Female wistar rats, conventional albino mice, and Chinese hamsters were given a single dose of
acrylonitrile, 0.5 or 0.75 mM/kg
body weight. The elimination in the urine of
thiocyanate, which is the main metabolite of
acrylonitrile, indicated a decreasing proportion of biotransformation after oral (over 20%), intraperitoneal, or subcutaneous (2 to 5%), and intravenous (1%) administration in rats.
Oral administration of
acrylonitrile in hamsters and mice was also followed by higher biotransformation than intraperitoneal administration. Pretreatment of rats with
phenobarbital,
SKF 525 A,
cysteine, or
dimercaprol did not significantly influence elimination of
thiocyanate in the urine after the administration of
acrylonitrile, but simultaneous administration of
thiosulfate significantly increased the metabolized portion of
acrylonitrile given intraperitoneally in rats (almost twice) and mice (more than three times).
Acrylonitrile was found to be strongly bound in blood. The study confirmed the marked effect of distribution (first-pass metabolic phenomenon) on the metabolic fate of foreign compounds. The strong
acrylonitrile binding and cyanoethylation are apparently responsible for the unusually high influence of the different routes of administration on the metabolic fate of
acrylonitrile.
Acrylonitrile was more effectively metabolized to
thiocyanate in mice than in rats after oral, intraperitoneal, and
intravenous administration. A greater response of
acrylonitrile to
thiocyanate metabolism and a larger decrease in its acute toxicity after
thiosulfate in mice than in rats indicate possible differences in the mechanism of
acrylonitrile toxicity in these animals.
Cyanide apparently plays a minor role in the
acrylonitrile toxicity in rats, but may play quite an important one in mice.