Application of titanium dioxide nanoparticles as a photocatalyst for the removal of micropollutants such as pharmaceuticals from water

Accepted Manuscript Application of titanium dioxide nanoparticles as a photocatalyst for the removal of micropollutants such as pharmaceuticals from water Waleed M.M. Mahmoud, Tushar Rastogi, Klaus Kümmerer PII:

S2452-2236(17)30029-9

DOI:

10.1016/j.cogsc.2017.04.001

Reference:

COGSC 66

To appear in:

Current Opinion in Green and Sustainable Chemistry

Received Date: 24 March 2017 Accepted Date: 3 April 2017

Please cite this article as: W.M.M. Mahmoud, T. Rastogi, K. Kümmerer, Application of titanium dioxide nanoparticles as a photocatalyst for the removal of micropollutants such as pharmaceuticals from water, Current Opinion in Green and Sustainable Chemistry (2017), doi: 10.1016/j.cogsc.2017.04.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Application of titanium dioxide nanoparticles as a photocatalyst for the removal of micropollutants such as pharmaceuticals from water

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Waleed M. M. Mahmoud§ 1,2, Tushar Rastogi§ 1, Klaus Kümmerer1*

Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

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1Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, Scharnhorststr. 1 C13, DE21335 Lüneburg, Germany.

Contributed equally to the article and share the first co-authorship

* Corresponding author

Email address: [email protected], [email protected] (W. Mahmoud), [email protected], [email protected] (T. Rastogi), [email protected] (K. Kümmerer)

ACCEPTED MANUSCRIPT Abstract The application of TiO2 nanoparticles as photocatalyst isn’t extensively used for the removal of micropollutants but also as an alternate to the traditional disinfection techniques. TiO2 photocatalysis is a more efficient method for the degradation of a lot of pharmaceuticals micropollutants

as

compared

to

photolysis.

Photocatalysis

often

degrades

those

micropollutants incompletely generating new molecules, the so-called transformation

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products (TPs). These TPs can retain the pharmacological activity, may be even more bioaccumulative and toxic than the parent compound, and/or can resist biodegradation. Thus, it is required to evaluate the risk associated with the presence of TPs generated during the treatment process. In this study, authors review recent research on the efficiency of TiO2

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photocatalysis for the removal of selected pharmaceuticals and possible formation of TPs. The review also discusses the existing knowledge gaps and addresses the need for further research

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into photocatalytic water treatment technology in the near future.

Keywords: Titanium dioxide nanoparticles; photocatalysis; mineralization; antibiotic; anti-

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inflammatory; toxicity

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1- Introduction More and more chemicals and pharmaceuticals are detectable in the aquatic cycle in the microgram per liter range ("micropollutants"). Pharmaceutical micropollutants are frequently detected in the different environmental compartments [1,2]. The increasing use of pharmaceuticals is raising questions about their potential risk to the environment and water

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quality in general [3]. Clean water and sustainable water management is one of the United Nations sustainable development goals (https://sustainabledevelopment.un.org/sdgs). In this context, micropollutants are one of the main challenges for water and wastewater treatment. Generally, conventional sewage treatment plants fail to remove pharmaceuticals completely

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from the water. This leads to an extensive R&D in the field of advanced water treatment technologies such as advanced oxidation processes (AOPs) [4] that can effectively remove

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these compounds. Photocatalytic processes using titanium dioxide (TiO2) nanoparticles are one of the promising AOPs for the removal of pharmaceuticals [5]. TiO2 is the most widely investigated photocatalyst as it is chemically and biologically inert, stable, and as a relatively low cost but highly photoactive semiconductor material without any loss of the catalytic activity with repeated use [6]. The TiO2 mediated photocatalytic mechanism has been well described in the literature [6,7]. When the TiO2 catalyst is irradiated

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with light of sufficient energy greater than the bandgap of the semiconductor, this leads to the generation of the positive hole in the valence band. These positive holes can generate effectively hydroxyl radicals in the water phase which in turn is a strong oxidant that is able to

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oxidize organic contaminants leading to mineralization [7]. The most common forms of TiO2 are anatase and rutile. TiO2 photocatalysts generally have a

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high share of anatase because of the higher photocatalytic activity of anatase. Researchers have compared the efficiency of different commercially available TiO2 nanoparticles such as Degussa P25; Hombicat UV-100; Tronox T-R; Tronox A-K-1; Tronox TR-HP-2; AldrichAnatase [8,9]. They have found out that Degussa P25 exhibits higher photocatalytic activity than the other commercially available TiO2 photocatalysts. They have attributed this to TiO2 structure having both forms such as anatase and rutile. Mixed phase TiO2 (anatase: rutile::75:25) has higher photocatalytic activity than pure crystalline phase for degradation of pharmaceuticals in the aqueous solutions. Several modifications were made for improving the efficiency of the TiO2 photocatalytic process such as increasing surface area and porosity, surface modifications, metal doping, and by integrating additional components in the TiO2 structure [10]. 2

ACCEPTED MANUSCRIPT Generally, TiO2 photocatalysis has a higher degradation rate constant than direct photolysis [11]. The TiO2 photocatalysis can also be coupled either with other AOPs and/or with biological treatment [12]. Moreover, TiO2 is also well known for its bactericidal action for the destruction of a broad spectrum of harmful microorganisms [13]. Therefore, TiO2 photocatalysis has advantages over the conventional disinfection techniques such as

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chlorination, which can generate highly toxic chloro-derivatives. Despite the merits of TiO2 photocatalysis, it also has a few drawbacks. Separation of TiO2 nanoparticles from the reaction mixture after its intended use is one of the challenges. Thus several attempts were made to immobilize TiO2 nanoparticles. Mineralization of contaminants

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is often incomplete and results in the formation of new, most often unknown and uncharacterized transformation products (TPs). These TPs can be either more toxic and/or more bioaccumulative compared to parent compounds. Also, TPs can have similar

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pharmacological potency as the parent compounds [14,15].

This review attempts to evaluate briefly the performance of TiO2 as photocatalysis for the removal of pharmaceutical residues in terms of inherent pharmacological potency and toxicity of generated TPs. Toxicity and residual pharmacological activity assessment of the generated TPs is an important step to assess the efficiency and efficacy of degradation processes and

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their environmental impacts (Figure 1). Authors have also tried to discuss the existing knowledge gaps and need for further innovative studies to promote photocatalytic water treatment technology.

Application of TiO2 photocatalysis in removal of pharmaceuticals

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Some pharmaceuticals are used as examples in the following for the sake of shortness. Table

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1 and 2 summarize the photocatalytic application of TiO2 nanoparticles for removal of different classes of pharmaceuticals (Tables 1-2). These were selected on the basis of their relevance to the environment and potential adverse effect. The collected data is arranged according to the therapeutic pharmacological action of the selected compounds. 2.1. Antibiotics

Antibiotics are widely used not only in human medicine but also for veterinary medicine. One of the main issues concerns the presence of antibiotics in the environment that it promotes the development of antibiotic resistance in bacteria and pathogens. Thus, antibacterial assay and ecotoxicological tests were performed for TiO2 photocatalytic samples in order to monitor the change in residual antibacterial activity and toxicity during the course of treatment. 3

ACCEPTED MANUSCRIPT Ciprofloxacin (CIP) is a fluoroquinolone antibiotic. Table 1 shows contradictions in the toxicity of samples resulting from the photocatalytic treatment of CIP aquatic solutions against Vibrio fischeri. This might be due to the difference in bacterial concentration applied in those tests leading to different test sensitivity and the usage of different light sources leading to formation of different TPs. Silva and co-workers, for example, have performed the

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test at a high bacterial concentration in order to have lower EC50 value of CIP. Interestingly, an aqueous solution of only TiO2 nanoparticles irradiated for 40 mins with UVA light shows toxicity against Vibrio fischeri [16]. This toxicity may be either due to the generation of reactive oxygen species which have the ability to destruct microorganisms and organic

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contaminants or the formation of hydrogen peroxide. The hydrogen peroxide has been reported to have inhibitory effects (toxicity) against Vibrio fischeri [17].

Due to the antibiotic resistance of bacteria, it is important to evaluate the residual antibacterial

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activity of the ciprofloxacin. Table 2 shows the efficiency of the TiO2 mediated photocatalytic process in decreasing the antibacterial activity of CIP. Paul and co-workers showed that photocatalysis has a higher degradation rate on the one hand and more TPs on the other compared to photolysis due to the complexity of the photocatalytic process [18]. Sulfamethoxazole (SMX) belongs to the sulfonamide group of antibiotics. TiO2

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photocatalysis was efficient in removal of SMX (Table 1) leading to the formation of TPs which are more toxic than SMX against Vibrio fischeri and Daphnia magna [12,19–21]. On the other hand, SMX’s TPs were less toxic to Chlorella vulgaris algae as well as more

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biodegradable as compared to SMX [22]. 2.2. Anticonvulsants

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Carbamazepine (CBZ) is one of the most prescribed antiepileptic drugs. CBZ and its metabolites are ubiquitous in the aquatic environment [23]. CBZ can be eliminated to a certain degree by TiO2 photocatalysis leading to the formation of different TPs depending on the applied irradiation sources (Table 1). The two hydroxylated TPs of CBZ formed during photocatalysis have been detected in the aquatic environment as CBZ human metabolites [24,25]. The TPs formed during the course photocatalytic treatment were reported to be highly toxic against Vibrio fischeri and Daphnia magna [25,26]. 2.3. Nonsteroidal anti-inflammatory drugs (NSAIDs) Diclofenac (DCF), commonly used as an analgesic, is one of the seven pharmaceuticals included in the European Union (EU) watch list of substances [27]. The presence of DCF has 4

ACCEPTED MANUSCRIPT been found both in surface water as well as in sewage effluent which causes different adverse effects [28]. For instance, the decline of vulture population in South Asian sub-continent causing ecological imbalance is due to DCF residues in dead animals which the vultures are feeding on [29]. Achilleos and co-workers [8] have reported a steep increase of toxicity against Daphnia

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magna during the photocatalysis (Table 1). This same phenomenon was also observed by Calza and co-workers [30]. They reported an increase in toxicity (up to 20 min) against Vibrio fischeri but no toxicity was reported after the 120 min of photocatalytic treatment due to 100% mineralization of DCF. The increase in the toxicity was due to the formation of highly

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toxic chlorinated derivatives (i.e. TPs) of DCF which have also degraded later on during the treatment. Rizzo and co-workers [31] have reported an increase in toxicity against Daphnia magna and Pseudokirchneriella subcapitata within the first 15 min of photocatalytic

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treatment, then a decrease and again a sudden increase in toxicity (Table 1). These examples demonstrate the significance and challenge of proper treatment time. Rizzo and co-workers also compared the photocatalytic treatment with photolysis. They observed that photolysis does not significantly degrade DCF as compared to photocatalysis. Another study has compared the toxicity of photocatalytic or photolytic treated DCF towards

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yeast [32]. The study reported the reduction of toxicity with the ongoing treatment, showing a higher decrease for the photocatalytic treated DCF solution as compared to photolytic treated solution. This demonstrates the significance of the endpoint used for toxicity assessment.

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2.4. Steroidal Estrogen

17 α-Ethinylestradiol (EE2), a steroidal estrogen, is the primary constituent in contraceptive

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pills. It is another pharmaceutical that is included in the EU watch list of substances [27]. This synthetic hormone can induce the feminization of male fish and falsify the reproductive potential of fish populations [33]. For the treatment of EE2, it is desirable that intermediates and/or final products should be at least less toxic and non-estrogenic in nature than EE2 in order to reduce the risk to the environment and humans. EE2 is reported to be phytotoxic towards Vigna radiata and Proteus vulgaris [34]. However, during the photocatalytic treatment of EE2 the phytotoxicity of the reaction mixture decreased (Table 1). The attacks of hydroxyl and superoxide radicals were proposed to be the main photocatalytic degradation pathways in that study.

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of EE2 could also remove the estrogenicity of the reaction mixture. However, it requires 2.4 times longer time to achieve the same result as compared to photocatalysis [36]. 2.5. β-Blockers

Several studies regarding the photocatalytic treatment of β-blockers reported the partial

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mineralization of parent compounds and indicated the formation of intermediate and stable TPs. The toxicity assessment of these TPs against Daphnia magna and Vibrio fischeri

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indicates the initial increase in toxicity followed by progressively decrease with treatment time as shown in Table 1[9,37–40]. During photocatalysis, the increase of biodegradability of the reaction mixture due to the generation comparatively more biodegradable TPs as compared to parent compounds were reported [38,39]. The increase of biodegradability of some TPs present reaction mixture during UVA photolysis as well as bio-persistence of others was reported by Rastogi and co-workers [41].

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3- Conclusions on gaps and needs

The literature suggests that TiO2 assisted photocatalysis may be potentially applicable for the removal of pharmaceuticals from water, given that some studies have reported on the

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complete mineralization of particular pharmaceuticals. The possibility of using solar energy also increases the economic viability of the process. However, there are still several open

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questions which need to be answered before photocatalytic water treatment technology can be safely operated in the near future: -

How do the concentration, matrix, and cocktail of different pharmaceuticals affect the photocatalytic process? Many available studies are based on single compounds and used the high concentrations, which hindered the understanding of the actual situation. A higher mineralization of the reaction mixture with pure water has been reported as compared to wastewater matrix [25]. Thus further research is needed for optimizing the photocatalytic conditions for mineralization of multiple pharmaceuticals in the presence of matrix interferences such as wastewater [42]. Also, the differences or similarities between laboratory scale, pilot, and industrial scale have not yet been credibly established. 6

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Uncertainty of generated TPs? Rarely photodegradation-generated TPs have been identified in the aquatic environment due to the lack of analytical standards and the complex matrix of environmental samples. It consequently still remains unclear whether the photoproducts determined during laboratory-scale treatment, especially when using ultrapure water matrix and single-compound solutions, are also formed under real

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conditions in the environment. This relates also to the significance quenchers on the one hand and photosensitizers on the other. -

Which toxicity endpoints and test organisms are relevant for assessing the generated TPs? The potentially additive, antagonistic and synergetic effects of TPs present in mixtures

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with parent compounds and other naturally occurring compounds and chemical elements also need to be investigated for both, acute and more importantly chronic effects focusing not only on ecotoxicity but also on mutagenicity and other relevant potential effects [43]. Are there optimum operating parameters for photocatalysis? And if yes, which ones are

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they? Nearly each publication on photocatalytic treatment of water has its own parameters set according to the needs of the individual study.. But the question arises whether these parameters can achieve the efficient treatment within a real wastewater operating scenario where pharmaceuticals will be present as a cocktail in a more or less complex matrix. An

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important parameter is the operating time. The intermittent occurrence of toxic and persistent TPs has often been reported, depending on the target compound, endpoint of toxicity selected and treatment time as well as other conditions. -

What parameters should be considered for deciding on the quality needed for the reuse of

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treated water? Global parameters such TOC, COD, etc. can no longer be the only basis of decisions on reuse of treated wastewater because the residual organic content of the

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effluent may be low but contain mixtures of parent compounds, their metabolites, and TPs of which the biological potency needs a careful assessment and consideration[14]. -

How can these TiO2 nanoparticles be safely disposed after their intended use? Proper removal and disposal methods for nanoparticles are needed because of their unique behavior, activity, and properties. The isolation and removal of TiO2 and other nanoparticles from the aquatic environment is still challenging [44,45].

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Are TiO2 nanoparticles themselves safe for humans and the environment if the removal is incomplete? TiO2 induces different toxicological effects such as genotoxicity and antibacterial effects due to the TiO2-medaited oxidative stress in cells [46–48]. The unintended releases of TiO2 to the aquatic environment raise questions about the

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development of chronic toxic effects.

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[46] R. Zhang, Y. Bai, B. Zhang, L. Chen, B. Yan, The potential health risk of titania nanoparticles, J. Hazard. Mater. 211-212 (2012) 404–413. [47]* T. Chen, J. Yan, Y. Li, Genotoxicity of titanium dioxide nanoparticles, J. Food Drug Anal. 22 (2014) 95–104. This review article reported genotoxicity results of TiO2 nanoparticles from different tests such as iComet assay, micronucleus assay, sister chromatid exchange assay, and mammalian cell. [48]** M. Skocaj, M. Filipic, J. Petkovic, S. Novak, Titanium dioxide in our everyday life; is it safe?, Radiol. Oncol. 45 (2011) 227–247. The review article provide a broad overview concerning the potential hazard of TiO2 for the human and environment [49] P. Calza, C. Medana, F. Carbone, V. Giancotti, C. Baiocchi, Characterization of intermediate compounds formed upon photoinduced degradation of quinolones by highperformance liquid chromatography/high-resolution multiple-stage mass spectrometry, Rapid Commun. Mass. Sp. 22 (2008) 1533–1552. [50] B. Czech, I. Josko, P. Oleszczuk, Ecotoxicological evaluation of selected pharmaceuticals to Vibrio fischeri and Daphnia magna before and after photooxidation process, Ecotox. Environ. Safe. 104 (2014) 247–253. [51] W. Li, C. Guo, B. Su, J. Xu, Photodegradation of four fluoroquinolone compounds by titanium dioxide under simulated solar light irradiation, J. Chem. Technol. Biotechnol. 87 (2012) 643–650. [52] K. Mao, Y. Li, H. Zhang, W. Zhang, W. Yan, Photocatalytic Degradation of 17αEthinylestradiol and Inactivation of Escherichia coli Using Ag-Modified TiO2 Nanotube Arrays, Clean Soil Air Water 41 (2013) 455–462. [53]** W. Zhang, Y. Li, Y. Su, K. Mao, Q. Wang, Effect of water composition on TiO2 photocatalytic removal of endocrine disrupting compounds (EDCs) and estrogenic activity from secondary effluent, J. Hazard. Mater. 215-216 (2012) 252–258. This review introduces various tests applied to evaluate the potential toxicity of TiO2 nanoparticles, for instance mammalian toxicity and ecotoxicty. The authors have disscussced the challenges in evaluating TiO2 toxicity.

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ACCEPTED MANUSCRIPT Figure caption

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Figure 1. Schematic consequences of TiO2 photocatalytic treatment for the degradation of pharmaceuticals micropollutants

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ACCEPTED MANUSCRIPT Table 1. Assessing the performance of TiO2 as photocatalysis for the removal of selected pharmaceuticals residues Pharmaceutic al compound (CAS No.)

Photocatalysis process

Transformation products and Elimination /mineralization

Test organism /Toxicity compared to parent compound

Addition findings (if any)

Reference

Antibiotics

• 6TPs were identified • 69-100% elimination

• Degussa P25 • 500-W xenon lamp (300800nm)

• 5 TPs during photolysis were identified • 100% elimination

• Degussa P25 • Hg–Ar lamp (UV-C)

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• Degussa P25 • UV light (LED lamp)

• 2 of the 5 major TPS were identified (sulfanilic acid and 3amino-5methylisoxazole) • 100% elimination • 2 intermediate were identified maleic and fumaric acids in case of O2/TiO2/UVA • 100% elimination

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• Degussa P25 • H.P. Hg lamp (700 W)

• Solid TiO2 • UV (40 W; λmax 366 nm)

Carbamazepine (CBZ; 298-464)

• Aeroxide P25 • UVA and SSI

• Vibrio fischeri • CIP was stable Neither CIP nor its under photolysis. TPs exhibit acute toxicity. • Vibrio fischeri • Photocatalysis No acute toxicity but showed higher increase in chronic removal efficiency toxicity (13–20%) than photolysis were observed • Vibrio fischeri Toxicity increased to • Photolysis showed 60% (30 min), then increase in toxicity immediately around 65% (30 decreased to 0 (60 min) then decrease min), then increase to until it has no toxic 40% (90 min) and effect at 180 min remain constant until 180 min

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• 10TPs were identified • Complete elimination of CIP

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• Degussa P25 • 1500W xenon lamp

• Vibrio fischeri Toxicity increased

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Sulfamethoxaz ole (SMX; 72346-6)

• 7 TPs were identified • 100% elimination after 45 min of CIP

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Ciprofloxacin (CIP; 8572133-1)

• TiO2 P25 • UVA

• Aqueous solutions of only TiO2 after photocatalysis present 38% toxicity

• Not identified • 100% elimination

• Daphnia magna Toxicity increased

• Toxicity increased in both photolysis and photocatalysis as the same TPs was formed in both.

• Daphnia magna O2/TiO2/UVA shows decrease in toxicity but TiO2/UVA shows increase in toxicity • Chlorella vulgaris, • SMX isn’t Beijerinck 1890, strain biodegradable but its A-8 TPs are TPs less toxic than biodegradable SMX

[16]

[49]

[19]

[20]

[21]

[12]

[22]

Anticonvulsants

• 9 TPs (UVA) and 8 TPS (SSI). Main TPs are monohydroxyderivatives 2-OHCBZ and 3-OH-CBZ • 75% elimination (45% mineralization; UVA/UPW), 69% elimination (40 % mineralization; SSI)

• Daphnia magna: 24h • Mineralization and 48 h toxicity tests increased with Decrease in toxicity increasing catalyst in case of UVA (24h loading. and 48 h) and SSI • Lower mineralization (24h). The 48h toxicity dropped after in wastewater and groundwater was 60min of SSI but obtained. reached 100% toxicity at 120 min.

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[25]

ACCEPTED MANUSCRIPT • Degussa P25 • M.P. Hg lamp (150W)

were obtained. • Not identified • 12-82% elimination depending on initial concentration

• Vibrio fisheri Increase in the toxicity

[26]

Nonsteroidal anti-inflammatory drug (NSAID)

• Anatase

• 80% primary • elimination • • Major TP: 8-chloro9H-(carbazol-1-yl) acetic acid.

• Degussa P25 • Xenon lamp (1500 W)

• 65 % removal of COD • TPs formed but not analyzed

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• Aeroxide P 25 • Fluorescent lamp (125 W)

• TiO2 nanotubes • UV LED lamp

Daphnia magna Toxicity steeply increases. Some of the TPs were highly toxic

Daphnia magna Vibrio fischeri Toxicity decreased

• D. magna is reported to be more sensitive compared to V. fischeri

Vibrio fischeri Toxicity first increased (up to 20 min) No toxicity after 120 min.

• Toxicity increase might be due to formation of chloroderivatives.

Daphnia magna Pseudokirchneriella subcapitata Toxicity first increased (up to 15min) then decreased and again at end increased. Artemia Salina It was not sensitive.

• Low adsorption (14%) of DCF onto TiO2 • Photolysis do not significantly degrade DCF

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(DCF; 1530786-5)

• 100 % mineralization • • Several hydroxyand bihydroxy-DCF derivatives • Further transformed into chloro or hydroxyl-phenol derivatives • •

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Diclofenac

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• 85% primary elimination • TPs formed but not analyzed

•

• 94 % primary elimination • Formed but not analyzed

•

• Degussa P25 was substantially more active than the other TiO2 samples • D. magna are more sensitive to TPs than to DCF itself

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• Degussa P25 • Hombicat UV-100 • Tronox T-R • Tronox A-K-1 • Tronox TRHP-2 • AldrichAnatase • UVA (9 W)

Yeast Toxicity reduced with treatment time.

[8]

[50]

[30]

[31]

• Slow reduction of toxicity for photolysis treatment

[32]

• Attack of hydroxyl and superoxide radical were the main degradation pathways

[34]

Steroid Estrogen 17 αethinylestradiol (EE2; 57-63-6)

• (Ag/Zr-TiO2) • Xenon Lamp (300W)

• Complete primary elimination with partial mineralization • TPs were formed and identified.

• Vigna radiata (Phytotoxicity) • Proteus vulgaris (Phytotoxicity) Phytotoxicity reduced

β-Blockers 15

ACCEPTED MANUSCRIPT

Atenolol & Propranolol

• Degussa P25 • Sunlight • Xe-OP lamp (1000W)

• Degussa P25 • Xe-OP lamp (1000W)

Propranolol (PPL; 525-666)

• Anatase

(MTL; 3735058-6)

[9]

• Daphnia magna Toxicity increased initially and then progressively decreased

• >81 % elimination and >30 % mineralization • Formed but not analyzed

• LuminoTox® Toxicity decreased with treatment time (sunlight irradiated samples).

• For sunlight irradiated samples biodegradability improved slightly after 270 min

[39]

• 100% elimination with 55% mineralization • 4 TPs were identified

• Vibrio fischeri Toxicity first increased then constantly decreases

• At the end, highly biodegradable TPs were formed.

[38]

• STP effluent spiked samples showed a very low rate for the photocatalytic process compared with pure water.

[40]

• 100% elimination with 17% mineralization • 31 TPs were identified

• 50% primary elimination • Major TPs: aromatic 4-(2methoxyethyl)phen ol

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Metoprolol

• Degussa P25 was substantially more active than the other TiO2 samples • Formation of some early-stage toxic TPs that could be further degraded by prolonged irradiation.

• Partial elimination and mineralization • TPs Formed but not analyzed

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• Ce-TiO2 • Xe-OP lamp (1000W)

[37]

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• Degussa P25 • Hombicat UV-100 • Tronox T-R • Tronox A-K-1 • Tronox TRHP-2 • AldrichAnatase • Xe-OP lamp (1000W)

• Vibrio fischeri (MicroTox) No toxicity observed.

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(ATL; 2912268-7)

• Complete mineralization • 23 TPs were identified

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• Degussa P25 • Xenon Lamp (1500W)

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Atenolol

• Pseudokirchneriella subcapitata • Vibrio fischeri Toxicity tend to decrease (STP effluent spiked samples) In pure water toxic TPs lead to the accumulate • Daphnia magna Toxicity decreased (~ 40%) • Vibrio fischeri Toxicity reduced 3 times

[50]

• 100% primary • Comparative elimination with more • Vibrio fischeri [38] 55% mineralization biodegradable Toxicity reduced • 3 TPs were TPs were formed identified H.P.: High Pressure, M.P.: Medium Pressure, UVA: ultraviolet A light, SSI: simulated solar irradiation, UPW: ultrapure water • Degussa P25 • Xe-OP lamp (1000W)

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ACCEPTED MANUSCRIPT Table 2- Evaluation of TiO2 photocatalysis treatment process on the basis of inherent pharmacological potency of TPs for selected compounds

Pharmaceutica l compound (CAS No.)

Photocatalysis process

Findings

Reference

Antibiotics (Antibacterial activity)

Steroidal Estrogen (Estrogenic activity) • TiO2 • H.P. Hg lamp (125 W) • TiO2/Ag-TiO2 nanotubes arrays • L.P. Hg lamp (8W) • TiO2 (Degussa P25) • L.P. Hg lamp (8W)

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[18]

[51]

• 100% removal of estrogenicity. • UVA photolysis took 2.4 times longer time to achieve the same results.

[36]

• >92 % primary elimination of EE2. • Estrogenicity was effectively decreased.

[52]

• Partial mineralization. • 12 TPs were Identified • Reduction in the estrogenicity.

[35]

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17 α-Ethinyl Estradiol (EE2; 57-63-6)

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• TiO2 (Degussa P25) • Xenon lamp (800 W)

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Ciprofloxacin (CIP; 8572133-1)

• TiO2 (Hombikat UV100) • Xenon lamp (450W) (Vis: > 400 nm, or Vis+UVA:> 324 nm)

• Decrease in the antibacterial potency of irradiated solutions against Escherichia coli • The degradation rate followed the trend Vis+UVA /TiO2>Vis-TiO2> Vis+UVA • 80% elimination (50min Vis-TiO2); 100% elimination (25min UVA-TiO2) • 2 and 6 TPs were identified during photolysis and photocatalysis, respectively. • The antibacterial activity against Bacillus subtilis was completely removed by the photocatalytic treatment. • 86-96% elimination

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• TiO2 (Degussa P 25) • Estrogenicity decrease. • Black light lamp (6W) H.P.: High Pressure; L.P.: Low Pressure; Vis: visible light; UVA: ultraviolet-A

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[53]

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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT Highlights TiO2 photocatalysis process is more promising as simple photolysis. TiO2 photocatalysis often leads to incomplete mineralization. The generated degradation products may be more toxic than parent compounds.

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Different toxicological endpoints are required to assess the risk of the treatment.

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Knowledge gaps still exist regarding photocatalytic treatment in real-world scenario.