Applications of dynamic models in predicting the bioaccumulation, transport and toxicity of trace metals in aquatic organisms

This review evaluates the three dynamic models (biokinetic model: BK, physiologically based pharmacokinetic model: PBPK, and toxicokinetic-toxicodynamic model: TKTD) in our understanding of the key questions in metal ecotoxicology in aquatic systems, i.e., bioaccumulation, transport and toxicity. All the models rely on the first-order kinetics principle of metal uptake and elimination. The BK model basically treats organisms as a single compartment, and is both physiologically and geochemically based. With a good understanding of each kinetic parameter, bioaccumulation of metals in any aquatic organisms can be studied holistically and mechanistically. Modeling efforts are not merely restrained from the prediction of metal accumulation in the tissues, but instead provide the direction of the key processes that need to be addressed. PBPK is more physiologically based since it mainly addresses the transportation, transformation and distribution of metals in the organisms. It can be treated conceptually as a multi-compartmental kinetic model, whereas the physiology is driving the development of any good PBPK model which is no generic for aquatic animals and contaminants. There are now increasingly applications of the PBPK modeling specifically in metal studies, which reveal many important processes that are impossible to be teased out by direct experimental measurements without adequate modeling. TKTD models further focus on metal toxicity in addition to metal bioaccumulation. The TK part links exposure and bioaccumulation, while the TD part links bioaccumulation and toxic effects. The separation of TK and TD makes it possible to model processes, e.g., toxicity modification by environmental factors, interaction between different metals, at both the toxicokinetic and toxicodynamic levels. TKTD models provide a framework for making full use of metal toxicity data, and thus provide more information for environmental risk assessments. Overall, the three models reviewed here will continue to provide guiding principles in our further studies of metal bioaccumulation and toxicity in aquatic organisms.