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Occurrence and Ecotoxicological Risk Assessment of 14 Cytostatic Drugs in Wastewater

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Abstract

Cytostatic drugs are pharmaceutically active compounds used in chemotherapy to prevent or disrupt cell division. Only a few environmental studies have been focused on cytostatic drugs, in spite of their toxicity, their increasing consumption, and their discharge into municipal sewage. This fact can be mainly due to the lack of methods for their simultaneous analysis. This research describes the occurrence of 14 cytostatic drugs in influent and effluent wastewater from four wastewater treatment plants located in Seville (Spain) during 1-year period. A preliminary environmental risk assessment was also carried out. Five cytostatic drugs (cytarabine, etoposide, gemcitabine, iphosphamide, and methotrexate) were detected in influent wastewater at concentration levels up to 464 ng L−1 (cytarabine). Six of them (cytarabine, doxorubicin, gemcitabine, iphosphamide, paclitaxel, and vinorelbine) were detected in effluent wastewater at concentration levels up to 190 ng L−1 (cytarabine). Most of the detected cytostatic drugs are not significantly removed during wastewater treatment. Nevertheless, neither ecotoxicological nor genotoxical risks are expected to occur at the measured concentrations on the aquatic environment.

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References

  • Besse, J. P., Latour, J. F., & Garric, J. (2012). Anticancer drugs in surface waters: what can we say about the occurrence and environmental significance of cytotoxic, cytostatic and endocrine therapy drugs? Environment International, 39, 73–86.

    Article  CAS  Google Scholar 

  • Buerge, I. J., Rudolfbuser, H., Poiger, T., & Muller, M. D. (2006). Occurrence and fate of the cytostatic drugs cyclophosphamide and ifosfamide in wastewater and surface waters. Environmental Science & Technology, 40, 7242–7250.

    Article  CAS  Google Scholar 

  • Camacho-Muñoz, M. D., Martín, J., Santos, J. L., Aparicio, I., & Alonso, E. (2010). Occurrence, temporal evolution and risk assessment of pharmaceutically active compounds in Doñana Park (Spain). Journal of Hazardous Materials, 183, 602–608.

    Article  Google Scholar 

  • Castiglioni, S., Bagnati, R., Calamari, D., Fanelli, R., & Zuccato, E. (2005). A multiresidue analytical method using solid-phase extraction and high-pressure liquid chromatography tandem mass spectrometry to measure pharmaceuticals of different therapeutic classes in urban wastewaters. Journal of Chromatography A, 1092, 206–215.

    Article  CAS  Google Scholar 

  • Catastini, C., Mullot, J. U., Boukari, S., Mazellier, P., Levi, Y., Cervantes, P., et al. (2008). Assessment of antineoplastic drugs in effluents of two hospitals. Journal Europeen d’Hydrologie, 39(2), 171–180.

    CAS  Google Scholar 

  • Cunningham, V. L., Binks, S. P., & Olson, M. J. (2009). Human health risk assessment from the presence of human pharmaceuticals in the aquatic environment. Regulatory Toxicology and Pharmacology, 53, 39–45.

    Article  CAS  Google Scholar 

  • Durán-Álvarez, J. C., Prado-Pano, B., & Jiménez-Cisneros, B. (2012). Sorption and desorption of carbamazepine, naproxen and triclosan in a soil irrigated with raw wastewater: estimation of the sorption parameters by considering the initial mass of the compounds in the soil. Chemosphere, 88(1), 84–90.

    Article  Google Scholar 

  • EMEA (2006). Guideline on the environmental risk assessment of medicinal products for human use. Doc. Ref. EMEA/CPMP/SWP/4447/00, London: European Agency for the Evaluation of Medicinal Products.

  • European Community (EC) (2003). Technical Guidance Document on Risk Assessment in support of Commission Directive 93/67/EEC on risk assessment for new notified substances, Commission Regulation (EC) no. 1488/94 on Risk Assessment for existing substances and Directive 98/8/EC of the European Parliament and of the council concerning the placing of biocidal products on the market, parts I, II and IV. European Communities, EUR 20418 EN/1.

  • FDA-CDER (1996). Retrospective review of ecotoxicity data submitted in environmental assessments. FDA Center for Drug Evaluation and Research, Rockville, MD, USA (Docket No. 96N–0057).

  • Ferk, F., Mišík, M., Grummt, T., Majer, B., Fuerhacker, M., Buchmann, C., et al. (2009). Genotoxic effects of wastewater from an oncological ward. Mutation Research, Genetic Toxicology and Environmental Mutagenesis, 672, 69–75.

    Article  CAS  Google Scholar 

  • Ferrando-Climet, L., Rodriguez-Mozaz, S., & Barceló, D. (2013). Development of a UPLC-MS/MS method for the determination of ten anticancer drugs in hospital and urban wastewaters, and its application for the screening of human metabolites assisted by information-dependent acquisition tool (IDA) in sewage samples. Analytical and Bioanalytical Chemistry, 405, 5937–5952.

    Article  Google Scholar 

  • Gómez-Canela, C., Cortés-Francisco, N., Oliva, X., Pujol, C., Ventura, F., Lacorte, S., et al. (2012). Occurrence of cyclophosphamide and epirubicin in wastewaters by direct injection analysis–liquid chromatography–high-resolution mass spectrometry. Environmental Science and Pollution Research, 19(8), 3210–3218.

    Article  Google Scholar 

  • Gómez-Canela, C., Cortés-Francisco, N., Ventura, F., Caixach, J., & Lacorte, S. (2013). Liquid chromatography coupled to tandem mass spectrometry and high resolution mass spectrometry as analytical tools to characterize multi-class cytostatic compounds. Journal of Chromatography A, 1276, 78–94.

    Article  Google Scholar 

  • Gracia-Lor, E., Sancho, J. V., Serrano, R., & Hernández, F. (2012). Occurrence and removal of pharmaceuticals in wastewater treatment plants at the Spanish Mediterranean area of Valencia. Chemosphere, 87(5), 453–462.

    Article  CAS  Google Scholar 

  • Johnson, A. C., Jürgens, M. D., Williams, R. J., Kümmerer, K., Kortenkamp, A., & Sumpter, J. P. (2008). Do cytotoxic chemotherapy drugs discharged into rivers pose a risk to the environment and human health? An overview and UK case study. Journal of Hydrology, 348(1–2), 167–175.

    Article  CAS  Google Scholar 

  • Kiffmeyer, T., Götze, H. J., Jursch, M., & Lüders, U. (1998). Trace enrichment, chromatographic separation and biodegradation of cytostatic compounds in surface water. Fresenius Journal of Analytical Chemistry, 361, 185–191.

    Article  CAS  Google Scholar 

  • Kosjek, T., & Heath, E. (2011). Occurrence, fate and determination of cytostatic pharmaceuticals in the environment. TrAC Trends in Analytical Chemistry, 30(7), 1065–1087.

    Article  CAS  Google Scholar 

  • Kovalova, L., Siegrist, H., Singer, H., Wittmer, A., & McArdell, C. S. (2012). Hospital wastewater treatment by membrane bioreactor: performance and efficiency for organic micropollutant elimination. Environmental Science and Technology, 46, 1536–1545.

    Article  CAS  Google Scholar 

  • Kümmerer, K., & Al-Ahmad, A. (1997). Biodegradability of the anti-tumour agents 5-fluorouracil, cytarabine and gemcitabine: impact of the chemical structure and synergistic toxicity with hospital effluent. Acta Hydrochimica et Hydrobiologica, 25, 166–172.

    Article  Google Scholar 

  • Kümmerer, K., Steger-Hartmann, T., & Meyer, M. (1997). Biodegradability of the anti-tumour agent ifosfamide and its occurrence in hospital effluents and communal sewage. Water Research, 31(11), 2705–2710.

    Article  Google Scholar 

  • Llorente, M. T., Parra, J. M., Sánchez-Fortún, S., & Castaño, A. (2012). Cytotoxicity and genotoxicity of sewage treatment plant effluents in rainbow trout cells (RTG-2). Water Research, 46(19), 6351–6358.

    Article  CAS  Google Scholar 

  • Mahnik, S. N., Lenz, K., Weissenbacher, N., Mader, R. M., & Fuerhacker, M. (2007). Fate of 5-fluorouracil, doxorubicin, epirubicin, and daunorubicin in hospital wastewater and their elimination by activated sludge and treatment in a membrane-bio-reactor system. Chemosphere, 66, 30–37.

    Article  CAS  Google Scholar 

  • Martín, J., Camacho-Muñoz, M. D., Santos, J. L., Aparicio, I., & Alonso, E. (2011). Simultaneous determination of a selected group of cytostatic drugs in water using high-performance liquid chromatography–triple-quadrupole mass spectrometry. Journal of Separation Science, 34, 3166–3177.

    Article  Google Scholar 

  • Martín, J., Camacho-Muñoz, M. D., Santos, J. L., Aparicio, I., & Alonso, E. (2012). Distribution and temporal evolution of pharmaceutically active compounds alongside sewage sludge treatment. Risk assessment of sludge application onto soils. Journal of Environmental Management, 102, 18–25.

    Article  Google Scholar 

  • Matamoros, V., Arias, C. A., Nguyen, L. X., Salvadó, V., & Brix, H. (2012). Occurrence and behavior of emerging contaminants in surface water and a restored wetland. Chemosphere, 88, 1083–1089.

    Article  CAS  Google Scholar 

  • Negreira, N., López de Alda, M., & Barceló, D. (2013). On-line solid phase extraction–liquid chromatography–tandem mass spectrometry for the determination of 17 cytostatics and metabolites in waste, surface and ground water samples. Journal of Chromatography A, 1280, 64–74.

    Article  CAS  Google Scholar 

  • Reyes-Contreras, C., Hijosa-Valsero, M., Sidrach-Cardona, R., Bayona, J. M., & Bécares, E. (2012). Temporal evolution in PPCP removal from urban wastewater by constructed wetlands of different configuration: a medium-term study. Chemosphere, 88, 161–167.

    Article  CAS  Google Scholar 

  • Sanderson, H., Johnson, D. J., Wilson, C. J., Brain, R. A., & Solomon, K. R. (2003). Probabilistic hazard assessment of environmentally occurring pharmaceuticals toxicity to fish, daphnids and algae by ECOSAR screening. Toxicology Letters, 144(3), 383–395.

    Article  CAS  Google Scholar 

  • Steger-Hartmann, T., Kiimmerer, K., & Schecker, J. (1996). Trace analysis of the antineoplastics ifosfamide and cyclophosphamide in sewage water by two-step solid-phase extraction and gas chromatography–mass spectrometry. Journal of Chromatography A, 726, 179–184.

    Article  CAS  Google Scholar 

  • Steger-Hartmann, T., Kümmerer, K., & Hartmann, A. (1997). Biological degradation of cyclophosphamide and its occurrence in sewage water. Ecotoxicology and Environmental Safety, 36, 174–179.

    Article  CAS  Google Scholar 

  • Verlicchi, P., Al Aukidy, M., & Zambello, E. (2012). Occurrence of pharmaceutical compounds in urban wastewater: removal, mass load and environmental risk after a secondary treatment—a review. Science of the Total Environment, 429, 123–155.

    Article  CAS  Google Scholar 

  • Weigt, S., Huebler, N., Strecker, R., Braunbeck, T., & Broschard, T. H. (2011). Zebrafish (Danio rerio) embryos as a model for testing proteratogens. Toxicology, 281(1–3), 25–36.

    Article  CAS  Google Scholar 

  • Zhang, J., Chang, V. W. C., Giannis, A., & Wang, J. Y. (2013). Removal of cytostatic drugs from aquatic environment: a review. Science of the Total Environment, 445–446, 281–298.

    Article  Google Scholar 

  • Zounkova, R., Odraska, P., Dolezalova, L., Hilscherova, K., Marsalek, B., & Blaha, L. (2007). Ecotoxicity and genotoxicity assessment of cytostatic pharmaceuticals. Environmental Toxicology and Chemistry, 26(10), 2208–2214.

    Article  CAS  Google Scholar 

  • Zounkova, R., Kovalova, L., Blaha, L., & Dott, W. (2010). Ecotoxicity and genotoxicity assessment of cytotoxic antineoplastic drugs and their metabolites. Chemosphere, 81(2), 253–260.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Andaluza de Tratamientos de Higiene S.A. (ATHISA) for its assistance in this work.

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Authors and Affiliations

  1. Department of Analytical Chemistry, Escuela Politécnica Superior, University of Seville, C/ Virgen de África 7, 41011, Seville, Spain

    Julia Martín, Dolores Camacho-Muñoz, Juan Luis Santos, Irene Aparicio & Esteban Alonso

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  1. Julia Martín
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  2. Dolores Camacho-Muñoz
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  3. Juan Luis Santos
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  4. Irene Aparicio
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  5. Esteban Alonso
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Correspondence to Juan Luis Santos.

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Martín, J., Camacho-Muñoz, D., Santos, J.L. et al. Occurrence and Ecotoxicological Risk Assessment of 14 Cytostatic Drugs in Wastewater. Water Air Soil Pollut 225, 1896 (2014). https://doi.org/10.1007/s11270-014-1896-y

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  • DOI: https://doi.org/10.1007/s11270-014-1896-y

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