Disposition of methacrylonitrile in rats and distribution in blood components

The interaction of 2[14C]methyl-2,3[14C]acrylonitrile (MeAN) with the components of blood and its disposition in male Sprague-Dawley rats has been investigated. Following an oral administration of 100 mg/kg (0.5 LD50, 8 microCi/kg), the rats excreted 43% of the [14C] in the urine, 15% in the feces and 2.5% in the expired air as 14CO2 in 5 days. Hydrogen cyanide (H14CN) was not detectable. The red blood cells retained significant amounts of radioactivity for more than five days after administration, whereas the [14C]-activity in plasma declined sharply. More than 50% of the radioactivity in erythrocytes was detected as covalently bound to cytoplasmic (hemoglobin) and membrane proteins. A small amount of radioactivity was also found in the heme fraction. About 13% of the total dose administered was recovered as thiocyanate in the plasma and the urine. These results suggest that the toxicity of MeAN may be attributable to the whole molecule and not entirely to the in vivo liberation of cyanide.