A substantial body of data exists that suggests benzene-mediated toxicity is caused by one or more of its metabolites. To induce hemotoxicity in experimental animals, benzene is often administered by injection or inhalation exposure at very high concentrations. These exposure methods ignore the fact that metabolism of benzene is capacity limited. A quantitative description of benzene metabolism at low exposure concentrations may provide information which can be translated to the exposed workforce. Gas uptake of benzene will be examined in mice, rats and guinea pigs. This method will be utilized to predict the toxicokinetics of inhaled benzene and the exposure concentration at which benzene metabolism is saturated. Data derived from this model will be utilized to try and index the rate of benzene metabolism in various species. To help validate this model in vivo quantitation of benzene and benzene metabolites will be performed after exposure to low levels of benzene. In addition to hemotoxicity benzene may also be immunotoxic. Alpha/Beta and gamma interferon titers will be quantitated in mice exposed to various concentrations of benzene. These experiments should help determine if benzene is immunotoxic and if immunotoxicity is expressed prior to hemotoxicity. Quantitation of interferon production may provide a rapid method of screening workers exposed to benzene.
| Wells, M S; Nerland, D E (1991) Hematotoxicity and concentration-dependent conjugation of phenol in mice following inhalation exposure to benzene. Toxicol Lett 56:159-66 |
| Nerland, D E; Pierce Jr, W M (1990) Identification of N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine as a urinary metabolite of benzene, phenol, and hydroquinone. Drug Metab Dispos 18:958-61 |
| Pierce Jr, W M; Nerland, D E (1988) Qualitative and quantitative analyses of phenol, phenylglucuronide, and phenylsulfate in urine and plasma by gas chromatography/mass spectrometry. J Anal Toxicol 12:344-7 |
