Dose-dependent promoting activity of chloroform in rat liver foci bioassay

Chloroform enhances dose-dependently the number of preneoplastic foci in livers of weanling female Sprague-Dawley rats. The preneoplastic foci were induced with a single dose of 8 mg diethylnitrosamine (DEN)/kg body wt. Thereafter chloroform was applied twice weekly for 11 consecutive weeks in doses of 100, 200 and 400 mg/kg body wt, respectively. This treatment raised the number of adenosine-5'-triphosphatase (ATPase)-deficient foci up to 5-fold, that of gamma-glutamyltranspeptidase (GGTase) and glycogen-positive foci 13- and 10-fold, respectively, after 12 weeks; 25 mg caused no effect compared to DEN-treated controls. In contrast, daily doses of chloroform only, 200 and 400 mg/kg body wt for 33 days, and 800 mg/kg body wt for 20 days given to 3-4-week-old female Sprague-Dawley rats did not lead to island formation, measured after 12 weeks, indicating a promoting rather than an initiating potency.