The effect of dose, dose rate, route of administration, and species on tissue and blood levels of benzene metabolites
- Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM (USA)
- National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)
Studies were completed in F344/N rats and B6C3F{sub 1} mice to determine the effect of dose, dose rate, route of administration, and rodent species on formation of total and individual benzene metabolites. Oral doses of 50 mg/kg or higher saturated the capacity for benzene metabolism in both rats and mice, resulting in an increased proportion of the administered dose being exhaled as benzene. The saturating air concentration for benzene metabolism during 6-hr exposures was between 130 and 900 ppm. At the highest exposure concentration, rats exhaled approximately half of the internal dose retained at the end of the 6-hr exposure as benzene; mice exhaled only 15% as benzene. Mice were able to convert more of the inhaled benzene to metabolites than were rats. In addition, mice metabolized more of the benzene by pathways leading to the putative toxic metabolites, benzoquinone and muconaldehyde, than did rats. In both rats and mice, the effect of increasing dose, administered orally or by inhalation, was to increase the proportion of the total metabolites that were the products of detoxification pathways relative to the products of pathways leading to putative toxic metabolites. This indicates low-affinity, high-capacity pathways for detoxification and high-affinity, low-capacity pathways leading to putative toxic metabolites. If the results of rodent studied performed at high doses were used to assess the health risk at low-dose exposures to benzene, the toxicity of benzene would be underestimated.
- DOE Contract Number:
- AC04-76EV01013
- OSTI ID:
- 7149622
- 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
Similar Records
Differences in the metabolism and disposition of inhaled (3H)benzene by F344/N rats and B6C3F1 mice
Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei
Related Subjects
560300* -- Chemicals Metabolism & Toxicology
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACUTE EXPOSURE
ANIMALS
AROMATICS
BENZENE
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CLEARANCE
DISTRIBUTION
DOSE RATES
EXCRETION
FECES
HYDROCARBONS
INHALATION
INTAKE
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLISM
METABOLITES
MICE
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
RATS
RODENTS
TISSUE DISTRIBUTION
URINE
VERTEBRATES
WASTES