Effect of dosing vehicle on the toxicity and metabolism of unsaturated aliphatic nitriles

The effect of dosing vehicle on toxicity and metabolism of unsaturated aliphatic nitriles was investigated in male Sprague-Dawley rats. Five unsaturated aliphatic nitriles--acrylonitrile, methacrylonitrile, allylnitrile, crotononitrile and fumaronitrile--were prepared in five different dosing vehicles--saline, corn oil, safflower oil, mineral oil, olive oil and Tween-20. Groups of six male rats were given 0.5 LD50 doses of the nitriles by gavage and they were observed for 12 It for cholinomimetic and central nervous system effects. Cyanide and glutathione levels were determined in blood and various organs at 1, 3 and 6 h after nitrile administration and thiocyanate levels were determined at 6 h after nitrile administration. The results indicate that all the vehicles studied potentiated the toxicity of all the nitriles compared to nitriles administered in saline and significantly increased their metabolism to cyanide and thiocyanate and nitrile-induced depletion of glutathione in rats. This behavior of vehicles illustrates the difficulty of identifying suitable vehicles for administration of lipophilic compounds in toxicology studies.