A physiologically based pharmacokinetic model for methyl mercury in the pregnant rat and fetus

Current methyl mercury (MeHg) guidelines for human exposure are not adequately protective against developmental effects in the children of women consuming MeHg-contaminated food. There is an urgent need to find ways to use human and/or animal studies of MeHg developmental toxicity to assess human health risk. To this end, a physiologically based pharmacokinetic model (PBPK) for methyl mercury in the pregnant rat and fetus has been developed. The cell membrane, blood-brain barrier, and the maternal/fetal placental membrane are the primary limitations to the distribution of MeHg in the pregnant rat and fetus. Individual fetal organs were modeled, including the fetal brain. Model results compare well with experimental data indicating that the model can be used to predict maternal or fetal organ MeHg concentrations for many dosing regimes. The model will allow the development of target organ (brain) dose-response relationships from studies of developmental toxicity in the rat which can be extrapolated to human physiology and used to develop exposure guidelines and standards that are protective against the MeHg exposure to the fetus.