Environmental fate and effect assessment of thioridazine and its transformation products formed by photodegradation.
Environmental fate and effect assessment of thioridazine and its transformation products formed by photodegradation.
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硫利达嗪及其光降解转化产物的环境归趋和影响评价
DOI：
10.1016/j.envpol.2016.03.018
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发表时间：
2016
影响因子：
8.9
通讯作者：
Marcelo Wilde
中科院分区：
文献类型：
--
作者：
Marcelo Wilde
采用实验和计算机定量构效关系（QSAR）方法研究抗精神病药物硫利达嗪（THI）的环境归趋和效应。使用氙弧灯模拟THI的日光驱动衰减。初始浓度为500 μg L− 1和50 mg L−1时，光照256 min后，光降解达到完全初级消除，而初级消除率为97%，矿化率为11%。采用了一种非目标方法来识别和监测转化产物。使用液相色谱-高分辨率质谱法（LC-HRMS）进一步阐明TP的结构。拟议的光降解途径包括磺化氧化、羟基化、脱羟基化以及S-和N-脱烷基化，同时考虑到在所研究的较高浓度下通过自敏化过程进行的直接和间接光解。根据OECD 301 D和301 F测试THI和THI的光解样品的生物降解性，表明THI和TP的混合物不容易生物降解。此外，改进的发光细菌法（Vibrio fischeri）显示THI对环境细菌有很强的毒性，光转化可显著降低THI的毒性，浓度-效应分析证实THI对硫利达嗪-2-亚砜和硫利达嗪-5-亚砜的毒性降低。此外，所应用的QSAR模型预测了通过亚砜消除形成的咔唑衍生物TP（TP 355和TP 339）的致突变活性的统计和基于规则的阳性警报，这需要在体外验证试验中进一步确认。
An experimental andin silicoquantitative structure-activity relationship (QSAR) approach was applied to assess the environmental fate and effects of the antipsychotic drug Thioridazine (THI). The sunlight-driven attenuation of THI was simulated using a Xenon arc lamp. The photodegradation reached the complete primary elimination, whereas 97% of primary elimination and 11% of mineralization was achieved after 256 min of irradiation for the initial concentrations of 500 μg L−1and 50 mg L−1, respectively. A non-target approach for the identification and monitoring of transformation products (TPs) was adopted. The structure of the TPs was further elucidated using liquid chromatography–high resolution mass spectrometry (LC–HRMS). The proposed photodegradation pathway included sulfoxidation, hydroxylation, dehydroxylation, and S- and N-dealkylation, taking into account direct and indirect photolysis through a self-sensitizing process in the higher concentration studied. The biodegradability of THI and photolytic samples of THI was tested according to OECD 301D and 301F, showing that THI and the mixture of TPs were not readily biodegradable. Furthermore, THI was shown to be highly toxic to environmental bacteria using a modified luminescent bacteria test withVibrio fischeri.This bacteriotoxic activity of THI was significantly reduced by phototransformation and individual concentration-response analysis confirmed a lowered bacterial toxicity for the sulfoxidation products Thioridazine-2-sulfoxide and Thioridazine-5-sulfoxide. Additionally, the applied QSAR models predicted statistical and rule-based positive alerts of mutagenic activities for carbazole derivative TPs (TP 355 and TP 339) formed through sulfoxide elimination, which would require further confirmatoryin vitrovalidation tests.
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尿液、血液、胆汁和粪便中 35S 标记的硫利达嗪的排泄和代谢。
影响因子：
5.8
作者：
S. Eiduson;E. Geller
通讯作者：
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影响因子：
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作者：
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DOI：
10.1016/0278-6915(93)90141-k
发表时间：
1993
期刊：
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
影响因子：
--
作者：
Weyand,EH;Defauw,J;McQueen,CA;Meschter,CL;Meegalla,SK;LaVoie,EJ
通讯作者：
LaVoie,EJ
影响因子：
17.3
作者：
Worthington RJ;Melander C
通讯作者：
Melander C
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影响因子：
3.5
作者：
R. Saiakhov;S. Chakravarti;A. Sedykh
通讯作者：
A. Sedykh