Rodenticide SecondaryExposure and RiskExposureandRiskCharacterizationExposureandRiskCharacterizationPresentation to the SAPNovember 29th, 2011Elizabeth Riley, M.S.ElizabethRiley,M.S.Environmental Fate and Effects Division12Outline•Quantitative ApproachQuantitativeApproach•Dose-Based RQ Analyses•Theoretical Exposure•Empirical Exposure•Dietary RQ AnalysesTh ti l E•TheoreticalExposure•Empirical Exposure•Opportunity for Lethal Exposure AnalysisOpportunityforLethalExposureAnalysis•Secondary Feeding Studies•Secondary Risk ConclusionsSecondaryRiskConclusions3Secondary Exposure and Risk•Secondary risk is influenced by:Secondaryriskisinfluencedby:•Toxicity of rodenticides to primary andsecondaryconsumers•Exposure accumulation and eliminationExposureaccumulationandeliminationof rodenticides in both primary andsecondary consumers•Time to death in primary consumer4Methodology flow chart: theoretically based preyconcentrationToxicity endpointsConcentration ofa.i. baitHalf-life inpreyScaled toxicityendpoints based1-day rodenticideintake inpreyviaBody burden inpreyforone dayand multipleendpointsbasedon body weightsp yallometric food intakeequationsy pday accumulationscenarios1d d i idDose-based exposure RQs basedon 1-day accumulation inprey-day rodenticideintake insecondaryconsumerviaallometric food intakeequationsDose-based exposure RQs based onmulti-day accumulation inprey5# ofpreyorganisms to reach LD50in secondary consumerAccumulation of Rodenticides•For rodenticides with delayed mortality, targetyganimals may:•Feed on bait for several days•Accumulate doses that exceed the median lethalAccumulatedosesthatexceedthemedianlethaldose•“Accumulation of dose” analysis assessed theaccumulation potential for the rodenticides inaccumulationpotentialfortherodenticidesinthe house mouse and Norway rat over time•Available empirical data were used to confirmestimated body burdens6Accumulation of Prey Body Burden:Assumptions•100% ofprey’s diet consists of drybaity y•100% of rodenticide residues in prey arebioavailable to the consumer•Assumed weights for target animals:Assumedweightsfortargetanimals:•house mouse = 23 g•Norwayrat = 485gg•Elimination half-lives•Based on liver for anticoagulants and bloodplasma for bromethalinplasmaforbromethalin•First order elimination equation7Elimination half-lives used to calculate dose accumulationRodenticide Test Species Compartment Eliminationhalf-life(days)Brodifacoum Mouse Liver 307.4Difethialone Mouse Liver 28.5Warfarin Mouse Liver66.8Chlorophacinone Mouse Liver 35.4DiphacinonePigLiver5 5.Bromethalin Rat Blood 5.68Accumulation Equation for HouseMouse and NorwayRatDt= (FI * C/(wt(g)/1000)) + d(t-1)* e-k9Window for Accumulation•Time to death:•Provides context for dose accumulation•Derived from available acute toxicityt disues10Rodenticide Body Burden in House Mouse Over Time1000.0

)Warfarin (0.054%)100.0

m g a.i./kg-bwWarfarin (0.025%)

o ncentration ( mBromethalin (0.01%)Brodifacoum (0.005%)Chlorophacinone (0.005%)Diphacinone (0.005%)Difethialone (0.00025%)10.0

R odenticide C o1.0123456

R123456Days11Rodenticide Body Burden in Norway Rat Over Time1000.0

)100.0

(mg a.i/kg-bwWarfarin (0 025%)Warfarin (0.054%)

C oncentrationWarfarin(0.025%)Brodifacoum (0.005%)10.0

R odenticide CBromethalin(0.01%)Brodifacoum(0.005%)Chlorophacinone (0.005%)Diphacinone (0.005%)Difethialone (0.0025%)1.0123456

R123456Days12Uncertainties•Elimination half-livesEliminationhalf•Liver half-lives not available for allchemicals•Different study designs may lead tolarge variation in half-lives reported•Different species used•Degree to which liver half-livesrepresent whole body elimination13Rodenticide Intake (mg a.i./kg-bw) in SecondaryConsumers Based on Consumption of Prey•Rodenticide intake was based on foodRodenticideintakewasbasedonfoodintake allometric equations and theconcentration of rodenticide in the targetconcentrationofrodenticideinthetargetspecies based on:•Theoretically based prey concentration•Empirically based prey concentration(di d l t )(discussedlater)14Body Weight Scaling of LD50s100 g bird 1000 g bird 5000 g birdAmerican kestrelRedTailed HawkBald EagleNational GeographicU.S. Fish and Wildlife ServiceU.S. Fish and Wildlife ServiceU.S. Fish and Wildlife ServiceAmericankestrelRed-TailedHawkBaldEagle50 g mammal1000 g mammal3000 g mammal15Least Weasel MinkKit FoxWikipediaWikipediaU.S. Fish and Wildlife ServiceU.S. Fish and Wildlife ServiceMethodology flow chart: theoretically based preyconcentrationToxicity endpointsConcentration ofa.i. baitHalf-life inpreyScaled toxicityendpoints based1-day rodenticideintake inpreyviaBody burden inpreyforone dayand multipleendpointsbasedon body weightsp yallometric food intakeequationsy pday accumulationscenarios1d d i idDose-based exposure RQs basedon 1-day accumulation inprey-day rodenticideintake insecondaryconsumerviaallometric food intakeequationsDose-based exposure RQs based onmulti-day accumulation inprey16# ofprey organismsto reach LD50in secondary consumerSecondary Bird RQs Based on 1-Day Accumulationin House MouseBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin100 g1000 g 5000 gRQ0.0001 0.001 0.01 0.1 1 10 100Level of Concern (0.5)171-day accumulation3-day accumulation6-day accumulationSecondary Bird RQs Based on 3-Day Accumulationin House MouseBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalinRQ0.0001 0.001 0.01 0.1 1 10 100100 g1000 g 5000 gLevel of Concern (0.5)181-day accumulation3-day accumulation6-day accumulationSecondary Bird RQs Based on 6-Day Accumulationin House MouseBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin*0.0001 0.001 0.01 0.1 1 10 100RQ100 g1000 g 5000 gLevel of Concern (0.5)19* Not applicable for 6 day1-day accumulation3-day accumulation6-day accumulationSecondary Bird RQs Based on 1-Day Accumulationin NorwayRatBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalinRQ0.00001 0.0001 0.001 0.01 0.1 1 10 100100 g1000 g 5000 gLevel of Concern (0.5)201-day accumulation3-day accumulation6-day accumulationSecondary Bird RQs Based on 3-Day Accumulationin Norway RatBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalinRQ0.00001 0.0001 0.001 0.01 0.1 1 10 100100 g1000 g 5000 gLevel of Concern (0.5)211-day accumulation3-day accumulation6-day accumulationSecondary Bird RQs Based on 6-Day Accumulationin Norway RatBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin*RQ0.00001 0.0001 0.001 0.01 0.1 1 10 100100 g1000 g 5000 gLevel of Concern (0.5)22* Not applicable for 6 day1-day accumulation3-day accumulation6-day accumulationSummary: 1-day and multi-daydose-based avian RQsChemicalDose-Based RQs Dietary-Based RQs OpportunitySecondaryFeeding Studies1 DayPreyMulti DayPreyEmpiricalPrey1 DayPreyEmpiricalPrey1 dayPreyMulti DayPreyBirdsBrodifacoumDifethialoneNo dataWarfarin(0 025%)(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo data No data No dataMammalsBrodifacoumDifethialoneNo data No data No dataWarfarin(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo data No data No data23All evidencesuggest riskPredominant evidenceof riskEquivocal evidenceof riskAll evidencesuggest low riskSecondary Mammal RQs Based on 1-Day Accumulationin House MouseBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin50 g1000 g3000 gRQ0.1 1 10 100Level of Concern (0.5)50g1000g3000g241-day accumulation3-day accumulation6-day accumulationSecondary Mammal RQs Based on 3-Day Accumulationin House MouseBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalinRQ0.1 1 10 10050 g1000 g3000 gLevel of Concern (0.5)2550g1000g3000g1-day accumulation3-day accumulation6-day accumulationSecondary Mammal RQs Based on 6-Day Accumulationin House MouseBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin*RQ0.1 1 10 10050 g1000 g3000 gLevel of Concern (0.5)26* Not applicable for 6 day50g1000g3000g1-day accumulation3-day accumulation6-day accumulationSecondary Mammal RQs Based on 1-Day Accumulationin Norway RatBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalinRQ0.01 0.1 1 10 10050 g1000 g3000 gLevel of Concern (0.5)2750g1000g3000g1-day accumulation3-day accumulation6-day accumulationSecondary Mammal RQs Based on 3-Day Accumulationin Norway RatBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalinRQ0.01 0.1 1 10 10050 g1000 g3000 gLevel of Concern (0.5)2850g1000g3000g1-day accumulation3-day accumulation6-day accumulationSecondary Mammal RQs Based on 6-Day Accumulationin Norway RatBrodifacoumDifethialoneWarfarin (0.025%)Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin*RQ0.01 0.1 1 10 10050 g1000 g3000 gLevel of Concern (0.5)29* Not applicable for 6 day50g1000g3000g1-day accumulation3-day accumulation6-day accumulationSummary: all 1-day and multi-day dose-based RQsChemicalDose-Based RQs Dietary-Based RQs OpportunitySecondaryFeeding Studies1 DayPreyMulti DayPreyEmpiricalPrey1 DayPreyEmpiricalPrey1 dayPreyMulti DayPreyBirdsBrodifacoumDifethialoneNo dataWarfarin(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo data No data No dataMammalsBrodifacoumDifethialoneNo data No data No dataWarfarin(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo data No data No data30All evidencesuggest riskPredominant evidenceof riskEquivocal evidenceof riskAll evidencesuggest low riskRQS BASED ONRQSBASEDONTHEORETICAL BODYBURDENS IDENTIFY RISKRQSBASEDONTHEORETICAL BODYBURDENS IDENTIFY RISKBURDENSIDENTIFYRISK...BURDENSIDENTIFYHOW DO EMPIRICAL DATA...HOWDOEMPIRICALDATACOMPARE?...HOWDOEMPIRICALDATACOMPARE?31Methodology flow chart: empirically based preyconcentrationMeasured bodyToxicity endpointsMeasuredbodyburden inprey1d d i idScaled toxicityendpoints based-day rodenticideintake insecondaryconsumerviaallometric foodon body weightsDose-based RQsintake equations32Mean Measured Rodenticide Residues in PrimaryConsumersB difroacoumDifethialoneWarfarinChlorophacinoneDiphacinoneB h li0.1 1 10 100 1000Bromethalinmg a.i./kw-bwMean residue value selected for RQ analysis33Comparison of Theoretical and EmpiricalBody-burden values(mga.i./kg-bw)Comparison of Theoretical and EmpiricalBody-burden values(mga.i./kg-bw)g gRodenticidemga.i./kgbaitTheoreticalEmpiricalSpeciesConcentration (1 - 6SpeciesMean Range ofbaitday feeding)Concentration ConcentrationsBrodifacoum 50 Norway Rat 2.1 – 12.5 Rat 6.98 1.39-25.97Difethialone 25 Norway Rat 1.0 – 5.9 Rat 3.1 1.9-4.3Warfarin 200HouseMouse31.7 – 185.1 Mouse 2.95 NAChlorophacin50House7.9–45.2Vole1.580.26-4.1one50Mouse7.945.2Vole1.580.264.1Diphacinone 50 Norway Rat 2.1 – 9.4GroundSquirrel1.4 1.4-3.434Secondary Bird Acute RQs: Empirically basedpreyconcentration analysisSecondary Bird Acute RQs: Empirically basedpreyconcentration analysisy yBrodifacoumDifethialoneWarfarinChlorophacinoneDiphacinoneBromethalin0.00001 0.0001 0.001 0.01 0.1 1 10 100Log scale RQ100 g1000 g 5000 gLevel of Concern (0.5)351-day accumulation6-day accumulation3-day accumulationEmpiricalSecondary Bird Acute RQs: Empirically basedpreyconcentration analysisSecondary Bird Acute RQs: Empirically basedpreyconcentration analysisy yBrodifacoumDifethialoneWarfarinChlorophacinoneDiphacinoneBromethalin*0.00001 0.0001 0.001 0.01 0.1 1 10 100Log scale RQ100 g1000 g 5000 gLevel of Concern (0.5)361-day accumulation6-day accumulation3-day accumulationEmpirical* No empirical dataSecondary Mammal Acute RQs: Empiricallybasedpreyconcentration analysisSecondary Mammal Acute RQs: Empiricallybasedpreyconcentration analysisy yBrodifacoumDifethialoneWarfarinChlorophacinoneDiphacinoneBromethalin0.01 0.1 1 10 100Log scale RQLevel of Concern (0.5)50 g1000 g 3000 g371-day accumulation6-day accumulation3-day accumulationEmpiricalSecondary Mammal Acute RQs: Empiricallybasedpreyconcentration analysisSecondary Mammal Acute RQs: Empiricallybasedpreyconcentration analysisy yBrodifacoumDifethialoneWarfarinChlorophacinoneDiphacinoneBromethalin*0.01 0.1 1 10 100Log scale RQLevel of Concern (0.5)50 g1000 g 3000 g381-day accumulation6-day accumulation3-day accumulationEmpirical* No empirical dataUncertainties•Whole carcass residue dataWholecarcassresiduedata•Difficult to quantify exposure in fieldt disues•No data available for bromethalin39Summary: all dose-based RQsChemicalDose-Based RQs Dietary-Based RQs OpportunitySecondaryFeeding Studies1 DayPreyMulti DayPreyEmpiricalPrey1 DayPreyEmpiricalPrey1 dayPreyMulti DayPreyBirdsBrodifacoumDifethialoneNo dataWarfarin(0 025%)(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo data No data No dataMammalsBrodifacoumDifethialoneNo data No data No dataWarfarin(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo data No data No data40All evidencesuggest riskPredominant evidenceof riskEquivocal evidenceof riskAll evidencesuggest low riskSINGLE DAY ANALYSES DO NOTSINGLEDAYANALYSESDONOTALLOW FOR ACCUMULATION INTHE SECONDARY CONSUMERSINGLEDAYANALYSESDONOTALLOW FOR ACCUMULATION INTHE SECONDARY CONSUMERTHESECONDARYCONSUMER...SECONDARYCONSUMER... IS THERE A WAY TO EMPIRICALLYACCOUNT FOR THIS?41Dietary-Based RQ Methods1.Estimate rodenticide concentration inprimary consumers•Theoretical analysis: single dayl ti iaccumuaon scenario•Empirical analysis: mean measuredwhole-carcass residuescarcassresidues2Compare the estimated concentration.Comparetheestimatedconcentrationin primary consumers to un-adjustedLC50toxicity values42Secondary Bird Dietary RQsBirdsChemicalTheoreticalEmpiricalConsumingHouse MouseConsumingNorway RatBrodifacoum17 8*4 71*5 25*Brodifacoum...Difethialone20.7* 5.48* 5.54*Warfarin (0.025%) 0.19 0.05< 0.01Warfarin (0.054%) 0.41 0.11Chlorophacinone 0.32 0.09 0.02Diphacinone 0.02 <0.01 < 0.01Bromethalin 0.20 0.05 No dataBolded (*) RQs exceedacute risk LOC (0.5).43Secondary Mammal Dietary RQsMammalsChemicalTheoreticalEmpiricalConsumingHouse MouseConsumingNorway RatBrodifacoum44 7*11 2*13 17*Brodifacoum...Difethialone No data No data No dataWarfarin (0.025%)26.6* 7.05*0.67*Warfarin (0.054%)57.5* 15.2*Chlorophacinone20.42* 5.41* 1.39*Diphacinone10.1* 2.68* 0.61*Bromethalin No data No data No dataBolded (*) RQs exceedacute risk LOC (0.5).44Summary: all RQ analysesChemicalDose-Based RQs Dietary-Based RQs OpportunitySecondaryFeeding Studies1 DayPreyMulti DayPreyEmpiricalPrey1 DayPreyEmpiricalPrey1 dayPreyMulti DayPreyBirdsBrodifacoumDifethialoneNo dataWarfarin(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo dataNo dataNo dataNodataNodataNodataMammalsBrodifacoumDifethialoneNo data No data No dataWarfarin(0.025%)Warfarin(0.054%)ChlorophacinoneDi h iphacinoneBromethalinNo data No data No data45All evidencesuggest riskPredominant evidenceof riskEquivocal evidenceof riskAll evidencesuggest low riskNOW THAT WE HAVENOWTHATWEHAVEIDENTIFIED AREAS OF RISK...NOWTHATWEHAVEIDENTIFIED AREAS OF RISK...... HOW PLAUSIBLE AREOURRISK CONCLUSIONS?46Methodology flow chart: relative opportunity forlethal exposureToxicity endpointsConcentration ofa.i. baitHalf-life inpreyScaled toxicityendpoints based1-day rodenticideintake inpreyviaBody burden inpreyforone dayand multipleendpointsbasedon body weightsp yallometric food intakeequationsy pday accumulationscenarios1d d i idDose-based exposure RQs basedon one-day accumulation inprey-day rodenticideintake insecondaryconsumerviaallometric food intakeequationsDose-based exposure RQs based onmulti-day accumulation inprey47# ofpreyorganisms to reach LD50in secondary consumerIS THIS REASONABLY EXPECTED TO OCCUR?100 g bird consuming house mouse: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of mice0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.0048IS THIS REASONABLY EXPECTED TO OCCUR?1000 g bird consuming house mouse: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of mice0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.0049IS THIS REASONABLY EXPECTED TO OCCUR?5000 g bird consuming house mouse: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of mice0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.0050IS THIS REASONABLY EXPECTED TO OCCUR?100 g bird consuming house mouse: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)# of mice0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.0051IS THIS REASONABLY EXPECTED TO OCCUR?1000 g bird consuming house mouse: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)# of mice0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.0052IS THIS REASONABLY EXPECTED TO OCCUR?5000 g bird consuming house mouse: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)# of mice0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.0053IS THIS REASONABLY EXPECTED TO OCCUR?100 g bird consuming Norway rat: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of rats0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.0054IS THIS REASONABLY EXPECTED TO OCCUR?1000 g bird consuming Norway rat: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of rats0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.0055IS THIS REASONABLY EXPECTED TO OCCUR?5000 g bird consuming Norway rat: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of rats0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.0056IS THIS REASONABLY EXPECTED TO OCCUR?100 g bird consuming Norway rat: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.00# of rats57IS THIS REASONABLY EXPECTED TO OCCUR?1000 g bird consuming Norway rat: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.00# of rats58IS THIS REASONABLY EXPECTED TO OCCUR?5000 g bird consuming Norway rat: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)0.01 0.10 1.00 10.00 100.00 1000.00 10000.00 100000.00# of rats59IS THIS REASONABLY EXPECTED TO OCCUR?50 g mammal consuming house mouse: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of mice0.01 0.10 1.00 10.00 100.0060IS THIS REASONABLY EXPECTED TO OCCUR?1000 g mammal consuming house mouse: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of mice0.01 0.10 1.00 10.00 100.0061IS THIS REASONABLY EXPECTED TO OCCUR?3000 g mammal consuming house mouse: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin0.01 0.10 1.00 10.00 100.00# of mice62IS THIS REASONABLY EXPECTED TO OCCUR?50 g mammal consuming house mouse: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)# of mice0.01 0.10 1.00 10.00 100.0063IS THIS REASONABLY EXPECTED TO OCCUR?1000 g mammal consuming house mouse: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)# of mice0.01 0.10 1.00 10.00 100.0064IS THIS REASONABLY EXPECTED TO OCCUR?3000 g mammal consuming house mouse: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)# of mice0.01 0.10 1.00 10.00 100.0065IS THIS REASONABLY EXPECTED TO OCCUR?50 g mammal consuming Norway rat: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of rats0.00 0.01 0.10 1.00 10.00 100.0066IS THIS REASONABLY EXPECTED TO OCCUR?1000 g mammal consuming Norway rat: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of rats0.00 0.01 0.10 1.00 10.00 100.0067IS THIS REASONABLY EXPECTED TO OCCUR?3000 g mammal consuming Norway rat: 1-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin# of rats0.00 0.01 0.10 1.00 10.00 100.0068IS THIS REASONABLY EXPECTED TO OCCUR?50 g mammal consuming Norway rat: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)# of rats0.00 0.01 0.10 1.00 10.00 100.0069IS THIS REASONABLY EXPECTED TO OCCUR?1000 g mammal consuming Norway rat: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)# of rats0.00 0.01 0.10 1.00 10.00 100.0070IS THIS REASONABLY EXPECTED TO OCCUR?3000 g mammal consuming Norway rat: 6-day accumulationBrodifacoumDifethialoneWarfarin(0.025%))Warfarin (0.054%)ChlorophacinoneDiphacinoneBromethalin(3 day)# of rats0.00 0.01 0.10 1.00 10.00 100.0071Summary: opportunity to feedChemicalDose-Based RQs Dietary-Based RQs OpportunitySecondaryFeeding Studies1 DayPreyMulti DayPreyEmpiricalPrey1 DayPreyEmpiricalPrey1 dayPreyMulti DayPreyBirdsBrodifacoumDifethialoneNo dataWarfarin(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo dataNo dataNo dataNodataNodataNodataMammalsBrodifacoumDifethialoneNo data No data No dataWarfarin(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo data No data No data72All evidencesuggest riskPredominant evidenceof riskEquivocal evidenceof riskAll evidencesuggest low riskAlternate Assumptions•Alternate assumptions that may alterAlternateassumptionsthatmayalterthese conclusions include:•Potential for increased sensitivity in somePotentialforincreasedsensitivityinsomespecies of secondary consumers•Potential that heavy rodent control in somePotentialthatheavyrodentcontrolinsomeareas may lead to more than a chanceencounter•Accumulation in secondary consumersover time73SECONDARY FEEDINGSECONDARYFEEDINGSTUDIES PROVIDE ANADDITIONAL LINE OFSECONDARYFEEDINGSTUDIES PROVIDE ANADDITIONAL LINE OFADDITIONALLINEOFEVIDENCE...ADDITIONALLINEOFEVIDENCE...... DO THEY SUPPORT OURRISK CONCLUSIONS?74Purpose•Secondarystudiesprovide:p•useful information on the potentialeffects from rodenticide exposure thatmay occur under field conditions•an empirical confirmation of estimatedprey concentration and subsequent RQanalyses75Uncertainties•Small N size•Different study designs•Difficult toquantifyexposureyp•Difficult to determine the sensitivity of theexposed animalsf•No bird or mammal data availableordifethialone•No bird data available for bromethalinNobirddataavailableforbromethalin76Types of Studies Available•Secondarytoxicitystudies are availableyfor several species of predator andscavenger birds and mammals, such as:Raptors passeriforms charadriiforms•Raptors,passeriforms,charadriiforms•Canids, mustelids, procyonids•Birds and mammals were fed:•Rats,micevoles fed on rodenticide bait,•Spiked meat77Secondary feeding study mortality occurrences(# of available studies)Chemical Birds MammalsBrodifacoum Yes (12) Yes (4)DifethialoneNodataNodataWarfarin Yes (4) Yes (7)ChlorophacinoneNo (8)Yes (8)Yes(8)Diphacinone Yes (3) Yes (3)Bromethalin No data No (1)78Summary: secondary feeding studiesChemicalDose-Based RQs Dietary-Based RQs OpportunitySecondaryFeeding Studies1 DayPreyMulti DayPreyEmpiricalPrey1 DayPreyEmpiricalPrey1 dayPreyMulti DayPreyBi drdsBrodifacoumDifethialoneNo dataWarfarin(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo data No data No dataMammalsBrodifacoumDifethialoneNo data No data No dataWarfarin(0.025%)Warfarin(0.054%)Chlorophacinone79DiphacinoneBromethalinNo data No data No dataAll evidencesuggest riskPredominant evidenceof riskEquivocal evidenceof riskAll evidencesuggest low riskSecondary Risk ConclusionsChemicalDose-Based RQs Dietary-Based RQsOpportunitySecondaryFeedingStudiesSecondaryRiskConclusionsTheoreticalPreyEmpiricalPreyTheoreticalPreyEmpiricalPreyBirdsBrodifacoumDifethialoneNo dataWarfarin(0 025%)(0.025%)Warfarin(0.054%)ChlorophacinoneDiphacinoneBromethalinNo data No data No dataMammalsBrodifacoumDifethialoneNo data No data No dataWfiararn(0.025%)Warfarin(0.054%)Chlorophacinone80DiphacinoneBromethalinNo data No data No dataAll evidencesuggest riskPredominant evidenceof riskEquivocal evidenceof riskAll evidencesuggest low risk