Document x1drGGG393jprGonamzMmgr11

AR226-2920 FOR DU PONT USE ONLY E. I. du Pant de Nemours end Company Inc. Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark. Delaware 19714 HASKELL LABORATORY REPORT NO. HLO-388-84 Haskell No. 15,305--- Other codes' Study Initiated/Completed ---- 0/12 /3 4 - 6/15/55 Material Subm^ted by sts Department Washington Works SKIN IRRITATION TEST ON RABBITS Haskell Evaluation: testing was followedl erythema in_J|h^^j procedure akelli Standard. terating Procedure for skin irritation rm Details are given in the appendix. was auuiied to the occluded skin of six rabbits , ___Jrate erythema in five of six rabbits and mild Effects appeared reversible. When tested by this .. * i s a moderate skin irritant. Composition ^Synonyma: - 1- . Com pany Sanitized. Does not contain TSCA CBt Report by: Carol S. Auletfca/Ira W. Daly Bio/dynamics Inc. Reviewed by: George W. Lovett, M.D. Skin and Eye Studies Coordinator Gerald L. Kennedy Sr. Section Supervisor Acute Investigations Approved by: GWL/egg Frank A. Bower Associate Director Date Issued: August 30, 1984 Haskell Lab. Report No. HL0-3B8-84 Appendix attached: 8 pp, Bio/dynamics Project No. 5228-84 Total pages in this report: 10 - 2Com pany Sanitized. Does not contain TSCA C rj Bio/clynamics Inc. Division of Biology and Safety Evaluation PROJECT NO.: 5228-84 PRIMARY DERMAL IRRITATION STUDY IN RABBITS (HASKELL SKIN IRRITATION TEST) TEST MATERIAL: HL 15,388 Submitted to: E.I. duPont de Nemours & Co. Haskell Laboratory for Toxicology and Industrial Medicine P.0. Box 50, Elkton Road Newark, Delaware 19711 Date: August 13, 1984 528Jp.aiv. jre=,j!Tti >.*.> ri -i ,ecr-c-lcontain "Ay l l U l l l i c l l l r -1 5228-84 I. INTRODUCTION This study was conducted for E.I. duPont de Nemours 4 Co. to evaluate the primary dermal irritation produced by HL 15,388 in rabbits. The study was performed at Bio/dynamics, Inc., Mettlers Road, East Millstone, New Jersey 08873. This report has been reviewed by the Quality Assurance Unit of Bio/dynamics, Inc. to assure its conformance with the protocol and raw data. All raw data, the original study protocol and final report will be retained on file in the Bio/dynamics Archives. II. DATES OF STUDY Animal Receipt: May 7, 1984 Initiation (Dosing): June 12, 1984 Termination (Last Observation): June 15, 1984 III. STUDY PERSONNEL Study Director: Laboratory Supervisor: Technician-i n-Charge: Carol S. Auletta, B.A., D.A.B.T. Donna L. Blaszcak, B.S., AALAS L.A.Tg. Dawn Areia, B.A., AALAS L.A.T. Study Monitor (Report Preparation): Donna L. Blaszcak, B.S., AALAS L.A.Tg. IV. MATERIALS A. Test Animals: Breed: Albino Rabbits New Zealand White Reason fc * Selection: Standard laboratory animal for dermal irritation studies. The New Zealand White breed was used because of its availability and because of the existing historical data base for comparative evaluation. Supplier: H'azleton-Dutchland, Inc. Denver, Pennsylvania ! IDompany Sanitized. Does not contain TS C A CB! IV. MATERIALS (cont.) Number: Age. Weight: (Pretest) Equilibration Period: Husbandry: Housing: Cages: Environmental Conditions: Food: Water: Identi rication; Six (2 males, 4 females) Young adults 3.0 to 3.2 kilograms 36 days Currently acceptable practices of good animal husbandry were followed, e.g., Guide for the Care and Use of Laboratory Animals; PHEW Publication No. (MiHt 78-23 Revised 1978. Individually housed Suspended, stainless steel. Temperature: 60-70F is considered an acceptable temperature range for rabbits; room temperature was monitored and recorded twice dally and maintained within this range to the maximum extent possible. Humidity: 30-702 is considered an acceptable hunldity range for rabbits; room humidity was monitored and recorded daily and maintained within this range to the maximum extent possible. Light Cycle: 12 hours light, 12 hours dark (controlled by an automatic timer). Lab Rabbit Chow HF (Purina #5326), ad libitum. Automatic watering system, ad libitum. Municipal water supply (Elizabethtown Water Co.) Each animal was Identified with a monel ear tag bearing a unique number prior to testing. Pompany Sanitized. Does no! contain t s c a f'* IV. MATERIALS (cont.) Hii>Aay nttmlcti Inr -3 5228-84 Selection: B. Test Material: Description: Date of Receipt: . Received from: Storage: V. METHODS Animals were randomly placed in cages upon receipt and were placed on study as available at the time of study initiation. Animals considered unsuitable for study because of poor health, unacceptable skin, or outlying body weights were excluded from selection. HL 15,388 White powder toy 21, 1984 E.I. duPont de Nemours & Co. Room temperature A. Preparation of Test Material: The test material was mixed with 0.9* saline to form a slurry. B. Preparation of Animals: On the day before dosing, the hair of each rabbit was closely clipped from the back with an electric clipper, so as to expose the back from the scapular to the lumbar region. The skin remained intact, i.e., no abrasions were made. C. Administration of Test Material: There was one test site on the back of each animal. 0.5 ml of the test material (as a slurry) was applied to each site beneath a surgical gauze square, l"xl", placed directly on the test site and held in place with tape. Plastic sheeting was then wrapped around the animal and secured with tape to retard evaporation and keep the test substance in contact with the skin without undue pressure. Elizabethan collars were then placed on the animals to prevent'd!'sruption of the wrappings and ingestion of the test material. Following approximately 24 hours of exposure, the wrappings and gauze squares were removed and the test sites gently wiped free of excess test material with gauze and water and dried with gauze. Com pany Sanitized. Does no! eoM ain T5C)S C B f AU i i ) d y n a m i c s I n r . 5228-84 VI. EXPERIMENTAL EVALUATION (In-Life) Viability Check: Twice Daily Evaluation of Skin Irritation: 1. Intervals: Approximately 24.5 (30 minutes after removal of wrappings), 48 and 72 hours after administration. 2. Methods: At each interval all sites were evaluated for erythema and edema or other evidence of dermal irritation according to the Draize scoring system (presented in Appendix A). Adjacent areas of untreated skin was used for comparison. Special notation was made of necrosis, eschar, or other evidence of irreversible alteration of tissue structure. Any abnormal pharmacologic or toxic signs were also noted. -5 5228-84 VII. RESULTS AND DISCUSSION Dermal observations are presented in Table I; the scoring system used is presented in Appendix A. HL 15,288 produced moderate to severe but reversible dermal irritation. Most of the animals had moderate to severe erythema with slight edema at 24.5 hours and very slight or well-defined erythema and edema at 48 hours. By the termination of the study (72 hours) most animals exhibited only slight erythema, with little or no edema. Carol S. Auletta, B.A., D.A.B.T. Study Director Manager, Acute Toxicology Date Company Sanitized. Doesliof contain TSfCA eg? -6 5228-84 TABLE I PRIMARY DERMAL IRRITATION STUDY IN RABBITS TEST MATERIAL: HL 15,388 INDIVIDUAL DERMAL IRRITATION SCORES* - 24.5. 48 AND 72 HOURS Time Interval T O kdi 1 ew ai v Observations Animal Number and 3925fT" 3238" J941M Left Front ER Right Back ED 3 2 3 1 3 L 2 p 33 21 2 48 Hours Left Front ER Right Back ED 2 1 2 1 2 c i i 1 0 1 1 72 Hours Left Front ER Right Back ED 1 0 1 1 2 1 i i 0 0 1 0 i ^Scored using scale presented in Appendix A. M-Male F-Female A-l 5228-84 APPENDIX A ORAIZE1 EVALUATION OF DERMAL IRRITATION Dermal Observations Erythema and Eschar Formation (Most severely affected area graded): ........ 0 No erythema........................................... Very slight erythema (barely perceptible)....................... 1 Well-defined erythema...................................... .. 2 Moderate to severe erythema..................................... 3 Severe erythema (beet redness).......................... ^ Eschar formation......................................... 4N Necrosis....................................................... Edema Formation (Most severely affected area graded). .......... 0 No edema............................................. Very slignt edema (barely perceptible).......................... 1 Slight edema (edges of area well-defined by definite raising).......................... ......................... Moderate edema (raised approximately 1 ......................... 2 j Severe edema (raised more than 1 mm and extending ^ beyond area of exposure)................................... >aize J H 1959 The Appraisal of Chemicals in Foods, Drugs, and osifttcs'. p. Association of Food and Drag officials of tha United States, Austin, Texas. Company Sanliized. Does ho! contain TSCA CBI