Comparative metabolism and disposition of ethyl carbamate (urethane) in male Fischer 344 rats and male B6C3F1 mice

Journal Article · Wed Feb 01 04:00:00 EST 1989 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(89)90326-8· OSTI ID:6071681

Nomeir, A A; Ioannou, Y M; Sanders, J M; Matthews, H B

The metabolism, disposition, and excretion of ethyl carbamate (EC) was investigated following oral or iv administration of a wide range of doses to male rats and mice. At a low dose, 4.75 mg/kg, administered iv, approximately 98% was exhaled as CO2 within 8 or 12 hr by mice or rats, respectively. However, as the dose increased, the percentage of dose eliminated as CO2 decreased in a dose-dependent manner which was much more pronounced in rats than mice. At all doses studied, mice eliminated EC as CO2 (as % dose) more rapidly than rats. Evidence of saturation of metabolism and elimination was observed at doses greater than 4.75 mg/kg in rats and greater than 47.5 mg/kg in mice. Following iv administration of 47.5 or 475 mg/kg, EC was initially evenly distributed in all tissues of each species except fat. After the initial time point (15 min), rat tissues contained higher concentrations of 14C compared to tissues of mice receiving the same dose. The disappearance of 14C from blood and various tissues followed monoexponential kinetics with rates dependent upon the species and the dose but independent of the tissue. Following oral administration, EC was completely absorbed from the gastrointestinal tracts of rats and mice at all doses studied. Approximately 5, 0.7, and 1% of the doses were excreted in urine, in feces, and as volatile organics, respectively. EC was neither an inducer nor an inhibitor of its own metabolism to CO2 following daily treatment of rats with oral doses of 47.5 mg/kg for 9 days. Only the parent compound was present in blood, lungs, skin, liver, kidney, muscle, and bile of treated rats. The urinary metabolic profile of EC was not affected by the route of administration in either species; however, in the rat but not in the mouse it was influenced by dose.

• Research Organization: National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)
• OSTI ID: 6071681
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 97:2; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

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560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL VARIABILITY
CARBAMATES
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARBON DIOXIDE
CARBON OXIDES
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACID SALTS
CHALCOGENIDES
CLEARANCE
COMPARATIVE EVALUATIONS
DISTRIBUTION
DOSE-RESPONSE RELATIONSHIPS
EXCRETION
GENETIC VARIABILITY
INJECTION
INTAKE
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
MICE
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
RATS
RODENTS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
URETHANE
VERTEBRATES