Atrazine Re-Evaluation:AtrazineReIntroduction & StatusAtrazineRe-Evaluation:Introduction & StatusPresentation to Scientific Advisory PanelJuly 2629 2011July26-29,2011ElizabethMéndezPh D,..Health Effects DivisionUSEPA Office of Pesticide ProgramsPeer ReviewPeerReview•1988 SAP:Evaluation of rat mammary gland tumors•2000 SAP:Evaluation of MOA•Mammary glandtumors reproductiveandMammaryglandtumors,reproductivedevelopmental findings in rats•Human relevanceHumanrelevance•2003 SAP:Evaluation of prostate cancer• Epidemiology study on relationship betweenatrazine exposure and prostate cancer in workers atatrazine manufacturing plant2Atrazine Human HealthRe-Evaluation•Goals of the Re-Evaluation• Determine if the risk assessment for atrazine should berevisedE l t d i t lt i l d t (d•Evaluatedexperimentaltoxicologydata(non-cancer ancancereffects)• Evaluated epidemiology data• Integrate experimental toxicology and epidemiology data• Ascertain if critical lifestages are adequately assessed• Ascertain if durations of exposure assessed are the mostappropriate• Identify methods for analyzing uncertainty in drinkingwater monitoring datawatermonitoringdata3AtrazineAtrazine 2010 SAP Meetings:2010 SAP Meetings:Human Health•Draft Framework: Incorporating epidemiology studiesHumanHealthFebruary 2010and human health incident data in risk assessment•Two atrazine case studiesApril 2010•Preliminary evaluation ofin vitro&in vivolaboratorystudies (non-cancer)•Frequency of atrazine monitoring in drinking watersources (proposed approaches)•Epidemiology studies: non-cancerSeptember 2010•Integration of epidemiology & experimental toxicologyinto hazard characterization for non-cancer4•Frequency of atrazine monitoring in drinking watersources (updated analyses)Atrazine 2010 SAP Meetings:Panel Conclusions & Recommendations•February 2010 SAP• In general, concurred with Agency’sproposed approach for evaluating•September 2010 SAP• Concurred with Agency’sconclusions/approaches on broadproposedapproachforevaluatingepidemiology data•April 2010 SAP• Reaffirmed conclusions of previousSAPs regarding cancer classificationconclusions/approachesonbroadrange of issues.• Mammary gland development• Use of internal dosimetry•LH suppression protective ofSAPsregardingcancerclassificationfor atrazine as “not likely to becarcinogenic to humans.”• Concurred with Agency’s conclusions•LHsuppressionprotectiveofother effects• Use of Cooper et al. (2010) datato establish PoD•No evidence of a higherthat atrazine-induced effects onneuroendocrine function are themost sensitive effects• RecommendedusinginternalNoevidenceofahighersensitivity of the young relativeto adults• Non-cancer findings inepidemiology studieseco e ded us g te adosimetry rather than externallyadministered dose• Noted that the toxicological durationof concern is key to determiningsampling frequency identifying• Recommended a combination ofstatistical and modeling methods toconsider in quantifying uncertainty inexposure estimates from monitoringdatasamplingfrequency,identifyingmethods for estimating exposurefrom monitoringdata5July 2011SAP: Human HealthNon-Cancer CancerJuly2011SAP:HumanHealthReview of new experimentaltoxicology studiesSpecies extrapolation from rat toEpidemiology studies: cancerhuman—duration of exposureLifestage sensitivity analysisApproaches for analyzing atrazineApproachesforanalyzingatrazinemonitoring data in drinking watersourcesUdt tpae on exposure assessmentcollaborative project with AHSIntegratedweightoftheevidencewithepidemiology&experimentalated e g t o t e e de ce t ep de o ogy & e pe e tatoxicology6

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o nCharacterizationCompoundsAssessBiologicalPerturbationAffectedPathwayDose ResponseAnalysis forPerturbationsof ToxicityPathwaysCalibratingin vitro and humanDosimetryExposureGuidelinePerturbationMeasures ofdose in vitroHuman ExposureDataMetabolite(s)Hazard CharacterizationExposure AssessmentRisk Characterization7PresentationsAtrazine: Adverse Outcomes and MOADr. Ralph C. CooperReview of Atrazine Cancer EpidemiologyDr. Carol H. ChristensenIntegration of Epidemiology and Toxicity Data into Health Risk AssessmentIntegrationofEpidemiologyandToxicityDataintoHealthRiskAssessmentDr. Elizabeth MéndezAtrazine: Updates to Dose-Response Assessmentwith Implications for Water MonitoringFrequencyyDr. Chester RodriguezEvaluating Atrazine Drinking Water MonitoringData For Use in Human Health AssessmentsMr. Nelson ThurmanAtrazine Re-Evaluation: Scientific Considerationsin Potential Sensitivity of Infants & ChildrenDr. Elizabeth MéndezCase Study: Implications of MOA and Toxicity Profile on Water MonitoringCaseStudy:ImplicationsofMOAandToxicityProfileonWaterMonitoringDr. Chester Rodriguez and Mr. Nelson Thurman8