Carcinogenesis, Vol. 22, No. 2, 279-286,
February 2001
© 2001 Oxford University Press
CARCINOGENESIS |
Urinary benzene as a biomarker of exposure among occupationally exposed and unexposed subjects
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7400, USA,
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA,
2 Istituti Clinici di Perfezionamento, Via S.Barnaba 8, I-20122 Milan, Italy,
3 School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA,
4 Lovelace Respiratory Research Institute, PO Box 5890, Albuquerque, NM 87185, USA and
5 Chinese Academy of Preventive Medicine, Institute of Occupational Medicine, Beijing, China
Urinary benzene (UB) was investigated as a biomarker of exposure among benzene-exposed workers and unexposed subjects in Shanghai, China. Measurements were performed via headspace solid phase microextraction of 0.5 ml of urine specimens followed by gas chromatography–mass spectrometry. This assay is simple and more sensitive than other methods (detection limit 0.016 µg benzene/l urine). The median daily benzene exposure was 31 p.p.m. (range 1.65–329 p.p.m.). When subjects were divided into controls (n = 41), those exposed to 
31 p.p.m. benzene (n = 22) and >31 p.p.m. benzene (n = 20), the median UB levels were 0.069, 4.95 and 46.1 µg/l, respectively (Spearman r = 0.879, P < 0.0001). A linear relationship was observed between the logarithm of UB and the logarithm of benzene exposure in exposed subjects according to the following equation: ln(UB, µg/l) = 0.196 + 0.709 ln (exposure, p.p.m.) (r = 0.717, P < 0.0001). Considering all subjects, linear relationships were also observed between the logarithm of UB and the corresponding logarithms of four urinary metabolites of benzene, namely t,t-muconic acid (r = 0.938, P < 0.0001), phenol (r = 0.826, P < 0.0001), catechol (r = 0.812, P < 0.0001) and hydroquinone (r = 0.898, P < 0.0001). Ratios of individual metabolite levels to total metabolites versus UB provide evidence of competitive inhibition of CYP450 enzymes leading to increased production of phenol and catechol at the expense of hydroquinone and muconic acid. Among control subjects UB was readily detected with a mean level of 0.145 µg/l (range 0.027–2.06 µg/l), compared with 5.63 µg/l (range 0.837–26.38 µg/l) in workers exposed to benzene below 10 p.p.m. (P < 0.0001). This suggests that UB is a good biomarker for exposure to low levels of benzene.
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