title: Chemical and biochemical characterization and in vivo safety evaluation of pharmaceuticals in drinking water.
abstract: The water constituents that are currently subject to legal control are only a small fraction of the vast number of chemical substances and microorganisms that may occur in both the environment and water resources. The main objective of the present study was to study the health impact resulting from exposure to a mixture of pharmaceuticals that have been detected in tap water at low doses. Analyses of atenolol, caffeine, erythromycin, carbamazepine, and their metabolites in blood, urine, feces, fat tissue, liver, and kidney after exposure to a mixture of these pharmaceuticals in treated drinking water were performed. The effects of this exposure were assessed in rats by measuring biochemical markers of organ injury or dysfunction. Simultaneously, the selected pharmaceuticals were also quantified in both physiological fluids and organ homogenates by liquid chromatography-tandem mass spectrometry (performed in multiple reaction monitoring mode and full scan mode). Following exposure of rats to a concentration of a pharmaceutical which was 10 times higher than the concentration known to be present in tap water, trace levels of some pharmaceuticals and their metabolites were detected in biological samples. This exposure did, however, not lead to significant organ injury or dysfunction. Thus, the authors report an experimental model that can be used to characterize the safety profile of pharmaceuticals in treated drinking water using a multiorgan toxicity approach. Environ Toxicol Chem 2016;35:2674-2682. © 2016 SETAC.
authors.affiliation: Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Lisbon, Portugal.
authors.forename: Vanessa
authors.initials: V
authors.lastname: de Jesus Gaffney
authors.affiliation: Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Lisbon, Portugal.|Department of Social Pharmacy, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
authors.forename: Helder
authors.initials: H
authors.lastname: Mota-Filipe
authors.affiliation: Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Lisbon, Portugal.|Department of Pharmacological Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
authors.forename: Rui Amaro
authors.initials: RA
authors.lastname: Pinto
authors.affiliation: Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Lisbon, Portugal.|The William Harvey Research Institute, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Thiemermann
authors.affiliation: Empresa Portuguesa das Águas Livres, S.A., Laboratories and Water Quality Control Department, Lisbon, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Loureiro
authors.affiliation: Empresa Portuguesa das Águas Livres, S.A., Laboratories and Water Quality Control Department, Lisbon, Portugal.
authors.forename: Vitor Vale
authors.initials: VV
authors.lastname: Cardoso
authors.affiliation: Empresa Portuguesa das Águas Livres, S.A., Laboratories and Water Quality Control Department, Lisbon, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Benoliel
authors.affiliation: Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Lisbon, Portugal. calmeida@ff.ulisboa.pt.|Department of Toxicological and Bromatological Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal. calmeida@ff.ulisboa.pt.
authors.forename: Cristina M M
authors.initials: CM
authors.lastname: Almeida
mesh_terms: D000818:Animals; D002110:Caffeine / Q000032:analysis / Q000652:urine; D002220:Carbamazepine / Q000032:analysis / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D060766:Drinking Water / Q000737:chemistry*; D004781:Environmental Exposure; D004917:Erythromycin / Q000032:analysis / Q000652:urine; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry; D018508:Water Purification / Q000379:methods*
chemical_list: D060766:Drinking Water; D004364:Pharmaceutical Preparations; D002220:Carbamazepine; D002110:Caffeine; D004917:Erythromycin
keywords: Analytical toxicology; Chronic exposure; Organ toxicity; Pharmaceutical; Rat; Water quality