Document ez9YLZMX2YYZa9JKXkYRYj4g

AR226-3111 TRADE SECRET Study Title H-23746 and H-23747: Skin Irritation Test in Rabbits Laboratory Project ID: DuPont-1977 AUTHOR: Carol Finlay, B.A. STUDY COMPLETED ON: January 25, 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 ^""""^""^"-"""".a.nTS^CB, Pagel of 12 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of the data obtained from this study. ,. FillibenDate Reviewed by:^lULUl Q. ^JLJUb<^ ]jTracyA. Toxicology Associate ^-J^l - tW ^ Issued by Study Director: _____^ <jL/lfrf^ ^.[A^_________ Carol ffinlay, B.A.JDate Toxicology Associate 't6 6-^\ - j^l<? Company SanHteed. Doe. no. contain TSCA CBI -2- H-23746 and H-23747: Skin Irritation Test in Rabbits STUDY INFORMATION Substance 11 li il nBll^^B^J Synonyms/Codes: H-23746 Haskell Number: 23746 Submitter's Notebook Number(s):i Composition DuPont-1977 D Known Impurities Physical Characteristics: Khaki fabric Substance Tested: Synonyms/Codes: H-23747 Haskell Number: 23747 Submitter's Notebook Number(s): Composition: Known Impurities: Physical Characteristics: Khaki fabric Stability: The test substances appeared to be stable under the conditions of the study; no evidence of instability was observed. Company Sanitized. Does not contain TSCA CB8 -3- STUDY PERSONNEL Study Director: Management: Primary Technician: Carol Finlay, B.A. Judith C. Stadler, Ph.D. Carol Finlay, B.A. Toxicology Report Preparation: Amy L. Williamson Laboratory Veterinarian: Wanda L. West, D.V.M., A.C.L.A.M. r^"-^ 5- SUMMARY H-23746 and H-23747 were evaluated for acute skin irritation potential in 6 male New Zealand White rabbits. An approximately 1-inch square of each test substance was applied directly on the skin on opposite sides of each rabbit beneath a 4-ply, 1-inch gauze square. The gauze square was held in place with non irritating tape for a 4-hour exposure. Approximately 1, 24,48, and 72 hours after test substance removal, 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-23746 produced slight erythema in 1 rabbit by 1 hour after test substance removal. No dermal irritation was observed in the remaining 5 rabbits. At 24 hours, no dermal irritation was observed in 4 rabbits, and slight or mild erythema was observed in 2 rabbits. At 48 hours, no dermal irritation was observed in 4 rabbits, and slight erythema was observed in 2 rabbits. At 72 hours, no dermal irritation was observed in 5 rabbits, and slight erythema and desquamation were observed in 1 rabbit. No edema was observed. H-23747 produced no dermal irritation by 1 hour after test substance removal. At 24 and 48 hours, no dermal irritation was observed in 4 rabbits, and slight or mild erythema was observed in 2 rabbits. The rabbit that exhibited mild erythema also exhibited mild and slight edema at 24 and 48 hours, respectively. At 72 hours, no erythema was observed in 4 rabbits, slight or mild erythema was observed in 2 rabbits, and desquamation was observed in 2 rabbits. No edema was observed in 5 rabbits. No clinical signs oftoxicity were observed. One rabbit exhibited weight loss of approximately 2% of initial body weight by study termination (72 hours). Under the conditions of this study, H-23746 and H-23747 were both mild skin irritants. gonyuay ttnttfeed. Do-- not contain TSCA CBI -6- INTRODUCTION The purpose of this study was to evaluate the skin irritation potential ofH-23746 and H-23747 when applied to the shaved, intact skin of New Zealand White rabbits. MATERIALS AND METHODS A. 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 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, Inc. Certified High Fiber Rabbit LabDiet 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. Water samples are periodically analyzed for total bacterial counts and for the presence ofcoliforms, 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 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 12 days. Animal rooms were maintained on a timer-controlled, 12-hour light/I 2-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. B. 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 of the back. The body weights of the rabbits ranged from 2298 to 2520 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 -7- Compay Sanitized. Does not contain TSCACBI during that time did not have access to food or water. Both test substances were thoroughly moistened with deionized water prior to treatment. An approximately 1-inch square ofH-23746 and H-23747 was applied directly to the skin on opposite sides of each rabbit beneath a 4-ply, 1-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. One other substance was tested on a separate, localized test site on the backs of 2 of these rabbits. Approximately 4 hours after application of the test substances, 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. 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 of dermal effects and were scored according to the Draize Scale (Table 1). The adjacent areas of the untreated skin were used for comparison. The rabbits were also examined for clinical signs oftoxicity at every dermal evaluation. RESULTS AND DISCUSSION H-23746 produced slight erythema in 1 rabbit by 1 hour after test substance removal; no dermal irritation was observed in the remaining 5 rabbits. At 24 hours, no dermal irritation was observed in 4 rabbits, and slight or mild erythema was observed in 2 rabbits. At 48 hours, no dermal irritation was observed in 4 rabbits, and slight erythema was observed in 2 rabbits. At 72 hours, no dermal irritation was observed in 5 rabbits, and slight erythema and desquamation were observed in 1 rabbit. No edema was observed. H-23747 produced no dermal irritation by 1 hour after test substance removal. At 24 and 48 hours, no dermal irritation was observed in 4 rabbits, and slight or mild erythema was observed in 2 rabbits. The rabbit that exhibited mild erythema also exhibited mild and slight edema at 24 and 48 hours, respectively. At 72 hours, no erythema was observed in 4 rabbits, slight or mild erythema was observed in 2 rabbits, and desquamation was observed in 2 rabbits. No edema was observed in 5 rabbits. No clinical signs oftoxicity were observed. One rabbit exhibited weight loss of approximately 2% of initial body weight by study termination (72 hours). Individual skin irritation scores are presented in Table 2. A summary of skin responses is presented in the following table. "D -8- Compwy Sanitized. Does not contain TSCACBl SUMMARY OF SKIN RESPONSES TO H-23746 HOURS AFTER TEST SUBSTANCE REMOVAL ERYTHEMA EDEMA RESPONSE 1 24 48 72 1 24 48 72 No Response 5/6 4/6 4/6 5/6 6/6 6/6 6/6 6/6 Slight 1/6 1/6 2/6 1/6 0/6 0/6 0/6 0/6 Mild 0/6 1/6 0/6 0/6 0/6 0/6 0/6 0/6 SUMMARY OF SKIN RESPONSES TO H-23747 HOURS AFTER TEST SUBSTANCE REMOVAL ERYTHEMA EDEMA RESPONSE 1 24 48 72 1 24 48 72 No Response 6/6 4/6 4/6 4/6 6/6 5/6 5/6 6/6 Slight 0/6 1/6 1/6 1/6 0/6 0/6 1/6 0/6 Mild 0/6 1/6 1/6 1/6 0/6 1/6 0/6 0/6 CONCLUSIONS Under the conditions of this study, H-23746 and H-23747 were both mild skin irritants. 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-23746 and H-23747 probably should not be classified as an irritant unless further 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). ^^,S.n^--------c>.."T3CACB. 9- 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) Abbreviations of other dermal effects are: - = No Effect I A = Abraded L B = Blanching N C = Eschar R D = Desquamation S F = Fissuring T G = Fissuring with Bleeding X H = Hyperkeratosis Intact Sloughing Necrosis Raw Areas Epidermal Scaling Thickening Compound Adhered to Skin 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. Company Sanitized. Does not contain TSCA CBI 10- TABLE 2 INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS H-23746 RABBIT NUMBER 33292 33296 33299 33300 33301 33304 HOURS AFTER TEST SUBSTANCE REMOVAL ERYTHEMA EDEMA 1 24 48 72 1 24 48 72 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 0 0 0 1 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 RABBIT NUMBER 33292 33296 33299 33300 33301 33304 HOURS AFTER TEST SUBSTANCE REMOVAL OTHER DERMAL EFFECTS 1 24 48 72 - - - - - - - - - - - - D - - - - - - - - - - - Symbols are defined on page 10. Company Sanitized. Does not contain TSCA CBI 11 - TABLE 2 (CONT.) INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS H-23747 RABBIT NUMBER 33292 33296 33299 33300 33301 33304 HOURS AFTER TEST SUBSTANCE REMOVAL ERYTHEMA EDEMA 1 24 48 72 1 24 48 72 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 2 1 0 2 1 0 0 0 0 2 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 RABBIT NUMBER 33292 33296 33299 33300 33301 33304 HOURS AFTER TEST SUBSTANCE REMOVAL OTHER DERMAL EFFECTS 1 24 48 72 - - - - - - - - - - - - D - - - D - - - - - - - Symbols are defined on page 10. iCompaBySan-ttzecf. Does nrtf e^ff-h TCA Cff^ 12- Sponsor: E. I. du Font de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: December 14,1998 / (see report cover page) In-Life Initiated/Completed: December 15,1998/'December 18, 1998 Sanmze<*. Ooe. not contain TSCA CBI Company -4-