Validation of biomarkers in humans exposed to benzene: Urine metabolites

Abstract

Background The present study was conducted among Chinese workers employed in glue‐ and shoe‐making factories who had an average daily personal benzene exposure of 31±26 ppm (mean±SD). The metabolites monitored were S‐phenylmercapturic acid (S‐PMA), trans, trans‐muconic acid (t,t‐MA), hydroquinone (HQ), catechol (CAT), 1,2,4‐trihydroxybenzene (benzene triol, BT), and phenol. Methods S‐PMA, t,t‐MA, HQ, CAT, and BT were quantified by HPLC‐tandem mass spectrometry. Phenol was measured by GC‐MS. Results Levels of benzene metabolites (except BT) measured in urine samples collected from exposed workers at the end of workshift were significantly higher than those measured in unexposed subjects (P < 0.0001). The large increases in urinary metabolites from before to after work strongly correlated with benzene exposure. Concentrations of these metabolites in urine samples collected from exposed workers before work were also significantly higher than those from unexposed subjects. The half‐lives of S‐PMA, t,t‐MA, HQ, CAT, and phenol were estimated from a time course study to be 12.8, 13.7, 12.7, 15.0, and 16.3 h, respectively. Conclusions All metabolites, except BT, are good markers for benzene exposure at the observed levels; however, due to their high background, HQ, CAT, and phenol may not distinguish unexposed subjects from workers exposed to benzene at low ambient levels. S‐PMA and t,t‐MA are the most sensitive markers for low level benzene exposure. Am. J. Ind. Med. 37:522–531, 2000. © 2000 Wiley‐Liss, Inc.

Monitoring Low Benzene Exposure: Comparative Evaluation of Urinary Biomarkers, Influence of Cigarette Smoking, and Genetic Polymorphisms

“…Again, the majority of our subjects experienced exposure below these thresholds. Interestingly, the levels of S-PMA determined in the present study were higher than expected, with values ranging from <0.2 and 182 Ag/L, and the median value in nonsmoking referents up to 9.0 Ag/L, whereas concentrations in the range from 1.5 to 2 Ag/g creatinine were reported in other studies (46)(47)(48). At the moment, the reason for this is unclear, but differences in the analytic procedure used may be important; in fact, an immunoassay technique was applied in this investigation (18), whereas high-performance liquid chromatography/ fluorescence, gas chromatography/mass spectrometry, and liquid chromatography/tandem mass spectrometry were used in all the other studies.…”

“…S-PMA is generally considered a very specific biomarker of benzene, successfully applied to distinguish exposed and nonexposed subjects (35,41,42,(46)(47)(48)(49) and correlated with personal exposure starting from low concentrations [reviewed by Dor et al (40)]. In the present study, S-PMA was also a poor biomarker of occupational exposure to benzene.…”

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Recommendations for the Use of Laboratory Tests to Support Poisoned Patients Who Present to the Emergency Department

“…Urinary phenol concentrations can increase with the consumption of some over-the-counter drugs, such as PeptoBismol and Chloraseptic (110 ). More specific urinary metabolites have been studied for toluene, such as o-cresol (111 ), S-p-toluylmercapturic acid (112 ), and trace concentrations of toluene itself (113 ), and for benzene, such as trans-muconic acid and S-phenylmercapturic acid (114 ). Assays for these metabolites are not in routine use at clinical laboratories.…”

Protective effect of 1,2,4-benzenetriol on LPS-induced NO production by BV2 microglial cells

“…BT has been known as one of benzene metabolites for years [4]. The urinary concentration of BT is increased linearly to the intensity of exposure to benzene in both men and women [5,6]. Surprisingly, coffee drinking increases urinary hydrogen peroxide (H 2 O 2 ) levels which are derived mainly from BT excreted in urine [7,8].…”