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EPA’s Endocrine Disruptor Screening Program (EDSP)

Use of Exposure Data in Priority Setting

Bill WoogeOffice of Science Coordination and Policy/OPPTS

U. S. Environmental Protection Agency

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EPA’s Statutory Authority

Food Quality Protection Act (FQPA) August 3, 1996 Amended the Federal Food, Drug, and Cosmetic Act

(FFDCA) Requires EPA to develop a screening program

(EDSP) using validated test systems and other scientifically relevant information, to identify chemicals that may have estrogenic effects in humans

Requires EPA to test all pesticide chemicals• Both active and inert ingredients

Authorizes EPA to obtain testing on:• Other endocrine effects, as designated by the EPA

Administrator (e.g., androgen and thyroid; endocrine effects in species other than humans)

• Other chemicals (non-pesticides) that “May have “an effect cumulative to that of a pesticide,” if a “substantial human population may be exposed” to the chemical

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EPA’s Statutory Authority

Amendments to the Safe Drinking Water Act (SDWA) Amendments• Allow EPA to require testing of chemical

substances that may be found in sources of drinking water, if a substantial human population may be exposed to the substance

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Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC)

Chartered Oct. 16, 1996 (www.epa.gov/scipoly/oscpendo)

39 members representing a wide range of stakeholders

Recommendations proposed in 1998:• Estrogen, androgen and thyroid• Human and ecological effects• Priority setting for broad universe of chemicals• 2-Tiered Approach

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EDSP Scope & Structure

Two-Tiered Approach• Tier 1

– In vitro and in vivo screens– Detect potential to interact with endocrine system

• Tier 2– Tier 2 data called in only after review of Tier 1 data– Multi-generation studies covering a broad range of taxa – Provide data for hazard assessment

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EDSP Tier 1 Screening Battery EDSP Tier 1 Screening Battery In vitro

Estrogen receptor (ER) binding – rat uterus

Estrogen receptor α (hERα) transcriptional activation - Human cell line (HeLa-9903) [OECD Test Guideline 455]

Androgen receptor (AR) binding – rat prostate

Steroidogenesis – Human cell line (H295R) [US lead, validated in OECD program]

Aromatase – Human recombinant

In vivo

Uterotrophic (rat) [OECD TG 440]

Hershberger (rat) [OECD TG 441]

Pubertal female (rat)

Pubertal male (rat)

Amphibian metamorphosis (frog) [OECD TG 231]

Fish short-term reproduction [OECD TG 229]

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Tier 2 Tests

Mammalian two-generation rat(may be replaced by Extended F1-Generation)

Avian reproduction(Japanese quail) [US lead, OECD validation program]

Amphibian growth/reproduction(Xenopus) [US lead, OECD validation program]

Fish life-cycle(medaka) [US lead, OECD validation program]

Mysid life-cycle [US lead, OECD validation program]

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EDSP Tier 2 Tests EDSP Tier 2 Tests

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EDSP Priority Setting

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Priority Setting

Selection of 50-100 Chemicals based on: • Candidate List from Pesticide Actives Exposure

Pathways– Highest priority for active ingredients identified in all

four pathways;– Decreasing priority for actives found in three, two, or

only one pathway– Within a group, giving precedence to actives that are

identified by the food and occupational pathways• Candidate List from Inerts/HPV Exposure Pathways

– Highest priority for Inerts/HPV chemicals identified for all four types of monitoring data

– Decreasing priority for Inerts/HPV chemicals found in three, two or only one type of monitoring data

– Within a group, giving precedence to Inerts/HPV chemicals that are present in human tissues, followed by presence in drinking water or indoor air, followed by presence in ecological tissues (e.g., fish)

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Exposure Compartments

Human biological monitoring data

Ecological biological monitoring data

Chemicals in food and drinking water

Chemicals in consumer and cosmetic products

Occupational exposure chemicals

Surface water monitoring data

Indoor air monitoring data

Outdoor air monitoring data

Sediments and soil monitoring data

Superfund data TRI environmental

releases Production/Import

volumes

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Pesticide Active Ingredients– Food Pathway

USDA Continuing Survey of Food Intake by Individuals (CSFII)

USDA Pesticide Data Program FDA Surveillance Monitoring

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Pesticide Active Ingredients– Water Pathway

EPA Pesticides in Groundwater Database EPA Chemical-specific Monitoring Data USGS/EPA Reservoir Monitoring Study EPA Environmental Monitoring and Assessment Program EPA National Sediment Inventory EPA National Drinking Water Chemical Occurrence

Database USGS National Stream Quality Accounting Network USGS National Water Quality Assessment Program USDA Pesticide Data Program Water Data

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Pesticide Active Ingredients– Residential and Occupational Pathways

Residential• EPA Pesticide Product Labeling Information

Occupational• Agricultural Reentry Task Force Transfer

Coefficients• USDA National Agricultural Statistics Service

Data• California Department of Pesticide Regulations

Data• AgroTrakTM

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HPV/Inerts– Human Biological Monitoring

NHANES III Priority Toxicant Reference Range Study

HHS/CDC National Report on Human Exposure to Environmental Chemicals

EPA National Human Adipose Tissue Survey

EPA Total Exposure Assessment Methodology (TEAM)

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HPV/Inerts– Ecological Biological Monitoring

EPA National Sediment Inventory Fish Tissue Data

EPA National Fish Tissue Study USGS National Water Quality Assessment

Program

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HPV/Inerts– Drinking Water Monitoring

EPA National Drinking Water Occurrence Database

EPA National Human Exposure Assessment Survey

EPA Total Exposure Assessment Methodology (TEAM)

USGS National Stream Quality Accounting Network

USGS National Water Quality Assessment Program

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HPV/Inerts– Indoor Air Monitoring

EPA/ORD Published Literature EPA National Human Exposure

Assessment Survey EPA Total Exposure Assessment

Methodology (TEAM)

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1st List

67 Chemicals Selected for Initial Screening• 58 Pesticide Active Ingredients and 9 High Production

Volume (HPV) Pesticide Inerts• Announced in Federal Register Notice April 15, 2009• List based on methodology described in Federal

Register Notice September 27, 2005 Inclusion on list based on potential human

exposure• Pesticide Active Ingredients with food, water,

residential, occupational exposure– Chemicals found in multiple pathways

• HPV Pesticide Inerts found– Human and eco biomonitoring– Water and air monitoring

Not a list of “known” or “likely” endocrine disruptors

EDSP Timeline

Proposed Chemical Selection Strategy

Tier I Validation

Tier II Development and Validation

Development of Procedural Framework

Initial List

Final

Tier IScreening

DraftInitial List

….2002 2003 2004 2005 2006 2007 2008 2009 2010 2011…

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EDSP Tier 1 Test Orders

Approximately 750 Test Orders have been issued to:• Registrants of the 58 pesticide active ingredients• Manufactures/importers of the 9 inert ingredients

Test Orders for chemicals are requiring all of the assays in the Tier 1 battery.

Responses to Test Orders due in 90 days Data due 24 months from Test Order issuance EPA will publically post responses

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Future Prioritization for EDSP Tier 1 Screening

Pesticide active ingredients• Current plan is to use EPA’s schedule for re-

evaluating registered active ingredients in the Registration Review program, consistent with EDSTAC and SAB/SAP recommendations

(http://www.epa.gov/oppsrrd1/registration_review/)

Inert ingredients and other chemicals• Develop in vitro and in silico tools that are

integrated with exposure-based metrics– ToxCastTM & ExpoCastTM

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Next Steps/Future Activities

Second List• 2010 Appropriations requires EPA to issue a

second list of at least 100 chemicals by October 30, 2010

• 2nd List will be composed of– Pesticides from Registration Review schedule

http://www.epa.gov/oppsrrd1/registration_review/

– Chemicals found in sources of drinking water

EDSP Tier 1 Test Orders for 2nd List• Begin Issuing test orders in late 2010• First data would be received in late 2012

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Next Steps/Future Activities

Evaluation of Tier 1 Data• In 2012 EPA will review Tier 1 test data from

the List 1 chemicals– Determine which chemicals need no further

testing

– Determine which chemicals need Tier 2 tests and which tests to require

– Analyze performance of the battery and compare Tier 1 with existing toxicological data used to support pesticide registrations

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Additional Information

General• www.epa.gov/endo

Policy and Procedures• www.regulations.gov docket # EPA-HQ-OPPT-2007-1080

Final list of Chemicals for Initial Screening• www.regulations.gov docket # EPA-HQ-OPPT-2004-0109

Protocols• www.epa.gov/oppts select “Test Methods & Guidelines”

Information Collection Request under the Paper Reduction Act (PRA)• www.regulations.gov docket # EPA-HQ-OPPT-2007-1081