The rat liver foci bioassay: I. Age-dependence of induction by vinyl chloride of ATPase-deficient foci.

The age-dependence of the induction of pre-neoplastic enzyme-altered hepatic foci was investigated. Rats were exposed (8 h/day, 7 days/week) to 2000 p.p.m. vinyl chloride (VC) either 'transplacentally' (exposure of pregnant females), or immediately after birth for different time intervals (5, 11, 17, 47, 83 days) or from an age of 7 or 21 days onwards. The animals were then kept without further treatment; livers were evaluated for ATPase-deficient foci at the age of 4 months. 'Transplacental' exposure and exposure from day 1 through 5 caused no increase over controls in ATPase-deficient foci, probably due to the lack of hepatocellular proliferation and the low rate of VC metabolism at this developmental stage. However, foci area was steeply increased when newborn rats were exposed for 11 and 17 days; but this was not further enhanced by a 47- or 83-day exposure. Only a few ATPase-deficient foci occurred when exposure started 21 days after birth. Exposure of adult rats did not result in more ATPase-deficient foci than were seen in untreated controls; control values could not be increased by a preceding partial hepatectomy. The results indicate that the induction of pre-neoplastic hepatocellular lesions in rats by VC is restricted to a well defined period (approximately day 7-21) in the early lifetime of the animals. This period of highest sensitivity is characterized by the beginning of rapid liver growth.