Acknowledgments We would like to thank the projects CTM2016-75908-R and CTM201570731-R and the Junta de Andalucía PAIDI Excellence Research Group RNM306 for their support.
MH is supported by the Spanish Ramón y Cajal funding scheme (contract reference RYC-201212217) of the Spanish Ministry of Economy, Industry and Competitiveness (MINECO).
References
1. Kümmerer K (2009) The presence of pharmaceuticals in the environment due to human use –
present knowledge and future challenges. J Environ Manage 90:2354–2366
2. COM (2011) 876, Proposal for a Directive amending the WFD (2000/60/EC) and EQSD
(2008/105/EC) as regards priority substances in the field of water policy, January 2012
3. Kolpin DW, Furlong EF, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002)
Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams,
1999À2000: a national reconnaissance. Environ Sci Technol 36(6):1202–1211
4. Bound JP, Voulvoulis N (2006) Predicted and measured concentrations for selected pharmaceuticals in UK rivers: implications for risk assessment. Water Res 40:2885–2892
5. Heberer T (2002) Occurrence, fate, and removal of pharmaceutical residues in the aquatic
environment: a review of recent research data. Toxicol Lett 131:5–17
6. Silva BFD, Jelic A, López-Serna R, Mozeto AA, Petrovic M, Barceló D (2011) Occurrence
and distribution of pharmaceuticals in surface water, suspended solids and sediments of the
Ebro river basin, Spain. Chemosphere 85:1331–1339
7. Bally M, Dendukuri N, Rich B, Nadeau L, Helin-Salmivaara A, Garbe E, Brophy JM (2017)
Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of
individual patient data. BMJ (Clin Res Ed) 357:j1909
8. Lanas A, Chan FK (2017) Peptic ulcer disease. Lancet 390(10094):613–624
9. EU TGD (2003) European Union. Technical guidance document on risk assessment in support
of the commission directive 93/67/EEC on risk assessment for new notified substances
Commission Regulation (EC) No 1488/94 on risk assessment for existing substances directive
98/8/EC of the European Parliament and of the council concerning the placing of biocidal
products on the market. Environmental Chemicals Bureau, Ispra, Italy
10. OECD (1992). Report of the OECD Workshop on the extrapolation of laboratory aquatic
toxicity data on the real environment. Organisation for Economic Cooperation and Development (OECD), OECD Environment Monographs No 59, Paris
11. Farré M, Perez S, Kantiani L, Barceló D (2008) Fate and toxicity of emerging pollutants, their
metabolites and transformation products in the aquatic environment. Trends Anal Chem
27:991–1007
12. De Lange HJ, Noordoven W, Murk AJ, Lürling M, Peeters ETHM (2006) Behavioural
responses of Gammarus pulex (Crustacea, Amphipoda) to low concentrations of pharmaceuticals. Aquat Toxicol 78:209–216
13. Ericson H, Thorsén G, Kumblad L (2010) Physiological effects of diclofenac, ibuprofen and
propranolol on Baltic Sea blue mussels. Aquat Toxicol 99:223–231
14. Nassef X, Matsumoto S, Seki M, Khalil F, Kang IJ, Shimasaki Y, Oshima Y, Honjo T (2010)
Acute effects of triclosan, diclofenac and carbamazepine on feeding performance of Japanese
medaka fish (Oryzias latipes). Chemosphere 80:1095–1100
15. De Lorenzo ME, Fleming J (2008) Individual and mixture effects of selected pharmaceuticals
and personal care products on the marine phytoplankton species Dunaliella tertiolecta. Arch
Environ Contam Toxicol 54:203–210
16. Cleuvers M (2004) Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen,
naproxen, and acetylsalicylic acid. Ecotoxicol Environ Saf 59:309–315
184
C. Trombini et al.
MH is supported by the Spanish Ramón y Cajal funding scheme (contract reference RYC-201212217) of the Spanish Ministry of Economy, Industry and Competitiveness (MINECO).
References
1. Kümmerer K (2009) The presence of pharmaceuticals in the environment due to human use –
present knowledge and future challenges. J Environ Manage 90:2354–2366
2. COM (2011) 876, Proposal for a Directive amending the WFD (2000/60/EC) and EQSD
(2008/105/EC) as regards priority substances in the field of water policy, January 2012
3. Kolpin DW, Furlong EF, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002)
Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams,
1999À2000: a national reconnaissance. Environ Sci Technol 36(6):1202–1211
4. Bound JP, Voulvoulis N (2006) Predicted and measured concentrations for selected pharmaceuticals in UK rivers: implications for risk assessment. Water Res 40:2885–2892
5. Heberer T (2002) Occurrence, fate, and removal of pharmaceutical residues in the aquatic
environment: a review of recent research data. Toxicol Lett 131:5–17
6. Silva BFD, Jelic A, López-Serna R, Mozeto AA, Petrovic M, Barceló D (2011) Occurrence
and distribution of pharmaceuticals in surface water, suspended solids and sediments of the
Ebro river basin, Spain. Chemosphere 85:1331–1339
7. Bally M, Dendukuri N, Rich B, Nadeau L, Helin-Salmivaara A, Garbe E, Brophy JM (2017)
Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of
individual patient data. BMJ (Clin Res Ed) 357:j1909
8. Lanas A, Chan FK (2017) Peptic ulcer disease. Lancet 390(10094):613–624
9. EU TGD (2003) European Union. Technical guidance document on risk assessment in support
of the commission directive 93/67/EEC on risk assessment for new notified substances
Commission Regulation (EC) No 1488/94 on risk assessment for existing substances directive
98/8/EC of the European Parliament and of the council concerning the placing of biocidal
products on the market. Environmental Chemicals Bureau, Ispra, Italy
10. OECD (1992). Report of the OECD Workshop on the extrapolation of laboratory aquatic
toxicity data on the real environment. Organisation for Economic Cooperation and Development (OECD), OECD Environment Monographs No 59, Paris
11. Farré M, Perez S, Kantiani L, Barceló D (2008) Fate and toxicity of emerging pollutants, their
metabolites and transformation products in the aquatic environment. Trends Anal Chem
27:991–1007
12. De Lange HJ, Noordoven W, Murk AJ, Lürling M, Peeters ETHM (2006) Behavioural
responses of Gammarus pulex (Crustacea, Amphipoda) to low concentrations of pharmaceuticals. Aquat Toxicol 78:209–216
13. Ericson H, Thorsén G, Kumblad L (2010) Physiological effects of diclofenac, ibuprofen and
propranolol on Baltic Sea blue mussels. Aquat Toxicol 99:223–231
14. Nassef X, Matsumoto S, Seki M, Khalil F, Kang IJ, Shimasaki Y, Oshima Y, Honjo T (2010)
Acute effects of triclosan, diclofenac and carbamazepine on feeding performance of Japanese
medaka fish (Oryzias latipes). Chemosphere 80:1095–1100
15. De Lorenzo ME, Fleming J (2008) Individual and mixture effects of selected pharmaceuticals
and personal care products on the marine phytoplankton species Dunaliella tertiolecta. Arch
Environ Contam Toxicol 54:203–210
16. Cleuvers M (2004) Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen,
naproxen, and acetylsalicylic acid. Ecotoxicol Environ Saf 59:309–315
184
C. Trombini et al.