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 μg/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 μg/L are 0.3 and 0.2 μg/kg/day, respectively. For the 99th percentile, this is half the value previously estimated by the U.S. EPA.

Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans

“…Stern (2005) reported that the mean half-lives of four studies increased with increasing MeHg doses, i.e. there was a positive correlation between the exposure dose and half-life, but our crude/recalculated half-lives under the exposure dose of 0.486 μg/kg BW/day did not seem to correspond with that result.…”

“…In past studies, the half-life in whole blood was around 50 days (Stern, 2005), as mentioned above. The average half-life in hair was calculated to be 72 (range, 35 to 189) days in Iraqi patients with high blood levels of T-Hg (Al-Shahristani and Shihab, 1974), and that in hair was 80 (33 to 120) days in volunteers having high MeHg intakes from fish (Birke et al, 1972).…”

Assessing determinants of maternal blood concentrations for persistent organic pollutants and metals in the eastern and western Canadian Arctic

“…While targeted mechanistic modeling suggests that advisories that temporarily eliminate or lower maternal fish consumption are unlikely to be effective in reducing prenatal, postnatal, and childhood exposures to long-lived persistent organic pollutants, lowering the consumption of food items that contain chemicals with elimination half-lives shorter than the period of dietary change may be highly effective for reducing these human exposures . For example, methyl mercury, which has a half-life of 40-60 days in people (Stern, 2005; Yaginuma-Sakurai et al, 2012), comprises a large fraction of total mercury in blood. Its presence in people is indicative of recent exposures from a diet that includes fish and other seafood or marine mammals.…”

“…The Northern Contaminants Program (NCP) of Aboriginal Affairs and Northern Development Canada supported maternal biomonitoring studies in the Inuvik Region of the Northwest Territories in 2005(Armstrong et al, 2007 and the Baffin Region of Nunavut (Potyrala et al, 2008(Potyrala et al, ) in 2005(Potyrala et al, -2007. All mothers who volunteered were sampled due to small population sizes in order to create these convenience samples of northern women.…”

Reverse dosimetry: interpreting trihalomethanes biomonitoring data using physiologically based pharmacokinetic modeling

“…Despite its well-accepted role as an analytical tool for improving the scientific basis of risk assessment procedures, the use of PBPK modeling has been applied only recently in estimating human exposures or health risks from biomonitoring data (Georgopoulos et al, 1994;Roy et al, 1996;Clewell et al, 1999;Sohn et al, 2004;Aylward et al, 2005;Stern, 2005;Gosselin et al, 2006). Biomonitoring data collected and reported in recent years are valuable for several roles: (1) establishing baseline measures of human exposure to environmental chemicals, (2) identifying subgroups with higher exposures, (3) tracking trends in exposure levels, and (4) setting priorities for research on human health effects (CDC, 2005).…”