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AR226-3042 Study Title Skin Irritation Test with H-21987 in Rabbits Laooratory Project ID Haskell Laboratory Report No. 605-96 Carol Finlay Study Compleied On August 26,1996 Performing Laboratory E. I. du Pont de Ncmours and Company Haskeii Laboratory for Toxicology and Industrial Medicine Elkton Road. P. 0. Box 50 Newark, Delaware 19714 Page 1 of 10 Company Sanitized. Does not contain TSCA CB1 Substance Tested: Synonyms: GENERAL INFORMATION Physical Form: Composition: Known Impurities: Purity: Structure: Tan liquid dispersion Submitter's Notebook No.: CAS Registry No.: Sponsor: Study Initiated - Completed: In Life Phase Initiated - Completed: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company WUmington. Delaware 7/26/96 - 8/26/96 7/30/96 - 8/2/96 SaniUzecL Does noirontain YSCA CBi E SF E Si ne TS iA Tssass By i Shute ng ins, Sk | ie as vy e a e LA . A ao 7 SRE L EA RER Ee ee s he riedT Li Bd e a Pr EnRERTLoh a EE Records ManagementCenter). Sh ERs TL 5 Seated SHE ae ee a a Bhs ian a | : a i dd s Hel ai es aE | a | i: ne i . te a | . a [ vi re [| = a Ii 8 Lei oin i eh Saluo done ana [lf | . aaa L dam L 2 2 E ama m B aE n CompanySantzed. Dossnotcontin TSCA Gai Skin Irritation Test with H-21987 in Rabbits SUMMARY DuPontHLR 605-96 H-21987 was evaluated for acute skin irritation potential in 6 male 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, die 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. Three rabbits exhibited no dermal irritation throughout the study. Two rabbits exhibited slight erythema but no edema only at the 1-hour observation. The remaining rabbit exhibited mild erythema but no edema at 1,24,48, and 72 hours after removal of the test substance. This rabbit also exhibited scaling and sloughing of the skin at 48 and 72 hours. Under the conditions of this study, H-21987 was a mild skin irritant. -4- C'offipany^anTlteea. DoesnolTOnlainTSCA^S Skin Irritation Test with H-21987 in Rabbits SIGNATURE PAGE DuPont HLR 605-96 Work by: ^k\l^ ( /L/LffC^ Car^lFinlay 0 Toxicology Associate Reviewed and Approved for Issue: ^ H^UfL ^kfs,,^,- (^arolFini^ ^ li^l^^ Study Director Oral, Ocular, and Dermal Toxicology CF/lrnp -5Company Sanitized. Does not contain TSCA C Skin lirilation Test with H-21987 in Rabbits INTRODUCTION DuPont HLR 605-96 The purpose of this study was to evaluate the skin irritation potential of H-21987 when applied to the shaved, intact skin of New Zealand White rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult male HM:(NZW)fBR New Zealand White rabbits were received from Hare Mariand, 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 pro^.ain. This program is monitored and administered by the Laboratory Veterinarian. Water samples are periodically analyzed for total bacterial counts and for the presence ofcoliforms. 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 io 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 rooms were maintained on a timer-controlled, 12hour light/12-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. 6Company Sanitized. I Skin Irrilation Test with H-21987 in Rabbits DuPont HLR 605-96 B. Protocol On the day prior to treatment, the hair of 6 male 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 2298 !o 2971 grains 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-21987 was applied directly on the test site beneath a 2inch 4-ply 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. In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. One other test substance was tested concurrently on a separate, localized test site on these rabbits. 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. ^Panyg^, {lDoe5not^r^ Skin Irritation Test with H-219K7 in Rabbits RESULTS AND CONCLUSIONS Dufont HLR <<Q5-96 Three rabbits exhibited no dermal irritation throughout the study. Two rabbits exhibited slight erythema but no edema only at the '-hour observation The remaining rabbit exhibited mild erythema but no edema at 1,24.48, and 72 hours after removal of the test substance. This rabbit also exhibited scaling and sloughing of me skin at 48 and 72 hours. Individual skin irritation scores are presented in Table B. A summary of skin responses is presented in the following table. Summary of Skin Responses to H-21987 Response No Response Slight Mild Erythema Edema Ihr 24 hr 48 hr 72 hr Ihr 24 hr 48 hr 72 hr 3/6 5/6 5/6 5/6 6/6 6/6 6/6 6/6 2/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 1/6 1/6 1/6 1/6 0/6 0/6 0/6 0/6 Under the conditions of this study, H-21987 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-21987 probably could be classified as "NON-IRRITANT" until further data is available. -8- Company Sanitized. Does not contain TSCA CBJ Skin In-itati.TO Te ;1 with H-21987 in Rabbits DuPontHLR6QS-06 IAPLE.[ DRAEZE' 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 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Edema formation: No edema Very slight edema (barely perceptible) Slight edema (edge: 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 I = Intact N = Necrosis T = Thickening G = Fissuring with C = Eschar Bleeding - = No Effect S = Epidermal B = Blanching Scaling L = R a X = SN = Sloughing Raw Areas Compound Adhered to Skin 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. 9Company Sanitized. Does not contain TSCAC^ Skin Irritation Test with H-2I9K7 in Rabbits DuPont HLR 605-96 TABLE 11 INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IN RABBITS Rabbit Number 31197 31180 31190 31191 31192 31193 Hours After Test Substance Removal Erythema Edema Other Dermal Effects Ihr 24 hr 48 hr 72 hr Ihr 24 hr 48 hr 72 hr Ihr 24 hr 48 hr 72 hr 10 0 0 0 00 0 - - - - 2 2 2 2 0 0 0 0 - 0 0 0 0 0 0 0 0 - - S.L S.L - - - 0 0 0 0 0 0 0 0 - - - - 0 0 0 0 0 0 0 0 - - - - 1 0 0 0 0 0 0 0 - - - - Symbols are defined on page 9. -10- Gompany Sanitized. Does not contain TSCA CBS