Document peoN74nkmRLaG3gzYr31BbRLB

SaAtZLeEeCEnN Roger G. Perkins, PhD 3 Toxicology Services Building 220-2-02 St. Paul, MN 55144-1000 FINAL REPORT AR226--003325 HWI Number: 40200469 Study Title: Primary Dermal Irritation/Corrosion Study of T-5898 in Rabbits (OECD Guidelines) Signed: EeEa Study Director Acute Toxicology . We pr HA FE ET EEA Sereeh TRS RECEIVER HAR 28 1994 ToxicXICOLOG - 005788 TERT HWI Number: 40200469 Sample: T-5898 SSttuedvyenDiM.recGtloarza Manager Steven R. Sorenson Study Coordinator Patricia Padgham In-1ife Supervisor Rose M. Bridge Report Supervisor Page 2 KEY PERSONNEL a tee), Nod ic DCiipnldoymaJt.e,CarAyC,LAMDVM Supervisor CONTENTS Page Key Personnel 2 Objective 3 Test Material 3 Test System 3 SPruomcaerdyureosf Results 54 Discussion 7 RAepfpeernednicxes- Raw Data 7 8 005789 HWI Number: 40200469 Sample: T-5898 Page 3 OBJECTIVE The objective of this study was to assess the relative level of primary skin irritation/corrosion conditions." of a test material on rabbits under semioccluded All procedures used in this study are in compliance with the Animal Welfare Act Regulations. In the opinion of the Sponsor and study director, the study did not unnecessarily duplicate any previous work. Identification TEST MATERIAL The test material was identified as T-5898 and described as a clear, lightyellow Tiquid. Purity and Stability The Sponsor assumes responsibility for purity and stability determinations (including under test conditions). StoanrdReategntieon The test material was stored at room temperature. Any unused test material will be returned to the Sponsor after issuance of the final report according to Hazleton Wisconsin (HWI) Standard Operating Procedure (SOP). Safety Precautions The test material handling procedures were according to HNI SOPs and policies. Test Animal TEST SYSTEM Adult albino rabbits of the Hra:(NZW)SPF strain were procured from HRP, Inc. and maintained at the Hazleton Wisconsin facility at 3802 Packers Avenue, Madison, Wisconsin. Animal husbandry and housing at HWI comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals".? The animals were individually housed in screen-bottom cages in temperature- and humidity-controlled quarters, provided access to water ad Iibitum and a measured amount of Laboratory Rabbit Diet HF #5326, PMI Feeds, Inc., and held _ for an acclimation period of at least 7 days. The feed is routinely analyzed 005790 HUI Number: 40200469 Page 4 Sample: T-5898 cSbyoanmtptalhmeeisnmaaonnftusftahecitnwuartteheerrffeoaerrdenouprterriwitaoitdoeinrcaaltlhlayctomawpnooaunlleydnztesdhavbaeyndHiAenInt.veirrfoTenhrmeeedrnetwaiwltehrecoornnotaamfkifnneoacwntntesd. the results of the study. paTenhrdrieoemda.ifnetnaaIilfneevdaarcicdalutirinionangtsedthferaonimstmuatdlhyse', riwneeqitugihrheeidnsgatmeefmrpmoeamrnan2te,ur9r6e1astanofdor3,h2ut0hn3eidiga,tcycwleicrmoeantdiisoteniloencsted tehxeistsetdu,dythoeutycowmeer.e doAcnuimmaelnstedweraendicdoennstiidfeirededbytoanhiamvael handumbneoradanvdersceorreefsfpeocntdionng weearretacgl.ippeOdn fthreeedaoyf hbaeifroretotroebattamiennta,n uthneblebmaicskheadnds/koirnflsaitnek.s of each animal cHihsotiocreicfaolrlye,valtuheatiNnegw tZheealaenfdfecWthitoef cahlebmiincoalrsabobnitthheasskbiene.n the animal of PROCEDURES Preparation of Test Material wTahse dteetsetrmmaitneerdiatlo wbaes7.a6d.ministered as received. The pH of the test material Treatment T(haepptreosxtimmaatteereixaploswuarse aarpepalieodf 6to.25thecn'i)ntianctthsekianmoounnteaocfh 0a.n5imnaLl.'s Tbhaeckarea of taapppel,icaTtoioosnelwyasovecrowvreraepdpedwiwtihtha 2Sa.r5a-ncmWrxap2.,5-camndgasuezceurepdatcwhithsecEulraesdtowpiltahstpaptearpe ttoestproavniidmealsa dsuermiinogcclthuesiv4e-hodurresseixnpgo.sureCoplelrairosd.were not used to restrain the Attestthesiteensd woefrethweas4h-ehdourusienxgpostauprewapetreiroda,ndthdeisppoatscahbelse wpearpeerrteomwoevlesd. andThethetest miartreirtiaatlingwastheremsokivne.d from the test sites as thoroughly as possible without Reasonfor RouteofAdministration Historically, the dermal route has been the route of choice based on the method of Draize.' 005791 HWT Number: 40200469 Page 5 Sample: T-5898 Observations teAeprcpyhrtnohixeqimumaeataen(ldryecedo3er0ndaemdinautatseestahcehaf4tte-eshrtourrseimotsvecaolrwea)so.fretSahduebstaeecqscutoerndmtiatnegerxiatamoli,ntahtetihoeDnrsadiewzgeerreee of made catomp2a4,ris4o8n,. and 72 hours. The untreated skin of cach animal was used for Animals were weighed just before test material adninistration. Termination Aetuthtaenrimziendatiaonnd doifsctahredeedx.perimental phase, all animals were designated to be Statistical Analyses No statistical analyses were required by the protocol. LocationofRawData,Records. andFinalReport Tahrechirvaewsdaotfa,HHIrecionrdasc,coradnadncaecowpiythoHfHItheSOPf.inal report will be retained in the 005792 HHT Number: 40200469 Sample: T-5898 Page 6 SUMMARY OF RESULTS Test Animal: Albino Rabbits - Hra: (NZW)SPF DSaotureceA:nimaHlRsP, ReIcnec.i,vedK:alam0a2z/o0o2,/94MI Experimental Start Date: 02/21/94 Experimental Termination Date: 02/24/94 Individual Dermal Irritation Scores --_ Hour AMnuinmbaelr Sex XT 2E6rythem4a8 12 F49385 r 0 0 0 0 0 F49364 F 0 0 0 0 0 F49398 F 0 0 0 0 0 #&Edem8a 2 0 0 0 0 0 0 J 0 0 Average Primary Dermal Irritation Scores* Observation Period (Hour) Average Score 4 0.0 24 0.0 48 0.0 72 0.0 * The average primary dermal irritation score is the total dermal irritation score for all the animals (erythema and edema) divided by the number of test sites (3) at each observation period. 005793 HHI Number: 40200469 Sample: T-5898 Page 7 DISCUSSION Application of T-5898 to the skin of rabbits under 4-hour semioccluded conditions resulted in no dermal irritation. REFERENCES 1. "Acute Dermal Irritation/Corrosion," Organisation for Economic Cooperation and Development's Guidelines for Testing of Chemicals, Section 404 (adopted May 12, 1981). 2. NIH Publication No. 86-23 (revised 1985). 3. Draize, J. H., "Primary Irritation of the Skin," In: Appraisal of the Safety of Chemicals Association of Food in and F oods, Drug Drugs an Officials d C of osmetics - the U.S., Dermal Toxicity, pp. 46-47 (1959). 005794 HHI Number: 40200469 Sample: T-5898 APPENDIX Raw Data Page 8 005795 PERSONNEL SIGNATURE SHEET ACUTE TOXICOLOGY HL: 0200069 lane. Rose M. Bridge Anthony Cass. Cindy J. Cary, DVM Donna J. Clemons, DVM, John A. Disch Charles W. Fritz Kari Garfoot Steven M. Glaza Kevin Grossman Jeff Hicks Sharen L. Howery Wayne A. Madison Doug McConnell Eileen McConnell Bud McDonald Albert Oleson Patricia Padghan Steven R. Sorenson Annette R. Turner Tamra L. Walker Lana M. Weeden Ehather 4.Weber Job Title Signaty 5 Initials. Report Supervisor GpedBrige KB Lab Animal Technician LolhonyCarn ac Lab Animal Veterinarian Ap). MS Lab AnimalVeterinarian & Lab Animal Caretaker Dirck 0 Lab Animal Technician Hale,22, 7 Lab Animal Technician i --ka Manager Lab Animal Caretaker 3, Se Eo. Lab Animal Technician ZH Research Assistant SH Supervisor [ANN um Lab Animal Technician LosdR (0 onl]Coen Staff Assistant Ci Whet bonri ectt Leer Study Coordinator LPdhonak) re Lab Mina Caretaker _COBAL)boon SO In-life Supervisor Lois Bd 2 Study Coordinator Se ALL SRS Staff Assistant ay Staff Assistant ad Staff Assistant Ka Petsa dos guid) abArivtal Carvtoder_ Alpthes)1). Dudas) ts) (62/10-06-93) 005796 hod JE --------~-------- waive dO200UE B wtAwtw_a7.rsre mroaryehEr tt rin: CLEAR (SULST YErty o 61) eCIrOyL eomotetie,msS:A3 EAo RI]2 sta bAeAst, SoeSE ite [otter trwig 1[oy [17[aca [TTwl rh [esos| Lomo TF TNT | =p----p--1] EER oT aE l =) Feeder] | 6 [Teed 2 Eee oo] ol [ao a Eo a A | eh [TeRi EE EN E he we To To Il T T7o N1 &| & [722 |goccaas ceoe c |oc loa] fz) wmJoToJoTT N71 o g 0.007294) EERET we |W TN IL HT1N 8 S r c tion [I= 17 71 otk wir TLOEOMAFERETL IRE ~~ INCSREELTDATE.Kan 2-21-T a men |Bp, % eeea-- Sa re reotettoedp ttr tttnrbytir.l et 0 ty tt. Tet, oy2 ZL frtigeswe tg or sen oh rs eran +GE (ABA art iin, 2 L222 HI No.: _<d020049 Primary Der(mDarlaiIzreriTteacthinoinquSec)oring Scale (1) Erythema and Eschar Formation No erythema VWeelrly-dselfiignhetdereyrtyhtheemmaa (barely perceptible) Moderate to severe erythema Sfeovremraetioenryt(hienmjauri(ebseetin rdeedpntehs)s) to slight eschar Highest possible erythema score 0 1 2 3 re 4 (2) Edema Formation No edema 0 Very slight edema (barely perceptible) 1 Slight edema (edges are well definedby definite raising) 2 MSoedveerraeteedeemdaema(ra(irsaeidsedapapprporxoixmiamtaetleyly1 m1mmna)nd 3 - extending beyond area of exposure) 4 Highest possible edema score 4 (55/01-07-91) 005798