Chemical and toxicological characterisation of anticancer drugs in hospital and municipal wastewaters from Slovenia and Spain

Abstract

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.

Active Pharmaceutical Principles and their Metabolites in the Environment: A Major Health Hazard to the Human Beings and Living Organisms

“…It has been reported that almost all the anticancer drugs are toxic to crustacean Ceriodaphnia dubia in chronic toxicity studies. Similar results have been demonstrated in the Zebra fish where comet assay showed fragmentation of DNA [14]. In all, there is requirement of research in this area especially when a "mixture" of anticancer drugs are present in a water body.…”

Antineoplastic Agents: Environmental Prevalence and Adverse Outcomes in Aquatic Organisms

“…In general, the highest reported concentrations of antineoplastics were found in hospital effluent and WWTP influent samples, with concentrations in the ng/L to µg/L range, depending on the pharmaceutical. For example, cyclophosphamide, which was detected the most frequently across studies (Figure 1), appeared in concentrations as high as 616 µg/L in hospital effluent (Isidori et al 2016) and 13.1 µg/L in WWTP influent (Gómez‐Canela et al 2012). Other antineoplastics commonly detected in these locations were 5‐fluorouracil, ifosfamide, methotrexate, and tamoxifen, with hospital effluent concentrations as high as 122 µg/L for 5‐fluorouracil (Mahnik et al 2004), 86.2 µg/L for ifosfamide (Gómez‐Canela et al 2014), 4.7 µg/L for methotrexate (Yin et al 2010), and 0.17 µg/L for tamoxifen (Ferrando‐Climent et al 2014).…”

Occurrence of anticancer drugs in the aquatic environment: a systematic review

“…In addition, it is faster than HPLC and inexpensive (Mahnik et al 2004(Mahnik et al , 2007. Inductively coupled plasma mass spectrometry was used for the detection of platinum-based anticancer drugs such as cisplatin (Vidmar et al 2015;Isidori et al 2016).…”