title: Hazard screening of photo-transformation products from pharmaceuticals: Application to selective β1-blockers atenolol and metoprolol.
abstract: The identification of toxic components in cocktail mixtures of pollutants, their metabolites and transformation products (TPs) generated from environmental and treatment processes remains an arduous task. This study expanded in this area by applying a combination of chemical analytics, a battery of in vitro bioassays and an in silico "testing battery" to UV photolysis mixtures of active pharmaceutical ingredients. The objectives were to understand the toxic nature of the mixtures and to prioritize photo-TPs for risk analysis. The selective β1-blockers Atenolol (ATL) and Metoprolol (MTL) that are ubiquitous in the aquatic environment were used as an example. The photolysis mixtures were cytotoxic to Vibrio fischeri and mammalian cells but not mutagenic in the Ames test or genotoxic in the in vitro micronucleus and umu tests. Potentially hazardous TPs were proposed by relating the observed effects to the kinetics of TP occurrence and applying in silico toxicity predictions for individual photo-TPs. This model study was done to identify principal mechanisms rather than accurately simulating environmental transformation processes. Several photo-TPs were proposed to present a greater hazard than the selected β-blockers and therefore fate and toxicity assessments may be required to determine their environmental relevance.
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Germany.. Electronic address: toolaram@leuphana.de.
authors.forename: Anju Priya
authors.initials: AP
authors.lastname: Toolaram
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Germany.. Electronic address: jakob.menz@uni.leuphana.de.
authors.forename: Jakob
authors.initials: J
authors.lastname: Menz
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of 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, Faculty of Sustainability, Leuphana University of 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, Faculty of Sustainability, Leuphana University of Lüneburg, Germany.. Electronic address: klaus.kuemmerer@uni.leuphana.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kümmerer
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Germany.. Electronic address: mschneid@leuphana.de.
authors.forename: Mandy
authors.initials: M
authors.lastname: Schneider
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000633:toxicity; D048908:Aliivibrio fischeri; D001262:Atenolol / Q000633:toxicity*; D003198:Computer Simulation; D007700:Kinetics; D008790:Metoprolol / Q000633:toxicity*; D010782:Photolysis; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000319:Adrenergic beta-Antagonists; D014874:Water Pollutants, Chemical; D001262:Atenolol; D008790:Metoprolol
keywords: Effect based analysis; Emerging contaminants; Mixture toxicity; Quantitative structure-activity relationship (QSAR); Risk assessment