Abstract

1. Thiacloprid (THI) is a widely used neonicotinoid insecticide where concerns have been raised regarding low absorption by crops, substantial distribution in surrounding areas, and potential adverse effects to terrestrial and aquatic organisms.

2. Prior to this study, there was very limited information addressing the ex vivo (precision-cut liver slices) metabolism of THI by fish species and the metabolic pathways regulating its potential for adverse effects.

3. The in vitro and ex vivo biotransformation pathway of THI is defined by the formation of three primary metabolites (TM1, TM2 and TM3) via separate paths differentiated by reductive decyanation, reductive dechlorination with hydration and dealkylation processes, respectively.

4. Kinetic rates were calculated for the rat microsomal decyanation of THI into TM1 (K_m = 299.2 µM and V_max = 5.3 pmol/min/mg), and for the dealkylation of THI into TM3 (K_m = 368.9 µM and V_max = 3.95 pmol/min/mg).

5. Formation confirmation and identity inference of THI metabolites in absence of standards were achieved by LC-UV and High Resolution-MS strategies.

6. The in vitro and ex vivo metabolic products of THI are conserved both across species (rat and Rainbow trout) and levels of biological organization (microsomes and liver slices), as previously reported for the neonicotinoid insecticides Imidacloprid and Acetamiprid.

摘要

1. 噻虫啉 (THI) 是一种广泛使用的新烟碱类杀虫剂，人们对作物吸收率低、在周边地区大量分布以及对陆地和水生生物的潜在不利影响提出了担忧。

2. 在这项研究之前，关于鱼类对 THI 的离体（精确切割的肝切片）代谢以及调节其潜在副作用的代谢途径的信息非常有限。

3. THI的体外和离体生物转化途径定义为三种初级代谢物（TM1、TM2 和 TM3）的形成，分别通过还原脱氰化、水合还原脱氯和脱烷基化过程区分。

4. 计算了 THI 大鼠微粒体脱氰成 TM1 的动力学速率（K _m = 299.2 µM 和V _max = 5.3 pmol/min/mg），以及 THI 脱烷基化成 TM3 的动力学速率（K _m = 368.9 µM 和V _max = 3.95 pmol/分钟/毫克）。

5. 在没有标准品的情况下，THI 代谢物的形成确认和身份推断是通过 LC-UV 和高分辨率-MS 策略实现的。

6. THI的体外和离体代谢产物在物种（大鼠和虹鳟鱼）和生物组织水平（微粒体和肝切片）中都是保守的，如先前对新烟碱类杀虫剂吡虫啉和啶虫脒的报道。