Document 0JBnj26mEdoD4rZ8NLyBp05md

Sxpertzent Hous contuctad aes sates contustats F---- prea shin Susisasion Seve IN tn Albino subnets esnasserse fsraetdheorloRgynaintvTiooexgtcsntodny auty 12, 1988 to avty 20, Tome 1s hrdeac, ory sechntctan S aiidy Oc. Senior Toxicologist Sheeedr , a h55 kLon mSomahns,e 00352 1. Summary The results of the primary skin irritation test conducted from July 17, 1984 to July 20, 1984 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3608 is non-irritating (0.0/8.0) to the skin of female albino rabbits. Neither erythema nor edema were noted at any time during the study. Introduction . The objective of this stuly was to determine the primary skin irritation potential of T-3608 to the skin of female albino rabbits. This study vas conducted for research and development purposes and is, therefore, 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 repopt are stored in the conducting laboratory's archives. 00353 2. Method ant Results Young albino rabbits of the New Zealand breed were used in the evaluation of the primary skin irritating properties of the test article. The test procedure wae modeled after shat of raisest 2b. one day prior to the application of the test article, the hair ws clipped from the back and flanks of each rabbit and tvo test sites selected lateral to the midline of the beck epproxisately ten centimeters apart. One of the two sites vas abraded by making four epidermal dactsions, two perpendicular to the other two, while the other test site remained intact. 0 test arvivle (0.5 yu) vas applied to each of the Test sites on sack abbit and immediately covered with two-inch square gauze patches. The patches, Vita vet osswt dinsinly os the VAsk sites, vers Semel with gees vEsg: The trunk of each anisal vas then wrapped vith impervious plastic sheeting "hich held the patches in position during the ane day exposure period. AC the end of one day, the plastic veappings, patches, and all residual test article vere removedd. one hour and 48 hours after removal of the test sttiving the Intact snd dhrated test sites wre erated anh scored segeravely for eryehesa and edema on a graded scale of 0 = 4. he average irritation produced was evaluated by adding the man scores for exythens and edema of the intact test sites one and 48 hours post rescval of the test article. Similarly, the man scores for erythems and edema of the abraded test sites vere added. Sussieton putchiand, nc. Denver, 2A oui Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics Lg1he0setxitne12egs,xar.Ht0ii0nc2oieiExstm.rsa Clear polyethylene sleeves, removed vith vater. PIC Industries, Inc., 00354 a hess two values vere totaled and divided by four to obtain the mean primary irritation index. The scoring criteria for erythesa and edema are shown below. Scoring Criteria for Skin Reactions Renee beserpter seers Erythema Stems B(aBrageelny poferacreepstibnloet defined ' FDeaflienirteed riendcoinlorcolaonrd aanrdesardeesfiwnealblle 23 GBeeteitneoar. crimson red in color . m(a3raegleys pofercaerpetaibnloet defined) 3 Atrheaan d1ef3imnable but not raised more 2 Aarpeparoxviemialtedleyfin1emda.and raised 3 Area assed more than 1 ma. ` Maxioun Primary Irritation score = 8 The folloving grading system vas used to arrive at a descriptive primary skin irritation rating: Mean P(raingsea.ryofIrvrailtuaetsi)on score Descriptive mating , 0.1 - 0.5 ois - 1.8 NMsoiunnieigimhxaerllilytyaItrIirrnirgtiattaitnigng 3TeDlsil shies RWoadelryateTlryriIartriintgating Severely Irritating ee Zao Extremely Irritating The rating for a test article may be increased if the reactions caused are beyond simple erythess 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. (0035S retry tn senttres tt ts atHnnetTsenre terwres sHtEnSi-- me, -- ris revo J g EI ges : appenpzx 1 Riker Experiment Noi22os0saz2so03s0e 000 PROTOCOL 5. ests Acute Primary Sin iran Test ronson: aM_ Comercial Cheatcals Division CONDUCTED BY: Safe Evalustion Laboratory, iker Laboratories, Inc, St. Paul, Minnesota TEST ARTICLE; T-3608 conmoLarmcte: Ma o PROPOSED STARTINGICOMPLETION DATE OF TesT:_Wad" TEST SYSTEM: Fomalo Now Zealand Whi Aino Rabi SOURCE: agoul st boi nne] OBJECTIVE: METHOD: , To determine the imation posal of the test ari 0 the skin of _a__ animals. Rabbis were sGeelneecrtaeldavaasltahbeiyte.st system due to their historical use, sensitivity to iitants, ease of handiing and Tho animals wil be housed in slandard wire-mesh cages in temperatur and humily coirolled rooms with food and water offered ad libitum. Each animal will be assigned a numbered ear tag, which will correspond to a card affixed to the outside of the cage. Prior to the application of the test article, theh|air `willbeciipped fromthebackandflanksof eachanimaland 2 testsitesselected lateral 10etheemidiitnoeoftohpeiabnamcaklaeppiriooxnisma.tewloy tpeonrcpeontnidmieatierasa10patrhte.G_eLr__woof,twheh_i2h_e_ ostitheesrwtilalsbesaibar)adweidl remain intact. The test article(0:2rems_)will be applied to 1 abraded and 1 ainTnoetnaca ltasfitoie(asnd)udeorianancrgehaanaccnahicma1atnldimaowayiltl,exsicpoonvwseiulrbreoe5d8wwpreeiraxtipaopmd,eidnOewnd8ienahhndoidumsrpceaornrveiddou4ss8empphxaiotruasarwsiselcaysufhroeeerredteriewrnimygtothwvhiaeg lmcahofa awnhidleu eotdeoz csmadae rocnh,o& EgVorraarledreodystwsvimcolameblaeeaanoonfasd0csaaetdrosoe4maDln.aodTrofchaehneahyvhaearcrbaytgaeooaiunrtrdit11aet6diho5enmphaireoodtafhuanhcdmeedea4nwab6irlnhlaopbdureeridsmeav1praosylstuttaart$eet1mdi6o5obvwnyailailndobddfeeitxnhageadnttcdheesehdtm.eaTerniahcanees.ssseicSgoinrtmeewidso- dosepive rman skin nation agas folows: Mean Primary tation Score [pe 0081-o1035 76-30 NSNoiVno-iinirdrlirttaatrninaggt.antgin"g { ||' =J 3S1i-l5a0s 66-80 SMEooxdvvaearrmaaetyllIyrmaaattntignig . T0ShiecirradetrionScgeiaoorrmeaadndttetsbthearntoiflclmerpamopanoyratnbwceielibn1ecrhseetaosreIeddnfntthtreeorFenaoctroifoLntahbcoarurasetesodruisse,s AbAelrycaohniwvdeG,earSytL.thgPeeamnuea,raaMtniedndnoebsdyoatDma.ea Diba ng EvoraCortesof ne Assocs of Foun On filof he ned Sts 2 Purina Rabbit Chow, Ralston Purina Co., St. Louis, Missouri b Draize: Appraisalofthe Safetyof Chemicals in Food, Drugs and Cosmetics (1965) `Sponsor Fam wrazewo, te `Study Director Date (00357 6. APPEWDIX II Nae G. E. Hart Principal Participating Personnel Involved in the Study Function Sr. Laboratory Technician Acute Toxicology X. D. O'Malley, BS SSteundiyorDTiorxeicctoolrogist KX. L. Ebbens, BS TSouxpiecrovliosgoyr Testing G. Cc. pecore ASunpiemravlisLoarboratory ` 00358 7. APPENDIX 111 Composition Characteristics his study is not regulated by the Good Laboratory Practice Act of 1978 and therefore information pertaining to composition characteristics is not applicable for inclusion in this study. ` 00359 . AppmNDIX TV guality Assurance Statement is study is not officially regulated by the Good Laboratory Practice Regulation of 1978, and therefore a statement signed and prepared by the Compliance Audit department is not applicable. he standard operating procedures of this laboratory does adhere to the general principles of this regulation. The Compliance Audit department does inspect different significant phases for studies wndervay in the Acute Toxicology Laboratory on a recurring cycle, and the facilities are examined on a three month schedule. In addition a select number of Research & Development studies are routinely picked at random from the Archives by the Coaplisnce Audit department for review. ` 00960