Document OOvOeQmvEDv22XGX1wyZ4bVQ

HAZLETON LABOR=CX:41ES APOERICA. INC 3;01KINSMAN BLVD. P.O.BOX 7545 MADISON, WISCONSIN 53707 Chemical& BioMedicalSciencesDivision PHONE (6082)41-4471 TLX 703956HAZRAL MDS UD FINAL REPORT ROGER G. MINNESOTA TOXICOLOGY ST. PAUL, PERKINS MINING & MANUFACTURING SERVICES MN 55101 COMPANY SAMPLE: T-4016 PURCHASE ORDER NUMBER: TB37389-410 712 SAMPLE NUMBER: SAMPLE REPORT ENTERED: PRINTED: 7010031@4 01/07/8/" 02/26.,'e,-@ ENCLOSED: PRIMARY DERMAL IRRITATION RAW DATA APPENDIX STUDY IN RABBITS METHOD, SUMMARY SIGNED: STEVEN STUDY ACUTE M. GLAZ DIRECTOR TOXICOLOGY DATE BY AND FOR HAZLETON LABORATORIES AMERICA, INC. RAW DATA FOR THIS STUDY AMERICA, INC., MADISON, ARE KEPT ON FILE WISCONSIN. AT HAZLETON LABORATORIES HAZLOOCON LA93CX4ATOPIES ANAERICA. INC 1 3301 KINSMAN BLVD. - P.O BOX 754 MADISON. WISCONSIN 5370 b Chemical& BloMedicalSciencesDivision PHONE (608) 241-471 TLX 703956 HAZRAL MDS UD SAMPLE NUMBER: 70100354 SAMPLE: T-4016 PAGE PRIMARY DERMAL IRRITATION Objective: To determine of a test material on the Federal Hazardous the relative level of primary skin irritation rabbits under occluded conditions according to Substances Act Regulations. Test Material: T-4016 Physical Description: Purity and Stability: Thick brown liquid Sponsor assumes responsibility stability determinations. for purity and Test Animal: Young adult rabbits Of the New '(7-ealandWhite procured, maintained individually in 5creen-bottom Cage5 strain were in temperature- and humidity-controlled quarters, provided access to water ad libitum and a measured amount of Purina High Fiber Rabbit Chow, and held for an acclimation period of at least 7 days. Three male and three female acclimated 2738 9, were chosen at random for the animals, weighing test, treated, and from 2414 maintained g to during the observation period as specified for the acclimation Test animals were identified by animal number and corresponding period. ear tag. Approximately twenty-four hours before treatment the hair was clipped from the back and flanks of each animal. Reason for Species Selection: albino rabbit has been the of chemicals on the skin. Historically, the New Zealand animal of choice for evaluating White the effect Preparation received. and Administration of Test The pH Wa5 not determined. Material: The 5ample was dosed as Treatment: Ju5t before the test material was applied, crisscross epidermal abrasions were made on one exposed abraded and one intact test 5itC. to penetrate the stratum corneum, area of each rabbit to provide (The abrasions were sufficiently but not deep enough to penetrate one deep to the dermal layer and cause bleeding.) The test material was applied to the two test site,- on each rabbit in the amount of 0.5 ml per site. Each treated area was covered with a 5.0 x 5.0-cm gauze patch secured with paper tape and overwrapped with Saran Ldrap and Ela5tOpia5t tape to maintain the test material in contact with the skin and decrease the rate of evaporation. Collars were Used to restrain the test animals during the 24-hour exposure period. Reason for Route of Administration: based on the method of Draize. Historically, the route of choice HAZLOTON LMBCnffC)RIES AN*RICA. INC Chemical& BioMedicalSciencesDivision 3301 KINSMAN BLVD. - P.O.BOX 7545- MADISON. WISCONSIN 53707 9 PHONE (6082)41-4471- TLX 703956HAZRAL MDS UD SAMPLE NUMBER: /-0100354 SAMPLE: T-4016 PAGE 3 PRIMARY DERMAL IRRITATION (CONTINUED) Observations: After the exposure period, the patches were removed. The te5t material was removed with acetone and then the te5t 5ite5 were washed U5ing lukewarm tap water and diSP05able paper towels. Care was taken to remove the te5t material 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. A 5econd reading was taken at 72 hours to determine the primary dermal irritation index for the 5ample. Additional obser- vation5 were conducted at 96 hours, and at @ and 14 days. Individual at weekly body weights were taken intervals throughout the Just prior to study study period. initiation and Pathology: At study termination all aniM815 were euthanatized and di5carded. HAZLEOCON LAEK3PATORIES AlvIERICA. INC .301 KINSMAN 3 BLVD. - P.O. BOX 7545 - MADISON, WISCONSIN Chemical& BioMedicalSciencesDivision 53707 - PHONE (608) 241-4471 - TLX 703956 HAZRAL MDS UD SAMPLE NUMBER: SAMPLE: T-4016 70100354 PAGE 4 PRIMAR',r' DERMAL IRRITATION SUMMARY (CONTINUED) Test Animal: Albino Rabbits - New Zealand White Source: Hazleton Research Products., Inc., Denver PA Date Animals Received: 12/16/86 [late Test Started: 01/08.,'8-/7 Date Test Completed: 01/'22/87 Primary Dermal Irritation Scores * Observation Period 6 Rabbit Mean 24 Hours: 72 Hours: 96 Hours: 7 Days: 14 Days: 2.0 1.8 1.4 0.7 o.0 Primary Dermal Irritation Index**: 1.9 The Primary Dermal Irritation Score is the total dermal irritation score for all the animals (erythema and edema) divided by the number of test sites (I'@1) at each observation period. **The Primary Dermal Irritation Index is the 5UM Of the 24 and primary dermal irritation scores, divided by two and rounded nearest tenth. 72-hour to the Comments: Tape or mechanical irritation was observed on the test 5iteS Of two animals. Orie animal exnibited 24 hours and within subcutaneous hemorrnaging within both test sites at the abraded test site at 72 and 96 hours. Slight scab formation was Observed within the abraded test site of this animal at Day 7. Conclusion: primary According to FHSA 5kin irritant. regulations, this test material '15 not a HAZLETON L"gCR=C)RIES APAERICA,Ir,C 3301 KINSMAN BLVD. - P.O.BOX 7545 - MADISON, WISCONSIN 53707 Chemical& B!oMedicalSciencesDivision PHONE (608)241-4471 TLX 703956 HAZRAL MDS UD SAMPLE NUMBER: 70100354 SAMPLE: T-4016 PAGE IF PRIMAR@' DERMAL IRRITATION (CONTINUED) References: 1. Code of Federal Requlation5, Title 16, Section 1500.3: Federal Hazardous Substances Act Regulations, pp. 325-34.1, (January 1, 1985). 2. Draize, J.H., "Appraisal OF the Safety of Chemicals in Food5, Druq5, and Cosmetics - Dermal Toxicity", A550Ci8tion of Food and Druq Officials Of the U.S., pp. 46-59 (1975). 21 CFR 58 (United States Food and Drug Admini5tration'5 3. Good Laboratory Practices Regulations for Nonclinical Laboratory Studies). 4. DHHS Publication No. (NIH 85-23 1985) Guide for the Care and Use of Laboratory Animals. PRn4ARY SKIN IRRITATION SCORING SCALE (1)Erythema and Eachar Formation No arythema 0 Very slight arythema (barely perceptible) 1 Well-defined erythema 2 Moderate to severe erythem 3 Severe erythema (beet redness) to slight eachar formation (injuries in depth) 4 Highest possible erythema score 4 (2)Edema Formation No ed@a 0 Very slight odena (barely perceptible) 1 Slight od@, (edges of area well-defined by definite raising) 2 Moderate edema (raised approximtaly 1 M) 3 Severe edma (raised more than 1 m and extending beyond area of exposure) 4 Highest possible edma score 4 c- Do CO 16 No 16 96 at cc 06 CL 0 fn L Lo oc 9@ol C:31 @oldq @Di Is c c0 Kt .4 C ri - IL 4 a a Al go 10 W'O 16.4 ai 4 16 18 4