Document BR7qd94zaXVxvbXB8G6g3ZGao

AR226-2935 % FOR DU PONT USE ONLY Du Pont HLR 801-88 Study Title Skin Irritation Test in Rabbits o Author William J. Brock Study Completed On December 14, 1988 Performing Laboratory Haskell E. I. du Pont de Nemours and Company, Inc. Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Laboratory Project ID Haskel! Laboratory Report No. 801-88 f^mSan^. Does ^ Page 1 of 7 ^.TSCA Off, Material Tested; Medical Research No. HaskeU No.: Physical Form: Purity: Synonyms: Contaminants: GENERAL INFORMATION Du Pont HLR 801-88 SubmiUer's Notebook No.: Stability: The test material was assumed to be stable under the conditions of administration. Sponsor: Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Milmington, Delaware Inc. Material Submitted By: Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Jackson Laboratory Deepwater, New Jersey Inc. In-Life Phase Initiated - Completed: 11/1.5/88 - 11/17/88 Notebook: There are 7 pages in this report. Distribution: o Company Sa^tized. Does not contain TSCA CB! _ . Du Pont HLR 801-88 Skin Irritation Test In Rabbits of SUMMARY evaluatedforacuteskirMrritation potential ir^^naTeand 2 female rabbits. No erythema or edema, was observed in any of the treated rabbits throughout the study. Under the conditions of this study, ^was not a skin irritant. Work by: (Sr^'i ^UoCiJndryvH^. _H_ah_n ____^2,/Qfi Technician Study Director: ,^^/Z^^ //Jl^fc^ H. f/2. I PSWill/^1 J. Brock.Ph.D. Research Toxicologist Acute and Developmental Toxicology Division Reviewed and Approved for Issue: Ui^^r^^^^ Win/yam J. Brock, Ph.D.. Study Director //y/^ yjB^jbrHLP.llO.S 3 - B^p^^^anWzecf. D?!0" ""? f^-iv r<;cA f*.w Du Pont HLR 801-88 QUALITY ASSURANCE DOCUMENTATION AUDITS: Items Audited Exposure of test system to test article (dosing) Audifc Dates 11/15/88 s^^fff SHORT-TERM AUDIT REPORT WPIBER DATE FINDINGS REPORTED TO MANAGEMENT AND STUDY DIRECTOR: 12/13/88 Reported by: t^J/ ^y^jS- ^ /r^Jc^keph c. Hamill lality Assurance Auditor I 2// J/f-f bate Z) ^n.^.-no.co^SC^ < Du Pont HLR 801-88 INTRODUCTION pose of this study was to evaluate the skin irritation potential --------i------Bl--------r when applied to the dipped, intact skin of New Zealand White rabbits. This study was conducted according to the applicable EPA Good Laboratory Practice Regulations. Areas of noncompliance are documented in the study records. No deviations existed that significantly affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult male and female New Zealand White rabbits were received from Hare Marland, 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 quarantine<T7 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% j_ 101. Any excursions outside these ranges were of small magnitude and/or brief duration and did not adversely affect the validity of the study. B. Protocol On the day prior to study initiation, the hair of 4 male and 2 female New Zealand White rabbits was closely clipped to expose the skin from the scapular to the lumbar region of the back. The rabbits weighed from 2942 to 3460 grams on the day of treatment. Each rabbit was placed into a stock which had been fitted with a . piece of rubber sheeting, approximately 8" x 18". The rabbits remained in the stocks throughout the exposure period and during that time did not i.Ave access to jood or water. A 0.5 gram aliquot of fB----------^ J------------------mtoistened with dimethyl phthalate (DMP), was applied directly to a 2-inch gauze square that was then placed on the test site. The patch was held in place with tape. The rubber sheeting was then wrapped around the animal and secured with clips to retard evaporation and to keep the test material in contact with the skin without undue pressure. 5- I Company Sanitized. Does not contain TSCACBB Ou Pont HLR 801-88 Approximately 24 hours after application of the test material, the rubber sheeting was loosened, and the skin at the corners of the gauze squares was marked with a waterproof pen; wrappings and gauze squares were then removed. The test sites were gently washed with warm water to remove excess test material. The skin was gently patted dry and the animals were returned to their cages. The material was moistened with DMP, but did not dissolve in DMP. Therefore, some of the compound may have fallen from the test site during the '"posure period. Approximately 24 and 48 hours after application of the test material, the test sites were evaluated for erythema, edema and other evidence of dermal, effects and were scored..accordi.ng. 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 final report will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Company, Inc., Newark, Delaware or in the Du Pont Records Management Center, Wilmington, Delaware. RESULTS AND CONCLUSIONS No erythema or edema_was observed in any of the rabbits treated with "^^^^"""^'^"""''^^^^^^"^'^ Under the conditions of this study, 'was not a skin irritant. Du Pont HLR 801-88 TABLE I DRAIZE* SCALE FOR SCORING PRIMARY SKIN IRRITATION Evaluation of Skin Reactions Erythema and eschar formation: No erythema Very slight erythema (barely perceptible) Well-defined erythema Moderate to severe erythema Severe erythema (beet redness) to slight eschar formation (injuries in depth) 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 than 1.0 mm extending beyond the area of exposure) Value 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) A = Abraded I = Intact T = Thickening C = Eschar - = No Effect B = Blanching F = Fissuring N = Necrosis G s Fissuring with Bleeding S = Epidermal Scaling L Sloughing R Raw Areas X Compound Adhered to Skin SN Superficial Necrosis Draize, J. H., "Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods. Drugs and Cosmetics. The Editorial Committee of the Association of Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. Company Sanitized. Does not contain TSCA CBS