Stern Alan H, Smith Andrew E
Division of Science, Research and Technology, New Jersey Department of Environmental Protection, PO Box 409, 401 E. State Street, Trenton, NJ 08625, USA.
Environ Health Perspect. 2003 Sep;111(12):1465-70. doi: 10.1289/ehp.6187.
In the current U.S. Environmental Protection Agency reference dose (RfD) for methylmercury, the one-compartment pharmacokinetic model is used to convert fetal cord blood mercury (Hg) concentration to a maternal intake dose. This requires a ratio relating cord blood Hg concentration to maternal blood Hg concentration. No formal analysis of either the central tendency or variability of this ratio has been done. This variability contributes to the overall variability in the dose estimate. A ratio of 1.0 is implicitly used in the model, but an uncertainty factor adjustment is applied to the central tendency estimate of dose to address variability in that estimate. Thus, incorporation of the cord:maternal ratio and its variability into the estimate of intake dose could result in a significant change in the value of the RfD. We analyzed studies providing data on the cord:maternal blood Hg ratio and conducted a Monte Carlo-based meta-analysis of 10 studies meeting all inclusion criteria to generate a comprehensive estimate of the central tendency and variability of the ratio. This analysis results in a recommended central tendency estimate of 1.7, a coefficient of variation of 0.56, and a 95th percentile of 3.4. By analogy to the impact of the similar hair:blood Hg ratio on the overall variability in the dose estimate, incorporation of the cord:maternal ratio may support a 3-fold uncertainty factor adjustment to the central tendency estimate of dose to account for pharmacokinetic variability. Whether the information generated in this analysis is sufficient to warrant a revision to the RfD will depend on the outcome of a comprehensive reanalysis of the entire one-compartment model. We are currently engaged in such an analysis.
在美国环境保护局当前的甲基汞参考剂量（RfD）中，单室药代动力学模型用于将胎儿脐带血汞（Hg）浓度转换为母亲的摄入剂量。这需要一个将脐带血汞浓度与母亲血汞浓度相关联的比率。尚未对该比率的集中趋势或变异性进行正式分析。这种变异性导致剂量估计中的总体变异性。模型中隐含使用的比率为1.0，但对剂量的集中趋势估计应用了不确定性因素调整，以解决该估计中的变异性。因此，将脐带与母亲的比率及其变异性纳入摄入剂量估计可能会导致RfD值发生重大变化。我们分析了提供脐带与母亲血汞比率数据的研究，并对符合所有纳入标准的10项研究进行了基于蒙特卡洛的荟萃分析，以全面估计该比率的集中趋势和变异性。该分析得出的推荐集中趋势估计值为1.7，变异系数为0.56，第95百分位数为3.4。类似于类似的头发与血汞比率对剂量估计总体变异性的影响，纳入脐带与母亲的比率可能支持对剂量的集中趋势估计进行3倍的不确定性因素调整，以考虑药代动力学变异性。该分析产生的信息是否足以保证对RfD进行修订将取决于对整个单室模型进行全面重新分析的结果。我们目前正在进行这样的分析。
