Aliphatic nitriles are a large class of chemicals used in the production of plastics and elastomers. Acrylonitrile (AN), the most used and most studied member of this chemical class, is a known animal carcinogen. Studies of the toxicity of N,N'-dimethylaminopropionitrile (DMAPN) in rats and mice demonstrated that the urinary bladder and the kidney are primary targets for DMAPN toxicity. DMAPN toxicity is associated with glutathione depletion and lipid peroxidation. Minimal information is available on the toxicity or fate of methacrylonitrile (MAN). The present studies were designed to study the fate and toxicity of MAN in rats. After gavage administration, MAN is primarily eliminated in the expired air. The percent of dose expired as CO2 decreased as the dose increased and varied from 25-70% of the dose administered. In contrast. the percent of dose exhaled as organic volatiles was directly proportional to dose and accounted for 9-40% of the administered dose. It is therefore apparent that saturation of MAN metabolism occurs at high doses (0.5 LD50). HPLC analysis of expired organic volatiles from MAN-treated rats showed that it contained two components which were identified as MAN and acetone. Urinary excretion of MAN ranged form 20-30% of the administered dose in 72 hr. Variations in the toxicity, metabolism, and disposition of HAN and AN indicate a need for more complete toxicological characterization of MAN.
