Research Strategy 2015-2019 - LRI Overview€¦ · LRI Research Strategy 2015-2019 2 II. LRI Research Strategy 2015-2019: Research to Support Advocacy Success The LRI Research Strategy

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


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.


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.


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.


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.


4

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.


5


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.


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.


6

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


7

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.


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


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.


10


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


11


Project Title


Management/Advocacy

Initiatives


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


12


Project Title


Management/Advocacy

Initiatives


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


13


Project Title


Management/Advocacy

Initiatives


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


14


Project Title


Management/Advocacy

Initiatives


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


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

Documents

Research Strategy 2015-2019 - LRI Overview€¦ · LRI Research Strategy 2015-2019 2 II. LRI Research Strategy 2015-2019: Research to Support Advocacy Success The LRI Research Strategy