Document 913z62dxR64QRyMzOJ76mpQYe

TRADE SECRET AR226-3177 DuPont-6087 Study Title H-24516: Skin Irritation Test in Rabbits Laboratory Project ED: DuPont-6087 AUTHOR: Carol Finlay, B.A. STUDY COMPLETED ON: April 9, 2001 PERFORMING LABORATORY: E. I. du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 .Company Sanitized. Does noi contain TSCA CB8 Page 1 of 13 H-24516: Skin Irritation Test in Rabbits DuPont-6087 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of the data obtained from this study. yJames Reviewed by.C. ,-,/g^tf^. ____C_.M_a_ck_ay_I_I Associate Scientist Issued by Study Director: ^^\ i ^ CL/L-^C ^-^ CarofFiinnllaayy,, B.A. ( Staff Scientist ^'/Lf^.'^'1 Date _4or-^^/ riate jCompany Sanitized. Does not contain TSCA CB8 .2- H-24516: Skin Irritation Test in Rabbits STUDY INFORMATION Substance Testedfjl Synonyms/Codes H-24516 Haskell Number: 24516 Composition: DuPont-6087 Known Impurities': Physical Characteristics: Pale to medium tan waxy solid Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. H-24516: Skin Irritation Test in Rabbits STUDY INFORMATION (Continued) Study Initiated/Completed: March 8,2001 / (see report cover page) In-Life Initiated/Completed: March 13,2001 / March 16,2001 DuPont-6087 .Company Sanitized. Does not contain TSCA ^e" H-24516: Skin Irritation Test in Rabbits STUDY PERSONNEL Study Director: Management: Primary Technician: Carol Finlay, B.A. Judith C. Stadler, Ph.D., D.A.B.T. James C. Mackay II Toxicology Report Preparation: Wanda F. Dinbokowitz Laboratory Veterinarian: Wanda L. West, D.V.M., A.C.L.A.M. DuPont-6087 Csmpany Sanitized. Does not contain TSCA OBI -5- H-24516: Skin Irritation Test in Rabbits DuPont-6087 SUMMARY H-24516 was evaluated for acute skin irritation potential in 6 male New Zealand White rabbits. Approximately 0.5 g of the test substance was applied to the shaved, intact skin of each rabbit and covered with a semi-dcclusive dressing for a 4-hour exposure. Approximately 1,24,48, and 72 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. No dermal irritation was observed in 4 rabbits throughout the study. The remaining 2 rabbits exhibited slight erythema and no or slight edema one hour after test substance removal. No dermal irritation was observed at 24, 48, or 72 hours. No clinical signs oftoxicity were observed, and no significant body weight loss occurred during the study. Under the conditions of this study, H-24516 was a slight skin irritant. Pompany Sanitized. Does not contain TSCA fw -6- H-24516: Skin Irritation Test in Rabbits DuPont-6087 INTRODUCTION The purpose of this study was to evaluate the skin irritation potential of H-24516 when applied to the shaved, intact skin of New Zealand White rabbits. MATERIALS AND METHODS A. Test Substance The test substance, H-24516, was supplied by the sponsor as a pale to medium tan waxy solid. The test substance appeared to be stable under the conditions of the study. No evidence of instability, such as a change in color, was observed. B. Animal Husbandry Young adult HM:(NZW)BR New Zealand White rabbits were received from Covance Research Products, Denver, Pennsylvania. 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. 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 ofPMI Nutrition International, me. Certified High Fiber Rabbit LabDiet 5325 daily during the study. Water was available ad libitum. As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity of the study: Water samples are analyzed for total bacterial counts, and the presence ofcoliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore and fungal counts. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity of the study. '''faWa^anWa.Do.Bnol.on.ainTSC.CBI H-24516: Skin Irritation Test in Rabbits_______ ____ DuPont-6087 The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Evaluation of these data did not indicate any conditions that affected the validity of the study. Rabbits were quarantined, weighed, and observed for general health for 7 days. 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 of20C 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. C. Protocol Approximately 24 hours prior to treatment, the hair of 6 male New Zealand White rabbits was closely shaved to expose the skin from the scapular to the lumbar region of the back. The rabbits weighed from 2049 to 2591 grams on the day of treatment. The area to be treated (approximately 6 cm2) was marked on each rabbit's back with a waterinsoluble marker. The test substance was liquefied by heating it in an approximately 90C water bath. For each animal, approximately 0.5 g of the liquefied test substance was applied evenly to a 2-ply, 1 inch square gauze pad. The gauze pad was then placed on the test site test substance side down. The pad was held in place with non-irritating tape. The trunk of each rabbit was wrapped with porous tape. The tape was farther secured with waterproof tape. The rabbits were returned to their cages after treatment. Three other test substances were tested concurrently on separate, localized test sites on the backs of these rabbits. Approximately 4 hours after application of the test substance, the rabbits were removed from their cages and the wrappings and gauze pads were removed. The test sites were gently washed with warm water to remove excess test substance and gently patted dry. The rabbits were then 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 evidence of dermal effects and were scored according to the Draize Scale (Table 1). A glossary of dermal effects and abbreviations is presented in Table 2. The adjacent areas of the untreated skin were used for comparison. The rabbits were also examined for clinical signs oftoxicity at every dermal evaluation. The rabbits were weighed on the day of treatment and at the last dermal evaluation. RESULTS AND DISCUSSION No dermal irritation was observed in 4 rabbits throughout the study. The remaining 2 rabbits exhibited slight erythema and no or slight edema one hour after test substance removal. No dermal irritation was observed at 24, 48, or 72 hours. No clinical signs oftoxicity were observed, and no significant body weight loss occurred during the study. Individual skin -8- Sampany .Sanitized. Does not contain TSCA cm H-24516: Skin Irritation Test in Rabbits DuPont-6087 irritation scores are presented in Table 3. A summary of skin responses is presented in the following table. SUMMARY OF SKIN RESPONSES TO H-24516 HOURS AFTER TEST SUBSTANCE REMOVAL ERYTHEMA EDEMA RESPONSE 1 24 48 72 1 24 48 72 No Response 4/6 6/6 6/6 6/6 5/6 6/6 6/6 6/6 Slight 2/6 0/6 0/6 0/6 1/6 0/6 0/6 0/6 Mild 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 Moderate 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 Severe 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 CONCLUSIONS Under the conditions of this study, H-24516 was a slight 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-24516 probably should not be classified as an irritant unless additional data proves otherwise. RECORDS AND SAMPLE STORAGE Specimens (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware (formerly known as the E. I. du Font de Nemours and Company Records Management Center). -9- Does not contain T8CA CBI H-24516: Skin Irritation Test in Rabbits DuPont-6087 TABLES .Company Sanitized. Does noS contain TSCA CBI H-24516: Skin Irritation Test in Rabbits DuPont-6087 TABLE 1 DRAIZE3 SCALE FOR SCORING SKIN IRRITATION Evaluation of Skin Reactions Score 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). 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 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) a 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. -ll :----pompany Santeed. u6S^^^-1^ CBI H-24516: Skin Irritation Test in Rabbits DuPont-6087 TABLE 2 GLOSSARY OF DERMAL EFFECTS Blanching Eschar Desquamation Fissuring Fissuring with Bleeding Hyperkeratosis Sloughing Necrosis Epidermal Scaling Thickening Ulceration white appearance to skin scab on the skin that is more superficial than necrosis. This is considered to be severe irritation. dry, flaking of the skin a split or cleft in the top layer of skin without bleeding a split or cleft in the skin with bleeding thick, dry discoloration (usually but not limited to brown or white in color) of the top layer of skin. This is considered to be severe irritation. peeling of the top layer of skin, and epidermal scaling that has detached area of rough/hard/dry black or dark colored skin that may crater. This is considered to be corrosion and an irreversible effect. platelike areas of the top layer of skin that have separated from but are still attached to viable skin. This may progress to sloughing skin is firm and/or dense to the touch. open sore representing loss of superficial tissue ABBREVIATIONS OF OTHER DERMAL EFFECTS - = A = B = C = D = F = G = H = No Effect Abraded Blanching Eschar Desquamation Fissuring Fissuring with Bleeding Hyperkeratosis I Intact L Sloughing N Necrosis R Raw Areas S Epidermal Scaling T Thickening X Compound Adhered to Skin D.------co^TSCACB, pompany sanded. - 12- H-24516: Skin Irritation Test in Rabbits DuPont-6087 TABLE 3 INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS RABBIT NUMBER 34923 34925 34927 34922 34928 34931 HOURS AFTER TEST SUBSTANCE REMOVAL ERYTHEMA EDEMA 1 24 48 72 1 24 48 72 0 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 RABBIT NUMBER 34923 34925 34927 34922 34928 34931 HOURS AFTER TEST SUBSTANCE REMOVAL OTHER DERMAL EFFECTS 1 24 48 72 - - - - - - - - - '- - - - - - - - - - - - - - - Symbols are defined in Table 2. - 13- Company Sanitized. Does not contain TSCA CP'