Document 8X5pMy2y8dJZ2jNRmp56Y8NK

AR226-3002 Study Title Skin Irritation Test with H-20431 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 51-94 Author Carol Finlay Study Completed On March 15, 1994 Performing Laboratory Haskell E. I. dn Pont de Nenours and Company Laboratory for Toxicology and Industrial Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Medicine Medical Research No. Pae 1 of 9 Company Sanitized. Does not contain TSCA CBI Substance Tested; Synonyms/Codes: GENERAL INFORMATION DuPont HLH 51-S Physical Form! P-rity: Composiiion; Contaminants; CAS Registry No.; Tan milky liquid Approximately 99.5% H-20431 2 - - ' -mpany Samfeed. Does not eor'tam TSCA CBt DuPont BLR 51-94 ! GENERAL INFORMATION (CONT.) Sponsor; Study Initiated - Completed; In Life Phase Initiated - Completed; Specialty Chenlcalfl P. I..dy Font de Neaours and Conpany Viloington, Delaware 1/5/94 - 3/15/94 1/11/94 - 1/14/94 t - 3 ~ company Sanitized. Does not contain TSCA CB1 DuPont HLR 51-94 Skin Irritation Test vith B-20431 in Rabbif SUMMARY H-20431 vas evaluated for acute skin irritation potential in 1 male and 5 female Nev Zealand White rabbits. A 0.5 mL aliquot of test substance was applied dir'ictly to the shaved, intact skin of each rabbit and covered with a seml-occlusive dressing. Approximately 24, 48, and 72 hours after application of the test substance, the test sites were evaluated fcr 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-20431 produced severe erythema and moderate edema in 5 rabbits and moderate erythema and mild edema in 1 rabbit by 24 hours after Superficial necrosis was observed in 5 rabbits by 48 hours and by 72 hours. One rabbit had a raw area in the test site which (eschar) by 48 hours. Eschar was also observed in this rabbit application. in all rabbits scabbed over at 72 hours. Sloughing of the skin was also observed during the study. Under the conditions of this study, H-20431 was a severe skin irritant. Work by: jt'^ ^ ^ /) A-C ^ , Carol/Finlay^ Toxicology Associate Approved by; ( Y J o h n ^jp*^--.^ L^ . JCt^vg-^ W, Sarver lexicologist Reviewed and Approved for Issue: t /?/t^c,^V^ Ca^ol Finid^ Study Director JS '^'^ CF/alw Company Sanitized. Does not contain TSCA CB1 INTRODUCTION DuPont HLR 51-94 The purpose of this study was to evaluate the skin irritation potential of H-20431 when applied to the shaved, intact skin of Nev Zealand White rabbits. MATERIALS AND METHODS A. Aniaal Husbandry Young adult male and female Nev Zealand White rabbits were received froR Hare Harland, Hevitt, 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 the rabbit's ear vith a vater insoluble marker. The rabbits were offered approximately 125 grams of Purlna Certified High Fiber Rabbit Chow9 15325 daily during the study. Water was available ad libitum except as noted under Protocol. Haskell Laboratory has a monitoring program which consists of periodic food and water analysis for contaminants. This program is monitored and administered by the Laboratory Veterinarian; data from this program are maintained separately from study records. 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 timercontrolled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20C 2C and relative humidity of 50X 10X. 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 1 male and 5 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 2487 to 2722 grams on the day of treatment. cmpany Sanitized. Does no! contain TSCA CBI DuPont HLR 51-94 Bach rabbit was placed into a stock which had been fitted with a piece of rubber sheeting, approxiaately 8" x 18". The rabblf regained in the stocks throughout the exposure period and during that time did not have access to food or water. A 0.5 aL aliquot of H-20431 vas applied directly on the test site beneath a 2-inch gauze square that waa held in place with non-irritating tape. The rubber sheeting vas then wrapped around the aniul 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 test substances were tested concurrently on separate, localized test sites on the backs of these rabbits. Approximately 24 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 warn water and Ivory* soap to remove excess test substance. The skin was gently patted dry, and the animals were returned to their cages. Approximately 24, 48, and 72 hours after application of the test substance, the test sites were evidence of dermal effects and (Table I). The adjacent areas comparison. evaluated for erythema, edema, and other were scored according to the Draize scale of the untreated skin were used for 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 Font de Nemours and Company, Newark, Delaware or in the DuPont Records Management Center, Vilmington, Delaware. company Sanitized. Does not contain TSCA CB1 RESULTS AND CONCLUSIONS DuPont BUt 51-94 Although the test substance adhered to the skin of 4 rabbits during the study, the test sites could be evaluated. H-20431 produced severe erythema and aoderate edeaa in 5 rabbits and moderate erytheBa and lld edeu in 1 rabbit by 24 hours after application. Superficial necrosis was observed in 5 rabbits by 48 hours and in all rabbits by 72 hours. Tvo rabbits exhibited severe erythema at 48 hours. No to moderate edeia was observed at 48 or 72 hours. One rabbit had a raw area in the test site which scabbed over (eschar) by 48 hours. Eschar was also observed in this rabbit at 72 hours. Sloughing of the skin was also observed during the study. Individual skin irritation scores are presented in Table II. presented in the following table. A summary of skin responses is Summary of Skin Responses to H-20431 Response No Response Slight Mild Moderate Severe 24 hr 0/6 0/6 0/6 1/6 5/6 Erythelma 48 hr 3/6 0/6 0/6 1/6 2/6 72 hr 6/6 0/6 0/6 0/6 0/6 - 24 hr 0/6 0/6 1/6 5/6 0/6 Edema 48 hr 1/6 1/6 1/6 3/6 0/6 72 hr 2/6 2/6 1/6 1/6 0/6 Response Other Dermal Effects 24 hr 48 hr 72 hr Superficial Necrosis 0/6 5/6 6/6 Sloughing 0/6 0/6 2/6 Eschar 0/6 1/6 1/6 Raw Areas 1/6 0/6 0/6 Under the conditions of this study, H-20431 was a severe 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 of European Communities (EEC Directive 91/325, Annex VI), H-20A31 probably should be classified as an "IRRITANT" until further data are available. company Sanitized. Does not contain TSCA CBI DuPont BLR 51-94 SKIN IRRITATION TEST VITB B-20431 TABLE I DRAIZEl SCALE FOR SCORING PRIMARY SKIN IRRITATION Evaluation of Skin Reactions Erythema and eschar format Ion: No erythema Very slight erythema (barely perceptible) Well-defined erythema Moderate to severe erythema Severe erythema (beet redness) to slight eschar formation (injuries in deptn) Value 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Edema formation: No edema Very slight edema (barely perceptible) Slight edema (edges of area veil defined by definite raising) Moderate edema (raised approximat^l; 1.0 mm) Severe edema (raised more than 1.0 mm extending beyond the area of exposure) 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other A = Abraded I = Intact T = Thickening C = Eschar - - No Effect B c Blanching dermal effects are: F = Fissuring N = Necrosis G a Fissuring with Bleeding S - Epidermal Scaling L Sloughing R Raw Areas X Compound Adhered to Skin SN Superficial Necrosis 1 Draize, J. H., "Dermal Toxiclty." Appraisal of the Safety of 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. Company Sanfflzed. Does nol certain TSCA CB1 DuPont HLR 51-94 SKIN IRRITATION TEST WITH H-20431 TABLE II INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS Rabbit Number 28770 28756 28773 28776 28777 28778 Erythem a 24 hr 48 hr 72 hr 4 4 0 'x o 0 4 4 0 4X" 0 0 4X- 0 0 3X 24 hr Edema 48 hr 72 hr 3 3 1 3 0 0 3 3 3 3 3 2 . 3 2 0 Other Denial Effects 24 hr 48 hr 72 hr SN" SN*>, L SN*> SN" R 0 SNb, Ce SNb SNb SNb SN>, L SNc SN> " Although the test substance adhered to the skin, the test site could be evaluated. b Approximately 4 en in diameter. c Approximately 1 cm in diameter. l) - 9 - Company Sanifizea. Does not contain TSCA CB1