Advertisement

Bioassays Currently Available for Evaluating the Biological Potency of Pharmaceuticals in Treated Wastewater

  • Marlen I. VasquezEmail author
  • Irene Michael
  • Klaus Kümmerer
  • Despo Fatta-Kassinos
Chapter
Part of the The Handbook of Environmental Chemistry book series (HEC, volume 44)

Abstract

Water deprivation with regard to quantity and quality is one of the most important environmental problems of the century. The increasing demand of water resources puts pressure on the utilization of alternative sources such as treated wastewater. In the context of “reduce, reuse, and recycle,” the inclusion of treated wastewater in the water cycle seems a promising practice for water management. The lack of general acceptance of stakeholders and public, however, still hinders the widespread application of wastewater reuse. A reason for this is, among others, the presence of contaminants of emerging concern in treated wastewater. This has led to an increased concern about direct and indirect effects to the environment and possible implications to human health. The development and application of bioassays able to identify and quantify the biological potency of treated wastewater is an ongoing research effort, especially when taking into consideration that a plethora of contaminants exist and interact in this complex matrix. This chapter summarizes available literature regarding the sensitivity of currently applied bioassays for assessing biological effects of treated wastewater and their correlation with chemical analysis. The focus is on pharmaceuticals since they represent one of the major groups of contaminants of emerging concern with many unanswered questions currently in place.

Keywords

Effect-directed bioassay Pharmaceutical Toxicity Wastewater reuse 

Abbreviations

CEC

Contaminants of emerging concern

COD

Chemical Oxygen Demand

COX

Cyclooxygenase

DTA

Direct toxicity assessment

EC

Effect Concentration

EROD

Ethoxyresorufin-O-deethylase

ISO

International Organization for Standardization

LC

Lethal Concentration

LOEC

Lowest Observed Effect Concentration

MIC

Minimum Inhibitory Concentration

NADPH

Nicotinamide adenine dinucleotide phosphate

NOEC

No Observed Effect Concentration

OECD

Organization for Economic Cooperation and Development

PGE2

Prostaglandin E2

PSII

Photosystem II

TU

Toxic unit

USEPA

US Environmental Protection Agency

WET

Whole effluent toxicity

Notes

Acknowledgments

This work was prepared in the framework of the PENEK/0609/24 research project “Development of novel methods for the toxicity assessment of the multi-component chemical mixtures to humans and the ecosystem” (TOMIXX), implemented within the framework of the program for research, technological development, and innovation “DESMH 2009–2010” and stimulated by NIREAS activities, the International Water Research Center of the University of Cyprus (ΝΕΑ ΥΠΟΔΟΜΗ/ΣΤΡΑΤΗ/0308/09). These projects are funded by the Cyprus Research Promotion Foundation, which is co-financed by the Republic of Cyprus and the European Regional Development Fund. The authors would also like to acknowledge the financial support provided by COST - European Cooperation in Science and Technology, to the COST Action ES1403: New and emerging challenges and opportunities in wastewater reuse (NEREUS).

Disclaimer

The content of this article is the authors’ responsibility and neither COST nor any person acting on its behalf is responsible for the use, which might be made of the information contained in it.

References

  1. 1.
    Doudoroff P, Katz M (1953) Critical review of literature on the toxicity of industrial wastes and their components to fish. II. The metals as salts. Sewage Ind Waste 25:802–839Google Scholar
  2. 2.
    Doudoroff P, Katz M (1950) Critical review of literature on the toxicity of industrial wastes and their components to fish. I. Alkalies, acids, and inorganic gases. Sewage Ind Waste 22:1432–1458Google Scholar
  3. 3.
    Wharfe J (2009) Historical perspective and overview. In: Thompson KC, Wadhia K, Loibner AP (eds) Environmental toxicity testing. Blackwell, Oxford, pp 1–32Google Scholar
  4. 4.
    Johnson I, Whitehouse P, Crane M (2009) Effective monitoring of the environment for toxicity. In: Thompson KC, Wadhia K, Loibner AP (eds) Environmental toxicity testing. Blackwell, Oxford, pp 33–60Google Scholar
  5. 5.
    Calow P (1989) The choice and implementation of environmental bioassays. Hydrobiologia 188–189:61–64CrossRefGoogle Scholar
  6. 6.
    van den Brink PJ, Sibley PK, Ratte HT et al (2008) Extrapolation of effects measures across levels of biological organization in ecological risk assessments. In: Solomon KR, Sibley PK, Sanderson H et al (eds) Extrapolation practice for ecological effect characterization of chemicals (EXPECT). SETAC, Pensacola, pp 105–134Google Scholar
  7. 7.
    Tchobanoglous G, Burton FL, Stensel HD (2003) Wastewater engineering, treatment, and reuse. McGraw-Hill, New YorkGoogle Scholar
  8. 8.
    Kümmerer K, Held M, Pimentel D (2010) Sustainable use of soils and time. J Soil Water Conserv 65:141–149CrossRefGoogle Scholar
  9. 9.
    Kümmerer K, Hofmeister S (2008) Sustainability, substance flow management and time. Part I: temporal analysis of substance flows. J Environ Manage 88:1333–1342CrossRefGoogle Scholar
  10. 10.
    Bixio D, Thoeye C, De Koning J et al (2006) Wastewater reuse in Europe. Desalination 187:89–101CrossRefGoogle Scholar
  11. 11.
    Brandes WF, Elder JR (1991) Toxicity control in the NPDES permit program. Nat Resour Environ 5:15–57Google Scholar
  12. 12.
    USEPA (1991) Technical support document for water quality-based toxics control. EPA/505/2–90001Google Scholar
  13. 13.
    Power EA, Boumphrey RS (2004) International trends in bioassay use for effluent management. Ecotoxicology 13:377–398CrossRefGoogle Scholar
  14. 14.
    Costan G, Bermingham N, Blaise C et al (1993) Potential ecotoxic effects probe (PEEP): a novel index to assess and compare the toxic potential of industrial effluents. Environ Toxicol Water Qual 8:115–140CrossRefGoogle Scholar
  15. 15.
    Yi X, Kim E, Jo H et al (2009) A toxicity monitoring study on identification and reduction of toxicants from a wastewater treatment plant. Ecotoxicol Environ Saf 72:1919–1924CrossRefGoogle Scholar
  16. 16.
    DLgs 152/2006 (2006) Decreto legislativo 3 april 2006, no. 152. Gazzeta Ufficiale 88:14-04Google Scholar
  17. 17.
    Law 106 (I)/2002 (2002) Water and soil pollution control law in cyprus, 12th July of 2002 (in greek). Cyprus Government Gazette 3621:2121–2151Google Scholar
  18. 18.
    Farré M, Klöter G, Petrovic M et al (2002) Identification of toxic compounds in wastewater treatment plants during a field experiment. Anal Chim Acta 456:19–30CrossRefGoogle Scholar
  19. 19.
    Jones OAH, Voulvoulis N, Lester JN (2007) The occurrence and removal of selected pharmaceutical compounds in a sewage treatment works utilising activated sludge treatment. Environ Pollut 145:738–744CrossRefGoogle Scholar
  20. 20.
    Stülten D, Zühlke S, Lamshöft M et al (2008) Occurrence of diclofenac and selected metabolites in sewage effluents. Sci Total Environ 405:310–316CrossRefGoogle Scholar
  21. 21.
    USEPA (2002) Methods for measuring the acute toxicity of effluents and receiving waters to freshwater and marine organisms. U.S. Environmental Protection Agency, Office of Water, WashingtonGoogle Scholar
  22. 22.
    Jo H, Park E, Cho K et al (2008) Toxicity identification and reduction of wastewaters from a pigment manufacturing factory. Chemosphere 70:949–957CrossRefGoogle Scholar
  23. 23.
    De Schepper W, Dries J, Geuens L et al (2010) Wastewater treatment plant modeling supported toxicity identification and evaluation of a tank truck cleaning effluent. Ecotoxicol Environ Saf 73:702–709CrossRefGoogle Scholar
  24. 24.
    Fang Y, Ying G, Zhang L et al (2012) Use of TIE techniques to characterize industrial effluents in the Pearl River Delta region. Ecotoxicol Environ Saf 76:143–152CrossRefGoogle Scholar
  25. 25.
    Grung M, Lichtenthaler R, Ahel M et al (2007) Effects-directed analysis of organic toxicants in wastewater effluent from Zagreb, Croatia. Chemosphere 67:108–120CrossRefGoogle Scholar
  26. 26.
    Smital T, Terzic S, Zaja R et al (2011) Assessment of toxicological profiles of the municipal wastewater effluents using chemical analyses and bioassays. Ecotoxicol Environ Saf 74:844–851CrossRefGoogle Scholar
  27. 27.
    Pessala P, Schultz E, Nakari T et al (2004) Evaluation of wastewater effluents by small-scale biotests and a fractionation procedure. Ecotoxicol Environ Saf 59:263–272CrossRefGoogle Scholar
  28. 28.
    Grothe DR, Dickson KL, Reed-Judkins DK (1996) Whole effluent toxicity testing: an evaluation of methods and prediction of receiving system impacts. Proceedings from a SETAC-sponsored pellston workshop. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USAGoogle Scholar
  29. 29.
    Mount DI (1998) Midcourse corrections in WET testing program. Soc Environ Toxicol Chem News 18:19–20Google Scholar
  30. 30.
    Vasquez M, Fatta-Kassinos D (2013) Is the evaluation of “traditional” physicochemical parameters sufficient to explain the potential toxicity of the treated wastewater at sewage treatment plants? Environ Sci Pollut Res Int 20:3516–3528CrossRefGoogle Scholar
  31. 31.
    Hernando MD, Petrovic M, Fernández-Alba AR et al (2004) Analysis by liquid chromatography-electrospray ionization tandem mass spectrometry and acute toxicity evaluation for β-blockers and lipid-regulating agents in wastewater samples. J Chromatogr A 1046:133–140Google Scholar
  32. 32.
    Roberts PH, Thomas KV (2006) The occurrence of selected pharmaceuticals in wastewater effluent and surface waters of the lower Tyne catchment. Sci Total Environ 356:143–153CrossRefGoogle Scholar
  33. 33.
    Kolpin DW, Furlong ET, Meyer MT et al (2002) Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: a national reconnaissance. Environ Sci Technol 36:1202–1211CrossRefGoogle Scholar
  34. 34.
    Carballa M, Omil F, Lema JM et al (2004) Behavior of pharmaceuticals, cosmetics and hormones in a sewage treatment plant. Water Res 38:2918–2926CrossRefGoogle Scholar
  35. 35.
    Ternes TA (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water Res 32:3245–3260CrossRefGoogle Scholar
  36. 36.
    Heberer T (2002) Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data. Toxicol Lett 131:5–17CrossRefGoogle Scholar
  37. 37.
    Sheila AD (1990) The membrane stabilizing and β1-adrenoceptor blocking activity of (+)- and (−)-propranolol on the rat left atria. Gen Pharmacol Vascul Syst 21:677–680CrossRefGoogle Scholar
  38. 38.
    Okine LKN, Ioannides C, Parke DV (1983) Studies on the possible mutagenicity of β-adrenergic blocker drugs. Toxicol Lett 16:167–174CrossRefGoogle Scholar
  39. 39.
    Carlsson C, Johansson AK, Alvan G et al (2006) Are pharmaceuticals potent environmental pollutants? Part I: environmental risk assessments of selected active pharmaceutical ingredients. Sci Total Environ 364:67–87CrossRefGoogle Scholar
  40. 40.
    Liu QT, Williams TD, Cumming RI et al (2009) Comparative aquatic toxicity of propranolol and its photodegraded mixtures: algae and rotifer screening. Environ Toxicol Chem 28:2622–2631CrossRefGoogle Scholar
  41. 41.
    Wharfe ES, Winder CL, Jarvis RM et al (2010) Monitoring the effects of chiral pharmaceuticals on aquatic microorganisms by metabolic fingerprinting. Appl Environ Microbiol 76:2075–2085CrossRefGoogle Scholar
  42. 42.
    Cleuvers M (2005) Initial risk assessment for three β-blockers found in the aquatic environment. Chemosphere 59:199–205CrossRefGoogle Scholar
  43. 43.
    Ferrari B, Mons R, Vollat B et al (2004) Environmental risk assessment of six human pharmaceuticals: are the current environmental risk assessment procedures sufficient for the protection of the aquatic environment? Environ Toxicol Chem 23:1344–1354CrossRefGoogle Scholar
  44. 44.
    Escher BI, Bramaz N, Eggen RIL et al (2005) In vitro assessment of modes of toxic action of pharmaceutical in aquatic life. Environ Sci Technol 39:3090–3100CrossRefGoogle Scholar
  45. 45.
    Küster A, Alder AC, Escher BI et al (2010) Environmental risk assessment of human pharmaceuticals in the European union: a case study with the β-blocker atenolol. Integr Environ Assess Manage 6:514–523Google Scholar
  46. 46.
    Pascoe D, Karntanut W, Müller CT (2003) Do pharmaceuticals affect freshwater invertebrates? A study with the cnidarian Hydra vulgaris. Chemosphere 51:521–528CrossRefGoogle Scholar
  47. 47.
    Huggett DB, Brooks BW, Peterson B et al (2002) Toxicity of select beta adrenergic receptor-blocking pharmaceuticals (β-blockers) on aquatic organisms. Arch Environ Contam Toxicol 43:229–235CrossRefGoogle Scholar
  48. 48.
    Triebskorn R, Casper H, Scheil V et al (2007) Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio). Anal Bioanal Chem 387:1405–1416CrossRefGoogle Scholar
  49. 49.
    Calleja MC, Persoone G, Geladi P (1994) Comparative acute toxicity of the first 50 multicentre evaluation of in vitro cytotoxicity chemicals to aquatic non-vertebrates. Arch Environ Contam Toxicol 26:69–78CrossRefGoogle Scholar
  50. 50.
    Parolini M, Quinn B, Binelli A et al (2011) Cytotoxicity assessment of four pharmaceutical compounds on the zebra mussel (Dreissena polymorpha) haemocytes, gill and digestive gland primary cell cultures. Chemosphere 84:91–100CrossRefGoogle Scholar
  51. 51.
    Winter MJ, Lillicrap AD, Caunter JE et al (2008) Defining the chronic impacts of atenolol on embryo-larval development and reproduction in the fathead minnow (Pimephales promelas). Aquat Toxicol 86:361–369CrossRefGoogle Scholar
  52. 52.
    Ericson H, Thorsén G, Kumblad L (2010) Physiological effects of diclofenac, ibuprofen and propranolol on Baltic Sea blue mussels. Aquat Toxicol 99:223–231CrossRefGoogle Scholar
  53. 53.
    Christen V, Hickmann S, Rechenberg B et al (2010) Highly active human pharmaceuticals in aquatic systems: a concept for their identification based on their mode of action. Aquat Toxicol 96:167–181CrossRefGoogle Scholar
  54. 54.
    Solé M, Shaw JP, Frickers PE et al (2010) Effects on feeding rate and biomarker responses of marine mussels experimentally exposed to propranolol and acetaminophen. Anal Bioanal Chem 396:649–656CrossRefGoogle Scholar
  55. 55.
    Bartram AE, Winter MJ, Huggett DB et al (2011) In vivo and in vitro liver and gill EROD activity in rainbow trout (Oncorhynchus mykiss) exposed to the beta-blocker propranolol. Environ Toxicol. doi: 10.1002/tox.20684 Google Scholar
  56. 56.
    Laville N, Aït-Ässa S, Gomez E et al (2004) Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes. Toxicology 196:41–55CrossRefGoogle Scholar
  57. 57.
    Kim JW, Ishibashi H, Yamauchi R et al (2009) Acute toxicity of pharmaceutical and personal care products on freshwater crustacean (Thamnocephalus platyurus) and fish (Oryzias latipes). J Toxicol Sci 34:227–232CrossRefGoogle Scholar
  58. 58.
    Owen SF, Huggett DB, Hutchinson TH et al (2009) Uptake of propranolol, a cardiovascular pharmaceutical, from water into fish plasma and its effects on growth and organ biometry. Aquat Toxicol 93:217–224CrossRefGoogle Scholar
  59. 59.
    Owen SF, Giltrow E, Huggett DB et al (2007) Comparative physiology, pharmacology and toxicology of β-blockers: mammals versus fish. Aquat Toxicol 82:145–162CrossRefGoogle Scholar
  60. 60.
    Burleson ML, Milsom WK (1990) Propranolol inhibits O2-sensitive chemoreceptor activity in trout gills. Am J Physiol 258:R1089–R1091Google Scholar
  61. 61.
    Giltrow E, Eccles PD, Winter MJ et al (2009) Chronic effects assessment and plasma concentrations of the β-blocker propranolol in fathead minnows (Pimephales promelas). Aquat Toxicol 95:195–202CrossRefGoogle Scholar
  62. 62.
    DellaGreca M, Iesce MR, Pistillo P et al (2009) Unusual products of the aqueous chlorination of atenolol. Chemosphere 74:730–734CrossRefGoogle Scholar
  63. 63.
    Stanley JK, Ramirez AJ, Mottaleb M et al (2006) Enantiospecific toxicity of the β-blocker propranolol to Daphnia magna and Pimephales promelas. Environ Toxicol Chem 25:1780–1786CrossRefGoogle Scholar
  64. 64.
    Brambilla G, Mattioli F, Robbiano L et al (2010) Genotoxicity and carcinogenicity testing of pharmaceuticals: correlations between induction of DNA lesions and carcinogenic activity. Mutat Res Rev Mutat Res 705:20–39CrossRefGoogle Scholar
  65. 65.
    Télez M, Ortiz-Lastra E, Gonzalez AJ et al (2010) Assessment of the genotoxicity of atenolol in human peripheral blood lymphocytes: correlation between chromosomal fragility and content of micronuclei. Mutat Res 695:46–54CrossRefGoogle Scholar
  66. 66.
    Uwai K, Tani M, Ohtake Y et al (2005) Photodegradation products of propranolol: the structures and pharmacological studies. Life Sci 78:357–365CrossRefGoogle Scholar
  67. 67.
    DeLorenzo 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 54:203–210CrossRefGoogle Scholar
  68. 68.
    Ferrari B, Paxéus N, Giudice RL et al (2003) Ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of carbamazepine, clofibric acid, and diclofenac. Ecotoxicol Environ Saf 55:359–370CrossRefGoogle Scholar
  69. 69.
    Ferrari B, Paxéus N, Giudice RL et al (2003) Erratum: ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of carbamazepine, clofibric acid, and diclofenac. Ecotoxicol Environ Saf 56:450 ((2003) Ecotoxicol Environ Saf 55:359–370)CrossRefGoogle Scholar
  70. 70.
    Oviedo-Gómez DGC, Galar-Martínez M, García-Medina S et al (2010) Diclofenac-enriched artificial sediment induces oxidative stress in Hyalella azteca. Environ Toxicol Pharmacol 29:39–43CrossRefGoogle Scholar
  71. 71.
    Schwaiger J, Ferling H, Mallow U et al (2004) Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part I: histopathological alterations and bioaccumulation in rainbow trout. Aquat Toxicol 68:141–150CrossRefGoogle Scholar
  72. 72.
    Parolini M, Binelli A, Provini A (2011) Assessment of the potential cyto-genotoxicity of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac on the zebra mussel (Dreissena polymorpha). Water Air Soil Pollut 217:589–601CrossRefGoogle Scholar
  73. 73.
    Quinn B, Schmidt W, O’Rourke K et al (2011) Effects of the pharmaceuticals gemfibrozil and diclofenac on biomarker expression in the zebra mussel (Dreissena polymorpha) and their comparison with standardised toxicity tests. Chemosphere 84:657–663CrossRefGoogle Scholar
  74. 74.
    Schmidt W, O’Rourke K, Hernan R et al (2011) Effects of the pharmaceuticals gemfibrozil and diclofenac on the marine mussel (Mytilus spp.) and their comparison with standardized toxicity tests. Mar Pollut Bull 62:1389–1395CrossRefGoogle Scholar
  75. 75.
    Cleuvers M (2004) Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid. Ecotoxicol Environ Saf 59:309–315CrossRefGoogle Scholar
  76. 76.
    Cleuvers M (2003) Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicol Lett 142:185–194CrossRefGoogle Scholar
  77. 77.
    Pomati F, Netting AG, Calamari D et al (2004) Effects of erythromycin, tetracycline and ibuprofen on the growth of Synechocystis sp. and Lemna minor. Aquat Toxicol 67:387–396CrossRefGoogle Scholar
  78. 78.
    Hayashi Y, Heckmann LH, Callaghan A et al (2008) Reproduction recovery of the crustacean Daphnia magna after chronic exposure to ibuprofen. Ecotoxicology 17:246–251CrossRefGoogle Scholar
  79. 79.
    Mehinto AC, Hill EM, Tyler CR (2010) Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow trout (Oncorhynchus mykiss). Environ Sci Technol 44:2176–2182CrossRefGoogle Scholar
  80. 80.
    Cuklev F, Kristiansson E, Fick J et al (2011) Diclofenac in fish: blood plasma levels similar to human therapeutic levels affect global hepatic gene expression. Environ Toxicol Chem 30:2126–2134CrossRefGoogle Scholar
  81. 81.
    Hoeger B, Köllner B, Dietrich DR et al (2005) Water-borne diclofenac affects kidney and gill integrity and selected immune parameters in brown trout (Salmo trutta f. fario). Aquat Toxicol 75:53–64CrossRefGoogle Scholar
  82. 82.
    Hong HN, Kim HN, Park KS et al (2007) Analysis of the effects diclofenac has on Japanese medaka (Oryzias latipes) using real-time PCR. Chemosphere 67:2115–2121CrossRefGoogle Scholar
  83. 83.
    Nassef M, Kim SG, Seki M et al (2010) In ovo nanoinjection of triclosan, diclofenac and carbamazepine affects embryonic development of medaka fish (Oryzias latipes). Chemosphere 79:966–973CrossRefGoogle Scholar
  84. 84.
    Nassef M, Matsumoto S, Seki M et al (2010) Acute effects of triclosan, diclofenac and carbamazepine on feeding performance of Japanese medaka fish (Oryzias latipes). Chemosphere 80:1095–1100CrossRefGoogle Scholar
  85. 85.
    Lee J, Ji K, Lim Kho Y et al (2011) Chronic exposure to diclofenac on two freshwater cladocerans and Japanese medaka. Ecotoxicol Environ Saf 74:1216–1225CrossRefGoogle Scholar
  86. 86.
    Hallare AV, Köhler H, Triebskorn R (2004) Developmental toxicity and stress protein responses in zebrafish embryos after exposure to diclofenac and its solvent, DMSO. Chemosphere 56:659–666CrossRefGoogle Scholar
  87. 87.
    van den Brandhof E, Montforts M (2010) Fish embryo toxicity of carbamazepine, diclofenac and metoprolol. Ecotoxicol Environ Saf 73:1862–1866CrossRefGoogle Scholar
  88. 88.
    Gagné F, Blaise C, André C (2006) Occurrence of pharmaceutical products in a municipal effluent and toxicity to rainbow trout (Oncorhynchus mykiss) hepatocytes. Ecotoxicol Environ Saf 64:329–336CrossRefGoogle Scholar
  89. 89.
    Flippin JL, Huggett D, Foran CM (2007) Changes in the timing of reproduction following chronic exposure to ibuprofen in Japanese medaka, Oryzias latipes. Aquat Toxicol 81:73–78CrossRefGoogle Scholar
  90. 90.
    Han S, Choi K, Kim J et al (2010) Endocrine disruption and consequences of chronic exposure to ibuprofen in Japanese medaka (Oryzias latipes) and freshwater cladocerans Daphnia magna and Moina macrocopa. Aquat Toxicol 98:256–264CrossRefGoogle Scholar
  91. 91.
    Gravel A, Vijayan MM (2007) Non-steroidal anti-inflammatory drugs disrupt the heat shock response in rainbow trout. Aquat Toxicol 81:197–206CrossRefGoogle Scholar
  92. 92.
    Gravel A, Wilson JM, Pedro DFN et al (2009) Non-steroidal anti-inflammatory drugs disturb the osmoregulatory, metabolic and cortisol responses associated with seawater exposure in rainbow trout. Comp Biochem Physiol C Toxicol Pharmacol 149:481–490CrossRefGoogle Scholar
  93. 93.
    Bhandari K, Venables B (2011) Ibuprofen bioconcentration and prostaglandin E2 levels in the bluntnose minnow Pimephales notatus. Comp Biochem Physiol C Toxicol Pharmacol 153:251–257CrossRefGoogle Scholar
  94. 94.
    David A, Pancharatna K (2009) Developmental anomalies induced by a non-selective COX inhibitor (ibuprofen) in zebrafish (Danio rerio). Environ Toxicol Pharmacol 27:390–395CrossRefGoogle Scholar
  95. 95.
    Quinn B, Gagné F, Blaise C (2008) An investigation into the acute and chronic toxicity of eleven pharmaceuticals (and their solvents) found in wastewater effluent on the cnidarian, Hydra attenuata. Sci Total Environ 389:306–314CrossRefGoogle Scholar
  96. 96.
    Ragugnetti M, Adams ML, Guimarães ATB et al (2011) Ibuprofen genotoxicity in aquatic environment: an experimental model using Oreochromis niloticus. Water Air Soil Pollut 218:361–364CrossRefGoogle Scholar
  97. 97.
    Richards SM, Cole SE (2006) A toxicity and hazard assessment of fourteen pharmaceuticals to Xenopus laevis larvae. Ecotoxicology 15:647–656CrossRefGoogle Scholar
  98. 98.
    De Lange HJ, Noordoven W, Murk AJ et al (2006) Behavioural responses of Gammarus pulex (Crustacea, Amphipoda) to low concentrations of pharmaceuticals. Aquat Toxicol 78:209–216CrossRefGoogle Scholar
  99. 99.
    Pounds N, Maclean S, Webley M et al (2008) Acute and chronic effects of ibuprofen in the mollusc Planorbis carinatus (Gastropoda: Planorbidae). Ecotoxicol Environ Saf 70:47–52CrossRefGoogle Scholar
  100. 100.
    Parolini M, Binelli A, Provini A (2011) Chronic effects induced by ibuprofen on the freshwater bivalve Dreissena polymorpha. Ecotoxicol Environ Saf 74:1586–1594CrossRefGoogle Scholar
  101. 101.
    Lawrence JR, Swerhone GDW, Topp E et al (2007) Structural and functional responses of river biofilm communities to the nonsteroidal anti-inflammatory diclofenac. Environ Toxicol Chem 26:573–582CrossRefGoogle Scholar
  102. 102.
    Paje MP, Kuhlicke UK, Winkler MW et al (2002) Inhibition of lotic biofilms by diclofenac. Appl Microbiol Biotechnol 59:488–492CrossRefGoogle Scholar
  103. 103.
    Lawrence JR, Swerhone GDW, Wassenaar LI et al (2005) Effects of selected pharmaceuticals on riverine biofilm communities. Can J Microbiol 51:655–669CrossRefGoogle Scholar
  104. 104.
    Brain RA, Johnson DJ, Richards SM et al (2004) Effects of 25 pharmaceutical compounds to Lemna gibba using a seven-day static-renewal test. Environ Toxicol Chem 23:371–382CrossRefGoogle Scholar
  105. 105.
    Elvers KT, Wright SJL (1995) Antibacterial activity of the anti-inflammatory compound ibuprofen. Lett Appl Microbiol 20:82–84CrossRefGoogle Scholar
  106. 106.
    Marco-Urrea E, Pérez-Trujillo M, Vicent T et al (2009) Ability of white-rot fungi to remove selected pharmaceuticals and identification of degradation products of ibuprofen by Trametes versicolor. Chemosphere 74:765–772CrossRefGoogle Scholar
  107. 107.
    Richards N, Cook G, Simpson V et al (2011) Qualitative detection of the NSAIDs diclofenac and ibuprofen in the hair of Eurasian otters (Lutra lutra) occupying UK waterways with GC-MS. Eur J Wildlife Res 57:1107–1114CrossRefGoogle Scholar
  108. 108.
    Oaks JL, Gilbert M, Virani MZ et al (2004) Diclofenac residues as the cause of vulture population decline in Pakistan. Nature 427:630–633CrossRefGoogle Scholar
  109. 109.
    Shultz S, Baral HS, Charman S et al (2004) Diclofenac poisoning is widespread in declining vulture populations across the Indian subcontinent. Proc Biol Sci 271:S458–S460CrossRefGoogle Scholar
  110. 110.
    Green RE, Newton I, Shultz S et al (2004) Diclofenac poisoning as a cause of vulture population declines across the Indian subcontinent. J Appl Ecol 41:793–800CrossRefGoogle Scholar
  111. 111.
    Naidoo V, Wolter K, Cuthbert R et al (2009) Veterinary diclofenac threatens Africa’s endangered vulture species. Regul Toxicol Pharmacol 53:205–208CrossRefGoogle Scholar
  112. 112.
    Hussain I, Khan MZ, Khan A et al (2008) Toxicological effects of diclofenac in four avian species. Avian Pathol 37:315–321CrossRefGoogle Scholar
  113. 113.
    Rattner BA, Whitehead MA, Gasper G et al (2008) Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac. Environ Toxicol Chem 27:2341–2345CrossRefGoogle Scholar
  114. 114.
    Brambilla G, Martelli A (2009) Update on genotoxicity and carcinogenicity testing of 472 marketed pharmaceuticals. Mutat Res 681:209–229CrossRefGoogle Scholar
  115. 115.
    Philipose B, Singh R, Khan KA et al (1997) Comparative mutagenic and genotoxic effects of three propionic acid derivatives ibuprofen, ketoprofen and naproxen. Mutat Res Genet Toxicol Environ Mutagen 393:123–131CrossRefGoogle Scholar
  116. 116.
    Brain RA, Ramirez AJ, Fulton BA et al (2008) Herbicidal effects of sulfamethoxazole in Lemna gibba: using p-aminobenzoic acid as a biomarker of effect. Environ Sci Technol 42:8965–8970CrossRefGoogle Scholar
  117. 117.
    Liu B, Nie X, Liu W et al (2011) Toxic effects of erythromycin, ciprofloxacin and sulfamethoxazole on photosynthetic apparatus in Selenastrum capricornutum. Ecotoxicol Environ Saf 74:1027–1035CrossRefGoogle Scholar
  118. 118.
    Pan X, Zhang D, Chen X et al (2009) Effects of levofloxacin hydrochloride on photosystem II activity and heterogeneity of Synechocystis sp. Chemosphere 77:413–418CrossRefGoogle Scholar
  119. 119.
    Smith AJ, Balaam JL, Ward A (2007) The development of a rapid screening technique to measure antibiotic activity in effluents and surface water samples. Mar Pollut Bull 54:1940–1946CrossRefGoogle Scholar
  120. 120.
    Baran W, Sochacka J, Wardas W (2006) Toxicity and biodegradability of sulfonamides and products of their photocatalytic degradation in aqueous solutions. Chemosphere 65:1295–1299CrossRefGoogle Scholar
  121. 121.
    Isidori M, Lavorgna M, Nardelli A et al (2005) Toxic and genotoxic evaluation of six antibiotics on non-target organisms. Sci Total Environ 346:87–98CrossRefGoogle Scholar
  122. 122.
    Flaherty CM, Dodson SI (2005) Effects of pharmaceuticals on Daphnia survival, growth, and reproduction. Chemosphere 61:200–207CrossRefGoogle Scholar
  123. 123.
    Kim Y, Cerniglia CE (2005) Influence of erythromycin A on the microbial populations in aquaculture sediment microcosms. Aquat Toxicol 73:230–241CrossRefGoogle Scholar
  124. 124.
    Rodgers FG, Tzianabos AO, Elliott TSJ (1990) The effect of antibiotics that inhibit cell-wall, protein, and DNA synthesis on the growth and morphology of Legionella pneumophila. J Med Microbiol 31:37–44CrossRefGoogle Scholar
  125. 125.
    Sofer D, Gilboa-Garber N, Belz A et al (1999) “Subinhibitory” erythromycin represses production of Pseudomonas aeruginosa lectins, autoinducer and virulence factors. Chemotherapy 45:335–341CrossRefGoogle Scholar
  126. 126.
    Tateda K, Hirakata Y, Furuya N et al (1993) Effects of sub-MICs of erythromycin and other macrolide antibiotics on serum sensitivity of Pseudomonas aeruginosa. Antimicrob Agents Chemother 37:675–680CrossRefGoogle Scholar
  127. 127.
    Alighardashi A, Pandolfi D, Potier O et al (2009) Acute sensitivity of activated sludge bacteria to erythromycin. J Hazard Mater 172:685–692CrossRefGoogle Scholar
  128. 128.
    Louvet JN, Giammarino C, Potier O et al (2010) Adverse effects of erythromycin on the structure and chemistry of activated sludge. Environ Pollut 158:688–693CrossRefGoogle Scholar
  129. 129.
    Migliore L, Civitareale C, Brambilla G et al (1997) Toxicity of several important agricultural antibiotics to Artemia. Water Res 31:1801–1806CrossRefGoogle Scholar
  130. 130.
    Kümmerer K, Alexy R, Hüttig J et al (2004) Standardized tests fail to assess the effects of antibiotics on environmental bacteria. Water Res 38:2111–2116CrossRefGoogle Scholar
  131. 131.
    Christensen AM, Ingerslev F, Baun A (2006) Ecotoxicity of mixtures of antibiotics used in aquacultures. Environ Toxicol Chem 25:2208–2215CrossRefGoogle Scholar
  132. 132.
    Kümmerer K, Al-Ahmad A, Mersch-Sundermann V (2000) Biodegradability of some antibiotics, elimination of the genotoxicity and affection of wastewater bacteria in a simple test. Chemosphere 40:701–710CrossRefGoogle Scholar
  133. 133.
    Amin MM, Zilles JL, Greiner J et al (2006) Influence of the antibiotic erythromycin on anaerobic treatment of a pharmaceutical wastewater. Environ Sci Technol 40:3971–3977CrossRefGoogle Scholar
  134. 134.
    Göbel A, Thomsen A, McArdell CS et al (2005) Occurrence and sorption behavior of sulfonamides, macrolides, and trimethoprim in activated sludge treatment. Environ Sci Technol 39:3981–3989CrossRefGoogle Scholar
  135. 135.
    Carballa M, Omil F, Ternes T et al (2007) Fate of pharmaceutical and personal care products (PPCPs) during anaerobic digestion of sewage sludge. Water Res 41:2139–2150CrossRefGoogle Scholar
  136. 136.
    Demoling LA, Bååth E, Greve G et al (2009) Effects of sulfamethoxazole on soil microbial communities after adding substrate. Soil Biol Biochem 41:840–848CrossRefGoogle Scholar
  137. 137.
    National Toxicology Program (1988) National Toxicology Program toxicology and carcinogenesis studies of erythromycin stearate (CAS No. 643-22-1) in F344/N rats and B6C3F1 mice (feed studies), 338Google Scholar
  138. 138.
    Chételat A, Albertini S, Gocke E (1996) The photomutagenicity of fluoroquinolones in tests for gene mutation, chromosomal aberration, gene conversion and DNA breakage (Comet assay). Mutagenesis 11:497–504CrossRefGoogle Scholar
  139. 139.
    Hussy P, Maass G, Tümmler B et al (1986) Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase alpha primase complex, topoisomerases I and II, and growth of mammalian lymphoblasts. Antimicrob Agents Chemother 29:1073–1078CrossRefGoogle Scholar
  140. 140.
    Li Q, Peng S, Sheng Z et al (2010) Ofloxacin induces oxidative damage to joint chondrocytes of juvenile rabbits: excessive production of reactive oxygen species, lipid peroxidation and DNA damage. Eur J Pharmacol 626:146–153CrossRefGoogle Scholar
  141. 141.
    Shen LL, Mitscher LA, Sharma PN et al (1989) Mechanism of inhibition of DNA gyrase by quinolone antibacterials: a cooperative drug-DNA binding model. Biochemistry 28:3886–3894CrossRefGoogle Scholar
  142. 142.
    Mandell G, Petri W (1996) Goodman and gilman’s the pharmacological basis of therapeutics. In: Goodman L, Limbird L, Millinof P, Ruddon R, Goodman Gilman A (eds) Antimicrobial agents: sulfonamides, trimethoprim-sulfamethoxazole, quinolones, and agents for urinary tract infections, vol 9. McGraw Hill, New York, pp 1057–1072Google Scholar
  143. 143.
    Stevenson AC, Clarke G, Patel CR et al (1973) Chromosomal studies in vivo and in vitro of trimethoprim and sulfamethoxazole (co-trimoxazole). Mutat Res 17:255–260CrossRefGoogle Scholar
  144. 144.
    Sørensen PJ, Jensen MK (1981) Cytogenetic studies in patients treated with trimethoprim—sulfamethoxazole. Mutat Res Genet Toxicol Environ Mutagen 89:91–94CrossRefGoogle Scholar
  145. 145.
    Abou-Eisha A, Marcos R, Creus A (2004) Genotoxicity studies on the antimicrobial drug sulfamethoxazole in cultured human lymphocytes. Mutat Res Genet Toxicol Environ Mutagen 564:51–56CrossRefGoogle Scholar
  146. 146.
    USEPA (1999) Toxicity reduction evaluation guidance for municipal wastewater treatment plants. EPA/833B-99/002:1–83Google Scholar
  147. 147.
    Ankley GT, Hockett JR, Mount DI et al (2011) Early evolution of the toxicity identification evaluation process: contributions from the United States environmental protection agency effluent testing program. Anonymous effect-directed analysis of complex environmental contamination. Springer, Berlin, pp 1–18Google Scholar
  148. 148.
    Vasquez MI, Lambrianides A, Schneider M et al (2014) Environmental side effects of pharmaceutical cocktails: what we know and what we should know. J Hazard Mater 279:169–189CrossRefGoogle Scholar
  149. 149.
    Tang JY, McCarty S, Glenn E et al (2013) Mixture effects of organic micropollutants present in water: towards the development of effect-based water quality trigger values for baseline toxicity. Water Res 47(10):3300–3314CrossRefGoogle Scholar
  150. 150.
    Burgess RM, Ho KT, Brack W et al (2013) Effects-directed analysis (EDA) and toxicity identification evaluation (TIE): complementary but different approaches for diagnosing causes of environmental toxicity. Environ Toxicol Chem 32:1935–1945CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Marlen I. Vasquez
    • 1
    • 2
    Email author
  • Irene Michael
    • 2
    • 3
  • Klaus Kümmerer
    • 4
  • Despo Fatta-Kassinos
    • 2
    • 3
  1. 1.Department of Environmental Science and TechnologyCyprus University of TechnologyLimassolCyprus
  2. 2.Nireas-International Water Research CenterNicosiaCyprus
  3. 3.Department of Civil and Environmental EngineeringUniversity of CyprusNicosiaCyprus
  4. 4.Institute of Sustainable and Environmental ChemistryLeuphana University LüneburgLüneburgGermany

Personalised recommendations