Exponent, Bellevue, WA, United States.
Exponent, Chicago, IL, United States.
Toxicology. 2014 Sep 2;323:78-94. doi: 10.1016/j.tox.2014.06.008. Epub 2014 Jun 20.
The U.S. Environmental Protection Agency (EPA) is developing an integrated assessment of non-cancer and cancer risk assessment of inorganic arsenic (iAs). Cardiovascular disease (CVD) in association with iAs exposure has been examined in a number of studies and provides a basis for evaluating a reference dose (RfD) for assessing potential non-cancer health risks of arsenic exposure. In this systematic review of low-level iAs exposure (i.e., <100-150μg/L arsenic water concentration) and CVD in human populations, 13 cohort and case-control studies from the United States, Taiwan, Bangladesh, and China were identified and critically examined for evidence for derivation of a RfD. Eight cross-sectional and ecological studies from the United States were also examined for additional information. Prospective cohort data from Bangladesh provided the strongest evidence for determining the point of departure in establishing a candidate RfD based on a combined endpoint of mortality from "ischemic heart disease and other heart diseases." This study as well as the overall literature supported a no-observed-adverse-effect level of 100μg/L for arsenic in water, which was equivalent to an iAs dose of 0.009mg/kg-day (based on population-specific water consumption rates and dietary iAs intake). The study population was likely sensitive to arsenic toxicity because of nutritional deficiencies affecting arsenic methylation and one-carbon metabolism, as well as increasing CVD risk. Evidence is less clear on the interaction of CVD risk factors in the United States (e.g., diabetes, obesity, and hypertension) with arsenic at low doses. Potential uncertainty factors up to 3 resulted in a RfD for CVD in the range of 0.003-0.009mg/kg-day. Although caution should be exercised in extrapolating these results to the U.S. general population, these doses allow a margin of exposure that is 10-30 times the current RfD derived by EPA (based on skin lesions in Southwest Taiwan). These findings suggest that the current EPA RfD is protective of CVD.
美国环保署（EPA）正在对无机砷（iAs）的非癌症和癌症风险评估进行综合评估。多项研究已经研究了与 iAs 暴露相关的心血管疾病（CVD），并为评估砷暴露潜在非癌症健康风险的参考剂量（RfD）提供了依据。在这项关于低水平 iAs 暴露（即<100-150μg/L 砷水浓度）和人类 CVD 的系统综述中，确定并批判性地审查了来自美国、中国台湾、孟加拉国和中国的 13 项队列和病例对照研究，以寻找推导 RfD 的证据。还审查了来自美国的 8 项横断面和生态学研究，以获取更多信息。来自孟加拉国的前瞻性队列数据为基于“缺血性心脏病和其他心脏病”的死亡率确定建立候选 RfD 的起点提供了最强的证据。这项研究以及总体文献支持将水中砷的无观察不良效应水平确定为 100μg/L，相当于水中砷的剂量为 0.009mg/kg-day（基于特定人群的水消耗量和饮食中 iAs 的摄入量）。由于影响砷甲基化和一碳代谢以及增加 CVD 风险的营养缺乏，研究人群可能对砷毒性敏感。在美国，CVD 危险因素与低剂量砷相互作用的证据不太明确（例如，糖尿病、肥胖和高血压）。高达 3 的潜在不确定性因素导致 CVD 的 RfD 在 0.003-0.009mg/kg-day 范围内。尽管在将这些结果推断到美国一般人群时应谨慎行事，但这些剂量允许的暴露量是 EPA （基于中国台湾西南部的皮肤损伤）目前推导的 RfD 的 10-30 倍。这些发现表明，目前的 EPA RfD 对 CVD 具有保护作用。
