Document 1rdXbGJZ2GyLqxEmyOLVK1ZE

Experiment No: Conducted At: Dates Conducted: Conducted By: Reviewed By: Primary Skin Irritation Test with T-3874 in Albino Rabbits 7 ! {omen \ LT 0386EBO135 Pathology and Toxicology RSti.kerPauLla,boMraitnonreiseost,a Inc. March 18, 1986 to March 20, 1986 As onsite G. L. Harris, BS Date Advanced Toxicologist Study Director : se C. F. Chesney, D.V.H., Ph.D. Date Manager, Pathology and Toxicology dc: K. L. Ebbens F. D. Griffith R. G. Perkins 0600052 1. Summary The results of the primary skin irritation test conducted from March 18, 1986 to March 20, 1986 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3874 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 study was to determine the primary skin irritation potential of T-3874 to the skin of female albino rabbits. This test was conducted to meet the Department of Transportations requirements for primary skin irritation. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives. 000053 2. Animals and Husbandry Young New Zealand White Rabbits? were used in the evaluation of the primary skin irritating properties of the test article. The rabbits were individually housed? in stainless steel cages, and food and water were available ad libitum. AT1 rabbits were individually identified with ear tags and considered to be in good health at study initiation. The rabbits were housed in a temperature and humidity controlled room. Room 1ighting was on a 12/12 hour light/dark cycle that was automatically timed. Met andhReo suld ts The test procedure was modeled after that of Draize et a1. One day prior to the application of the test article, the hair was clipped from the back and flanks of each rabbit and the test site was selected lateral to the midline of the back approximately ten centimeters apart. The test article (0.5 ml) was applied to the intact test site on each rabbit and immediately covered with two-inch square gauze patches. The patch, which was placed directly over the test site, was secured with gauze wrap. The trunk of each animal was then wrapped with impervious plastic sheeting which held the patches in position during the four hour exposure period. 8 HAaPnuziblmleaitlcosantiwoeDnruetcNohh.ioaun7sd8e,-d23iInnc(.aN,cIHc)oD:rednavenRrce,eviwsPieAtdh 19r7e6com"mGeuniddeatiFoonrsthceonCtaairneedandinUsDeHEoWf 4 PLuarbionraatoLraby additional ARnaibmbailts,Chowe roughage. and rabbits may be offered Alfalfa Cubes for o CDorsamizeet:icsAp(p1r9a6i5s)a.l of the Safety of Chemicals in Foods, Drugs and W1h0eexli1n2g,x i.L002 Extra Clear polyethylene sleeves, PPC Industries, Inc., 000054 3. At the end of four hours, the plastic wrappings, patches, and all residual test article were removed by washing with water. One hour and two days after removal of the test article, the abraded test site was examined and scored for erythema and edema on a graded scale of 0- 4. The average irritation produced was evaluated by adding the mean scores for erythema and edema of the abraded test site one hour and two days post removal of the test article. This value was divided by two to obtain the mean primary irritation index. The scoring criteria for erythema and edema are shown below. Reaction Erythema Edema -_ Scoring Criteria for Skin Reactions Description Score B(aErdegelsy pofercaerepatibnloet defined) 1 DPeafleinirteed rinedcoilnorcolaonrd aanrdeaardeeafiwnealblle defined. 23 BBeaertelyorpecrrciempstoinblreed in color 41 A(rEedagedsefoifnaabrleea bnuott dneoftinreadi)sed more 2 Atrheaan 1 mm. well defined and raised 3 Aarpeparorxaiimsaetdelmyor1emmt.han 1 mm. 4 Maximum Primary Irritation Score = 000055 4. The following grading system was used to arrive at a descriptive primary skin irritation rating: Mean Primary Irritation Score Range of Values 0 0.1 -0.5 0.6 - 1.5 1.6 - 3.0 3.1 - 5.0 5.1 - 6.5 6.6 - 8.0 : escriptive Rating Non-Irritating Minimally Irritating Slightly Irritating Mildly Irritating Moderately Irritating Severely Irritating Extremely Irritating The rating for a test article may be increased if the reactions caused are beyond simple erythema 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. 000056 5. Table 1 Primary Skin Irritation Test - Albino Rabbits with T-3874 Animal Number 680394 680397 680389 680392 680395 680398 Irritation Scores for Intact Skin Sites after Removal: Ee Hore 0 0 0 0 0 0 0 0 0 0 0 0 Er ov 2 Ed. 0 0 0 0 0 0 0 0 0 0 0 0 Mean Subtotal 0.0 0.0 0.0 0.0 0.0 Rating: Non-irritating Primary Irritation Index: 0.0/8.0 Key: Er. = Erythema Ed. = Edema 000057 TesT:__ Acute Primary Skin Iitaton Test APPENDIIX PROTOCOL Riker Experiment No. 0386EBOe13S SPONSOR: 3M_ CommercialChemical ~~~ pivisien CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, nc., St. Paul, Minnesota TestammolE_ 0 T370 24 00000000000 CONTROLARTICLE: Nene 0000 PROPOSED STARTING/COMPLETION DATE OF TesT: 3 /fle -- Up TEST SYSTEM: Female New Zealand White Albino Rabbits source: -_-- HA=ted = Dudchhase Dene , Pa OBJECTIVE: gTseeolneedcretateledramvaaisinletahbteihtetyeisrtristaytsiotnempotdeunetiatlo otfheitrhehitsetsotriacratliculsee,to stenhseitsikviintyof10_iSriiaXn_t_s, aeniamsaelso.f Rhaabnbdiitnsgwaenrde METHOD: cwTiohtrehreafsnopi0omdan8ldsatnowdiaclwlaabrteedhraoouffsffeerdiedtnxao tdeshtdeafnbodiutatursmd.idweiEorafec-thmheeacsnahigmceaa.lgewPisrliionbr ettoeatmshspeieganrpepadltiauacnrnadtueimoohbfunemrtihedeidttyeeasctronaftrarigca,llelw,ehdtihcrehoohwmaisil.r owitllhbeemcildiipnpeedoffftohme bthaeckbaacpkpraonxidmfaltaenlkystoefnecaecnhtimaentiemrasl aapnardt,oNonn e ofe tho _otneest_ssiitteessswielllebcoteadblraatderoadl rbeymmaaikniinngtacfto.urTehpeidteesrtmaalrtiicnlceis(ion0s,.tw5omperpLendi)cularwi1l0bteheaoptphleiredtwtoo, whi0l.e_theabortahedredteastndsit-e(osn) ewi.l "inTthaecttrsuintke(osf) oeancehaacnhimaanlimwaill, tchoevnerbeedWwriatphpged waithuimpzervieous aplnadstsicecsuhreeedtiwngihwhgichawilluocczludee the gttehrseatdiaenrtdtaiccstlceaalndeudroaifnbg0rattdohee4dbx.ktedsTathyseietaxevpseowrsiaulgrebeeipeieraxitaoidm.oinnOepndreoadhnuodcuesrdcaownriedld4bs8eepheaovruaalrtusealatyfetfdeorrbreyeramydotdvhiaenlmgaotfahnetdhmeeetdaeesntmsaarcotoinrcleeas, lfaorrlye.rythtehemmeaaanndsceodreesmafoorfetrhyetihnetmacat atensdt seidteesmoanoofatnhde4a8bhroaudresdptoesstt rsietmeosvawillobfteheadtdeestd.artTichlee.seSitmwio: vaadleusecsriwpitllivbeepfroimaalreydsaknidn rdiavtiidoednbaytifnoguratsofOobltoawisn: the mean primary irfation index and then assigned Mean Primary Iritation Score 01-o05 0166--1350 5311--5605 66-80 Descriptive Rating MNionni-miarltlaytiInrgtating MSiigdhtIniirttaatitnigng MSeovdeerrealtyelIyaIliiantging Extremely Imitating "~~~ I" i: vw i SLL] aTnhde arrateindgefeomreadtteostbaertoifcliemmpoarytabneceinincrtehaeseidnteifrptrheetarteiaocntoifonthceauresseudltsi.s Ablelyroanwddeartyatgheenmearaatneddebdyetmhae study director and the final report wil be stored in the Riker Laboratories' Archive, St. Paul, Minnesota. 2 PDPruuarbiiiznesa:heRadAbpbbpiyrttaChiehsoEaowdlif.totRrhaieallsStaCofonemtPmyuiortfienCaeheComof.itchaSelt.sAsLisonouFciiosa,otdMi,iosnDsrooufurgFisooadndaCnodsDmreutgicOsff(i1ci9a6l5s)of the United States RAE 4-hour exp8os/uarze/pebriod; for DOT see attached from 49CFRITS. Sponsor ate "Study Director EY Date 7. APPENDIX Principal Participating Personnel Involved in the Study Name G. L. Harris, BS 6. E. Hart K. L. Ebbens, BS G. C. Pecore Function Advanced Toxicologist Study Director Sr. Laboratory Technician Acute Toxicology Supervisor Toxicology Testing Supervisor Animal Laboratory 000059 8. APPENDIX II CompositionCharacteristics This 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. 000060 9. APPENDIX Tv Quality AssuranceStatement . This 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 differenct 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 review. from the Archives by the Compliance Audit department for 600061