Acrylonitrile Pharmacodynamics and Mutagenesis

摘要

A study was made of the pharmacokinetics of acrylonitrile (107131) (AN) with emphasis on routes of elimination and mechanisms of metabolism. Rats were given intraperitoneal injections of AN at 5 to 60mg/kg. Two AN analogues, crotononitrile (4786203) (CN) and methacrylonitrile (126987) (MN), were also studied. CN and MN concentrations in blood followed a first order kinetic elimination. AN demonstrated a biphasic kinetic elimination. AN was measurable in fat, liver and blood for 18 hours after a 37mg/kg dose. Fecal excretion was significant at levels of 3 to 9 parts per million (ppm) at 3 hours after exposure. Urine levels of 0.03ppm were registered after 5.3mg/kg dose levels and 0.1ppm after 81mg/kg. Total AN in feces, urine and tissues even at very short intervals after intraperitoneal administration represented only 3 to 30 percent of the administered dose. The fast AN metabolic pathway was consistent with Michael addition to AN or its analogs and would readily account for cyanide formation.