Desalination 250 (2010) 653–659

Contents lists available at ScienceDirect

Desalination
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / d e s a l

Comparison of removal of pharmaceuticals in MBR and activated sludge systems☆

Jan Sipma a,⁎, Begoña Osuna b, Neus Collado a, Hector Monclús a, Giuliana Ferrero a,
Joaquim Comas a, Ignasi Rodriguez-Roda a
a
Laboratory of Chemical and Environmental Engineering (LEQUIA), University of Girona, Science and Technologic Park. Ed. Jaume Casademont,
c/Pic de Peguera 15, E17003, Girona, Spain
b
Group of Limnology-Department of Continental Ecology, Centre d'Estudis Avançats de Blanes, CEAB-CSIC, Acces Cala St. Francesc, Blanes, Girona, Spain

a r t i c l e i n f o a b s t r a c t

Article history: Membrane bioreactors (MBRs) nowadays attract serious attention for the treatment of municipal
Accepted 22 June 2009 wastewater, due to recent technical innovations and drastic cost reductions of the employed membranes.
Available online 7 October 2009 Especially the high biomass concentrations and long sludge retention times are favorable for the
biodegradation of organic pollutants, resulting in high rate treatment systems. These characteristic features
Keywords:
of MBR technology are not merely advantageous for organic matter removal, but also likely promote a higher
Membrane bioreactor
Conventional activated sludge systems
biodegradation efficiency of refractory organic pollutants. The increasing concern about the potential
Microbial dynamics accumulation of micro-pollutants such as pesticides, pharmaceuticals and personal care products, in the
Biodegradation aquatic environment triggered many investigations into their biological degradation or fate in wastewater
Micro-pollutants treatment systems. In this work a short overview is presented on the current knowledge of removal of
Pharmaceuticals pharmaceuticals in MBRs compared to their removal in conventional activated sludge treatment system. In
general, for slowly degradable pharmaceuticals the removal in MBRs is better due to the relatively long
sludge ages, which leads to the development of distinct microbial communities in MBRs compared to
activated sludge plants. Nevertheless, from the literature results it could not be concluded that
pharmaceutical removal in MBR reactors is better as many other factors have been indicated that may
affect biodegradation rates, which are not directly related to the reactor configuration.
© 2009 Elsevier B.V. All rights reserved.

1. Introduction detected these contaminants in widely varying concentrations in 80%

The presence of micro-pollutants, such as pesticides, pharmaceu-
ticals and personal care products, ubiquitous contaminants of
municipal wastewater, is nowadays considered as a serious problem,
that may have subtle detrimental effects on aquatic organisms, and
possibly also on human health despite the usually low concentrations
at which they occur. The risks of pharmaceuticals, or pharmaceutically
active compounds, remain poorly understood [1]. Kolpin et al. [2]
have stressed that we unfortunately know very little about the
environmental implications of pharmaceuticals and personal care
products in relation to their transport, occurrence, and fate of many of
the synthetic chemicals that are released into the global environment
by human activities. These authors provided the first reconnaissance
of 95 organic wastewater contaminants in fluvial ecosystems and
☆ Presented at the Conference on Membranes in Drinking and Industrial Water
Production, 20–24 October 2008, Toulouse, France.
⁎ Corresponding author. Laboratory of Chemical and Environmental Engineering
(LEQUIA), University of Girona, Spain. Tel.: +34 972183249.
E-mail addresses: jsipma@lequia.udg.cat (J. Sipma), bosuna@ceab.csic.es (B. Osuna),
neus.collado@lequia.udg.cat (N. Collado), hector@lequia.udg.cat (H. Monclús),
giuliana@lequia.udg.cat (G. Ferrero), quim@lequia.udg.cat (J. Comas),
ignasi@lequia.udg.cat (I. Rodriguez-Roda).
of the 139 streams sampled. Due to their intrinsic properties, i.e. often
high polarity and persistence, many pharmaceuticals are likely to
reach and possibly accumulate in the aquatic environment. Although
there is a great deal of uncertainty concerning the potential
detrimental effects on the aquatic ecosystems, the precautionary
principle, or new scientific evidence, will likely give rise to more
stringent demands on wastewater treatment in the future [1,3]. This
new views on wastewater treatment includes a wide range of micro-
pollutants, that with sophisticated modern analytical techniques have
been discovered in wastewater as well as in the aquatic environment.
In this paper the focus will be on pharmaceutical compounds, which
are mainly introduced into the aquatic ecosystem via municipal
wastewater treatment works [4].
Some pharmaceuticals have been found to be endocrine disrupting
chemicals, i.e. these chemicals interfere with the normal functioning of
the hormone system, although this ability has been found in a wide
range of synthetic chemicals, especially pesticides and plasticizers.
Studies have shown that compounds like alkylphenol ethoxylates,
bisphenol A, estrone, 17β-estradiol, 17α-ethinylestradiol may have a
high specific biological estrogenic activity even at extremely low
concentrations [5]. Endocrine disrupting chemicals have been demon-
strated to cause a wide range of adverse effects on aquatic organisms,

0011-9164/$ – see front matter © 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.desal.2009.06.073
654 J. Sipma et al. / Desalination 250 (2010) 653–659

e.g., feminization of male fish, masculinization of snails, growth result in significant stripping at facilities employing fine air bubbling [9].
inhibition, immobilization, mutagenicity, mortality, and changes in Table 1 shows some values of Henry coefficients for selected pharmaceu-
population density (as reviewed in [5]). ticals. Aeration in an MBR is typically higher, especially stripping
The low concentrations at which they occur in municipal wastewater efficiencies increase in the membrane compartment where coarse bubble
treatment facilities makes their efficient removal a challenge. Micro- aeration is applied for membrane scouring, so that for pharmaceuticals
pollutant removal during wastewater treatment occurs through various with a relative high Henry coefficient some stripping might occur.
mechanisms, including biodegradation, abiotic transformations and Since wastewater treatment plants (WWTPs) are usually operated
sorption to biomass or suspended solids. In general sorption processes in an open environment, which exposes wastewater to direct sunlight
and biodegradation are considered the most important removal photo-degradation may occur. Although the turbidity of wastewater
mechanisms for micro-pollutants, although these do not follow a blocks most sunlight, water in the top layer and water in secondary
general rule as their relative contribution depends on the physico- clarifiers is exposed to sunlight irradiation, especially in summer [8].
chemical properties of the pollutant, the origin and composition of the Therefore, some contaminants may be affected by photo-transforma-
wastewater and the characteristics of the wastewater treatment facility tion, i.e. those with high photo-degradation rates. The effect of photo-
[5]. Whereas many micro-pollutants are reasonably well removed via degradation in MBRs is considerable smaller as no secondary clarifiers
sorption to the sludge due to their apolar nature, many pharmaceuticals are used and the sludge concentrations are usually much higher
or pharmaceutically active compounds are highly polar, either as they limiting the penetration of sunlight into the facility.
have been synthesized this way to warrant a high mobility within a
patient or have been formed after biotransformation to enable their final
excretion with the urine. Therefore, for an efficient removal of 3. Pharmaceutical removal via sorption to suspended solids
pharmaceutical compounds the stimulation of their biodegradation or
the use of advanced oxidation processes will probably be the most For the estimation of the removal via sorption to suspended solids
effective removal strategy. and biomass solid–water distribution coefficients (Kd) have been
Whereas advanced oxidation processes require additional invest- introduced, which are defined as the ratio between the concentrations
ments and increase operational costs, mainly due to increased energy of a substance in the solid and in the aqueous phase at equilibrium
demands or consumption of chemicals, they are able to oxidize many conditions [10]. This coefficient takes into account the two main
organic pollutants, which could lead to their removal or the formation of sorption mechanisms [10]: absorption (hydrophobic interactions
intermediates that are more amendable to biodegradation, depending
on the advanced oxidation process employed. Nevertheless, since most
wastewater treatment is based on biological conversions, optimization
of the biodegradation capacity could be an elegant way of micro- Table 1
pollutant removal. However, the degradation characteristics of many of Physico-chemical characteristics of selected pharmaceutical compounds.
these chemicals are unknown, as are the chemical properties of their
Pharmaceutical Molar Octanol–water Sorption Henry pKa
byproducts [6]. Furthermore, due to the relative low sludge age in weight partitioning constant coeff.
conventional activated sludge (CAS) systems combined with the low (Mw) Log Kow Kd L/kg SS Air/water
biomass concentrations present, the biodegradation potential of micro- g.mol− 1 [−]
pollutants, such as pharmaceutically active compounds, is generally low Acetaminophen 151.2 0.27 0.4 2.63e−11 9.4
[4]. Therefore, biodegradation of pharmaceuticals in CAS systems ranges Diclofenac 294 4.02 16 1.93e−10 4.51
from almost no biodegradation to virtually complete biodegradation Ibuprofen 206.3 3.79 7 6.21e−06 4.91
Indomethacin 357.8 4.27 28 4.5
depending on the type of pharmaceutical and its ready biodegradability. Ketoprofen 254.3 3 16 8.67e−10 4.45
Membrane bioreactors (MBRs) hold a promise for the degradation of Mefenamic acid 241.3 5.28 434 1.05e−09 4.2
micro-pollutants, which could be ascribed especially to the high sludge Naproxen 230.3 3.1 13 1.38e−08 4.15
concentration and relative high sludge age at which they operate. This Propyphenazone 230.3 2.05 7.50e−08
Erythromycin 734.5 2.48 160 2.22e−27 8.88
makes the presence of microorganisms that are capable of degrading the
Roxithromycin 837 2.1–2.8 200–400 9.2
specific micro-pollutants present more likely. Ofloxacin 361.4 0.84–2.1 6.05 and
This paper presents a brief overview of the potentials of membrane 8.22
bioreactor (MBR) technology for the removal of pharmaceuticals from Sulfamethoxazole 253.3 0.48 200–400 3.91e−11 5.5
municipal wastewater. The reported literature on removal of Trimethoprim 290.3 0.73 200 9.76e−13 7.12
Bezafibrate 361.8 4.25 8.67e−14 3.61
pharmaceuticals is compared between MBR and CAS systems. The Clofibric acid 214.65 2.84 5 8.96e−07 3.18
present paper does not attempt to give an exhaustive description of Gemfibrozil 250.3 4.77 75 4.88e−07 4.75
the knowledge available on biodegradation of pharmaceuticals, but Pravastatin 424.5 2.23 4.7
intends to give the most important general views and trends on the Atenolol 266.3 0.1–0.57 64 9.4
Metoprolol 267.4 1.6–1.8 9.68
biodegradation of pharmaceuticals as this group of micro-pollutants is
Propanolol 259.3 3.0–3.1 366 9.14
enormous in number, i.e. about 3000 substances are registered in the Sotalol 257.4 0.85 8.3 and 9.8
EU for pharmaceutical purposes alone [7]. Famotidine 337.45 − 2.1 to − 0.4 6.76↔6.98

2. Removal mechanisms of pharmaceuticals during wastewater Loratidine 382.9 3.8–5.94 3321 4.9
Ranitidine 314.4 1.23–1.30 8.2 and 2.7
treatment
Carbamazepine 236.3 2.25 0.1 4.40e−09 7
Fluoxetine 309.3 4.05 10.1
The removal of pharmaceuticals in activated sludge processes includes Paroxetine 329.3 3.1 9.9
four mechanisms, i.e: biotransformation, sorption, air-stripping and Iopromide 791.1 − 2.05 11 10.2
Glibenclamide 494 4.79 239 3.09e 6.5
photo-transformation [8]. The latter two mechanisms are generally
−07
considered to be insignificant in wastewater treatment plants. Air- Hydrochlorothiazide 297.7 − 0.50 to − 0.07 20 7.0 and 9.2
stripping efficiency depends on the Henry coefficient of a specific
compound and the aeration flow rates applied to the biological treatment. Physico-chemical information was obtained from [7,30,32,42,49] and from the
Since pharmaceuticals have Henry values smaller than 10− 5, whereas following websites: www.chemspider.com; www.drugbank.ca; www.druginfosys.
values larger than 10− 3 (dimensionless air water KH) are required to com; www.drugs.com.
 J. Sipma et al. / Desalination 250 (2010) 653–659
characterized by the Kow value) and adsorption (electrostatic interac-
tions characterized by the dissociation constant; pKa). Compounds with
a high Kow value in principle have more affinity for the solid fraction, but
a good correlation of the Kow and Kd values could not be demonstrated
as mentioned by Ternes et al. [9] and they suggest that Kd values should
be experimentally determined.
In general, sorption to activated sewage sludge is of minor
importance for many pharmaceuticals, as shown by their relative low
sorption constants (Kd). According to Ternes et al. [9], compounds with a
Kd < 500 L/kg are eliminated by less than 10% through sorption onto
activated sludge at an average specific sludge production of 200 g m− 3.
This also explains why in general removal efficiencies during primary
treatment are generally low as has been observed amongst others by
Göbel [11]. Table 1 shows some values for Kd, which agree with the
previous statement that pharmaceutical removal by sorption will be a
minor removal pathway in the overall mass balance of wastewater
treatment. Only loratidine showed a high Kd value, for which sorption
can be considered as a significant removal pathway in WWTPs. Many
pharmaceuticals are relatively hydrophilic and thus sorption will be
limited. However, fluoroquinolone antibiotics, although very hydro-
philic, are mainly eliminated from the aqueous phase by sorption to
sludge presumably via electrostatic interactions [11,12]). For micro-
pollutants with a high adsorption potential the removal efficiency in an
MBR may be slightly higher due to the absence of suspended solids in
the effluent [27].
4. Pharmaceutical removal via biodegradation
Despite that many pharmaceuticals were designed to be persis-
tent, biodegradation of many pharmaceuticals has been observed in
WWTP [13] and actually represents the most important removal
mechanism in WWTP. The large number of different pharmaceuticals,
with highly variable molecular structures complicates their efficient
removal. Structure–biodegradability relationships obtained for a large
data set of organic chemicals showed that compounds including
esters, nitriles and aromatic alcohols have functional groups that may
increase biodegradability, whereas aromatic amines, iodide, nitro and
azo groups increases a compound's persistence [14]. Jones et al. [15]
also reported that long and highly branched side chains render a
compound more persistent, whereas unsaturated aliphatic com-
pounds are more biodegradable than saturated analogues or aromatic
compounds with complicated aromatic ring structures and sulfate or
halogen groups. Nevertheless, various investigators have reported on
the absence of a relationship between the structure and biodegrad-
ability for pharmaceuticals [16–18].
5. Conceptual advantages of membrane bioreactors
for biodegradation of pharmaceuticals
MBR technology in municipal wastewater treatment is currently
challenging traditional methods, due to recent technical innovations
and drastic cost reductions of the employed membranes [19]. MBR
technology offers several advantages over CAS plants, e.g. operation at
high biomass concentrations [20], reduced excess sludge production
[21], extremely low suspended solid concentrations in the treated
effluent [22], drastically enhanced elimination of pathogens and viruses
[23,24], and a superior effluent quality [24–26]. Furthermore, the high
biomass concentration and long sludge retention times (SRT) in MBR
plants positively affects the overall activity of slow growing micro-
organisms acting in e.g. nitrification [24] or degradation of specific
refractory pollutants, e.g. micro-pollutants [25,27]. Schröder [25]
suggested that MBR systems provide a competitive advantage for
organisms capable of degrading recalcitrant compounds by eliminating
bacterial washout. However, the latter obviously is governed by the
required sludge wastage to maintain a more or less constant biomass
concentration in the MBR, thus limiting the SRT. Furthermore, the high
655
biomass concentrations in an MBR not merely lead to a decreased sludge
production, but also a higher stability and persistence to shock loads
[23,28].
The high biomass concentrations in MBRs, also affects the food to
microorganisms (F/M) ratio, which is the organic matter that is
available for a certain mass of microorganisms and is usually low in an
MBR. The relative shortage in (biodegradable) organic matter may
force microorganisms to metabolize also poorly degradable com-
pounds. This is one explanation why removal of poorly degradable
pollutants may be superior in MBR systems and why this can be
achieved at lower HRT [29]. The combination of high solid retention
times and reduced F/M ratios may result in an increased biodiversity,
and positively affect the elimination of compounds undergoing co-
metabolism, as assumed for antimicrobials [11]. Furthermore,
pharmaceuticals present at environmental relevant concentrations
for WWTP, i.e. often at enzyme subsaturating levels, require an
oligotrophic metabolism favored by low F/M ratios [30].
The high sludge concentrations in a MBR is not only beneficial for
biodegradation of pharmaceuticals, but is also presumed to have a
beneficial effect on the removal efficiency of micro-pollutants that
tend to accumulate in the sludge, either due to their intrinsic
hydrophobicity or via electrostatic interactions with the biomass.
Since, the latter removal mechanism is rather a concentration than
elimination of the micro-pollutants, subsequent treatment of the
produced sludge, usually via incineration, is required to prevent it
from ending up in the aquatic environment, which is likely to occur
when this sludge would be applied for agricultural purposes.
Cicek et al. [31] reported that the biomass in a MBR has a higher
viable fraction compared to CAS systems, which could be attributed to
an improved mass transfer due to the presence of smaller flocs and a
large fraction of planktonic microorganisms. The smaller average size,
resulting in a drastically enhanced specific surface area of the
microorganisms, combined with the general high sludge concentrations
in MBRs, favors the contact between microorganisms and pollutants and
stimulates their biological degradation. Furthermore, some enzymatic
activities increase proportionally to the higher specific surface area of
MLSS, which is directly related to the floc-structure [5].
Whereas nanofiltration and reversed osmosis membranes effi-
ciently remove various pharmaceuticals [35], the microfiltration and
ultrafiltration membranes used in MBR technology were shown to
reject very few target compounds, although some loss of steroidal
type compounds was observed [32]. Since the pharmaceuticals are
small molecules, mostly around 200–300 Da, it is not surprising that
direct membrane rejection does not play a role, as the pharmaceu-
ticals are at least 100 times smaller than the molar weight cut off
(MWCO) of the used membranes in MBR processes [18].
The typical process characteristics of the MBR technology are in
principle favorable for enhanced removal of micro-pollutants from
wastewater compared to CAS treatment systems, although a direct
rejection of pharmaceuticals due to the application of membranes
cannot be expected. Whereas, this enhanced removal would be
sufficient for ensuring a high quality of the aquatic environment needs
to be evaluated. However, for this not only knowledge on the
biodegradation efficiency is required, but also on the potential risks of
these micro-pollutants on the aquatic environment. The latter will not
be addressed further in this overview.
6. Comparison of pharmaceuticals removal in CAS and MBRs
Table 2 presents the average removal efficiency of 30 pharmaceu-
ticals which has been documented for both CAS and MBR treatment
facilities. The average results of different treatment facilities have been
used, not taking into account the reported standard deviations in the
original publications, and resulting average efficiencies for both reactor
types have been calculated as well as their standard deviations. Since
original standard deviations were not taken into account, minimum and
656 J. Sipma et al. / Desalination 250 (2010) 653–659

maximum removal efficiencies have been presented as well to give an
idea of the variability. From the Table it can be seen that easily removed
pharmaceuticals are equally well removed in both systems, i.e.
acetaminophen, ibuprofen and paroxetine. Nevertheless, in most cases
the removal efficiency of moderately or slightly removed pharmaceu-
ticals in CAS is better in an MBR, although the removal efficiency in most
cases is far from complete. In some cases, i.e. sotalol and hydrochloro-
thiazide the removal efficiencies reported in an MBR were worse than
the reported values in a CAS. It should be noted that for some
pharmaceuticals the number of different treatment facilities analyzed
is rather limited.
The results in Table 2 further show that for some compounds the
average removal can be negative, indicating that effluent concentra-
tions were higher than influent concentrations. This phenomenon has
been frequently encountered for carbamazepine, which usually is
not eliminated during biological treatment. For carbamazepine, the
elevated effluent concentrations are most likely due to enzymatic
cleavage of the glucuronic conjugate of carbamazepine and release of
the parent compound in the treatment plant [12]. Negative elimina-
tion has also been found for some macrolides [11], for which the
presence of conjugated metabolites is unlikely. Since they are mainly
excreted with bile and feces, they could be enclosed in feces particles
and released during biological treatment, suggesting that the
pharmaceutical load is underestimated when based exclusively on
the dissolved fraction and the fraction sorbed to the suspended solids
[11].
Cirja et al. [5] reported that they did not find a real difference
between CAS and MBRs, concerning the removal of micro-pollutants.
Although they noted that the removal rates differed from one
compound to another, which can likely be ascribed to the physical–
chemical characteristics of the xenobiotics. The huge number of
potential micro-pollutants that may enter a wastewater treatment

Table 2
Average removal efficiencies of selected pharmaceuticals in CAS and MBR.

Pharmaceutical Pharmaceutical CAS MBR

class
Averagea Min.b Max.b Nc Refs. Average Min. Max. N Refs.
Removal % Rem. % Rem. % Removal % Rem. % Rem. %
( SD) (± SD)

Analgesics
Non-NSAID Acetaminophen 99.1 (± 0) 98.4 99.9 5 [16,17,34,51,54] 99.8 (± 0) 99.6 99.9 3 [17,34]

NSAIDs Diclofenac 21 (± 41) − 143 80 49 [16–18,27,34,38–40,51–53,55,59] 34 (± 25) −8 87.4 18 [17,18,27,34,35,38,39,56]

Ibuprofen 93.5 (± 7) 52 99.7 64 [16–18,27,34,35,38– 97.3 (± 3) 89 99.8 18 [17,18,27,34,35,38,39,56]
40,48,50,51,53,55,57–59]
Indomethacin 15 (± 32) − 41 63 6 [17,34,40] 43 (± 3) 39.7 46.6 3 [17,34]
Ketoprofen 47 (± 21) 9 91.1 28 [16,17,34,35,40,53,57,58] 72 (± 23) 43.9 97 6 [17,34–56]
Mefenamic acid 27 (± 21) 0 51 3 [17,34,35] 63 (± 21) 35.5 89 5 [17,34,35]
Naproxen 66 (± 23) −2 98 46 [16–18,34,35,40,50,53,55,57–59] 85 (± 10) 71 99.3 9 [17,18,34–56]
Propyphenazone −72 (±213) − 693 86.4 17 [17,34,57] 63 (± 2) 60.7 64.6 3 [17,34]
Antibiotics
Macrolides Erythromycin 2 (± 19) − 22 35.4 7 [11,17,34] 45 (± 17) 25.2 67.3 3 [17,34]
Roxithromycin 25 (± 26) − 20 66 19 [11,18,39] 55 (± 15) 33 75 4 [18,39]
Fluoroquinolone Ofloxacin 75 (± 19) 23.8 93 11 [12,17,34] 93.5 (± 2) 91.3 95.2 3 [17,34]
antibiotics
Sulfonamides Sulfamethoxazole 33 (± 64) − 138 99 20 [11,17,18,34,39,50,54] 73 (± 11) 57 90 7 [17,18,34,39]
Dihydrofolate Trimethoprim 11 (± 31) − 40 40.4 12 [11,34,55] 57 (± 10) 47.5 66.7 2 [34]
reductase
inhibitors
Lipid regulators
Bezafibrate 77 (± 26) 21.2 99.3 21 [17,27,34,38,39] 90 (± 8) 76 97 13 [17,27,34,38,39,56]
Clofibric acid 16 (± 13) 0 30 5 [17,35,48,52,53] 67 (± 20) 41 71.8 3 [17,35]
Gemfibrozil 51 (± 22) 0 75 14 [16,17,34,40,55] 55 (± 25) 32.5 89.6 3 [17,34]
Pravastatin 61 (± 1) 59.4 61.8 2 [17,34] 87 (± 3) 83.1 90.8 3 [17,34]
Β-blockers
Atenolol 44 (± 32) 0 97 18 [12,17,34,55] 71 (± 5) 65.5 76.7 3 [17,34]
Metoprolol 23 (± 21) −1 77 18 [12,17,34,55] 44 (± 12) 29.5 58.7 3 [17,34]
Propanolol 59 1 [34] 72 (± 6) 65.5 77.6 2 [34]
Sotalol 55 (± 14) 21.4 75 11 [12,34] 42 (± 11) 30.4 53.1 2 [34]
Antihistamines
Famotidine 60 1 [34] 56 (± 9) 47.4 64.6 2 [34]
Loratidine 15 1 [34] 17 (± 17) 0 33.5 2 [34]
Ranitidine 34 (± 9) 24.7 42.2 2 [34] 56 (± 28) 29.5 95 3 [17,34]
Anticonvulsant
Carbamazepine − 8 (± 32) − 122 58 69 [12,17,18,27,34,38,39,51,52, 0 (± 11) − 22 23 15 [17,18,27,34,38,39]
54,55,57–59]
Antidepressant
Fluoxetine 33 1 [34] 98 (± 0) 98 98 2 [34]
Paroxetine 91 1 [17] 90 1 [17]
X-ray contrast media
Iopromide 51 (± 19) 25 90 10 [18,39] 59 (± 14) 40 75 3 [18]
Hypoglycaemic agent
Glibenclamide 45 (± 1) 44.5 46.1 2 [17,34] 75 (± 20) 47.3 95.6 3 [17,34]
Diuretics
Hydrochlorothiazide 38 (± 38) 0 76.3 2 [17,34] 22 (± 31) 0 66.3 3 [17,34]
a
Average removal was obtained as the average of elimination values reported in literature.
b
Minimum and maximum removal efficiencies found in literature.
c
number of different biological treatment plants measured.
 J. Sipma et al. / Desalination 250 (2010) 653–659
facility makes direct comparisons rather complicated. In contrast,
Bernard et al. [33] reported that treatment by MBR resulted in
significant better removals compared to activated sludge treatment
for poorly biodegradable persistent polar pollutants, such as diclofe-
nac, mecoprop and sulfophenylcarboxylates, which was ascribed to
the employed long sludge retention times. Also Radjenovic et al.
[17,34] reported that the removal of pharmaceuticals in an MBR was
superior for several compounds and at least similar for others, and
furthermore, that the range of variation of the removal efficiency in
the MBR system was smaller for most of the compounds. Obviously,
non-degradable micro-pollutants, such as EDTA and carbamazepine
were not eliminated at all by any treatment process [33]. Kimura et al.
[35] found that compounds with a complex chemical structure, e.g.
ketoprofen and naproxen, were not eliminated in a CAS treatment
process, but could be eliminated by a MBR. These authors found
further that for several other pharmaceuticals the treatment efficien-
cies were comparable. Others have also reported on similar removal
efficiencies between MBR and CAS [18,27].
7. Effect of environmental and operational parameters in the
removal of pharmaceuticals
The solids retention time (SRT) has been regarded as one of the
most important parameters affecting the biodegradation of micro-
pollutants, such as pharmaceuticals. Strenn et al. [36] found a clear
dependence of the removal rates on the sludge retention time was
observed for ibuprofen and bezafibrate. The positive effect of a long
sludge retention time was also reported by Lesjean et al. [37], who
found that the removal of pharmaceuticals increased with a sludge
age of 26 days and inversely decreased when the sludge age was set at
8 days. Clara et al. [38] reported that at a sludge retention time of
2 days no tested pharmaceuticals were removed, whereas at high
sludge retention times the removal efficiency exceeded 80%. At high
loaded activated sludge plants operated at extreme low SRTs
(<2 days), sorption is the most important removal mechanism [39].
In another study, Clara et al. [27] reported that they did not find
significant differences in the removal efficiency of selected pharma-
ceuticals between CAS and MBR systems when operated at similar
sludge retention times, which suggests that the reactor type is of less
importance than the sludge retention time.
Although, SRT has been reported as determinative for pharmaceu-
tical biodegradation, the effect of SRT does not become clear from
literature as several investigators did not find clear correlations between
SRT and biodegradation of pharmaceuticals [8,12,40]. Often very
fluctuating removal efficiencies are encountered with increasing SRT.
In case a specific substance is degraded in dependency on the SRT,
Clara et al. [38] suggested that a critical value for the sludge age can be
determined. With regard to ibuprofen, bezafibrate and natural
estrogens a strong correlation between achievable effluent concen-
trations and the SRT10 °C (temperature corrected SRT) was observed
[38]. For these substances a critical value was identifiable for the
SRT10 °C amounting to approximately 10 days, but for diclofenac and
17a-ethinylestradiole contradictory results were obtained and beside
the SRT other influences seem to be of importance [38]. These authors
concluded that for WWTPs operated at SRTs10 °C higher than 10 days
low effluent concentrations can be achieved for many biodegradable
micro-pollutants, which corresponds to an SRT required for efficient
nitrogen removal.
Increasing the SRT beyond 30 days does not seem to improve the
removal for most pharmaceuticals [30]. An explanation could be in the
fact that biodegradation of micro-pollutants is most likely performed in
a co-metabolic manner as the low concentrations do not likely sustain
growth for specific microorganisms, because in this case the SRT
necessary for an efficient biodegradation of the primary substrate is the
relevant parameter.
657
Besides SRT, a relation between HRT and biodegradation of
pharmaceuticals could be expected as this determines the contact
time between the pollutant and the microorganisms. Under normal
operation, however, no clear relation could be found in the literature
except for periods with heavy rain, which resulted in a decrease of the
HRT and deteriorated elimination of β-blockers [12]. Besides due to a
decreased contact time, deterioration could be as well due to a decrease
of the biodegradation rate when assuming a first-order biodegradation.
Joss et al. [7] observed pseudo first-order degradation kinetics for many
micro-pollutants down to the ng L− 1 concentrations, indicating that
biodegradation rates are directly influenced by the micro-pollutant
concentration. Göbel et al. [11] found that removal efficiencies were
similar between a CAS operated at an HRT of 31 h and a fixed bed reactor
operated at an HRT as low as 1 h, which was ascribed to a higher
bioactivity of the sludge per reactor volume. However, assuming first-
order kinetics the plug flow regime in the fixed bed reactor results in
higher micro-pollutant concentrations at the bottom and consequently
higher biodegradation rates. Therefore it could be postulated that
staging of bioreactors, leading to locally elevated micro-pollutant
concentrations would have a beneficial effect on their biodegradation.
Improved elimination could also be expected with implementation of
wastewater segregation, especially via urine separation. Since urine
contains most of the pharmaceuticals excreted after human consump-
tion, but constitutes only a minor fraction of the total wastewater, the
resulting concentrations of pharmaceuticals will be 100–500 times
higher [3]. Besides urine separation, also decentralized wastewater
treatment is supposed to result in higher pharmaceutical concentrations
[41]. Whereas, concentrations of pharmaceuticals are expected to be
relatively constant in large catchments, in decentralized treatment
systems it varies strongly as a result of their irregular consumption, and
concentrations have been estimated to be a factor of 50–1000 higher
[41]. However, the reliability of an efficient pharmaceutical removal as a
function of their irregular presence in the wastewater treatment should
be investigated further.
Whereas, a direct influence of the HRT on biodegradation of
pharmaceuticals does not become clear from the literature, an increased
contact time between pharmaceutical and biomass has been suggested
as the reason for an improved biodegradation of several acidic
pharmaceuticals at a decreased pH [42]. At lower pH, these pharma-
ceuticals adsorbed better to the sludge particles, but did not accumulate
in the solid phase within the reactor, indicating that the removal was of
biological origin [42]. The acidity or alkalinity at which the process
operates thus influences the removal of pharmaceuticals, either by
influencing the physiology of the microorganisms, or by altering the
solubility of the pharmaceuticals present. Cirja et al. [5] report that
depending on the pKa value, a pharmaceutical can exist in various
protonation states due to pH variation, which results in changing
hydrophobicity at different pH values.
Temperature affects biological activity and therefore is expected to
affect micro-pollutant degradation as well, but clear effects cannot be
drawn from the presented data in the literature. Some researchers found
no difference in compound removal based on incubation temperature
[11], others did find that temperature was responsible for differences in
eliminations [43].
Besides physico-chemical conditions of the treatment process, also
the treatment process configuration may affect the removal of
pharmaceuticals as has been shown by significant higher removal
rates with nitrifying activated sludge compared to CAS [44]. Nitrifying
bacteria have been found capable of co-metabolizing a wide range of
refractory organic micro-pollutants [44]. This could be related to the
wide substrate spectrum employed by the key enzyme for nitrification,
i.e. ammonium monooxygenase [45]. Perez et al. [46] showed that an
activated sludge treatment comprising a nitrification process was the
only treatment capable to eliminate trimethoprim. Besides the presence
of carbon and nitrogen sources, also the depletion of one or both may
result in degradation of pharmaceuticals as has been shown the case for
658 J. Sipma et al. / Desalination 250 (2010) 653–659
sulfamethoxazole, whereas in the presence of acetate and ammonium
this pharmaceutical was not degraded [47]. Furthermore, wastewater
treatment processes employing a complete biological nutrient removal
are characterized by separate zone with aerobic, anoxic and anaerobic
conditions to optimize the nutrient removal, which may affect micro-
pollutant removal as well. In fact, Zwiener and Frimmel [48] showed
that diclofenac was not degraded in short-term biodegradation test
under aerobic conditions, whereas it was degraded under anoxic
conditions. They suggest that the applied anoxic–oxic ratios may
influence the removal of specific pharmaceuticals.
8. Conclusions and challenges
Nowadays, MBR technology is considered an interesting option for
upgrading of existing wastewater treatment plants as well as providing
small communities with high quality wastewater treatment systems,
especially when wastewater reclamation is considered. MBRs, combine
relative long sludge retention times with high biomass concentrations,
which are generally thought to be beneficial for the biodegradation of
refractory compounds such as is the case with many micro-pollutants
encountered in wastewater nowadays. A class of micro-pollutants that
is receiving increasing attention is that of pharmaceuticals and
pharmaceutically active compounds as their effect on the aquatic
environment after passing through a wastewater treatment facility is
largely unknown. A large number of these pharmaceutically active
compounds are highly polar. Therefore, biodegradation is presumed to
largely determine the overall removal of these pollutants and their
efficiency needs to be maximized.
In general it can be stated that an MBR is neither superior for well
degradable compounds that are already extensively degraded in CAS
treatment nor for recalcitrant compounds that are not amenable to
biodegradation. For most pharmaceuticals of intermediate removal in
CAS treatment, the MBR seems to be superior. However, despite of this
benefit, the effect is not pronounced enough to serve as a sole
argument for employing MBR in municipal wastewater treatment.
Furthermore, care should be taken when elimination is based simply
on influent and effluent concentrations of a specific pharmaceutical,
when degradation pathways are largely unknown and intermediates
still cannot be analyzed. Furthermore, since most reports merely focus
on the elimination of the parent compound and detailed specifications
of the wastewater treatment process are usually lacking direct
comparison of different treatment facilities is complicated and little
can be concluded on the effects of individual process parameters.
Since these pollutants occur at trace levels, their biological
degradation remains subject to many uncertainties. Information on
biodegradation mechanisms is largely lacking and without knowledge
on degradation pathways, and the possibility to analyze intermediates,
complete mineralization of a specific pharmaceutical cannot be
guaranteed. The microbial communities degrading also deserve further
research, as knowledge whether pharmaceuticals are degraded by
specific microorganisms or via symbiotic interactions of various
populations would be useful in our understanding of the process and
may ultimately aid in the optimization of pharmaceutical degradation
during wastewater treatment. Investigations into the need for adapta-
tion of a community for biodegradation of a specific pharmaceutical are
highly interesting, especially when focused on the specific pool of
enzymes required for its biodegradation. This indicates that still much
research is required to gain a better insight into the biodegradation
potential of pharmaceuticals in biological wastewater treatment.
Acknowledgements
This research project has been funded by the Spanish Ministry of
Education and Science DPI2006-15707-C02-01 and DPI2006-15707-
C02-02.
References
[1] N.A. Doerr-MacEwen, M.E. Haight, Expert stakeholders' views on the management
of human pharmaceuticals in the environment, Environ. Manage. 38 (2006)
853–866.
[2] 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 U.S. streams, 1999–2000: a national reconnaissance, Environ. Sci. Technol. 36
(2002) 1202–1211.
[3] T.A. Larsen, J. Lienert, A. Joss, H. Siegrist, How to avoid pharmaceuticals in the
aquatic environment, J. Biotechnol. 113 (2004) 295–304.
[4] T.A. Ternes, A. Joss, H. Siegrist, Scrutinizing pharmaceuticals and personal care
products in wastewater treatment, Environ. Sci. Technol. (2004) 393A–399A.
[5] M. Cirja, P. Ivashechkin, A. Schäffer, P.F.X. Corvini, Factors affecting the removal of
organic micropollutants from wastewater in conventional treatment plants (CTP)
and membrane bioreactors (MBR), Rev. Environ. Sci. Biotechnol. 7 (1) (2008) 61–78.
[6] B.A. Wilson, V.H. Smith, F. Denoyelles Jr., C.K. Larive, Effects of three pharmaceu-
tical and personal care products on natural freshwater algal assemblages, Environ.
Sci. Technol. 37 (2003) 1713–1719.
[7] A. Joss, S. Zabczynski, A. Göbel, B. Hoffmann, D. Löffler, C.S. McArdell, T.A. Ternes, A.
Thomsen, H. Siegrist, Biological degradation of pharmaceuticals in municipal
wastewater treatment: proposing a classification scheme, Water Res. 40 (2006)
1686–1696.
[8] Y. Zhang, S.-U. Geißen, C. Gal, Carbamazepine and diclofenac: removal in wastewater
treatment plants and occurrence in water bodies, Chemosphere 73 (2008) 1151–1161.
[9] T.A. Ternes, M.-L. Janex-Habibi, T. Knacker, N. Kreuzinger, H. Siegrist. Assessment
of technologies for the removal of pharmaceuticals and personal care products in
sewage and drinking water facilities to improve the indirect potable water reuse.
POSEIDON, detailed report related to the overall duration. Contract No. EVK1-CT-
2000–00047 (2006).
[10] M. Carballa, F. Omil, J.M. Lema, Removal of cosmetic ingredients and pharmaceu-
ticals in sewage primary treatment, Water Res. 39 (2005) 4790–4796.
[11] A. Göbel, C.S. McArdell, A. Joss, H. Siegrist, W. Giger, Fate of sulfonamides,
macrolides, and trimethoprim in different wastewater treatment technologies,
Sci. Total Environ. 372 (2007) 361–371.
[12] N. Vieno, T. Tuhkanen, L. Kronberg, Elimination of pharmaceuticals in sewage
treatment plants in Finland, Water Res. 41 (2007) 1001–1012.
[13] B. Halling-Sørensen, S. Nors Nielsen, P.F. Lanzky, F. Ingerslev, H.C. Holten Lützhøfl,
S.E. Jørgensen, Occurrence, fate and effects of pharmaceutical substances in the
environment — a review, Chemosphere 36 (2) (1998) 357–393.
[14] J. Tunkel, P.H. Howard, R.S. Boethling, W. Stiteler, H. Loonen, Predicting ready
biodegradability in the Japanese ministry of international trade and industry test,
Environ. Toxicol. Chem. 19 (2000) 2478–2485.
[15] O.A.H. Jones, N. Voulvoulis, J.N. Lester, Human pharmaceuticals in wastewater
treatment processes, Crit. Rev. Environ. Sci. Technol. 35 (2005) 401–427.
[16] J.T. Yu, E.J. Bouwer, M. Coelhan, Occurrence and biodegradability studies of
selected pharmaceuticals and personal care products in sewage effluents, Agric.
Water Manag. 86 (2006) 72–80.
[17] J. Radjenovic, M. Petrovic, D. Barceló, Analysis of pharmaceuticals in wastewater and
removal using a membrane bioreactor, Anal. Bioanal. Chem. 387 (2007) 1365–1377.
[18] A. Joss, E. Keller, A.C. Alder, A. Göbel, C.S. McArdell, T. Ternes, H. Siegrist, Removal
of pharmaceuticals and fragrances in biological wastewater treatment, Water Res.
39 (2005) 3139–3152.
[19] A.G. Fane, S.A. Fane, The role of membrane technology in sustainable decentralized
wastewater systems, Water Sci. Technol. 51 (10) (2005) 317–325.
[20] R. Witzig, W. Manz, S. Rosenberger, U. Kruger, M. Kraume, U. Szewzyk,
Microbiological aspects of a bioreactor with submerged membranes for aerobic
treatment of municipal wastewater, Water Res. 36 (2002) 394–402.
[21] J. Wagner, K.-H. Rosenwinkel, Sludge production in membrane bioreactors under
different conditions, Water Sci. Technol. 41 (10–11) (2000) 251–258.
[22] M.A. Gander, B. Jefferson, S.J. Judd, Membrane bioreactors for use in small wastewater
treatment plants: membrane materials and effluent quality, Water Sci. Technol. 41 (1)
(2000) 205–211.
[23] T. Melin, B. Jefferson, D. Bixio, C. Thoeye, W. De Wilde, J. De Koning, J. Van der
Graaf, T. Wintgens, Membrane bioreactor technology for wastewater treatment
and reuse, Desalination 187 (2006) 271–282.
[24] P. Côté, M. Masini, D. Mourato, Comparison of membrane options for water reuse
and reclamation, Desalination 167 (2004) 1–11.
[25] H.Fr. Schröder, Mass spectrometric monitroing of the degradation and elimination
efficiency for hardly eliminable and hardly biodegradable polar compounds by
membrane bioreactors, Water Sci. Technol. 46 (3) (2002) 57–64.
[26] B. Jefferson, A.L. Laine, T. Stephenson, S.J. Judd, Advanced biological unit processes
for domestic water recycling, Water Sci. Technol. 43 (10) (2001) 211–218.
[27] M. Clara, B. Strenn, M. Ausserleitner, N. Kreuzinger, Comparison of the behaviour
of selected micropollutants in a membrane bioreactor and a conventional
wastewater treatment plant, Water Sci. Technol. 50 (2004) 29–36.
[28] W. Lee, S. Kang, H. Shin, Sludge characteristics and their contribution to microfiltration in
submerged membrane bioreactors, J. Membr. Sci. 216 (2003) 217–227.
[29] S. Weiss, T. Reemtsma, Membrane bioreactors for municipal wastewater
treatment — a viable option to reduce the amount of polar pollutants discharged
into surface waters? Water Res. 42 (2008) 3837–3847.
[30] S. Suarez, M. Carballa, F. Omil, J.M. Lema, How are pharmaceutical and personal care
products (PPCPs) removed from urban wastewaters? Rev. Environ. Sci. Biotechnol. 7
(2008) 125–138.
[31] N. Cicek, J.P. Franco, M.T. Suidan, U. Vincent, J. Manem, Characterization and
comparison of a membrane bioreactor and a conventional activated sludge system
 J. Sipma et al. / Desalination 250 (2010) 653–659
in the treatment of wastewater containing high-molecular weight compounds,
Water Environ. Res. 71 (1) (1999) 64–70.
[32] S.A. Snyder, S. Adham, A.M. Redding, F.S. Cannon, J. DeCarolis, J. Oppenheimer, E.C.
Wert, Y. Yoon, Role of membranes and activated carbon in the removal of endocrine
disruptors and pharmaceuticals, Desalination 202 (2007) 156–181.
[33] M. Bernhard, J. Müller, T.P. Knepper, Biodegradation of persistent polar pollutants
in wastewater: comparison of an optimised lab-scale membrane bioreactor and
activated sludge treatment, Water Res. 40 (2006) 3419–3428.
[34] J. Radjenovic, M. Petrovic, D. Barceló, Fate and distribution of pharmaceuticals in
wastewater and sewage sludge of the conventional activated sludge (CAS) and
advanced membrane bioreactor (MBR) treatment, Water Res. 43 (3) (2009)
831–841.
[35] K. Kimura, H. Hara, Y. Watanabe, Removal of pharmaceutical compounds by
submerged membrane bioreactors (MBRs), Desalination 178 (2005) 135–140.
[36] B. Strenn, M. Clara, O. Gans, N. Kreuzinger, Carbamazepine, diclofenac, ibuprofen
and bezafibrate — investigations on the behaviour of selected pharmaceuticals
during wastewater treatment, Water Sci. Technol. 50 (5) (2004) 269–276.
[37] B. Lesjean, R. Gnirss, H. Buisson, S. Keller, A. Tazi-Pain, F. Luck, Outcomes of a 2-year
investigation on enhanced biological nutrients removal and trace organics elimination
in membrane bioreactor (MBR), Water Sci. Technol. 52 (10–11) (2005) 453–460.
[38] M. Clara, N. Kreuzinger, B. Strenn, O. Gans, H. Kroiss, The solids retention time—a
suitable design parameter to evaluate the capacity of wastewater treatment plants
to remove micropollutants, Water Res. 39 (2005) 97–106.
[39] N. Kreuzinger, M. Clara, B. Strenn, H. Kroiss, Relevance of the sludge retention time
(SRT) as design criteria for wastewater treatment plants for the removal of
endocrine disruptors and pharmaceuticals from wastewater, Water Sci. Technol.
50 (5) (2004) 149–156.
[40] 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.
[41] C. Abegglen, A. Joss, C.S. McArdell, G. Fink, M.P. Schlüsener, T.A. Ternes, H. Siegrist,
The fate of selected micropollutants in a single-house MBR, Water Res. 43 (7)
(2009) 2036–2046.
[42] T. Urase, C. Kagawa, T. Kikuta, Factors affecting removal of pharmaceutical
substances and estrogens in membrane separation bioreactors, Desalination 178
(2005) 107–113.
[43] N.M. Vieno, T. Tuhkanen, L. Kronberg, Seasonal variation in the occurrence of
pharmaceuticals in effluents from a sewage treatment plant and in the recipient
water, Environ. Sci. Technol. 39 (21) (2005) 8220–8226.
[44] A.L. Batt, S. Kim, D.S. Aga, Enhanced biodegradation of iopromide and trimethoprim
in nitrifying activated sludge, Environ. Sci. Technol. 40 (2006) 7367–7373.
[45] L. Berthe-Corti, S. Fetzner, Bacterial metabolism of n-alkanes and ammonia under
oxic, suboxic and anoxic conditions, Acta Biotechnol. 22 (3–4) (2002) 299–336.
659
[46] S. Perez, P. Eichhorn, D.S. Aga, Evaluating the biodegradability of sulphamethazine,
sulphamethoxazole and trimethoprim at different stages of sewage treatment,
Environ. Toxicol. Chem. 24 (6) (2005) 1361–1367.
[47] P. Drillia, S.N. Dokianakis, M.S. Fountoulakis, M. Kornaros, K. Stamatelatou, G.
Lyberatos, On the occasional biodegradation of pharmaceuticals in the activated
sludge process: the example of the antibiotic sulfamethoxazole, J. Hazard. Mat.
122 (2005) 259–265.
[48] C. Zwiener, F.H. Frimmel, Short-term tests with a pilot sewage plant and biofilm
reactors for the biological degradation of the pharmaceutical compounds clofibric
acid, ibuprofen, and diclofenac, Sci. Total Environ. 309 (2003) 201–211.
[49] M. Salgot and E. Huertas. Report on the definition of key water quality parameters.
Aquarec – integrated concepts for reuse of upgraded wastewater. Workpackage 2.
EU – project, contract number EVK1-CT-2002–00130 (2006).
[50] M. Carballa, F. Omil, J.M. Lema, M. Llompart, C. Garcia, I. Rodriguez, M. Gomez, T.
Ternes, Behaviour of pharmaceuticals and personal care products in a sewage
treatment plant of northwest Spain, Water Sci. Technol. 52 (8) (2005) 29–35.
[51] M.J. Gomez, M.J. Martinez Bueno, S. Lacorte, A.R. Fernandez-Alba, A. Agüera, Pilot
survey monitoring pharmaceuticals and related compounds in a sewage
treatment plant located on the Mediterranean coast, Chemosphere 66 (2007)
993–1002.
[52] Th. Heberer, K. Reddersen, A. Mechlinski, From municipal sewage to drinking
water: fate and removal of pharmaceutical residues in the aquatic environment in
urban areas, Water Sci. Technol. 46 (3) (2002) 81–88.
[53] T. Kosjek, E. Heath, B. Kompare, Removal of pharmaceutical residues in a pilot
wastewater treatment plant, Anal. Bioanal. Chem. 387 (2007) 1379–1387.
[54] A.D. Levine, M.T. Meyer, G. Kish, Evaluation of the persistence of micropollutants
through pure-oxygen activated sludge nitrification and denitrification, Water
Environ. Res. 78 (2006) 2276.
[55] N. Paxéus, Removal of selected non-steroidal anti-inflammatory drugs (NSAIDs),
gemfibrozil, carbamazepine, β-blockers, trimethoprim and triclosan in conven-
tional wastewater treatment plants in five EU countries and their discharge to the
aquatic environment, Water Sci. Technol. 50 (5) (2004) 253–260.
[56] J.B. Quintana, S. Weiss, T. Reemtsma, Pathways and metabolites of microbial
degradation of selected acidic pharmaceutical and their occurrence in municipal
wastewater treated by a membrane bioreactor, Water Res. 39 (2005) 2654–2664.
[57] N. Nakada, T. Tanishima, H. Shinohara, K. Kiri, H. Takada, Pharmaceutical chemicals
and endocrine disrupters in municipal wastewater in Tokyo and their removal during
activated sludge treatment, Water Res. 40 (2006) 3297–3303.
[58] J.L. Santos, I. Aparicio, E. Alonso, Occurrence and risk assessment of pharmaceu-
tically active compounds in wastewater treatment plants. A case study: Seville city
(Spain), Environ. Int. 33 (2007) 596–601.
[59] S. Suarez, M. Ramil, F. Omil, J.M. Lema, Removal of pharmaceutically active
compounds in nitrifying–denitrifying plants, Water Sci. Technol. 52 (8) (2005)
9–14.