Comparison of 14- and 90-day tests in rats for liver enlargement and stimulation of drug-metabolizing enzymes induced by the agricultural fungicide EL 241

Abstract

The relationship between liver enlargement and stimulation of hepatic drug-metabolizing enzymes was studied after feeding various dietary concentrations of the agricultural fungicide EL 241 [α,α-bis( p-chlorophenyl)-3-pyridinemethanol] to weanling male rates for 14 or 90 days. The dietary concentrations of EL 241 ranged from 15 to 2500 ppm. Weight gain was not affected unless the dietary concentration exceeded 200 ppm. Concentrations of 30–200 ppm increased the rate of p-nitroanisole O-demethylation in proportion to the log dose. Above 200 ppm, there was no further increase. Liver weight was increased by dietary concentrations greater than 50 ppm. Although the absolute liver weight reached a maximum at 310 ppm, the relative liver weight (g liver/100 g body weight) increased in proportion to the log dose throughout the dose range. The concentration of microsomal protein was increased in all animals that had an increased rate of p-nitroanisole metabolism. Except for the magnitude of the changes, the doseresponse relationships for induction of liver enlargement and stimulation of drug-metabolizing enzymes were comparable after either a 14- or 90-day treatment period.