Comparative toxicokinetics of 2,3-14C-and 1-14C-acrylonitrile in the rat.

The tissue distribution, elimination and covalent binding of 2,3-14C-and 1-14C-acrylonitrile (VCN) were studies in male Sprague-Dawley rats given an oral dose of 46.5 mg kg-1. Exhalation of unchanged VCN, 14CO2 and H14CN was monitored at selected intervals. Only 5% of the total dose administered was recovered was unchanged VCN. Rate given 2,3-14C-VCN exhaled only 2% of 14C activity was 14CO2 and none was recovered as H14CN, whereas rats given 1-14C-VCN exhaled about 12% of 14C activity as 14CO2 and 0.5% as H14CN. In the initial 24 h, 40% of radioactivity from 1-14C-VCN appeared in urine, while 60% was recovered in the urine of rats given 2,3-14C-VCN. The red blood cells retained significant amounts of radioactivity from both the compounds for more than 10 days after administration, whereas the 14C activity in plasma declined sharply. The highest level of radioactivity from both compounds was recovered in the gastrointestinal tract. In liver, kidney, brain, spleen, adrenal, lung and heart tissues the unbound percent radioactivity decreased, while irreversible percent covalent binding to macromolecules in relation to total increased concomitantly. Subcellular fractionation of the tissues showed that most of the covalently bound radioactivity was distributed in non-cytosolic fractions. As compared to 1-14C-VCN administered animals, the percentage of covalent binding of 2,3-14C-VCN was significantly higher even 72 h after dosing. The relationship between covalent binding and acrylonitrile toxicity is discussed.