Hepatotoxicity of orally and intraperitoneally administered folpet in male rats

An ip LD50 value (68 mg/kg) for folpet, a widely used fungicide, was determined using adult male Sprague-Dawley rats. Next, the compound in sublethal doses was given to the animals orally as well as intraperitoneally (ip), and its effects on the levels of hepatic drug-metabolizing enzymes and serum glutamic oxalacetic transaminase (SGOT) were compared. An ip dose as small as 50 mg/kg was able to significantly alter the levels of these enzymes reflecting on liver damage, while an oral dose up to 10 times the ip dose did not have an appreciable effect on the enzymes and did not cause any visible toxic symptoms in the animals. In vitro incubation of folpet with rat liver microsomes with and without an NADPH-generating system showed that the fungicide may not require metabolism to exert inhibitory effect on the microsomal enzymes. In fact, the data suggest that the parent compound or its nonenzymatic degradation product(s) caused destruction of microsomal cytochrome P-450 in vitro. However, this loss of the hemoprotein by folpet could be prevented by prior addition of reduced glutathione in the incubation media.