Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
Carcinogenesis. 2012 Aug;33(8):1538-41. doi: 10.1093/carcin/bgs191. Epub 2012 Jun 4.
Epidemiological studies suggest that trichloroethylene (TCE) exposure may be associated with renal cancer. The biological mechanisms involved are not exactly known although nephrotoxicity is believed to play a role. Studies on TCE nephrotoxicity among humans, however, have been largely inconsistent. We studied kidney toxicity in Chinese factory workers exposed to TCE using novel sensitive nephrotoxicity markers. Eighty healthy workers exposed to TCE and 45 comparable unexposed controls were included in the present analyses. Personal TCE exposure measurements were taken over a 2-week period before urine collection. Ninety-six percent of workers were exposed to TCE below the current US Occupational Safety and Health Administration permissible exposure limit (100 ppm 8h TWA), with a mean (SD) of 22.2 (35.9) ppm. Kidney injury molecule-1 (KIM-1) and Pi-glutathione S transferase (GST) alpha were elevated among the exposed subjects as compared with the unexposed controls with a strong exposure-response association between individual estimates of TCE exposure and KIM-1 (P < 0.0001). This is the first report to use a set of sensitive nephrotoxicity markers to study the possible effects of TCE on the kidneys. The findings suggest that at relatively low occupational exposure levels a toxic effect on the kidneys can be observed. This finding supports the biological plausibility of linking TCE exposure and renal cancer.
流行病学研究表明,三氯乙烯(TCE)暴露可能与肾癌有关。虽然认为肾毒性起作用,但涉及的生物学机制尚不清楚。然而,关于人类 TCE 肾毒性的研究很大程度上并不一致。我们使用新型敏感肾毒性标志物研究了接触 TCE 的中国工厂工人的肾毒性。本分析纳入了 80 名接触 TCE 的健康工人和 45 名可比未接触对照者。在收集尿液前,进行了为期两周的个人 TCE 暴露测量。96%的工人接触的 TCE 低于当前美国职业安全与健康管理局允许的暴露限值(100ppm8hTWA),平均(SD)为 22.2(35.9)ppm。与未接触对照者相比,暴露组的肾脏损伤分子-1(KIM-1)和 Pi-谷胱甘肽 S 转移酶(GST)α升高,并且 TCE 暴露个体估计值与 KIM-1 之间存在强烈的暴露-反应关联(P<0.0001)。这是首次使用一组敏感肾毒性标志物研究 TCE 对肾脏可能产生的影响的报告。这些发现表明,在相对较低的职业暴露水平下,可观察到对肾脏的毒性作用。这一发现支持了将 TCE 暴露与肾癌联系起来的生物学合理性。