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

University of California, Berkeley, Berkeley, California, United States
Carcinogenesis (Impact Factor: 5.33). 05/2006; 27(4):772-81. DOI: 10.1093/carcin/bgi297
Source: PubMed


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 approximately 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 (micromol/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.

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    • "ations of ∑BT and 8 - OHdG were observed in this study . The results agreed with several previous reports ( Fan et al . , 2012a ; Buthbumrung et al . , 2008 ) . Some of the studies showed strong and positive relation - ships between urinary 8 - OHdG concentration and PAH exposure ( Lee et al . , 2012 ; Kuang et al . , 2013 ) and benzene exposure ( Kim et al . , 2006a ) . For example , Kuang et al . ( 2013 ) recruited 1333 coke oven workers and found that the ∑OH - PAHs in the urine and the benzo [ a ] pyrene - r - 7 , t - 8 , t - 9 , c - 10 - tetrahydotetrol - albumin adducts in the plasma could cause significant dose - related increases in the oxidative damage to DNA and lipids . The high PAH expos"
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    • "Urinary benzene and SPMA. Similar trends are seen for urinary benzene (Ayi Fanou et al., 2006; Bergamaschi et al., 1999; Fustinoni et al., 2005a,b; Ghittori et al., 1995; Kim et al., 2006a; Kivisto et al., 1997; Kok & Ong, 1994; Lagorio et al., 1998; Maestri et al., 1993; Ong et al., 1996; Pezzagno et al., 1999; Waidyanatha et al., 2001) and SPMA (Aston et al., 2002; Ayi Fanou et al., 2006; Boogaard & van Sittert, 1996; Crebelli et al., 2001; Einig et al., 1996; Fustinoni et al., 2005a; Garte et al., 2005; Ghittori et al., 1995, 1999; Hotz et al., 1997; Kim et al., 2006a; Kivisto et al., 1997; Maestri et al., 1993, 2005; Melikian et al., 1999b, 2002; Navasumrit et al., 2008; Pople et al., 2002; Stommel et al., 1989; Waidyanatha et al., 2004) biomonitoring data from North America, Europe, Asia and Africa (Figures 4 and 5). As expected, the urinary benzene and SPMA concentrations for smokers were generally higher than for non-smokers. "
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    • "Furthermore, some evidence shows that benzene metabolism favors the production of the toxic metabolites hydroquinone and muconic acid at low exposures (Kim et al. 2006a). This is especially important because hydroquinone is the precursor of 1,4-benzoquinone, which is generally regarded as the most hematotoxic metabolite of benzene (Kim et al. 2006a). The nonlinear production of benzene's toxic metabolites would have important consequences for risk assessment because one would expect this to result in a nonlinear relationship between benzene exposure and health outcomes as well. "
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