Document zzMnN9ZNnJZXoEqmX8B8qq9nB

PrimarySkin IrritationTest with T-3874 in Albino Rabbits Experiment No: Conducted At: Dates Conducted: Conducted By: Reviewed By: 0386EB0135 Pathology and Toxicology Riker Laboratories,Inc. St. Paul, Minnesota March 18, 1986 to March 20, 1986 rris, BS Date Advanced Toxicologist Study Director We' -+/@,t(. C. F. Chesney,D.V.-M.P,h.D. Date Manager, Pathology and Toxicology dc: K. L. Ebbens F. D. Griffith R. G. Perkins Summary The resultsof the primaryskin irritationtest conductedfrom March 18, 1986 to March 20, 1986 at Riker Laboratories,Inc., St. P.aul, Minnesotaindicatethat T-3874 is non-irritating(0.0/8.0)to the skin of female albino rabbits. Neither erythemanor edema were noted at any time during the study. Introduction The objectiveof this study was to determinethe primary skin irritationpotentialof T-3874to the skin of femalealbinorabbits. This test was conducted to meet the Department of Transportationsrequirements for primaryskin irritation. The raw data generatedby the Study Director and the final report are stored in the conductinglaboratory'sarchives. 2. Animals and Husbandry Young New Zealand White Rabbits@ were used in the evaluation of the primary skin irritatingpropertiesof the test article. The rabbits were b individually housed in stainless steel cages, and foodc and water were available ad libitum. All rabbitswere individuallyidentifiedwith ear tags and considered to be in good health at study initiation. The rabbits were housed in a temperature and humidity controlled room. Room lighting was on a 12/12 hour light/dark cycle that was automatically timed. Method and Results d. The test procedure was modeled after that of Draize et al One day prior to the applicationof 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 approximatelyten 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. a Hazleton Dutchland, Inc., Denver, PA Animals were housed in accordance with recommendations contained in DHEW Publication No. 78-23 (NIH): Revised 1978 "Guide For the Care and Use of c Laboratory Animals. Purina Lab Rabbit Chow6 and rabbits may be offered Alfalfa Cubes for d additional roughage. Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1965). e 10 x 12 x .002 Extra Clear polyethylene sleeves, PPC Industries, Inc., Wheeling, IL 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 irritationindex. The scoring criteria for erythema and edema are shown below. Scoring Criteria for Skin Reactions Reaction Erythema Edema Description Score- Barely perceptible I (Edges of area not defined) Pale red in color and area definable 2 Definite red in color and area well 3 defined. Beet or crimson red in color 4 Barely perceptible 1 (Edges of area not defined) Area definable but not raised more 2 than I mm. Area well defined and raised 3 approximately I mm. Area raised more than 1 mm. 4 Maximum Primary Irritation Score 8 4. The following grading system was used to arrive at a descriptive primary skin irritationrating: 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 Descriptive Rating Non-Irritating Minimally Irritating SlightlyIrritating 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 characteristicsand Quality Assurance statement are contained in Appendices I - IV. 5. Table I Primary Skin IrritationTest - Albino Rabbits with T-3874 Animal Number 6BO394 6BO397 6BO389 6BO392 660395 6BO398 IrritationScores for Intact Skin Sites after Removal: 1 Hour Er. Ed. Day 2 Er. Ed. 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Mean 0.0 0.0 0.0 0.0 Subtotal 0.0 Rating: Non-irritating Primary IrritationIndex: 0.0/8.0 Key: Er. = Erythema Ed. = Edema TEST: Acute PrimarySkinIrritatiToenst APPENDIX I RikerExperimentNo.: 0386EB01 35 PROTOCOL SPONSOR: 3M Commercial Chemical CONDUCTED BY: SafetyEvaluationLaboratory,RikerLaboratoriesI,nc.,St.Paul,Minnesota TEST ARTICLE: T-3874 CONTROL ARTICLE: None PROPOSED STARTING/COMPLETION DATE OF TEST: TEST SYSTEM: Female New Zealand WhiteAlbinoRabbits SOURCE: 6. Division OBJECTIVE: To determinethe irritatipontentiaolf the testarticlteo the skinof six animals.Rabbitswere selectedas the testsystem due to theirhistoricuasle,sensitivittoyirritanetass,e of handlingand generalavailability. METHOD: The animalswillbe housed instandardwire-meshcages intemperatureand humiditycontrollerdooms withfood@ and water offeredad libitumE.ach animalwillbe assigneda numbered ear tag,which will correspondto a card affixedtotheoutsideofthecage.Priortothe applicationfthetestarticlet,hehair willbe clippedfrom theback and flanksof each animaland one - testsitesselectedlateral tothe midlineoftheback approximateltyencentimeteraspart.None ofthe one siteswillbe abraded by making fourepidermalincisiontsw,o perpendiculatrothe othertwo,whilethe othertestsite(sw)ill remain intactT.he testarticl(e ()--m'l; ) willbe appliedto no abradedand one intactsite(so)n each animal,coveredwith g;lll7.P and securedwith i2auze The trunkof each animalwillthenbe wrapped withimperviousplastischeetingwhich willoccludethe testarticldeuringtheaday exposureperiod.One hourand 48 hoursafterremovalof thetestarticle, the intacatnd abradedtestsiteswillbe examined and scored separatelfyorerythema and edema on a graded scaleof0 to 4@.The average irritatipornoduced willbe evaluatedby addingthe mean scores forerythema and edema ofthe intactestsitesone and 48 hourspostremovalofthe testarticleS.imi- larlyt,he mean scoresforerythema and edema of the abraded testsiteswillbe added. These two valueswillbe totaledand dividedby fourto obtainthe mean primaryirritationndexand thenassigned a descriptivperimaryskinirritatiroantingas follows: Mean PrimaryIrritatiSocnore 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 DescriptivReating Non-irritating MinimallyIrritating SlightlIyrritating MildlyIrritating ModeratelyIrritating Severelylrdtatin'q ExtremelyIrritating The ratinfgora testarticlmeay be increasedifthe reactioncaused isbeyond erythema and edema and aredeemed to be ofimportanceintheinterpretatioofnthe resultsA.llraw data generatedby the studydirectoarnd the finarleportwillbe storedinthe RikerLaboratoriesA'rchive,St.Paul,Minnesota. Sponsor Form 19 171-12-B-PWO Pudna RabbitChow, RalstonPurinaCo.,St.Louis,Missouri Draize:AppraisaloftheSafetyofChemicalsinFood, Drugs and Cosmetics(1965) Publishedby the EditoriaClommittee oftheAssociatioonf Food and Drug Officialosfthe UnitedStates. 4-hour exposure period; for DOT see attache rom 49CFRI73. a Date Study Director Date 7. APPENDIX 11 Principal Participating Personnel Involved in the StLdy Name G. L. Harris, BS G. 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 APPENDIX III Composition Characteristics This study is not regulated by the Good Laboratory PracticeAct of 1978 and therefore informationpertainingto composition characteristicsis not applicablefor inclusionin this study. 9. APPENDIX TV Ouality Assurance St-atement 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 principlesof 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 from the Archives by the Compliance Audit department for review.