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.
Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Shuangqing RD 18, Beijing 100085, China.
Ecotoxicol Environ Saf. 2019 Apr 30;171:247-255. doi: 10.1016/j.ecoenv.2018.12.094. Epub 2019 Jan 3.
Enantioselective toxicokinetics, accumulation, and toxicity of myclobutanil were investigated by oral exposure of myclobutanil enantiomers to lizards. After a single oral administration, the absorption half-lives ( [Formula: see text] ) and elimination half-lives (t) were in the range of 0.133-14.828 and 3.641-17.682 h, respectively. The absorption and elimination half-lives of (+)-myclobutanil showed no significant differences from those of (-)-myclobutanil in lizard blood, whereas preferential enrichment of (-)-enantiomer was observed in the liver, fat, skin, intestine, lung and kidney. In the bioaccumulation experiments, the residue of (-)-myclobutanil was detected in most tissues at 7, 14, and 28 days, while (+)-myclobutanil was found only in lizard skin, at a concentration lower than that of (-)-myclobutanil. Thus, (-)-myclobutanil was preferentially accumulated in lizards. The transcriptional responses of metabolic enzyme genes indicated that cytochrome P450 1a1 (cyp1a1), cyp2d3, cyp2d6, cyp3a4 and cyp3a7 played a crucial role in the metabolism of (+)-myclobutanil, whereas cyp1a1, cyp2d3, cyp2d6, cyp2c8, and cyp3a4 contributed to the metabolism of (-)-myclobutanil. The difference in metabolism pathways may be a reason for the enantioselectivity of myclobutanil in lizard. Myclobutanil also affected the expression of antioxidant enzyme genes, and the (+)-myclobutanil treatment might produce higher oxidative stress in lizard liver when compared with its antipode. Hepatic histopathological changes such as hepatocellular hypertrophy, nuclear pyknosis, vacuolation, and non-zonal macrovesicular lipid accumulation were observed in the liver of lizards for both (+)-myclobutanil and (-)-myclobutanil treatments. Thus, myclobutanil could affect lizard liver upon multiple exposure. The findings of this study provide specific insights into the enantioselective metabolism and toxicity of chiral triazole fungicides in lizards.
通过蜥蜴口服暴露于咪鲜胺对映异构体来研究咪鲜胺的对映选择性毒代动力学、积累和毒性。单次口服后，吸收半衰期（[公式：见文本]）和消除半衰期（t）分别在 0.133-14.828 和 3.641-17.682 h 范围内。(+) - 咪鲜胺和（-）-咪鲜胺在蜥蜴血液中的吸收和消除半衰期没有显著差异，而（-）-对映体在肝脏、脂肪、皮肤、肠道、肺和肾脏中优先富集。在生物积累实验中，7、14 和 28 天时，大多数组织中都检测到（-）-咪鲜胺的残留，而（+）-咪鲜胺仅在蜥蜴皮肤中被发现，浓度低于（-）-咪鲜胺。因此，（-）-咪鲜胺在蜥蜴体内优先积累。代谢酶基因的转录反应表明，细胞色素 P450 1a1（cyp1a1）、cyp2d3、cyp2d6、cyp3a4 和 cyp3a7 在（+）-咪鲜胺的代谢中起着关键作用，而 cyp1a1、cyp2d3、cyp2d6、cyp2c8 和 cyp3a4 有助于（-）-咪鲜胺的代谢。代谢途径的差异可能是咪鲜胺在蜥蜴体内对映选择性的原因。咪鲜胺还影响抗氧化酶基因的表达，与对映体相比，（+）-咪鲜胺处理可能在蜥蜴肝脏中产生更高的氧化应激。在（+）-咪鲜胺和（-）-咪鲜胺处理的蜥蜴肝脏中均观察到肝组织病理学变化，如肝细胞肥大、核固缩、空泡化和非区域大泡状脂肪堆积。因此，咪鲜胺多次暴露可能会影响蜥蜴肝脏。本研究的结果为手性三唑类杀菌剂在蜥蜴体内的对映选择性代谢和毒性提供了具体的见解。
