Comparative Disposition of Acrylonitrile and Methacrylonitrile: Quantitative Whole-Body Autoradiographic Studies in Rats

Following intravenous administration of an equimolar (0.216 mmol/kg) radioactive dose of acrylonitrile (2-[14C]VCN, 11.5 mg/kg) or methacrylonitrile (2-[14C]MeVCN, 14.5 mg/kg), the tissue distribution, covalent interaction, and elimination were compared (at 5 min to 48 hr) in male Fischer 344 rats using whole-body autoradiography (WBA). Autoradiographs obtained from freeze-dried or acid-extracted sections of animals treated with 2-[14C]VCN showed that radioactivity accumulated in the liver, lung, bone marrow, adipose tissues, kidney, gastrointestinal tract, and spleen. In animals treated with 2-[14C]MeVCN, the respiratory tissues contained high levels of 14C at an early period (5 min), while the gastrointestinal mucosa, adrenal cortex, liver, and kidney contained high levels of radioactivity at later periods (8, 24, and 48 hr). Quantitatively, lower uptake and irreversible interactions of 14C were observed in autoradiographs of rats treated with 2-[14C]MeVCN compared with those treated with 2-[14C]VCN. Rats given 2-[14C]VCN eliminated only 27% of administered radioactivity (exhaled air, urine, and feces), whereas rats treated with 2-[14C]MeVCN eliminated, by all routes, 65% of the total radioactive dose. Both WBA and elimination studies indicated that 2-[14C]VCN and/or its metabolites were rapidly distributed, extensively bound, and slowly eliminated from tissues. 2-[14C]MeVCN and/or its metabolites, however, were rapidly distributed and eliminated, mostly via the lung. The study indicated that the substitution of a methyl group on the alpha-carbon of the alpha-beta unsaturated aliphatic nitrile VCN, to form MeVCN, imparted qualitative and quantitative differences in the disposition of these two compounds.