Distribution and covalent interactions of [1-14C]acrylonitrile in the rat.

The tissue distribution, elimination and covalent binding of [1-14C]-acrylonitrile (VCN) have been investigated in the rat. Rats, given an oral dose of 46.5 mg/kg (0.5 LD50) VCN, excreted 40% of the 14C in urine, 2% in feces, 9% in expired air as 14CO2, 0.5% as H14CN and 4.8% as unchanged VCN in 24 h. Bile flow increased 3 times after the administration of VCN and over a period of 6 h, 27% of the 14C was recovered in bile. The red blood cells retained significant amounts of radioactivity for more than 10 days after treatment, whereas the 14C activity declined sharply in plasma. Initially, the highest levels of radioactivity were found in the stomach and stomach content followed by the intestine. In liver, kidney, brain, spleen, adrenal, lung and heart tissues the radioactivity of the acid soluble fractions declined while covalent binding to macromolecules remained unchanged. In subcellular fractions of liver, kidney, spleen, brain, lung, and heart, 20-40% of the total radioactivity was bound to nuclear, mitochondrial and microsomal fractions whereas in cytosol only 6-14% was bound over a period of 6 h.