Predicting the toxicity of chemical mixtures is difficult because of the additive, antagonistic, or synergistic interactions among the mixture components. Antagonistic and synergistic interactions are dominant in metal mixtures, and their distributions may correlate with exposure concentrations. However, whether the interaction types of metal mixtures change at different time points during toxicodynamic (TD) processes is undetermined because of insufficient appropriate models and metal bioaccumulation data at different time points. In the present study, the generalized linear model (GLM) was used to illustrate the combined toxicities of binary metal mixtures, such as Cu–Zn, Cu–Cd, and Cd–Pb, to zebrafish larvae (Danio rerio). GLM was also used to identify possible interaction types among these method for the traditional concentration addition (CA) and independent action (IA) models. Then the GLM were applied to quantify the different possible interaction types for metal mixture toxicity (Cu–Zn, Cu–Cd, and Cd–Pb to D. rerio and Ni–Co to Oligochaeta Enchytraeus crypticus) during the TD process at different exposure times. We found different metal interaction responses in the TD process and interactive coefficients significantly changed at different exposure times (p < 0.05), which indicated that the interaction types among Cu–Zn, Cu–Cd, Cd–Pb and Ni–Co were time dependent. Our analysis highlighted the importance of considering joint actions in the TD process to understand and predict metal mixture toxicology on organisms. Moreover, care should be taken when evaluating interactions in toxicity prediction because results may vary at different time points. The GLM could be an alternative or complementary approach for BLM to analyze and predict metal mixture toxicity.

由于混合物成分之间存在加成，拮抗或协同作用，因此很难预测化学混合物的毒性。拮抗和协同相互作用在金属混合物中占主导地位，它们的分布可能与暴露浓度相关。但是，由于在不同时间点的适当模型和金属生物积累数据不足，因此尚不确定在毒理动力学（TD）过程中金属混合物的相互作用类型是否在不同时间点改变。在本研究中，使用广义线性模型（GLM）来说明二元金属混合物（例如Cu-Zn，Cu-Cd和Cd-Pb）对斑马鱼幼虫的综合毒性（Danio rerio）。对于传统的浓度增加（CA）模型和独立作用（IA）模型，GLM还用于识别这些方法之间可能的相互作用类型。然后，将GLM应用于量化TD工艺在不同暴露时间下金属混合物毒性（Cu–Zn，Cu–Cd和Cd–Pb对D. rerio和Ni–Co对Oligochaeta Enchytraeus crypticus）的不同可能的相互作用类型。。我们发现TD过程中的金属相互作用不同，并且在不同的暴露时间下，相互作用系数显着变化（p < 0.05），这表明Cu-Zn，Cu-Cd，Cd-Pb和Ni-Co之间的相互作用类型是时间依赖性的。我们的分析突出了考虑在TD过程中采取联合行动以了解和预测金属混合物对生物体的毒理学的重要性。此外，在评估毒性预测中的相互作用时应格外小心，因为结果可能在不同的时间点有所不同。GLM可能是BLM分析和预测金属混合物毒性的替代方法或补充方法。