Spatial distribution and removal performance of ...

Science of the Total Environment 586 (2017) 1162–1169

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Spatial distribution and removal performance of pharmaceuticals in municipal wastewater treatment plants in China Hou-Qi Liu a,c, James C.W. Lam b,d, Wen-Wei Li a,c, Han-Qing Yu a,⁎, Paul K.S. Lam b,⁎ a

CAS Key Laboratory of Urban Pollutant Conversion, Department of Chemistry, University of Science & Technology of China, Hefei 230026, China State Key Laboratory in Marine Pollution (SKLMP), Research Centre for the Oceans and Human Health, Shenzhen Key Laboratory for Sustainable Use of Marine Biodiversity, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, China c Suzhou Institute for Advanced Study, USTC, Suzhou, Jiangsu 215123, PR China d Department of Science and Environmental Studies, The Education University of Hong of Kong, Hong Kong SAR, China b

H I G H L I G H T S

G R A P H I C A L

A B S T R A C T

• Caffeine showed the highest influent concentration than other pharmaceuticals. • WWTPs in north China had higher influent level of total pharmaceuticals. • Pharmaceuticals removal performance was associated with the treatment processes. • Several high-risk pharmaceuticals to the environment were identified.

a r t i c l e

i n f o

Article history: Received 7 January 2017 Received in revised form 12 February 2017 Accepted 13 February 2017 Available online 20 February 2017 Editor: Jay Gan Keywords: Pharmaceuticals Antibiotics Wastewater treatment plants Removal efficiency Regional distribution Risk assessment

a b s t r a c t Municipal wastewater treatment plants (WWTPs) are an important source of pharmaceuticals released into the environment. Understanding how various pharmaceuticals are distributed and handled in WWTPs is a prerequisite to optimize their abatement. Here we investigated the spatial distribution and removal efficiencies pharmaceuticals in China's WWTPs. A total of 35 pharmaceuticals in wastewater samples from 12 WWTPs at different cities of China were analyzed. Among these detected pharmaceuticals, caffeine showed the highest concentration (up to 1775.98 ng L−1) in the WWTP influent. In addition, there were significant regional differences in pharmaceutical distribution with higher influent concentrations of total pharmaceuticals detected in WWTPs in the northern cities than the southern ones. The state-of-the-art treatment processes were generally inefficient in removing pharmaceuticals. Only 14.3% of pharmaceuticals were removed effectively (mean removal efficiency N 70%), while 51.4% had a removal rate of below 30%. The anaerobic/anoxic/oxic (AAO)-membrane bioreactor (MBR) integrated process and sequencing batch reactor (SBR) showed better performance than the AAO and oxidation ditch (OD) processes. Ofloxacin, erythromycin-H2O, clarithromycin, roxithromycin and sulfamethoxazole in WWTP effluents exhibited a high or medium ecological risk and deserved special attention. © 2017 Elsevier B.V. All rights reserved.

1. Introduction ⁎ Corresponding authors. E-mail addresses: [email protected] (H.-Q. Yu), [email protected] (P.K.S. Lam).

http://dx.doi.org/10.1016/j.scitotenv.2017.02.107 0048-9697/© 2017 Elsevier B.V. All rights reserved.

Water contamination by pharmaceuticals, especially antibiotics, has become a serious global issue (Gao et al., 2012). Various unconsumed

H.-Q. Liu et al. / Science of the Total Environment 586 (2017) 1162–1169

pharmaceuticals and their metabolites mostly enter municipal wastewater treatment plants (WWTPs) via the sewer system (Al-Rifai et al., 2010). However, the existing treatment facilities, which are designed for removing biodegradable organics and nutrients, cannot effectively eliminate these recalcitrant chemicals, leading to considerable discharge of pharmaceuticals into aquatic environments (Liu and Wong, 2013; Tamtam et al., 2011). In particular, pharmaceutical contamination is very severe in China, which has the world's highest production and use of pharmaceuticals yet extremely underdeveloped treatment facilities. Therefore, enhancing pharmaceutical removal in China's WWTPs is an urgent task, which entails good knowledge of the distribution characteristics and fates of pharmaceuticals in WWTPs. Many developed countries started to collect information about pharmaceutical removal in WWTP decades ago, but in China such studies are still at the very beginning. To date, a few case studies about the occurrence and removal of pharmaceuticals in several individual WWTPs of China have been reported, focusing on only a few groups of pharmaceuticals (mainly antibiotics) (Chen and Zhang, 2013; Gao et al., 2012; Leung et al., 2011; Li et al., 2013; Wen et al., 2016; Wu et al., 2016; Zhou et al., 2013). However, the overall spatial distribution and removal performance of pharmaceuticals in China's WWTPs is still poorly understood. The present study aims to bridge this knowledge gap. We investigated the regional distributions and removal levels of 35 pharmaceutical compounds at 12 WWTPs in different cities of mainland China. In addition, the potential ecological risks of the residual pharmaceuticals in WWTP effluent were assessed using risk quotients (RQs) (Hernando et al., 2006a). This study may provide useful information to guide the design and operation of WWTPs in China for more efficient pharmaceutical removal.

2. Materials and methods 2.1. Chemicals and reagents All the chemicals used were of analytical grade or above. Ultrapure water (18.2 MΩ cm) produced from the Milli-Q system was used throughout the study. Antibiotic standards, HPLC-grade methanol, formic acid (99%) and disodium ethylenediamine tetraacetate (Na2ETDA) were purchased from Sigma-Aldrich. Oasis hydrophilic-lipophilic balanced (HLB, 200 mg, 6CC, Waters, USA) solid phase extraction (SPE) cartridges were purchased from Waters Co. Ltd. Individual stock solutions of pharmaceuticals and isotope-labeled internal standards were prepared according to the method proposed by Leung et al. (2011). All samples and stock solutions were stored in the dark at −20 °C. Working standard solutions of pharmaceuticals at different concentrations (5, 10, 20, 50 and 100 ng L−1) were prepared freshly in Milli-Q water from the stock solutions prior to use.

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2.2. Sampling Influent and effluent samples were collected from 12 WWTPs during October to November 2015. The studied WWTPs were located in 12 representative major cities in China. Details of the WWTPs, including locations, treatment process, wastewater sources and actual daily loads of each WWTPs, are summarized in Table 1. Samples at each site were collected in duplicate. The collected samples were immediately stored in 1 L polypropylene bottles wrapped with aluminum foil to avoid photo-degradation, and then filtered through 0.45 μm glass fiber filters. After filtration, the samples were stored at 4 °C in a refrigerating cabinet in the dark, extracted within 24 h, and stored in a −20 °C freezer until analysis. 2.3. Sample extraction and analytical procedures The samples were subjected to solid phase extraction (SPE) and analyzed by liquid chromatography coupled with tandem mass spectrometry. Briefly, 50 μL of the internal standards (mixed pharmaceuticals, 1 mg L−1) were spiked into 50 mL filtered sewage water samples prior to extraction. After full mixing and equilibration for 30 min at ambient temperature, 1 mL of Na2EDTA (5%, m/v) and 0.25 mL NaN3 (100 g L− 1) were added to each sample. The mixture was diluted to 250 mL using Milli-Q water and its pH was adjusted to 2.5 by adding 5 M formic acid. The resulting solution was concentrated by SPE using the Oasis HLB cartridges. Oasis HLB cartridges were preconditioned with 4 mL of methanol and 4 mL of ultrapure water prior to use. Subsequently, the samples were loaded into the cartridges at a flow rate of b3 mL min− 1, and each cartridge was rinsed with 4 mL of ultrapure water to remove Na2EDTA and other impurities. The cartridges were centrifuged at ×4000g for 5 min and 4 mL of methanol eluates containing the target compounds were evaporated to 0.2–0.3 mL using a gentle stream of nitrogen. Then, the liquid volume was adjusted to 0.5 mL with Milli-Q water and centrifuged (×4000g, 5 min). The supernatant was transferred to a 0.35 mL amber vial. The analyte identification and quantification were performed using a liquid chromatography-tandem mass spectrometer system (LC-MS/MS) consisting of an Agilent 1290 Infinity LC (Agilent Technologies, Palo Alto, CA, USA) coupled to AB SCIEX QTRAP 3200 (Minh et al., 2009). Each sample was analyzed in duplicate. 2.4. Method validation and quality control The target analytes were identified by comparing the retention time and the ratio (within 20%) of the two selected multiple reaction monitoring transitions with those of standards. The calibration curves were obtained by using pharmaceuticals within a concentration range of 5–100 ng L−1. The average procedure blank plus three times the standard deviation (n = 10) was set as the method detection limit (MDL)

Table 1 Description of 12 studied WWTPs in this work. Location

Average daily flow (×103 m3 day−1)

Wastewater source

Population served

Treatment process

Shanghai Xi'an Guangzhou Hangzhou Changsha Chengdu Beijing Chongqing Harbin Nanjing Hefei Jinan

60 100 300 600 40 1000 43.9 40 25 100 180 300

Sewage Sewage + industrial waster Sewage Sewage + industrial waster Sewage Sewage Sewage Sewage Sewage + small portion of pharmaceutical wastewater Sewage Sewage Sewage

105,000 400,000 1000,000 1,500,000 133,000 3,000,000 100,000 100,000 60,000 200,000 304,000 540,000

AAO AAO AAO AAO SBR AAO AAO SBR AAO AAO + MBR OD AAO

Notes: AAO, Anaerobic/Anoxic/Oxic; SBR, Sequencing Batch Reactor; MBR, Membrane Bioreactor; OD, Oxidation Ditch.

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Table 2 Ecological risk assessment of pharmaceuticals into receiving aquatic environment. Compound

Test organism EC50 (mg L−1)

Mean RQs

Reference

Amoxicillin Erythromycin-H2O Clarithromycin Roxithromycin Norfloxacin Ofloxacin Levofloxacin

M. aeruginosa P. subcapitata P. subcapitata P. subcapitata V. fisheri V. fisheri Anabaena CPB4337 S. leopolensis R. salina M. aeruginosa

0.004 0.020 0.020 0.004 0.022 0.014 4.800

b0.01 3.43 2.61 3.09 0.59 3.30 b0.01

0.027 16.000 0.050

0.86 b0.01 0.03

(Lützhøft et al., 1999) (Isidori et al., 2005) (Isidori et al., 2005) (Yang et al., 2008) (Backhaus et al., 2000) (Backhaus et al., 2000) (González-Pleiter et al., 2013) (Ferrari et al., 2004) (Lützhøft et al., 1999) (Halling-Sørensen, 2000) (Isidori et al., 2005) (Lützhøft et al., 1999) (Backhaus et al., 2000) (Ferrari et al., 2004) (Huggett et al., 2002) (Ferrari et al., 2004) (Farré et al., 2002) (Farré et al., 2002) (Calleja et al., 1994) (Ferrari et al., 2004)

Sulfamethoxazole Trimethoprim Chlortetracycline Lincomycin Metronidazole Flumequine Clofibric acid Metoprolol Diclofenac Ibuprofen Salicylic acid Caffeine Carbamazepine

P. subcapitata Chlorella sp. V. fisheri S. leopolensis C. dubia V. fisheri V. fisheri V. fisheri D. magna C. dubia

0.070 38.800 0.019 40.200 8.800 11.450 12.100 43.100 15.960 0.025

0.42 b0.01 0.22 b0.01 b0.01 b0.01 b0.01 b0.01 b0.01 0.17

level to offset the background contamination and matrix effect. The linear range of the calibration curves varied for different detected chemicals, but all showed good linearity (R2 N 0.995). In LC-MS/MS analysis, the complicated matrix of wastewater may influence the analytical

sensitivity and reliability. Isotopically-labeled surrogates were used to compensate for experimental losses and matrix effect. The analyte recovery percentages in the influent and effluent were 59%–100% and 66%–104%, respectively. Repeatability was determined by analyzing triplicate of wastewater samples and the relative standard deviations were in a range of 2–13%. Blank controls free of pharmaceuticals were used to verify that the examples were not contaminated by ions during the extraction and analysis procedures. Statistical analysis was performed using IBM SPSS Statistics (version 20). The removal efficiencies (RF, %) of pharmaceuticals in WWTPs were calculated according to the influent and effluent concentrations (Leung et al., 2011; Subedi et al., 2015). RF ¼

CI F CE F 100% CI F

where CIF and CEF are the concentrations (ng L−1) of a given analyte in the influent and effluent, respectively. 2.5. Environmental risk assessment The potential risks of the pharmaceuticals were assessed following the European Medicines Agency guidelines. The risk quotient (RQ), which defines the potential ecological risk of a given pharmaceutical in relation to the aquatic environment, was calculated based on the toxicological data and the measured effluent concentrations. RQ is defined as the ratio of the measured concentration to the predicted no-effect concentration. The value of predicted no-effect concentrations were

Fig. 1. Map showing the locations and ratios of 35 detected pharmaceuticals concentrations at 12 representative WWTPs in China. The area size of the pie chart represents the ratios of influent concentration of all detected pharmaceuticals, different colors represent the pharmaceuticals concentrations ratio of treated (removed) and untreated (effluent residual), respectively.


extrapolated from mean EC50 values divided by an assessment factor of 1000 in acute toxicity test (Thomaidi et al., 2015). Three risk levels are defined according to the RQ values: ‘low risk’ (from 0.01 to 0.1); ‘medium risk’ (from 0.1 to 1); and ‘high risk’ (N1) (Hernando et al., 2006b). The detailed toxicity data are shown in Table 2. 3. Results and discussion 3.1. Detected species of pharmaceuticals in WWTPs Among 50 tested pharmaceuticals, 35 were detected in the influent and/or the effluent samples from the 12 representative WWTPs in China (Fig. 1). The detection frequency of these 35 pharmaceuticals varied significantly in different WWTPs (Fig. 2). In all, 25.7% of the pharmaceuticals had a detection frequency of below 50% in the influent; 40% of the pharmaceuticals showed high detection frequencies of over 75.0%. Erythromycin-H2O, sulfamethoxazole, lincomycin and hydrochlorothiazide were detected by 100%. The detection frequencies of roxithromycin, norfloxacin, ofloxacin, metronidazole, caffeine and Nacetyl sulfamethoxazole were also above 90.0%. In all, the most frequently detected pharmaceuticals included macrolides, quinolones, lincosamides, amphenicols, stimulant and anti-blood pressure pharmaceuticals, indicating a wide use of these pharmaceuticals in China. 3.2. Regional distribution of pharmaceuticals in WWTP influent The total pharmaceuticals in WWTP influents exhibited obviously unbalanced regional distribution (Fig. 1). Generally, the concentrations were lower in the south than in the north cities, likely due to the higher rainfall that to a certain extent dilutes the wastewater and the better developed sewer systems in the southern cities. One exception is the WWTP in Shanghai, which had the highest cumulative concentration levels of total pharmaceuticals in the influent (9988.08 ng L−1), attributed to its high population density. The influent concentrations of different pharmaceutical species varied substantially (Fig. 3). Among all the detected pharmaceuticals, caffeine showed the highest concentration (average value = 1775.98 ng L−1, median value = 1414.57 ng L−1) in the influent of all WWTPs. Acetaminophen, N-acetyl sulfamethoxazole, norfloxacin, ofloxacin, lincomycin, chloramphenicol, erythromycin-H2O and azithromycin also had relatively high concentrations (average concentration N 100 ng L−1, median concentration N 25 ng L−1).

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Most of the detected high-concentration pharmaceuticals belong to antibiotics (Fig. 3), which are of considerable environmental concern. Therefore, we specifically studied the concentration distribution of nine groups of antibiotics (including 17 different antibiotics) in the WWTPs (Fig. 4). The Harbin WWTP had the highest concentrations of total antibiotics (4019.18 ng L−1) and individual antibiotics (Azithromycin, 1592.53 ng L−1) in the influent, possibly due to mixed wastewater sources (i.e., a small portion of pharmaceutical wastewater after preliminary treatment also flows into the WWTP in Harbin). High concentrations of total antibiotics (around 2000 ng L− 1) were also found in WWTPs of Shanghai, Xi'an and Chongqing. The dominant species of antibiotics varied significantly among the different regions. Quinolones were the dominant antibiotic species in the influent of most of the WWTPs, while amphenicols dominated in Shanghai and Xi'an WWTPs and macrolides accounted for over 65% of the influent antibiotics in Harbin WWTP. To understand what was responsible for such an unbalanced regional distribution of pharmaceuticals, we analyzed whether the total pharmaceuticals concentration was related to the population served of the selected WWTPs, and found a poor correlation between them (R2 = 0.030) (Fig. 5). Also, the total pharmaceuticals concentration and water consumption per capita showed no significant correlation (R2 = 0.012). In addition, neither the total pharmaceuticals concentrations nor average usage of pharmaceuticals in the studied regions were significantly correlated to the average GDP per capita. In all, the influent concentration of total pharmaceuticals in the WWTPs was not substantially affected by the serviced population, average GDP per capita and water consumption per capita. However, a high correlation coefficient (R2 = 0.895) was found between the total pharmaceutical concentrations and pharmaceutical usage amount per capita. Therefore, the different influent total concentrations and species of pharmaceuticals in the studied WWTPs should be attributed mainly to the different usage amount and habit in these regions. 3.3. Removal efficiencies of pharmaceuticals After treatment, a considerable amount of pharmaceuticals remained in the WWTP effluent (Fig. 2). The removal efficiencies of total pharmaceuticals (i.e., 35 pharmaceuticals together) varied substantially among the 12 WWTPs (Fig. 2). To find out whether the different treatment performances were associated with the adopted treatment processes, we classified the 12 WWTPs into four groups

Fig. 2. Detection frequency (%) of 35 detected target pharmaceuticals in influents and effluents in 12 representative WWTPs in China.

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Fig. 3. Individual concentrations (ng L−1) of 35 pharmaceuticals in 12 WWTPs.

according to the applied secondary treatment process, and compared their total pharmaceutical removal efficiencies. The four groups of WWTPs adopt different treatment processes, including sequencing batch reactor (SBR), anaerobic/anoxic/oxic (AAO), oxidation ditch (OD), and AAO-membrane bioreactor (MBR) integrated process (Table 1). To our surprise, the mean removal efficiencies in the WWTPs were all pretty high (from 85.9% to 98.5%) despite of the different treatment processes (Fig. 6a), which is in contradictory with the generally low removal efficiencies obtained for most individual pharmaceuticals (only 2 of the 35 pharmaceuticals were removed by over 80%) (Fig. 7). Specifically, caffeine and N-acetyl sulfamethoxazole exhibited an extremely high removal efficiency of 89.2% and 90.3%%, respectively. Previous studies also reported that caffeine can be removed almost completely due to its easy adsorption and biodegradation (Liu and Wong, 2013; Zhou et al., 2010). In our study, 16 of the 35 pharmaceuticals had very poor removal efficiencies of 5.6%–29.5%, while only 5 pharmaceuticals

had removal efficiencies of above 70%. Besides N-acetyl sulfamethoxazole and caffeine, the other three efficiently removed pharmaceuticals included norfloxacin (79.6%), acetaminophen (72.7%) and chloramphenicol (71.9%). The inconsistency of removal efficiencies for total and individual pharmaceuticals here was mainly caused by a few pharmaceuticals that had extremely high concentrations and high removal efficiencies, which raised the overall removal efficiency of total pharmaceuticals and resulted in the overestimated treatment performance. These interrupting pharmaceuticals included acetaminophen, caffeine, salicylic acid, lincomycin, azithromycin and chloramphenicol. Given that these pharmaceuticals can be more readily degraded in environments and are of lower environmental concern (Leung et al., 2011; Subedi et al., 2015; Yan et al., 2013; Zhang et al., 2012; Zhou et al., 2010), we eliminated them from the total pharmaceutical count so that the real impacts of treatment processes on the removal of

Fig. 4. Concentrations of detected 9 groups of antibiotics in the WWTP influent and effluent.


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Fig. 5. Correlation between the total concentration of 35 pharmaceuticals and the population served by WWTP, GDP per capita, average water consumption and pharmaceutical usage amount per day in the WWTP-located region.

pharmaceuticals could be revealed. The result shows that, after excluding the 6 high-concentration pharmaceuticals, the total removal efficiencies of the rest 29 pharmaceuticals in the four treatment processes were much lower, and their difference became more distinct (Fig. 6a). The SBR and AAO + MBR processes showed obviously better performance than the AAO and OD processes, which might be associated with the lower washout of slow-growing functional microorganisms in these two systems as a result of significantly increased sludge retention time (SRT) (Batt et al., 2006; Jeong et al., 2010; Silva et al., 2015) and a prolonged treatment time of pharmaceuticals in the MBR system (Long and Hawkes, 2007; Sahar et al., 2011). These results demonstrate

that the treatment process did have non-ignorable impact on the pharmaceutical removal performance. In addition to the treatment process, many other factors also affected pharmaceutical removal performance. To exclude the influence from treatment process, we compared the total removal efficiencies of the 29 pharmaceuticals in 5 different WWTPs that all adopted the same AAO treatment process and had similar sewage source. The removal efficiencies in these WWTPs varied substantially from 37.4% to 64.1%. Here, the WWTPs in Shanghai, Guangzhou and Jinan showed relatively higher removal efficiencies than those in Beijing and Chengdu, which might be associated with the regional differences in pharmaceutical

Fig. 6. Mean removal efficiencies (%) in WWTPs with different treatment processes (a), removal efficiencies of pharmaceuticals in WWTPs with AAO treatment process (b).

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Fig. 7. Removal efficiencies of 35 individul pharmaceuticals in the WWTPs.

concentrations and compositions that considerably affect their degradation. More pharmaceuticals (such as erhthromycin-H2O, norfloxacin, ofloxacin and levofloxacin, etc.) with relative high concentrations and removal efficiencies were found in the WWTPs in Shanghai, Guangzhou and Jinan. In addition, the relatively high temperature might also have contributed to the very high overall removal efficiencies in Shanghai and Guangzhou WWTPs. Previous studies have shown that temperature is an important factor affecting the removal of pharmaceuticals (Sui et al., 2011). 3.4. Ecological risk assessment The concentrations of some pharmaceuticals in WWTP effluent were still very high and may cause non-negligible environmental risks (Fig. 4). Since it is difficult to eliminate all pharmaceuticals, it is

important that special controls should be implemented for some priority pollutants that have high risks. The RQ values of the 20 pharmaceuticals in the WWTP effluent were estimated and summarized in Fig. 8 and Table 2. Specifically, ofloxacin posed high risk to aquatic organisms, the occurrence probability of high risk in the 12 WWTPs was 58.3%, implying a high potential environmental risk of these pharmaceuticals. Therefore, it should be listed as a priority pollutant to be controlled in China. Tang et al. (2014) have been reported that ofloxacin presented a significant environmental risk to aquatic organisms. Four pharmaceuticals, including erythromycin-H2O, clarithromycin, sulfamethoxazole and carbamazepine, posed at least medium risk in most WWTPs, the occurrence probability of causing medium or above risk by these compounds in the 12 WWTPs were 83.8%, 50.0%, 91.7% and 58.3%, respectively. Similar results were reported by Zhang et al. (2012) and Yan et al. (2013), who

Fig. 8. Risk quotients (RQs) for 20 pharmaceuticals in the WWTP effluents.


found that sulfamethoxazole showed high or medium risk to aquatic organisms. The rest pharmaceuticals in the most selected WWTPs presented low or no obvious risk to sensitive aquatic organisms. Nevertheless, the mixture toxicity of these pharmaceuticals and the long-term environmental impact and ecological risks of the pharmaceuticals were not considered here, which warrants future investigations. 4. Conclusions The spatial distribution and removal performance of pharmaceuticals in 12 typical WWTPs in China were investigated. The concentrations of detected pharmaceuticals varied significantly among different pharmaceutical species and different WWTPs. The concentrations of total pharmaceuticals in WWTP influent were generally higher in north China than in the south. Among the 35 detected pharmaceuticals in WWTP influents, caffeine was the most dominant species, while quinolones and macrolides were also abundantly found in most WWTPs. The removal efficiencies of total pharmaceuticals varied significantly under different treatment processes. A higher removal was found in SBR and AAO + MBR processes than in AAO and OD processes due to the less washout of slow-growing biomass and prolonged treatment time in these two systems. A considerable amount of pharmaceuticals remained in the WWTP effluents, among which ofloxacin, erythromycin-H2O, clarithromycin, roxithromycin and sulfamethoxazole exhibited high or medium ecological risks. Thus, these pharmaceuticals need to be considered as priority contaminants in future wastewater management in China. Acknowledgements This work was supported by the National Natural Science Foundation of China (51522812, 51538012, 41276111); the NSFC-RGC fund (21261160489), the National Natural Science Foundation of China (NFSC)-Research Grants Committee Joint Research Scheme (N_CityU127/12), the General Research Fund (CityU 11338216, 11100614), Science Technology and Innovation Committee of Shenzhen Municipality (JCYJ20130401145617289) and the Collaborative Innovation Center of Suzhou Nano Science and Technology of the Ministry of Education of China for the partial support of this study. References Al-Rifai, J.H., Khabbaz, H., Schäfer, A.I., 2010. Removal of pharmaceuticals and endocrine disrupting compounds in a water recycling process using reverse osmosis systems. Sep. Purif. Technol. 77, 60–67. Backhaus, T., Scholze, M., Grimme, L.H., 2000. The single substance and mixture toxicity of quinolones to the bioluminescent bacterium Vibrio fischeri. Aquat. Toxicol. 49, 49–61. Batt, A.L., Kim, S., Aga, D.S., 2006. Enhanced biodegradation of iopromide and trimethoprim in nitrifying activated sludge. Environ. Sci. Technol. 40, 7367. Calleja, M.C., Persoone, G., Geladi, P., 1994. Comparative acute toxicity of the first 50 multicentre evaluation of in vitro cytotoxicity chemicals to aquatic non-vertebrates. Arch. Environ. Contam. Toxicol. 26, 69–78. Chen, H., Zhang, M., 2013. Occurrence and removal of antibiotic resistance genes in municipal wastewater and rural domestic sewage treatment systems in eastern China. Environ. Int. 55C, 9–14. Farré, M.L., Ferrer, I., Ginebreda, A., Figueras, M., Olivella, L., Tirapu, L., Vilanova, M., Barceló, D., 2002. Determination of drugs in surface water and wastewater samples by liquid chromatography–mass spectrometry: methods and preliminary results including toxicity studies with Vibrio fischeri. J. Chromatogr. A 938, 187–197. Ferrari, B., Mons, R., Vollat, B., Fraysse, B., Paxēaus, N., Giudice, R.L., Pollio, A., Garric, J., 2004. Environmental risk assessment of six human pharmaceuticals: are the current environmental risk assessment procedures sufficient for the protection of the aquatic environment? Environ. Toxicol. Chem. 23, 1344–1354. Gao, L., Shi, Y., Li, W., Niu, H., Liu, J., Cai, Y., 2012. Occurrence of antibiotics in eight sewage treatment plants in Beijing, China. Chemosphere 86, 665–671. González-Pleiter, M., Gonzalo, S., Rodea-Palomares, I., Leganés, F., Rosal, R., Boltes, K., Marco, E., Fernández-Piñas, F., 2013. Toxicity of five antibiotics and their mixtures

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