Lack of enhancing effects of fenvalerate and esfenvalerate on induction of preneoplastic glutathione S-transferase placental form positive liver cell foci in rats

Abstract

The modifying effects of fenvalerate and esfenvalerate administration on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given fenvalerate at dietary levels of 1500, 500, 150, 50 and 15 parts per million (ppm), esfenvalerate at 500 ppm, or 2-acetylamino-fluorene (2-AAF) at 200 ppm and sodium phenobarbital (PB) at 500 ppm as positive controls for 6 weeks. At week 3 following DEN administration, all animals were subjected to partial hepatectomy. Prominent neurologic signs and moderate retardation of body weight were observed in the groups given 1500 ppm fenvalerate and 500 ppm esfenvalerate, although no adverse effects on survival were evident. While statistically significant increases in relative liver weights were noted in rats given fenvalerate at doses of 1500 or 500 ppm, no toxic hepatocyte lesions were found. Neither fenvalerate nor esfenvalerate significantly increased the numbers or areas of glutathione S-transferase placental form (GST-P) positive liver cell foci observed after DEN initiation, in clear contrast to the positive controls, 2-AAF and PB. The results thus demonstrated that fenvalerate and esfenvalerate are non-toxic for rat hepatocytes and lack modifying potential for liver carcinogenesis in our medium-term bioassay system.