Anticancer drugs in Portuguese surface waters - Estimation of concentrations and identification of potentially priority drugs

Anticancer drugs, used in chemotherapy, have emerged as new water contaminants due to their increasing consumption trends and poor elimination efficiency in conventional water treatment processes. As a result, anticancer drugs have been reported in surface and even drinking waters, posing the environment and human health at risk. However, the occurrence and distribution of anticancer drugs depend on the area studied and the hydrological dynamics, which determine the risk towards the environment. The main objective of the present study was to evaluate the risk of anticancer drugs in Portugal. This work includes an extensive analysis of the consumption trends of 171 anticancer drugs, sold or dispensed in Portugal between 2007 and 2015. The consumption data was processed aiming at the estimation of predicted environmental loads of anticancer drugs and 11 compounds were identified as potentially priority drugs based on an exposure-based approach (PECb> 10 ng L-1 and/or PECc> 1 ng L-1). In a national perspective, mycophenolic acid and mycophenolate mofetil are suspected to pose high risk to aquatic biota. Moderate and low risk was also associated to cyclophosphamide and bicalutamide exposition, respectively. Although no evidences of risk exist yet for the other anticancer drugs, concerns may be associated with long term effects

5-Fluorouracil and Its Prodrug Capecitabine: Occurrence, Fate and Effects in the Environment

In this chapter, we examine the available literature on the cycling and effects of 5-flourouracil (5-FU) and capecitabine (CAP) residues in the aqueous environment. The aim is to understand better their environmental occurrence, fate and potential toxic effects. Physicochemical properties of 5-FU and CAP suggest that they are more likely to remain in aqueous environment than adsorbed to solid particles. Detectable levels have been reported in hospital effluents (< 122 μg/L) and in municipal wastewaters (< 280 ng/L), but rarely in surface waters (only 5-FU in one study: < 160 ng/L). Among different water treatments available, the most promising for removing 5-FU and CAP are the advanced oxidation processes (AOPs). So far, indirect photolysis has been most widely applied and is capable of almost completely removing both compounds (to < LOD) and in some cases resulting in complete mineralization. However, these treatments have been mostly tested in MilliQ or potable water and their suitability for complex matrices like wastewaters is questionable and biodegradation is still treatment of choice for these matrices. In other studies, a variety of transformation products has been identified adding to the overall environmental burden. Toxicity tests on single parent compounds have shown that they may have effects above the concentrations of environmental relevance. The studies of complex mixtures of parent compounds highlight that the actual ecological risk posed by mixtures of these compounds is difficult to evaluate. Overall, the main finding from this review is that a real need exists for further studies on the chemical and toxicological effects of environmental mixtures of cytotoxic compounds

Occurrence of Cytostatics in Different Water Compartments

The chapter deals with the occurrence of a selection of anticancer drugs in 5 different water environments: hospital wastewater, wastewater treatment plant influ- 6 ents and effluents, surface water, sea water, and drinking water. Unfortunately, no 7 data are available for groundwater up to now. The chapter presents and discusses 8 measured environmental concentrations of anticancer drugs collected in 56 peer- 9 reviewed papers referring to investigations carried out in 18 countries all over the 10 world. It focuses on the variability of observed concentrations in the different 11 environments, and it highlights the importance of planning efficient sampling 12 strategies in order to obtain representative water samples. 13 The highest concentrations in hospital effluents were found for platinum-based 14 compounds and 5-fluorouracil (> 10 15 5 ng L1), in the influent for ciprofloxacin (> 10 16 3 ng L1), in the effluent for platinum-based compounds, ifosfamide and bicalutamide (> 10 17 3 ng L1), and in surface water for cyclophosphamide, tamoxifen, ciprofloxacin, and bicalutamide (> 10 18 2 ng L1). In addition, a comparison is provided between measured and predicted concentrations of some anticancer drugs 19 and a brief discussion of the strengths and weaknesses of the two approaches is 20 reported

Human metabolites and transformation products cyclophosphamide and ifosfamide: analysis, occurrence and formation during abiotic treatments

This study describes a gas chromatography-mass spectrometry analytical method for the analysis of cytostatic cyclophosphamide (CP), ifosfamide (IF) and their selected metabolites/transformation products (TPs): carboxy-cyclophosphamide (carboxy-CP), keto-cyclophosphamide (keto-CP) and 3-dechloroethyl-ifosfamide/N-dechloroethyl-cyclophosphamide (N-decl-CP) in wastewater (WW). Keto-cyclophosphamide, CP and IF were extracted with Oasis HLB and N-decl-CP and carboxy-CP with Isolute ENV+ cartridges. Analyte derivatization was performed by silylation (metabolites/TPs) and acetylation (CP and IF). The recoveries and LOQs of the developed method were 58, 87 and 103 % and 77.7, 43.7 and 6.7 ng L−1 for carboxy-CP, keto-CP and N-decl-CP, respectively. After validation, the analytical method was applied to hospital WW and influent and effluent samples of a receiving WW treatment plant. In hospital WW, levels up to 2690, 47.0, 13,200, 2100 and 178 ng L−1 were detected for CP, IF, carboxy-CP, N-decl-CP and keto-CP, respectively, while in influent and effluent samples concentrations were below LOQs. The formation of TPs during abiotic treatments was also studied. Liquid chromatography-high-resolution mass spectrometry was used to identify CP and IF TPs in ultrapure water, treated with UV and UV/H2O2. UV treatment produced four CP TPs and four IF TPs, while UV/H2O2 resulted in five CPs and four IF TPs. Besides already known TPs, three novel TPs (CP-TP138a, imino-ifosfamide and IF-TP138) have been tentatively identified. In hospital WW treated by UV/O3/H2O2, none of the target metabolites/TPs resulted above LOQs