Physiologically based toxicokinetic and toxicodynamic (PBTK-TD) modelling of Cd and Pb exposure in adult zebrafish Danio rerio: Accumulation and toxicity

Abstract

Accurately predicting the accumulation and toxicity of metals in organisms is a challenging work in ecotoxicology. Here, we developed and validated a physiologically based toxicokinetic and toxicodynamic (PBTK-TD) model for adult zebrafish exposed to Cd and Pb. The model included the gill, liver, intestine, gonad, carcass, and brain, which were linked by blood circulation in the PBTK process and by dynamic relationships between the target organ concentrations and mortality in the TD process. Results showed that the PBTK sub-model can accurately describe and predict the uptake, distribution and disposition kinetics of Cd and Pb in zebrafish. The exchange rates and the accumulation of the metals in the organs were significantly different. For Cd, the highest exchange rate was between blood and liver, and the greatest accumulation of Cd occurred in the liver. For Pb, the greatest accumulation occurred in the gill. The TD sub-model further indicated that metal concentrations in the gill may effectively act as more suitable indicator of Cd and Pb toxic effect than whole body or other organs. The proposed PBTK-TD model is helpful to understanding the fundamental processes by which zebrafish regulate the uptake and disposition of metal and to quantitatively predicting metal toxicity.

Keywords: Metal toxicity; Physiologically based toxicokinetics; Toxicodynamics; Zebrafish.