EPA Benzisothiazolin Red

8/10/2019 EPA Benzisothiazolin Red

1/60

Reregistration Eligibility

Decision (RED) for

Benzisothiazoline-3-oneSeptember 29, 2005


2/60

United States Office of Prevention, Pesticides 739-R-05-007Environmental Protection and Toxic Substances September 2005Agency (7510C)

Reregistration

Eligibility Decision for1,2-Benzisothiazolin-3-one

(BIT)


3/60

UNITEDSTATESENVIRONMENTALPROTECTIONAGENCYWASHINGTON,D.C. 20460

OFFICEOF

PREVENTION,PESTICIDESANDTOXICSUBSTANCES

CERTIFIEDMAIL

DearRegistrant:

ThisistoinformyouthattheEnvironmentalProtectionAgency(hereafterreferredtoasEPAortheAgency)hascompleteditsreviewoftheavailabledataandpubliccomments

receivedrelatedtothepreliminaryriskassessmentsfortheantimicrobial1,2-benzisothiazolin-3-one(hereafterreferredtoasBIT). TheenclosedReregistrationEligibilityDecision(RED)

documentwasapprovedonSeptember29,2005. Publiccommentsandadditionaldatareceivedwereconsideredinthisdecision.

Basedonitsreview,EPAisnowpublishingitsReregistrationEligibilityDecision(RED)

andriskmanagementdecisionforBITanditsassociatedhumanhealthandenvironmentalrisks.ANoticeofAvailabilitywillbepublishedinthe Federal Registerannouncingthepublicationof

theRED.

TheREDandsupportingriskassessmentsforBITareavailabletothepublicinEPAsPesticideDocketOPP-2005-0200at:http://www.epa.gov/edocket.

TheBITREDwasdevelopedthroughEPAspublicparticipationprocess,publishedin

theFederalRegisteronJuly20,2005,whichprovidesopportunitiesforpublicinvolvementintheAgencyspesticidetolerancereassessmentandreregistrationprograms.Developedwith

inputfromEPAsadvisorycommitteesandothers,thepublicparticipationprocessencouragesrobustpublicinvolvementstartingearlyandcontinuingthroughoutthepesticideriskassessment

andriskmitigationdecisionmakingprocess.Thepublicparticipationprocessencompassesfull,modified,andstreamlinedversionsthatenabletheAgencytotailorthelevelofreviewtothe

levelofrefinementoftheriskassessments,aswellastotheamountofuse,risk,publicconcern,andcomplexityassociatedwitheachpesticide.Usingthepublicparticipationprocess,EPAis

attainingitsstrongcommitmenttobothinvolvethepublicandmeetstatutorydeadlines.

PleasenotethattheBITriskassessmentandtheattachedREDdocumentconcernonlythisparticularpesticide.ThisREDpresentstheAgencysconclusionsonthedietary,drinking

water,occupationalandecologicalrisksposedbyexposuretoBITalone.Thisdocumentalsocontainsbothgenericandproduct-specificdatathattheAgencyintendstorequireinDataCall-

Ins(DCIs).NotethatDCIs,withallpertinentinstructions,willbesenttoregistrantsatalaterdate.Additionally,forproduct-specificDCIs,thefirstsetofrequiredresponseswillbedue90


4/60

daysfromthereceiptoftheDCIletter. ThesecondsetofrequiredresponseswillbedueeightmonthsfromthereceiptoftheDCIletter.

AspartoftheRED,theAgencyhasdeterminedthatBITwillbeeligibleforreregistration

providedthatalltheconditionsidentifiedinthisdocumentaresatisfied,including

implementationoftheriskmitigationmeasuresoutlinedinSectionIVofthedocument.SectionsIVandVofthisREDdocumentdescribelabelingamendmentsforend-useproductsanddatarequirementsnecessarytoimplementthesemitigationmeasures.Instructionsforregistrantson

submittingtherevisedlabelingcanbefoundinthesetofinstructionsforproduct-specificdatathataccompaniesthisdocument.

Shouldaregistrantfailtoimplementanyoftheriskmitigationmeasuresoutlinedinthis

document,theAgencywillcontinuetohaveconcernsabouttherisksposedbyBIT. WheretheAgencyhasidentifiedanyunreasonableadverseeffecttohumanhealthandtheenvironment,the

Agencymayatanytimeinitiateappropriateregulatoryactiontoaddressthisconcern.Atthattime,anyaffectedperson(s)maychallengetheAgencysaction.

Ifyouhavequestionsonthisdocumentorthelabelchangesnecessaryforreregistration,

pleasecontacttheChemicalReviewManager,RebeccaM.Miller,at(703)305-0012.

Sincerely,

Frank T. Sanders Director, Antimicrobials Division


5/60

REREGISTRATIONELIGIBILITYDECISION

for1,2-Benzisothiazolin-3-one(BIT)

ListCCASE3026

Approved By:

Frank T. Sanders Director, Antimicrobials Division

Attachment


6/60

TableofContents

BITReregistrationTeam iGlossaryofTermsandAbbreviations... ii

ExecutiveSummary..... iv

I.Introduction.. 1II.ChemicalOverview. 3

A.RegulatoryHistory.. 3B.ChemicalIdentification ... 4

C.UseProfile... 5III.SummaryofBITRiskAssessments 6

A.HumanHealthRiskAssessment... 61.ToxicityofBIT. 6

2.FQPASafety 93.PopulationAdjustedDose(PAD)... 10

a.AcutePAD 10b.ChronicPAD 10

4.DietaryExposureAssumptions.. 105.Dietary(Food)RiskAssessment. 11

a.AcuteandChronicDietaryRisk 11b.DietaryExposureforInertIngredientUses. 12

c.DietaryRiskfromDrinkingWater 156.ResidentialRiskforActiveIngredientUses. 15

a.Toxicity. 16 b.ResidentialHandlerScenarios... 17

i.ExposureScenarios,DataandAssumptions.. 17ii.ResidentialHandlerRiskEstimates.. 18

c.ResidentialPost-ApplicationExposure. 19i.ExposureScenarios,DataandAssumptions.. 19

ii.ResidentialPost-ApplicationRiskEstimates 197.ResidentialRiskforInertIngredientUses.... 20

8.AggregateRisk. 22a.AcuteandChronicAggregateRisks.. 22

b.Short-andIntermediate-TermAggregatesExposuresandRisks.. 23

9.OccupationalRisk... 26a.OccupationalToxicity. 26

b.OccupationalHandlerExposure 27c.OccupationalHandlerRiskSummary... 28

d.OccupationalPost-ApplicationExposure. 29B.EnvironmentalRiskAssessment... 30

1.EnvironmentalFateandTransport... 302.EcologicalRisk. 30

3.ListedSpeciesConsideration.. 32


7/60

IV.RiskManagement,Reregistration,andToleranceReassessmentDecision 34A.DeterminationofReregistrationEligibility. 34

B.PublicCommentsandResponses. 34C.RegulatoryPosition 35

1.FoodQualityProtectionActFindings... 35

a."RiskCup"Determination. 35b.DeterminationofSafetytoU.S.Population.. 35c.DeterminationofSafetytoInfantsandChildren. 35

d.CumulativeRisks.... 36 e.EndocrineDisruptorEffects... 36

2.ToleranceSummary 37a.TolerancesCurrentlyorProposedtobeListed 37

b.CodexHarmonization. 37D.RegulatoryRationale.. 38

1.HumanHealthRiskManagement. 38a.Dietary(Food)RiskMitigation.. 38

b.DrinkingWaterRiskMitigation 38c.ResidentialRiskMitigation 38

d.OccupationalRiskMitigation 39i.HandlerExposure. 39

ii.Post-ApplicationRiskMitigation.. 392.EnvironmentalRiskManagement. 39

3.ListedSpeciesConsiderations 39a.TheEndangeredSpeciesProgram. 39

b.GeneralRiskMitigation. 40

V.WhatRegistrantsNeedtoDo 41A.ManufacturingUseProducts. 43

1.AdditionalGenericDataRequirements 432.LabelingforTechnicalandManufacturingUseProducts.. 43

B.End-UseProducts... 441.AdditionalProduct-SpecificDataRequirements. 44

2.LabelingforEnd-UseProducts.. 45

VI.Appendices. 46A.TableofUsePatternsforBIT... 47

B.TableofGenericDataRequirementsandStudiesUsedtoMaketheReregistrationDecision.. 62

C.TechnicalSupportDocuments.. 67D.BibliographyCitations... 68

E.GenericDataCall-In.. 143F.ProductSpecificDataCall-In 144

G.BatchingofEnd-UseProducts.. 145H.ListofAllRegistrantsSenttheDataCall-In... 150

I.ListofAvailableForms... 151


8/60

BITReregistrationTeam

HealthEffectsRiskAssessmentMelbaMorrowCassiWallsTimMcMahonMichelleCentraTimothyLeighton

EnvironmentalFateandEcologicalAssessmentNajmShamimKathrynMontague

UseAnalysisRebeccaMiller

RiskManagementRebeccaMiller

RegistrationSupportKarenAngulo

i


9/60

GLOSSARYOFTERMSANDABBREVIATIONS

a.i. ActiveIngredientaPAD AcutePopulationAdjustedDoseAPHIS AnimalandPlantHealthInspectionServiceARTF AgriculturalRe-entryTaskForce

BCF BioconcentrationFactorCDC CentersforDiseaseControlCDPR CaliforniaDepartmentofPesticideRegulationCFR CodeofFederalRegulationsChEI CholinesteraseInhibitionCMBS CarbamateMarketBasketSurveycPAD ChronicPopulationAdjustedDoseCSFII USDAContinuingSurveysforFoodIntakebyIndividualsCWS CommunityWaterSystemDCI DataCall-InDEEM DietaryExposureEvaluationModelDL Doublelayerclothing{i.e.,coverallsoverSL}DWLOC DrinkingWaterLevelofComparisonEC EmulsifiableConcentrateFormulation

EDSP EndocrineDisruptorScreeningProgramEDSTAC EndocrineDisruptorScreeningandTestingAdvisoryCommitteeEEC EstimatedEnvironmentalConcentration. Theestimatedpesticideconcentrationinan

LC

environment,suchasaterrestrialecosystem.EP End-UseProductEPA U.S. EnvironmentalProtectionAgencyEXAMS TierIISurfaceWaterComputerModel FDA FoodandDrugAdministrationFFDCA FederalFood,Drug,andCosmeticActFIFRA FederalInsecticide,Fungicide,andRodenticideActFOB FunctionalObservationBatteryFQPA FoodQualityProtectionActFR Federal Register GL Withgloves

GPS GlobalPositioningSystemHIARC HazardIdentificationAssessmentReviewCommitteeIDFS IncidentDataSystemIGR InsectGrowthRegulatorIPM IntegratedPestManagementRED ReregistrationEligibilityDecisionLADD LifetimeAverageDailyDose

50 MedianLethalConcentration.Statisticallyderivedconcentrationofasubstanceexpectedtocausedeathin50%oftestanimals,usuallyexpressedastheweightofsubstanceperweightorvolume

LD

ofwater,airorfeed,e.g.,mg/l,mg/kgorppm.LCO LawnCareOperator

50 MedianLethalDose.Statisticallyderivedsingledosecausingdeathin50%ofthetestanimalswhenadministeredbytherouteindicated(oral,dermal,inhalation),expressedasaweightofsubstanceperunitweightofanimal,e.g.,mg/kg.

LOAEC LowestObservedAdverseEffectConcentrationLOAEL LowestObservedAdverseEffectLevelLOC LevelofConcernLOEC LowestObservedEffectConcentrationmg/kg/day MilligramPerKilogramPerDayMOE MarginofExposureMP Manufacturing-UseProductMRID MasterRecordIdentification(number). EPAssystemofrecordingandtrackingstudies

submitted.MRL MaximumResidueLevel


10/60

N/A NotApplicableNASS NationalAgriculturalStatisticalServiceNAWQA USGSNationalWaterQualityAssessmentNG NoGlovesNMFS NationalMarineFisheriesServiceNOAEC NoObservedAdverseEffectConcentrationNOAEL NoObservedAdverseEffectLevel

NPIC NationalPesticideInformationCenterNR NorespiratorOP OrganophosphorusOPP EPAOfficeofPesticideProgramsORETF OutdoorResidentialExposureTaskForcePAD PopulationAdjustedDosePCA PercentCropAreaPDCI ProductSpecificDataCall-InPDP USDAPesticideDataProgramPF10 Protectionsfactor10respiratorPF5 Protectionfactor5respiratorPHED PesticideHandlersExposureDataPHI Pre-harvestIntervalppb PartsPerBillion

PPE PersonalProtectiveEquipmentPRZM PesticideRootZoneModelRBC RedBloodCellRED ReregistrationEligibilityDecisionREI RestrictedEntryIntervalRfD ReferenceDoseRPA ReasonableandPrudentAlternativesRPM ReasonableandPrudentMeasuresRQ RiskQuotientRTU (Ready-to-use)RUP RestrictedUsePesticideSCI-GROW TierIGroundWaterComputerModelSF SafetyFactorSL Singlelayerclothing

SLN SpecialLocalNeed(RegistrationsUnderSection24CofFIFRA)STORET StorageandRetrievalTEP TypicalEnd-UseProductTGAI TechnicalGradeActiveIngredientTRAC ToleranceReassessmentAdvisoryCommitteeTTRS TransferableTurfResiduesUF UncertaintyFactorUSDA UnitedStatesDepartmentofAgricultureUSFWS UnitedStatesFishandWildlifeServiceUSGS UnitedStatesGeologicalSurveyWPS WorkerProtectionStandard

iii


11/60

EXECUTIVESUMMARY

TheEnvironmentalProtectionAgency(hereafterreferredtoasEPAortheAgency)hascompleteditsreviewofpubliccommentsonthehumanhealthandenvironmentalrisk

assessmentsfor1,2-benzisothiazolin-3-one(hereafterreferredtoasBIT)andisissuingitsriskmanagementdecision.TheAgencyhasdecidedBITiseligibleforreregistrationprovidedallmeasuresoutlinedinthisdocumentareimplemented.BITisanantimicrobialthatisusedasanindustrialpreservativefortheprotectionofwater-basedadhesives,caulks,sealants,grouts,spackling,ready-mixedcements,ready-mixedwallboardcompounds,aqueouscompositionssuchasemulsionpaints,aqueousslurries,homecleaningandcarcareproducts,laundrydetergents,fabricsofteners,stainremovers,inks,photographicprocessingsolutions,paintsandstains,titaniumdioxideslurries,oilinwateremulsions,latices,metalworkingfluids,casein/rosindispersions,textilespin-finishsolutions,pesticideformulations,tapejointcompound,leatherprocessingsolutions,preservationoffreshanimalhidesandskins,andforoffshoreandterrestrialgas/oildrillingmudsandpackerfluidspreservation.1,2-Benzisothiazolin-3-oneisalsousedasaninertingredientinavarietyofproductsasamaterialspreservative.Exposuresandrisksfrom

theuseofproductscontaining1,2-benzisothiazolin-3-oneasboththeactiveandinertingredientsareassessedinthisreregistrationeligibilitydecision(RED). End-useproductsareformulatedaseitherasoluble,ready-to-use,orflowableconcentrates(allofwhichareconsideredtobeliquids).

Overall Risk Summary

TheAgencyshumanhealthriskassessmentindicatesfewrisksofconcern.AcuteandchronicdietaryexposureisbelowtheagencyslevelofconcernforgeneralU.S.populationsand

allpopulationsubgroups.Likewise,itwasconcludedthatriskfromexposureofBITindrinkingwaterwouldalsonotrepresentariskofconcernbecauseitisnotlikelytobeindrinkingwater

sourcesatsubstantialconcentrations.ThisisbasedonthefactthatBITreadilybiodegrades,isappliedtocropsviainertuseinsmallamountsandisonlylikelytocomeintocontactwithsoil/surfacewaterviapaintusesinsmallamounts.Theacuteandchronicaggregatedietaryrisk

assessmentestimatesassociatedwiththeuseofBITasaninertoractiveingredientarebelowtheAgencyslevelofconcern.

Shortandintermediatetermresidentialpost-applicationandhandlerexposures(dermal,

inhalationorincidentaloral)fromhardsurfaceresiduesdidnotexceedtheAgencyslevelofconcern.Forresidentialexposureandrisk,thetoddlerpost-applicationdermalexposurescenario

fromresiduesremainingonpetsfromtheinertuse,themarginofexposure(MOE)isbelowthetargetedMOE,indicatingthatthisscenarioisariskofconcern.

Foraggregateexposure,theriskestimatesassociatedwithBITarebelowtheAgencys

levelofconcern.Incaseswhereanaggregateriskindex(ARI)wasusedtoassessriskbecauseofthedifferentuncertaintyfactorsfororal,dermalandinhalationexposurescenarios,therisk

indicessuggestedthatthereisreasonablecertaintyofnoharmfromusingproductscontainingBIT. Basedontheinformationprovided,inhalationexposureswerenotconsideredtobeof

concernwithregardtoinhalationriskfromoccupationalhandlerscenarios;howeverthedermalMOEindicatedthatthedermalriskforoccupationalhandlerswasbelowthetargetMOEforone


12/60

scenario,handlersofBIT-containingpaintusinganairlesssprayer.Whiletheinhalationriskmaybeanunderestimationbasedonextrapolationfromanoralstudy,thedermalriskisbasedon

anumberofconservativeassumptionsandarenotofconcern.DermalandinhalationexposurestobystandersfromtheoccupationaluseofBITarealsoexpectedtobeminimal.

TheindoorusesofBITmakeitunlikelythatanyappreciableexposuretoterrestrialoraquaticorganismswouldoccur.FacilitiesusingBITforindoorindustrialapplicationsarerequiredtohaveNPDESpermitsbeforedischargingeffluentsintoreceivingwaters.

1,2-Benzisothiazolin-3-onesreadybiodegradationinsoilandsmallapplicationamountgreatlyreducetheexposurepotentialforterrestrialandaquaticorganisms.Run-offintosurfacewaterfrompesticidalusesislikelytobelowanditisnotlikelytobepresentinwatersourcesatsubstantialconcentrations.TheecologicalrisksfromtheuseofBITsuggestthatbecauseofthehightoxicityofBITtogreenalgaeandinvertebratespecies,adverseeffectstotheenvironmentcouldresultfromcontaminationfromBIT-treatedoilrecoveryfluids.

Dietary Risk

TheAgencyhasconductedadietaryexposureandriskassessmentforuseof1,2-benzisothiazolin-3-oneasapulpandpapermillslimicide,andapreservativeinpapercoatingsandpaperadhesives,allofwhichmayendinindirectfoodcontactscenarios.Forboththeacuteandchronicdietaryexposure,theriskishighestforchildren(21.8%oftheacuteandchronicPAD).Foranadult,theacuteandchronicdietaryexposureis9.4%oftheacuteandchronicPAD.AlldietaryexposurescalculatedarebelowtheAgencyslevelofconcern(100%ofaPADorcPAD)fornon-cancerrisk.Furthermore,giventheconservativenatureoftheassumptionsusedintheinertdietaryexposureandriskassessment,risksofconcernfromfoodarenotlikelyfromtheuseof1,2-benzisothiazolin-3-oneasinertingredientsinpesticideproducts.Adietarycancerriskassessmentcouldnotbeperformedastherearenocarcinogenicitydatafor1,2-benzisothiazolin-3-one.

Drinking Water Risk

Basedonenvironmentalfatedata,1,2-benzisothiazolin-3-onebindsmoderatelywithsoilandmaypotentiallymovewiththesoilduringrainfalleventsandreachsurfacewaters.Although,1,2-benzisothiazolin-3-onehasbeenshowntobehydrolyticallystablewithahalflifeof>30days,itbreaksdownfairlyquicklyinaerobicsoils.Outdoorusepatternsof1,2-benzisothiazolin-3-onewhichmayleadtocontactwithsoiland/orsurfacewaterinclude:1)theapplicationofagriculturalpesticidesthatcontain1,2-benzisothiazolin-3-oneasaninertingredient,and2)theapplicationofpaintsthatcontain1,2-benzisothiazolin-3-one.Considering1,2-benzisothiazolin-3-onereadilybiodegradesandthesmallamount(0.02lbs.peracre)that

maybeappliedtocropsviatheinertuseandthesmallamountlikelytocomeintocontactwithsoils/surfacewatersviathepaintuse,1,2-benzisothiazolin-3-oneisnotlikelytobepresentindrinkingwatersourcesatsubstantialconcentrations.

v


13/60

Residential Risk

Toaddressresidentialexposuredermal,inhalationandincidentaloralriskswereassessedfortheactiveandinertingredientusesofBIT. Theresidentialhandlerscenariosevaluatedare

consideredtoberepresentativeofallpossibleexposurescenarios.Noneoftheresidential

handlerexposurescenariosorpost-applicationexposurescenariosexceededtheAgencyslevelofconcern.

FortheinertusesofBIT,noneoftheresidentialhandlerexposurescenariosexceededtheAgencyslevelofconcern.Althoughmostofthepost-applicationexposuresdidnotexceedtheAgencyslevelofconcern,thetoddlerpost-applicationdermalexposurescenariotoresiduesremainingonpetsresultedinaMOEof33whichislowerthanthetargetMOEof100resultinginrisksofconcern.

Aggregate Risk

Theacuteandchronicaggregateriskassessmentsgenerallyincludeonlydietaryand

drinkingwaterexposures.Sincedrinkingwaterexposureisnotexpectedfromanyoftheindoororoutdoorusesof1,2-benzisothiazolin-3-oneusedaseitheraninertoractiveingredient,theacuteandchronicaggregateassessmentsonlyincludeddietaryexposuresfromtheactiveindirectfooduses(i.e.,useinfood-contactpackaging)andinertdietaryexposuresfromagriculturalpesticideuses.Theacuteandchronicaggregateriskestimatesassociatedwith1,2-benzisothiazolin-3-onearewellbelowtheAgencyslevelofconcernwhere,theadultsriskswere17.1%oftheaPADand12.2%ofthecPAD,andthechildrensriskswere44.1%oftheaPADand31.8%ofthecPAD.

Theshort-andintermediate-termaggregateassessmentswereconductedforadultsandchildren.Sincethetoxicityendpointsforalloftheroutesofexposure(oral,dermaland

inhalation)arebasedonthesamestudyandsametoxiceffect,allroutesareaggregatedtogether.However,theaggregateriskindex(ARI)methodwasutilizedintheassessment. Thismethod

wasusedbecausetheoral,dermalandinhalationendpointshavedifferentuncertaintyfactorsthatneedtobeapplied.For1,2-benzisothiazolin-3-one,allendpointsforexposurewerederivedfrom

asubchronicoralstudyindogshowever,theuncertaintyfactors(i.e.,targetMOEs)fororal,

dermalandinhalationroutesare300,100and100,respectively.Ariskindex$

1indicatesnoriskofconcern. Theshort-termARIsforadultsandchildrenwere6.8and1.9,respectively,

whiletheintermediate-termARIsforadultsandchildrenwere7.5and1.9,respectively.Therefore,short-andintermediate-termaggregatecalculatedrisksarebelowtheAgencyslevel

ofconcern.Pleasenotethattheinertuseinpetproductsisconsideredtoresultinintermittentexposuresand,assuch,werenotincludedintheaggregateassessment.

Occupational Risk

Toaddressoccupationalexposure,short-terminhalation,andintermediate-term

combineddermalandinhalationriskswereassessed. Theinhalationexposuresarenotof

concernfortheanyofthehandlerscenariosassessed(i.e.,MOEs$

1,000). However,for

handlersusingBIT-treatedpaintviaanairlesssprayer,thedermalMOEof90indicatesariskofconcern(i.e.,MOEs


14/60

Postapplicationexposuresmayoccurinindustrialsettingsaroundthewatersystemsviainhalation,anddermalexposuresmayoccurwhilemaintainingindustrialequipment. However,occupationalpost-applicationdermalandinhalationexposuresto1,2-benzisothiazolin-3-onearelikelytobeminimalwhencomparedtohandlerexposurebecauseofdilutionduringprocessingorwhencomparedtomachinistsusingthemetalworkingfluid.Inhalationexposuresareexpectedtobeminimalbecauseaerosolgenerationisnotexpectedandthevaporpressureof1,2-benzisothiazolin-3-oneislow.

Ecological Risk

Basedonacutetoxicityinformation,1,2-benzisothiazolin-3-onedisplayslowtomoderatetoxicitytobirdsandmammals.Itismoderatelytoxictofreshwaterfishandinvertebrates,

slightlytoxictomarine/estuarinefish,andhighlytoxictomarine/estuarineinvertebrates.

TheindoorusesofBITconsideredinthisREDmakeitunlikelythatanyappreciableexposuretoterrestrialoraquaticorganismswouldoccur.FacilitiesusingBITforindoor

industrialapplicationsarerequiredtohaveNPDESpermitsbeforedischargingeffluentsintoreceivingwaters.Thepotentialexposuretoterrestrialandaquaticspeciesfromtheoilrecovery

usesofBITcannotbeestimatedatthistime,asthereiscurrentlynovalidatedmodelavailableforsuchapurpose.ThehightoxicityofBITtogreenalgaeandinvertebratespeciessuggeststhat

potentialadverseacuteeffectscouldoccurtosomespeciesifenvironmentalcontaminationfromBIT-treatedoilrecoveryfluidsoccurs.

1,2-Benzisothiazolin-3-oneisusedasaninertingredientinpesticideproductsbuttheallowableamountthatcanbeappliedissmall(notmorethan0.1%formulationand0.02lbs.peracre). Dataindicatethat1,2-benzisothiazolin-3-onebreaksdownquicklyinaerobicsoils(halflife


15/60

1. Theallowableamountthatcanbeappliedissmall(notmorethan0.1%formulationand0.02lbs.peracre).

2. Dataindicatethat1,2-benzisothiazolin-3-onebreaksdownquicklyinaerobicsoils(half-life


16/60

I. Introduction

TheFederalInsecticide,Fungicide,andRodenticideAct(FIFRA)wasamendedin1988toacceleratethereregistrationofproductswithactiveingredientsregisteredpriortoNovember1,1984andamendedagainbythePesticideRegistrationImprovementActof2003tosettimeframesfortheissuanceofReregistrationEligibilityDecisions.TheamendedActcallsforthedevelopmentandsubmissionofdatatosupportthereregistrationofanactiveingredient,aswellasareviewofallsubmitteddatabytheU.S.EnvironmentalProtectionAgency(EPAortheAgency).Reregistrationinvolvesathoroughreviewofthescientificdatabaseunderlyingapesticidesregistration.ThepurposeoftheAgencysreviewistoreassessthepotentialhazardsarisingfromthecurrentlyregisteredusesofthepesticide;todeterminetheneedforadditionaldataonhealthandenvironmentaleffects;andtodeterminewhetherornotthepesticidemeetsthenounreasonableadverseeffectscriteriaofFIFRA.

OnAugust3,1996,theFoodQualityProtectionActof1996(FQPA)wassignedintolaw.ThisActamendsFIFRAtorequiretolerancereassessment. TheAgencyhasdecidedthat,

forthosechemicalsthathavetolerancesandareundergoingreregistration,thetolerancereassessmentwillbeinitiatedthroughthisreregistrationprocess. TheActalsorequiresthatby2006,EPAmustreviewalltolerancesineffectonthedaybeforethedateoftheenactmentoftheFQPA.FQPAalsoamendstheFederalFood,Drug,andCosmeticAct(FFDCA)torequireasafetyfindingintolerancereassessmentbasedonfactorsincludingconsiderationofcumulativeeffectsofchemicalswithacommonmechanismoftoxicity.ThisdocumentpresentstheAgencysrevisedhumanhealthandecologicalriskassessments;andtheReregistrationEligibilityDecision(RED)for1,2-benzisothiazolin-3-one(BIT).

BITisanantimicrobialthatisusedasanindustrialpreservativefortheprotectionofwater-basedadhesives,caulks,sealants,grouts,spackling,ready-mixedcements,ready-mixedwallboardcompounds,aqueouscompositionssuchasemulsionpaints,aqueousslurries,home

cleaningandcarcareproducts,laundrydetergents,fabricsofteners,stainremovers,inks,photographicprocessingsolutions,paintsandstains,titaniumdioxideslurries,oilinwateremulsions,latices,metalworkingfluids,casein/rosindispersions,textilespin-finishsolutions,pesticideformulations,tapejointcompound,leatherprocessingsolutions,preservationoffreshanimalhidesandskins,andforoffshoreandterrestrialgas/oildrillingmudsandpackerfluidspreservation.Thespecificantimicrobialusecategoriesincludethefollowinggeneralusepatterns:materialpreservatives(indoorfoodandindoor/outdoornon-food),industrialprocessesandwatersystems(indoornonfood),andindoorandoutdoorresidentialuses.1,2-Benzisothiazolin-3-oneisalsousedasaninertingredientinavarietyofproductsasamaterialspreservative.Exposuresandrisksfromtheuseofproductscontaining1,2-benzisothiazolin-3-oneasboththeactiveandinertingredientswereassessed.

TheAgencyhasconcludedthattheFQPASafetyFactorfor1,2-benzisothiazolin-3-oneshouldberemoved(equivalentto1X)basedon(1)thelackofevidenceofincreasedsusceptibilityinthe2-generationreproductiontoxicitystudyandtheavailabledevelopmentaltoxicitydata;and(2)theriskassessmentdoesnotunderestimatethepotentialriskforinfantsandchildren.

1


17/60

Riskssummarizedinthisdocumentarethosethatresultonlyfromtheuseoftheactiveingredient1,2-benzisothiazolin-3-one. TheFoodQualityProtectionAct(FQPA)requiresthattheAgencyconsideravailableinformationconcerningthecumulativeeffectsofaparticularpesticidesresiduesandothersubstancesthathaveacommonmechanismoftoxicity.Thereasonforconsiderationofothersubstancesisduetothepossibilitythatlow-levelexposurestomultiplechemicalsubstancesthatcauseacommontoxiceffectbyacommontoxicmechanismcouldleadtothesameadversehealtheffectthatwouldoccuratahigherlevelofexposuretoanyofthesubstancesindividually.UnlikeotherpesticidesforwhichEPAhasfollowedacumulativeriskapproachbasedonacommonmechanismoftoxicity,EPAhasnotmadeacommonmechanismoftoxicityfindingfor1,2-benzisothiazolin-3-oneandanyothersubstances.1,2-benzisothiazolin-3-onedoesnotappeartoproduceatoxicmetaboliteproducedbyothersubstances.Forthepurposesofthisaction,therefore,EPAhasnotassumedthat1,2-benzisothiazolin-3-onehasacommonmechanismoftoxicitywithothersubstances.ForinformationregardingEPAseffortstodeterminewhichchemicalshaveacommonmechanismoftoxicityandtoevaluatethecumulativeeffectsofsuchchemicals,seethepolicystatementsreleasedbyEPAsOfficeofPesticideProgramsconcerningcommonmechanismdeterminationsandproceduresforcumulatingeffectsfromsubstancesfoundtohaveacommonmechanismon

EPAswebsiteathttp://www.epa.gov/pesticides/cumulative .

ThisdocumentpresentstheAgencysdecisionregardingthereregistrationeligibilityoftheregisteredusesofBIT.InanefforttosimplifytheRED,theinformationpresentedhereinissummarizedfrommoredetailedinformationthatcanbefoundinthetechnicalsupportingdocumentsforBITreferencedinthisRED. Therevisedriskassessmentsandrelatedaddendaarenotincludedinthisdocument,butareavailableinthePublicDocketathttp://www.epa.gov/edocket .

Thisdocumentconsistsofsixsections.SectionIistheintroduction.SectionIIprovidesachemicaloverview,aprofileoftheuseandusageofBIT,anditsregulatoryhistory.SectionIII,SummaryofBITRiskAssessment,givesanoverviewofthehumanhealthand

environmentalassessments,basedonthedataavailabletotheAgency.SectionIV,RiskManagement,Reregistration,andToleranceReassessmentDecision,presentsthereregistrationeligibilityandriskmanagementdecisions.SectionV,WhatRegistrantsNeedtoDo,summarizesthenecessarylabelchangesbasedontheriskmitigationmeasuresoutlinedinSectionIV.Finally,theAppendiceslistallusepatternseligibleforreregistration,bibliographicinformation,relateddocumentsandhowtoaccessthem,andDataCall-In(DCI)information.


18/60

II. ChemicalOverview

A. RegulatoryHistory

Thereare43activeproductscontaining1,2-benzisothiazolin-3-oneasanactiveingredient,3ofwhicharetechnicalproducts,registeredunderSection3oftheFederalInsecticide,Fungicide,andRodenticideAct(FIFRA).Therearehundredsofproductsthathaveinertusesfor1,2-benzisothiazolin-3-one.Thefirstproductcontaining1,2-benzisothiazolin-3-onewasregisteredonApril4,1973.

B. ChemicalIdentification - TechnicalBIT

S

NH

O

Commonname: BIT

Chemicalname: 1,2-Benzisothiazolin-3-one

ChemicalFamily: Isothiazolines

Empiricalformula: C7H5NOS

CASRegistryNo.: 2634-33-5

Casenumber: 3026

OPPChemicalCode:098901

Molecularweight: 151.9

Tradename(s): IPX,Proxan,Proxel,NipacideBIT,MergalBIT

Basicmanufacturer: PromChem,ArchChemicals,ISP,ClariantCorp.,andTroyCorp.

TechnicalBITisintheformofasolidpasteandisoff-whitetobrownincolor. BIThasameltingpointof159.5-160

oC. Threeseparatewatersolubilitieswereprovidedbydifferent

registrants:1118ppmat20oC,1380ppmat24

oC,EPAdatabase(EPISuite)liststhesolubilityof

3


19/60

2.1g/Lat25oC.BIThasavaporpressureof4.4x10

-7mmHgat20

oC,9.8x10

-7mmHgat

25oC,and2.78x10

-6mmHgat25

oC

C. UseProfile

ThefollowingisinformationonthecurrentlyregisteredusesofBITproductsandanoverviewofusesitesandapplicationmethods. AdetailedtableoftheusesofBITeligibleforreregistrationiscontainedinAppendixA.

TypeofPesticide: Fungicide/Fungistat

Bacteriostat Microbicide/Microbistat

Disinfectant(Bacteriocide/Germicide)

SummaryofUse:

Food: BITisusedasaninertingredientonmanycropsincludingCaneberries,Blackberries, Blueberries,Cranberries,Strawberries,Citrus,Almond,Apples,Pears,Apricots,Cherries,Nectarines,Peaches,Plums,Prunes,Cantaloupes,CasabaMelons,CrenshawMelons,HoneydewMelons,Muskmelons,Watermelons,Tomatoes,Broccoli,Brussel Sprouts,Cabbage,Cauliflower,Collards,Kale,Endive,Spinach,Lettuce,Carrots,Onions,Radishes,Rutabagas,Guar,Ginseng,Beets,andMustard.

Non-Food: BITisalsousedasaninertingredientonConiferPlantings,OrnamentalFloweringPlants,OrnamentalLawns,OrnamentalWoodyShrubs,Roses,EnglishIvy,OrnamentalTrees,WeepingFig,Elm,Oak,Palm,ArizonaCypress,andIrish

Moss.

Residential: BITisusedasanactiveingredientforNonagriculturalBuildings,PerimeterSoilTreatment,DomesticDwellings(Outdoor),andHardNonporousSurfaces.

Industrial: BITisusedasanactiveingredientforPulpandPaperMillSystems,SecondaryOilRecoveryInjectionWater,andHeatExchangerWater.

MaterialsPreservatives:BITisusedasanactiveingredientforAdhesives,PreservativeIncorporation,Adhesives(Gums,JointCements,Latex,TapeMuds,Proteinbased,Starchbased,Synthetic),CaulkingCompounds,Grouts,Starch,WallboardJointCompounds,

Mastics,Sealants,Coatings(Aqueous,Lacquer,Rosin,Wood,ProteinandStarchbased),Films,Coatings(Paper,PaperProductsandPaperboard),HidesandLeatherProducts,LeatherProcessingLiquors(PreservativeIncorporation),MetalworkingCuttingFluids(PreservativeIncorporation),OilRecoveryDrillMudsandPackerFluids(PreservativeIncorporation),Paints(Acrylic,EmulsionandLatex),SyntheticPolymers,LatexandLatexEmulsions,ResinEmulsions,Cleansers,PhotographicSolution,Polishes,Soap,Wax,Inks,LiquidDetergents,Dyes,PowderedDetergents,FloorWax,FabricSofteners,TarnishAgents,AirFresheners,CarpetShampoos,Canvas,Cordage,rope,twine,Fabrics,Casein,


20/60

ClaySlurries,StarchSolutions,PrintingPastes,Stains(preservativeincorporation),WaterBasedPaints,andConcreteMixtures.

TargetPests: Staphylococcusaureus,pseudomonasaeruginosa,rhizopusstolonifer,aspergilluspencilloides,aspergillusniger,alternariaradicina,tricophytonmentagrophytes,salmonellatyphosa,klebsiellapneumoniae,bacillussubtilis,bacillusmegaterium,escherichacoli,proteusvulagris.

FormulationTypes: Granularpowder,flowableconcentrate,solubleconcentrate,readytousesolution.

MethodandRatesofApplication :AllproductscontainingBITasanactiveingredient,includingready-to-usesolutions,areusedinmanufacturingprocessesonly.Forlaundrydetergents,householdcleaningproducts,andcarcareproducts,0.10%to0.30%ofBITisaddedbyweight.Whenusedasamaterialspreservative,0.05%to1%ofBITis

addedbyweight.PleaserefertoAppendixAformoredetailedapplicationrates.

5


21/60

III. SummaryofBITRiskAssessments

Thepurposeofthissummaryistoassistthereaderbyidentifyingthekeyfeaturesandfindingsoftheseriskassessments,andtohelpthereaderbetterunderstandtheconclusionsreachedintheassessments. ThehumanhealthandecologicalriskassessmentdocumentsandsupportinginformationlistedinAppendixCwereusedtoformulatethesafetyfindingandregulatorydecisionforBIT.Whiletheriskassessmentsandrelatedaddendaarenotincludedinthisdocument,theyareavailablefromtheOPPPublicDocketandmayalsobeaccessedontheAgencyswebsiteathttp://epa.gov/docket.HardcopiesofthesedocumentsmaybefoundintheOPPpublicdocketunderdocketnumberOPP-2004-0200. TheOPPpublicdocketislocatedinRoom119,CrystalMallII,1801BellStreet,Arlington,VA,andisopenMondaythroughFriday,excludingFederalholidays,from8:30a.m.to4:00p.m.

A. HumanHealthRiskAssessment

1. ToxicityofBIT

AbriefoverviewofthetoxicitystudiesusedfordeterminingendpointsinthehumanhealthdietaryriskassessmentsareoutlinedinTable2. FurtherdetailsonthetoxicityofBITcanbefoundinthedocumentsHumanExposureAssessmentforaReregistrationSubmissionfor1,2-Benzisothiazolin-3-one(BIT),datedJuly11,2005;DietaryRiskAssessmentof1,2-Benzisothiazolin-3-one(BIT)forReregistrationEligibilityDecision(RED)Document,datedJuly12,2005;and1,2-Benzisothizolin-3-one(BIT)-RevisedReportoftheAntimicrobialsDivisionsToxicologyEndpointSelectionCommittee(ADTC),datedApril22,2005. ThesedocumentsareavailableonAgencyswebsiteintheEPADocketat http://www/epa.gov/edocket.

TheAgencyhasreviewedalltoxicitystudiessubmittedforBITandhasdeterminedthat

thetoxicologicaldatabaseissufficientforreregistration.Thestudieshavebeensubmittedtosupportguidelinerequirements. Majorfeaturesofthetoxicologyprofilearepresentedbelow.Acutetoxicitydatashowthat1,2-benzisothiazolin-3-oneismoderatelytoxicbytheoralanddermalroutes(ToxicityCategoryIIIforbothstudies),butthatthischemicalisasevereeyeirritant(ToxicityCategoryI).Irritationtotheskinfromacutedatashowonlymildskinirritation(ToxicityCategoryIV),butrepeateddermalapplicationindicatedamoresignificantskinirritationresponse.

Table1.AcuteToxicityof1,2-Benzisothiazolin-3-oneTechnical

Guideline

No.

StudyType MRID#(s) Results Toxicity

Category

870.1100 AcuteOral 41022101;42858101

LD50=670mg/kg(M);784mg/kg(F)

III

870.1200 AcuteDermal 41022102;42858102

LD50>2000mg/kg III

870.1300 AcuteInhalation waivergranted


22/60

GuidelineNo.

StudyType MRID#(s) Results ToxicityCategory

870.2400 PrimaryEyeIrritation

42905102 severeeyeirritant I

870.2500 PrimarySkinIrritation

42905101 slightirritant IV

870.2600 Dermal 41750001; moderatedermal NotApplicableSensitization 42858103 sensitizer

ThedosesandtoxicologicalendpointsselectedforthedietaryexposurescenariosaresummarizedinTable2below.

Table2.ToxicologicalEndpointsforBIT(Dietary)

Exposure DoseUsedinRisk TargetMOE,UF, Study andToxicologicalEffects

Scenario Assessment SpecialFQPASF,for(mg/kg/day) RiskAssessment

AcuteDietary

Generalpopulation,

NOAEL=5mg/kg/day UF=100(10xinter-species

extrapolation,10xintra

speciesvariation)

Co-Criticalstudies:

Subchronictoxicity,dog,NOAEL=5

mg/kg/daybasedonincreasedincidence

includinginfants FQPASF=1 ofemesisandclinicalchemistry

andchildren DBUF=3 alterationsat20mg/kg/day.

AcuteRfD=0.017 andmg/kg/day Subchronictoxicity,rats,NOAEL=

8.42mg/kg/daybasedonmacroscopicandmicroscopiclesionsinthenon-

glandularandglandularregionsofthe

stomach.

ChronicDietary

Allpopulations

NOAEL=5mg/kg/day UF=100(10xinter-species

extrapolation,10xintraspeciesvariation)

Co-Criticalstudies:

Subchronictoxicity,dog,NOAEL=5mg/kg/daybasedonincreasedincidence

FQPASF=1 ofemesisandclinicalchemistry

DBUF=3 alterationsat20mg/kg/day.

ChronicRfD=0.017 andmg/kg/day Subchronictoxicity,rats,NOAEL=

8.42mg/kg/daybasedonmacroscopic

andmicroscopiclesionsinthenon-

glandularandglandularregionsofthe

stomach.

Cancer:Nocancerdataavailablefor1,2-benzisothiazolin-3-oneUF=uncertaintyfactor,FQPASF=SpecialFQPAsafetyfactor,NOAEL=noobservedadverseeffectlevel,LOAEL=lowestobservedadverseeffectlevel,PAD=populationadjusteddose,(a=acute,c=chronic)RfD=referencedose,MOE=marginofexposure,N/A=NotApplicable

7


23/60

Developmentaltoxicitystudieswereconductedinratswithmaternaleffectsincludingdecreasedbodyweightgain,decreasedfoodconsumption,andclinicaltoxicitysigns(audible

breathing,haircoatstainingoftheanogenitalregion,drybrownmaterialaroundthenasalarea)aswellasincreasedmortality.Developmentaleffectsconsistedofincreasesinskeletal

abnormalities(extrasitesofossificationofskullbones,unossifiedsternebra)butnotexternalor

visceralabnormalities.

Inatwo-generationreproductionstudy,parentaltoxicitywasobservedat500ppmand

wascharacterizedbylesionsinthestomach.Inpups,toxiceffectswerereportedat1000ppmandconsistedofpreputialseparationinmalesandimpairedgrowthandsurvivalinbothsexes.

Thereproductionstudydidnotshowevidenceofincreasedsusceptibilityofoffspring.

GeneralToxicityObservations

Subchronicoraltoxicitystudiesshowedsystemiceffectsafterrepeatedoraladministrationincludingdecreasedbodyweight,increasedincidenceofforestomachhyperplasia,

andnon-glandularstomachlesionsinrats. Indogs,theeffectsoccurredatlowerdosesthaninrats,andincludedalterationsinbloodchemistry(decreasedplasmaalbumin,totalprotein,and

alanineaminotransferase)andincreasedabsoluteliverweight.

TheAgencyhasconcludedthatthereisnotaconcernforneurotoxicityresultingfromexposureto1,2-benzisothiazolin-3-one.Theneurotoxicityobservedintheratacuteoraltoxicity

study(piloerectionandupwardcurvatureofthespineat300mg/kgandabove;decreasedactivity,prostration,decreasedabdominalmuscletone,reducedrightingreflex,anddecreased

rateanddepthofbreathingat900mg/kg)andtheacutedermaltoxicitystudy(upwardcurvatureofthespinewasobservedinincreasedincidence,butthiswasabsentafterday5post-doseata

doseof2000mg/kg)werefelttobeatexposuresinexcessofthoseexpectedfromtheusepatternofthispesticideandthatsucheffectswouldnotbeobservedatestimatedexposuredoses.

Dietary:TheacuteandchronicRfDsare0.017mg/kg/day.Theseendpointsarebasedon

asubchronictoxicitystudyindogswithareportedNOAELof5mg/kg/dayandwhichindicatedincreasedincidencesofemesisandclinicalchemistryalterationsattheLOAELof20mg/kg/day.

Anuncertaintyfactorof300(10xforinterspeciesextrapolation,10xforintraspeciesvariability,and3xfordatabaseuncertainty)wasappliedtotheNOAELtoobtaintheacuteandchronic

RfDs.Thedatabaseuncertaintyfactorof3xisappliedtoaccountfororaldatabaseconcernsbasedonthelackofreliabledevelopmentaltoxicitydatawithrespecttomaternaltoxicity.

IncidentalOral:Theshort-andintermediate-termoralendpointis5mg/kg/dayandis

basedonincreasedincidenceofemesisandclinicalchemistryalterationsat20mg/kg/dayinasubchronictoxicitystudyindogs.Thetargetmarginofexposure(MOE)is300.

Dermal:Theshort-,intermediate-,andchronic-termdermalendpointis5mg/kg/dayand

isbasedonincreasedincidenceofemesisandclinicalchemistryalterationsat20mg/kg/dayinasubchronictoxicitystudyindogs. ThetargetMOEis100forresidentialandoccupational

exposure.


24/60

Inhalation:Theshort-,intermediate-,andchronic-terminhalationendpointis5mg/kg/dayandisbasedonincreasedincidenceofemesisandclinicalchemistryalterationsat20

mg/kg/dayinasubchronictoxicitystudyindogs. ThetargetMOEis100foroccupationalandresidentialexposure;howeveriftheresultingMOEisnotatleast1000,theAgencycanrequesta

repeatdoseinhalationstudyofatleast28daysinduration.(TheMOEof1000isbasedonthe

applicationofa10Xuncertaintyfactorforinterspeciesextrapolation,a10Xuncertaintyforintraspeciesvariabilityanda10Xforthelackofaninhalationstudy).

DermalPenetration:Adermalpenetrationstudywasconductedinratsinwhicha10mg/kgdermaldoseof1,2-benzisothiazolin-3-onewasappliedtotheskinfordurationsof4,8,

24,48or72hours. At72hoursamaximumdermalpenetrationof40.6%wasachieved.

Mutagenicity: Allacceptablemutagenicitystudiesshowedanegativemutagenicresponseforthischemical.

Carcinogenicity: Carcinogenicitydataarenotavailablefor1,2-benzisothiazolin-3-one.Thesedataarerequiredtosupportthemetalworkingfluiduse.

EndocrineDisruptionPotential: EPAisrequiredundertheFederalFoodDrugandCosmeticAct(FFDCA),asamendedbyFQPA,todevelopascreeningprogramtodeterminewhethercertainsubstances(includingallpesticideactiveandotheringredients)mayhaveaneffectinhumansthatissimilartoaneffectproducedbyanaturallyoccurringestrogen,orothersuchendocrineeffectsastheAdministratormaydesignate. Whentheappropriatescreeningand/ortestingprotocolsbeingconsideredundertheAgencysEndocrineDisruptingScreeningProgram(EDSP)havebeendeveloped,1,2-benzisothiazolin-3-onemaybesubjectedtoadditionalscreeningand/ortestingtobettercharacterizeeffectsrelatedtoendocrinedisruption.

2. FQPASafetyFactor

TheFQPASafetyFactor(asrequiredbytheFoodQualityProtectionActof1996)isintendedtoprovideanadditional10-foldsafetyfactor(10X),toprotectforspecialsensitivityininfantsandchildrentospecificpesticideresiduesinfood,drinkingwater,orresidentialexposures,ortocompensateforanincompletedatabase.TheFQPASafetyFactorhasbeenremoved(i.e.,reducedto1X)for1,2-benzisothiazolin-3-onebasedon(1)thelackofevidenceofincreasedsusceptibilityinthe2-generationreproductiontoxicitystudyandtheavailabledevelopmentaltoxicitydata;and(2)theriskassessmentdoesnotunderestimatethepotentialriskforinfantsandchildren.TheFQPASafetyFactorassumesthattheexposuredatabases(food,drinkingwater,andresidential)arecomplete,theriskassessmentforeachpotentialexposurescenarioincludesallmetabolitesand/ordegradatesofconcern,anddoesnotunderestimatethepotentialriskforinfantsandchildren.Thesecriteriahavebeenmetfor1,2-

benzisothiazolin-3-one.Basedontheanalysisofsubmitteddevelopmentaltoxicitystudies,theAgencydeterminedthatnospecialFQPASafetyFactorwasneededsincetherewerenoresidualuncertaintiesforpre-and/orpostnataltoxicity.

9


25/60

3. PopulationAdjustedDose(PAD)

DietaryriskischaracterizedintermsofthePopulationAdjustedDose(PAD),whichreflectsthereferencedose(RfD),eitheracuteorchronic,thathasbeenadjustedtoaccountfor

theFQPASafetyFactor(SF). Thiscalculationisperformedforeachpopulationsubgroup. Ariskestimatethatislessthan100%oftheacuteorchronicPADisnotofconcern.

a. AcutePAD

AcutedietaryriskforBITisassessedbycomparingacutedietaryexposureestimates(inmg/kg/day)totheacutePopulationAdjustedDose(aPAD).Acutedietaryriskisexpressedasa

percentoftheaPAD.TheaPADistheacutereferencedose(0.017mg/kg/day)modifiedbytheFQPAsafetyfactor. Theacutereferencedosewasderivedfromasubchronictoxicitystudyin

dogsinwhichboththeNOAEL(5.0mg/kg/day)andtheLOAEL(20.0mg/kg/day)weredeterminedbasedontheincidenceofemesisandclinicalchemistryalterationsinbothsexes.

ThisstudywasfurthersupportedbyasubchronictoxicitystudyinratsinwhichboththeNOAEL(8.42mgai/kg/day)andtheLOAEL(25.26mgai/kg/day)weredeterminedbasedon

theincidenceofmacroscopicandmicroscopiclesionsinbothsexes.TheBITaPADis0.017mg/kg/daybasedonareferencedoseof0.017mg/kg/day,andincorporatingtheFQPAsafety

factorof1XfortheoverallU.S.populationoranypopulationsubgroups.

b. ChronicPAD

ChronicdietaryriskforBITisassessedbycomparingchronicdietaryexposureestimates(inmg/kg/day)tothechronicPopulationAdjustedDose(cPAD). Chronicdietaryriskis

expressedasapercentofthecPAD.ThecPADisthechronicreferencedose(0.017mg/kg/day)

modifiedbytheFQPAsafetyfactor. ThecPADwasderivedfromasubchronictoxicitystudyindogsinwhichboththeNOAEL(5.0mg/kg/day)andtheLOAEL(20.0mg/kg/day)weredeterminedbasedontheincidenceofemesisandclinicalchemistryalterationsinbothsexes.

ThisstudywasfurthersupportedbyasubchronictoxicitystudyinratsinwhichboththeNOAEL(8.42mgai/kg/day)andtheLOAEL(25.26mgai/kg/day)weredeterminedbasedon

theincidenceofmacroscopicandmicroscopiclesionsinbothsexes.TheBITcPADis0.017mg/kg/daybasedonareferencedoseof0.017mg/kg/day,whichincludestheincorporationof

theFQPAsafetyfactor(1X)fortheoverallU.S.populationoranypopulationsubgroups.

4. DietaryExposureAssumptions

DietaryexposuretoBITresiduesoccursprimarilyfromtheantimicrobialpaperuseswhichinclude:slimicideuseinpaper/pulpmanufacturing,papercoatingspreservative,andpaper

adhesivepreservatives.AcuteandchronicdietaryexposureassessmentswereconductedusingFDAsCenterforFoodSafety&AppliedNutritions(CFSAN)screening-levelapproachas

presentedinPreparationofFoodContactNotificationsandFoodAdditivePetitionsforFoodContactSubstances:ChemistryRecommendationsdatedApril2002.Usingthemaximum

applicationratesandUSFDAsdefaultassumptions,worst-casedietaryconcentrationvalueswerecalculatedbytheAgency.


26/60

FDAsmethodutilizesanumberofgeneralassumptionsforcalculatingtheamountof

BITinfoodfromcontactingtreatedpapersurfaces. Theseassumptionsincludethefollowing:1)thefoodcontactcanresultfromaonetimeuseorarepeatuseofthepaper;2)theconsumption

factor(CForfractionoffoodthatcontactsthepackagingsurface)representsaratiooftheactual

weightoffoodthatcomesintocontactwiththepaperpackagingtothetotalweightofthefoodpackagedwiththepaper;3)theCFvariesbasedontypeofpackaging;and4)100%oftheantimicrobialpresentinthepackagingmigratesintothefoodcommodities.

5. Dietary(Food)RiskAssessment

a. AcuteandChronicDietaryRisk

Generally,adietaryriskestimatethatislessthan100%oftheacuteorchronicPADdoesnotexceedtheAgencysriskconcerns.SincethePADsforacuteandchronicexposuresareidentical,thedietaryriskestimatesarethesameforbothdurationsofexposureinthiscase. AsummaryofacuteandchronicriskestimatesareshowninTable3.

RiskestimatesarebelowtheAgencyslevelofconcern.Foradults,thecombinedacuteandchronicdietaryriskestimateis9.4%oftheacutePADandchronicPAD.Forchildren,themosthighlyexposedpopulationsubgroup,thecombinedacuteandchronicdietaryriskestimateis21.8%oftheacutePADandchronicPAD.Therefore,acuteandchronicdietaryriskestimatesarebelowtheAgencyslevelofconcernforallpopulationsubgroups.

Table3.SummaryofDietaryExposureandRiskfor1,2-Benzisothiazolin-3-one

Population

Subgroup

Adult

Child

Adult

Child

Adult

Child

AcuteandChronicDietaryEDI

(: g/person/day)Dietary

Exposurea

(mg/kg/day)

%aPADand

%cPADb

Slimicide

14.1 0.0002 1.2

7.05 0.00047 2.8

PaperAdhesivePreservative

21.0 0.0003 1.8

10.5 0.0007 4.1

PaperCoatingPreservative

75.0 0.0011 6.5

37.5 0.0025 14.7

11


27/60

Population

Subgroup

EDI

(: g/person/day)

AcuteandChronicDietary

Dietary

Exposurea

(mg/kg/day)

%aPADand

%cPADb

Combined

Adult 110.1 0.0016 9.4

Child 55.1 0.0037 21.8

a--Foradults,acuteandchronicexposureanalysisisbasedonabodyweightof70kg. Forchildren,exposureis

basedonabodyweightof15kg.b--%PAD=dietaryexposure(mg/kg/day)*100/aPADorcPAD,whereaPADandcPADforadultsandchildren=0.017mg/kg/day

b. DietaryExposureforInertIngredientUses

IncludedinthisREDisthereassessmentof1,2-benzisothiazolin-3-onewhenusedasaninertingredientinpesticideproducts.1,2-Benzisothiazolin-3-oneisusedasa

preservative/stabilizerinawidevarietyofresidentialuseandagriculturalpesticideproducts,includingoutdooryard,garden,andturfproducts,andagriculturalcropproducts.

InertDietaryExposureAssumptions

Adietaryexposureanalysisfortheinertingredientuseof1,2-benzisothiazolin-3-onewas

conductedusingthegenericscreeningmodelforestimatinginertingredientdietaryexposureasabasisforestimating1,2-benzisothiazolin-3-onedietaryexposure.Thegenericmodelsoutput

wasadjustedtoreflectthetoleranceexemptionlimitationgivenin40CFR180.920whichstatesthat1,2-benzisothiazolin-3-onecannotbeappliedatmorethan0.02lbsperacre. The

genericscreeningmodeldoesnotspecificallyincludeanapplicationrateinput,ratheritisbasedontolerancesforpesticideactiveingredientswithapplicationratesgenerallyrangingfrom1to5

lbai/acre.Therefore,tomoreaccuratelyestimateresiduesresultingfromthelowerapplicationratelimitationof0.02lbs/acreof1,2-benzisothiazolin-3-one,theresultsfromthegenericmodel

wereadjustedbyafactorof50(usingtheratioof1lb.peracre0.02lbsperacre)and250(usingtheratioof5lbs.peracre0.02lbs/acre)toreflectresiduelevelsresultingfromthe

specifiedmaximumapplicationrateof1,2-benzisothiazolin-3-one.

Thedietaryassessmentisunrefinedandextremelyconservativeinnaturebecausethe

screeningmodelassumesthattheinertingredientisusedonallcommodities,andthat100percentofcropsaretreatedwiththeinertingredient. Further,themodelassumesresidueswillbepresentforeveryconsumedcommodity(includingmeat,milk,poultryandeggs)thatis

includedintheDietaryExposureEvaluationModel(DEEM).Additionally,inthecaseof1,2-benzisothiazolin-3-one,thechoiceofanadjustmentfactorbasedonmaximumapplicationrateis

conservativeinnature,becausetheuseofanadjustmentfactorbasedonconcentrationinformulationresultsinexposureslessthanhalfofthelowestvaluesfortheU.S.populationandall

populationsubgroupsreportedinTables8and9.


28/60

InertDietaryRiskfromFood

Thetablesbelowprovideasummaryoftheresultsoftheacuteandchronicdietaryrisk

estimatesfor1,2-benzisothiazolin-3-one.Onlyonepopulationsubgrouphadanestimated

exposureover100%ofeitherPADsatthe95

th

percentileofexposure Children(1-2years)had112%oftheaPADbutthiswasonlyatthehighendofexposure. Consideringtheunrefinedandextremelyconservativenatureofthisscreeninglevelmodel(e.g.,inclusionofall

commodities;100%ofcommoditiesaretreated;adjustmentfactorforapplicationrate),theresultsforallpopulationsubgroupsareconsiderednottobeofconcern.

Itshouldbenotedthatwhiletheresultsfromthescreeninglevelmodeldonotraisea

dietaryconcern,themodelingresultswouldbeevenlowerifanalternateadjustmentfactorhadbeenused.AsdescribedintheExposureAssumptionssectionabove,1,2-benzisothiazolin-3-

onesmaximumapplicationrateof0.02lbs/acrewasadjustedby50and250inthegenericmodel.Insteadofadjustingforapplicationrate,themodelcouldhavebeenadjustedforthe

concentrationof1,2-benzisothiazolin-3-oneinthepesticideformulation,whichislimitedtoamaximumof0.1%under40CFR180.920(theproposedtoleranceexemptionforuseon

animalsunder180.930hasthesamelimitation).Adjustingthemodelfortheconcentrationintheformulationwouldmeanusingafactorof500.

Theadjustmentfactorusingformulationconcentrationis500,whichiscalculatedusing

1,2-benzisothiazolin-3-onesmaximumconcentration(0.1%)andavalueusedinthescreenlevelmodelof50%,whichrepresentsagroupofactiveingredientsthataretypicallyfoundin

agriculturalfooduseproductsatconcentrations>50%. Usingtheadjustmentfactorof500(50%0.1%)toaccountfortheeffectofthelimitationof0.1%of1,2-benzisothiazolin-3-onein

pesticideformulationsonresiduelevelswouldcertainlylowerthemodelresultsevenfurtherthatwhatarepresentedintheTables4and5,below.

Thisdietaryassessmentincludestheexistinguseof1,2-benzisothiazolin-3-oneasa

pesticideinertingredientusedongrowingcropsunder40CFRpart180.920.Inaddition,theAgencyhasreceivedapetitiontoestablishanexemptionfromtherequirementforatolerancefor

theuseof1,2-benzisothiazolin-3-oneasaninertingredientinpesticidesappliedtoanimalsunder40CFRpart180.930withthesamelimitationsascurrentlyexistunder180.920. Thisdietary

assessmentalsoincludesanimalsasacommodity.Therefore,theresultsofthisassessmentcoverallexistingandcurrentlyproposedinertingredientusesof1,2-benzisothiazolin-3-one.

Dietaryexposuresofconcernfromfoodarenotlikelyfromtheuseof1,2-benzisothiazolin-3-oneasinertingredientsinpesticideproducts.

13


29/60

Table4.EstimatedAcuteDietary(Food)RiskEstimatesforInertUsesofBIT

PopulationSubgroup95th Percentile of Exposure

BITEstimated

Exposure,mg/kg/day

%aPAD1/

U.S.Population(total) 0.0013 - 0.007 8% - 40%

Allinfants(


30/60

PopulationSubgroup BITEstimatedExposure,mg/kg/day

%cPAD2/

Adults(50+years) 0.00034 - 0.0017 2% - 10%

Females(13-49years) 0.00035 - 0.0017 2% - 10%

2/cPAD=0.017mg/kg/day

c. DietaryRiskfromDrinkingWater

Drinkingwaterexposuretopesticidescanoccurthroughgroundandsurfacewatercontamination.Inassessingdrinkingwaterrisks,EPAconsidersacute(oneday),chronic(longterm)and,ifapplicable,cancer(overall)exposure,anduseseithermodelingormonitoringdata,

ifavailable,toestimatethoserisks.Todeterminethemaximumcontributionfromwaterallowedinthediet,EPAfirstlooksathowmuchoftheoverallallowableriskiscontributedbyfoodandthencalculatesadrinkingwaterlevelofcomparison(DWLOC)todeterminewhethermodeledormonitoredexposureestimatesexceedtheallowablerisklevel.Estimateddrinkingwaterconcentrations(EDWCs)thatareabovethecorrespondingDWLOCexceedtheAgencyslevelofconcern.

Basedonenvironmentalfatedata,1,2-benzisothiazolin-3-onebindsmoderatelywithsoilandmaypotentiallymovewiththesoilduringrainfalleventsandreachsurfacewaters.Although,1,2-benzisothiazolin-3-onehasbeenshowntobehydrolyticallystablewithahalflifeof>30days,itbreaksdownfairlyquicklyinaerobicsoils.Outdoorusepatternsof1,2-benzisothiazolin-3-onewhichmayleadtocontactwithsoiland/orsurfacewaterinclude:1)the

applicationofagriculturalpesticidesthatcontain1,2-benzisothiazolin-3-oneasaninertingredient,and2)theapplicationofpaintsthatcontain1,2-benzisothiazolin-3-one.Considering1,2-benzisothiazolin-3-onesreadybiodegradationandthesmallamountof(0.02lbs.peracre)thatmaybeappliedtocropsviatheinertuseandthesmallamountlikelytocomeintocontactwithsoils/surfacewatersviathepaintuse,1,2-benzisothiazolin-3-oneisnotlikelytobepresentindrinkingwatersourcesatsubstantialconcentrations. Thereforeaquantitativedrinkingwaterassessmentwasnotconducted.

6. ResidentialRiskforActiveIngredientUses

Residentialexposureassessmentconsidersallpotentialpesticideexposure,otherthanexposureduetoresiduesinfoodanddrinkingwater. Exposuremayoccurduringandafterapplicationmethodsincludingpaintingviabrush/rollerandairlesssprayer;handlingBIT-containingcleaningproductsthroughlow-pressurespray,wiping,andmopping;andthewashingofclothing/textileswithBIT-containinglaundrydetergents. Eachrouteofexposure(oral,dermal,inhalation)isassessed,whereappropriate,andriskisexpressedasaMarginofExposure(MOE),whichistheratioofestimatedexposuretoanappropriateNoObservedEffectLevel(NOAEL)does. Basedontheapplicationmethods,BIThasbeenassessedfortheresidential

15


31/60

mixing/loading/applicator(orhandler)exposureandforchildrenspost-applicationexposurethatmayoccurfromclothing/textileandviafloor-cleaningproducts.

a. Toxicity

Thetoxicologicalendpointsandassociateduncertaintyfactorsusedforassessingthenon-dietaryrisksforBITarelistedinTable6.

AMOEgreaterthanorequalto100isconsideredadequatelyprotectiveforthe

residentialexposureassessmentforthedermal,incidentaloralandinhalationroutesofexposure.TheMOEof100includes10xforinterspeciesextrapolation,10xforintraspeciesvariation.

Table6.ToxicityEndpointsSelectedforAssessingOccupationalandResidentialRiskfor

BIT

Exposure DoseUsedinRisk TargetMOE,UF, Study andToxicologicalEffects

Scenario Assessment SpecialFQPASF,for

(mg/kg/day) RiskAssessment

IncidentalOral NOAEL=5 MOE=300(10x Co-Criticalstudies:

(shortandintermediate

mg/kg/day interspeciesextrapolation,10x

Subchronictoxicity,dog,NOAEL=5mg/kg/daybasedon

term intraspeciesvariation)FQPASF=1

increasedincidenceofemesisandclinicalchemistryalterationsat20

DBUF=3 mg/kg/day.

andSubchronictoxicity,rats,NOAEL

=8.42mg/kg/daybasedonmacroscopicandmicroscopic

lesionsinthenon-glandularandglandularregionsofthestomach.

Dermal NOAEL=5 MOE=100(10x Co-Criticalstudies:

Alltimeperiods(occupational

mg/kg/day interspeciesextrapolation,10x

Subchronictoxicity,dog,NOAEL=5mg/kg/daybasedon

andresidential) intraspeciesvariation) increasedincidenceofemesisandclinicalchemistryalterationsat20

mg/kg/day.

andSubchronictoxicity,rats,NOAEL


lesionsinthenon-glandularand

glandularregionsofthestomach.


32/60

Exposure DoseUsedinRisk TargetMOE,UF, Study andToxicologicalEffectsScenario Assessment SpecialFQPASF,for

(mg/kg/day) RiskAssessment

Inhalation NOAEL=5 MOE=100 Co-Criticalstudies:

Alltimeperiods(occupationalandresidential)

mg/kg/day (10xinter-speciesextrapolation,10xintraspeciesvariation)

Anadditional10x

route-to-route

Subchronictoxicity,dog,NOAEL=5mg/kg/daybasedonincreasedincidenceofemesisand

clinicalchemistryalterationsat20mg/kg/day.

andextrapolationisusedto

determineifaninhalationtoxicitystudy

iswarranted.

Subchronictoxicity,rats,NOAEL


lesionsinthenon-glandularandglandularregionsofthestomach.

Cancer Nocancerdataavailablefor1,2-benzisothiazolin-3-one

Notes:UF=uncertaintyfactor,FQPASF=FQPAsafetyfactor,NOAEL=noobservedadverseeffectlevel,

LOAEL=lowestobservedadverseeffectlevel,DBUF=databaseuncertaintyfactor,LOC=levelofconcern,

MOE=marginofexposure

b. ResidentialHandlerScenarios

i. ExposureScenarios,DataandAssumptions

1,2-Benzisothiazolin-3-onemaybeaddedtoresidential-useproductsusedtocontrolbacteriaandfungi,includingasapreservativeforpaint(e.g.,EPAReg.No.72674-15)and

householdcleaningproducts. TheresidentialhandlerscenariosevaluatedincludinghandlingBIT-containingpaintthroughbrush/rollerandairlesssprayapplicationmethodsandhandling

BIT-containingcleaningproductsthroughlow-pressurespray,wiping,andmoppingapplicationmethods.Wherethedatawereavailable,residentialassessmentassumedthatthehandlerswouldbewearingshort-pantsandshort-sleevedshirts

Therearenochemical-specificexposuredatatoassesspaintapplications.Therefore,

dermalandinhalationexposureswereassessedforbrushandairlesssprayerapplicationsusingsurrogatedata.Specifically, PHED Version 1.1 valuesfoundintheResidential Exposure SOPs

(U.S.EPA,1997a)wereused(shortpants,short-sleevedshirts).Allhomeownerpaintingscenariosarebelievedtobebestrepresentedbytheshort-termexposureduration.

ThefollowingtwoscenarioswereconsideredforresidentialhandlersofBIT-containing

cleaningproducts:

Useofcleanerasawipeonhardnon-poroussurfaces,and

Useofcleanerformoppinghardnon-poroussurfacessuchasfloors.

17


33/60


34/60

c. ResidentialPost-ApplicationExposure

i. ExposureScenarios,DataandAssumptions

Residentialpostapplicationexposuresresultwhenbystanders(adultsandchildren)come

incontactwithBITinareaswherepesticideend-useproductshaverecentlybeenapplied(e.g.,treatedhardsurfaces/floors),orwhenchildrenincidentallyingestthepesticideresiduesthrough

mouthingthetreatedendproducts/treatedarticles(i.e.,hand-to-mouthorobject-to-mouthcontact). Theresidentialpost-applicationscenariosconsideredinthisassessmentareexposureto

residuesfromhardsurfaces(i.e.,floors)thathavebeenmoppedwithaproductcontaining1,2-benzisothiazolin-3-oneandtheuseoflaundrydetergentscontaining1,2-benzisothiazolin-3-one

whereresiduescouldremainonclothingarticlesafterlaundering.

Thereisthepotentialfordermalexposuretotoddlerscrawlingonthefloor.Inadditiontodermalexposure,infantscrawlingontreatedfloorswillalsobeexposedto1,2-benzisothiazolin-

3-oneviaincidentaloralexposure. Tocalculateincidentalingestionexposureto1,2-

benzisothiazolin-3-oneduetohand-to-mouthtransfer,thescenariosestablishedinEPAsStandard Operating Procedures (SOPs) for Residential Exposure Assessments wereused.

BITlabelsalsoincludeamicrobiocideuseinlaundrydetergents,fabricsofteners,andstainremovers(EPAReg.No.67071-23). Todeterminedermalandincidentaloralexposureto

treatedclothing,theguidanceprovidedintheHumanandEnvironmentalRiskAssessment(HERA)GuidanceDocument(2003)wasusedforindirectskincontactfromwearingclothesand

oralexposurefrommouthingorsuckingontreatedfabric.

ii. ResidentialPost-ApplicationRiskEstimates

Basedontoxicologicalcriteriaandpotentialforexposure,theAgencyhasconducteddermalandincidentaloralexposureassessments.AMOEgreaterthanorequalto100is

consideredadequatelyprotectivefortheresidentialexposureassessmentforthedermal,incidentaloralandinhalationroutesofexposure. TheMOEof100includes10xforinterspecies

extrapolationand10xforintraspeciesvariation.

AsummaryoftheresidentialhandlerexposuresandriskarepresentedonTable8. TherisksfromdermalandincidentaloralexposuresforallscenariosarebelowtheAgencyslevelof

concern.

19


35/60

Table8.SummaryofShort-andIntermediate-TermResidentialPostapplicationExposuresandRisksforBIT

ScenarioDose

(mg/kg/day)MOE

(TargetMOE>100for

dermal;>300fororal)

DermalExposureTreatedFloors Residential

Setting(Children)

0.00055 9,200

Treatedclothing Adults0.00045 11,000

Children0.00070

7,200

IncidentalOralExposure

TreatedFloors ResidentialSetting

(Children)

0.00016(ST)7.7E-5(lT)

31,000(ST)65,000(IT)

Treatedclothing Children0.003

1,700

7. ResidentialRiskforInertIngredientUses

1,2-Benzisothiazolin-3-oneisaninertingredientinover900differentproductsandis

usedprimarilyasamaterialspreservative.Thetypesofproductsthatcontain1,2-benzisothiazolin-3-oneasaninertingredientincludeturfinsecticides,fungicidesandherbicides;

gardenandornamentalinsecticides;fleaandtickcontrolproductsforpets;indoorcrackand

creviceinsecticides;paints;andhouseholdcleaners.Since1,2-benzisothiazolin-3-oneisalsousedasanactiveingredientinpaintsandhouseholdcleanersatahigherpercentformulationthantheinert,theinertexposureassessmentdidnotincludeananalysisofthepaintandcleaning

products.TheresidentialexposureassessmentaddressestheseexposuresandshowsthattheMOEsareabovetheAgencyslevelofconcern.Furthermore,theinertassessmentdidnot

specificallyevaluateindoorcrackandcreviceusessinceitwasanticipatedtheapplicatorexposuresresultingfromtheoutdoorlawnproducts(where1,2-benzisothiazolin-3-oneisaninert

ingredient)wouldresultinhigherexposuresbasedontheamountusedperday.Additionally,itwasanticipatedthepost-applicationexposuresresultingfromtheuseofindoorresidential

cleaners(where1,2-benzisothiazolin-3-oneisanactiveingredient)wouldresultinhigherexposureswhenconsideringthefactthatexposuretoresiduesfromafloorcleaneraremuch

moreaccessiblethanresiduesappliedincracks/crevicesandalongbaseboards.Aninertexposureassessmentwasconductedforseveralrepresentativeresidentialproductssuchas

variousformulationsofturfandgardenproductsaswellas,fleaandtickpetsprayproducts.

AlloftheinputparametersusedinthisassessmentaredefaultsprovidedintheAgencysResidentialSOPs(USEPA,1997and2001). Thepercentformulationof0.1%usedinthis

assessmentwasbasedonthetoleranceexemptionlimitationasspecifiedin40CFR180.920andareviewofseveralConfidentialStatementsofFormula(CSFs)forthevarioustypesofproducts.


36/60

Tables9-11providetheinputparametersandresultingexposuresandMOEsfortheinertuses.

Table9.ApplicatorShort-termExposuresandMOEsfor1,2-Benzisothiazolin-3-oneusedasan

InertIngredientinAerosolPetFleaandTickProducts

Exposure=UExARxN/BW

UnitExposure(mg/lbai) UE Dermal Inhalation220 2.4ApplicationRate(lbai/can) AR 0.0004 0.0004

Numberofcans/day N 0.5 0.5

PercentAbsorption 41% 100%

Bodyweight(kg) BW 70 70

DailyDose(mg/kg/day) 2.52E-04 6.70E-06

OralNOAEL(mg/kg/day) 5 5

TargetMOE 100 100

MOE 20,000 750,000

TotalMOE 19,000

Table10. ToddlerShort-termPost-applicationDermalExposureandMOEfor1,2-

Benzisothiazolin-3-oneusedasanInertIngredientinAerosolPetFleaandTickProducts

Exposure=ARxTxSAxDA/BW

ApplicationRate(mg/cm2ofanimal) AR 0.015

TransferableFraction T 20%

Surfaceareaofachildhug(cm2) SA 1,875

DermalAbsorption DA 41%

Bodyweight(kg) BW 15

DailyDose(mg/kg/day) 0.15

OralNOAEL(mg/kg/day) 5

TargetMOE 100

MOE 33

Table11. ToddlerShort-termPost-applicationIncidentalOralExposureandMOEfor1,2-

Benzisothiazolin-3-oneusedasanInertIngredientinAerosolFleaandTickPetProducts

Exposure=ARxTxSAxSExFQ/BWApplicationRate(mg/cm

2ofanimal) AR 0.015

TransferableFraction T 20%

Surfaceareaofachildshand(cm2) SA 20

SalivaExtraction SE 50%

Frequency(events/day) FQ 1

Bodyweight(kg) BW 15

21


37/60

DailyDose(mg/kg/day) 0.0020

OralNOAEL(mg/kg/day) 5

TargetMOE 300

MOE 2,500

BecausethedermalandoraltoxicologicaleffectsarethesamebutthetargetMOEs

differ,ittypicallywouldbenecessarytoestimateanARIforthetotaltoddlerexposuretothepetproductresidues.However,sincethedermalMOEislessthanthetargetMOEof100,itwasnot

necessarytoestimateanARIbecauseitwouldresultinavaluelessthan1. Therefore,thedermalriskandresultingtotalrisk(ARI)fortoddlersexposedto1,2-benzisothiazolin-3-one

residuesinpetproductsareofconcern.Itshouldbenotedthattheseexposuresarebasedonveryconservativemodelsanddefaultinputparameters.Thetransferablefractionparameterisa

valuethatcouldbefurtherrefinedwithchemicalspecificdata. Howeveratthistime,thepercenttransferfactorfrompetfurtoskinisconsideredadatagapandisnecessarytoappropriately

refinethisdermalexposure.

Theresultsfromtheexposureandriskassessmentfor1,2-benzisothiazolin-3-oneusedasaninertingredientinotherresidentialproducts(i.e.,turf,garden,indoorcrackandcrevice,paint,

andcleaningproducts)showthatalloftheindividualMOEs,totalMOEsandARIsareabovetheAgencyslevelofconcern.

8. AggregateRisk

TheFoodQualityProtectionActamendmentstotheFederalFood,Drug,andCosmetic

Act(FFDCA,Section408(b)(2)(A)(ii))requirethatthereisareasonablecertaintythatnoharmwillresultfromaggregateexposuretopesticidechemicalresidue,includingallanticipated

dietaryexposuresandotherexposuresforwhichtherearereliableinformation.Aggregateexposurewilltypicallyincludeexposuresfromfood,drinkingwater,residentialusesofa

pesticide,andothernon-occupationalsourcesofexposure.

a. AcuteandChronicAggregateRisks

Theacuteandchronicaggregateriskassessmentsgenerallyincludeonlydietaryanddrinkingwaterexposures.Drinkingwaterexposureisnotexpectedfromanyoftheindoororoutdoorusesof1,2-benzisothiazolin-3-oneusedaseitheraninertoractiveingredient. Table12presentsasummaryoftheseexposures,aswellastheaggregaterisks.Theacuteandchronicaggregateriskestimatesassociatedwith1,2-benzisothiazolin-3-onearebelowtheAgencyslevel

ofconcern.ItshouldbenotedthattheacuteandchronicdietaryexposuresfromtheinertuseswereselectedfromthelowrangevaluesaspresentedinTables14and15.Itisreasonabletousethelowrangevaluesintheaggregateassessmentgivennumberofconservativeassumptionsthatwerethebasisfortheinertdietaryassessment.


38/60


39/60

benzisothiazolin-3-one,homeownerpaintingactivitiesoccuronlyonceortwiceayear,whiletheuseofturf/gardenandpetproductsoccursonanintermittentbasis.Thereforetheprobabilityof

co-occurrenceandthepotentialforexposuretoresiduesfromtheseproductsonthesamedayishighlyunlikely.However,itislikelythatsomeonecouldcleanthekitchen(moppingandwiping

activities)aswellas,wearclothingtreatedwith1,2-benzisothiazolin-3-oneduringthesameday.

Table13summarizesthescenariosincludedintheshort-andintermediate-termaggregateassessments.

Table13.ExposureScenariosIncludedintheAggregateAssessments

Short-termAggregate Intermediate-TermAggregate

Adults chronicdietary-inert

chronicdietary-active

handlingcleaningproducts

wiping

chronicdietary-inert

chronicdietary-active

treatedclothing

handlingcleaningproducts

mopping

treatedclothing

Children chronicdietary-inert chronicdietary-inert

chronicdietary-active chronicdietary-active

post-apptocleaningproduct

mopping

treatedclothing

post-apptocleaningproduct- mopping

treatedclothing

Thechronicdietaryexposureswereusedinboththeshort-andintermediate-termaggregateassessmentbecausechronicdietaryexposuresoccurnearlyeveryday(asopposedto

acutedietaryexposuresoccurringonaone-timebasis). Therefore,short- orintermediate-term

non-dietaryexposureshaveamuchhigherprobabilitytoconcurwiththechronicdietaryintakeratherthantheacutedietaryintake.

Cleaningactivitiesinaresidentialsettingoccuronashort-termbasis.However,theBIT-containingcleaningproductsarealsolabeledforuseininstitutionalsettingssuchasdaycare

facilitieswherecleaningactivitiescanoccuronanintermediate-termbasis.Therefore,childrencouldhaveexposuretocleaningproductresiduesonamorecontinuousbasisinadaycare

facilitythus,thesepost-applicationscenarioswereincludedintheintermediate-termaggregateassessment.

Sincethetoxicityendpointsforalloftheroutesofexposure(oral,dermalandinhalation)arebasedonthesamestudyandsametoxiceffect,allroutesareaggregatedtogether.However,theaggregateriskindex(ARI)methodoutlinedinOPPguidanceforaggregateriskassessment(September1,2000,StandardOperatingProcedure(SOP)forIncorporatingScreeningLevelEstimatesofDrinkingWaterExposureintoAggregateRiskAssessments)wasutilizedintheassessment. Thismethodwasusedbecausetheoral,dermalandinhalationendpointshavedifferentuncertaintyfactorsthatneedtobeapplied. Ariskindex

$

1indicatesariskofnoconcern.Theshort-termARIsforadultsandchildrenwere6.8and1.9,respectively,whiletheintermediate-termARIsforadultsandchildrenwere7.5and1.9,respectively.Thereforeshort-termandintermediate-termaggregaterisksarebelowtheAgencyslevelofconcern.


40/60

Tables 14 and 15 present the resulting ARIs for the short- and intermediate term aggregate assessments, r

Table 14. Short-term Aggregate Risks

Wipe

NA NA NA NA

NA NA NA NA NA

NA NA NA NA

NA

930 NA NA

NA NA NA NA NA NA NA NA NA NA NA NA

Dietary Clothing Hard Surface Cleaning

Exposure Routes Active Inert Total Post-App Applicator Post-App

Mop

Adults

Oral Ingestion MOEs 3,100 10,000 2,400

Inhalation MOEs 160,000 590,00 1

Dermal MOEs 11,000 9,100 50,000

Total MOE 8,600 46,000

Toddlers

Oral Ingestion MOEs 1,400 2,900 1,700 31,000

Inhalation MOEsDermal MOEs 7,100 9,100

ARI 5.2 48.5

25


41/60

leaning

Es

Table15.Intermediate-termAggregateRisks

Dietary Clothing HardSurface

ExposureRoutes Active Inert Total Post-App Post-App ARI

Mop

AdultsOralIngestion 3,100 10,000 2,400 NA NA

InhalationMOEs NA NA NA NA NA

DermalMOEs NA NA NA 11,000 NA

7.5

Toddlers

OralIngestion 1,400 2,900 930 1,700 31,000

InhalationMOEs NA NA NA NA NA

DermalMOEs NA NA NA 7,100 9,100

ARI 5.2 48.5 1.9

9. OccupationalRisk

Workerscanbeexposedtoapesticidethroughmixing,loading,and/orapplyingapesticide,orre-enteringtreatedsites.OccupationalhandlersofBITincludeformulatedproducthandlers,materialpreservativehandlers,andmetalworkingfluidshandlers.OccupationalriskforallofthesepotentiallyexposedpopulationsismeasuredbyaMarginofExposure(MOE)whichdetermineshowclosetheoccupationalexposurecomestoaNoObservedAdverseEffectLevel(NOAEL)fromtoxicologicalstudies.InthecaseofBIT,MOEsgreaterthan100arenotofconcerntotheAgency.ThisMOEincludesthestandardsafetyfactorsof10Xforintraspecies

variability(i.e.,differencesamonghumans)and10Xforinterspeciesvariability(differencesbetweenhumansandanimals).

Occupationalriskisassessedforexposureatthetimeofapplication(termedhandlerexposure)andisassessedforexposurefollowingapplication,orpost-applicationexposure.Applicationparametersaregenerallydefinedbythephysicalnatureoftheformulation(e.g.,formulaandpackaging),bytheequipmentrequiredtodeliverthechemicaltotheusesite,andbytheapplicationraterequiredtoachieveanefficaciousdose.

FormoreinformationontheassumptionsandcalculationsofpotentialriskofBITtoworkers,seetheOccupationalExposureAssessmentsectionintheHumanHealthRiskAssessment(Revised),datedJuly11,2005.

a. OccupationalToxicity

PleaseseeTable4asitprovidesalistingofthetoxicologicalendpointsusedintheoccupationalriskassessmentforBIT.


42/60

b. OccupationalHandlerExposure

FormulatedProductHandlers:

EPAhasassessedtheexposuretohandlersmixing/loading/applyingproductscontaining

theactiveingredient. Thefollowinghandlerexposurescenarioswhichinvolvehandlingtheformulatedproductwereassessedfor1,2-benzisothiazolin-3-onetorepresentthehighendofindustrialusesoftheformulatedproduct.

Pouring the BIT-containing liquid biocide preservative into industrial process

intermediatematerials(dispersions,slurries,emulsions,solutions,etc.)

Pouring theBIT-containingliquidbiocidepreservative intoindustrialprocesswaterfor

leatherandphotoprocessingsystems PouringtheBIT-containingliquidbiocidepreservativeintometalworkingfluid

PouringtheBIT-containingliquidbiocidepreservativeduringoilfieldactivities

Therearenochemical-specificexposuredatatoassessprimaryhandlerapplications.Therefore,dermalandinhalationexposureswereassessedusingCMAsurrogateexposuredata.

Specifically,theliquidpourforpreservativedatafromCMAwereusedassurrogatedataforthescenariosinvolvingthepouringofliquidpreservativesintoindustrialprocessintermediate

materials,leatherandphotoprocessingsystems,andoilfields;theliquidpourformetalworkingfluiddatafromCMAwereusedassurrogatedatafortheliquidpouringofpreservativesinto

metalworkingfluid;theliquidpumpforpreservativedatafromCMAwereusedassurrogatedatafortheliquidpumpingofpreservativesintooilfields.Inaddition,productlabelmaximum

applicationrates,relateduseinformation,andAgencystandardvalueswereusedtoassessexposures.

MaterialPreservativeHandlers:

EPAhasassessedtheexposuretohandlersmixing/loading/applyingproductscontaining

theactiveingredientasamaterialpreservative,nottheformulatedproduct(previouslydefinedassecondaryhandlers).Thisincludesthoseindividualsexposedtotheactiveingredientasa

directresultofitsincorporationintoanenduseproduct(e.g.,individualsusingcaulkorpaintthatinitselfisnotaregisteredproduct). Thescenariosassessedhavebeenselectedtorepresent

thehighendofexposuretothesetypesofproductssuchasapplicationofstains,water-basedadhesives,caulks,sealants,grouts,spackling,ready-mixedcements,andready-mixedwallboard

compounds.Basedonend-useproductapplicationmethods,itisassumedthatexposureswhileapplyingpaintswillbeequaltoorgreaterthanexposureswhileapplyingbuildingmaterials.

(Note:metalworkingfluidsformachinistsareassessedseparatelybelow.)Thefollowingmaterialuseswereassessedtorepresentthehighendofexposureto1,2-benzisothiazolin-3-one:

Handling BIT-containing paint through brush/roller and airless sprayer application

methods.

Handling BIT-containing cleaning products through wiping and mopping application

methods.

27


43/60

Thesehandlerexposurescenarioswereassessedusingsurrogateunitexposuredatafrom

PHED Version 1.1forthepaintingscenariosandusingsurrogateunitexposurefromCMAforthecleaningproductscenarios.Forthepaintingscenarios,itwasassumedthatcommercial

paintersapply5gallons(50lbs)ofpaintthroughbrush/rollerapplicationmethodsand50gallons

(500lbs)ofpaintthroughairlesssprayerapplicationmethods. Forthecleaningproductscenarios,itwasassumedthatoccupationalhandlers(i.e.,janitors)use1literforwipingand2gallonsformopping.

MetalWorkingFluidsHandlers:

Thepotentialinhalationanddermalexposuremayexistwhenusingtreatedmetal

workingfluid.Ascreening-levellong-terminhalationexposureestimatefortreatedmetalworkingfluidshasbeendevelopedusingtheOSHAPELforoilmist. TheAgencyconducted

thescreeninglevelassessmentformetalworkingfluidsusingtheUSEPA/OPPTSChemicalEngineeringBranch(CEB)model(U.S.EPA,1991). TheCEBmodelusesmeasuredand/or

assumedairborneoilmistconcentrationsformetalworkingoperations.Sincenomeasuredconcentrationsareavailablefor1,2-benzisothiazolin-3-one,thehigh-endoilmistconcentrationis

basedontheOSHAsPermissibleExposureLimit(PEL)of5mg/m3

(NIOSH,1998). EPAReg.No.72674-15indicatesthat0.25%(i.e.,0.0025)ofthelabelproductisaddedtometalworking

fluidsandofthat,only19.3%istheactiveingredient(1,2-benzisothiazolin-3-one).Therefore,theupperboundairconcentrationof1,2-benzisothiazolin-3-onethataworkerisexposedtois5

3mg/m

3x0.0025x0.09oranairconcentrationof0.0011mg/m . Additionally,thefollowing

assumptionsweremadeintheassessment:theinhalationrateforadultsis1.25m3/hr;the

exposuredurationis8hours;andbodyweightis70kg.

Ascreening-levellong-termdermalexposureestimatewasderivedfromthe2-HandDermalImmersioninLiquidModelinChemSTEER(EPA/OPPT). Theweightfractionof1,2-

benzisothiazolin-3-oneinmetalworkingfluidsis0.00048(0.0025formulatedproductaddedtooilx0.193aiinformulatedproduct=0.00048),calculatedfromEPAReg.No.72674-15. Based

onthemodelforemersionofhandsinmetalworkingfluids,thelong-termabsorbeddermaldoseisestimatedat0.025mg/kg/day.

c. OccupationalHandlerRiskSummary

TheresultsoftheMOEanalysisarepresentedinTable16.Thecalculatedshort-and

intermediate-termdermalMOEsaregreaterthanthetargetMOEs,andtherefore,arenotofconcernwiththeexceptionofthedermalMOEforcommercialpaintingwithanairlesssprayer

whichis90.However,itisbelievedthatthepaintmatrixhasthepotentialtoreducethedermalexposure.Moreover,thedermalabsorptionfactorof41percentwasnotadjustedtoaccountfor

thepotentialreductionofthebioavailabilityofBITinpaintbecauseofalackofchemical-specificdata. Therefore,thedermalMOEof90fortheairlesssprayermaybeanoverestimateof

risk.Inaddition,thetotalMOEs(inhalation+dermal)havebeenpresented. ThetotalMOEsareallgreaterthan100,indicatingnorisksofconcern,exceptforthecommercialpaintingwithan

airlesssprayerwherethetotalMOE=85. Asmentionedabove,theAgencybelievesthatactual


44/60


45/60

likelytobeminimalwhencomparedtohandlerexposurebecauseofdilutionduringprocessingorwhencomparedtomachinistsusingthemetalworkingfluid.Nopostapplicationexposure

datahavebeensubmittedtotheagencytodeterminetheextentofpostapplicationexposuresintheindustrialsettings.Inhalationexposuresareexpectedtobeminimalbecauseaerosol

generationisnotexpectedandthevaporpressureof1,2-benzisothiazolin-3-oneislow.

B. EnvironmentalRiskAssessment

AsummaryoftheAgencysenvironmentalriskassessmentispresentedbelow.ThefollowingriskcharacterizationisintendedtodescribethemagnitudeoftheestimatedenvironmentalrisksforBITusesitesandanyassociateduncertainties.

Fordetaileddiscussionsofallaspectsoftheenvironmentalriskassessment,seethedocumentEnvironmentalRiskAssessmentandCharacterization-1,2-Benzisothiazolin-3-one(BIT),datedJuly7,2005.

1. EnvironmentalFateandTransport

Theenvironmentalfateassessmentfor1,2-benzisothiazolin-3-onewasbasedonlimited

information;datawereonlyavailableforhydrolysis,aerobicsoilmetabolism,andadsorption/desorption.Thesedataindicatethat1,2-benzisothiazolin-3-oneishydrolytically

stable(half-life>30days),butbreaksdownfairlyquicklyinaerobicsoils(half-life


46/60

--- ---

---

--- ---

Table17.AcuteOralToxicityof1,2-Benzisothiazolin-3-one

Species LD50/LC50

(mg/kg)

NOAEL/NOAEC ToxicityCategory

Bird

Bobwhitequail(Colinus virginianus)

453 NA Moderatelytoxic

Mammal

Rat 650-males784-females

Table18.AcuteEcotoxicityof1,2-Benzisothiazolin-3-one

Species LD50/LC50(mg/kg)

NOAEL/NOAEC ToxicityCategory

FreshwaterFish

RainbowTrout

(Oncorhynchus mykiss)

1.3 0.74 Moderatelytoxic

RainbowTrout 1.6 Moderatelytoxic(Oncorhynchus mykiss)

FreshwaterInvertebrate

Waterflea

(Daphnia magna)


Waterflea(Daphnia magna)


Estuarine/MarineFish

Sheepsheadminnow

(Cyprinodon variegatus)

12.2 3.3 Slightlytoxic

Estuarine/MarineInvertebrates

Mysidshrimp(Mysidopsis bahia)

0.99 0.25 Highlytoxic

Pacificoyster(Crassostrea gigas)

0.047 0.024 Veryhighlytoxic

AquaticAlgae

Greenalgae,speciesnot 0.15(72-hourindicated EC50)

31


47/60

--- ---

--- --- ---

---

Table19.OtherToxicityStudiesof1,2-Benzisothiazolin-3-one

Species LD50/LC50 NOAEL/ LOAEL/ ToxicityCategory(mg/kg) NOAEC LOAEL

SubacuteDietaryToxicityof1,2-Benzisothiazolin-3-onetoBirds

Bobwhitequail >5620 Practicallynon-toxic(Colinus virginianus)

AcuteDermalToxicityof1,2-Benzisothiazolin-3-onetoRats

Rats >2000

DevelopmentalToxicityof1,2-Benzisothiazolin-3-onetoRats

Rats --- 40 100

TheindoorusesofBITconsideredinthisREDmakeitunlikelythatanyappreciable

exposuretoterrestrialoraquaticorganismswouldoccur.FacilitiesusingBITforindoorindustrialapplicationsarerequiredtohaveNPDESpermitsbeforedischargingeffluentsintoreceivingwaters.Thepotentialexposuretoterrestrialandaquaticspeciesfromtheoilrecovery

usesofBITcannotbeestimatedatthistime,asthereiscurrentlynovalidatedmodelavailableforsuchapurpose.

1,2-Benzisothiazolin-3-oneisusedasaninertingredientinpesticideproductsbuttheallowableamountthatcanbeappliedissmall(notmorethan0.1%formulationand0.02lbs.peracre). Dataindicatethat1,2-benzisothiazolin-3-onebreaksdownquicklyinaerobicsoils(halflife


48/60

TofacilitatecompliancewiththerequirementsoftheEndangeredSpeciesActsubsection(a)(2)theEnvironmentalProtectionAgency,OfficeofPesticideProgramshasestablished

procedurestoevaluatewhetheraproposedregistrationactionmaydirectlyorindirectlyreduceappreciablythelikelihoodofboththesurvivalandrecoveryofalistedspeciesinthewildby

reducingthereproduction,numbers,ordistributionofanylistedspecies(U.S.EPA2004). After

theAgency=

sscreening-levelriskassessmentisperformed,ifanyoftheAgency=

sListedSpeciesLOCCriteriaareexceededforeitherdirectorindirecteffects,adeterminationismadetoidentify

ifanylistedorcandidatespeciesmayco-occurintheareaoftheproposedpesticideuse.Ifdeterminedthatlistedorcandidatespeciesmaybepresentintheproposeduseareas,further

biologicalassessmentisundertaken.Theextenttowhichlistedspeciesmaybeatriskthendeterminestheneedforthedevelopmentofamorecomprehensiveconsultationpackageas

requiredbytheEndangeredSpeciesAct.

Forcertainusecategories,theAgencyassumestherewillbeminimalenvironmentalexposure,andonlyaminimaltoxicitydatasetisrequired(OverviewoftheEcologicalRisk

AssessmentProcessintheOfficeofPesticideProgramsU.S.EnvironmentalProtectionAgency

EndangeredandThreatenedSpeciesEffectsDeterminations,1/23/04,AppendixA,SectionIIB,pg.81).Chemicalsinthesecategoriesthereforedonotundergoafullscreening-levelriskassessment,andareconsideredtofallundera

A

noeffect@

determination.Theactiveingredient

usesof1,2-benzisothiazolin-3-onefallintothiscategory.

Theinertusesof1,2-benzisothiazolin-3-onearealsoconsideredtofallunderanoeffect

determination,forthefollowingreasons:

Theallowableamountthatcanbeappliedissmall(notmorethan0.1%formulationand0.02lbs.peracre).

Dataindicatethat1,2-benzisothiazolin-3-onebreaksdownquicklyinaerobicsoils(halflife


49/60


50/60

C. RegulatoryPosition

1. FoodQualityProtectionActFindings

a. RiskCupDetermination

AspartoftheFQPAtolerancereassessmentprocess,EPAassessedtherisksassociatedwithBIT. TheAgencyhasconcludedthatthetoleranceexemptionfortheuseofBITasaninertingredientmeetstheFQPAsafetystandardsandthattheriskfromdietary(foodsourcesonly)exposureiswithintheriskcup.Anaggregateassessmentwasconductedforexposuresthroughfoodandresidentialexposure. TheAgencyhasdeterminedthatthehumanhealthrisksfromthesecombinedexposuresarewithinacceptablelevels.Inreachingthisdetermination,EPAhasconsideredtheavailableinformationonthespecialsensitivityofinfantsandchildren,aswellasaggregateexposurefromfoodandwater.

b. DeterminationofSafetytoU.S. Population

AspartoftheFQPAtolerancereassessmentprocess,EPAassessedtherisksassociatedwithBIT. TheAgencyhasdeterminedthattheestablishedtoleranceexemptionforBITmeetsthesafetystandardsundertheFQPAamendmentstosection408(b)(2)(D)oftheFFDCA,andthatthereisareasonablecertaintynoharmwillresulttothegeneralpopulationoranysubgroupfromtheuseofBIT. Inreachingthisconclusion,theAgencyhasconsideredallavailableinformationonthetoxicity,usepracticesandexposurescenarios,andtheenvironmentalbehaviorofBIT.

Theacuteandchronicaggregateriskassessmentsgenerallyincludeonlydietaryanddrinkingwaterexposures.Sincedrinkingwaterexposureisnotexpectedfromanyoftheindoororoutdoorusesof1,2-benzisothiazolin-3-oneusedaseitheraninertoractiveingredient,theacuteandchronicaggregateassessmentsonlyincludeddietaryexposuresfromtheactiveindirect

fooduses(i.e.,useinfood-contactpackaging)andinertdietaryexposuresfromagriculturalpesticideuses.Theacuteandchronicaggregateriskestimatesassociatedwith1,2-benzisothiazolin-3-onearewellbelowtheAgencyslevelofconcern.

Theshort-andintermediate-termaggregateassessmentswereconductedforadultsandchildren.Sincethetoxicityendpointsforalloftheroutesofexposure(oral,dermalandinhalation)arebasedonthesamestudyandsametoxiceffect,allroutesareaggregatedtogether.Theaggregateriskindex(ARI)methodwasutilizedintheassessment. Short-andintermediate-termaggregatecalculatedrisksarebelowtheAgencyslevelofconcern.

c. DeterminationofSafetytoInfantsandChildren

EPAhasdeterminedthattheestablishedtoleranceexemptionfor1,2-benzisothiazolin-3-one,withamendmentsandchangesasspecifiedinthisdocument,meetthesafetystandardsundertheFQPAamendmentstosection408(b)(2)(C)oftheFFDCA,thatthereisareasonablecertaintyofnoharmforinfantsandchildren.Thesafetydeterminationforinfantsandchildrenconsidersfactorsofthetoxicity,usepractices,andenvironmentalbehaviornotedaboveforthegeneralpopulation,butalsotakesintoaccountthepossibilityofincreaseddietaryexposuredue

35


51/60


52/60

Whentheappropriatescreeningand/ortestingprotocolsbeingconsideredundertheAgencysEDSPhavebeendeveloped,1,2-benzisothiazolin-3-onemaybesubjectedtoadditionalscreeningand/ortestingtobettercharacterizeeffectsrelatedtoendocrinedisruption.

2. ToleranceSummary

NopesticidetoleranceshavebeenestablishedforBIT. BITcurrentlyhasoneinert

ingredientexemptionfromtherequirementofatoleranceforresiduesasrequiredundertheFoodQualityProtectionAct(FQPA)section408.Theexistingexemptionisforuseongrowingcrops

under40CFRpart180.920andisconsideredreassessed.Inaddition,theAgencyhasreceivedapetitiontoestablishanexemptionfromtherequirementforatolerancefortheuseof1,2-

benzisothiazolin-3-oneasaninertingredientinpesticidesappliedtoanimalsunder40CFRpart180.930.Theriskassessmentsinthisdocumenttookintoconsiderationanimalsasacommodity.

Therefore,theresultsofthisassessmentcoverall