LACK OF PROMOTING ACTIVITY OF 4 PESTICIDES ON INDUCTION OF PRENEOPLASTIC LIVER-CELL FOCI IN RATS

Four pesticides were examined for hepatopromoting activity using a med ium-term bioassay based upon induction of glutathione S-transferase pl acental form (GST-P) positive foci in the rat liver. Male F344 rats we re initially injected with diethylnitrosamine (DEN; 200 mg/kg body wei ght) intraperitoneally and 2 weeks later were treated with O-ethyl O-4 -nitrophenyl phenylphosphonothioate (EPN; 75 and 150 ppm), diazinon (5 00 and 1,000 ppm), phenthoate (500 and 1,000 ppm), or iprobenfos (500 and 1,000 ppm) in the diet for 6 weeks and then killed, all rats being subjected to partial hepatectomy at week 3. All of the pesticides gav e negative results, the numbers and areas of GST-P positive foci not e xceeding the control values for animals given DEN alone. Indeed, a sig nificant reduction of foci development was seen for EPN (75 ppm). Thes e findings provide experimental evidence that the presently examined f our pesticides do not have hepatocarcinogenic potential in rats. (C) 1 996 Wiley-Liss, Inc.