A physiologically based toxicokinetic model for methylmercury in female American kestrels

A physiologically based toxicokinetic (PBTK) model was developed to describe the uptake, distribution, and elimination of methylmercury (CH ₃Hg) in female American kestrels. The model consists of six tissue compartments corresponding to the brain, liver, kidney, gut, red blood cells, and remaining carcass. Additional compartments describe the elimination of CH₃Hg to eggs and growing feathers. Dietary uptake of CH ₃Hg was modeled as a diffusion-limited process, and the distribution of CH₃Hg among compartments was assumed to be mediated by the flow of blood plasma. To the extent possible, model parameters were developed using information from American kestrels. Additional parameters were based on measured values for closely related species and allometric relationships for birds. The model was calibrated using data from dietary dosing studies with American kestrels. Good agreement between model simulations and measured CH₃Hg concentrations in blood and tissues during the loading phase of these studies was obtained by fitting model parameters that control dietary uptake of CH ₃Hg and possible hepatic demethylation. Modeled results tended to underestimate the observed effect of egg production on circulating levels of CH₃Hg. In general, however, simulations were consistent with observed patterns of CH₃Hg uptake and elimination in birds, including the dominant role of feather molt. This model could be used to extrapolate CH ₃Hg kinetics from American kestrels to other bird species by appropriate reassignment of parameter values. Alternatively, when combined with a bioenergetics-based description, the model could be used to simulate CH ₃Hg kinetics in a long-term environmental exposure.