Studies on the Toxic Effect of Acrylonitrile

The male rabbits were exposed to 20ppm of acrylonitrile for 8 hours a day, once a week for 8 continuous weeks, during which the daily amounts of free acrylonitrile and thiocyanate excreted in urine were measured. The activity in the acrylonitrile metabolism was also determined as the amounts of cyanide and thiocyanate formed after the addition of acrylonitrile in the extirpated liver homogenate of those rabbits.In another experiment, to investigate the distribution in the tissues and the excretion of the substance, 14C-acrylonitrile was administered once to rabbits subcutaneously, and 14C radioactivities were determined by liquid scintillation counting.1) The excreted amount of free acrylonitrile in urine increased at every exposure from the 1st to the 3rd time, and after the 4th an equilibrium state was reached by the exposure of 20ppm of acrylonitrile once a week, repeatedly.2) The excreted amount of thiocyanate in urine increased about sixfold in the 1st acrylonitrile exposure, then decreased a little the 2nd time, and thereafter reached an equilibrium state.3) The activity in the acrylonitrile metabolism of the liver (measured as mentioned above) was lowered during the 1st, 2nd and 3rd exposures.4) The amount of thiocyanate accumulation in the liver also decreased during the 1st, 2nd and 3rd exposures.5) Experiment of subcutanious 14C-acrylonitrile injection revealed that an insoluble acrylonitrile complex, inseparable by boiling with acid, remained within the blood and tissues even 48 hours after the administration.Most of the acrylonitrile was metabolised to some soluble substances (most of them was thiocyanate), and consequently about 90% of injected acrylonitrile was excreted in urine as such metabolites.6) From the above results, it is considered that part of acrylonitrile absorbed in the body is combined strongly with the tissues by the cyanoethylation and this combined complex brings about inhibition of enzyme activity, etc., lowering the metabolism of acrylonitrile.