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Assessment of urinary 6-hydroxy-2,4-cyclohexadienyl mercapturic acid as a novel biomarker of benzene exposure

Supporting Files
File Language:
English


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  • Alternative Title:
    J Anal Toxicol
  • Personal Author:
  • Description:
    Assessing benzene exposure is a public health priority due to its deleterious health effects and ubiquitous industrial and environmental sources of exposure. Phenyl mercapturic acid (PhMA) is a commonly used urinary biomarker to assess benzene exposure. However, recent work has identified significant interlaboratory variation in urinary PhMA concentrations related to methodological differences. In this study, we present urinary 6-hydroxy-2,4-cyclohexadienyl mercapturic acid (pre-PhMA), a metabolite that undergoes acid-catalyzed dehydration to form PhMA, as a novel and specific urinary biomarker for assessing benzene exposure. We developed and validated the first quantitative liquid chromatography-tandem mass spectrometry assay for measuring urinary concentrations of pre-PhMA. The pH effect on the method of ruggedness testing determined that pre-PhMA is stable across the normal human urine pH range and that neutral conditions must be maintained throughout quantification for robust and accurate measurement of urinary pre-PhMA concentrations. The method exhibited below 2 ng/mL sensitivity for pre-PhMA, linearity over three orders of magnitude, and precision and accuracy within 10%. Urinary pre-PhMA concentrations were assessed in 369 human urine samples. Smoking individuals exhibited elevated levels of pre-PhMA compared to non-smoking individuals. Furthermore, the relationship between benzene exposure and urinary pre-PhMA levels was explored by examining the correlation of pre-PhMA with 2-cyanoethyl mercapturic acid, a smoke exposure biomarker. The urinary biomarkers exhibited a positive correlation (r = 0.720), indicating that pre-PhMA levels increased with benzene exposure. The results of this study demonstrate that urinary pre-PhMA is a rugged and effective novel biomarker of benzene exposure that can be widely implemented for future biomonitoring studies.
  • Subjects:
  • Source:
    J Anal Toxicol. 47(7):597-605
  • Pubmed ID:
    37632692
  • Pubmed Central ID:
    PMC10935563
  • Document Type:
  • Funding:
  • Volume:
    47
  • Issue:
    7
  • Collection(s):
  • Main Document Checksum:
    urn:sha256:3843454785a9a1cf4488532fc65f1135a489aa93f50bcfbe5b00658fb3788870
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  • File Type:
    Filetype[PDF - 856.70 KB ]
File Language:
English
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