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Alan H. Stern^1,2 and Andrew E. Smith³

¹Division of Science, Research and Technology, New Jersey Department of Environmental Protection, Trenton, New Jersey, USA; ²University of Medicine and Dentistry of New Jersey, School of Public Health, Piscataway, New Jersey, USA; ³Environmental Toxicology Program, Bureau of Health, Maine Department of Human Services, Augusta, Maine, USA

Abstract
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. Key words: blood, cord blood, fetus, maternal, mercury, methylmercury, ratio, reference dose, RfD. Environ Health Perspect 111:1465-1470 (2003) . doi:10.1289/ehp.6187 available via http://dx.doi.org/ [Online 19 May 2003]