Document 2RDy3Rv1G7rr3xgGR2MMMEYv7

AR226-2920 FOR DU PONT USE ONLY Copies to: Haskell E. I. du Pant de Nemours and Company Inc. Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box SO Newark, Delaware 19714 HASKELL LABORATORY REPORT NO. HLO-58B-B4 Haskell"NoT" 15.3BB---- Cither lodes Study Initiated/Completed ----6/12/84 - 6/15/84---- f C------P-- _^ Material Submitted by ~^ PoTyBBrr^Hfflrets Department Washington Works SKIN IRRITATION TEST ON RABBITS i' ' . Haskell Evaluation; HaskelliStandard _Qperatina Procedure for skin irritation .t|Hes--ti--ng--w--as----fo--llo--w--ed--U--B--I^^B^B^B^B^MB^K^A^^DTteeotdaitlhse are given in occluded skin the appendix. of six rabbits "^^^^^fflffl^flfffl^B^^^^morerate erythema in five of six rabbits and mild erythema in the _^xttit__Efffects appeared reversible. When tested by this *Purity; Composition ^Synonyms; 1 - 'Company Sanitized. Does not contain TSCA CBl Report by: Carol S. Auletfca/Ira W. Paly Bid/dynamics Inc. Reviewed by: ^ ^ ' ^ n ^ George W. Lovefcfc, M.O. Skin and Eye Studies Coordinator dZ^vjLjL ^f. Kfto^^t \ Gerald L. Kennedy 3lr.l Section Supervisor Acute Investigations Approved by: GWL/egg s^^^/y.Fx^e^ Frank A. Bower Associate Director Date Issued: August 30, 1984 Haskell Lab. Report No. HLO-388-84 Appendix attached: 8 pp, Bio/dynamics Project No. 5228-84 Total pages in this report: 10 2 - ^CompanySanitized. Does not contain TSCA CPU Bio/aynamics 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.O. Box 50, Elkton Road Newark, Delaware 19711 Attn: Date: August 13, 1984 ,.^B5pa^ ^<^. ^ '^ contam T^ ^ ""/^ IIUDlIrM I'tc -1- 5ZZ8-84 I. INTRODUCTION This study was conducted for E.I. duPont de Nemours & 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 Sic/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: Study Monitor (Report Preparation); IV. MATERIALS A. Test Animals: Breed: 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. Donna L. Blaszcak, B.S., AALAS L.A.Tg. 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: Hazleton-Dutchland, Inc. Denver, Pennsylvania iRompanySanitized. Does not contain TSCA CBI IV. MATERIALS (cont.) Number: Age. Meight: (Pretest) Equilibration Period; Husbandry: Housing: Cages: Environmental Conditions: Food: Hater: Identi '''cation: lltljAily. numlru Inr. -2- 5228-84 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 Uo. {HlH) 76-23 Revised 1978. Individually housed Suspended, stainless steel. Temperature: 60-70? is considered an acceptable temperature range for rabbits; room temperature was monitored and recorded twice daily and maintained within this range to the maximum extent possible. Humidity: 30-702 is considered an acceptable humidity 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 libltum. Automatic watering system, ad libltum. Municipal water supply (Ellzabethtown Water Co.) Each animal was Identified with a monel ear tag bearing a unique number prior to testing. FbffipanySanWzea.Does noi confa'n TS^S ^ ^yna.tnica Inv. -3- 5228-84 IV. MATERIALS (cont.) Selection: 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. B. Test Material: HL 15,388 Description: White powder Date of Receipt: May 21, 1984 . Received from: Storage: E.I. duPont de Nemours & Co. Room temperature V. METHODS 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 dipped from the back with an electric dipper, 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, T'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'disruption 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. CennpanySanlffzea. Uses ffof eofflaTn fSCK CCT ._.HIM/t/l,ynHnitcB Inc. 5228-84 VI. EXPERIMENTAL EVALUATION (In-Ufe) 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. t/'ff^(;fiI^^'<;o. k."..--:.; .''ui ;:o'f!(ajri FSCA < "<"/r/iynamica Inf. -5- 5228-84 VII. RESULTS AND DISCUSSION Dermal observations are presented in Table I; the scoring system used is presented in Appendix A. HL 15.388 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. Study Director Manager, Acute Toxicology l-/^/Y T3ate------ -4rLu\-)\-\. hra . Paly^P^.. D.A.B.T. Director of Toxicology ^ / ^ BaTe----r~ Company Sannizea. DoesftolcoWaTnr^-ew -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 Patch Sites & Observation! 24.5 Hours Left Front ER Right Back ED 48 Hours Left Front ER Right Back ED 72 Hours Left Front ER Right Back ED 3&24F 3 2 2 1 1 0 Ant mal Numbier and Sx 3925M 3238F 3M1M ssya'ar'vicr 3 3 2 3 1 2 2 2 2 2 1 1 1 2 1 0 1 2 1 0 1 1 1 0 TO5HT < 9<7fc0r 3 2 1 1 1 0 Scored using scale presented in Appendix A. M-Male F-Female ER-Erythema ED-Edema any SaniHzetl, Does not contain TSCA APPENDIX A ORAIZE1EVALUATION OF DERMAL IRRITATION A-1 5228-84 Dermal Observations Erythema and Eschar Formation (Most severely affected area graded): No erythema..................................................... 0 Very slight erythema (barely perceptible)....................... 1 Well-defined erythema........................................... 2 Moderate to severe erythema..................................... 3 Severe erythema (beet redness).................................. 4 4E Eschar Necrosi f o r m a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4N s...................................................... Edema Formation (Most severely affected area graded): No edema........................................................ 0 Very s1ignt edema (barely perceptible).......................... 1 Slight edema (edges of area well-defined by definite 2 raising)................................................... Moderate edema (raised approximately 1 iron)...................... 3 Severe edema (raised more than 1 mm and extending beyond area of exposure)................................... 4 Braize, J.H. 1959. The Appraisal of Chemicals in Foods, Drugs, and Cosmetics, p. 48. Association of Food and Drug Officials of the United States, Austin, Texas. SfeTiipanSyanIHzed. Does not contain TSCA CBI