Physiologically Based Pharmacokinetic Model for Inorganic and Methylmercury in a Marine Fish

Abstract

A physiologically based pharmacokinetic (PBPK) model was developed to simulate the uptake, distribution, and elimination of inorganic mercury [Hg(II)] and methylmercury (MeHg) in a marine fish, Terapon jarbua. In this model, fish were schematized as a six-compartment model by assuming that blood was the medium linking the exchange between the different compartments. The transfer rates between blood and other compartments were determined during a period of 10-day dietary Hg(II) or MeHg exposure, followed by a 30-day depuration. For both Hg species, the exchange rates between liver and blood were high, indicating that liver served as a "transferring station" in the distribution. Their accumulation in the kidney was relatively constant and low. The carcass (mainly muscle) represented a large sink for both Hg(II) and MeHg with the highest input rate constants and relatively lower output rate constants. Significant differences were observed in the rate constants between the two Hg species, suggesting great variations in their exchange and transportation routes. Modeling simulation for the first time demonstrated that the gill was the most important route in Hg(II) elimination in marine fish, with a rate constant of 0.90 d(-1). A long time frame is needed to study the exact rate of MeHg elimination in marine fish. This study showed that the PBPK modeling provided critical information for the uptake, distribution and elimination of Hg(II) and MeHg in the fish body, especially in elucidating the role of each compartment.