Traditional risk assessments of chiral pesticides mainly depend on racemic form, which is often incomprehensive. This study conducted systemic investigations on the bioactivity, toxicity, and ecotoxicological effects of hexythiazox (HTZ) at the enantiomer level. The elution order and absolute configuration of HTZ enantiomers were determined. ()-(+)-HTZ exhibited 708 and 1719 times higher bioactivity against and eggs than ()-(−)-HTZ, respectively. Molecular docking indicated greater interactions between ()-(+)-HTZ and chitin synthase leading to higher bioactivity of ()-(+)-HTZ. However, ()-(−)-HTZ induced greater changes in protein and malondialdehyde content, and antioxidant and detoxification enzyme activities than ()-(+)-HTZ in earthworms. Furthermore, integrated biomarker response results indicated ()-(−)-HTZ exhibited higher toxic effects on earthworms than ()-(+)-HTZ. Finally, significant differentially expressed genes (DEGs) were observed in earthworms after exposure to ()-(+)-HTZ and ()-(−)-HTZ, respectively. These DEGs were mainly enriched in glycolysis/gluconeogenesis and purine metabolism pathways in earthworms. Additionally, six metabolism pathways were also enriched, including pyruvate metabolism, fatty acid biosynthesis, oxidative phosphorylation, citric acid cycle, fatty acid degradation, and ATP-binding cassette transporters. These findings suggest that earthworms exhibited enantiomer-specific responses to ()-(+)-HTZ and ()-(−)-HTZ. This study provides systemic insight into the toxicity mechanism of HTZ at the enantiomer level and the potential to develop ()-(+)-HTZ as a high-efficiency and low-risk pesticide.

中文翻译：

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新型杀螨剂噻唑嗪在对映体水平上改善生物活性和降低风险的系统评价

传统的手性农药风险评估主要依赖于外消旋形式，这往往不全面。本研究在对映体水平上对噻唑嗪（HTZ）的生物活性、毒性和生态毒理学效应进行了系统研究。确定了 HTZ 对映体的洗脱顺序和绝对构型。 ()-(+)-HTZ 对卵的生物活性分别是 ()-(−)-HTZ 的 708 倍和 1719 倍。分子对接表明 ()-(+)-HTZ 和几丁质合酶之间存在更大的相互作用，导致 ()-(+)-HTZ 具有更高的生物活性。然而，与()-(+)-HTZ相比，()-(−)-HTZ在蚯蚓中引起的蛋白质和丙二醛含量以及抗氧化和解毒酶活性的变化更大。此外，综合生物标志物反应结果表明，()-(−)-HTZ 对蚯蚓的毒性作用高于 ()-(+)-HTZ。最后，分别暴露于()-(+)-HTZ和()-(−)-HTZ后，在蚯蚓中观察到显着的差异表达基因(DEG)。这些DEG主要富集在蚯蚓的糖酵解/糖异生和嘌呤代谢途径中。此外，还丰富了六种代谢途径，包括丙酮酸代谢、脂肪酸生物合成、氧化磷酸化、柠檬酸循环、脂肪酸降解和ATP结合盒转运蛋白。这些发现表明，蚯蚓对 ()-(+)-HTZ 和 ()-(−)-HTZ 表现出对映体特异性反应。本研究从对映体水平系统地了解了 HTZ 的毒性机制，以及开发 ()-(+)-HTZ 作为高效、低风险农药的潜力。