Physiologically based pharmacokinetic model revealed the distinct bio-transportation and turnover of arsenobetaine and arsenate in marine fish

Arsenobetaine (AsB) is the major form of arsenic in marine fish; however, its biodynamics within the fish tissues is not well understood. This study simulated the biodynamics and biotransportation (absorption, distribution, and elimination) of dietary AsB and arsenate [As(V)] in the marine grouper Epinephelus fuscoguttatus, by constructing a physiologically based pharmacokinetic (PBPK) model. The transfer rates between different compartments (gill, intestine, liver, heart, kidney, and muscle) and blood were modeled during exposure (14 d) and depuration (20 d). The model showed that AsB had a weak ability to cross the intestinal membranes and circulated slowly in the blood. The newly AsB absorbed from the blood did not enter the hepatointestinal circulation for elimination, but was effectively distributed in liver. Thereafter, it was slowly absorbed and finally stored in the muscle, the most important organ for AsB deposition, at a constant rate of 63.5 d(-1). In contrast, As (V) displayed a dynamic behavior, including rapid crossing through the intestinal membranes, quick circulation in the blood and transportation to other tissues, and elimination. Biodynamics coupled with biotransformation illustrated, for the first time, the unique strategies of dietary AsB that passed slowly through the fish intestine with the highest deposition rate in the muscle, thereby contributing to the high AsB bioaccumulation in the muscle tissue of marine fish.