- Email: [email protected]
Seasonal occurrence and removal of pharmaceutical products in municipal wastewaters
Journal of Environmental Chemical Engineering 2 (2014) 495–502
Contents lists available at ScienceDirect
Journal of Environmental Chemical Engineering journal homepage: www.elsevier.com/locate/jece
Seasonal occurrence and removal of pharmaceutical products in municipal wastewaters Manuel Ferna´ndez a, Mo´nica Ferna´ndez b, Amanda Laca c, Adriana Laca a, Mario Dı´az a,* a
Department of Chemical Engineering and Environmental Technology, University of Oviedo, C/Julia´n Claverı´a s/n. 33071 Oviedo, Spain Anes Innovacio´n S.L. Avenida de Galicia, 31. 33005 Oviedo, Spain c Scientist-Technical Services, University of Oviedo, C/Fernando Bonguera s/n. 33071 Oviedo, Spain b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 11 November 2013 Accepted 30 January 2014
The occurrence in municipal wastewaters of six pharmaceutical products, paracetamol, ibuprofen, naproxen, diclofenac, caffeine and carbamazepine, which belong to different therapeutic classes (analgesic drugs, anti-inflammatory, antiepileptic and stimulant compounds), have been investigated. Influent and effluent water samples from two conventional wastewater treatment plants (WWTPs) of the North of Spain were collected at different seasons and analyzed. Ranges of PPCPs concentrations were similar to levels reported in other studies worldwide. Influent concentrations ranges were 2.3– 42 mg/L for ibuprofen and naproxen, 0.04–7.8 mg/L for caffeine and paracetamol, and 0.03–0.4 mg/L for carbamazepine and diclofenac. The highest concentrations were found for ibuprofen in the untreated municipal wastewaters. Effluent concentrations were always below 5.7 mg/L. Diclofenac and carbamazepine persisted in WWTP effluents, whereas paracetamol, ibuprofen, naproxen and caffeine showed removal efficiencies between 75% and 99%. Considering first-order kinetics for the biodegradation of these compounds, apparent kinetic constants were calculated and similar values were obtained for both WWTPs, although one of them resulted to be more sensitive to temperature changes. ß 2014 Elsevier Ltd. All rights reserved.
Keywords: Seasonal Wastewater PPCPs Treatment WWTP
Introduction Pharmaceutical and personal care products (PPCPs) and their metabolites are contaminants extensively found in the aquatic environment [1]. These emerging environmental pollutants deserve special attention due to the fact that some of them may cause ecological and health harm [2–4]. Increasing numbers of water samples obtained from lakes, streams, aquifers and municipal supplies across the world have been found to be contaminated by trace quantities of such residues [5]. These compounds might be excreted by patients or be improperly disposed by users and end up in municipal wastewaters. One of the major sources of PPCPs in the aquatic environment is the effluent discharge from wastewater treatment plants (WWTPs) [1,6]. Current municipal wastewater treatment processes are insufficient at degrading many PPCPs and removal rates vary depending on the treatment technology used and the compound considered. Hence, variable amounts of PPCPs are continuously released into surface, ground and coastal waters [7].
The concentration of pollutants in influents and effluents of WWTPs are routinely monitored in many countries [5]. Despite of the fact that little attention has been paid to seasonal variation of PPCPs, results of different studies showed that the concentrations of PPCPs in municipal wastewater and their treated effluents may vary along the year [8–11]. Furthermore, diurnal variation patters in specific PPCPs that correlates with daily drug administration have also been identified in some cases [12]. The goal of this work was to assess the occurrence and removal of selected pharmaceutical products from municipal wastewaters in the North of Spain. As far as we know, this is the first study of this kind carried out in this region. With this aim, samples from two WWTPs were collected and analyzed along the four seasons in one year. Additionally, local hospital effluents were also analyzed. Moreover the seasonal variability in PPCPs occurrence and removal was also investigated. Materials and methods Selected PPCPs
* Corresponding author. Tel.: +34 985103439; fax: +34 985103434. E-mail addresses: [email protected], [email protected] (M. Dı´az). 2213-3437/$ – see front matter ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jece.2014.01.023
The PPCPs considered in this study include: paracetamol, ibuprofen, naproxen, diclofenac, caffeine and carbamazepine.
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
496 Table 1 Sampling details. Date
Week day
Sampling time
20/12/2010
Monday
22/02/2011
Tuesday
19/05/2011
Thursday
25/07/2011
Monday
8:30 (WWTP1) 10:00 (WWTP2) 11:00 (Hospital) 8:30 (WWTP1) 10:00 (WWTP2) 11:00 (Hospital) 8:30 (WWTP1) 10:00 (WWTP2) 11:00 (Hospital) 8:30 (WWTP1) 10:00 (WWTP2) 11:00 (Hospital)
Average day temperature (8C)
Average day precipitations (mm)
9
0.2
12
3.6
15
0.6
19
0.4
These compounds were chosen to represent different groups of pharmaceutical products widely reported to occur in aquatic systems, specifically: analgesic, anti-inflammatory, antiepileptic and stimulant drugs. Caffeine is among the 30 most frequently detected organic wastewater pollutants and carbamazepine, diclofenac and ibuprofen are among the top 10 high priority pharmaceuticals identified in a European assessment of PPCPs due to their high consumption [4,7]. Sample collection Wastewater was sampled from influent and effluent flows of two local water utilities (WWTP1 and WWTP2) and effluents from the University Central Hospital of Asturias (HUCA). This hospital has 1324 beds and the wastewater is directly discharged into the public sewage system. All facilities were located in Asturias, a region sited in the North of Spain. Grab samples were collected in autumn, winter, spring and summer (see Table 1) using a sample device consisting in a plastic bottle attached to a stick. After collection, samples were transferred to 2.5 L glass bottles and transported to laboratory. The same day of collection, samples were adjusted to pH 2.00 0.10 using hydrochloric acid 3.5 M and stored at 4 8C in the dark until extraction (maximum 12 h). Description of treatment plants The treatment in WWTP1 consists of screening, grit and grease removal, primary clarification, activated sludge treatment to achieve removal of biochemical oxygen demanding organic compounds (BOD), nitrogen and phosphorus and, finally, a secondary clarification (Fig. 1). The biological degradation takes place in a ‘‘channel type’’ bioreactor with anaerobic/anoxic/aerobic zones and an average retention time of 8 h. The influent samples were taken after screening and the effluent samples were taken after secondary clarification. The treatment in WWTP2 consists of screening, grit and grease removal, activated sludge treatment to achieve removal of BOD and nitrogen and, finally, secondary clarification (Fig. 1). The biological degradation takes place in a ‘‘carrousel type’’ bioreactor with anoxic/aerobic zones and an average retention time of 10 h. In this case, the influent samples were taken after sand and grease removal and the effluent samples were taken after secondary clarification. Both facilities receive a day contaminant charge between 1 and 2 kgCOD/m3d, being the BOD5/COD relationship upon 0.4–0.9, so these are middle or easily biodegradable wastewaters. However, WWTP1 receives a 25% of industrial wastewater and 75% municipal wastewater, whereas WWTP2 receives only municipal wastewater that includes several hospital effluents (around 3% of
the total wastewater that arrives to WWTP2 comes from hospitals). WWTP1 and WWTP2 serve a population equivalent of 260,000 and 20,000 respectively. Removal of micropollutants within activated sludge systems can be associated to three main mechanisms: volatilization to air, sorption to the sludge and biological conversion. Models referring to pharmaceutical compounds usually did not include volatilization because it is not considered a significant removal mechanism for this family. Additionally, sorption mechanism is complex and still remains not sufficiently documented [13]. In this work, only degradation in the biological reactors was considered to determine apparent kinetic constants. Large municipal wastewater treatment plants could be represented as plug flow or ideally mixed tank in series [14]. Equations for biodegradation modeling usually consider the degradation of dissolved micropollutant concentration following a first-order kinetic [13]. Plug flow and first-order transformation kinetics were assumed in this case: ln
Ci ¼ ku Ce
(1)
where Ci is the pollutant influent concentration, Ce the pollutant effluent concentration, k is the apparent kinetic constant for contaminant removal and u is the hydraulic retention time of the biological reactor. In order to calculate apparent activation energy, an Arrhenius type equation was employed: k ¼ k0 eEa =RT
(2)
where k0 is the pre-exponential factor, Ea is the apparent activation energy, T is the absolute temperature and R is the universal gas constant. Analytical methodology As first step, wastewater samples underwent vacuum filtration twice (20–25 mm Whatman filter paper and 0.45 mm Albet Labscience nitrocellulose filter). Solid-phase extraction (SPE) method was employed to concentrate the analytes from the aqueous samples; MCX 3cc/60 mg, 60 mm (Waters Oasis) cartridges were used and 0.5 L of influent samples and 1 L of effluent samples were loaded. Recovery values for MCX extraction are reported in Table 2. The volumes of sample to be filtered were selected considering previous works [15,16] and the cartridge manufacturer’s instructions. After SPE, cartridges were dried for 1 h, the analytes were eluted (3 mL of ethyl acetate, 3 mL of 50/50 ethyl acetate/acetone and 3 mL of 48/48/2 ethyl acetate/acetone/ammonium hydroxide) and extracts were evaporated to dryness under a nitrogen stream. Ethyl acetate (99.8%, Sigma–Aldrich) (1.5 mL) was used for reconstitution and the reconstituted samples were filtered (0.20 mm Whatman nylon filter) [15]. All compounds, except caffeine, were analyzed after a derivatization step with N-Methyl-N(trimethylsilyl)trifluoroacetamide (MSTFA) (Sigma–Aldrich). For this purpose, 100 mL of MSTFA were added to 100 mL of the reconstituted sample and this mixture was kept for 35 min in an oven at 65 8C. Amber autosampler vials were employed. Finally, samples were injected onto a GC/MS (Agilent Technologies; 6890 N Network GC System, 5975 inert Mass Selective Detector, 7683B Series injector, 7683 series Autosampler) fitted with a column HP-5MS (30 m 0.25 mm id 0.25 mm, 19091S433, Agilent Technologies). The carrier gas was ultrapure helium at a constant flow of 1.3 mL/min. The oven temperature was held at 50 8C for 30 s, and then programmed at 10 8C/min to 250 8C with the final temperature being held for 5 min A sample volume of 1 mL was injected in the splitless mode. The transfer line and ion source were set at 280 8C and 230 8C, respectively. Each compound
[(Fig._1)TD$IG]
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
497
Fig. 1. Schematic representation of studied WWTPs indicating points of sampling.
Table 2 LOD, LOQ, RSD and recovery values for each compound. PPCP
WWTPs influents and hospital effluent a
Caffeine Paracetamol Naproxen Carbamazepine Ibuprofen Diclofenac a b
a
LOD (ng/L)
LOQ (ng/L)
RSD (%)
LOD (ng/L)
2.6 2.3 2.0 1.7 3.5 3.4
8.7 7.6 6.8 5.5 11.6 11.2
<16 <25 <25 <21 <10 <25
1.3 1.1 1.0 0.8 1.7 1.6
Values obtained in this work. Values reported by Togola and Budzinski [15].
MCX extraction recovery valuesb
WWTPs effluents a
a
LOQ (ng/L)
RSD (%)
4.4 3.8 3.4 2.8 5.8 5.6
<8 <18 <25 <25 <12 <22
68 76 90 120 80 76
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
498
Table 3 Levels of PPCPs in the WWTPs 1 and 2 (average concentrations SD and minimal and maximum values) compared with values reported by other authors. Average concentrations were obtained by employing all the concentrations measured during the year. PPCP
Caffeine Paracetamol Naproxen Carbamazepine Ibuprofen Diclofenac
Average concentrations (mg/L) SD
Concentration range (minimum–maximum) (mg/L)
WWTP1
This work
WWTP2
Literature
Influent
Effluent
Influent
Effluent
Influent
Effluent
Influent
References
Effluent
References
2.3 1.7 0.35 0.60 3.5 1.1 0.10 0.10 11.2 4.0 0.16 0.06
0.02 0.01 0.01 0.00 0.71 0.33 0.16 0.13 1.6 2.8 0.55 0.41
5.4 2.6 2.3 1.2 11.6 1.9 0.13 0.07 30.5 10.0 0.30 0.11
0.05 0.05 0.03 0.04 0.57 0.68 0.19 0.10 0.91 1.04 0.39 0.18
0.8–7.8 0.04–4.0 2.3–14 0.03–0.3 6.5–42 0.08–0.4
n.d.-0.1 0.004–0.1 0.1–1.6 0.08–0.4 0.03–5.7 0.2–1.1
0.2–63 0.07–26 1.1–53 n.d.-3.7 8.8–168 n.d.-5.0
[17,21,29] [26,30] [3,17,31] [3,5,17,21,29] [31,33] [3,17,31,33]
0.002–9.9 n.d.-5.9 0.2–6.2 n.d.-6.2 n.d.-3.8 n.d.-2.5
[15,17,21,29] [26,30] [3,15,17,31] [3,5,17,21,29] [15,31–33] [3,15,17,31–33]
n.d.: not detected.
was firstly characterized individually in scan mode in order to identify the main ions (m/z ratio) constituting the mass spectrum and to choose the ions for quantification. PPCP GC grade reference standards were supplied by Sigma– Aldrich. The recovery values, the RSD (Relative Standard Deviation) and the limits of detection (LOD) and quantification (LOQ) were compound dependent (see Table 2). The correlation coefficient (r2) of the calibration curves was always higher than 0.990. Results and discussion PPCP occurrence As can be seen in Tables 3 and 4, the compounds with the highest concentrations in the influents in both WWTPs and also in the hospital wastewaters were ibuprofen, paracetamol, naproxen and caffeine. This is not surprising given that ibuprofen, paracetamol and naproxen are painkillers found in numerous over-the-counter medications commonly used in hospitals but also in households. Additionally to its use in pharmaceutical products, caffeine is frequently employed in beverages and foods as a stimulant. It should be also pointed out that, as it is shown in Table 3, average parameter values are much higher (excepting for carbamazepine, in two-fold concentration or even more) in WWTP2 than in WWTP1. When the amount of PPCPs that arrived to the WWTPs per capita was calculated, similar values were found for both facilities in the case of carbamazepine and diclofenac, whereas four-fold values were found for paracetamol and two-fold values were found for the rest of the compounds. WWTP2 receives only municipal and hospital wastewaters, whereas WWTP1 receives municipal wastewaters but also wastewaters from commercial and industrial parks. Obviously, the wastewaters coming from commercial and industrial facilities would not contribute much to the pharmaceutical loads. Surprisingly, and Table 4 Levels of PPCPs in hospital wastewaters (average concentrations SD and minimal and maximum values) compared with values reported by other authors. Average concentrations were obtained by employing all the concentrations measured during the year. PPCP
Concentrations (mg/L) SD
Concentration range (minimum–maximum) (mg/L) This work
Literature
References
Caffeine Paracetamol Naproxen Carbamazepine Ibuprofen Diclofenac
24.0 22.7 0.92 1.01 1.3 0.4 0.06 0.11 13.1 8.6 0.12 0.07
8.5–50.0 0.1–2.1 0.9–1.6 n.d.–0.19 4.5–21.7 0.04–0.2
12.3–42.0 3.1–21.2 n.d.–21.8 n.d.–2.0 1.5–151 n.d.–6.9
[22] [22] [22,34] [15,22,34] [15,22,34] [15,22,34]
n.d.: not detected.
excepting for caffeine, in general, hospital values were on the same order of magnitude as those obtained for both WWTPs (Table 4). Therefore, in this case hospital effluents could not be considered as responsible for increasing the concentration of these pharmaceuticals in the untreated wastewaters. The ranges of PPCPs concentrations detected in the influents of both WWTPs were comparable to concentrations reported in other studies worldwide (see Table 3). Particularly, caffeine, carbamazepine, and naproxen concentrations were similar to average values observed by Santos et al. [17] (4.9–7.4 mg/L, 0.4–0.5 mg/L and 4.3– 8.1 mg/L respectively) in different WWTPs located in the south of Spain, whereas ibuprofen and diclofenac influent concentrations were similar to those reported by Hijosa-Valsero et al. [18] (8.4– 24.2 mg/L and 0.4–0.8 mg/L respectively) in WWTPs located in the center of Spain. Regarding WWTPs effluents, caffeine, carbamazepine, ibuprofen and naproxen, concentration levels were in general lower than those reported for several WWTPs located in the Spanish south (0.2–2.4 mg/L, 0.2–0.7 mg/L, 0.06–10.2 mg/L and 0.8–4.4 mg/L respectively) [17,19], whereas most of diclofenac concentrations were slightly higher than average values reported by these authors (n.d.–0.24 mg/L). Table 4 compares the PPCPs levels observed here in the hospital wastewater with those found in the literature. With the exception of caffeine, our results were slightly lower. However, ibuprofen and carbamazepine mean value concentrations were comparable to those reported by Go´mez et al. [20] (19.8 mg/L and 0.04 mg/L respectively) in wastewaters from a private healthcare center located in the southeast of Spain. PPCPs concentrations in municipal effluents depend on different factors, such as influent composition, removal efficacies, WWTP performance, season or localization. In general, the outcoming concentrations measured here were within the range found in literature for WWTPs worldwide (see Table 3). As it can be seen, maximum values were lower than the upper values reported by other authors, excepting for ibuprofen. Minimum values were slightly higher, with the exception of naproxen. Considering only studies carried out in Spanish WWTPs, concentrations ranges found in this work were included in the range described by Santos et al. [17] and Hijosa-Valsero et al. [18] for caffeine (0.17–12.8 mg/ L), naproxen (0.05–5.1 mg/L), carbamazepine (<0.02–1.29 mg/L) and ibuprofen (0.002–55.0 mg/L), whereas diclofenac maximum value was higher than those reported by these authors (0.14– 0.66 mg/L). Removal efficiencies Percentages of PPCPs removal in the aqueous phase during wastewater treatment were calculated for both facilities ([influent] [effluent]/[influent] 100). Removal efficiencies were calculated for the four seasons and values shown in Fig. 2 were evaluated on the basis of the average of these four values.
[(Fig._2)TD$IG]
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
Fig. 2. Average removal efficiency for paracetamol, ibuprofen, naproxen and caffeine in both WWTPs. Bars indicate SD.
Therefore, it was considered the removal of PPCPs by degradation, but also by absorption phenomena. Diclofenac and carbamazepine persisted in WWTP effluents with similar or even slightly higher concentrations than those [(Fig._3)TD$IG]
499
measured in the untreated sewages (see Table 3). This phenomenon was also described by other authors [21–23]. The persistence of these compounds in the water would indicate that conventional wastewater treatment process is not effective in breaking down these compounds. The higher concentration levels found in the effluent could be explained by the formation of products of human metabolism and/or transformation products (e.g. hydroxyl- and epoxy-derivatives or glucuronides) which may act as a reservoir from which a later yield of the parent substance can occur [10,22– 24]. Additionally, it is necessary to take into account that the measured concentrations for these compounds are near to the detection limit, thus relative SDs are quite high. The removal values calculated for diclofenac and carbamazepine were very low or even negative, so they were omitted in Fig. 2, which shows the treatment removal efficiency for caffeine, paracetamol, ibuprofen and naproxen (calculated with average values). The average removal efficiencies for these compounds were higher than 95% in WWTP2. These values were similar to those reported for WWTPs sited in Europe and USA that included primary and biological treatment [17,25,26]. Concerning WWTP1, the average removal efficiencies were around 80% for paracetamol, naproxen and ibuprofen and 99% for
Caffeine
Carbamazepine 0,3
60
Concentration (µg/L)
Concentration (µg/L)
50 40 30 20 10 0
0,2
0,1
0,0 Autumn
Winter
Spring
Summer
Autumn
Autumn
Winter
Spring
Spring
Summer
Ibuprofen
4,5 4,0 3,5 3,0 2,5 2,0 1,5 1,0 0,5 0,0
Concentration (µg/L)
Concentration (µg/L)
Paracetamol
Winter
45 40 35 30 25 20 15 10 5 0 Autumn
Summer
Naproxen
Winter
Spring
Summer
Diclofenac 0,5
16 Concentration (µg/L)
Concentration ( µg/L)
14 12 10 8 6 4
0,4 0,3 0,2 0,1
2 0
0 Autumn
Winter
Spring
Summer
Autumn
Winter
Spring
Summer
Fig. 3. Seasonal influent concentrations of studied PPCPs in both WWTPs and hospital wastewater (~ WWTP1; & WWTP2; Hospital). Hospital autumn sample is missing, carbamazepine was not detected in winter and spring hospital samples.
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
500
caffeine. Despite of being less efficient than WWTP2, naproxen and ibuprofen removal values were still slightly higher than those cited by Blair et al. [27] (73% and 88% respectively) for North American WWTPs that included preliminary, primary and biological treatment and chlorine disinfection. Regarding removal efficiencies for BOD5 and nitrogen, again the average values are slightly higher in WWTP2 than in WWTP1 (99% and 80%, 98% and 68%, respectively). The higher efficiency removals observed in WWTP2 could be explained because the hydraulic retention time of the biologic reactor was higher in WWTP2 than in WWTP1 (10 and 8 h, respectively). Besides, the presence of pollutants coming from industrial wastewaters may interfere in the elimination process, decreasing biodegradation rates in WWTP1. Finally, it is important to point out that the primary clarification previous to biological treatment and the anaerobic step in WWTP1 did not contribute to improve the PPCPs removal efficiencies. Seasonality Samples taken in autumn, winter, spring and summer were compared to examine seasonal trends in PPCPs concentration (Fig. 3). Excepting for the increase detected in spring in hospital wastewater, the seasonal variation of caffeine in WWTP influents was minimal. Regarding carbamazepine, the highest value was observed in winter in WWTP1 influent and in summer in WWTP2 and hospital wastewater (0.25, 0.22 and 0.19 mg/L, respectively). The increase of the concentration observed in WWTP2 coincided
[(Fig._4)TD$IG]
[(Fig._5)TD$IG]
BOD 5
600
with an increase in hospital wastewater which is understandable as this hospital wastewater is treated in WWTP2. Paracetamol increased notably in all effluents in summer, while ibuprofen had a maximum in winter in WWTP2 and hospital wastewaters. Variations in naproxen were minimal for hospital wastewaters, whereas in WWTP1, the concentrations measured in spring and summer were double than those obtained in autumn and winter. On the opposite, the highest values for WWTP2 were found in autumn and winter. Minimum values of diclofenac were found in autumn and summer for both WWTPs and hospital wastewaters, observing a maximum in spring for WWTP2. Considering all these data, tendencies in the PPCPs concentrations of the untreated wastewaters could not be established, depending the followed pattern on the compound and specific water. It is necessary to take in mind that several factors are involved to determine the composition of these wastewaters, mainly the amount of PPCPs released and the abundance of rainfall that dilute the contamination (there is no separation between rainwater and sewage). Seasonal influent concentrations of BOD5 and total nitrogen were higher in WWTP2 than in WWTP1, with the exception of summer total nitrogen data (see Fig. 4). This can be due to the fact that, as it was mentioned above, the service area of WWTP2 is municipal, while WWTP1 serves a mix of municipal and industrial wastewaters that are likely to have lower concentrations of these contaminants. Fig. 5 shows the seasonal variation of removal efficiencies for PPCPs (caffeine, paracetamol, carbamazepine and ibuprofen), BOD5 and total nitrogen. PPCPs removal efficiencies in WWTP2 were higher than 95% with the exception of ibuprofen and naproxen values in autumn, which were lower that 90%. Values higher than
WWTP1
% Removal Efficiency
Concentration (mg/L)
500 400 300 200 100
100 95 90 85 80 75 70 65 60 55 50
0
5
Autumn
Winter
Spring
8
11
Summer Autum
14 T (ºC)
Winter
Total N
17
Spring
20
23
Summer
WWTP2
60 100 % Removal Efficiency
Concentration (mg/L)
50 40 30 20
95 90 85 80 75 70
10
5
0
8 Autum
Autumn
Winter
Spring
11
14 T (ºC)
Winter
Spring
17
20
23
Summer
Summer
Fig. 4. Seasonal influent concentrations of water parameters in both WWTPs (~ WWTP1; & WWTP2) (data from the ‘‘Consorcio de Aguas de Asturias’’).
Fig. 5. Seasonal variation of removal efficiency in both WWTPs for: ^ Caffeine, & Paracetamol, ~ Naproxen, Ibuprofen, * BOD5 and + Total N. Arrows indicate the sampling season that corresponds to each temperature.
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
501
Table 5 Seasonal values of apparent kinetic constant (k) (h1) for different contaminant removal in both WWTPs. Pollutants
WWTP1
WWTP2
Autumn
Winter
Spring
Summer
Autumn
Winter
Spring
Summer
BOD5 Total N Caffeine Paracetamol Naproxen Ibuprofen
0.41 0.10 0.46 0.20 0.19 0.38
0.43 0.13 0.58 0.22 0.22 0.06
0.51 0.18 0.65 0.24 0.23 0.54
0.53 0.19 0.69 0.71 0.12 0.63
0.44 0.13 0.52 0.31 0.21 0.22
0.46 0.18 0.43 0.41 0.38 0.34
0.50 0.20 – 0.52 0.46 0.71
0.45 0.14 0.46 0.64 0.35 0.58
Table 6 Values of apparent activation energy (kJ/mol) for different contaminants in both WWTPs. Pollutant
WWTP1
WWTP2
BOD5 Total N Caffeine Paracetamol Naproxen Ibuprofen
18.4 46.4 26.5 21.4 21.0 34.1
15.6 52.5 – 50.0 86.1 63.6
95% were also obtained in WWTP1 for caffeine and ibuprofen. In the case of naproxen and paracetamol the values in WWTP1 were below 85% during all the year, excepting for paracetamol removal efficiency in the summer sample that was above 95%. Considering the exact date of sampling, average day temperatures were 9 8C, 12 8C, 15 8C and 19 8C for autumn, winter, spring and summer respectively. Therefore, as it was reported in other works [18,26], the seasonal differences of PCPP removal levels reflected that in general treatment processes were more effectively for warmer temperatures. This trend was clearly observed in WWTP1, with the exception of naproxen whose lowest value was reached in summer. Regarding removal efficiencies for BOD5 and total nitrogen, WWTP2 values for these parameters did not show a clear tendency, whereas in case of WWTP1 achieved a maximum in summer. The apparent kinetic constants (k) for the removal of the studied contaminants were calculated for both WWTPs (Table 5). The expected increase in k values with temperature was clearly observed in WWTP1 with only two anomalous values (naproxen in summer and ibuprofen in winter). In the case of WWTP2, almost all the summer values were lower than expected. This behavior is likely to be related with some kind of modification in microbial community running, as a consequence of a drastic change in temperature or composition of the water suffered in previous days. A lack of tendency was also observed for caffeine in WWTP2, but this can be explained because concentrations measured in the effluent were very low, near LOD and therefore, these measurements have larger uncertainty. It is important to remark that k values are within the same order in both WWTPs (between 0.06 and 0.71 h1 in all cases), observing values slightly higher in WWTP2 for naproxen and paracetamol. Ferguson et al. [28] observed a negative correlation between temperature and total pharmaceutical abundance in an USA lake. This indicated that lower temperatures reduce the rate of biodegradation of these PPCPs in surface water and sewage treatment plants, finding that temperature is more important to degradation of some pollutants than another. With the aim of determining the relation between the k constants and temperature, an Arrhenius type equation was employed. Values with anomalous behavior (showed in gray in Table 5) were not considered in the calculation of the apparent activation energy. Apparent activation energy values for BOD5 and
total N were similar in both WWTPs, whereas WWTP2 showed values twice or three times higher for paracetamol, naproxen and ibuprofen (see Table 6). This indicated that, the PPCP removal process is much more sensible to temperature in case of WWTP2 than in WWTP1. Conclusions Among the six PPCPs considered in this study, ibuprofen, paracetamol, naproxen and caffeine were the compounds detected in higher levels in the analyzed wastewaters. Tendencies throughout the year could not be established for PPCPs concentrations found at the entrance of the WWTPs. Results showed that traditional treatment for municipal wastewaters were not effective in removing diclofenac and carbamazepine, whereas paracetamol, ibuprofen, naproxen and caffeine concentrations decreased between 75% and 99% during the process. Differences of PCPP removal levels found in samples taken at different seasons reflected that, in general, the treatment throughout the WWTPs were more effectively for warmer temperatures. Additionally, one of the studied WWTP resulted to be more sensible to temperature changes, as it was showed by kinetic parameter values. Further research would be interesting in order to complete the conclusions here achieved and establish the convenience of controlling certain of these pollutants in municipal WWTPs in a systematic way. Acknowledgments The authors thank the ‘‘Consorcio de Aguas de Asturias’’ (Government of Asturias, Spain) and the ‘‘Hospital Universitario Central de Asturias’’ (HUCA) for supplying the samples and MEDYCSA for funding the project. References [1] C. Reyes-Contreras, V. Matamoros, I. Ruiz, M. Soto, J.M. Bayona, Evaluation of PPCPs removal in a combined anaerobic digester-constructed wetland pilot plant treating urban wastewater, Chemosphere 84 (2011) 1200–1207. [2] V.L. Cunningham, M. Buzby, T. Hutchinson, F. Mastrocco, N. Parke, N. Roden, Effects of human pharmaceuticals on aquatic life: next steps, Environ. Sci. Technol. 40 (2006) 3456–3462. [3] M. Al Aukidy, P. Verlicchi, A. Jelic, M. Petrovic, D. Barcelo`, Monitoring release of pharmaceutical compounds: occurrence and environmental risk assessment of two WWTP effluents and their receiving bodies in the Po Valley, Italy, Sci. Total Environ. 438 (2012) 15–25. [4] X. Yang, R.C. Flowers, H.S. Weinberg, P.C. Singer, Occurrence and removal of pharmaceuticals and personal care products (PPCPs) in an advanced wastewater reclamation plan, Water Res. 45 (2011) 5218–5228. [5] Y. He, W. Chen, X. Zheng, X. Wang, X. Huang, Fate and removal of typical pharmaceuticals and personal care products by three different treatment processes, Sci. Total Environ. 447 (2013) 248–254. [6] T. Heberer, D. Feldmann, Contribution of effluents from hospitals and private households to the total loads of diclofenac and carbamazepine in municipal sewage effluents-modeling versus measurements, J. Hazard. Mater. 122 (2005) 211–218. [7] D.W. Kolpin, E.T. Furlong, M.T. Meyer, E.M. Thurman, S.D. Zaugg, L.B. Barber, H.T. Buxton, Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999–2000: a national reconnaissance, Environ. Sci. Technol. 36 (2002) 1202–1211.
502
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
[8] N.M. Vieno, T. Tuhkanen, L. Kronberg, Seasonal variation in the occurrence of pharmaceutical sin effluents from a sewage treatment plant and in the recipient water, Environ. Sci. Technol. 39 (2005) 8220–8226. [9] G.A. Loraine, M.E. Pettigrove, Seasonal variations in concentrations of pharmaceuticals and personal care products in drinking water and reclaimed wastewater in southern California, Environ. Sci. Technol. 40 (2006) 687–695. [10] Q. Sui, J. Huang, S. Deng, G. Yu, Q. Fan, Occurrence and removal of pharmaceuticals, caffeine and DEET in wastewater treatment plants of Beijing, China, Water Res. 44 (2010) 417–426. [11] P. Verlicchi, M. Al Aukidy, A. Galletti, M. Petrovic, D. Barcelo`, Hospital effluent: investigation of the concentrations and distribution of pharmaceuticals and environmental risk assessment, Sci. Total Environ. 430 (2012) 109–118. [12] B. Gy Plo´sz, H. Leknes, H. Liltved, K.V. Thomas, Diurnal variations in the occurrence and the fate of hormones and antibiotics in activated sludge wastewater treatment in Oslo, Norway, Sci. Total Environ. 408 (2010) 1915–1924. [13] M. Pomie`s, J.M. Choubert, C. Wisniewski, M. Coquery, Modelling of micropollutant removal in biological wastewater treatments: a review, Sci. Total Environ. 443 (2013) 733–748. [14] M. Novak, P. Horvat, Mathematical modelling and optimisation of a waste water treatment plant by combined oxygen electrode and biological waste water treatment model, Appl. Math. Model. 36 (2012) 3813–3825. [15] A. Togola, H. Budzinski, Multi-residue analysis of pharmaceutical compounds in aqueous samples, J. Chromatogr. A 1177 (2008) 150–158. [16] S.S. Verenitch, C.J. Lowe, A. Mazumder, Determination of acidic drugs and caffeine in municipal wastewaters and receiving waters by gas chromatography-ion trap tandem mass spectrometry, J. Chromatogr. A 1116 (2006) 193–203. [17] J. Santos, I. Aparicio, M. Callejo´n, E. Alonso, Occurrence of pharmaceutically active compounds during 1-year period in wastewaters from four wastewater treatment plants in Seville (Spain), J. Hazard. Mater. 164 (2009) 1509–1516. [18] M. Hijosa-Valsero, V. Matamoros, J. Martı´n-Villacorta, E. Be´cares, J. Bayona, Assessment of full-scale natural systems for the removal of PPCPs from wastewater in small communities, Water Res. 44 (2010) 1429–1439. [19] M.D. Camacho-Mun˜oz, J.L. Santos, I. Aparicio, E. Alonso, Presence of pharmaceutically active compounds in Don˜ana Park (Spain) main watersheds, J. Hazard. Mater. 177 (2010) 1159–1162. [20] M. Go´mez, M. Patrovic, A. Ferna´ndez-Alba, D. Barcelo´, Determination of pharmaceuticals of various therapeutic classes by solid-phase extraction and liquid chromatography-tandem mass spectrometry analysis in hospital effluent wastewaters, J. Chromatogr. A 1114 (2006) 224–233.
[21] A. Spongberg, J. Witter, Pharmaceutical compounds in the wastewater process stream in Northwest Ohio, Sci. Total Environ. 397 (2008) 148–157. [22] C. Kosma, D. Lambropoulou, T. Albanis, Occurrence and removal of PPCPs in municipal and hospital wastewaters in Greece, J. Hazard. Mater. 179 (2010) 804–817. [23] A. Jelic, M. Gros, A. Ginebreda, R. Cespedes-Sa´nchez, F. Ventura, M. Petrovic, D. Barcelo´, Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during wastewater treatment, Water Res. 45 (2011) 1165–1176. [24] T. Rauch-Williams, C. Hoppe-Jones, J. Drewes, The role of organic matter in the removal of emerging trace organic chemicals during managed aquifer recharge, Water Res. 44 (2010) 449–460. [25] S. Zorita, L. Ma˚rtensson, L. Mathiasson, Occurrence and removal of pharmaceuticals in a municipal sewage treatment system in the south of Sweden, Sci. Total Environ. 407 (2009) 2760–2770. [26] J.T. Yu, E.J. Bouwer, M. Coelthan, Occurrence and biodegradability studies of selected pharmaceuticals and personal care products in sewage effluent, Agric. Water Manage. 86 (2006) 72–80. [27] B.D. Blair, J.P. Crago, C.J. Hedman, R.J.F. Treguer, C. Magruder, L.S. Royer, R.D. Klaper, Evaluation of a model for the removal of pharmaceuticals, personal care products, and hormones from wastewater, Sci. Total Environ. 444 (2013) 515–521. [28] P.J. Ferguson, M.J. Bernot, J.C. Doll, T.E. Lauer, Detection of pharmaceuticals and personal care products (PPCPs) in near-shore habitats of southern Lake Michigan, Sci. Total Environ. 458–460 (458) (2013) 187–190. [29] A.Y.C. Lin, T.H. Yu, S.K. Lateef, Removal of pharmaceuticals in secondary wastewater treatment processes in Taiwan, J. Hazard. Mater. 167 (2009) 1163–1169. [30] P.H. Roberts, K.V. Thomas, The occurrence of selected pharmaceuticals in wastewater effluent and surface waters of the lower Tyne catchment, Sci. Total Environ. 356 (2006) 143–153. [31] L. Lishman, S.A. Smyth, K. Sarafin, S. Kleywegt, J. Toito, T. Peart, B. Lee, M. Servos, M. Beland, P. Seto, Occurrence and reductions of pharmaceuticals and personal care products and estrogens by municipal wastewater treatment plants in Ontario, Canada, Sci. Total Environ. 367 (2006) 544–558. [32] T. Ternes, Occurrence of drugs in German sewage treatment plants and rivers, Water Res. 32 (1998) 3245–3260. [33] K. Fent, A.A. Weston, D. Caminada, Ecotoxicology of human pharmaceuticals, Aquat. Toxicol. 76 (2006) 122–159. [34] L.H.M.L.M. Santos, M. Gros, S. Rodriguez-Mozaz, C. Delerue-Matos, A. Pena, D. Barcelo´, M.C.B.S.M. Montenegro, Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: identification of ecologically relevant pharmaceuticals, Sci. Total Environ. 461–462 (461) (2013) 302–310.
Contents lists available at ScienceDirect
Journal of Environmental Chemical Engineering journal homepage: www.elsevier.com/locate/jece
Seasonal occurrence and removal of pharmaceutical products in municipal wastewaters Manuel Ferna´ndez a, Mo´nica Ferna´ndez b, Amanda Laca c, Adriana Laca a, Mario Dı´az a,* a
Department of Chemical Engineering and Environmental Technology, University of Oviedo, C/Julia´n Claverı´a s/n. 33071 Oviedo, Spain Anes Innovacio´n S.L. Avenida de Galicia, 31. 33005 Oviedo, Spain c Scientist-Technical Services, University of Oviedo, C/Fernando Bonguera s/n. 33071 Oviedo, Spain b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 11 November 2013 Accepted 30 January 2014
The occurrence in municipal wastewaters of six pharmaceutical products, paracetamol, ibuprofen, naproxen, diclofenac, caffeine and carbamazepine, which belong to different therapeutic classes (analgesic drugs, anti-inflammatory, antiepileptic and stimulant compounds), have been investigated. Influent and effluent water samples from two conventional wastewater treatment plants (WWTPs) of the North of Spain were collected at different seasons and analyzed. Ranges of PPCPs concentrations were similar to levels reported in other studies worldwide. Influent concentrations ranges were 2.3– 42 mg/L for ibuprofen and naproxen, 0.04–7.8 mg/L for caffeine and paracetamol, and 0.03–0.4 mg/L for carbamazepine and diclofenac. The highest concentrations were found for ibuprofen in the untreated municipal wastewaters. Effluent concentrations were always below 5.7 mg/L. Diclofenac and carbamazepine persisted in WWTP effluents, whereas paracetamol, ibuprofen, naproxen and caffeine showed removal efficiencies between 75% and 99%. Considering first-order kinetics for the biodegradation of these compounds, apparent kinetic constants were calculated and similar values were obtained for both WWTPs, although one of them resulted to be more sensitive to temperature changes. ß 2014 Elsevier Ltd. All rights reserved.
Keywords: Seasonal Wastewater PPCPs Treatment WWTP
Introduction Pharmaceutical and personal care products (PPCPs) and their metabolites are contaminants extensively found in the aquatic environment [1]. These emerging environmental pollutants deserve special attention due to the fact that some of them may cause ecological and health harm [2–4]. Increasing numbers of water samples obtained from lakes, streams, aquifers and municipal supplies across the world have been found to be contaminated by trace quantities of such residues [5]. These compounds might be excreted by patients or be improperly disposed by users and end up in municipal wastewaters. One of the major sources of PPCPs in the aquatic environment is the effluent discharge from wastewater treatment plants (WWTPs) [1,6]. Current municipal wastewater treatment processes are insufficient at degrading many PPCPs and removal rates vary depending on the treatment technology used and the compound considered. Hence, variable amounts of PPCPs are continuously released into surface, ground and coastal waters [7].
The concentration of pollutants in influents and effluents of WWTPs are routinely monitored in many countries [5]. Despite of the fact that little attention has been paid to seasonal variation of PPCPs, results of different studies showed that the concentrations of PPCPs in municipal wastewater and their treated effluents may vary along the year [8–11]. Furthermore, diurnal variation patters in specific PPCPs that correlates with daily drug administration have also been identified in some cases [12]. The goal of this work was to assess the occurrence and removal of selected pharmaceutical products from municipal wastewaters in the North of Spain. As far as we know, this is the first study of this kind carried out in this region. With this aim, samples from two WWTPs were collected and analyzed along the four seasons in one year. Additionally, local hospital effluents were also analyzed. Moreover the seasonal variability in PPCPs occurrence and removal was also investigated. Materials and methods Selected PPCPs
* Corresponding author. Tel.: +34 985103439; fax: +34 985103434. E-mail addresses: [email protected], [email protected] (M. Dı´az). 2213-3437/$ – see front matter ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jece.2014.01.023
The PPCPs considered in this study include: paracetamol, ibuprofen, naproxen, diclofenac, caffeine and carbamazepine.
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
496 Table 1 Sampling details. Date
Week day
Sampling time
20/12/2010
Monday
22/02/2011
Tuesday
19/05/2011
Thursday
25/07/2011
Monday
8:30 (WWTP1) 10:00 (WWTP2) 11:00 (Hospital) 8:30 (WWTP1) 10:00 (WWTP2) 11:00 (Hospital) 8:30 (WWTP1) 10:00 (WWTP2) 11:00 (Hospital) 8:30 (WWTP1) 10:00 (WWTP2) 11:00 (Hospital)
Average day temperature (8C)
Average day precipitations (mm)
9
0.2
12
3.6
15
0.6
19
0.4
These compounds were chosen to represent different groups of pharmaceutical products widely reported to occur in aquatic systems, specifically: analgesic, anti-inflammatory, antiepileptic and stimulant drugs. Caffeine is among the 30 most frequently detected organic wastewater pollutants and carbamazepine, diclofenac and ibuprofen are among the top 10 high priority pharmaceuticals identified in a European assessment of PPCPs due to their high consumption [4,7]. Sample collection Wastewater was sampled from influent and effluent flows of two local water utilities (WWTP1 and WWTP2) and effluents from the University Central Hospital of Asturias (HUCA). This hospital has 1324 beds and the wastewater is directly discharged into the public sewage system. All facilities were located in Asturias, a region sited in the North of Spain. Grab samples were collected in autumn, winter, spring and summer (see Table 1) using a sample device consisting in a plastic bottle attached to a stick. After collection, samples were transferred to 2.5 L glass bottles and transported to laboratory. The same day of collection, samples were adjusted to pH 2.00 0.10 using hydrochloric acid 3.5 M and stored at 4 8C in the dark until extraction (maximum 12 h). Description of treatment plants The treatment in WWTP1 consists of screening, grit and grease removal, primary clarification, activated sludge treatment to achieve removal of biochemical oxygen demanding organic compounds (BOD), nitrogen and phosphorus and, finally, a secondary clarification (Fig. 1). The biological degradation takes place in a ‘‘channel type’’ bioreactor with anaerobic/anoxic/aerobic zones and an average retention time of 8 h. The influent samples were taken after screening and the effluent samples were taken after secondary clarification. The treatment in WWTP2 consists of screening, grit and grease removal, activated sludge treatment to achieve removal of BOD and nitrogen and, finally, secondary clarification (Fig. 1). The biological degradation takes place in a ‘‘carrousel type’’ bioreactor with anoxic/aerobic zones and an average retention time of 10 h. In this case, the influent samples were taken after sand and grease removal and the effluent samples were taken after secondary clarification. Both facilities receive a day contaminant charge between 1 and 2 kgCOD/m3d, being the BOD5/COD relationship upon 0.4–0.9, so these are middle or easily biodegradable wastewaters. However, WWTP1 receives a 25% of industrial wastewater and 75% municipal wastewater, whereas WWTP2 receives only municipal wastewater that includes several hospital effluents (around 3% of
the total wastewater that arrives to WWTP2 comes from hospitals). WWTP1 and WWTP2 serve a population equivalent of 260,000 and 20,000 respectively. Removal of micropollutants within activated sludge systems can be associated to three main mechanisms: volatilization to air, sorption to the sludge and biological conversion. Models referring to pharmaceutical compounds usually did not include volatilization because it is not considered a significant removal mechanism for this family. Additionally, sorption mechanism is complex and still remains not sufficiently documented [13]. In this work, only degradation in the biological reactors was considered to determine apparent kinetic constants. Large municipal wastewater treatment plants could be represented as plug flow or ideally mixed tank in series [14]. Equations for biodegradation modeling usually consider the degradation of dissolved micropollutant concentration following a first-order kinetic [13]. Plug flow and first-order transformation kinetics were assumed in this case: ln
Ci ¼ ku Ce
(1)
where Ci is the pollutant influent concentration, Ce the pollutant effluent concentration, k is the apparent kinetic constant for contaminant removal and u is the hydraulic retention time of the biological reactor. In order to calculate apparent activation energy, an Arrhenius type equation was employed: k ¼ k0 eEa =RT
(2)
where k0 is the pre-exponential factor, Ea is the apparent activation energy, T is the absolute temperature and R is the universal gas constant. Analytical methodology As first step, wastewater samples underwent vacuum filtration twice (20–25 mm Whatman filter paper and 0.45 mm Albet Labscience nitrocellulose filter). Solid-phase extraction (SPE) method was employed to concentrate the analytes from the aqueous samples; MCX 3cc/60 mg, 60 mm (Waters Oasis) cartridges were used and 0.5 L of influent samples and 1 L of effluent samples were loaded. Recovery values for MCX extraction are reported in Table 2. The volumes of sample to be filtered were selected considering previous works [15,16] and the cartridge manufacturer’s instructions. After SPE, cartridges were dried for 1 h, the analytes were eluted (3 mL of ethyl acetate, 3 mL of 50/50 ethyl acetate/acetone and 3 mL of 48/48/2 ethyl acetate/acetone/ammonium hydroxide) and extracts were evaporated to dryness under a nitrogen stream. Ethyl acetate (99.8%, Sigma–Aldrich) (1.5 mL) was used for reconstitution and the reconstituted samples were filtered (0.20 mm Whatman nylon filter) [15]. All compounds, except caffeine, were analyzed after a derivatization step with N-Methyl-N(trimethylsilyl)trifluoroacetamide (MSTFA) (Sigma–Aldrich). For this purpose, 100 mL of MSTFA were added to 100 mL of the reconstituted sample and this mixture was kept for 35 min in an oven at 65 8C. Amber autosampler vials were employed. Finally, samples were injected onto a GC/MS (Agilent Technologies; 6890 N Network GC System, 5975 inert Mass Selective Detector, 7683B Series injector, 7683 series Autosampler) fitted with a column HP-5MS (30 m 0.25 mm id 0.25 mm, 19091S433, Agilent Technologies). The carrier gas was ultrapure helium at a constant flow of 1.3 mL/min. The oven temperature was held at 50 8C for 30 s, and then programmed at 10 8C/min to 250 8C with the final temperature being held for 5 min A sample volume of 1 mL was injected in the splitless mode. The transfer line and ion source were set at 280 8C and 230 8C, respectively. Each compound
[(Fig._1)TD$IG]
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
497
Fig. 1. Schematic representation of studied WWTPs indicating points of sampling.
Table 2 LOD, LOQ, RSD and recovery values for each compound. PPCP
WWTPs influents and hospital effluent a
Caffeine Paracetamol Naproxen Carbamazepine Ibuprofen Diclofenac a b
a
LOD (ng/L)
LOQ (ng/L)
RSD (%)
LOD (ng/L)
2.6 2.3 2.0 1.7 3.5 3.4
8.7 7.6 6.8 5.5 11.6 11.2
<16 <25 <25 <21 <10 <25
1.3 1.1 1.0 0.8 1.7 1.6
Values obtained in this work. Values reported by Togola and Budzinski [15].
MCX extraction recovery valuesb
WWTPs effluents a
a
LOQ (ng/L)
RSD (%)
4.4 3.8 3.4 2.8 5.8 5.6
<8 <18 <25 <25 <12 <22
68 76 90 120 80 76
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
498
Table 3 Levels of PPCPs in the WWTPs 1 and 2 (average concentrations SD and minimal and maximum values) compared with values reported by other authors. Average concentrations were obtained by employing all the concentrations measured during the year. PPCP
Caffeine Paracetamol Naproxen Carbamazepine Ibuprofen Diclofenac
Average concentrations (mg/L) SD
Concentration range (minimum–maximum) (mg/L)
WWTP1
This work
WWTP2
Literature
Influent
Effluent
Influent
Effluent
Influent
Effluent
Influent
References
Effluent
References
2.3 1.7 0.35 0.60 3.5 1.1 0.10 0.10 11.2 4.0 0.16 0.06
0.02 0.01 0.01 0.00 0.71 0.33 0.16 0.13 1.6 2.8 0.55 0.41
5.4 2.6 2.3 1.2 11.6 1.9 0.13 0.07 30.5 10.0 0.30 0.11
0.05 0.05 0.03 0.04 0.57 0.68 0.19 0.10 0.91 1.04 0.39 0.18
0.8–7.8 0.04–4.0 2.3–14 0.03–0.3 6.5–42 0.08–0.4
n.d.-0.1 0.004–0.1 0.1–1.6 0.08–0.4 0.03–5.7 0.2–1.1
0.2–63 0.07–26 1.1–53 n.d.-3.7 8.8–168 n.d.-5.0
[17,21,29] [26,30] [3,17,31] [3,5,17,21,29] [31,33] [3,17,31,33]
0.002–9.9 n.d.-5.9 0.2–6.2 n.d.-6.2 n.d.-3.8 n.d.-2.5
[15,17,21,29] [26,30] [3,15,17,31] [3,5,17,21,29] [15,31–33] [3,15,17,31–33]
n.d.: not detected.
was firstly characterized individually in scan mode in order to identify the main ions (m/z ratio) constituting the mass spectrum and to choose the ions for quantification. PPCP GC grade reference standards were supplied by Sigma– Aldrich. The recovery values, the RSD (Relative Standard Deviation) and the limits of detection (LOD) and quantification (LOQ) were compound dependent (see Table 2). The correlation coefficient (r2) of the calibration curves was always higher than 0.990. Results and discussion PPCP occurrence As can be seen in Tables 3 and 4, the compounds with the highest concentrations in the influents in both WWTPs and also in the hospital wastewaters were ibuprofen, paracetamol, naproxen and caffeine. This is not surprising given that ibuprofen, paracetamol and naproxen are painkillers found in numerous over-the-counter medications commonly used in hospitals but also in households. Additionally to its use in pharmaceutical products, caffeine is frequently employed in beverages and foods as a stimulant. It should be also pointed out that, as it is shown in Table 3, average parameter values are much higher (excepting for carbamazepine, in two-fold concentration or even more) in WWTP2 than in WWTP1. When the amount of PPCPs that arrived to the WWTPs per capita was calculated, similar values were found for both facilities in the case of carbamazepine and diclofenac, whereas four-fold values were found for paracetamol and two-fold values were found for the rest of the compounds. WWTP2 receives only municipal and hospital wastewaters, whereas WWTP1 receives municipal wastewaters but also wastewaters from commercial and industrial parks. Obviously, the wastewaters coming from commercial and industrial facilities would not contribute much to the pharmaceutical loads. Surprisingly, and Table 4 Levels of PPCPs in hospital wastewaters (average concentrations SD and minimal and maximum values) compared with values reported by other authors. Average concentrations were obtained by employing all the concentrations measured during the year. PPCP
Concentrations (mg/L) SD
Concentration range (minimum–maximum) (mg/L) This work
Literature
References
Caffeine Paracetamol Naproxen Carbamazepine Ibuprofen Diclofenac
24.0 22.7 0.92 1.01 1.3 0.4 0.06 0.11 13.1 8.6 0.12 0.07
8.5–50.0 0.1–2.1 0.9–1.6 n.d.–0.19 4.5–21.7 0.04–0.2
12.3–42.0 3.1–21.2 n.d.–21.8 n.d.–2.0 1.5–151 n.d.–6.9
[22] [22] [22,34] [15,22,34] [15,22,34] [15,22,34]
n.d.: not detected.
excepting for caffeine, in general, hospital values were on the same order of magnitude as those obtained for both WWTPs (Table 4). Therefore, in this case hospital effluents could not be considered as responsible for increasing the concentration of these pharmaceuticals in the untreated wastewaters. The ranges of PPCPs concentrations detected in the influents of both WWTPs were comparable to concentrations reported in other studies worldwide (see Table 3). Particularly, caffeine, carbamazepine, and naproxen concentrations were similar to average values observed by Santos et al. [17] (4.9–7.4 mg/L, 0.4–0.5 mg/L and 4.3– 8.1 mg/L respectively) in different WWTPs located in the south of Spain, whereas ibuprofen and diclofenac influent concentrations were similar to those reported by Hijosa-Valsero et al. [18] (8.4– 24.2 mg/L and 0.4–0.8 mg/L respectively) in WWTPs located in the center of Spain. Regarding WWTPs effluents, caffeine, carbamazepine, ibuprofen and naproxen, concentration levels were in general lower than those reported for several WWTPs located in the Spanish south (0.2–2.4 mg/L, 0.2–0.7 mg/L, 0.06–10.2 mg/L and 0.8–4.4 mg/L respectively) [17,19], whereas most of diclofenac concentrations were slightly higher than average values reported by these authors (n.d.–0.24 mg/L). Table 4 compares the PPCPs levels observed here in the hospital wastewater with those found in the literature. With the exception of caffeine, our results were slightly lower. However, ibuprofen and carbamazepine mean value concentrations were comparable to those reported by Go´mez et al. [20] (19.8 mg/L and 0.04 mg/L respectively) in wastewaters from a private healthcare center located in the southeast of Spain. PPCPs concentrations in municipal effluents depend on different factors, such as influent composition, removal efficacies, WWTP performance, season or localization. In general, the outcoming concentrations measured here were within the range found in literature for WWTPs worldwide (see Table 3). As it can be seen, maximum values were lower than the upper values reported by other authors, excepting for ibuprofen. Minimum values were slightly higher, with the exception of naproxen. Considering only studies carried out in Spanish WWTPs, concentrations ranges found in this work were included in the range described by Santos et al. [17] and Hijosa-Valsero et al. [18] for caffeine (0.17–12.8 mg/ L), naproxen (0.05–5.1 mg/L), carbamazepine (<0.02–1.29 mg/L) and ibuprofen (0.002–55.0 mg/L), whereas diclofenac maximum value was higher than those reported by these authors (0.14– 0.66 mg/L). Removal efficiencies Percentages of PPCPs removal in the aqueous phase during wastewater treatment were calculated for both facilities ([influent] [effluent]/[influent] 100). Removal efficiencies were calculated for the four seasons and values shown in Fig. 2 were evaluated on the basis of the average of these four values.
[(Fig._2)TD$IG]
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
Fig. 2. Average removal efficiency for paracetamol, ibuprofen, naproxen and caffeine in both WWTPs. Bars indicate SD.
Therefore, it was considered the removal of PPCPs by degradation, but also by absorption phenomena. Diclofenac and carbamazepine persisted in WWTP effluents with similar or even slightly higher concentrations than those [(Fig._3)TD$IG]
499
measured in the untreated sewages (see Table 3). This phenomenon was also described by other authors [21–23]. The persistence of these compounds in the water would indicate that conventional wastewater treatment process is not effective in breaking down these compounds. The higher concentration levels found in the effluent could be explained by the formation of products of human metabolism and/or transformation products (e.g. hydroxyl- and epoxy-derivatives or glucuronides) which may act as a reservoir from which a later yield of the parent substance can occur [10,22– 24]. Additionally, it is necessary to take into account that the measured concentrations for these compounds are near to the detection limit, thus relative SDs are quite high. The removal values calculated for diclofenac and carbamazepine were very low or even negative, so they were omitted in Fig. 2, which shows the treatment removal efficiency for caffeine, paracetamol, ibuprofen and naproxen (calculated with average values). The average removal efficiencies for these compounds were higher than 95% in WWTP2. These values were similar to those reported for WWTPs sited in Europe and USA that included primary and biological treatment [17,25,26]. Concerning WWTP1, the average removal efficiencies were around 80% for paracetamol, naproxen and ibuprofen and 99% for
Caffeine
Carbamazepine 0,3
60
Concentration (µg/L)
Concentration (µg/L)
50 40 30 20 10 0
0,2
0,1
0,0 Autumn
Winter
Spring
Summer
Autumn
Autumn
Winter
Spring
Spring
Summer
Ibuprofen
4,5 4,0 3,5 3,0 2,5 2,0 1,5 1,0 0,5 0,0
Concentration (µg/L)
Concentration (µg/L)
Paracetamol
Winter
45 40 35 30 25 20 15 10 5 0 Autumn
Summer
Naproxen
Winter
Spring
Summer
Diclofenac 0,5
16 Concentration (µg/L)
Concentration ( µg/L)
14 12 10 8 6 4
0,4 0,3 0,2 0,1
2 0
0 Autumn
Winter
Spring
Summer
Autumn
Winter
Spring
Summer
Fig. 3. Seasonal influent concentrations of studied PPCPs in both WWTPs and hospital wastewater (~ WWTP1; & WWTP2; Hospital). Hospital autumn sample is missing, carbamazepine was not detected in winter and spring hospital samples.
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
500
caffeine. Despite of being less efficient than WWTP2, naproxen and ibuprofen removal values were still slightly higher than those cited by Blair et al. [27] (73% and 88% respectively) for North American WWTPs that included preliminary, primary and biological treatment and chlorine disinfection. Regarding removal efficiencies for BOD5 and nitrogen, again the average values are slightly higher in WWTP2 than in WWTP1 (99% and 80%, 98% and 68%, respectively). The higher efficiency removals observed in WWTP2 could be explained because the hydraulic retention time of the biologic reactor was higher in WWTP2 than in WWTP1 (10 and 8 h, respectively). Besides, the presence of pollutants coming from industrial wastewaters may interfere in the elimination process, decreasing biodegradation rates in WWTP1. Finally, it is important to point out that the primary clarification previous to biological treatment and the anaerobic step in WWTP1 did not contribute to improve the PPCPs removal efficiencies. Seasonality Samples taken in autumn, winter, spring and summer were compared to examine seasonal trends in PPCPs concentration (Fig. 3). Excepting for the increase detected in spring in hospital wastewater, the seasonal variation of caffeine in WWTP influents was minimal. Regarding carbamazepine, the highest value was observed in winter in WWTP1 influent and in summer in WWTP2 and hospital wastewater (0.25, 0.22 and 0.19 mg/L, respectively). The increase of the concentration observed in WWTP2 coincided
[(Fig._4)TD$IG]
[(Fig._5)TD$IG]
BOD 5
600
with an increase in hospital wastewater which is understandable as this hospital wastewater is treated in WWTP2. Paracetamol increased notably in all effluents in summer, while ibuprofen had a maximum in winter in WWTP2 and hospital wastewaters. Variations in naproxen were minimal for hospital wastewaters, whereas in WWTP1, the concentrations measured in spring and summer were double than those obtained in autumn and winter. On the opposite, the highest values for WWTP2 were found in autumn and winter. Minimum values of diclofenac were found in autumn and summer for both WWTPs and hospital wastewaters, observing a maximum in spring for WWTP2. Considering all these data, tendencies in the PPCPs concentrations of the untreated wastewaters could not be established, depending the followed pattern on the compound and specific water. It is necessary to take in mind that several factors are involved to determine the composition of these wastewaters, mainly the amount of PPCPs released and the abundance of rainfall that dilute the contamination (there is no separation between rainwater and sewage). Seasonal influent concentrations of BOD5 and total nitrogen were higher in WWTP2 than in WWTP1, with the exception of summer total nitrogen data (see Fig. 4). This can be due to the fact that, as it was mentioned above, the service area of WWTP2 is municipal, while WWTP1 serves a mix of municipal and industrial wastewaters that are likely to have lower concentrations of these contaminants. Fig. 5 shows the seasonal variation of removal efficiencies for PPCPs (caffeine, paracetamol, carbamazepine and ibuprofen), BOD5 and total nitrogen. PPCPs removal efficiencies in WWTP2 were higher than 95% with the exception of ibuprofen and naproxen values in autumn, which were lower that 90%. Values higher than
WWTP1
% Removal Efficiency
Concentration (mg/L)
500 400 300 200 100
100 95 90 85 80 75 70 65 60 55 50
0
5
Autumn
Winter
Spring
8
11
Summer Autum
14 T (ºC)
Winter
Total N
17
Spring
20
23
Summer
WWTP2
60 100 % Removal Efficiency
Concentration (mg/L)
50 40 30 20
95 90 85 80 75 70
10
5
0
8 Autum
Autumn
Winter
Spring
11
14 T (ºC)
Winter
Spring
17
20
23
Summer
Summer
Fig. 4. Seasonal influent concentrations of water parameters in both WWTPs (~ WWTP1; & WWTP2) (data from the ‘‘Consorcio de Aguas de Asturias’’).
Fig. 5. Seasonal variation of removal efficiency in both WWTPs for: ^ Caffeine, & Paracetamol, ~ Naproxen, Ibuprofen, * BOD5 and + Total N. Arrows indicate the sampling season that corresponds to each temperature.
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
501
Table 5 Seasonal values of apparent kinetic constant (k) (h1) for different contaminant removal in both WWTPs. Pollutants
WWTP1
WWTP2
Autumn
Winter
Spring
Summer
Autumn
Winter
Spring
Summer
BOD5 Total N Caffeine Paracetamol Naproxen Ibuprofen
0.41 0.10 0.46 0.20 0.19 0.38
0.43 0.13 0.58 0.22 0.22 0.06
0.51 0.18 0.65 0.24 0.23 0.54
0.53 0.19 0.69 0.71 0.12 0.63
0.44 0.13 0.52 0.31 0.21 0.22
0.46 0.18 0.43 0.41 0.38 0.34
0.50 0.20 – 0.52 0.46 0.71
0.45 0.14 0.46 0.64 0.35 0.58
Table 6 Values of apparent activation energy (kJ/mol) for different contaminants in both WWTPs. Pollutant
WWTP1
WWTP2
BOD5 Total N Caffeine Paracetamol Naproxen Ibuprofen
18.4 46.4 26.5 21.4 21.0 34.1
15.6 52.5 – 50.0 86.1 63.6
95% were also obtained in WWTP1 for caffeine and ibuprofen. In the case of naproxen and paracetamol the values in WWTP1 were below 85% during all the year, excepting for paracetamol removal efficiency in the summer sample that was above 95%. Considering the exact date of sampling, average day temperatures were 9 8C, 12 8C, 15 8C and 19 8C for autumn, winter, spring and summer respectively. Therefore, as it was reported in other works [18,26], the seasonal differences of PCPP removal levels reflected that in general treatment processes were more effectively for warmer temperatures. This trend was clearly observed in WWTP1, with the exception of naproxen whose lowest value was reached in summer. Regarding removal efficiencies for BOD5 and total nitrogen, WWTP2 values for these parameters did not show a clear tendency, whereas in case of WWTP1 achieved a maximum in summer. The apparent kinetic constants (k) for the removal of the studied contaminants were calculated for both WWTPs (Table 5). The expected increase in k values with temperature was clearly observed in WWTP1 with only two anomalous values (naproxen in summer and ibuprofen in winter). In the case of WWTP2, almost all the summer values were lower than expected. This behavior is likely to be related with some kind of modification in microbial community running, as a consequence of a drastic change in temperature or composition of the water suffered in previous days. A lack of tendency was also observed for caffeine in WWTP2, but this can be explained because concentrations measured in the effluent were very low, near LOD and therefore, these measurements have larger uncertainty. It is important to remark that k values are within the same order in both WWTPs (between 0.06 and 0.71 h1 in all cases), observing values slightly higher in WWTP2 for naproxen and paracetamol. Ferguson et al. [28] observed a negative correlation between temperature and total pharmaceutical abundance in an USA lake. This indicated that lower temperatures reduce the rate of biodegradation of these PPCPs in surface water and sewage treatment plants, finding that temperature is more important to degradation of some pollutants than another. With the aim of determining the relation between the k constants and temperature, an Arrhenius type equation was employed. Values with anomalous behavior (showed in gray in Table 5) were not considered in the calculation of the apparent activation energy. Apparent activation energy values for BOD5 and
total N were similar in both WWTPs, whereas WWTP2 showed values twice or three times higher for paracetamol, naproxen and ibuprofen (see Table 6). This indicated that, the PPCP removal process is much more sensible to temperature in case of WWTP2 than in WWTP1. Conclusions Among the six PPCPs considered in this study, ibuprofen, paracetamol, naproxen and caffeine were the compounds detected in higher levels in the analyzed wastewaters. Tendencies throughout the year could not be established for PPCPs concentrations found at the entrance of the WWTPs. Results showed that traditional treatment for municipal wastewaters were not effective in removing diclofenac and carbamazepine, whereas paracetamol, ibuprofen, naproxen and caffeine concentrations decreased between 75% and 99% during the process. Differences of PCPP removal levels found in samples taken at different seasons reflected that, in general, the treatment throughout the WWTPs were more effectively for warmer temperatures. Additionally, one of the studied WWTP resulted to be more sensible to temperature changes, as it was showed by kinetic parameter values. Further research would be interesting in order to complete the conclusions here achieved and establish the convenience of controlling certain of these pollutants in municipal WWTPs in a systematic way. Acknowledgments The authors thank the ‘‘Consorcio de Aguas de Asturias’’ (Government of Asturias, Spain) and the ‘‘Hospital Universitario Central de Asturias’’ (HUCA) for supplying the samples and MEDYCSA for funding the project. References [1] C. Reyes-Contreras, V. Matamoros, I. Ruiz, M. Soto, J.M. Bayona, Evaluation of PPCPs removal in a combined anaerobic digester-constructed wetland pilot plant treating urban wastewater, Chemosphere 84 (2011) 1200–1207. [2] V.L. Cunningham, M. Buzby, T. Hutchinson, F. Mastrocco, N. Parke, N. Roden, Effects of human pharmaceuticals on aquatic life: next steps, Environ. Sci. Technol. 40 (2006) 3456–3462. [3] M. Al Aukidy, P. Verlicchi, A. Jelic, M. Petrovic, D. Barcelo`, Monitoring release of pharmaceutical compounds: occurrence and environmental risk assessment of two WWTP effluents and their receiving bodies in the Po Valley, Italy, Sci. Total Environ. 438 (2012) 15–25. [4] X. Yang, R.C. Flowers, H.S. Weinberg, P.C. Singer, Occurrence and removal of pharmaceuticals and personal care products (PPCPs) in an advanced wastewater reclamation plan, Water Res. 45 (2011) 5218–5228. [5] Y. He, W. Chen, X. Zheng, X. Wang, X. Huang, Fate and removal of typical pharmaceuticals and personal care products by three different treatment processes, Sci. Total Environ. 447 (2013) 248–254. [6] T. Heberer, D. Feldmann, Contribution of effluents from hospitals and private households to the total loads of diclofenac and carbamazepine in municipal sewage effluents-modeling versus measurements, J. Hazard. Mater. 122 (2005) 211–218. [7] D.W. Kolpin, E.T. Furlong, M.T. Meyer, E.M. Thurman, S.D. Zaugg, L.B. Barber, H.T. Buxton, Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999–2000: a national reconnaissance, Environ. Sci. Technol. 36 (2002) 1202–1211.
502
M. Ferna´ndez et al. / Journal of Environmental Chemical Engineering 2 (2014) 495–502
[8] N.M. Vieno, T. Tuhkanen, L. Kronberg, Seasonal variation in the occurrence of pharmaceutical sin effluents from a sewage treatment plant and in the recipient water, Environ. Sci. Technol. 39 (2005) 8220–8226. [9] G.A. Loraine, M.E. Pettigrove, Seasonal variations in concentrations of pharmaceuticals and personal care products in drinking water and reclaimed wastewater in southern California, Environ. Sci. Technol. 40 (2006) 687–695. [10] Q. Sui, J. Huang, S. Deng, G. Yu, Q. Fan, Occurrence and removal of pharmaceuticals, caffeine and DEET in wastewater treatment plants of Beijing, China, Water Res. 44 (2010) 417–426. [11] P. Verlicchi, M. Al Aukidy, A. Galletti, M. Petrovic, D. Barcelo`, Hospital effluent: investigation of the concentrations and distribution of pharmaceuticals and environmental risk assessment, Sci. Total Environ. 430 (2012) 109–118. [12] B. Gy Plo´sz, H. Leknes, H. Liltved, K.V. Thomas, Diurnal variations in the occurrence and the fate of hormones and antibiotics in activated sludge wastewater treatment in Oslo, Norway, Sci. Total Environ. 408 (2010) 1915–1924. [13] M. Pomie`s, J.M. Choubert, C. Wisniewski, M. Coquery, Modelling of micropollutant removal in biological wastewater treatments: a review, Sci. Total Environ. 443 (2013) 733–748. [14] M. Novak, P. Horvat, Mathematical modelling and optimisation of a waste water treatment plant by combined oxygen electrode and biological waste water treatment model, Appl. Math. Model. 36 (2012) 3813–3825. [15] A. Togola, H. Budzinski, Multi-residue analysis of pharmaceutical compounds in aqueous samples, J. Chromatogr. A 1177 (2008) 150–158. [16] S.S. Verenitch, C.J. Lowe, A. Mazumder, Determination of acidic drugs and caffeine in municipal wastewaters and receiving waters by gas chromatography-ion trap tandem mass spectrometry, J. Chromatogr. A 1116 (2006) 193–203. [17] J. Santos, I. Aparicio, M. Callejo´n, E. Alonso, Occurrence of pharmaceutically active compounds during 1-year period in wastewaters from four wastewater treatment plants in Seville (Spain), J. Hazard. Mater. 164 (2009) 1509–1516. [18] M. Hijosa-Valsero, V. Matamoros, J. Martı´n-Villacorta, E. Be´cares, J. Bayona, Assessment of full-scale natural systems for the removal of PPCPs from wastewater in small communities, Water Res. 44 (2010) 1429–1439. [19] M.D. Camacho-Mun˜oz, J.L. Santos, I. Aparicio, E. Alonso, Presence of pharmaceutically active compounds in Don˜ana Park (Spain) main watersheds, J. Hazard. Mater. 177 (2010) 1159–1162. [20] M. Go´mez, M. Patrovic, A. Ferna´ndez-Alba, D. Barcelo´, Determination of pharmaceuticals of various therapeutic classes by solid-phase extraction and liquid chromatography-tandem mass spectrometry analysis in hospital effluent wastewaters, J. Chromatogr. A 1114 (2006) 224–233.
[21] A. Spongberg, J. Witter, Pharmaceutical compounds in the wastewater process stream in Northwest Ohio, Sci. Total Environ. 397 (2008) 148–157. [22] C. Kosma, D. Lambropoulou, T. Albanis, Occurrence and removal of PPCPs in municipal and hospital wastewaters in Greece, J. Hazard. Mater. 179 (2010) 804–817. [23] A. Jelic, M. Gros, A. Ginebreda, R. Cespedes-Sa´nchez, F. Ventura, M. Petrovic, D. Barcelo´, Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during wastewater treatment, Water Res. 45 (2011) 1165–1176. [24] T. Rauch-Williams, C. Hoppe-Jones, J. Drewes, The role of organic matter in the removal of emerging trace organic chemicals during managed aquifer recharge, Water Res. 44 (2010) 449–460. [25] S. Zorita, L. Ma˚rtensson, L. Mathiasson, Occurrence and removal of pharmaceuticals in a municipal sewage treatment system in the south of Sweden, Sci. Total Environ. 407 (2009) 2760–2770. [26] J.T. Yu, E.J. Bouwer, M. Coelthan, Occurrence and biodegradability studies of selected pharmaceuticals and personal care products in sewage effluent, Agric. Water Manage. 86 (2006) 72–80. [27] B.D. Blair, J.P. Crago, C.J. Hedman, R.J.F. Treguer, C. Magruder, L.S. Royer, R.D. Klaper, Evaluation of a model for the removal of pharmaceuticals, personal care products, and hormones from wastewater, Sci. Total Environ. 444 (2013) 515–521. [28] P.J. Ferguson, M.J. Bernot, J.C. Doll, T.E. Lauer, Detection of pharmaceuticals and personal care products (PPCPs) in near-shore habitats of southern Lake Michigan, Sci. Total Environ. 458–460 (458) (2013) 187–190. [29] A.Y.C. Lin, T.H. Yu, S.K. Lateef, Removal of pharmaceuticals in secondary wastewater treatment processes in Taiwan, J. Hazard. Mater. 167 (2009) 1163–1169. [30] P.H. Roberts, K.V. Thomas, The occurrence of selected pharmaceuticals in wastewater effluent and surface waters of the lower Tyne catchment, Sci. Total Environ. 356 (2006) 143–153. [31] L. Lishman, S.A. Smyth, K. Sarafin, S. Kleywegt, J. Toito, T. Peart, B. Lee, M. Servos, M. Beland, P. Seto, Occurrence and reductions of pharmaceuticals and personal care products and estrogens by municipal wastewater treatment plants in Ontario, Canada, Sci. Total Environ. 367 (2006) 544–558. [32] T. Ternes, Occurrence of drugs in German sewage treatment plants and rivers, Water Res. 32 (1998) 3245–3260. [33] K. Fent, A.A. Weston, D. Caminada, Ecotoxicology of human pharmaceuticals, Aquat. Toxicol. 76 (2006) 122–159. [34] L.H.M.L.M. Santos, M. Gros, S. Rodriguez-Mozaz, C. Delerue-Matos, A. Pena, D. Barcelo´, M.C.B.S.M. Montenegro, Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: identification of ecologically relevant pharmaceuticals, Sci. Total Environ. 461–462 (461) (2013) 302–310.