Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Shuangqing RD 18, Beijing, 100085, China.
Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Shuangqing RD 18, Beijing, 100085, China; University of the Chinese Academy of Sciences, Yuquan RD 19 a, Beijing, 100049, China.
Chemosphere. 2021 May;271:129482. doi: 10.1016/j.chemosphere.2020.129482. Epub 2021 Jan 3.
The enantioselective accumulation, elimination and metabolism of fenbuconazole in lizards were determined following a single-dose (25 mg/kg) exposure to racemic or enantiomeric fenbuconazole. Accumulation of fenbuconazole was found in lizard fat with rac-form > enantiopure enantiomers. The enantiomer fractions (EFs) were higher than 0.5 in the blood, while EFs were less than 0.5 in the liver, brain, skin and stomach. There was conversion from (+)-fenbuconazole to (-)-fenbuconazole in lizard liver and conversion from (-)-fenbuconazole to (+)-fenbuconazole in lizard liver and blood. The results showed that enantioselective accumulation appeared in lizards, but the direction varied among blood and different tissues. The elimination half-lives (t) of (+)-fenbuconazole were higher than those of (-)-fenbuconazole in the blood and liver, suggesting that (-)-fenbuconazole eliminated faster than (+)-fenbuconazole in these tissues. In addition, both (+)-fenbuconazole and (-)-fenbuconazole eliminated faster in the liver and stomach exposed to racemate than those exposed to enantiopure enantiomers. On the contrary, the form of racemate decreased the elimination rate of fenbuconazole in lizard fat. Synergistic elimination may occur when two enantiomers coexisted in lizard liver and stomach, while the racemate produced antagonistic elimination in lizard fat. Simultaneously, three metabolites, RH-6467, RH-9029&RH-9030 and keto-mchlorophenol, were discovered in lizard liver. Only two metabolites, RH-6467 and RH-9029&RH-9030, were found in lizard blood. RH-9029&RH-9030 were the major metabolites. The discovered enantiomers of (+)-fenbuconazole metabolites were different from those of (-)-fenbuconazole. The findings of this study may provide a better understanding of the enantioselective behaviors of chiral triazole fungicides in reptiles.
在蜥蜴中进行了单次剂量（25mg/kg）暴露于外消旋或对映纯芬布康唑后，测定了芬布康唑的对映选择性积累、消除和代谢。在蜥蜴脂肪中发现了芬布康唑的积累，其中 rac 形式>对映纯对映体。在血液中，对映体分数（EF）高于 0.5，而在肝脏、大脑、皮肤和胃中，EF 小于 0.5。在蜥蜴肝脏中，（+）-芬布康唑向（-）-芬布康唑转化，在蜥蜴肝脏和血液中，（-）-芬布康唑向（+）-芬布康唑转化。结果表明，对映选择性积累出现在蜥蜴中，但在血液和不同组织之间的方向不同。（+）-芬布康唑在血液和肝脏中的消除半衰期（t）高于（-）-芬布康唑，表明（-）-芬布康唑在这些组织中的消除速度快于（+）-芬布康唑。此外，在暴露于外消旋体的肝脏和胃中，（+）-芬布康唑和（-）-芬布康唑的消除速度均快于暴露于对映纯对映体的情况。相反，在外消旋体中，芬布康唑在蜥蜴脂肪中的消除率降低。当两种对映体在蜥蜴肝脏和胃中共存时，可能会发生协同消除，而在外消旋体中，在蜥蜴脂肪中产生拮抗消除。同时，在蜥蜴肝脏中发现了三种代谢物 RH-6467、RH-9029&RH-9030 和酮基-M 氯苯酚，而在蜥蜴血液中仅发现了两种代谢物 RH-6467 和 RH-9029&RH-9030。RH-9029&RH-9030 是主要代谢物。（+）-芬布康唑代谢物的发现对映体与（-）-芬布康唑的代谢物不同。本研究的结果可能为了解手性三唑类杀菌剂在爬行动物中的对映选择性行为提供了更好的认识。
