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 effectof vinyl chloride (VC) hepatocellular ATPase-deflcient fociwere evaluated after subchronic exposure of newborn rats. Wistarrats 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-deficientfoci were quantitated. For a subsequent investigation lowerdose range groups of female and male Wistar and Sprague-Dawleyrats 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 lastedfor 3 weeks. After cessation of exposure the animals were maintainedfor 10 weeks without further treatment until ATPase-deflcientfoci were quantitated. Both sets of experiments revealed a straightlinear relationship between the dose of VC and the % foci areainduced. Within the dose range investigated, no obvious thresholdfor the induction of pre-neoplastic foci by VC was observed.