3t~62 FederalRe~isterI Vol. 52, No. 163 / Monday, August 24, 1937 / Rules and Regulations

ENVtRONMENTALPROTECTIONAGE?JCY

40 CFR Part 799

[OPTS-42061A; FRL-3130’-8(a)J

OIey~amine;Tasting Requirements

AGENCY: Environmental ProtectionAgency[EPA). -

ACTION Final Rule.

SUMMARY: EPA is issuing a final nileunder section 4(a)of theToxicSubstances Control Act (TSCA)requiring manufacturers and processorsof oieviarnine (9-octadecenylamine orODA. CAS Number 112-90—3)to test thischemical for developmental toxicity,and for mutagenicity using a two-tieredsnhem~’.The need far third-tiermutagenicity and for oncogenicitytesting will be determined by EPAfoiluwirig a public program review ofdata. EPA is terminating rulemaking forthe proposed YG-day dermal subchronictesting which was to includeneurohehaviorai observations. eruphanson reproductive system histopethology,and a dermal absorption determination.Thesubstance. 9-octadecenylami ne. wiltbe reP rred to in this document as“QUA”, and th~term oleyianiiue” willrt’fer to cummercial fatty aminen;\t~r~c)ntaining 55 to ~6 percent0t)A. Procosed standards for testing

a~ar elsewhere in this issue ofthe Federal Register.O4TES: In accordance with 40 CFR Z3.5,this ru~e~hsdibe promulgated forparpoens of judicial review at 1 p.m.eastern 1”ddylight” or “standard” asappropriate) time on September 8. 1957’.“L’r.ts rule shall become effective.on

FOWFURThER ~NFCRMM1ONCON7AC7:Edward Klein. D:rector, TSCAAssistance Office (TS—~99).Office ofToxIc Substances. Rm. E—54~,401 M Sf,.SW., V,’:shinnion, DC 294n’l, (202—554---i4f~4l.3UPFLEMENT~RY NFORMATION: TheEPAis prruauiga hog a final rule ~orecuirethe es~ugof Of) \ for dev~lc;:-neriIalto\ tuity, mutsuentuity and oncogenicityf ~er~ roihegenicito he’,t results are

a ‘~:vs.2?:\ will conduct a publicp~ui’n “e’.tew bet-are reiuiri:c~

al the lea-tI ~rmate~anicitya: cc eenic~tyh:’’t.

I. l~ttrc~h-ytion‘pe .~j; tr;oh’~u~urall

cc -~ouat e~br’ Toxic~ (-utrat yct [T~~A,?i~c.I..

1 ... ~, wcch cc:- ~s:b. cityat: t.P~\:0 P qure ci~,a op~n~ntof data

relevantto~assessingthe risks. to~bealth.andthe environment posed by exposure~to particular chemical substances or-mixtures.

Undersection4(a)(1)of TSCP~,EPAmust require testing of a chemicaitsubstanceto develophealth or

• environmental data if the Agency’ fü’idg~-that: -~

(A)(i) themanufacture,.distributionjncommerce,processing,use,or disposaL

— of a chemical substanceor mixtures or-that any combination of suchacti~itiesamay present an unreasonablerisk ofinjury to health or the environment.

(ii) there are insufficient data an~experienceupon which the effeetsofsuch manufacture, distribution in~cojnmerce, processing,use,or dIsposatof suchsd~stanceor mixture or ofanycombination of suchactivitieson healthor the environment can reasonablybe’determined or predicted, and

(iii) testing of such substance ormixture with respect to such effects. is-necessary to develop such data: or-

(B)~i)a chemical substance ormixture~is or will be produced in substantialquantities, and(I) it entersor mayreasonably be anticipated to enter theenvironment in substantial quantitiesor(H) there is or may be significant~orsubstantial human exposure to such-substance or mixture,

(ii) there are insufficient data andexperience upon which the effects of themanufacture, distribution in commerce.processing, use, or disposal of suchsubstance or mixture or of anycombination ofsuch activitios art healthor the environment can reasonably bedetermined or predicted, and

(iii}testingofsuch substance ormixture with respect to such effects isnecnssar~to-develop such data.

For a more. complete understanding ofthe statutory section 4 findings, thereaderfs dtrected-to the Agency’~f~rs~.proposed testing rule package(chico nuc ace and c~dorinatebenzenes, published in the FederalRegister of July 18, 1980 (45 FR 4$5.10JJ.and to the second package(dichiorom.sthane, nitrohenzene and1,1,1-crichloroethane, published in the-Federal Rayister of June 5,1981 L~FR803C0JJ for in-depth discussions of thegeneral issues applicable to this section..

11, Bacbground

A. ~

Oft\ .‘f\$ 5:c~hu:’112—t’C---JIis a:1 ~cv -1 r. Ph dn ern:nrni~oaiodor

a; an: ne a:iature [IfCL\ ~-~a huihc~range of ~T~—3:340.at 75uno’ fig ann a saec:fio gravity of0 ~t P. 01) _ )I~‘CI~_~e

- is eshic-eted to he 4.5x10 ~mg/or less

at 20 ‘C, its estimatedvaporpressureis0:5x-~mm Hg at 10 ‘C and its esimaledlog-P (octanol-water partition

- coefficient) ranges from 7.5 to 8.1 (Ref.- 1); The formula of 9-octa-decenylainine

is. as follows:

CH~(CH2bCH=CHlCH~bCH2NH2 -

TheU.S. InternationalTradeC’ommission(US1TC)reported1982ODA productionto be 4.952millionpounds(Ref. 2). This productionfigure isfor fatty aminemixturescalled -

oteylamineby theproducers.EPAestimatedthat theODA containedin allthefatty amine mixtures produced in1982 amountedto between18 and29million.pouads(Ref. 21), In 1984, theUSITCreportedODA productionto be8.643 million pounds(Ref. 3). ODA isproducedat nine sites by six firms:Ak2o ChemieAmerica;Witco ChemicalCOrp.: Jetco Chemicals,Inc.; SherexChemicalCompany,Inc.: Borg-WarnerCbt-p.: andTomahProducts,iflC. Akzouses a continuous reactionprocessandthe-others use closed-batch reactors.Akzo produces over 50 percent of thetotal U.S. production. ODA’s majorusein which human exposure is probable isas~anadditive to petroleum lubricants orasan intei mediate for suchadditives.Itis. also used in a collector agent in oreflotation, in asphalt preparation, in aconcrete mold release agent, and in themanufactute of paper, paperhoard, ardglues. For a more detailed discussion ofproperties, production, uses, andexposure of oleylamine and other ODA-containing mixtures, seethe oleylaminesupport document availablefrom theTSCA Assistance Office (Ref. 1).

ff~JTCRecommendations

In theThirteenthReportof theInteragencyTestingCommittee(ITC).publishedin theFederalRegisterofDecember14 1983, the !TC designatedQUA for prioity considoratiori for astaged testing program, beginning withtoxicokinetics and then testing formutagenicity and teratogenictty ifpercutaneous absorption isdemonstra ted.

C..Prop~sedRule

EPA issued a proposed rule publishedin the Federal Register of dovemher 19,1904 [49 FR 453101, requiring, for ODA,oral developmental toxicity testhag, atiered otutagenichy teatng scHme ~rjIbcanacity r~tricqer once4aaioityand u 0l~daydermal uhchrooie a’:which we Ad ia lucia riecr:ahaviorjobserve dons, erogoasis on rep:adueltvr’

:51cm . a~:,o.P cPa,,a: C laabsorption deter:n:nation.

Federal Register / Vol. 52, No. 163 I Monday, August 24, 1987 / Rules and Regulations 319f~3

‘10

t test :eqU~en-ecra based on theauthorttv of section 4(aJ(1)(A) and (31 of1 SPA were ptopoaed in 40 CFR 799.3300tea toeticing recodifad cc 40 CFR71(3175.

‘la: ti;c a -thority of section41: (Ia J~Aj,EPA made a proposed finding4-ri lIe use of QUA may pascal ancc-t.asonable risk to human health fromde~e(-opment-al toxicit . This was basedon ar cUbIc animal studies (Refs. 4through 9) suggesting that oleylamineniav cause such effects and on thepotentattexposure of app oxirnateiv 28million muchanics and oIlers in relatedtrades(Ref. 10).

Under 4-c authority of section4(a)(1)113).EP~made the proposedfindings that oluy1~ouineis producedinsubstantialquanti tiles (EPAestimateof18 to 29 million poundsper year), andthat thereis substantialexposureto thissubstance (approximately2.8 millionworkers)(Ref. 10).

EPA found that therewereinsufficientdataavailableto ~esonablydetermineorpredictthe effectsof this exposurein theabove-nuentionodareas and tht testingof ODA wasnecessaryto developsuchdata.

The analysisandfindings on whichthe above determinationswere basedare presentedin the Olcg]amineSupportl)ocument (Ref. 1), which is availablefrom the Office of ‘I’oxic Substances’TSCA AssistanceOffice andin thepublic recordfor this rulemaking.

EPA did not proposeanoncogenicitybioassay based on thesection4(aJ(~)(B)finding becauseEPA consideredthereouiredmutagenicitvtestsenappropriatefir-st tier for orcogenicityforthis substance,However,EPA foundthat if certainof the requiredmutagenicitytestsproducedpositiveresults,this would be sufficienttoindicatethat ODA maypresentanunreasonablerisk of oncogeniceffects.In suchcircumstances,EPA foundthatwithout datafrom a 2—yearbioassaytherewould be insufficientdatatopredictoncogenicity,and testingwouldbenecessaryto developoncogenicitydata.

III. Public CommentsTheAgencyreceivedcommentsfrom

onesource,theOleylamineProgramPanelof’ theChemicalManufacturersAssociation(CMA). The commentsaddressedtheproposedhealtheffectstestingrequirements,datainterpretation,humanexposure,testsubstanceconcentration,andeconomics.

A. Health Effects Testing

ThePanel commentedthat a 28-daydermal toxicity test is adequate to

to ac ,ential subchron,u effects.The Panel also believes that as’-ociatedneerobehavioral and e~’roc(ucttceto stem tc-stin0 l~not 1CLCr 4- RiA is :,o

r requiring these tests (see UnitIV.). -

The Panelcommentedthat there is noneed for a devc lopnuental toxicity studybecauseexposer-cis not as high as EPAinitially indicated, only 2,000mehanicsarewomen(Ref. 10), andbecauseanimal studiesby Eifinger and KoehlerandBio/dynamics (Refs. 4 through 9) donot support i’. Although EPA hasadjustedtheQUA humanexposurefiguredownward(somepotentialexposure groupswere double counted)to artproxinuctely 2 mitien (Ref. 101.mechanicsand people in related trades,of whomapproximately27,000arewomen,arestill potentiallyexposed.EPA still believesthat thereis sufficientinformation to indicatethat oleylaminemay producedevelopmentallytoxiceffects (seeUnit V.A). However,thedataareinsufficient to adequatelycharacterizethis potential, andappropriate testing is needed to do so.

ThePanel commented that shouldEPA require a developmenttoxicitystudy of QUA, the dermalratherthanoral route should be used because -

human contact is expected to be dermal,however, if the oral route is required,ODA should be incorporated in the feedrather than given by gavage. The Panelmaintained that a feeding study woulddecreasethe effect of bolusadministration by gavageandwouldalsoeliminatetheadditional stressfactorwhichgevageintroduces.EPAbelievestheoral routeis themostappropriatebecausethereis a sufficientdatabaseby which to evaluatetheresultsof oral developmentaltoxicitystudyandinsufficient dermaldata.Also,thecorrosiveeffectof thedermalapplicationof ODA may causedevelopmentaltoxicity becauseof stresstherebyproduced.The oralrouteviadiet such asin the feedwill be anacceptablemeansof exposureprovidedthe test sponsor can accuratelydocumenttheamountof ODA consumeddaily.

The Panelcommentedthat theNationalInstitutefor OccupationalSafety and Health conducted a HealthHazard Evaluation in 1979 (Ref. Ii) ofoneof Akzo’s plants which showednoexcessive numberof deathsdue tocanceor heart disease. EPA does notagree with the Panelthat the studyalleviatesconcernfor ODA’s effects,butinstead agreeswith the author of thesurveythat serious limitations in thedata, including few deathsand -

incompienessof personnelrecords, -

preclude any definitive conclusions.

thePanel commented that anyqu~sOon of cacegerticity testing sha.aidbe deferred unt:l a’tcr the results cf themuteganicty teats iave been re,tev. ~darid discussed EPA agrees that thedecision to inhtl~tethe oncogencitlstud~(if trIggered by positive results inoneor more of the specifiedmotagencity tests) should await theoutcome of all of the second tiermutagenicitvtesting and a programrevicw;EPA hasincluded this stepinthe final rule.

The Panelcommentedthat thedevelopmentaltoxicity study should heconductedon only onespeciesbecausesomedevelopmentaleffectsdata areavailable.EPA hasreviewedthedatareferred to by thePanelandconcludestheyindicatethepossibilityofdevelopmentaleffectsas a resultofexposureto oleylaminebut are notadequateto characterizeODA’sdevelopmentaltoxicity in thespeciestested.TheTSCA testguidelinesrequirethat thedevelopmentaltoxicity studybeperformed on at least two mammalianspecies.

ThePanelcommented that a negativein vitro cytogenetics assay neednot befollowed by an fri viva mammalian bonemarrow cytogenetics test to determinechromosomal aberration. This judgmentis based on a review of the literaturewhich thePanelcontends showsthat nochemical testing negatively in an in vitromammalian cytogenetics assay has beenfound positive in in vivo cytogeneticstests. EPA has in past section 4 testrules included bothin vitro and imr iivocytogenetics testing in its first tier oftestingto maximize detection ofpotentially clastogenic agents. e.g., forcresols(51 FR15771;April 28, 1986)andC~aromatic hydrocarbons (50 FR 20662;May7, 1985). The Agencybelievesthatthe in vitro assayis subjectto safficient

,limitations, particularly in the use of frivitro metabolic activation systems,thata negativeresponse,especiallyin casesof technical difficulties with themetabolic activation systemor of erraticor narrowly-defined toxicity curves,should be confirmed in an in viva test.The information presentedby the Panelor otherwiseavailable to the Agency isnot sufficient to warrant a changein thisview at this time.

The Panel commentedthat mouthrinse and toothpastestudies (Refa.12through 14) support their belief thatODA causesnolong-term health effects.EPA believesthat thesehuman clinicaltrials, conductedto determineifmixtures of hydrofluorides of oleylamineand other arnines could prevent theformation of cariesand plaque, can rotbe usedto determineODA’s toxic

31~ti~tL FederalResister/ Vo+. 52~No. 163W /. Mondalt,, August. 24, 198T / Rules and Regulaticrrts~

potential. In generaL toothpaste~andjormouthwashis in the mouthfor relativelyshortperiodsof time whereupon.the.mouth is rinsed_Thelevelof human.exposure to oleylamine hydrofluoridieintheseclinical trials waspossiblyverylow andin any casels unknowr~Thu8,.even if theseclinicaLtrials wereotherwise.adequate,.becauseof a Iacko~exposure data theycannot be-usedIto~determine thetoxicity that.olaylaminemay present.

ThePanelcommented thaLEPA didnot useall availabledatain arri.vingatits testingdecisions[or ODA. was-inconsistentin drawing. conclusions,.andtuseddatainabiasedway which-leads.to moretesting,EPA.did reviewallavailable dataandfound that_inall but’theEifingerandKoehierstudy (Ref..4)~the testsubstanceswereother thanoleylamine,although someof thesetests-substances-were cfoaeiy. relatedto QUA.Indeed, the PaneLwas-especiallycriticalof EPA’s useofdataon QUA analogs.(Refs. 5 through9,. ~ and23). However,EPA hasbeencarefulto distinguishbetweentheuseof analogdata tosuggestapotentialconcernandtheir useto determinethat data areadequateForexample.dodecyidimethylarnineoxide(DDAO), which canbeconsideredanalbgousto QUA only [or the purposeof qualitatively estimatingits skinpenetrating potential.,has undergone.rather extensiVe pharmacokineticstudies (Ref. 17). As partof theabsorptionprofile, topicaL radlolabeleddosesof DDAO were applied to humans,rats, mice, andrabbits.The resultsindicatea fair degreeofabsorbtioninthelower mammalskinsandan.extremelypoordegreeof absorptioninthehumanskin.The studyis. flawed.howe’,’er, sincethehumanexposurepenodswereonly 11 percentof thetotalexposureperiodsfor the rats,miceandrabbits. Nevertheless,,the study diddemonstratetheability of DDAO topenetratethe human skin albeit verypoorly.This is particularlysignificantsince,by virtueof its polarnature.DUAO is less likelEthanoleylaminetopenetratehumanskib. Data on DL’)AO:rre~notadequateto makequantitativeinfen——acesabout ODA. For acluaat;tative analysis. specriic skinpeneration testing of QUA would benecass ccv.

Tb m Esnet commented that EPA- -m tiy ua~dthe derrrisl absoriatiuri

r- Oi S—due iplein and Elank (ft-al.15) -a -Pacts QUA’s potential sidea ~‘—-. duo Py mechanics becana-.flc~m:;2 ratd mr tiTn octan(,i sboaftj 9 sebeer; mae I ,~sthe rnodeicompound; 12)on ilcehol rather than a water ‘ehicieshould have aeon assumed; mind

hydrated- abdominal skinas:used~in this~methodoirerstates-absorption. - - -

conditions-for mechanics’..EPA believes-that thedermalahsorptionrate’of O~Acannot be conclusivelydeterminedb~rthe. useof octanol or decanolas amodeLFor example; theiruse’ ignores—thecontribution of ODAs amine group’to theskin penetrationproperties.A-reliableabsorption.rate for QUA can bedeterminedoniy by theuseofQUA as-thetest substance~In any case~EPA is-withdrawingtherequirenient.ofa~- - -

dermalabsorptiontest_TheAgencyplans tnproposethat acomparativeoral-dermal absorption,.distribution.,metabolism,.excretionassay—becarriedout for ODA..This proposal will-be-finalized if tOe developmentaltoxicitytest reqm~redin this notice-is positive;

The Panelcommented-that a skin~irritation test on-rats-conducted with,QUA produced perceptible well-definederythema with 0.3-percentQUAconcentrations and severe sioughing:with 1.5 percent QUA (Ref. 16). BecauseQUA concentrations- in petroleumlubricants amaaoproxhuately 0~3to 1.0-percent (,4g FR45610; November 19,1984), thePanel believesthatth~expected irritation- would constitute an“early warningsystem”whichwocickcausea-mechanicto washhis handsatintervalsor takeotherprecautionsprecludinglong-termexposure.EPAdisagrees.In the 14-daytest, theapplication-siteswerecoveredby gauze:dressingswhich.could have accentuated-theerythemaof therats.Also~rat skinhasbeen.considered to-be- more-permeablethan—humanskirt and,therefore,more readily irritated(Refa. 20--and,2~j.The Panelhasnot demonstratedthatautomotivemechanicsandothers:exposedto.petroleumlubricants-experience erythemaor sloughingand-find it necessaryto take-precautionarymeasures.Eventhough.humans-mayabsorb.less.QUA. andexperience-noerytherna at thedosestestedin the-I-I-clay study.iLtO crIpoasioeto determinethepotentiaLtoxic effectsof doestowhichhumans. are exposedwithoutfurther testing. 1-lowevea. EPA does.believe that the l4~daystudy rest—irs doindicate tne nee,g. to change the route ofQUA administrationto the oncogenicitytest from dermal,as -arooosed in theFederal Register of November19. 1984(49 FR 45810). to oral to aiinri’matesktnirritation as a corcuttcating tactor.

E. Test Scb;rL-an’mC,jncn-n--nt:o.r

The Panel cu-na: named b EPA’sbelief that 97 p:.ru t C!P\ ,--asosailabte wear Ia’ ~a :5 4-at the F~stscla--t--ince should be uP porunot ODAbecause ‘5-re attaiomem:t of a blob—sr ODAcone: atm tim, is m ear a t4-i ft ‘it

given- the’ similarity’oil boiling pointsroftheG~alkylamines-ofwhi~OOAIs amember, EPA- accepts-the-commentantiagrees that not-only would-furtherconcentration of ODA be extremelydifficult, bnt 91Japercent- ODPzis ofsufficient purity to-adequately test its-properties. The Agencyhas-thus--modified this requirement in’ this’ [hialtrule.

C. Economics

The Panelcommented’ that- total’andannualized testingcostswereincorrect.EPA based-these’costs-on-quotes-byvarious testing laboratoriest Cost rangeswere given rather than- specific’ costs~because of uncertainty oftthe- specific-details-of the testingprotocols-at thetime of po’oii’cation of the-noticeofproposedrulemaking (Ref 18).

The-Panel commented that EPA’sbeliefthat demand for ODA wassufficiently inelastic so thatmanufacturers could passtestCOStS topurchasers-was incorrect. EPA based itsbeii-eion the following:

I.. QUA is used as a component inrnany’alkylamine products, therebydispersing its demand over numerousend markets.

2. The alkyfamineproductswhichcontain QUA tend to have relm,tivelvsecure andspecialized applications thatare dictated by performanceadurrntages/considerations in theirmarkets.

3. Cationic.surfactants,, such as thealkylamines.. normally-are used in smallamounts leg,. between less- than land-10 percent) in relation to the weight orfinal products. ihereby suggesting thatthey compose’aminor shareof actual’end-product cost [Ref. 18),.

The Agency believes- this analysis isstill correct, and therefore, disagreeswiththe-conimenL

The- Panel commented that EPA’s-estimated test costsare givenin- terms-of 1983dollar-n end arc out of date.EW.considersthis. pointto-bewell taken-aridhasdevelopedmore recent-figures-which are found in Unit VI.

IV. Deci’don to Terr,rirrataRuiemakiriyProcess for SuhehronicToxicity, Dermal -

Absorption. Neurabehavioral andReproductise System Tasting for QUA

In the propusasti test rule for QUA (47FR 4551Cr Novenher19, 1934), EPAincluded a 9(t—d-:g her-cal subchronicto-src:tcOr-mr. - is test, in addition to thrau.st,nl s ubchror4-. n:e,rsm‘emsmots. Was toi n4-ude her-road - i~-a-m.t:rcm,neroi-hohr~vjornl4-se ‘vu tions, a:md

on rer-rnduc:ivehtstc-pathoingr..Sirrcethis tact ts:is

a 4--do, -turF Si rum ~ -tm - 0”

Federal Register / Vol. 52, No. 163 / Monday, August 24,-1987 / Rules and Regulatjon~- 31965

rat studyhas beendone-with ODA bythe Panel.Thetestshowederythemaandsloughingatdosagesof 12.5 to 61.5mg/kg/day(Ref. 16).To producesystemic effectsat levelsbelow this~thematerial would have to be verypotent.However,existing chronic. data onmixtures containing ODA do not Suggestsuchpotency.Two-year studieson dogsand rats with oral administration ofsalts of ODA and an analogproducedonly minimal toxic effectsand nospecific organ effects (Refs.27 and28).Also, review of structural analogdataby EPA does not suggestthat oleylaminewould be toxic at very low dosesinrepeatedexposuresfor 90 days(Refs.29aol 30). EPA believesthat thesedatacon be used to reasonably predict thesystemictoxicity of QUA at levels towhich humans are exposed. For thesereasons. the Agency will no longerrequire the 9~daysubchronic, denualabsorption, neurobehavioral, andreproductive tests and is hereby -‘

nodlying the public of this decision.However, EPA remains concerned aboutthe developmental, rnutagenic, andoncogenichazardpotentialsODA mayposeto humanhealthandis requiringthis testing as describedbelow (see UnitV.}.

V. Final Test Rule for ODA

/1, IaYnjipys

EPA is basing the final testingrequirementsfor QUA on theauthorityof section4(a)(1)tA) and(B) of TSCA.

The section4T5)tT)fA1ffisdTh~sfordevelopmental toxtcity are as la.llows:

EPA finds that the useof QUA maypresent an unreasonable risk of injury tohumanhealth from developmentalto-duity because: (1) Theavailahleanimal studies suggest that ODA has adevelopmental toxicity potential: and(2}approximately 2 million individuals in1965 were potentially exposed to QUAas a result of its mani’tro-tore,processing, and use (Ref. 19).

EPA also finds that there areinsufficient animal and humandatatoreasc,nahiydetermineor predict thedr. eicpmeotul toxicity of QUA -and thattesting is necessary to cievelon eachdata 149 FR 45r510).Tie 4(a)(i~~A)finning of ‘may present an unreasonableritA’ uf devetopmentnl ;o-tictty is basedon ~a-railable animal s9udb’s (Refs. 4tl:ririr-,h 9) nhicb s-re-oman thotc,l,’a, is rntrae racy carla” -a’ n.h r- meets,

9 lao serriol 1(,’5fi’ ‘-I4

ndO-”, forda’,’t’b prceotal to -Pc ly ‘nd a ta-a -dcautagerrialty tes° g ~-4-emrr aebtus n-~ivnrjic-rlo, the n-so,, Pr n:aco,4an9,ity

ta3’ny, ore as ft a Laws:ODA is pre-ducasri to em-b,, a

qudrltities. The most recent production

figure for oleylaminewasreportedby -

the USITCto be8.643-million poundsin1984(Ref. 3). Productionestimatesby -

EPA for QUA, however, range from 18 to.29 million poundsfor 1982when-theODA portion of captive production as—well as production of all commercialODA-containing-substancesare taken -

into account-.The estimatedexposureof2 million peoplein 1985as a result ofmanufacture, processing,and useisclearly substantial (Ref. 19). EPA findsthat there are-insufficient animal andhumandata to reasonably determine orpredict thedevelopmental,mutagenic, oroncogeniceffectsof QUA and thattesting is necessaryto develop suchdata. -

B. Hr~piiredTesting

The Agencybelievesthat an oraldevelopmentaltoxicity study, a tieredoral (where applicable)mutagenicitytesting scheme,and possiblyoncogenicitytesting should beconducted for QUA. The OleylamineProgram Panel of the ChemicalManufacturers Associations has,voluntarily conductedmutagenicity testsconsistingof the following: Amesassay.chroniosomal aberration assayinChinesehamsterovary cells,and CHO!HGRPTmutation assayin the presenceof exogenousmetabolic activation (Refs.24 through26). TheAmes andchromosomalaberrationassaysarenegativeandsatisfy theseportions oftheAgency’scurrent first-tiermutagenicitytestbattery.TheCl-ID!HGPRTmutationassayresults areequivocalandaretestwill be requiredin a differentcell line [seeOleylamine:ProposedTestStandardselsewhereintoday’sFederalRegister.)The assayprovidessome indIcatIon ofgenotoxicity,both without and withmetabolicactivation.Apparentlybecauseof thehigh toxicity of thechemicalin this test system,the activitytier :rostrn1~,t e’, a aO’, - tic a—mrdifferentdosesand over repeat tests,and even within repeats for replicate(parallel) cultures of the same dose-point. No dose respnn~ewas observed.This may be due to dtfricuttie-c in precisedose application in narnoliter parmilliliter cuncent--er

mcns, The

rn-amr-oration cell g”rae mm. tottan r’atcst Iraa dialer-cot ii line and the 1.-i a-laomamm-aliar-r hone-marrow cvtogeneticstesrwill -na’—agie’e 4-c first tie:- of thetrio tag-,:tai’v I’n Item y, If io’l tca ted byfir -,‘~l’ora ~.-‘-d’a,sr-er nd-tier

-‘ a:-, :v a ora.istto-g cf-a ‘talent0- ~u sut.’ ,or cb, oromnaim’ I

aba tm’m,’,’F~,-m-rd/or a sex-bakedrem-~ri-.’:~-d -d assayI—a Drcs’-a-chiki

- - ore n.m ne mastbe cor:~macted.The third tier of

mutàgenicitytestingis conditional updtipositive second’tiermutagenicity testresults.The oncogenicitybioassayisconditional uponpositive results in oneor more of the following mutagenicity -

tests:in viva mammalian bonemarrowcytogenetics,detectionof genemutationin somaticcells in culture, and sexlinked recessive test in DrosophiLamelanogaster.However, EPA will notrequire initiation of the third-tiermutagenicity test(s)or oncogenicily testuntil all second-tierrnutagenicity testshave beencompleted and a publicreview of the data is-held by EPA. Testsponsorswill be notified by FederalRegisternotice or certified letter ofthird-tier mutagenicity and oncogeriic}tytesting decisions.The route of -

administration of QUA in theoncogenicitytest, if required, shall beoral as explainedin Unit U1.A. EPA isproposing teststandards for thesetestselsewhere in today’s Federal Register.The testsare to be conductedinaccordance with EPA’s TSCA GoodLaboratory Practices standardsunder40GFR Part ‘YZ. -

Although the anticipated routeofhumanexposure to ODA is dermal, therouterequiredfor testingis oral, for thereasons stated in Unit IILA. In suchcases, EPA uses pharmacokinetic datato extrapolate between routes ofexposure for risk assessment purposes.As these data are not available forQUA, the Agency intends to propose acomparative oral/dermalpharmacokinetics study for QUA afterpublication of this final role.

G, TestSubstance -

EPA is requiringthatQUA of at least90.0percentpuritybeusedas the testsubstance. The vehicle should beonesuchas mineral oil for which therearehistorical toxicological data and whichwill not interferewith testresults.

I). Pa-rrarojas Required3o Test

Eection 4~b)1Il(B)specifiesthat theactivities for which theAgency makessecrion 4(a) findings (manufacturing,processing, distribution, use and/or-dtsposrri) Ceterroine who hears therespora~ih-:lityfor testing, Manut’am’t’arersare required to test f the findinos arebased on rnaaufactm’rtr’ag (“a:amr-mfacture”is defined n -mactiara 3(7) of T14-5\ to1.-elude “import’’). Processor-s rat:raatiuiri’ d to t”~ti~the fiadtmr-.amm - a a basedon pr-om:estag. ISraction 311 9 ofc-:f:i,es “Coonass as the pr-ac araFI-rO ofa ohen:ic;aai subst~u:ceor asmxtrare, r~tarits o-o-raaf,:ctu.re,fur disirihe’r,,n ancun’n:er-ce I Pete man—:iaotmarerc‘ar-Iprccc-.s’:~a umtaamlarJto a.r- -

exposures gwlng rise to the potcr-.rtal

3oFederal Register/VoL 32, Na. 1b3 / Mbnday, August 24. 1987 / Rules and Regulations

risk occur duringuse, distribution, ordisposal. -

Because EPA has found that existingdataareinadequateto assesshealthrisks from the manufacture, processingand use of QUA, EPA is requiring thatpersons who manufacture or process, orwho intend to manufacture or processQUA at any time from the effective dateof this test rule to the end a-f thereimbursement period are subject to thetesting requirements of this rule. Theendof the reimbursementperiodwill be5 yearsafter thesubmissionof the finalreportrequiredunderthetestrule. Asdiscussedin theAgency’sTestRuleDevelopmentandExemptionProcedures(40CFR Part790), EPA expectsthatmanufacturerswill conducttesting andthat processors will ordinarily beexempted from testing.

Because TSCA contains provisions toavoid duplicative testing, not everyperson subject to this rule mustindividually conduct testing. Section4(b)(3)(A) of TSCA provides that EPAmay permit two or more manufacturerscr processors who rare subject to the ruleto designate one such person or aqualified third person to conduct thetests and submit data on their behalf.Section 4(c) provides that any personsrequired to test may apply to EPA for anexemption from that requirement. TheAgency expects that the currentmanufacturers of QUA will form thereimbursement pooi and sponsor thetesting required. Manufacturers andprocessors who are subject to the testingrequirements of this rule must complywith the testrules and exemptionprocedures in 40 CFR Part 790.

Manufacturers (including importers)subject to this rule are required tosubmit eithera letter or intent toperform testing or an exemptionapplication within 30 days after theeffective date of the final test rule. Therequired procedures for submitting suchlettersandapplicationsare describedin40 CFR Part 790.

Processorssubject to this rule, unlessthey are also manufacturers, will not berequired to submit letters of intent orexemption applications, or to conducttesting, unless manufacturers fail tosubmit notices of intent to test or latea-fail to sponsor the required tests. TheAgency expects that the manufacturerswili pass an appropriate portion of thecosts of testing on to processors throughthe pricing of theIr products orreimbursement mechanisms, ifmanufacturers perform rail the requiredtests, processors will he grantedexemptions a ntomutacuiiy. Ifmanufacturers fail to smabanit notices ofintent to test or foil to sponsor all therequired tests, the Agency will publish a

separatenoticein. the,FederalRegisterto notify processorsto respond;thisprocedure is describedin 40 CFR Part790.

S. TestRuleDevelopmentandExemptions - -

Elsewherein-this issueof the FederalRegister, the Agencyis proposingin arelated document [OPTS-.42061B) thatTSCA test guidelines be utilized astheteststandards for the developmentofdata under this rule for QUA. Asdiscussedin that documentand in theFederal Register of May 17, 1985 (50FR20652), EPA has reviewed the methodfor thedevelopmentof test rules andhasdecidedthat for mostsection4rulemakings,theAgencywill utilizesingle-phaserulemaking.In light of this&cisior~EPA hasreevaluated theprocess for developingtest standardsforsection 4 rulemakingsinitiatedunderatwo-phaseprocessand has determinedthat for certainof thesetwo-phaserules,TSCA testguidelinesareavailableforpromulgationasrelevantteststandards.EPA hasdecidedthat whereTSCA orother appropriatetest guidelines areavailable-,the Agencyin mostcaseswillpropose therelevantguidelinesasthe -

test standards for thoserules.EPA believesthat, in line with its

commitment to expeditethe section4rulemaking process,it is appropriatetopropose the applicable TSCA testguidelines as test standards at the sametime as a PhaseI final test rule is issued.With regard to the rulemaking for QUA,TSCA test guidelines are available forthe testing requirements included in thisPhaseI final rule. Thus, in theaccompanyingdocumentthe Agency isproposing theseTSCA test guidelines astest standards.

The public, including themanufacturers and pI-ocessorssubject tothe PhaseI rule, will have anopportunity to commenton the use ofthe TSCA test guidelines.The Agencywill review the subrnittarrd comments andwill modify the TSCA guidelines, whereappropriate, whenthe test standardsarepromulgated.

During the developmentof the testrule under the two-phaseprocess,personssubject to the PhaseI final ruleare normaily required to submitproposed studyplans (see 40 CFR79050(a)(2))~Dow-aver, because EP.A isproposing appiicable TSCA testguidelines as the test standards for thestudies required by this Phase I finalrule, persons soblect to the rule, i,e.,manufacturers and pi-ocearsors of QUA,are not required to submit proposedstudy plans for the required testing.Personssubject to this rule, however,are still required to submit noticer of

intent to test or exemption applicationsin accordance with 40 CFR 790.45.Moreover, oncethe teststandardsarepromulgated,personswho havenotifiedEPA of their intent to test mustsubmitstudy plans (which adhereto thepromulgated test standards) no laterthan 45 daysbefore the initiation ofeachrequired test.(See40CFR790.50(a)(1)). -

Processorsof ODA subject to- thisrule, unlessthey are also manufacturers,will not be required to submit letters ofintent, exemptionapplications, or studyplans (before testingis initiated) unlessmanufacturers fail to sponsortherequired tests.The basis for thisdecisionis that manufacturers areexpectedto passan appropriate portionof the test costson to processorsthrough the pricing of productscontaining ODA.

EPA’s final regulations for theissuanceof exemptionsfrom testingrequirements are in 40 CFR Part 790. Inaccordancewith thoseregulations, anymanufactureror processorsubject tothis PhaseI test rulemay submit armapplicationto EPA for anexemptionfrom conductinganyor all of thetestsrequiredunderthis rule. Ifmanufacturersperformall the requiredtesting,processorswill be grantedexemptionsautomaticallywithouthaving to file applications.

In therelated FederalRegisterdocument,citedin thefirst paragraphofUnit V.E. andappearingelsewhereinthis issueof the Federal Register,EPA isproposingdeadlinesfor thesubmissionof testdata.

F. ReportingRequirements

EPAis requiringthatall datadeveloped underthis rulebe reported inaccordance with the EPA GoodLaboratory Practice (GLP) standardspursuant to 40 CFR Part792.

EPA is required by TSCA section4(b)(1)(C) to specify the time periodduring which personssubject to a testrule must submit testdata.TheAgencyis proposingthese deadlines in therelateddocumentappearing el-mew-herein this issueof theFederalRegister,

TSCA section12(b) requiresthatpersonswho exportor intend to exportto a foreign countryanysubstancesubjectto testingrequirementsunderTSCA section4 notify EPA of suchexportation or intent to export. Whiletheresults of requiredtesting may riotbe available for some time, a notice tothe foreign government about the exportof such substances subject to test rulesserves to alert them to the Agency’sconcern aboutthe substances. It givesth�ase.governrraentsthe oppea-tunity to

FederalRegister / Vol. 52, No. 163 / Monday, August 24. 1987 / Rules ao~dRegulations 31967

request suchdatathat the Agency maycurrently possess plus whatever datamay become available asaresultoftestingactivities.Thus,upon the

- .~,ffectivedateof this rule, parsonswho~r intend to export QUA must

submit noticesto the Agencypursuantto TSCA section12(b)(1) and 40 CFRPart 707 (see45 FR 82844;December16.1980).

TSCA section14(b)governsAgencydisclosure of all test data submittedpursuant to section4 of TSCA. Uponreceiptof datarequiredby this rule, theAgencywill announcethereceiptwithin15 daysin theFederalRegisterasrequired by section 4(d).Test datareceivedpursuant to this rulewill bemadeavailablefor public inspection byany person exceptin thosecaseswheretheAgencydeterminesthatconfidentialtreatmentmustbeaccordedpursuanttosection14(b)of TSCA.

C. Enforcement Provisions

The Agencyconsidersfailure tocomply with anyaspectof a section4rule to he a violation of section 13 ofTSCA. Section15(l) of TSCAmakesitunlawful for anypersonto fail or refuseto comply with anyruieororder issuedundersection4. Section15(3)of TSCAmakes it unlawful for anyperson to failor refuseto: (1) Establishor maintainrecords;or (2) submit reports, notices,or

- otherrecordsrequiredby the Act or anyregulationsissued underTSCA.

Additionally, TSCA section15(41 -

makesit unlawful for anypersonto failor refuseto permitentry or inspectionasrequiredby section11. Section11appliesto army “establishment,facility.or otherpremisesin whichchemicalsubstancesor mixturesaremanufactured,processed.stored,or heldbeforeor after theirdistribution incommerce.. .“ TheAgencyconsidersatestingfacility to be aplacewherethechemicalis held or stored and,therefore,subjectto inspection.Laboratoryauditsand/orinspectiunswill heconductedperiodicallyinaccordancewiht the proceduresoutlinedin TSCA section11 by designatedrepresentatives of the EPA tr’r thepurpose of determining compliance withthe final r-aica for QUA. Theseinspection-a ma’,’ be conducreci furpurpa ses ~hieh include varification thattestiog has h�-non. that srahed-des areheiocrapa-a~,that reports decurri’ely reflectti-f aaa1~era’in” raw data and

‘Or n3 and evalu ‘etir’ns thereof.a a jI tI--at ‘) - ~Judies are b~’iaa-4rued’ accc --lao y’ tf’~’t,Cl P ‘,ter,d uris ~:ol t~

- at -i-aa’’at:r-~~qt:tbii5

ad ha Jut scrood- -f Peas rralenaakiaup

FR-\3 -ari).i~rityt~ia’--1~et-i tr’~iingfacnlity ~baoderives front section -4(h~i1)

of TSCA. which directs EPA topromulgate standards for thedevelopment of test data.Thesestandards are defined in section3(2)(BJof TSCA to mnciude thoserequirementsnecessaryto assurethat data developedundertestingrulesarereliableandadequate,and suchother requirementsas are necessaryto provide suchassurance.The Agency maintains thatlaboratory inspectionsare necessarytoprovide this assurance.

\‘ioiatorsof TSCA are subject tocriminal andcivil liability. Personswhosubmit materiallymisleadingor falseinformation in connection with therequirementof anyprovisionof this rulemay besubjectto penaltiescalculatedas if they had neversubmitted theirdat.-i~Undarthepenaltyprovisionsofsection 15 of TSCA, dray person whoviolates section 15 could besubject to acivil penalty of up to $25,000per day foreachviolation. l’his provision would beapplicable primarily to manufacturers orprocessors who will fail to submit aletter of intent or art exemption reauestand who continue manufacturing orprocessing after the deadlines for suthsubmissions. This provision would alsoapplyto processorsthat fail to submit aletter of intent or an exemptionapplication and continue processingafter the Agency has notified them oftheir obligation to submit suchdocuments (see40 CFR 790.48(h)).Intentional violations could lead to theimposition of criminal penalties up to$25,000for each dayof violation andimprisonment for up to 1 year. Otherremedies are a’~aiiabieto EPA unde~sections7 to 17 of TSCA. suchasseekingan injunction to restrainviolations of TSCA section4.

Individuals aswell ascorporationscould be subject to enforca-ment actions.Sections15 and16 of TSCA applyto“any person’Swho violatesvariousprovisionsof TSCA. EPA may. at itsdiscretion.p uceedar4nir-’ - iraft~-iduarlsas well as co~c~paniestheu,selves. inparticular,this includesindividuals whoreport false information orwho causeitto be reported.In addition, thesuhraaission of faise, fioritlous, orfraudulent statements is a viol-a tionunder 18 USC. 11)01.

VI. Economic Analysis ui Final TestRule

To assess the econo~amcimp-act of thisrule, EPA has orepat ad an economicnoofysis thate~ agesbe potential foraoniPoant ecinarca ic rut tots Di ti aarnie riry as as roeoi a of if-ac atestan4,The eceouc -c ta~nh’sisear)e’n,atestb-a costs of conda’ctin~the required1cr’ lam-’ nod e’-a1uat--~s~ - :~oir id n,,. -

signiJcant advease economic impact e~,

a result of thesetestcostsby examiningfourmarketcharacteristicsof QUA: (1)Pricesensitivityof demand,(2) industrycost characteristics,(3) industrystructure,and (4) market expectations.

Total testing costs for the final rule forQUA areestimatedto rangefrom$775,290to $1,020,200.This estimateincludesthe costs for both the requiredminimumseriesof testsand theconditionalones.Theannualizedtestcosts(using a costof capitalof 25percentovera periodof iS years)rangefrom$200,908to 5264.37&

Becauseof the extensiveoccurrenceof ODA in numerousmixedalkylamineproducts.total productionof thischemicalis not representedby thedatapublishedfor oleylamineby the USITC(Ref. 3). EPA estimated total QUAproductionin 1984. containedin -

alkylamineproducts.to be 17 to 2l~million pounds.Using thelower-boundproductionfigure of 17 million pounds,theaverageunit testcostsfor allproductswould thenrangefrom 1.2 to1.6 cents per pound of the QUAcontained in the amine products. EPAestimates that under worst.caseassumptionsthis costis onepercentoftotal 1984 productvalueof themajoraikylamineswhich containQUA. -

Basedon thesecostsandthemarketcharacteristicsof QUA, theeconomicanalysisindicatesthat the potentialfomsignificantadverse economic impact asaresultof this test rule is low. Thisconclusionis basedon thefollowingobservations:(1) Theestimatedunit testcosts are small, and (2} the demand foeQUA manufacture is inelastic (Ref. 23).

VII. Availability of Test Facilities andPersonnel

Section 4(h)(1) of TSCA requires EPAto consider “the reasonably forsecableavailability of the facilities andpersonnel needed to perform the testingrequired under the ride,” Therefore, EPAconducted a study to assess thuavailability of test facilities andpersonnel to handle theadditionaldemand for testing services creamedbysection 4 test rules. Copies of the study.“Chemical Testing Industry: Profile ofToxicological Testing”. October 1931,can be obtained through the NTIS Underpublication number PB 82—141)773.

On the basis of this study, the Agencybelieves that rhere wiil be available testfnmcilbies and personnel to perform Inctesting rcqu~roiin tiris ta-st rule,

Vill. Ruleurmbing Rocord

EPA has ea)-hlished a public recordfor this rulemaking (docket numberO)’3’3-421je1 \). TIn’; r,-e’nrd incIaa-~e-sti-basic informnataon the Agency

31968 FederalRegister I Vol. 52, No. 163 / Monday, August 24, 1987 / Rules and Regulations

consideredin developing this rule, andappropriateFederalRegisternotices.

This recordincludesthe followinginformation: -

A. SupportingDocumentation

(1) Federal Registernotices pertainingto this action consistingof:

(a) Notice containing the ThirteenthITC Report designatingoleylaminetothe Priority List (48FR 55674,Dec.14,1983), and commentsreceived inresponsethereto.

(b) Notice of the proposedtest rule onoleylamineandcommentsreceivedinresponse(49FR 45610,Nov. 19, 1984).

(c) Notice announcing the finaldecision to require testing of oleylamine.

(d) Notice adding oleylamineto thelist of chemicalssubject to thepreliminary assessmentinformation rule(48 FR 55685. Dec.14. 1983).

(a)Notice of final rule on EPA’s TSCAGoodLaboratoryPracticeStandards(48FR 53922, Nov. 29, 1983).

(11 Notice of final rule on test ruledevelopment and exemption procedures(49ER 39774,Oct. 10, 1984).

(g) Notice of final rule concerning datareimbursement (40 FR 41786,Sept.19,1983).

(h) Notice of intarina final rule on testrule development and exemptionprocedures(50FR 201152, May 17, 1985).

(i) Notice of extension of commentperiodof proposedtestrule forole~lamine (50FR 3808, jan. 28, 1955).

(j) Toxic SubstanceControl ActGuidelines:Final Rule (50FR 39252,Sept. 27. 1985).

(2) Support documents consisting of:(a) Oleylaminetechnicalsupport

documentfor proposedrule.(h) Economicimpactanalysisof

noticeof proposed rulemakingforol eylamine.

(c) Economicimpactanalysisof finaltest rule for oieyiamine.

(3) Communicationsconsisting of:(a) Written public and batraagencyor

interagencymemorandaand comments.(b) Summariesof telephone

conversations.(c) Summariesof meetings.(4) Reports—published and

unpcbii~hedfactual mateniai3, includingcon Ira actors’ reports.

B. Be~f-arermces

(i~USEIN\. IS. En~mmmcm ml Proie’:tionA~oacv.Assessrn~n-I ofTa, tin;Q(ei i,rnaiire (9~octit’romotlm n-) supportdnmr,m’nc’at, 1,~’,:slOnaItu’t. IJ)3 p

3c~I:- of T’--’T:

Suhstrmmnr,, s- II ni PC, 1 ti. In-ca, - ml Trade

Corn ‘ni,Ara-r. Svaili~rtim:Ontanc Craemi~nts.U.S. Prudrctmora intl 3-ala”, c.msc. U-’.tatniatytan,DC: US. Cov,’ar.mni’nt Pr’rtram,t Offi’:m, USI’) Cpub. 14.2. (1583)

(3) USITC. U.S. International TradeCommission. Synthetic Organic Chemicals.U.S. ProductionandSales,i9~.i. Washington,DC: U.S. Government Printing Office, USITCpub. 1745. (1985) - - - -

(4) Eifinger, F.F.and Koehler, F.“Comparative teratoiogical studieswithorganic fluoride compounds,their basesandamines”. GermanDentalJournal32:861—866.(In German; English translation.) (1977)

(5) Bio/dynamics Inc. A SegmentIIIPerinatal and Postnatal Study of AmineFluoride 335/242in Rats, Proiect No. 72R-.-819.Philadelphia,PA: Manley & JamesLaboratories.(1973)

(6) Bio/dynamicsInc. A SegmentI RatFertility Studyof Amine Fluoride335/242.ProJectNo. 72R—817.Philadelphia,PA:Menley & JamesLaboratories.(1973)

(7) Bio/dynamicsInc. Amine Fluoride335/242 SegmentII RabbitTeratologyStudy.projectN~.72R—818.Philadelphia,PA:Menley & JamesLaboratories.(19i3)

(8) Bio/dynamnicsInc. A SegmentII RatTeratologyStudy of Amine Fluoride335/242.ProjectNo. 72R—820.Philadelphia,PA:Menley & lamesLaboratories.(1973)

(9) Bio/dynamics Inc. SegmentII RatTeratologyStudyof Amine Fluoride335/242(repeat of previousstud3).ProtectNo. 73R—580. Philadelphia. PA: Manley 8Laboratories.(1973)

(10) BLS. Bureauof LaborStaristics.US.Departmentof Labor,U.S. DOL 1983 AnnualSurvey.Washington,DC {1984)

(11) Akzo ChemieAmerica,McCook,Illinois, fla~ithHazardEvaluationReport79—140—1038,(1982)

(12) Laden, MM. Flardang.E.’i’. andYarkull.S.L. “Salivary giycoiysis after morthrinses”.HelveticaOluntoIopi a .4c;a/Sm-pplernerntumVIII 18:54—62,(1974)

(13) Shneider. P~H.and ,Mrahturnann, HR.“The antiglyuoiytic action of amine flourideson dentalplaque” - l5’ivs’tico OdontologicaActo/SuppleiriemrtumI’ll! 18:53—71;.(1974)

(14) Silvera. R.A.. Gebathuler, H. andMuhluniann, HR. “Salivary flounide levelsaftermouthrinsing with inorganic flourideand amine flouride”. HelveticaOdontologicaAeta/SupplemennimV/Ill 8:79—uI (1974)

(15) Scheuplein.R.j. andBlank, I.H.“Mechanismof percutaneousabsorption.IV.Penetrationof nonelectrolytes(alcohols)fromaqueoussolutionsand from pareOquids”.The forir~-oi uI Ina’est.fyatia-~.DerrmatcJogy60:286—296.(1973)

(16) CMA. Chemical ManufacturersAssociation,2.501 M Street, NW..Washington,DC 2(8)37. 1-1-Day DermalToxicity Range-FindingStudyof Oievlaaninein Rats, Protocol No. CMA—SC, (10853

(17) Rice. UP, “The ahsorptron, tissuedistribution.and excretion ofdodecyidim’n’hvlarnineo~ida(DDAO) inselected animal ,p-’:ies and the-absorptionarid excretion of Di)AO In man”. Toxicoioyvand kntmiim~,— Th-;,-mr’n oieyy33:377—359.(1a77)

(mu) t SFP\. tS. Eaaviiunaren a) b’~teciion,\gmncy. \3~’.;,,a~,rmcrrfrom Units Call tofob Sa,rtord. 3 ‘m’n’m-.- to Ira drrstry Cc-romeo .

Rep-u-dana d,s 3 - ,om,mc ,‘ano~‘mis of QUA,Washiaa a’ c’:: [‘(3. ‘map

(19) 81,3. Ytaamammma ~f Labor Statistics, US,a leer) ~t’ Lada mm. U.S t3UL [P15 Paroanal

Sua~ny.,\ m~ma .,-atora, DU. 13901

(20) Tregear,R.T. “Molecular movement, -

thepermeabilityof skin”. In PhysicalFunctionsof Skinpp. 1-62.New York:Academic.(3966) -

(21) USEPA. U,S.Environmental ProtectionAgency.EconomicImpact Analysis ofProposedTestRule for 9-Qctadecenylamine.Washington,DC, Otticeof Toxic Substances.(1984)

(22) Bartek,M.J., Labudde,j.A., andMaibach,H.l. “Skin permeabilityin vivo:Comparison in rat, rabbit, pig and man”.Journalof InvestigativeDermatology58:114—123. (1972)

(23) USEPA.U.S. Environmental ProtectionAgency.EconomicimpactAnalysesof FinalTestRule for 9-.Octadecenylamine(Oleylamine]. Washington.DC, Office ofToxic Substances.(1986)

(24) CMA. ChemicalManufacturersAssociation,2510M Street,NW..Washington,DC 2u037.Solmorzeila/Maanmalian-MicrosomePlate IncorporationMutagenicityAssay(AmesTest), (1985).

(25) CM?~.ChemicalManufacturersAssociation,2510 M Street,NW,,Washington,DC 20037. ChromosomeAbei’ration Assayin ChineseHamsterOvary(CHO) Cells. (1985)

(26) CMA. Chemical ManufacturarsAssociatron,2510 M Street,NW,,Washington,DC 20037.CEIO/HGPRTMutation Assayin thePresenceandAbsenceof ExogenousMetabolicActivation. (1935)

(27) Bio/dynamicsInc. A Two YearOralToxicity Studyof Amine Fluorides335/242inRats.ProjectNo. 72R—816.Philadelphia,PA:Manley& JamesLaboratories.(1975)

(28) Bio/dynarmmicsInc. A ChronicOralToxicity Study ofAnaine Fluorides335/242 inDogs.ProjectNo, 72R—815.Philadelphia.PA:Mentey& Jameslaboratory.(15751

(29) Ueichmann IV. etal. “j’he chronictoxicity of octadecylamnine”. AM.4 Archi’.’esollndustrial Health3a:483—487.119581

(30) McDonald W., et al. “The chronictoxicity of octadecylaminein therat—asupplementalreport”. ToxicologyandAppliedPharmacology4:61O-~12,(1961)

Confidential BusinessInformation(CBI), while part of the record, is notavailable for public review.A publicversionof therecord, from which CBIhoc beendeleted,is available forinspectionfrom 8 a,ni. to 4 pin., MondaythroughFriday. exceptlegal holidays,inRm. NE-G004, 401 Ni St., SW.,Washington,DC.

IX. Other RegulatoryRequirements

.4. CLassificationof Ru/n

Under ExecutiveOrder 12291,EPAmust judge whether a regulation is“major” and thereforesubject to t8erampuiremnent of a Reoulatory Impact.\ncml~Sen.EPA hasdeterminedInn-i’ it:tmast it mO is not major because It dam -m nm.rae-a alp of the cmitc’a-i a set forth itsection [(b) of the Order; i.e., it as all :Im’chave -an annual effect on the CCora’mcae Ut

at least $100million, will nut can’.; am

major nncrenase in pa ices, and v. ill aant

FederalRegisterI Vol. 52. No. 163 / Monday, August 24, -1987 7 Rules and Regulations 31969

have a significant adverseeffectoncompetition or the ability of U.S.enterprisesto competewith foreignenterprises. - - .. -

This regulationwassubmitted to theOffice ofManagementand Budget(0MB) for reviewas requiredbyExecutiveOrder12291.Any writtencommentsfrom 0MB to EPA, and anyEPA responseto thosecomments,are.includedin therulemakingrecord.

B. RegulatoryFlexibility Act -

- Under the Regulatory Flexibility Act(15 U.S.C.601 etseq~,Pub. L 99—354,September19, 1980)rEPA certifiesthatthis test rulewill rmt have a significantimpact on a substantial number of smallbusinessesfor the following reasons:

1. Thereareno smallmanufacturersoiloleylamineknownto EPA.

2. Small processorsarenot likely to-performtestingthemselves,or toparticipatein theorganizationof thetesting effort. -

3. Small processorswill experienceonly minor costsin securingexemptionfrom testing requirements.

4. Small processorsare unlikely to beaffectedby reimbursementrequirements.

C’. Paperas’orkReductionAct

The Office of ManagementandBodget(0MB) hasapprovedthe informationcollectionrequirementscontainedin thisfinal rule undertheprovisionsof thePaperworkReductionAct of 1980, 44U.S.C.3501ci seq.,andhasassigned0MB control number2070—0033.

List of Subjectsin 40 CFR Part799

Testing,Environmentalprotection,Ha~ardoussubstances,Chemicals.Recordkeepingandreportingrequirements. - -

Dated August 7 1987

J.A. Moore,AssistantAdministratorfarPesticidesaridToxicSubstances.

Therefore.Part 799 is amendedas -

follows:

PART 799—~AMENDED]

1, Theaaatharitycitation for Part 799Cont;nues to read as follows:

2. New § 7993175is addedto readasfollows: -

§ 799.3175 Oleylamine.(a) Identification of testsubstance.(1)

9-Octadecenylarnine(hereafter ODA)(CASNumber 112—90-3)shall be testedin accordancewith this section.

(2) The ODA testsubstanceshailbeat least90 percentODA. Thevehicleshall be onesuchasmineraloil for -

which there are adequate historicaltoxicological dataandwhich will notinterferein the testresults. --

(b) Personsrequiredto submitstudyplans,conducttests,andsubmitdata. -

(1) All personswho manufactureorprocessODA (otherthanasanimpurity)from October7, 1987 to theendof thereimbursementperiodshall submit1ette~sof intent to conducttesting orexemptionapplications,studyplans,and/arshall conducttestsin accordancewith Part792 of this chapter,andsubmitdataas specifiedin this section,SubpartA andPart790of this chapter.

(2) Personssubject to this sectionarenot subjectto the requirements§ 790.50(a)(2),(5), and (6) and(bJ and§ 790.87(a)(1)(iijof this chapter.

(3) Personswho notify EPA of- theirintent to conduct testsin compliancewith the requirements of this sectionmast submit plans for thosetestsnolater than45 daysbefore theinitiation ofeachof those tests. - -

(4) In addition to the requirements of -

§ 790.37(a)~2)and(3) of this chapter.- EPA will conditionally approveexernpLion applicationsfor this rule if

EPA hasreceiveda letterof intent toconductthe testtngfrom whichexemptionis soughtandEPA hasadoptedteststandardsandschedulesina final PhaseII test rule.

(c) Healtheffectstesting—(1)Developmentaltoxicity—(i)Requiredtesting.An oraldevelopmentaltoxicitystudyshall beconductedwith ODA intwo mammalianspecies,rat andrabbit.

(ii) (Reserved) -

(2) Mutageniceffects—chromosamalaherrations—(i)Requiredtesting.(A) - -

An oral in viva mammalianbonemarrow cytogenetics test: Chromnsomnalanalysisshati be conductedfor ODA.

(B) An oral rodentdominantletlanl- assayshail be conducted for ODA if itproducesa positive result in the in via-a

mammalianbonemarrowcytogenetics--

testconductedpursuantto paragraph(c)(2)(i)(A) of this section.-

(C) An oral rodent heritable - - - : - -

transloc-ation assayshah be conductedfor ODA if it producesa positiveresuit

- in the rodent dominant lethal assayconducted pursuant to paragraph(c)(2)(i](B) of this sectionand if sorequired in a Federal Registernoticeorcertified letter sent to-testsponsors. --

(ii) [Reserved)(3) Mutageniceffects—gene -

- mulations—{i)Requiredtesting.(A) Adetectionof genemutationin somaticcells-in culture assayshall be conducted-with ODA. - -

(B) An oral sex-linkedrecessive-lethaltestin Drosophila meianogastershall beconductedfor ODA if it producesapositiveresultin thedetectionof gonemutationassayin somaticcells incultureconductedpursuantto paragraph(cJ(3)(i)(A) of this section.

(C)-An oral mousevisible specific -

locustestshall beconductedfor ODA ifit producesa positiveresult in the sexlinked recessivelethaltest in -

Drosophilarnelanagosterconducted -

pursuantto paragraph(c)(3)(i)(B) of thissectionandif so requiredin a Federal- -

Registernoliceor certifiedlettersentto -

testsponsors.(ii) (Reserved) - - -

(4) Qzacogenicity—{i)Requiredlestiiaq~-Anoncogenicitybioassayshall be - --

conductedorally far ODA if positiveresultsoccurin anyof thefollowingtestsandif so requiredin a FederalRegisternoticeor certified lettersent totest sponsors:

(A) In viva mammalianbonemarrowcytogeneticstestsconductedpursuantto -

paragraph(c)(2)(i)(A) of this section.(B) Detectionof genemutationin

somaticcells in cultureassayconducted -

pursuantto paragraph(c)(3)(i)(A) of thissection. - - - -

(C) Sexlinked recessivelethal test inDrosophilarne!anogasIea--,conductedpursuantto paragraph(c)(3)(i)(B) of thissection. - - - — - - - -- -

(ii) [Reserved) - -

[lnformma lion cottectaon reqaairammaanlsarapros’ed he the Office of Manmagennent andBairIget under control number 2U70—IJnmPP.)

[ER Doc. 87-49309Elted 8—21--87;8:45 mam~

muuascoos esso—to-~ -Authority: 35 U.S.C. 2503. 2611, 2625.