丙烯腈暴露勞工之尿液生物指標研究

Abstract

Acrylonitrile (AN) is a probable human carcinogen and is also a widely-used monomer in industries. Workers might be exposed to AN in workplace. Tobacco smoke has been shown as the major source for non-occupational exposure. The objective of the study was to develop an ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method to simultaneously and quantitatively profile the major mercapturic acids (MAs) of AN: N-acetyl-S-(2-cyanoethyl)cysteine (CEMA), N-acetyl-S-(2-hydroxyethyl)cysteine (HEMA), and N-acetyl-S-(1-cayno-2-hydroxyethyl)cysteine (CHEMA), and cotinine (COT), the major metabolite of nicotine in samples collected from occupationally-exposed people in order to validate MAs as proper biological markers for AN exposures and to study AN metabolism in humans. This UPLC-MS/MS method was successfully developed with excellent reproducibility, specificity, and sensitivity with limits of quantification (LOQ) at 0.1, 0.1, 1, 0.05 μg/L for HEMA, CEMA, CHEMA, and COT, respectively. The results from profiling MAs showed that the exposed workers excreted significantly higher MAs than the non-exposed workers. Analysis of data with linear regression demonstrated linear correlations between AN exposure and MAs concentrations. Further analysis with multiple regression revealed that personal AN exposures, COT levels, and working shift were significantly associated with these urinary MAs. By using the ratios of (HEMA+CHEMA)/CEMA and CHEMA/CEMA, the proportions of AN absorbed that metabolized to 2-cyanoethylene oxide (CEO) could be approximately estimated. Our analysis first reported that both ratio among 26 workers with detectable AN exposures were significantly higher at the post-shift than those at the pre-shift. In summary, our results not only validate that CEMA and CHEMA+HEMA can serve as biological markers for AN exposures either in workplaces and from tobacco smoke, but also suggest that potential induction of cytochrome p450 2E1 (CYP2E1) by low AN exposures which may have important implication in assessment of cancer risk for AN.