Environmental fate and effect assessment of thioridazine and its transformation products formed by photodegradation. (June 2016)

• Record Type: Journal Article
• Authors: Wilde, Marcelo L.; Menz, Jakob; Trautwein, Christoph; Leder, Christoph; Kümmerer, Klaus
• Is Part Of: Environmental pollution. Volume 213(2016)
• Page Start: 658
• Page End: 670
• Publication Date: 2016-06
• Subjects: Photodegradation -- Thioridazine -- Transformation products -- Risk assessment -- Toxicity -- QSAR; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2016.03.018
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: An experimental and in silico quantitative 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 −1 and 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 with Vibrio 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 confirmatory in vitro validation tests. Graphical abstract: Highlights: Photodegradation of thioridazine (THI) was assessed through simulated sunlight irradiation. Transformation products (TPs) of THI were determined by high resolution mass spectrometry. THI and TPs of THI were not readily biodegradable in OECD 301 D and 301 F tests. Phototransformation significantly reduced the toxicity of THI towards bacteria. In silico QSAR models predicted positive alerts for mutagenicity and genotoxicity in two TPs. Abstract : An experimental and in silico QSAR approach was applied to assess the environmental fate and effects of the antipsychotic drug thioridazine and phototransformation products.