Chemical and toxicological characterisation of anticancer drugs in hospital and municipal wastewaters from Slovenia and Spain.
Anticancer drugs are continuously released into hospital and urban wastewaters, where they, most commonly, undergo conventional treatment in wastewater treatment plants (WWTPs). Wastewaters contain complex mixtures of substances including parent compounds, their metabolites and transformation products (TPs). In this study, samples of hospital effluents and WWTP influents and effluents from Slovenia and Spain were analyzed for twenty-two selected anticancer drugs, their metabolites and transformation products. Acute and chronic toxicity tests were performed on the crustacean Ceriodaphnia dubia, genotoxicity was determined with Tradescantia and Allium cepa micronucleus (MN) assays and in vitro comet assay in zebrafish (Danio rerio) liver cell line (ZFL cells). Sixty of the two hundred-twenty determinations revealed detectable levels of anticancer drug residues. Among the targeted compounds, platinum based were most frequently detected (90%). Furthermore, erlotinib was detected in 80%, cyclophosphamide and tamoxifen in 70% and methotrexate in 60% of the samples. Seven of ten samples were toxic to C. dubia after acute exposure, whereas after chronic exposure all samples reduced reproduction of C. dubia at high sample dilutions. Allium cepa proved insensitive to the potential genotoxicity of the tested samples, while in Tradescantia increased MN frequencies were induced by a hospital effluent and WWTP influents. In ZFL comet assay all but one sample induced a significant increase of DNA strand breaks. Correlations of chemotherapeutics or their TPs were detected for all bioassays except for Allium cepa genotoxicity test, however for each test the highest correlations were found for different substances indicating differential sensitivities of the test organisms.
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta, Italy. Electronic address: marina.isidori@unina2.it.
Marina
M
Isidori
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta, Italy.
Margherita
M
Lavorgna
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta, Italy.
Chiara
C
Russo
Institute of Environmental Health, Center for Public Health, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria. Electronic address: michael.kundi@meduniwien.ac.at.
Michael
M
Kundi
National Institute of Biology, Department for Genetic Toxicology and Biology of Cancer, Ljubljana, Slovenia.
Bojana
B
Žegura
National Institute of Biology, Department for Genetic Toxicology and Biology of Cancer, Ljubljana, Slovenia; Ecological Engineering Institute, Maribor, Slovenia; Jozef Stefan International Postgraduate School, Ljubljana, Slovenia.
Matjaž
M
Novak
National Institute of Biology, Department for Genetic Toxicology and Biology of Cancer, Ljubljana, Slovenia.
Metka
M
Filipič
Institute for Cancer Research, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Miroslav
M
Mišík
Institute for Cancer Research, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Siegfried
S
Knasmueller
Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain.
Miren López
ML
de Alda
Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain; Catalan Institute of Water Research, c/Emili Grahit, 101, Edifici H2O, Parc Científic i Tecnològic de la Universitat de Girona, E-17003 Girona, Spain.
Damià
D
Barceló
Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain.
Božo
B
Žonja
Jožef Stefan Institute, Department of Environmental Sciences, Ljubljana, Slovenia; Jozef Stefan International Postgraduate School, Ljubljana, Slovenia.
Marjeta
M
Česen
Jožef Stefan Institute, Department of Environmental Sciences, Ljubljana, Slovenia; Jozef Stefan International Postgraduate School, Ljubljana, Slovenia.
Janez
J
Ščančar
Jožef Stefan Institute, Department of Environmental Sciences, Ljubljana, Slovenia; Jozef Stefan International Postgraduate School, Ljubljana, Slovenia.
Tina
T
Kosjek
Jožef Stefan Institute, Department of Environmental Sciences, Ljubljana, Slovenia; Jozef Stefan International Postgraduate School, Ljubljana, Slovenia. Electronic address: ester.heath@ijs.si.
Ester
E
Heath
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis* / Q000633:toxicity*; D001681:Biological Assay; D002947:Cities; D020552:Comet Assay; D003445:Crustacea / Q000187:drug effects; D003520:Cyclophosphamide / Q000032:analysis / Q000633:toxicity; D006761:Hospitals; D008506:Medical Waste / Q000032:analysis; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D019697:Onions / Q000187:drug effects; D017524:Slovenia; D013030:Spain; D034823:Tradescantia / Q000187:drug effects; D062065:Wastewater / Q000032:analysis* / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000633:toxicity*; D015027:Zebrafish
D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D008506:Medical Waste; D062065:Wastewater; D014874:Water Pollutants, Chemical
Anticancer drugs; Cytotoxicity; Genotoxicity; Hospital effluents; Toxicity; Wastewater influents and effluents