The joint toxicity effects of mixtures, particularly reproductive toxicity, one of the main causes of aquatic ecosystem degradation, are often overlooked as it is impractical to test all mixtures. This study developed and evaluated three types of models aiming to predict the concentration response curve concerning the joint reproductive toxicity of mixtures of three bisphenol analogues (BPA, BPF, BPAF) on the rotifer Brachionus calyciflorus: concentration addition (CA) and independent action (IA). Deep neural network models using the ratios of chemicals in mixtures as input variables (DNN-Ratio). Additionally, the quantitative structure-activity relationship (QSAR) theory was employed as a basis to compute mixture descriptors and combined them with DNN to develop DNN-QSAR models. Descriptors related to molecular mass were found to be of greater importance and exhibited a proportional relationship with toxic effects. The results indicate that the range of correlation coefficients (R2) between predicted and measured values for various mixture rays by CA and IA models is 0.372 to 0.974 and - 0.970 to 0.586, respectively. The R2 values for DNN-Ratio and DNN-QSAR were 0.841 to 0.984 and 0.834 to 0.991, respectively, demonstrating that models developed by DNN significantly outperform traditional models in predicting the joint toxicity of mixtures. Furthermore, DNN-QSAR not only predicts mixture toxicity but also provides accurate toxicity predictions for BPA, BPF, and BPAF, with R2 values of 0.990, 0.616, and 0.887, respectively, while DNN-Ratio yields values of 0.920, 0.355, and - 0.495. The study also found that the joint effects of mixtures are primarily influenced by the total concentration of the mixtures, and an increase in total concentration shifts the joint effects towards addition. This study introduces a novel approach to predict joint toxicity and analyze the influencing factors of joint effects, providing a more comprehensive assessment of the ecological risk posed by mixtures.