Document B8LKoaqMmGbQXwp1Kv6q8Xn7X

Experiment No.: Conducted At: Dates Conducted: F--r-- Reviewed By: Primary Skin Irritation Test with 7-3493 in Albino Rabbits Y ceayain | FT 20x110605S0t 0884280009 - RSiakfeertyLaEbvoarlautaotriioens,LabInocr.atory st. Paul, Minnesota January 17, 1984 to January 20, 1984 D. nW. .FarkU os, n or., b 53 mSotxuidcyolDoigriescttor 2/eDfaete XJ. "oi'alley, Datf e SAecnuitoerTTooxxitccoollooggyist de: MX.oTL.. CEaosbeens FWu. DC.. GMcrCioerfmiitchk 005198 - 1 summary Ihe results of the prisary skin irritation test conducted fron January 17, 1984 to January 20, 1984 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3453 is non-irritating (0.0/8.0) to the skin of female albino rabbits. Neither erythem nor edema vere noted at any time during the study. ' Introsuction Ihe objective of this stuy vas to deternine the primary skin irritation potential of T-3493 to the skin of female albino rabbits. This study is not regulated by the Food and Drug Adainistration's Good Laboratory Practice Regulation of 1976, 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. 005199 R 2 Method and Results Young albino rabbits of the New zealand breed? vere used in the evaluation of the prisary skin irritating properties of the test article. The test procedure vas modeled after that of Draizestail. One day prior to the application of the test article, the hair vas clipped rom the back and flanks of each rabbit and two test sites selected lateral to the midline of the back approximately ten centimeters apart. One of the two sites vas abraded by making four epidermal incisions, two perpendicular to the other tuo, vhile the other test site remained intact. Ihe test article (0.5 5) vas applied to each of the test sites on each rabbit and immediately covered with two-inch square gauze patches. The patches, Which were placed directly over the test sites, were secured with gauze weap. The trunk of each anisal vas then vrapped with impervious plastic sheoting Vhich held the patches in position during the one day exposure period. At the end of one day, the plastic wrappings, patches, and all residual test article were removeal, One hour and 48 hours after removal of the test article, the intact and abraded test sites vere examined and scored separately for erythesa and edesa on a graded scale of 0 - 4. Ihe average irritation produced vas evaluated by adding the mean scores for erythesa and edema of the intact test sites one and 48 hours post removal of the test article. Sinilarly, the mean scores for erythema and edema of the abraded test sites vere saded. BLraasizseet:on Apuptpcrhaliasnadl, ofInct.h,e SDaenfveetry, ofEAChemicals in Foods, Drugs and Cosmetics Sne1al0in1g2,x I+l0l0i2nopiest.ra Clear polyethylens sleeves, FEC Industries, nc. Sme test article vas removed vith vater. 005200 . 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 Westibesn eription Score Erythema Baena Barely (BAges pofercareepatibnolte defined 1 Pale red Definite in color and red in color aanrdeaardeeafiwnealblle 2 3 defined. Beet or crinson red in color 4 Barely (Edges poefrcaerpetaibnloet defined) 1 Area definable but not raised more 2 than Area w1 emlml.defined and raised 3 aAprpearoxriamisaetdelmyor1 eomt.han 1 mm. 4 Maximum Primary Irritation Score = 8 The following grading system was used to arrive at a descriptive primary skin irritation rating: Mean P(rRiamnagreyofIrvrailtuaetsi)on Score Descriptive Rating 0.1 - 0.5 0.6 - 1.5 1.6 - 3.0 3.1 - 5.0 5.1 - 6.5 6.6 - 8.0 NMoinn-iimrarliltyatIirnrgitating SMliilgdhltylyIrrIirtraittiantging SMeovdeerrealtyelyIrIrrirtiattaitnigng Extremely Irritating The rating for a test article may be increased if the reactions caused are beyond simple erythera 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. 005201 sv tn ies oi I mise ee sm on see t men Antal aber wt wt", J A or o Mean. 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 ` 8 primary trritation mex: 0.0/8.0 2 wr EEEre i ! Lot | TEST. Moule PrimarySkinitatonTest PaRpOEwTpOrCxO1L.Riker Experiment Nos"04720so00+0 i SPONSOR: 3M CommercialChemicals Division CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, Inc. St. Paul, Minnesota estamos Tes conmoLarmiowe: Neve | PROPOSEDSTANTNGIGOPLETON DATE ores tfi HF ; TEST SYSTEM: FomaloNewZeaWlhiatenAbidno Rabbis i| source: Dureiant Lass Dene, TA ;a i i OBJECTIVE: wTaorodetseelremcitneedt8hae iprhiomearsyt isrytsattieomn dpouteenttoiatlhoefithhiesttoroiscaalruiscee, tsoetnhseitsikiyntoof i--tGan_s_, eaanismealosf.hRaanbdbintgs and general availability. 3 METHOD: The animals wil be housed Instandardwire-meshcages in temperature and humiditycontrolled rooms wCiotrhtfeospoodn2datnodawcaatredraoffffiexerdedtadthfeiobuitsuimd.eoEafcthhaenciamgael.wPirlilobretaostshioagpnpeldicaantiuomnboefrteh dteeasrtteargi,cwehitchhehwielllr `will be clippedfromthe back andflanks of eachanimal and 2 testsitesselected lateral } r1ob0mytamhieanlmiinidtniaicfntoe.uorTfhotephitedebasratmcaakrltaiicnplceips(iorns,o0t2xw6oit2epnmercapeennttdiiemceultl)eawyrrisltalopbaterhtea.pG_ptlLhie_er_dttowoof,t_hw_eh1_i_2__th_aebsoirttaehdserewditaelsntbdesh--aab(1sr)_adw_eid_l | iniac ste) on bach animal, covered with __Caze and socured wih S iii wi c | The trunk of each animal will then be wrapped with impervious plastic sheeting which will occlude the i testarticle duringthe 1 dayexposure period.Onehourand48hoursafterremovalofthetestarticle, i: | ftaahorreayaidnndttyahiscehct,oaammlneaedaaoannfbsdrc0aeoddr0eoe4dsbm.atfeoTosfrthseeirhtayeevtsehiwrnietlamalgacetbaeoniseidtxtseaaitmdtieioesnnmpeoardnaoodnfuadtcnshedced4oawr8ibehlrdloasbudeerepesdavprfaoaolstsuettalrtyseefemdobosrveywarilayldotdbfhieotnhmgaadtatdenhesedtdmae.edTrsehenem.ssaceSooitrnmwelos-a . :i Vadaelsucersiwpitlivbeaprtiomtaalreydasknidn rdiavtidieodnbryaftionugatsfolbotwaisn:themean primary ation indexandthen assigned | MoanPrimary IritionScore Descriptive Ring o Non-iritating Fe hr] ! 001616.--103550 SMMiiilngdihlmtyaylIlriytnaIatrtiriintgnagting a | 31-50 Moderataly Iating - i 6561.-8605 ExSrevoemraellyyIrIrrittaattiinngg ii i Tahned raarteidngefoomr aedtteosbtaarotifclIemmpaorytbaneceiinnctrheeaseIdntIefrtprheetrateiaocntoifotnhcearuesseuldtiss. Abelyroanwddeartyatghoenmaaraanldodebdyetmhao `studydirector and the final report will be stored in the Riker Laboratories' Archive, St. Paul, Minnesota. 2 Purina Rabbit Chow, Ralston Purina Co., St. Louis, Missouri : PDrbaliszeh:odApopyrtaihsealEodftotnhaelSComamiof tfteCe hoemft itchay elAsssinocFioaotdi,onDorfugFsoaonddanCdosDmreutgiOcfsfi(c1a9l65)ofthe UnitedStates Sp2onEsarfos 12fslDeine S DbwadA ymDer3edi|o fn)r Das om anu 005203 = 6. APPENDIX II Principal participating Personnel Involved in the Study 0 wee FPweuln D. M. Marke, Jr., BS TStouxdiycolDoigriescttor } X. L. Ebbens, BS sTuopxeircvoilsoogry Testing X. D. O'malley, BS sAecnuitoerTToxoixciocloolgoygist G. C. pecore sMunpiesravlisLoarboratory 005204 : 7. APPENDIX 111 Composition Characteristics his study is not regulated by the Good Laboratory Practice Act of 1978 ana therefore information pertaining to composition characteristics is not applicable for inclusion in this study. 005205 - e. APPENDIX TV QualityAssuranceStatement his 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. The 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 underway 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 Compliance Audit department for review. 005206