Document baqVrMrpGp68pax0bx6D5Jg6o

AR226-3038 Study Title Skin Irritation Test with H-2I460 in Rabbits Laboratory Project ID Haskell 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 Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. O. Box 50 Newark, Delaware 19714 Page 1of 10 Company Sanitized. Does not contain TSCA CBS Substance Tested: Synonyms: Physical Form: GENERAL INFORMATION DuPont HLR 83-96 Contaminants: Puritv: 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 Wilmington, Delaware 1/15/96 - 2/26/96 1/16/96- 1/18/96 T Company Sanitized. Does not contain TSCA CBi DuPont HLR 83-96 Skin Irritation Test with H-21460 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 o f 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 ,o 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 rabbits by 48 hours after the test substance was removed. No edema and no clinical signs o f toxicity were observed during the study. Under the conditions of this study, H-21460 was a mild skin irritant. - 3 - Company Sanitized. Does not contain TSC CB! SIGNATURE PAGE DuPont HLR 83-96 Report by: Amy L. Williamson Secretary Work bv> J ( M J jy Tracy A. Filliben Toxicology Associate Reviewed and Approved for I s s u Qt . X 12 J Tracy A. Filliben Study Director TF/alw - 4 - Oompany Sanitized. Does not contain TSCA CBS INTRODUCTION DuPont HLR 83-96 The purpose o f this study was to evaluate the skin irritation potential o f 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 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 o f the identification number were written on the inside o f 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 o f coliforms, 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. Anirm.' feed is certified by the manufacturer to meet specified nutritional requirements and to be free o f a list o f specified contaminants. On the basis o f 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, 12-hour light/12 hour dark - 5 - Company Sanitized. Does not contain TSCA CBI DuPont HLR 83-96 cycle. Environmental conditions o f the rooms were targeted for a temperature of 20C lC and relative humidity of 50% 10%. Excursions outside these ranges were judged to have been o f 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 o f 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 comers 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 I. 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 - 6 - 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 o f 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 1 hour after test substance removal. By 24 hours, 4 rabbits were clear of dermal irritation; 2 rabbits exhibited slight erythema. All 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 o f skin responses is presented in the following table. Summary o f Skin Responses to H-21460 Response No Response Slight Mild Erythema 1 hr 24 hr 48 hr 0/6 4/6 6/6 3/6 2/6 0/6 3/6 0/6 0/6 Edema I hr 24 hr 48 hr 6/6 6/6 6/6 0/6 0/6 0/6 0/6 0/6 0/6 Under the conditions of this study. H-21460 was a mild skin irritant. - 7 - Company Sanitized. Does not contain TSCA CBI If these test scores are abelingofdangeroussu Directive 93/21, Annex furtherdata is available. 1 `t I i j Company Sanitized. Does not contain i SCA CBI 8 I jl DuPont HLR 83-96 SKIN IRRITATION TEST WITH H-2I460 TABLE I DRAIZE1SCALE FOR SCORING PRIMARY SKIN IRRITATION Evaluation o f 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 (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 o f exposure) 0 I (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 = Sloughing R = Raw Areas X = Compound Adhered to Skin SN = Superficial Necrosis Draize, J. H., "Dermal Toxicity." Appraisal o f the Safety o f 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. - 9 - Company Sanitized. Does not contain TSCA CB1 DuPont HLR 83-96 SKIN IRRITATION TEST WITH H -21460 TABLE rr INDIVIDUAL SKIN IRRITATION SCORES .SKIN RESPONSES OBSERVED IN RABBITS Rabbit Number 30562 30646 30650 30621 30654 30655 Erythema Ihr 24 hr 48 hr 10 0 10 0 10 0 2 10 200 2 10 Edema 1 hr 24 hr 48 hr 000 000 000 000 000 000 - 10- Company Sanitized. Does not contain TSCA CBf