Application of PBPK Model for Assessment of the Lactational Transfer of MEHG to Nursing Infant. J. Z. Byczkowski, TN & Associates, Inc.; and J. C. Lipscomb, U.S. EPA National Center for Environmental Assessment, Cincinnati, OH
Exposure of developing humans and animals to high concentrations of methylmercury (MeHg) may have catastrophic results to their central nervous system. Due to outbreaks of MeHg poisoning that occurred in Minimata Bay, Japan, and in Iraq, the developmental toxicity produced by MeHg has been well-documented in human subjects. While several pharmacokinetic models have been developed to address the transplacental transfer of MeHg in humans and animals, to date there was no report in the peer-reviewed literature about the construction of a functional physiologically based pharmacokinetic (PBPK) model for MeHg lactational transfer in humans. The goal of the present study was to develop a PBPK model which could be applied to the assessment of lactational transfer of MeHg from mother to the nursing infant. The PBPK model was based on information published by Gearhart et al. (1995) describing MeHg kinetics in the pregnant woman and fetus. An additional module was developed to describe the breast milk compartment, with subsequent delivery of MeHg with milk to the nursing infant. It was assumed that the concentration of MeHg in maternal blood plasma rapidly equilibrates with the aqueous phase of breast milk. The PBPK model for lactational transfer of MeHg was initially calibrated with experimental data from rats. Then, it was allometrically scaled to humans, and finally verified with the available data from mothers and their nursing infants. The model predicts kinetics of MeHg excretion with milk and the daily intake by infant, depending on current and previous maternal exposures to MeHg. There is close agreement between the data of Amin-Zaki et al. (1976) and predictions of concentrations of MeHg in breast milk and infants’ blood produced by this model.
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