Metabolism and disposition of cyclohexanone oxime in male F-344 rats. 1991

D Parmar, and L T Burka
National Toxicology Program, NIEHS, Research Triangle Park, NC 27709.

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.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D008297 Male Males
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D003512 Cyclohexanones Cyclohexane ring substituted by one or more ketones in any position.
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012869 Skin Absorption Uptake of substances through the SKIN. Absorption, Skin,Intracutaneous Absorption,Intradermal Absorption,Percutaneous Absorption,Transcutaneous Absorption,Transdermal Absorption,Absorption, Intracutaneous,Absorption, Intradermal,Absorption, Percutaneous,Absorption, Transcutaneous,Absorption, Transdermal,Absorptions, Intracutaneous,Absorptions, Intradermal,Absorptions, Percutaneous,Absorptions, Skin,Absorptions, Transcutaneous,Absorptions, Transdermal,Intracutaneous Absorptions,Intradermal Absorptions,Percutaneous Absorptions,Skin Absorptions,Transcutaneous Absorptions,Transdermal Absorptions
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

Related Publications

D Parmar, and L T Burka
June 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology,
D Parmar, and L T Burka
August 1989, Toxicology and applied pharmacology,
D Parmar, and L T Burka
December 1983, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association,
D Parmar, and L T Burka
January 2002, Journal of applied toxicology : JAT,
D Parmar, and L T Burka
February 1996, Drug metabolism and disposition: the biological fate of chemicals,
D Parmar, and L T Burka
January 1986, Xenobiotica; the fate of foreign compounds in biological systems,
D Parmar, and L T Burka
April 2000, Drug metabolism and disposition: the biological fate of chemicals,
D Parmar, and L T Burka
December 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association,
D Parmar, and L T Burka
October 1994, Fundamental and applied toxicology : official journal of the Society of Toxicology,
Copied contents to your clipboard!