Document 65b86JekgLDy7a6B2mMR1eNo6

AR226-3038 Study Title Skin Irritation Test with H-21460 in Rabbits Laboratory Project ID Haskeil Laboratory Report No. 83-96 Author Tracy A. Filliben Study Completed On February 26,1996 Performing Laboratory E. I. du Pont de Nemours and Company Haskeil Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark. Delaware 19714 Page I of 10 Company Sanitized. Does not contain TSCA CBI Substance Tested: Svnonvmi;: Physical Form: Composition: Contaminants: Purity: Submitter's Notebook No.: CAS Registry No.: Sponsor: Study Initiated - Completed: In Life Phase Initiated - Completed: DuPont HLR 83-96 GENERAL INFORMATION c c Yellow liquid Ci c Ci 1:1 0 DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington, Delaware 1/15/96 - 2/26/96 1/16/96-1/18/96 ITS DuPont HLR 83-96 Skin Irritation Test with H-2146Q in Rabbits SUMMARY H-21460 was evaluated for acute skin irritation potential in 2 male and 4 female New Zealand White rabbits. Approximately 0.5 mL of the test substance was applied directly to the shaved, intact skin of each rabbit and covered with a semi-occlusive dressing for a 4-hour exposure. Approximately 1, 24. and 48 hours after application of the test substance, the test sites were evaluated for erythema, edema, and other evidence of dermal effects and were scored according 10 the Draize Scale. The adjacent areas of untreated skin were used for comparison. H-21460 produced slight or mild erythema by 1 hour after test substance removal. By 24 hours, no or slight erythema was observed. All dermal irritation had cleared in the treated i-abbits by 48 hours after the test substance was removed. No edema and no clinical signs of toxicity were observed during the study. Under the conditions of this study, H-21460 was a mild skin irritant. - -^ - Company Sanitized. Does not eonlain T5CA CBI SIGNATURE PAGE DuPunt HLR 83-96 Report by: t^L* QJ LvLj^-c----y^ (^\ AA--m--y..TL. IWI7i"lHlia:-m__s_o_n_ eS^ e_ cre. - tary Work bv:^J^U^^. ^-^JUUH,^ JTracy A. FiSliben Toxicology Associate /^1>----/ /"~^--/ Reviewed and Approved tor Issue^VA^^^ / ^^^t/^-A, i/ Tracy A. Filliben Study Director 3- /3 ^/^^ Company Sanitized. Does not contain TSCA CB8 -4 INTRODUCTION DuPont HLR 83-96 The purpose of this study was to evaluate the skin irritation potential of H-21460 when applied to the shaved, intact skin of New Zealand White rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult male and female HM:(NZW)fBR 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. 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. Anim;.' 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 rffayhave 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 u timer-controlled, 12-hour light/12-hour dark 5 - - Company Sanitized. Does not contain TSCA CBI DuPont HLR 83-96 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. B. Protocol On the day prior to treatment, the hair of 2 male and 4 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 2833 to 3263 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-21460 was applied directly on the skin beneath a 2-inch 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. Three other substances were tested concurrently on separate, localized test sites on the backs of 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 Ivory soap and warm water to remove excess test substance. The skin was gently patted dry, and the animals were returned to their cages. Approximately 1, 24, and 48 hours after removal of the test substance, the test sites were evaluated for erythema, edema, and other evidence of dermal effects and were scored . (,. Company Sanitized. Does not contain TSCA CBI DuPont HLR 83-96 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, Newark, Delaware or in the DuPont Records Management Center, Wilmington, Delaware. RESULTS AND CONCLUSIONS H-21460 produced slight erythema in 3 rabbits and mild erythema in 3 rabbits by I hour after test substance removal. By 24 hours, 4 rabbits were clear of dermal irritation; 2 rabbits exhibited slight erythema. AH dermal irritation had cleared in the treated rabbits by 48 hours after the test substance was removed. No edema and no clinical signs of toxicity were observed during the study. Individual skin irritation scores are presented in Table II. A summary of skin responses is presented in the fcilowing table. Summary of Skin Responses to H-21460 Response No Response Slight Mild Erythema Ihr 24 hr 48 hr 0/6 4/6 6/6 3/6 2/6 0/6 3/6 0/6 0/6 Edema Ihr 24 hr 6/6 6/6 0/6 0/6 0/6 0/6 Under the conditions of this study. H-21460 was a mild skin in-itant. 48 hr 6/6 0/6 0/6 7- Company Sanitized. Does not contain TSCA CBI If these test acmes un to he used for EEC/OECDclttdfieiition. according to the (Ui^ tothe :^ ^ , fabelinf of du3eroussubtncespublishedm the 0^^^ Directive 93^1. Aimsx VI). H-21460 probAly could bs disified u "NO? ftulherdttaisavntebte. ' ".."^--r'l^-:'; ^% ::.';:,?^.iN'g.t '.%^il||,lij ' .... 's. ^s: V.^ .-^'i^ ..yQ ; i ^'^ ^^ -:: ^^^tfSISIBS B Company Sanitized. Does not contain TSCA CBI 'o " DuPont HLR 83-96 SKIN IRRITATION TEST WITH H-21460 TABLE I DRAIZE' SCALE FOR SCORING PRIMARY SKIN IRRITATION Evaluation of Skin Reactions Value 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) 0 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 r using) Moderate edema (raised approximately 1.0 mm) Severe edema (raised more than 1.0 mm extending beyond the area of exposure) 0 (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 = Eschsir Bleeding - = No Effect S = Epidermal B = Blanching Scaling L = R = X = SN = Sloughing Raw Areas Compound Adhered to Skin Sugerficial Necrosis Draize, J. H., "Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods. Drugs and Cosmetics. The Editorial Committee oflhe Association of Food and Drug Officials of the Uniled States, Austin. Texas. 1959, pp. 46-59. -9 Company Sanitized. Does not contain TSCA CBI DuPont HLR 83-96 SKIN IRRITATION TEST WITH H-21460 TABLEP INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IN RABBITS Rabbit Number 30562 30646 30650 30621 30654 30655 Erythema Ihr 24 hr 48 hr 1 0 0 1 0 0 1 0 0 2 1 0 2 0 0 2 1 0 Edema Ihr 24 hr 48 hr 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 10- Sanitized. Do-as not contain TSCA CB!