Document 9kQdqgEp4Op19jXadmLQzjmR

. i . -I V U ^ 1 1 AR226-3017 Study Title Skin Irritation Test with H-21095 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 311-95 Author M. Scott Karr Study Completed On April 26, 1995 Performing Laboratory E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Hedicine Elkton Road, P. 0. Box 50 Newark, Delaware 1971A Medical Research No. Company Sanitized. Does not contain TSCACBf Page 1 of 8 Substance Tested: Synonyms/Codes ; Physical Form : Compos ition : Transparent tan M q u i d H-21095 contains: Contaminants: Puri ty: CAS R e g i s t N o .: Spo n s o r : Study Initiated Completed In Life Phase Initiated - Completed: 302 None available DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington. Delavare 3/2/95 4/26/95 3/21/95 - 3/24/95 DuPont HLR 311-95 Skin Irritation Test with H-21095 in Rabbits SUMMARY H-21095 was evaluated for acute skin irritation potential in 6 Bale New Zealand White rabbits. A c.5 mL aliouot of the test substance was applied to the shaved, intact skin of each rabbit and covered with a semi-occlusive 5i dressing. The rabbits were exposed for 4 hours after which the test substance was removed. Approximately 1, 24, 48, and 72 hours after removal of the test substance, the rest sites were evaluated for erythema, edema, and other evidence of dermal effects and were scored according to the Draize Scale. The adjacent areas -f untreated skin were used for comparison. The test substance adhered to the sk.i.n of the rabbits; however, the test ^ sites could still be evaluated. Slight to moderate erythema and no edema ' were observed in the rabbits by 1 hour after removal of the test substance. By 24 hours, slight or mild erythema and no to mild edema were observed. By 48 and 72 hours, the rabbi exhibited no or slight erythema and no edema. No clinical signs of toxicity were observed during this study. Under the conditions of -his study. H-21095 was a moderate skin irritant. Work Reviewed and Approved for Is C.lkMi____ __ -------------------- C^trol Finlay Study Director Acknowledgments: Bryan V. C:ossley also, participated in the conduct of this study. CP/alw Company Sanitized. Does not eonta'n TSCA CBI 3 IliP 1 DuPont HLR 311-95 INTRODUCTION The purpose of this study was to evaluate the skin irritation potential of H-21095 when applied to the shaved, intact skin of New Zealand tfhi o rabbi ts. MATERIAL? a n d m e t h o d s A. Animal Husbandly Young adult male .-M:<NZV)fBF. New Zealand White rabbits were rereived fro- Hare Harlani. Hewitt. New Jetsey. The -abbits were housed singly in ^ , r-nued, stii ,'**ss steel.' mesh cages. Each rabbit was assigned a jR-'a ' * i mbi.r vni.h was recorded on a card affixed to the cager The last 3 axgiis o. the identification number were written on the inside of each rabbit's ear with a water insoluble marker. The rabbits were offered approximately 125 giams of Purina Ceitified High Fiber P.abhtt rho-.'*1 #5325 d=i'- during the study. Water was available ad. V( . ; . -r period while the animals were in Haske' ' =Sora to!v has an an - 1 hea'tn monitoiing program. This -ijy t *c . C > Hillln .i , r J Lv the Ia h m a t o r y Veterinar'an. * .! ..an.p.es - t ,J . , T or ; total bacterial counts and for :he prt t-i.ce of coli form* '-` `d. au<i otr.w. cont: minants. Additionally, samples . i om i r e s . . . ; , - a s ! - cages and cage racks are periodically analyzed to assure adequate sanitation by the cagewashers. Data from this program are maintained separately from study records. Animal feed is ceitified by the manufacturer to meet specified nutritional requirements ...id to -e free of a list of specified '-ontaminants. On the oasis <f *hese analyses, there is no evidence suggesting that conta*-nant; -< present in the f *-.i or water in amounts w h ''''-' may have interfer *0 vir:. the results of this studj. Rabbits tie qt in. eig`ec, and observed for general health for anpeoximately / - ri.iic.."1 rooms were ma.ntained on a timer- controlled, I'-hou. m.: 12 ..fir dark cycle. Environmental conditions of the rooms were ta.* ttii ter a temperature of ^C t at'd -ative humidity of 50X loX. E--x-c-u-rsions outside these - mges vert nidged to have been of insufficient magnitude and/oi durati nave adversely affected the validity of the study. JCompany Sanitized. Does - 4 not contain TSCACBf EflKSH B. Protocol On the day prior to treatment, the hair of 6 male New Zealand Vhltc rabbits was closely shaved to expose the skin from the scapular to the luabar region of the back. The body veights of the rabbits ranged froa 1930 to 2174 grass on the day of treataent. Each rabbit vas placed into a stock which had been fitted with a piece of rubber sheeting, approximately 8" x 18*. The rabbits reaalned in the stocks throughout the exposure period and during that time did not have access to food or water. A 0.5 mL aliquot of H-21095 was applied directly on the test site beneath a 2-inch gauze square that vas 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. Up to 3 other test substances were tested concurrently on separate, localised test sites on the backs of these rabbits. Approximately 4 hours after application of the test substance, 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 to remove excess test substance. The skin was gently patted dry, and the animals were returned to their cages. Approximately 1, 24, 48, and 72 hours after removal of the test substance, the test sites were evaluated for erythema, edema, and other "vIJence of dermal effects and were scored according to the Oraisa scale (Table I). The adjacent areas of the untreated skin were used for comparison. In addition, the rabbits were observed for clinical signs of toxicity at each observation. 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 Nemours and Company, Newark, Delaware or in the DuPont Records Management Center, Wilmington, Delaware. __ RESULTS AND CONCLUSIONS The test substance adhered to the skin of the rabbits; however, the test sites could still be evaluated. H-21095 produced slight erythema in 4 rabbits, mild erythema in 1 rabbit, and moderate erythema in 1 rabbit by 1 hour after removal of the test substance. No edema was observed at 1 hour -5- Company Sanitized. Does not contain T SC A GBI DuPont H U 311-95 By 24 hours, 3 rabbits exhibited slight erytheaa but no edeaa, and 3 exhibited aild erytheaa and no to nild edeaa. By 48 hours, 2 rabbit* exhibited no deraal irritation, and 4 exhibited slight erytheaa but no adaaa. By 72 hours, 3 rabbits exhibited no deraal irritation, and 3 exhibited slight erytheaa but no edeaa. No clinical signs of toxicity vere observed during this study. Individual skin irritation scores are presented in Table II. A suaaary of skin responses is presented in the following table. Summary of Skin Responses to H-21095 Response * No Response Slight Mild Moderate Erythema 1 hr 24 hr 48 hr 72 hr 0/6 0/6 2/6 . 3/6 4/6 3/6 4/6 3/6 1/6 3/6 0/6 0/6 1/6 0/6 0/6 0/6 Edema 1 hr 24 hr 48 hr 72 hr 6/6 4/6 6/6 6/6 0/6 1/6 0/6 0/6 0/6 1/6 0/6 0/6 0/6 0/6 0/6 0/6 Under the conditions of this study, H-21095 vas a moderate skin irritant. If these test scores are to be used for EEC/OECD classification, according to the guide to the labeling of dangerous substances published in the Official Journal of European Communities (EEC Directive 93/21, Annex VI), H-21095 probably could be classified as a "NON-IRRITANT" until further data is available. -6 - S Company Sanitized.. D oes not c o 'tfafo TSSCA CB1 SKIN IRRITATION TEST WITH H-21095 TABLE I M A I Z E * SCALE FOR SCORING PRIMARY SKIN IRRITATION Evaluation of Skin Reactions Erythema and eschar formation: No erythema Very slight erythema (barely perceptible) Well-defined erythema Moderate to severe erythema 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 veil defined by definite raising) Moderate edema (raised approximately 1.0 nun) Severe edema (raised more than 1.0 mm extendinj 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 G = Fissuring with C - Eschar Bleeding - No Effect S = Epidermal B - Blanching Scaling L = Sloughing R = Rav Areas X = Compound Adhered to Skin SN - Superficial Necrosis 1 Oraize, J. H . , "Dermal Toxici ty-" Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics * The Editorial Committee of the Association of Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. Com pany Sanitized. Does not contain TSCA CBI -7- Ii Durone BLR 311-95 SKIN IRRITATION TEST WITH H-210S5 TABLE II INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IN RABBITS Rabbit Number 29985 29986 29987 29994 29995 29996 Erythema 1 hr 24 hr 48 hr 72 hr 2X* 2X IX I X * IX I X o x * I X I X 0X o x * 3X 2X IX I X IX 2X IX IX I X I X o x * 0X -* ft Edema 1 hr 24 hr 48 hr ?2 hr 000 0 000 0 000 0 0 20 0 0100 000 0 Although the test substance adhered to the skin of the rabbits, the test sites could be evaluated. ' company Sanitized. Does not contain TSCA CBI