Document 85xM08me1n1R6qnXmodgYz9V5

AR226-3050 Study Title Skin Irritation Test with H-21946 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 784-96 Author Tracy A. Rlliben Study Completed On September 4,1996 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 Page I of 10 Company Sanitizeti. Does no5 contain TSCA CB1 Substance Tested: Synonyms: GENERAIrlNFORMATlON- Physical Form: Composition: Light beige, opaque liquid Contaminants: Purity: Submitter's Notebook No. CAS Registry No.: Sponsor: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington, Delaware -1 - Company SanFfFzed. Doss not contain TSfa e^ Skin Irritation Test with H-21446 in Rabbits General Information (Continued) DuPont HLR 784-96 Study Initiated - Completed: In Life Phase Initiated - Completed: 6/24/96-9/4796 6/24/96 - 6/27/96 All raw data and the final report will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pom de Nemours and Company, Newark, Delaware or in the DuPont Records Management Center, Wilmington, Delaware. -3- Company Sanitized. Does not contain TSCA CBJ Skin Irritation Test with H-21946 in Rabbits SUMMARY, DuPontHLR 784-96 H-21946 was evaluated for acute skin irritation potential in 6 female New Zealand White rabbits. Approximately 0.5 mL of the test substance was applied to the shaved, intact skin of each rabbit and covered with a semi-occlusive dressing for a 4-hour exposure. Approximately 1, 24,48, and 72 hours after removal 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. The adjacent areas of untreated skin were used for comparison. H-21946 produced slight or mild erythema but no edema by 1 hour after test substance removal. By 24 hours, 5 rabbits were cle.ir of all dermal irritation, and mild erythema but no edema was observed in 1 rabbit By 48 hours after the test substance was removed, this rabbit exhibited only slight erythema. Desquamation but no erythema or edema was observed in this .rabbit by 72 hours after test substance removal. No clinical signs of toxicity were observed during this study. Under the conditions of this study, H-21946 was a mild skin irritant ^^S.nlted.B^nrtc.n.alnTSeAea Skin Irritation Test with H-21946 in Rabbits SIGNATURE PAGE DuPont HLR 784-96 Report hv^^y/J 0. ^KPfJft^ ^/TracyA.Fillibcn Toxicology Associate ^/4/? Work by: CfJ/fJn^ QTracyA.FUlibcn Toxicology Associate Reviewed and Approved for Issue\J^X/ Q. ^JL{jJ>U^ 0Tracy A. FUUben Study Director 9 / ^//^fc TF/alw Company Sanitized. Does not contain TSCA CBI -5- Skin Irritation Test with H-21946 in Rabbits________________ DuPoni HLR 784*96 INTRODUCTION The purpose of this study was to evaluate the skin irritation potential of H-21946 when applied to the shaved, intact skin of New Zealand White rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult female HM:(NZW)fBR New Zealand White rabbits were received from Hare Mariana, 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. The last 3 digits of the identification number were written on the inside of each rabbit's ear with a water insoluble marker. The rabbits were offered approximately 125 grams of Purina Certified High Fiber Rabbit Chow #5325 daily during the study. Water was available ad libitum except during the exposure period while the animals were in stocks. Haskell Laboratory has an animal health monitoring program. This program is monitored and administered by the Laboratory Veterinarian. Water samples are periodically analyzed for total bacterial counts and for the presence of colifonns, lead, and other contaminants. Additionally, samples from freshly washed cages and cage racks are periodically analyzed to assure adequate sanitation by the cagewashers. Data from this program are maintained separately from study records. Animal feed is certified by the manufacturer to meet specified nutritional requirements and to be free of a list of specified contaminants. On the basis of these analyses, there is no evidence suggesting that contaminants were present in the feed or water in amounts which may have interfered with the results of this study. Rabbits were quarantined, weighed, and observed for general health for approximately 2 weeks. Animal ro'-ms were maintained on a timer-controlled, 12-hour light/I 2-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20C 1C and relative humidity of 50% 10%. Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study. compwtsattuw-0----^^ ... Skin Irritation Test with H-21946 in Rabbits_________ -B^Protocol-- ___ DuPoni HLR 784-96 On the day prior to treatment, the hair of 6 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 2203 to 2403 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 have access to food or water. Approximately 0.5 mL of H-21946 was applied directly on the test site beneath a 2inch gauze square that was held in place with non-irritating tape. The rubber sheeting was then wrapped around the animal and secured with cups to retard evaporation and to keep the test substance in contact with the skin without undue pressure. Two other test substances were tested concurrently on separate, localized test sites on the backs of these rabbits. In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. Approximately 4 hours after application of the test substance, 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 substance. The skin was gently patted dry, and the animals were returned to their cages. Approximately 1, 24, 48, and 72 hours after removal 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. The rabbits were also observed for clinical signs of toxicity at each dermal evaluation. ISompany Sanitized. Does not contain TSCA CBS .7- Skin Irritation Test with H-21946 in Rabbits RESULTS AND CONCLUSIONS DuPoni HLR 784-96 H-21946 produced slight erythema in 3 rabbits and mild erythema in 3 rabbits by I hour after test substance removal. By 24 hours, 5 rabbits were clear of all dermal irritation; one rabbit exhibited mild erythema. Slighterythema was observed in this rabbit by 48 hours. By 72 hours after test substance removal, this rabbit exhibited desquamation but no erythema. No edema or clinical signs of toxicity were observed during the study. Individual skin irritation scores are presented in Table II. responses is presented in the following table. A summary of skin Summary of Skin Responses to H-21946 Response No Response Slight Mild Erythema Edema Ihr 24 hr 48 hr 72 hr Ihr 24 hr 48 hr 72 hr 0/6 5/6 5/6 6/6 6/6 6/6 6/6 6/6 3/6 0/6 1/6 0/6 0/6 0/6 0/6 0/6 3/6 1/6 0/6 0/6 0/6 0/6 0/6 0/6 Under the conditions of this study, H-21946 was a mild skin irritant. If these test scores are to be used for EEC/OECD classification, according to the guide to the labeling of dangerous substances published in the Official Journal of European Communities (EEC Directive 93/21, Annex VI). H-21946 probably could be classified as "NON-IRRITANT" until farther data is available. Company Sanitized. Does not contain TSCA CB1 8- Skin Irritation Test with H-21946 in Rabbits DuPont HLR 784-96 -TABLEL 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) Value 0 I (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 than 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 Is Intact T= Thickening C = Eschar N= Necrosis G = Fissuring with Bleeding - = No Effect B = Blanching S = Epidermal Scaling D = Desquamation L = R = X = SN = Sloughing Raw Areas Compound Adhered to Skin Superficial Necrosis Draize, J. H., "Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods. Drags 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 TSCACBj 9- Skin Irritation Test with H-21946 in Rabbits DuPontHLR 784-96 TABLEII INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IN RABBITS Rabbit Number 31079 31083 31080 31081 31087 31091 Hours After Test Substance Removal Erythema Edema Ihr 24 hr 48 hr 72 hr Ihr 24 hr 48 hr 72 hr 1 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 2 2 1 OD 0 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 - 10- Company Sanitized. Does not contain TSCA CBI