Document NX5KQM7qe9RQ782Rwvmb0xZb

AR226-3136 DuPont-3606 TRADE SECRET Study Title H-24256: Skin Irritation Test in Rabbits Laboratory Project ID: DuPont-3606 Author: Deborah A. Vick, A.A.S. Study Completed on: November 29,1999 Performing Laboratory: E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 MWork Request Number: Service Code Number: Company Sanitized. Does not contain T SC A C BI Page 1 of 12 H-24256: Skin Irritation Test in Rabbits DuPont-3606 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation o f the data obtained from this study. Review ed b y : ___________C (i 4l'/U <U.^-------------------- Carol Fyilay, B.A. ^ Associate Scientist '2 3 -/1 0 0 -1 1 1 1 Date Issued bv Studv Director: Deborah A. Vick, A.A.S. Associate Scientist Date Company Sanitized. Does not contain T S C A C B I -2 - H-24256: Skin Irritation Test in Rabbits DuPont-3606 TABLE OF CONTENTS Page C E R T IFIC A TIO N .............................................................................................................................. 2 STUDY INFORMATION.................................................................................................................. 4 STUDY PERSONNEL....................................................................................................................... 5 SUMMARY...........................................................................................................................................6 INTRODUCTION............................................................................................................................... 7 MATERIALS AND M ETHODS......................................................................................................7 A. Test Substance...........................................................................................................................7 B. Animal Husbandry................................................................................................................... 7 C. Protocol.................. 8 RESULTS AND DISCUSSION........................................................................................................8 CONCLUSIONS................................................................................................................................. 9 RECORDS AND SAMPLE STORAGE......................................................................................... 9 TABLES.............................................................................................................................................. 10 1. DRAIZE SCALE FOR SCORING SKIN IRRITATION........................................................................................11 2. INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS............ 12 com pany Sanitized. Does not contain T S C A CBl -3- H-24256: Skin Irritation Test in Rabbits STUDY INFORMATION DuPont-3606 Haskell Number: 24256 Stability: The test substance appeared to be stable under the conditions of the study; no evidence o f instability was observed. Sponsor: E. I. du Pont de Nemours and Company Wilmington; Delaware 19898 U.S.A. Study Initiated/Completed: October 19,1999 / (see report cover page) In-Life Initiated/Completed: November 9, 1999 / November 12, 1999 Company Sanitized. Does not contain T S C A CBt -4- H-24256: Skin Irritation Test in Rabbits STUDY PERSONNEL Study Director: Deborah A. Vick, A.A.S. Management: Nancy C. Chromey, Ph.D. Primary Technician: Deborah A. Vick, A.A.S. Toxicology Report Preparation: Bonnie J. Bieber, B.A. Laboratory Veterinarian: Wanda L. West, D.V.M., A.C.L.A.M. DuPont-3606 Company Sanitized. Does not contain T S C A CBi -5- H-24256: Skin Irritation Test in Rabbits DuPont-3606 SUMMARY H-24256 was evaluated for acute skin irritation potential in 6 male New Zealand White rabbits. Approximately 0.5 mL of the test substance was applied to the shaved, intact skin o f each rabbit and covered with a semi-occlusive dressing for a 4-hour exposure. Approximately 1, 24,48, and 72 hours after removal o f the test substance, the test sites were evaluated for erythema, edema, and other evidence o f 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 on the treated rabbits during the study. Three o f the treated rabbits exhibited body weight losses o f up to 3% of the initial body weight by study termination (72 hours). No clinical signs of toxicity were observed in the treated rabbits. Under the conditions o f this study, H-24256 was not a skin irritant. Company Sanitized. Does not contain T S C A CB1 -6- H-24256: Skin Irritation Test in Rabbits DuPont-3606 INTRODUCTION The purpose of this study was to evaluate the skin irritation potential of H-24256 when applied to the shaved, intact skin o f New Zealand White rabbits. MATERIALS AND METHODS A. Test Substance The test substance, H-24256, was supplied by the sponsor a s ; l ^ ^ m ^ T h e test substance appeared to be stable under the conditions o fth ^ s tu a ^ N o evidence o f instability, such as a change in color or physical state, was observed. B. Animal Husbandry Young adult HM:(NZW)fBR 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 a unique identification number which was recorded on a card affixed to the cage. The last 3 digits o f 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 PMI Nutrition International, Inc. Certified High Fiber Rabbit LabDiet 5325 daily during the study. Water was available ad libitum except dining 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. Water samples are periodically analyzed for total bacterial counts and for the presence o f coliforms, lead, and other contaminants. Additionally, samples from freshly washed cages and cage racks are periodically analyzed to ensure adequate sanitation by the cagewashers. Data from this program are maintained separately from study records. Animal feed is certified by the manufacturer to meet specified nutritional requirements and to be free o f a list o f specified contaminants. On the basis o f 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 o f this study. Rabbits were quarantined, weighed, and observed for general health for 11 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 of 20C 1C and relative humidity of 50% 10%. Excursions outside these ranges were judged to have been o f insufficient magnitude and/or duration to have adversely affected the validity of the study. Company Sanitized. Does not contain T S C A CEfl -7 - H-24256: Skin Irritation Test in Rabbits DuPont-3606 C. Protocol On the day 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 o f the back. The body weights o f the rabbits ranged from 2140 to 2485 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. Approximately 0.5 mL of H-24256 was applied directly on the skin beneath a 1-inch, 2-ply 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. One other test substance was tested concurrently on a separate, localized test site 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 comers 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 evidence o f dermal effects and were scored according to the Draize Scale (Table 1). The adjacent areas o f the untreated skin were used for comparison. The rabbits were also examined for clinical signs of toxicity 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 on the treated rabbits during the study. Three o f the treated rabbits exhibited body weight losses o f up to 3% o f the initial body weight by study termination (72 hours). No clinical signs o f toxicity were observed in the treated rabbits. Individual skin irritation scores are presented in Table 2. A summary of skin responses is presented in the following table. RESPONSE No Response Slight Mild Moderate SUMMARY OF SKIN RESPONSES TO H-24256 HOURS AFTER TEST SiUBSTANCE REMOVAL ERYTHEMA ED EMA 1 24 48 72 1 24 48 6/6 6/6 6/6 6/6 6/6 6/6 6/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 0/6 72 6/6 0/6 0/6 0/6 Company Sanllized. D o ss not contain T SC A CB1 H-24256: Skin Irritation Test in Rabbits Severe 0/6 0/6 0/6 0/6 0/6 0/6 DuPont-3606 0/6 0/6 CONCLUSIONS Under the conditions of this study, H-24256 was not a skin irritant. If these test scores are to be used for EEC/OECD classification, according to the guide to the labeling o f dangerous substances published in the Official Journal o f European Communities (EEC Directive 93/21, Annex VI), H-24256 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. Company Sanitized. Does not contain T S C A CB1 -9- H-24256: Skin Irritation Test in Rabbits DuPont-3606 TABLES -10- Comoany Sanitized. Does not conjoin troa,CBl H-24256: Skin Irritation Test in Rabbits DuPont-3606 TABLE 1 DRAIZE3 SCALE FOR SCORING SKIN IRRITATION Evaluation of Skin Reactions Score Erythema and eschar formation: No erythema..................................................................................................................0 Very slight erythema (barely perceptible)................................................................... 1 (Slight) Well-defined erythema.................................................................................................2 (Mild) Moderate to severe erythema........................................................................................................... 3(Moderate) Severe erythema (beet redness) to slight eschar formation (injuries in depth)...... 4 (Severe) Edema formation: No edema............................ 0 Very slight edema (barely perceptible)...................................................................... 1 (Slight) Slight edema (edges o f area well defined by definite raising)..................................2 (Mild) Moderate edema (raised approximately 1.0 mm)....................................................... 3 (Moderate) Severe edema (raised more than 1.0 mm extending beyond the area of exposure).................................................................................................................4 (Severe) Abbreviations of other dermal effects are: - = No Effect I Intact A = Abraded L = Sloughing B = Blanching N = Necrosis C = Eschar R = Raw Areas D ; Desquamation S = Epidermal Scaling F = Fissuring T = Thickening G = Fissuring with Bleeding X = Compound Adhered to Skin H = Hyperkeratosis a Draize, J. H., "Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods. Drugs and Cosmetics The Editorial Committee of the Association o f Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. -11 - Company Sanitized. Does not contain TSC A C B l H-24256: Skin Irritation Test in Rabbits DuPont-3606 TABLE 2 INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS RABBIT NUMBER 34057 34058 34059 34060 34061 34062 HOURS AFTER TESTS UBSTANCE REMOVAL ERYT]HEMA EDEMA 1 24 48 72 1 24 48 72 00000000 00000000 00000000 00000000 0 00 0 0 0 0 0 00000000 # Company Sanitized. Does not contain T S C A CBI - 12-