CSIRO Publishing blank image blank image blank image blank imageBooksblank image blank image blank image blank imageJournalsblank image blank image blank image blank imageAbout Usblank image blank image blank image blank imageShopping Cartblank image blank image blank image You are here: Journals > Environmental Chemistry   
Environmental Chemistry
Journal Banner
  Environmental problems - Chemical approaches
 
blank image Search
 
blank image blank image
blank image
 
  Advanced Search
   

Journal Home
About the Journal
Editorial Boards
Contacts
Content
Online Early
Current Issue
Just Accepted
All Issues
Virtual Issues
Special Issues
Research Fronts
Sample Issue
Call for Papers
For Authors
General Information
Notice to Authors
Submit Article
Open Access
For Referees
Referee Guidelines
Review an Article
For Subscribers
Subscription Prices
Customer Service

blue arrow e-Alerts
blank image
Subscribe to our Email Alert or RSS feeds for the latest journal papers.

red arrow Connect with us
blank image
facebook twitter youtube

 

Open Access Article << Previous     |     Next >>   Contents Vol 11(4)

Recalcitrant pharmaceuticals in the aquatic environment: a comparative screening study of their occurrence, formation of phototransformation products and their in vitro toxicity

Marlies Bergheim A B F , Richard Gminski A , Bernd Spangenberg C , Malgorzata Dębiak D , Alexander Bürkle D , Volker Mersch-Sundermann A , Klaus Kümmerer A E and Reto Gieré B

A University Medical Center Freiburg, Department of Environmental Health Sciences, Section of Toxicology, Breisacher Strasse 115B, D-79106 Freiburg, Germany. Email: richard.gminski@uniklinik-freiburg.de; volker.mersch-sundermann@uniklinik-freiburg.de
B Institute of Earth and Environmental Sciences, University of Freiburg, Albertstrasse 23b, D-79104 Freiburg, Germany. Email: giere@uni-freiburg.de
C University of Applied Sciences, Process Engineering and Environmental Technologies, Badstrasse 24, D-77652 Offenburg, Germany. Email: spangenberg@hs-offenburg.de
D Molecular Toxicology Group, Department of Biology, University of Konstanz, Universitätsstrasse 10, D-78457 Konstanz, Germany. Email: alexander.buerkle@uni-konstanz.de; debiakma@yahoo.com
E Present address: Leuphana University Lüneburg, Institute of Sustainable and Environmental Chemistry, Scharnhorststraße 1/C13, D-21335 Lueneburg, Germany. Email: klaus.kuemmerer@uni.leuphana.de
F Corresponding author. Email: marlies.bergheim@gmail.com

Environmental Chemistry 11(4) 431-444 http://dx.doi.org/10.1071/EN13218
Submitted: 1 December 2013  Accepted: 9 April 2014   Published: 11 July 2014


 
 Full Text
 PDF (592 KB)
 Supplementary Material
 Export Citation
 Print
  

Environmental context. Many pharmaceuticals on the market have not undergone detailed evaluation for potential aquatic toxicity. We found that most tested pharmaceuticals were persistent, that phototransformation products were likely to be formed as a result of UV treatment of wastewater and that some transformation products were more toxic to bacteria than their precursor pharmaceutical compound. Thus UV treatment of wastewater does not seem appropriate to completely degrade or transform micropollutants into harmless compounds.

Abstract. Data allowing for a complete environmental risk assessment of pharmaceuticals and their photoderatives in the environment are still scarce. In the present study, in vitro toxicity and both bio- and photopersistence of various pharmaceuticals (aciclovir, allopurinol, cetirizine, cimetidine, fluconazole, hydrochlorothiazide, lisinopril, phenytoin, primidone, ranitidine, sotalol, sulpiride, tramadol and valsartane) as well as their phototransformation products were evaluated in order to fill data gaps and to help prioritise them for further testing. Twelve out of the fourteen compounds investigated were found to be neither readily nor inherently biodegradable in the Organisation of Economic Cooperation and Development-biodegradability tests. The study further demonstrates that the photo-induced transformation of the pharmaceuticals was faster upon irradiation with a Hg lamp (UV light) than with a Xe lamp emitting a spectrum that mimics sunlight. Comparing the non-irradiated with the respective irradiated solutions, a higher acute and chronic toxicity against bacteria was found for the irradiated solutions of seven compounds (cetirizine, cimetidine, hydrochlorothiazide, ranitidine, sulpiride, tramadol and valsartane). No cyto- and genotoxic effects were found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their phototransformation products. This comparative study documents that phototransformation products can arise as a result of UV treatment of wastewater containing these pharmaceuticals. It further demonstrates that some phototransformation products may have a higher environmental risk potential than the respective parent compounds because some phototransformation products exhibited a higher bacterial toxicity.

Additional keywords: biodegradation, HeLa cells, Hep-G2 cells, irradiation, predicted environmental concentrations (PECs), UV, Vibrio fischeri.


References

[1]  T. Heberer, Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data. Toxicol. Lett. 2002, 131, 5.
CrossRef | CAS | PubMed |

[2]  A Comprehensive Literature Review: Monitoring Data on the Occurrence of Pharmaceuticals in the Environment from the German Federal Environmental Agency (UBA) 2011 (German Federal Environmental Agency: Dessau-Rosßlau).

[3]  R. Loos, B. M. Gawlik, G. Locoro, E. Rimaviciute, S. Contini, G. Bidoglio, EU-wide survey of polar organic persistent pollutants in European river waters. Environ. Pollut. 2009, 157, 561.
CrossRef | CAS | PubMed |

[4]  P. Bottoni, S. Caroli, A. Caracciolo, Pharmaceuticals as priority water contaminants. Toxicol. Environ. Chem. 2010, 92, 549.
CrossRef | CAS |

[5]  J. B. Quintana, S. Weiss, T. Reemtsma, Pathway’s and metabolites of microbial degradation of selected acidic pharmaceutical and their occurrence in municipal wastewater treated by a membrane bioreactor. Water Res. 2005, 39, 2654.
CrossRef | CAS | PubMed |

[6]  C. Zwiener, S. Seeger, T. Glauner, F. H. Frimmel, Metabolites from the biodegradation of pharmaceutical residues of ibuprofen in biofilm reactors and batch experiments. Anal. Bioanal. Chem. 2002, 372, 569.
CrossRef | CAS | PubMed |

[7]  M. Addamo, V. Augugliaro, A. Di Paola, E. Garcia-Lopez, V. Loddo, G. Marci, L. Palmisano, Removal of drugs in aqueous systems by photoassisted degradation. J. Appl. Electrochem. 2005, 35, 765.
CrossRef | CAS |

[8]  A. L. Boreen, W. A. Arnold, K. McNeill, Photochemical fate of sulfa drugs in the aquatic environment: sulfa drugs containing five-membered heterocyclic groups. Environ. Sci. Technol. 2004, 38, 3933.
CrossRef | CAS | PubMed |

[9]  R. Skibiński, Identification of photodegradation product of amisulpride by ultra-high-pressure liquid chromatography-DAD/ESI-quadrupole time-of-flight-mass spectrometry. J. Pharmaceut. Biomed. 2011, 56, 904.
CrossRef |

[10]  C. Sirtori, A. Aguera, W. Gernjak, S. Malato, Effect of water-matrix composition on Trimethoprim solar photodegradation kinetics and pathways. Water Res. 2010, 44, 2735.
CrossRef | CAS | PubMed |

[11]  S. K. Khetan, T. J. Collins, Human pharmaceuticals in the aquatic environment: a challenge to green chemistry. Chem. Rev. 2007, 107, 2319.
CrossRef | CAS | PubMed |

[12]  W. d. Püttmann, F. Keil, J. Oehlmann, U. Schulte-Oehlmann, Strategy to reduce pharmaceuticals in drinking water – technical approach. Wassertechnische Strategien zur Reduzierung der Trinkwasserbehandlung durch Arzneimittelwirkstoffe 2008, 20, 209.

[13]  M. J. Gómez, C. Sirtori, M. Mezcua, A. R. Fernández-Alba, A. Agüera, Photodegradation study of three dipyrone metabolites in various water systems: identification and toxicity of their photodegradation products. Water Res. 2008, 42, 2698.
CrossRef | PubMed |

[14]  M. Isidori, A. Parrella, P. Pistillo, F. Temussi, Effects of ranitidine and its photoderivatives in the aquatic environment. Environ. Int. 2009, 35, 821.
CrossRef | CAS | PubMed |

[15]  Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use 2006 (European Medical Agency: Brussels).

[16]  M. Bergheim, R. Gieré, K. Kümmerer, Biodegradability and ecotoxicity of tramadol, ranitidine, and their photoderivatives in the aquatic environment. Environ. Sci. Pollut. R. 2012, 19, 72.
CrossRef | CAS |

[17]  U. Schwabe, D. Paffrath, Pharmaceutical Prescriptions in Germany 2011 2010 (Springer: Berlin).

[18]  A. Seigel, A. Schroeck, R. Hauser, B. Spangenberg, Sensitive quantification of Diclofenac and Ibuprofen using thin layer chromatography coupled with a Vibrio fisheri bioluminescence Assay. J. Liq. Chromatogr. R. T. 2011, 34, 817.
CrossRef | CAS |

[19]  G. Repetto, A. del Peso, J. L. Zurita, Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat. Protoc. 2008, 3, 1125.
CrossRef | CAS | PubMed |

[20]  M. Moreno-Villanueva, R. Pfeiffer, T. Sindlinger, A. Leake, M. Müller, T. B. Kirkwood, A. Bürkle, A modified and automated version of the ‘fluorimetric detection of alkaline DNA unwinding’ method to quantify formation and repair of DNA strand breaks. BMC Biotechnol. 2009, 9, 39.
CrossRef | PubMed |

[21]  M. Moreno-Villanueva, T. Eltze, D. Dressler, J. Bernhardt, C. Hirsch, P. Wick, G. von Scheven, K. Lex, A. Bürkle, The automated FADU-assay, a potential high-throughput in vitro method for early screening of DNA breakage. ALTEX 2011, 28, 295.
CrossRef | PubMed |

[22]  M. Dębiak, A. Panas, D. Steinritz, K. Kehe, A. Bürkle, High-throughput analysis of DNA interstrand crosslinks in human peripheral blood mononuclear cells by automated reverse FADU assay. Toxicology 2011, 280, 53.
CrossRef | PubMed |

[23]  J. Durner, M. Dębiak, A. Bürkle, R. Hickel, F.-X. Reichl, Induction of DNA strand breaks by dental composite components compared to X-ray exposure in human gingival fibroblasts. Arch. Toxicol. 2011, 85, 143.
CrossRef | CAS | PubMed |

[24]  M. Gros, M. Petrovic, D. Barcelo, Tracing pharmaceutical residues of different therapeutic classes in environmental waters by using liquid chromatography/quadrupole-linear ion trap mass spectrometry and automated library searching. Anal. Chem. 2009, 81, 898.
CrossRef | CAS | PubMed |

[25]  N. M. Vieno, H. Harkki, T. Tuhkanen, L. Kronberg, Occurrence of pharmaceuticals in river water and their elimination a pilot-scale drinking water treatment plant. Environ. Sci. Technol. 2007, 41, 5077.
CrossRef | CAS | PubMed |

[26]  A. Y. C. Lin, T. H. Yu, C. F. Lin, Pharmaceutical contamination in residential, industrial, and agricultural waste streams: risk to aqueous environments in Taiwan. Chemosphere 2008, 74, 131.
CrossRef | CAS |

[27]  D. Fatta-Kassinos, M. I. Vasquez, K. Kümmerer, Transformation products of pharmaceuticals in surface waters and wastewater formed during photolysis and advanced oxidation processes – degradation, elucidation of byproducts and assessment of their biological potency. Chemosphere 2011, 85, 693.
CrossRef | CAS | PubMed |

[28]  M. DellaGreca, M. R. Lesce, M. Isidori, S. Montanaro, L. Previtera, M. Rubino, Phototransformation of amlodipine in aqueous solution: toxicity of the drug and its photoproduct on aquatic organisms. Int. J. Photoenergy 2007, 2007, 63 459.
CrossRef |

[29]  D. M. Leech, M. T. Snyder, R. G. Wetzel, Natural organic matter and sunlight accelerate the degradation of 17 beta-estradiol in water. Sci. Total Environ. 2009, 407, 2087.
CrossRef | CAS | PubMed |

[30]  D. E. Latch, B. L. Stender, J. L. Packer, W. A. Arnold, K. McNeill, Photochemical fate of pharmaceuticals in the environment: cimetidine and ranitidine. Environ. Sci. Technol. 2003, 37, 3342.
CrossRef | CAS | PubMed |

[31]  Y. Kim, K. Choi, J. Jung, S. Park, P. G. Kim, J. Park, Aquatic toxicity of acetaminophen, carbamazepine, cimetidine, diltiazem and six major sulfonamides, and their potential ecological risks in Korea. Environ. Int. 2007, 33, 370.
CrossRef | CAS | PubMed |

[32]  R. M. Bianchini, P. M. Castellano, T. S. Kaufman, Characterization of two new potential impurities of Valsartan obtained under photodegradation stress condition. J. Pharm. Biomed. Anal. 2011, 56, 16.
CrossRef | CAS | PubMed |

[33]  I. Vaz-Moreira, O. C. Nunes, C. M. Manaia, Diversity and antibiotic resistance in Pseudomonas spp. from drinking water. Sci. Total Environ. 2012, 426, 366.
CrossRef | CAS | PubMed |

[34]  N. J. Palleroni, The Pseudomonas story. Environ. Microbiol. 2010, 12, 1377.
CrossRef | CAS | PubMed |

[35]  G. Neumann, Y. Veeranagouda, T. B. Karegoudar, O. Sahin, I. Mausezahl, N. Kabelitz, U. Kappelmeyer, H. J. Heipieper, Cells of Pseudomonas putida and Enterobacter sp. adapt to toxic organic compounds by increasing their size. Extremophiles 2005, 9, 163.
CrossRef | CAS | PubMed |

[36]  M. Vodovnik, M. Bistan, M. Zorec, R. M. Logar, Membrane changes associated with exposure of Pseudomonas putida to selected environmental pollutants and their possible roles in toxicity. Acta Chim. Slov. 2012, 59, 83.
| CAS | PubMed |

[37]  OECD Guideline for testing of chemicals: In vitro 3T3 NRU phototoxicity test 2004 (Organisation of Economic Cooperation and Development: Paris).

[38]  K. D. Han, K. M. Bark, E. P. Heo, J. K. Lee, J. S. Kang, T. H. Kim, Increased phototoxicity of hydrochlorothiazide by photodegradation. Photodermatol. Photo. 2000, 16, 121.
CrossRef | CAS |

[39]  A. A. Chételat, S. Albertini, E. Gocke, The photomutagenicity of fluoroquinolones in tests for gene mutation, chromosomal aberration, gene conversion and DNA breakage (Comet assay). Mutagenesis 1996, 11, 497.
CrossRef | PubMed |

[40]  K. Yu, B. Li, T. Zhang, Direct rapid analysis of multiple PPCPs in municipal wastewater using ultrahigh performance liquid chromatography–tandem mass spectrometry without SPE pre-concentration. Anal. Chim. Acta 2012, 738, 59.
CrossRef | CAS | PubMed |

[41]  J. Fick, H. Soderstrom, R. H. Lindberg, C. Phan, M. Tysklind, D. G. J. Larsson, Contamination of surface, ground, and drinking water from pharmaceutical production. Environ. Toxicol. Chem. 2009, 28, 2522.
CrossRef | CAS | PubMed |

[42]  J. Kosonen, L. Kronberg, The occurrence of antihistamines in sewage waters and in recipient rivers. Environ. Sci. Pollut. R. 2009, 16, 555.
CrossRef | CAS |

[43]  B. Kasprzyk-Hordern, R. M. Dinsdale, A. J. Guwy, The removal of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs during wastewater treatment and its impact on the quality of receiving waters. Water Res. 2009, 43, 363.
CrossRef | CAS | PubMed |

[44]  K. Choi, Y. Kim, J. Park, C. K. Park, M. Kim, H. S. Kim, P. Kim, Seasonal variations of several pharmaceutical residues in surface water and sewage treatment plants of Han River, Korea. Sci. Total Environ. 2008, 405, 120.
CrossRef | CAS | PubMed |

[45]  D. W. Kolpin, E. T. Furlong, M. T. Meyer, E. M. Thurman, S. D. Zaugg, L. B. Barber, H. T. Buxton, Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999–2000: a national reconnaissance. Environ. Sci. Technol. 2002, 36, 1202.
CrossRef | CAS | PubMed |

[46]  J. W. Kim, H. S. Jang, J. G. Kim, H. Ishibashi, M. Hirano, K. Nasu, N. Ichikawa, Y. Takao, R. Shinohara, K. Arizono, Occurrence of pharmaceutical and personal care products (PPCPs. in surface water from Mankyung River, South Korea. J. Health Sci. 2009, 55, 249.
CrossRef | CAS |

[47]  H. Lindberg, J. Fick, M. Tysklind, Screening of antimycotics in Swedish sewage treatment plants – waters and sludge. Water Res. 2010, 44, 649.
CrossRef | CAS |

[48]  M. Kahle, I. J. Buerge, A. Hauser, M. D. Mueller, T. Poiger, Azole fungicides: occurrence and fate in wastewater and surface waters. Environ. Sci. Technol. 2008, 42, 7193.
CrossRef | CAS | PubMed |

[49]  D. Calamari, E. Zuccato, S. Castiglioni, R. Bagnati, R. Fanelli, Strategic survey of therapeutic drugs in the rivers Po and Lambro in northern Italy. Environ. Sci. Technol. 2003, 37, 1241.
CrossRef | CAS |

[50]  E. Zuccato, S. Castiglioni, R. Fanelli, G. Reitano, R. Bagnati, C. Chiabrando, F. Pomati, C. Rossetti, D. Calamari, Pharmaceuticals in the environment in Italy: causes, occurrence, effects and control. Environ. Sci. Pollut. R. 2006, 13, 15.
CrossRef | CAS |

[51]  T. Heberer, Tracking persistent pharmaceutical residues from municipal sewage to drinking water. J. Hydrol. 2002, 266, 175.
CrossRef | CAS |

[52]  M. J. Benotti, R. A. Trenholm, B. J. Vanderford, J. C. Holady, B. D. Stanford, S. A. Snyder, Pharmaceuticals and endocrine disrupting compounds in US drinking water. Environ. Sci. Technol. 2009, 43, 597.
CrossRef | CAS | PubMed |

[53]  G. M. Bruce, R. C. Pleus, S. A. Snyder, Toxicological relevance of pharmaceuticals in drinking water. Environ. Sci. Technol. 2010, 44, 5619.
CrossRef | CAS | PubMed |

[54]  D. Hummel, D. Loeffler, G. Fink, T. A. Ternes, Simultaneous determination of psychoactive drugs and their metabolites in aqueous matrices by liquid chromatography mass spectrometry. Environ. Sci. Technol. 2006, 40, 7321.
CrossRef | CAS | PubMed |

[55]  B. Morasch, F. Bonvin, H. Reiser, D. Grandjean, L. F. de Alencastro, C. Perazzolo, N. Chevre, T. Kohn, Occurrence and fate of micropollutants in the Vidy Bay of Lake Geneva, Switzerland. Part II: micropollutant removal between wastewater and raw drinking water. Environ. Toxicol. Chem. 2010, 2259, 1658.

[56]  Y. C. Guo, S. W. Krasner, Occurrence of primidone, carbamazepine, caffeine, and precursors for n-nitrosodimethylamine in drinking water sources impacted by wastewater. J. Am. Water Resour. Assoc. 2009, 45, 58.
CrossRef | CAS |

[57]  S. Castiglioni, R. Fanelli, D. Calamari, R. Bagnati, E. Zuccato, Methodological approaches for studying pharmaceuticals in the environment by comparing predicted and measured concentrations in River Po, Italy. Regul. Toxicol. Pharmacol. 2004, 39, 25.
CrossRef | CAS | PubMed |

[58]  J. Fick, R. H. Lindberg, L. Kai, E. Brorstoem-Lundén, Results from the Swedish National Screening programme 2010 2011 (IVL Swedish Environmental Research Institute: Stockholm, Sweden).

[59]  H. D. Zhou, C. Y. Wu, X. Huang, M. J. Gao, X. H. Wen, H. Tsuno, H. Tanaka, Occurrence of selected pharmaceuticals and caffeine in sewage treatment plants and receiving rivers in Beijing, China. Water Environ. Res. 2010, 82, 2239.
CrossRef | CAS |

[60]  T. Okuda, Y. Kobayashi, R. Nagao, N. Yamashita, H. Tanaka, S. Tanaka, S. Fujii, C. Konishi, I. Houwa, Removal efficiency of 66 pharmaceuticals during wastewater treatment process in Japan. Water Sci. Technol. 2008, 57, 65.
CrossRef | CAS | PubMed |


   
 
    
Legal & Privacy | Contact Us | Help

CSIRO

© CSIRO 1996-2014