Document rpxr7wBLbzyk709mYQ8v6pp3q

HAZLETON l a b o r a t o r ie s AMERICA, in c . fyH 2 2 G '0 2 ^ 3 Chemical & BioMedical Sciences Division 3301 KINSMAN BLVD. P.0. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD FINAL REPORT JANINE GLEASON MINNESOTA MINING & MANUFACTURING COMPANY TOXICOLOGY SERUICES ST. PAUL, MN 55101 SAMPLE: T-3752 PURCHASE ORDER NUMBER: T357842, REL. #513 si'fU! \ SAMPLE NUMBER: 50503500 SAMPLE ENTERED: 05/15/85 REPORT PRINTED: 06/21/85 ENCLOSED: PRIMARY DERMAL IRRITATION - METHOD, SUMMARY QAU REPORT RAW DATA APPENDIX SIGNED STEUEN M. GLAZA STUDY DIRECTOR ACUTE TOXICOLOGY O ..................... DATE BY AND FOR HAZLETON LABORATORIES AMERICA, INC. RAW DATA FOR THIS STUDY ARE KEPT ON FILE AT HAZLETON LABORATORIES AMERICA, INC., MADISON, WISCONSIN. 001061 HAZLETON LABORATORIES AMERICA, INC. Chemical & BioMedical Sciences Division 3301 KINSMAN BLVD. P.O.BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD SAMPLE NUMBER: 50503500 SAMPLE: T-3752 PAGE 2 OECD SKIN IRRITATION Objective: To determine the relative level of primary skin irritation of a test material on rabbits under semioccluded conditions according to the Organisation of Economic Cooperation and Development's Guidelines for Testing Chemicals, 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 stability determinations on file. 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 held for an acclimation period of at least 7 days. Three acclimated animals, weighing from 2212 to 2323 g, were chosen at random for the test, treated, and maintained during the observation period as specified for the acclimation period. Test animals were identified by animal number and corresponding ear tag. Approximately twenty-four hours before treatment the hair was clipped from the back of each an ima1. Reason 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. Preparation and Administration of Test Material: The sample was dosed as received. Treatment: The test material was applied to the intact skin of each rabbit in the amount of 0.5 g per site and moistened with 0.9% saline. The treated area was covered with a 2.5 x 2.5-cm gauze patch secured with paper tape and overwrapped with Saran Wrap and Elastoplast tape to provide a semiocclusive dressing. Collars were applied to restrain the test animals for the 4-hour exposure period. 001062 H A Z i e t o r c LABORATORIES AMERICA, INC. Chemical & BioMedical Sciences Division 3301 KINSMAN BLVD. P.O. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD SAMPLE HUMBER: 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 disposable 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 24, 48 and 72 hours after patch removal. Individual body weights were taken just prior to study initiation. Pathology: At study termination all animals were euthanatized and discarded. *Draize, J. H., "Appraisal of 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). 001063 ^ H A ZLETO N ____________ Chemical & BloMedlcal Sciences D.vtsion 3301 KINSMAN BLVD. P.0. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD SAMPLE NUMBER: 50503500 SAMPLE: T-3752 PAGE 4 OECD SKIN IRRITATION (CONTINUED) SUMMARY Test Animal: Albino Rabbits - New Zealand White Source: Hazleton Research Products, Inc., Denver PA Date Animals Received: 05/21/85 Temperature and Humidity of Animal Room: 21 - 23 Degrees C .j 46 - 64Si Relative Humidity Date Test Started: 05/29/85 Date Test Completed: 06/01/85 Jehicle: Moistened with 0.99i saline An ima 1 Number F08693 FQ8704 FO8690 Mean Individual Dermal Irritation Scores Test Material': T-3752 Erythema Score Hours 4 24 48 72 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 0.0 0.0 0.0 0.0 0.0 0.0 o o 0.0 0.0 0.0 O o 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 ResuIts: No dermal irritation was observed at any time during the study period. Deviation from the protocol: The test material was moistened with 0.99i 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. 0 1 0 8 4 HAZLETON LABORATORIES AM ERICA, INC. Chemical & BioMedical Sciences Division 3301 KINSMAN BLVD. * P.0. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD SAMPLE NUMBER: 50505500 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., "Appraisal of 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). 001065 PAGE 6 ' QUALITY ASSURANCE STATEMENT Primary Dermal Irritation Study in Rabbits Study No. 50503500 The report as herein attached for the above-mentioned study has been reviewed by the assigned Quality Assurance Unit of Hazleton Laboratories America Inc. in accordance with the Good Laboratory Practice Regulations as set forth in 21 CFR 58.35 (b) (6) (7). It has been found to accurately identify and/or describe the authorized methods and standard operating procedures followed in the conduct of the study and that the reported data accurately reflect the raw data of the laboratory study. Furthermore, the Quality Assurance Unit has conducted the following inspections of the testing facilities utilized in the conduct of this study and has submitted written reports of said inspections to the study director and/or management. Date of Inspection 5/21-23/85 6/10/85 Type of InspectionProcess Audit Report Review Date Issued to Management 5/23/85 6/10/85 \ Diana E. Skalitzky/ && Inspector, Quality Assurance Unit Date 001066 o 3s& PRIMARY SKIN IRRITATION SCORING SCALE (1) Erythema and Eschar Formation No erythema Very slight erythema (barelyperceptible) Well-defined erythema Moderate to severe erythema Severe erythema (beet redness) to slight eschar formation (injuries in depth) Highest possible erythema score 0 1 2 3 4 4 (2) Edema Formation No edema Very slight edema (barely perceptible) Slight edema (edges of area well-defined by definite raising) Moderate edema (raised approximately 1 mm) Severe edema (raised more than 1 mm and extending beyond area of exposure) 0 1 2 3 __4 Highest possible edema score 4 / *01067 O Test Compound: 3 -} S o i o,*s __ Q : -$ . f it k Date Antisala Received: S " " ! ~ $ f T Dale Animals Clipped! 5 ~ 3 % Skin Preparation: In _____ PRIMARY DERMAL IRRITATION STUDY BLA Number: S < 0 5 ~ d > 3 S 'O Q . Vehicle: QSbC ffln i U n iA UJiib P *" ! _ f J & Source: b t 'Z .lt.-h o rt P fo d u iJ-f* toosi tomber: f (p /* 3 ________________ Tech: C- M . Initiated by: /* bate: f T j/ 3 ^ / ^ T . '__________ Reviewed by: '______ Dale: ^ / Q .et^ 'S S _. NA - Not applicable. A - Subcutaneous hemorrhage. I - Blanching. N - Possible necrulic area. (T)rt+stj t-Cfoil CK 5-31-1$ & error S'-il-SS" Reviewed by: Dale: 6r5 *S . 142VW 890T00 H A Z L E T O N LABORATORIES AMERICA, INC. 3301 KINSMAN BLVD. P.O. BOX 7545 MADISON, Wl 53707 (608) 241-4471 TLX 703956 HAZRAL MDS UD PROTOCOL TP2071 Primary Dermal Irritation Study in Rabbits (OECD Guidelines) Study No. 50503500 MAY 2 41385 ** Hl\Ar / /ri for 3M St. Paul, Minnesota by Hazleton Laboratories America, Inc. Life Sciences Division 3301 Kinsman Boulevard Madison, Wisconsin 53704 May 21, 1985 0 1985, Hazleton Laboratories America, Inc. Chemical & BioMedical Sciences Division 001069 1 PROTOCOL TP2071 Primary Dermal Irritation Study in Rabbits (OECD Guidelines) Study N o . Study Location 50503500 Hazleton Laboratories America, 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 2 7, 1985 Week of May 27, 1985 Week of June 24, 1985 001070 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^ and the Principles 2 of Good Laboratory Practice. All procedures will be done according to Hazleton Laboratories America, Inc. (HLA) Standard Operating Procedures (SOPs) referenced in this protocol. TEST MATERIAL Test Material: T-3752. Physical Description: Brown granular solid. Purity and Stability: 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 t` 0 1 0 7 1 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). o Temperature: 21C +2 o Relative humidity: 50% +20% o Air change: At least 10 changes an hour of filtered 100% outside air o Light cycle: 12 hours light/12 hours dark 001072 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 screen-bottom stainless steel cages (heavy gauge) held on racks, with absorbent pan liners in the urine- and feces-collecting pans. 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 2.0-3.5 kg. Each animal will serve as its own control. PROCEDURES Preparation and Administration of Test Material TVenty-four hours prior to test material administration, the hair will be clipped from the back and flanks of each animal. The treatment sites will be inspected for interfering lesions, irritation, or defects that would preclude the use of any of the animals. 2 The test material will be applied to the test area (approximately 6 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-cra x 2.5-cra gauze patch 001073 4 secured with paper tape and loosely overwrapped with Saran Wrap and Elastoplast tape to provide a semiocclusive dressing. 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 irritating the 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 establish reversibility. If irritation is increasing in severity at the 72-hour examination period, observations will 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. Pa thology All animals, whether dying on test or sacrificed at study termination, will be discarded. 001074 5 Report The final report will present a description of the test material, a description of the test system, dates of study initiation and termination, a tabulation of irritation data, and a description of 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 Qiidelines for Testing Chemicals, Section 404, May 12, 1981. 2. Organisation for Economic Cooperation and Development's Principles of Good Laboratory Practice, Annex 2, 1981. 3. DHEW Publications No. (NIH) 78-23 (1978). 4. Draize, J. H., "Dermal Toxicity," Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics, Association of Food and Drug Officials of the .S., Topeka, Kansas, pp. 46-59 (1959). 001075 6 PROTOCOL APPROVAL G X qa Jdniie Gleason Sponsor's Representative 3M Steven M. Glaza Study Director Group Leader, Acute Toxicology Hazleton Laboratories America, Inc (1108S/tji) 5 lu k < ^ Date > 1 Date S -'Z-lL-'g.S 001076 ATTACHMENT I PRIMARY SKIN IRRITATION SCORING SCALE 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 2. Edema Formation No edema Very slight edema (barely perceptible) Slight edema (edges of area well-definedby definite raising) Moderate edema (raised approximately 1 mm) Severe edema (raised more than 1 mm and extending beyond area of exposure) Highest possible edema score 0 1 2 3 _4_ 4 0 1 2 3 _4_ 4 001077