Document YGVQMDNvwa9MpK64LBMxkLrE0

AR226-3042 Study.Titfe Skin Irritation Test with H-2I987 in Rabbits Laooratorv Project ID Haskell Laboratory Report No. 605-96 Author Carol Finlay Study Completed On August 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 Hage I of 10 Company Sanitized. Does not contain TSCA CBI Skin Irritation Test with H-21987 in Rabbits GENERAL INFORMATION Substance Tested: Svnonvms: DuPont HLR 605-96 Physical Form: C om position: Known Impurities: Purity: Structure: Submitter's Notebook No.: CAS Registry N o.: Sponsor: Study Initiated - Completed: In Life Phase Initiated - Completed: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington, Delaware 7/26/96 - 8/26/96 7/30/96 - 8/2/96 'Company Sanitized, Does not contain TSG CBJ Company Sanitized. Does not contain TSCACBI Skin Irritation Test with H-21987 in Rabbits SUMMARY DuPont HLR 605-96 H-21987 was evaluated for acute skin irritation potential in 6 male New Zealand White rabbits. Approximately 0.5 mL o f the test substance was applied to dm shaved, intact skin o f 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 o f this study, H-21987 was a mild skin irritant. -4- Company Sanitized. Does notcontain TSCABI Skin hritation Test with H-21987 in Rabbits SIGNATURE PAGE DuPont HLR 605-96 Work by: (..L/loL jflKi Carm Finlay Q Toxicology Associate Reviewed and Approved for Issue: i/JUL flU/U Carol Finly Study Director Oral, Ocular, and Dermal Toxicology CF/lmp -5- otnpany Sanitized. Does not contain TSCA CBS Skin Irritation Test with H-21987 in Rabbits INTRODUCTION DuPont HLR 605-96 The purpose of this sfudy was to evaluate the skin irritation potential o f H-21987 when applied to the shaved, intact skin o f New Zealand White rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult male HM:(NZW)fBR New Zealand White rabbits were received from Hare Marland, Hewitt, New Jersey. The rabbits were housed singly in suspended, gtainless 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 M except during the exposure period while the animals were in stocks. Haskell Laboratory has an animal health monitoring prog.au. This program is monitored and administered by the Laboratory Veterinarian. W ater samples are period;cally 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. Animal 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 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 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. -6- Company Sanitized. Does not contain TSCA CBI Skin Irritation Test with H-2I987 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 o f the The body weights o f the rabbits ranged from 2298 to 2971 grains on the day o f 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-21987 was applied uirectly 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 mH. pressure. In the absence o f visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. One o tte r test gnhc*TM 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 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 suhstqppf 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. -7- ^mpany San/ifee* Does not contain' Skin Irritation Tesi with H-2I987 in Rabbits DuHmt HLR M)5-96 i RESULTS AND CONCIJISIONS 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 hows after removal o f the test substance. This rabbit also exhibited scaling and sloughing of die skin at 48 and 72 hours. Individual skin irritation scores are presented in Table D. A summary o f skin responses is presented in the following table. Summary o f Skin Responses to H-21987 Response No Response Slight Mild Erythema Edema 1 hr 24 hr 48 hr 72 hr 1 hr 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 o f 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 o f dangerous substances published in the Official Journal o f 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 GBJ Ski Irritati.in Te ;! with H -21987 in Rabbits DuPont HLR 605-96 TABLE * DRAKE ' SCALE 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 (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 o f 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 = 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 o f Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. -9 - Company Sanitized. Does not contain TSCAC Skin Irritation Test with H-21987 in Rabbits DuPont HLR 605-96 TABLE II INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IN RABBITS Rabbit Number 31197 31180 31190 31191 31192 31193 Eryfhema 1 hr J 24 hr 48 hr 10 0 222 000 000 0 00 10 0 Hours After Test Substance Removal Edema Other Dermal Effects 72 hr Ih r 24 hr 48 hr 72 hr I h r 24 hr 48 hr 72 hr 00000 - 20000 00000 - - SX sx - 0000 0 - . 00000 - * _ 2 J0 0 0 0 - - -- Symbols are defined on page 9. -10- Company Sanitized. Does not contain TSCA CB!