Concentration addition and independent action model: Which is better in predicting the toxicity for metal mixtures on zebrafish larvae

Highlights: • Joint toxicity was predicted by concentration addition (CA) and independent action (IA) models. • The IA model simulated the Cu-Pb mixture toxicity significantly better than the CA model. • The CA model simulated the CuCd and CdPb mixture toxicity better than the IA model. • For the Cu-Zn mixtures, it was difficult to recognize which of the two models was better. • CA and IA model are consistent in specifying interaction patterns of binary metal mixtures. The joint toxicity of chemical mixtures has emerged as a popular topic, particularly on the additive and potential synergistic actions of environmental mixtures. We investigated the 24 h toxicity of Cu–Zn, Cu–Cd, and Cu–Pb and 96 h toxicity of Cd–Pb binary mixtures on the survival of zebrafish larvae. Joint toxicity was predicted and compared using the concentration addition (CA) and independent action (IA) models with different assumptions in the toxic action mode in toxicodynamic processes through single and binary metal mixture tests. Results showed that the CA and IA models presented varying predictive abilities for different metal combinations. For the Cu–Cd and Cd–Pb mixtures, the CA model simulated the observed survival rates better than the IA model. By contrast, the IA model simulated the observed survival rates better than the CA model for the Cu–Zn and Cu–Pb mixtures. These findings revealed that the toxic action mode may depend on the combinations and concentrations of tested metal mixtures. Statistical analysis of the antagonistic or synergistic interactions indicated that synergistic interactions were observed for the Cu–Cd and Cu–Pb mixtures, non-interactions were observed for the Cd–Pb mixtures, and slight antagonistic interactions for the Cu–Zn mixtures. These results illustrated that the CA and IA models are consistent in specifying the interaction patterns of binary metal mixtures.