Document 9vvGwxL0K8w5JRD0gYgLJQKL

Experinent No. Conducted At: Dates Conducted: Conducted By: Reviewed By: Primary Skin Irritation Test with T-3494 in Albino Rabbits . o88azB0012 FE 3 FEB 01984 ) EAS > RSiakfeertyLaEbvoarlautaotriioens,LabIoncr.atory St. paul, Minnesota January 17, 1984 to January 20, 1984 DBo n. .TarkUoms,a9r%f,o5e5 d n ate STotxuidcyolpiorgeicattor < KSeons5iosroTmDoaxliOlceoylN,ogist0 Acute Toxicology oAlr e= doi MX.oT5.. CEabsbeens FW.. Dc.. GMrciCfofrmiitchk 005520 - 1. Sumnary {he results of the primary skin irritation test conducted from January 17, 1984 to January 20, 1984 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3494 is slightly irritating (0.7/8.0) to the skin of female albino rabbits. Slight erythema with no accompanying edema was noted at the one hour evaluation following a one day occluded contact period. No irritation was noted at the day two evaluation. Introduction The objective of this study was to determine the primary skin irritation potential of T-3494 to the skin Of female albino rabbits. Tis study is not regulated by the Food and Drug Administration's Good Laboratory Practice Regulation of 1978, although the standard operating procedures of this laboratory adhere to the general principles of this regulation. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives. 005521 2. < Hethod ant posuite Lown aibine rabbits of the New Zealand breed were used in the evaluation at the primary skin irritating properties of the test article. The test procedure vas modeled after that of Draize et ai. one day prior to the application of the test article, the hair vas clipped from the back and flanks of each abit and to test sites selected lateral to tne midline of the back approwisately ten centimeters apart. One of the two sites vas abraded by making fous epidermal incisions, two perpendicular to the ether tuo, vail the other test site remained intact. he test article (0.5 3) vas applied o each of the test sites on each fasbit and insediately covered with two-inch square gauze patches. The patches, hich ware placed dizectly over She test sites, vere secured with gasse Vea. Ihe tru of each animal was then zapped with ispervious plastic sheeting \hich held the patches in position during the one day exposure period. A the end of one day, the plastic weappings, patches, and all residual test article were removedd, One hour and 48 hours after removal of the test article, the intact and abraded test ites vere exasined and scored separately for erythema and sdema on a graded scale of - 4 he average irritation produced vee evaluated by adding the sean scores for eeythena and edema of the intact est sites one and 48 hours post removal of the `ast article. sisilarly, the pean scores for erythess and edesa of the abraded cast sites were added. ZtasietteonBbeutchiand, ofmeth.t BDaefnveeurr, oBfAChemicals in Foods, Droge and Cosmetics SSoieneit'iwt1nag3e,xar2i0it0ki2icnlcBeiustw.raae Clear polyethylene slesves, removed vith water. PEC Industries, Inc. 005522 3= These two values were totaled and divided by four to obtain the mean primary irritation index. The scoring criteria for erythema and edema are shown below. Scoring Criteria for Skin Reactions . Teaction - Erythema Edema. Description Score Barely (Bages poferacreepatinbolte defined 1 Pale red Definite in color and red in color aanrdeaardeeafinwaelblle 2 3 dBeefeitneodr. crimson red in color 4 B(aRraegleys poefrcaerpetaibnloet defined) 1 Area definable but not raised more 2 than Area 1 ma. well defined and raised 3 aAprperaoxriamiasteedlmyor1emmt.han 1 ma. 4 Maximum Primary Irritation Score = 8 e eee ee The following grading systen was used to arrive at a descriptive primary skin irritation rating: Mean Primary Irritation Score (Range of Values) Descriptive Rating 0.10 = 0.5 0.6 = 1.5 31..16 -- 53..00 5.1 6.6 - 6.5 8.0 NMoinn-iimrarliltyatIirnrgitating Slightly Irritating MMiolddelryateIlryriItrartiitnagting SEexvterreemleylyIrIrrirtiattaitnigng he rating for a test article may be increased if the reactions caused are beyond simple erythema and edema, e.g. necrosis, escherosis, hemorrhage. The results are presented in Table 1. The protocol, principal personnel involved in the study, composition characteristics and Quality Assurance statement are contained in Appendices I = IV. 005523 wins te in nse ses i HSS J [ A-- ets eattaion scTeefeor vTassh pr ww wh : os Te 0 eee Jd Ve oe Lo) ve ee + oo os oe , ss ---------- ea--_ae ree sa Mean 0.8 0.0 "0.0 0.0 0.5 0.0 in0.0 0.0 ! ratings sabe destuasios a| J mm t j=r,.-* ~ EEE 1 ie Sports, Tm . PROTOCOL 5. a TEST: ---------- SPONSOR: 3M__-- Cormerci-- alChemica-- ls --------Division CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, Inc., St. Paul, Minnesota. TEsTARTOLE_T:3e4 ! contROLARTICLE: Nee PROPOSED STARTINGICOMPLETION DATE OF TEST: [54 - 4[35 | TEST SYSTEM: Fomelo Now Zealand White Albino Rabbits ; ounce: Dimeiard Lies , DENVER, Px ------ ' OBJECTIVE: To detmeermiion tahe phroimfaorsytisnytsattoimn dpuoleetnoitalheorf thihsttoersitcaalrulscee, tsoentshietslktiyntoof i_ha&nts--, eaanismealosf,hRaantdiitnsg and general availability. "METHOD: "Twihtehanfiomoda?lsanwdillwbateehrooufsfeerdedinasdtalnidbiatrudm.wiEraec-hmeasnhimcaalge`wsillinbeteamspseirganteudreaannudmhbuemriedidtyeacronttargo,llwehdicrhoowimlsl 1 ! oronrtboehspcoinepdpteodo8frctoahmredtbahfaefcbikxaeacdkpoatnphderofuloatnsxkistdioeefonmfcetaeanhcttehicaamanegiltemea.yrlPsraianopradrtto,2 _thLe a_p--polifctahtieo2 notefstthessittteossstswaaritlliecblceee,adtblhraetahedraealrd bay maokin. g fouTrhepoitdoesr!maalrmianc,cic(soiv0oenr,5etd5wwoi2 ptehr_pe_n) dgiacuulzawreitlobtohaepoptlehineerddsttweooc,u_wrLeh_dl_w_itthaheb_rotaShdeeerpdteae=snSdaCt1 eLsL) Cw.il1 : ITnerotueasrciatoarsta1itc0lt(.a3o)nfudorcanialnceyghaatcdhaehneaidtmn1adeilsawtyisletlxotpshowesinublrebewpereeraxipaopmdei.dnOewndietahhnodIumsrpceaornrveidod4uss8epphlaoarusatrtiseclasyfhtoerertreiernmygotwvhhaeimlcoahfanwtidhleeoecdcsoltmuaadreotinhse,& | reaedeeidesrcmalae aofnd0o1d0o4m2.aTohftehaeveirnaacgtetersatsieosnopnroedauncded4w8ihlobuorsopvoasutatreedmbovyaaldodfitnhgettheesmtaorteicles.cSoirmeis ! vJaalruy,estwhiellmbeeatnostcaolerde`safnodrdievriydtehdebmya faonurdteodoebtmaainotfhethmeeaabnrpardiemdatreysitristiatetsiownililnbdeoxaadnddetdh.enTahsessiegtnweod `a descriptive primary skin imitation ratingas follows: `Mean PrimaryIortation Score: 01-05 DNesocnrdiipatitvienRgating Minimally rating - 0166--1350 SMiigdntyItiantaitnigng Let \ 31-50 Moderately Iitating 6651--8605 ExStevreormeellyyIIrrrtitaattiinng,g 5 i TsthuedryaatadiainrSgecfhtooarrmaaantdeostthbaear.fioicnflalirmmeppaooryrtbtawneiclelinbncerte`hsaetsoeridenidtfeirtnphrteehteraetRiaiocknetorofnLtcahbaeourrsateeosdruIises.s'bAaAlyrcrohaniwdveed,raySltta.hgPeeamnuale,raanMtidendenedbsyeotmtaha.e . 8b DPruariiznea:RaAbpbpriatiCshalowo,f tRhaelsStaoentPuyroifnGahCeom.i,caSti.siLonuiFso,odM,isDsrouurgis and Cosmetics (1965) ood and DrugOffclsofthe United State ! wt Dibianod oy heEdtoral Commitee oftheAssociaton ofF Lonel, 1f2f2> Donn Canes 3 12/7/50 `Sponsor ate" `Study Director " Date Fom wir. 005525 . . AppmuDIX 11 principal participating personnel Involved in the Study sane 0. he Hazkos, Ir. 35 Xo 5. mbens, 5S K. Dv o'malley, BS G. c. pecore Function -- Say piector Tsuopxeircvoilsoogry Testing sHeenuitoerTTooxxiiccoolloongist sFuipnearlvisEoarporatory 005526  7. APPENDIXIIT - composition Characteristics mis study is not regulated by the Good Laboratory Practice Act of 1678 and therefore information pertaining to composition characteristics 4s not applicable for inclusion in this study. 005527  5. appENDTXIV. quality AssuranceStatement This study is not officially regulation of 1976, and therefore regulated by the Good LaboratoryPractice & statement signed and prepared by che | Compliance Autit department me standard operating is not applicable. procedures of this laboratory does adhers to the general principles of this regulation. The Compliance Ault dupartsert does inspect different significant phases socioolosy aberatory on a recurring for studies ndemvey in the Acute cycle, aad the facilities are exasined on + thes ution month schedule. In addition a are routinely picked at random select number of Teseazch & Development from the Archives by the Comlisnce Audit department for review. 005528