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AR226-3027 Study Title Skin Irritation Test with H-21209 in Rabbits Laboratory Project ID Haskell Laboratory Report No. 623-95 Author Tracy A. Filliben Study Completed On September 22, 1995 Performing Laboratory Haskell I. E. du Font de Nenours and Company Laboratory for Toxicology and Industrial Elk ton Road, P. 0. Box 50 Newark, Delaware 19714 Medicine Page 1 of 8 Compa' ny S^annifienezsd"-D" oes "el contain TSCACB1 Substance Tested: Synonyms/Codes; Physical Form; Composition: GENERAL INFORMATION DuPont HLR 623-95 Contaminants; Purity: Submitter's Notebook No.: CAS Registry No.: Sponsor; Study Initiated - Completed: In Life Phase Initiated - Completed; DuPont Specialty Chemicals E. I. du Font de Nemours and Company Vilmington, Delaware 7/14/95 - 9/22/95 7/19/95 - 7/21/95 2 - Conaswv ^.^--"""mtr''" ^.^.^^M^.j^afitat^^^^Saa^fcarika^^-6^^^^-j^^^^^^^ .E^al DuPont HL8 623-95 Skin Irritation Test vith H-21209 in Rabbits i SUMMARY H-21209 was evaluated for acute skir. irritation potential in 6 male New Zealand White rabbits. Approximately 0.5 mL of the test substance was applied to the shaved, intact skin of each rabbit and covered with a semi-occlusive dressing for a 4-hour exposure. Approximately 1, 24 and 48 hours after removal 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. The adjacent areas of untreated skin were used for comparison. H-21209 produced no or slight erythema but no edema by 1 hour after removal of the test substance. By 24 hours, slight or mild erythema and no or slight edema were observed. By 48 hours after removal of the test substance, no or slight erythema and no or slight edema were observed. In addition, 3 rabbits exhibited epidermal desquamation. No clinical signs of toxicity were observed during the study. Und.'r the conditions of this study, H-21209 was a mild skin irritant. Report by: /^^a^^/- ^ y/y' '2^ (/, -^ tfarKJ. Barczewski Toxicology Associate Work by. ^KU<J- Q,. ^^M^-<-^J Tracy A. Filliben Toxicology Associate ^/-^L^^ Approveror Issue ^JM^WL 0.. ______,____T^ra^c^y ^A. Filliben St-uciv Director 9 /^/ ^ TAF/lrnp 1 Company Sanitized. Does not contain TSCA C@S INTRODUCTION DuPont HLR 623-95 The purpose of this st'<dy was to evaluate the skin irritation potential of H-21209 when applied to the shaved, intact skin of New Zealand White rabbits. MATERIALS AND METHODS A. Animal Husbandry Young adult male HMs(NZW)fBR New Zealand White rabbits w<_-e received from Hare Marland, Hewitt, New Jersey. The rabbits were hou^pd 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. The last 3 digits of the identification number were written on the inside of each rabbit's ear with a water insoluble marker. The rabbits were offered approximately 125 grams of Purlna Certified High Fiber Rabbit Chow #5325 daily during the study. Water was available ad libitum except during the exposure period while the animals were in stocks. Haskell Laboratory has an animal health monitoring program. This program is monitored and administered by the Laboratory Veterinarian. Welter samples are periodically analyzed for total bacterial counts and for the presence of coliforms, lead, and other contaminants. Additionally, samples from freshly washed 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 cartified by the manufacturer to meet specified nutritional requirements and to be free of a list of specified contaminants. On the basis of these analyses, there is no evidence suggesting that contaminants were present in the feed or water in amounts which may have interfered with the results of this study. Rabbits were quarantined, weighed, and observed for general health for approximately 2 weeks. Animal rooms were maintained on a timercontrolled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20C 1C and relative humidity of 50% 10%. Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Protocol On the day prior to treatment, the hair of '" male New Zealand White rabbits was closely shaved to expose the skin from the scapular to the lumbar region of the back. The body weights of the rabbits ranged from 207A to 2162 grams on the day of treatment. Company Sanitized. Does not obtain TSCA C9J vsstiisim.sasust.si.sas DuPont HLR 623-95 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. Approximately 0.5 mL of H-21209 was applied directly on the test site beneath a 2-inch gauze square that 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 substance in contact with the skin without undue pressure. Three other test substances were tested concurrently on separate, localized test sites on the backs of these rabbits. In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. 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 narked with a waterproof pen, wrappings and gauze squares were then removed. The test sites were gently washed with Ivory soap and warm water to remove excess test substance. The skin was gently pat tad dry, and the animals were returned to their cages. Approximately 1, 24 and 48 hours aftar removal of the test substance, th test sites were evaluated for ervfhema, edema, and other evidence of Tdhe.e-ii.a-^c!'jeacffeenct tsareaansd woferethescuornetdreaatcecdordsikning wtoeretheuseDdrafiozer scocmalpear(iTsoanb.le I). Additionally, the rabbits were examined for clinical signs of toxicity at each dermal evaluation. 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 Font de Nemours aiid Company, Newark, Delaware or in the DuPont Records Management Center, Wilmington, Delaware. 5 ' ^p.nyS^z.""--------"TM^61 DuPont HLR 623-95 RESULTS AND CONCLUSIONS H-21209 produced no erythema in 1 rabbit and slight erythema in 5 rabbits by 1 hour after removal of the test substance; no edema was observed. By 24 hours, 2 rabbits exhibited slight erythema but no edema, and 4 rabbits exhibited mild erythema and slight edema. By 48 hours, 2 rabbits were clear of all irritation, 1 rabbit exhibited slight erythema and slight edema, and 3 rabbits exhibited slight erythema but no edema. Desquaroation vas observed 3 rabbits during the study. No clinical signs of toxicity were observed during 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 H-21209 Response None Slight Mild 1 hr 1/6 5/6 0/6 Erythema "SA^hr 0/6 2/6 4/6 48 hr 2/6 4/6 0/6 1 hr 6/6 0/6 0/6 Edema 24 hr 2/6 4/6 0/6 48 hr 5/6 1/6 0/6 Under the conditions of this study, H-21209 was a mild 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-21209 probably could be classified as a "NON-IRRITANT" until further data is available. 6 - - Company Sanitized. Dcss not contain TSCA C81 -s- SKIN IRRITATION TEST ITH H-21209 TABLE I DRAIZEl 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 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Edema formation: No edema Very slight edeoa (barely perceptible) Slight edema (edges of area veil 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) 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other A = Abraded I = Intact T = Thickening C == Eschar - = No Effect B = Blanching D = Desquamation dermal effects are: F = Fissuring N = Necrosis G = Fissuring with Bleeding S = Epidermal 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 of the United States, Austin, Texas, 1959, pp. 46-59. 7 - Company Sanitized. Doss not contain TSCA CBS ^ '^: ^ -^^ 'y^' SL^S^H^S ^ ;; -"^l^ ^: "' ^ffs.^^1 ;'< SKIN JSlKrSHStfW TEST tlt6 WilS^" Ti(^BLE II INDIVIDUAL SKIN IRKI rATION S(;OKES "f, .;^ SKIN BBSPONSES OBS1SRVED IN RABBITS Rabbit Number 30374 30383 30384 30385 30386 30392 Erythema 1 hr 24 hr 48 hr 0 2 I 1 1 0 1 2 ID 1 2D ID 1 2D ID 1 1 0 D = Desquamation 1 hr 0 Edeima 24 hr 1 7458" hr 1 0 0 0 0 1 0 0 1 0 0 1 0 0 0 0