Document dQ9wV1D3YE72kJO4p3DMrL64R

W 1-niS&2C O NkzSra^lj %N!. POST OFFICE FOX 7545 M A D t S O N, W I P 3 7 0 7 - 7 5 4 5 FINAL REPORT A R 2 M -0 3 0 5 Roger G. Perkins, PhD 3M Toxicology Services Building 220-2E-02 St. Paul, MN 55144-1000 HWI Number: 40200469 Study Title: Primary Dermal Irritation/Corrosion Study of T-5898 in Rabbits (OECD Guidelines) Signed: \\\. Steven M. Glaza Study Director Acute Toxicology u 3-^3-^ Date deceived 005788 HWI Number: 40200469 Sample: T-5898 Acute Toxicology Steven M. Glaza Study Director Manager Steven R. Sorenson Study Coordinator Patricia Padgham In-life Supervisor Rose M. Bridge Report Supervisor Page 2 KEY PERSONNEL Laboratory Animal Medicine Cindy J. Cary, DVM Dipl ornate, ACLAM Supervisor CONTENTS Key Personnel Objective Test Material Test System Procedures Summary of Results Discussion References Appendix - Raw Data Page 2 3 3 3 4 6 7 7 8 005789 HWI Number: 40200469 Sample: T-5898 Page 3 OBJECTIVE The objective of this study was to assess the relative level of primary skin irritation/corrosion of a test material on rabbits under semioccluded conditions.1 All procedures used in this study are in compliance with the Animal Welfare Act Regulations. In the opinion of the Sponsor and study director, the study did not unnecessarily duplicate any previous work. TEST MATERIAL Identification The test material was identified as T-5898 and described as a clear, lightyellow liquid. Purity and Stability The Sponsor assumes responsibility for purity and stability determinations (including under test conditions). Storage and Retention The test material was stored at room temperature. Any unused test material will be returned to the Sponsor after issuance of the final report according to Hazleton Wisconsin (HWI) Standard Operating Procedure (SOP). Safety Precautions The test material handling procedures were according to HWI SOPs and policies. TEST SYSTEM Test Animal Adult albino rabbits of the Hra:(NZW)SPF strain were procured from HRP, Inc. and maintained at the Hazleton Wisconsin facility at 3802 Packers Avenue, Madison, Wisconsin. Animal husbandry and housing at HWI comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals".2 The animals were individually housed in screen-bottom cages in temperature- and humidity-controlled quarters, provided access to water ad libitum and a measured amount of Laboratory Rabbit Diet HF #5326, PMI Feeds, Inc., and held for an acclimation period of at least 7 days. The feed is routinely analyzed 005790 HWI Number: 40200469 Sample: T-5898 Page 4 by the manufacturer for nutritional components and environmental contaminants. Samples of the water are periodically analyzed by HWI. There were no known contaminants in the feed or water that would have interfered with or affected the results of the study. Three female acclimated animals, weighing from 2,961 to 3,203 g, were selected and maintained during the study in the same manner as for the acclimation period. If variations from the required temperature and humidity conditions existed, they were documented and considered to have had no adverse effect on the study outcome. Animals were identified by animal number and corresponding ear tag. On the day before treatment, the back and/or flanks of each animal were clipped free of hair to obtain an unblemished skin site. Justification for Species Selection Historically, the New Zealand White albino rabbit has been the animal of choice for evaluating the effect of chemicals on the skin. PROCEDURES Preparation of Test Material The test material was administered as received. The pH of the test material was determined to be 7.6. Treatment The test material was applied to the intact skin on each animal's back (approximate exposure area of 6.25 cm2) in the amount of 0.5 mL. The area of application was covered with a 2.5-cm x 2.5-cm gauze patch secured with paper tape, loosely overwrapped with Saran Wrap, and secured with Elastoplast tape to provide a semiocclusive dressing. Collars were not used to restrain the test animals during the 4-hour exposure period. At the end of the 4-hour exposure period, the patches were removed and the test sites were washed using tap water and disposable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin. Reason for Route of Administration Historically, the dermal route has been the route of choice based on the method of Draize.3 005791 HWI Number: 40200469 Sample: T-5898 Page 5 Observations Approximately 30 minutes after removal of the test material, the degree of erythema and edema at each test site was read according to the Draize technique (recorded as the 4-hour score). Subsequent examinations were made at 24, 48, and 72 hours. The untreated skin of each animal was used for comparison. Animals were weighed just before test material administration. Termination At termination of the experimental phase, all animals were designated to be euthanized and discarded. Statistical Analyses No statistical analyses were required by the protocol. Location of Raw Data. Records, and Final Report The raw data, records, and a copy of the final report will be retained in the archives of HWI in accordance with HWI SOP. 005792 HWI Number: 40200469 Sample: T-5898 Page 6 SUMMARY OF RESULTS Test Animal: Albino Rabbits - Hra:(NZW)SPF Source: HRP, Inc., Kalamazoo, MI Date Animals Received: 02/02/94 Experimental Start Date: 02/21/94 Experimental Termination Date: 02/24/94 Animal Number F49385 F49364 F49398 Individual Dermal Irritation Scores Sex 4 Ervthema 24 48 Hour 72 4 Edema 24 48 F0000000 F0000000 F0000000 72 0 0 0 Average Primary Dermal Irritation Scores* Observation Period (Hour! Average Score 4 0.0 24 0.0 48 0.0 72 0.0 * The average primary dermal irritation score is the total dermal irritation score for all the animals (erythema and edema) divided by the number of test sites (3) at each observation period. 005793 HWI Number: 40200469 Sample: T-5898 Page 7 DISCUSSION Application of T-5898 to the skin of rabbits under 4-hour semioccluded conditions resulted in no dermal irritation. REFERENCES 1. "Acute Dermal Irritation/Corrosion," Organisation for Economic Cooperation and Development's Guidelines for Testing of Chemicals, Section 404 (adopted May 12, 1981). 2. NIH Publication No. 86-23 (revised 1985). 3. Draize, J. H., "Primary Irritation of the Skin," In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity, Association of Food and Drug Officials of the U.S., pp. 46-47 (1959). 005794 HWI Number: 40200469 Sample: T-5898 APPENDIX Raw Data Page 8 005795 PERSONNEL SIGNATURE SHEET ACUTE TOXICOLOGY HWI : 70.2rWi/>9 Name Rose M. Bridge Job Title Report Supervisor Signature Initial es Anthony Cass Cindy J. Cary, DVM Lab Animal Technician Lab Animal Veterinarian Cni>h. nU -4 . ( W Donna 0. Clemons, DVM, MS Lab Animal Veterinarian John A. Disch Lab Animal Caretaker \j U -- . <&<^cA ac CM-- "X Co A3 ` 379 Charles W. Fritz Lab Animal Technician CJ) Kari Garfoot Lab Animal Technician Steven M. Glaza Manager Kevin Grossman Lab Animal Caretaker Jeff Hicks Lab Animal Technician -JZL Sharen L. Howery Research Assistant Wayne A. Madison Supervisor Doug McConnell Lab Animal Technician Eileen McConnell Bud McDonald Albert Oleson Patricia Padgham Staff Assistant Study Coordinator Lab Animal Caretaker In-life Supervisor Mestati' BudP'hmt____ <p*LaHtibQJh" Jo _ _fYZ- Steven R. Sorenson Study Coordinator JS5- Annette R. Turner Staff Assistant Tamra L. Walker Staff Assistant Lana M. Weeden j&fAer M. idthey No.Y'k-f1^ Staff Assistant ^LaSH. Jii. Lah Arrfitd L fD tM j& L - ijv J - Wi\o^\\NAakCarfcVdcer ~~ kJ_A11 (G2/10-06-93) 005796 hui No.-. i J n z m a t i Q DERMAL IRRITATION/BOOY VEI6HT RECORD (4-HOUR EXPOSURE) Test Material: 7 ~ - g a g s ________________________________________ Physical Description: y^ .( l<~ui) U G l O / A Dose: < Q . 5 /uiL Per Site /vJA Moistened with 0.9% Saline; Mfg/Lot No./Exp. Date: _________ [_______ A J A .________ / fJA pH Result: ________with Corning pH Meter No. 05510 Skin Preparation: v^"*' Intact r O A A braded (with a clipper blade) Species/Source Straln/Locatlon: Rabblt/Hra:(NZW)SPF/A// I Date Animals Received: ~7 -- ~> _ C V 4-______ Initiated in Room No.: / Q 3 Technician/Date/T1me Animals Clipped: 12.- 2 0 - Q c J / JCi: 005797 ^ Storage conditions of test material: < XXTl 1 -P.________________________ C A T E j. IG 2.-3Ll-<^4 NA Not applicable. B Blanching. A Subcutaneous hemorrhage. N Possible necrotic area. U Unable to determine pH. * Animal(s) shaved prior to dermal observation by technician. Animals were weighed and appeared normal before test material administration on the day of dosing. Technician/Oate: ^ Surviving animals designated for sacrifice and discard. Technician/Date: QC / (S2/12-09-92) Final data review by/Date: / 2 . - ? is= *4 .7?/ / HWI No.: *-J 2 Q Q l4Cc Primary Dermal Irritation Scoring Scale (Draize Technique) (1) 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) Highest possible erythema score 1--4 CM CO 4 (2) Edema Formation No edema Very slight edema (barely perceptible) Slight edema (edges are well defined by definite raising) Moderate edema (raised approximately 1 mm) Severe edema (raised approximately 1 mm and extending beyond area of exposure) Highest possible edema score (S5/01-07-91) 0 1 2 3 4 4 005798