Occupational Medicine, Department of Medicine and Public Health, University of Verona, Piazzale L.A. Scuro 10-37134 Verona, Italy.
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Oct 1;878(27):2515-9. doi: 10.1016/j.jchromb.2010.04.022. Epub 2010 Apr 21.
N,N-dimethylacetamide (DMA) is used in the textile and plastics industry as a solvent alternative to more toxic N,N-dimethylformamide. Here we studied toxicokinetics of two major urinary metabolites of DMA, namely, S-(acetamidomethyl)mercapturic acid (AMMA) and N-methylacetamide (NMA). Urine samples were collected from workers exposed to DMA in a factory manufacturing acrylic fibers. AMMA and NMA were determined by HPLC/MS and GC/MS, respectively. The working scheme in the factory consisted of periods of three consecutive working shifts alternated regularly with two days off work. In the first stage of the study, NMA and AMMA were determined in urine samples collected before, in the middle, and at the end of one working shift. In the second stage, urine was collected five times during three consecutive days after a two-day rest: before and at the end of the first and second working shifts and before the third shift. It was found that the end-of-shift NMA levels were several folds higher than the pre-shift levels of the same day and dropped significantly until the next shift. On the other hand, there were no significant differences in AMMA levels before and at the end of the same shift but a continuous rise during the three-day working period was observed. Median values of NMA concentrations at the end of working shifts were between 10.1 and 17.3 mg/g creatinine, median AMMA concentrations in the second or third day of the working period varied between 12.4 and 38.1 mg/g creatinine. The approximate half-lives of NMA and AMMA (means) in the exposed workers were about 9 and 29 h, respectively. Thus, while NMA in the end-of-shift urine samples remains a preferential biomarker of DMA exposure during that shift, AMMA determined at the end of a work-week reflects cumulative exposure over the last few days. Further studies are needed to determine AMMA concentrations corresponding to the threshold limit value of DMA.
N,N-二甲基乙酰胺（DMA）在纺织和塑料行业中用作更有毒的 N,N-二甲基甲酰胺的替代溶剂。在这里，我们研究了 DMA 的两种主要尿代谢物，即 S-（乙酰氨甲基）硫代尿酸（AMMA）和 N-甲基乙酰胺（NMA）的毒代动力学。尿样取自一家生产丙烯腈纤维的工厂中接触 DMA 的工人。AMMA 和 NMA 分别通过 HPLC/MS 和 GC/MS 测定。工厂的工作方案由连续三个工作班次交替进行，每个班次之间定期休息两天组成。在研究的第一阶段，在一个工作班次开始前、中间和结束时收集尿样，测定 NMA 和 AMMA 的含量。在第二阶段，在两天休息后的三个连续工作日内五次收集尿液：在第一个和第二个工作班次开始前和结束时以及第三个工作班次开始前。结果发现，工作结束时的 NMA 水平比当天同一班次的开始时水平高出数倍，并在下次班次前显著下降。另一方面，同一班次开始时和结束时的 AMMA 水平没有差异，但在三天工作期间观察到持续升高。工作班次结束时 NMA 浓度的中位数在 10.1 至 17.3mg/g 肌酐之间，工作期间第二或第三天的 AMMA 浓度中位数在 12.4 至 38.1mg/g 肌酐之间变化。暴露工人中 NMA 和 AMMA 的近似半衰期（平均值）分别约为 9 和 29 小时。因此，虽然工作班次结束时的尿样中 NMA 仍然是该班次 DMA 暴露的首选生物标志物，但工作周结束时的 AMMA 反映了过去几天的累积暴露。需要进一步的研究来确定与 DMA 的阈限值相对应的 AMMA 浓度。
