title: Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.
abstract: The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water).
authors.affiliation: UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), UPRES EA 4258-FR CNRS 3038 INC3M, Bd Becquerel, F-14032 Caen, France; Laboratoire de Mathématiques de Bretagne Atlantique, Université de Bretagne Sud et UMR CNRS 6205, Campus de Tohannic, 56017 Vannes, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Villain
authors.affiliation: Normandie Univ., France; UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), UPRES EA 4258-FR CNRS 3038 INC3M, Bd Becquerel, F-14032 Caen, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Minguez
authors.affiliation: Normandie Univ., France; UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), UPRES EA 4258-FR CNRS 3038 INC3M, Bd Becquerel, F-14032 Caen, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Halm-Lemeille
authors.affiliation: Laboratoire de Mathématiques de Bretagne Atlantique, Université de Bretagne Sud et UMR CNRS 6205, Campus de Tohannic, 56017 Vannes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Durrieu
authors.affiliation: Normandie Univ., France; UNICAEN, CERMN (Centre d'Etudes et de Recherche sur le Médicament de Normandie), UPRES EA 4258-FR CNRS 3038 INC3M, Bd Becquerel, F-14032 Caen, France. Electronic address: ronan.bureau@unicaen.fr.
authors.forename: Ronan
authors.initials: R
authors.lastname: Bureau
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000633:toxicity*; D000928:Antidepressive Agents / Q000633:toxicity*; D000460:Chlorophyta / Q000187:drug effects*; D017291:Clarithromycin / Q000633:toxicity; D004364:Pharmaceutical Preparations / Q000145:classification*; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D012995:Solubility; D023382:Toxicity Tests, Acute; D014867:Water; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D004364:Pharmaceutical Preparations; D014874:Water Pollutants, Chemical; D014867:Water; D017291:Clarithromycin
keywords: Acute toxicity for algae; Mode of action; Pharmaceuticals; Quantile regression