Toxicity and tissue distribution of methacrylonitrile in rats

The toxicity, uptake, tissue distribution, elimination, and covalent binding of 2-[14C]methyl-[2.3-14C]acrylonitrile (MeAN) in male Sprague-Dawley rats were investigated. Following an oral administration of 100 mg/Kg body weight (0.5 LD50, 8 microCi/Kg bw) the rats exhibited several signs of toxicity including ataxia, convulsions, mild diarrhea, salivation, lacrimation, and bladder urine retention. The treated animals excreted 43% of the 14C in the urine, 14% in the feces, and 2.5% in the expired air as 14CO2 in 10 days. Hydrogen cyanide was not detectable. Red blood cells retained significant amounts of radioactivity for more than 10 days after treatment. MeAN was extensively absorbed through the gastrointestinal tract and distributed in all the tissues of the rats. The major concentrations of the radioactivity were found with up to 25% of the administered dose in bone, liver, spleen, kidney, blood, and the gastrointestinal tract. This study indicates that MeAN is rapidly absorbed and distributed and the major route of excretion is urinary.