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AR226-2991 Study Title Skin Irritation T--t with H-20056 in Rabbif Author John V. Sarvr itudy Coaplcfd On Juna 3, 1993 Pgrforaing Laboratory Hafkell B. I. du IPont d NMour nd Coapany Laboratory cor Toxicology and Industrial Bikton Road, P* 0. Box 50 Ncrark, Delaware 19714 Medicine laboratory Project ID Haskell Laboratory Report No. 282-93 Page 1 of 10 DuPont HLR 282-93 COOP LABORATORY PRACTICE COMPLIANCE STATEMENT Thia study vas conducted according to EPA TSCA Good Laboratory Practice Standards (40 CFB 792). Any ^reas of noncoBplianee are documented in the study records. No deviations Iexisted that affected the validity of the study. : SubBitteri B. I. du Font de Neuours and Coapany Sponsor* DuPont Cheaicals B. I. du Font de Neaours and Coipany Stuuy Oirectoct -i^Kjf-i Ci^^T^yo.^-^^wn. 6/3 1^3 Toxicologist 2 - - SeffipsnySlatiiSgeei Dees i Substance Tested; Synonyas/Codes; GENERAL INFORMATION DuPont HLR 282-93 Physical POCTH CoBpogitiom Purityt Subaitter's Notebook No.8 CAS Regitry No.t Sponsor Study Initiated - Coinpletedt In Life Phaae Initiated - Coaplefdt None aulcitted DuPont CheKieale B. I> du Font de Heaour* and Coapany VILiinxton, Delaware 3/15/93 - 6/3/93 3/16/93 - 3/19/93 company 'Sanitized. Does noi contain TSCA CB! 3 - DuPont HLR 282-93 Skin Irritation Test with H-20056 in Rabbits SUMMARY H-20056 was evaluated o^acute skin Irritation potential in 6 feule rabbits. Slight or lld erytheaa but no edeaa was observed in the rabbits by 24 hours following application. By 46 and 72 hours, nild or moderate erythema and no or slight edeu were observed. Under the conditions of this study, H-20056 was a moderate skin irritant. Work byt ^ ( f e1. Scott Karr Toxicology Technician Reviewed and i Approved for Issue < Su^n Q.'Yn^w^^^^-5^!^^^ /<f3 John V. Sarver Study Director Acknowledgeaent< Bryan V. Crossley also participated in the conduct of this study. JVS/alw 'Company Sanitized. Does not contain TSCA CBI 4 - DuPont HLR 282-93 QUALITY ASSURANCE DOCUMENTATION (H-20056) Dates of Inspection; Conduct - March 16, 1993 Records, Report(a) - May 25, 26, 1993 Date(s) Findings Reported to Study Director - June 1, 1993 Hanag--ent - June 1, 1993 t e a ^ ^ Reported by Quality Assurance Auditor 5 ompany Sanitized Does not Gongaia TSGA CE INTRODUCTION DuPont HLR 282-93 The purpose of this study was to evaluate the skin irritation potential of H-20056 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. Areas of noncoapliance are documented in the study records. No deviations existed that affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult female New Zealand White rabbits were received from Hare Marland, Hevitt, Nev Jersey. The rabbits were housed singly in suspended, stainless steel, vire-nesh cages. Bach rabbit was assigned a unique identification number which vas recorded on a card affixed to the cage. The rabbits were offered approximately 125 grams of Purina Certified High Fiber Rabbit Chow* #5325 dally during the study and water was available ad lib!turn except as noted under Protocol. Rabbits were quarantined, weighed, and observed for general health for approximately 2 weeks. Animal rooms were maintained on a timer-controlled, 12-hour llght/12-hour dark cycle. Environmental conditions of the rooms were targeted for a tcRperature of 20*'C 2<tC and relative humidity of 50X 10X. Any excursions outside these ranges were of small magnitude and/or brief duration and did not adversely affect the validity of the study. 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 2568 to 3124 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 food or water. Approximately 0.5 mL aliquot of H-20056 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 animal 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. One other test substance was tested on a separate test site on these rabbits. 6 -- -- ompanySanifeed.DoesnoteoniaSnTSCArc' DuPont HLR 282-93 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 Barked with a Waterproof pen; vrapplngs 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 Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Font de Nemi-jrs and Company, Newark, Delaware or in the DuPont Records nanagement Center, Vilmlngton, Delaware. RESULTS AM) CONCLUSIONS By 24 hours following application, H-20056 produced slight erythema with no edema in 1 rabbit and mild erythema with no edema in 5. By 48 hours, mild erythema with no edema was observed in 3 rabbits and moderate erythema with slight edema was observed in 3. By 72 hours, mild erythema with no edema was observed in 3 and moderate erythema with slight edema was observed in 3. 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-20056 Response No Response Slight Mild Moderate Severe _2_4_h_r_Ery4t6hherma_7_2_h_r_- 0/6 0/6 0/6 1/6 0/6 0/6 5/6 3/8 3/6 0/6 3/6 3/6 0/6 0/6 0/6 _2_4_h_r_ E d46e mhr a _ _7_2_h_r_ 6/6 3/6 3/6 0/6 3/6 3/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 Company ^wo,c.n..^ DuPont oLR 282-93 Under the condition! of this study, H-200S6 was a Moderate kin irritant. ft If th cores are to tr uid tor BBC/OKD clarification, accordinx to rh |uid to th labeling of danrroul lubitancw publichwl in the Official Jo.nal ,of Buropwan CoiMunltias (EEC Directive 83/467, Annex VI), H-20056 probably should be classified as an "IRRITANT" until further data is available. 8 - - SSsa^alyglazed. Dees nog eontain^CAGBj DuPont HLR 282-93 TABLE I DRAIZEl SCALE FOR SCORING PRIMARY SKIN IRRITATION Evaluation of Skin Reactions Erytheaa and eschar foroatlont No erytheaa Very slight erythema (barely perceptible) Veil-defined erythema Moderate to severe erythema Severe erythema (beet redness) to slight eschar foroation (Injuries in depth) Edema formation: No edema Very slight ede-- (barely perceptible) Slight edeaa (edges of area veil defined by definite raising) Moderate edeaa (raised approximately 1.0 mm) Severe edeaa (raised ore than 1.0 BUR extending beyond the area of exposure) Value 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) 0 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other A Abraded I Intact T Thickening C Eschar - No Effect B Blanching dermal effects are: F Pissuring N Necrosis G Pissuring with Bleeding S Bpideraal Scaling L Sloughing R Raw Areas X Compound Adhered to Skin SN Superficial Necrosis 1 Draize, J. H., "Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. The Editorial Committee of the Association of Food and Drug Officials ot the United States, Austin, Texas, 1959, pp. 46-59. Company Sanitized. Does not contain TSCA Q'BI DuPont HLR 282-93 TABLE II INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSESOBSERVED IN TEST RABBITS POLUWING TOPICAL EXPOSURE TO H-20056 Rabbit Nubr 27770 27843 27845 27846 27891 27894 Bryith--a M.JSE 46hr ZLhi 1 2 2 2 2 2 2 3 3 2 2 2 2 3 3 2 3 3 Edeaa 24 hr 46 hr 72 hr 0 0 0 0 0 0 0 1 1 0 0 0 0 1 1 0 1 1 ompany Sanitized. Baes noit contain TSCA C'S.1 10