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

Environmental Science and Pollution Research (2020) 27:1339–1347 https://doi.org/10.1007/s11356-019-07045-2 REVIEW ARTICLE Occurrence of anticancer drugs in the aquatic environment: a systematic review Carla Nassour 1 1 1 2 & Stephen J. Barton & Shereen Nabhani-Gebara & Yolande Saab & James Barker 1 Received: 3 August 2019 / Accepted: 12 November 2019 / Published online: 12 December 2019 # The Author(s) 2019 Abstract Water contamination with pharmaceutical products is a well-studied problem. Numerous studies have demonstrated the presence of anticancer drugs in different water resources that failed to be eliminated by conventional wastewater treatment plants. The purpose of this report was to conduct a systematic review of anticancer drugs in the aquatic environment. The methodology adopted was carried out in compliance with the PRISMA guidelines. From the 75 studies that met the specific requirements for inclusion, data extracted showed that the most common anticancer drugs studied are cyclophosphamide, tamoxifen, ifosfamide and methotrexate with concentrations measured ranging between 0.01 and 86,200 ng/L. There was significant variation in the methodologies employed due to lack of available guidelines to address sampling techniques, seasonal variability and analytical strategy. The most routinely used technique for quantitative determination was found to be solid-phase extraction followed by LC-MS analysis. The lowest reported recovery percentage was 11%, and the highest limit of detection was 1700 ng/L. This indicated the inadequacy of some methods to analyse anticancer drugs and the failure to obtain reliable results. The significant heterogeneity within methodologies made it difficult to compare results and draw conclusions, nevertheless, this study aids in the extrapolation of proposed recommendations to guide future studies and reviews. Keywords Systematic review . Pharmaceuticals . Anticancer drugs . Sampling . Analytical techniques . Aquatic environment Introduction Pharmaceuticals are currently identified as pseudo-persistent compounds seeing that they are constantly released into the aquatic environment (Ebele et al. 2017). In fact, studies conducted as early as the 1970s in the USA revealed the presence of numerous pharmaceuticals in wastewater. Since then, many improvements in analytical methodologies have facilitated the detection of very low concentrations of pharmaceuticals in Responsible editor: Ester Heath Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11356-019-07045-2) contains supplementary material, which is available to authorized users. * Carla Nassour 1 School of Life Sciences, Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston Upon Thames KT1 2EE, UK 2 School of Pharmacy, Lebanese American University, Beirut, Lebanon surface water, wastewater, groundwater and drinking water (World Health Organization 2012). According to a critical review conducted by Stephen R. Hughes et al. in 2013, antibiotics, antiepileptics, cardiovascular drugs and painkillers are the most studied compounds possibly due to frequent consumption worldwide. In contrast, other potentially toxic therapeutic classes such as anticancer drugs have not received much attention (Hughes et al. 2013). Anticancer drugs are categorised by the Anatomical Therapeutic Chemical (ATC) classification system into two groups according to their therapeutic, pharmacological and chemical characteristics: antineoplastic agents (L01) and endocrine therapy (L02) (Besse et al. 2012). Antineoplastic drugs are classified into five groups: L01A alkylating agents, L01B antimetabolites, L01C plant alkaloids and other natural products, L01D cytotoxic antibiotics and related substances and L01X other antineoplastic agents. Meanwhile, in endocrine therapy, hormones (L02A), anti-hormones and related agents (L02B) are utilised (Besse et al. 2012; Xie 2012). The production and consumption of anticancer drugs are on the rise corresponding to the increased incidence of cancer worldwide (Ferrando-Climent et al. 2014). Considering their 1340 significant effect on human cells and hormone systems, there is concern about the environmental risk of anticancer drugs (Besse et al. 2012). For this reason, several studies have investigated the acute and chronic effects of anticancer drugs in the aquatic environment: for acute toxicity, concentrations that are likely to cause negative effects on aquatic organisms are found to be greater than the concentrations detected in water, except in a case of a spill (Fent et al. 2006). That means that acute effects are very improbable. Despite the fact that there are not many studies on chronic toxicity, some tests showed that the concentrations detected in water were higher than the EC50 (half maximal effective concentration) which implies that trace concentrations of anticancer drugs in the water may provoke adverse effects on the long-term or/and when they are present in a mixture (Xie 2012; Booker et al. 2014; Franquet-Griell et al. 2017; Santos et al. 2017). Previous studies and reviews examining the occurrence of anticancer drugs in environmental samples mainly focused on the analytical techniques applied to detect these compounds and their physico-chemical properties that affect their presence in the aquatic environment (Kosjek and Heath 2011; Nussbaumer et al. 2011; Gómez-Canela et al. 2013; Santana-Viera et al. 2016). Therefore, the aim of this report was to conduct an exhaustive systematic review of all available studies that have investigated the presence of anticancer drugs in the aquatic environment to date, in compliance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. In addition, the corresponding sampling strategies and methodologies adopted were discussed in an effort to assess the quality and validity of the included studies. Throughout this review, surface water, groundwater, wastewater and drinking water will be referred to using the term “aquatic environment”. Selection process A preliminary literature search was conducted on different databases and PROSPERO to check if the subject is qualified for a review by the number and type of publications found and to ensure that a similar review was not already published. Following the scoping searches, a review protocol was made and registered in PROSPERO (number of registration: CRD42018100457). In order to develop the inclusion criteria, a PICO table, shown in Table 1, was generated including the Population, Intervention, Comparator, Outcome and the Study Design. All original studies written in English, published or not (Grey literature), that assess at least one anticancer drug were included in this review with no restriction on the year of the study. Also, all types of findings were included (positive and negative) in a way to reduce publication bias and to have a Environ Sci Pollut Res (...truncated)