~cte~ai t<.egister / VoL. 50, No. 250 1 Monday, December30, 1985 / Rules and Regulations 53145

ENVIRONMENTAL PROTECTIOW

AGENCY

40 CFR Part 799

(OPTS-42048B;FRL.-2944—9J

Hydroquinone Testing Requirements

AGENCY:EnvironmentalProtectionAgency(EPA).ACTION: Final rule.

SUMMARY: On January4. 1984, the EPAproposed,undersection4 (a) of theToxic SubstancesControlAct (TSCA),that manufacturersandprocessorsofhydroquinone(CASNo. 123—31—9)conducthealthandenvironmentaleffectstestingof that chemical(49 FR438). EPA hasreviewedthecommentson theproposalaswell asnewtestingresultsandadditionaldatathathavebecomeavailablesincethepublicationof the proposedrule. Basedon thesereviewstheAgencyis todaypromulgatinga final testrule thatrequiresmanufacturersandprocessorsof hydroquinoneto evaluatehydroquinone’stoxicokineticsandtodetermineits potentialto producenervoussystem.reproductiveandteratogeniceffects.DArES In accordancewith 40 CFR23.5(So FR 72fl: February21, 1985), this ruleshallbepromulgatedfor purposesofjudicial reviewat 1 p.m.ea.sterit(“daylight” or“standard”asappropriatejtimeon January13, 1988.Thisrule shallbecomeeffectiveonFebruary12.1988.FOR FURTHER INFORMAT1ON COHTACTEdwardA. Klein. Director.TSCAAssistanceOffice (1’S—799),Office ofToxic Substances,Rni. E—~43.401 M St..SW.. Washington,DC20460.Toll free(800—424—9065),In WashingtonD.C.:(554—1404),OutsidetheUSA: (Operator.202—554—1404).SUPPLEMENTARY INFOR~ATtOtCEPAisrequiringhealtheffectstestingofhydroquinoneas statedin this final rule.L Introduction

This noticeis partof theoverallimplementationof section4 of theToxicSubstancesControlAct (TSCA. Pub.L94—489 90 Stat. 2008etseq.:15 U.S.C.2603at seq.)which containsauthorityforEPA to requiredevelopmentof datarelevantto assessingtherisks to healthandthe environmentposedby exposureto particularchemicalsubstancesormixtures.

Undersection4(a)(1)of TSCA, EPAmustrequiretestingof a chemicalsubstanceto develophealthor

53148 FederalRegisterI Vol. 50, No. 250 / Monday, December30, 1985 / Rules and Regulations

environmentaldataif theAdministratorfinds that:

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Fora morecompleteunderstandingofthestatutorysection4 findings, thereaderis directedto the Agency’sfirstproposedtestrulepackage(chioromethaneandchlorinatedbenzeries,publishedin the FederalRegisterof july 18, 1980 (45FR 48510).)and to the secondpackage(dichioromethane,nitrobenzeneandi.i,i-trichloroethane,publishedin theFederalRegisterof June5. 1981;(46 FR30300)) for in-depthdiscussionsof thegeneralissuesapplicableto this action.

On january4, 1984, EPAproposed,undersection4(a) of TSCA. thatmanufacturersandprocessorsofhydroquinoneconducthealthandenvironmentaleffectstestingof thatchemical(49FR 438). EPA, in responseto requestsby GoodyearTire andRubberCompanyandtheChemicalManufacturer’sAssociationforadditional time to comment,publishedanoticein theFederalRegisterof March9, 1984 (49FR8969) extendingthe60-daycommentperiodanadditional30-daystoApril 3,1984.OnApril 18. 1984.EPAalsohelda public meetingto allowinterestedpersonsto presentoralcommentson theproposedrule.

IL Background

A. ProfileHydroquinone(CH4(OHh,CAS No.

123-31—9)is a white crystallinesolidatroom temperatureandis verysolubleinwater,ethanol,andacetone.It actschemicallyasareducingagent,beingoxidized to quinone.

Hydroquinoneis producedin aphotographicgradefor useasadevelopingagentandin a technicalgradewhich is primarily usedasachemicalintermediatein theproductionof rubberchemicals.Most of thetechnicalgradehydroquinoneisconvertedinto chemicalfor useinpolymers.Smalleramountsof thetechnicalgradeare usedaspolymerizationinhibitorsduring themanufactureof vinyl monomers,as

inhibitors forstabilizingunsaturatedpolyesterresinsandasa chemicalintermediateto prepareotherderivativessuchas dyesandpigments.Hydroquinor.eis alsousedinderrnatologic preparationsdesignedtobleachhyperpigmentedskin, andassuchis regulatedby theFoodandDrugAdministration.

TheannualU.S.productionvolumeofphotograde,technical,andothergradesof hydroquinoneis estimatedto be ashigh as27 million pounds(Ref. 37).U.Simportsof technicalgradehydroquinonein 1981totaled50 thousandpounds(Ref.32).TheU.S. importsof photographicgradearenegligible.Themanufacturersof hydroquinonehavecommentedthat28 million poundsof the chemicalaremanufacturedand importedannually(Ref. 1).

B~ITC RecommendationsSection4(e) of TSCA establishedan

InteragencyTestingCommiUee(ITC) torecommendto EPAa list of chemicalstobeconsideredfor testingundersection4(a)of theAct. The ITC designatedhydroquinoneforpriority considerationin its Filth Reportpublishedin theFederalRegisteron December7, 1979(44FR70884).TheITC recommendedthathydroquinonebeconsideredfor testingfor carcinogenicityandteratogencityandthatepidemiology,humanmetabolismandenvironmentalfatestudiesalso beconsidered.

TheITC’s recommendationswerebasedon thewidespreaduseof thechemicalsubstanceby peoplehavinglittle knowledgeof its healthandenvironmentaleffects.TheITCestimatedthat theU.S.productionofhydroquinonen 1977 wasabout11million pounds.Thecarcinogenicityandteratogenicityrecommendationswerealso basedon suggestiveevidencederivedfrom animal studies.

C. ProposedRuleEPA publisheda proposedrulein the

FederalRegisterof January4, 1984(49FR438)which wouldrequirehealtheffects,chemicalfateandenvironmentaleffectstestingfor hydroquinone.

in evaluatingtheITC’s testingrecommendationsforhydroquinone.EPA consideredall available relevantinformation includinginformationpresentedin theITC’s reportrecommendingtestingconsideration:productionvolume,use.exposure,andreleaseinformation reportedbymanufacturersof hydroquinoneunderTSCA section8(a) (40 CFRPart712.—ChemicalInformationRule,SubpartB—ManufacturersReporting—PreliminaryAssessmentInformation):unpublished

healthandsafetystudiessubmittedbymanufacturers,processorsanddistributorsof hvdroquir.oneundertheTSCA section8(d) HealthandSafetyDataReportingRule (40 CFRPart71C~:andotherpublishedandunpublisheddataavailableto the Agency.On thebasisof the evaluation,as describedintheproposedrule and the accompanyingtechnicalsupportdocument,EPAproposedmetabolism(toxicokinetics),nervoussystemeffects.reproductiveeffectives,teratogenicity(developmentaltoxicity), andmutagenicitytestingrequirements.aswell as epidemiologicstudies,for hydroquinoneunderbothsections4(a)(1)(A)and4(a)(1)(B) ofTSCA. EPAalso proposedchemicalfateandenvironmentaleffectstestingrequirementsfor hydryquinoneundersection4(a)(1)(A)of TSCA. By theseactions.EPA respondedto theITC’sdesignationof hydroquinone.

In basingits proposedhydroquinonehealtheffectstestingon the authorityofsection4(a)(1) (A) and (B) of TSCA

1. EPA found thathydroquinoneisproducedin substantialquantities.andthat themanufacture,processinganduseof hydroquinonemayresult insubstantialhumanexposureto thechemical.Furthermore.EPA foundthatthereare insufficientdataavailabletoreasonablydetermineor predicteithertheresultof this exposurein theareasofcarcinogenic,mutagenic.teratogenic.nervoussystem..and reproductivehealtheffectsor the incidenceofhydroquinone-relatedeffectsamonghumans.Finally,EPAfound that testing~of hydroquinonefor thesehealtheffectsandepidemiologicparametersisnecessaryto developdataneededtoevaluatethehealthrisksposedbyexposureto hydroquinone.

Thefindings werebasedon thefollowing inforrnatioru

a.Therearesubstantialamountsofhydroquinoneproducedin the UnitedStateseachyear.TheannualU.S.productionvolumeof hydroquinoneisestimatedto beas high as27 millionpounds(Ref. 37).

b. In 1980theNationalInstituteforOccupationalSafetyand Healthestimatedthatapproximately470.000U.S.workers,in 137 occupations,arepotentiallyexposedto hydroquinoneannually.Of majorconcernto theAgencywastheestimated2.2 millionphotohobbyistswho developtheirownfilm andprints, becausemuch of thisinvolve. thedevelopmentof black andwhite film usingsolutionscontaininghydroquinone.TheAgency believedthatbothworkersandhobbyistswouldreceiveinhalationanddermalexposure.

— FederalRegisterI Vol. 50. No. 250 / Monday, December30, 1985 / Rules and Regulations 53147

2. In addition,EPAfoundthat themanufacture,processinganduseofhydroquinonemaypresentanunreasonablerisk of injury to human’health.Therewasevidenceof potentialhumanhealthrisks from nervoussystem.rnutagenic.teratogenic.reproductive,andcarcinogeniceffectsresultingfrom themanufacture,processing.anduseactivitiesas8ofnatedwith hydroquinone.Exposuretohydroquinonemay besufficient toresultin sucheffects.The existingdatawereinadequateto reasonablypredictordeterminetheeffectsof theseexposuresto hydroquinoneandtestingwasnecessaryfor theseeffects.Therefore,EPAbelievedthat requiringepidemiologicstudiesandtestingofhydroquinonefor nervoussystemeffects,rnutagenicity,teratogenicity,reproductiveeffects,andcarcinogenicitycouldalsobebaseduponsection4(a)(1)(A) of TSCA.

EPAdid notproposeoncogenicitytestingof hydroquinone,sincetheNationalToxicologyProgram(NTP) iscurrentlyconductinga 2-yearbioassayon hydroquinone.However,theAgencydid proposesomemetabolism(toxicokinetic)studiesofhydroqui.nonevia dermalandoral routesof exposure.Thesestudieswould providea reliablemeansby which theinternaldoseadministeredin theNTPbioassaycouldberelatedto dosesexpectedto bereceivedby workersandhobbyists.

In addition,theAgencyconcludedthat theacutetoxicity (lethality) and thesubchronictoxicity of hydroquinonewereadequatelycharacterizedand.therefore,no further testingwould berequiredat this time.

TheAgencybasedits chemicalfateandenvironmentaleffectstestingontheauthorityof section4(a)(1)(A)of TSCA.(1) EPAfoundthattherewasevidenceof potentialenvironmentalrisks toaquaticorganismsresultingfrom theprocessinganduseactivitiesassociatedwith hydroquinone.(2)While therewereexistingdatato supportthis beliefwithrespectto theseeffects.thedatawereinadequateto reasonablypredictordeterminetheeffectsof theseexposuresto hydroquinone.(3)Testingwasnecessaryto developdatawith respectto theseeffects.

Althoughthe l’l’C did notrecommendenvironmentaleffectstestingforhydroquinone.theAgencywasconcernedwith effluentsfromphotoprocessingfacilitiesandproposeda seriesof environmentaleffectstests.Basedon existingaquatictoxicity dataand.the limited dataonphotoprocessingeffluents. iie Agencybelievedthat thelevels of hydroquinonein theseeffluents,althoughnot so substantialas

to dictatea section4(a)(1)(BJfinding.maypresentanunreasonablerisk(section4(a)(l)(A)) to aquaticorganisms.Testingwasneededto providedatatoestablishwhetheranunreasonableriskto freshwaterandsaltwateraquaticspeciesexisted.

TheAgency alsoproposedchemicalfate testingfor hydroquinone.EPAbelievedthat this testingwasessential,becausetheexistingchemicalfatedataarelimited andmoredataare neededtoassessthemagnitudeof the possiblerisks to aquaticorganisms.EPA neededinformationto establishbiodegradationratesin orderto assessthelevelsofhydroquinoneexposureto aquaticorganisms.

T*~t.~1—TES11NQ REcOMMENDATiONS FORHYOROQUINONE

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ID. Responseto PublicCommentsThecommentsreceivedby the

Agencyin responseto theproposedrulefor hydroquinonewerefrom individualcompanies.theNationalAssociationofPhotographicManufacturers,andtheChemicalManufacturers’Association.TheAgencydid notreceiveanycommentswhich,in theAgency’sjudgment.rebuttedthe substantialproductionandsubstantialhumanexposurefindingsfoz~hydroquinone.However,newinformationconcerningtheenvironmentalreleaseofhydroquinonehasbecome availablesincepublicationof theproposedruleandhasled EPAto reconsideritschemicalfateandenvironmentaleffectstestingrequirementMaforissuesidentifiedduring thecommentperiodare discussedbelow.A. HumanExposure

EPAcitedtheNOHS (1980)surveythatestimatedthatapproximately470,000U.S.workers,in 137 occupations,arepotentiallyexposedto hydroquinoneannually.Also of concernwere theestimated2.2m.iillonphotohobbyistswho developtheir own film andprints.becausemuchof this involvesthedevelopmentof blackandwhite filmandtheprocessutilizeshydroquinone.Workersandhobbyistsmayreceiveinhalationanddermalexposures.

EPAalsofoundthat themanufacture,processinganduseof hydroquinonemay presentan unreasonablerisk ofinjury to humanhealth.

The industryhascommentedthatthereare two majorusesforhydroquinone,photographicusesandrubberchemicaluses.Regardingthephotographicuses,theyreportthatonlyfcur percentof still picturestakenbyamateursarein blackandwhite (Ref. 2)and that only 30.000kg (66000Ibs) (Ref.2) of hydroquinoneare usedbyiiomedarkroomhobbyistseachyearandthisuseis in dilute solutions(0.2.—0.3percent)(Refs. 3, 5. and27).

The industryestimatesthat about800,000peopleuseblackandwhitedeveloper-sin homedarkrooms(Ref, 1).Eachpersonaverageseightse~sionsper-year.with theaverageexposuretimeof5 to 10minuteseachof thesedevelopingandprintingsessions(Refs.1 and5). Asa resultof theselimited periodsandlabel warningson containers.corumentersbelievedermalabsorptionof hydroquinoneis extremelyminimaland that inhalationexposureis alsounlikely becauseof hydroquinoneslowvaporpressure(Ref. 5).

TheAgencybelievesthat in manyinstancestheindustry’sconclusion,thatconsequentialexposureofphotohobbyiststo hydroquinoneisunlikely, maybe accurate.It alsoappearsthat boththenumberofphotohobbyistspotentiallyexposedtohydroquinoneandthelevelsof exposurearemuch lowerthanthe Agency’searlierestimates.However.EPAstillbelievesthereare a substantialnumberof photohobbyiststhatare intensivelyinvolved inblackandwhitephotographymuchmorefrequentlythanthe“average”photohobbyistprofiled bytheindustry.Thiswould result in longerandmorefrequentexposureperiodsfortheseindividuals.

Regardingexposureof individualsemployedat photoprocessingplants,theindustryreportsthatatleast90 percentof thephotoflthshthgdollar volumeiscolornegativefilms andprints,whereno hydroquinoneis used(Refs.1 and5).The industry,estimatingthereare 2.000photofinishinglabsin theU.S.(Refs. 1and5) versustheAgency’sestimateof10,000,statesthatonly someof thesefacilities processblackandwhitenegativefilm andpaperusingdeveloperscontaininghydroquinone.Additionally, sincemostlabs useautomaticprocessingequipment.anyexposurewould belikely to involve onlyone-halfhour for oneworkermixingchemicalsoncea week(Refs. 1 and5).The industrycites botha NIOSHreportconcerninga photofinishinglab andan

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industrystudyof airbornehydroquinoneina darkroomthat showednohydroquinortedetectedat a 0.02mg/rn3

limit of detection(Refs. 4 and 63.While automatedlabsmay result in

minimal workerexposuretohydroquinone,theAgency believestherearevaryingamountsof automationf.~tmdin thephotoprocessinglabsin theU.S.that developblackandwhite filmsandpapers.Older,lesssophisticatedoperathnswill involvemoredirectworker involvementwith hydroquinoneandgreaterexposure,especiallydernial,will result.Moreover, themonitoringdataprovidedto theAgencyareextremelylimited; thus, theAgencycannotbeassuredthat thedataare trulyrepresentativeof all photoprocessinglabs.

The industryhasdefinedthegroupofhydroquinonemanufacturingworkersas80 individualsat two plants(Ref. 1).T~ieyclaim xrnnirnalworker inhalationexposuredueto theclosedproductionprocesses.with one facility reporting“an arithmeticalaverageconcentrationof 0.79mg/rn3(±0.52standarddeviation)” and the other reportingthe“highestaverageconcentrationas0.2mg/rn” (Ref. 1). Oneproductionfacilityreportedthe arithmeticaverageairconcentrationin theunloadingareaas0.13mg/rn3(standarddeviation±0.15mg/rn~(Ref. 1). Thesesummarydataweresuppliedby theindustry EPAisunableto interpretthesefurthersincefrequency,averagingtimeandothersupportingdocumentationwerenotprovided.

TheAgencyagreesthat exposureofcnrtainmanufacturingworkerstohydroquuionemaybelimited.However,while the industryhasdescribed itsproductionworkforceasessentially80workers,theNIOSHNOHS Surveyhasestimatedthat,overall. approx.irnately470,000U.S. workers in 137 occupationsare potentially exposedtohydroquinone.Workersinvolved indistributingand processinghydroquinor.eas it is incorporatedintorubberchemicalsandother usesandtheactualpotential forexposuresthroughtheseactivitieshave not beencharacterizedby the industry.While theAgencybelievesthe 470,000figuremayoverestimatethe number of workersactually exposedto hydroquinone, theAgencybelievesthat the availableinformationindicatesthat substantialnumbers of personsin the workplace areor may be receivingdermalandinhalation exposureto hydroquinone.B. HumanHealthEffects

1. Metabolism(Toxicokinetics).EPAstatedin the support document to theproposedrule that although 92 to 97

percentof hydroquinoneadministeredtorats is excretedin the urine,stutlies inman. dog and rabbit showconsiderablylowerpercentagesof hydroquinoneabsorption/excretion.Thesestudieswere incompleteanddeficientin severalareas.TheAgencybelievedthat thecurrently availabledatawerenotsufficient forpurposesof reasonablypredictingthetoxicokineticofhydroquinone.Toxicokineticstudiesviadermaland oral routeswere proposedbecause:(1) Theprimary routeof humanexposuretohydroquinoneis expectedtobedirectderxnalcontact.althoughthepotentialexistsfor somedirectocularcontactandinhalationof dustorvapors:and(2) the NTPis curgentlyperforn’Iinga 2-yearbioassayon hydroquinone viaan oral exposureroute (gavage).

The industryhas supplied the Agencywith numerouscommentson thetoxicokineticsof hydroquinone basedonnew data and ongoingtestprograms.Also, theyhave discussed(1) the derrnaluptake of hydroquinone, basedon astudyby Marty eta). (Ref. 7), wherethechemical wasapplied to rodentandhumanskinand(2) a dermalabsorptionstudyin dogs by Kodak (Ref. 8). Basedon theMarty studyandthe preliminaryresultsof the Kodakstudy, the industryconcludesthat hydroquinoneis poorlyabsorbedthroughthe skin.

With regardto theMarty study. theAgency believesthehydroquinoneformulationused,andto a lesserextentthe methodology,render the useof thisstudy,qnestionableasan accuratecharacterizationof actual hydroquinonepenetration of human skin in the.workplace.A major concernwith thisstudyis the useo a preparationofhydroquinone which contained75percentwater. Hydroquinone is watersolubleandwhenadministered to theskinin a predominately aqueousform, itmay have a tendencyto stay in thesolvent ratherthanpenetratethe lipidmembrane of the skis.Becauseof theexpectedlow- diffusional driving force ofan aqueoussolutionof hydroquinone ascomparedto theexpectedhigherdiffusionaldriving force ofhydroquinone itself, the Marty studymayunderestimateactual hydroquinonapenetration that personswouldexperiencewhenexposedto non-aqueous(e.g.powdered)forms of thechemical.

Umitationsto the studyarealsoImposedby the useof rats for theparenteral dosing while micewereusedfor in vivotopical administration.Whileboth speciesare equally sensitiveto thetoxic effectsof orally administeredhydroquinone.usuallytheexcretionkinetics of parenteral dosing aredevelopedutilizing the samespecies:

theremaybesignificant speciesdifferenceswith respect tobiotransformationandexcretionofhydroquinone~

Theindustryhasinformed theAgencyof an ongoing testing program that w:1explore the areaof metabolic fate ofhydroquinone. percutaneousabsornt:onand blood elimination kinetics. Althoughthedata from thesestudiesmay provideadequateinformation to relate doselevelsof hydroquinonefrom expectedhumanexposuresto dosesadministeredin a bioassaybeing conductedby theNationalToxicologyProgram.theAgency.doesnotcurrently havethecompleteindustrystudiesin hand forevaluation.Therefore.theAgency isrequiringthemetabolismtestingdelineatedin theproposedrule.

2.Developmentaltoxlcit.vandreproductiveeffect.s.At oral dosesoi30mg/kg/day and higher, Racz reportedthat hydroquinoneprolongedthediestrusperiodof thesexualcycle infemaleaibino rats (Ref. 9). Skalka(Ref.10), subcutaneouslyinjecting male ratsat a doseof 100 mg/kg/dayfor 51 days.reporteddecreasedweightsin testes.epididyinides,seminalvesiclesandadrenalglands:histologicalchangesintestesindicatingdisruptedsperiniogenesis;anddiminishedDNAcontentof spermheads.Telfordet 01.reportedthatat a doselevel of 0.5gof~hydroquinonein thediet administeredtofemale rats duringpregnancy.fetalresarptionsresulted (Ref. 11).Becauseoftheaforementionedreproductivesystemeffects,theAgencyproposedreproductiveeffectstestingforhydroquinone.

Therewereno reports in the literatureof hydroquinonestudiesexplicitlydealingwith teratogerucordevelopmentallytoxic effects:howeverbecauseof theevidenceof fetalresorptions,theAgency determinedthattestingof hydroquinonefordevelopmentaltoxicity is warranted.

The industry,commentingon EPA’sbasinghydroquinone’steratogenicactivity on theTelfordet al. study(Ref.111,statedthat the increasedfetalresorptlonsare not necessarilyIndicativeof terata formation andmoreover, the studyis incompletelydescribed.The industrycommentedthatthe poor quality of the study and the towhuman exposuredo not justifyteratology testing.

Concerningreproductive effects,theindustry statedthat in a study by Ameset a!. (Ref. 12), feeding hydroquinone ata levelof 0.3 percent in the diet offemale rats for 10daysprior toinsemination causedno impairment.They alsocommentedthat the results of

r~oeratKegister / Vol. 50, No. ~50 / Monday. December30,. 1985 / Rules and Regulations 53149

theRaczstudydo not suggesta femalereproductiveproblem.They expressedno surpriseat reproductiveeffectsinmalerats in theSkalkastudy(Ref. 10)because51 subcutaneousinjectionsof100 mg/kg wereusedwhile thesubcutaneousLD~in ratshasbeenreportedto be between300 and350 mg/kg.

The industryhaspointedout that theAgency’squestionsraisedby thesepapersare beingaddressdby adominantlethalassayanda teratologystudy,bothbeingconductedby Kodak.Industryarguesthatpreliminaryevidenceindicatestheabsenceofadverseeffectsin thesestudiesandrefutesany suggestionof reproductivetoxicity by thedataof SkalkaandTeltord.

While the industry’s commentsrelativeto teratogenicityandreproductiveeffectsare valid in somerespects,theydo notalleviatetheAgency’sconcerns.The AgencyconsiderstheTelford et ci. study(Ref.11) showingresorptionsverymeaningful.Although theindustry’scommentthat resorptionsdo notnecessarilyindicateterataisvalid.resorptionsdo indicatesometypeofdevelopmentaltoxicity of which terataare butoneaspect.The Agency’sconcern,therefore,is over thepotentialof hydroquinoneto bea developmentaltoxicant.Thefour manifestationsofdevelopmentaltoxicity are aeath(whichincludesresorptions).malformations(terata),growthretardation,andfunctionaldeficits,

It is truethat theAmesataLreproductivestudy(Ref. 12) wasnegative;however,doselevelsmaynothavebeenhighenough;no toxic effectsof anykind were reported.Thisstudymaybea falsenegative.

EPA andCMA disagreeon thedosingregimenandlevelsin theRaczat a!.study(Ref. 9). 1! the industry’scontentionthat theanimalsfirstreceiveda high dose,whichwasloweredlater,is correct,thenthis studyis of questionablevalue.

TheSkalkastudy(Ref. 10) showedcleartesticulartoxicity via thesubcutaneousroute.Althceghsubcutaneousdosingis notrepresentativeof expectedroutesofhumanexposureto hydroquinone,theresultsof this studysuggestthat ifhydroquinoneis absorbedas a resultofdermalor inhalationexposuresit couldproducetesticulartoxicity. Theindustryis correctin pointingout thatthe~testiculareffectswerenotedat about0.3

a high dose.However,EPA cannotignorethe positiveeffectsnotedandcannctpredictthe effectsof otherdoselevelsandother routesof exposure.The

Agencyneedsfurtherdatabeforethiseffectcanbeassessed.

BecauseEPA’s concernsin theareasof developmentaltoxicity andreproductiveeffectshavenot been’allayed,theAgencyis requiringtestingin theseareasas describedin theproposedrule.

3. Oncogenicity.EPAreportedthatseverallong.termanimalbioassays(rruce) werenegativealthoughtheydidnot meetcurrenttestingstandards,Inonestudy(Ref. 13) bladdercarcinomaswereproducedin miceimplantedwithcholesterolpelletscontaininghydroquinone.This testis not .recognizedas a valid measureofcarcinogenicpotentiaLHowever,becauseof this positiveresultand thepositiveresult in a in vitro celltransformationassay(Ref. 14), furtheroncogenicitytestingis warranted.BecausetheNTPis conductinga 2.yearbioassaywith hydroquinone.noadditionaloncogenicitystudieswereproposedin therule.

Industryhascommentedthat.althoughtheAgencyhasassertedthathydroquinoneis a suspectedcarcinogen.EPAhasprovidedno supportandindustryis unawareof anystudiesinanyanimalspeciesthatdemonstratethis assertion.

While the two studiescitedareviewedby EPAas suggestivethat thecompoundmaybecarcinogenic,theNTP bioassayis neededto confirmorrefute thesuspicions.Thisstudyisplannedto be completedby mid-1986.

4. MutagenicityandCytotoxicity.TheAgency concludediii theproposedrulepublishedin theFederalRegisterofJanuary4, 1984(49 FR 438), that themutagenici~tystudiesinvolvinghydroquinoneshowedequivocalresults.Hydroquinonehadbeenreported.(a) tobemutagenicin oneSalmonellatest(Ref. 33), (b) to bemutagerucin abacterialDNA repairassay(Ref. 34).and(c) by theNationalToxicologyProgram,to inducesisterchrornatidexchangesandchromosomalaberrationsin Chinesehampsterovarycells(Ref. 35).Priorto issuanceof theproposedrule, Goodyear(Ref. 38)submitteddataincluding: (i) DNAdamagein & coil. (ii) sex-linkedrecessivelethal (SLRL) assayinDrosophilain.. (by ServaandMurphy)(iii) Salmonellamicrobialassay(Ames),and(iv) in vitro cell transformationassay.The DNA damageassayandthecell transformationassaywerereportedaspostive,while theSalmonellamicrobialassaywasnegative.TheSLRLassaywasreportednegativebuttherewereinadequaciesin theprotocolandreporting.With postiveresultsincytogeneticsandsisterchromatid -

exchangein testsby theNTP. EPAconsidereda dominantlethal testinmice to be the appropriatenextstep intestingfor chrornosomaleffects.

Hydroquinonehadnotbeenadequatelytestedfor its ability toinducegenemutations.Becauseofequivocalresult in theSc/manilafyphirnurium/mammalianrnicrosomalassay.EPA proposedthathydroquinortebe testedfor its ability to inducegenemutationsin mammaliancells in culture.Positiveresultsin this testwould dictatea SLRL assayin Drosophila,and, if thelattertestwaspositive, a mousespecificlocus assay.

With regardto theproposedgenemutationtestrequirement,GoodyearTire andRubberCompanyhasnowsubmitteda completereportof theDrosophilaSLRL testby ServaandMurphy (Ref. 15). TheAgencyhasreviewedthe dataandagreesthat thistestadequatelydemonstratesthathydroquinonedoesnotincreaserecessivelethal mutationsunderthe testconditions.A secondDrosophila testwaspartof a batteryof threeassaysreportedby Gockeat ci. (Ref. 16) whichincludedtheSalmonella/mammalianliver microsometest(Ames test),theBascteston Drosophiladetectingsex-linked recessivelethal mutations,andthemicronucleustestdetectingchromosomeaberrationsin mousebone-marrowcells,ThissecondDrosopnziatestalso providessufficient informationto indicateno increasein recessivelethal mutationsunderthe testconditions.Therefore,EPAfinds nofurthergenemutationtestingofhydroquinoneto be necessaryat thistime.

With regardto theproposedchromosornalaberrationtests,positiveresultswerereportedin themousebonemarrow micronucleustestby Gocke(Ref. 16). Becausehydroquinonecauseda dose-dependentincreasein thenumberof micronclelfoundin mousebonemarrow,a dominantlethal testinrodentswasindicated.

Kodakhassubmitteda dominantlethalassayof hydroquinonein rats(Ref. 17) andtheAgencyhasreviewedthis study.Thisassayshowednolethalityup to a dosecausingsignsofclir.ical toxicity andsomespontaneousdeath.

Sincenegativeresultshavebeenreportedin two SLRL testsand thedominantlethal assayinratssubmittedby Kodak is alsonegative.EPAconcludesthat no further testingforgenemutationsor chromosomalaberrationsis necessaryat this time.

5. Ner.’ousSystemEffects.TheAgency concludedthat the testdata

~)1.)U ~C~~14Z ~3t~T / VOl. bO, INO. 250 1 Monday, December30. 1985 / Rules and.Regulations

identifieddid not adequatelycharacterizethepossibleneurotoxiceffectsof hydroquinone~Proposedtestingincludeda functionalobservationalbattery,neuropathologyandmotoractivity oroperantbehavior.

The industryhascommentedthat theinformationrequestedby theAgency iseitheralreadyavailableor maybe’readilyavailablefrom ongoingtestingprograms.Theystatethatonly acutetests.conductediii intactanimalsprovideanymeaningfuldata-becausetheyaccountfor the blood-brainbarrierrresearchtype rteuropharrnacologicandneurophysiologicstudiesareinapplicable.

ThecommentersstatethattheNTPhydroquirroneoncogenicityandchronictoxicity studieswill generatedatasimilarto thosedevelopedinafunctionalobservationaLbattery.Ther.europathotogydatacansimilarly beobtainedfrom modifiedNTPstudies..Finally, theybelievethatmotoractivitydatahavealreadybeenreportedbyChristianet ci. (Ref. 18).EPA agreesthatthe motoractivity dataderivedfrorn.thisstudysatisfythemotor-activityoroperantbehaviortestingendpointEPA..however,disagreesthatongoingandplannedNTP testingcouldgeneratedatasimilar to’ afunctionalobservationalbatterybecausetheNTPprotoeol~developedfor thepurposesofoncogenicitytestingrseverelylimit thequality ~ndextentof clinicalobservation.Therefore~afunctionalobservationalbatteryis. requiredasproposed.

Theindustryhas.alsostatedthat theNT? studiescould.be.readilymodifiedto adequatelyscreenforneuropathology.While this maybetrue,thetwo-yearbioassayfor hydroquinone-hasalreadyprogressedto thestageof

sacrificing of testanimalsandthisoption,is. no longeravailable.,Therefore,neuropathologytestingfor h.ydroquinone.is required.

6.Epidemiology.TheITCrecommendedepidemiologicstudies.for

- . hydroquinoneif anappropriatecohortcould he identified.

Limited epidemologicstudiesinvolving exposureto hydroquinonehavebeenidentifiedby theAgency.Theexistingliteratureincludesoccupationalcr,ss-sectionalstudiesandcasereportsof ex,osureof populationsthroughdermalapplicationandaccidentalingestion.aswell asexperimentalexposureto hydroqulnonebyeither

ingestion or topical application.To date,the mostreliablereportedhumaneffectsattributedto hydroqoinoneexposurehavebeenrestrictedto theeyeandskin.A positivecorrelationbetweenthedegreeof eyeinjuryanddurationof

occupationalexposuretohydroquinortehasbeenreported(Refs.19 through2Z).

Additionalconcernfor potentialhumanrisk,comesfrom two studiesofKodakemployees.First, a case-controlstudyofbraincancers.by Greenwaldetci. (Ref. 24) observedelevatedoddsratio withblac.kandwhite developerexposure.Hydroquinoneisknownto bea componeulofblackandwhitedevelopermixes.Secondly,acohortstudyof photographicprocessorsin nineEastmanKodakColorPrint andprocessinglaboratoriesalsoreportsanexcessof braincancermortality.Individual exposureswerenot examinedin this study,buthydroquinoneandquinonewereidentifiedamongthemanypossibleexposures(Ref. 23).’

EPA proposedthata cohortstudybeconducted.designedto detecta 50percentincreasein totalcancerincidencewith at least80percentprobabiUty whenbothraqdomandnonrandomsourcesof errorhavebeenconsidered.Incidenceandmortalityfrom a full spectrumof endpointswereto’ beexamined(e.g.,specificforms.ofcancer,andavarietyof’ oculareffectsincludinglossof visualacuityandconjunctivalorcornealchanges).Additionally, to addresstheAgency’sconcernsregardingthepossibility ofteratogernc.effectsandadversereproductiveeffects,theAgencybelievedastudyof theseareaswouldbe appropriate.Sucha study,preferably’prospectiveandincludingbothspouses..wouldcomplementtheAgency’srequestforanimal teratologyandreproductivestudies.

Theindustrycommentersbelieveasuitablestudypopulationdoesnotexist.Cooimenters.identifiedtwo populationsfor-possiblestudy,manufacturingworkersandphotohobbyists.andstatedthata studyof eitherpopulationis notfeasible(Ref. 5). A smallnumberofemployeesworkin the manufacturingofbydroqurnone.totaling100workersbetweentwo differentplants.Industrystatedthatepidemiologicstudyof thispopulation-would havelow powertodetectsmallrelativerisks forcancer-orreproductiveendpoints.TheAgencyagreeswith this comment.EPAalsoagreeswith thecommentthatphotohobbyistsmaynotbe a feasiblepopulationforstudythe to potentiallylowerexposurelevelsandmultiplechemicalexposures(Ref.1).

TheAgencyhasbeenunabletoidentify anothergroup,asidefrom theaforementioned.thatmayproveto be asuitablepopulationfor epidemiologiqstudy.Therefore,theAgencyis.notrequiringepidemiologicstudiesat thistime.

C. ChemicalFateand£‘~vironmetuaJEffects

TheITC, in its Fifth Report,statedthat thereis substantialopportunityforhumanandenvironmentalexposuretohydroquinone’andpossiblyto itsoxidationproducts.semiquinoneandquinone,andrecommendedenvironmentalfatetesting. - =

TheAgencybasedits chemicalfateand,environmentaleffectstestingforhydroquinoneon theauthority of section4(a)(1)(A)0ITSCA.

Although the ITC did not recommendenvironmentaleffectstestingforhydroquinone.the Agency wasconcernedwitheffluentsfromphotoprocessingfacilities andproposeda seriesof environmentaleffectstests.Basedon existingaquaiictoxi~tydata-andthelimited,dataon photoprocess±ngeffluents,theAgencybelievedthat thelevelsof hycfroquinonein thoseeffluentsalthoughnotso substantialasto indicatea section4(a)(1)(B) finding.couldpresentan unreasonablerisk toaquaticorganisms.

TheAgency proposedchemicalfatetesting.for hydroquinonebecause.theexistingchemicalfatedatawerelimitedandmoredatawereneededto assessthemagnitudeof thepossibleriskstoaquaticorganisms.EPAneededinformationto establishbiodegradationratesin, orderto assess.the levels ofhydroquinoneexposureto aquaticorganisms.

In the“EnvironmentalRelease”sectionof its technicalsupportdocumentfor theproposedrule, EPAreportedthatconcentrationsofhydroquinonein photographicprocessingeffluentsrangefrom 10 to 390ppmandnotedthat therewasnoinformationregardingthetotalvolumeof release.A pilot plantstudyofphotographiceffluentsby EastmanKodakreportedhydroquinoneconcentrationstobeless than0.04mg/I.(0.04 ppm)afterbiodegradationbytreatmentwith anactivatedsludge(Ref.25).However,althoughnaturalaquaticecosystemsmaycontainacclimatedorganisms,theability of theseecosystemsto degradevariousconcentrationsof hydruquinoneandquinoneis unknown.

The Agencyproposedchemicalfatetestingof hydroqwnonethat wouldestablishtherateof biodegradationinorderto assesspossiblerisksto aquaticorganisms.

EPA.wasconcernedwith thelevelsofhydroquinoneremainingin effuentsfrom phutoprocessingactivities(aftertreatmentlbecauseat levelsapproachingO.O4rng/L hydroquinone

FederalRegister I Vol. 50, No.. 250 / Monday, December30, 1985 / Rules and Regulations 53151

couldpresentanunreasonablerisk ofinjury to aquaticorganisms.TheAgencyproposedaquatictestingto providedataregardingno-.effectlevels,LC50’s anddose.responserelationships.Thesetestswould involve both freshwaterandsaltwaterorganismsand includedacutetests.acute.chronicratiosin aquaticanimals,testswithalgaeor chronictestingwith vascularplants.and

- bioconcentratiorrtestsin aquaticanimalspecies.This varietyof testswouldprovidesufficientdatato supportregulatoryaction undertheCleanWaterA~ct. -

The commentsthe Agencyhasreceivedfrom the industryadequatelysupporttheir contentionthatmanufacturingprocessesanddarkroomhobbyistsdo not provideconsequentialenvironmentalreleasesofhydroquinone.

With regardto possiblereleasesofhydroquinonefrom photopror.essors,theresultsof a Kodaksurveyby Ambroseeta!. (Ref. 26) suggestthat themajority of34 plantssampleddischargedeffluentscontaining30 Mg/I. to mg/L ofhydroquinone.Irrespectiveof dilution.theconcentrationof hydroquinonewillbereducedto 50 ~g/L from mg/I. if 95percentremovaloccursas in typicalPOTW(Ref. 28). Further,the combinedeffectsof dilution with domesticandotherwastesenteringthePOTWanddilution after dischargeto theriverwillnormally ieadto at leastanadditional10 to 100 fold reductionin hydroquinoneconcentration(0.5—5~g/L)(Ref. 28).Therefore,sinceit appearsthat thesampleis representativeof the industry, -

EPAconsidersit is reasonabletoestimatethatmaximumin~streamhydroquinoneconcentrationsshouldnotexceed5~g/I...

Additionally, theindustryhasprovidedinformation that indicateshydroquinoneandquinonewill bereleasedfrom photoprocessingplantsashydroquinonemonosulfonatewhich islesstoxic to aquaticlife (Ref. 1).

TheAgency alsowasconcernedwiththepossibledirectdischargeofhydroquinoneand hydroquinonemonosulfonatefrom photoprocessingplantsto receivingwaters.ThestudybyAmbroseet ci. (Ref. 28) suggeststhatmotion picturephotofinishersrepresenta categorythat may deservemoreattention.Only five labs weresampled,.but two of thosedischargedeffluentscontaining3—6.9mg/I. of hydroquinoneand18.4—41.2mg/I. of hydroquinonemonosulfonate.All four samplesfromthesetwo labscontainhydroquinoneandhydroquinonemonosulfonate.

The industry, however,has providedinformation on the useof hydroquinonefor motion pictureprocessing.According

to Kodak(Refs.29 and 30). thiè usehassubstantiallydecreasedin the last5yearsfrom 14.000kg/yr to less than4,000kg/yr. Furthermore,Kodak statesthat “all” largephotoprocessorsarelocatedin urbanareasandare.therefore,likely to dischargeto POTW’sand thatanydirect dischargerswouldbe subject to the NPDESpermit programandeffluent limitations andguidelinesof 40 CFRPart459.Kodak alsohas -

providedstatisticsto showthatcurrentlythereare 500 motion pictureprocessorsin theU.S.(Ref. 30). -

The industry’scommentsdo notcompletelysupporttheir statementthat“no consequentialenvironmentalreleaseoccursfrom photoprocessingoperations”(Ref. 1). Thecommentersstatethat gg percentof the plantsdischargeinto POT’W’s: theremaining1percentmustbeassumedto bedischargingdirectly to receivingwaters(Ref. 1). TheAgency hasonly beenableto identify limited informationregardingtheactualnumberof plantsthatwouldcomprisethis 1 percent.andhasnoinformationregardingthevolumeofdischargesor theflow of the receivingwaters.However, in conductinga searchthroughEPA’s WaterPermitComplianceSystemsrecords(Ref. 31), the indicationwasthat this segment(approximately40dischargers)is averyminorsegmentofthe entirehydroquinone/hydroquinonemonosulfonatedischargein termsoftotal releases.Additionally, thedeclinein useof hydroquinoneandtheswitchingto new products should lowerrisk from directdischargesofhydroquinone. In summary. given thatmost of the releasesof hydroquinoneandhydroquinonemonosulfonateareprocessedthroughPOTW’sand shouldnot be releasedinto receiving waters atconcentrationslikely to poseanyunreasonablerisk, and that the 40processorswho maybedirectdischar’gersdo not appear to representamajoror significantportionof the totaldischarge,theAgencyis notrequiringchemicalfateandenvironmentaleffectstestingaspart of the hydroquinone finalrule. -

D. Ongoing Testing

On June15. 1983.industryrepresentativesnotified EPA that theywereplanningto conductvarioushealtheffectstestsin thenearfuture.EastmanKodak CompanyprovidesEPAwithprotocolsfor testingin theareasofmetabolicfate. percutaneousabsorption.bloodeliminationkinetics,mutagenicity.teratology and reproductive effectsandrequestedEPA’s commentsontheadequacyof theseprotocols.HavingreceivedtheAgency’scomments,theindustryembarkedon manyof these

studiesandEPAanticipatesthat manyof thesewill meetthetestingrequirementsestablishedby the Agencyin the hydroquinonefinal rule. However.sincemanyof thesestudieshaveonlyrecentiyreachedcompletionor arest~ilunderway,EPA currentlyhasreceivedin manycasesonlysummaryor interimreports.BecauseEPA hasnot yetreceivedsufficientraw dataandotherbackupmaterialsrelatingto the alreadycompletedstudiesandonly progressreportsin thecaseof ongoingstudies.theAgency presentlyhasinsufficientdatato reasonablypredictor determinethe humanhealtheffectsresuiting fromexposureto hydroquinone.

IV. FInal Test Rule for Hydroquinone

.4. Findings

EPA is basingits hydroquinor.ehealtheffectstestingrequirementson theauthorityof sections4(a)(’L) (A) and (B)of TSCA.

1. EPA finds that hydroquinoneisproducedin substantialquantities,andthat theprocessing,distribution andu~eof hydroquinonemay result insubstantialhumanexposureto thischemical.

Thesefindingsarebasedon thefollowing information:

a.Therearesubstantialamountsofhydroqurnoneproducedin the (JnrtedStateseachyear.TheannualU.S.productionvolume of hydroquinoneisestimatedto beas high as27 millionpounds.

b. in 1980. theNationalInstituteforOccupationalSafetyandHealthestimatedthatapproximately470.000U.S.workers,in 137 occupations.arepotentiallyexposedto hydroquinoneannually.Although this figuremayoverestimatethenumberof workersactuallyexposedto hydroquinone,evena few percentof theestimatewould besubstantial.

TheAgency believestherearesubstantialnumbersof people in theworkplace involved in distributing andprocessinghydroquinoneas it isincorporatedinto rubberchemical~andother uses.

-EPA also believesthat therearevarying amountsof automationfoundinthe2.000photofinishinglabs reportedbythe industry; older operations, andspecificallythosedealingwith largevolumesof blackandwhite developing.may resultin significant workerexposure.

By industryestimates,thereare800.000peoplewho usephotographicdevelopersin homedarkrooms.TheAgencybelievesthat’includedin thisgroup aresomehobbyistsand

531~ Fe~fe~alRegister/ Vol. 50, Nc~,250 / Monday, December30,1985’ / Rules and Regnlatforrs

ind~viduaIsinvolved in specialtyworkwho, becausetheyareirrtertsivelyinvolved in blackanrf white’pholography-,wilt havemotefrequentexposuresfor longerperiodstohydroquinonethan the“average”ptiotohobbyist.

TheAgency believesthat theseworkersandhobbyistsmay receivebothinhalathsnanddermalexposuretohydroquinnne.

2. In addition.EPA hasfoundthattheprocessingand.useof hydroquinonemaypresentanunreasonablerisk ofinjury to humanhealthfrom nervoussystem,developmentallytoxic,reproductive,andcarcinogeniceffects..TheAgency’sbasisfor thesefindings ispresentedin thetechnicalsupportdocumentfor theproposedruleandinUnit JILB. of this preamble.

3. EPAfinds thatexistingdataandexperienceare inadequateto reasonablypredictor determinethedevelopmentaltoxicity andnervoussystem.reproductiveandcarcinogeniceffectsofexposuresto hydroouinone.The -

Agencysbasisfor thesefindingsispresentedin thetechnicalsupportdocumentfor the proposedruleand,inUnit 111.8.of this preamble.

4. EPAalsofindsthat,exceptin the’caseof carcinogenicitywhere.adequatetestingby NTP’is ongoing-.testingisnecessaryfor theseeffects~

Toxicokinetictestingisalsonecessary- for thepurposeof reasonablypredictingthe-toxicokineticbehaviorofhydroquinoneand tohelp interprettheothertestingbem~requiredby EPAandperformdby NTP’, TheAgency isrequitinglimited metabolism(toxicokinetic)studiesofhydroquinonavia dermalandoral routesof exposure.These-studieswill, provideareliablemeansby which theinternaldoseadministeredin theNTPbioassayandEPA-requiredstudiescan.berelated.todosesexpectedto bereceived,byworkersandhobbyists..

EPA doesnot belieuethatthis- rulewill result in a loss to societyof thebenefitsof hydroquinone’becausetheAgency’seconomicevaluationhasshownthattheeconomicimpactof the’testingbeingrequiredfor thissubstancewill beminimal.

~ RequiredTesting

EPAis requiringthat hydroquinonebetestedfoereprodiretive.teratogenicandnervoussysteareffectsand that itstoxicokineticsbee~lested.

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t~ot~.ogoxed becauae NTP e con~~c~iga Z-ysubsouuv.Aoe~ata date on moloi acbetp have beevt recoeilI~fl~Nooatflo4ogyand teatfn9 vi a hnctionaf oOu1i~axofl~baoey ~e aix, needed.

‘EPA agrees eim ~OmITIe1ixW*that pa*za4. ~Iort*cannot be x’-rrthed at t am.

0110 ovox—aed fl respa~eto proooa.~ru’e affow laC* ~sutf’cx,nt e vo(vnenlaI concenvaDons to sugpofl lesang.

C. TestSubstanceEPA is requiringthathydroquinoneof

at least99 percentpurity, availablecommercially,beusedas the testsubstance.EPAhas-specifiedarelativelypuresubstancefor testingbecausetheAgency is interestedinevaluatingthe’effectsattributedtohydroquinoneitselLThis requirementwill increasethelikelthoodthat.anytoxic effectsobservedare relatedtohydroquinoneandnotto anyimpurities,

D. PersonsR~quiredToTestSection4(b)(3)(B) of TSCAspecifies

that theactivitiesforwhich theAgencymakessection4(alfindings(manufacture,processing,distrihution.useand/ordisposal)determinewhobearstheresponsibditiesfor testing,Manufacturersare.requiredto testif thefindingsarebasedonmanufacturing(“manufacture”isdefinedin. section3(71of TSCA to include“imporf).Processorsarerequiredto testif thefindingsarebasedon processing,Bothmanufacturersandprocessorsarerequiredto testif theexposuresgivingriseto thepotentialrisk occurduringuse.distribution,or disposaLBecauseEPAhasfoundthat the-processing.distributionin commerce,anduseofhydroquinonegivesrise to substantialhumanexposure~to the’ chemicalandthatsuchactivitiesmaypresentunreasonablerisks tohumanhealth.EPAis requiringthatpersonswhomanufacture’or process.orwho intendto manufactureorprocessthis chemical.at anytimefronsthe’effective’dateofthis testruleto’ theendof thereimbursementperiod,be subjectto therule. Theendof the-reimbursementperiodwilibe 5-year’safterthefinalhydroquinone.reproductiveeffectsreportis submitted.As discussedin the

Agency’stestruleandexemptionprocedures(40GRPart790),EPAexpectsthat manufacturerswill conducttestingand thatprocessorswillordinarily be exemptedfrom testing.

EPA is. however,exemptingfromthesetestingrequirementsthosemanufacturersandprocessorswhichproduceandprocesshydroquinoneonlyas animpurity. “Impurity” is definedin40CER790.3 to mean“a chemicalsubstancewhich is unintentionallypresentwith anotherchemical.substance.”TheAgency is exemptingthosemanufacturersandprocessorsbecausethe EPA’s findings undersections4(a)(1)(A)and4(a)(1)(B) arebasedon exposuresto hydroquinonewhich area result of intentionalprocessing.distribution in commerceanduseandwhich representa potentialunreasonable.risk.The Agencywouldfind it difficult to applyboththeexemptionandreimbursementprocessesto thosewho manufactureand/orprocesshydroquinonesolelyasanimpurity, In fact, the Agency’sreimbursementregulationsissuedpursuantto section4(c) statethat thosemanufactureorprocesschemicalsubstancesasimpuritieswill notbesubjectto testrequirementsunlessthe-rulespecificallystatesotherwise(40CFR 791.48b).

BecanseTSCA containsprovisionsto~avoidduplicativetesting,not everypersonsubjectto this rulemustindividually conducttesting.Section4(b)(3)(A) of TSCA providesthat EPAmaypermit two or moremanufacturersor procrssorswho are subjectto-atestrule to designateonesuchpersonor-aqualified third personto conductthetestsandsubmitdataon theirbehalf.Section4(c) providesthatanypersonrequired to testmayapply to EPAfor anexemption-from that requirement.TheAgencyanticipatesthat thecurrentmanufacturersof hydroquinonewiltform thereimbursementpoolandsponsorthetestingrequired.Manufacturersandprocessorswho are’subjectto thetestingrequirementsofthisrulemustcomplywith the testruleandexemptionproceduresin 40 CFRPart790. EPAis notrequitingthesubmissionof equivalencedataasaconditionforexemptionfrom therequiredtesting.As notedin. Unit IV. B,EPAis interestedinevaluatingtheeffectsattn butableto hydroquinoneitself andhasspecifieda relativelypuresubstancefor testing.

£ TestRule-Developmentand£remplieas

Elsewherein today’sFederalRegister.theAgencyis proposingthatcertain

ceder-a!Register I Vol. 50, No,. 250 1 Monday, December3.0,. 1985 I Rulesand Regulations 53153.

01’StestguidelinesandEPA-approvedindustryprotocolsbe utilized as test.standardsfor thedevelopmentof dataunder this rule for hydroquinone.Asdiscussedin that noticeandin previousnotices(50 FR 20652),EPA hasreviewedthemethodfor developmentof testrulesandhasdecided-thatformostsection4rulemakings..theAgency-wilt utilize’singi-ph.~erulemaking.In light of thisdecision,EPAhasreevaluated-theprocessfor developingteststandardsforsection4 rulemakingsinitiated urideratwo.phaseprocessandhasdeterminedthat for certainof thesetwo-phaserules,,OTStestguidelinesare availableforpromulgationas relevantteststandards.EPAhasdecidedthatwhereOTSorother appropriate testguidelinesare’available,theAgency in moatcases.willproposetherelevant guidelinesastheteststandardsfor those.rules;

EPAbelievesthat,.in line’ with its-commitmentto- expeditethesection4rulemakingprocess,it is appropriateto’proposethe applicable01’S testguidelinesas teststandardsat thesameasa PhaseF final testrule is issued..With regardto therulemakingforhydroquinone..01’S.testguidelinesandEPA.approveiiindustryprotocolsare

- - available for all~the testing-requirement,includedin thisPhasetfinairule. Thus,in theaccompanyingnotice,theAgencyis proposingthese01’Stestguidelines

and industryprotoeols.a,teststandards;The’public, including;the

- manufActurersandprocessorssubjecttothePhaseI rule,,will, have anopportunityto.commenton. theuse.of --

the01’S- testgutdelines.andindustryprotocols.The Agencywill review-thesubmittedcommentsandwill modify the.01’Sguidelines,where.appropriate.whenthe teststandardsare’promulgated.

During the-developmentof a testrule -

underthe two-phase’process,personssubjectto the Phaseifinal rule are.normally requiredtosubmitproposed.studyplans.within.9Qdays.altertheeffectivedate ofthe Ph-ase~Irulemaking..See4GCFR79O.3o(a~(,Z).However.because.EPAis proposing;applicable01’S testguidelinesas the teststandardsfor thestudiesrequiredbythis PhaseI final rule, personssubjecttothe rule. i.e.,manufacturersandprocessorsof hydroquinone,are-notrequiredto submitproposedstudyplansfor therequiredtestingat this. time,Personssubject to this rule,,however,are still requiredto submitnoticesointentto testor-exemptionapplicationsin accordancewith 40-CFR790.25.Forthe rule, oncetheteststandardsare’promulgated.personswho have-notifiedEPAof their intentto testmustsubmit

studyplans(which adhere to thepromulgatedteststandards)no laterthan30 daysbeforethe initiation ofeachrequiredtest.- Processorsofhydroquinonesubjectto-this rule, unlesstheyarealsomanufacturers,will not berequiredtosubmit lettersof intent, exemptionapplications or study plans (beforetestingis initiated) unlessmanufacturersfail to sponsortherequiredtests;Thebasisfor’ this decisionis thatmanufacturersare expectedto passanappropriateportioriof the testscostsonto processorsthroughthepricing ofproductscontaininghydroquinone.

EPA’s.final regulationsfor the-issuanceof exemptionsfrom testingrequirementsare in40 CFR Part790.Inaccordance.with thoseregulations,anymanufacturerorprocessor’subjectto’this Phase1 testrulemaysubmitanapplicationto EPA for an exemption.from conductinganyorall of thetestsrequiredunderthis rule. Ifmanufacturersperform all therequired.testing,processorswill be granted-

exemptionsautomaticallywithouthavingto file applications.

Becausepersonasubjectto this rulefoehydroquinonearenutrequiredtosubmit proposedstudyplansforapproval,EPAwilt grantconditional.exemptionsunderthis rule. Theseexemptions.will be grantedfollowingEPA’s receiptof a letter of intent toconductthe-required-testsratherthanafterreceiptandapproval- of a study-plan. Noticeof EPA’sadoptionof theproposed.teststandardsanddeadlines-will beannouncedin afinal PhaseIL testrule.

In the.accompanyingFederalRegistestnotice,EPAis proposingdeadlinesforthesubmissionof testdata..Suchdeadlinesare requiredundersection4(b)(.1)(C) oLTSCA..Theseproposed.datasubmission.deadlinesareopenforpublic commentandmaybemodified.where appropdatL when- the final PhaseII testrule is promulgated.

F. ReportingRequirementsEPAis.requiringthat alt data

developedunder this rule be reported in.accordancewith theEPAGood.Laboratory Practice(GLP) standardspursuantto 40 CFRPart792..published.in the-FederalRegisterof November29,1983 (48 FR 539227.

EPAis requiredby TSCAsection4(b)(1)(C) to specifythetimeperiodduringwhich personssubject to a testrulemustsubmittestdata.The- AgencyIs proposing:thesedeadlines,elsewherein today’sFederalRegister;

TSCA.section12(b.) requiresthatpersonswho exportor-intendto-exportto a foreign countryany hydroquinone’

subjectto the testingrequirementsofthis rule notify EPAof suchexportationor intentto export.While theresultsofrequiredtestingmay not be availableforsometime, a notice to theforeigngovernmentthat theseexported-

substancesaresubjectto testruiesservesto alertthemto theAgency’sconcernaboutthesubstances.It givesthesegovernmentsthe opportunitytorequestsuchdatathat theAgency maycurrently possessplus whateverdatamaybecomeavailableas a resultoftestingactivities.Thus,upontheeffectivedateof this rule, personswhoexportor intend toexport hydroquinonemustsubmitnoticesto theAgencypursuantto TSCA section12(b)(1) and40 CFR Part 707, Foradditionalinformation,seethe FederalRegisterofNovember19, 1984 (49FR 45581).

TSCA section14(b)governsAgencydisclosureof all testdatasubmittedpursuantto section4 of TSCA. Uponreceiptof data requiredby this rule, theAgencywill announcethe receiptwithin15 daysin the FederalRegister-as

- required,by section4(d). Testdatareceivedpursuantto- this rulewill be-madeavailableforpublic-inspectionbyanypersonexcept in’ thosecaseswheretheAgency determinesthat condifentialtreatmentmust be accordedpursuant tosection.14(b)-of TSCA.

C. EnforcementProvisions

TheAgencyconsidersfailure tocomply with any aspectof a section4rule to beaviolationof section15 ofTSCA. Section15(1) of TSCA makes itunlawful for any personto fail or refuseto comply with any rule or orderissuedunder section4. Section 15(3) of TSCAmakes it unlawful for anypersonto failor refuseto:(1) Establishormaintainrecords,(2) submit reports. notices,orotherinformation,or (3) permit accesstoor copying of recordsrequiredby theAct or any regulationissuedunderTSCA. -

Additionally, TSCA section15(4)makesit- unlawful for any personto failor refuseto permit entryor inspectionasrequiredby section11, Section11applies to any- “establishment, facility..or other premisesin which chemicalsubstancesor mixturesaremanufactured..processed.stored, or heldbeforeor aftertheir distribution incommerce. . . .~‘The Agencyconsidersa testingfacility to bea placewherethechemicalis heldor’ storedand.therefore,subjectto inspection.Laboratory audits/inspectionswill beconductedperiodically in accordancewith theproceduresoutlinedin TSCAsection 11 by designatedrepresentativesof the EPAfor-thepurposeof

—- ‘‘‘ ‘#“ ‘‘~&l £%,.%.~SI’J’-.A ~ •.*4t..J~tS~’A £S%.~5~444A~4~L4.2

determiningcompliancewith thefinalrulefor hydroquinone.These -

inspectionsmaybeconductedforpurposeswhich includeverification thattestinghasbegun,thatschedulesarebeingmet,that reportsaccuratelyreflecttheunderlyingrawdataandinterpretationsandevaluationsthereof.and that thestudiesare beingconductedaccordingto theTSCA CLI’ standardsand in ti’e teststandardsproposedruleof this rulemaking.

EPA’s authorityto inspecta testingfacility alsoderivesfrom section4(b)(1)of TSCA. whichdirectsEPAtopromulgatestandardsfor the~ievelopmentof testdata.

Thesestandardsare definedinsection3(12)(B)of TSCA to includethoserequirementsnecessaryto assurethatdatadevelopedundertestingrulesarereliableandadequate.andsuchother’ requirementsas arenecessarytoprovidesuchassurance.TheAgencymaintainsthat laboratoryinspectionsare necessaryto provide this assurance.

Violatorsof TSCA aresubjecttocriminal andcivil liability. Personswho-submit materiallymisleadingor falseinformationin connectionwith therequirementof anyprovisionof this rulemaybesubjectto penaltiescalculatedasif theyhadneversubmittedtheirdata.Underthepenaltyprovisionofsection16 of TSCA. anypersonwhoviolatessection15 couldbesubjectto acivil penaltyof up to$25,000perdayforeachviolation. Intentionalviolationscould leadto the impositionof criminalpenaltiesof up to $25,000for eachdayofviolation and imprisonmentof up to 1year.Otherremediesare availabletoEPAundersections7 and17 of TSCAsuchas seekingan injunctionto restrainviolationsof TSCA section4.

Individualsaswell ascorporationscouldbesubjectto enforcementactions.Sections15and16of TSCA apply to“anyperson”who violatesvariousprovisionsof TSCA.

EPA~may,atits discretion,proceedagainstindividualsaswelt ascompaniesthemselves.In particular’.this includesindividualswho reportfalse~nformatioaor whocauseit to bere’ported. In addition, thesubmissionoffalse,fictitious, or fraudulentstatementsis a violation under18 U.S.C.1001.

V. EconomicAnalysisof Rule

To assessthepotentialeconomicimpactof this proposedrule, EPA haspreparedaneconomicimpactanalysisthatexaminesthecostof therequiredtestingandanalyzesfour marketcharacteristicsof thechemicaLsubstance:(1) Demandsensitivity. (2)costcharacteristics,(3) industrystructure,and(4) marketexpectations.

Th(economicanalysisof this final- -

hydroquinonetestrule, which estimatesthetotal testingcoststo rangefrom$202,200to $607,700,indicatesthat thepotential for adverseeconomiceffectsdueto theestimatedtestingcostsis low,Thisconclusionis basedon thefollowingobservations;

1. Therelativemagnitudeof the testcost isminor. On anannualizedunitcost basis,the hydroquinonetestcostsare estimatedto rangefrom 0.19 to0.57centsperpound.Theunit costsrepresent0.10 to 0.29percentof thecurrentpriceof technicalgradehydroquinone.

2,Marketgrowth forhydroquirtoneisexpectedto remainstable.

3. The priceelasticityof demandforhydroquinonein its primary usesisrelativelyinelastic.

Fora detaileddiscussionofhydroquinoriemarkets-andthecriteriafor evaluatingthe potentialForeconomicimpact.seetheEconomicImpactAnalysis of the FinalTestRule forHydroquinone(Ref. 37).

Vi. Availability of TestFacilitiesandPersonnel

Section4(bJ(1)of TSCA requiresEPAto consider“the reasonablyforeseeableavailability of thefacilities andpersonnelneededto perform thetestingrequiredundertherule.” Therefore.EPAconducteda studyto assesstheavailability of testfacilitiesandpersonnelto handletheadditionaldemandfor testingservicescreatedbysection4 testrules.Copiesof thestudy.“ChemicalTestingIndustry:Profile ofToxicologicalTesting.”October,1981.canbeobtainedthroughtheNationalTechnicalInformationService,5285PortRoyalRoad.Springfield.VA 22181 (P8-82—140773).

On thebasisof this study. theAgencybelievesthat thereWill beavailabletestfacilitiesandpersonnelto perform thetestingrequiredin this testrule.

VII. PublicRicord

EPA hasestablisheda recordfor thisrulemaking(docketnumberOPTS—420488),ThisrecordincludesthebasicinformationtheAgencyconsideredindevelopingthis rule. andappropriateFederalRegisternotices.The Agencywilt supplementthe recordwithadditionalinformationasit is received.

Thisrecordincludesthefollowinginformation:

.4. Supporting Documentation(1) Federal.Regislernoticespertainingto

this ruleconsistingof.(a! Noticeof final ruleon hydruqutnone.(bEN’otice of proposedrule on

hydroquinone (January 4. 1984. 49 FR 438).

(c) Noticecontainingthe LTC designation01hydroquinoneto the Priority List (December7, 1979.44 FR 706841_

(d) Noticeof final rule onEPA’s ‘I’SCAGoodLaboratoryPracticeStandards(November29. 1983. 48 FR 53923).

(e) Noticeof final rule on testruledevelopmentand exemptionprocedures -

(October10. 1984.49 FR 39774).(F) Interim final rulefor Test Rule

DevelopmentandExemptionProcedures(May 17. 1985. 50FR20652).

(g) Noticeof final rule concerningdatareimbursement(July11. 1983. 48 FR 31786).

(2) Supportdocumentsconsistingofi(a)Hydroquinonetechnicalsupport

documentfor proposedtestrule.(bI Economicimpactanalysisof final test

rule for hydroquinone.(3) Communicationsconsistingof:(a)Written public comments.(b) Summariesof telephoneconversations-(ci Meetingsummariesincluding transcript

of publicmeetingon proposedtestrule.(d) Reports—publishedandunpublished

factualmaterials,including contractor-sreports.

8. References(1) Commentson EPAProposedTestRule

for Hydroquinone.ChemicalManufacturersAssociation.April 10. 1984.

(2) Testimonyof theNationalAssociationof PhotographicManufacturers.(nc.ProposedTestRulesfor Hydroquinone/Quinone:ThomasJ. Dufficy. Esq..April 18.1984.

(3) EastmanKodak.“CommentsbyEastmanKodakCompanyon EPA’s ProposedTestRules.Hvdroquinone49 FR 438andQutnone49 FR 456,April 10. 1984.Appentli~B.

(4) EastmanKodak. “CommentsbyEastmanKodakCompanyon EPA’s ProposedTestRules.Hydroquinone49 FR 438andQuinone49 FR 458.Apnl 10. 1984..\ppendixL

(51 EastmanKodak. “CommentsbyEastmanKodakCompanyon EPA’s ProposedTestRules.Hydroquinone49 FR 438andQuinone49 FR 458.April tO :984.

10) Chrostek,W.).. Healthil,’izardEvaluation/ToxicityDeterminationReport:

- InstantCopyService.Philadelphia.PA:NIOSH-TR~UIlE~7584—235. 1975. -

(7) Marty. eta!.“PharmacocinetiquePercutaneeDe L~1Iydroquinone“C.” Co:~’E~’.Biophorm.Pharmococin.’u. 22.21—2Za.wtt~.TranslationprovidedbyCMAI Marty.es a!. “Rateof percutaneousabsorptionoft4C.hydroquinone,”CR. EuropeanCongressof fliokinetic PharmacologyIV. 1981. 2Z21—~I.1981.

(8) Guest,D., Hamilton.M.L ‘i’ercutaneousabsw’piionoff “Cf hydroquirtonein do~ts.”summaryreportappearingin April 10, 1984commentsof EastmanKodakonHydroquinoneProposedRule (SeeRef. St.1984. Full report not completed.- (9) Racz.G..eta!. “Effect of hydroquinoneandphlonzinon theovariancycleof rats.”Rev.Med (Tirgu.Mures.Rom.) 1959.

(10) Skalka.P. “The influenceofhydroqutnoneon thefertility of male rats”

Federal Register / Vol. 50. No. 230 I Monday. December30. 1985 / Rules and Regulations 53135

Sb. V~vs.$k. Zemed, Brne, RodaB, 12.491—494.1964.

(11)Telford.LR., Woodruff,C.S..andLinford. R H. “Fetal resorptionto therat asinfluenceaby certainanuoxidants:Am./.Anal. 11()’.23—38~1962.

(12) Ames.S.R. eta!. “Effects of DPPD,methyleneblue, 3HT, andhydroquinoneonreproductiveprocessin the rat.” Proc. SocExp.Thai. Med. 93:39—42.1958.

(13) Bo~and.E. etai~“Furthere.v,perirnentson impiantationof materialsinto theuninarybladderof mice.” Br.f. Cancer18:575-.531.196~

(14) Lit~n.“Evaluationof hydrcquinoneinthe in vitro transf3rmationof BALB/3T3 cells.assay.”~981.(Submittedby W.D. DavisofGoodyearTre andRubberCo. on May 27.1983).

(15) Serva,R.J.. Murphy, S.J.“EvaluationofhydroquinoneusingtheDrosophilamcJonogonszer/sex.iinkedrecessivelethaltest.”Submittedascompletestudy(incompleteversionsubmittedMay 27. 1983by Guo-,lvrar)by GoodyearTire andRubberCompanyaspartof April 2. l984~commentsto the nydroquinoneproposedtestrule. 1981.

(16) Gocke,etci. “Mutagenicityof cosmeticingredientslicensedby theEuropeancommunities,”MuLolion Resaarca9091—109.1981.

(17) Krasavage.W.J.“Hydroquinone:Adominantlethalassayin malerats.” 1984.Submitted by Eastn~aftKodakCompanyonAugust24. 1984.

(18) Christian.R.T..at0/. “Thedevelopmentof a testfor thepotability of -

watertreated’by adirectreusesystem.’~U.S.Army MedicalResearchandDevelopmentCommand..Wash,D.C..2031~t.ContractNo.DADA-17-73-G-3o13.Uiu~iersttyof-Cincinnati.1980.

(‘19) Anderson.B. “Observationon-comeaPandconjunctivalpigmentationoccurringamongworkersengagedin themanufacture.of hydroquinone.”Trens.Am. Qphtha/mal.Soc.44:345-394.1946.

(20) Sterner.J.H.. Oglesby,FL., andAnderson..&”Quinonevaporsandtheirharmful effects.Cornea)and’conjunctivalinjuries~’J. Lad, H,v~To.vicoi.- 29:80.73,.1947.

(21)Aaderson..L“CorneaLand.conjunctivalpigmentationamongworkera -

engagedin manufactureof hydroquinone.”Arch. Ophthalmol.38:812-828.194g.

(22) Anderson.B.. Oglesby,F. “Conicalchangesfrom quinana’hydroquinoneexposure.”Arch.OphthalthoL59~495.-6OL1956.

(23) Friedlander.B.R., Hearne,F.T., andNewman,B,J..“Mortality cancerincidence.andsickness.absenceinphotographicprocessors:anepidemiologicstudy.”JOM24~(8). 605-613,19132.

(24) Creenwald,P.eta!. “Diagnosticsensitivitybias—Anepidemiologic-explanationfor an~apparent—braintumorexcess.”/OM 24 (8), 690.494.1981.

(25) Hartzison.K.C.,Belly,. Ri’. “Thebiodegredationof hydroquinoue~.”Rochester.NY: EasiznanKodakCampany~TechnicaLReport..Masch.W~

(28) Ambrose.R.T eta!. “A surveyofphotographicprocessingefituents.”Technical

Memordndurn.KodakResearchLaboratories.Rochester.N.Y.Augu.st1. 1977.

(27) National Associationof PhotographicManufacturers.LettertoDavid Price.Test

- RulesDevelopmentBranch.Officeof ToxicSubstances.EPA. August23. 1984:

(28) USEPA. MemorandumfromExposureEvaiu~ttonDivision to TestRulesDevelopmentBranch.July 30. 1984.

(29) USEPA,Conferencecall betweenEPAandCMA, KodakandG~ooyear.Discussionof varioustssues.I’.ugust20. 1984.

(30) EastmanKodakCompany.LettertoDavidPrice,Test RulesDevelopmentBranch.Office of Toxic Substance,Follow-updiscussionof pointscoveredin August20.1984conferencecall (ReL 29). IncludesappendicesA—E and ‘1983—84WolfmunReportasappendixB. August27,1984.,

(31) USEPA.Memoranduntfrom HealthandEnvironmentalReview-Di.ision to Test’RulesDevelopmentBranch,September7. 19S4.

(32) MathtechInc. Economicimpactanalysisof proposedtestrulefor quinoneandhydroquinone.Washington.0-C. Office ofPesticidesandToxic Substances.U,S.EnvironmentalProtectionAgsncy.C-~ntract68-01—6630.December5, 1983.

(33) Cotruvo.J,A..et ci. Investigationofirrutageniceffectsof productsof ozonationreactionsin- water.Ann.N.Y. Aced.Sci.298:124—140.1977.

(34) Bilimoria, M.H. Thedetectionofmutagenioactivityof chemicalsandtobacco’smokein abacterialsystem.Mutat~Has.31:328.1975

(35) EMTDP.EnvironmentalMutagenesisTestingDevelopmentProgram.Computer -

Printout.NationalToxicology Program.December3. 1982.

(36) Davis.W.D. TheGoodyear-TireandRubberCompany,Akron. Ohio’44318—0001.Letter-taD.Price,Office of ToxicSubstances..U.S.Ent..ronrnentalProtectionAgency.Washington.D.C 20480.1983.

(37) Mathtech,Inc. Economicimpactanalysisof final testrulefor quinoneandhydroquinone.F’uial Report.Washington.U.C.:Office ofPesticidesandToxicSubstances,U.S.Environmental ProtectionAgency.Contract88-01-6630.1985.-

ConfidentialBusinesslnformatiog(CBII. while partof the record,,is notavailablefor publicreview.A publicversionof therecord,.from whichC~Ihas-beendeleted.isavailableforinspectionfrom B a.m. to4p.m.,Monda~’throug~Friday.exceptlegalholidays.i~Rin. E—107,.401M Street.SW,Washington;D.C.VUL OtherRegulatoryRequitement~i-I. ClassificationofRule

UnderExecutiveOrder12291,EPAmustjudge whethera regulationis“major” and.therefore,subjecttotherequirement of a RegulatoryImpactAnalysis.Theregulationfor this. -

chemicalsubstanceis notmajorbecauseIt doe,notmeetanyof thEcriteriaset-forth in’ section1(b) of the order.First,the annual costsof testing~e expected

to range from S52.000to 5158,000overthe expectedma:ket life ofhydroquinorie(Ref. 37). Second.becausethe cost of the requiredtestingwill bedistributedovera largeproductionvolume,therulewill haveonly veryminor effectson producers’Costsofusers’pricesfor this chemicalsubstance.Finally, taking into accountthenatureof themarketfor thissubstance.the low level of costsinvolved, and the expectednatureof ihemechanicmsforsharing the cç,s~sof therequiredtesting.EPAconclud~sthattherewill beno significantadverseeconomicimpactof any type asa resultof this rule.

Thisregulationwassubmittedto theOffice of ManagementandBudget(0MB) for review asrequired~yExecutiveOrder12291.Any co?nmensfrum 0MB to EPA. and EPA resDu~.setothosecomments,areincludedin thepublic record.

3. RegulatoryFlexibility act

UndertheRegulatoryFlexibility Act(15 U.S.C.601 et seq..Pub.L 96—354.September19, 1980).EPA certifies thatthis testrulewill not haveasignificantimpacton a substantialnumberof sir.ailbusinessesfor the following reasons:

1. Thereareno smallmanufacturersofhydroquinone.

2, Smallprocessorsare not expectedto perform testing themselves,or toparticipatein the organizationof thetestingeffort.

3. Small processorswill experienceonly minor costs if anyin securingexemptionfrom testingrequirements.

4. Small processorsareunlikely to beaffectedby reimbursementrequirements.

EPAconcludesthat therewill be nosignificantadverseeconomicimpactofany type asaresult of this rule. - -

CPaperworkReductionAct

The information collectionrequirements contained in this rule havebeenapproved by the Office ofManagementand Budget (0MB) underthe provisionsof thePaperworkReductionAct of 1980. 44 U.S.C.3301 etseq.,and have beenassigned0MBcontrolnumber2070—0033.

List of Subjectsin- 40 CFRPart799

Testing.- Environmentalprotection.Hazardoussubstances,Chemicals.Recordkeepingandreportingrequirements.

-- - 53156 Federal Resister/ Vol. 50, No. 250 / Monday, December30, 1985 / Rules and_Regulations

Dated: December20. 1865. -

J. A. Moot,.AssistantAdministratorfor PesticidesandToxicSubstances.-

PART 799—(AMENOEDJ

Therefore, 40 CFRPart 799 isamendeda~follows:

1. Theauthoritycitation for Part799

continuesto readas follows:Authority 15 U.S.C.2603.2811,2825.-2. Section799.2200is added.to read

as follows:

~799.2200 Hydroquinon.(a) Identificationoftestsubstance.(1)

Flydroquinone (CAS No. 123—31—9)shallbe testedin accordancewith thissection.

(2) Hydroquinoneof at least99percentpurity shallbeusedas thetestsubstance.

(b) Personsrequiredto submitstudyplans.conducttestsandsubmitdata. (1)i’~llper-sons who manufacture or processhydroquinone.otherthanasanimpurity.from January13. 1986to theendof thereimbursementperiodshallsubmitlettersof intent to test,exemptionapplications,andshallconducttestsandsubmit dataasspecifiedin this section.SubpartA of this Part andPart790ofthis chapterfor two-phaserulemaking.

(2) Personssubject to this sectionarenot subject to the requirements of§ 790.30(a)(2), (5), (6), and(b). and§ 790.87(aWl)(ii) of this chapter.

(3) Personsw’rrn notify EPAof theirintentof conducttestsin compliancewith therequirementsof this sectionmust submitplansfor thosetestsnolaterthan30 daysbefore the initiation ofeachof thosetests.

(4) In additionto therequirementsof§ 790.87(a)(2) and(3) of this chapter.EPA will conditionally approveexemptionapplications for this rule ifEPA hasreceivetla letter of intent toconductthe testingfrom whichexemptionis soughtandEPAhasadoptedteststandardsandschedulesIna final Phase11 testrule.

(c) Health effectstesting—(1)Toxicokineticstudies—{i)Requiredtesting.Skin and oral dosingstudies,which will providedataregardingbothrateandextent of absorption, shall beconductedwithhydroquinone..

(ii) Teststandards.(Reserved](iii) Reportingrequirements.

(Reserved) -

(2) DevelopmentalToxicity—(i)Requiredtesting.Developmentaltoxicity studiesinboth a rodent andnonrodentspeciesshallbe conductedwith hydroquinone.Thesetestsmustbeconductedusing the oral route ofexposure.

- (ii) Teststandards.[Reserved)(iii) Reportingrequirements.

[Reserved)(3) ReproductiveEffects—(i)Required

testing.A two-generationreproductiveeffectsstudyin a rodentspeciesshallbeconductedwith hydroquinone.This testmustbeconductedusingtheoral routeof exposure.

(ii) Teststandard.[Reserved)(iii) Reportingrequirements,

[Reserved)(4) Neurotoxicity—{i)Required

testing.Thefollowing neurotoxicitytestingshall beconductedforhydroquinoneusingoral exposureof arodentspecies:

(A) A functionalobservationalbattery.

(B) A neuropathologytest.(ii) Teststandards.[Reserved)(iii) Reportingrequirements.

(Reserved](Informationcollectionrequirementshavebeenapprovedby theOffice of ManagementandBudgetundercontrolnumber2070-0033)

[FR Doc.85—30722Filed 12—27-85:8:45am)SILUNG CODE 5Sso—2O—~