Document x5w4KNwqbxoBgwy92zp7xVEJy

PROPOSED PROTOCOL SINGLE, MASSIVE, ACUTE VINYL CHLORIDE EXPOSURE The purpose of this experiment is to evaluate the risk of oncogenesis from the exposure of a community containing a spectrum of age groups to a single, massive dose of vinyl chloride that might result from a "worst credible accident" to tank cars or barge transporting vinyl chloride through an urban area. It is proposed to expose rats in the following cate gories to the highest single acute exposure that the most sensi tive members of the exposure groups can tolerate without signi ficant acute mortality. The groups will consist of: E-l -- lactating dams; E-2 -- nursing pups; E-3 -- immature rats of both sexes; E-4 -- young adults of both sexes; E-5 -- pregnant (8-day) females; E-6 -- animals exposed in utero as the fetuses of group E-5. In order to maintain synchrony among the various groups, and thus to minimize the control groups required, it is proposed to start with a colony of synchronously bred females, and to expose selected families from the colony as groups E-l and E-2 one week after whelping. Control group C-l would be ramdomly selected from other members of the colony, and the re mainder of the first generation colony sacrificed after weaning of their pups. CMA102137 2- - All remaining test and control groups would be selected from the second generation animals or their offspring as por trayed schematically on the attached flow sheet. All animals would be observed for the remainder of their normal life spans, and surviving animals then sacrified for histological study. CAM 102138 Colony stock of synchronously bred female rats, to whelp on day "0" 2 4 Group E--1 - 50 first-generation females exposed as lactating dams 100 second-generation rats of each sex exposed as nursing pugg excess pups at weaning p C--1 - 50 first-generation nnexposed females excess dams at weaning of pups T - 100 second-generation rats of each sex exposed as 5-week jjawjfftures Discard excess pups at weaning 4 Group E--4 - 100 second-generation rats of each sex exposed as 2d--week old young adults 14 ill........... ? Group E-5 - 50 second-generation females exposed on eighth day of pregnancy 3 Group E-6 100 third-generation rats of each sex exposed in utero Discard excess pups at weaning Control Group C-2 - 200 second-generation rats of each sex, unexposed controls for exposure groups E-2, E-3, and E-4 2 Control Group C-5 - 50 second-generation bred females V- 8 18 20 22 3 Control Group C-6 - 100 third-generation unexpos rats of each sex excess pups at weaning 34 36 38 40 42 44 CMA 102139 Legend: 1 = time of br time of whelping, 3 = time of weaning, 4 = time of exposure