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TRAC0 @ 0@` (#(#ToleranceReassessmentAdvisoryCommitteeUSDA @ 0 @` U.S.DepartmentofAgriculture  )n$(  @  @`  @  @ L 3#L%   I.0 @ INTRODUCTION g  0 @ %   A.0@` (#(#Background kh h 0 @  @` OnApril7,1999theU.S.EnvironmentalProtectionAgency(EPA),OfficeofPesticidePrograms(OPP)issuedintheFederalRegister(64FR16967)aNoticeofAvailability  p (alongwitharequestforcomment)forasciencepolicypaperentitled"DataforRefiningAnticipatedResidueEstimatesUsedinDietaryRiskAssessmentsforOrganophosphatePesticides,"(EPA1999a)hereafterreferredtoasthe"AR(anticipatedresidue)paper."Thisdocumentdescribedthetypesofdatathatcanbeusedtorefineresidueestimatesfordietaryexposureassessments.Thepurposeofthepaperwastwofold:(1)toexplainwhenandhowEPAcouldusethesetypesofdata;and(2)todeterminetheextenttowhichsuchdatawerealreadyavailable.AfterreviewingthecommentsandinformationreceivedinresponsetotheARpaper(submittedunderdocketOPP-00591),OPPdraftedspecificguidelinesforconductingbridgingandresiduedeclinestudies.ThesetwosubsequentguidancedocumentswerealsomadeavailableforpubliccommentthroughanoticeintheFederalRegister(64FR42372)onAugust T 4,1999(EPA1999b;1999c).0 @  @` Atotalof14commentswerereceivedontheARpaper(submittedunderdocketOPP-00591);sixcommentswerereceivedonthebridgingandresiduedeclinestudyguidance(submittedunderdocketOPP-00616).Becausethesepapersandthecommentsreceivedareverycloselyrelated,OPPhaschosentorespondtothecommentsonallthreepapersinthisonedocument.Commentersincludedpesticideregistrants,environmentalandpublicinterestgroups,consultants,privatecitizens,professionalsaffiliatedwithlandgrantuniversities,andtheFQPAImplementationWorkingGroup(IWG),aswellasnumerousindividualstatefarmbureausthatsupporttheIWG.AllcommentsandrecommendationswerereviewedbyOPPandincorporated,asappropriate,intoonerevisedsciencepolicydocument.Alistingofthenamesandaffiliationsofthepartiessubmittingcommentsisprovidedattheendofthisdocument(seeSectionIV!ListofCommenters).  !   @ 0 @ %   B.0@` (#(#OrganizationofthisDocument {q  0 @  @` ThisdocumentcontainsOPPsresponsestothecommentsraisedonthreedraftsciencepolicypapers.Thedocumentisorganizedbytopicarea,eachofwhichcontainsabriefsummaryoftherelevantsectionsofthedraftsciencepolicies,asynopsisofthepubliccommentsthatweresubmitted,andtheAgencysresponse.TheseresponsesincludediscussionofthecommentsreceivedonspecificquestionsposedbyOPPineachofthesciencepolicypapers.ThespecificquestionsposedintheARpaperwere:L sv`3L 3   0 @ 0@` (#(#3Lt2sv3  0@ ` (#` (#  EPAproposesto:reviewexistingbridging,residuedecline,andotherdata;and   developguidanceforconductingthesekindsofstudies.Thepurposeofthesemultirate,multipreharvestinterval(PHI)studiesistobeabletousethefullrangeofexpectedresiduevalues(basedonthefullrangeofapplicationratesandPHIs)indietaryexposureassessmentsandtherebyproducemorerealisticestimatesofdietaryrisk.Isthisareasonableandefficientapproach?WhatotherapproachesshouldEPAconsider?3Ltt݌̌   3   0 @ 0@` (#(#3%w2sv3  0@ ` (#` (#  EPAbelievesthatbetweenoneandthreefieldtrialsconductedatdifferentlocations  (withthreedifferentapplicationratesateachfieldtrialandthreeindependentsamplescollectedateachrateorPHI)areneededtodemonstratethemathematicalrelationshipbetweenapplicationrateorPHIandamountofresidue.Isthissamplingregimeadequatetocharacterizetherangeofpotentialresidues?3%wpw݌̌   3   0 @ 0@` (#(#3y2sv3  0@ ` (#` (#  Indevelopingitsguidance,EPAhasassumedthattherelationshipbetween ,| applicationratesand/orPHIsandresultingresiduelevelsisnotnecessarilythesameforallchemicals.Isthereanyinformationavailabletosuggestthatthisassumptionisincorrect?Isthereanyinformationavailabletosuggestthattherelationshipbetweenapplicationratesand/orPHIsandresultingresiduelevelsfortheorganophosphates(OPs)asaclassmaybesimilar?3yy݌̌   3   0 @ 0@` (#(#3.|2sv3  0@ ` (#` (#  EPAiswillingtoconsiderdataontheprevalenceoffoodprocessingpractices,along v!  withdatatoquantifyresiduereductionsfromsuchpractices.Shouldinformationontheextentoffoodprocessingpracticesbevalidated?Ifso,howcouldthisbeaccomplished?3.|y|݌̌   %^ $ 0 @  @` Duetothesimilarityinthemethodsandtechniquesofthecompanionpaperspresentingdraftguidanceforconductingbridgingandresiduedeclinestudies,EPAposedthesamequestionsforeachofthesedocuments,asfollows:L sv``L 3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  Istheguidanceprovidedinthesedraftdocumentsclearandcomplete?Ifnot,whynot . ~ andwhatadditionalguidanceisneeded?3݌̌   3   0 @ 0@` (#(#3Հ2sv3  0@ ` (#` (#  Aretheresiduestudiesdescribedinthesedocumentsadequateforgeneratingrefined  0 acutedietaryprobabilisticexposureandriskassessments?Ifnot,whynotandhowshouldtheybemodified?3Հ ݌̌   3   0 @ 0@` (#(#3i2sv3  0@ ` (#` (#  OPPhasproposedthatbetweenoneandthreefieldtrialsbeconducted,thatatleast x  threeapplicationratesand/orfivePHIsbetested,andthatthreecompositesamplesbecollectedateachapplicationrateorPHI.Dotheserecommendationsappeartobereasonableandsufficienttoestablisharatevs.residueorPHIvs.residuerelationship? *z  Aredataavailablethatindicatethattheseguidelinesareadequateforthepurposesintended?Explain.3i݌̌   3   0 @ 0@` (#(#3#2sv3  0@ ` (#` (#  OPPhasstatedthatitbelievesthatthefieldtrialsperformedforbridgingstudy/residue  declinepurposesshouldbeconductedatanexaggeratedrate,ifnecessary,suchthatallresiduesare"quantifiable"(i.e.,atorgreaterthantheLOQ).Wehavestatedthatit  wouldbeconsideredinappropriatetoderiveaquantitativerelationshipbetweenapplicationrateandresiduelevelonresiduesthatarebelowtheLOQasthiscouldintroducesubstantialuncertaintyintotheestimatedrelationship.Pleasecommentonthisproposedrestriction.Pleasealsocommentontherecommendationthatstudiesbeconductedatanexaggeratedrate,ifnecessary,toavoidthepotentialproblemassociatedwithnondetectable(ND)residues.3#n݌̌   3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  OPPstatesthatextrapolationofdatabetweensimilarcropsmaybeallowedona  casebycasebasisconsideringsimilarculturalpracticesandapplicationpatterns.Shouldtheseextrapolationsbelimitedtocropswithinacropsubgroup/grouporshouldmoreextensiveextrapolationsbetweengroupsbepermitted?Ifso,onwhatbasisshouldmoreextensiveextrapolationsbepermitted?32݌̌   @#"  3   0 @ 0@` (#(#3N2sv3  0@ ` (#` (#  Fortherelationshipproducedbybridgingorresiduedeclinedatatobeusedinan  exposureassessment,itisnecessarytohavereliableusagedataconcerningapplicationratesand/orPHIs.Forexample,ifresiduesresultingfromthefull(maximum)applicationrate,threequartersofthemaximumapplicationrate,andonehalfthemaximumapplicationaredetermined,itisnecessarytoalsohaveinformation . ~ onthepercentage(orfraction)ofthetimeeachoftheseapplicationratesareused.AsimilarsituationexistsforPHIs.Isthisinformationavailablefromeitherpublicorproprietarysources?Ifso,fromwhichsourcescanthesedatabeobtainedandhowreadilyavailablearethey?3N݌̌   3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  Theproposedmethodologyuseswhatisbelievedtobethestatisticallymore   appropriate"lackoffit"(LOF)testtodetermineifthehypothesizedmodel(e.g.,linear x  relationshipbetweenapplicationrateandresiduelevel,firstorderdecayinresidueconcentrationwithtime,etc.)isadequatetodescribethedata.Pleasecommentonthis F  proposedapproachandcompareitwiththemorewidelyusedcoefficientofdetermination(r2).Underwhatcircumstancesmighttheuseofr2tojudgeafitadequate d bepreferredtothe"lackoffit"test?Shouldthetwobeusedinconjunctionwithoneanotherandifso,how?Theremaybeinstanceswherethe lackoffittestrevealsthatthehypothesizedlinearassociationcanberejected,butthecoefficientofdeterminationshowsthatthelinearrelationshipaccountsforasignificantportionofthevariability.Whatstatisticaltests,ifany,shouldbeusedtojudgewhetherther2issignificant?3H݌  Ќ   3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  OPPwillrequirethatcompositesamplesbecollectedaspartofreducedusefieldtrials ^ toretaincomparabilitywithearliermaximumrate/minimumPHIfieldtrialsconductedtosupporttolerancedecisions.Nevertheless,OPPstillhasconcernsabouttheeffectcompositingmayhaveonunittounitvariation.WhenresidueestimatesaregeneratedfrommaximumapplicationrateandminimumPHIs(worstcaseconditions),OPPbelievesthatthereisanadequatedegreeofcompensatingoverestimationsuchthatindividualunitvariationisnotofconcern.ByincorporatingtherangeofapplicationratesandPHIsinaprobabilisticscenario,theconservatismbuiltintoEPAsuseoffieldtrialdataiserodedandmayrequiretheAgencytocompensateforthiswithstatisticallyvaliddataonindividualsamplesand/orunittounitvariation.OPPisproposingthatchemicalspecificconsiderationsbeconsideredtodeterminewhethertheuseofcompositedatafromreducedratefieldtrialsareacceptable.Alternatively,a"decomposition"proceduremaybejudgedappropriate.Pleasecommentonwhethertheseconcernsarejustifiedand,ifso,howtheyshouldbeaddressedbyOPP.3E݌̌   3   0 @ 0@` (#(#3x2sv3  0@ ` (#` (#  Inperformingtheregressionanalysisforbridgingstudies,OPPhaselectednotto &*"& "force"theregressionrelationshipthroughzero,despitethefactthatanapplicationrateof0lbsai/Awouldbeexpectedtoresultinazeroppmconcentrationintheplantorplantpart.Pleasecommentonthisdecisionandanyrequiredchangesininterpretationofthestatisticalparameterswhichadecisiontoforcetheregressionthroughzerowouldentail.3xÙ݌̌   >,',  3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  OPPintendstocombinethebridgingstudyandresiduedeclinestudyguidance  documentsintoonedocument.Insodoing,woulditbeusefultoexpandthesectiononmultipleregressiontechniques?Howusefulwouldthisexpansionbeandarethereanyrecommendationsonhowthiscouldbestbedone?3h݌̌   3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  Whatotherdataorinformationsimilartothatdescribedinthisguidancedocument . ~ wouldprovideasound,empiricalbasisfordeterminingresiduesattypicalapplicationratesforriskmitigationpurposes?3d݌̌  0 @  @` Toorganizethecommentsreceivedonthesethreepapers,OPPhascombinedthemintoseverallargertopicareas: L sv``L 3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  ScienceandPolicy3݌ x  Ќ   3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  RiskManagementIssues3ޡ݌ D  Ќ   3   0 @ 0@` (#(#3}2sv3  0@ ` (#` (#  GeneralApproachtoBridgingandResidueDeclineData3}Ȣ݌ ` Ќ   3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  Processing/Cooking/ResidueDegradationData3У݌ , Ќ   3   0 @ 0@` (#(#32sv3  0@ ` (#` (#  ResiduesinMeatandMilk3Τ݌  Ќ   3   0 @ 0@` (#(#3o2sv3  0@ ` (#` (#  SpecificGuidanceforConductingBridgingandResidueDeclineStudies3o݌ t Ќ  0 @ 0@` (#(#%   II.0 @ RESPONSETOCOMMENTS  @   \ 0 @ %   A.0@` (#(#ScienceandPolicy 8 @  .  @ 0 @`  @ 0 @ 0@` (#(# Overview .SeveralcommentersfeltthattheARpaperandothersintheTolerance  ReassessmentAdvisoryCommittee(TRAC)serieswereactuallyriskmanagementpoliciesthataresciencebased,ratherthansciencepolicies.OnecommenterquestionedthevalueofpolicypapersiftheAgencycoulddeviatefromthepolicyatitsdiscretion.AnumberofcommentsindicatedalackofclarityregardingthescopeandapplicabilityoftheARpaperwhichhadfocusedonOPpesticides. >$# 0 @ 0@` (#(# %   1.0@ ` (#` (#SeparatingScienceandPolicy ,   &\!% 0 @ 0@` (#(#0@ ` (#` (# @ Comment .SeveralcommentersfeltthatmanyofEPA's"sciencepolicies"are '.#' mislabeled.Theyareactuallyriskmanagementpoliciesthataresciencebased.Assuchtheyshouldremainflexibleenoughtoallowincorporationofevolvingscientificknowledge. |+&+ 0 @ 0@` (#(#0@ ` (#` (# @ Response. OPPacknowledgesthattherearebothscienceandriskmanagement  policymattersdiscussedintheARpaperandinothersciencepolicypapers.Forexample,thenumberoffieldtrialsandresiduesamples,aswellastheanalyticalandstatisticalmethodsforevaluatingthemmaybeconsideredscienceissues.Whereas,whatconstitutesalevelofconcernforfoodriskorwhatmarginofsafetyisadequateareriskmanagementdecisions,albeitinformedbyscientificconsiderations.Further,OPPagreesthatitisimportanttoidentifyscienceissuesandtoseparatethemfromriskmanagement.Forthatreason,thereisaseparatesectioninthisdocumentforriskmanagementissuesraisedbycommenters.Regardlessofwhetherthesepapersareregardedasriskmanagementdocuments,sciencepolicydocuments,oramixtureofboth,OPPbelievesthattheideastheycontainareworthyofawideairingandpublicdiscussion.  ~  0 @ 0@` (#(# %   2.0@ ` (#` (#ThePracticalValueofThesePolicyPapers Q   0 @ 0@` (#(#0@ ` (#` (# @ Comment .OnecommenterbelievedthattheAgencysdescriptionofthesepolicy h paperswouldleadonetoquestiontheirpracticalvalue.TheFederalRegisternoticefor T eachpaperdescribesitasapolicydocumentandnotabindingrule;thecommenterwasconcernedwiththephraseinthedocument onacasebycasebasis,EPAwilldecidewhetheritisappropriatetodepartfromtheguidance....Hestatedthatthephrase casebycasecancovera multitudeofsins,andthat oneisleftwiththeimpressionofdocumentswritteninsand.ThecommenterstatedthattheFederal  $  RegisternoticescommittheAgencytoexplainitsdeparturesfromthepolicydocuments   andtheAgencyshouldholdtothiscommitmentstrictly,makingcleartheimpactofeachdeviationonparticularriskassessments.̀0 @ 0@` (#(#0@ ` (#` (#  @ Response .AnydeviationswillbeexplainedinOPPsriskassessmentsandwillbe V  supportedbyafullandopenriskcharacterization.AninherentfeatureofguidanceisthatitisnotbindingoneithertheAgency,theregulatedindustry,ormembersofthepublic.Decisionsfollowingtheguidanceciteitnotasauthorityforthedecisionbutasanexplanationforthereasonablenessofthedecision.IfOPPdepartsfromtheguidance,itwillseparatelyprovideanexplanationforitsdecision.0 @ 0@` (#(# %   3.0@ ` (#` (#ScopeandApplicabilityoftheAnticipatedResiduePaper ,   0 @ 0@` (#(#0 @ 0@` (#(#0@ ` (#` (# @ Comment .ManycommentersnotedthattheapproachdescribedintheARpaperfor ^ usingvarioustypesofdatatorefineresidueestimatesshouldextendtoallofEPA'spesticideresidueassessments,notjusttheOPassessmentscurrentlyunderway. 0 @ 0@` (#(#0@ ` (#` (# @ Response .InthedraftARpaper,theAgency'sintentwastoseekinformationfromthe L publiconthenatureandextentofexistingdataofthesortdescribedinthepaperforallpesticides.ThedraftpapernotedaspecificinterestinthesetypesofdataforOPsbecausethatlargeclassofpesticideswas(andstillis)underevaluationbyEPA.TheAgencydidnotintendtolimittheproposedpolicyonlytoOPs.Thereviseddocumentincludesthisclarification. @  @`  @ 0 @ 0@` (#(#0@ ` (#` (# @ Comment. Onerespondentsuggestedthatbeforeanydataaredeveloped,EPAand L$# registrantsshoulddeterminewherethesedatawouldhaveameaningfuleffect.Ifagivencropisnotasignificantcontributortoriskorifresiduesatthelimitofdetection(LOD)orlimitofquantification(LOQ)alreadypresentariskconcern,additionaldatawouldnotlikelyaddresstheriskadequately.0 @ 0@` (#(#0@ ` (#` (# @ Response. OPPagreesthatfocusingonrisk"drivers"isprudent.Becausethedrivers )%) inadietaryriskassessmentbasedonresiduesinfoodarenotalwaysobvious,OPPhasincorporatedintoitsassessmentaCEC(CriticalExposureContributors)analysis +&+ featureoftheDietaryExposureEvaluationModel(DEEM))softwarethatenablesOPPtoidentifyforregistrantsandallotherinterestedstakeholderswhichcommoditiesarethegreatestcontributorstothedietaryriskfromfoodforaspecificchemical.Furthermore,aspartofthepublicparticipationprocessdevelopedbyTRACfortheOPs,andsoontobeextendedtoallchemicalsinreregistration,theAgencygeneratesa"Summary"and"Overview"oftheriskassessmentidentifyingrisksofconcernandthesignificantriskdriversifany.Itshouldbenotedthatnotalldietaryassessmentshavedrivers.Insomeinstances,manycommoditieshaveessentiallysimilarcontributionstotheoverallrisk.  (# (# Ѐ0  0` (#(# %   4.0 ` (#` (#RoleofMonitoringDatainRefiningAnticipatedResidues  (# (#  0  0` (#(#0 ` (#` (#  Comment .Severalcommentersnotedthatwhiletheyhad  noobjectiontotheAgency'suseofbridging,decline,andotherdatatorefineresidueestimates,itwouldbefarpreferabletoexpandtheU.S.DepartmentofAgricultures(USDA)PesticideDataProgram(PDP)andothermonitoringprograms.Monitoringdata,theypointedout,arethemostrealisticdataavailablesincetheyrepresenttheamountofpesticideresiduefoundonfoodsnearthepointofconsumption.  (# (#    ` 0 0 (# (# (#(# 3  0(#% 3 0  0` (#(#0 ` (#` (#   Response. EPAacknowledgesitspreferenceforusingPDP  andotherappropriatemonitoringdatainmostinstancesforassessingdietaryriskfromresiduesinfood,whensuchdataareavailable.TheAgencyhasdevelopedmethodstousePDPdatatothegreatestextentpossibleinitsassessments(EPA1999h).Forexample,PDPdataareanalyzedascompositesamples,andEPAhadpreviouslyusedthesedataonlyforblendedcommodities.However,theAgencyandotherinterestedpartiesrecentlypresentedtotheFIFRAScientificAdvisoryPanel(SAP)severalstatisticalmethodsto"_decomposite_"thesamples.Thisallowsforestimationoftherangeofpossibleresiduevaluesinsinglefooditemswithinacompositesample.Furthermore,OPPtranslatesresiduevaluesfromsampledcommoditiestosimilarcommoditiestreatedwiththesamepesticide.OPP,forexample,wouldgenerallyusethesampledresiduevaluefromorangesforgrapefruit,andothercitrusfruits,ifnosampleswereavailableforthoseotherfruits.  (# (# 0  0` (#(#0 ` (#` (#  Itmustbenoted,however,thatduetothecostofmonitoringandthelimitsonavailablefunding,PDPandothermonitoringdataarenotavailableforallfoodcommodities,noraretheyavailableforallpesticides.EPAworkscloselywithUSDA,theagencythatadministersthePDPprogram,todeterminewhichpesticides,metabolites,andfoodcommoditiesaremostcriticaltomonitor,andwhatmodificationscanbemadetotheprogrameachyear.  @  (# (# 0  0` (#(#0 ` (#` (#  Insummary,forconductingdietaryassessmentsforresiduesinfood,monitoringdataaregenerallypreferabletoresiduedeclineorbridgingdata.Cookingandprocessingdatacanbeusedinadditiontomonitoringdatatofurtherrefinesuchestimates.  (# (# 0  0` (#(#0 ` (#` (#  Finally,indiscussingtheapplicabilityofresiduedeclineandbridgingstudies,itshouldbenotedthethesetypesofdatahaveutilitybeyonddietaryriskassessments.Forexample,bridgingdatacanbeusedtoestimateanappropriatemodifiedapplicationrate,ifapesticide'sapplicationrateneedstobereducedduetoriskconcerns.Similarly,residuedeclinedatacouldbeusedtoestablishanappropriatePHI.Inbothcases,itwouldbelesscostlytoconductdeclineand/orbridgingstudiesthantorecreatetheentireresiduedatasetforagivencrop.  (# (# /  */&( / 0  0` (#(# %   5.0 ` (#` (#OtherSourcesofMonitoringData   (# (# 0  0` (#(#0 ` (#` (#  Comment .Severalindividualssuggestedothersourcesof  monitoringdataincludingbothpublicandprivatesources,andforeignfieldresidue,processing,andmonitoringdata.Forexample,thehightemperaturehydrolysisstudyrequiredbytheEuropeanUnionmaybeusefulinprovidingresiduedegradationinformationasitmimicstheeffectsofcooking.  (# (# 0  0` (#(#0 ` (#` (#  Response .InsomeinstancesOPPhascontacted V  commentersregardingtheavailabilityofmonitoringdata.Ingeneral,OPPhasfoundthatmanyprocessorsmonitorforpesticideresidues,butfewofthesemonitoringprogramsareabletolinkactualpesticidetreatmentsinthefieldtoresiduesinthefinishedcommodity!informationthatisessentialtodeterminetherateorpercentageofresiduedecline.Furthermore,mostcompaniesandprocessorsarewillingtoprovidemonitoringdataonlywhenaspecificneedisidentifiedbyOPP.  (# (# 3 3   0 ` %   6.0 ` (#` (#RefinementsShouldNotbeAppliedinSomeInstances  1 (# (# 0  0` (#(#0 ` (#` (#  Comment .EPAassessmentsneedtotakeintoaccountthe ( factthatfarmchildrenaremorelikelytoconsumefoodsshortlyafterharvest,andthuswithmoreresidues,than_nonfarm_consumers.Residuedegradationanddeclinestudieswouldapplymuchlesstothesechildrenthantothe"average"population.OthersituationsnotaccountedforinEPA'sdraftpolicyarefamilieswhogrowtheirownfood,pickyourownfarmoperations,androadsidestands.EPAneedstoaccountforthechildwho"binges"ongrapesorpeachesatcertaintimesoftheyear.EPAshouldnotassume100%cookingorpeeling,notevenforpotatoesormeat(manyeatmeatveryrareorassteaktartare).0 (# (#0 (#(#o$! (# (# 0  0` (#(#  ` (#` (# / / /  W&!# /   0 ` 0 ` (#` (#  Response. OPPdoesnotassesspotentialexposuresfrom  foodthatmightbeobtainedfromroadsidestandsor"pickyourown"operationsperseduetolackofdataonhowmanypeople  consumefoodsfromthesesourcesandwhatproportionoftheirindividualdietsisfromsuchsources.However,OPPanticipatesthataverysmallpercentageoftheU.S.populationderivesmorethananegligibleportionoftheirfoodinthismanner.Moreover,someharvestedcropsaredistributedsoquicklytowholesaleandretailoutletsthattheresiduesinthemwouldbeverysimilartothelevelsincropssoldnearwheretheyaregrown.  (# (#    `     h 0  0` (#(#0 ` (#` (#  OPPrecognizesthatbingeeatingcanoccur(andisnotuncommonamongchildrenwhomaypreferentiallyconsumeonefoodorclassoffoods).ThisphenomenoniscapturedbythefoodconsumptionsurveydatabasethatOPPusesinitsassessments(USDA'sContinuingSurveyofFoodIntakebyIndividuals,whichiscommonlyknownasCSFII).InadditionwenotethattheUSDASupplementalChildrensSurvey,whichwasdevelopedbyUSDAatEPAsrequest,willsoonbeincorporatedwiththe199496CSFIIandwillincreasebyfivefoldthenumberofchildrenagesonetofivesampled.Furthermore,bylookingatthe99.9%ofexposure,OPPsassessmentscapturethoseindividualswhoconsumelargeamountsofagivenfooditem.  (# (# 0  0` (#(#0 ` (#` (#  Finally,withregardtotheassumptionsthatOPPusesrelatedtocookingandpeeling,theUSDAconsumptionsurveycontainsspecificinformationabouttheformofthefoodthatisconsumed.If,forexample,anindividualinthesurveyreportseatinganuncookedpotato,or_unpeeled_Ԁkiwifruit,OPPwouldnotapplyacookingfactororpeelingfactortothecommodityconsumedbythatindividual.Inthe198991and199496consumptionsurveys,forexample,noindividualreportedeatinguncookedmeat.  (# (# /  3$! / 0   (#(# 0  %   B.0` (#(#RiskManagement {` (#` (#  0   ` Overview .Avarietyofcommentswererelatedtoriskmanagement  issuesassociatedwiththeAgency'sproposedpolicytousevarioustypesofdatatorefineresidueestimates.Thedraftpolicydidnotspecificallyaddressriskmanagementandstatedonlythatifdataweredeemedtobeadequateforriskassessmentpurposes,theywouldbeconsideredintheongoingreviewsoftheOPs.TheprocessforpublicinvolvementinreviewingtheOPswasdevelopedbytheTRAC,andconsistsofsixPhases,includingtwopubliccommentperiods!onefocusedonthepreliminaryriskassessmentandanotherfocusedondevelopmentofappropriateriskmitigation.ThetimeforsubmittingdatatorefineARsideallywouldbenolaterthanduringthe60daypubliccommentperiodontheindividualactiveingredientPhase3oftheTRACprocess.Thedraftpolicyfurthernotedthatevenifthedietaryriskfromanindividualchemicalwasnotofconcern,registrantsorothersmightwishtodevelopdatatofurtherrefineresidueestimatespriortothecumulativephaseoftheOPassessment.Severalcommentsarebeyondthescopeofthecurrentguidance.Nonetheless,theyaresummarizedherewithreferencestoother,moreappropriatepolicypapersandareasfordiscussion.Additionalclarificationisprovidedbelow. (#(#    ` %   1.0 ModifyLabelstoReflectLowerRates   (# (#   0 `  ` (#` (# 0  0` (#(#0 ` (#` (#  Comment .OnecommenterfeltthatifEPAusedarangeof  "typical"applicationrates(andresidues)initsassessments,thenpesticideproductlabelsshouldbeamendedtoreflectthosemorerestrictiveparameters.ThereisnomechanismtoenforcetypicaluseratesandPHIs,andunlesslabelsaremodified,typicalusepatternscouldshifttowardhigherresiduesovertime.  (# (# 0   (#(# 0  0` (#(#0 ` (#` (#  Response .OPPdesirestoproducepesticideexposure T! estimatesthatapproximate,ascloselyaspossible,actualexposuresthatoccurintherealworld.ItisalsoOPPsintentionthatitsexposureandriskestimatesnotunderestimateactual ?$! exposures,andOPPsriskassessmentpracticesandpoliciesaredevelopedandimplementedwiththisgoalinmind.ThecommenterappearstobelievethattheuseofarangeoftypicalapplicationratesinaprobabilisticriskassessmentnecessitatesthatthelabelsbeamendedtoreflectthesemorerestrictiveparametersandisconcernedthatthereisnomechanismtoenforcetypicaluseratesandPHIs.OPPdisagreeswiththecommenter.Thepurposeofaprobabilisticriskassessmentisnottorestrictusageorenforce +/') ratesperse,butrathertodevelopestimatesofexposureandrisk  thatreflectasaccuratelyaspossibleactualuseandusage  practices,whichincludetherangeoftypicalapplicationrates.OPP  believesthatappropriatelyconsideringthefullrangeandprobabilitiesassociatedwithrealworldpesticideapplicationpracticesand,whenavailable,incorporatingthisinformationintoAgencyriskassessmentsisconsistentwiththespirit,intent,andintrinsicprinciplesofprobabilisticriskassessmentandwithEPAsresponsibilitytoassurethattolerancesaresafe.  (# (# 0  0` (#(#0 ` (#` (#  OPP,however,doesagreewiththecommenterthattypicalusepatternscouldshifttowardincreaseduseandincreasedresidues.TheFoodQualityProtectionActof1996(FQPA)requirestheAgency,inthoseinstanceswhereanticipatedresidueestimatesareincorporatedintoanOPPassessment,toverifyinfiveyears,andthereafterasEPAdeemsappropriate,thattheestimatesincorporatedbyOPPinitsriskassessmentarestillvalid(seesection408(b)(2)(E)(ii)).Thus,thecommenteriscorrectinthatshiftingtypicalusepatternscouldresultinhigherresidueswithtime,butunderFQPAtheAgencyisrequiredtoperiodicallyreevaluatethesedataandadjustitsriskestimates,whennecessary.  (# (# 0  0` (#(#0 ` (#` (#  OPPalsodoesagreethatundercertaincircumstanceslabel  modificationtoreflectlowerapplicationratesand/orincreasedPHIswillbenecessary.Forexample,ifEPAsprobabilisticassessmentindicatedthatdietaryexposuresareabovelevelsofconcern,theAgencycouldrequirethatlabelsbemodifiedtoreflectthelowerapplicationratesorlongerPHIsthatreflectmoretypicalratesorPHIs.However,thisresultingloweringoflabelratesisaresultofriskmitigation/managementactivities,notaresultofaneedto lockinmaximumlabelapplicationratesusedintheriskassessment.  (# (# 0   0 1 1 1  $$t! 1 0  0` (#(# %   2.0 ` (#` (#HowDataWillBeUsed     (# (# 0  0` (#(#0 ` (#` (#  Comment .Somecommentersindicatedthatitwasnot  clearhowthetypesofdatadescribedinthedraftpolicywouldbeused.OnecommenternotedthatthepolicysuggestsEPAcannotdepartfromtheuseoftoleranceorfieldtrialvaluesunlessithaschemical/cropspecificdata.  (# (# 0  0` (#(#0 ` (#` (#  Response .EPAagreesthatitisimportanttoputthe n  proposedresiduerefinementsintotheproperperspective.OPPhasmadeseveralclarificationstothepolicy.First,asdiscussedaboveinresponseA4,OPPusesPDPandothermonitoringdatatothegreatestextentpossibleinbothacuteandchronicdietary(food)riskassessments.Residuedecline,degradation,andbridgingdatawouldgenerallybeofgreatestvalueifPDPorothermonitoringdatawerenotavailable,orifthemonitoringdatadonotrepresentrecentchangestotheusepractices.Cookingorprocessingdatahowever,couldbeusedinadditiontomonitoringdatatofurtherrefineresidueestimates.Forexample,PDPmayhaveresiduedataforaspecificpesticideusedonpotatoes.ThesedataalreadyreflecttherangeofapplicationratesandPHIsthatwereactuallyused.However,residuereductionfactorsderivedfromcookingdata(e.g.,boiling,baking,_microwaving_,frying)could % stillbeappliedbecausethesewouldreflectchangesinresiduelevelssubsequenttoPDPsampling.  (# (#    ` 0  0` (#(#0 ` (#` (#  Whichrefinementsaremostappropriateforaspecificcropandchemicalmaydifferdependingonthepropertiesofthechemicalandthetypesofcropstreatedwithit.Forexample,isthecropeatenfresh,isittypicallystoredforalongperiodoftime,isittypicallywashed,peeled,cannedorfrozen,etc.u! (# (# 1  ]#  1 0  0` (#(# %   3.0 ` (#` (#AShortTermManagementStrategyisNeeded    (# (# Ѐ    0  0` (#(#0 ` (#` (#  Comment .Severalcommentersfeltthatthedraftpolicydid  notaddresstheshorttermproblem,i.e.,theneedforappropriate  datatorefineresidueestimatesfortheOPpesticidesthatarecurrentlyunderreview.OnecommentersuggestedthatFFDCAsection408(b)(2)(E)allowsEPAtoestimateanticipatedresiduelevelsevenifnoactualcropspecificdataareavailablesolongasEPAcallsinconfirmatorydatawithinfiveyears.  (# (#    `  0  0` (#(#0 ` (#` (#  Response .EPA,inconjunctionwiththeTRAC,has J  establishedaprocessforpublicreviewandparticipationofthetolerancereassessmentoftheOPs.WithinthisprocessEPAmakespreliminaryriskassessmentsavailableandholdsstakeholdermeetingsandtechnicalbriefingstoexplaintheassessmentsanddiscussdatagaps.ItisduringthisprocessthatEPAmeetswithregistrants,growers,andotherinterestedpartiestodeterminewhatrefinementscanorshouldbemadetoriskassessmentsandtodevelopinterimriskmitigationstrategies.EPAdoesnotbelievethataseparateshorttermmanagementstrategyisneededbecausetheTRACprocesshasproventobeaneffectivewayofworkingthroughriskrefinementsandmitigation,includingidentifyinganddevelopingdatathatmaybenecessarytoconfirmthatresiduesareactuallylowerthanpreliminaryestimatessuggest.  (# (# 0  0` (#(#0 ` (#` (#  EPAagrees,inpart,withthecommenter'sconstructionofsection408(b)(2)(E).ThatprovisionstatesthatEPA"mayconsideravailabledataandinformationontheanticipatedresiduelevelsofthepesticidechemicalinoronfoodandtheactualresiduelevelsofthepesticidechemicalthathavebeenmeasuredinfood,includingresiduedatacollectedbytheFoodandDrugAdministration."IfEPAreliesonsuchdataorinformation,itmustcall-indatatobeprovidedfiveyearsafterthetoleranceaction,"andthereafteras[EPA]deemsappropriate,demonstratingthatsuchresiduelevelsarenotabovethelevelssoreliedon."EPAwouldagreethatthisprovisiondoesnotlimitEPAtoestimatinganticipatedresiduelevelsonlywhereactualcrop-specificdataonthefoodinquestionareavailable.Byreferringto"availabledata"theAgencyisgivendiscretiontoconsideranydatathatbearonresiduelevels,includingdatafromthesamepesticideonothercropsorsimilarpesticides.Suchdatacouldbeusedtoextrapolateormodel +A') anticipatedresiduelevelsinthefoodinquestioninappropriatecircumstances.EPA'suseofsuchextrapolationsormodelsistempered,asalways,bysection408(b)(2)(D)'scommandthatEPAconsiderthereliabilityoftheavailabledata.EPAdoesnotagreewiththecommenter'sinterpretationofsection408(b)(2)(E)totheextentthatthecommenterissuggestingthatCongressintendedthattheinitialestimateofanticipatedresiduesneedbenomorethanamere"prediction"ofresiduelevelswiththesubsequentdatabeingusedtoconfirmthatprediction.Rather,EPA'sviewisthattheinitialestimateofanticipatedresiduesmustbereasonablebasedontheavailabledata.Subsequentdatacall-inswouldthenbeusedtoverifythat,overtime,conditionshadnotchangedsuchthattheanticipatedresiduelevelshadrisentosuchalevelthatariskofconcernwascreated.Forexample,thestatutespecificallyauthorizesuseofFoodandDrugAdministration(FDA)monitoringdatainmakinganestimateofanticipatedresidues.Wherethatisthecase,EPAwouldprobablyrequiresubmissionofsimilarmonitoringdatabeprovidedfiveyearslatertoverifythatusepatternshadnotsignificantlyalteredresiduelevels.  (# (#    ` %   4.0 DoNotDelayRiskManagementPendingDataDevelopment +  (# (# 0  0` (#(#0 ` (#` (#  Comment .SeveralcommentersurgedEPAnottowaitfor  data(includingthetypesofresiduerefinementdatadescribedinthedraftpolicy),ifthereareotherrisksofconcern;forexample,highrisktoworkershandlingandapplyingthepesticide.Delayingactioninthenameof"refinements"issidesteppingtheAgency'sresponsibilitytoprotectchildren'shealthandworkers.ThecommentercitedareportbytheEnvironmentalWorkingGroup(EWG)thatusedgovernmentresiduedataandshowedsomeresiduesonsingleservingsizesaloneexceedEPAslevelofconcern.AnothercommenternotedthattoavoidwastingresourcesEPAshouldevaluatetheutilityofadditionalstudiesinthecontextoftheoverallriskofthechemical.PesticideswithunacceptablerisksusingmethodlimitshaveoutstrippedourabilitytomeasureandEPAshoulddiscourageuseofthese.  (# (# 1  (b#% 1 0  0` (#(#0 ` (#` (#  Response. Generally,EPAconductsafullexposureand  riskassessmentbasedonthebestavailabledata.FortheOPs,theTRACprocessprovidesforpublicreview,refinementofEPAsassessmentsanddevelopmentofriskmitigationonanorderly,equitableschedule.DuringthisprocessEPAdoesevaluatetheoverallriskofthechemicalandwouldnotdelayworkerorecologicalmitigationpendingdevelopmentofdatatorefinethedietaryassessment.AprocesssimilartotheTRACprocessforOPshasbeenproposedforallchemicalsinreregistration(see65FR14199;March15,2000).Registrantsmaychoosetoconduct G  additionalbridgingorresiduedeclinestudiesandsubmittheminatimelymannerforEPAtouseinrefiningitsdietaryexposureestimates,butEPAwillnotdelaytheprocess.  (# (# 1 1 3 3    ` %   5.0 PresumptiveUseofthe10FoldSafetyFactor # O (# (#   0  0` (#(#0 ` (#` (#  Comment .OnecommenterfeltthatEPAshouldmake F "presumptive"useofthe10foldsafetyfactorbasedon:failureofcurrentrequiredtoxicityteststoassessalltoxiceffectsofconcernforfetus,infant,andchild;untestedpotentialforendocrinedisruption;failureofcurrenttestingregimetomonitoreffectstotestanimalforafulllifetime;EPA'suseofconstantlymorerefinedestimatesthatremoveprevious,moreprotectiveassumptionsthatprovidedsomemarginofsafety;lackofcomprehensiveandreliabledataonchildren's_nondietary_Ԁexposure;andlackofgoodmonitoringdatafordrinkingwater.  (# (#    ` 0  0` (#(#0 ` (#` (#  Response. EPA'spositionontheuseofthe10foldsafety   factorisbeyondthescopeofthispolicypaper.Forinformationonthattopic,thereaderisreferredtothedraftpolicypapersentitled,".XXXXStandardOperatingProceduresfortheHealthEffectsDivision l#  FQPASafetyFactorCommittee#XXX.XZ(#"(EPA1999d)and .XXXXTheOfficeof `$! PesticideProgramsPolicyonDeterminationoftheAppropriateFQPASafetyFactor(s)forUseintheTolerance-SettingProcess#XXX.X )# H&!# (EPA1999e).Bothareavailableonthe_internet_;theaddressesarelistedintheReferences.ThiscommentwillbeconsideredasEPAreviewsothercommentssubmittedonthesetwopapersanddecideswhetherandhowtorevisethem.  (# (# 1   +\&( 1   0  %   C.0` (#(#GeneralApproachtoBridgingandResidueDeclineData +` (#` (#  0  0` (#(# Overview. IntheARpaper,EPAwasseekinginformationfromthe  publiconthenatureandextentofexistingdatathatcouldbeusedtorefineresidueestimates.TheAgencyhadhopedtogathercommentsdrawingonthecombinedexperienceofthosewhohadconductedthesetypesofstudiespreviouslyandapplythemtothedevelopmentofAgencyguidanceforconductingbridgingandresiduedeclinestudies.Whilemanycommenterssupportedthegeneralapproachoutlinedinthepaper,onlyonecompanymadereferencetomarketbasketdataunderdevelopment,andnoactualdatawereprovidedduringthecommentperiod.Severalcommentswerereceivedonspecificaspectsofthegeneralapproachandthepolicyhasbeenrevisedtoreflectmostofthese. [ ` (#` (# 1 1 0  0` (#(# %   1.0 ` (#` (#ExistingData / @ (# (#  0  0` (#(#0 ` (#` (#  Comment .Ageneralthemethroughoutthecommentswas 7 thatthetypesofdatadescribedintheARpaperwerenotcommonlyavailable.Onecommenternotedthatcompaniesrarelygeneratemultipleapplicationratedataduetocost,andthatresiduedeclinedataarepartofthecurrentresiduechemistryguidelines,butarenotgenerallyavailableforolderpesticides.Anothernotedthatfewsuchstudiesexistbecauseuptonowtherehadbeennoneedtoperformthem.  (# (#  0  0` (#(#0 ` (#` (#  Response .EPAappreciatesthisinformation.Absentthese  data,OPPwillrelyonitsstandardpracticesandprocedures.Thepolicydoesnotrequireneworadditionaldata,ratheritpermitsthesedatatobeusediftheyareavailable.  (# (# 1 1 1  ]#  1 0  0` (#(# %   2.0 ` (#` (#RelationshipBetweenApplicationRate/PHIandtheResulting  Residues 4  (# (#  0  0` (#(#0 ` (#` (#  Comment .Severalcommentersaddressedthenatureof  therelationshipbetweenreducedapplicationratesandresultingresidues,andincreasedPHIsandresultingresidues.Onenotedaclearlineartrendbetweenresiduelevelandapplicationrateundercertaincircumstanceswhenlookingataverageresiduevaluesforeachapplicationrate.ThesamecommenteragreedwithEPAsassertionthatthereisnotageneralrelationshipbetweendifferentPHIsandresiduelevels.Othercommentersnotedthattherelationshipbetweendifferentapplicationratesandresidueswasnotlinear,andtherelationshipbetweendifferentPHIsandresiduesischemistrydependent.Noactualdatawereprovidedtosupportthesehypotheses.  (# (# 0  0` (#(#0 ` (#` (#  Response. EPA'spurposeinposingthequestionaboutthe m relationshipbetweenapplicationrates/PHIsandresidueswastodeterminewhetherornotexistingbridgingorresiduedeclinedatacouldlegitimatelybetranslatedamongchemicalsand/orcrops.Intheabsenceofabodyofdatatodemonstratethenatureandpredictabilityoftheserelationships,suchgeneralizationscannotbemade.  (# (# 2 2 3 3 2   2 3   3 0  0` (#(# %   3.0 ` (#` (#NumberandLocationofFieldTrialandSamples q:  (# (#  0  0` (#(#0 ` (#` (#  Comment .Manycommentersagreedthatthreereplicates  persiteandonetothreesitesperstudywereappropriate.Noalternativesamplingregimesweresuggested.Onecommenterdidnotethatthreereplicateswasadeparturefromthecurrentrequirementoftworeplicatesforresiduework.ThesamecommenterurgedEPAtoreconsiderthespecificationtohavethethreefieldtrialsintheareaofhighestproduction,theareaofhighestaveragefieldtrial(HAFT)value,andtheareaofthesecondHAFT.Therationaleforthisrequestwassothatbridgingand/ordeclinedatacouldbedoneconcurrentlywithmagnitudeoftheresidueprograms,i.e.,theinitialbatteryofresidueteststhatare N(#% conductedtosupportregistrationofachemicalforafooduse.Thecommenterfurthersuggestedthat,intheabsenceofexistingmagnitudeoftheresiduedata,thediversityofgeographicconditionscouldbecaptured,forexample,byconductingonetrial ,n') inCalifornia,oneintheSouth,andoneinthemidWest.AnothercommenterechoedthesentimentbysuggestingthatEPAcouldincorporateadditionaltreatmentregimesmorerepresentativeoftypicaluseratesintothepreexistingguidelines(_OPPTS_Ԁ860.1520;EPA1996a).  (# (#  0  0` (#(#0 ` (#` (#  Response .EPAacknowledgesthatthreereplicatesisa h  departurefromcurrentguidance,butbelievestheadditionalreplicateisjustifiedbybetteraccountingfortruevariability.TheAgencyalsoagreesthatmodifyingtheguidancetoallowforconcurrentdevelopmentofmagnitudeoftheresidueandbridgingdataisappropriateandhasdoneso.  (# (#   0  0` (#(#0 ` (#` (#  Comment .Arelatedcommentrequestedclarificationon #s  whethertheAgencyintendedtousesingledatapoints(replicates)oraveragesofthedatapoints.  (# (#    ` 0  0` (#(#0 ` (#` (#  Response .OPPhasclarifiedtheguidancetoreflectits R intentiontousesingledatapointsratherthanaverages.  (# (# 3 3 3 3   0   ` %   4.0 (#(#RoleofUsageData D1 (# (#  0  0` (#(#0 ` (#` (#  Comment .SeveralcommentersrequestedthatOPPclarify ( whatwasmeantby"reliableusagedata."Thedraftpolicyindicatedthatbridginganddeclinedatacouldonlybeusedinprobabilisticdietaryassessmentsifcoupledwithreliableusagedataindicatingwhatpercentageofthecropistreatedatvariousapplicationratesandwhatpercentageofacropisharvestedatvariousintervalsafterthelastpesticideapplication.Othercommentersfeltthatthelackofusagedatashouldnotbeanimpediment.TheIWGandotherssuggestedthattheFFDCAsection408(b)(2)(E)supportsusing"availabledataandinformation"andrequiringactualdatawithinfiveyearstoverifythattheanticipatedresiduehasnotincreased.  (# (# 3  W&!# 3 0  0` (#(#0 ` (#` (#  Response .Themostcompletedescriptionof"reliable  usagedata"canbefoundinacompanionsciencepolicypaperentitled,".XXXXTheRoleoftheUse-RelatedInformationinPesticideRisk  AssessmentandRiskManagement#XXX.XRI#"(EPA1999f).Itwasissuedfor  commentinJuly1999,andareviseddocumentisexpectedshortly.Tosummarizebriefly,EPAprimarilyreliesonUSDAsourcesandlandgrantuniversitiesaswellasproprietarysources,suchas_Doane_sforuseandusage.Thesesourcestakentogetheraregenerallyadequatetodeterminetherangeoftypicalapplicationratesformajorcrops.InformationontherangeoftypicalPHIsisnotreadilyavailable.Forminorcropsandunusualsituations,EPAusuallycontactsfieldextensionoffices,cropadvisors,registrants,orgrowers.Inactualpractice,EPAmakeseveryefforttoobtainandverifyappropriateusagedataforitsassessments.RecentexamplesincludetheTechnicalBriefingsthatOPPhasheldformostOPpesticides,whereOPPhasidentifiedareaswhereusagedatawouldbehelpfulinrefiningriskestimatesandgrowershaveprovidedit.Alsoofnotearethe CropProfilesdevelopedbyEPAandUSDA.AsindicatedaboveinB.3.,EPAdoesnotagreewiththeIWGcommenttotheextentitsuggeststhatavailabledataonanticipatedresiduesneednotbereliable.  (# (# 0  0` (#(#  ` (#` (# 0  0` (#(#%   5.0 ` (#` (#UseofPercentCropTreatedforAcuteDietaryAssessments ,O (# (# 0  0` (#(#0 ` (#` (#  Comment .OnecommenterfeltthatOPPshouldnotuse  percentcroptreated(_PCT_)calculationsinacutedietaryriskassessments.Theyreasonedthatanyamountofacroptreatedatalevelthatwillrenderacuteharm(e.g.,thehotpotato)tosomeone   cannotbecharacterizedasassuring"reasonablecertaintyofnoharm."Accordingtothecommentersinterpretation,section408(b)(2)(F)ofFFDCAspecificallyauthorizesEPAtoconsider_PCT_"whenassessingchronicdietaryrisk..."andthenonlyiftheAdministratormakesspecificfindingsaboutdatareliability.ThisexpressstatementgivesrisetotheirconclusionthatCongressdidnotintendforEPAtouse_PCT_Ԁinestimatingacutedietaryrisk.  (# (#    `     h      p 3  3)$& 3 0  0` (#(#0 ` (#` (#  Response. TheFederalInsecticide,Fungicide,and  RodenticideAct(FIFRA)andFQPAaresilentontheissueofwhetherEPAcanuse_PCT_Ԁadjustmentsforacutedietary(food)riskassessments.Infact,thestatutorylanguageisconstructedtoplacecertainrestrictionsontheuseof_PCT_ԀinformationinchronicriskassessmentswhichsuggeststhatCongresswasmerelysettingoutrulesfortheuseof_PCT_Ԁinformationinthesesituations,notmakingabroaderstatementaboutuseofthisinformationgenerally.Furthermore,andperhapsmoreimportantly,theuseof_PCT_informationinprobabilisticacuteassessmentsnotonlyallowstheAgencytotakeintoaccountthe"hotpotato,"butalsotheprobabilitythatahighlevelofexposurewilloccur.Inotherwords,ifsomepercentageofacropisnottreatedthiswouldlowertheprobabilitythataconsumerwouldeatatreatedcommodity,butnotaltertherangeofestimatesoftheresiduelevelsonthattreatedcommodity.  (# (# 0  0` (#(# ` (#` (# 0  0` (#(# %   6..XXXX0 ` (#` (##XXX.XY#ExtrapolationtoSimilarCrops  YԀ C (# (#    `  0  0` (#(#0 ` (#` (#  Comment .Severalcommenterssupportedtheideaof : extrapolatingresiduedeclineandbridgingdatatosimilarcrops.OnesuggestedthatEPAneedstodevelopandissuealistofsurrogatecrops.Anothersuggestedusingcropgroupingsor"indicator"cropstoallowfortranslatingdata.He% > ԀfurtherobservedthatitshouldbepossibletoexamineresiduedataregardingcropsforwhichtherearebothfieldtrialandPDPdata,determinetheratiooftherespectiverangesofthevalues,anddevelopreasonablerulesforshorttermusetoconvertfieldtrialvaluesdownwardforcropswherePDPdataarelacking.Anothercommentexpandedthisideatoincludetranslatingdataamongsimilarpesticidesonaparticularcrop.  (# (#  0  0` (#(#0 ` (#` (#  Response .EPAbelievesthatitisreasonabletousethe ]#  samecropgroupingsforbridginganddeclinestudiesasthoseusedforotherresiduedatadevelopment(see40_CFR_180.41).For T% " example,ifbridgingdataweredevelopedforaspecificchemicalonarepresentativepomefruitcommodity,e.g.,applesorpears,the <'"$ resultingfactorscouldalsobeappliedtoallmembersofthepomefruitgroup.Asadditionaldatabecomeavailable,thesetranslationgroupsmaybeexpanded.However,EPAcurrentlyhasnoreasontobelievethatdevelopinggenericratiosbetweenfieldtrialvaluesandPDPmonitoringvaluesforapplicationtocropsthatarenot ,P') monitoredbyPDPwouldbescientificallyvalid,oradequatelyprotectiveofpublichealth.Wenotethattherecanbetremendouspesticidechemicaltopesticidechemicalvariabilitywithrespecttodegradation/metabolism,systemvs.nonsystemicnatureofthepesticidechemical,applicationmethod,etc.Developingsuch roughrulesofthumbwouldbeproblematicforcroptocroptranslationsaswellsincetimingandrateofapplication,cropmorphology,harvesttimes,etc.couldvarysignificantly.Nevertheless,ifaregistrantisabletogenerateadequatejustificationandscientificsupportforsuchextrapolations,thisinformationcouldbeconsideredonacasebycasebasis.  (# (#    `    SeealsoresponseF5,below   `    0  0` (#(# %   7.0 ` (#` (#ResidueDataShouldReflectAllMetabolitesofConcern d L (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommentervoicedtheconcernthatifthe C Agencydoesallowsubmissionofadditionalresiduedata,thosedatashouldreflectallresiduesoftoxicologicalconcern.Inaddition,wherefieldtrialsareconductedatPHIs,or_preslaughter_Ԁintervalsforlivestock,longerthancurrentlabelintervals,additionalmetabolitesmaybeproducedduringthelongerintervals.TheAgencyshouldrequiremetabolismstudiesconsistentwiththelongerintervals,ifsuchdataarenotalreadyavailable.Thecommenter'sconcernwasbasedonhisbeliefthattheconventionalchemicalmodelforOPcholinesteraseinhibitionisaP=O(orP=S)bond,andthreebondsofPORand/orPSR,whereRrepresentssidechainssuchas_aryl_Ԁoralkylgroups.MetabolismthatmodifiessidechainswithoutcleavingORorSRbondswillretain,orevenincrease,cholinesteraseinhibition.  (# (#    ` 0  0` (#(#0 ` (#` (#  Response .EPAacknowledgesthatthescenariosuggested N#  istheoreticallypossiblebutnotlikely.ThepreponderanceofevidenceintheopenliteraturesuggeststhatOPsbreakdownreadilyandthattheP=Obondisthefirsttobreak,renderingtheresultingmoietiesincapableofinhibitingcholinesterase.EPA'scurrentdatadevelopmentprocessprovidesfortheidentificationofmetabolitesofconcernbasedonnatureoftheresiduestudies.Magnitudeoftheresiduestudiesinplantsand/orlivestockarethenrequiredtomeasurethemagnitudeoramountofeachmetaboliteofconcern.Iftherewerereasontosuspectthatneworhigherlevels +A') ofpreviouslyidentifiedmetabolitesofconcernwouldbeproducedunderconditionsoflongerPHIs,EPAwouldrequirethesedata.InthecaseoftheOPs,thisdoesnotappeartobewarranted.  (# (# Ѐ0  %   D.0` (#(#Processing/Cooking/ResidueDegradationData l` (#` (#   0   ` Overview .ThedraftARpaperalsodescribedprocessing,cooking, w  marketbasketandresiduedegradation(storage)data,althoughinlessdetailthanthebridginganddeclinedata,andhowthesedatacouldalsobeusedtorefineanticipatedresidueestimates.Relativelyfewcommentsaddressedthesestudies.Onecommenterprovidedreferencestonumerousdegradationandprocessingstudiesthathiscompanyhadconducted.> (#(# 3 3   0  0` (#(# %   1.0 ` (#` (#FoodProcessingPractices o #s  (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenternotedthatinbriefdiscussions j withthefoodprocessingindustry,hefoundthatprocessingproceduresvarybyregionandprocessor.Includedwiththecommentswasalistingofprocessingstudiesperformedwith_methomyl_Ԁthatthecommenterfeltwereexcellentexamplesoffoodindustryandhouseholdpreparationprocessingstudies,andrecommendedthattheAgencydevelopfutureguidelinesforthesetypesofstudiesbasedonthesestudydesignsfor_methomyl_.Finally,henotedthatdramaticreductionsofresiduelevelswereseenafterfollowingtypicalfoodindustryandhouseholdpreparationpractices.Someofthetopicsaddressedinthe_methomyl_Ԁstudiesare:themagnitudeofresiduesinheadlettuceafternormaltrimmingandwashing,magnitudeofresiduesinapplefruitafterpackingplantprocessingandcooking,magnitudeofresidueinfreshandcannedsucculentgreenbeans,andmagnitudeoftheresidueinorangefruitprocessedthroughapackingline.  (# (#   3  ]#  3 0  0` (#(#0 ` (#` (#  Response .EPAagreesthatsignificantreductioninresidue  levelsarecommonlyseenfollowingtypicalfoodindustryandhouseholdpreparationpractices.ForthisreasontheAgencyencouragessubmissionofstudiesthatallowustoquantifythesereductions.EPAalsoagreesthatprocessingpracticesvaryfromregiontoregionandfromprocessortoprocessor.Forthisreason,severalprocessingstudiesmaybeneededtoadequatelycharacterizethevariabilityinprocessingpractices.EPAalsoagreesthatthereferenced_methomyl_Ԁstudiesareacceptableexamplesofprocessingstudiesandhasusedthisinformationinitsdietaryassessmentof_methomyl_Ԁforreregistration.  (# (#   0  0` (#(# %   2.0 ` (#` (#ConsiderMetabolitesProducedfromHeating/Cooking vx #s  (# (#  0  0` (#(#0 ` (#` (#  Comment .OnecommentercautionedthatiftheAgency j allowscookingstudies,itshouldrecognizethatmetabolitesproducedbyheatmaybedifferentfromthoseproducedduringuseoncropsandlivestock.TheAgencyshouldrequirethatheatingandcookingstudiesbeconductedsimilarlytometabolismstudies,soadditionalresiduesoftoxicologicalconcernmaybeidentified.BecauseOPscomprisearangeofchemicalstructuresandsidechains,extrapolationofheatingandcookingdatafromoneOPtoanothershouldgenerallynotbedone.  (# (#   0  0` (#(#0 ` (#` (#  Response .BasedonexistingliteraturefortheOPs,these  compoundsappeartobreakdownrapidlyonheating.OPPwouldnotrequireadditionalmetabolismdataforcookingstudieswithOPs.  (# (# 0  0` (#(# %   3.0 ` (#` (#NoGuidanceforDegradationStudies } x" (# (#  0  0` (#(#0 ` (#` (#  Comment .OnecommenternotedthatOPPcurrentlydoes o$! nothaveguidanceforconductingdegradationstudies.  (# (#    `  0  0` (#(#0 ` (#` (#  Response .OPPdoesnothaveseparateguidancefor Z'"$ residuedegradationstudies,i.e.,studiesthatmeasureresidue ](#% declineincommoditiesthataretypicallystoredforlongperiodsoftime.However,methodsforconductingdegradationstudieswouldparallelthoseforresiduedeclinestudies.  (# (#  -,}') 0  0` (#(# ` (#` (# 0  %   E.0` (#(#ResiduesinMeatandMilk ` (#` (# 0   ` Overview .InthedraftARpaper,EPAdescribedanumberofstudiesthat  couldbeusedtorefineestimatesofpesticideresidues,particularlyOPs,inmeatandmilk.Onlytwocommentersaddressedthistopic. (#(# 0  0` (#(#%   1.0 ` (#` (#UseaMoreRealisticAnimalDiet ^ t  (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommentersuggestedthatsuch k   refinementsasindicatedintheARpaperwereappropriate,butfeltthatitwouldbemoreproductiveforEPAtousemorerealisticassumptionsrelatedtoactualanimaldiets.  (# (#  0  0` (#(#0 ` (#` (#  Response .OPP'sassessmentscurrentlyassumethata >  relativelylargeportionofananimal'sdietcouldbecomposedofitemstreatedwiththepesticidebeingassessed.However,OPPwouldnotgenerallyassumeforapesticideusedonapplesand )y cottonthatlivestockwouldconsumebothapplepomaceorcotton m gintrashsincetheseitemsarepresentinlivestockdietsonlyinsomeregionsofthecountryandduringcertaintimesoftheyearandwouldnotgenerallybeexpectedtobesimultaneouslypresentinanygivenanimalsdiet.Thisassumptionisbasedonthefactthatitisnoteconomicallyfeasibletotransporttheseregionalbyproductsoutoftheareawherethecommoditiesareproduced.OPPiswillingtomodifyitshighendanimaldietsifdataaremadeavailablefromgrowers,processorsorothersources.  (# (#  0  0` (#(#0 ` (#` (#  Wenote,too,thatcookingdataformeatandprocessing  (pasteurization)dataformilkwouldyieldthemostusefulrefinementssincetheywouldpermitfactorstobeusedtoadjustresiduesinmeatandmilkthatreflectresiduesonan asconsumedbasis.  (# (# 3  ]% " 3 0  0` (#(# %   2.0 ` (#` (#NoFiniteResiduesofOrganophosphates ɉ  (# (#  0  0` (#(#0 ` (#` (#  Comment .OnecommenterfeltthatallOPtolerancesfor  meatandmilkshouldberevokedunder40_CFR_180.6(a)since  thereisalreadyampleevidencethatOPresiduesarenotfoundinthesecommodities.Thesamecommenterprovidedreferences,butnoactualdata,tosupporthisassertionthatmeatandmilktolerancesarenotneededforOPs.Theseincludedreferenceto:PDPmonitoringdataformilkfor19961997showingonlyonedetectionofanOP(_dichlorvos_Ԁat0.003ppm)inapproximately60,000samples;USDAsFoodSafetyInspectionService(.XXXX_FSIS_#XXX.X+#) J  previoustestingofmeat;andFARAD(FoodAnalysisResidueAvoidance_Databank_)data.  (# (#  0  0` (#(#0 ` (#` (#  Response .EPAagreesthatexistingPDPandother j monitoringdata,aswellasinformationintheliterature,suggestthatOPresiduesarenotgenerallyfoundinappreciablequantitiesinprocessed(pasteurized)milk.Nevertheless,thecriteriafordeterminingwhetheratoleranceisnecessaryisnotbasedon I whetheractualdetectionsinmonitoringdataormarketbasketsurveysarecommon,butratherwhetherthereis"noreasonableexpectationoffiniteresidues"inmeat,milk,poultryandeggsfollowingexaggeratedratefeedingstudiesasprescribedunder40_CFR_180.6.Itwouldservelittlepurpose,forexample,torevokea   tolerancesimplybecauseapesticidechemicalisrarelyusedif,for  example,residuesdidappearwhenitwasused. (# (# 0  0` (#(#0 ` (#` (#  However,itisimportantforthecommentertorememberthatifmonitoringdataareavailablethatshowno(orveryfew)detectionsofapesticidechemical,thenitisthesemonitoringdata,andnotthetolerance,thatisusedintheriskassessment.FortheexamplecitedbythecommenterinwhichamplePDPdataonmilkwereavailableshowingno(orveryfew)detections,theriskassessmentwouldrelynotonthetolerance(representingthemaximumlegallimit),butratherontheactualresiduesfoundinthemonitoringprogram.  (# (# 3  !(q#% 3 0  0` (#(#0 ` (#` (#  Finally,OPPwouldliketoclarifythecommentersremarkonthenumbersamplesofmilkcollectedbyofPDPduring19967.The60,000samplesreferredtobythecommenterisactually  60,000databaserecordswhereadatabaserecordisgeneratedfor  eachsample_analyte_Ԁcombination.Thus,ifonesamplewerecollectedandanalyzedfor30analytes,atotalof30recordswould h  begenerated.SincePDPanalyzesitssamplesformanypesticides,thereareasignificantlygreaternumberofPDPdatabaserecordsthantherearesamples.During1996,1997,and1998,PDPactuallycollectedandanalyzed575,732,and595milksamples,respectively.  (# (# 3  d  3 3 3 0  %   F.0` (#(#SpecificGuidanceforConductingBridgingandResideDecline  Studies 0` (#` (# 0   ` Overview. Anumberofcommentersrespondedspecificallytothe   questionsposedinEPA'sdraftguidancedocuments.Theircommentsandresponsesaredetailedbelow. (#(# 3 3 L e(`L0   ` %   1.0 (#(#ClarityandCompletenessofGuidance  n   (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenterindicatedthattheguidance e  providedinthedocumentisclearandcomplete.However,thecommenterindicatedthathehadsomeconcernthattheproposedproceduresfordealingwiththeresiduedatawereoverlyprescriptiveandtoodependentuponhypothesistestingandthatthismightleadtousefuldatabeingrejectedforuseindietaryriskassessment.Thecommentersuggestedthatsimplerandmorepragmaticinterpretationsofthedatamightbemoreappropriateandwouldleadtomoreefficientuseofallavailabledata.Anothercommenterstatedthattheguidancedocumentprovidesexplicitinstructionsontheanalysisandinterpretationofthepotentialresultsfromthesestudies,butbelievedthatastrictprescriptiononanalyticalmethodscanbeproblematic.Thestatisticalproceduresfordealingwiththeresiduedatafromthesetrials,thecommenterbelieved,areoverlycomplexandprescriptive,andtoodependentonhypothesistesting.Thecommentercontinued,statingthatusefuldatamayberejectedforuseindietaryriskassessmentandthatsimplerandmorepragmaticinterpretationsofthedatamightbemoreappropriateandleadtolesswasteofusefulandexpensivedata.  (# (# 3  " 3 0  0` (#(#0 ` (#` (#  Response .OPPappreciatesthecommentsprovided,and  recognizesthattheguidancemaybeseenasoverlyprescriptiveinthatitdescribesspecificmethodsforestimatingarelationshipbetweenapplicationrateandresiduelevelorPHIandresiduelevel.However,registrantsorotherdatasubmittersarenotboundorcommittedtofollowingthisguidanceinestimatingthatrelationship;theguidanceisonlyonemeansofestimatingthisrelationshipwhichOPPwillfindsufficientlystatisticallyrigorousforuseinquantitativeriskassessment.Itisnotastrictprescriptiveprocedure.AcceptanceorrejectionofstudiesbyOPPreviewersisnotbasedon_unwaivering_Ԁadherencetoguidelinerecommendations,butratheronthejudgementofthereviewerofthespecificstudysscientificrigorandvalidity.OPPdoesnotandwillnotautomaticallyrejectusefuldataforuseindietaryriskassessmentbasedsolelyonwhetherornotguidelinerecommendationsareadheredto.TheguidancepresentedhereisonlyonemethodthatattemptstotakeintoaccountmanyoftheconcernsOPPmayhaveaboutextrapolatingsimpleratiosdeterminedatonesiteatoneapplicationratetomanydiversesitesatmanypotentiallyverydifferentapplicationrates.  (# (#  0  0` (#(#%   2.0 ` (#` (#AdequacyoftheResidueStudiesforGeneratingRefined  AcuteDietaryProbabilisticExposureandRiskAssessments   (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenterindicatedthattheapproach  recommendedbyOPPissensible;itisanalogoustoprocessingstudiesinwhichtheobjectiveistoestablishtherelationshipbetweenresiduesintherawagriculturalcommodity(RAC)andthoseintheprocessedcommodityandNOTtodeterminethemagnitudeofresiduesintheprocessedcommodity.However,thecommenterrecommendedthatalimitednumberofstudiesbeconductedingreenhouses.Thisapproachwoulddemonstratetherelationshipbetweenapplicationrateandresiduelevels,butwouldnotbeinfluencedbyweatherconditionsandother weatheringinfluences.  (# (# 3  0(#% _3 3 3 _0  0` (#(#0 ` (#` (#  AnothercommenterindicatedthatthestudieswouldbehelpfulforrefiningtheestimatedexposurethatwouldbesuggestedbyuseofworstcasefieldtrialdataatmaximumapplicationratesandminimumPHI.However,thecommenterstatedthatmonitoringinformationordinarilywillbeevenmoreusefulinrefiningexposureandriskassessments.  (# (#  0  0` (#(#0 ` (#` (#  Response .Withrespecttothecommentconcerningthe \  conductofthesestudiesingreenhouses,OPPbelievesthatthiscouldnotbeusedforresiduedeclinestudies,butcouldbeconsideredforbridgingstudies.OPPwouldrecommendthatanyinterestedpartycontactOPPforadditionalinformationregardingsuchgreenhousetrialspriortostudyinitiation.  (# (# 0  0` (#(#0 ` (#` (#  OPPagreeswiththecommenterthatmonitoringinformationismoreusefulthanfieldtrialdatainrefiningexposureandriskassessments.Asarule,monitoringdatawillhaveprecedenceover adjustedfieldtrialvaluesintheriskassessmentprocess.Onlywhenadequatemonitoringdataarenotavailablewillvaluesfromexperimentalcropfieldtrials(adjustedornot)potentiallybeusedinariskassessment.  (# (#    0 ` %   3.0 ` (#` (#AdequacyofRecommendedStudiestoEstablishaRatevs.  ResidueorPHIvs.ResidueRelationship   (# (#  0  0` (#(#0 ` (#` (#  Comment .Severalcommentersindicatedthatthese  recommendationsarereasonableandshouldprovideusefuldatatogenerateprobabilisticexposureandriskinformation.  (# (# 3 3 3 3 0  0` (#(#0 ` (#` (#  Anothercommenterindicatedthattheresiduestudiesappeartostrikeareasonablebalancebetweentheexpenseofconductingafullsuiteofstudiestoattempttodeterminetherelationshipofinterestvs.asmallersetofbridgingstudyorresidue `$! declinestudies.Specifically,theschemetolinkthenumberofbridgingstudiestothenumberoffieldtrialsrequiredforsettingtolerancesisreasonableandthenumberoftrialsappearstobeinkeepingwiththenumbersoftrialsrequired.However,thecommenterquestionedwhethertherequirementforthreecompositesampleswillincreasetheamountofinformationenoughtojustifyincreasingstudyanalyticalcostsbyatleastonethird.Requestingtriplicatecompositesamplesateachtimepointimplies ,P') thatthevariabilityateachtimepointisthekeysensitivityintheoveralldietaryassessment.Thecommenterbelievedthatthistheorywasuntestedandthatadditionaleffortandexpensemightbebetterspentongettingbetterprecisionontheuseratedistributionassumptionsormarketshare.Thecommenternotedthattheresiduechemistryguidelinesrecommendtwosamples,althoughonesampleisacceptable.  (# (# 0  0` (#(#0 ` (#` (#  Anothercommenterstatedthatintheexperienceofatleastoneregistrant,dataofthesortdiscussedinthepolicypapertendtoshowalinearrelationshipbetweeninitialapplicationrateandresiduesatagivenPHI.Inmanycases,thelineisverygoodandparallellineswillbeobtainedfordifferentPHIsfromstudiesdoneatthesametimeandsite.However,studiesatdifferentsitesmayvaryconsiderablyduetothedifferencesingrowingconditions.TheexamplesgivenbyEPAdemonstrateanalyzingthedataforallsitesincombination,andprovidesomealternativesinthecaseswheredifferentsitesgivedifferentresults.Thecommenterwasunsurewhetherfindingsimilarresultsinwidelyvariedgeographicalareaswillbetheexceptionandnottherule.ThecommenteralsoremindedtheAgencythatdeclinestudieswouldneedtobefreeofanyunusualrainfalleventsorotherweatherrelatedconditionsthatcouldskewtheresiduedata.Thus,thestudiessubmittedwouldallhavetoyieldacceptabledata.  (# (# 0  0` (#(#0 ` (#` (#   Response .OPPbelievesthatthreecompositesamples  strikeareasonablebalancebetweentheanalyticalcostofathirdsampleandtheadditionalinformationregardingwithinfieldvariability.Theuseofthreesamplesalsohelpstoconfirmtheabsenceof_heterskedasticity_ԀwhichisanimportantprerequisiteforOrdinaryLeastSquaresRegressionandtheresultingstatisticalinferencesregardingsignificance.Inaddition,currentOccupationalandResidentialguidelinesrecommendtriplicateanalysisofallsamples.  (# (# 3  &k!# 3 0   ` %   4.0 (#(#AppropriatenessofDerivingaQuantitativeRelationship  BetweenApplicationRateandResidueLevelonResiduesThatAreBelowtheLimitof_Quantification_Ԁ +  (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenterdisagreedwiththe   recommendationagainsttheuseofratesthatwouldleadto_nonquantifiable_Ԁresiduesandbelievesthatthisdecisionshouldbemadeonacasebycasebasisbytheregistrant.Thecommenteragreedthataquantifiedvaluewillbeneededtorepresenttheresiduefromamaximumrate/minimumPHIapplication,butstatedthatthisshouldnotberequiredforseedtreatmentstudiesorlowerrate/longerPHIresiduetesting.TheLOQ,thecommenterstated,couldbeusedasaconservativesurrogateandanyresultinguncertaintywouldresultfromoverestimationofexposure,notunderestimation.Thecommenteragreedthattheregistrantorotherstudycontractorshouldbefreetoseekafullyquantifiedratiobyuseofexaggeratedrates,butthatitshouldnotberequired.  (# (# 0  0` (#(#0 ` (#` (#  Anothercommenteragreedwiththepreviouscommenterthathavingquantifiedvaluesforallpointstobeusedinthecomparisonsishighlydesirable,thatquantifiedresidueswillbeneededtorepresenttheresiduesresultingfrommaximumrate/minimumPHI,andthatusefulinformationcouldbederivedbyusinganLOQasaconservativesurrogatefortheNDvalues.Thecommenterstatedthatitwouldbehardtoderiveaquantitativerelationshipbetweenrateand/orPHIontheonehandandresiduelevelontheotherifsomeresiduesfallbelowtheLOD(butnottheLOQ).However,thecommenterindicatedthatthereisstillvalueiftheresiduelevelsarebetweentheLODandLOQandthatitisacceptabletoestimatearesiduelevelbetweenLOQandLODforuseindevelopingthequantitativerelationship,giventhelargeinherentvariationnormallyassociatedwithresiduetesting,evenatresiduelevelsabovetheLOQ.Thecommenteracknowledged,however,thatitwouldnotbeappropriatetouseLOQresiduevaluesindeterminingresiduedeclinecurves.  (# (# 3  <'"$ 3 0  0` (#(#0 ` (#` (#  Anothercommenterbelievedthatthesuggestiontouseexaggeratedapplicationratestoachievequantitativemeasurementsisreasonable.However,thecommenterbelievedthattheconstraintregardingtheadjustmentof_nonquantitative_residuesshouldbereconsideredforatleastonecase.IfvaluesarebelowtheLOD,thecommenterbelieveditappropriatetodividethestudyLOQbytheexaggerationfactor.  (# (#  0  0` (#(#0 ` (#` (#  Response .Thepurposeofthepolicyguidancedocument D   recommendationthatmeasurementsbelowtheLOQnotbeusedinquantitativeregressionanalysisindeterminingtheeffectapplicationrate(orPHI)hasonresiduelevelsistoencouragetheuseofexaggeratedratessuchthatresiduemeasurementscanbeadequatelyquantified.TheOPPreviewer,inallcases,canusehisorherjudgementandconcludethatincorporationofbelow_quantification_Ԁlevel(BQL)orbelowdetectionlevel(BDL)measurementsintoquantitativeestimatesofthisrelationshipisappropriate,dependingonthespecificsofthecase.Inthesesituations,OPPwilllikelyinvestigatetherobustnessoftheregressionanalysisbyperformingasensitivityanalysisoftheregressionrelationship.Thatis,thesensitivityofthefinalestimatedrelationshiptoassumptionsregardingthevalueassociatedwiththeBQLorBDLcanbeassessedtodetermineifincorporationofBQLorBDLmeasurementmightsignificantlyaffecttheoutcomeofthestudyorassessment.< #  1      ׀ (# (# 0  0` (#(#0 ` (#` (#  Nevertheless,OPPbelievesthattheconcernaboutapotentialpreponderanceofBQLorBDLvalueswhenfieldtrialsareconductedat1xandlowerratesismisplaced.BDLandBQLvaluesgenerallydonotaffectOPPdietaryriskestimatesanditisdoubtfulthatbridgingorresiduedeclinestudieswouldbeconductedoncropsforwhichBQLorBDLresiduesareexpected.  (# (#  3  '%w " 3 0   ` %   5.0 (#(#ExtrapolationofDatabetweenSimilarCrops   (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenterbelievedthatexpanded  extrapolationsshouldbeconsidered.Forexample,ifapesticidesusedirectionsarethesameforseveralcropgroups(e.g.,leafy   vegetables,fruitingvegetables,_cucurbit_Ԁvegetables,andBrassica   vegetables)orsimilarcropsubgroups(e.g.,leafygreensandleafy   Brassicagreens)andhaveresultedinthesameestablished }  tolerancesforeachofthecropgroups,thendatashouldbeabletobetranslatedbetweenthosegroups/subgroups.  (# (# 0  0` (#(#0 ` (#` (#  AnothercommenterbelievedthattheHealthEffectsDivisionsStandardOperatingProcedure(SOP)99.3onpermissiblecroptranslations(EPA1999g)wouldprovideagoodrationalefortheextrapolationofdata.Itisbasedonthecropgroupings,isquiteclear,andshouldbesuitableasastartingpoint.Thecommenterstatedthatmoreextensiveextrapolationacrosscropgroupsfromthedatamaybeappropriateaswell.Thecommentersuggested,forexample,thatextrapolationshouldbeallowedamongleafyvegetables,Brassicavegetables,leaveofroot = andtubervegetables,andfoliageoflegumecrops;andamongrootandtubervegetablesandbulbvegetables.Additionaltranslationacrossothercropgroupsshouldbemorefullyexplored.ThecommenteralsoindicatedthehopethatOPPwillmakeanefforttoincludeinanydatatranslationschemethosecropsthatarenotassignedtocropgroups(e.g.,grapes,peanuts,strawberries,etc.).  Thecommenterbelievedthatsimilarratesofdeclinewillgenerallybeseenregardlessofthecrop.Inaddition,thecommenterbelievedthatifalinearrelationshipisobservedacrosssuitablerepresentativecrops(e.g.,fruit,leafyvegetables,andcerealcrop), u! thentheAgencyshouldconcludeforthisproductthatalinearrelationshipexistsbetweentheapplicationrateandresiduelevelforallcrops.  (# (# 3  E% " _3 3 3 _0  0` (#(#0 ` (#` (#  Anothercommenterbelievedthatextrapolationbetweencropsoutsidethesamecropgroupcanbemadeaslongasthegeneralcrop_morphologies_,culturalpractices,andusepatternsaresimilar.Forexample,ifusepatternsaresimilar,itmaybereasonabletoextrapolatebetweenpomefruitsandstonefruits,butnotbetweenpomefruitsand_caneberries_.Thecommenterbelievedthatsuchanextrapolationisreasonablebecausethepointoftheexerciseisnottoextrapolateresiduevaluesbetweenthecrops,rathertoextrapolaterelationshipsbetweendifferentPHIs(andapplicationrates).  (# (# 0  0` (#(#0 ` (#` (#  Anothercommenterindicatedthattheguidanceprovidedinthedocumentwasclear,butadditionalexamplesshouldbeprovidedforcrop_surrogation_.Inparticular,thecommenterindicatedthatanexampledatasetforwhichextrapolationwouldbeacceptedwouldbequiteinstructiveandthatsuchexamplescouldincludetherationaleforwhyextrapolationwouldorwouldnotbedeemedappropriate.  (# (#  0  0` (#(#0 ` (#` (#  Response .Thedocumenthasbeenrevisedtomakeclear  therecommendedcroptocropextrapolations.Specifically,thecropgrouporsubgroupextrapolationsdescribedin40_CFR_are  recommended.Atthistime,anyfurtherextrapolationswillbemadeonlyonacasebycasebasisasdeterminedbytheOPPreviewer.Inthefuture,croptocropextrapolationsmaybeexpanded,perhapsconsiderably,asadditionalstudiesaresubmittedforreviewandOPPgainsexperienceacrossadditionalcropsandtrials.Withverylittledatainhand,OPPisreluctanttoexpandtheseextrapolationproceduresconsiderablybeyondthosecurrentlyusedforcropfieldtrialguidelines.  (# (# 0  0` (#(#0 ` (#` (#  Withrespecttothecommenter'srequestforadditionalexamplesoncrop_surrogation_,thedocumenthasbeenrevisedsuchthatacrop_surrogation_Ԁschemehasbeenmorefullydescribed.Specifically,thecrop_surrogation_Ԁschemethatwillbeusedtoextendresultsfrommaximumapplicationscenariosforfieldtrialsusedtodeterminethetoleranceto realworldtypicalapplicationrateswillbethesameasthatusedtodeterminetolerances.Thatis,thecrop_surrogation_Ԁschemeappearingin40_CFR_180.41willalsoapplytobridgingandresiduedeclinestudies. );%' Onacasebycasebasis,itmaybefurtherextended.  (# (#  +#') 0   ` %   6.0 (#(#NecessityofHavingReliableUsageDataConcerning  ApplicationRatesand/or_Preharvest_ԀIntervals qԀ  (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenterstatedthattheavailabilityof   reliableusedataisstillevolving.Manyorganizations,thecommenterstated,areworkingondevelopingbetterusedataforcropprotectionproducts.EPA,USDA,growergroups,andindustryneedtoworkcooperativelytodevelopbetterdataonfrequencyofuseofspecificapplicationratesandPHIsforaproduct.  (# (#  0  0` (#(#0 ` (#` (#  Response .OPPagreeswiththecommenterandisworking e  withindustry,USDA,andgrowergroupstodevelopthisinformation.  (# (# 3 3 0   ` %   7.0 (#(#"LackofFit"Test q D  (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenterindicatedthecoefficientof ; determinationisameasureofthe strengthofthelinearrelationshipbetweenthedependentandindependentvariables,ascalculatedbytheproportionatereductioninthevarianceofthedependentvariablethatisduetoconditioningontheindependentvariable.Itisnota testoffitperse.The lackoffittest,onthe ^ otherhandisusedtotestwhethermorecomplexmodelsprovideabetterfitthanthemodelunderconsideration.  (# (#  0  0` (#(#0 ` (#` (#  Response .OPPagreeswiththecommenter.Ifagraphical . representationofthedataindicatessignificantdeparturefromthe_linearity_Ԁassumption,useofthe_LOF_Ԁtestmayberecommended.Nevertheless,OPPwilltakeintoaccountallavailableinformation(coefficientofdetermination,graphicalandresidualanalyses,and_LOF_Ԁtests)indeterminingwhetheranadequateregressionequationhasbeendeveloped.  (# (# 3  $! 3 0   ` %   8.0 (#(#TheEffectofCompositingonUnittoUnitVariation   (# (#   0  0` (#(#0 ` (#` (#  Comment .Onecommenterstatedthatheappreciated  OPPsconcernabouterodingtheinherentsafetymarginbybasingprobabilisticassessmentsonworstcaseconditions.Theconcernarises,thecommenterexplained,becausealthoughcompositingreducesthepotentialvariability,thisreductioninvariabilitywas counteredbythefactthatresiduesweregeneratedundertheworstcaselabelconditions.ThecommenterexplainedthattheissueofconcernisifoneusesfieldtrialdataconductedatlongerPHIsorlowerapplicationrates,thentheamountofconservatismthatwasduetoworstcaselabelconditionsislost.  (# (# 0  0` (#(#0 ` (#` (#  Anothercommenterindicatedhisbeliefthatlargesampletosamplevariationinresiduelevelsisnotcommonforsingleservingcommodities.Thecommentercontinued,statingthatstudiesbyUSDAonsingleservingvs.compositeresiduevariabilityshould R providesomeinsightonthesignificanceoftheconcernonthisissue.Thecommenterstatedthatwhilesomedecompositingmethodsareviable,theystilloverestimatetherangeofresiduesontheindividualsampleswithinthecompositesample.  (# (# 0  0` (#(#0 ` (#` (#  Thecommenterexpressedconcernaboutthepolicydocumentstatementthatguidanceforacompositevs.single  servingvariabilitystudycanbeprovidedifaregistrantbelievesthatsignificantissuesassociatedwithvariabilitymayoccur.Thecommenterindicatedthatthisguidanceshouldbeprovidedaspartofthepolicysinceregistrantsneedtounderstandalloftheoptionsbeforestartingbridgingandresiduedeclinework.  (# (#  0  0` (#(#0 ` (#` (#  Response .OPPiscurrentlyinvestigatingtheissueof Z" decompositionandpresentedthistotheSAPinMarch2000(EPA,2000a).AfinalSAPreportonthisissueisexpected_inJune_.OPPwillcarefullyconsidertherecommendationsoftheSAPandtheresultsofitsinvestigationindeterminingiftheremightbesignificantconcernaboutbridgingandresiduedeclinestudieserodingthesafetymarginsimpliedbythemaximumrate/minimumPHIstudies.  (# (# 3  )e$& 3 0   ` %   9.0 (#(#Not"Forcing"theRegressionRelationshipthroughZero   (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenterstatedthatthe forcingthe  regressionthroughzeromaygiveaspuriousappearancetotheregressionlineandresultsofsuchregressionmodelscannotbecomparedtoresultsofregressionmodelsthatincludeanintercept.Iftheestimateoftheinterceptisnotfoundtobesignificantlydifferentfromzero,thismaybeusedasanindicationthattheregressioncanbeforcedthroughzero.However,withthetypeofdataconsideredforbridgingstudies,theinterceptisexpectedtobesmallifthelinearmodelprovidesagoodrepresentationofthedata,andincludingitintheregressionmodeldoesnotimpacttheresults.  (# (#  0  0` (#(#0 ` (#` (#  Response .OPPagreeswiththecommenter.The &v  regressionrelationshipis(inthevastmajorityofcases)expectedtogothroughzeroforbridgingstudyresults,butshouldnotbe forcedthrough.Inanycase,minimaleffectshouldbeseen,particularlyifrecommendationsarefollowedsuchthattheminimumandmaximumlabelratesarebothusedinestablishingtheregressionrelationshipandextrapolationbeyondthisrangeisnotrequired.  (# (#   3 3 0  0` (#(# %   10.0 ` (#` (#MultipleRegressionTechniques    (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenterrecommendedexpandingthe  discussiononmultipleregressiontechniques,especiallythediscussionofassumptionsunderlyingthesemethods.Forinstance,thecommenterindicatedthattheusersoftheapproachneedtobeawareoftheindependence,normality,andequalvarianceassumptionsthatareneededinlinearregressionmodels.ThedocumentsuggeststestingtheequalvarianceassumptionthroughtheuseofBartlettorLevinestests,butnotesthatBartlettstestissensitivetodeparturesfromnormalitywhileLevinestestisnot.Thedocumentdoesnotmentiontheneedtotestfornormalityortheneedtotransformdata.  (# (# 3  3)$& 3 0  0` (#(#0 ` (#` (#  Onecommenterindicatedthatmanyfactorsaffectcropresidues,andthesepapersonlyaddresstwoofthesefactors(applicationrateandPHI).TheAgencysuggestsusingmultiplelinearregressionofthesetwofactorstodevelopamathematicalmodeltopredictcropresidues.Thisisapotentiallyusefulapproachthatcouldbeextended.Otherfactorssuchasthenumberofapplications,applicationinterval,weathervariables,andcropgrowthalsoaffectcropresidues.Iftheeffectsofthesefactorswerereallyunderstood,thenamoregeneralmathematicalapproachcouldbedeveloped.Thiswouldhavebenefitsinenablingdietaryriskassessmentstobefurtherrefined,therebynarrowingthegapbetweenregulatoryexposureassessmentandexposureofconsumersintherealworld.  (# (#  0  0` (#(#0 ` (#` (#  Response .Atthistime,OPPdoesnotintendtoexpandthe X  discussiononmultipleregressiontechniques.Registrantsandotherdatasubmitters,however,areencouragedtoperformsimultaneousrate/residuedeclinestudiesiftheseareperceivedtobeeconomicalwaysofgeneratingdata.  (# (# 0  0` (#(#0 ` (#` (#  Withrespecttothecommentontheassumptionsunderlyingthemethodspresentedinthedocument,thedocumenthasbeenrevisedtoexplicitlydescribetheneedfortestingnormality,transformingdata,orinvestigatingthecharacteristicsofresiduals.  (# (#    ` 0   ` %   11.0 (#(#OtherDataorInformationforDeterminingResiduesatTypical  ApplicationRatesforRiskMitigationPurposes    (# (#  0  0` (#(#0 ` (#` (#  Comment .Onecommentersuggestedthatifresidue   studiesshowalinearrelationshipbetweenapplicationrateandresiduelevelsoverarangeofcrops,thatdatashouldbesufficienttoallowdevelopmentofalinearextrapolationmodelforresiduesatlowerapplicationrates.  (# (#  0  0` (#(#0 ` (#` (#  Response .Thisissuehasbeendetailedinaprevious H&!# response.  (# (# 3  3)$& 3   0  0` (#(# %   12. CropEnforcementMethod  ` (#` (#  0  0` (#(#0 ` (#` (#  Comment .Onecommenterstatedthatitwasnotapparent  inthetwopolicypapersifthecropenforcementmethodmustbeusedforthisworkandaskedifitwouldbepermissibletouseamoresensitivemethodinsteadoftheenforcementmethod.Iftheenforcementmethodwasnotused,wouldsomeadditionalbridgingworkberequiredtoshowequivalencyofthemethods?  (# (#  0  0` (#(#0 ` (#` (#  Response .OPPhasmodifiedtodocumenttoclarifythis V  issue.Theuseofananalyticalmethodthatismoresensitivethantheenforcementmethodispermittedandevenencouraged.Noadditionalbridgingworkwouldberequiredtoshowtheequivalencyofthetwomethods.  (# (# 4 4 5 4 4  U 5 L 9U((L%   III0  REFERENCES U(#(# .XXXXEPA1996a. ResidueChemistryTestGuidelines_OPPTS_Ԁ860;August1996.4?ergO  5  _http_://_www.epa.gov_/docs/_OPPTS_Harmonized_/860_Residue_Chemistry_Test_ @ Guidelines/Series/6gOher  7An *#XXX.XY#.XXXXԀ(EPA712-C-96-169).#XXX.X{#.XXXX 4    `     h      p      x  EPA1999a. DataforRefiningAnticipatedResidueEstimatesusedinDietaryRiskAssessmentsforOrganophosphatePesticide;"draftdocument.March26,1999.#XXX.X#.XXXXԀ  4|regO  5  http://www.epa.gov/fedrgstr/EPA-PEST/1999/April/Day-07/6033.pdf6gOdue  7reԀ(#XXX.X\#.XXXX64FR16967).#XXX.X#.XXXXԀ#XXX.X#  .XXXX   `     h      p      x #XXX.XG#.XXXXEPA1999b.#XXX.X#.XXXX GuidancefortheConductofBridgingStudiesforUseinAcuteDietary  ProbabilisticRiskAssessment;draftdocument.July29,1999.#XXX.X\#.XXXX   4OhogO  5  _http_://_www.epa.gov_/_fedrgstr_/EPA-PEST/1999/August/Day-04/p20042.htm6sgO(#   7(#Ԁ(64FR ! #XXX.X?#.XXXX42372#XXX.X#.XXXX).#XXX.XF#.XXXX x" #XXX.X#.XXXXEPA1999c."GuidancefortheConductofResidueDeclineStudiesforUseinAcute `$! DietaryProbabilisticRiskAssessment;"draftdocument.#XXX.X#.XXXXJuly29,1999.#XXX.X#.XXXXԀ T% " 4HragO  5  .&%X.X_http_://_www.epa.gov_/_fedrgstr_/EPA-PEST/1999/August/Day-04/p20042.htm6HgO\or  7raԀ#.XX%.&ؔ#(64FR#XXX.X#.XXXX42372#XXX.X!#.XXXX)..&%X.X#&%%.&I!#.&%%& H&!# #&%%.&ج!##XX%&j!#5  <'"$ 5 .XXXXEPA.1999d.#XXX.XF"#.XXXX"#XXX.X"#.XXXXStandardOperatingProceduresfortheHealthEffectsDivisionFQPA  SafetyFactorCommittee;#XXX.X"#.XXXX"#XXX.X##.XXXXԀdraftdocument.April26,1999.  4;ltgO  5  _http_://_www.epa.gov_/_fedrgstr_/EPA-PEST/1999/September/Day-07/p23197.htm6"$gO6$onb  7laSd$Ԁ(64FR  48617)#XXX.X##.    .XXXXEPA1999e. TheOfficeofPesticideProgramsPolicyonDeterminationofthe h  AppropriateFQPASafetyFactor(s)forUseintheTolerance-SettingProcess;"draftdocument.May10,1999.4=ltgO  5  _http_://_www.epa.gov_/_fedrgstr_/EPA-PEST/1999/September/Day-07/p23197.htm6&gO&onb  7laS'Ԁ(64FR D   48617)#XXX.X%#.XXXX.#XXX.Xc(#.XXXX 8  #XXX.X(#.XXXXEPA1999f. TheRoleoftheUse-RelatedInformationinPesticideRiskAssessmentandRiskManagement;"draftdocument.June29,1999.4@oggO  5  _http_://_www.epa.gov_/_fedrgstr_/EPA-PEST/1999/July/Day-14/p17318.htm6)gO)op  7l)Ԁ#XXX.X(#.XXXX(64FR37977).#XXX.X+# X  EPA1999g.MemorandumfromMargaret_Stasikowski_,DirectorHealthEffectsDivisiontoHealthEffectsDivisionStaff. TranslationofMonitoringData.HEDStandardOperatingProcedure99.3(3/26/99);March26,1999..XXXXEPA1999h. UseofthePesticideDataProgram(PDP)inAcuteRiskAssessment;draftdocument.#XXX.X,#.XXXXMay5,1999#XXX.X,-#.XXXX.  4GagO  5  http://www.epa.gov/fedrgstr/EPA-PEST/1999/May/Day-26/p13034.htm6-gO-ncer  7a-Ԁ(64FR28485).#XXX.Xy-#.XXXX  #XXX.X.#.XXXXEPA2000a.BackgroundDocumentfortheMarch1,2000MeetingoftheFIFRAScientificAdvisoryPanel. OfficeofPesticidePrograms'Comparisonof_Allender_,_RDFgen_,andMaxLIPDecompositionProcedures;February1,2000.4AgO  5  http://www.epa.gov/scipoly/sap/index.htm6g0gO{0efo  7an0Ԁ#XXX.X"/#.XXXX l #XXX.XX1#Ԁ `    `  'D#% L -((9L 3    3d22IV3  0    %  LISTOFCOMMENTERS 23d22݌(#(# Ќ     `     h __  Becauseofsignificantoverlapintheindividualsandorganizationsthatcommentedonallthreepapers,EPAhaschosentocombinethelistofcommenters.Thedraftpaperentitled,"DataforRefiningAnticipatedResidueEstimatesUsedinDietaryRiskAssessmentsforOrganophosphatePesticides"wasidentifiedbyDocketControlNumberOPP00591andthetwodraftGuidancedocumentswereidentifiedbyDocketControlNumberOPP00616.*Yddd Xdd Xdd X(#(#,/ dd , dd +  9K$ G  29XXCommenter   [docket] UK@+ "K2 2UAffiliation <20 "  K2 <ArthurL.Craigmill,Ph.D.,_DABT_,ExtensionToxicologySpecialist,etal.    _EXTOXNET_Ԁ    MichaelA.Kamrin,Ph.D.ProfessorandCoordinatorofEducationandOutreachPrograms[02/OPP00591] 'S 'InstituteforEnvironmentalToxicology $  $CharlesS.Baer,Ph.D.RegistrationandRegulatoryAffairs[03/OPP00591and03/OPP00616]  k DuPontAgriculturalProducts   DaveWhitacreVicePresident,Science[04/OPP00591]  3# NovartisCropProtection  |$ JacquelineHamiltonSeniorProjectAttorney   a& .NaturalResourcesDefense D' Council#.O:#  a(    .) DavidB.WeinbergAttorney,_Howrey_Ԁ&Simon   #\+ onbehalfof:_Makhteshim_Ԁ_Agan_ofNorthAmerica,Inc.   #\- JohnAbbots[07/OPP0059]  &W!0 privatecitizen  m$1 MarkMaslynChairman[08/OPP00591andL004/OPP00616]  )%5 FQPAImplementationWorkingGroup(IWG)  5(#7 WilliamPatrickCockrell,DirectorAgriculturalPolicy [09/OPP00591]    FloridaFarmBureauFederation(PartofIWG)  '1 FrankPriestley,President̀[10/OPP00591]     IdahoFarmBureauFederation  " ,  JacquelineHamiltoǹSeniorProjectAttorney[L001/OPP00591]    NaturalResourcesDefenseCouncil   SamMoore,President[11/OPP00591]    KentuckyFarmBureauFederation    DaveWhitacre,̀SeniorVicePresident,Science[OPP00591andL002/OPP00616]  GQ NovartisCropProtection,Inc.    ЀJackLaurie,President   MichiganFarmBureau   Ѐnoname    PennsylvaniaFarmBureau    PaulH._Gosselin_,̀ActingChiefDeputyDirector̀[L001/OPP00616  " CaliforniaDepartmentofPesticideRegulation  7A$ nonamegiveǹ[04/OPP00616]   ' NovigenSciences,Inc.Washington,DC   ) nonamegiveǹ[05/OPP00616]  #, _Zeneca_ԀAgProducts -"7-