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AR226-3044 Study Title Skin Irritation Test with H-21951 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 782-96 Author Tracy A. Filliben Study Completed On August 30, 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 Pupe I ol 10 Company Sanitized. Does not contain TSCA CBI Substance Tested: Synonyms: GENERAL INFORMATION Physical Form: Composition: Opaque tan to white liquid Contaminants: Purity: Submitter's Notebook No.: CAS Registry No,: Sponsor: Sn.Hy Initiated - Completed: In Life Phase Initiated - Completed: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington, Delaware 6/21/96-8/30/96 6/24/96 - 6/27/96 2. Company Sanitized. Does not contain TSCA CB8 CompanjpSanitized. Does not contain TSCA CBH Skin Irritation Test with H-2I9SI in Rabbits SUMMARY DuPont HLR 782-96 H-21951 was evaluated lor acute skin irritation potential in 6 female New Zealand White rabbits. Approximately 0.5 mL of the lest 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 -7 |9 5 l produced slight or mild erythema by 1 and 24 hours after test substance removal. By~48 hours, no or slight erythema was observed. All rabbits were clear of erythema by 72 hours after the test substance was removed. In addition, 1 rabbit exhibited desquamation at 48 hours, and 4 rabbits exhibited desquamation at 72 hours. No edema or clinical signs o f toxicity were observed during the study. Under the conditions of this study, H-219 5 1 was a mild skin irritant. -4 - Company Sanitized. Does not contain TSCA CBf Skin Irritation Test with H-2I95I in Rahhits SIGNATURE PAGE DuPont HLR 782-96 Report b y : \ 0racy A. Filliben Toxicology Associate Work by: Q . '3 u M J * C 4 ^ U TraaccyyA, . Filliben Toxicology Associate Reviewed and Approved for Issue: TF/alw ! SJoic/^ ti3o, Tracy A. Filliben Study Director -5- Company Sanitized. Does not contain TSCA CBI INTRODUCTION The purpose of this study was to evaluate the skin irritation potential of H-21951 when applied to the shaved, intact skin o f New Zealand White rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult 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 rabbits 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 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. 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 rooms were maintained on a timer-controlled, 12-hour 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. ' I - 6 - Company Sanitized. Does not contain TSCA CB Skin Imiuiion Test with H-2I95I in Rabbity DuPont HI.R 7K2-96 B. Protocol On the day prior to treatment, the hair of 6 female New Zealand White rabhitswas closely shaved to expose the skin from the scapular to the lumbar reg.on ol 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 l o o d o r water. Approximately 0.5 mL of H-21951 was applied directly on the test site beneath a 2inch gauze square that was held in place with non-imtating 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. Two other test substances were tested concurrently on separate, localized test sites on the back 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 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 skm was gently patted dry, and the animals were returned to their cages. Approximately I, 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. - 7- not contain TSCA CBS Company Sanitized. Does Skin Irritation Tost with H-21951 in Rabbits RESULTS AND CONCLUSIONS DuPont HLR 782-96 H-^ 1951 produced slight erythema in 3 rabbits and mild erythema in 3 rabbits by I and 24 hours after test substance removal. By 48 hours, 3 rabbits were clear of all erythema, and 3 rabbits exhibited slight erythema. All rabbits were clear of erythema by 7 ? hours after the test substance was removed. In addition I rabbit exhibited desquamation at 48 hours, and 4 rabbits exhibited desquamation at 72 hours. 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-21951 Response No Response Slight Mild Erythema 1 hr 24 hr 48 hr 72 hr 0/6 0/6 3/6 6/6 3/6 3/6 3/6 0/6 3/6 3/6 0/6 0/6 Ede ma 1 hr 24 hr 48 hr 7? hr 6/6 6/6 6/6 5/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 1 0/6 Under the conditions of this study, H-21951 was a mild skin irritant. 1Cthese test scores are to be used for E6C/OECD classificalion, according to the guide to the labeling o f dangerous substances published in the Official Journal o f European C o m m u n e s (EEC Ditecdve 93/21, Annex VI). H-21951 probably could be classified as `NON-IRRITANT" until further data is available. - 8 not contain TSCACBl Company Sanitized. Des TABLES PRAZE1SCALEJOR S C O M IQ M M A R Y ^S KIN IRRITATION Evaluation f Skin Reactions Erythema and eschar formation: No erythema Very slight erythema (barely perceptible) Well-defined erythema MSeovdeereraetreyttohesmevaer(ebeeertytrhedemneass) to slight eschar formation (injuries in depth) Value g 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) . in . Moderate edema (raised approximately 1.0 mm) Severe edema (raised more than 1.0 mm extending bevond the area of exposure) 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other dermal effects are. A = Abraded F = Fissunng I = Intact T = Thickening C = Eschar - = No Effect B = Blanching N = Necrosis G = Fissuring with Bleeding S = Epidermal Scaling D = Desquamation L = Sloughing R = Raw Areas X = Compound Adhered to Skin SN = Superficial Necrosis of the United States, Austin, Texas, 1959, pp. 46 . I I -9- Company Sanitized. Does not contain TSCA Skin Irritaiion Test with H-2I9SI in Rahhils DuPont HLR 7X2-96 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 1 hr 24 hr 48 hr 72 hr 1 1 0 OD 0 0 0 0 2 2 1 OD 0 0 0 0 2 l 0 OD 0 0 0 0 1 10 0 0 0 0 0 2 2 10 0 0 0 0 1 z. ID OD 0 0 0 0 - 10- Gompany Sanitized. Does not contain TSCA CBl