Removal of Antibiotics in Biological Wastewater Treatment Systems - A Critical Assessment Using the Activated Sludge Modeling Framework for Xenobiotics (ASM-X)

Environmental Science and Technology

Volumn 50, Issue 19, 2016, Pages 10316-10334

  Polesel, Fabio ^a   Andersen, Henrik R ^a   Trapp, Stefan ^a   Plósz, Benedek Gy ^a  

^a TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED SLUDGE PROCESS; BIOCHEMISTRY; BIOLOGICAL WATER TREATMENT; CATCHMENTS; EFFICIENCY; EFFLUENTS; METABOLITES; REMOVAL; WASTEWATER TREATMENT;

ACTIVATED SLUDGE MODEL; BIOLOGICAL TREATMENT SYSTEMS; BIOLOGICAL WASTE WATER TREATMENT; CONJUGATED METABOLITES; ENVIRONMENTAL EXPOSURE; METHODOLOGICAL APPROACH; REMOVAL EFFICIENCIES; WASTEWATER TREATMENT PLANTS;

ANTIBIOTICS;

ANTIBIOTIC AGENT; CIPROFLOXACIN; SULFAMETHOXAZOLE; TETRACYCLINE; XENOBIOTIC AGENT; ANTIINFECTIVE AGENT; SEWAGE; WASTE WATER; WATER POLLUTANT;

ACTIVATED SLUDGE; ANTIBIOTICS; ASSESSMENT METHOD; METABOLITE; MODELING; POLLUTANT REMOVAL; POLLUTION EXPOSURE; WASTEWATER TREATMENT; WASTEWATER TREATMENT PLANT; XENOBIOTICS;

ACTIVATED SLUDGE; CATCHMENT; EFFLUENT; ENVIRONMENTAL EXPOSURE; METHODOLOGY; RETENTION TIME; REVIEW; WASTE WATER MANAGEMENT; HUMAN; SEWAGE; WASTE WATER; WATER POLLUTANT;

ANTI-BACTERIAL AGENTS; HUMANS; SEWAGE; WASTE DISPOSAL, FLUID; WASTE WATER; WATER POLLUTANTS, CHEMICAL; XENOBIOTICS;

EID: 84989961954     PISSN: 0013936X     EISSN: 15205851     Source Type: Journal    
DOI: 10.1021/acs.est.6b01899     Document Type: Review

References (245)

1. Grung, M.; Källqvist, T.; Sakshaug, S.; Skurtveit, S.; Thomas, K. V. Environmental assessment of Norwegian priority pharmaceuticals based on the EMEA guideline Ecotoxicol. Environ. Saf. 2008, 71 (2) 328-340 10.1016/j.ecoenv.2007.10.015
2. Ort, C.; Hollender, J.; Schaerer, M.; Siegrist, H. Model-based evaluation of reduction strategies for micropollutants from wastewater treatment plants in complex river networks Environ. Sci. Technol. 2009, 43 (9) 3214-3220 10.1021/es802286v
3. European Commission. Commission implementing Decision (EU) 2015/495 of 20 March 2015establishing a watch list of substances for Union-wide monitoringin the field of water policy pursuant to Directive 2008/105/EC ofthe European Parliament and of the Council, (2015).
4. Kümmerer, K.; Henninger, A. Promoting resistance by the emission of antibiotics from hospitals and households into effluent Clin. Microbiol. Infect. 2003) 9 (12) 1203-1214 10.1111/j.1469-0691.2003.00739.x
5. Kümmerer, K. Antibiotics in the aquatic environment-A review-Part II Chemosphere 2009, 75 (4) 435-441 10.1016/j.chemosphere.2008.12.006
6. Michael, I.; Rizzo, L.; McArdell, C. S.; Manaia, C. M.; Merlin, C.; Schwartz, T.; Dagot, C.; Fatta-Kassinos, D. Urban wastewater treatment plants as hotspots for the release of antibiotics in the environment: A review Water Res. 2013, 47 (3) 957-995 10.1016/j.watres.2012.11.027
7. Rodriguez-Mozaz, S.; Chamorro, S.; Marti, E.; Huerta, B.; Gros, M.; Sànchez-Melsió, A.; Borrego, C. M.; Barceló, D.; Balcázar, J. L. Occurrence of antibiotics and antibiotic resistance genes in hospital and urban wastewaters and their impact on the receiving river Water Res. 2015, 69, 234-242 10.1016/j.watres.2014.11.021
8. Clouzot, L.; Choubert, J. M.; Cloutier, F.; Goel, R.; Love, N. G.; Melcer, H.; Ort, C.; Patureau, D.; Plósz, B. G.; Pomiès, M. et al. Perspectives on modelling micropollutants in wastewater treatment plants Water Sci. Technol. 2013, 68 (2) 448-461 10.2166/wst.2013.272
9. Plósz, B. G.; Benedetti, L.; Daigger, G. T.; Langford, K. H.; Larsen, H. F.; Monteith, H.; Ort, C.; Seth, R.; Steyer, J. P.; Vanrolleghem, P. A. Modelling micro-pollutant fate in wastewater collection and treatment systems: Status and challenges Water Sci. Technol. 2012, 67 (1) 1-15 10.2166/wst.2012.562
10. Oulton, R. L.; Kohn, T.; Cwiertny, D. M. Pharmaceuticals and personal care products in effluent matrices: A survey of transformation and removal during wastewater treatment and implications for wastewater management J. Environ. Monit. 2010, 12 (11) 1956-1978 10.1039/c0em00068j
11. Johnson, A. C.; Dumont, E.; Williams, R. J.; Oldenkamp, R.; Cisowska, I.; Sumpter, J. P. Do concentrations of ethinylestradiol, estradiol, and diclofenac in European rivers exceed proposed EU environmental quality standards? Environ. Sci. Technol. 2013, 47 (21) 12297-12304 10.1021/es4030035
12. Luo, Y.; Guo, W.; Ngo, H. H.; Nghiem, L. D.; Hai, F. I.; Zhang, J.; Liang, S.; Wang, X. C. A review on the occurrence of micropollutants in the aquatic environment and their fate and removal during wastewater treatment Sci. Total Environ. 2014, 473-474, 619-641 10.1016/j.scitotenv.2013.12.065
13. Polesel, F.; Plósz, B. G.; Trapp, S. From consumption to harvest: Environmental fate prediction of excreted ionizable trace organic chemicals Water Res. 2015, 84, 85-98 10.1016/j.watres.2015.06.033
14. Eggen, R. I. L.; Hollender, J.; Joss, A.; Schärer, M.; Stamm, C. Reducing the discharge of micropollutants in the aquatic environment Environ. Sci. Technol. 2014, 48 (14) 7683-7689 10.1021/es500907n
15. Bundschuh, M. The Challenge: Chemical and ecotoxicological characterization of wastewater treatment plant effluents Environ. Toxicol. Chem. 2014, 33 (11) 2407 10.1002/etc.2713
16. Johnson, A. C.; Sumpter, J. P. Improving the quality of wastewater to tackle trace organic contaminants: Think before you act! Environ. Sci. Technol. 2015, 49 (7) 3999-4000 10.1021/acs.est.5b00916
17. Stamm, C.; Eggen, R. I. L.; Hering, J. G.; Hollender, J.; Joss, A.; Schärer, M. Micropollutant removal from wastewater: Facts and decision-making despite uncertainty Environ. Sci. Technol. 2015, 49 (11) 6374-6375 10.1021/acs.est.5b02242
18. Richardson, M. L.; Bowron, J. M. The fate of pharmaceutical chemicals in the aquatic environment J. Pharm. Pharmacol. 1985, 37 (1) 1-12 10.1111/j.2042-7158.1985.tb04922.x
19. Halling-Sorensen, B.; Nors Nielsen, S.; Lanzky, P. F.; Ingerslev, F.; Holten Lützhøft, H. C.; Jorgensen, S. E. Occurrence, fate and effects of pharmaceutical substances in the environment-A review Chemosphere 1998, 36 (2) 357-393 10.1016/S0045-6535(97)00354-8
20. Daughton, C.; Ternes, T. Pharmaceuticals and personal care products in the enviornment: Agents of subtle change? Environ. Health Perspect. 1999, 107 (Suppl 6) 907-938 10.1289/ehp.99107s6907
21. Ternes, T. A.; Joss, A.; Siegrist, H. Scrutinizing pharmaceuticals and personal care products in wastewater treatment Environ. Sci. Technol. 2004, 38 (20) 392A-399A 10.1021/es040639t
22. Cirja, M.; Ivashechkin, P.; Schäffer, A.; Corvini, P. F. X. Factors affecting the removal of organic micropollutants from wastewater in conventional treatment plants (CTP) and membrane bioreactors (MBR) Rev. Environ. Sci. Bio/Technol. 2008, 7 (1) 61-78 10.1007/s11157-007-9121-8
23. Kümmerer, K. Antibiotics in the aquatic environment-A review-Part I Chemosphere 2009, 75 (4) 417-434 10.1016/j.chemosphere.2008.11.086
24. Miège, C.; Choubert, J. M.; Ribeiro, L.; Eusèbe, M.; Coquery, M. Fate of pharmaceuticals and personal care products in wastewater treatment plants-Conception of a database and first results Environ. Pollut. 2009, 157 (5) 1721-1726 10.1016/j.envpol.2008.11.045
25. Onesios, K. M.; Yu, J. T.; Bouwer, E. J. Biodegradation and removal of pharmaceuticals and personal care products in treatment systems: A review Biodegradation 2009, 20 (4) 441-466 10.1007/s10532-008-9237-8
26. Le-Minh, N.; Khan, S. J.; Drewes, J. E.; Stuetz, R. M. Fate of antibiotics during municipal water recycling treatment processes Water Res. 2010, 44 (15) 4295-4323 10.1016/j.watres.2010.06.020
27. Zhang, T.; Li, B. Occurrence, transformation, and fate of antibiotics in municipal wastewater treatment plants Crit. Rev. Environ. Sci. Technol. 2011, 41 (11) 951-998 10.1080/10643380903392692
28. Verlicchi, P.; Al Aukidy, M.; Zambello, E. Occurrence of pharmaceutical compounds in urban wastewater: Removal, mass load and environmental risk after a secondary treatment-A review Sci. Total Environ. 2012, 429, 123-155 10.1016/j.scitotenv.2012.04.028
29. Van Doorslaer, X.; Dewulf, J.; Van Langenhove, H.; Demeestere, K. Fluoroquinolone antibiotics: An emerging class of environmental micropollutants Sci. Total Environ. 2014, 500-501, 250-269 10.1016/j.scitotenv.2014.08.075
30. Petrie, B.; Barden, R.; Kasprzyk-Hordern, B. A review on emerging contaminants in wastewaters and the environment: Current knowledge, understudied areas and recommendations for future monitoring Water Res. 2015, 72, 3-27 10.1016/j.watres.2014.08.053
31. Gerbersdorf, S. U.; Cimatoribus, C.; Class, H.; Engesser, K. H.; Helbich, S.; Hollert, H.; Lange, C.; Kranert, M.; Metzger, J.; Nowak, W. et al. Anthropogenic Trace Compounds (ATCs) in aquatic habitats-Research needs on sources, fate, detection and toxicity to ensure timely elimination strategies and risk management Environ. Int. 2015, 79, 85-105 10.1016/j.envint.2015.03.011
32. Plósz, B. G.; Leknes, H.; Thomas, K. V. Impacts of competitive inhibition, parent compound formation and partitioning behavior on the removal of antibiotics in municipal wastewater treatment Environ. Sci. Technol. 2010, 44 (2) 734-742 10.1021/es902264w
33. Plósz, B. G.; Langford, K. H.; Thomas, K. V. An activated sludge modeling framework for xenobiotic trace chemicals (ASM-X): Assessment of diclofenac and carbamazepine Biotechnol. Bioeng. 2012, 109 (11) 2757-2769 10.1002/bit.24553
34. Plósz, B. G.; Reid, M. J.; Borup, M.; Langford, K. H.; Thomas, K. V. Biotransformation kinetics and sorption of cocaine and its metabolites and the factors influencing their estimation in wastewater Water Res. 2013, 47 (7) 2129-2140 10.1016/j.watres.2012.12.034
35. Stadler, L. B.; Ernstoff, A. S.; Aga, D. S.; Love, N. G. Micropollutant fate in wastewater treatment: Redefining "removal. Environ. Sci. Technol. 2012, 46 (19) 10485-10486 10.1021/es303478w
36. Gruengerich, F. P. Oxidative, reductive, and hydrolytic metabolism of drugs. In Drug Metabolism in Drug Design and Development; Zhang, D.; Zhu, M.; Griffith Humphreys, W., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, 2008; pp 15-31.
37. Testa, B.; Pedretti, A.; Vistoli, G. Reactions and enzymes in the metabolism of drugs and other xenobiotics Drug Discovery Today 2012, 17 (11-12) 549-560 10.1016/j.drudis.2012.01.017
38. Andersen, H.; Siegrist, H.; Halling-Sørensen, B.; Ternes, T. A. Fate of estrogens in a municipal sewage treatment plant Environ. Sci. Technol. 2003, 37 (18) 4021-4026 10.1021/es026192a
39. Joss, A.; Andersen, H.; Ternes, T.; Richle, P. R.; Siegrist, H. Removal of estrogens in municipal wastewater treatment under aerobic and anaerobic conditions: consequences for plant optimization Environ. Sci. Technol. 2004, 38 (11) 3047-3055 10.1021/es0351488
40. Gomes, R. L.; Scrimshaw, M. D.; Lester, J. N. Fate of conjugated natural and synthetic steroid estrogens in crude sewage and activated sludge batch studies Environ. Sci. Technol. 2009, 43 (10) 3612-3618 10.1021/es801952h
41. Ternes, T. A. Occurrence of drugs in German sewage treatment plants and rivers Water Res. 1998, 32 (11) 3245-3260 10.1016/S0043-1354(98)00099-2
42. Joss, A.; Keller, E.; Alder, A. C.; Göbel, A.; McArdell, C. S.; Ternes, T.; Siegrist, H. Removal of pharmaceuticals and fragrances in biological wastewater treatment Water Res. 2005, 39 (14) 3139-3152 10.1016/j.watres.2005.05.031
43. Vieno, N.; Tuhkanen, T.; Kronberg, L. Elimination of pharmaceuticals in sewage treatment plants in Finland Water Res. 2007, 41 (5) 1001-1012 10.1016/j.watres.2006.12.017
44. Bahlmann, A.; Brack, W.; Schneider, R. J.; Krauss, M. Carbamazepine and its metabolites in wastewater: Analytical pitfalls and occurrence in Germany and Portugal Water Res. 2014, 57, 104-114 10.1016/j.watres.2014.03.022
45. Miao, X.-S.; Yang, J.-J.; Metcalfe, C. D. Carbamazepine and its metabolites in wastewater and in biosolids in a municipal wastewater treatment plant Environ. Sci. Technol. 2005, 39 (19) 7469-7475 10.1021/es050261e
46. Gurke, R.; Rößler, M.; Marx, C.; Diamond, S.; Schubert, S.; Oertel, R.; Fauler, J. Occurrence and removal of frequently prescribed pharmaceuticals and corresponding metabolites in wastewater of a sewage treatment plant Sci. Total Environ. 2015, 532, 762-770 10.1016/j.scitotenv.2015.06.067
47. Lee, H. J.; Lee, E.; Yoon, S. H.; Chang, H. R.; Kim, K.; Kwon, J. H. Enzymatic and microbial transformation assays for the evaluation of the environmental fate of diclofenac and its metabolites Chemosphere 2012, 87 (8) 969-974 10.1016/j.chemosphere.2012.02.018
48. Vieno, N.; Sillanpää, M. Fate of diclofenac in municipal wastewater treatment plant-A review Environ. Int. 2014, 69, 28-39 10.1016/j.envint.2014.03.021
49. García-Galán, M. J.; Silvia Díaz-Cruz, M.; Barceló, D. Identification and determination of metabolites and degradation products of sulfonamide antibiotics TrAC, Trends Anal. Chem. 2008, 27 (11) 1008-1022 10.1016/j.trac.2008.10.001
50. Celiz, M. D.; Tso, J.; Aga, D. S. Pharmaceutical metabolites in the environment: analytical challenges and ecological risks Environ. Toxicol. Chem. 2009, 28, 2473-2484 10.1897/09-173.1
51. Griffith, D. R.; Kido Soule, M. C.; Matsufuji, H.; Eglinton, T. I.; Kujawinski, E. B.; Gschwend, P. M. Measuring free, conjugated, and halogenated estrogens in secondary treated wastewater effluent Environ. Sci. Technol. 2014, 48 (5) 2569-2578 10.1021/es402809u
52. Brown, A. K.; Wong, C. S. Current trends in environmental analysis of human metabolite conjugates of pharmaceuticals Trends Environ. Anal. Chem. 2015, 5, 8-17 10.1016/j.teac.2015.01.002
53. van der Ven, A. J.; Vree, T. B.; Ewijk-Beneken Kolmer, E. W.; Koopmans, P. P.; van der Meer, J. W. Urinary recovery and kinetics of sulphamethoxazole and its metabolites in HIV-seropositive patients and healthy volunteers after a single oral dose of sulphamethoxazole Br. J. Clin. Pharmacol. 1995, 39 (6) 621-625 10.1111/j.1365-2125.1995.tb05721.x
54. Vree, T. B.; van der Ven, A. J. A. M.; Koopmans, P. P.; van Ewijk-Beneken Kolmer, E. W. J.; Verwey-van Wissen, C. P. W. G. M. Pharmacokinetics of sulfamethoxazole with its hydroxy metabolites and N4-acetyl-, N1-glucuronide conjugates in healthy human volunteers Clin. Drug Invest. 1995, 9 (1) 43-53 10.2165/00044011-199509010-00008
55. Göbel, A.; Thomsen, A.; McArdell, C. S.; Joss, A.; Giger, W. Occurrence and sorption behavior of sulfonamides, macrolides, and trimethoprim in activated sludge treatment Environ. Sci. Technol. 2005, 39 (11) 3981-3989 10.1021/es048550a
56. Göbel, A.; McArdell, C. S.; Joss, A.; Siegrist, H.; Giger, W. Fate of sulfonamides, macrolides, and trimethoprim in different wastewater treatment technologies Sci. Total Environ. 2007, 372 (2-3) 361-371 10.1016/j.scitotenv.2006.07.039
57. Joss, A.; Zabczynski, S.; Göbel, A.; Hoffmann, B.; Löffler, D.; McArdell, C. S.; Ternes, T. a; Thomsen, A.; Siegrist, H. Biological degradation of pharmaceuticals in municipal wastewater treatment: proposing a classification scheme Water Res. 2006, 40 (8) 1686-1696 10.1016/j.watres.2006.02.014
58. Falås, P.; Longrée, P.; la Cour Jansen, J.; Siegrist, H.; Hollender, J.; Joss, A. Micropollutant removal by attached and suspended growth in a hybrid biofilm-activated sludge process Water Res. 2013, 47 (13) 4498-4506 10.1016/j.watres.2013.05.010
59. Senta, I.; Terzic, S.; Ahel, M. Occurrence and fate of dissolved and particulate antimicrobials in municipal wastewater treatment Water Res. 2013, 47 (2) 705-714 10.1016/j.watres.2012.10.041
60. García-Galán, M. J.; Frömel, T.; Müller, J.; Peschka, M.; Knepper, T.; Díaz-Cruz, S.; Barceló, D. Biodegradation studies of N4-acetylsulfapyridine and N4-acetylsulfamethazine in environmental water by applying mass spectrometry techniques Anal. Bioanal. Chem. 2012, 402 (9) 2885-2896 10.1007/s00216-012-5751-y
61. Stadler, L. B.; Su, L.; Moline, C. J.; Ernstoff, A. S.; Aga, D. S.; Love, N. G. Effect of redox conditions on pharmaceutical loss during biological wastewater treatment using sequencing batch reactors J. Hazard. Mater. 2015, 282, 106-115 10.1016/j.jhazmat.2014.08.002
62. Wang, J.; Gardinali, P. R. Identification of phase II pharmaceutical metabolites in reclaimed water using high resolution benchtop Orbitrap mass spectrometry Chemosphere 2014, 107, 65-73 10.1016/j.chemosphere.2014.03.021
63. Bonvin, F.; Omlin, J.; Rutler, R.; Schweizer, W. B.; Alaimo, P. J.; Strathmann, T. J.; McNeill, K.; Kohn, T. Direct photolysis of human metabolites of the antibiotic sulfamethoxazole: Evidence for abiotic back-transformation Environ. Sci. Technol. 2013, 47 (13) 6746-6755 10.1021/es303777k
64. Radke, M.; Lauwigi, C.; Heinkele, G.; Mürdter, T. E.; Letzel, M. Fate of the antibiotic sulfamethoxazole and its two major human metabolites in a water sediment test Environ. Sci. Technol. 2009, 43 (9) 3135-3141 10.1021/es900300u
65. Bergan, T.; Dalhoff, A.; Rohwedder, R. Pharmacokinetics of ciprofloxacin Infection 1988, 16 (S1) S3-S13 10.1007/BF01650500
66. Rohwedder, R. W.; Bergan, T.; Thorsteinsson, S. B.; Scholl, H. Transintestinal elimination of ciprofloxacin Diagn. Microbiol. Infect. Dis. 1990, 13 (2) 127-133 10.1016/0732-8893(90)90095-D
67. Tanimura, H.; Tominaga, S.; Rai, F.; Matsumoto, H. Transfer of ciprofloxacin to bile and determination of biliary metabolites in humans Arzneimittelforschung 1986, 36 (9) 1417-1420
68. D'Ascenzo, G.; Di Corcia, A.; Gentili, A.; Mancini, R.; Mastropasqua, R.; Nazzari, M.; Samperi, R. Fate of natural estrogen conjugates in municipal sewage transport and treatment facilities Sci. Total Environ. 2003, 302 (1-3) 199-209 10.1016/S0048-9697(02)00342-X
69. Kumar, V.; Johnson, A. C.; Nakada, N.; Yamashita, N.; Tanaka, H. De-conjugation behavior of conjugated estrogens in the raw sewage, activated sludge and river water J. Hazard. Mater. 2012, 227-228, 49-54 10.1016/j.jhazmat.2012.04.078
70. Kunin, C. M.; Dornbush, A. C.; Finland, M. Distribution and excretion of four tetracycline analogues in normal young men J. Clin. Invest. 1959, 38 (11) 1950-1963 10.1172/JCI103974
71. Kunin, C. M. Comparative serum binding, distribution and excretion of tetracycline and a new analogue, methacycline Exp. Biol. Med. 1962, 110 (2) 311-315 10.3181/00379727-110-27501
72. Steigbigel, N. H.; Reed, C. W.; Finland, M. Absorption and excretion of five tetracycline analogues in normal young men Am. J. Med. Sci. 1968, 255, 296-312 10.1097/00000441-196805000-00005
73. Agwuh, K. N.; MacGowan, A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines J. Antimicrob. Chemother. 2006, 58 (2) 256-265 10.1093/jac/dkl224
74. Eisen, D. P. Tetracycline. In Kucers' The Use of Antibiotics-A Clinical Review of Antibacterial, Antifungal and Antiviral Drugs; Grayson, M. L., Ed.; CRC Press: Boca Raton, FL, U.S., 2010; pp 843-850.
75. McCormick, J. R. D.; Fox, S. M.; Smith, L. L.; Bitler, B. a.; Reichenthal, J.; Origoni, V. E.; Muller, W. H.; Winterbottom, R.; Doerschuk, A. P. Studies of the reversible epimerization occurring in the tetracycline family. The preparation, properties and proof of structure of some 4-epi-tetracyclines J. Am. Chem. Soc. 1957, 79 (11) 2849-2858 10.1021/ja01568a050
76. Halling-Sørensen, B.; Sengeløv, G.; Tjørnelund, J. Toxicity of tetracyclines and tetracycline degradation products to environmentally relevant bacteria, including selected tetracycline-resistant bacteria Arch. Environ. Contam. Toxicol. 2002, 42 (3) 263-271 10.1007/s00244-001-0017-2
77. Kühne, M.; Ihnen, D.; Möller, G.; Agthe, O. Stability of tetracycline in water and liquid manure J. Vet. Med., A 2000, 47 (6) 379-384 10.1046/j.1439-0442.2000.00300.x
78. Sengeløv, G.; Halling-Sørensen, B.; Aarestrup, F. M. Susceptibility of Escherichia coli and Enterococcus faecium isolated from pigs and broiler chickens to tetracycline degradation products and distribution of tetracycline resistance determinants in E. coli from food animals Vet. Microbiol. 2003, 95 (1-2) 91-101 10.1016/S0378-1135(03)00123-8
79. Jacobsen, A. M.; Halling-Sørensen, B. Multi-component analysis of tetracyclines, sulfonamides and tylosin in swine manure by liquid chromatography-tandem mass spectrometry Anal. Bioanal. Chem. 2006, 384 (5) 1164-1174 10.1007/s00216-005-0261-9
80. Remmers, E. G.; Sieger, G. M.; Doerschuk, A. P. Some observations on the kinetics of the C-4 epimerization of tetracycline J. Pharm. Sci. 1963, 52 (8) 752-756 10.1002/jps.2600520809
81. Hussar, D. A.; Niebergall, P. J.; Sugita, E. T.; Doluisio, J. T. Aspects of the epimerization of certain tetracycline derivatives J. Pharm. Pharmacol. 1968, 20 (7) 539-546 10.1111/j.2042-7158.1968.tb09802.x
82. Hlavka, J. J.; Boothe, J. H. The Tetracyclines. In Progress in Drug Research; Jucker, E., Ed.; Birkhauser Verlag: Basel, Switzerland, 1973; pp 210-240.
83. Pena, A.; Paulo, M.; Silva, L. J. G.; Seifrtová, M.; Lino, C. M.; Solich, P. Tetracycline antibiotics in hospital and municipal wastewaters: A pilot study in Portugal Anal. Bioanal. Chem. 2010, 396 (8) 2929-2936 10.1007/s00216-010-3581-3
84. Kim, M.; Guerra, P.; Shah, A.; Parsa, M.; Alaee, M.; Smyth, S. A. Removal of pharmaceuticals and personal care products in a membrane bioreactor wastewater treatment plant Water Sci. Technol. 2014, 69 (11) 2221-2229 10.2166/wst.2014.145
85. Jewell, K. S.; Wick, A.; Ternes, T. A. Comparisons between abiotic nitration and biotransformation reactions of phenolic micropollutants in activated sludge Water Res. 2014, 48 (1) 478-489 10.1016/j.watres.2013.10.010
86. Skotnicka-Pitak, J.; Khunjar, W. O.; Love, N. G.; Aga, D. S. Characterization of metabolites formed during the biotransformation of 17α-ethinylestradiol by Nitrosomonas europaea in batch and continuous flow bioreactors Environ. Sci. Technol. 2009, 43 (10) 3549-3555 10.1021/es8026659
87. Gaulke, L. S.; Strand, S. E.; Kalhorn, T. F.; Stensel, H. D. 17α-ethinylestradiol transformation via abiotic nitration in the presence of ammonia oxidizing bacteria Environ. Sci. Technol. 2008, 42 (20) 7622-7627 10.1021/es801503u
88. Gaulke, L. S.; Strand, S. E.; Kalhorn, T. F.; Stensel, H. D. Estrogen nitration kinetics and implications for wastewater treatment Water Environ. Res. 2009, 81 (8) 772-778 10.2175/106143009X407285
89. Khunjar, W. O.; MacKintosh, S. A.; Skotnicka-Pitak, J.; Baik, S.; Aga, D. S.; Love, N. G. Elucidating the relative roles of ammonia oxidizing and heterotrophic bacteria during the biotransformation of 17α-ethinylestradiol and trimethoprim Environ. Sci. Technol. 2011, 45 (8) 3605-3612 10.1021/es1037035
90. Chiron, S.; Gomez, E.; Fenet, H. Nitration processes of acetaminophen in nitrifying activated sludge Environ. Sci. Technol. 2010, 44 (1) 284-289 10.1021/es902129c
91. Osorio, V.; Sanchís, J.; Abad, J. L.; Ginebreda, A.; Farré, M.; Pérez, S.; Barceló, D. Investigating the formation and toxicity of nitrogen transformation products of diclofenac and sulfamethoxazole in wastewater treatment plants J. Hazard. Mater. 2016, 309, 157-164 10.1016/j.jhazmat.2016.02.013
92. Pérez, S.; Barceló, D. First evidence for occurrence of hydroxylated human metabolites of diclofenac and aceclofenac in wastewater using QqLIT-MS and QqTOF-MS Anal. Chem. 2008, 80 (21) 8135-8145 10.1021/ac801167w
93. Osorio, V.; Imbert-Bouchard, M.; Zonja, B.; Abad, J. L.; Pérez, S.; Barceló, D. Simultaneous determination of diclofenac, its human metabolites and microbial nitration/nitrosation transformation products in wastewaters by liquid chromatography/quadrupole-linear ion trap mass spectrometry J. Chromatogr. A 2014, 1347, 63-71 10.1016/j.chroma.2014.04.058
94. Nödler, K.; Licha, T.; Barbieri, M.; Pérez, S. Evidence for the microbially mediated abiotic formation of reversible and non-reversible sulfamethoxazole transformation products during denitrification Water Res. 2012, 46 (7) 2131-2139 10.1016/j.watres.2012.01.028
95. Kern, S.; Baumgartner, R.; Helbling, D. E.; Hollender, J.; Singer, H.; Loos, M. J.; Schwarzenbach, R. P.; Fenner, K. A tiered procedure for assessing the formation of biotransformation products of pharmaceuticals and biocides during activated sludge treatment J. Environ. Monit. 2010, 12 (11) 2100-2111 10.1039/c0em00238k
96. Kovalova, L.; Siegrist, H.; Singer, H.; Wittmer, A.; McArdell, C. S. Hospital wastewater treatment by membrane bioreactor: performance and efficiency for organic micropollutant elimination Environ. Sci. Technol. 2012, 46 (3) 1536-1545 10.1021/es203495d
97. Brayfield, A. Martindale: The Complete Drug Reference; Pharmaceutical Press: London, UK, 2013; www.medicinescomplete.com.
98. Nielsen, P.; Gyrd-Hansen, N. Bioavailability of enrofloxacin after oral administration to fed and fasted pigs Pharmacol. Toxicol. 1997, 80 (5) 246-250 10.1111/j.1600-0773.1997.tb01967.x
99. Kumar, N.; Singh, S. D.; Jayachandran, C. Pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin and its interaction with diclofenac after intravenous administration in buffalo calves Vet. J. 2003, 165 (3) 302-306 10.1016/S1090-0233(02)00248-4
100. Slana, M.; Pahor, V.; Cvitkovic Maricic, L.; Sollner-Dolenc, M. Excretion pattern of enrofloxacin after oral treatment of chicken broilers J. Vet. Pharmacol. Ther. 2014, 37 (6) 611-614 10.1111/jvp.12130
101. Wetzstein, H.-G.; Schneider, J.; Karl, W. Patterns of metabolites produced from the fluoroquinolone enrofloxacin by basidiomycetes indigenous to agricultural sites Appl. Microbiol. Biotechnol. 2006, 71 (1) 90-100 10.1007/s00253-005-0178-4
102. Burhenne, J.; Ludwig, M.; Nikoloudis, P.; Spiteller, M. Primary photoproducts and half-lives Environ. Sci. Pollut. Res. 1997, 4 (1) 10-15 10.1007/BF02986257
103. Merton Boothe, D. Tetracyclines. In Merck Veterinary Manual; Aiello, S. E., Ed.; Merck Sharp & Dohme Corp.: Kenilworth, N.J., U.S.A., 2012. Available at www.merckmanuals.com/vet/index.html.
104. Lindberg, R. H.; Olofsson, U.; Rendahl, P.; Johansson, M. I.; Tysklind, M.; Andersson, B. A. V. Behavior of fluoroquinolones and trimethoprim during mechanical, chemical, and active sludge treatment of sewage water and digestion of sludge Environ. Sci. Technol. 2006, 40 (3) 1042-1048 10.1021/es0516211
105. Jia, A.; Wan, Y.; Xiao, Y.; Hu, J. Occurrence and fate of quinolone and fluoroquinolone antibiotics in a municipal sewage treatment plant Water Res. 2012, 46 (2) 387-394 10.1016/j.watres.2011.10.055
106. Terzić, S.; Senta, I.; Ahel, M.; Gros, M.; Petrović, M.; Barcelo, D.; Müller, J.; Knepper, T.; Martí, I.; Ventura, F. et al. Occurrence and fate of emerging wastewater contaminants in Western Balkan Region Sci. Total Environ. 2008, 399 (1-3) 66-77 10.1016/j.scitotenv.2008.03.003
107. Gao, L.; Shi, Y.; Li, W.; Niu, H.; Liu, J.; Cai, Y. Occurrence of antibiotics in eight sewage treatment plants in Beijing, China Chemosphere 2012, 86 (6) 665-671 10.1016/j.chemosphere.2011.11.019
108. Oertel, R.; Schubert, S.; Mühlbauer, V.; Büttner, B.; Marx, C.; Kirch, W. Determination of clindamycin and its metabolite clindamycin sulfoxide in diverse sewage samples Environ. Sci. Pollut. Res. 2014, 21 (20) 11764 10.1007/s11356-013-2333-2
109. Marx, C.; Günther, N.; Schubert, S.; Oertel, R.; Ahnert, M.; Krebs, P.; Kuehn, V. Mass flow of antibiotics in a wastewater treatment plant focusing on removal variations due to operational parameters Sci. Total Environ. 2015, 538, 779-788 10.1016/j.scitotenv.2015.08.112
110. Siegrist, H. Micropollutants-New Challenge in Wastewater Disposal? EAWAG News 2003, 57, 7-10
111. Holbrook, R. D.; Love, N. G.; Novak, J. T. Investigation of sorption behavior between pyrene and colloidal organic carbon from activated sludge processes Environ. Sci. Technol. 2004, 38 (19) 4987-4994 10.1021/es035115s
112. Barret, M.; Patureau, D.; Latrille, E.; Carrère, H. A three-compartment model for micropollutants sorption in sludge: methodological approach and insights Water Res. 2010, 44 (2) 616-624 10.1016/j.watres.2009.08.029
113. Barret, M.; Carrère, H.; Latrille, E.; Wisniewski, C.; Patureau, D. Micropollutant and sludge characterization for modeling sorption equilibria Environ. Sci. Technol. 2010, 44 (3) 1100-1106 10.1021/es902575d
114. Khunjar, W. O.; Love, N. G. Sorption of carbamazepine, 17α-ethinylestradiol, iopromide and trimethoprim to biomass involves interactions with exocellular polymeric substances Chemosphere 2011, 82 (6) 917-922 10.1016/j.chemosphere.2010.10.046
115. Delgadillo-Mirquez, L.; Lardon, L.; Steyer, J.-P.; Patureau, D. A new dynamic model for bioavailability and cometabolism of micropollutants during anaerobic digestion Water Res. 2011, 45 (15) 4511-4521 10.1016/j.watres.2011.05.047
116. Larsen, T. A.; Harremoës, P. Degradation mechanisms of colloidal organic matter in biofilm reactors Water Res. 1994, 28 (6) 1443-1452 10.1016/0043-1354(94)90312-3
117. Guellil, A.; Boualam, M.; Quiquampoix, H.; Ginestet, P.; Audic, J. M.; Block, J. C. Hydrolysis of wastewater colloidal organic matter by extracellular enzymes extracted from activated sludge flocs Water Sci. Technol. 2001, 43 (6) 33-40
118. Serrano, D.; Omil, F.; Lema, J. M.; Patureau, D. Application of a three-compartment model as a tool to understand the partition of 17α-ethinylestradiol in mixed liquor systems Environ. Prog. Sustainable Energy 2013, 32 (2) 257-262 10.1002/ep.11618
119. Carmosini, N.; Lee, L. S. Ciprofloxacin sorption by dissolved organic carbon from reference and bio-waste materials Chemosphere 2009, 77 (6) 813-820 10.1016/j.chemosphere.2009.08.003
120. Sithole, B. B.; Guy, R. D. Models for Tetracycline in Aquatic Environments Water, Air, Soil Pollut. 1987, 32 (3) 315-321 10.1007/BF00225117
121. Golet, E. M.; Xifra, I.; Siegrist, H.; Alder, A. C.; Giger, W. Environmental exposure assessment of fluoroquinolone antibacterial agents from sewage to soil Environ. Sci. Technol. 2003, 37 (15) 3243-3249 10.1021/es0264448
122. Kim, S.; Eichhorn, P.; Jensen, J. N.; Weber, A. S.; Aga, D. S. Removal of antibiotics in wastewater: Effect of hydraulic and solid retention times on the fate of tetracycline in the activated sludge process Environ. Sci. Technol. 2005, 39 (15) 5816-5823 10.1021/es050006u
123. Li, B.; Zhang, T. Biodegradation and adsorption of antibiotics in the activated sludge process Environ. Sci. Technol. 2010, 44 (9) 3468-3473 10.1021/es903490h
124. Polesel, F.; Lehnberg, K.; Dott, W.; Trapp, S.; Thomas, K. V.; Plósz, B. G. Factors influencing sorption of ciprofloxacin onto activated sludge: Experimental assessment and modelling implications Chemosphere 2015, 119, 105-111 10.1016/j.chemosphere.2014.05.048
125. Nowara, A.; Burhenne, J.; Spiteller, M. Binding of fluoroquinolone carboxylic acid derivatives to clay minerals J. Agric. Food Chem. 1997, 45 (4) 1459-1463 10.1021/jf960215l
126. Tolls, J. Sorption of veterinary pharmaceuticals in soils: A review Environ. Sci. Technol. 2001, 35 (17) 3397-3406 10.1021/es0003021
127. Figueroa, R. A.; Leonard, A.; Mackay, A. A. Modeling tetracycline antibiotic sorption to clays Environ. Sci. Technol. 2004, 38 (2) 476-483 10.1021/es0342087
128. Sassman, S. A.; Lee, L. S. Sorption of three tetracyclines by several soils: Assessing the role of pH and cation exchange Environ. Sci. Technol. 2005, 39 (19) 7452-7459 10.1021/es0480217
129. MacKay, A. A.; Canterbury, B. Oxytetracycline sorption to organic matter by metal-bridging J. Environ. Qual. 2005, 34 (6) 1964-1971 10.2134/jeq2005.0014
130. Vasudevan, D.; Bruland, G. L.; Torrance, B. S.; Upchurch, V. G.; MacKay, A. A. pH-dependent ciprofloxacin sorption to soils: Interaction mechanisms and soil factors influencing sorption Geoderma 2009, 151 (3-4) 68-76 10.1016/j.geoderma.2009.03.007
131. MacKay, A. A.; Vasudevan, D. Polyfunctional ionogenic compound sorption: Challenges and new approaches to advance predictive models Environ. Sci. Technol. 2012, 46 (17) 9209-9223 10.1021/es301036t
132. Yi, T.; Harper, W. F., Jr. The effect of biomass characteristics on the partitioning and sorption hysteresis of 17α-ethinylestradiol Water Res. 2007, 41 (7) 1543-1553 10.1016/j.watres.2006.12.023
133. Wu, C.; Spongberg, A. L.; Witter, J. D. Sorption and biodegradation of selected antibiotics in biosolids J. Environ. Sci. Health, Part A: Toxic/Hazard. Subst. Environ. Eng. 2009, 44 (5) 454-461 10.1080/10934520902719779
134. Ekama, G. A.; Wentzel, M. C. Nitrogen Removal. In Biological Wastewater Treatment: Principles, Modelling and Design; Henze, M.; van Loosdrecht, M. C. M.; Ekama, G.; Brdjanovic, D., Eds.; IWA Publishing: London, U.K., 2008; pp 87-138.
135. Vader, J. S.; Van Ginkel, C. G.; Sperling, F. M. G. M.; De Jong, J.; De Boer, W.; De Graaf, J. S.; Van Der Most, M.; Stokman, P. G. W. Degradation of ethinyl estradiol by nitrifying activated sludge Chemosphere 2000, 41 (8) 1239-1243 10.1016/S0045-6535(99)00556-1
136. Shi, J.; Fujisawa, S.; Nakai, S.; Hosomi, M. Biodegradation of natural and synthetic estrogens by nitrifying activated sludge and ammonia-oxidizing bacterium Nitrosomonas europaea Water Res. 2004, 38 (9) 2323-2330 10.1016/j.watres.2004.02.022
137. Batt, A. L.; Kim, S.; Aga, D. S. Enhanced biodegradation of lopromide and trimethoprim in nitrifying activated sludge Environ. Sci. Technol. 2006, 40 (23) 7367-7373 10.1021/es060835v
138. Yi, T.; Harper, W. F. The link between nitrification and biotransformation of 17α-ethinylestradiol Environ. Sci. Technol. 2007, 41 (12) 4311-4316 10.1021/es070102q
139. Ren, Y. X.; Nakano, K.; Nomura, M.; Chiba, N.; Nishimura, O. Effects of bacterial activity on estrogen removal in nitrifying activated sludge Water Res. 2007, 41 (14) 3089-3096 10.1016/j.watres.2007.04.028
140. Forrez, I.; Carballa, M.; Boon, N.; Verstraete, W. Biological removal of 17α-ethinylestradiol (EE2) in an aerated nitrifying fixed bed reactor during ammonium starvation J. Chem. Technol. Biotechnol. 2009, 84 (1) 119-125 10.1002/jctb.2016
141. De Gusseme, B.; Pycke, B.; Hennebel, T.; Marcoen, A.; Vlaeminck, S. E.; Noppe, H.; Boon, N.; Verstraete, W. Biological removal of 17α-ethinylestradiol by a nitrifier enrichment culture in a membrane bioreactor Water Res. 2009, 43 (9) 2493-2503 10.1016/j.watres.2009.02.028
142. Tran, N. H.; Urase, T.; Kusakabe, O. The characteristics of enriched nitrifier culture in the degradation of selected pharmaceutically active compounds J. Hazard. Mater. 2009, 171 (1-3) 1051-1057 10.1016/j.jhazmat.2009.06.114
143. Suarez, S.; Lema, J. M.; Omil, F. Removal of pharmaceutical and personal care products (PPCPs) under nitrifying and denitrifying conditions Water Res. 2010, 44 (10) 3214-3224 10.1016/j.watres.2010.02.040
144. Fernandez-Fontaina, E.; Omil, F.; Lema, J. M.; Carballa, M. Influence of nitrifying conditions on the biodegradation and sorption of emerging micropollutants Water Res. 2012, 46 (16) 5434-5444 10.1016/j.watres.2012.07.037
145. Sathyamoorthy, S.; Chandran, K.; Ramsburg, C. A. Biodegradation and cometabolic modeling of selected beta blockers during ammonia oxidation Environ. Sci. Technol. 2013, 47 (22) 12835-12843 10.1021/es402878e
146. Kreuzinger, N.; Clara, M.; Strenn, B.; Kroiss, H. Relevance of the sludge retention time (SRT) as design criteria for wastewater treatment plants for the removal of endocrine disruptors and pharmaceuticals from wastewater Water Sci. Technol. 2004, 50 (5) 149-156
147. Clara, M.; Kreuzinger, N.; Strenn, B.; Gans, O.; Kroiss, H. The solids retention time-A suitable design parameter to evaluate the capacity of wastewater treatment plants to remove micropollutants Water Res. 2005, 39 (1) 97-106 10.1016/j.watres.2004.08.036
148. Clara, M.; Strenn, B.; Gans, O.; Martinez, E.; Kreuzinger, N.; Kroiss, H. Removal of selected pharmaceuticals, fragrances and endocrine disrupting compounds in a membrane bioreactor and conventional wastewater treatment plants Water Res. 2005, 39 (19) 4797-4807 10.1016/j.watres.2005.09.015
149. Wick, A.; Fink, G.; Joss, A.; Siegrist, H.; Ternes, T. A. Fate of beta blockers and psycho-active drugs in conventional wastewater treatment Water Res. 2009, 43 (4) 1060-1074 10.1016/j.watres.2008.11.031
150. Falås, P.; Baillon-Dhumez, A.; Andersen, H. R.; Ledin, A.; la Cour Jansen, J. Suspended biofilm carrier and activated sludge removal of acidic pharmaceuticals Water Res. 2012, 46 (4) 1167-1175 10.1016/j.watres.2011.12.003
151. Ziels, R. M.; Lust, M. J.; Gough, H. L.; Strand, S. E.; Stensel, H. D. Influence of bioselector processes on 17α-ethinylestradiol biodegradation in activated sludge wastewater treatment systems Environ. Sci. Technol. 2014, 48 (11) 6160-6167 10.1021/es405351b
152. Weiss, S.; Reemtsma, T. Membrane bioreactors for municipal wastewater treatment-A viable option to reduce the amount of polar pollutants discharged into surface waters? Water Res. 2008, 42 (14) 3837-3847 10.1016/j.watres.2008.05.019
153. Koh, Y. K. K.; Chiu, T. Y.; Boobis, A. R.; Scrimshaw, M. D.; Bagnall, J. P.; Soares, A.; Pollard, S.; Cartmell, E.; Lester, J. N. Influence of operating parameters on the biodegradation of steroid estrogens and nonylphenolic compounds during biological wastewater treatment processes Environ. Sci. Technol. 2009, 43 (17) 6646-6654 10.1021/es901612v
154. Sipma, J.; Osuna, B.; Collado, N.; Monclús, H.; Ferrero, G.; Comas, J.; Rodriguez-Roda, I. Comparison of removal of pharmaceuticals in MBR and activated sludge systems Desalination 2010, 250 (2) 653-659 10.1016/j.desal.2009.06.073
155. Vuono, D. C.; Benecke, J.; Henkel, J.; Navidi, W. C.; Cath, T. Y.; Munakata-Marr, J.; Spear, J. R.; Drewes, J. E. Disturbance and temporal partitioning of the activated sludge metacommunity ISME J. 2015, 9, 425-435 10.1038/ismej.2014.139
156. Bernhard, M.; Müller, J.; Knepper, T. P. Biodegradation of persistent polar pollutants in wastewater: Comparison of an optimized lab-scale membrane bioreactor and activated sludge treatment Water Res. 2006, 40 (18) 3419-3428 10.1016/j.watres.2006.07.011
157. Kimura, K.; Hara, H.; Watanabe, Y. Elimination of selected acidic pharmaceuticals from municipal wastewater by an activated sludge system and membrane bioreactors Environ. Sci. Technol. 2007, 41 (10) 3708-3714 10.1021/es061684z
158. Zuehlke, S.; Duennbier, U.; Lesjean, B.; Gnirss, R.; Buisson, H. Long-term comparison of trace organics removal performances between conventional and membrane activated sludge processes Water Environ. Res. 2006, 78 (13) 2480-2486 10.2175/106143006X111826
159. Radjenović, J.; Petrović, M.; Barceló, D. Fate and distribution of pharmaceuticals in wastewater and sewage sludge of the conventional activated sludge (CAS) and advanced membrane bioreactor (MBR) treatment Water Res. 2009, 43 (3) 831-841 10.1016/j.watres.2008.11.043
160. Sui, Q.; Huang, J.; Deng, S.; Chen, W.; Yu, G. Seasonal variation in the occurrence and removal of pharmaceuticals and personal care products in different biological wastewater treatment processes Environ. Sci. Technol. 2011, 45 (8) 3341-3348 10.1021/es200248d
161. Sahar, E.; Messalem, R.; Cikurel, H.; Aharoni, A.; Brenner, A.; Godehardt, M.; Jekel, M.; Ernst, M. Fate of antibiotics in activated sludge followed by ultrafiltration (CAS-UF) and in a membrane bioreactor (MBR) Water Res. 2011, 45, 4827-4836 10.1016/j.watres.2011.06.023
162. Dolar, D.; Gros, M.; Rodriguez-Mozaz, S.; Moreno, J.; Comas, J.; Rodriguez-Roda, I.; Barceló, D. Removal of emerging contaminants from municipal wastewater with an integrated membrane system, MBR-RO J. Hazard. Mater. 2012, 239-240, 64-69 10.1016/j.jhazmat.2012.03.029
163. Xia, S.; Jia, R.; Feng, F.; Xie, K.; Li, H.; Jing, D.; Xu, X. Effect of solids retention time on antibiotics removal performance and microbial communities in an A/O-MBR process Bioresour. Technol. 2012, 106, 36-43 10.1016/j.biortech.2011.11.112
164. Johnson, D. R.; Goldschmidt, F.; Lilja, E. E.; Ackermann, M. Metabolic specialization and the assembly of microbial communities ISME J. 2012, 6 (11) 1985-1991 10.1038/ismej.2012.46
165. Johnson, D. R.; Helbling, D. E.; Lee, T. K.; Park, J.; Fenner, K.; Kohler, H. P. E.; Ackermann, M. Association of biodiversity with the rates of micropollutant biotransformations among full-scale wastewater treatment plant communities Appl. Environ. Microbiol. 2015, 81 (2) 666-675 10.1128/AEM.03286-14
166. Helbling, D. E.; Johnson, D. R.; Lee, T. K.; Scheidegger, A.; Fenner, K. A framework for establishing predictive relationships between specific bacterial 16S rRNA sequence abundances and biotransformation rates Water Res. 2015, 70, 471-484 10.1016/j.watres.2014.12.013
167. Dalton, H.; Stirling, D. I. et al. Co-metabolism Philos. Trans. R. Soc., B 1982, 297 (1088) 481-496 10.1098/rstb.1982.0056
168. Grady, C. P. L. J. Biodegradation: Its measurement and microbiological basis Biotechnol. Bioeng. 1985, 27 (5) 660-674 10.1002/bit.260270516
169. Kovárová-Kovar, K.; Egli, T. Growth kinetics of suspended microbial cells: From single-substrate-controlled growth to mixed-substrate kinetics Microbiol. Mol. Biol. Rev. 1998, 62 (3) 646-666
170. Egli, T. How to live at very low substrate concentration Water Res. 2010, 44 (17) 4826-4837 10.1016/j.watres.2010.07.023
171. Ihssen, J.; Egli, T. Global physiological analysis of carbon- and energy-limited growing Escherichia coli confirms a high degree of catabolic flexibility and preparedness for mixed substrate utilization Environ. Microbiol. 2005, 7 (10) 1568-1581 10.1111/j.1462-2920.2005.00846.x
172. Tan, D. T.; Arnold, W. A.; Novak, P. J. Impact of organic carbon on the biodegradation of estrone in mixed culture systems Environ. Sci. Technol. 2013, 47 (21) 12359-12365 10.1021/es4027908
173. Helbling, D. E.; Johnson, D. R.; Honti, M.; Fenner, K. Micropollutant biotransformation kinetics associate with WWTP process parameters and microbial community characteristics Environ. Sci. Technol. 2012, 46 (19) 10579-10588 10.1021/es3019012
174. Smook, T. M.; Zho, H.; Zytner, R. G. Removal of ibuprofen from wastewater: Comparing biodegradation in conventional, membrane bioreactor, and biological nutrient removal treatment systems Water Sci. Technol. 2008, 57 (1) 1-8 10.2166/wst.2008.658
175. Abegglen, C.; Joss, A.; McArdell, C. S.; Fink, G.; Schlüsener, M. P.; Ternes, T. A.; Siegrist, H. The fate of selected micropollutants in a single-house MBR Water Res. 2009, 43 (7) 2036-2046 10.1016/j.watres.2009.02.005
176. Fernandez-Fontaina, E.; Pinho, I.; Carballa, M.; Omil, F.; Lema, J. M. Biodegradation kinetic constants and sorption coefficients of micropollutants in membrane bioreactors Biodegradation 2013, 24 (2) 165-177 10.1007/s10532-012-9568-3
177. De Wever, H.; Weiss, S.; Reemtsma, T.; Vereecken, J.; Müller, J.; Knepper, T.; Rörden, O.; Gonzalez, S.; Barceló, D.; Dolores Hernando, M. Comparison of sulfonated and other micropollutants removal in membrane bioreactor and conventional wastewater treatment Water Res. 2007, 41 (4) 935-945 10.1016/j.watres.2006.11.013
178. Majewsky, M.; Gallé, T.; Yargeau, V.; Fischer, K. Active heterotrophic biomass and sludge retention time (SRT) as determining factors for biodegradation kinetics of pharmaceuticals in activated sludge Bioresour. Technol. 2011, 102 (16) 7415-7421 10.1016/j.biortech.2011.05.032
179. Ort, C.; Schaffner, C.; Giger, W.; Gujer, W. Modelling stochastic load variations in sewer systems Water Sci. Technol. 2005, 52 (5) 113-122
180. Ort, C.; Gujer, W. Sampling for representative micropollutant loads in sewer systems Water Sci. Technol. 2006, 54 (6-7) 169-176 10.2166/wst.2006.591
181. Rieckermann, J.; Anta, J.; Scheidegger, A.; Ort, C. Assessing wastewater micropollutant loads with approximate bayesian computations Environ. Sci. Technol. 2011, 45 (10) 4399-4406 10.1021/es1030432
182. Ort, C.; Gujer, W. Sorption and high dynamics of micropollutants in sewers Water Sci. Technol. 2008, 57 (11) 1791-1797 10.2166/wst.2008.309
183. Plósz, B. G.; Leknes, H.; Liltved, H.; Thomas, K. V. Diurnal variations in the occurrence and the fate of hormones and antibiotics in activated sludge wastewater treatment in Oslo, Norway Sci. Total Environ. 2010, 408 (8) 1915-1924 10.1016/j.scitotenv.2010.01.042
184. Salgado, R.; Marques, R.; Noronha, J. P.; Mexia, J. T.; Carvalho, G.; Oehmen, A.; Reis, M. A. M. Assessing the diurnal variability of pharmaceutical and personal care products in a full-scale activated sludge plant Environ. Pollut. 2011, 159 (10) 2359-2367 10.1016/j.envpol.2011.07.004
185. Coutu, S.; Wyrsch, V.; Wynn, H. K.; Rossi, L.; Barry, D. A. Temporal dynamics of antibiotics in wastewater treatment plant influent Sci. Total Environ. 2013, 458-460, 20-26 10.1016/j.scitotenv.2013.04.017
186. Marx, C.; Mühlbauer, V.; Schubert, S.; Oertel, R.; Ahnert, M.; Krebs, P.; Kuehn, V. Representative input load of antibiotics to WWTPs: Predictive accuracy and determination of a required sampling quantity Water Res. 2015, 76, 19-32 10.1016/j.watres.2015.02.049
187. Snip, L. J. P.; Flores-Alsina, X.; Plósz, B. G.; Jeppsson, U.; Gernaey, K. V. Modelling the occurrence, transport and fate of pharmaceuticals in wastewater systems Environ. Model. Softw. 2014, 62, 112-127 10.1016/j.envsoft.2014.08.007
188. Ort, C.; Lawrence, M. G.; Rieckermann, J.; Joss, A. Sampling for pharmaceuticals and personal care products (PPCPs) and illicit drugs in wastewater systems: are your conclusions valid? A critical review Environ. Sci. Technol. 2010, 44 (16) 6024-6035 10.1021/es100779n
189. Ort, C.; Lawrence, M. G.; Reungoat, J.; Mueller, J. F. Sampling for PPCPs in wastewater systems: Comparison of different sampling modes and optimization strategies Environ. Sci. Technol. 2010, 44 (16) 6289-6296 10.1021/es100778d
190. Teerlink, J.; Hering, A. S.; Higgins, C. P.; Drewes, J. E. Variability of trace organic chemical concentrations in raw wastewater at three distinct sewershed scales Water Res. 2012, 46 (10) 3261-3271 10.1016/j.watres.2012.03.018
191. Castiglioni, S.; Bijlsma, L.; Covaci, A.; Emke, E.; Hernández, F.; Reid, M.; Ort, C.; Thomas, K. V.; Van Nuijs, A. L. N.; De Voogt, P. et al. Evaluation of uncertainties associated with the determination of community drug use through the measurement of sewage drug biomarkers Environ. Sci. Technol. 2013, 47 (3) 1452-1460 10.1021/es302722f
192. Majewsky, M.; Gallé, T.; Bayerle, M.; Goel, R.; Fischer, K.; Vanrolleghem, P. A. Xenobiotic removal efficiencies in wastewater treatment plants: residence time distributions as a guiding principle for sampling strategies Water Res. 2011, 45 (18) 6152-6162 10.1016/j.watres.2011.09.005
193. Weissbrodt, D.; Kovalova, L.; Ort, C.; Pazhepurackel, V.; Moser, R.; Hollender, J.; Siegrist, H.; Mcardell, C. S. Mass flows of x-ray contrast media and cytostatics in hospital wastewater Environ. Sci. Technol. 2009, 43 (13) 4810-4817 10.1021/es8036725
194. Ort, C.; Lawrence, M. G.; Reungoat, J.; Eaglesham, G.; Carter, S.; Keller, J. Determining the fraction of pharmaceutical residues in wastewater originating from a hospital Water Res. 2010, 44 (2) 605-615 10.1016/j.watres.2009.08.002
195. Baker, D. R.; Kasprzyk-Hordern, B. Critical evaluation of methodology commonly used in sample collection, storage and preparation for the analysis of pharmaceuticals and illicit drugs in surface water and wastewater by solid phase extraction and liquid chromatography-mass spectrometry J. Chromatogr. A 2011, 1218 (44) 8036-8059 10.1016/j.chroma.2011.09.012
196. Hillebrand, O.; Musallam, S.; Scherer, L.; Nödler, K.; Licha, T. The challenge of sample-stabilisation in the era of multi-residue analytical methods: A practical guideline for the stabilisation of 46 organic micropollutants in aqueous samples Sci. Total Environ. 2013, 454-455, 289-298 10.1016/j.scitotenv.2013.03.028
197. Fedorova, G.; Golovko, O.; Randak, T.; Grabic, R. Storage effect on the analysis of pharmaceuticals and personal care products in wastewater Chemosphere 2014, 111, 55-60 10.1016/j.chemosphere.2014.02.067
198. Khunjar, W. O.; Chandran, K.; Stanford, B. Developing a Standardized Protocol for Assessing the Biodegradability of Trace Organic Compounds (WERF U3R10) wio 2014, 10.2166/9781780405162
199. Boethling, R. S.; Alexander, M. Effect of concentration of organic chemicals on their biodegradation by natural microbial communities Appl. Environ. Microbiol. 1979, 37 (6) 1211-1216
200. Alexander, M. Biodegradation of organic chemicals Environ. Sci. Technol. 1985, 19, 106-111 10.1021/es00132a602
201. Fischer, K.; Majewsky, M. Cometabolic degradation of organic wastewater micropollutants by activated sludge and sludge-inherent microorganisms Appl. Microbiol. Biotechnol. 2014, 98 (15) 6583-6597 10.1007/s00253-014-5826-0
202. Collado, N.; Buttiglieri, G.; Ferrando-Climent, L.; Rodriguez-Mozaz, S.; Barceló, D.; Comas, J.; Rodriguez-Roda, I. Removal of ibuprofen and its transformation products: Experimental and simulation studies Sci. Total Environ. 2012, 433, 296-301 10.1016/j.scitotenv.2012.06.060
203. Onesios-Barry, K. M.; Berry, D.; Proescher, J. B.; Ashok Sivakumar, I. K.; Bouwer, E. J. Removal of pharmaceuticals and personal care products during water recycling: Microbial community structure and effects of substrate concentration Appl. Environ. Microbiol. 2014, 80 (8) 2440-2450 10.1128/AEM.03693-13
204. Jewell, K. S.; Castronovo, S.; Wick, A.; Falås, P.; Joss, A.; Ternes, T. A. New insights into the transformation of trimethoprim during biological wastewater treatment Water Res. 2016, 88, 550-557 10.1016/j.watres.2015.10.026
205. Nyholm, N.; Berg, U. T.; Ingerslev, F. Environmental Project 337: Activated Sludge Biodegradability Simulation Test; The Danish Environmental Protection Agency: Copenhagen, Denmark, 1996.
206. Rittmann, B. E. Microbiological detoxification of hazardous organic contaminants: The crucial role of substrate interactions Water Sci. Technol. 1992, 25 (11) 403-410
207. Liu, L.; Binning, P. J.; Smets, B. F. Evaluating alternate biokinetic models for trace pollutant cometabolism Environ. Sci. Technol. 2015, 49 (4) 2230-2236 10.1021/es5035393
208. Gulde, R.; Helbling, D. E.; Scheidegger, A.; Fenner, K. pH-dependent biotransformation of ionizable organic micropollutants in activated sludge Environ. Sci. Technol. 2014, 48 (23) 13760-13768 10.1021/es5037139
209. Berg, U. T.; Nyholm, N. Biodegradability simulation studies in semicontinuous activated sludge reactors with low (μg/L range) and standard (ppm range) chemical concentrations Chemosphere 1996, 33 (4) 711-735 10.1016/0045-6535(96)00213-5
210. Tan, D. T.; Temme, H. R.; Arnold, W. A.; Novak, P. J. Estrone degradation: Does organic matter (quality), matter? Environ. Sci. Technol. 2015, 49 (1) 498-503 10.1021/es504424v
211. Su, L.; Aga, D.; Chandran, K.; Khunjar, W. O. Factors impacting biotransformation kinetics of trace organic compounds in lab-scale activated sludge systems performing nitrification and denitrification J. Hazard. Mater. 2015, 282 (314) 116-124 10.1016/j.jhazmat.2014.08.007
212. Yang, X.; Flowers, R. C.; Weinberg, H. S.; Singer, P. C. Occurrence and removal of pharmaceuticals and personal care products (PPCPs) in an advanced wastewater reclamation plant Water Res. 2011, 45 (16) 5218-5228 10.1016/j.watres.2011.07.026
213. Escolà Casas, M.; Chhetri, R. K.; Ooi, G.; Hansen, K. M. S.; Litty, K.; Christensson, M.; Kragelund, C.; Andersen, H. R.; Bester, K. Biodegradation of pharmaceuticals in hospital wastewater by a hybrid biofilm and activated sludge system (Hybas) Sci. Total Environ. 2015, 530-531, 383-392 10.1016/j.scitotenv.2015.05.099
214. Escolà Casas, M.; Chhetri, R. K.; Ooi, G.; Hansen, K. M. S.; Litty, K.; Christensson, M.; Kragelund, C.; Andersen, H. R.; Bester, K. Biodegradation of pharmaceuticals in hospital wastewater by staged Moving Bed Biofilm Reactors (MBBR) Water Res. 2015, 83, 293-302 10.1016/j.watres.2015.06.042
215. Henze, M.; Comeau, Y. Wastewater Characterization. In Biological Wastewater Treatment: Principles Modelling and Design.; Henze, M.; van Loosdrecht, M. C. M.; Ekama, G.; Brdjanovic, D., Eds.; IWA Publishing: London, UK, 2008; pp 33-52.
216. European Chemicals Agency. Environmental exposure assessment. Guidance on Information Requirements and Chemical Safety Assessment; European Chemicals Agency: Helsinki, Finland, 2016; Chapter R.16.
217. García Galán, M. J.; Díaz-Cruz, M. S.; Barceló, D. Removal of sulfonamide antibiotics upon conventional activated sludge and advanced membrane bioreactor treatment Anal. Bioanal. Chem. 2012, 404 (5) 1505-1515 10.1007/s00216-012-6239-5
218. Johnson, A. C.; Williams, R. J. A model to estimate influent and effluent concentrations of estradiol, estrone, and ethinylestradiol at aewage treatment works Environ. Sci. Technol. 2004, 38 (13) 3649-3658 10.1021/es035342u
219. Jelic, A.; Rodriguez-Mozaz, S.; Barceló, D.; Gutierrez, O. Impact of in-sewer transformation on 43 pharmaceuticals in a pressurized sewer under anaerobic conditions Water Res. 2015, 68, 98-108 10.1016/j.watres.2014.09.033
220. Vree, T. B. et al. Pharmacokinetics of sulphamethoxazole in man: Effects of urinary pH and urine flow on metabolism and renal excretion of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole Clin. Pharmacokinet. 1978, 3 (4) 319-329 10.2165/00003088-197803040-00005
221. Thomas, K. V.; Dye, C.; Schlabach, M.; Langford, K. H. Source to sink tracking of selected human pharmaceuticals from two Oslo city hospitals and a wastewater treatment works J. Environ. Monit. 2007, 9, 1410-1418 10.1039/b709745j
222. Le Corre, K. S.; Ort, C.; Kateley, D.; Allen, B.; Escher, B. I.; Keller, J. Consumption-based approach for assessing the contribution of hospitals towards the load of pharmaceutical residues in municipal wastewater Environ. Int. 2012, 45 (1) 99-111 10.1016/j.envint.2012.03.008
223. Verlicchi, P.; Al Aukidy, M.; Galletti, A.; Petrovic, M.; Barceló, D. Hospital effluent: Investigation of the concentrations and distribution of pharmaceuticals and environmental risk assessment Sci. Total Environ. 2012, 430, 109-118 10.1016/j.scitotenv.2012.04.055
224. Herrmann, M.; Olsson, O.; Fiehn, R.; Herrel, M.; Kümmerer, K. The significance of different health institutions and their respective contributions of active pharmaceutical ingredients to wastewater Environ. Int. 2015, 85, 61-76 10.1016/j.envint.2015.07.020
225. Coutu, S.; Rossi, L.; Barry, D. A.; Rudaz, S.; Vernaz, N. Temporal variability of antibiotics fluxes in wastewater and contribution from hospitals PLoS One 2013, 8 (1 e53592 10.1371/journal.pone.0053592
226. Kuroda, K.; Itten, R.; Kovalova, L.; Ort, C.; Weissbrodt, D.; Mcardell, C. S. Hospital-use pharmaceuticals in Swiss waters modeled at high spatial resolution Environ. Sci. Technol. 2016, 50 (9) 4742-4751 10.1021/acs.est.6b00653
227. van der Ven, A. J.; Mantel, M. A.; Vree, T. B.; Koopmans, P. P.; van der Meer, J. W. Formation and elimination of sulphamethoxazole hydroxylamine after oral administration of sulphamethoxazole Br. J. Clin. Pharmacol. 1994, 38 (2) 147-150 10.1111/j.1365-2125.1994.tb04339.x
228. Vree, T. B.; Hekster, Y. A. Sulphamethoxazole Antibiot. Chemother. 1987, 37, 100-113 10.1159/000414197
229. Zhou, L.-J.; Ying, G.-G.; Liu, S.; Zhao, J.-L.; Yang, B.; Chen, Z.-F.; Lai, H.-J. Occurrence and fate of eleven classes of antibiotics in two typical wastewater treatment plants in South China Sci. Total Environ. 2013, 452-453, 365-376 10.1016/j.scitotenv.2013.03.010
230. Petrie, B.; Mcadam, E. J.; Lester, J. N.; Cartmell, E. Obtaining process mass balances of pharmaceuticals and triclosan to determine their fate during wastewater treatment Sci. Total Environ. 2014, 497-498, 553-560 10.1016/j.scitotenv.2014.08.003
231. Aga, D. S.; Lenczewski, M.; Snow, D.; Muurinen, J.; Sallach, J. B.; Wallace, J. S. Challenges in the measurement of antibiotics and in evaluating their impacts in agroecosystems: A critical review J. Environ. Qual. 2016, 45 (2) 407-419 10.2134/jeq2015.07.0393
232. Beier, S.; Cramer, C.; Köster, S.; Mauer, C.; Palmowski, L.; Schröder, H. F.; Pinnekamp, J. Full scale membrane bioreactor treatment of hospital wastewater as forerunner for hot-spot wastewater treatment solutions in high density urban areas Water Sci. Technol. 2011, 63 (1) 66-71 10.2166/wst.2011.010
233. Mauer, C. Technische und ökonomische Aspekte der separaten Erfassung und Behandlung von Krankenhausabwasser. PhD Dissertation, RWTH Aachen University, Aachen, Germany, 2011. Available at http://darwin.bth.rwth-aachen.de/opus3/volltexte/2011/3750/pdf/3750.pdf.
234. Batt, A. L.; Kim, S.; Aga, D. S. Comparison of the occurrence of antibiotics in four full-scale wastewater treatment plants with varying designs and operations Chemosphere 2007, 68 (3) 428-435 10.1016/j.chemosphere.2007.01.008
235. Johnson, A. C.; Ternes, T.; Williams, R. J.; Sumpter, J. P. Assessing the concentrations of polar organic microcontaminants from point sources in the aquatic environment: Measure or model? Environ. Sci. Technol. 2008, 42 (15) 5390-5399 10.1021/es703091r
236. European Medicines Agency. Questions and Answers on "Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use" European Medicines Agency: London, U.K., 2011.
237. Ankley, G. T.; Brooks, B. W.; Huggett, D. B.; Sumpter, J. P. Repeating history: Pharmaceuticals in the environment J. Public Health Policy 1980, 1 (3) 195-197 10.2307/3342084
238. Oldenkamp, R.; Huijbregts, M. A. J.; Hollander, A.; Ragas, A. M. J. Environmental impact assessment of pharmaceutical prescriptions: Does location matter? Chemosphere 2014, 115 (1) 88-94 10.1016/j.chemosphere.2014.01.012
239. Oldenkamp, R.; Hendriks, H. W. M.; Van De Meent, D.; Ragas, A. M. J. Hierarchical bayesian approach to reduce uncertainty in the aquatic effect assessment of realistic chemical mixtures Environ. Sci. Technol. 2015, 49 (17) 10457-10465 10.1021/acs.est.5b02651
240. Lombardo, A.; Franco, A.; Pivato, A.; Barausse, A. Food web modeling of a river ecosystem for risk assessment of down-the-drain chemicals: A case study with AQUATOX Sci. Total Environ. 2015, 508, 214-227 10.1016/j.scitotenv.2014.11.038
241. Ågerstrand, M.; Berg, C.; Björlenius, B.; Breitholtz, M.; Brunström, B.; Fick, J.; Gunnarsson, L.; Larsson, D. G. J.; Sumpter, J. P.; Tysklind, M. et al. Improving environmental risk assessment of human pharmaceuticals Environ. Sci. Technol. 2015, 49 (9) 5336-5345 10.1021/acs.est.5b00302
242. Nelson, E. D.; Do, H.; Lewis, R. S.; Carr, S. A. Diurnal variability of pharmaceutical, personal care product, estrogen and alkylphenol concentrations in effluent from a tertiary wastewater treatment facility Environ. Sci. Technol. 2011, 45 (4) 1228-1234 10.1021/es102452f
243. Escher, B. I.; Fenner, K. Recent advances in environmental risk assessment of transformation products Environ. Sci. Technol. 2011, 45, 3835-3847 10.1021/es1030799
244. Larcher, S.; Yargeau, V. Biodegradation of sulfamethoxazole: Current knowledge and perspectives Appl. Microbiol. Biotechnol. 2012, 96 (2) 309-318 10.1007/s00253-012-4326-3
245. Falås, P.; Wick, A.; Castronovo, S.; Habermacher, J.; Ternes, T. A.; Joss, A. Tracing the limits of organic micropollutant removal in biological wastewater treatment Water Res. 2016, 95, 240-249 10.1016/j.watres.2016.03.009