Critical issues in benzene toxicity and metabolism: The effect of interactions with other organic chemicals on risk assessment
- Chemical Industry Institute of Toxicology, Research Triangle Park, NC (United States)
Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene are well documented and include aplastic anemia and pancytopenia. Some individuals exposed repeatedly to cytotoxic concentrations of benzene develop acute myeloblastic anemia. It has been hypothesized that metabolism of benzene is required for its toxicity, although administration of no single benzene metabolite duplicates the toxicity of benzene. Several investigators have demonstrated that a combination of metabolites (hydroquinone and phenol, for example) is necessary to duplicate the hematotoxic effect of benzene. Enzymes implicated in the metabolic activation of benzene and its metabolites include the cytochrome P450 monooxygenases and myeloperoxidase. Since benzene and its hydroxylated metabolites (phenol, hydroquinone, and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. Other organic molecules that are substrates for cytochrome P450 can inhibit the metabolism of benzene. For example, toluene has been shown to inhibit the oxidation of benzene in a noncompetitive manner. Enzyme inducers, such as ethanol, can alter the target tissue dosimetry of benzene metabolites by inducing enzymes responsible for oxidation reactions involved in benzene metabolism. 24 refs., 6 figs., 2 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 494142
- Report Number(s):
- CONF-9207255-; ISSN 0091-6765; TRN: 97:002100-0005
- Journal Information:
- Environmental Health Perspectives, Vol. 102, Issue Suppl.9; Conference: 4. European ISSX meeting: toxicological evaluation of chemical interactions: relevance of social, environmental and occupational factors, Bologna (Italy), 3-6 Jul 1992; Other Information: PBD: Nov 1994
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
55 BIOLOGY AND MEDICINE
BASIC STUDIES
BENZENE
TOXICITY
TOLUENE
EXHAUST GASES
PETROLEUM PRODUCTS
OCCUPATIONAL EXPOSURE
BONE MARROW
ETHANOL
METABOLIC ACTIVATION
METABOLISM
MICE
OXIDATION
RISK ASSESSMENT
UNLEADED GASOLINE
INHALATION
CYTOCHROMES
PEROXIDASES