Document RxDj8j9q5y7xZemXRrbBZyQV

AR226-3050 Study Title Skin Irritation Test with K-21946 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 784-96 Authpr Tracy A. FUIiben 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. O. Box 50 Newark, Delaware 19714 Page I of 10 Company Sanitized. Does not contain TSCA CBI Skin Irritation Test with H-21946 in Rabbits Substance Tested: Svnonvms: r.ENERAIrlNFORMATIQN DuPont HLR 784-96 Physical Form: Composition: Light beige, opaque liquid Contaminants: Punty: Submitter's Notebook No.: CAS Registry No.: Sponsor: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington, Delaware 2- Company SanFtFzed. Does no? contain TSCA CPS Skin Irritation Test with H-21946 in Rabbits General Information (Continued) DuPont HLR 784-96 Study Initiated - Completed: In Life Phase Initiated - Completed: 6/24/96 - 9/4/96 6/24/96 - 6/27/96 All raw data and the final tepori 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. -3- Company Sanitized. Does no! contain TSCA CBi Skin Irritation Test with H-21946 in Rabbits SUMMARY DuPont HLR 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 o f each rabbit and covered with a semi-occlusive dressing for a 4-hour exposure. Approximately I, 24,48, and 72 hours after removal o f 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 o r mild erythema but no edema by I 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 4 `W n y S e iz e d . Does no. copain TSCA e Skin Irritation Test with H-21946 in Rabbits SIGNATURE PAGE DuPbnt HLR 784-96 R e p o r t $ . 0 Tracy A. FUliben Toxicology Associate Work by: u Tracy A. FUliben Toxicology Associate SFMh^Reviewed and Approved for Issues u u m Q Tracy A. FUliben Study Director 9,4rii TF/alw Company Sanitized. Does not contain TSCA CBI m- Skin Irritation Test with H-21946 in Rabbits DuPont HLR 784-96 INTRODUCTION The purpose o f 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 Mariand, Hewitt, New Jersey. The rabbits were housed singly in suspended, ctainiftss 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 of each rabbit's ear with a water insoluble marker. The rabbits were offered approximately 125 grams o f Purina Certified High Fiber Rabbit Chow #5325 daily during the study. W ater was available gd 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. W ater samples are periodically analyzed for total bacterial counts and for the presence of coliforms, lead, and other contaminants. Additionally, samples from fleshly 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 flee o f 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/12-hour dark cycle. Environmental conditions o f 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. . -C--o-m--p--a-n--y-s--a-n- ffized uDooeess nolrnnta^Ts ^ Skin Irritation Test with H-21946 in Rabbits DuPont HLR 784-96 B. Protocol------------------------------------------------------------------------------------------------ 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 treatm ent. 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 o r 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 clips to retard evaporation and to k*rp 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 o f 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 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 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 o f the test substance, the test sites were evaluated for erythema, edema, and other evidence o f dermal effects and were scored according to the Draize scale (Table I). The adjacent areas o f the untreated skin were used for comparison. The rabbits were also observed for clinical signs o f toxicity at each dermal evaluation. Company Sanitized. Does not contain TSCA CBS Skin Irritation Test with H-21946 in Rabbits RESULTS AND CONCLUSIONS DuPont HLR 784-96 H-21946 produced slight erythema in 3 rabbits and mild erythema in 3 rabbits by 1 hour after test substance removal. By 24 hours, 5 rabbits were clear o f all dermal irritation; one rabbit exhibited mild erythema. Slight erythema 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. A summary of skin responses is presented in the following table. Summary of Skin Responses to H-21946 Response No Response Slight Mild Eryt iema Edema 1 hr 24 hr 48 hr 72 hr I hr 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 o f European Communities (EEC Directive 93/21, Annex VI). H-21946 probably could be classified as "NON-IRRITANT" until further data is available. Company Sanitized. Does not contain TSCA CBI Skin Irritation Test with H-21946 in Rabbits DuPont HLR 784-96 ________________________ TABLE!________________________ nPA fT F1s rA lF . 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) ValH6 , I (Slight) 2 (Mild) 3(M oderate) 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 (M oderate) 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 D = Desquamation L = Sloughing R = Raw Areas X = Compound Adhered to Skin SN = Superficial Necrosis ' Draize, J. H., "Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods. Drug s and Cosmetics. The Editorial Committee of the Association o f Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. Company Sanitized. Does not contain TSCACBi Skin Irritation Test with H-21946 in Rabbits DuPont HLR 784-96 ----------------------- TABLE 11----------------------INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IN RABBITS Rabbit Number 31079 31083 31080 31081 31087 31091 Hours After Test Substance Removal Erythema Edema 1 hr 24 hr 48 hr 72 hr Ih r 24 hr 48 hr 72 hr 10 0 0 0 0 0 0 20000000 20000000 2 2 1 OD 0 0 0 0 10 0 0 0 0 0 0 10 0 0 0 0 0 0 - toCompany Sanitized. Does not contain TSCA CBI