Document VJ5ORkww9X58wKLMa9kpVJ1qN

AR226-3001 Performing Laboratory Haskell E. I. du Font de Necours and Company and Industrial Laboratory for Toxicology Box 50 Elkton Road, P. 0. Newark, Delaware 19714 Medicine ^ ^ , noes- ,5^^ ,sc^1 Page 1 of 8 Study Initiated - Completed; In Life Phase Initiated - Completed: 12/6/93 - 2/25/94 12/7/93 - 12/10/93 2 - DuFont BUt 4-94 Skin Irritation Teat with H-20349 In Rabbif SUMMARY H-20349 vas evaluated for acute skin irritation potential in 6 --Ie rabbits. The test substance produced slight erytheu in 2 rabbits by 24 hours after application that was still present at 48 hours. By 72 hours no erythema vas observed. Four rabbits exhibited no erytheu during the study. No edeaa vas observed in any of the rabbits during this study- Under the conditions of this study, H-20349 vas a slight skin Irritant. Work by: ^f.M^------. M. Scott Karr Toxicology Technician Reviewed and Approved for Issue: ~7\John C~\ f, <--^^<->^- C/ Lj. <OflJ^j-e-^ V. Sarver Study Director S /af/'s Acknovledgeaent: Bryan Crossley also participated in the conduct of this study. JVS/alv Company Sanitized. Does not contain TSCA CBi 3 - INTRODUCTION DuPont HUL 4-94 The purpose of this study v&s to evaluate the skin Irritation potential of H-20349 when applied to the shaved, intact skin of New Zealand White rabbits. This study was conducted according to the applicable EPA Good Laboratory Practice Standards. MATERIALS AND METHODS A. Animal Husbandry Young adult male New Zealand White rabbits were received from Hare Mar land, 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 vere written on the inside of the rabbit's ear with a vater insoluble Barker. The rabbits were offered approximately 125 grass of Purina Certified K High Fiber Rabbit Chow* #5325 daily during the study. Water was available ad libitua. Haskell Laboratory has a Bonitoring program which consists of periodic food and water analysis for contaminants. This program is nonitored and adainistered by the Laboratory Veterinarian; data froa this program are oaintalned separately froa study records. On the basis of these analyses," there is ho evidence suggesting that contaninants were present in the feed or water in anounts which may have interfered with the results of this study. Rabbits were quarantined, weighed, and observed for general health foi approximately 2 weeks. Animal rooas were maintained on a timercontrolled, 12-hour llght/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20C 2C and relative humidity of 50Z * 102. Excursions outside these ranges were judged to have been of insufficient eagnitude and/or duration to have adversely affected the validity of the study. B. Protocol On the day prior to treatment, the hair of 6 male New Zealand White rabbits was closely shaved to expose the skin fron the scapular to the lumbar region of the back. The body weights of the rabbits ranged froB 1916 to 2346 grass on the day of treatment. Company Sanitized. Does not contain TSCA CBt DuPoot BLR 4-94 Bach rabbit vau placed into a stock which had ban ittd with a piece of rubber sheeting, approximately 8" x 18". The rabbi ta re--ined in the stocks throughout the exposure period and during that tiBC did not have access to food or water. Approximately 0.5 L aliquot of H-20349, heated to 50"C was applied directly on the test site beneath a 2-inch gauze square that was held in place with non-irritating tape. The rubber sheeting was then wrapped around the aniaal 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 vas assumed to be stable under the conditions of adainistration. Two other substances were tested concurrently on separate localized test sites on 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 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 24, 48, and 72 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 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 of Baskell Laboratory for Toxicology and Industrial Medicine, E. I. du Font de Memours and Company, Newark, Delaware or in the DuPont Records Management Center, Vilmlngton, Delavare. RESULTS AND CONCLUSIONS H-20349 produced slight erythema with no edema in 2 rabbits and no dermr erythema or edema in 4 rabbits by 24 and 48 hours following application. By 72 hours, no dermal irritation was observed in the treated rabbits. Individual skin irritation scores are presented in Table II. A summary of skin responses is presented in the folloving table. Company Sanitized. Does not contain TSC. ,,; 5 - Under the conditions of this study, H-20349 was a slight skin irritant. If these test scores are to be used offordaEnEgCer/OoEuCsDscublasstasnicfeicsatpiuobnl,ished in according to the guide to the labeling Co--unities (EEC Directive 91/325, Annex VthIe), OHf-f2i0c3i4a9l Jporoubrnaballyocf oEuuldropbeeanclassified as a "NOH-IRRITAHT" until further data are available. Company Sanitized. Doss not contain TSCA Co; 6 - .^,..-.,. ... . ....i^-.^l DuToet BLR4-94 SKIN IRRITATION TEST 9TH! H-20349 TABLB I DRAIZEl SCALE FOR SCORING PRItUK? 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) Value 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Edema fornation: No edema Very slight edema (barely perceptible) Slight edema (edges of area veil defined by definite raising) Moderate edema (raised approximately 1.0 nun) Severe edema (raised more than 1.0 HUB extending beyond the area of exposure) 0 (Slight) 2 (Mild) 3 (Moderate) A (Severe) Abbreviations of other A Abraded I - Intact T - Thickening C * Eschar - - No Effect B Blanching dermal effects are: F - Fissuring N B Necrosis G - Fissuring with Bleeding S Epidermal Scaling L Sloughing R Raw Areas X Compound Adhered to Skin SN Superficial NecLosis Draize, j. H., "Derssal Toxicity." Appraisal of the Safety of Cheeicals in Poods, Drugs and Cosmetics. The Editorial Committee or the Association of Food and Drug Officials of the United States, Austin, Texas, 1959. pp. 46-59. eampaRy ?d- ^ ^co^iac^ - 7 - SKIN :[BRITATION TEST WITH E- 20349 I[ABLE II INDIW[DUAL SKIH IBBrr ATION ! ICORES SKIN R ESPONSES OBSERVtED IN RJIBBITS Rabbit Number 28733 28734 28735 28736 28738 28740 E rytheni 24 Jhr 48 hr 72 hr 0 0 0 1 1 0 0 0 0 1 I 0 0 0 0 0 0 0 24 hr 0 Edna w nr 0 v/* mi.-. 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Company Sanitized. Does not contain TSCA CBi 8 -