Journal Article

Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism

Sungkyoon Kim, Roel Vermeulen, Suramya Waidyanatha, Brent A. Johnson, Qing Lan, Nathaniel Rothman, Martyn T. Smith, Luoping Zhang, Guilan Li, Min Shen, Songnian Yin and Stephen M. Rappaport

in Carcinogenesis

Volume 27, issue 4, pages 772-781
Published in print April 2006 | ISSN: 0143-3334
Published online December 2005 | e-ISSN: 1460-2180 | DOI:
Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism

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Although the toxicity of benzene has been linked to its metabolism, the dose-related production of metabolites is not well understood in humans, particularly at low levels of exposure. We investigated unmetabolized benzene in urine (UBz) and all major urinary metabolites [phenol (PH), E,E-muconic acid (MA), hydroquinone (HQ) and catechol (CA)] as well as the minor metabolite, S-phenylmercapturic acid (SPMA), in 250 benzene-exposed workers and 139 control workers in Tianjin, China. Median levels of benzene exposure were ∼1.2 p.p.m. for exposed workers (interquartile range: 0.53–3.34 p.p.m.) and 0.004 p.p.m. for control workers (interquartile range: 0.002–0.007 p.p.m.). (Exposures of control workers to benzene were predicted from levels of benzene in their urine.) Metabolite production was investigated among groups of 30 workers aggregated by their benzene exposures. We found that the urine concentration of each metabolite was consistently elevated when the group's median benzene exposure was at or above the following air concentrations: 0.2 p.p.m. for MA and SPMA, 0.5 p.p.m. for PH and HQ, and 2 p.p.m. for CA. Dose-related production of the four major metabolites and total metabolites (μmol/l/p.p.m. benzene) declined between 2.5 and 26-fold as group median benzene exposures increased between 0.027 and 15.4 p.p.m. Reductions in metabolite production were most pronounced for CA and PH <1 p.p.m., indicating that metabolism favored production of the toxic metabolites, HQ and MA, at low exposures.

Keywords: BO, benzene oxide; CA, catechol; CV, coefficient of variation; EI, electron ionization; GC-MS, gas chromatography-mass spectrometry; GM, geometric mean; HQ, hydroquinone; LOD, limit of detection; MA, E,E-muconic acid; PH, phenol; SPMA, S-phenylmercapturic acid; TMS, trimethylsilyl derivative; UBz, urinary benzene.

Journal Article.  6743 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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