Document JN0wmM4XXdE1q6e4M0Rnp3zMX

H A L L:-L'-'-L W I@.fl,/ISCONI SIN POST OF@ lf-E rr-,X 7 '@45 1,4A D I S 0 14. W ( F-:,7 (,7 - 7 5 4 5 FINAL REPORT 1-ibcator%,: Roger G. Perkins, PhD 3M Toxicology Services Building 220-2E-02 St. Paul, MN 55144-1000 HWI.Number: 40200469 Stu v Title: PrimaryDermal Irritation/Corrosion Study of T-5898 in Rabbits (OECD Guidelines) Signed: Steven M. Glaza Date Study Director Acute Toxicology FIECEI\/ED -MAR .28 7994 3ivl OX'COLO( o n E! 60 2 4 1 -4 4 7 1 F z, F C@,, F,- F' F' c,'S IV.A I L P) E L I V E R Y: @'3 0 1 1'1 S t@l, N' E; @jI-E A F@,D. 1,@i @i 1 1: @_,i!. 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 Diplomate, ACLAM Supervisor CONTENTS Paqe Key Personnel 2 Objective 3 Test Material 3 Test System 3 Procedures 4 Summary of Results 6 Discussion 7 References 7 Appendix - Raw Data 8 HWI Number: 40200469 Sample: T-5898 Page 3 OBJECTIVE The objectiveof this study was to assessthe relativelevel of primary skin irritation/corrosioonf a test materialon rabbitsunder semioccluded conditions.' All proceduresused in this study are in compliancewith the Animal Welfare Act Regulations. In the opinionof the Sponsor and study director,the study did not unnecessarilyduplicateany previouswork. TEST MATERIAL Identification The.testmaterialwas identifiedas T-5898 and describedas a clear, lightyellow liquid. Purity and Stability The Sponsor assumesresponsibilityfor purity and stabilitydeterminations (includingundertest conditions). Storage and Retention The test materialwas stored at room temperature. Any unused test material will be returnedto the Sponsorafter issuanceof the final report according to Hazleton Wisconsin (HWI) StandardOperating Procedure (SOP). Safety Precautions The test material handling procedureswere according to HWI SOPs and policies. TEST SYSTEM Test Animal Adult albino rabbitsof the Hra:(NZW)SPFstrainwere 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 LaboratoryAnimals".' The animals were individuallyhoused in screen-bottomcages in temperature-and humidity-controlledquarters, provided access to water ad 7ibitum and a measured amount of Laboratory Rabbit Diet HFID#5326, PMI Feeds, Inc., and held for an acclimationperiodof at least 7 days. The feed is routinelyanalyzed HWI Number: 40200469 Sample: T-5898 Page 4 by the manufacturerfor nutritionalcomponentsand environmentalcontaminants. Samples of the water are periodicallyanalyzed by HWI. There were no known contaminantsin the feed or water that would have interferedwith or affected the resultsof the study. Three female acclimatedanimals,weighing from 2,961 to 3,203 g, were selected and maintainedduring the study in the same manner as for the acclimation period. If variationsfrom the requiredtemperatureand humidityconditions .existed,they were documented and considered to have had no adverse effect on the study outcome. Animals were identifiedby animal number and corresponding ear tag. On the day before treatment,the back and/orflanks of each animal were clippedfree of hair to obtain an unblemishedskin site. Justificationfor Species Selection Historically,the New Zealand White albino rabbit has been the animal of choice for evaluatingthe effect of chemicalson the skin. PROCEDURES Preparationof Test Material- The test materialwas administeredas received. The pH of the test material was determined to be 7.6. Treatment The test materialwas appliedto the intact skin on each animal's back (approximateexposurearea of 6.25 cm2) in the amount of 0.5 mL. The area of applicationwas covered with a 2.5-cm x 2.5-cm gauze patch secured with paper tape, loosely overwrappedwith Saran WrapO, and secured with ElastoplastOtape to provide a semiocclusivedressing. Collarswere not used to restrainthe test animals during the 4-hour exposureperiod. At the end of the 4-hour exposure period, the patches were removed and the test sites were washed using tap water and disposablepaper towels. The test materialwas removed from the test sites as thoroughlyas possiblewithout irritatingthe skin. Reason for Route of Administration Historically,the dermal route has been the route of choice based on the method of Draize.3 HWI Number: 40200469 Sample: T-5898 Page 5 Observations Approximately30 minutesafter removalof the test material,the degree of erythema and edema at each test site was read accordingto the Draize technique (recordedas the 4-hour score). Subsequentexaminationswere made at 24, 48, and 72 hours. The untreatedskin of each animalwas used for comparison. Animals were weighed just before test material administration. Termination At terminationof the experimentalphase, all animalswere designatedto be euthanized and discarded. StatisticalAnalyses No statisticalanalyseswere requiredby the-protocol. Location of Raw Data, Records, and Final Report The raw data, records,and a copy of the final reportwill be retained in the archives of HWI in accordance with HWI SOP. 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 IndividualDermal IrritationScores Animal Number Sex Erythema 24 48 Hour 7@ 4 Edema 24 48 72 F49385 F 0 0 0 0 0 0 0 0 F49364 F 0 0 0 0 0 0 0 0 F49398 F 0 0 0 0 0 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 observationperiod. HWI Number: 40200469 Sample: T-5898 Page 7 DISCUSSION Applicationof T-5898 to the skin of rabbits under 4-hour semioccluded conditionsresultedin no dermal irritation. REFERENCES 1. "Acute Dermal Irritation/Corrosion," Organisation for Economic Cooperation and Deve7opment's Guidelines for Testing of Chemicals, Section 404 (adoptedMay 12, 1981). 2. NIH PublicationNo. 86-23 (revised1985). 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). HWI Number: 40200469 Sample: T-5898 APPENDIX Raw Data Page 8 PERSONNEL SIGNATURE SHEET ACUTE TOXICOLOGY HWI: qD2.COqL Name Job Title sbli"natunei Rose M. Bridge Report Supervisor Anthony Cass Lab Animal Technician C" Cindy J. Cary, DVM Lab Animal Veterinarian V.CANAA, Donna J. Clemons, DVM, MS Lab Animal Veterinarian John A. Disch Lab Animal Caretaker CharlesW. Frit'z Lab Animal Technician CIL4,& V, q,.a, Kari Garfoot Lab Animal Technician Anh-; v4n@A ietn@.+ Steven M. Glaza Manager Kevin Grossman Jeff Hicks Lab Animal Caretaker PAj.:"L Lab Animal Technician C2 Sharen L. Howery Research Assistant Wayne A. Madison Supervisor (Al Doug McConnell Lab Animal Technician Liz. A Eileen McConnell Staff'Assistant Bud McDonald Study Coordinator Albert Oleson Lab Animal Caretaker Patricia Padgham In-lifeSupervisor Steven R. Sorenson Study Coordinator Annette R. Turner Staff Assistant Tamra L. Walker Staff Assistant Lana M. Weeden Staff Assistant Initials C, W@k,\ (G2/10-06-93) %wall, HWINo.:6t2L2" KRNAL IRRITATION/MWDETIGHTRECORD(4-MM EMSME) TestMaterial: PhysiDceaslcriptrito@n-:-.aje Dose: ll.n &&L- PerSite it!& Moistenedwith 0.9% Saltne; Mfg/Lot No./Exp.Date: bjA pH Result: -).C-b with Corning pH Meter No. 05510 Skin Preparation:v-**@Intact Species/SourceStrain/Location: Rabbit/Hra:(NZW)SPFIA,41 Date Animals Received: 2- - 2- -ck4 Technician/Date/TimeAnimals Clipped: /.2 - 2-C) -qc4 io: 32- le,-iij) t-10.,.Abrade(dwith a Initiatedin Room Animal Ntmber/Sex E!A InitialBody Weight (g)_ Day 7 Body Weight (g) Observations Technician Recorded By Date M2 *I ------ Scale 1.-,q Irr 4 Hour Erythem Edema LI'll 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Erythema C) Edema 0 Erythema Edema o@ Eryth@ C) Edema C> Erythema Edema Erythema Edema C) C) C) 0 n0 ac C)CL o. Storage conditionsof test material: P-t-A*-Jad :Z3EZ&,&.delz@ NA Not applicable. B Blanching. A Subcutaneous hemorrhage. N Possible necroticarea. U Unable to determine pH. Animal(s) shaved prior to dermal observationby technician. Animals were weighed and appeared normal before test material administrationon the day of dosing. Technictan/Date: Surviving animals designatedfor sacrifice and discard. TechnicIan/Date: CXC /g-91-9y-- (S2/12-09-92) Final data review by/Date: -7,V HWINo.: 402JO014(49 PrimaryDermalIrritationScoringScale (DraizeTechnique) (1) Erythema and Eschar Formation No erythema 0 Very slight erythema (barely perceptible) 1 Well-defined erythema 2 Moderate to severe erythema 3 Severe erythema (beet redness) to slight eschar formation(injuriesin depth) 4 Highest possible erythema score 4 (2) Edema Formation No edema 0 Very slight edema (barely perceptible) I Slight edema (edges are well defined by definiteraising) 2 Moderate edema (raised approximately I mm) 3 Severe edema (raised approximately 1 mm and extending beyond area of exposure) 4 Highest possible edema score 4 (S5/01-07-91)