title: Environmental fate and effect assessment of thioridazine and its transformation products formed by photodegradation.
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.
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable Environmental Chemistry, Leuphana University Lüneburg, C13, DE-21335 Lüneburg, Germany. Electronic address: marcelolw@gmail.com.
authors.forename: Marcelo L
authors.initials: ML
authors.lastname: Wilde
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable Environmental Chemistry, Leuphana University Lüneburg, C13, DE-21335 Lüneburg, Germany. Electronic address: jakob.menz@uni.leuphana.de.
authors.forename: Jakob
authors.initials: J
authors.lastname: Menz
authors.affiliation: Karlsruhe Institute of Technology, Institute of Microstructure Technology, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany. Electronic address: christoph.trautwein@kit.edu.
authors.forename: Christoph
authors.initials: C
authors.lastname: Trautwein
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable Environmental Chemistry, Leuphana University Lüneburg, C13, DE-21335 Lüneburg, Germany. Electronic address: cleder@leuphana.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Leder
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable Environmental Chemistry, Leuphana University Lüneburg, C13, DE-21335 Lüneburg, Germany. Electronic address: klaus.kuemmerer@uni.leuphana.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kümmerer
mesh_terms: D048908:Aliivibrio fischeri / Q000187:drug effects*; D014150:Antipsychotic Agents / Q000032:analysis / Q000528:radiation effects / Q000633:toxicity; D001673:Biodegradation, Environmental; D002851:Chromatography, High Pressure Liquid; D004784:Environmental Monitoring; D013058:Mass Spectrometry; D010782:Photolysis; D021281:Quantitative Structure-Activity Relationship; D013881:Thioridazine / Q000032:analysis* / Q000528:radiation effects / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000528:radiation effects / Q000633:toxicity
chemical_list: D014150:Antipsychotic Agents; D014874:Water Pollutants, Chemical; D013881:Thioridazine
keywords: Photodegradation; QSAR; Risk assessment; Thioridazine; Toxicity; Transformation products