Physiologically based pharmacokinetic modeling of the lactational transfer of methylmercury

The developmental neurotoxicity of methylmercury (MeHg) in humans has been described following catastrophic events in Minamata Bay, Japan and in Iraq, and following the exposure to lower doses elsewhere in the world. The most common route of MeHg exposure in humans is through the intake of contaminated food, especially fish. Although the precautions against the ingestion of potentially contaminated food during pregnancy are well recognized, precautions against the ingestion of MeHg during lactation are not so uniformly recognized. However, the continued development of the central nervous system during the early postnatal period serves to prolong the period during which this critical system is susceptible to the toxic insult of MeHg. Because no direct method is available to quantitatively assess the lactational transfer of MeHg to humans, a computer-aided simulation method was developed. An available gestational physiologically based pharmacokinetic model was refined and expanded to include parameters and algorithms specific for the elimination of MeHg in breast milk. The predictions of the completed model were compared with experimental data obtained from rodents, and the model parameters were allometrically scaled to humans. Finally, the model was validated by comparing its predictions against the available clinical data for MeHg distribution and elimination in mothers and their nursing infants. This model incorporated current and previous maternal exposures to MeHg to accurately predict the kinetics of MeHg excretion in breast milk and the daily intake by the nursing infant. This model may be used to quantify MeHg intake by the nursing infant, under different rates of maternal MeHg ingestion.