OBJECTIVE: To carry out a comprehensive field investigation to evaluate various conventional and recently developed biomarkers for exposure to low concentrations of benzene. METHODS: Analyses were carried out on environmental air, unmetabolised benzene in blood and urine, urinary trans, transmuconic acid, and three major phenolic metabolites of benzene: phenol, catechol, and hydroquinone. Validations of these biomarkers were performed on 131 never smokers occupationally exposed to the time weighed average benzene concentration of 0.25 ppm (range, 0.01 to 3.5 ppm). RESULTS: Among the six biomarkers studied, unmetabolised benzene in urine correlated best with environmental benzene concentration (correlation coefficient, r = 0.76), followed by benzene in blood (r = 0.64). When urinary metabolites were compared with environmental benzene, trans, trans-muconic acid showed a close correlation (r = 0.53) followed by hydroquinone (r = 0.44), and to a lesser extent with urinary phenol (r = 0.38). No correlation was found between catechol and environmental benzene concentrations. Although unmetabolised benzene in urine correlates best with benzene exposure, owing to serious technical drawbacks, its use is limited. Among the metabolites, trans, trans-muconic acid seems to be more reliable than other phenolic compounds. Nevertheless, detailed analyses failed to show that it is specific for monitoring benzene exposures below 0.25 ppm. CONCLUSION: The overall results suggest that most of the currently available biomarkers are unable to provide sufficient specificity for monitoring of low concentrations of benzene exposure. If a lower occupational exposure limit for benzene is to be considered, the reliability of the biomarker and the technical limitations of measurements have to be carefully validated.
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