Document yrMYRBwxmJ27rQyjmxQ3Om7p3

AR226-3002 Study Title Skin Irritation Test with H-20431 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 51-94 Author Carol Finlay Study Completed On March 15, 1994 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 Medical Research No.& Page 1 o f 9 Company Sanitized. Does not contain TSCA CBI Substance Tested; Synonyms/Codes: GENERAL INFORMATION DuPont HLR 51-94 Physical Form: Purity: Composition; Contaminants: CAS Registry No.: ! I i -- >. impany SanrffeedL Does not contain TSC CBI DuPont BLR 51-94 GENERAL INFORMATION (CONT.) Sponsor: Study Initiated - Completed: In Life Phase Initiated - Completed; Specialty Chemicals p. I..p Pont de Nenours and Coapany Wilmington, Delavare 1/5/94 - 3/15/94 1/11/94 - 1/14/94 i - 3 - Company Sanitized. Does not contain TSCA CB! DuPont BLR 51-94 Skin Irritation Test vlth H-20431 In Rabbiti SUMMARY H-20431 vas evaluated for acute skin irritation potential in 1 sale and 5 female Nev Zealand Vhite rabbits. A 0.5 mL aliquot of test substance was applied directly to the shaved, intact skin of each rabbit and covered with a semi-occlusive dressing. Approximately 24, 48, and 72 hours after application of the test substance, the test sites vere evaluated for erythema, edema, and other evidence of dermal effects and vere scored according to the Draize Scale. The adjacent areas of untreated skin vere used for comparison. H-20431 produced severe erythema and moderate edema in 5 rabbits and moderate erythema and mild edema in 1 rabbit by 24 hours after application. Superficial necrosis vas observed in 5 rabbits by 48 hours and in all rabbits by 72 hours. One rabbit had a rav area in the test site vhich scabbed over (eschar) by 48 hours. Eschar was also observed in this rabbit at 72 hours. Sloughing of the skin vas also observed during the study. Under the conditions of this study, H-20431 was a severe skin irritant. Approved by: Revieved .-- 1 Approved Toxicologist CF/alw - 4Company Sanitized. Does not contain TSCA CBI DuPont BLR 51-94 INTRODUCTION The purpose of this study vas to evaluate the skin irritation potential of H-20431 when applied to the shaved, intact skin of Nev Zealand Vhite rabbits. MATERIALS AND METHODS A. Anleal Husbandry Young adult male and female Nev Zealand Vhite rabbits were received fro Hare Marland, Hevitt, Nev Jersey. The rabbits vere housed singly in suspended, stainless steel, vire-mesh cages. Each rabbit vas assigned a unique identification number which vas recorded on a card affixed to the cage. The last 3 digits of the identification number vere written on the inside of the rabbit's ear with a vater insoluble marker. The rabbits vere offered approximately 125 grams of Purina Certified High Fiber Rabbit Chow* #5325 daily during the study. Vater vas available ad libitum except as noted under Protocol. Haskell Laboratory has a monitoring program which consists of periodic food and vater analysis for contaminants. This program is monitored and administered by the Laboratory Veterinarian; data from this program are maintained separately from study records. On the basis of these analyses, there is no evidence suggesting that contaminants vere present in the feed or vater in amounts which may have interfered with the results of this study. Rabbits vere 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 vere targeted for a temperature of 20C 2C and relative humidity of 50Z 10X. Excursions outside these ranges vere judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Protocol On the day prior to treatment, the hair of 1 male and 5 female Nev Zealand Vhite rabbits vas closely shaved to expose the skin from the scapular to the lumbar region of the back. The body veights of the rabbits ranged from 2487 to 2722 grams on the day of treatment. company Sanifized. Does no conlain T S C A CBI DuPont BLU 51-94 Bach rabbit vas placed into a stock which had bean fitted with a piece of rubber sheeting, approximately 8" x 18". Th# rabbits remained in the stocks throughout the exposure period and during that time did not have access to food or water. A 0.5 aL aliquot of H-20431 was applied directly on the test site beneath a 2-inch gauze square that was held in place with non-irritating tape. The rubber sheeting vas then wrapped around the aninal and secured vith clips to retard evaporation and to keep the test substance in contact vith the skin vithout undue pressure. In the absence of visible evidence to the contrary, the test substance vas assumed to be stable under the conditions of administration. Three other test substances vere tested concurrently on separate, localized test sites on the backs of these rabbits. Approximately 24 hours after application of the test substance, the rubber sheeting vas loosened, and the skin at the corners of the gauze squares vas marked vith a waterproof pen; vrappings and gauze squares vere then removed. The test sites vere gently washed vith warm water and Ivory soap to remove excess test substance. The skin vas gently patted dry, and the animals vere returned to their cages. Approximately 24, 48, and 72 hours after application of the test substance, the test sites vere evaluated for erythema, edema, and other evidence of dermal effects and vere scored according to the Draize scale (Table I). The adjacent areas of the untreated skin vere used for comparison. Records Retention All raw data and the final report will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, B. I. du Pont de Nemours and Company, Newark, Delaware or in the DuPont Records Management Center, Wilmington, Delaware. - 6- Company Sanitized. Does not contain TSCA CB1 t DuPont BLR 51-94 RESULTS AND CONCI/JSIOBS Although the test substance adhered to the skin of 4 rabbits during the study, the test sites could be evaluated. H-20431 produced severe erythema and moderate edema in 5 rabbits and moderate erythema and mild edema in 1 rabbit by 24 hours after application. Superficial necrosis was " ved in 5 rabbits by 48 hours and in all rabbits by 72 hours. Two rabbits exhibited severe erythema at 48 hours. No to moderate edema was observed at 48 or 72 hours. One rabbit had a raw area in the test site which scabbed over (eschar) by 48 hours. Eschar was also observed in this rabbityat 7Z nours. Sloughing of the skin was also observed during the study. Individual skin irritation scores are presented in Table II. A summary of skin responses is presented in the following table. Summary of Skin Responses to H-20431 Response No Response Slight Hild Moderate Severe 24 hr 0/6 0/6 0/6 1/6 5/6 48 hr 3/6 0/6 0/6 1/6 2/6 72 hr 6/6 0/6 0/6 0/6 0/6 . Edema 24 hr 48 hr 0/6 1/6 0/6 1/6 1/6 1/6 5/6 3/6 0/6 0/6 72 hr 2/6 2/6 1/6 1/6 0/6 Response Other Dermal Effects 24 hr 48 hr 72 hr Superficial Necrosis 0/6 5/6 6/6 Sloughing 0/6 0/6 2/6 Eschar ' 0/6 1/6 1/6 - Rav Areas 1/6 0/6 0/6 Under the conditions of this study, H-20431 was a severe skin irritant. If these test scores are to be used for EEC/OECD classification, ccording to the guide to the labeling of dangerous substances published in he Official Journal of European Communities (EEC Directive 91/325, Annex I), H-20431 probably should be classified as an "IRRITANT" until further ata are available. Company Sanitized. Does not contain TS CA CBI a OB n DuPont BLR 51-94 SKIN IRRITATION TBST VITB H-20431 TABLE I DRAIZB1 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 deptn) Value 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Edema formation: No edema Very slight edema (barely perceptible) Slight edema (edges of area veil 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) 0 1 (Slight) 2 (Hild) 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 i 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. - 8- Company Sanifized. Does not certain TSCA CB1 DuPont HLR 51-94 SKIN IRRITATION TEST VITH H-20431 TABLE II INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS Rabbit Number 28770 28756 28773 28776 28777 28778 Erythema 24 hr 48 hr il hr 440 >X* 0 44 0 0 4X 0 4X* 0 0 0 3X* 3 0 Edema 24 hr 48 hr 72 hr 331 300 333 3. 3 32 2 0 211 Other Dermal Effects 24 hr 48 hr 72 hr - SNb SN>, L - SNb SNb R Cc SNb, C= - SNh SNh - StP SNb, L SNe SNb * Although the test substance adhered to the skin, the test site could be evaluated. b Approximately 4 cm in diameter. c Approximately 1 cm in diameter. -9- company Sanitized. Does not contain TSCA CB1