Validation of biomarkers in humans exposed to benzene: urine metabolites

Am J Ind Med. 2000 May;37(5):522-31. doi: 10.1002/(sici)1097-0274(200005)37:5<522::aid-ajim8>;2-g.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / urine
  • Adhesives
  • Adult
  • Benzene / analysis*
  • Benzene / metabolism
  • Biomarkers / urine
  • Catechols / urine
  • China
  • Chromatography, High Pressure Liquid
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Half-Life
  • Humans
  • Hydroquinones / urine
  • Male
  • Mass Spectrometry
  • Mutagens / analysis
  • Occupational Exposure / analysis*
  • Phenol / urine
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Shoes
  • Sorbic Acid / analogs & derivatives
  • Sorbic Acid / analysis


  • Adhesives
  • Biomarkers
  • Catechols
  • Hydroquinones
  • Mutagens
  • hydroxyhydroquinone
  • Phenol
  • muconic acid
  • S-phenyl-N-acetylcysteine
  • Benzene
  • catechol
  • Acetylcysteine
  • Sorbic Acid
  • hydroquinone