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AR226-2982 t$ art Rabbits &"ball tabot trial I4sdiains al Haskell Laboratory 4,801V# 14 . 20-93 DU Poet trio 2$ -!I WDLaboratory man Compliance Statement This study was conducted according to, So TM Good Laboratory Practice Standards (40 CFR 792) . Any areas of noncompliance are documented in the study records . No deviations .*fetid tat 11 . affected the validity of the study . 1 :9- 1 , du Pont do Nemours and ComSubmitor pany chose" lout am : Sponsr I . du lout do "amours and Company study Directors . ampany Sanitized. Does not contain TSCA C81 Substance Tested : : Synoms/Cde GENERAL INFORMATION Du Pont HLR 29-93 Physical Form : ositn Comp J Purity : Submitter's Notebook No . : CAP Registry No.: MA INFORMATION (M -I w Du Pont HLR 28-93 "*I Sponsor: Du Pont Chemicals .j R . I . du Pont de Nemours and Company Wilmington, Delaware Study Initiated - Completed : 12/7/92 - 2/2/93 In Life Phase Initiated - Completed= 12/8/92 - 12/11/92 AWAKE Du Pont HLR 28-93 Skin IrritationTest withN-19913 in Rabbits 8-19913 van evaluated for acute skin irritation potential in 6 female rabbits . The test substance produced mild or moderate arythema and no or slight edema by 24 hours following application . By 48 hours slight to moderate arythema and no to mild edema were observed . By 72 hours the rabbits exhibited slight or mild erythema and no or mild edema . Under the conditions of this study, N-19913 was a moderate skin irritant . York by' O'Ij 6-4 4 N . Scott Karr Toxicology Technician Reviewed OW Approved for Issuer John V . Sarver Study Director JWS/alW Acknovledgements: Tracy Pilliben and Bryan Crossley also participated in the conduct of this study . 5 x_ipany Sanitized . Does not contain TSCA CU1 Du Pont HLR 28-93 MM AS DO ,NATION (8-19913) Datesoflnspections Conduct - 12/8/92 Records, Report(s) - 1/26/93 Date(s) Findings Repor ted To: study Director - 1/26/93 Management - 2/1/93 Reported by Donna Donna K . No t Quality Assurance Auditor 6 otnparay Sanitized . Does not cor tasn `ISC :A CBI INTRODUCTION Du Pont HLR 28-93 The purpose of this study was to evaluate the skin irritation potential of H-19913 when applied to the shaved, intact skin of New Zealand White rabbits . MATERILS ND HO A . Animal Husbandry Young adult female Near Zealand White rabbits were received from Hare Marland, Hewitt, New JerSEy or Hazleton Research Products, Denver, Pennsylvania . The rraabbbbiit"wewreerehoused singly in suspended, stainless steel, wire-mesh cages . P rabbit vas assigned a unique identification number which was recorded' on a card affixed to the cage . The rabbits were offered approximately 125 grams of Purina Certified High Fiber Rabbit Move #5325 daily during the study and water was available ad libitum except as noted under Protocol . Rabbits were quarantined, weighed g e , and observed for general health for approximately 2 weeks . Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle . Environmental conditions of the rooms were targeted for a temperature of 20"C * 2o C and relative humidity of 30X * 10X . Any excursions outside these ranges were 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 New 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 2947 to 3320 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 . In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration . Approximately 0 .5 mL of H-19913 was 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 *rapped around the animal and secured with clips to retard evaporation and to keep the test substance in contact with the skin without undue pressure . 7 ompany Sanitized. o s me ~8~3k kA, t;til Du Pont SLR 28-93 Approximately 24 hours after application of the test substance, the rubber sheeting was loosed, and the skin at the corners of the gauze gently squares was marked with a waterproof pens wrappings and gauze squares were then removed . The test sites wove washed with Ivory* soap and warm water to remove access test substance . The skin was gently patted dry, and the animals vote returned to their cages . Approximately 24, 48, and 72 hours after application of the test substance, the test sites :veto evaluated for erythema, edema, and other evidence of dermal effect and were scored according to the Draise scale (Table 1) . The adjacent :to" of the untreated skin were used for comparison . No other teat substances veto tested on these rabbits . 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 do Nemours and Company, Newark, Delaware or in the Du Pont Records Management Contor t Wilmington, Delaware, LUSION AND CO RESULT H-19913 produced mild erytHEMA with no edema in 5 rabbits and moderate erythema with slight edema in 1 rabbit by 24 hours following a pplication . by 48 hours slight erythema with no edema was observed in 1 rabbit, mild erythema with no or slight edema was observed in 3 rabbits, and moderate erythema with slight or mild edema was observed in 2 rabbits . 8y 72 hours 2 rabbits exhibited slight erythema with no edema and 4 rabbits exhibited mild erythema with no or mild edema . 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 N-19913 Response No Response Slight Mild Moderate 4 hr 0/6 0/6 3/6 1/6 __ . . 7 Erythema f. hr 0/6 0/6 1/6 2/6 3/6 4/6 2/6 0/6 24 hr 5/6 1/6 0/6 0/6 Edema 48 hr 3/6 2/6 1/6 0/6 72 hr 5/6 0/6 1/6 0/6 Under the conditions of this study, U-19913 was a moderate skin irritant . Sanitized . Does not c ;:ac-1Ya,n ;~ Ca sl If these test scores are to be used for EEC/OECD , according to the guide to the labeling of dangerous substances published in the of icial Journal of European Com unities (E C Directive 83/467, Annex VI), H-19913 probably should be classified as an "IRRITANT" until further data is available . data is available -9 Du Pont HLR 28-93 Table I DRAIZE1 SCALE FO R SCORING PRIMARY SKIN IRRITATION Evaluation of Skin Reactions Erythema and eschar formations No erythema Very slight erythema (barely perceptible) Yell-defined erythema Moderate to severe erythema Severe erythema (beet redness) to slight eschar formation (injuries in depth) Value 0 1 (Slight) 2 (Mild) (Moderate) 4 (Severe) Edema formations No edema Very slight edema (barely perceptible) Slight edema (edges of area wall defined by definite raising) Moderate edema (raised approximately 1 .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 ores A - Abraded F - Fissuring I - Intact N - Necrosis T - Thickening G - Fissuring with C - Eschar Bleeding - - No Effect S - Epidermal B - Blanching Scaling L - Sloughing R - Rev Areas X - Compound Adhered to Skin SN - Superficial Necrosis 1 Draize, J . H ., "Dermal Toxicity ." Appraisal of theSafety f Chemicals inFoods,Drugsand Cosmetics . The Editorial Committee of the Association of Food and Drug Officials of the United States, Austin, Texas, 1959, pp . 46-59 . - 10 - ,,j any Sanitized . Does not cointa!n TSCA CBi TABLE II Du Pont MR 28-93 INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IN TEST RABBITS FOLLOWING TOPICAL EXPOSURE TO H-19913 Rabbi t Number 27558 27659 27662 27663 27664 27665 Erythem 34 hr j hr 72 h 2 3 2 2 3 2 2 2 2 3 2 2 2 2 1 2 1 1 a Edema 24 hr 48 hr 72 hr 0 2 0 0 1 0 0 0 0 1 1 2 0 0 0 0 0 0 - 11 - Company Sanst z cL, L#9@ Taut (;oindsct t za4 v