Rapid determination of six urinary benzene metabolites in occupationally exposed and unexposed subjects

A gas chromatography-mass spectrometry method for measurement of the main urinary metabolites of benzene, namely, phenol, catechol, hydroquinone, 1,2,4-trihydroxybenzene (trihydroxybenzene), t,t-muconic acid (muconic acid), and S-phenylmercapturic acid (phenylmercapturic acid), is reported. The method is considerably simpler than existing assays. It was applied to urine from benzene-exposed subjects and controls from Shanghai, China. When subjects were divided into controls (n = 44), those exposed to less than or equal to31 ppm benzene (n = 21), and those exposed to >31 ppm benzene (n = 19), Spearman correlations with exposure category were greater than or equal to0.728 (p < 0.0001) for all metabolites except trihydroxybenzene. When exposed subjects were compared on an individual basis, all metabolites, including trihydroxybenzene, were significantly correlated with benzene exposure (Pearson r greater than or equal to 0.472, p less than or equal to 0.002) and with each other (Pearson r greater than or equal to 0.708, p < 0.0001). Ratios of individual metabolite levels to total metabolite levels provided evidence of competitive inhibition of CYP 2E1 enzymes leading to increased production of phenol, catechol, and phenyhmercapturic acid at the expense of hydroquinone, trihydroxybenzene, and muconic acid. Since all metabolites were detected in all control subjects, the method can be applied to persons exposed to environmental levels of benzene. (C) 2004 Elsevier Inc. All rights reserved.