Document zQ3o85on5Z7Zo6vLQM8DzDErz

FOR DU PONT USE ONLY AR226-2939 Du Pont HLR 360-89 Study T^tia Skin Irritation Test In Rabbits of Author John H. Sarver Study Completed On June 29, 1989 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 Haskell Laboratory Report No. 360-89 Page 1 of 8 Company Sanffized. Doies not contain TSCA CB^ Material Tested; Medical Research No. Haskett No.: Physical Form: Purity: Composition; GENERALINFORMATION Du Pont HLR 360-89 17,869 White dispersion Synonyms: Other Code: 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, Inc. Jackson Laboratory Deepwater, New Jersey In-Life Phase Initiated - Completed: 6/14/89 - 6/16/89 Notebook; There are 8 pages in this report Distribution: v - 2 Company Sanitized. Does not contain TSCA CBI Du Pont HLR 360-89 Skin Irritation Test In Rabbits of SUMMARY irritation potentia^r^nefeniaTeand 5 male rabbits. No dermal Irritation was observed throughout the study. Under the conditions of this study, ^was not a skin irritant, Work by: y^tMCcarr6o.1l^Ffi/nm.l.a,r^t Te--c1h-n-'icia-n"" Study Director: t^>. QoJ^Ar-tf^ John W. Sarver Technologist Approved, by: ^Si.^p.UK Dolores E. Maiek, Ph.D. Research Toxicologist Acute and Developmental Toxicology Division Reviewed and Approved for Issue: t " 0" . J o0<w^n h1n--.W . "SAa"r"v er. Study Director 6/y?/^ Acknowledgment: Lisa Lewis also participated in the conduct of this study. JWS:air:HLRZ9.9 - 3 - Company Sanitized. Does not contain TSCA C8i Du Font HLR 360-89 QUALITY ASSURANCE DOCUMENTATION STUDY: iH^9 Skin Irritation Test in Rabbits of AUDITS; Items Audited Audit Dates w Evaluation of Skin Response to Test Article 6/15/89 SHORT-TERM AUDIT REPOP" NUHBER:W^f DATE FINDINGS REPORTE TO MANAGEMENT AND STUDY DIRECTOR: 6/22/89 Reported by: \L-^PA^^- ^^^ Joseph C. HamillDate ility Assurance Auditor ^f^/^ u Company Sanitized. Does not contain TSCA CBS Du Pont HLR 360-89 INTRODUCTION ^fRwhen The purpose of this study was to evaluate the skin Irritation potential of applied to the clipped. Intact skin of New Zealand White rabbits. This study was conducted according to the applicable EPA Good Laboratory Practice Regulations. Areas of noncompllance 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 Marl and, Hewitt, Mew 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 iS'5325 and water were available ad Hbltum except as noted under Protocol. Rabbits were quarantined, 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 t 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. Protocol On the day prior to study initiation, the hair of one female male New Zealand White rabbits was closely clipped to expose the from the scapular to the lumbar region of the back. The rabbits from 2773 to 3145 grams on the day of treatment. and 5 skin weighed 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_ha_ time did not have access to food or water. A 0.5 mL aliquot of f^------I was applied directly on the test site beneath a 2-inch gauze square that 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. Company Sanitized. Does not contain TSCA CB1 Du Pont HLR 360-89 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 mm water to remove excess test material. The skin was gently patted dry and the animals were returned to their cages. Approximately 24 ahd 48 hours after application of the test material, the test sites were evaluated for erythema, edema and other evidence of dermal effects and werie 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 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, wllinington, Delaware. RESULTS AND CONCLUSIONS D ^UJ^as evaluated for icute skin Irritation potential in one female and 5 male rabbits. No dermal irritation was observed throughout the study. Individual skin Irritation scores are presented in Table II. A summary of responses is presented In the following table. Summary of Skin Responses toj Response No Response Erythema "24~Rr--WW 6/6 6/6 Edema "24~hr--4TnF 6/6 6/6 Under the conditions of this study, ^was not a skin irritant. Company Sanitized. Does not coniain TSCA CBB Du Pont HLR 360-89 TABLE I DRAIZE- SCALEFOR SCORING PRIMARY SKIN IRRITATION Evaluation of $k1n 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) Value 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 mi) Severe edema (raised more than 1.0 mm extending beyond the area of exposure) 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 = Fissuring with Bleeding S = Epidermal Scaling L = R = X = SN = Sloughing Raw Areas Compound Adhered to Skin Superficial Necrosis Draize, <h H., "Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. The Editorial Committee or the Association of Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. Company Sanitized. Does not contain TSCACffi Du Pont HLR 360-89 TABLE II RABBIT SKIN IRRITATION TEST SKINjRESPONSEOSBSERVEDIN TEST. RABBITS FOLLpHINTSOPICAL EXPOSURE TO Rabbit Number 23913 23917 23918 23919 23920 23924 Erythema 24 ^r 46 hr- 0 0 0 0 0 0 0 0 0 0 0 0 Edema 24 hr 46 hr 0 0 0 0 0 0 0 0 0 0 0 0 .-""'-',, - 8 - Company Sanitized. Does not contain TSCA CB|