The US EPA reference dose for methylmercury: sources of uncertainty
The US EPA reference dose for methylmercury: sources of uncertainty
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DOI：
10.1016/j.envres.2003.08.013
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发表时间：
2004-07-01
影响因子：
8.3
通讯作者：
Rice, DC
中科院分区：
文献类型：
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作者：
Rice, DC
2001年，美国环境保护署（EPA）根据国家科学院国家研究理事会（NRC）的广泛分析得出了甲基汞的参考剂量。NRC对三项纵向前瞻性研究（塞舌尔群岛、法罗群岛和新西兰研究）的多个终点进行了基准剂量分析。后两项研究报告了不利影响，但塞舌尔的研究没有报告。NRC还对所有三项研究进行了综合分析。EPA使用一室药代动力学模型进行脐带血或母体头发汞浓度的剂量转换。人体内药代动力学和药效学变异性的总不确定因子为10。NRC/EPA做出的许多决定可能会极大地影响参考剂量（RfD）的值。其中包括选择汞身体负荷与神经心理学表现之间关系的线性模型，选择P-0值和基准反应，使用"关键研究/关键终点"方法解释与RfD对应的母体身体负荷，在一室药代动力学模型中使用中心趋势，而不是纳入育龄妇女人群的变量分布，假设胎儿脐带血与母亲血液中甲基汞浓度的比率为1，选择总数为10作为不确定性因子，以及缺乏对心血管疾病等其他健康影响的剂量反应分析。此外，鉴于现有数据似乎没有设定不良神经心理影响的阈值，因此可能会认为，推导出甲基汞的参考剂量是不适当的。(C)2003年爱思唯尔公司All rights reserved.
The US Environmental Protection Agency (EPA) derived a reference dose for methylmercury in 2001, based on an extensive analysis by the National Research Council (NRC) of the National Academy of Sciences. The NRC performed benchmark dose analysis on a number of endpoints from three longitudinal prospective studies: the Seychelles Islands, the Faroe Islands, and the New Zealand studies. Adverse effects were reported in the latter two studies, but not in the Seychelles study. The NRC also performed an integrative analysis of all three studies. Dose conversion from cord blood or maternal hair mercury concentration was performed by EPA using a one-compartment pharmacokinetic model. A total uncertainty factor of 10 was applied for intrahuman pharmacokinetic and pharmacodynamic variability. There are numerous decisions made by the NRC/EPA that could greatly affect the value of the reference dose (RfD). Some of these include the choice of a linear model for the relationship between mercury body burden and neuropsychological performance, the choice of values of P-0 and the benchmark response, the use of the "critical study/critical endpoint" approach in the interpretation of the maternal body burden that corresponds to the RfD, the use of central tendencies in a one-compartment pharmacokinetic model rather than the inclusion of the distributions of variables for the population of reproductive-age women, the assumption of unity for the ratio of fetal cord blood to maternal blood methylmercury concentrations, the choice of a total of 10 as an uncertainty factor, and the lack of dose-response analysis for other health effects such as cardiovascular disease. In addition, it may be argued that derivation of a RfD for methylmercury is inappropriate, given that there does not appear to be a threshold for adverse neuropsychological effects based on available data. (C) 2003 Elsevier Inc. All rights reserved.