Acrylonitrile: in vivo metabolism in rats and mice.
Acrylonitrile (VCN) is metabolized to cyanide in rats and mice. Cyanide levels following oral administration of an LD50 of VCN or KCN were determined in blood and organs of treated rats and mice. After administration of VCN, cyanide levels were significantly lower than those following treatment with KCN in rats, whereas in mice the difference was not significant. Differences in VCN toxicity signs were observed in rats and mice. In rats, early VCN toxicity signs were cholinomimetic such as: salivation, diarrhea, peripheral vasodilatation, and excessive gastric secretion. These signs differed from the central nervous system disturbances (depression, convulsions and respiratory failure) observed following KCN. In mice, however, the only signs of VCN toxicity were central nervous system effects, identical to those following KCN. Blood cyanide concentrations after VCN were dose-dependent in both species. Maximum blood cyanide concentrations were observed 1 hr after dosing in mice but at 3 hr in rats. Treatments with phenobarbital or Aroclor 1254, or fasting, increased blood cyanide concentrations after VCN. Treatments with cobaltous chloride or SKF 525-A resulted in decreased blood cyanide concentrations after VCN. These data indicate that there are species differences in VCN toxicity and metabolism and suggest that VCN is metabolized to cyanide via a mixed-function oxidase enzyme system.
D000181:Acrylonitrile / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D003486:Cyanides / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009570:Nitriles / Q000378:metabolism*; D011190:Potassium Cyanide / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D014018:Tissue Distribution
D003486:Cyanides; D009570:Nitriles; D000181:Acrylonitrile; D011190:Potassium Cyanide