Determination of the Low Hg Accumulation in Rabbitfish (Siganus canaliculatus) by Various Elimination Pathways: Simulation by a Physiologically Based Pharmacokinetic Model

Mercury (Hg) in fish poses a great threat to human health. Consumption of low-Hg-level fish species (e.g., rabbitfish, Siganus canaliculatus) could be one possible solution to balance the nutrient benefits and Hg exposure. However, the underlying mechanisms for the low Hg accumulation in rabbitfish remain unclear. This study quantitatively described the disposition of inorganic Hg(II) and methylmercury (MeHg) in rabbitfish under different exposure routes by constructing a physiologically based pharmacokinetic (PBPK) model. The results strongly suggested that effective elimination (estimated rate constant of 0.060, 0.065, and 0.020 d^-1 for waterborne Hg(II)-, dietary Hg(II)-, and MeHg-exposed fish, respectively) was the main reason for the low Hg accumulation in rabbitfish. By quantifying the possible pathways for Hg elimination, our study revealed that biliary coupled with fecal excretion played an important role in the elimination of dietary Hg. Although the biliary excretion rate for MeHg was remarkable (6.8 ± 2.2 d^-1) and the excreted amount per day could reach up to 790 ng, most of the MeHg in the bile was reabsorbed by the intestine and transferred back to the liver through enterohepatic circulation, leading to a prolonged retention time in the fish body. Moreover, branchial excretion dominated the Hg(II) elimination following aqueous exposure, suggesting a flexible alteration on elimination pathways against different exposure scenarios. The present study provided important understanding of the unique strategies adopted by rabbitfish to maintain the low Hg levels.