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

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

doi:10.1016/0041-008X(89)90326-8

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

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Abstract

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 ratsmore »« less

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

Publication Date:: Wed Feb 01 00:00:00 EST 1989

Research Org.:: National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)

OSTI Identifier:: 6071681

Resource Type:: Journal Article

Journal Name:: Toxicol. Appl. Pharmacol.; (United States)

Additional Journal Information:: Journal Volume: 97:2

Country of Publication:: United States

Language:: English

Subject:: 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; URETHANE; METABOLISM; CARBON 14 COMPOUNDS; CARBON DIOXIDE; COMPARATIVE EVALUATIONS; DOSE-RESPONSE RELATIONSHIPS; EXCRETION; GENETIC VARIABILITY; INTRAVENOUS INJECTION; MICE; ORAL ADMINISTRATION; RATS; TISSUE DISTRIBUTION; TRACER TECHNIQUES; ANIMALS; BIOLOGICAL VARIABILITY; CARBAMATES; CARBON COMPOUNDS; CARBON OXIDES; CARBONIC ACID DERIVATIVES; CARBOXYLIC ACID SALTS; CHALCOGENIDES; CLEARANCE; DISTRIBUTION; INJECTION; INTAKE; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; OXIDES; OXYGEN COMPOUNDS; RODENTS; VERTEBRATES; 560300* - Chemicals Metabolism & Toxicology; 550501 - Metabolism- Tracer Techniques

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                    Nomeir, A A, Ioannou, Y M, Sanders, J M, and Matthews, H B. Comparative metabolism and disposition of ethyl carbamate (urethane) in male Fischer 344 rats and male B6C3F1 mice.  United States: N. p., 1989. 
        Web.  doi:10.1016/0041-008X(89)90326-8.

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                    Nomeir, A A, Ioannou, Y M, Sanders, J M, & Matthews, H B. Comparative metabolism and disposition of ethyl carbamate (urethane) in male Fischer 344 rats and male B6C3F1 mice.  United States.  https://doi.org/10.1016/0041-008X(89)90326-8

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                    Nomeir, A A, Ioannou, Y M, Sanders, J M, and Matthews, H B. 1989.  
        "Comparative metabolism and disposition of ethyl carbamate (urethane) in male Fischer 344 rats and male B6C3F1 mice".  United States.  https://doi.org/10.1016/0041-008X(89)90326-8.

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@article{osti_6071681,

  title        = {Comparative metabolism and disposition of ethyl carbamate (urethane) in male Fischer 344 rats and male B6C3F1 mice},

  author       = {Nomeir, A A and Ioannou, Y M and Sanders, J M and Matthews, H B},

  abstractNote = {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.},

  doi          = {10.1016/0041-008X(89)90326-8},

  url          = {https://www.osti.gov/biblio/6071681},
  journal      = {Toxicol. Appl. Pharmacol.; (United States)},
number       = ,

  volume       = 97:2,

  place        = {United States},

  year         = {Wed Feb 01 00:00:00 EST 1989},

  month        = {Wed Feb 01 00:00:00 EST 1989}

}

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