Metabolism and disposition of cyclohexanone oxime in male F-344 rats.

Cyclohexanone oxime (CHOX), an intermediate used in the synthesis of Polycaprolactam/Nylon, was found to be rapidly absorbed and cleared from the body within 24 hours after a single oral administration of 1, 10 and 30 mg/kg of [14C]-CHOX to the adult male Fischer rats. The majority of the CHOX derived radioactivity (65-90% of the dose) was excreted in the urine. Elimination in the feces accounted for 5-10% of the dose and very low levels of radioactivity (2-3%) were retained in the tissues 24 hours after exposure. After iv administration of 1 mg/kg of [14C]-CHOX, the oxime was rapidly cleared from plasma with half-lives of 1.6 (alpha phase) and 18.2 min (beta phase). However, when CHOX was applied dermally (30 mg/kg), only about 4-5% of the dose was recovered in urine, feces and the tissues. The majority of the dose volatilized from the skin surface. However, the absorbed oxime was readily distributed and excreted, and its metabolic fate was no different than observed after oral administrations. HPLC analysis of urine showed that the majority of the radioactivity excreted was in the form of three metabolites, cyclohexylglucuronide and the monoglucuronides of cis- and trans-cyclohexane-1,2-diol. In vitro studies showed that these metabolites arise primarily by hydrolysis of the oxime to cyclohexanone which is then reduced to cyclohexanol and eliminated as the glucuronide conjugate. The cyclohexanol, in turn could be metabolized to cis- and trans-cyclohexane-1,2-diols, which excreted as their monoglucuronides.