title: Transformation products in the water cycle and the unsolved problem of their proactive assessment: A combined in vitro/in silico approach.
abstract: Transformation products (TPs) emerging from incomplete degradation of micropollutants in aquatic systems can retain the biological activity of the parent compound, or may even possess new unexpected toxic properties. The chemical identities of these substances remain largely unknown, and consequently, the risks caused by their presence in the water cycle cannot be assessed thoroughly. In this study, a combined approach for the proactive identification of hazardous elements in the chemical structures of TPs, comprising analytical, bioanalytical and computational methods, was assessed by the example of the pharmaceutically active micropollutant propranolol (PPL). PPL was photo-transformed using ultraviolet (UV) irradiation and 115 newly formed TPs were monitored in the reaction mixtures by LC-MS analysis. The reaction mixtures were screened for emerging effects using a battery of in vitro bioassays and the occurrence of cytotoxic and mutagenic activities in bacteria was found to be significantly correlated with the occurrence of specific TPs during the treatment process. The follow-up analysis of structure-activity-relationships further illustrated that only small chemical transformations, such as the hydroxylation or the oxidative opening of an aromatic ring system, could substantially alter the biological effects of micropollutants in aquatic systems. In conclusion, more efforts should be made to prevent the occurrence and transformation of micropollutants in the water cycle and to identify the principal degradation pathways leading to their toxicological activation. With regard to the latter, the judicious combination of bioanalytical and computational tools represents an appealing approach that should be developed further.
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststr. 1/C13, DE-21335 Lüneburg, Germany. Electronic address: jakob.menz@leuphana.de.
authors.forename: Jakob
authors.initials: J
authors.lastname: Menz
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststr. 1/C13, DE-21335 Lüneburg, Germany. Electronic address: anjutoolaram@yahoo.com.
authors.forename: Anju Priya
authors.initials: AP
authors.lastname: Toolaram
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststr. 1/C13, DE-21335 Lüneburg, Germany. Electronic address: tushar.rastogi@leuphana.de.
authors.forename: Tushar
authors.initials: T
authors.lastname: Rastogi
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststr. 1/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 and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststr. 1/C13, DE-21335 Lüneburg, Germany. Electronic address: oliver.olsson@leuphana.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Olsson
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststr. 1/C13, DE-21335 Lüneburg, Germany. Electronic address: klaus.kuemmerer@leuphana.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kümmerer
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststr. 1/C13, DE-21335 Lüneburg, Germany. Electronic address: mandy.schneider@leuphana.de.
authors.forename: Mandy
authors.initials: M
authors.lastname: Schneider
mesh_terms: D048908:Aliivibrio fischeri; D002853:Chromatography, Liquid; D003198:Computer Simulation; D013058:Mass Spectrometry; D010782:Photolysis; D011433:Propranolol / Q000737:chemistry / Q000528:radiation effects; D012486:Salmonella typhimurium; D018675:Toxicity Tests; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry*; D058438:Water Cycle; D014874:Water Pollutants, Chemical / Q000737:chemistry*; D018508:Water Purification
chemical_list: D014874:Water Pollutants, Chemical; D014867:Water; D011433:Propranolol
keywords: (Q)SAR; Emerging contaminant; Hazard assessment; Micropollutant; Propranolol; Risk assessment