Slide 1 of 15HighThroughputForwardPredictionofHumanExposureHighThroughputForwardPredictionofHumanExposurePresentedbyPeterP.Egeghy,Ph.D.M.P.H.NationalExposureResearchLaboratoryOfficeofResearchandDevelopmentPresentedbyPeterP.Egeghy,Ph.D.M.P.H.NationalExposureResearchLaboratoryOfficeofResearchandDevelopmentSlide2 of15PresentationRoadmapIntroductionHighThroughputExposure(HTE)EstimationHighThroughputToxicokinetics(HTTK)andReverseToxicokinetics(RTK)OngoingResearch• Frameworkoverview•HTEForwardDataandModels• HTEReverseDataandModels• SEEMAnalysisandHTEEstimatesFutureApplicationsSlide3 of15ProvidebackgroundonSEEManalysisPresenttheexposuredata“landscape”DescribeourprocessforidentifyingandevaluatingHTEmodelsExplainhowchemicaluseprofilingdatawasobtainedandintegratedintoSEEManalysisObjectivesSlide4 of15ForwardPredictionofExposureChemicalManufactureConsumerBuildingMaterialsProducts,Articles,BuildingMaterialsEnvironmentalReleaseFoodAir,Soil,WaterAir,Dust,SurfacesNear‐FieldDirectNear‐FieldIndirectHumanEcologicalFloraandFaunaDietary Far‐FieldDirectUse(e.g.,lotion)ResidentialUse(e.g.,flooring)MONITORINGDATARECEPTORSMEDIAEXPOSUREPATHWAY(MEDIA+RECEPTOR)BiomarkersofExposureBiomarkersofExposureMediaSamplesEcologicalWasteDataandModelsSlide5 of15AvailableData:“ExposureSpace”ExposurePotentialChemicalPropertiesLifeCyclePropertiesEmissionsCharacteristicsExposurePathwaysLogKowLogKoaVPMWProductionVolumeProductFormulationUseCategoriesMassEmittedReceptorMediaContactMediaEnvironmentalMediaBiologicalMediaActivityPatternsJ.Mitchelletal./PLoS one8.8(2013)e70911P.P.Egeghyetal./ScienceoftheTotalEnvironment414(2012)159–166Slide6 of15TabularData,LinkstoWebResourcesChemicalID,StructureChemicalInternetSearchesACToRAPIToxRefDBhttp://actor.epa.gov/ToxCastDBExpoCastDBInVivoData(ORD,OPP)ToxCastData(ORD,Collaborators)ExposureandBiomonitoringData(ORD)ACToRCoreCPCatChemical,UseandProductCategoryData(ORD)ACToR:EPA’sAggregatedComputationalToxicologyResourceSlide6 of15Slide7 of15Thevastmajorityofchemicals:•Unmeasuredintheenvironment•UnknownenvironmentalfateandexposurepotentialLimitedresourcesavailabletoincreasemeasurementsNeedforhighthroughputexposuremodelingusingbroadsurrogatesExposureInformation:LimitedChemicalCoverageP.P.Egeghyetal./ScienceoftheTotalEnvironment414(2012)159–166“EPAstudyrevealsbarrenexposuredatalandscape”‐EDFChemicals&NanomaterialsBlog,March16,2012Slide8 of15Goal:CollaborativelydevelopcapacityforrapiddeterminationofexposurepotentialforthousandsofchemicalsIdentifyexistingapproaches•CommunityofPractice:2008‐2010Enlistbroad‐basedsupportofthescientificcommunitythroughfirstoffourExpoCastWorkshops•Surveyedmandatesforchemicalprioritizationandrelatedexposurescienceneeds•Systematicallyevaluatedapproacheson15relevantfactors•Publication:“Exposure‐basedprioritizationofchemicalsforriskassessment,”ES&P,2011•FosteredengagementindemonstratingtheapplicationofexistingtoolstoHTassessmentofexposurepotentialLeveragingExistingToolsforRapidDeterminationofExposurePotentialSlide9 of15HighThroughputExposureModelChallenge9Mitchelletal.,Sci TotalEnviron,2013Slide10 of15FourkeycriteriaforHTEmodels:•Parameterizedfromminimaldatasets•Broadlyapplicableacrossmanychemicalschemicalclasses•Operatedinanautomated(batch)manner•Capableofmakingquantitativeofhumanexposurepredictions(e.g.,mg/kg‐BW/day)EvaluationofModelsagainstKeyCriteriaSlide11 of15Model FullNameRAIDARRiskAssessmentIDentification AndRanking Yes Yes Yes YesUSEtoxTMUNEP‐SETACToxicityModel Yes Yes Yes YesEFAST2ExposureandFateAssessmentScreeningToolv2.0AlmostYes YesGExFRAME/ScibinGeneralizedExposureFramework Yes YesPRoTEGEPrioritization/RankingofToxicExposureswithGISExtensionYes Yes3MRAMultimedia,Multipathway,andMultireceptor ExposureandRiskAssessment Yes Yes YesAPEXAirPollutantsExposureModelYes YesChemSTEERChemicalScreeningToolForExposures&EnvironmentalReleasesYes YesDEEMTMDietaryExposureEvaluationModelYes YesEMSOFTExposureModelforSoil‐OrganicFateandTransport Yes YesFIRSTFQPAIndexReservoirScreeningToolHAPEMHazardousAirPollutantExposureModelYes YesHEMHumanExposureModelYesLifeLineTMModelTheLifelineGroupLifeLineTMModelYes YesMCCEMMulti‐ChamberConcentrationAndExposureModelAlmostYes YesPIRATPesticideInertRiskAssessmentToolYesPRZMandEXAMSPesticideRootZoneModelandExposureAnalysisModelingSystemReachScanReachScanYesSHEDSStochasticHumanExposureandDoseSimulation Yes Yes YesSOFEAandFEMSSoilFumigantExposureAssessmentandFumigantExposureModelingSystemYesSOPsStandardOperatingProceduresforResidentialPesticideExposureAssessment YesSRDSourceRankingDatabaseYes Yes YesSTIRScreeningToolforInhalationRisk Yes YesSWIMODELSwimmerExposureAssessmentModelYes YesTRIM.FaTETotalRiskIntegratedMethodologyYes YesWPEMWallPaintExposureAssessmentModelYesEvaluationofModelsagainstKeyCriteriaSlide12 of15HighThroughputExposureModelsModelsmeetingallfourcriteriaforhighthroughputexposureassessmentSlide13 of15CASRN Category1 Category 2 ...Category 1265277‐42‐10 1 ...050‐41‐9 1 1 ...0...... ... ......CASRN Category1 Category 2 ...Category 1265277‐42‐1 0 10 ... 150‐41‐9 31 7 ... 3...... ... ......BinarymatrixTable:HitsperusecategoryforagivenchemicalWorkbyAliciaFrame,KathieDionisio,RichardJudsonDionisioetal.manuscriptinpreparationChemicalUse Categories:•15distinctchemicalusecategoriesderivedfromACToR•Datasources(“assays”)manuallyassignedtocategories•ChemicalsindatasourcescomputationallyassignedtocategoriesChemicalUseCategoriesAntimicrobials HerbicidesChemicalWarfareIndustrialProcessConsumerUse PersonalCareProductsDyesandColorants PesticidesFertilizersPesticideInertFlameRetardantsPetrochemicalsFoodAdditivePharmaceuticalsFragrances OtherHeuristicsforChemicalUse:CreationofACToR UseDBSlide14 of15Vastmajorityofchemicalsdonothaveexposure‐relatedinformationavailableSystematicevaluationof“off‐the‐shelf”exposuremodelsfoundfewarecapableofHTEestimationOnlyFate&TransportmodelsaresuitableforHTEpurposes,butignoreresidentialsourcesUseprofilinginformationhasbeencuratedtosupplementF&Tmodelswith“nearfield”sourceinformationSummarySlide15 of15IllustrationoftheSEEMFrameworkEstimateUncertaintyEDSPChemicalsQSARsandHTEDataBiomonitoringData Inferred (Reverse) ExposureModel1Model2...CalibratemodelsApplycalibrationanduncertaintytootherchemicalsEvaluateModelPerformanceandRefineModelsForwardPredictionsExposureInferenceDataset1Dataset2...