The rat liver foci bioassay: II. Investigations on the dose-dependent induction of ATPase-deficient foci by vinyl chloride at very low doses.

In order to study the dose-dependence of the genotoxic effect of vinyl chloride (VC) hepatocellular ATPase-deficient foci were evaluated after subchronic exposure of newborn rats. Wistar rats were exposed from day 1 after birth over 10 weeks to 10, 40, 70, 150, 500 and 2000 p.p.m. VC (8 h/day; 5 days/week). One week after cessation of exposure hepatic ATPase-deficient foci were quantitated. For a subsequent investigation lower dose range groups of female and male Wistar and Sprague-Dawley rats were exposed (8 h/day; 5 days/week) to 2.5, 5, 10, 20, 40 and 80 p.p.m. VC. Exposure started at day 3 of life and lasted for 3 weeks. After cessation of exposure the animals were maintained for 10 weeks without further treatment until ATPase-deficient foci were quantitated. Both sets of experiments revealed a straight linear relationship between the dose of VC and the % foci area induced. Within the dose range investigated, no obvious threshold for the induction of pre-neoplastic foci by VC was observed.