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Assessment of the Acute Toxicity, Uptake and Biotransformation Potential of Benzotriazoles in Zebrafish (Danio rerio) Larvae Combining HILIC- with RPLC-HRMS for High-Throughput Identification
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2018-04-30 , DOI: 10.1021/acs.est.8b01327
Dimitrios E. Damalas 1 , Anna A. Bletsou 1 , Adamantia Agalou 2 , Dimitris Beis 2 , Nikolaos S. Thomaidis 1
Affiliation  

The current study reports on the toxicity, uptake, and biotransformation potential of zebrafish (embryos and larvae) exposed to benzotriazoles (BTs). Acute toxicity assays were conducted. Cardiac function abnormalities (pericardial edema and poor blood circulation) were observed from the phenotypic analysis of early life zebrafish embryos after BTs exposure. For the uptake and biotransformation experiment, extracts of whole body larvae were analyzed using liquid chromatography–high-resolution tandem mass spectrometry (UPLC-Q-TOF-HRMS/MS). The utility of hydrophilic interaction liquid chromatography (HILIC) as complementary technique to reversed phase liquid chromatography (RPLC) in the identification process was investigated. Through HILIC analyses, additional biotransformation products (bio-TPs) were detected, because of the enhanced sensitivity and better separation efficiency of isomers. Therefore, reduction of false negative results was accomplished. Both oxidative (hydroxylation) and conjugative (glucuronidation, sulfation) metabolic reactions were observed, while direct sulfation proved the dominant biotransformation pathway. Overall, 26 bio-TPs were identified through suspect and nontarget screening workflows, 22 of them reported for the first time. 4-Methyl-1-H-benzotriazole (4-MeBT) demonstrated the highest toxicity potential and was more extensively biotransformed, compared to 1-H-benzotriazole (BT) and 5-methyl-1-H-benzotriazole (5-MeBT). The extent of biotransformation proved particularly informative in the current study, to explain and better understand the different toxicity potentials of BTs.

中文翻译:

结合HILIC-和RPLC-HRMS评估斑马鱼(Danio rerio)幼虫中苯并三唑类化合物的急性毒性,吸收和生物转化潜能,以鉴定高通量

本研究报告了暴露于苯并三唑(BTs)的斑马鱼(胚胎和幼虫)的毒性,摄取和生物转化潜力。进行了急性毒性试验。从BTs暴露后的早期斑马鱼胚胎的表型分析中观察到心脏功能异常(心包水肿和血液循环不良)。为了进行吸收和生物转化实验,使用液相色谱-高分辨串联质谱法(UPLC-Q-TOF-HRMS / MS)分析了全身幼虫的提取物。研究了亲水相互作用色谱法(HILIC)作为反相液相色谱法(RPLC)在鉴定过程中的补充技术。通过HILIC分析,发现了其他生物转化产物(bio-TPs),因为异构体具有更高的灵敏度和更好的分离效率。因此,减少了假阴性结果。观察到氧化(羟基化)和结合(葡萄糖醛酸化,硫酸化)代谢反应,而直接硫酸化证明了主要的生物转化途径。总体而言,通过可疑和非靶标筛选工作流程鉴定出26种生物TP,其中22种为首次报道。4-甲基-1- 其中22个是首次报告。4-甲基-1- 其中22个是首次报告。4-甲基-1-ħ苯并三唑(4- MEBT)表现出最高的毒性潜力,并更广泛地生物转化,相对于1- ħ -苯并三唑(BT)和5-甲基-1- ħ苯并三唑(5-MEBT)。在当前的研究中,生物转化的程度被证明特别有用,可以解释和更好地理解BTs的不同潜在毒性。
更新日期:2018-05-01
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