Modeling interactions and toxicity of Cu-Zn mixtures to zebrafish larvae

- A developed TK-TD model was used to model interactions and toxicity of Cu−Zn mixtures.
- Zn behaved as competitive inhibitors of Cu uptake at high Zn2+ levels.
- Taking metal interactions into TK model increase the predictive ability of Cu-Zn mixtures toxicity.

Quantitative predictions of metal-metal interactions and toxicity in aquatic organisms meet a unique challenge. Accumulation and toxicity of Cu and Zn mixtures in zebrafish larvae has been quantified in binary metal system with variable combinatorial concentrations in order to understand the interactions between essential trace metals and assess availability of the toxicokinetic-toxicodynamic (TK-TD) model which simulated the uptake of metals over time as well as metal toxicity after 24 h of exposure. Competitive uptake experiments showed a straightforward antagonistic competition, as would be predicted by Michaelis-Menten competitive equilibrium model. Zn uptake decreased significantly in the presence of Cu2+ concentrations higher than 10−6 M. Cu2+ was shown to compete strongly with Zn for uptake, having a higher affinity constant to biotic ligand (BL) sites (KCuBL=105.42 M−1) than Zn (KZnBL=104.13 M−1). TK-TD model considering potential metal-metal antagonism interactions showed good predictive power in predicting accumulation and toxicity of Cu-Zn mixtures in zebrafish larvae with the high coefficient of determination (r2) and significant level (p). In particular, with the elevated Zn concentrations in mixtures, the TD model showed better predictive power in predicting toxicity of 10−6 M Cu concentration in Cu-Zn mixtures. The TK-TD analysis provided some new insights into the interactive mechanism of binary Cu and Zn exposure in aquatic animals and may have important implications for our understanding of quantitative predictions of metal-metal interactions and toxicity in a field where animals are simultaneously exposed to several metals.