Bayer AG Division Crop Science, Alfred-Nobel-Strasse 50, 40789, Monheim, Germany.
Chemosphere. 2021 Aug;277:130254. doi: 10.1016/j.chemosphere.2021.130254. Epub 2021 Mar 20.
Liver S9 fractions from common carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) were incubated with seven pesticides (fenamidone, fenoxaprop-p-ethyl, penflufen, spirotetramat, tebuconazole, tembotrione and trifloxystrobin) and the metabolic pathways of the applied chemicals were determined by HPLC-high-resolution mass spectrometry. Five of the seven pesticides (fenamidone, penflufen, spirotetramat, trifloxystrobin and fenoxaprop-p-ethyl) revealed a higher metabolic capacity of rainbow trout liver fractions compared to carp liver fractions. The other two pesticides (tebuconazole and tembotrione) showed a similar and marginal biotransformation for liver S9 fractions of both species. Furthermore, four compounds (penflufen, spirotetramat, tembotrione and tebuconazole) were incubated with cryo-preserved hepatocytes of rainbow trout showing additional conjugated metabolites compared to liver S9 fractions. The incubations were performed with concentrations of 1 and 10 μM for experiments with liver S9 fractions and 5 μM with hepatocytes for up to 120 (liver S9 fractions) or 240 min (hepatocytes). A set of positive controls was used to confirm the metabolic capability of the in vitro systems. The comparison of the in vitro results from hepatocyte assays of penflufen and tebuconazole with the data from corresponding in vivo studies performed according to OECD (Organisation for Economic Co-operation and Development) guideline 305 exhibited a similar metabolic behavior for these pesticides and emphasizes the reliability of the in vitro assays. Besides investigation of the metabolism of plant protection products for research purposes, inter-species comparison by in vitro assays and the use of PBTK modelling approaches will allow improved environmental and dietary risk assessments.
采用高效液相色谱-高分辨质谱法，研究了 7 种农药（环丙唑醇、精噁唑禾草灵、苯霜灵、螺虫乙酯、戊唑醇、溴苯腈和三氟羧草醚）在鲤鱼（Cyprinus carpio）和虹鳟（Oncorhynchus mykiss）肝 S9 中的代谢途径。结果表明，与鲤鱼肝 S9 相比，这 7 种农药中有 5 种（环丙唑醇、苯霜灵、螺虫乙酯、三氟羧草醚和精噁唑禾草灵）对虹鳟肝 S9 具有更高的代谢能力。另外两种农药（戊唑醇和溴苯腈）对两种鱼的肝 S9 表现出相似的、微弱的生物转化能力。此外，与肝 S9 相比，四种化合物（苯霜灵、螺虫乙酯、溴苯腈和戊唑醇）在与冷冻保存的虹鳟肝细胞孵育时产生了更多的结合代谢产物。实验采用 1μM 和 10μM 两种浓度进行肝 S9 孵育，采用 5μM 浓度进行肝细胞孵育，孵育时间长达 120min（肝 S9 孵育）或 240min（肝细胞孵育）。采用阳性对照来验证体外系统的代谢能力。通过将苯霜灵和戊唑醇的肝细胞实验与 OECD（经济合作与发展组织）指导方针 305 中相应的体内研究数据进行比较，发现这些农药的代谢行为相似，这也强调了体外实验的可靠性。除了用于研究目的的植物保护产品代谢研究外，通过体外实验进行种间比较并利用 PBTK 建模方法，将有助于改善环境和饮食风险评估。
