title: A revised probabilistic estimate of the maternal methyl mercury intake dose corresponding to a measured cord blood mercury concentration.
abstract: In 2001, the U.S. Environmental Protection Agency (EPA) adopted a revised reference dose (RfD) for methyl mercury (MeHg) of 0.1 microg/kg/day. The RfD is based on neurologic developmental effects measured in children associated with exposure in utero to MeHg from the maternal diet. The RfD derivation proceeded from a point of departure based on measured concentration of mercury in fetal cord blood (micrograms per liter). The RfD, however, is a maternal dose (micrograms per kilogram per day). Reconstruction of the maternal dose corresponding to this cord blood concentration, including the variability around this estimate, is a critical step in the RfD derivation. The dose reconstruction employed by the U.S. EPA using the one-compartment pharmacokinetic model contains two areas of significant uncertainty: It does not directly account for the influence of the ratio of cord blood: maternal blood Hg concentration, and it does not resolve uncertainty regarding the most appropriate central tendency estimates for pregnancy and third-trimester-specific model parameters. A probabilistic reassessment of this dose reconstruction was undertaken to address these areas of uncertainty and generally to reconsider the specification of model input parameters. On the basis of a thorough review of the literature and recalculation of the one-compartment model including sensitivity analyses, I estimated that the 95th and 99th percentiles (i.e., the lower 5th and 1st percentiles) of the maternal intake dose corresponding to a fetal cord blood Hg concentration of 58 microg/L are 0.3 and 0.2 microg/kg/day, respectively. For the 99th percentile, this is half the value previously estimated by the U.S. EPA.
authors.affiliation: Division of Science Research and Technology, New Jersey Department of Environmental Protection, Trenton, New Jersey 08625, USA. Alan.Stern@dep.state.nj.us
authors.forename: Alan H
authors.initials: AH
authors.lastname: Stern
mesh_terms: D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008628:Mercury / Q000097:blood*; D008767:Methylmercury Compounds / Q000097:blood / Q000493:pharmacokinetics*; D008954:Models, Biological; D009010:Monte Carlo Method; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011336:Probability; D018570:Risk Assessment; D035501:Uncertainty
chemical_list: D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D008628:Mercury