Identification of Unknown Antiandrogenic Compounds in Surface Waters by Effect-Directed Analysis (EDA) Using a Parallel Fractionation Approach
- 19 December 2017
- journal article
- research article
- Published by American Chemical Society (ACS) in Environmental Science & Technology
- Vol. 52 (1), 288-297
- https://doi.org/10.1021/acs.est.7b04994
Abstract
Among all the nuclear-receptor mediated endocrine disruptive effects, antiandrogenicity is frequently observed in aquatic environments and may pose a risk to aquatic organisms. Linking these effects to responsible chemicals is challenging and a great share of antiandrogenic activity detected in the environment has not been explained yet. To identify drivers of this effect at a hot spot of antiandrogenicity in the German river Holtemme, we applied effect-directed analysis (EDA) including a parallel fractionation approach, a downscaled luciferase reporter gene cell-based anti-AR-CALUX assay and LC-HRMS/MS nontarget screening. We identified and confirmed the highly potent antiandrogen 4-methyl-7-diethylaminocoumarin (C47) and two derivatives in the active fractions. The relative potency of C47 to the reference compound flutamide was over 5.2, whereas the derivatives were less potent. C47 was detected at a concentration of 13.7 μg/L, equal to 71.4 μg flutamide equivalents per liter (FEq/L) in the nonconcentrated water extract that was posing an antiandrogenic activity equal to 45.5 (±13.7 SD) FEq/L. Thus, C47 was quantitatively confirmed as the major cause of the measured effect in vitro. Finally, the antiandrogenic activity of C47 and one derivate was confirmed in vivo in spiggin-gfp Medaka. An endocrine disrupting effect of C47 was observed already at the concentration equal to the concentration in the nonconcentrated water extract, underlining the high risk posed by this compound to the aquatic ecosystem. This is of some concern since C47 is used in a number of consumer products indicating environmental as well as human exposure.Keywords
Funding Information
- Seventh Framework Programme (603437)
This publication has 58 references indexed in Scilit:
- The Discovery of Novel Human Androgen Receptor Antagonist Chemotypes Using a Combined Pharmacophore Screening ProcedureChemMedChem, 2013
- Effect of Ozonation on the Estrogenicity and Androgenicity of Oil Sands Process-Affected WaterEnvironmental Science & Technology, 2011
- Identification strategy for unknown pollutants using high-resolution mass spectrometry: Androgen-disrupting compounds identified through effect-directed analysisAnalytical and Bioanalytical Chemistry, 2011
- Optimization and prevalidation of the in vitro AR CALUX method to test androgenic and antiandrogenic activity of compoundsReproductive Toxicology, 2010
- MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile dataBMC Bioinformatics, 2010
- Masking effect of anti-androgens on androgenic activity in European river sediment unveiled by effect-directed analysisAnalytical and Bioanalytical Chemistry, 2009
- Statistical Modeling Suggests that Antiandrogens in Effluents from Wastewater Treatment Works Contribute to Widespread Sexual Disruption in Fish Living in English RiversEnvironmental Health Perspectives, 2009
- Toxic equivalent concentrations (TEQs) for baseline toxicity and specific modes of action as a tool to improve interpretation of ecotoxicity testing of environmental samplesJournal of Environmental Monitoring, 2008
- Determination of the androgenic potency of whole effluents using mosquitofish and trout bioassaysAquatic Toxicology, 2006
- CHANGES IN ESTROGENIC AND ANDROGENIC ACTIVITIES AT DIFFERENT STAGES OF TREATMENT IN WASTEWATER TREATMENT WORKSEnvironmental Toxicology and Chemistry, 2002