A dose-based modeling approach for accumulation and toxicity of arsenic in tilapia Oreochromis mossambicus

We proposed an approach to relate metal toxicity to the concentrations of arsenic (As) in specific target organs of tilapia Oreochromis mossambicus. The relationships among As exposure, uptake, accumulation, and toxicity of tilapia were investigated using kinetic and dynamic modeling. The biouptake rate of waterborne As through the gills of fish was dependent on exposure concentrations, in that the relationship was well described by incorporating Michaelis-Menten type uptake kinetics. The fitted bioaffinity parameter and limiting uptake flux were 3.07 +/- 2.21 microg/mL(-1) (mean +/- SD) and 2.17 +/- 0.38 microg/mL(-1)/d(-1), respectively, suggesting that a low As binding affinity of tilapia gills, yet a relatively high binding capacity was obtained. The toxicity of As was analyzed by determining the lethal exposure concentration associated with a mortality of 50% (LC50) at different integration times. Our results demonstrate that 96-h and incipient LC50s for tilapia are 28.68 (95% CI: 15.98-47.38) and 25.55 microg/mL(-1), respectively. The organ-specific internal residue associated with 50% mortality was estimated by combining the model-predicted toxicokinetic parameters and the area-under-curve (AUC)-based time-integrated concentration toxicity model. A physiologically based toxicokinetic model was constructed to elucidate the principle mechanisms that account for the observed data and to predict the kinetics of As in tilapia under different water exposure scenarios. We employed the Hill equation model to predict the organ-specific dose-response relationships. We used the liver as a surrogate of target sites to assess the As toxicity to tilapia because of its higher sensitivity to As toxic effects. The predicted mortalities never reach 50% when the tilapia were exposed to waterborne As <2 microg/mL(-1). The predicted mortality is, however, slightly higher than the observed values before the 10th day in that the profile reached the 70% maximum mortality, which is comparable to the observed data when the tilapia were exposed to 4 microg/mL(-1). Our results show that a dose-based toxicokinetic and toxicodynamic modeling approach successfully links metal exposure to bioavailability, bioaccumulation, and toxicity, under variable exposure scenarios.