Document K6e2pzdJmXBb4GJpE3a33mJm0

Experiment No.: Conducted At: Dates Conducted: Conducted By: Reviewed By: Primary Skin Irritation Test with T-3493 in Albino Rabbits F(-F.EE[B31,-11934 NLJ 0884EB0009 Safety Evaluation Laboratory Riker Laboratories, Inc. St. Paul, Minnesota January 17, 1984 to January 20, 1984 IV D. M. Markoe, Jr., BS Toxicologist Study Director V(olt4- Date x. o Malley, 'BS A senior Toxicologist Acute Toxicology Date dc: M. T. Case K. L. Ebbens P. D. Griffith W. C. McCormick Summary The results 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-3493 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-3493 to the skin of female albino rabbits. This study is not regulated by the Food and Drug Administration's Good Laboratory Practice Regulation of 1.978,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 bree(P-were used in the evaluation of the primary skin irritatingproperties of the test article. The test procedure was modeled after that of Draize et al=b. 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 removed=. 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). -ElD x 12 x .002 Extra Clear polyethylene sleeves, Wheeling, Illinois. d The test article was 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 mm. 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 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 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. Animal Number 3B3021 3B3024 3B3073 3B3074 3B3075 3B2178 Table 1 Primary Skin Irritation Test with T-3493 Albino Rabbits Irritation Scores for Abraded Skin Sites after Removal: 1 Hour 48 Hours Er. Ed. 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 Irritation Scores for Intact Skin Sites after Removal: 1 Hour 48 Hours Er. Ed. 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 Irritation Index: 0.0/8.0 Key: Er. - Erythema Ed. = Edema 0.0 0.0 0.0 0.0 0.0 APPEMIX I P@ROTOCOL Riker Experiment No.: ooo 5. TEST: Acute Primary Skin IrritatiToenst SPONSOR: 3M Co ...e..rei,,' Clie,,:!icals Division CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories,Inc.,St.Paul, Minnesota TESTARTICLE: CONTROL ARTICLE: PROPOSED STARTINGICOMPLETION DATE OF TE=ST- TEST SYSTEM: Female New Zealand White AlbinoRabbits SOURCE: OBJECTIVE: METHOD: To determine the primary irritatipoontentialof the testarticlteo the skin of animals. Rabbits were selected as the testsystem due to theirhistoricaulse, sensitivittyo irritantse,ase of handling and general avoiability. The animals willbe housed instandard wire-mesh cages intemperature and humidity controlledrooms with foodg and water offeredad libitum.Each animal willbe assigned a numbered ear tag, which will correspond to a card affixedto the outsideof the cage. Priorto the applicationof the testarticlet,he hair willbe clippedfrom the back and flanksof each animal and to the midlineofthe back approximatelyten centimetersapart. 2 - testsitesselectedlateral I ofthe 2 siteswillbe abraded by making fourepidermal incisionst,wo perpendicularto the other two, while the other testsite(s)will remain intact.The test article' 0,1 fl7.-9 ) vallbe appliedto abraded and I intactsite(so)n each animal,covered with !,a,ize and secured with -ta@:c- The trunkof each animal willthen be wrapped with impervious plasticsheetingwhich willocclude the' testarticledudng the 1 day exposure period.One hour and 48 hours afterremoval of the testarticle, the intactand abraded testsiteswillbe examined and scored separatelyforerythema and edema on a graded scale of 0 to 4. The average irritatipornoduced willbe evaluated by adding the mean scores forerythema and edema of the intacttestsitesone and 48 hours post removal of the testarticleS.imilady,the mean scores forerythema and edema of the abraded testskes willbe added. These two values willbe totaledand dividedby four to obtainthe mean primary irritatiionndex and then assigned a descriptiveprimary skinirdtatiornatingas follows: Mean Primary lnfttionScore 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 Descdp Non-irritating Minimally Irritating SlightlyIrritating MildlyIrritating Moderately Irritating Severely Irritating Extremely lrdtatng The ratingfor a testarticlemay be increased ifthe reactioncaused isbeyond erythema and edema and are deemed to be of importance in the interpretatioonf the resuftsA.llraw data generated by the study directorand the finalreportwillbe stored inthe Riker Laborato6es'Archiv'e,St.Paul, Minnesota. Pufina Rabbit Chow, Ralston Pudna Co., St.Louis,Missouri Draize: Appraisalofthe Safetyof Chemicals in Food, Drugs and Cosmetics (1965) Published by the EditoriaClommittee of the Associationof Food and Drug Officialosf the United States. Sponsor C, lai7i-lo-r-pwn Da@-t@e Study Director Date 6. APPENDIX Il Principal participating personnel Involved in the Study Name D. M. Markoe, Jr., ES 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. 8. APPENDIX 3:V Ouality 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 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.