Slide 1 of 24 EPA’s Endocrine Disruptor Screening Program (EDSP) Use of Exposure Data in Priority Setting Bill Wooge Office of Science Coordination and Policy/OPPTS U. S. Environmental Protection Agency

Slide 2 of 24 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 2

Slide 3 of 24 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 3

Slide 4 of 24 Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC)  Chartered Oct. 16, 1996 (  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

Slide 5 of 24 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 5

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] 6 Slide 6 of 23

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] Slide 7 of 23 EDSP Tier 2 Tests

Slide 8 of 24 EDSP Priority Setting

Slide 9 of 24 Priority Setting  Selection of 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)

Slide 10 of 24 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

Slide 11 of 24 Pesticide Active Ingredients – Food Pathway  USDA Continuing Survey of Food Intake by Individuals (CSFII)  USDA Pesticide Data Program  FDA Surveillance Monitoring

Slide 12 of 24 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

Slide 13 of 24 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 AgroTrak TM

Slide 14 of 24 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)

Slide 15 of 24 HPV/Inerts – Ecological Biological Monitoring  EPA National Sediment Inventory Fish Tissue Data  EPA National Fish Tissue Study  USGS National Water Quality Assessment Program

Slide 16 of 24 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

Slide 17 of 24 HPV/Inerts – Indoor Air Monitoring  EPA/ORD Published Literature  EPA National Human Exposure Assessment Survey  EPA Total Exposure Assessment Methodology (TEAM)

Slide 18 of 24 1 st 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 I Screening Draft Initial List … … 19 Slide 19 of 23

Slide 20 of 24 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 20

Slide 21 of 24 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 ( /)  Inert ingredients and other chemicals Develop in vitro and in silico tools that are integrated with exposure-based metrics –ToxCast TM & ExpoCast TM

Slide 22 of 24 Next Steps/Future Activities  Second List 2010 Appropriations requires EPA to issue a second list of at least 100 chemicals by October 30, nd List will be composed of –Pesticides from Registration Review schedule –Chemicals found in sources of drinking water  EDSP Tier 1 Test Orders for 2 nd List Begin Issuing test orders in late 2010 First data would be received in late 2012

Slide 23 of 24 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

Slide 24 of 24 Additional Information  General  Policy and Procedures docket # EPA-HQ-OPPT  Final list of Chemicals for Initial Screening docket # EPA-HQ-OPPT  Protocols select “Test Methods & Guidelines”  Information Collection Request under the Paper Reduction Act (PRA) docket # EPA-HQ-OPPT