Methacrylonitrile (MAN) is used in the production of plastics and elastomers and is structurally related to the known carcinogen, acrylonitrile (AN). Present work was undertaken to investigate the biological fate of MAN in male F344 rats. Following gavage administration, MAN was rapidly absorbed from the GI tract and distributed to all major tissues. After administration of 1.15, 11.5, or 115 mg/kg, 2-14C-MAN is primarily eliminated in the expired air. Sixty to 70% of the low and medium doses were exhaled as 14C02 in 72 hr compared to 25% of the highest dose. While 40% of the high dose was expired as organic volatiles in 72 hr. only 9-12% of the low and medium doses were exhaled as such. It is therefore apparent that saturation of MAN metabolism occurs at the high dose. HPLC analysis of expired organic volatiles from MAN-treated rats showed that it contained two components which were identified as unchanged MAN and acetone. The MAN/acetone ratio was directly proportional to dose and decreased as a function of time. Urinary excretion accounted for 20- 30% of all MAN doses within 72 hr after dosing. Administration of MAN (115 mg/kg) in oil resulted in the death of rats within 24 hr after treatment. Monitoring the fate of MAN in these rats prior to death showed that a significantly higher % of the dose was eliminated in urine and expired air. Expired air from these animals contained significantly more acetone and less unchanged MAN than rats receiving MAN in water. Comparison of the metabolism and disposition of MAN in F344 and SD rats showed minor differences between the two strains. Further, administration of MAN to SD rats in oil caused minimal change in MAN disposition and had no lethal effect on this strain of rats.
