Methods and rationale for derivation of a reference dose for methylmercury by the US EPA
Methods and rationale for derivation of a reference dose for methylmercury by the US EPA
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DOI：
10.1111/1539-6924.00294
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发表时间：
2003-02-01
期刊：
影响因子：
3.8
通讯作者：
Mahaffey, K
中科院分区：
文献类型：
--
作者：
Rice, DC;Schoeny, R;Mahaffey, K
2001年，美国环境保护署得出了甲基汞的参考剂量（RfD），这是一种可能在一生中没有明显有害影响风险的每日摄入量。这一推导使用了一系列基准剂量（BMD）分析，这些分析由国家研究理事会（NRC）专门小组提供，该小组负责评估甲基汞对健康的影响。对来自三项关于子宫内接触甲基汞的神经心理后果的大型纵向队列研究（法罗群岛、塞舌尔群岛和新西兰研究）的多个终点进行了分析。在法罗群岛和新西兰的研究中发现了不利影响，但在塞舌尔群岛没有发现。NRC还对所有三项研究进行了综合分析。EPA对人体内毒代动力学和毒代动力学变异性和不确定性采用的总不确定因子（UF）为10。使用一室模型进行了从脐带血汞浓度到母体甲基汞摄入量的剂量转换。从法罗群岛研究的许多终点推导出的潜在RfD收敛于0.1 μ g/kg/天，所有三项研究的综合分析也是如此。环境保护局确定了几个需要进一步信息或分析的领域。也许最直接相关的是脐带血与母体血汞浓度的比率，以及围绕该比率的可变性。美国环保署在其剂量转换中假设该比率为1.0;然而，现有数据表明该比率可能为1.5-2.0。对偏离1的验证可能会直接转化为参考剂量的可比减少。环境保护局确定的其他需要进一步关注的重要领域是甲基汞暴露的心血管后果，以及由于以前的发育或成人暴露而导致的衰老期间的延迟神经毒性。
In 2001, the U.S. Environmental Protection Agency derived a reference dose (RfD) for methylmercury, which is a daily intake that is likely to be without appreciable risk of deleterious effects during a lifetime. This derivation used a series of benchmark dose (BMD) analyses provided by a National Research Council (NRC) panel convened to assess the health effects of methylmercury. Analyses were performed for a number of endpoints from three large longitudinal cohort studies of the neuropsychological consequences of in utero exposure to methylmercury: the Faroe Islands, Seychelles Islands, and New Zealand studies. Adverse effects were identified in the Faroe Islands and New Zealand studies, but not in the Seychelles Islands. The NRC also performed an integrative analysis of all three studies. The EPA applied a total uncertainty factor (UF) of 10 for intrahuman toxicokinetic and toxicodynamic variability and uncertainty. Dose conversion from cord blood mercury concentrations to maternal methylmercury intake was performed using a one-compartment model. Derivation of potential RfDs from a number of endpoints from the Faroe Islands study converged on 0.1 mug/kg/day, as did the integrative analysis of all three studies. EPA identified several areas for which further information or analyses is needed. Perhaps the most immediately relevant is the ratio of cord:maternal blood mercury concentration, as well as the variability around this ratio. EPA assumed in its dose conversion that the ratio was 1.0; however, available data suggest it is perhaps 1.5-2.0. Verification of a deviation from unity presumably would be translated directly into comparable reduction in the RfD. Other areas that EPA identified as significant areas requiring further attention are cardiovascular consequences of methylmercury exposure and delayed neurotoxicity during aging as a result of previous developmental or adult exposure.