Document 2qLk81KraBOMovQbzK0w60mGR

ears ssn orsreson mee LP, -- 2, : in albino rabbits u, Experiment Nou: Conducted at: Dates Conducted: conductea ny: / ECE2) || AUG23 1955 2 0e0m108 Revieved By: osssesozes SRaifkeetryLavbaolruaattoiroiens,LabIoner.atory Se Faun, Hnmesota Sune 15, 1983 to June 18, 1983 D 3aakons,anSrvf, o5e d 5B5atse TSotxuidcyoDliorgeicsttor CabneenLeOY ole, olEeQ RSeonuitoerTTooxxiiccootloongyist G SpEG ermvismor,eTe oarcology Test<ing4te4es; "emWac.biMeicoirsEicmk 00137 1. : Summary The results of the primary skin irritation test conducted from June 15, 1983 to June 18, 1983 at Riker Laboratories, Inc., st. Paul, Minnesota indicate that T-3421 is moderately irritating (3.2/8.0) to the skin of ferale albino rabbits. Mild erythema and edema were noted at the one hour evaluation following a one day occluded contact period. The erythema persisted at the 48 hour evaluation while the edema subsided slightly. Introduction The objective of this study was to determine the primary skin irritation potential of T-3421 to the skin of female albino rabbits. This study was conducted in accordance with the Food and Drug Administration's Good Laboratory Practice Regulation of 1978. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives. 00138 2 Method and Resuies GF Young albino rabbits of the New Zealand the primary skin frritating properties of breed? were used in the evaluation the test article. Te test Procedure was modeled after that of Draize etaif, one doy prior to the application of the test article, the hair sas clipped fron the back and Elarks of each rabbit and two test sites selected laters so the midline of the back approximately ten centineters apart. One of the two sites was abraded by making four epidemal incisions, two perpendicular to the other two, while the other test site remained intact. Te test article (0.5 5) vas applied to each of the test sites on each Fab and samediately covered with two-inch square gauze patches. he patches, "hich vere Placed Girectly over the test sites, vere secured vith gauss weap, The trurk of each animal was then wrapped "hich held the patches in position during with impervious plasticsheeting the one day exposure period. A the end of one day, the plastic wrappings, patches, and all restdse test article vere removeed. one hour and 48 hours after removal of the test article, the intact and abraded test sites wore examined and scored separates for eryshena and edema on a graded scale of 0 - 4. The average irritation produced vas evaluated by adding the mean scores for exythess and edema of the intact test sites one and 48 hours post removal of he test article. Similarly, the sean scores for erythema and edema of the abraded test sites were adted. BZouasssizeet:on ADupspcrhaiiasnadl, oftnteh.e Sbaefnveetry, of7aChesicals in Foods, Drugs and Cosmetics 21g1e0ms.5t1ien3nge,xaHr0ti0ii2cnieebreeverarss Clear potyechyiens sieeves, removed with acetone. Bre srbmeenien, Doe 00139 oo 3. These 0 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 Reaction -_-- beserption seem Erythema dena B(aErdegelsy opferacreepatibnolte defined 1 DFeaflienirteed riendcionlocrolaonrd aanrdeaardeeafiwnealblle 2 3 defined. BBaereetlyorpecrrcienpstoinblreed in color 14 A(rEedagedsefoifnaabrleea bnuott ndoetfinreadi)sed more 2 than Area w1 emlal. defined and raised 3 aArpeparoxriamiasetdelymor1 emnt.han 1 mn. 4 -_-- Maximum Primary Irritation Score = 8 The following grading system vas used to arrive at a descriptive primary skin irritation rating: Mean P(rRiamnagreyofIrrVailtuaetsi)on Score Descriptive Rating 0.1 - 0.5 06 = 1.5 NMoinn-iimrarliltyatIirnrgitating 1.6 3.1 = - 3.0 500 SMliilgdhltylyIrrIirtraittiantging Moderately Irritating 5.1 6.6 = 6.5 8.0 ESxetvreermeellyyIIrrrriittaattiingng The rating fora test article may be increased if the reactions caused 27 beyond siuple erythens and edema, e.g. necrosis, escharosis, 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. --i------------------ 600140 | . niet . | Primary Skin Teitation Test - Albino Rabbits [Pp smal maser w traf risateon seoTrhe eewefoormenca"ted Srtsontnion soroennfeoSeemnentna:ct tt", = S2$ w0s m co: 2 sa a 2 g2Baam e z " 2a \ o FE 2 1' 1 :2 a o oa a an [EE son FE soa. aa mre ern s eto se sa esresom e ------a0--t-- e -- oe -- J " Ratios: voters deriation os Pinury sritation taien 2.2/0.0 PmEimI e * rest.(pAocuetePPriimnaryaySSkniniIarittatoionnTTeest 20PEOIN PROTOCOL Aker Experimanio:_SSBIER0S . SPONSOR: aM__CoCommemrecrciiaallCChheemiccaall 000000 Division CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, nc., St. Pau, Minnesota TEsTaRmOlE 0 Tse 00000000 conteotarmowe: Mow: PROPOSED STARTINGICOMPLETION DATE OF TEST: 8%.= TEST SYSTEM: Fame Now Zealand Whe Abin Rais 42 REST COPY AVAILABLE SOURCE: Tu riit,ayy `pz, AEpnER "bE --_-- OBJECTIVE: gTseeonleedrceattleedarvmaaisinleatbhitelhtelye.sirtristaytsiotnempotdeunetiatlo otfheitrhehitsetsotriacratliculsee,10 stehnesiskviiny o1f0 _T_a6s__, aanismaelso.f Rhaabnbdiitnsg.wmearge METHOD: cTwiohtrehreafsnopioomnadldsatnowdialwcabateredrhaoouxfseeerddetdionastdthaeInbodiuattursmd.idweiEroaefc-thmheeasnchiamgcaea.lgewPislrliinboetr0eamtphseesraaeptpudlriecaaatnniuodnmhboufemrtiehdedittyweascroanartgire,oilelw,eidtehrneohoemlse b{woyitlmhbaeekmicinldgilpilpnoeeudorffertpohimedebtrahmecakblaaicpnpkcriaosxinoidnmsfa,ltaetnlwkyostpoefenrecpaeencntdhiimcaeuntlieamrrasl1aapntahdrei 13.of her two, hioZ.--as--t whia 1 sstess6 other swielleecstesd oIroenss test sete xa lremtainsoinlta)ct.onTheeacthestaanraiclle c(o_v0re.dS_wighzai ns--z ) wile be appalinead sfeoc1 ured wihabS rsasdepI d angZ1 ET _ htTehesetiantrtraiuccntlkeaondfudreaianbcgrhatdahneeidm1atedlsatwyisllietxtepshoewsnilulbrebeewpreeraxipaodpm.eidnOenwdietahnhodiumsrpceoarrvneiddou4ss3epphaloarusarttiseclaysfhtfeeorertreiernmgyotwvhhaeilmcaohfawntihdlesotcoecsmtluaadreoientlha,e vlfgaoarrrllauyed.erestydhtwehsicelmamlbeaeeaaonfnfodas0cleoetdordee4asm2.nafdoTordhfieevtrihayedvteiehdnretbamaycgatefatoieunrsrdrti0tseaitdtioeobenstmapoairnnoeodtfahuecnthedmede4awa8ibnlrhloapbudrereisdmeavprtaoeylssuttraaritteetmidsoobvnwyailialndodfdbeietxnhgeaadntfddhoesedtt.hmaeenrTachsne.essascSmomrereyns 2 descripive primary skin ration rating as folows Mean Primary Iraton Score Descriptive Rating ++ 2+mm rec amy Noniriating Sn 0061--1055 16-30 SMiingimnaylltyaItririntgatin}g| 11% i333 i | Mildly Iritating i 31-50 6551.-8605 Moderately Irritating i od SEexvterreemleylyirIriittaattiinn_gg ~ = ~~S+ o akrareni] aTnhde arrateindgeefomreadtteosbeartoifcliempmoarytabneceinincrtehaeseidnleilrptrheetarteiaonctoifonthceauresseudltsi.s bAlelyroanwddeartyatgheenmearaatneddeodyetmnae study director and the final report will be stored in the Riker Laboratories' Archive, St. Paul, Minnesota. 2 PDruariiznea: RaAbpbpirtaCihsoaw.l oRftahelsStaofentyPourfinCahCeom,icSat.lLionuFso,odM,isDsrouugris and Cosmetics (1965) o Soooensror0 H.C HicPenCgorntby he Edioa ?gal6C-o9m0m-8i3tCeoeieof the AC Sstsuodcyiiyd atDiroeDnicre ioofrFoon d aa6nadn0rDd 0riu1gnOn 4.ff5i)ci) als of tohloee;UlniteedDnSattaetes. -- 6. Aepmvorx11 Principal participating Personnel Involved in the stusy Nase be ul Markos, Jr. Bs Ke L. Eobens, 3s XK. 0. O'Malley, Bs a. c. recore Function TStouxdiycodliorgeicsttor TSouxpiecrovliosgoyr Testing sAecnuisoerTomxoixcioctoolsoygist SiunpaerlvisLoarboratory 000143 repr 111 7 Test and/or Contre Article Characterization KT2-ss (ccs3/-07) TEs 1. The identity Ge serengeh, uniformity, Rn conpToHrEiAtiooonn,EpEuritSy oLr STt2herHpEper-- - 2. TfThrreaotmusse.oitenhgoldythoefsesynatmhmeesnitsavorsyeosoraigimnethofondotohfe Hteismtemannsd cSoonrttrroolL siubbsstteanncceess, 3. Tmhienedscoaxbiwliicly obef dtehetertmeistnedands/so'orfcon2tr5ol Jsuubistanc3esohnavecudbeoep ddee[resl -- The above information and documentation are located in the sponsor's re- " Son8e 12.4 s/hsals3 cc yD. adec 236-28 - Ww. Cc. he WK 230-26 I A WH. feodu. 223-656 aT : 0 way3a1 1y983 000144 PEED JUN 131983 | . AspsnoIx1v ares asses sym heute Toxtcology Laboratory studies Study No.: C2323: 020 is short em sey vas astited by Compliance Audits and the final report examined against Te results of the awitt vere the raw data on reported to the Lig wu Zl7 (175 scedy dhrector and to samagesens on __ fe rs or. In adastion to the data aut, itfersns significant phases for ctudtes underway in the Acute Toxicology avoratory are Snspected veekly on a recurring cycle, and the facilities are examines by Gonpliance Audis on a three month scnedule. - Te Go fod Poi Lege < Ly c222 00145 oo