Presentation on theme: "Perspectives from EPA’s Endocrine Disruptor Screening Program"— Presentation transcript:
1 Perspectives from EPA’s Endocrine Disruptor Screening Program David J. Dix, Ph.D.Director, Office of Science Coordination and PolicyOffice of Chemical Safety and Pollution PreventionCLAApril 10, 2014
2 1996 Legislative Mandate1996 Federal Food, Drug and Cosmetic Act, section 408(p)Requires the U. S. EPA to develop a screening program using appropriate validated test systems and other scientifically relevant methods to determine whether certain substances may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effect as the Administrator may designate.1996 Safe Drinking Water Act Amendments, section 1457Testing of chemical substances that may be found in sources of drinking water, if substantial human populations may be exposed.
3 1998 Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) EDSTAC Key Recommendations:Expand Protection to Include Human Health and WildlifeInclude Estrogen, Androgen and Thyroid PathwaysDevelop a Two-Tiered Screening and Testing Program:EDSTAC Conceptual Framework:Tier 1 Screening for Potential to InteractPotential to interact with the estrogen, androgen or thyroid hormone systemsTier 2 Testing to determine Interaction with the endocrine systemIf endocrine-mediated adverse effects then quantify dose-response relationship
4 EDSP ImplementationEPA has reviewed ~500 studies required on EDSP List 1Initiated WOE evaluations of 52 chemicals for estrogen, androgen and thyroid (E, A & T) interactionsAgency currently reviewing Tier 1 data and other scientifically relevant information (OSRI)Initial WOE evaluation of 12 chemicals completedBased on the first WOE reviews:EPA may not require many (if any) Tier 2 studies to assess human health risks for EDSP List 1 pesticidal chemicalTier 2 ecological studies may be required for some chemicals
5 EDSP Chemical Universe EDSP ImplementationEDSP List 2 ChemicalsDraft EDSP List 2 chemicals for Tier 1 screening released (2010)EPA issued revised EDSP List 2 with 109 chemicals (2013)- Selection based on registration review schedule of 41 pesticidal chemicals and 68 drinking water contaminantsEDSP Chemical Universe10,000 chemicals(FIFRA & SDWA)EDSP List 2109 ChemicalsEDSP List 152 ChemicalsSlide 6
6 Evolution of the EDSPBased on current pace it could take decades to screen all 10,000 chemicals for potential to interact with the endocrine systemRecent advances in computational toxicology herald an important “evolutionary turning point” and an accelerated pace of screening and testingTo address thousands of chemicals for potential to interact with the endocrine system, we must implement a more strategic approach to prioritize chemicals for targeted screening
7 Utility of Computational Toxicology Rapidly screen chemicals and use predictive models to evaluate thousands of chemicals for potential risk to human health and environmentIncrease capacity to prioritize, screen and predict chemical toxicity and exposureOvercome throughput limitations of traditional chemical toxicity testing, augmenting current data sourcesEventual replacement of some existing tests with non-animal alternativesPartner across EPA, with other federal agencies, state agencies, industry and non-governmental organizations to validate and apply toolsProvide open access to data and adverse outcome pathway (AOP) risk predictions
8 Risk-Based Prioritization ToxCastExpanding use of CompTox (Phys-chem properties, QSARS, etc.) to support risk based prioritizationTransparent and collaborativeExpoCastRapid exposure estimation based on readily available chemical use and production dataUse toxicokinetics to bridge in vitro, concentration-based ToxCast data to in vivo, dose-based Exposures from ExpoCastToxCastHigh Throughput Risk-Based PrioritizationExpoCast
9 Risk-Based Prioritization EDSP Chemical Universen = 10,000Prioritize and target screening and testing of List 2 chemicals using new CompTox toolsRisk-based prioritization of 10,000 chemical universe for List 3EDSP Universe (phys-chem filters)n = ~5000Risk-Based PrioritizationLower PriorityChemicalsEDSP List 2109 ChemicalsEDSP List 3EDSP List 152 ChemicalsExposure-based listsCompTox → Risk-Based Prioritization
10 Adverse Outcome Pathways (AOP) AOP Support:Developing and applying lower tiered tests & non-animal modelse.g., QSAR, in vitro, HTSForming Chemical Categories & Read Across methodsBetter dosimetry and biomarkers in experimental studies, epidemiology, population monitoringSpecies extrapolation
11 EDSP Relevant AOP Estrogen, Androgen and Thyroid (EAT) Risk-based AOP prioritization and assessment requiresMeasurement or prediction of in life dose-responseMonitoring or prediction of real-world exposuresLinkages between exposure – activity - adversityConsistent with 2013 SAP recommendations on use of Physical Chemical Properties, QSAR/HTS, and Exposure PredictionsEDSP21 is focused on developing high throughput, risk-based AOP methods to prioritize targeted testing
12 Current Status of EDSP Prioritization and Screening 52 List 1 chemicals with complete Tier 1 datasets undergoing weight-of-evidence determination of EAT endocrine activity and possible Tier 2 testing109 List 2 chemicals going through OMB review for Tier 1 screeningEDSP Universe of chemicals being prioritized for EDSP screening using computational toxicology and other toolsScience Advisory Panel peer reviews being planned:Exposure Prediction ModelsRisk-Based Prioritization
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