Document Y7ObGDNjvL9rXD5D2KOqEXv0

HAZLOTON LABCFUCCRiEs APAERICA. INC. 3301 KINSMAN BLVD. P.O.BOX 7545 MADISON, WISCONSIN 53707 Chemical& BloMedicalSciencesDivision PHONE (608)241-4471 TLX 703956HAZRAL MOS UD FINAL REPORT JANINE GLEASON MINNESOTA MINING & MANUFACTURING TOXICOLOGY SERVICES ST..PAUL, MN 55101 COMPANY SAMPLE: T-3752 PURCHASE ORDER NUMBER: T357842p REL. 4@513 SAMPLE NUMBER: SAMPLE ENTERED: REPORT PRINTED: 50503500 05/15/85 06/21/85 e ENCLOSED: PRIMARY DERMAL IRRITATION QAU REPORT RAW DATA APPENDIX METHOD, SUMMARY SIGNED: .. .......... STEVEN M. GLAZA' STUDY DIRECTOR ACUTE TOXICOLOGY ........(C.)..... DATE ....... BY AND FOR HAZLETON LABORATORIES AMERICA, INC. RAW DATA FOR THIS STUDY AMERICA, INC., MADISON, ARE KEPT ON FILE WISCONSIN. AT HAZLETON LABORATORIES HAZLOTON LAECXRMXX41EB ARIERICA. INC. Chemical& BioMedicalSciencesDivision 3301 KINSMAN BLVD. * P.O.BOX 7645 0 MADISON, WISCONSIN 53707 o PHONE (608)241-4471a TLX 703956HAZRAL MDS UD SAMPLE NUMBER: 50503500 SAMPLE: T-3752 PAGE 2 OECD SKIN IRRITATION Objective: To determine the relative level of primary skin irritatio n of a test material on rabbits under 5emioccluded conditions according to the Organi5ation of Economic Cooperation and Development's Guidelines for Testing Chemical5, Section 404, Acute Dermal Irritation/Corrosion, adopted May 12, 1981. Test Material: T-3752 Physical Description: Purity and Stability: Brown granular solid Sponsor has purity and on f i 1a., 5tability determinations Test Animal: Young adult rabbits (approximately 14 weeks of age) of the New Zealand White strain were procured, maintained individually in screen-bottom cages in temperature- and humidity-controlled quarters, provided continuous access to Purina High Fiber Rabbit Chow and water, and hold for an acc.limation period of at*lea5t 7 days. Three acclimated animals, weighing from 2212 to 2323 g, were chosen at random for the te5t., treated, and maintained during the observation period as specified for the acclimation period. Test animal5 were identified by animal number and corresponding ear tag. Approximately twenty-four hours before treatment the hair was clipped from the back of each animal. Reason.for Species Selection: albino rabbit has been the of chemicals on the skin. Hi5torically, the New Zealand animal of choice for evaluating White the effect Preparation received. and Administration of Test Material: The sample was dosed as Treatment: Th e test material rabbit in the' amount of 0.5 The treated area was covered was applied to the intac-t skin of each g per site and moistened with 0.9% 5aline. with a 2.5 x 2.5-cm gauze patch secured with paper to provide tape and overwrapped with a semiocclu5ive dressing.. Saran Wrap and Elastopla5t tape Collars were applied to restrain the test animal5 for the 4-hour exposure period. (@v:)HAZLEZON LAECF%MTLRIEB AIVERICA. INC. Chemical& BloMedicalSciencesDivision 3301 KINSMAN BLVD. o P.O.BOX 7MS - MADISON, WISCONSIN 53707 - PHONE (608)241-4471o TLX 703956HAZRAL MDS UD SAMPLE NUMBER: 50503500 SAMPLE: T-3752 PAGE 3 OECD SKIN IRRITATION (CONTINUED) Observations: After the exposure period, the patches were removed. The test sites were washed using lukewarm tap water and.di5po-sable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin. Thirty minutes following removal of the test material, the degree of erythema and edema was read according to the Draize* technique. Subsequent examinations were made at 2411 48 and 72 hours after patch removal. Individual body weights were taken just prior to study initiation. Pathology: At-5tudy termination all animal5 were euthanatized and discarded. *Draize, J. H., "Appraisal of The Safety of Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity." A550Ciation of Food and Drug Officials of the U.S.,, Topeka, Kansas, pp. 461-59 (1959). HAZLOMON LAECNMORIES AKAERICA, INC. 3301 KINSMAN BL.I;Da. P.O.SO)t7545 MADISON, WISCONSIN 53707 Chemical& BloMedicalSciencesDivision PHONE (608)241-4471 TLX 703956HAZRAL MDS UD SAMPLE NUMBER: 50503500 SAMPLE: T-3752 PAGE 4 OECD SKIN IRRITATION SUMMARY (CONTINUED) Test Animal: Albino Rabbits - New Zealand White Source: Hazleton Research Products, Inc., Denver PA Date Animals Received: 05/21/85 Temperature and Humidi ty of Animal Room: 21 - 23 Degrees C.; 46 - 64% Relative Humidity Date Test Started: Vehicle: Moistened 05/29/85 Date Test Completed: with 0.9% saline 06/01/85 Animal Number F08693 F08704 F08690 Mean Individual Test Dermal Materia Irritation 1': T-3752 Scores Erythema Score Hours 4 24 48 72 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Edema Score Hours 4 24 48 72 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 .0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Primary Dermal Irritation Scores Observation Period 3 Rabbit Mean 4 Hours: 24 Hours: 48 Hours: 72 Hours: 0.0, 0.0 0.0 0.0 Results: No dermal irritation was observed at any time during the 5tudv period. Deviation from the protocol: The test material was moistened with 0.9% saline rather than deionized water as stated in the protocol. This deviation is not considered to have had an effect on the validity of the study. (VDHAZLOZON LABCFUCMRIEB AF.AERICA. INC. 3301 KINSMAN BLVD. 9 P.O.BOX 7545 MADISON, WISCONSIN 53707 Chemical& BloMedicaSlciencesDivision PHONE (6082)41-4471 TLX 703966HAZRAL MDS UD SAMPLE NUMBER: 50503500 SAMPLE: T-3752 PAGE 5 OECD SKIN IRRITATION (CONTINUED) References: 1. Organisation for Economic Cooperation and Development's Guidelines for Testing of Chemicals, Section 404, Acute Dermal Irritation/ Corrosion, adopted May 12., 1981. 2. Draize, J.H., '.'Apprai5alof the Safety of Chemicals in Foods, Drugs, and Cosmetics - Dermal Toxicity", Association of Food and Drug Officials of the U.S., Topeka, Kansas, pp. 46-59 (1959). PAGE 6 QUALITY,ASSMANCE STATEMENT Primary Dermal Irriiation Study in Rabbits Study No. 50503500 The report as herein attacbed.for the above-mentioned study has been reviewed by the assigned Quality Assurance Unit of Bazleton Laboratories knerica- Inc. in accordance with the-Good Laboratory Practice Regulations as set forth in 21 CPR 58.35 (b) (6) (7).. It has been found to'accuriltelyidentify And/or describe the authorized methods and standard operating procedures followed in the conduct of the study and that the reported data accurately reflect tba-raw . data of.the laboratory study. Furthermore, the Qmality Assurance Unit has conducted the following inspectiono*of the testing facilitiesutilizedin the conduct of this study and.bas submitted written reports of said inspections.,to. the study director.and/ot usima'gamimt.. Date-of inspection 5/21-23/85 6/10/85 Type-of Inspection Process AuditReport Review Date Issued to Management 5/23/85 6/10/85 Diana E. SkiLlitzky/ Inspector, Quality Assurance Unit Date. 6,05-,c3>57co PRIMARY SKIN IRRITATION SCORING SCALE (1) Erythema and Eachar Formation No erythems 0 Very slight crythema (barely perceptible) I Well-defined erythema 2 Moderate to severe erythems 3 Severe orythema (beet redness) to slight exchar formation'(injuriesin depth) 4 Highest possible arythema score 4 (2)Edema Formation No edema Very slight edema (barely perceptible) Slight edema (edges of area vell-defined by definite raisitkg) 2 Moderate edema (raised approximately 1 m) 3 Severe edema (raised more than 1 mm and extending beyond area of exposure) 4 Highest possible edema score 4 Test Compound: 0.6 Date Animle Receiveds note Animals clippedt Skin Preparation$ 1'ml Numberl$*AF6- milial ftdy Weiakt (1) Pseerrivoadties grftb@ 4 Hours Ed@ ECIL" 24 lhours Edam licytb@ 0 411Hours Hours 19tyLbom gdmo 96 Houra 7 Days llama cryth@ gde@ '17 I DayBodyWeight "A - Not applitaiia. A - StsbcuLaneous bmmrrmg*. 6 - slancisioir. " - Possiblenecroticowes. P-firo$2cK P-,Crc c 1&qm IRIMT DGML IRRITATION STUDI e)2%4 Sources-t+47,lfkitabi Techo CK Initiatebdy: ikewlew4bys ULA Umbers Resott: All@. Rom Ombe.ir Y, Bceo.rded locksiciam by CK c le- Reviewd by: Date& HAZLrz'CDNLABORATORIES 3301 KINSMAN BLVD. P.O. BOX 7545 AMERICA, INC. MADISON, Wi 53707 (608)241-4471 TLX 703956 HAZRAL MDS UD PROTOCOL TP2011 Primary Dermal Irritation Study in Rabbits (OECD Guidelines) Study No. 50503500 t@' till A Y I 4- for 3M St. Paul, Minnesota' by Hazleton Laboratories America, Life Sciences Division 3301 Kinsman Boulevard Madison, Wisconsin 53704 Inc. May 21, 1985 1985, Hazleton Laboratories America, Inc. Chemical & BioMedical Sciences Division PROTOCOL TP2071 Primary Dermal Irritation Study in Rabbits (OECD Guidelines) Study No. Study Location 50503500 Hazleton Laboratories .4merica, Inc. Life Sciences Division 3301 Kinsman Boulevard Madison, Wisconsin 53704 Test Material T-3752 Sponsor's Representative Study Director Janine Gleason Steven M. Glaza Proposed Timetable Starting Date Completion Date Final Report Date Week of May 27, 1985 Week of May 27, 1985 Week of June 24, 1985 OBJECTIVE The objective of this study is to determine the relative level of primary skin irritation of a test material on rabbits under semioccluded conditions. All aspects of this study will conform to the Organisation for Economic Cooperation and Development's Guidelines for Testing Chemicals, Section 404, Acute Dermal Irritation/Corrosion, Adopted May 12, 1981 1 and the Principles 2 of Good Laboratory Practice. All procedures will be done according to Hazleton Laboratories America, Inc. (HU) Standard Operating Procedures (SOPS) referenced in this protocol. TEST MATERIAL Test Material: Physical Description: Purity and Stability: T-3752. Brown granular solid. Sponsor has purity and stability determinations on file. Storage Conditions: Store at room temperature. Test Material Retention: Any unused test material will be returned to the Sponsor'30 days after issuance of the final report*. Safety Precautions: Laboratory personnel will take-the normal necessary precautions in handling a substance of unknown toxicity. Laboratory clothing, latex gloves, safety glasses, and a particle mask approved for toxic dusts must be worn. TEST SYSTEM Test Animal Young adult albino rabbits of either sex of the New Zealand White strain, approximately 14 weeks of age, will be obtained from Hazleton Research 2 Products Inc., Denver, Pennsylvania. An adequate number of extra animals will be purchased so that no animal in obviously poor health is placed on test. Historically, the New Zealand White albino rabbit has been the animal of choice for evaluating the effect of chemicals on the skin. Acclimation Upon receipt, the animals will be taken to a designated animal room where they will be acclimated for at least 1 week before being placed on test (OP-GENB 36). During acclimation, the animals will-be examined for clinical abnormalities indicative of health problems (e.g., diarrhea, ectoparasites, rough hair coat, nasal or ocular discharge, evidence of injury, etc.). Any animals regarded as unsuitable for study purposes because of poor physical condition will not be released from acclimation and the reason(s) will be documented. Identification Each animal in the study will be assigned a permanent identification number and will*be identified with a metal ear tag (OP-GENB 24). All data collected from an animal will be recorded and filed under its identification number. Housing and Maintenance The following environmental conditions will be maintained in the animal room used for this study (OP-TARC 230). 0 Temperature: 21*C +20 0 Relative humidity: 50% +20% 0 Air change: At least 10 changes an hour of filtered 100% outsiae air 0 Light cycle: 12 hours light/12 hours dark 3 Temperature and humidity will be monitored throughout the study. Variations from prescribed environmental conditions will be documented. Animal husbandry and housing at HLA comply with standards outlined in the 3 "Guide for the Care and Use of Laboratory Animals." Care will be taken to ensure that the animals are not disturbed for reasons other than data collection and routine maintenance. The animals will be housed individually in screeri7bottomstainless steel cages (heavy gauge) held on racks, with absorbentpan liners in the urine- and feces-collectingpans. Pan liners will be changed at least three times each week. Feed and water will be provided ad libitum. The diet will be Purina High Fiber Rabbit Chow. No contaminants are expected to be present in the feed or water which would interfere and affect the results of the study. Study Design Three rabbits will be selected at random based upon health and a body weight of 2.0-3.5kg. Each animal will serve as its own control. PROCEDURES Preparation and Administration of Test Material Twenty-fourhours prior to test material administration,the hair will be clipped from the back and flanks of each animal. The treatment-siteswill be inspected for interferinglesions, irritation,or defects that would preclude the use of any of the animals. 2 The test material will be applied to the test area (approximately6 cm on each rabbit, in the amount of 0.5 g and will be moistened with deionized water.. The treated area will be covered with a 2.5-cm x 2.5-cm gauze patch 4 secured with paper tape and loosely overwrapped with Saran Wrap and Elastoplast tape to provide a semiocclusivedressing. Collars will be used to restrain the animals during the 4-hour exposure period. Reason for Route of Administration 4 Historically,the route of choice based on the method of Draize. Ob servations After the 4 hours of exposure the patches and the test material will be removed as thoroughly as possible.using water or an appropriate solvent without irritatingthe skin. Thirty minutes after removing the patches, the degree of erythema and edema will be recorded.according to the Draize Technique (Attachment 1). Subsequent readings will be taken at 24, 48, and 72 hours after patch removal. Further observations may-be recorded, as necessary,to establishreversibility. If irritationis increasingin severity at the 72-hour examination period, observationswill be repeated at 96 hours and at 7 and 14 days, if applicable. Body weights will be taken just prior to test material administration and at weekly intervals during the study. observations and body weights will be recorded in the study notebook. Pathology All animals, whether dying on test or sacrificedat study termination, will be discarded. 5 Report The final report will present a descriptionof the test material, a descriptionof the test system, dates of study initiationand termination,a tabulationof irritationdata, and a descriptionof any toxic effects other than dermal irritation. Maintenance of Raw Data and Records Original data or copies thereof will be available at HLA to facilitate auditing the study during its progress and prior to acceptance of the final report. When the final report is completed,all original paper data, as well as the final report, will be retained in the archives of HLA, Madison, Wisconsin (OP-GEN 44). REFERENCES 1. "Acute Dermal Irrita-tion/Corrosion",OECD Guidelines for Testing Chemicals, Section 404, May 12, 1981. 2. Or ganisation for Economic Cooperation and Development's Principles of Good Laboratory Practice, Annex 2, 1981. 3. DHEW Publications No. (NIB) 78-23 (1978). 4. Draize, J. H., "Dermal Toxicity," Upra3.sal_of the Safety of Ch micals in Foods, Drugs, and Cosmetics, Association of Food and Drug officials of the U.S., Topeka, Kansas, pp. 4tt-.)t9l959). 6 PROTOCOL APPROVAL .Jhs;@*eGleason Spo@hhor's Representative 3M Steven M. Glaza Study Director Group Leader, Acute Toxicology Hazleton Laboratories America, Inc. (1108S/tji) Date Date ATTACHMENT I PRIMARY SKIN IRRITATION SCORING SCALE 1. Erythema and Eschar Formation 0 No erythema 1 Very slight erythema (barely perceptible) 2 Well-defined erythema 3 Moderate to severe erythema Severe erythema (beet redness) to slight eschar formation 4 (injuries in depth) 4 Highest possible erythema score 2. Edema Formation 0 No edema 1 Very slight edema (barely perceptible). Slight edema (edges of area well-defined by definite raising) 2 3 Moderate edema (raised approximately 1 mm) Severe edema (raised more than 1 mm and extending beyond 4 area of exposure) 4 Highest possible edema score