Trends in Fenton and photo-Fenton processes for degradation of antineoplastic agents in water matrices: current knowledge and future challenges evaluation using a bibliometric and systematic analysis.

Antineoplastic agents present potential hazards to human health and the environment. For this reason, these compounds have attracted a great deal of attention from researchers in the environmental sciences field. In order to help guide future research, it is important to understand the current state of investigation of the occurrence of these microcontaminants and methods for their removal, especially focusing on Fenton and photo-Fenton processes applied to various aqueous matrices in which this class of pharmaceuticals is present. For this purpose, a systematic review of these topics was performed by bibliometric analysis of articles published during the last decade and available in the Scopus and Web of Science databases. This study enables visualization of the current panorama and trends in this field, providing a guide for future collaborative research and exchange of knowledge. Various strategies have been suggested to improve the efficiency of Fenton and photo-Fenton processes, mainly by means of the application of multiples additions of iron, the use of heterogeneous catalysts, and/or the use of chelating agents. Some studies have evaluated different radiation sources employed for photo-Fenton processes, such as solar and/or artificial radiation. In turn, the identification of transformation products generated by Fenton and photo-Fenton treatments, together with their evaluation by in silico (Q)SAR predictions or experimental toxicological bioassays, are related subjects that have been less reported in published works and that should be studied in depth. These subjects can support treatment evaluations that are more realistic, considering their limitations or potentials.

Solar photo-Fenton treatment of the anti-cancer drug anastrozole in different aqueous matrices at near-neutral pH: Transformation products identification, pathways proposal, and in silico (Q)SAR risk assessment.

Anastrozole (ANZ) is a breast cancer drug that was introduced onto the pharmaceutical market in the 1990s and is still one of the most widely consumed cytotoxic compounds. Due to the persistence of the drug, its continued presence after passing through wastewater treatment plants can lead to harm to aquatic environments. The present study investigates use of the solar photo-Fenton (SPF) process applied for ANZ degradation, considering the fate of ANZ and its transformation products (TPs). The SPF process was performed using different concentrations of ferrous iron (Fe2+) and H2O2 in solutions produced with deionized water (DW) and hospital wastewater (HWW), at pH close to neutrality. When solar irradiation in the SPF process was carried out the best ANZ removal rates were found under the following conditions: (i) for the DW matrix, [ANZ]0 = 50 µg L-1, [Fe2+] = 5 mg L-1, and [H2O2]0 = 25 mg L-1, achieving 95% primary ANZ elimination; (ii) for the HWW matrix, [ANZ]0 = 50 µg L-1, [Fe2+] = 10 mg L-1(multiple additions), and [H2O2]0 = 25 mg L-1, achieving 51% primary ANZ elimination. LC-QTOF MS analysis allowed to identify tentatively five transformation products (TPs) formed during the ANZ degradation process in DW, and two TPs when HWW was used. The main proposed degradation pathways were demethylation and hydroxylation. Different in silico models free available (quantitative) structure-activity relationship ((Q)SAR) software were used to predict the ecotoxicities and environmental fates of ANZ and the TPs. The in silico (Q)SAR predictions indicated that ANZ and the TPs were non-biodegradable compounds. In silico (Q)SAR predictions for mutagenicity and carcinogenicity end-points identified some TPs that require further study. Attention is drawn to the formation of several TPs for which statistical and rule-based positive alerts for mutagenic activities were found, requiring further confirmatory in vitro validation tests.

Combination of solar photo-Fenton and adsorption process for removal of the anticancer drug Flutamide and its transformation products from hospital wastewater.

The anti-cancer drug Flutamide (FLUT) is widely used and is of great environmental concern. The solar photo-Fenton (SPF) process can be an effective treatment for the removal of this type of micropollutant. The use of a single addition of 5 mg L-1 of Fe2+ and 50 mg L-1 of H2O2 achieved 20% primary degradation and only 3.05% mineralization. By using three additions of 5 mg L-1 Fe2+, with an initial H2O2 concentration of 150 mg L-1, 58% primary degradation was achieved, together with 12.07% mineralization. Consequently, thirteen transformation products (TPs) were formed. The SPF process was further combined with adsorption onto avocado seed activated carbon (ASAC) as an environmentally friendly approach for the removal of remained FLUT and the TPs. Doehlert design was used to assess the behavior of 13 TPs by optimizing the contact time and the adsorbent mass load. The optimal conditions for removal of FLUT and the TPs were 14 mg of ASAC and a contact time of 40 min. Remained FLUT and the TPs were totally removed using the adsorption process. The mechanisms of adsorption of FLUT and the TPs were strongly influenced by their polarity and π-π interactions of the TPs onto ASAC.

Degradation of the anticancer drug flutamide by solar photo-Fenton treatment at near-neutral pH: Identification of transformation products and in silico (Q)SAR risk assessment.

Flutamide (FLUT) is a non-steroidal drug mainly used in the treatment of prostate cancer and has been detected in the aquatic environment at ng L-1 levels. The environmental fate and effects of FLUT have not yet been studied. Conventional treatment technologies fail to completely remove pharmaceuticals, so the solar photo-Fenton process (SPF) has been proposed as an alternative. In this study, the degradation of FLUT, at two different initial concentrations in ultra-pure water, was carried out by SPF. The initial SPF conditions were pH0 5, [Fe2+]0 = 5 mg L-1, and [H2O2]0 = 50 mg L-1. Preliminary elimination rates of 53.4% and 73.4%. The kinetics of FLUT degradation could be fitted by a pseudo-first order model and the kobs were 6.57 × 10-3 and 9.13 × 10-3 min-1 t30W and the half-life times were 95.62 and 73.10 min t30W were achieved for [FLUT]0 of 5 mg L-1 and 500 µg L-1, respectively. Analysis using LC-QTOF MS identified thirteen transformation products (TPs) during the FLUT degradation process. The main degradation pathways proposed were hydroxylation, hydrogen abstraction, demethylation, NO2 elimination, cleavage, and aromatic ring opening. Different in silico (quantitative) structure-activity relationship ((Q)SAR) freeware models were used to predict the toxicities and environmental fates of FLUT and the TPs. The in silico predictions indicated that these substances were not biodegradable, while some TPs were classified near the threshold point to be considered as PBT compounds. The in silico (Q)SAR predictions gave positive alerts concerning the mutagenicity and carcinogenicity endpoints. Additionally, the (Q)SAR toolbox software provided structural alerts corresponding to the positive alerts obtained with the different mutagenicity and carcinogenicity models, supporting the positive alerts with more proactive information.

Combination of experimental and in silico methods for the assessment of the phototransformation products of the antipsychotic drug/metabolite Mesoridazine.

The lack of studies on the fate and effects of drug metabolites in the environment is of concern. As their parent compounds, metabolites enter the aquatic environment and are subject to biotic and abiotic process. In this regard, photolysis plays an important role. This study combined experimental and in silico quantitative structure-activity relationship (QSAR) methods to assess the fate and effects of Mesoridazine (MESO), a pharmacologically active human drug and metabolite of the antipsychotic agent Thioridazine, and its transformation products (TPs) formed through a Xenon lamp irradiation. After 256min, the photodegradation of MESO⋅besylate (50mgL-1) achieved 90.4% and 6.9% of primary elimination and mineralization, respectively. The photon flux emitted by the lamp (200-600nm) was 169.55Jcm-2. Sixteen TPs were detected by means of liquid chromatography-high resolution mass spectrometry (LC-HRMS), and the structures were proposed based on MSn fragmentation patterns. The main transformation reactions were sulfoxidation, hydroxylation, dehydrogenation, and sulfoxide elimination. A back-transformation of MESO to Thioridazine was evidenced. Aerobic biodegradation tests (OECD 301 D and 301F) were applied to MESO and the mixture of TPs present after 256min of photolysis. Most of TPs were not biodegraded, demonstrating their tendency to persist in aquatic environments. The ecotoxicity towards Vibrio fischeri showed a decrease in toxicity during the photolysis process. The in silico QSAR tools QSARINS and US-EPA PBT profiler were applied for the screening of TPs with character of persistence, bioaccumulation, and toxicity (PBT). They have revealed the carbazole derivatives TP 355 and TP 337 as PBT/vPvB (very persistent and very bioaccumulative) compounds. In silico QSAR predictions for mutagenicity and genotoxicity provided by CASE Ultra and Leadscope® indicated positive alerts for mutagenicity on TP 355 and TP 337. Further studies regarding the carbazole derivative TPs should be considered to confirm their hazardous character.

Fenton process on single and mixture components of phenothiazine pharmaceuticals: Assessment of intermediaries, fate, and preliminary ecotoxicity.

Pharmaceuticals do not occur isolated in the environment but in multi-component mixtures and may exhibit antagonist, synergistic or additive behavior. Knowledge on this is still scarce. The situation is even more complicated if effluents or potable water is treated by oxidative processes or such transformations occur in the environment. Thus, determining the fate and effects of parent compounds, metabolites and transformation products (TPs) formed by transformation and degradation processes in the environment is needed. This study investigated the fate and preliminary ecotoxicity of the phenothiazine pharmaceuticals, Promazine (PRO), Promethazine (PRM), Chlorpromazine (CPR), and Thioridazine (THI) as single and as components of the resulting mixtures obtained from their treatment by Fenton process. The Fenton process was carried out at pH7 and by using 0.5-2mgL-1 of [Fe2+]0 and 1-12.5mgL-1 of [H2O2]0 at the fixed ratio [Fe2+]0:[H2O2]0 of 1:10 (w:w). No complete mineralization was achieved. Constitutional isomers and some metabolite-like TPs formed were suggested based on their UHPLC-HRMSn data. A degradation pathway was proposed considering interconnected mechanisms such as sulfoxidation, hydroxylation, N-dealkylation, and dechlorination steps. Aerobic biodegradation tests (OECD 301 D and OECD 301 F) were applied to the parent compounds separately, to the mixture of parent compounds, and for the cocktail of TPs present after the treatment by Fenton process. The samples were not readily biodegradable. However, LC-MS analysis revealed that abiotic transformations, such hydrolysis, and autocatalytic transformations occurred. The initial ecotoxicity tested towards Vibrio fischeri as individual compounds featured a reduction in toxicity of PRM and CPR by the treatment process, whereas PRO showed an increase in acute luminescence inhibition and THI a stable luminescence inhibition. Concerning effects of the mixture components, reduction in toxicity by the Fenton process was predicted by concentration addition and independent action models.

Environmental fate and effect assessment of thioridazine and its transformation products formed by photodegradation.

An experimental and in silico quantitative structure-activity relationship (QSAR) approach was applied to assess the environmental fate and effects of the antipsychotic drug Thioridazine (THI). The sunlight-driven attenuation of THI was simulated using a Xenon arc lamp. The photodegradation reached the complete primary elimination, whereas 97% of primary elimination and 11% of mineralization was achieved after 256 min of irradiation for the initial concentrations of 500 µg L(-1) and 50 mg L(-1), respectively. A non-target approach for the identification and monitoring of transformation products (TPs) was adopted. The structure of the TPs was further elucidated using liquid chromatography-high resolution mass spectrometry (LC-HRMS). The proposed photodegradation pathway included sulfoxidation, hydroxylation, dehydroxylation, and S- and N-dealkylation, taking into account direct and indirect photolysis through a self-sensitizing process in the higher concentration studied. The biodegradability of THI and photolytic samples of THI was tested according to OECD 301D and 301F, showing that THI and the mixture of TPs were not readily biodegradable. Furthermore, THI was shown to be highly toxic to environmental bacteria using a modified luminescent bacteria test with Vibrio fischeri. This bacteriotoxic activity of THI was significantly reduced by phototransformation and individual concentration-response analysis confirmed a lowered bacterial toxicity for the sulfoxidation products Thioridazine-2-sulfoxide and Thioridazine-5-sulfoxide. Additionally, the applied QSAR models predicted statistical and rule-based positive alerts of mutagenic activities for carbazole derivative TPs (TP 355 and TP 339) formed through sulfoxide elimination, which would require further confirmatory in vitro validation tests.

Degradation of ß-blockers in hospital wastewater by means of ozonation and Fe2+/ozonation.

This study investigates the degradation of the ß-blockers in hospital wastewater by direct ozonation and Fe2+/ozonation with a focus on measurements at different initial pHs and Fe2+ concentrations, and the determination of kinetic constants. The results showed that these 'emerging contaminants' were completely degraded, when the removal rate of organic matter reached 30.6% and 49.1% for ozonation and Fe2+/ozonation, respectively. Likewise, the aromaticity removal rates were 63.4% and 77.9% for ozonation and Fe2+/ozonation, respectively. The experimental design showed that pH was the variable which had the greatest effect on the Fe2+/ozonation. The kinetic constants of atenolol, metoprolol and propranolol degradation by direct ozonation complied with pseudo-first-order conditions, while Fe2+/ozonation was suited to a biphasic degradation model. The k obs tended to rise when the pH increases; propranolol showed high k obs, which can be attributed to the naphthalene group (an electron-rich moiety). The identification of degradation products was carried out in aqueous solution using HPLC-MS2, followed by a suggestion of degradation pathways by means of ozonation. The degradation products proved to be dependent on the initial pH, and followed pathways that are based on direct ozonolysis and free radicals.

Oxidation-coagulation of ß-blockers by K2FeVIO4 in hospital wastewater: assessment of degradation products and biodegradability.

This study investigated the degradation of atenolol, metoprolol and propranolol beta-blockers by ferrate (K2FeO4) in hospital wastewater and in aqueous solution. In the case of hospital wastewater, the effect of the independent variables pH and [Fe(VI)] was evaluated by means of response surface methodology. The results showed that Fe(VI) plays an important role in the oxidation-coagulation process, and the treatment of the hospital wastewater led to degradations above 90% for all the three ß-blockers, and to reductions of aromaticity that were close to 60%. In addition, only 17% of the organic load was removed. In aqueous solution, the degradation of the ß-blockers atenolol, metoprolol and propranolol was 71.7%, 24.7% and 96.5%, respectively, when a ratio of 1:10 [ß-blocker]:[Fe(VI)] was used. No mineralization was achieved, which suggests that there was a conversion of the ß-blockers to degradation products identified by liquid chromatography/mass spectrometry tandem. Degradation pathways were proposed, which took account of the role of Fe(VI). Furthermore, the ready biodegradability of the post-process samples was evaluated by using the closed bottle test, and showed an increase in biodegradability. The use of the ferrate advanced oxidation technology seems to be a useful means of ensuring the remediation of hospital and similar wastewater.

Photocatalytic degradation of brilliant red dye and textile wastewater.

The degradation of textile wastewater and brilliant red dye solutions in a coil photoreactor provided with recirculation, assisted by powdered TiO2 and medium-pressure mercury lamp irradiation, was investigated. Factorial design was used for the attainment of the best conditions for COD and color abatement. pH and TiO2 loading showed to be critical variables for the photocatalytic degradation process for both textile wastewater and aqueous reactive dye solutions (25 mg L(-1)). For both substrates, the optimized process conditions by factorial design were almost the same (pH 2-3, 444 mg TiO2 L(-1) loading, 5 L h(-1) recirculation flow-rate). A 41% COD abatement for textile wastewater was obtained with a 120 min treatment. For the Brilliant Red dye solutions, a 20 min treatment resulted in about 90% decolorization (517 nm, pH 5), as well as in a reduction of 66% of the integrated absorbance (200-600 nm, pH 5).

Influence of variables of the combined coagulation-Fenton-sedimentation process in the treatment of trifluraline effluent.

The effluent stream from the industrial production of the herbicide trifluraline (amination water) was submitted to a combined treatment of a physical-chemical process (coagulation) with an advanced oxidation process (Fenton). The recovering of the residual sludge was performed. The combined coagulation-Fenton-sedimentation process proved to be very suitable for wastewater color reduction (91.6%), promoting considerable abatement of the organic load (63.4% COD reduction). According to the fractionary factorial design, the main effects of pH (A) and Fenton sludge (B) variables were considered statistical fluctuations of the process (and not decisive), while the main effects of Fe(3+) (C), Fe(2+) (D) and H(2)O(2) (E), as well as the interactions between variables A and B, A and E, C and D and C and E were considered significant. The obtained results suggest that the combined process can be advantageous for the treatment of recalcitrant industrial effluents, such as the amination water from the trifluraline production.