Document ev976rpz3Va7J2XE9ynNedxQy

Experiment No.: Conducted At: Dates Conducted: Conducted By: Primary Skin Irritation Test with T-3608 in Albino Rabbits 0984EB0368 Pathology and Toxicology Riker Laboratorier., Inc. St. Paul, Minnesota July 17, 1984 to July 20, 1984 r e-,L* S.@Eyrt ratory Technician Acute Toxicology fflis / tq Date K. D. O'Malley, BEt Senior Toxicologist Study Director Date dc: X. L. Ebbens Fe Do Griffith. W. C. McCormick Summary The results of the primary skin irritation test conducted from July 17, 1984 to July 20, 1984 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3608 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-3608 to the skin of female albino rabbits. This study was conducted for research and development purposes and is, therefore, 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 repoqt are stored in the conducting laboratory's archives. 2. Method and Results Young albino rabbits of the New Zealand breeds 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 gm) was applied to each of the test sites on eacb 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. The trunk of each animal was then wrapped with impervious plastic sheeting c 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 eryt"ma and edema of the intact test sites one and 48 hours post r oval 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 --'@@aize: Appraisal of the Safety of Chemicals in (1965). -SIO 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 I ma. 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: man 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.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 4Bll46 4BI149 4BI152 4BI155 4BI147 4Bll5O Table I Primary Skin Irritation Test with T-3608 Albino Rabbits Irritation Scores for Abraded Skin Sites after Removal: I Hour Er. Ed. 48 Hour Er. :d. 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 Int Skin Sites after Remova 1 Hour 48 Hou Er. Ed. Er. 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nean Subtotal 010 010 0.0 0.0 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 TEST: Acute Primary Skin IrritatiToenst SPONSOR: 3M Commercial Chemicals APPEMIX I FtkerEitperimentNo.: PROTOCOL 0984EB0368 5. Division CONDUCTED BY: Safety Evaluation Laboratory, Riker LaboraUwies, Inc.,St.Paul, Minnesota TEST ARTICLE: T-3608 CONTROL ARTICLE: t41 P, PROPOSED STARTING/COMPLETION DATE OF TEST: TEST SYSTEM: Female New Zealand White Albino Rabbits SOURCE: OBJECTIVE: METHOD: To determine the irritatipoontentialof the test articlteo the skin of animals. Rabbits were selectedas the test system due to theirhistoricaulse, sensitivittyo irritantesa,se of handling and general availability. The animals willbe housed in standard wire-mesh akjes in temperature and humidity controlledrooms with food! and water offeredad libitum.Each animal willbe assigned a numbered ear tag, which will correspond to a card affixedto the outside of the cage. Priorto the applicationof the testarticlet,he hair willbe clippedfrom the back and flanksof each anirrwand 2 - testsitesselectedlateral tothe midlineof the back approximatelyten centimetersapart. 1 ofthe 2 siteswillbe abraded by making fourepidermal incisionst,wo perpendicutw to ft othertwo, whilethe othertestsite(sw)ill remain intactT.he testarticl(e 0. -grams intactsde(s)on each animal,covered Wff -j willbe appliedto 1 abraded and I and - od:xecured with gali7e The trunkof each animal willthen be wrapped withirnperaousplasticsheetingwhich willocclude the testarticleduring the I day exposure period.One hdur 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.imi- larlyt,he mean scores for erythema and edema of the abraded test siteswillbe added. These two values willbe totaledand dividedby fourto obtainft mean primary irritatiionndex and then assigned a descriptiveprimary skin irritatiroantingas follows: Mean Primary lriitatioSncore 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 DescriptiveRating Nor?.4mwng WinimaNy lnftung SlightlyIrritating MildlyIrritating Moderately Irritating SeverelyIrritati,ng Extremely Irritating,- The ratingfor a testarticlemay be increased ifthe reactioncaused is beyond erythema and edema and are deemed to be of importance in the interpretationf the results.Allraw data generated by ft study directorand the finalreportwillbe stored intt* Riker Laboratories'Archive,St.Paul, Minnesota. Purina Rabbit Chow, Ralston Purina Co., St.Louis,Missouri Draize: Appraisal-ofthe Safety of Chemicals in Food, Drugs and Cosmetics (1965) tp-ijbllsbbayd the EditoriaClQmmittee of the Associationof Food and Drug Officialosf the United States. Sponsor Fwm19171-12-1@.PWO -b-We/ sw* Director Dite' 6. APPENDIX 11 Principal Participating Personnel Involved in the Study Name Function G. E. Hart Sr. Laboratory TechniciaLn Acute Toxicology X. D. O'Malley, BS Senior Toxicologist Study Director K. L. Ebbens, BS Supervisor Toxicology Testing G. C. Pecore 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. f APPENDIX IV Quality Assurance statement This study is not officially regulatod by the Good Laboratory Practice Regulation of 1978, and therefore a statement signed and prepared by the C=pliance 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.