Document dYVqgnZp2Z02b5dyZdQmqONm6

Primary Sin Irritation Test wien 3071 n Mbino Rabbits Experiment o.: Conducted At: iViaa conducted By: | JUL 201983 o70e0195 Revievad By: oseazmo0ts SRiakfeertyLaEbvoarlautaotriioens,LabIoncr.atory Se. Pasl, Minnesots March 1, 1983 to March 17, 1583 DToaxoiRc.eola.orgiisect,aJrr.bBo.57d ssfbate Stuey Director +5.ier, SAecnuitoerTToocxoircoolgoynst Misfweem cm FKbL GcBarosiveteenisen WC wecormiox 00097 - 1 Sussary The results of the ICAO skin irritation test conducted from March 1, 1983 to arch 17,1963 at Riker Laboratories, Inc.. St. Paul, Minnesota indicate that 7-337) produced irreversible tissue damage to the skin of female albino rabbits following a four hour, a one hour, and a three minute contact period. Moderate erythess and edema, as well as, chemical burn, eschar and necrosis vere produced following all three contact periots. An endpoint, as required by ICAO, was not achieved due to the extreme irritation folloving each contact period. Introduction The objective of this study vas to deterine the ICAO skin irritation potntial of T-3371 to the skin of female albino rabbits. is study is not regulated by the Food and Drug Adinistration's Good Laboratory Practice Regulation of 1978, althoush the standard operating procedures of this laboratory adhere to the general principles of this regulation. The Fav data generated by the Study Director and the final report are stored in the conducting laboratory's archives. G00098 2 tethod ang messice Young albino rabbits of the New Zealand breed were used in the evaluation of the prissy skin Lrritating properties of the test article. he test procedure vas modeled after that of brazestail. ome day prior to the application of the test aruicie, the hair vas Chipped from the back and flanks of each FaBbLE and two test sites selected Lacersd to the midline of the back spprosisately ten centimeters apart. he test article (0.5 5) vas applied o each of the cert sites on each abbit and immediately covered vith tvo-inch square gaue patches. The Patches, which vere place directly ow the test sites, vere secured vith gauze veap. The trunk of esch anisal vas then veapped vith fmpervious Plastic sheeting which held the patches in position during ekeher & four hour, one hour or three minute exposure period. A the and of the exposure period, the plastic wrappings, pacehes, and S11 restaun test article wre removed. One, 24 and 48 hours after remomal of the test article, the test sites vere examined for frrevsaible aanage ant scored separately for erythesa and edems on a graded scale of o- 4 (Table 1). The length of the exposure period i reduced until an endpoint of no srreversible damage is reached, if possible. he xesults are presences in Tables 2-4. The protocol, principal personnel involved in the sca, cosposition characteristics and Quality Assurance statement are contained in Appendices I = IV. SBSuoaezniae"c!on obuptrcanitsanndt, ofnct.h,e Svaefmveecry, ofmAChesicals in Foods, Drugs and Cometics 1Sh0eexti1n3g,x H00i2nEexrtra Clear polyethylene sleeves, PIC Industries, Inc. eare es errr eseed WE water. 00099 a Table 1 Scoring Criteria for Skin Reactions Reaction besemipmen seers Erythema dena B(aBrigeelsy opferacreepatibnloet defined ' DPeaflienirteed riendcionlocrolaonrd aanrdesardeesfivnealblle 23 dBeefeitneodr.crimson red in color B(aBraegleys poefrcaerpetaibnloet defined) ' Ahraena d1efzai.nable but not raised more 2 aAprperaoxwiemlaltedleyfin1esda.and raised 3 Area raised sore than 1 ma. ` Maximum Primary Irritation Score = 8 G00100 a Table 2 Primary sin Irritation Dest - Albino Rabbits with T-3371 (four hour contact) - IrritationSSictoersesArftoerr RReisgohvtalIntact Skin ANnuimmbae)r I=medtatel=y =24 Hours= =48 Hours= 38358 28 a 28: 3 2m 2 8350 28 4 2m 3 im 2 38383 2` 2m 3 2x 2 NAunsibmear) mse 3s3s0 38353 IrricationSSitceosresAftfeorr LReemfotvaIlntact Skin I=nsetatel=y =24 Hours= =48 Hours= 24 2: 3 2m 3 28 4 2m 3 2m 2 2 ` 2: 3 2m 3 Xey: C== CEhsecmhaircal burn NX == NEepcirtohseilsial sloughing EERD == dEreytmhema 00101 5. Table 3 Primary Skin Irritation Test - Albino Rabbits ith T-3371 (one hour contact) - IrritationSSictoersesAfftoerr RReimgohvtalIntact Skin ANunmtbmearl. I=mmediatel=y =24 Hours =8 Hours= 38348 '2 2c 3 2m 3 38384 , ' 2c 2 EE mss. '2 2c 2 im 2 IrritationSSitceosresAftfeorr LReemfotvaIlntact Skin Haunmibmearl Im=mediatel=y =24 Hours= =48 Hours m3e9 ' 2 2c 3 2m 2 3m380 ' ' 2c 2 ze 2 38385 '2 2c 2 ame 2 Key: C == CEhsecmhiercal burn NX == HEpeictrhoesliisal sloughing DER == EZrdyetmhaema 00102 : 5. Table Primary Skin Irritation Test - Albino Rabbits ith 7-3371 (three minute contact) - AMnuismbaelr 38397 3m305 38394 IrritationSSictoersesArftoerr RReimgohvtalIntact Sin T=asectately =24 Hours= =48 Hours 25 1 2wx 2 wx 2 28 1 2m 2 2m 2 23 a 2m 2 awk 2 ANnuismbae)r 38397 anes. 38394 IrritationSiStceosresAftfeorr RLeesfotvaIlntact Skin Ia=sediatel=y =24 Hours= =48 Hours,= 28 1 2m 2 2wx 2 2p 1 2k 2 2m 2 25 1 2m 2 2m 2 Xey: XB== BEpliatnhceilnigal sloughing N == NEesccrhoesris 0ER == pErayctehsesa 00103 oC ou Le 7e5t,___ AcePriSimraaiornTyest aremDI1X RarEpedm08a02O:n80Tt7E tos PROTOCOL 2. _ SPONSOR: aM_Conmeccial Chemicals Division CONDUCTEBYD: SatetyEvaluationLaboratory,RikerLaboratories,inc. S.Paul, Minnesota TESTARTCLE:Y=2om covmoLAROl Sens PROPOSEDSTARTNGIOFTCESTO: 2M/2P=oL/Es TIONDATE TEST SYSTEM: FemaleNowZealandWhoAbino Rabi SOURCE: Dire pmury Lps, LEWES, Pi OBJECTIVE: STeoldeectetrami3nehteheistryamnapodleet1i0lohfotihePtteotdaerli3l6.1sehnessikino1f0_F_ais__,aanaismeaol.fRpaanbcbitnsgwaenrde evra avasabiny. METHOD: GmTVehisena1pn0oi0mn0adlsanwi8lvbcaeathadoaoufastereddinoast0taenAoduoatrsldiw.derEoeafcmthahascrhacmgaaeg.wPesrlionDa01m4ptho4eraa6ptpu3lrieca&atrniuodnmohofrtueoidteac!oan5rvo,slewe,hdirfchohohwmaisrl Vil cpp HomtabackanTanks ofe4ch rma nd 2 ltsi slot ater br10yotmhaaenmviiidinianoe.uoTrfhstapheteboramcakraipncperao,sx(oimna,t5ewloytpeenrcpenetnidmectuewrrsia1pbarehtaa.Gp_opQur_ed_uottof,twheh_e2_ha_ebsriiatvedeserwdielaslbnsedoablr)aw=dield_ Toinetactusikte(os)f eoanceharchaanlimwall "tchoavnerboed waithb_d_wi2aimpuerziotus aansdkssechuoreodtwitwhhchSewireoCcod.T.e. + gtnreesatdaeratdcisctcleandluedroaifng0t1h0e421.d05aTyhe1xa0pvoewsrulargbeepsmeaxrtiioaodnOpnnreoadhnuodcuesrcdaownis4bs8onescpvualrrodotyBeitdoebrrroyeamyodvnaelgofathtnehmetedeasontmasrct0ioc0rlee8s, fiorterytthmemeaaandsecdoreemsafofotrheaintmact festsiotedsoanmt-and4S8-hhaoudrspo0s5t-reamsovtekso0f0th-e0t0e0s0ta.rtTihclees.sStmwo vaalSueessewnipltlvbeertomtaalendsannddivaitdeidnbya-nfogdatsolOobtwasin:themean primaryimitation indexandthen assigned 2 lmer centet CFonl ntre:t: est 00 MoonPriry wiatonScore 010s FDeNisicrrmispativneaRastiing --NW\EE|D ee wabick 0501s Signy rang. FEB 211983 wu IeATihg To a16i-s3e0 51.65 NSMeiovleddrlyeilaryriltattiaintgsinigng TY CYALU0A1T1IiONi Seles Ermer man aTnhcdeyrraertiSongcoifoorradandt1estibeaonncfllirnmepaopnytanbwclain5icrsSeahsoedraierthteereaakctrioofLntacnba.urrsaeesiduossi.s'AbAleryceohnwedSe,raSytt.ghBeomaan,aanMdodraebdysema 2BPurinr a Rao Chnowe, Roalrstomn PuorintaCoo.mSe. Lnodis,SMistsourEi preu ATES 117sDPBruaneckees: CAoocteyhsSneeiatEefdouoep)oSnaCtoranyeotsfesshoomofifhceltAsesgsnhocFaoStoidp,onaDrofudgFseooadnadnCdnodsLmDereontpeO(h119i6T5ao)f.toUniedSi"tes EoLC Se S7sGaesrttTaCy vEacEa AT apaBiisc 00104 . : Riker Experiment wo.:__ 088380079 6 AppE(cNoncDluIdedX). 1. In adaition to the four hour and one hour contact applications an addition application of three minute contact with three animals vill be dosed Dn. canbed --_----e 2. Due to a delay in report processing the proposed completion date should be amended to 6/83. TO.on Arbor dg 100 wm omer mee 31 ce erme rvmre eerre eeeert------------------ gamer ae . EE -- 5 wy omewr an 00105 . 5. Aepmworx 11 Principal parcicipating personnel Involved in the Study vase bo N. Markos, Jr., BS Ke 1. bens, 35 X. D. o'Malley, Bs 6. c. pecore Function TstouxdiycoDloigriescttor sTuopxeircvoilsoogry Testing cseuntieorToTxoixcioclolooggyist sMunpienravlisLoarboratory 00106 10. apmOIX 111 Composition Characteristics his study is not regulated by the Good Laboratary Practice Act of 1978 and therefore information pertaining to composition characteristics is not applicable for inclusion in this study. 600107 a fr---- gusttey resumes sasenens is study La not officially replated by che Good Laboratory Practice Pagulacion of 1978, and therefore a statement signed and prepared by the Compliance Audie department La not applicable. he standard operating proceduses of his Laborsiory does adhere to the seneral principles of this replation. Tha Compliance Audis Grparcaent does inspect @ieferent significant shases for studies ndeay in the Acuce noxicotogy taboratory on 4 securing cycle, and She facilicies are examined on 4 three month scheduld, In dfition a select mimber of Research Development ctuties ace routinely $icked at random from the Azchives By she Compliance Audis depaciaens for xeview. \ 00108