Document ymwrq4bDVB6V6314mBg6pzqv2

AR226-2991 Study Title Skin Irritation Tact with H-20056 in Rabbits Author John V. Sarwar Study Coupletad On !!! June 3, 1993 Perforaing Laboratory B. I. du Pont da Neaours and Coapany Haskell Laboratory for Toxicology and Industrial Medlcina Blkjton Road, P. 0. Box 50 Newark, Delaware 19714 _ Laboratory Project ID Haskell Laboratory Report No. 282-93 Page 1 of 10 Bm noiconiato TSCAOBi DuPont BLR 282-93 COOP LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted Recording to EPA TSCA Good Laboratory Practice Standards (40 CFR 792). Any areas of noncoapliance are docuaented in the study records. No deviations:existed that affected the validity of the study. ; Subaitter: B. I. du Pont de Nenours and Conpany Sponsor DuPont Cheaicals B. I. du Pont de Nemours and Coapany Stuy Director John v. server Toxicologist /93 -2- ^BlnfSpaiSanitized, Does riot'eontafn TSCA C & Substance Tested: SynonyBa/Code3; GENERAL INFORMATION DuPont HLR 282-93 Physical For Coaposltiom Purity Subaittar's Notebook Ho.t Nona subaitted m CAS Registry Wo.i Sponsor DuPont Cheaicels B. I. du Pont da Naaours and Coapany Vllaington, Delaware Study Initiated - Coaplatadt 3/15/93 - 6/3/93 In Life Phase Initiated - Coaplatadt 3/16/93 - 3/19/93 ! Company Sanitized. Does not contain TSCACSJ - 3- DuPont HLR 282-93 Skin Irritation Tost with H-20056 in Rabbits SUMMARY H-20056 vas evaluated fo^r acute skin irritation potential in 6 ferale rabbits. Slight or elld eryjthew but no edera vas observed in the rabbits by 24 hours follovlng application. By 48 and 72 hours, mild or moderate erythema and no or slight edjera vere observed. Under the conditions of this study, H-20056 vas a moderate skin irritant. Toxicology Technician Revicved and Approved for Issue: C John V. Server Study Director Acknovledgerantt Bryan V. Crossley also participated in the conduct of this study. JVS/alv -4 - Company Sanitized. Does not contain TSCA Ci! , r DuPont HLR 282-93 QUALITY ASSURANCE DOCUMENTATION (H-20056) Dates of Inspection: Conduct - March 16, 1993 Records, Report(s) - May 25, 26, 1993 Date(s) Findings Reported to Study Director - June 1, 1993 Management - June 1, 1993 Reported byt Quality Assurance Auditor 6-m Date - 5 Sompany Sanitized, Does not contain TSCA CBI DuPont HLR 282-93 INTRODUCTION The purpose of this study was to evaluate the skin irritation potential of H-20056 vhen applied to the shaved, intact skin of Nev Zealand White rabbits. This study vas conducted according to the applicable EPA Good Laboratory Practice Standards Areas of noncompliance 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 Nev Zealand White rabbits were received from Hare Marland, Hevitt, Nev Jersey. The rabbits vere housed singly in suspended, stainless steel, vire-mesh cages. Bach rabbit vas assigned a unique identification number which vas recorded on a card affixed to the cage. The rabbits vere offered approximately 125 grams of Purina Certified High Fiber Rabbit Chov* #5325 daily during the study and water vas available ad libitum except as noted under Protocol. Rabbits vere quarantined, weighed, and observed for general health for approximately 2 weeks. Animal rooms vere maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms vere targeted for a temperature of 20*C 2#C and relative humidity of 50* 10X. Any excursions outside these ranges vere of small magnitude and/or brief duration and did not adversely affect the validity of the study. B. Protocol On the day prior to treatment, the hair of 6 female Nev Zealand White rabbits vas 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 vas 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 vas applied directly on the test site beneath a 2-inch gauze square that vas held in place with non-irritating tape. The rubber sheeting vas then wrapped around the animal and secured vith clips to retard evaporation and to keep the test substance in contact vith 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 administration. One other test substance vas tested on a separate test site on these rabbits. - 6- Company SanUfced. Does not contain TSCA C DuPont HLR 282-93 Approximately 24 hours after application of the test substance# the rubber sheeting vas loosened, and the skin at the corners of the gause squares was Barked with a waterproof pen; wrappings and gause squares were then removed. The test sites were gently washed with Ivory* soap and warn water to remove excess test substance The skin was gently patted dry, and the animals were returned to their cages. Approximately 24, 48, *nd 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 Pont de Nemurs and Company, Newark, Delaware or in the DuPont Records Management Center, Vilmington, Delaware. RESULTS AMD CONCLUSIONS By 24 hours following application, H-20056 produced slight erythema with no edema in 1 rabbit and mild erythena with no edema in 5. By 48 hours, mild erythema with no edema was observed in 3 rabbits and moderate erythema with slight edema vas observed in 3. By 72 hours, mild erythema with no edema vas observed in 3 and moderate erythena 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 ____ Erythema 24 hr 48 hr T T E T 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 Edema 24 hr 48 hr 6/6 3/6 0/6 3/6 0/6 0/6 0/6 0/6 0/6 0/6 H 'W 3/6 3/6 0/6 0/6 0/6 -7- , Sanitize* Ooes noi Company If tlmi tut scores srs to bs used for BBC/OICD classification, according to the guide to the labeling of dangerous substances published in the Official Journal .of European Coanunlties (BBC Directive 83/467, Annex VI), H-20056 probably should be classified as an "IRRITANT" until further data is available. D 8- - Baalibed. Does notcontain YgQA DuPont HLR 282-93 TABLE I DRAIZEi SCALE FOR SCORING PRIMARY SKIN IRRITATION Evaluation of Skin Reactions Erythcaa and eschar formation: No erytheaa Very slight erythema (barely perceptible) Veil-defined erythema Moderate to severe erythema Severe erytheaa (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 (edges of area veil defined by definite raising) Moderate edema (raised approximately 1.0 am) Severe edema (raised more than 1.0 mm extending beyond the area of exposure) 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other dermal effects are: A Abraded F m 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 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 o the United States, Austin, Texas, 1959, pp. 46-59. Company Sanitized. Does not contain TSCA CB3 DuPont HLR 282-93 TABLE II INDIVIDUAL SKIM IRRITATION SCORES SKIN RESPONSES OBSERVED IN TEST RABBITS FOLLO]WING TOPICAL EXPOSURE TO H-20056 Rabbit Number 27770 27843 27845 27846 27891 27894 1Srytheaa 24 hr 4jl hr 72 hr 122 222 233 222 233 233 Bdeaa 24 hr 48 hr >2 hr 000 000 011 000 0 11 0 11 - 10 - (Sompany Sanitized. Does not contain TSCA 21