Document DDexdQObEGK9BKYOYYY5v5E1d

D u P o n t-1 139 AR226-3099 Ijll TRADE SECRET Study Title H-23269: S kin Irritation Test in Rabbits Laboratory Project ID: D uPont- 1139 A u t h o r : Carol Finlay, B.A. Stud y C o m pl e t e d o n : July 21,1998 P e r f o r m in g L a b o r a t o r y : 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 gom pany ST--aBrnii PoesBajcm aain. TSCGB1 Page 1 o f 12 H-23269: Skin Irritation Test in Rabbits DuPont-1139 CERTIFICATION I, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Issued by: * $LtL-t /}.L< Carci Finlay, B.$. Toxicology Associate Study Director i/u h f -Date Company Sanitized. Does not contain TSCA CBi H-23269: Skinlm tation Test in Rabbits STUDY INFORMATION Substance Tested- Synonvms/Codesr H-23269 Haskell Number: j f 3269 Submitter's Notebook NnmherAiy Composition DuPont-1139 1 Known ImpuritiesPhysical Characteristics: White fabric SM aiitt: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. -Bonson E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Compaq TSCACB --* H-23269: Skin Irritation Test in Rabbits STUDY INFORMATION (CONT.) Study Initiated/Completed: June 8, 1998 / (see report cover page) In-Life Mtiated/Comnleted: June 9, 1998 / June 12, 1998 DuPont-1139 Company Sanitized. Does not contain TSCA CBI * H-23269: Skin Irritation Test in Rabbits ----- ----------------------------------------- --------------- ----------- ------------------------------------- ,, _ A1 DuPont-1139 STUDY PERSONNEL Study Director: Carol Finlay, B.A. - Management: Judith C. Stadler, Ph.D. Primary Technician: Carol Finlay, B.A. Toxicology Report Preparation: Bonnie J. Bieber, B.S. Laboratory Veterinarian: Charles E. Cover, V.M.D. Company Sanitized. D oes not contain TSCA CBI 5 H-23269: Skin Irritation Test in Rabbits -- ---------------------- ------------------- -- ---------------_______ _______ ____________________________ _ _ ,, D u P o n t- 1 139 SUMMARY W3S evaluf ted for acute sldn ^ ^ 0 1 1 potential in 6 male New Zealand White rabbits. H-23269 was tested dry and wet on intact and abraded skin. An approximately 1-inch square o f the test substance was applied directly on the skin beneath a 1-ply 1-inch gauze square that was held m place with non irritating tape 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 o f untreated skin were used for comparison. Noi dermal hritation was observed on any test site during the study. No clinical signs o f toxicity or body weight losses were observed during the study. Under the conditions o f this study, H-23269 was not a skin irritant. Company Sanitized. not aomssn TSCA CBi H-23269: Skin Irritation Test in Rabbits DuPont-1139 INTRODUCTION The purpose o f this study was to evaluate the skin irritation potential o f H-23269 when applied to the shaved, intact or abraded skin o f New Zealand White rabbits. MATERIALS AND METHODS A. Animal Husbandry Youngadult maleHM:(NZW)fBR New Zealand White rabbits were received from Hare " 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 o f each rabbit's ear with a water insoluble marker. The rabbits were offered approximately 125 grams o f PMI 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 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 of 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 13 days. This exceeded the laboratory standard o f approximately 1 week because the rabbits were not released from quarantine as early as they could have been. Animal rooms were maintained on a timer controlled, 12-hour light/12-hour dark cycle. Environmental conditions o f the rooms were targeted for a temperature o f 20C 1C and relative humidity o f 50% 10%. Excursions outside these ranges were judged to have been o f insufficient magnitude and/or duration to have adversely affected the validity o f the study. , B. Protocol On the day prior to treatment, the hair o f 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 2108 to 2296 grams on the day of treatment. Company Sanitized. Does not contain TSCA CBS _7 . " " H-23269: Skin Irritation T est in Rabbits DuPont-1139 H-23269 was tested dry and wet on intact and abraded skin. Deionized water was used to thoroughly moisten the samples that were tested wet. Each rabbit was placed into a stock which had been fitted with a piece o f 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. The 2 test sites on one side o f the rabbits were abraded by gently dragging the abrader across the skin. No bleeding was observed. The 2 test sites on the other side o f the rabbits remained intact. An approximately 1-inch square o f H-23269 was applied directly on the skin beneath a 1-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. No other substances were tested on the backs o f these rabbits. Approximately 4 hours after application o f the test substance, the rubber sheeting was loosened, and the skin at the comers o f 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 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 o f toxicity at every dermal evaluation. RESULTS AND DISCUSSION No dermal irritation was observed on any test site during the study. No clinical signs o f toxicity or body weight losses were observed during the study. Individual skin irritation scores are presented in Tables 2 through 5. A summary o f skin responses is presented in the following table. SUMMARY OF SKIN RESPONSES TO H-23269 RESPONSE No Response ERY1'HEMA 1 hour 24 hours 48 hours 72 hours 6/6 6/6 6/6 6/6 ED EMA 1 hour 24 hours 48 hours 72 hours 6/6 6/6 6/6 6/6 CONCLUSIONS Under the conditions o f this study, H-23269 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 Company Sanitized. Does not contain TSC CBS -8 - H-23269: Skin Irritation Test in Rabbits DuPont-1139 (EEC Directive 93/21, Annex VI), H-23269 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 Pont de Nemours and Company Records Management Center). Gm apm sg Saroiiaesk. DaesnaLeonfain.TS9CA.CjBI -9 - H-23269: Skin Irritation Test in Rabbits DuPont-1139 I II ' ,) TABLE 1 DRAIZE3SCALE 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 erythem a..................................................... Severe erythema (beet redness) to slight eschar formation (injuries in depth). 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Edema formation: No edem a................ ............................................................. Very slight edema (barely perceptible)............................................ Slight edema (edges o f area well defined by definite raising)............... Moderate edema (raised approximately 1.0 m m )..................................... Severe edema (raised more than 1.0 mm extending beyond the area o f exposure).......................................................................... 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other dermal effects are: - - No Effect L = Sloughing A = Abraded N = Necrosis B = Blanching R = Raw Areas C = Eschar S = Epidermal Scaling D = Desquamation SN = Superficial Necrosis F = Fissuring T = Thickening G = Fissuring with Bleeding X = Compound Adhered to Skin I = Intact 3 J` H >"Dermal Toxicity." Appraisal of the Safety of Chemicals in Foods. Drugs and ftemrtir. 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 INTACT SKIN/SAMPLE TESTED DRY RABBIT NUMBER 32921 32922 32923 32926 32927 32928 ... 1 0 0 10 0 0 0 H 0U RS AFTER TEST SUBSTANCE REM OVat ERYTHEMA 24 48 72 1 000 0 ..... 0 . . 0 a 0 0000 0 0 h0 0 00 0 0 0 0 o 10 EDEMA 24 48 00 00 00 0 10 00 00 ' 72 0 G 0 0 o 0 TABLE 3 INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS INTACT SKIN/SAMPLE TESTED WET RABBIT NUMBER 32921 32922 32923 32926 32927 32928 .. h o u r s AFTER TEST SUBSTANCE REMOVA T. ERYTHEMA EDEMA 1 24 48 72 1 24 48 72 0000 0000 0000 0 0 0 0 0 000 0 0 0 0 0000 0000 0000 00 00 00000000 Company Sanitised. Does not contain TS C A C B f H-23269: Skin Irritation Test in Rabbits DuPont-1139 TABLE 4 INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS ABRADED SKIN/SAMPLE TESTED DRY RABBIT NUMBER 32921 32922 32923 32926 32927 32928 HOURS AFTER TEST SUBSTANCE REMOVAT. ERYTHEMA EDEMA 1 24 48 72 1 24 48 72 00000000 0 0 . .0 0 0 0 0 0 0000 0 00 0 0 0 0 r0 0 0 0 0 000 0 0 00 0 000 0 00 0 0 TABLE 5 ") INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS ABRADED SKIN/SAMPLE TESTED WET RABBIT NUMBER 32921 32922 32923 32926 32927 32928 HOURS AFTER TEST SUBSTANCE REMOVAL ERYTHEMA EDEMA 1 24 48 72 1 24 48 72 00000000 00000000 00000000 00000000 00000000 00000000 f tip t S u m ! Bern noteonMn TSCACffl