Document Ex69E2MQEV94JYYV4XdD6GN6j

gfltt Ml POUT USE ORLY AR226-2952 Du Pont HLR 101-91 Skin Irritation Test with in Rabbits Author John W. Sarver Study Competed On March 1, 1991 E. I. du Pont de Nemours and Company^ Haskell Laboratory for Toxicology and Industria, n e d i c m e Elkton Road, P. 0. Dox 50 Newark, Delaware 19714 laboratory Project ID Haskell Laboratory Report No. 101-91 .Company Sanitized. Does not contain T SC A C8 Page 1 of 9 RFtffBAL INFORMATION Ou Pont HLR 101-91 Material Tested: Medical Research Ho.: Hastell Mo.: Haskell Test Code Ho.: Physical Fona: Purity: Composition: 18,790 Milky-white liquid 1 I Contaminants: Synonyms: Other Codes: Stability: Sponsor: Material Submitted^ : Study Initiated - Completed: In-l1fe Phase Initiated - Completed: 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 E. I. du Pont de Nemours and Company Wilmington, Delaware E. !. du Pont de Nemours and Company Technical Lab Deepwater, New Jersey 1/29/91 - 3/1/91 1/29/91 - 2/1/91 i 2 .Company Sanitized. Does not contain T SC A CB1 -- M SB GEHERAL INFORMATION (COHT.) Du Pont HLR 101-91 ! - 3 Company Sanitized. Does not contain TSC A CB? % Du Pont HLR 101-91 Skin Irritation Test rit In Rabbits SUMMARY was evaluated for acute skin Irritation The test material produced slight erythema but no edema In 3 rabbits by 24 hours following application. At 48 hours, slight erythema but no edema was observed in 1 rabbit. No dermal irritation was observed at 72 hours. Three rabbits exhibited nodennalirritation throughout the study. Under the conditions of this s t u d y f l | [ H w a s a slight skin irritant. Work by: C ClaatL. rfsCt* Carol Finlay 7j Technician u Approved by: Nanjjy C. Chromey.lJPh.D. Manager Acute Toxicology Reviewed and Approved for Issue: u O - -C-l_______ John W. Server Study Director 3 / \ /'U Acknowledgment: Craig Lightcap also participated in the conduct of this study. JWS: sfl :HIR(49.9) - 4 pompany Sanitized. Does not contain t s c a : bp Du Pont BLR 101-91 QUALITY ASSURANCE DOCUMENTATION STUDY H# 18/790 skin Irritation Test with 'in Rabbits AUDITS: Items Audited Protocol, conduct Records, final report Audit Dates 1/31/91 2/26/91 SHORT-TERM AUDIT REPORT NUMBER: DATE FINDINGS REPORTED TO MANAG; ENT AND STUDY DIRECTOR: 2 / 2 6 / 9 1 Re ported by: tfiames Kackay l i / Quality Assurance Auditor Date Company Sanitized. Does not contain TSCA r n 5 INTRODUCTION Du Pont HLR 101-91 r i D D I U . n i l s 3U1UJT w u k w i -- -- Z , rr ------ ,________. j J _ Laboratory Practice Regulations. Areas of noncempliance are documented in the study records. No 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 unique identification number which was recorded on a card affixed to ti cage. Purina Certified High Fiber Rabbit Cho'rf #5325 and water were available ad 1iblturn except as noted under Protocol. Rabbits were quarantined weighed and observed for general health for approximately ? weeks. Animal rooms were maintained on a timer-controlled, 12-hour brief duration and did not adversely affect tne v a n o i c y or m e UUJ. 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. Each rabbit was placed into a stock which had been fitted with a "iece of rubber sheeting, approximately 3 " x 18" . The rabbits remained iii'the stocks throughout the exposure period and during t h ^ ^ ^ ^ d i d not have access to food or water. Approximately 0.5 mL of applied directly to a 2-inch gauze square that was then placed on tne 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. Company Sanitized. Does not contain t s o a 6- Du Pont HLR 101-91 Annritttmatelv 24 hours after application of the test material, the rubber^sheeting^was^loosened, and the skin at the corners of the gauze squares as marked with a waterproof pen; " TM p p i n g s a n dt^wari^water were then removed. The test sites were gentiy washed with warn wat and Ivory" soap to remove excess test material. The skin was gent y patted dry and the animals were returned to their cages. annwixlmatelv 24 48 and 72 hours after application of the test material, the test sites'were evaluated ^ erythema.jiden.a evidence of dermal effects and were scored according to the Draize scaie (Table I). The adjacent areas of the untreated skin were used f comparison. C. Records Retention All raw data and the final report will *>e stored in th, arch'ives of Hackell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont Management Center, Wilmington, Delaware. RESULTS AND CONCLUSIONS ^ D r o d u c e d slight erythema but no edema in 3 rabbits by >4 hour' f o l d i n g application of the test material. At ?8 .h0V ^ * IbSSd f f d ^ ^ ! m i S b^:<*5rvlM n ^ b b its ~ Summary of Skin Responses Response NO Response SIight Erythema 24 hr 48 hr 3/6 5/6 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. was a slight skin ! i I - 7 - Company Sanitized. Does not contain TSCA Cllf kJ ^T\ Du Pont HLR 101-91 TABLE I DBAIZE1 SCALE FOR SCORING PRIMARY SKIM IRRITATION Evaluation of Skin Reactions Erythema and eschar formation: No erythena Very slight erythena (barely perceptible) teJl-defjjned ejythema-----Moderate to severe erythena Severe erythema (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 well defined by definite raising) Moderate edema (raised approximately :.0 mm) 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 * Fissuring I = Intact N = Necrosis T = Thickening C = Eschar - = No Effect G = Fissuring with Bleeding S = Epidermal B = Blanching Seali ng L = Sloughing R = Raw Areas X = Compound Adhered to Skin SN = Superficial Necrosi s 1 Draize. J. H.. "Dermal Toxicity." Appraisal of the Safety of Chemical^ in Foods. Druas and Cosmetics. The Editorial committee ot the Association of Tood an'O r u g Officials of the United States. Austin, Texas, 1959, pp. 46-59. -8- - . ---H^n?WYrtaTn T S C A C Du Pont HLR 101-91 TABLE II RABBIT SKIN IRRITATION TEST SKIN RESPONSES OBSERVED IN TEST RABBITS r m IOWING TOPICAL EXPOSURE T O j ~ Rabbit Number 25682 25603 25684 25685 25686 :?587 Erythema 24 -hr 48-hn 72 hr 0 00 100 1 10 0 00 0 00 1 00 Edema 24 hr 48 hr /2 nr 000 000 00 0 000 000 00 0 Company Sanitized. Does not contain TSCA CBl - 9-