Document JaZerLVMrMv4DxNmZxx2wdGa

Huntingdon Life Science - 18 April 1997 Ms. Wendy Sherman Chemical Manufacturers Association Chemstar Department 1300 Wilson Boulevard Arlington, VA 22209 RE: Huntingdon Life Sciences Study No. 98-4080; Vinyl Chloride Combined Inhalation TwoGeneration Reproduction and Developmental Toxicity Study in CD Rats: Progress Reports Reproduction and Developmental Phase. Dear Ms. Sherman, Enclosed are progress reports for the reproduction and developmental phases of the referenced study. As I indicated this afternoon, I will be out next week but if you need additional information on for these reports please call Mr. Gary Hoffman (908) 873-2550 Ext 2920 and he should be able to help you. Best Regards Raymond E. Schroeder, M.S., D.A.B.T. Study Director Enclosures cc: Mr. Gary Hoffman (Huntingdon Life Sciences) Huntingdon Life Sciences Inc. PO Box 2360, Mettlers Road, East Millstone. NJ 08875-2360 USA. Tel. +1 908 873 2550 Fax- +1 908 873 3992 CMA 118580 5 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats 1 Progress Report Reproduction Phase In this study, parental (P1,P2) generation animals (30/sex/group) are being treated via whole-body inhalation to vinyl chloride at exposure levels of 0, 10, 100 and 1100 ppm. The study is currently in the gestation/lactation periods of the PI parental generation to produce the FI litters. These animals have completed a 10 week premating treatment period (exposures were 6 hrs/day, 5 days/week - January 7 March 18, 1997) and a 20 day mating period (exposure 6 hrs/day, 7 days/week - March 18 - April 6, 1997). Once mated, females were treated 6 hrs/day from Days 0-20 of gestation and females delivering litters will be treated from Days 4-25 of lactation). Following is a timetable for key events through the remainder of the study. Event Proposed Date P2 premating treatment period (6 hrs/day, 5 days/week): Initiate Complete May 20, 1997 July 29, 1997 Mating period P2 - F2 litters (6 hrs/day, 7 days/week): Initiate Complete July 29, 1997 August 12, 1997 Gestation/Lactation of F2 litters Initiate Complete July 30, 1997 September 23, 1997 Sacrifice Schedule: PI Males PI Females P2 Males P2 Females April 28 & 29, 1997 May 19 & 20, 1997 September 15 & 16, 1997 September 24 & 25, 1997 Submission of the audited draft report Week of March 23, 1998 Study Comments: The start of the study was delayed by approximately two months from the contract date (anticipated start October 28, 1996). Animals for the study (PI) arrived December 23, 1996. This delay was attributed to the following: additional time required to set up the chamber generation system (test material in a one ton cylinder arrived September 19, 1997) and monitor for leaks; GLP characterization of the lot of test material received; and calibration of the gas chromatograph for the periodic monitoring of the exposures concentrations for comparison with the infrared spectrophotometer (MIRAN) results. Mating period was extended by six days to achieve more matings. CMA 118581 2 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats Progress Report Developmental Phase In this study, mated rats (24/group) were treated with vinyl chloride via whole-body exposure (6 hrs/day) over the Day 6-19 gestation period (day of mating evidence = Day 0 of gestation). Body weight, food consumption and clinical findings were recorded periodically throughout gestation. Animals were sacrificed on Day 20 of gestation and corpora lutea/uterine implantation data recorded. Fetuses were weighed, sexed and given a gross external examination. One-half of the fetuses in each litter were evaluated for visceral malformations/variations (microdissection procedure) and the remaining fetuses are being stained with Alizarin Red S for skeletal examination. Females were given a gross postmortem examination and liver, kidney and gravid uterine weights recorded. Gross lesions, kidneys and liver tissue were taken and preserved. Exposures and the Day 20 gestation maternal sacrifices have been completed for the developmental phase. Dates for these events are as follows: Mating imitated: March 12, 1997 Treatment period (Days 6-19 of gestation, 6 hrs/day): March 19 - April 10, 1997 Maternal Day 20 gestation sacrifices: April 2-11, 1997 Submission of the audited draft final report: Week of August 25, 1997 Study comments: Animals in the developmental phase were exposed along with the animals in the reproduction phase of the study. The fetal evaluations are on-going. Title: For: Raymond E. Schroeder, M.S., DABT Study Director Huntingdon Life Science Inc. CMA 118582