Influence of ethanol on the in vivo and in vitro metabolism of nitriles in mice.

The effect of ethanol on metabolism of 20 nitriles was studied in vivo and in vitro in mice. The hepatic microsomal metabolizing activity for nitriles was at a maximum 13 h after ethanol dosing (4.0 g/kg). Using microsomes from mice pretreated with ethanol under the above conditions, enhancement of the in vitro metabolism of nitriles was 1.00-1.83 compared with the glucose-treated control. When mice were orally given nitriles 13 h after dosing with either ethanol (4.0 g/kg) or glucose (7.0 g/kg), the hepatic metabolizing activity of nitriles for the ethanol-treated group was always higher than that for the glucose group, although no change in the content of hepatic microsomal P-450 was observed between the two groups. However, ethanol added to the incubation mixture inhibited the in vitro metabolism of most nitriles. The results in the present study suggest that ethanol can enhance the acute toxicity of nitriles.