Document DGx20pN3yNLE4Nxyj7XnBZQOa

Experiment No.: Conducted At: Dates Conducted: Conducted By: Reviewed By: Primary Skin Irritation Test with T-3494 in Albino Rabbits FEB I rF -3 0884EB0012 safety Evaluation Laboratory Riker Laboratories, Inc. St. Paul, Minnesota January 17, 1984 to January 20m, 1984 "@D, D. M*. Markoe, Jr., BS ae Toxicologist study Director K@ D. O'Malley, BS Senior Toxicologist Acute Toxicology dc: M. To Case K. L. Ebbens P. D. Griffith W. C. McCormick summary The re@ults of the primary skin irritation test conducted from January 17, 1984 to January 20, 1984 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3494 is slightly irritating (0.7/8.0) to the skin of female albino rabbits. Slight erythema with no accompanying edema was noted at the one hour evaluation following a one day occluded contact period. No irritation was noted at the day two evaluation. introduction The objective of this study was to determine the primary skin irritation potential of T-3494 to the skin of female albino rabbits. This study is 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 report are stored in the conducting laboratory's archives. 2. Method and Results Young albino rabbits of the New Zealand breee were used in the evaluation of the primary skin irritating properties of the test article. b procedure was modeled after that of Draize et al.@--. The test one day prior to the application of the test article, the hair was clipped from 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 was abraded by making four epidermal incisions, two perpendicular to the other two, while the other test site remained intact. The test article (0.5 g) was 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 wrap. c The trunk of each animal was then wrapped with impervious plastic sheeting which held the patches in position during the one day exposure period. At the end of one day, the plastic wrappings, patches, and all residual d test article were removecl@--.one hour and 48 hours after removal of the test article, the intact and abraded test sites were examined and scored separately 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 intact test sites one and 48 hours post removal of the test article. Similarly, the mean scores for erythema and edema of the abraded test sites were added. a Hazleton Dutchland, Inc., Denver, PA -b@--Draize:Appraisal of the Safety of Chemicals in (1965). -ElO x 12 x .002 Extra Wheeling, Illinois. d @--Thetest article was Clear polyethylene sleeves, removed with water. Foods, Drugs and Cosmetics PPC Industries, Inc., 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 Reaction Description Score Erythema Edema Barely perceptible 1 (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 1 mm. Area well defined and raised 3 approximately 1 inm. Area raised more than 1 mm. 4 maximum Primary Irritation Score 8 The following grading system was used to arrive at a descriptive primary skin irritation rating: Mean Primary Irritation Score (Range of Values) Descriptive Rating 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 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.ge 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. Animal Number 3B3025 3B3028 3B3031 3B3034 3B3026 3B3029 Table 1 Primary skin Irritation Test with T-3494 Albino Rabbits Irritation Scores for Abraded Skin Sites after Removal: I Hour Er. Ed. 48 Hours Er. Ed. 1 0 0 0 1 0 0. 0 0 0 0 0 1 0 0 0 1 0 0 0 1 0 0 0 irritation Scores for Intact Skin Sites after Removal: 1 Hour Er. Ed. 48 Hours Er. Ed. 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 Mean Subtotal 0.8 0.0 0.0 0.0 0.8 Rating: Slightly irritating Primary Irritation Index: 0.7/8.0 Key: Er. m Erythema Ed. - Edema 0.5 0.0 0.0 0.0 0.5 APPEMIX I RikeErxperimeritNo.:- PR COL TEST: AcutePrimarySkin IrritatiToenst SPONSOR: 3M Ccnnercial Che,,ticals CONDUCTED BY: SafetyEvaluationLaboratory,RikerLaboratoriesI,nc.,St.Paul,Minnesota TEST ARTICLE: T-34c'4 CONTROLARTICLE: PROPOSED STARTINC,/COMPLETION DATE OF TEST: TEST SYSTEM: Female New ZealandWhite AlbinoRabbits SOURCE: D,rT -,J PA Division OBJECTIVE: METHOD: To determinetheprimaryirritatipontenfiaolfthetestarticlteo thesldnof animals.Rabbits were selectedas the testsystem due to theirhistoricuasle, sensitivittoyirritantesa,se of handling and generalavailability. The animalswillbe housed instandardwire-meshcages intemperatureand humidityponwied rooms withfoodg and water offeredad libitum.Each animalwillbe assigneda numbered ear tag,which will correspondtoa card affixetdothe outsideofthecage.Priortotheapplicatioonfthetestarticlteh,e hair willbe clippedfrom the back and flanksofeach animaland 2 - testsitesselectedlateral tothemidlineoftheback approximateltyoncentimeteraspart-.L ofthe 2 siteswillbe abraded by making fourepidermalincisionst,wo perpendiculatro theothertwo,whiletheothertestsite(sw)ill remain intactT.he testarticle 0$ i iz willbe appliedtD abraded and intacstke(s)on each animal,coveredwith gauze and secured with -tart= The trunkof each animalwillthen be wrapped withimperviousplastischootingwhich willoccludethe testarticldeuringthe 1 day exposureperiod.One hour and 48 hoursafterremovalof ft testarticle, the intacatnd abraded testsiteswillbe examined and scoredseparatelfyorerythema and edema on a gradedscaleof0 to 4.The average irritatipornoducedwillbe evaluatedby adding#* mean scores fororythemaand edema of theintactestsitesone and 48 hourspostremovalofthe testardcle.Simi- lady,the mean scores forerythema and edema of the abraded testsitesWillbe added. These two valueswillbe totaledand divkiedby fourtoobtainthe mean primaryirritatiIonndexand thenassigned a descriptivperimaryskinirritabornatingas 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-irrftadng MinimallyIrritating SlightlIyrritating I MildlyIrritating L; Moderatelylrdmgng SeverelyIrritating ExtremelyIrdtafing The ratingfora testarticlmeay be increasedffthereactioncaused Isbeyond erythema and edema and aredeemed to be of importanceintheinterpretatioofntheresultsA.llraw data generatedby the studydirectoarnd the finalreportwillbe storedinthe RikerLaboratoriesA'rchive,St.Paul,Minnesota. Sponsor Form 19171-12-CPWO PurinaRabbitChow. RalstonPudna Co.,St.Louis,Missouri Dralze:AppraisaloftheSafetyof ChemicalsinFood,Drugs and Cosmetics(1965) Publishedby the EditoriaClommittee ofihe AssociatioonfFood and Drug Officialosf the UnitedStates. Date--- Study Director 7 Date 6. APPENDIX II principal Participating Personnel Involved in the Study Name D. M. Markoe, Jr., BS K. L. Ebbens, BS K. D. O'Malley, BS G. C. PeCore Function Toxicologist Study Director Supervisor Toxicology Testing Senior Toxicologist Acute Toxicology Supervisor Animal Laboratory 7. APPENDIX III Composition Characteristics 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. B omlity APPENDIX IV Assurance Statement 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 different significantphases 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.