, is an essential component for ACC advocacy
success.
LRI Research Strategy 2015-2019
1
I. The LRI - Addressing Challenges to the Chemical Industry
Around the world, the chemical industry faces multiple challenges regarding chemical risk
assessment. Scientific research on chemicals is essential for addressing these challenges and
for providing the basis for sound decision making regarding the safe use of chemicals. The
Long-Range Research Initiative (LRI) Program at the American Chemistry Council (ACC) is
industry’s investment in research that affirms its commitment to determine the safety of its
products and supports responsible product stewardship. Current challenges addressed in the
LRI program include:
Lack of Exposure Data for Chemicals Currently in Commerce.
Increasing Public Demand for Safe Products.
Sole Reliance on Hazard Data for Regulatory Decision Making.
The LRI research program advances chemical safety assessment through innovative
approaches and methodologies for evaluating chemicals and products. ACC member
companies can apply these new approaches and methodologies as part of their own efforts to
address issues in hazard, exposure, and risk assessment for their products and to meet the
public demands for product safety information.
The research supported by the LRI is directly relevant to chemical management and advocacy
initiatives within the ACC. This includes Toxic Substances Control Act (TSCA) reform advocacy,
the product research and defense interests of specific panels in ACC’s Chemical Product and
Technology Division (CPTD) and the Plastics Division, and ACC’s Value Chain Outreach
initiative. In each of these areas, the need for high quality and reliable exposure modeling tools
and approaches is paramount to ensuring that risk, and not hazard alone, is the basis for
decision-making about chemicals, whether by regulators, retailers, or the general public.
The LRI Research Strategy 2015-2019 was developed by the ACC’s LRI Strategic Science
Team (SST), which provides oversight and direction for the program. The SST’s deliberations to
develop the LRI Research Strategy 2015-2019 were informed by presentations and by
discussions with members of the Board Science and Research Subcommittee, ACC staff, LRI
investigators, including those from the Hamner Institute for Health Sciences, and
representatives from the United States Environmental Protection Agency (EPA), all of which
provided valuable insights for shaping this document.
LRI Research Strategy 2015-2019
2
II. LRI Research Strategy 2015-2019: Research to Support Advocacy
Success
The LRI Research Strategy 2015-2019 integrates three research areas that focus on developing
solutions to the challenges facing the chemical industry. This section explains the basis for
selection of the three research areas, the proposed research project areas, and the potential
value of the research for the chemical industry.
The overwhelming focus of the LRI Research Strategy 2015-2019 is the challenges presented
by the lack of exposure information on chemicals and by the lack of reliable models for
estimating chemical exposures as well as the need to develop tools to extrapolate exposure
information from test conditions to real-world, human-relevant conditions.
Thus, major projects under the program are oriented toward:
Further development and use of predictive exposure models.
Refinement of tools and approaches that can extrapolate results from in vitro high-
throughput assays to real-world human exposures.
Development of fit-for-purpose assays that consider specific chemical properties and
their relevance to adverse human health effects, such as obesity and diabetes. These
assays will provide targeted assessments for chemicals not currently provided by the
EPA’s ToxCast® assays that were gathered primarily from pharmaceutical sources and
that characterize a broad range of chemical properties.
The LRI Research Strategy 2015-2019 also aims to leverage the valuable collaborative
relationships established during the last five years among the ACC, its LRI investigators, and
scientists from the federal and regulatory agencies. These relationships have been critical in
facilitating acceptance by the broader scientific community of outcomes from LRI research in
chemical safety assessment. These collaborations have been and will continue to be integral for
LRI research for innovations in chemical testing technologies and exposure science. In short,
the LRI program has:
Leveraged ACC research funds with those of governmental agencies.
Optimized use of financial resources for research in areas of mutual interest for chemical
safety assessment with governmental agencies.
Fostered transparency of information related to both methods development and data
generation.
The LRI program thus helps demonstrate the industry’s value as a constructive partner in
providing credible scientific research that focuses on solutions and ensures that industry has a
seat at the table as new technologies for chemical safety assessment are developed and
implemented.
The LRI Research Strategy 2015-2019 proposes three research areas to address the industry
challenges.
LRI Research Strategy 2015-2019
3
A. Advance Understanding of Consumer Exposures: Predictive Models for
Generating Exposure Estimates
The absence of exposure data for the majority of chemicals currently in commerce is a
significant obstacle that limits meaningful assessment of the potential health risks. Indeed, the
chemical industry’s continuing call for risk-based decision-making is likely to fall far short of
expectations if the industry, as a major source for such information, does little or nothing to
address the lack of exposure information.
The importance of exposure information for determining potential risks from chemicals is
highlighted by the proposed legislation to revise TSCA under consideration in both the Senate
and the House of Representatives. Both proposals describe a regulatory approach that relies on
exposure information as the key determinant for chemical risk or safety.
The LRI Research Strategy 2015-2019 will address current gaps in exposure data through
several approaches.
Research Objectives
Develop and improve predictive models for generating exposure estimates. These
exposure estimates will be used for developing a functional tiered framework for
prioritization of chemicals.
Increase information about consumer exposures through innovative approaches to
collate data from industry resources regarding chemical properties as well as product
composition and use information that will comply with concerns about confidential
business information.
Refine the exposure models using the new collated data to capture a broad continuum of
exposure scenarios, particularly for consumer exposures, that can be used by industry
and regulatory agencies for chemical risk assessments.
Value to the Chemical Industry
LRI research can provide exposure information critical for appropriate assessment of the
potential health and environmental risks from chemicals that are the basis for consumer
concerns about industry’s products. This information is relevant to regulatory
determinations, marketplace product defense, and company research efforts.
Predictive models can efficiently and cost-effectively generate estimates for consumer
exposures and decrease the likelihood of premature decisions about chemical
substances based on hazard data alone.
Exposure science research can accelerate evaluation of alternative chemicals and green
chemistry products by more rapidly identifying those new chemical products and
processes that meet safety criteria, have potentially negative health or environmental
impacts, and support sustainable chemical design.
LRI Research Strategy 2015-2019
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B. Integrate Hazard and Exposure to Assess Risks from Chemicals: New Tools for
Linking the Data
Public demands for information about product safety are being driven by ongoing media reports
about epidemiological studies that link detection of chemicals in the body to a variety of adverse
health effects, such as obesity and diabetes. In the absence of adequate scientific information to
respond to these claims, retailers and product manufacturers are opting to de-select certain
chemicals in products, often without a sound scientific basis.
Both hazard and exposure information are essential for determining risk. Recent developments
in chemical testing technologies are revolutionizing chemical safety assessment and rapidly
generating large volumes of hazard data for chemicals; however, these efforts have not been
matched by generation of the exposure data needed to properly characterize risk. Research that
integrates both hazard and exposure information is the key to assessing the potential health
risks of chemicals and assuring their safe use.
Research funded by the LRI during the past decade has been fundamental in developing
innovative tools that link exposure and hazard data and address the public’s health concerns
about risks from chemicals. These tools are based on life stage physiologically based
pharmacokinetic (PBPK) models that were developed through LRI support at the Hamner
Institutes for Health Sciences (Hamner). PBPK models are designed to consider how chemicals
taken into the body are distributed and metabolized and then result in the chemical
concentrations that are measured in tissues, blood, and other fluids.
The LRI-developed PBPK models provide the needed scientific tools to:
Evaluate whether a scientific basis exists for the reported epidemiological associations
between chemical exposures and health effects.
Develop approaches to extrapolate results from in vitro experimental data to real-world
human exposures.
The LRI Research Strategy 2015-2019 outlines research to advance the development and the
use of PBPK models in several project areas.
Research Objectives
Apply PBPK tools to determine whether normal changes in human life-stage and
physiology rather than chemicals per se may account for the reported epidemiological
associations between chemical exposures and human health effects.
Continue support for Hamner’s current collaborative research with the EPA to combine
the human exposure and dose information generated by their PBPK models with hazard
data from the EPA’s ToxCast® high-throughput assays to provide estimates of health
risks.
Refine the generic PBPK models to provide estimates of internal doses of chemicals and
extend development of PBPK models to evaluate different classes of chemicals.
LRI Research Strategy 2015-2019
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Value to the Chemical Industry
LRI research in innovative approaches to provide estimates of internal human doses of
chemicals provides the data needed to advance assessment of risks that can result from
exposures to chemicals.
Development of generic PBPK tools that can be used by companies to assess the
scientific basis for reported epidemiological associations between exposures to their
chemicals and health outcomes, thus decreasing the likelihood of product de-selection
and mischaracterization of potential risks.
C. Improve Chemical Safety Testing Technologies: Design Fit-for-Purpose Assays
and Advance Data Interpretation
The chemical value chain, consultancies, and even governments have found that use of hazard
data alone to support decision making is significantly less costly and burdensome than the
efforts required to develop risk estimations that require exposure information. Indeed, the
emergence of a significant amount of hazard information, including data emerging from EPA’s
ToxCast assays and the Endocrine Disruptor Screening Program, and new tools to use that
information, such as EPA’s ChemView web-based analytical information databases, are making
the job of hazard-based decision making even easier. In the absence of exposure data, some
international agencies and groups are using simple checklist approaches of standard
toxicological tests for the purpose of hazard identification and classification of chemicals.
The LRI Research Strategy 2015-2019 continues work begun in previous years to apply current
innovations in testing technology and leverage emerging technologies.
Research Objectives
Design the next generation of fit-for-purpose assays to address public health concerns
about chemicals. The goal here is to develop specific assays for screening chemicals
that will consider the relevant chemical properties as well as metabolism of chemicals.
Develop multi-tissue bioreactors that combine human cells and tissues to better simulate
chemical exposures and chemical metabolism. The bioreactors will provide results about
chemical metabolites that can be integrated into the fit-for-purpose assay studies and
provide more relevant information about the potential health implications of metabolites.
Benchmark the results from the ToxCast high-throughput assays on chemicals by
comparing those results with results from the very same assays on fruit and vegetable
extracts. The comparison will provide a real-world context for interpreting the ToxCast
assay data in a way that is readily understandable to government regulators, the value
chain, and the public.
Value to the Chemical Industry
Innovations in fit-for-purpose chemical testing will expedite new product development,
sustainable design of new materials, and development of new chemical solutions by
shortening testing times and increasing cost efficiencies.
LRI Research Strategy 2015-2019
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LRI research in new chemical testing technologies can be a key resource for ACC
companies and EPA to address potential requirements under the proposed TSCA reform
legislation and provide an important complement to ACC’s ongoing risk assessment
reform advocacy.
III. Building on a Foundation of Success
Figure 1 describes the evolution in research directions for the LRI program.
The research topics selected for LRI support between 2001 and 2008 are listed on the left side
of Figure 1. This research provided the basis for research suppported between 2008 and 2014,
when the LRI program modified its focus to respond to the growing gap between advancements
in the new technologies and the science needed to interpret and understand the emerging data.
The program topic areas proposed for the 2015-2019 timeframe similarly build on the previous
successes of LRI research.
Since the LRI’s beginning, research conducted at the Hamner has been a core part of the LRI
program and it has yielded significant benefits. The benefits include fostering a well-regarded
center of expertise in chemical safety assessment and research. Hamner researchers have also
served key roles in fostering research collaborations with EPA and other federal agencies;
former senior Hamner and LRI staff members now number among the most active program
managers in EPA’s Office of Research and Development (ORD).
Figure 1. Evolution of the LRI Research Program
LRI Research Strategy 2015-2019
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Building on Success – New Technologies and Chemical Safety Assessment
Results from multiple LRI studies during the past five years were integrated into a risk
assessment framework for data-driven approaches to 21st century toxicology developed
by an international coalition led by Hamner scientists. The framework provides a
practical and risk-based approach to facilitate the use of data from new technologies for
cost-effective and health-protective decisions regarding chemicals.
Collaboration with the EPA’s National Center for Computational Toxicology (NCCT)
resulted in the use of an innovative LRI-supported methodology to incorporate exposure
and dose information with the EPA’s ToxCast® hazard data. This research influenced
EPA’s thinking on chemical prioritization and demonstrated that including exposure
information resulted in better estimations of potential risks.
Hamner investigators challenged the statistical outcomes for the ToxCast® data reported
by the EPA. This project highlighted the unique perspective that industry can bring to
research in chemical safety assessment to provide a critical view of data for evaluating
the potential hazards of chemicals. The outcome of this challenge was that the EPA
acknowledged that the ToxCast data was relevant primarily to chemical prioritization,
and not for complete risk assessments.
The LRI and Hamner’s collaboration with the EPA’s National Center for Environmental
Assessment (NCEA) developed new approaches for integrating genomics into risk
assessment. This research provides important alternative approaches that use shorter
study timeframes, fewer animals, and provide significant cost savings for studies to
evaluate potential chemical toxicity.
Building on Success – Advancing Exposure Science
LRI’s program in exposure science began in 2009, well in advance of the recent interest
in current exposure data gaps that challenge meaningful chemical safety assessment.
LRI‘s foresight in exposure science research is now contributing to an ACC initiative to
provide exposure data relevant to the demands of the proposed TSCA reform legislation.
Three LRI investigator groups are developing predictive models that can provide
exposure estimates for rapid prioritization of chemicals in consumer products. These
models have the potential to be key tools for addressing the current lack of exposure
data for the majority of chemicals currently in commerce and to advance approaches for
high-throughput exposure assessment.
In 2012, the LRI began its ExpoDat Initiative to address an immediate need for exposure
information for human dose estimates for ToxCast chemicals that lack adequate
exposure data. This initiative successfully engaged the three LRI-funded exposure
modeling groups as well as exposure science experts from the EPA, Europe, and
Canada to focus on approaches for maximizing the use of available information to
efficiently provide estimates of exposure. The ExpoDat Initiative demonstrates the LRI’s
ability to bring together the resources and thinking needed to address key issues in
exposure science.
LRI Research Strategy 2015-2019
8
Hamner investigators have incorporated exposure information into the development of
new approaches for evaluating the scientific basis for reported epidemiological
associations between everyday exposures to chemicals and health outcomes. The
Hamner research has provided an approach for alternative interpretations of the
epidemiological studies that can help forestall product mischaracterization and de-
selection.
IV. Defining Future Success for the LRI Program
The LRI Research Strategy 2015-2019 provides an opportunity to foster the early identification
of research results that can be adapted to support shorter-term advocacy and research needs.
Figure 2 identifies three areas where the LRI program will be particularly focused.
Figure 2. Elements for LRI Success
Improved Chemical
Safety Assessment
ACC Advocacy and
Public Policy
Advances in
Communication
Innovations in predictive
models for exposure data
that can fill existing
information gaps and
advance assessment of risks
from chemicals
Development of evidence-
based science that
supports ACC’s advocacy
initiatives
Research outcomes that
increase public confidence
in the products of the
chemical industry
Approaches that integrate
new technologies and
exposure science for
chemical risk assessment
Research approaches for
addressing compliance with
potential TSCA reform
requirements
Quality LRI research that
advances the credibility of
industry science
Approaches for evaluating
new chemicals that more
rapidly and cost-effectively
identify products and
processes that meet the
safety criteria
Continued research
collaborations that provide
a seat at the table with EPA
and other agencies
Effective communication of
research outcomes
regarding advances in
chemical safety for business
executives, the public, and
others
Innovations in chemical
testing to support company
product-defense efforts, new
product development, and
sustainable design of new
materials
Research approaches that
address public demands for
more information about
product safety
Communication of results
from studies that critically
evaluate the scientific basis
for epidemiological studies
linking chemical exposures
to adverse health outcomes
LRI Research Strategy 2015-2019
9
V. LRI Research Portfolio 2015-2019
Table 1 summarizes the LRI 2015-2019 Research Portfolio, including project titles and
comments on each project’s relevance to advocacy and its scientific relevance; the anticipated
budget requirement for each project is also presented. The Gantt chart in Figure 3 illustrates the
timeline and milestones for each of the research projects.
LRI Research Strategy 2015-2019
10
Table 1. LRI Research Portfolio – Addressing Challenges to the Chemical Industry
Project Title
Relevance to Chemical
Management/Advocacy
Initiatives
Project Objectives Collaboration
Opportunities
Estimated
Budget
Advance Understanding of Consumer Exposures: Predictive Models for Generating Exposure Estimates
Develop Predictive Models for
Generating Exposure Estimates
Project 1: Complete the Current ExpoDat Initiative
Project 2: Develop Methods and Approaches to Obtain Key Exposure Factor Data for Predictive Models
Project 3: Refine the Predictive Models Using New Key Exposure Factor Data
Both hazard and exposure information
are essential for proper assessment of
health and environmental risks from
chemicals.
A current concern is that, globally,
regulatory programs are assessing
chemical risks and prioritizing
chemicals using hazard-only
approaches due to the lack of
exposure information.
The goal for these projects is to
provide exposure tools that would be
used for both chemical screening and
prioritization, such as for high-
throughput chemical testing
assessments, as well as more
comprehensive chemical risk
assessments.
Complete a functional tiered framework for prioritization of chemicals that includes the exposure estimates during the first year.
Develop innovative approaches that collate data from industry resources regarding chemical properties as well as product composition and use that will comply with concerns about confidential business information by the end of the third year.
Refine the predictive exposure models with the data from Project 2 to capture a broad continuum of exposure scenarios, particularly for consumer exposures, that can be used by industry and by regulatory agencies for risk assessments.
University of
California, Davis;
University of
Michigan; ARC
Consulting
EPA’s National
Center for
Computational
Toxicology (NCCT)
ExpoCast TM
Program
EPA’s National
Exposure
Research
Laboratory (NERL)
International
regulatory
participation on
ExpoDat
Companies
affiliated with
ACC's value chain
outreach efforts
Project 1:
$150K/2 years
Project 2:
$200K/year
Project 3:
$150K/First 2
years
$300K/Last 3
years
LRI Research Strategy 2015-2019
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Table 1. LRI Research Portfolio – Addressing Challenges to the Chemical Industry
Project Title
Relevance to Chemical
Management/Advocacy
Initiatives
Project Objectives Collaboration
Opportunities
Estimated
Budget
Integrate Hazard and Exposure to Assess Risks from Chemicals: New Tools for Linking the Data
Use PBPK Tools to Evaluate the
Scientific Basis for
Epidemiological Associations
between Chemical Exposures
and Health Outcomes
Evaluate factors, such as life stage, health status, and exposures to other chemicals, that may impact epidemiological associations
Evaluate different classes of chemicals using PBPK tools
Create generic tools that can be used by industry to assess the basis for epidemiological associations
Media reports about epidemiological
studies that link chemicals detected in
the human body to possible adverse
health effects have increased public
demands for more information about
product safety.
This project will provide the tools to
evaluate epidemiological associations
between chemicals and health effects.
Apply PBPK tools and approaches to determine whether normal changes in human life-stage and physiology (rather than chemicals) may account for the epidemiological associations between chemical exposures and human health effects.
Refine the generic PBPK models to provide estimates of internal doses of chemicals, and extend development of PBPK models to evaluate different classes of chemicals.
National Institute of
Environmental
Health Sciences
National
Toxicology
Program
(NIEHS/NTP);
NCCT ExpoCast
Program; NERL
$750K/year
LRI Research Strategy 2015-2019
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Table 1. LRI Research Portfolio – Addressing Challenges to the Chemical Industry
Project Title
Relevance to Chemical
Management/Advocacy
Initiatives
Project Objectives Collaboration
Opportunities
Estimated
Budget
Integrate Hazard and Exposure to Assess Risks from Chemicals: New Tools for Linking the Data
Advance the Use of PBPK
Approaches to Extrapolate from
Experimental Data to Real-World
Exposures
Develop generic PBPK models
Assess key PBPK model parameters
Develop reverse dosimetry and biomarker applications for exposure estimates
Benchmark exposure model outcomes with biomonitoring data
Decision making about how potential
risks from chemicals without the
relevant exposure data may result in
misclassification of risk, product de-
selection, and inappropriate
restrictions on products.
This research will develop tools and
procedures to better estimate internal
concentrations of chemicals from
realistic external exposures.
Continue support for Hamner’s current collaborative research with the EPA to combine the human exposure and dose information generated by their PBPK models with hazard data from the EPA’s ToxCast
® high-throughput assays to
provide estimates of health risks.
NCCT; Centers for
Disease Control
and Prevention;
NIEHS/NTP; The
Center for Food
Safety and Applied
Nutrition (CFSAN);
Integrated
Research
Application
System (IRAS);
National Institute
for Public Health
and the
Environment
(RIVM)/ the
European Centre
for the Validation
of Alternative
Methods (ECVAM)
$1.25M/year
LRI Research Strategy 2015-2019
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Table 1. LRI Research Portfolio – Addressing Challenges to the Chemical Industry
Project Title
Relevance to Chemical
Management/Advocacy
Initiatives
Project Objectives Collaboration
Opportunities
Estimated
Budget
Improve Chemical Safety Testing Technologies: Design Fit-for-Purpose Assays and Advance Data Interpretation
Design the Next Generation of
Fit-for-Purpose Assays
Develop assays designed to evaluate metabolic diseases, such as obesity and diabetes, and specific chemical groups, such as endocrine disruptors
Develop a multi-tissue bioreactor
Assays are under development to
screen for factors that may cause
human diseases, such as obesity and
diabetes. Unfortunately, many of these
assays are not designed to consider
the specific chemicals or their
properties.
This research will design fit-for-
purpose (predictive) assays for health
effects of concern for the chemical
industry.
Design the next generation of fit-for-purpose assays to address public health concerns. The goal is to develop specific assays for screening chemicals that will consider the relevant chemical properties of concern as well as metabolism of chemicals.
Develop multi-tissue bioreactors that combine human cells and tissues to better simulate chemical exposures and metabolism. The bioreactors will provide results about chemical metabolic reactions that can be integrated into the fit-for-purpose assay studies and provide more relevant information about the potential health implications of the metabolites.
NCCT;
NIEHS/NTP;
National Institutes
of Health/National
Center for
Advancing
Translational
Sciences
(NIH/NCATS)
$1.25M/year
LRI Research Strategy 2015-2019
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Table 1. LRI Research Portfolio – Addressing Challenges to the Chemical Industry
Project Title
Relevance to Chemical
Management/Advocacy
Initiatives
Project Objectives Collaboration
Opportunities
Estimated
Budget
Improve Chemical Safety Testing Technologies: Design Fit-for-Purpose Assays and Advance Data Interpretation
Providing Context for ToxCast:
Comparing High-Throughput
Assay Results from Chemicals
with Results from Foods/Dietary
Supplements
“The Fruits and Veggies Project”
This project will compare ToxCast
assay results between chemicals and
every day foods and will provide a
real-world context for interpreting the
ToxCast assay data in a way that is
readily understandable by
governmental regulators, the value
chain, and the public.
Benchmark the results of high-throughput ToxCast assays for chemicals by comparing them to results from those same assays on fruit and vegetable extracts. Additional studies would include comparisons with dietary supplements.
NCCT;
NIEHS/NTP;
NIH/NCATS
$750K/year
LRI Research Strategy 2015-2019
15
Figure 3. LRI Research Portfolio 2015-2019: Timeline and Milestones
Project Name 2015 2016 2017 2018 2019
Advance Understanding of Consumer Exposures
Develop Predictive Models for Generating Exposure Estimates
Project 1: Complete the Current ExpoDat
Initiative
Project 2: Develop Methods and Approaches
to Obtain Key Exposure Factor Data for
Predictive Models
Project 3: Refine the Predictive Models Using
New Key Exposure Factor Data
Integrate Hazard and Exposure to Assess Risks from Chemicals
Use PBPK Tools to Evaluate the Scientific
Basis for Epidemiological Associations
between Chemical Exposures and Health
Effects
Advance the Use of PBPK Approaches to
Extrapolate from Experimental Data to Real-
World Exposures
Improve Chemical Safety Testing Technologies
Design the Next Generation of Fit-for-Purpose
Assays
Provide a Context for ToxCast: Comparison of
High-Throughput Assay Results between
ToxCast Chemicals and Foods/Dietary
Supplements
Milestones
Advance Understanding of Consumer
Exposures
Integrate Hazard and Exposure to Assess Risks
from Chemicals
Improve Chemical Safety Testing
Technologies
1. Pilot a tiered high-throughput exposure chemical prioritization approach
2. Complete a functional tiered framework for prioritization of chemicals that includes exposure estimates
3. Update EPA’s product use categorization database in collaboration with the EPA
4. Develop innovative methods for determining key physical/chemical properties
5. Complete an approach for identifying product composition for selected sentinel products
6. Develop a database of product composition and use information
7. Use information from Project 2 to improve predictive models that capture a broad continuum of exposure scenarios, particularly for consumer exposures
1. Evaluate persistent chemicals using PBPK tools
2. Evaluate non-persistent chemicals using PBPK tools
3. Evaluate factors that may impact epidemiological associations, such as life stage and disease states
4. Design generic tools for assessing basis of epidemiological associations for use by industry
5. Assess key PBPK model parameters
6. Develop reverse dosimetry/biomarker applications for exposure estimates
7. Benchmark exposure estimates with biomonitoring data
8. Complete development of generic PBPK models
1. Develop a multi-tissue bioreactor
2. Develop fit-for-purpose assays that address metabolic diseases, such as obesity and diabetes, and specific chemical groups, such as endocrine disruptors
3. Provide a real-world context for interpreting the ToxCast assay data
1 2 3 4
5 7 8
1 2
3
1 2
3 4 5 6
7
6