Garry Michael R, Santamaria Annette B, Williams Amy L, DeSesso John M
Exponent, 15375 SE 30th Place, Suite 250, Bellevue, WA, 98007, USA.
Rimkus Consulting Group, 8 Greenway Plaza, Suite 500, Houston, TX, 77046, USA.
Regul Toxicol Pharmacol. 2015 Oct;73(1):378-90. doi: 10.1016/j.yrtph.2015.07.023. Epub 2015 Jul 31.
In its review of the U.S. Environmental Protection Agency's toxicological review of inorganic arsenic (iAs), the National Academy of Sciences identified carcinogenic endpoints among the highest priority health effects of concern and stated the need to consider evidence that early life exposures may increase the risk of adverse health effects. Recent studies in mice suggest that in utero exposure to arsenic increases susceptibility to cancer later in life. These data are striking in light of the general lack of evidence for carcinogenicity in rodents exposed to iAs. To evaluate the transplacental carcinogenic potential of iAs, a detailed analysis of the toxicology literature evaluating the role of in utero arsenic exposure in carcinogenesis was conducted. Bladder, lung, and skin tumors, which are the tumor types most consistently reported in humans exposed to high arsenic levels, were not consistently increased in mouse studies. There was also a lack of concordance across studies for other tumor types not typically reported in humans. Therefore, we considered methodological and other critical issues that may have contributed to variable results and we suggest additional studies to address these issues. It was concluded that the available data do not provide evidence of a causal link between in utero arsenic exposure and cancer or indicate early life-stage susceptibility to arsenic-induced cancer, particularly at environmentally relevant doses.
美国国家科学院在对美国环境保护局关于无机砷（iAs）的毒理学审查中，确定致癌终点是最受关注的最高优先健康影响之一，并指出需要考虑早期生命暴露可能增加不良健康影响风险的证据。最近对小鼠的研究表明，子宫内暴露于砷会增加生命后期患癌症的易感性。鉴于一般缺乏暴露于iAs的啮齿动物致癌性的证据，这些数据令人震惊。为了评估iAs的经胎盘致癌潜力，对毒理学文献进行了详细分析，以评估子宫内砷暴露在致癌过程中的作用。膀胱、肺和皮肤肿瘤是高砷暴露人群中最常报告的肿瘤类型，但在小鼠研究中并未持续增加。对于人类通常未报告的其他肿瘤类型，各研究之间也缺乏一致性。因此，我们考虑了可能导致结果差异的方法学和其他关键问题，并建议进行更多研究以解决这些问题。得出的结论是，现有数据并未提供子宫内砷暴露与癌症之间存在因果关系的证据，也未表明生命早期阶段对砷诱导癌症的易感性，特别是在环境相关剂量下。
