咪康唑是一种以两种对映体存在的手性农药,R-(-)-烯立康唑和S-(+)-烯立康唑,R-对映体比S-对映体活性大得多。先前对酮唑的对映选择性毒理学研究主要集中在简单的环境模型生物上。在这项研究中,我们评估了两种烯立康唑对映体在大鼠和小鼠中的毒代动力学,以提供更全面的风险评估。两种对映异构体在体内立体选择性含量上显示出明显差异。R-(-)-烯立康唑的t1/2为7.06±3.35h,而S-(+)-烯立康唑为9.14±4.60h,表明R-(-)-烯立康唑在体内消除更快。R-(-)-烯立康唑和S-(+)-烯立康唑的排泄率分别为4.08±0.50%和2.68±0.58%,分别,表明R-(-)-烯立康唑的排泄更多。S-(+)-烯立康唑的生物利用度高于R-(-)-烯立康唑(52.19%vs.42.44%)。在胃等组织中也发现了相对较高的丰度。大肠,小肠,盲肠,肝脏,肾,大脑,和睾丸,丰度是R-(-)-烯立康唑的1.71-2.48倍。两种对映体在组织中的选择性降解及其在体内的相互转化均未观察到,这可能表明构型转化对组织中对映异构体含量的差异没有贡献。相反,这种差异主要是由每种对映体对组织的亲和力差异引起的。此外,对土壤中光学纯R-(-)-烯立康唑和S-()-烯立康唑单体之间的相互转化的研究表明,没有相互转化。所有上述结果表明R-(-)-烯立康唑和S-(+)-烯立康唑在体内和土壤中没有相互转化,S-(+)-烯立康唑倾向于具有更大的体内积聚潜力。因此,如果只使用R-(-)-烯立康唑作为杀虫剂,对哺乳动物和环境的负面影响将会减少,这表明在农业中,光学纯R-(-)-烯立康唑的应用可能是更好的策略。
Diniconazole is a chiral pesticide that exists in two enantiomers, R-(-)-diniconazole and S-(+)-diniconazole, with the R-enantiomer being much more active than the S-enantiomer. Previous enantioselective toxicology studies of diniconazole focused mostly on simple environmental model organisms. In this study, we evaluated the toxicokinetics of the two diniconazole enantiomers in rats and mice to provide a more comprehensive risk assessment. The two enantiomers displayed clear differences in their stereoselective contents in vivo. The t1/2 of R-(-)-diniconazole was 7.06 ± 3.35 h, whereas that of S-(+)-diniconazole was 9.14 ± 4.60 h, indicating that R-(-)-diniconazole was eliminated faster in vivo. The excretion rates of R-(-)-diniconazole and S-(+)-diniconazole were 4.08 ± 0.50 % and 2.68 ± 0.58 %, respectively, indicating more excretion of R-(-)-diniconazole. S-(+)-diniconazole had a higher bioavailability than R-(-)-diniconazole (52.19 % vs. 42.44 %). S-(+)-Diniconazole was also found in relatively high abundance in tissues such as the stomach, large intestine, small intestine, cecum, liver, kidney, brain, and testes, with the abundance being 1.71-2.48-fold that of R-(-)-diniconazole. The selective degradation of both enantiomers in the tissues and their mutual conversion in vivo were not observed, and this could indicate that configuration conversion did not contribute to the differences in the content of enantiomers in the tissues. Instead, such differences were mainly caused by the differences in affinity of each enantiomer for the tissues. Furthermore, investigation of the interconversion between optically pure R-(-)-diniconazole and S-(+)-diniconazole monomers in soil revealed no interconversion. All of the above results indicated no interconversion between R-(-)-diniconazole and S-(+)-diniconazole in vivo and in the soil, and that S-(+)-diniconazole tends to have a greater potential to accumulate in vivo. Thus, if only R-(-)-diniconazole is used as a pesticide, the negative impact on mammals and the environment will be reduced, suggesting that in agriculture, the application of optically pure R-(-)-diniconazole may be a better strategy.