基于代谢组学的手性新烟碱类农药呋虫胺在大鼠体内立体行为与毒理研究

The extensive use of chiral neonicotinoid pesticides poses high exposure risk to biological safety and human health. Due to the biotoxicity differences are significant between enantiomers of chiral neonicotinoids, the study of the enantioselective fate and toxicology in model animals will propose new ideas and methods for solving these scientific problems. A typical chiral neonicotinoid dinotefuran is selected to investigate the enantioselective absorption, distribution, transformation, metabolism and excretion in rats. The major metabolites of dinotefuran enantiomers and their metabolic pathways will be clarified in tissues and organs of rats. Then, the toxic effect of dinotefuran enantiomers are evaluated based on metabolomics from the perspective of systems biology, which aim to elucidate the effect of long-term dietary exposure on the growth, damage and metabolism of rats, and further to reveal the toxicology of the two enantiomers and the dominant regulations of the high exposure risk. This study will provide data support to establish a risk assessment system in mammals and theoretical foundation for risk warning of biological safety and human health.

手性新烟碱类农药使用量大，对生物安全和人类健康暴露风险高。研究表明，手性新烟碱类农药对映体间生物毒性差异显著，开展其在模式动物体内的立体行为与毒理研究能为上述科学问题的解决提供新思路和新方法。本项目选取典型手性新烟碱类农药呋虫胺，从对映体水平探究其在大鼠体内的选择性吸收、分布、转化、代谢和排泄特征，明确主要代谢产物及其不同组织器官中的代谢途径；进而，从系统生物学角度对呋虫胺对映体的毒性效应进行代谢组学解析，阐明长期膳食暴露对大鼠生长发育、功能损伤和机体代谢的影响，揭示呋虫胺对映体的毒性作用机理和高暴露风险的主导调控途径，为哺乳动物体内风险评估体系的建立提供数据支撑，为生物安全和人类健康的风险预警提供理论依据。