Imatinib: Major photocatalytic degradation pathways in aqueous media and the relative toxicity of its transformation products.

Imatinib (IMA) is a highly potent tyrosine kinase inhibitor used as first-line anti-cancer drug in the treatment of chronic myeloid leukemia. Due to its universal mechanism of action, IMA also has endocrine and mutagenic disrupting effects in vivo and in vitro, which raises the question of its environmental impact. However, to date, very little information is available on its environmental fate and the potential role of its transformation products (TPs) on aquatic organisms. Given the IMA resistance to hydrolysis and direct photolysis according to the literature, we sought to generate TPs through oxidative and radical conditions using the AOPs pathway. Thus, the reactivity of the cytotoxic drug IMA in water in the presence of OH and h+ was investigated for the first time in the present work. In this regard, a non-targeted screening approach was applied in order to reveal its potential TPs. The tentative structural elucidation of the detected TPs was performed by LC-HRMSn. The proposed approach allowed detecting a total of twelve TPs, among which eleven are being described for the first time in this work. Although the structures of these TPs could not be positively confirmed due to lack of standards, their chemical formulas and product ions can be added to databases, which will allow their screening in future monitoring studies. Using the quantitative structure-activity relationship (QSAR) approach and rule-based software, we have shown that the detected TPs possess, like their parent molecule, comparable acute toxicity as well as mutagenic and estrogenic potential. In addition to the in silico studies, we also found that the samples obtained at different exposure times to oxidative conditions, including those where IMA is no longer detected, retained toxicity in vitro. Such results suggest further studies are needed to increase our knowledge of the impact of imatinib on the environment.

Light at night as an environmental endocrine disruptor.

Environmental endocrine disruptors (EEDs) are often consequences of human activity; however, the effects of EEDs are not limited to humans. A primary focus over the past ∼30years has been on chemical EEDs, but the repercussions of non-chemical EEDs, such as artificial light at night (LAN), are of increasing interest. The sensitivity of the circadian system to light and the influence of circadian organization on overall physiology and behavior make the system a target for disruption with widespread effects. Indeed, there is increasing evidence for a role of LAN in human health, including disruption of circadian regulation and melatonin signaling, metabolic dysregulation, cancer risk, and disruption of other hormonally-driven systems. These effects are not limited to humans; domesticated animals as well as wildlife are also exposed to LAN, and at risk for disrupted circadian rhythms. Here, we review data that support the role of LAN as an endocrine disruptor in humans to be considered in treatments and lifestyle suggestions. We also present the effects of LAN in other animals, and discuss the potential for ecosystem-wide effects of artificial LAN. This can inform decisions in agricultural practices and urban lighting decisions to avoid unintended outcomes.

Environmental photochemistry of dienogest: phototransformation to estrogenic products and increased environmental persistence via reversible photohydration.

Potent trienone and dienone steroid hormones undergo a coupled photohydration (in light)-thermal dehydration (in dark) cycle that ultimately increases their environmental persistence. Here, we studied the photolysis of dienogest, a dienone progestin prescribed as a next-generation oral contraceptive, and used high resolution mass spectrometry and both 1D and 2D nuclear magnetic resonance spectroscopy to identify its phototransformation products. Dienogest undergoes rapid direct photolysis (t1/2 ∼ 1-10 min), forming complex photoproduct mixtures across the pH range examined (pH 2 to 7). Identified products include three photohydrates that account for ∼80% of the converted mass at pH 7 and revert back to parent dienogest in the absence of light. Notably, we also identified two estrogenic compounds produced via the A-ring aromatization of dienogest, evidence for a photochemically-induced increase in estrogenic activity in product mixtures. These results imply that dienogest will undergo complete and facile photolytic transformation in sunlit surface water, yet exhibit greater environmental persistence than might be anticipated by inspection of kinetic rates. Photoproduct mixtures also include transformation products with different nuclear receptor binding capabilities than the parent compound dienogest. These outcomes reveal a dynamic fate and biological risk profile for dienogest that must also take into account the composition and endocrine activity of its transformation products. Collectively, this study further illustrates the need for more holistic regulatory, risk assessment, and monitoring approaches for high potency synthetic pharmaceuticals and their bioactive transformation products.

Photocatalytic decomposition of selected estrogens and their estrogenic activity by UV-LED irradiated TiO2 immobilized on porous titanium sheets via thermal-chemical oxidation.

The removal of endocrine disrupting compounds (EDCs) remains a big challenge in water treatment. Risks associated with these compounds are not clearly defined and it is important that the water industry has additional options to increase the resiliency of water treatment systems. Titanium dioxide (TiO2) has potential applications for the removal of EDCs from water. TiO2 has been immobilized on supports using a variety of synthesis methods to increase its feasibility for water treatment. In this study, we immobilized TiO2 through the thermal-chemical oxidation of porous titania sheets. The efficiency of the material to degrade target EDCs under UV-LED irradiation was examined under a wide range of pH conditions. A yeast-estrogen screen assay was used to complement chemical analysis in assessing removal efficiency. All compounds but 17ß-estradiol were degraded and followed a pseudo first-order kinetics at all pH conditions tested, with pH 4 and pH 11 showing the most and the least efficient treatments respectively. In addition, the total estrogenic activity was substantially reduced even with the inefficient degradation of 17ß-estradiol. Additional studies will be required to optimize different treatment conditions, UV-LED configurations, and membrane fouling mitigation measures to make this technology a more viable option for water treatment.

Comparison of UV photolysis, nanofiltration, and their combination to remove hormones from a drinking water source and reduce endocrine disrupting activity.

A sequential water treatment combining low pressure ultraviolet direct photolysis with nanofiltration was evaluated to remove hormones from water, reduce endocrine disrupting activity, and overcome the drawbacks associated with the individual processes (production of a nanofiltration-concentrated retentate and formation of toxic by-products). 17ß-Estradiol, 17α-ethinylestradiol, estrone, estriol, and progesterone were spiked into a real water sample collected after the sedimentation process of a drinking water treatment plant. Even though the nanofiltration process alone showed similar results to the combined treatment in terms of the water quality produced, the combined treatment offered advantage in terms of the load of the retentate and decrease in the endocrine-disrupting activity of the samples. Moreover, the photolysis by-products produced, with higher endocrine disrupting activity than the parent compounds, were effectively retained by the membrane. The combination of direct LP/UV photolysis with nanofiltration is promising for a drinking water utility that needs to cope with sudden punctual discharges or deterioration of the water quality and wants to decrease the levels of chemicals in the nanofiltration retentate.

Simultaneously photocatalytic treatment of hexavalent chromium (Cr(VI)) and endocrine disrupting compounds (EDCs) using rotating reactor under solar irradiation.

In this study, simultaneous treatments, reduction of hexavalent chromium (Cr(VI)) and oxidation of endocrine disrupting compounds (EDCs), such as bisphenol A (BPA), 17α-ethinyl estradiol (EE2) and 17ß-estradiol (E2), were investigated with a rotating photocatalytic reactor including TiO2 nanotubes formed on titanium mesh substrates under solar UV irradiation. In the laboratory tests with a rotating type I reactor, synergy effects of the simultaneous photocatalytic reduction and oxidation of inorganic (Cr(VI)) and organic (BPA) pollutants were achieved. Particularly, the concurrent photocatalytic reduction of Cr(VI) and oxidation of BPA was higher under acidic conditions. The enhanced reaction efficiency of both pollutants was attributed to a stronger charge interaction between TiO2 nanotubes (positive charge) and the anionic form of Cr(VI) (negative charge), which are prevented recombination (electron-hole pair) by the hole scavenging effect of BPA. In the extended outdoor tests with a rotating type II reactor under solar irradiation, the experiment was extended to examine the simultaneous reduction of Cr(VI) in the presence of additional EDCs, such as EE2 and E2 as well as BPA. The findings showed that synergic effect of both photocatalytic reduction and oxidation was confirmed with single-component (Cr(VI) only), two-components (Cr(VI)/BPA, Cr(VI)/EE2, and Cr(VI)/E2), and four-components (Cr(VI)/BPA/EE2/E2) under various solar irradiation conditions.

Stability of bisphenol A (BPA) in oil-in water emulsions under riboflavin photosensitization.

UNLABELLED: Effects of riboflavin photosensitization on the degradation of bisphenol A (BPA) were determined in oil-in-water (O/W) emulsions containing ethylenediaminetetraacetic acid (EDTA) or sodium azide, which are a metal chelator or a singlet oxygen quencher, respectively. Also, the distribution of BPA between the continuous and dispersed phases in O/W emulsions was analyzed by high-performance liquid chromatography (HPLC). The concentration of BPA in O/W emulsions significantly decreased by 38.6% after 2 h under visible light irradiation and in the presence of riboflavin (P < 0.05). Addition of EDTA and sodium azide protected the decomposition of BPA significantly in a concentration dependent manner (P < 0.05), which implies both transition metals and singlet oxygen accelerate the photodegradation of BPA in O/W emulsions. Approximately 21.7% of the BPA was distributed in the 2.5% (w/v) dispersed lipid particles and 78.3% was in the continuous aqueous phase of the emulsions. The amount of BPA in aqueous phase decreased faster than the amount of BPA in the lipid phase during riboflavin photosensitization (P < 0.05). Thus, the BPA in the aqueous phase was the major target of riboflavin photodegradation in O/W emulsions. PRACTICAL APPLICATION: Concentration of BPA, an endocrine disrupting chemical, was decreased significantly in oil-in-water emulsions under riboflavin and visible light irradiation. BPA in continuous aqueous phase was major target of riboflavin photosensitization. However, BPA was distributed more densely in lipid phase and more protected from riboflavin photosensitized O/W emulsions. This study can help to decrease the level of BPA in foods made of O/W emulsions containing riboflavin, which could be displayed under visible light irradiation.

Effect of water composition on TiO2 photocatalytic removal of endocrine disrupting compounds (EDCs) and estrogenic activity from secondary effluent.

The effect of inorganic ions and dissolved organic matter (DOM) on the TiO(2) photocatalytic removal of estrogenic activity from secondary effluents of municipal wastewater treatment plants was investigated. The presence of HPO(4)(2-), NH(4)(+), and HCO(3)(-) resulted in a significantly negative impact on the photocatalytic removal of estrogenic activity from synthetic water due to their strong adsorption on the surface of TiO(2). However, only a weak impact was noted during photocatalytic removal of estrogenic activity from secondary effluent with these ions added, since the presence of DOM in real wastewater played a more important role in inhibiting photocatalytic removal of estrogenic activity than inorganic ions. By investigating the effect of different DOM fractions on photocatalytic removal of estrogenic activity, polar compounds (PC) were found to cause a temporary increase in estrogenic activity during TiO(2) photocatalysis. Fluorescence spectroscopy and molecular weight (MW) analysis on secondary effluent spiked with PC during TiO(2) photocatalysis suggest that large MW organic matter (>4.5kDa) in secondary effluent, such as humic/fulvic acid, not only could play an important role in inhibiting photocatalytic removal of estrogenic activity but also is responsible for the temporary increase in estrogenic activity during the same process.

Endocrine disruptive estrogens role in electron transfer: bio-electrochemical remediation with microbial mediated electrogenesis.

Bioremediation of selected endocrine disrupting compounds (EDCs)/estrogens viz. estriol (E3) and ethynylestradiol (EE2) was evaluated in bio-electrochemical treatment (BET) system with simultaneous power generation. Estrogens supplementation along with wastewater documented enhanced electrogenic activity indicating their function in electron transfer between biocatalyst and anode as electron shuttler. EE2 addition showed more positive impact on the electrogenic activity compared to E3 supplementation. Higher estrogen concentration showed inhibitory effect on the BET performance. Poising potential during start up phase showed a marginal influence on the power output. The electrons generated during substrate degradation might have been utilized for the EDCs break down. Fuel cell behavior and anodic oxidation potential supported the observed electrogenic activity with the function of estrogens removal. Voltammetric profiles, dehydrogenase and phosphatase enzyme activities were also found to be in agreement with the power generation, electron discharge and estrogens removal.

Environmental factors affecting ultraviolet photodegradation rates and estrogenicity of estrone and ethinylestradiol in natural waters.

The environmental fate and persistence of steroidal estrogens is influenced by their photodegradation. This can potentially occur both in the presence of the ultraviolet (UV) portion of solar radiation and in tertiary wastewater treatment plants that use UV radiation for disinfection purposes. To determine patterns of UV photodegradation for estrone (E1) and 17α-ethinylestradiol (EE2), water samples containing these compounds were exposed to levels of UVB radiation that would simulate exposure to ambient sunlight. E1 degraded with a pseudo-first-order rate law constant that was directly proportional to UVB radiation intensity (R² = 0.999, P < 0.001) and inversely proportional to dissolved organic carbon (DOC) concentration (R² = 0.812, P = 0.037). DOC acted as a competitive inhibitor to direct photolysis of E1 by UV. In contrast to E1, EE2 was more persistent under similar UVB treatment. A reporter gene assay showed that the estrogenicity of UVB-exposed estrogens did not decrease relative to non-UVB-exposed estrogens, suggesting that some of the photoproducts may also have estrogenic potency. These results show that environmental degradation rates of steroidal estrogens are predictable from the UV intensity reaching surface waters, and the DOC concentrations in these surface waters.

Sonophotocatalysis of endocrine-disrupting chemicals.

Sonolysis and photolysis often exhibit synergistic effects in the degradation of organic molecules. An assay of fish oocyte maturation provides an appropriate experimental system to investigate the hormonal activities of chemical agents. Oocyte maturation in fish is triggered by maturation-inducing hormone (MIH), which acts on receptors on the oocyte surface. A synthetic estrogen, diethylstilbestrol (DES), possesses inducing activity of fish oocyte maturation, and a widely used biocide, pentachlorophenol (PCP), exhibits a potent inhibitory effect on fish oocyte maturation. In this study, the effects of the combined treatment by sonolysis with photolysis (sonophotocatalysis) to diminish the hormonal activity of DES and the maturation preventing activity of PCP was examined. By sonophotocatalysis, hormonal activity of DES was completely lost within 30 min and the inhibiting activity of PCP was lost within 120 min. These results demonstrated that sonophotocatalysis is effective for diminishing the endocrine-disrupting activity of chemical agents.

UV/H2O2 degradation of endocrine-disrupting chemicals in water evaluated via toxicity assays.

Due to rising concern regarding the presence of endocrine-disrupting chemicals (EDCs) in surface water and groundwater throughout the United States, Asia and Europe, treatment of these chemicals in drinking water and wastewater to protect human health and the environment is an area of great interest. Many conventional treatment schemes are relatively ineffective in removing EDCs from water and wastewater. This is concerning because these chemicals are biologically active at very low concentrations and effects of mixtures are relatively unknown. 17-alpha-oestradiol (E2) and 17-beta-ethinyl-oestradiol (EE2), suspected EDCs, were degraded significantly by the UV/H2O2 AOP. The UV/H2O2 processes using either low or medium pressure lamps were degraded EDCs by between 80 and 99.3% at a 15 ppm H2O2 concentration and a UV dose of 1,000 mJ/cm2. Significantly greater removal was noted when the removal was based on total oestrogenic activity using a yeast oestrogen screen (YES) assay. These data indicated that a dose of less than 200 mJ/cm2 completely removed oestrogenic activity in lab water. Values for natural waters were slightly higher. A steady state model was developed to determine EDC destruction efficiency in waters of differing quality. The model effectively predicted destruction in water, where concentrations of all scavenging species were known. Based on these results it was concluded than complete destruction of oestrogenic activity was possible under practical advanced oxidation conditions for a variety of water qualities.

Effect of alumina on photocatalytic activity of iron oxides for bisphenol A degradation.

To study the photodegradation of organic pollutants at the interface of minerals and water in natural environment, three series of alumina-coupled iron oxides (Al(2)O(3)-Fe(2)O(3)-300, Al(2)O(3)-Fe(2)O(3)-420, and Al(2)O(3)-Fe(2)O(3)-550) with different alumina fraction were prepared and characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) and Barret-Joyner-Halender (BJH), and Fourier transform infrared spectra (FTIR). The XRD results showed that existence of alumina in iron oxides could hinder the formation of maghemite and hematite, and also the crystal transformation from maghemite to hematite during sintering. It has been confirmed that the BET surface area and micropore surface area of Al(2)O(3)-Fe(2)O(3) catalysts increased with an increased dosage of alumina and with decreased sintering temperature. The pore size distribution also depended on the fraction of alumina. Furthermore, all Al(2)O(3)-Fe(2)O(3) catalysts had a mixed pore structure of micropore, mesopore and macropore. FTIR results showed that FTIR peaks attributable to Fe-O vibrations of maghemite or hematite were also affected by alumina content and sintering temperature. It was confirmed that the crystal structure and crystalline, the surface area and pore size distribution of Al(2)O(3)-Fe(2)O(3) catalysts depend strongly on the content of alumina and also sintering temperature. Bisphenol A (BPA) was selected as a model endocrine disruptor in aquatic environment. The effects of alumina on the photocatalytic activity of iron oxides for BPA degradation were investigated in aqueous suspension. The experimental results showed that the dependence of BPA degradation on the alumina content was attributable to the crystal structure, crystalline and also the properties of their surface structures. It was confirmed that the mixed crystal structure of maghemite and hematite could achieve the higher photocatalytic activity than maghemite or hematite alone.

Degradation of endocrine disrupting bisphenol A by 254 nm irradiation in different water matrices and effect on yeast cells.

The photodegradation of bisphenol A (BPA) in pure water, surface water and wastewater effluents was studied. The effect of different hydrogen peroxide concentrations on degradation was investigated. The rate of BPA photolysis in the presence of hydrogen peroxide was lower in wastewater effluent than in purified water. Phenol, 1,4-dihydroxylbenzene and 1,4-benzoquinone were identified by means of HPLC as intermediate products of the photodegradation of bisphenol A. In addition, the disappearance of the estrogenic activity of bisphenol A during irradiation was shown by the YES test. Based upon the YES test results, there was a strong decrease of estrogenic activity of parent compound after 120 min irradiation in the presence of hydrogen peroxide.

Photodegradation of endocrine disrupting chemical nonylphenol by simulated solar UV-irradiation.

The photolysis of nonylphenol (NP) was investigated using a solar simulator in the absence/presence of dissolved organic matter (DOM), HCO3-, NO3- and Fe(III) ions. The effects of different parameters such as initial pH, initial concentration of substrate, temperature, and the effect of hydrogen peroxide concentration on photodegradation of nonylphenol in aqueous solution have been assessed. The results indicate that the oxidation rate increases in the presence of H2O2, Fe(III) and DOM with dissolved organic carbon concentrations not higher than 3 mg L(-1). Phenol, 1,4-dihydroxylbenzene and 1,4-benzoquinone were identified as intermediate products of photodegradation of nonylphenol, through an HPLC method. In addition, the disappearance of the estrogenic activity of nonylphenol during irradiation using YES test was investigated. Based upon the YES test results, there was a strong decrease of estrogenic activity of nonylphenol after 80 h irradiation in the presence of hydrogen peroxide.