基于毒代-毒效动力学（TK-TD）过程的水环境重金属联合毒性机制及预测模型研究

重金属的联合毒性在实际环境中普遍存在，目前常用基于无相互作用的相加或独立模型来预测重金属的联合毒性，从而带来重金属的环境风险评价和基准值的不确定性。本项目突破传统将受试生物体看作黑箱的联合毒性预测理论体系，采用系统毒理学的方法，以斑马鱼为受试生物，选择分子水平（如抗氧化响应、金属硫蛋白响应）和个体水平（致死效应）等效应指标，研究Cu、Zn、Cd等典型重金属在生物体内吸收、转化和排出过程以及毒效过程中的相互作用及其规律，量化重金属之间在生物体内毒代和毒效过程中的联合作用效应，建立基于毒代和毒效动力学过程的预测重金属拮抗或协同作用的新方法，研发水环境重金属Cu、Zn、Cd的二元混合物联合毒性预测模型，评估模型的不确定性和适用性。研究结果对于揭示重金属联合效应的形成机理，准确预测和评价水环境重金属的联合毒性及其生态风险有重要意义，同时也有助于进一步科学制定和改进重金属的环境基准与环境容量。

The joint toxicity of heavy metals is ubiquitous in the real world. At present, the concentration addition or independent action model based on no interactions is commonly used to predict the joint toxicity of heavy metals, thus bringing uncertainty in assessing the environmental risk and setting the criteria values for heavy metals. This project breaks through the traditional theoretical system of the toxicity prediction in which the tested organism is regarded as a black box. In this study, by selecting different toxicological endpoint indicators in the molecular level (such as antioxidant response and metallothionein response) and the individual Level (lethal effect), we will investigate the toxicological interactions of the typical binary metals mixture (Cu, Zn, Cd) in toxicokinetics (TK) such as absorption, transformation, excretion and toxicodynamics (TD) processes respectively, with the Zebrafish (Danio rerio) as the tested organism. In addition, by quantifying the interactions strengths of heavy metals in the toxicokinetcs and toxicodynamics, we aim to establish a new approach to predict heavy metal antagonism or synergism with the TK-TD model considering the metal interactions. Furthermore, the project will develop a joint toxicity prediction model for binary mixtures of Cu, Zn and Cd in aquatic environment and evaluate the uncertainty and applicability of the model in different environmental conditions. The results of this study are of great significance to reveal the mechanism of the joint effects of heavy metals and to predict and evaluate the joint toxicity and ecological risk of heavy metals in water environment. The metal mixture toxicological model also helps to further develop and improve the aquatic criteria and environmental capacity for heavy metals more scientifically.