A. C. Johnson, E. Dumont, R. J. Williams, R. Oldenkamp, I. Cisowska et al., Do Concentrations of Ethinylestradiol, Estradiol, and Diclofenac in European Rivers Exceed Proposed EU Environmental Quality Standards?, Environmental Science & Technology, vol.47, issue.21, 2013.
DOI : 10.1021/es4030035

J. Zha, L. Sun, Y. Zhou, P. A. Spear, M. Ma et al., Assessment of 17a-ethi- nylestradiol effects and underlying mechanisms in a continuous, multigeneration exposure of the Chinese rare minnow (Gobiocypris rarus), Toxicol. Appl. Pharmacol, vol.226, issue.298, 2008.

A. R. Schwindt, D. L. Winkelman, K. Keteles, M. Murphy, and A. M. Vajda, An environmental oestrogen disrupts fish population dynamics through direct and transgenerational effects on survival and fecundity, Journal of Applied Ecology, vol.11, issue.suppl. 6, 2014.
DOI : 10.1023/A:1021053217513

H. Segner, A. Casanova-nakayama, R. Kase, and C. R. Tyler, Impact of environmental estrogens on Yfish considering the diversity of estrogen signaling, General and Comparative Endocrinology, vol.191, 2013.
DOI : 10.1016/j.ygcen.2013.05.015

L. Vigan-o, J. L. Loizeau, A. Mandich, and G. Mascolo, Medium- and Long-Term Effects of Estrogenic Contaminants on the Middle River Po Fish Community as Reconstructed from a Sediment Core, Archives of Environmental Contamination and Toxicology, vol.13, issue.409, pp.244-260, 2016.
DOI : 10.1039/C0EM00473A

K. A. Kidd, P. J. Blanchfield, K. H. Mills, V. P. Palace, R. E. Evans et al., Collapse of a fish population after exposure to a synthetic estrogen, Proc. Natl. Acad. Sci, 2007.
DOI : 10.1897/1551-5028(2001)020<2370:ADOLSA>2.0.CO;2

M. Carere, S. Polesello, R. Kase, and B. M. Gawlik, The Emerging Contaminants in the Context of the EU Water Framework Directive, Emerg. Contam. River Ecosyst. Occur. Eff. Under Mult. Stress Cond, pp.197-215, 2015.
DOI : 10.1007/698_2015_5011

. J. Off and . Eur, Union L 226 56 Directive 2013/39/EU of the European Parliament and of the Council of 12, EC as Regards Priority Sin the Field of Water Policy, vol.60105, 2000.

. J. Off and . Eur, Union L 78 Commission Implementing Decision (EU) 2015/495 of 20 Establishing a Watch list of Substances for Union-wide Monitoring in the Field of Water Policy Pursuant to Directive, EC of the European Parliament and of the Council, p.40, 2008.

E. Commission, D. Of, . European, . Parliament, . Of et al., EC as Regards Priority Substances in the Field of, Water Policy, COM, vol.60105, pp.876-20110429, 2000.

R. Kase, R. I. Eggen, M. Junghans, C. G?-otz, and J. Hollender, Assessment of micropollutants from municipal wastewater-combination of exposure and ecotoxicological effect data for Switzerland, ISBN: 978-953-307-233-3, in: Wastewater -Evaluation and Management,Fernando Sebasti an García Einschlag, Available at, pp.32-55, 2011.

W. Unep, State of the science of endocrine disrupting chemicals-2012, An Assessment of the State of the Science of Endocrine Disruptors Prepared by a Group of Experts for the United Nations Environment Programme (UNEP) and World Health Organization (WHO), 2013, 2017.

R. N. Carvalho, A. Arukwe, S. Ait-aissa, A. Bado-nilles, S. Balzamo et al., Mixtures of Chemical Pollutants at European Legislation Safety Concentrations: How Safe Are They?, Toxicological Sciences, vol.5, issue.1, p.141, 2014.
DOI : 10.1002/etc.311

URL : https://hal.archives-ouvertes.fr/ineris-01855038

, Community Strategy for Endocrine Disrupters " a Range of Substances Suspected of Interfering with the Hormone Systems of Humans and Wildlife (COM, European Commission, 4th Report on the SEC(2011) 1001 final, p.706, 1999.

, European CommissAssessment of Micropollutants from Municipal Wastewater-Combination of Exposure and Ecotoxicological Effect Data for Switzerlandion, Communication from the Commission to the Council, Chemical mixtures. COM, vol.2012, pp.252-255, 2017.

W. Brack, V. Dulio, M. Ågerstrand, I. Allan, R. Altenburger et al., Towards the review of the European Union Water Framework Directive: Recommendations for more efficient assessment and management of chemical contamination in European surface water resources, Towards the review of the European Union Water Framework management of chemical contamination in European surface water resources, pp.720-737, 2017.
DOI : 10.1016/j.scitotenv.2016.10.104

URL : https://hal.archives-ouvertes.fr/ineris-01853418

R. Kase, H. Clayton, and F. Martini, Science-Policy Interface (SPI) Activity on Prioritization of Research Needs, Knowledge Availability and Dissemination for the Working Group E (Chemical Aspects) Available at: https://circabc.europa, pp.5-63, 2010.

C. , D. Paolo, R. Ottermanns, S. Keiter, S. Ait-aissa et al., Bioassay battery interlaboratory investigation of emerging contaminants in spiked water extracts e towards the implementation of bioanalytical monitoring tools in water quality assessment and monitoring, Water Res, vol.104, pp.473-484, 2016.

M. Hecker and H. Hollert, Endocrine disruptor screening: regulatory perspectives and needs, Environmental Sciences Europe, vol.23, issue.1, pp.2190-4715, 2011.
DOI : 10.1007/s11368-009-0104-y

R. , T. Slootweg, and C. Houtman, Evaluatie van hormonale activiteit gemeten in de Rijn bij Lobith http://www.riwa-rijn.org/evaluatie- van-hormonale-activiteit-gemeten-in-de-rijn-bij-lobith, 2010.

M. K?-onig, B. I. Escher, P. A. Neale, M. Krauss, K. Hilscherov-a et al., Impact of untreated wastewater on a major European river evaluated with a combination of in vitro bioassays and chemical analysis, Environ. Pollut, vol.220, 2017.

B. Jaro-sov-a, A. Ersekov-a, K. Hilscherov-a, R. Loos, B. M. Gawlik et al., Bl aha, Europe-wide survey of estrogenicity in wastewater treatment plant effluents: the need for the effect-based monitoring, Environ. Sci. Pollut. Res. Int, vol.21, pp.11356-11370, 2014.

F. D. Leusch, C. De-jager, Y. Levi, R. Lim, L. Puijker et al., Comparison of Five in Vitro Bioassays to Measure Estrogenic Activity in Environmental Waters, Environmental Science & Technology, vol.44, issue.10, pp.44-3853, 2010.
DOI : 10.1021/es903899d

P. Schr?-oder, B. Helmreich, B. Skrbi-c, M. Carballa, M. Papa et al., Status of hormones and painkillers in wastewater effluents across several European states???considerations for the EU watch list concerning estradiols and diclofenac, Environmental Science and Pollution Research, vol.309, issue.1???4, pp.12835-12866, 2016.
DOI : 10.1016/S0048-9697(03)00002-0

P. Y. Kunz, C. Kienle, M. Carere, N. Homazava, and R. Kase, In vitro bioassays to screen for endocrine active pharmaceuticals in surface and wastewaters, J. Pharm. Biomed. Anal, vol.106, issue.107, 2015.

R. Kase, P. Y. Kunz, H. Hollert, I. Werner, and R. Loos, Analytical Methods Relevant to the European Commission's 2012 Proposal on Priority Substances Under the Water Framework Directive, Contribution on Bioanalytical Assays for Steroidal Estrogens, 2012.

A. Wernersson, M. Carere, C. Maggi, P. Tusil, P. Soldan et al., The European technical report on aquatic effect-based monitoring tools under the water framework directive, Environmental Sciences Europe, vol.78, issue.4, pp.27-12302, 2015.
DOI : 10.1016/j.aquatox.2006.04.008

URL : https://hal.archives-ouvertes.fr/ineris-01862522

A. Wernersson, Technical Report on Aquatic Effect-Based Monitoring Tools, 2014.
DOI : 10.1186/s12302-015-0039-4

URL : https://hal.archives-ouvertes.fr/ineris-01862522

C. Heiss, B. Gawlik, B. Von-danwitz, D. Wilke, G. Reifferscheid et al., Recommendation for a Monitoring Strategy for Estrogens in Coastal and Continental Surface Waters, 2013.

V. Dulio and R. Kase, Recommendations for the use of effect-based methods for monitoring of estrogens in surface waters e Outcomes of the Dübendorf Workshop, 2017. Available at, 2017.

S. Jobling, R. Williams, A. Johnson, A. Taylor, M. Gross-sorokin et al., Predicted Exposures to Steroid Estrogens in U.K. Rivers Correlate with Widespread Sexual Disruption in Wild Fish Populations, Environmental Health Perspectives, vol.114, issue.S-1, 2005.
DOI : 10.1289/ehp.8050

URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874167/pdf/ehp0114s1-000032.pdf

N. Bolong, A. F. Ismail, M. R. Salim, and T. Matsuura, A review of the effects of emerging contaminants in wastewater and options for their removal, Desalination, vol.239, issue.1-3, pp.239-229, 2009.
DOI : 10.1016/j.desal.2008.03.020

M. O. Barbosa, N. F. Moreira, A. R. Ribeiro, M. F. Pereira, and A. M. Silva, Occurrence and removal of organic micropollutants: an overview of the watch list of EU Decision, Water Res, vol.495, issue.257, 2015.

B. Jarosova, L. Blaha, J. P. Giesy, and K. Hilscherova, What level of estrogenic activity determined by in vitro assays in municipal wastewaters can be considered as safe?, Environ. Int, vol.64

F. D. Leusch, H. F. Chapman, M. R. Van-den-heuvel, B. L. Tan, S. R. Gooneratne et al., Bioassay-derived androgenic and estrogenic activity in municipal sewage in Australia and New Zealand, Ecotoxicology and Environmental Safety, vol.65, issue.3, 2006.
DOI : 10.1016/j.ecoenv.2005.07.020

A. C. Johnson and R. J. Williams, A Model To Estimate Influent and Effluent Concentrations of Estradiol, Estrone, and Ethinylestradiol at Sewage Treatment Works, Environmental Science & Technology, vol.38, issue.13, 2004.
DOI : 10.1021/es035342u

S. K?-onemann, R. Kase, E. Simon-b, K. Swart, S. Buchinger et al., Effect-based and chemical analytical methods to monitor estrogens under the European Water Framework Directive, Carere, Effect-Based and Chemical Analytical Methods to Monitor Estrogens Under the European Water Framework Directive, pp.225-235, 2018.
DOI : 10.1016/j.trac.2018.02.008

F. Martini, C. Fragakis, S. Michel, A. Natacha, G. Kinga et al., ScienceePolicy Interface in Support of the Water Framework Directive, 2013.

R. Van-der-oost, G. Sileno, M. Su-arez-mu~-noz, M. T. Nguyen, H. Besselink et al., SIMONI (Smart Integrated Monitoring) as a novel bioanalytical strategy for water quality assessment: Part I-model design and effect-based trigger values, Environmental Toxicology and Chemistry, vol.544, issue.9, 2017.
DOI : 10.1016/j.scitotenv.2015.11.102

O. and T. Guideline, Stably Transfected Human Estrogen Receptor-a Transcriptional Activation Assay for Detection of Estrogenic Agonist-Activity of Chemicals, 2009.

R. Huang, S. Sakamuru, M. T. Martin, D. M. Reif, R. S. Judson et al., Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway, Sci. Rep, 2014.

A. Kortenkamp, Ten Years of Mixing Cocktails: A Review of Combination Effects of Endocrine-Disrupting Chemicals, Environmental Health Perspectives, vol.115, issue.S-1, 2007.
DOI : 10.1289/ehp.9357

A. Kortenkamp, Low dose mixture effects of endocrine disrupters and their implications for regulatory thresholds in chemical risk assessment, Current Opinion in Pharmacology, vol.19, issue.105, 2014.
DOI : 10.1016/j.coph.2014.08.006

A. Kortenkamp, T. Backhaus, and M. Faust, State of the art report on mixture toxicity, 2009.

L. Sachs, Angewandte Statistik: Anwendung Statistischer Methoden, 1999.
DOI : 10.2307/2533881

. J. Off and . Eur, Union L 201, COMMISSION DIRECTIVE Laying Down, Pursuant to Directive, EC of the European Parliament and of the Council, Technical Specifications for Chemical Analysis and Monitoring of Water status, p.36, 2000.

B. I. Escher and F. D. Leusch, Bioanalytical Tools in Water Quality Assessment

P. Y. Kunz, E. Simon, N. Creusot, B. S. Jayasinghe, C. Kienle et al., Effect-based tools for monitoring estrogenic mixtures: Evaluation of five in??vitro bioassays, Water Research, vol.110, issue.378, 2017.
DOI : 10.1016/j.watres.2016.10.062

URL : https://hal.archives-ouvertes.fr/ineris-01853425

D. J. Caldwell, B. Mertens, K. Kappler, T. Senac, R. Journel et al., A risk-based approach to managing active pharmaceutical ingredients in manufacturing effluent, Environmental Toxicology and Chemistry, vol.10, issue.4, pp.813-822, 2016.
DOI : 10.1002/ieam.1551

B. Jarosova, L. Blaha, B. Vrana, T. Randak, R. Grabic et al., Changes in concentrations of hydrophilic organic contaminants and of endocrine-disrupting potential downstream of small communities located adjacent to headwaters, Environment International, vol.45
DOI : 10.1016/j.envint.2012.04.001

M. D. Jurgens, K. I. Holthaus, A. C. Johnson, J. L. Smith, R. J. Hetheridge et al., The potential for estradiol and ethinylestradiol degradation in english rivers, Environmental Toxicology and Chemistry, vol.44, issue.195, 2002.
DOI : 10.1002/etc.5620200610

F. D. Leusch, P. A. Neale, A. Hebert, M. Scheurer, and M. C. Schriks, Analysis of the sensitivity of in vitro bioassays for androgenic, progestagenic, glucocorticoid, thyroid and estrogenic activity: Suitability for drinking and environmental waters, Environment International, vol.99, issue.120, 2017.
DOI : 10.1016/j.envint.2016.12.014

E. J. Tiedeken, A. Tahar, B. Mchugh, and N. J. Rowan, Monitoring, sources, receptors, and control measures for three European Union watch list substances of emerging concern in receiving waters ??? A 20 year systematic review, Science of The Total Environment, vol.574
DOI : 10.1016/j.scitotenv.2016.09.084

A. C. Mehinto, A. Jia, S. A. Snyder, B. S. Jayasinghe, N. D. Denslow et al., Interlaboratory comparison of in??vitro bioassays for screening of endocrine active chemicals in recycled water, Water Research, vol.83, issue.303, 2015.
DOI : 10.1016/j.watres.2015.06.050

B. I. Escher, M. Allinson, R. Altenburger, P. A. Bain, P. Balaguer et al., Benchmarking organic micropollutants in wastewater, recycled water and drinking water with in vitro bioassays, p.48, 2014.

T. F. Omar, A. Ahmad, A. Z. Aris, and F. M. Yusoff, Endocrine disrupting compounds (EDCs) in environmental matrices: Review of analytical strategies for pharmaceuticals, estrogenic hormones, and alkylphenol compounds, TrAC Trends in Analytical Chemistry, vol.85, issue.241, 2016.
DOI : 10.1016/j.trac.2016.08.004

C. Kienle, R. Kase, and I. Werner, Evaluation of Bioassays and Wastewater Quality: in vitro and in vivo Bioassays for the Performance Review in the Project, Strategy MicroPoll, 2011.

A. R. Ribeiro, O. C. Nunes, M. F. Pereira, and A. M. Silva, An overview on the advanced oxidation processes applied for the treatment of water pollutants defined in the recently launched Directive, Environ. Int, vol.39, issue.33, 2013.

J. Rivera-utrilla, M. Polo, M. A. Ferro-garcía, G. Prados-joya, and R. Ocampo-p-erez, Pharmaceuticals as emerging contaminants and their removal from water. A review, Chemosphere, vol.93, issue.7
DOI : 10.1016/j.chemosphere.2013.07.059

E. Wg-chemicals and A. Tools, METHODS for WG Chemicals as Part of the Water Framework Directive CIS Work Programme (2016-2018) Endorsed by the Water Directors, 2016. Terms of References for the Effect-Based Activity -08-07-2016.docx, https, Draft, pp.39-53, 2017.

E. Wg and C. , Priority Substances e Outcome of Water Directors Meeting Chem 2016e12 (10) WD2016 outcome_Priority Substances.pdf, https:// circabc.europa, pp.96-103, 2016.

K. Bernhard, C. Stahl, R. Martens, H. K?-ohler, R. Triebskorn et al., Two novel real time cell-based assays quantify beta-blocker and NSAID specific effects in effluents of municipal wastewater treatment plants, Water Research, vol.115, issue.74, 2017.
DOI : 10.1016/j.watres.2017.02.036

R. Kase and A. Duffek, Applied Effect-Based Monitoring of EU Watch List Samples, pp.209-179, 2017.