拟除虫菊酯是一类广泛、高频应用于工农林业和室内除虫的杀虫剂，在饮用水和食物中普遍残留，人类主要通过膳食受到暴露。拟除虫菊酯是典型的手性化合物，表现出生物学效应（例如吸收、转运、代谢、毒性等）上的对映体差异。然而目前多数拟除虫菊酯杀虫剂的健康风险评估以及毒理机制研究没有考虑其对映体选择性，难以真实反映其对人类健康的潜在风险。本项目拟以使用最为广泛的典型I型和II型拟除虫菊酯- - 氯菊酯和氯氰菊酯为对象，研究人肠上皮细胞中拟除虫菊酯对映体的转运动力学参数和转运蛋白介导机制；甄别人肝微粒体中拟除虫菊酯对映体的代谢通路、动力学参数和特定酶分子，揭示人肝细胞中拟除虫菊酯对映体选择性诱导或抑制CYP450酶活性的分子机制；系统性比较和探讨1RS、3RS和αRS这3个手性中心分别影响拟除虫菊酯对映体选择性转运和代谢的规律。这些研究数据对于准确评价手性农药的人类健康风险具有很强的科学价值和现实意义。

Pyrethroids, a class of synthetic pesticides, are widely used for agricultural and indoor insect control. Pyrethroid residues are frequently detected in surface water and agricultural products. Human are mainly exposed to pyrethroids through consumption of contaminated foods and drinking water. Pyrethroids are typical chiral compounds, exhibit enantioselectivity in biological processes, such as absorption, transportation, metabolism, toxicity, etc. However, most health risk assessments and toxicological studies of chiral pyrethroids ignore their enantioselectivity and failed to accurately evaluate their potential risk to human health. This project intends to investigate the enantioselectivity of permethrin and cypermethrin, the most widely used type I and type II pyrethroids, in transporter kinetic parameters and the mechanism of transporter protein in the human intestinal epithelial cells; identify the metabolic pathways, kinetic parameters and specific metabolic enzyme for pyrethroid enantiomers in human liver microsomes and reveal the enantioselective induction or inhibition in CYP450 activity by pyrethroids enantiomers in human hepatocytes; systemically compare and explore the effects of the three chiral centers (1RS, 3RS and αRS) on the laws of the pyrethroids enantiomers transportation and metabolism. These studies are scientifically valuable and significant for accurate evaluation of chiral pesticide risks to human health.