Document yp47XR90m5VopwBwJq887bpZr

HAZLETON soonwones semcane Chemical & BiAotRoa2io2al6Sc-ie0nc2es4D3ivision " 3301 KINSMAN BLVD. + P.O. BOX 7545 + MADISON,WISCONSIN53707 + PHONE(808)241-4471 + TLX 703956 HAZRAL MDS UD. ine spoT HE 1| ; SsIioOEonNeaeIDnNTSs,ELseEssRFsScIOoeNNiI|cNeseercruging corey cree e372 incre OROER NBER: TIS7R4Z, REL. 913 sorpLE nurses: s0s83500 soreLe EnreseD: 8155 ecpoRr PRINTED: 06/21/85 ercuosco: BiprRueinB2 aERRYTGERI (RRITATION - ETH, SUHHARY stove: R o SMTRenDA eIEa EtTen Nae. sN hit ES. e6r 7rncbatR eFORromHAZTLHEIRSTONSATULDAYBORA AARTEORKIEEPST OANTERFIICLAE, TC. AT HAZLETON LABORATORIES 01061 HAEZeLETON ernoeonWeawaorEcnCeeONSE FChOoBmolNeaalE& BoM7dTiXcaTlENSAciPeAnZcEeAsLDOiSvisUi0on SovPLE MurBER: 50503500 snp: 1-372 ree 2 CECD SKIN IRRITATION omsjFreeacctTtiievveermr TToomddetaretremrimnieno e tthheer rreelaltieve llevuelboBfearpnsorasinoesImreynidroistpkiirtoinonosnniisr3ssor.vcirstGiaauoatrrniddioeionteningn,es ffroarreaBtrianng eSoaisneot Ee ts TessEitryrsiHecaattleartBiiensstlesrliTpT3t3i77o52n2s aBprroooumnSlgaralnualarr2so0lidting stability determinations esi NStewfZmo einaallm sanUdYnnoiautgngegestardeuI ilnt rbaebrbeitpsoe(spproxiCniatFneeitlbyenirn1e4Rtdabursiisn+kdasihvlolionfduduaagioqelnu)ydartosifenertset,rhse BTTnrrneesnascdvceolliinenmraatrtaeddoe ananiiemmaaleel;se ,weuisgR hiisnhgianr g(troinfor2onant22p2el11re2ieo%0tdt:%o72d3SuT2arev3isetn.gg,antwiheemraelosbscehvraevsreaention r ee pemrnie aond specifimeedFoe ente the" boisnaaansaro113ep3e.d fArpormoxtihenetbeaclky fenS sssoonnftoe orrSSppeemsiihueessSeSellea eccttiioonn:: HiHsitsotroireicelly, theerNevwaiZoenstlainndg Uhneiteoffect ereppoarrattioan and Administration of Test Materials The sample ues dosed sx IreFTsIosBnRttImLerenotn:rtei:stnedtTThhhaeeereasttmeesseattsmnmaecttoeoerrviifeesllreuwasSdsEaPpEpliSsaEdtantSorEesnthaennpheieranegntddaaucatzEpewrpiasliskPeheiascntpo0lnot9ofo%sstecrcaseucasthrliaierpndeaei.n HHEopedee i ope ereeee eposure Pario 01062 @ HAA ZLEETEON onreos eosnenEcaceoFr PCRhefmOiocaNl &E7Bio+aXtiTaR! ASciAeEnTcAesLDOivSision SrpLE numBER: 50503500 powig: Tame wr 3 OECSDesTsSoheKreruIvTnNaettsiiItooRnnRissI::tTeAAsTIfAOftNtyoeerrerttwhahseehes suwppeeosiuunrerg BpeeLA riKod,cRcothneSTPivpuaaEtvDcen)hteesrtheawnedrteesdtirsepmSooivrteaads.ie30 affBehelairrroouueeisnhgelyareasmspoovseiainbglolefe A i athett3n2htioumo rsneaflu gtelr.e opat)chheegrEteihmEeiasnvL.aelqo:fueTnsheriritssyhxeenmmsiinnsaanttdai.sonssdena I rordunl body weights were taken Fathotosy: At study termination oll just prior to study initistion. aninsls vers suthenstized and discarded. oaDvnrdianiSzeoel,,me3t3i.Hcs.e.=D"EeeprrpmereosliaTsOolxioTcfitTyeh:e S5SeaofCettiyosofensCh!afmicalFsoodinanFsoodbsr,igDrOufgfsicials 01063 @ HAZLETON veonone woenne Chomleal & BloMtdical Sciences Division : 3301 KINSMAN BLVD. + P.0. BOX7545 + MADISON, WISCONSIN 53707 + PHONE(808) 241-4471 + TLX 703956 HAZRAL MDS UD corPLE nureER: 50503500 rE: Tess -- GED SKIN IRRITATION coon iEDs sumer TUfoesetmnAmmiezl: nAblnbiSneoaRabbits2ae-dsvNeerwe,Zeailnaen.d UDneintveer PA Lnmerature and Humidity of Aninsl Room: 221 = 2I3 Degress C.;misty Date Test Started: 15/29/85 dote Test Completed: 06/01/85 Gehicle: Hoistensd with 0.9% saline i anima ecRoensers dean IndividEual t Dermae l Irritotion Scares PEryRthaonLnsesSours PGRoenTnCasSsoJore SS0.sh0 b00.hd0 b0E.do0 o0i.en0 80B 0 00.H s0 0w.e0R0B.d0 0.0 0.0 0.0 0.0 60 0.0 0.0 0.0 orinory Dermal Irritation Scores Observation Period MI 2234 tetooueurrsrs:: 4 fos: ==0.0 BH I Ne dermal ieritotion ues sbserved at any tine during the study peried. sev8Si.ia3%toioSnnatfifrnaremamrtaththheeeprrprtehotatneorcdoelT tsoniTzheede tevset tmaotelrisalteumdsoemIno.risttheeonnePdtrhoewtietvhaal!idity SRC 601064 . @ HASZSLETON oteroos ~ nMaswoonmWeencosNSN S77 FChOomfoiNca2l1E& 1BioMeTdXicTalOSAciWeAnTcReAsLDNiEvRisUiDon SarPLE nurBER: 50503500 serpLe: T3792 we 5 OECD SKIN IRRITATION cconTINED) fororansant 1. rOrguanmisesttioonnFoforEEseonoemic oCoopeeratikoasn, anhdeurDeeusDloorpamnentI'rsriGtuaitdieolnines 2. fDaOonrrrdeeiilCzozeete,nm3ei3tni.c4s, "apppDrraareeiesslalT3o o3x,oife"lTttoyheeS iSSafaetytSofetCoehnem5iatca5lFso5ndin)anFdoodDsr,iDrugs, 010865 - PAGE 6 QUALITY ASSURANCE STATEMENT Primary PR Dermal Irritation Study in Rabbits T7ScTemeaandeGteeseh cctnd oe x he shoinevsmitionLeoamemesatdeibaeassssdoteveoerctnehviionsed S E s21arCFiRs58f.an35O (b)t(h6)o(e i7)d.eeetIthhaR s beenEfoounrdchuiptetoeiaapaecsecbiuLrrnyaasthpeAloeiyftrsseaioestdiesooaprstansififcadyfraaoosnectidi/oovoonnercs1hr2toor the study director and/or management. O bate of Tospestios Ire of Inspection Date Tasued to Hanageseot 5/21-23/85 " enores Process Audit Report Review 5/23/85 6/10/85 gB BnARuA E o FED arn ca~ne woteh a=lls-- 01066 S0503500 PRIARY SKIN IRRITATION SCORING SCALE (1) Erythema and Eschar Formation VNVoeerleylr-ydJteihfiiegnnhestdereyrtyhcehsess(barely perceptible) 022 Yoserace to severe ecythems 5 Severefoerrmyatthieomna (i(nbejeutriersednieossd)epttho) slight eschar . fighest possible exythess score . 0 adeas (2) Edema Formation 0 VSerTyisleigmhtaed(eemiagen(boafrealyxepservceeLpit-idbeltei)ond by 1 0 MrodeerdaBeteefSyionanadidetneasrareas(oirsoaeifinsgee)dmxopsropsepurraeo)xnias1tmelmyan1dmme)xtending 23 . Highest possible edeas score ` i emer 04067 - |o | 0 o re om, so rn _ | | T ee e tme teoats p. cebvets _28-2g/-E85 TweansevnerGHKaOzlnttlonmRautsienearcertPeroldAuydsCmE eeennsA fo"rdH A h-- tnroperions _Todect arto tf ater - Pim OE 2 ~ y Afra Bre E TH oT--N SE--10K [cx 8 |sl00Dd . | [ree fom EE i Ee OSC on Lae | 38 A h hom e m e ee e ree e Sy | a i| | 0D l I O liIna TTlet 3t %e le } : @ HAZLETON LABORATORIES AMERICA INC. 3301 KINSMAN BLVD. + P.O. BOX7545 + MADISWION37,07 + (608) 2414471 "TLX703056 HAZRALMDS UD eroTocOL P2071 EE, Primary BeraalOEICrDriGtuaitdieeolininneSests.u)dy in Rabbits Study No. 50503500 {Di oWwaevrzeisisses T| Yaspd/ "iEgnL iaS" for . aM ; Sc. Paul, Minnesota by HazletoTnitLeabSocriaetnocreisesDiAvmiesriiocna, Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704 vay 21, 1985 1985, Hazleton Laboratories America, Inc. Chemical & BioMedical Sciences Division 01069 i Study No. Study Location Test Material PROTOCOL TP2071 primary Dermal Irritation Study in Rabbits (OECD Guidelines) 50503500 Hazleton Laboratories America, Inc. Life 3301 KSciinesnmcaens BDoiuvliesviaornd Madison, Wisconsin 53704 1-3752 Sponsor's Representative Study Director Janine Gleason Steven M. Glaza Proposed Timetable . Starting Date CFoimnpalletRieopnorDtatDeate Week of May 27, Week of May 27, 1985 1985 Week of June 26, 1985 : 01070 opsECTIVE Ihe objective of this study is to determine the relative level of prisary "kin irritation of a test material on rabbits under semioccluded conditions. ALL aspects of this study vill confora to the Organisation for Economic cooperation and Development's Guidelines for Testing Chemicals, Section 40k, cute Dermal Tericacion/Corrosion, Moped May 12, 19811 and the Principles of Good Laboratory Practice.? ALL procedures will be done according to Haaleton Laboratories America, Tnc. (BLA) Standard Operating Procedures (50Ps) ceferenced in this protocol. Test Material: Physical Description: purity and Stability: Storage Conditions: est Material Retention: Safety Precautions: TEST MATERIAL 1-752. Brown granular solid. Sopnonsfiolre.has purity and stability decerminssions Store at room temperature. ASnpyonusnours3e0d dtaeysst amfatteerriailssuwainlcleboefrtehteurnfeindalto the report: LnUeancbkeonsrosawatnroyrtyopnrpieeccriastuoytn.inoenllsawbiiolnrlahtaotnardkyleicntlghoet&hnisonurgbm,satllaancceex of YSlpovvreosv,edsaffoertytogxliacssdeuss,tsanmdusat pbaertwiocrlne. mask TEST SYSTEM Test tinal Young adult albino rabbics of either sex of the New Zealand White scrain, approximately 14 weeks of age, will be obtained fron Hazleton Reseasch 01071 2 Products Inc., Denver, Pennsylvania. An adequate number of extra animals will be purchased so that no animal in obviously poor health is placed on test. istorically, the New Zealand White albino rabbit has been the animal of choice for evaluating the effect of chemicals on the skin. Acclimation Upon receipt, the animals will be taken to a designated aninal room where they will be acclimated for at least 1 week before being placed on test (0P-GENB 36). During acclimation, the animals will be examined for clinical bnormalities indicative of health problems (e.g., diarrhea, ectoparasites, rough hair coat, nasal or ocular discharge, evidence of injury, ete). May animals regarded as unsuitable for study purposes because of poor physical condition will not be released from acclimation and the reason(s) will be documente.d Identification Each animal in the study will be assigned a permanent identification umber and will'be identified with a metal ear tag (OP-GEND 24). All data collected from an animal will be recorded and filed under itsidentification number. Housing and Maintenance Ihe following environmental conditions will be maintained in theaninal room used for this study (OP-TARC 230). o o Temperature: 21C Relative humidity: 32 50% +20% ir change: Act least 10 changes an hour of filtered 100% outsice air Light cycle: 12 hours light/12 hours dark 01072 3 Temperature snd humidity will be monitored throughout the study. Variations from prescribed environmental conditions will be documented. Jnimal husbandey and housing at HLA comply with standards outlined in the `Guide for the Care and Use of Laboratory Animals," Care will be taken to ensure that the animals are not disturbed for ressons other than data collection and routine maintenance. The animals will be housed individually in screen-botton stainless steel cages (heavy gauge) held on racks, vith absorbent pan liners in the urine- and feces-collecting pans. Pan liners will be changed at least three times each week. Feed and water vill be providedad libitum. The diet will be Purina High Fiber Rabbit Chow. No contaminants are expected to be present in the feed or water vhich would interfere and affect the results of the study. Study Design ' hres rabbits will be selected at random based upon health and a body weight of 2.0-3.5 kg. Each animal will serve as its own conerol. PROCEDURES Preparation and Administration of Test Material venty-four hours prior to test material administration, the hair will be clipped from the back and flanks of each animal. The treatment sites will be inspected for interfering Lesions, irritation, or defects that vould preclude the use of any of the animals. The test material will be applied to the test area (approximately 6 ea?) on cach rabbit, in the amount of 0.5 g and will be moistened with deionized water. The treated area will be covered vith a 2.5-cm x 2.5-cm gauze pacch 01073 a secured with paper tape and loosely overvrapped with Saran Wrap and Elastoplast tape to provide a semiocclusive dressing. Collars will be used to restrain the animals during the 4-hour exposure period. Reason for Route of Mministration siotorically, the route of choice based on the method of Draize.* Observations After the 4 hours of exposure the patches and the test material will be removed as thoroughly as possible using water or an appropriate solvent without irritating the skin. Thirty minutes after removing the patches, the degree of erythema and edema will be recorded according to the Draize Jechnique (Attachment 1). Subsequent readings will be taken at 26, 48, and 72 hours after patch removal. Further observations may be recorded, as necessary, to establish reversibility. If irritation is increasiog in severity at the 72-hour examination period, observations will be repeated at 96 hours and at 7 and 14 days, if applicable. Body weights will be taken just prior to test material administration and at weekly intervals during the study. Observations and body weights vill be recorded in the study notebook. Pathology ALL animals, vhether dying on test or sacrificed at study termination, will be discarded. 01074 5 Report The final report will present a description of the test material, a description of the test system, dates of study initiation and termination, & tabulation of irritation data, and a description of any toxic effects other than dermal irritation. Maintenance of Rav Data and Records original data or copies thereof will be available at HLA to facilitate auditing the study during its progress and prior to acceptance of the final report. When the final report is completed, all original paper data, as vel as the final report, will be retained in the archives of HLA, Madison, Wisconsin (OP-GEN 44). REFERENCES 1. "CAhceumtiecalDser,maSlecItrirointa4t04i,on/MCaoyrr1o2s,io1n9"8,1.OECD Guidelines for Testing 2. LoarbgoarniastaotriyonPrafocrtiEcceo,noAmnincexCo2o,pe1r9a8t1i.on and Development's Principles of Good 3. DHEW Publications No. (NIH) 78-23 (1978). 4 DFroaoidzse,,DrJu.gsH,.,an"dDeCromsamletTiocxsi,cia ty," AppraisaFl oafdtheandSaDfreutgy oOfFFiCchieamliscalosf ithne T.5., Topeka, Kansas, pp- 46-59 (1959). G01075 6 2R0T0COL APPROVAL The Gleason Blears 3HSponbor's Representative SeevWen e. Gelaze TM ) CHSertsouludepycoDLeniardLeeacrbt,oorraAtcourtieesToAxmiecroilcoag,y Inc. (11088/ 35) Bate5 [a4[g5" EE s-2mas : 01076 ATTACRMENT 1 PRIMARY SKIN IRRITATION SCORING SCALE 1. Erythema and Sschar Formation 0 VYeoryersyltihgehmta erythema (barely perceptible) 1 2 WMEeoldleer-adteefaicntyeotdhseeenvrseyrt(ehbeemeeartytrheedmnaess) to slight escher formation 3 4 (injuries in depth) Highest possible erythema score 4 2. Edema Formation 0 YVCoeordyeetdreasmtlaeiignhetdaemeda(ecma(agreasi(sbeaordfelaayprpepraeorxwcieemlpaltt-iedblelyfei)n1emd )by definite raising) 1 23 Mre edema (raised more than | mn and extending beyond " Biagrheeastofpoesxspiobslueree)dema score " 601077