Differences in the pathways for metabolism of benzene in rats and mice simulated by a physiological model
- Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM (USA)
- National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)
Studies conducted by the National Toxicology Program on the chronic toxicity of benzene indicated that B6C3F{sub 1} mice were more sensitive to the carcinogenic effects of benzene than were F344 rats. A physiological model was developed to describe the uptake and metabolism of benzene in rats and mice. The objective was to determine if differences in toxic effects could be explained by differences in pathways for benzene metabolism or by differences in total uptake of benzene. Compartments incorporated into the model included liver, fat, a poorly perfused tissue group, a richly perfused tissue group, an alveolar or lung compartment and blood. Metabolism of benzene was assumed to take place only in the liver and to proceed by four major competing pathways. These included formation of hydroquinone conjugates (HQC), formation of phenyl conjugates (PHC), ring-breakage and formation of muconic acid (MUC), and conjugation with glutathione with subsequent mercapturic acid (PMA) formation. Model simulations confirmed that during and after 6-hr inhalation exposures mice metabolized more benzene on a {mu}mole per kilogram body weight basis than did rats. After oral exposure, rats metabolized more benzene than mice at doses above 50 mg/kg because of the more rapid absorption and exhalation of benzene by mice. Increased metabolism of benzene through the HQC and MUC pathways in mice is consistent with the observed susceptibility of this species to benzene toxicity.
- DOE Contract Number:
- AC04-76EV01013
- OSTI ID:
- 7150346
- Journal Information:
- Environmental Health Perspectives; (USA), Journal Name: Environmental Health Perspectives; (USA) Vol. 82; ISSN 0091-6765; ISSN EVHPA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALDEHYDES
ANIMALS
AROMATICS
BENZENE
BIOLOGICAL MODELS
BIOLOGICAL PATHWAYS
BODY
COMPARTMENTS
DIGESTIVE SYSTEM
DRUGS
GLANDS
GLUTATHIONE
HYDROCARBONS
INHALATION
INTAKE
LIVER
MAMMALS
METABOLISM
MICE
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
QUINONES
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
TOXICITY
UPTAKE
VERTEBRATES