典型过渡金属水生生物急性毒性阈值预测研究

Toxic potency such as acute toxicity threshold is the basis for study of environmental toxicology, which is one of the important parameters for the environmental standards development, risk assessment and damage identification. However, due to tests for determining toxic potencies are often costly and time-consuming, it is difficult but desirable to directly predict the unknown toxicity threshold of pollutants using minimal toxic data. This project plans to choose representative transition metals as study objects and establish a quantitative structure-activity relationship (QSAR) prediction model for the acute toxicity thresholds of representative transition metals to aquatic organisms. On the basis of existing research, with respect to metal bioavailability revised by the characteristics of the external environment condition, we improve nonparametric kernel density estimation method to propose a high-precision optimization model in order to derive accurate acute toxicity threshold of transition metals. Then we estimate novel structure parameters such as thermodynamic parameters by use of computational quantum chemistry method and comprehensively analyze the mechanism of toxicity and correlation between the parameters and acute toxicity threshold. Therefore, practical and theoretical prediction model of physicochemical properties - toxicity thresholds of transition metals will be established based on modern mathematical and statistical methods. Finally, further toxicity tests on model organisms such as Parva would be carried out to calibrate and validate the predicted model parameters, by use of which threshold concentrations for data-poor transition metals would be predicted. These findings will become a beneficial supplement to the researches of traditional environmental toxicology, provide a theoretical basis for risk assessment and controlling of metals, and enrich metal predictive toxicology.

生物毒性如急性毒性阈值是环境毒理研究的基础，是制定环境标准、风险评估与损害鉴定的重要参数之一。但由于污染物毒性实验需要耗费大量的人力、物力和财力，如何利用已有的污染物毒性数据预测未知毒性阈值是国际预测毒理领域的难点和趋势。项目拟以典型过渡金属为研究对象，开展基于定量构效关系的水生生物急性毒性阈值预测理论与实验研究。在前期工作基础上，综合主要水化学条件，改进非参数核密度估计方法，提出高精度过渡金属急性毒性阈值优化推导模型。采用量子化学方法准确估算如热力学常数的过渡金属各理化结构参数，解析主要参数与急性毒性阈值间的相关关系，阐述影响毒性阈值的理化结构机制和生物毒性机理。以现代数学统计方法为基础，构建过渡金属理化性质-毒性阈值预测理论和实用模型。通过麦穗鱼等模式生物室内毒性实验，开展模型校验研究及预测。成果将为传统环境毒理学研究提供有益补充，为金属风险评估与控制提供理论依据，丰富金属预测毒理学。

生物毒性是环境毒理研究的基础，毒性阈值则是制定环境标准、风险评估与损害鉴定的重要参数之一。但由于污染物毒性实验需要耗费大量的人力、物力和财力，如何利用已有的污染物毒性数据预测未知毒性阈值是国际预测毒理学领域的难点和趋势。项目以典型过渡金属为研究对象，通过改进非参数核密度估计方法，构建了十余种过渡金属急性毒性NPKDE-SSD模型，揭示了不同类别的水生生物对过渡金属的毒性敏感性变化规律。搜集整理并估算了过渡金属理化结构参数，建立了10种过渡金属的31种理化结构参数数据库，确定了主要结构参数与急性毒性/基准阈值间的相关关系，阐述了影响阈值的理化结构机制和致毒机理，构建了过渡金属理化性质-毒性/基准阈值理论预测模型，开展了过渡金属铜的室内急性毒性实验检验，同时预测了其他过渡金属急性毒性/基准阈值。项目还以现代数学统计方法为基础，将定量构效关系预测模型拓展至过渡金属慢性基准阈值和过渡金属人体健康效应剂量阈值的预测研究中，预测结果表现出方法学优势，在一定程度上完善了以保护水生态系统和人体健康为目标的水环境基准方法体系。成果将为传统环境毒理学研究提供有益补充，为金属风险评估与控制提供理论依据，丰富金属预测毒理学。