Hematotoxicity and concentration-dependent conjugation of phenol in mice following inhalation exposure to benzene.
Benzene is metabolized to one or more hematotoxic species. Saturation of benzene metabolism could limit the production of toxic species. Saturation of phase II enzymes involved in the conjugation of the phenolic metabolites of benzene also could affect the hematotoxicity of benzene. To investigate the latter possibility, we exposed male Swiss mice, via the inhalation route, to various concentrations of benzene for 6 h per day for 5 days. Following termination of the final exposure the mice were killed and the levels of phenylsulfate and phenylglucuronide in the blood determined. Spleen weights were recorded and the number of white blood cells counted. At low benzene exposure concentrations phenylsulfate is the major conjugated form of phenol in the blood. At high exposure concentrations, phenylglucuronide is the predominant species. The reductions in spleen weight and white blood cell numbers correlated with the concentration of phenylsulfate in the blood, but are most probably not causally related.
Wells
M S
MS
Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, KY 40292.
Nerland
D E
DE
D000280:Administration, Inhalation; D000818:Animals; D001554:Benzene / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005965:Glucuronates / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010198:Pancytopenia / Q000209:etiology; D010636:Phenols / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D013154:Spleen / Q000033:anatomy & histology; D013463:Sulfuric Acid Esters / Q000097:blood
D005965:Glucuronates; D010636:Phenols; D013463:Sulfuric Acid Esters; C025298:phenylglucuronide; C025208:phenylsulfate; D001554:Benzene