title: Identification of synthetic steroids in river water downstream from pharmaceutical manufacture discharges based on a bioanalytical approach and passive sampling.
abstract: A bioanalytical approach was used to identify chemical contaminants at river sites located downstream from a pharmaceutical factory, where reproductive alterations in wild fish have been previously observed. By using polar organic compound integrative samplers (POCIS) at upstream and downstream sites, biological activity profiles based on in vitro bioassays revealed the occurrence of xenobiotic and steroid-like activities, including very high glucocorticoid, antimineralocorticoid, progestogenic and pregnane X receptor (PXR)-like activities (μg standard-EQ/g of sorbent range), and weak estrogenic activity (ng E2-EQ/g of sorbent range). Chemical analyses detected up to 60 out of 118 targeted steroid and pharmaceutical compounds in the extracts. In vitro profiling of occurring individual chemicals revealed the ability of several ones to act as agonist and/or antagonist of different steroids receptors. Mass balance calculation identified dexamethasone, spironolactone, and 6-alpha-methylprednisolone as major contributors to corticosteroid activities and levonorgestrel as the main contributor to progestogenic activities. Finally, RP-HPLC based fractionation of POCIS extracts and testing activity of fractions confirmed identified compounds and further revealed the presence of other unknown active chemicals. This study is one of the first to report environmental contamination by such chemicals; their possible contribution to in situ effects on fish at the same site is suggested.
authors.affiliation: Institut National de l'Environnement Industriel et des Risques (INERIS), Unité Écotoxicologie in vitro et in vivo, Parc ALATA, BP2, F-60550 Verneuil-en-Halatte, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Creusot
authors.forename: Selim
authors.initials: S
authors.lastname: Aït-Aïssa
authors.forename: Nathalie
authors.initials: N
authors.lastname: Tapie
authors.forename: Patrick
authors.initials: P
authors.lastname: Pardon
authors.forename: François
authors.initials: F
authors.lastname: Brion
authors.forename: Wilfried
authors.initials: W
authors.lastname: Sanchez
authors.forename: Eric
authors.initials: E
authors.lastname: Thybaud
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Porcher
authors.forename: Hélène
authors.initials: H
authors.lastname: Budzinski
mesh_terms: D000818:Animals; D059001:Aquatic Organisms / Q000187:drug effects; D001681:Biological Assay / Q000379:methods*; D002460:Cell Line; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D052244:Endocrine Disruptors / Q000032:analysis / Q000633:toxicity; D004784:Environmental Monitoring / Q000379:methods*; D005602:France; D019015:Geologic Sediments / Q000737:chemistry; D006801:Humans; D009930:Organic Chemicals / Q000032:analysis; D004364:Pharmaceutical Preparations / Q000032:analysis*; D045483:Rivers / Q000737:chemistry*; D013256:Steroids / Q000032:analysis* / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000633:toxicity
chemical_list: D052244:Endocrine Disruptors; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D013256:Steroids; D014874:Water Pollutants, Chemical