State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China.
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China.
Sci Total Environ. 2017 Jul 15;590-591:50-59. doi: 10.1016/j.scitotenv.2017.03.038. Epub 2017 Mar 11.
Understanding the metabolism of chemicals as well as the distribution and depuration of their main metabolites in tissues are essential for evaluating their fate and potential toxicity in vivo. Herein, we investigated the metabolism of six typical organophosphate (OP) flame retardants (tripropyl phosphate (TPRP), tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tri-p-cresyl phosphate (p-TCP)) in adult zebrafish in laboratory at three levels (0, 1/150 LC (environmentally relevant level), and 1/30 LC per OP analog). Twenty main metabolites were detected in the liver of OPs-exposed zebrafish using high resolution mass spectrometry (Q-TOF). The reaction pathways involving scission of the ester bond (hydrolysis), cleavage of the ether bond, oxidative hydroxylation, dechlorination, and coupling with glucuronic acid were proposed, and were further confirmed by the frontier electron density and point charge calculations. Tissue distribution of the twenty metabolites revealed that liver and intestine with the highest levels of metabolites were the most active organs for OPs biotransformation among the studied tissues of intestine, liver, roe, brain, muscle, and gill, which showed the importance of hepatobiliary system (liver-bile-intestine) in the metabolism and excretion of OPs in zebrafish. Fast depuration of metabolites from tissues indicated that the formed metabolites might be not persistent in fish, and easily released into water. This study provides comprehensive information on the metabolism of OPs in the tissue of zebrafish, which might give some hints for the exploration of their toxic mechanism in aquatic life.
了解化学物质的代谢以及其主要代谢物在组织中的分布和消除对于评估其在体内的命运和潜在毒性至关重要。在此，我们在实验室中研究了六种典型有机磷（OP）阻燃剂（磷酸三丙酯（TPRP）、磷酸三丁酯（TNBP）、磷酸三（2-丁氧基乙基）酯（TBOEP）、磷酸三（2-氯乙基）酯（TCEP）、磷酸三（1,3-二氯-2-丙基）酯（TDCIPP）和磷酸三对甲酚酯（p-TCP））在成年斑马鱼体内的代谢情况，分为三个水平（0、1/150 LC（环境相关水平）和 1/30 LC/OP 类似物）。使用高分辨率质谱（Q-TOF）在暴露于 OP 的斑马鱼肝中检测到 20 种主要代谢物。提出了涉及酯键断裂（水解）、醚键断裂、氧化羟化、脱氯和与葡萄糖醛酸偶联的反应途径，并通过前沿电子密度和点电荷计算进一步证实。20 种代谢物的组织分布表明，肝脏和肠道是 OP 生物转化最活跃的器官，在研究的肠道、肝脏、鱼卵、大脑、肌肉和鳃等组织中，肝脏和肠道是 OP 代谢和排泄的最重要的器官，这表明了肝胆系统（肝-胆汁-肠道）在斑马鱼中 OP 代谢和排泄中的重要性。代谢物从组织中的快速消除表明形成的代谢物可能在鱼类中不持久，并且容易释放到水中。这项研究提供了关于 OP 在斑马鱼组织中代谢的全面信息，这可能为探索其在水生生物中的毒性机制提供一些线索。
