# L-Glutamic

Acid (LGA)

and Gamma-Amino

butyric

Acid (GABA) (PC Codes:

374350

and 030803) 

# Preliminary

Work

Plan

and Summary

Document Registration

Review:

Initial Docket September

2014 Case.

6025 Approved



# by: Robert McNally,

Director Biopesticides

and Pollution Prevention

Division Date:L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govTABLEOFCONTENTSI.PRELIMINARYWORKPLAN......................................................................................................4A.Overview....................................................................................................................................4B.StatutoryandRegulatoryAuthority.......................................................................................4C.BackgroundandRegulatoryInformation..............................................................................5D.AnticipatedDataNeedsandRiskAssessments......................................................................8E.RisktoThreatenedandEndangeredSpecies.......................................................................10F.EndocrineEffects....................................................................................................................10G.H.I.J.Incidents....................................................................................................................................11Timeline...................................................................................................................................12GuidanceforCommenters.....................................................................................................12NextSteps................................................................................................................................14II.BIBLIOGRAPHY..;........................................................................................................................14A.StudiesSupportingRegistrationReviewofL-GlutamicAcidandGamma-AminobutyricAcid.........................................................................................................................................15B.U.S.EnvironmentalProtectionAgencyRiskAssessmentMemoranda.............................212L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govACRONYMSANDABBREVIATIONSBPPDTheEPA'sBiopesticidesandPollutionPreventionDivisionCFRCodeofFederalRegulationsDCIDataCall-InEDSPEndocrineDisruptorScreeningProgramEPAU.S.EnvironmentalProtectionAgencyFFDCAFederalFood,Drug,andCosmeticActFIFRAFederalInsecticide,Fungicide,andRodenticideActFQPAFoodQualityProtectionActFRFederalRegisterFWPFinalWorkPlanIDSIncidentDataSystemMRIDNo.MasterRecordIdentificationNumber:TheEPA'ssystemofrecordingandtrackingstudiessubmittedtotheOfficeofPesticideProgramsMRLMaximumResidueLimitOPPTheEPA'sOfficeofPesticideProgramsPCCodePesticidechemicalcode:asix-digitnumberassignedbyOPPtoidentifypesticidechemicalsPWPPreliminaryWorkPlanTGAITechnicalgradeoftheactiveingredientTMDLTotalMaximumDailyLoadusUnitedStates3L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)I.PRELIMINARYWORKPLANA.OverviewEPA-HQ-OPP-2014-0I09www.regulations.govThedocket(EPA-HQ-OPP-2014-0109)forL-glutamicacid(LGA)andgamma-aminobutyricacid(GABA)isnowopen,initiatingthefirstpubliccommentperiodforRegistrationReviewCase6025.Currently,thereisoneregisteredproductcontainingLGAandGABAasactiveingredients(AuxigroWPPlantMetabolicPrimer,EPARegistrationNumber70810-1),aplantgrowthregulator(PGR)intendedforusetoenhancedevelopmentandgrowthinnumerousplantspeciesandinduceplantresistancetocertainplantpathogens.ThisPreliminaryWorkPlan(PWP)explainswhattheU.S.EnvironmentalProtectionAgency's(EPA)OfficeofPesticidePrograms(OPP)knowsaboutLGAandGABA,highlightsanticipateddataandassessmentneeds,identifiestypesofinformationthatwouldbeespeciallyusefultotheAgencyinconductingthereview,andprovidesananticipatedtimelineforcompletionoftheregistrationreviewprocess.Theregistrationreviewprocesswasdesignedtoincludeapublicparticipationcomponenttosolicitinputfrominterestedstakeholders.Bysharingthisinformationinthedocket,theEPAintendstoinformthepublicofwhatitknowsaboutLGAandGABA,andwhattypesofnewdataorotherinformationthatwouldbehelpfultoreceiveasitmovestowardadecisionaboutLGAandGABA.TheEPAencouragesallinterestedstakeholderstoreviewthisPWPandtoprovidecommentsandadditionalinformationthatwillhelptheEPA'sdecision-makingprocessforthesebiochemicalpesticides.Inadditiontogeneralareasonwhichpersonsmaywishtocomment,therearesomeareasidentifiedinthePWPaboutwhichtheEPAspecificallyseekscommentsandinformation.Interestedstakeholderscouldincludethefollowing:environmentainonprofitorinterestgroups;pesticidemanufacturers;agriculturallabororcommoditygroups;commercial,institutional,residential,andotherusersofpesticides;orthepublicatlarge.ThePWPbeginsbydescribingthestatutoryandregulatoryauthoritiesforregistrationreview.Next,itprovidesbackgroundonLGAandGABA,whichincludesadescriptionoftheirmodeofaction,thecurrentlyregisteredpesticideproduct,applicationratesandmethods,usesites,andtoleranceexemptioninformation.Then,itliststheanticipateddataneeds,riskassessments,andaprojectedregistrationreviewtimelineforthiscase.Finally,thePWPprovidesguidanceforcommenters,explainsthenextstepsEPAwillbetaking,summarizesbackgroundinformation,andlistssupportingstudies,riskassessments,andotherdocuments.Furtherinformationaboutthiscase,includingbackgroundandsupportingdocuments,isavailableathttp://www.regulations.gov(under"SEARCHfor:Rules,Comments,AdjudicationsorSupportingDocuments,"thenenterthedocketidentificationnumber,whichisindicatedabove).B.StatutoryandRegulatoryAuthorityTheFoodQualityProtectionAct(FQPA)of1996mandatedaRegistrationReviewprogram.AllpesticidesdistributedorsoldintheUnitedStates(U.S.)mustgenerallyberegisteredbytheEPA,basedonscientificdatashowingthattheywillnotcauseunreasonableriskstohumanhealthortheenvironmentwhenusedasdirectedontheproductlabeling.Theregistrationreviewprogramisintended4L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govtomakesurethat,astheabilitytoassessriskevolvesandaspoliciesandpracticeschange,allregisteredpesticidescontinuetomeetthestatutorystandardofnounreasonableadverseeffectstohumanhealthortheenvironment.Changesinscience,publicpolicy,andpesticideusepracticeswilloccurovertime.ThroughtheRegistrationReviewprogram,theEPAperiodicallyreevaluatespesticidestomakesurethat,aschangeoccurs,productsinthemarketplacecancontinuetobeusedsafely.InformationonthisprogramisprovidedontheEPA'swebsite.1TheEPAisimplementingtheRegistrationReviewprogrampursuanttoFederalInsecticide,Fungicide,andRodenticideAct(FIFRA)section3(g)andwillrevieweachregisteredpesticideevery15yearstodeterminewhetheritcontinuestomeettheFIFRAstandardforregistration.TheregulationsgoverningRegistrationReviewbeginat40C.F.R.§155.40.TheEPAwillconsiderbenefitsinformationanddataasrequiredbyFIFRA.Thepublicphaseofregistrationreviewbeginswhentheinitialdocketisopenedforeachcase.ThedocketistheEPA'sopportunitytostatewhatitknowsaboutthepesticideandwhatadditionalrisk analysesanddataorinformationitbelievesareneededtomakearegistrationreviewdecision.Afterreviewingandrespondingtocommentsanddatareceivedinthedocketduringthisinitialcommentperiod,theEPAwilldevelopaFinalWorkPlan(FWP)andanticipatedschedulefortheregistrationreviewofLGAandGABA.C.BackgroundandRegulatoryInformationi.SummaryoftheActiveIngredient,UsageandAssociatedPesticideProductsLGAandGABAarefoundinvirtuallyalllivingorganisms.Inpureform,bothactiveingredientsarepowders.LGAisoneofthemajoraminoacidsinplantandanimalproteins.Enzymesinplants,humans,andanimalsconvertLGAtoGABA,andbothactiveingredientsareinvolvedinmanyphysiologicalfunctions.Forexample,humansreadilymetabolizeingestedLGAsothatconcentrationsinthebodyremainconstant,andLGAandGABAareneurotransmittersinthebrain.LGAis"GenerallyRecognizedasSafe"(GRAS)bytheFoodandDrugAdministration(referto21CFR§186.1256),andareregisteredPGRsforuseoncertainfruitsandvegetables,treenuts,peanuts,grains,animalfeedcrops,lawnandturfgrasses,andornamentalstoincreasebothyieldandquality.Theyalsoareregisteredforusetopreventpowderymildewongrapes,andsuppresscertainothercropdiseases.Theend-useproductisappliedbysprayingfromthegroundortheair,bydrenchingthesoil,orthroughcertainirrigationsystems.(U.S.EPA1997,FactSheetandTechnicalDocument,1998).1Seehttp://www.epa.gov/oppsrrdl/registrationreview/.5L-Glutamic.Acid

(LGA)

and Gamma-Aminobutyric

Acid (GABA)

EPA-HQ-OPP-20

14-0109 www

. regulations

. gov Table

1. Chemical

Facts

for LGA PC code

374350 Case Number

6025 CAS Number

- 56-86-0 Year

first registered

1998 Pesticide

Type

Plant growth regulator Chemical

class

Biochemical Reregistration

Eligibility

LGA

was registered

after November

1984

and

was

not subject

to reregistration

. Decision

(RED) Tolerance Reassessment

LGA

is exempt

from

the requirement

of

a tolerance

and

was

not subject

to

a Eligibility

Decision

(TRED)

tolerance reassessment. Cumulative

group

LGA

is not

a member

of

a cumulative

group

that shares

a common mechanism

of toxicity. 40 CFR Citation

40 CFR

§ 180.1187

- Exemption

from

the requirement

of

a tolerance. Non-pesticidal

uses

LGA

is

a major

amino

acid

in human,

plant

and animal proteins,

and

is

a brain neurotransmitter

in humans

and animals

. The daily intake

in

a 70

kg human

is estimated

to

be 10.4

g or 150 mglkg.

Human

milk contains

small amounts

of free LGA; estimated

intake

by newborns

is 20

. 6 rr1glkg/day

. Table

2. Chemical

Facts

for GABA PC code

030802 Case Number

6025 CAS Number

56-12-2 Year

first registered

1998 Pesticide

Type

Plant growth regulator Chemical

class

Biochemical Reregistration

Eligibility

GABA

was registered

after November

1984

and

was

not subject

to reregistration

. Decision

(RED) Tolerance Reassessment

GABA

is exempt

from

the requirement

for

a tolerance

and

was

not subject

to

a Eligibility

Decision

(TRED)

tolerance reassessment. Cumulative

group

GABA

is not

a member

of

a cumulative

group

that shares

a common mechanism of toxicity. 40 CFR Citation

40 CFR

§ 180.1188

- Exemption

from

the requirement

of

a tolerance. Non-pesticidal

uses

GABA

is

an amino

acid

in human,

plant

and animal proteins

, and

is

a brain neurotransmitter

in humans

and animals. 6L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govTable3.InformationAbouttheCurrentlyRegisteredL-GiutamicandGABAPesticideProductEPARegistrationProductNameDateApplicationRatesApplicationUseSitesNumber(%AI)RegisteredMethodsMultipleapplicationsat1-4Terrestrialfoodcropsoz.perapplication,toaSoil,soildrenchTerrestrialfeedcropsTerrestrialnonfoodAuxigroWPPlantJanuary14,maximumannualrateof1.5Foliar/ground70810-1MetabolicPrimerlb/acre(0.45lbsofeachAerialcrops(29.2%)1998ailacre)onfoodcropsand8Chemigation-Aquaticfoodcropslbs/acre(2.4lbseachpotatoesonlyGreenhousefoodcropsai/acre)onornamentals.LawnandturfgrassesOrnamentalsii.ToleranceActionsLGAisexemptfromtherequirementofatoleranceasfollows:40C.F.R.§180.1187L-GlutamicAcid;exemptionfromtherequirementofatolerance:L-GlutamicAcidisexemptfromtherequirementofatoleranceonallfoodwhenusedinaccordancewithgoodagriculturalpractices.FederalRegisterCitation-FinalRule66FR33198,June21,2001.Gamma-Aminobutyricisexemptfromtherequirementofatoleranceasfollows:40C.F.R.§180.1188GammaAminobutvricAcid;exemptionfromtherequirementofatolerance:GammaAminobutyricAcidisexemptfromtherequirementofatoleranceonallfoodcommoditieswhenusedinaccordancewithgoodagriculturalpractices.FederalRegisterCitation-FinalRule66FR33198,June21,2001.D.AnticipatedDataNeedsandRiskAssessmentsThefollowingtableslistthecurrentdatarequirementsforbiochemicalpesticidesassetforthin40CFR§158,subpartU.Theyarearrayedbyscientificdiscipline(i.e.,productchemistry,humanhealthassessment,nontargetorganisms,andenvironmentalfate)anddescriptionsareincludedregardinghowthedatarequirementshavebeenfulfilled(forexample,withastudy,publicliterature,ordatawaiver),notrequired,orarenotsatisfied.ThemostrecentcomprehensiveriskassessmentforLGAandGABAwascompletedOctober6,1997(U.S.EPA,1997)insupportofthefirstbiochemicalregistrationofLGAandGABA,whichoccurredonJanuary14,1998.Atthistime,nodatagaps (anticipateddataneeds)forLGAandGABAhavebeenidentified.BecausetherearenodatagapsforL-GlutamicAcidandGABA,theAgencydoesnotanticipatetheneedtoconductnewhumanhealthorecologicalriskassessmentsduringregistrationreview.7L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govi.ProductAnalysis(40C.F.R.§158.2030)Table4.SummaryofProductAnalysisDataforLGAandGABAHarmonizedHasDataRequirementMRIDNo.orOtherGuidelineDataRequirementNumberBeenAddressed?How?Source880.1100ProductIdentityandCompositionYes-Study44296801880.1200DescriptionofStaringMaterials,Production,Yes-Study44296801andFormulationProcess880.1400DiscussionofFormationofIm_puritiesYes-Study44296801830.1700PreliminaryAnalysisYes-Study44296801830.1750CertifiedLimitsYes-Study44296801830.1800EnforcementAnalyticalMethodYes-Study44296801Table5.SummaryofPhysicalandChemicalCharacteristicsforLGAandGABAHarmonizedHasDataRequirementMRIDNo.orOtherGuidelineDataRequirementNumberBeenAddressed?How?Source830.6302ColorYes-Study44296801830.6303PhysicalStateYes-Study44296801830.6304OdorYes-Study44296801830.6313StabilitytoNormalandElevatedYes-Study44296801Temperatures,MetalsandMetalIons830.6315FlammabilityNotrequired-productdoesnotcontaincombustibleliquids830.6317StorageStabilityYes-Study46653801830.6319MiscibilityNotrequired-productisnotanemulsifiableliquidandwillnotbedilutedwithpetroleumdistillates830.6320CorrosionCharacteristicsYes-Waived(Doesnot44368801'interactwithpackagingmaterials)830.7000pHYes-Study44296801830.7050UVNisibleLightAbsorptionYes-Study44296801830.7100ViscosityNotrequired-productisnotaliquid830.7200MeltingPoint/MeltingRangeYes-Study44296801830.7220BoilingPoint/BoilingRangeNotrequired-TGAIisnotaliquidatroomtemperature830.7300Density/RelativeDensity/BulkDensityYes-Study44296801(SpecificGravity)830.7520ParticleSize,FiberLength,andDiameterNotrequired-TGAisarewatersoluble,notfibrousDistribution830.7550Notrequiredfororganicchemicalsthatcompletely830.7560PartitionCoefficient(n-OctanolWater)830.7570dissociateinwater830.7840WaterSolubilityYes-Study44296801830.7950VaporPressureWaived-TGAisarecrystallinesolids8L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govii.HumanHealthAssessment(40C.F.R.§158.2050)AcutehumanhealthtoxicitystudiesindicateverylowmammaliantoxicityforLGAandGABA(ToxicityCategoryIVforacuteoraltoxicity(LD50>5050mg/kg),acutedermaltoxicity(LD50>5050mg/kg),andacuteinhalationtoxicity(LC50>2.58mg/L)andprimarydermalirritation;andToxicityCategoryIIIforprimaryeyeirritation),andthattheseactiveingredientsarenotdermalsensitizers.SubchronicmammaliantoxicitystudieswerewaivedbaseduponthenaturaloccurrenceofLGAandGABAinhumans,animalsandplants;therapidmetabolisminhumansofingestedglutamate;noeffectsonneurologicalorhepaticfunctioninhumanadultmalesgivenupto137 gglutamicaciddailyfor14-41days;andthelackofpersistence/shorthalf-lifeoftheseaminoacidsintheenvironment.(U.S.EPA,1997).Table6.SummaryofHumanHealthAssessmentDataforLGAandGABAHarmonizedHasDataRequirementMRIDNo.orOtherGuidelineDataRequirementNumberBeenAddressed?How?Source870.1100AcuteOralToxicity-RatYes-Study44296802870.1200AcuteDermalToxicityYes-Study44296803870.1300AcuteInhalationToxicity-RatYes-Study44296804870.2400PrimaryEyeIrritationYes-Study44296805870.2500PrimaryDermalIrritationYes-Study44296806870.2600DermalSensitizationYes-Study44296807870.310090-DayOral(onespecies)Yes-DataWaiver44296206870.325090-DayDermal-RatYes-DataWaiverU.S.EPA,1997870.346590-DayInhalation-RatYes-DataWaiverU.S.EPA,1997870.3700PrenatalDevelopmental-RatPreferablyYes-Publicliterature44296410Notrequiredsincetheuseisnotlikelytoresultinsignificanthumanexposure,andneitherLGAnor870.5100BacterialReverseMutationAssayGABAarestructurallyrelatedtoaknownmutagenorbelongstoachemicalclassofcompoundscontainingaknownmutagenNotrequiredsincetheuseisnotlikelytoresultin870.5300significanthumanexposure,andneitherLGAnor870.5375nvitroMammalianCellAssayGABAarestructurallyrelatedtoaknownmutagenorbelongstoachemicalclassofcompoundscontainingaknownmutagen.9L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.goviii.NontargetOrganismsandEnvironmentalFate(40c:F.R.§158.2060)Table7.SummaryofNontargetOrganismDataforLGAandGABAHarmonizedHasDataRequirementBeenMRIDNo.orOtherGuidelineDataRequirementNumberAddressed?How?Source850.2100AvianAcuteOralToxicityYes-DataWaiverU.S.EPA,1997850.2200AvianDietaryToxicityYes-DataWaiverU.S.EPA,1997850.1010AquaticInvertebrateAcuteToxicity,Yes-Study44405701Freshwater850.1075FishAcuteToxicity,FreshwaterYes-Study44405702880.4300NontargetPlantsYes-DataWaiverU.S.EPA,1997880.4350NontargetInsectTestingYes-DataWaiverU.S.EPA,1997E.RisktoThreatenedandEndangeredSpeciesThedatarequirementsfornontargetbirds(avianacuteoralanddietarytoxicitystudies),plants,andinsectswerewaived,baseduponthelowacutetoxicityofLGAandGABAinmammalianspecies,theirnaturaloccurrence,biodegradabilityintheenvironment2,andthepresenceofthesesubstancesinvirtuallyalllivinganimals,plants,andhumans.Fromthesubmittedstudies,the96hourLC50infreshwaterfish(speciestestedwastherainbowtrout,Oncorhynchusmykiss)andthe48hourEC50valueforthefreshwaterinvertebrate,Daphniamagna,are>100mg/L.TheNoObservedEffectConcentration(NOEC)valuewasdeterminedtobe100mg/L,baseduponnomortalityatthehighestconcentrationtestedinthesestudies,whichclassifiesLGAandGABAaspracticallynontoxictotheseorganisms.BaseduponthelowtoxicityofLGAandGABAdemonstratedinthemammalianacutetoxicitystudies(seesectionD.ii.ofthisdocument)andthenontargetfreshwaterinvertebrateandfishstudies,theirubiquityinlivingorganisms,andthelowapplicationratesasPGRs,theAgencyhasconcludedthattheriskstonontargetspecies,includingfederallylistedthreatenedorendangeredspecies(listedspecies)and/ortheirdesignatedcriticalhabitat,fromtheuseofLGAandGABAasPGRsarenegligible,andwillhave"noeffect"onlistedspeciesand/ortheirdesignatedcriticalhabitat.EPAanticipatesconductingnofurtheranalysisofpotentialriskstoendangeredorthreatenedspecies,unlessdataorinformationareobtainedduringtheregistrationreviewprocessthatwouldindicatesuchanassessmentwouldbeneededtoinformtheAgency'sdecision.F.EndocrineEffectsAsrequiredbytheAdministratorundertheFederalFood,Drug,andCosmeticAct(FFDCA)section408(p),theEPAhasdevelopedtheEndocrineDisruptorScreeningProgram(EDSP)andhasbeguntoimplementthescreeningprogramthatistobeusedtotestallpesticidesinordertodeterminewhethercertainsubstances(includingpesticideactiveandotheringredients)mayhaveaneffectinhumansor2Half-lifeinwater=8.7days;insoil=17.3days-LevelIIIFugacityModel,generatedusingUSEPA's"EPISuiteTM"http://www.chemspider.com/Chemical-Structure.116.html10L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govwildlifesimilartoaneffectproducedbya"naturallyoccurringestrogen,orothersuchendocrineeffectsastheAdministratormaydesignate."FFDCAsection408(p)(4)authorizestheAdministrator,byorder,toexemptfromtherequirementsoftheEstrogenicSubstancesScreeningProgramabiologicsubstanceorothersubstanceifadeterminationismadethatthesubstanceisnotanticipatedtoproduceanyeffectinhumanssimilartoaneffectproducedbyanaturallyoccurringestrogenicsubstance.BetweenOctober2009andFebruary2010,theEPAissuedtestorders/datacall-insforthefirstgroupof67chemicals,whichcontains58pesticideactiveingredientsand9inertingredients.Asecondlistofchemicals3identifiedforEDSPscreeningwaspublishedonJune14,2013,andincludessomepesticidesscheduledforregistrationreviewandchemicalsfoundinwater.LGAandGABAarenotamongthegroupofpesticideactiveingredientsontheliststobescreenedundertheEDSP.TheEPA,aspartofthisPreliminaryWorkPlan,believesthatLGAandGABAaresubstancesthatwouldnotlikelyproduceanyeffectinhumanssimilartoaneffectproducedbyanaturallyoccurringestrogenicsubstance.Assuch,pursuanttoSection408(p)(4),theEPAwilldetermineinthefuturewhetheritcanexemptLGAandGABAfromtherequirementsoftheSection408(p)EDSP.IntheeventtheEPAdoesdeterminetoexemptthissubstancefromtheEDSP,anorderwillbeissued.ForfurtherinformationonthestatusoftheEDSP,thepoliciesandprocedures,thelistsofchemicals,futurelists,thetestguidelinesandtheTier1screeningbattery,pleasevisitourwebsiteathttp://www.epa.govlendo/.G.IncidentsFromJanuary14,1998(thefirstdateofLGAandGABApesticideregistration)throughJanuary29,2014,theOfficeofPesticidePrograms'(OPP's)IncidentDataSystem(IDS)indicatestworeportsofadverseeffectsinhumansfromtheuseofapesticideproductcontainingLGAandGABAastheiractiveingredients.Thereportedincidentsinvolvedanadultmandevelopingmigraines,vertigo,tinnitus,dizzinessandblurredvisionafterbeingexposedtotheproductcontainingbothactive ingredients,andanadultwomanthatdevelopedsensitivitytoglutamateandmonosodiumglutamatefoodcoloringandfoundthatshebecamesickaftereatingMexicanvegetablesthatwereexposedtotheregisteredproductcontainingLGAandGABAasitsactiveingredients.Therewerenoreportedincidents todomesticanimals,drinkingwater,surfacewater,groundwater,plants,wildlifeorothernon-targetsduringthatsametimeperiod.AsearchofOPP'sEnvironmentalIncidentInformationSystem(EllS)revealednoincidentsassociatedwithLGAandGABA.Thedatabasecontainsinformationdatingbacktothe1970s.TheEPAwillconsideranyincidentdataorcommentssubmittedinresponsetothisPreliminaryWorkPlan.3Seehttp://www.regulations.gov/#!documentDetaii;D=EPA-HQ-OPPT-2009-0477-0074forthesecondlistofchemicals.11L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)H.TimelineEPA-HQ-OPP-2014-0109www.regulations.govBelowistheprojectedtimelineforRegistrationReviewcase6025:LGAandGABA.ActivitiesEstimatedMonth/Year*OpeningtheDocketOpenDocketand60-DayPublicCommentPeriodSeptember2014ClosePublicCommentPeriodNovember2014CaseDevelopmentIssueFinalWorkPlanMarch2015IssueDataCall-inN/ADataSubmissionNIAOpen30-DayPublicCommentPeriodforDraftRiskAssessmentsNIAClosePublicCommentPeriodNIARegistrationReviewDecisionOpen60-DayPublicCommentPeriodforProposedRegistrationReviewDecember2015DecisionClosePublicCommentPeriodFebruary2016FinalDecisionJune2016EstimatedTotal(years)1yearand9months..*ThisscheduleISsubjecttorevision.ShouldunforeseenIssuesansedurmgtheregistrationreviewprocess(I.e.,newlyanticipateddataneedsorthefailuretoacquireanEDSPexemption),thenewschedulewillbesetforthintheFinalWorkPlanoranamendedFinalWorkPlanforthiscase.I.GuidanceforCommentersThepublicisinvitedtocommentontheEPA'sPreliminaryWorkPlanandrationale.TheareasbelowhighlighttopicsofspecialinteresttotheEPAwherecomments,informationanddata,orreferencetosourcesofadditionalinformationcouldbeofparticularuse.TheEPAwillconsiderallcomments,aswellasanyadditionalinformationordataprovidedinatimelymanner,priortoissuingaFinalWorkPlanforthiscase.i.EnvironmentalJusticeTheEPAseekstoachieveenvironmentaljustice,thefairtreatmentandmeaningfulinvolvementofallpeople,regardlessofrace,color,nationalorigin,orincome,inthedevelopment,implementation,andenforcementofenvironmentallaws,regulations,andpolicies.Tohelpaddresspotentialenvironmentaljusticeissues,theEPAseeksinformationonanygroupsorsegmentsofthepopulationwho,asaresultoftheirlocation,culturalpractices,orotherfactors,mayhav.eunusuallyhighexposuretothepesticidaluseofLGAorGABA,comparedtothegeneralpopulation.Pleasecommentifyouareawareofanysubpopulationsthatmayhaveatypical,unusuallyhighexposurecomparedtothegeneralpopulation.12L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)ii.WaterQualityEPA-HQ-OPP-2014-0109www.regulations.govLGAandGABAarenotidentifiedasacauseofimpairmentforanywaterbodieslistedasimpairedundersection303(d)oftheCleanWaterAct.4Inaddition,noTotalMaximumDailyLoads(TMDLs)havebeendevelopedforLGAorGABA.5MoreinformationonimpairedwaterbodiesandTMDLscanbefoundonEPA'swebsite.6TheEPAinvitessubmissionofwaterqualitydataforthispesticide.Totheextentpossible,datashouldconformtothequalitystandardsinAppendixAoftheOfficeofPesticidePrograms(OPP)StandardOperatingProcedure:InclusionofImpairedWaterBodyandOtherWaterQualityDatainOPPsRegistrationReviewRiskAssessmentandManagementProcess7toensuretheycanbeusedquantitativelyorqualitativelyinpesticideriskassessments.iii.TradeIrritantsThroughtheRegistrationReviewprocess,theEPAintendstosolicitinformationontradeirritantsand,totheextentfeasible,takestepstowardfacilitatingirritantresolution.TheEPAwillworktoharmonizetoleranceandinternationalMaximumResidueLimits(MRLs),and,ifnecessary,maymodifytolerancelevelstodoso.GrowersandotherstakeholdersareaskedtocommentonanytradeirritantissuesresultingfromthelackofMRLsordisparitiesbetweenU.S.tolerancesandMRLsinkeyexportmarkets,providingasmuchspecificityaspossibleregardingthenatureoftheconcern.PesticidaluseofLGAandGABAinoronfoodandanimalfeedcommoditiesarecoveredunderanexistingexemptionfromtherequirementofatolerance.Moreover,therearenoknownMRLsforLGAorGABA.Therefore,theEPAdoesnotanticipatethatcurrentusesofLGAandGABAwillposeconcernsastradeirritants.iv.AdditionalInformationStakeholdersarealsospecificallyaskedtoprovideinformationanddatathatwillassisttheEPAinrefiningtheriskassessments.TheEPAisalsointerestedinobtainingthefollowinginformationregarding-GlutamicAcidandGamma-AminobutyricAcid:.,..CommentsregardingtheclarityofthedirectionsforuseonthelabelforAuxigroWPPlantMetabolicPrimer(EPARegistrationNumber70810-1):-Sitesofapplication-Applicationmethodsandequipment-Maximumapplicationrates-Applicationtiming(frequencyofapplication,applicationintervals,andmaximumnumberofapplications)-Reentryintervals-Pre-harvestintervals.,..Monitoringdata.,..Userestrictions(Stateandlocal)4Basedoninformationprovidedathttp://www.epa.gov/owowltmdll.5Basedoninformationprovidedathttp://iaspub.epa.gov/tmdlwaterslO/textsearch.tmdlsearch(orm.6Seehttp://www.epa.govlowowltmdl/.7Thisdocumentcanbefoundathttp://www.epa.gov/oppsrrdl/registrationreview/waterqualitvsop.htm.13L-Glutamic Acid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.gov..,.ForeigncompanieswhosupplytechnicalLGAandGABAtotheUSmarketJ.NextStepsAfterthe60-daycommentperiodcloses,theEPAwillreviewandrespondtoanycommentsreceivedinatimelymanner,thenissueaFinalWorkPlanforcase6026:L-GlutamicAcidandGammaaminobutyricacid.14L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govII.BIBLIOGRAPHYA.StudiesSupportingRegistrationReviewofLGAandGABA.MRIDCitationReceiptDateAuxeinCorp.(1997)SubmissionofMetabolismandToxicologyDatainSupportofthe44268800ApplicationforExperimentalUsePermitforAuxiGroPlantGrowthEnhancer.Transmittalof28-Apr-19977Studies.44268801Mahler,H.;Cordes,E.(1966)Generalaspectsofaminoacidmetabolism.P.685inBiological28-Apr-1997Chemistry.NewYork,NY:Harper&Row.44268802McGilvery,R.(1979)Amines.P.616-618inBiochemistry:AFunctionalApproach,2nded.28-Apr-1997Philadelphia:W.B.SaundersCo.144268803Tower,D.(1960)Theadministrationofgamma-aminobutyric acidtoman:Systemiceffectsandanticonvulsantaction.P.562-578inInhibitionintheCentralNervousSystemand28-Apr-199.7Gamma-AminobutyricAcid.Ed.byE.Roberts.NewYork,NY:PergamonPress.IKuhn,J.(1997)AcuteOralToxicityStudyinRats:AuxiGro:FinalReport:LabProject44268804Number:3288-97:S9-FF81-1.UnpublishedstudypreparedbyStillmeadow,Inc.11p.28-Apr-1997144268805Kuhn,J.(1997)AcuteDermalToxicityStudyinRabbits:AuxiGro:FinalReport:LabProject28-Apr-1997Number:3289-97:S9-FF81-2.UnpublishedstudypreparedbyStillmeadow,Inc.13p.IKuhn,J.(1997)PrimaryDermalIrritationStudyinRabbits:AuxiGro:FinalReport:Lab144268806ProjectNumber:3292-97:S9-FF81-5.UnpublishedstudypreparedbyStillmeadow,Inc.13p.28-Apr-1997144268807Narayan,V.;Nair,P.(1990)Metabolism,enzymologyandpossiblerolesof4-aminobutyrate28-Apr-1997inhigherplants:Reviewarticlenumber51.Phytochemistry29(2):367-375.IAuxeinCorp.(1997)SubmissionofMetabolismandToxicologyDatainSupportofthe44296200PetitionforToleranceforgamma-AminobutyricAcidonAllAgriculturalCommoditi,es.12-Jun-1997Transmittalof6Studies.144296201Meldrum,B.(1982)PharmacologyofGABA.ClinicalNeuropharmacology5(3):293-316.12-Jun-1997144296202McGilvery,R.;Goldstein,G.(1979)Amines.P.616-618inBiochemistry,AFunctional12-Jun-1997Approach,2nded.Philadelphia/London/Toronto:W.B.SaundersCo.IMeister,A.(1979)Biochemistryofglutamate:Glutamineandglutathione.P.69-84in44296203GlutamicAcid:AdvancesinBiochemistryandPhysiologybyL.Filer,eta!.,ed.NewYork,12-Jun-1997INY:RavenPress.Munro,H.(1979)Factorsintheregulationofglutamatemetabolism.P.55-68inGlutamic44296204Acid:AdvancesinBiochemistryandPhysiologybyL.Filer,eta!.,ed.NewYork:Raven12-Jun-1997Press.Fonnum,F.;Hassel,B.(1995)Glutamatesynthesis,metabolism,anduptake.P.19-34inCNS44296205NeurotransmittersandNeuromodulators:GlutamatebyT.Stone,ed.NewYork,NY:CRC12-Jun-1997Press.Tower,D.(1960)Theadministrationofgamma-aminobutyricacidtoman:Systemiceffects44296206andanticonvulsantaction.P.562-578inInhibitionintheCentralNervousSystemand12-Jun-1997gamma-AminobutyricAcid.NewYork,NY:PergamonPress.15L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govMRIDCitationReceiptDate44296400AuxeinCorp.(1997)SubmissionofToxicity,ResidueandSafetyDatainSupportofthe12-Jun-1997PetitionforL-Glutamicacid.Transmittalof21Studies.Giacometti,T.(1979)Freeandboundglutamateinnaturalproducts.P.25-34inGlutamic44296401Acid:AdvancesinBiochemistryandPhysiologybyL.J.Filer,Jr.,etal.,ed.NewYork,NY:12-Jun-1997RavenPress.Meister,A.(1979)Biochemistryofglutamate:glutamineandglutathione.P.69-84in44296402GlutamicAcid:AdvancesinBiochemistryandPhysiologybyL.J.Filer,etal.,ed.NewYork,12-Jun-1997NY:RavenPress.IMunro,H.(1979)Factorsintheregulationofglutamatemetabolism.P.55-68inGlutamic44296403Acid:AdvancesinBiochemistryandPhysiologybyL.J.Filer,Jr.,etal.,ed.NewYork,NY:12-Jun-1997RavenPress.44296404Fonnum,F.;Hassel,B.(1995)Glutamatesynthesis,metabolism,anduptake.P.19-34inCNS12-Jun-1997NeurotransmittersandNeuromodulators:GlutamatebyT.Stone,ed.NewYork:CRCPress.44296405Meldrum,B.(1982)PharmacologyofGABA.ClinicalNeuropharmacology5(3):293-316.12-Jun-1997CommitteeonGrasListSurvey-PhaseIII(1976)Estimatingdistributionofdailyintakeof44296406monosodiumglutamate(MSG),AppendixE.P.1-10inEstimatingDistributionofDaily12-Jun-1997IntakesofCertainGRASSubstances.WashingtonDC:NationalAcademyofSciences.44296407Ebert,A.(1970)ChronictoxicityandteratologystudiesofL-monosodiumglutamateand12-Jun-1997relatedcompounds.ToxicologyandAppliedPharmacology17:274.44296408Owen,G.;Cherry,C.;Prentice,D.;etal.(1978)Thefeedingofdietscontainingupto4%12-Jun-1997monosodiumglutamatetoratsfor2years.ToxicologyLetters1:221-226.44296409Owen,G.;Cherry,C.;Prentice,D.;etal.(1978)Thefeedingofdietscontainingupto10%12-Jun-1997monosodiumglutamatetoBeagledogsfor2years.ToxicologyLetters1:217-219.44296410Semprini,M.;D'Amicis,A.;Mariani,A.(1973)Effectofmonosodiumglutamateonfetusand12-Jun-1997newbornmouse.Nutr.Metab16:276-284.Semprini,M.;Conti,L.;Ciofi-Luzzatto,A.;etal.(1974)Effectoforaladministrationof44296411monosodiumglutamate(MSG)onthehypothalamicarcuateregionofratandmouse:A12-Jun-1997histologicalassay.Biomedicine21:398-403.IWen,C.;Kenneth,C.;Gershoff,S.(1973)EffectsofdietarysupplementationofMSCon44296412infantmonkeys,weanlingratsandsucklingmice.TheAmericanJournalofClinicalNutrition12-Jun-199726:803-813.USDepartmentofHealthandHumanServices.(1986)(Summarytoxicitydata).P.2522-442964132527inNIOSHRegistryofToxicEffectsofChemicalSubstances(RTECS)-(1985-1986),v.12-Jun-1997344296414Olney,J.(19?.?)Brainlesions,obesityandotherdisturbancesinmicetreatedwith12-Jun-1997monosodiumglutamate.Science164:719-721.Heywood,R.;Worden,A.(1979)Glutamatetoxicityinlaboratoryanimals.P.203-215in44296415GlutamicAcid:AdvancesinBiochemistryandPhysiology,byL.J.Filer,Jr.,etal.,ed.New12-Jun-1997York:RavenPress.44296416Oser,B.;Morgareidge,K.;Carson,S.(1975)Monosodiumglutamatestudiesinfourspecies12-Jun-1997ofneonatalandinfantanimals.FoodCosmet.Toxicol.13:7-14.16L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govMRIDCitationReceiptDate44296417Olney,J.;Sharpe,L.;Feigin,R.(19??)Glutamate-inducedbraindamageininfantprimates.J.12-Jun-1997Neuropathol.Exp.Neurol.,31:464-488.44296418Newman,A.;Heywood,R.;Reynolds,A.;eta!.(1973)Theadministrationofmonosodium-L-12-Jun-1997glutamatetoneonatalandpregnantrhesusmonkeys.ToxicologyI:197-204.44296419Stegink,L.;Pitkin,R.;Reynolds,A.;eta!.(1974)Placentaltransferofglutamateandits12-Jun-1997metabolitesintheprimate.AmJ.Obstet.Genecol.,I22:70-78.Airoldi,L.;Bizzi,A.;Salmona,M.;eta!.(1979)Attemptstoestablishthesafetymarginfor44296420neurotoxicityofmonosodiumglutamate.P.321-331inGlutamicAcid:Advancesin12-Jun-1997BiochemistryandPhysiologybyL.Filer,Jr.,eta!.,ed.NewYork:RavenPress.Adams,C.(1975)NutritiveValueofAmericanFoodsinCommonUnits,Agriculture44296421HandbookNo.456.PreparedbyUnitedStatesDepartmentofAgriculture;availablefromtheI2-Jun-I997GovernmentPrintingOffice.144296800AuxeinCorp.(1997)SubmissionofProductChemistryandToxicityDatainSupportoftheI2-Jun-I997ApplicationforRegistrationofAuxiGroWPEnd-UseProduct.Transmittalof7Studies.ILake,L.(1997)ProductChemistryDataforAuxiGroWP,FormulaID:Aux01F03:Lab144296801ProjectNumber:AUX01F03.UnpublishedstudypreparedbyAuxeinCorp.68p.{OPPTS12-Jun-1997880.1100,880.1200,880.1400,880.1600,880.1700,830.6302,830.6303,830.6304,830.7300,830.7000,830.6313,830.6320}144296802Kuhn,J.(1997)AcuteOralToxicityStudyinRats:AuxiGro:FinalReport:LabProject12-Jun-I997Number:3288-97:S9-FF8I-l.UnpublishedstudypreparedbyStillmeadow,Inc.IIp.IKuhn,J.(1997)AcuteDermalToxicityStudyinRabbits:AuxiGro:FinalReport:LabProject44296803Number:3289-97:S9-FF81-2.UnpublishedstudypreparedbyStillmeadow,Inc.13p.12-Jun-1997IBennick,J.(1997)AcuteInhalationToxicityStudyinRats:AuxiGro:FinalReport:Lab44296804ProjectNumber:3290-97:S9-FF81-3.UnpublishedstudypreparedbyStillmeadow,Inc.18p.12-Jun-1997IKuhn,J.(I997)PrimaryEyeIrritationStudyinRabbits:AuxiGro:FinalReport:LabProject144296805Number:329I-97:S9-FF81-4.UnpublishedstudypreparedbyStillmeadow,Inc.20p.12-Jun-1997144296806Kuhn,J.(1997)PrimaryDermalIrritationStudyinRabbits:AuxiGro:FinalReport:Lab12-Jun-1997ProjectNumber:3292-97:S9-FF81-5.UnpublishedstudypreparedbyStillmeadow,Inc.13p.44296807Kuhn,J.(1997)DermalSensitizationStudyinGuineaPigs:AuxiGro:FinalReport:Lab12-Jun-1997ProjectNumber:3293-97:S9-FF81-6.UnpublishedstudypreparedbyStillmeadow,Inc.18p.44368800AuxeinCorp.(1997)SubmissionofProductChemistryandToxicityDatainSupportofthe03-Sep-1997ApplicationforRegistrationofAuxiGroTechnical.Transmittalof2Studies.Lake,L.(1997)ProductChemistryDataforAuxiGroTechnical(MUP)FormulaID:44368801AuxOIF04:LabProjectNumber:283-0985-0:T-0318.Unpublishedstudypreparedby03-Sep-1997AuxeinCorp.43p.{OPPTS880.1100,880.1200,880.1400,880.1600,880.1700,830.6302,830.6303,830.6304,830.7300,830.7000,830.6313,830.6320}44368802Kuhn,J.(1997)PrimaryEyeIrritationStudyinRabbits:AUX-1-A:FinalReport:LabProject03-Sep-1997Number:3443-97:S9-FF81-4.UnpublishedstudypreparedbyStillmeadow,Inc.20p.44405700AuxeinCorp.(1997)SubmissionofToxicologyDatainSupportoftheApplicationforthe17-0ct-1997RegistrationofAuxiGroWPPlantGrowthEnhancerEP.Transmittalof2Studies.17L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govIIIMRIDCitationReceiptDate144405701Kranzfelder,J.;Liu,H.(1997)Aux01F03:AcuteToxicitytotheWaterFlea,Daphniamagna,UnderStaticConditions:LabProjectNumber:J9707002A.Unpublishedstudypreparedby17-0ct-1997IToxikonEnvironmentalSciences.23p.IKranzfelder,J.;Liu,H.(1997)Aux01F03:AcuteToxicitytoRainbowTrout,Oncorhynchus44405702mykiss,UnderStaticTestConditions:LabProjectNumber:197070028.Unpublishedstudy17-0ct1997IpreparedbyToxikonEnvironmentalSciences.23p.AuxeinCorp.(1998)SubmissionofProductChemistryDatainsupportoftheApplicationfor44538700RegistrationofAuxiGroWPPlantMetabolicPrimerandAuxiGroTech.Transmittalof119-Feb-1998Study.Grimm,D.(1997)DeterminationofFree(gamma)-AminobutyricAcidandGlutamicAcidin44538701AgriculturalProducts:LabProjectNumber:7-97-1:AUX7001.Unpublishedstudyprepared19Feb-1998bySouthernTestingandResearchLabs.,Inc.30p.AuxeinCorporation(1999)SubmissionofProductChemistry,ExposureandRiskAssessment44805300DatainSupportoftheRegistrationofAuxiGroWPPlantMetabolicPrimer.Transmittalof102-Apr-1999Study.Sandberg,G.(1999)DataandInformationSubmittedinSupportofRemoving30DayPhi44805301fromConsiderationforAuxigroLabel:FinalReport:LabProjectNumber:GR-0331-99.02-Apr-1999UnpublishedstudypreparedbyAuxeinCorporation,Inc.164p.45117700AuxeinCorp.(2000)SubmissionofProductChemistryDatainSupportoftheApplicationfor09-May-2000RegistrationofAuxiGroSGPlantMetabolicPrimer.Transmittalof1Study.45117701Bahn,R.(2000)IdentityoflnertIngredient:AuxiGroSGPlantMetabolicPrimer.09-May-2000UnpublishedstudypreparedbyGrainProcessingCorp.6p.45118000AuxeinCorporation(2000)SubmissionofEfficacyDatainSupportoftheRegistrationof09-May-2000AuxiGroPlantMetabolicPrimer.Transmittalof16Studies.Bauer,B.(1998)AuxGroControlofPowderyMildewonGrapes-MelloRanch,Ripon,CA45118001(1998);LabProjectNumberUS01/29/0100101.UnpublishedstudypreparedbyAuxein09-May-2000Corporation.IIBauer,B.(1998)AuxiGrowControlofPowderyMildewonGrapes-GuintoliRanch,Escalon45118002CA(1998):LabProjectNumber:US501/98/0200102.Unpublishedstudypreparedby09-May-2000AuxeinCorporation.34p.IBauer,B.(1998)AuxiGrowControlofPowderyMildewonGrapes-Rodoani-Hazelhurst,45118003EscalonCA(1998):LabProjectNumber:US501/98/0100101.Unpublishedstudyprepared09-May-2000IbyAuxeinCorporation.34p.Bauer,B.(1998)AuxiGroControlofPowderyMildewonGrapes-RodoaniVineyard,45118004Escalon,CA(1998):LabProjectNumber:US501/98/0200101.Unpublishedstudyprepared09-May-2000byAuxeinCorporation.34p.Bauer,B.(1998)AuxiGroControlofPowderyMildewonGrapes-FischerRanch,Ripon,CA45118005(1998):LabProjectNumber:US501/98/0300101.UnpublishedstudypreparedbyAuxein09-May-2000Corporation.22p.18IL-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-20I4-0I09www.regulations.govMRIDCitationReceiptDateBauer,B.(1998)AuxiGroControlofPowderyMildewonGrapes-Pando!&Sons,Delano,45II8006CA(I998):LabProjectNumber:US501/98/0300I03.Unpublishedstudypreparedby09-May-2000AuxeinCorporation.20p.Bauer,B.(1998)AuxiGroControlofPowderyMildewonGrapes-StokesFarms,Galt,CA45II8007(1998):LabProjectNumber:US5I0/98/0IOOI04.UnpublishedstudypreparedbyAuxein09-May-2000Corporation.I7p.Bauer,B.(1999)AuxiGroControlofPowderyMildewonGrapes-MelloRanch,Ripon,CA45II8008(1999):LabProjectNumber:US500/99/0I00I0I.UnpublishedstudypreparedbyAuxein09-May-2000Corporation.4Ip.Bauer,B.(I999)AuxiGroControlofPowderyMildewonGrapes-GuintoliRanch,Escalon,45II8009CA(I999):LabProjectNumber:US500/99/0200I0I.Unpublishedstudypreparedby09-May-2000AuxeinCorporation.40p.Bauer,B.(1999)AuxiGroControlofPowderyMildewonGrapes-GuintoliRanch,Escalon,451180IOCA(1999):LabProjectNumber:US500/99/0300IGI.Unpublishedstudypreparedby09-May-2000AuxeinCorporation.3Ip.Bauer,B.(1999)AuxiGroControlofPowderyMildewonGrapes-VillanuevaRanch,Ripon,45II8011CA(1999):LabProjectNumber:US500/99/0200I02.Unpublishedstudypreparedby09-May-2000AuxeinCorporation.40p.Bauer,B.(1999)AuxiGroControlofPowderyMildewonGrapes-VillanuevaRanch,Ripon,45II80I2CA(1999):LabProjectNumber:US500/99/0I00I02.Unpublishedstudypreparedby09-May-2000AuxeinCorporation.39p.Gubler,D.(I999)GrapePowderyMildewFungicidalTrials,I999-U.C.Davis,Sacramento45II80I3County,Ca:LabProjectNumber:US500/99/0IOOIAI.Unpublishedstudypreparedby09-May-2000UniversityofCaliforniaatDavis.24p.Hale,E.(1999)AuxiGroControlofPowderyMildewonGrapes-HaleResearch&Ag.45II80I4Consulting,SantaMaria,CA(1999):LabProjectNumber:US500/99/04000AI.09-May-2000UnpublishedstudypreparedbyHaleResearch&Ag.Consulting.43p.Zaccaria,J.(1999)AuxiGroControlofPowderyMildewonGrapes-ZaccariaAgricultural45II80I5·Consulting,KernCounty,CA(1999):LabProjectNumber:US500/99/04OOI01.09-May-2000UnpublishedstudypreparedbyZaccariaAgriculturalConsulting.33p.Leavitt,G.;Martin-Duvall,T.(I999)PowderyMildewControlStudyI999-GeorgeLeavitt,45II80I6FarmAdvisor(UCExtension)andTomeMartin-Duvall,SRAII,Madera,CA.Unpublished09-May-2000studypreparedbyUniversityofCaliforniaExtension.8p.45135400AuxeinCorporation(2000)SubmissionofEfficacyDatainSupportoftheRegistrationofOI-Jun-2000AuxiGroPlantMetabolicPrimer.Transmittalof2Grove,G.;Davis,G.;Bennett,L.(I999)AuxiGroControlofPowderyMildewonGrapes--4513540IWashingtonStateUniversity,Prosser,WA (I999):LabProjectNumber:US500/99/09002OI-Jun-2000AI.UnpublishedstudypreparedbyWashingtonStateUniversity.IOp.Schreiber,A.(1999)AuxiGroControlofPowderyMildewonGrapes--Agricultural45135402DevelopmentGroup,YakimaValley,WA(I999):LabProjectNumber:US500/99/09002OI-Jun-2000AI.UnpublishedstudypreparedbyAgriculturalDevelopmentGroup,Inc.13p.19L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulations.govMRIDCitationReceiptDate46653800EmeraldBioAgricultureCorporation(2005)SubmissionofProductChemistryDatain28-Sep-2005SupportoftheRegistrationofAuxiGro.Transmittalof1Study.Donehoo,M.(2005)StabilityStudyofFreeGamma-AminobutyricAcidandGlutamicAcid46653801inAgriculturalProducts:FinalReport.ProjectNumber:7/97/2,AUX/7002,FN/1/1.28-Sep-2005UnpublishedstudypreparedbySouthernTesting&ResearchLabs,Inc.43p.49249700CPBio,Inc.(2013)SubmissionofProductChemistryandToxicityDatainSupportofthe06-Nov-2013ApplicationforRegistrationofGABATechnical.Transmittalof10Studies.49249701Kaminsky,M.(2013)GABA99%TechnicalProductChemistry.ProjectNumber:17233/13.06-Nov-2013UnpublishedstudypreparedbyStillmeadow,Inc.16p.Kaminsky,M.(2013)GABA99%Technical:PreliminaryAnalysisofaTestSubstance(549249702BatchAnalysis).ProjectNumber:17231113.UnpublishedstudypreparedbyStillmeadow,06-Nov-2013Inc.55p.49249703Kaminsky,M.(2013)GABA99%Technical:EnforcementAnalyticalMethod.Project06-Nov-2013Number:17255/13.UnpublishedstudypreparedbyStillmeadow,Inc.16p.49249704Kuhn,J.(2012)GABA99%Technical:AcuteOralToxicity(UDP)inRats.ProjectNumber:06-Nov-201316713/12.UnpublishedstudypreparedbyStillmeadow,Inc.lOp.49249705Kuhn,J.(2012)GABA99%Technical:AcuteDermalToxicityInRats.ProjectNumber:06-Nov-201316714/12.UnpublishedstudypreparedbyStillmeadow,Inc.lip.49249706Kuhn,J.(2012)GABA99%TechnicalAcuteEyeIrritationinRabbits.ProjectNumber:06-Nov-201316716/12.UnpublishedstudypreparedbyStillmeadow,Inc.16p.49249707Doig,A.(2012)GABA99%Technical:AcuteInhalationToxicityinRats.ProjectNumber:06-Nov-201316715/12.UnpublishedstudypreparedbyStillmeadow,Inc.17p.49249708Kuhn,J.(2012)GABA99%Technical:AcuteDermalIrritationinRabbits.ProjectNumber:06-Nov-201316717/12.UnpublishedstudypreparedbyStillmeadow,Inc.lOp.49249709Kuhn,J.(2012)GABA99%Technical:SkinSensitizationinGuineaPigs.ProjectNumber:06-Nov-201316718/12.UnpublishedstudypreparedbyStillmeadow,Inc.15p.49249710Yowell,J.(2013)ProductChemistry:OriginalGRASSubmissiontoUSDA.Unpublished06-Nov-2013studypreparedbyCPBio,Inc.154p.49336700CPBio,Inc.(2014)SubmissionofProductChemistryDatainSupportoftheApplicationfor07-Mar-2014RegistrationofCP810GABATechnical.Transmittalof1Study.CPBio,Inc.(2014)GABATechnical:ProductChemistrytoEstablishaToleranceExemption49336701andApplicationforaTechnicalProductRegistration.ProjectNumber:CPB/201204.07-Mar-2014UnpublishedstudypreparedbySpringTradingCompany.39p.49345800CPBio,Inc.(2014)SubmissionofToxicityDatainSupportoftheApplicationfor24-Mar-2014RegistrationofCPBioGABATechnical.Transmittalof1Study.CPBio,Inc.(2014)GABATechnical:ToxicityStudiestoSupporttheRevisedDataMatrix49345801foraTechnicalProductRegistration:GABATechnical:ProductChemistrytoEstablisha24-Mar-2014ToleranceExemptionandApplicationforaTechnicalProductRegistration.ProjectNumber:FCT/7837,16714/12,16715/12.Unpublishedstudy.117p.20L-GlutamicAcid(LGA)andGamma-AminobutyricAcid(GABA)EPA-HQ-OPP-2014-0109www.regulatio!"'s.govMRIDCitationReceiptDate49362500CPBio,Inc.(2014)SubmissionofProductChemistryDatainSupportoftheApplicationfor16-Apr-2014RegistrationofGABATechnical.Transmittalof1 Study.Yowell,J.(2014)GABATechnical:ProductChemistrytoEstablishaTolerance Exemption49362501and;ApplicationforaTechnicalProductRegistration.ProjectNumber:FLUKA/93300,16-Apr-2014SIGMA/ALDRICH/A6141,UnpublishedstudypreparedbyCPBio,Inc.39p.B.U.S.EnvironmentalProtectionAgencyRiskAssessmentMemorandaU.S.EPA.1997.RegistrationofAuxiGro(EPAFileSymbol70810-R)andExemptionfromtherequirementofatoleranceforGABA(pp#7F4843)andL-GlutamicAcid(PP#7F4842)onallRAWAgriculturalCommodities(RACs).ReviewofProductChemistry,MammalianToxicologyandEco-ToxicityStudies.(ChemicalNos.030802and374350);MRIDNos.442962-01to07,442964-01to21;and442962-01to442962-06).MemorandumfromFreshtehToghroltoEdwardAllen.U.S.EnvironmentalProtectionAgency(U.S.EPA).October06,1997.U.S.EPA.1998.ReviewofFreshwaterAcuteToxicityStudies,ChemicalNo.030802,374350;MRIDNos.444057-01and02.MemorandumfromEdwardAllentoFreshtehToghrol.U.S.EnvironmentalProtectionAgency(U.S.EPA).April13,1998U.S.EPA.1998.GABAandL-GlutamicAcid(030802,374350)TechnicalDocument.U.S.EnvironmentalProtectionAgency(U.S.EPA).IssuedSeptember,1998.Availableat:http://www.epa.gov/oppOOOO1/chemsearch/regactions/registration/relatedpc..:0308021-Sep-98.pdfU.S.EPA.2004.GABAandL-GlutamicAcid(030802,374350)FactSheet.IssuedOctober19,2004.Availableat:http://www.epa.gov/oppOOOO1Ichemsearch/regactions/registration/fsG-13219-0ct04.pdf21