Document jgLpJgvM0okDb64XwgEjE0em2

FOR DU PONT PSE ONLY AR226-2969 Du Pont BLR 802-91 Study Title Skin Irritation Test vith n Rabbits Author John V. Sarver Study Completed On February 13, 1992 Performing Laboratory E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Laboratory Project IP Haskell Laboratory Report No. 802-91 CompanySanHiaad Dees notcontain TSC# CBI Page 1 of 9 GENERAL INFORMATION Du Pont BLR 802-91 Substance Tested: Medical Research Ho.: Haskell Ho.8 Haskell Test Code Mo.: Physical Form: Composition: 19,173 Contaminants: Purity: Synonym: Submitter's Notebook Ho: CAS Registry Ho.: Stability: In the absence of visible evidence to the contrary, the test substance vas assumed to be stable under the conditions of administration. Sponsor: Du Pont Chemicals E. I. d . Pont de Nemours and Company Vilmington, Delavare Substance Submitted By: Study Initiated - Completed: Du Pont Chemicals E. I. du Pont de Nemours and Company Deepvater, Nev Jersey 10/31/91 - 2/13/92 In-Life Phase Initiated - Completed: Notebook: There are 9 pages in this report. SspRj iSftRIzed. Poes Do! contain TSCA cm Distribution: Du Pont BLR 802-91 GENERAL INFORMATION (CQHT'D) t 4 -3 t itiy.h Skin Irritation Test with! Du Pont HLR 802-91 in Rabbits SUMMARY [(1002 pure) m s evaluated for acute skill irritation potential in 5 female rabbits. The test substance adhered to the skin of the rabbits throughout the study. No dermal irritation vas observed in any of the rabbits by 24 or 48 hours after administration of the test substance. At 72 hours, 1 rabbit exhibited slight erythema. Under the conditions of this test but only after prolonged exposure (gri a slight skin irritant, '48 hours). (fork by: <5 Cindy H. Hahn Technician Study Director: John V. Sarver Technologist Approved by: Nancy C. qhromey, Ph.D. Manager Acute Toxicology Reviewed and Approved for Issue: L . AArt-^ John W. Sarver Study Director Acknowledgments: Carol Finlay, Bryan Crossley, and Terri Settlemyre also participated in the conduct of this study. JWS/imr -4- Company SanKfaed. Does not contain TSCA Du Pont HLR 802-91 QO&LIYY ASSURANCE DOCUMENTATION Audit Dates In-life-Observatiom 11/6/91 Records, Final Report: 1/24,28/92 DATE FINDINGS REPORTED TO STUDY DIRECTOR: 1/28/92 - TO MANAGEMENT: 2/11/92 Reported Donna R. Holt Quality Assurance Auditor [ll9 0 - Oaf: i*. -5- Du Pont HLR 802-91 INTRODUCTION The purpose of this study was to evaluate the skin irritation potential of HPD-"110 when applied to the shaved, intact skin of New Zealand White rabbits. This study was conducted according to the applicable PA Good Laboratory Practice Regulations. Areas of noncompliance are documented in the study records. Ho deviations existed that affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult male and female New Zealand White rabbits were received from Bare Harland, Hewitt, New Jersey. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit was assigned a unique identification number which was recorded on a card affixed to the cage. Purina Certified High Fiber Rabbit Chow #5325 and water were available ad libitum except as noted under Protocol. Rabbits were quarantinedT weighed, and observed for general health for approximately 2 weeks. Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20C 2C and relative humidity of 50% 10*. Any excursions outside these ranges were of small magnitude and/or brief duration and did not adversely affect the validity of the study. B. Protoeoi On the day prior to treatment, the hair of 5 male and 1 female New Zealand White rabbits was closely shaved to expose the skin from the scapular to the lumbar region of the back. The body weights of the rabbits ranged from 2665 to 3123 grams on the day of treatment. Each rabbit was placed into a stock which had been tiffed vith * piece of rubber sheeting, approximately 8" x 18". Ihe rabbits remained in the stocks throughout the exposure period and durin^fla| time did not have access to food or water. A 0.5 mL aliquot o f ^ p R B m s applied directly on the test site beneath a 2-inch gauze square that was held in place with non-irritating tape. The rubber sheeting was then wrapped around the animal and secured with clips to retard evaporation and to keep the test substance in contact with the skin without undue pressure. Du Pont HLR 802-91 Approximately 24 hours after application of the test substance, the rubber sheeting was loosened, and the skin at the corners of the gauze squares as narked with a waterproof pen; wrappings and gauze squares were then removed. The test sites were gently washed with warn water, Ivory* soap, and acetone to remove excess test substance. The skin was gently patted dry, and the animals were returned to their cages. Approximately 24, 48, and 72 hours after application of the test substance, the test sites were evaluated for erythema, edema, and other evidence of dermal effects and were scored according to the Draize scale (Table I). The adjacent areas of the untreated skin were used for comparison. C. Records Retention All raw data and the fil! report will be stored in the archives of B a g o l i Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Company, Newark, Delaware or in the Du Pont Records Management Center, Wilmington, Delaware. RESULTS AND CONCLUSIONS A l t h o u g h H M H v d h e r e d to the skin of all rabbits, the test sites could be evaluated for dermal irritation. No dermal irritation was observed in any of the rabbits at 24 or 48 hours after application of the test substance. Slight erythema was observed in one rabbit 72 hours after application. iSdividuaT skin lrrttat'ion scores are presented in Table II. A summary of skin responses is presented in the following table. Summary of Skin Responses Response No Response Slight Erythema 24 hr 48 hr 72 hr 6/6 6/6 5/6 0/6 0/6 1/6 Edema 24 hr 48 hr 6/6 6/6 0/6 0/6 72 hr 6/6 0/6 Under the conditions of this s t u d y , | B l l H H ras a slight skin irritant, but only after prolonged exposure (greater than 48 hours). Doss noi cot*8'" T sra r; - 7 'Comp30? SanRfc3 Du Pont BLR 802-91 table I PRAIZB* SCALE FOR SCORING PRIMARY SKIN IRRTTATTnw Evaluation of skin Reactions Erythena and eschar formation: Mo erythena Very slight erythema (barely perceptible) Well-defined erythema Moderate to severe erythema Seve orythema (beet redness) to slight eschar formation (injuries in depth) Value 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Edema formation: No edema Very slight edema (barely perceptible) Slight edema (edges of area well defined by definite raising) ...... Moderate edema (raised approximately 1.0 mm) Severe edema (raised more them 1.0 mm extending beyond the area of exposure) 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other dermal effects are: A Abraded F Fissuring I = Intact N Necrosis T = Thickening G Fissuring with C Eschar Bleeding - No Effect S * Epidermal B = Blanching Scaling L Sloughing R Raw Areas X Compound Adhered to Skin SN Superficial Necrosis Draize, J. B., "Dermal Toxicity." Appraisal of the Safety of Chemicals ^n Foods, Drugs and Cosmetics. Thes Editorial uCommamtituteece orf ctnhe aAssoeciatiicon and Dru8 Officials of the United States, Austin, Texas, 1959, pp. 4wTM59 Vm pm - a- des ut dMa** * * * * Da Pont BLR 802 TABLE II INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IN RABBITS FOLLOWING TOPICAL EXPOSURE n Rabbit Number 26791 26792 26794 26795 26796 26800 Erythema 24 hr 48 hr 72 hr ax OX OX OX OX OX OX OX OX OX OX OX OX OX IX ox OX OX Edema 24 hr 48 hr 72 hr 000 000 000 000 000 000