Document YjbVBj3XEwkzwZpqqpnvgdnjn

AR226-2952 FOR W POUT USE ONLY Du Pont HLR 101-91 Study Title Skin Irritation Test wIthllHHBin Rabbits Author John M. Sarver Study Completed On March 1, 1991 Performing laboratory Haskell E. I. QU Poht de Nemours and Company Laboratory for Toxicology and Industrial Elk ton Road, P. 0. Box 50 Newark, Delaware 19714 Medicine K) laboratory Project ID Haskell Laboratory Report No. 101-91 .Company Sanitized. Does not contain TSCA CBJ Page 1 of 9 Material Tested: Medical Research NO.: Hasten no.: Haskell Test Code No. Physical Fon: Purity: CMBposHion: SEtgRAL IHFORHATIOM OU Pont HLR 101-91 18,790 HlUy-whIte liquid Contaminants; Synonyms: Other Codes: Stability: Material Subaltted By: Study In11 i ated - Compisted: In-Life Phase Initiated - Coapleted: Notebook: In the absence of visible evidence to the contrary, the test material was assumed to be stable under the conditions of administration. Du Pont Chemicals I. E. du Pont de Nemours and Company Ullmlngton, Delaware ouPontChenTceT? E. I. du Pont de Nemours and Company Technical Lab Deepwater, Now Jersey 1/29/91 - 3/1/91 - 2 - .CompanySanitized. Does nol contain TSCA CB GENERAL INFORMATION (COMT.) There are 9 pages in this report. Distribution: Du Pont HLR 101-91 - 3 - Company Sanitized. Does nol contain TSCAJCBI? Skin Irritation Test tril Du Pont HLR 101-91 i In Rabbits SUMMARY B w a s po no edema In 3 rabbits erythema but no edema observed at 72 hours. the study. Under the evaluated for acute skin Irritation The test material produced slight erythema but by 24 hours following application. At 48 hours, slight was observed In 1 rabbit. No denial irritation was Three rabbits exhibited no dermal Irritation throughout conditions of this study,--------------uas a slight s!":n Irritant. york by: Ji^^ C riA^, CartH Full ay!\ Tencchhnnilcfian U Study Director: 7ljohn '-^CU^ j^). ^_)Ct^v^\ C/ w.Sarver Technologist Approved by: ^ IUUM (LCL.v^u^p9 Nantfy C. Chromey.UPh.D. Manager Acute Toxicology Reviewed and Approved for Issue: ^y^n t^.John W. Sarver Study Director 3/1 /ell Acknowledgment: Cralg Ughtcap also participated In the conduct of this study. JWS:sf1:HLR(49.9) - 4 - KompanySanitized. Does not contain TSCA fcap Du Font HLB 101-91 QUALITY ASSURANCE DOCUMENTATION STUDY: H# 18, Skin irrita.tion Test with 4n Rabbits AUDITS: Items Audited Protocol, conduct Records, final report Audit Dates 1/31/91 2/26/91 SHORT-TERK AUDIT REPORT NUMBER:! DATE FINDINGS REPORTED TO HAHAG! IT AND STUDY DIRECTOR: 2/26/91 Reported by: ^^.yat^ifnl^e-ystfi-Ka^ctkta^yMliy^ jt Quality Assurance Auditor - 5 - ^"PanySaniHzed. Does not conta.nSTfi^A ^nt Du Font HLR 101-91 INTRODUCTION J ipose of this study was to evaluate the skin irritation potential when applied to the clipped, Intact skin of New Zealand White rabbits." This study was conducted according to the applicable EPA Good Laboratory Practice Regulations. Areas of nonccnpliance are documented in the study records. Ho deviations existed that significantly affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult male New Zealand White rabbits were received from Hare Marland, Hewitt, 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. Purina Certified High Fiber Rabbit Chow* #5325 and water were available ad 1ibi turn except as noted under Protocol. Rabbits were quarantineST weighed and observed for general health for approximately t) 2 weeks. Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environsental conditions of the rooms were targeted for a temperature of 20C ^ 2C and relative humidity of 50% ^ 10%. Any excursions outside these ranges were of small magnitude and/or brief du-ation and did not adversely affect the validity of the study. B. Protocol On the day prior to treatment, the hair of 6 male New Zealand White rabbits was closely clipped to expose the skin from the scapular to the lumbar region of the back. The body weights of the rabbits ranged from 2769 to 3082 grams on the day of treatment. JBBiBwas 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 tha^^ime did not have access to food or water. Approximately 0.5 fflL of applied directly to a 2-inch gauze square that was then placed on the test site. The patch 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 material in contact with the skin without undue pressure. ^Sffipany Sanitized. Does not contain TSCS ^i Du Pont HLR 101-91 Approximately 24 hours after application of the test material, 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 warm water and Ivory" soap to remove excess test oaterial. 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 material, the test sites were evaluated fcr 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 AH raw data and the final report will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pent de Hemours and Company, Newark, Delaware cr in the Ou Pont Records Management Center, Wilmington, Delaware. RESULTS AND CONCLUSIONS fUB----k produced slight erythema but no edema in 3 rabbits by 24 hour^onoKing application of the test material. At 48 hours, slight erythema but no edema was observed in 1 rabbit. No derroa'i irritation was observed at 72 hours. No.dermal irritation was observed in 3 rabbits throughout the study. 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( Response No Response Slight 24 hr ErytHema 48 hr 3/6 S/5 3/6 1/6 72 hr 6/6 0/6 24 hr 6/6 0/6 Edema 48 hr 6/6 0/6 72 hr 6/5 0/6 Under the conditions of this study, irritant. kwas a slight skin .,. ^"^""^.Do^o.co,,,,,,,^, t) Du Pont HLR 101-91 TABLE I DRAIZE1SCALE FOR SCORING PRIMARY SKIN IRRITATION Evaluation of Skin Reactions Erythema and eschar tor-nation: No erythema Very slight erythema (barely perceptible) Hell-defined erythema Moderate to severe erythema Severe erythema (beet redness) to slight eschar formation (injuries in depth) Value 1 (Slight) 2 (H1M- 3 (Moderate) 4 (Severe) Edema formation: No edema Very slight edema (barely perceptible) Slight edema (edges of area well defined by definite raising) Moderate edema (raised approximately '.0 nn) Severe edema (raised more than 1.0 ran extending beyond the area of exposure) 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other Abraded Intact Thickening Eschar No Effect Blanching dermal effects are: Fissuring Necrosis Fissuring with Bleeding Epidermal Scaling L = R = X = SN = Sloughing Raw Areas Compound Adhered to Skin Superficial Necrosis 1 Draize, J. H., "Dermal Toxiclty." Appraisal of the Safety of Chemicals in Foods. Drugs and Cosmetics. The Editorial Coimiittee of the Association of Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. ig^-eii^ffew"^"^^ Du Pont HLR 101-91 TABLE II RABBIT SKIN IRRITATION TEST SKIN RESPONSES OBSERVED !N TEST RABBITS FOLLOWING TOPICAL EXPOSURE T0< ReS^it Number 25682 25683 25684 25685 25686 :?a87 Erythema___ 24-hr 4B.hr. ?2.hr 24 hr 4E8dehmr af_^__^_ iewnpany Sanitized. Does not contain T8CA CBl 9 -