Pharmaceutical chemicals and endocrine disrupters in
municipal wastewater in Tokyo and their removal during
activated sludge treatment
Norihide Nakada, Toshikatsu Tanishima, Hiroyuki Shinohara, Kentaro Kiri,
Laboratory of Organic Geochemistry (LOG), Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology,
Fuchu, Tokyo 183-8509, Japan
a r t i c l e i n f o
Received 26 March 2006
Received in revised form
24 June 2006
Accepted 29 June 2006
Available online 30 August 2006
Sewage treatment plant
Activated sludge treatment
Endocrine disrupting chemicals
A B S T R A C T
We measured six acidic analgesics or anti-inflammatories (aspirin, ibuprofen, naproxen,
ketoprofen, fenoprofen, mefenamic acid), two phenolic antiseptics (thymol, triclosan), four
amide pharmaceuticals (propyphenazone, crotamiton, carbamazepine, diethyltoluamide),
three phenolic endocrine disrupting chemicals (nonylphenol, octylphenol, bisphenol A),
and three natural estrogens (17b-estradiol, estrone, estriol) in 24-h composite samples of
influents and secondary effluents collected seasonally from five municipal sewage
treatment plants in Tokyo. Aspirin was most abundant in the influent, with an average
concentration of 7300ng/L (n ¼ 16), followed by crotamiton (921ng/L), ibuprofen (669ng/L),
triclosan (511ng/L), and diethyltoluamide (503ng/L). These concentrations were 1 order of
magnitude lower than those reported in the USA and Europe. This can be ascribed to lower
consumption of the pharmaceuticals in Japan. Aspirin, ibuprofen, and thymol were
removed efficiently during primary+secondary treatment (490% efficiency). On the other
hand, amide-type pharmaceuticals, ketoprofen, and naproxen showed poor removal
(o50% efficiency), which is probably due to their lower hydrophobicity (logKowo3). Because
of the persistence of crotamiton during secondary treatment, crotamiton was most
abundant among the target pharmaceuticals in the effluent. This is the first paper to report
ubiquitous occurrence of crotamiton, a scabicide, in sewage. Because crotamiton is used
worldwide and it is persistent during secondary treatment, it is a promising molecular
marker of sewage and secondary effluent.
& 2006 Elsevier Ltd. All rights reserved.
The ubiquitous occurrence of a wide range of pharmaceu-
ticals has been reported in sewage effluents (e.g., Ternes,
1998; Gross et al., 2004; Paxeus, 2004; Glassmeyer et al., 2005;
Lindqvist et al., 2005). Although their effects on aquatic
organisms and humans are still unknown, their presence may
raise concerns about adverse effects on organisms living in
the receiving waters and on the recycling of effluent. In these
contexts, we conducted a broad-spectrum analysis of muni-
cipal wastewaters to gain a comprehensive understanding of
the concentration range of pharmaceuticals and endocrine
disrupting chemicals (EDCs) in sewage and sewage effluents
in Tokyo, Japan. Although many papers have reported
concentration ranges of pharmaceuticals and EDCs in sewage
effluents, only a few (Carballa et al., 2004; Gross et al., 2004;
ARTICLE IN PRESS
0043-1354/$-see front matter & 2006 Elsevier Ltd. All rights reserved.
E-mail address: email@example.com (H. Takada).
Glassmeyer et al., 2005) have dealt comprehensively with
organic micropollutants. The present paper covers a wide
range of organic micropollutants, including one compound
(crotamiton) whose environmental occurrence has not been
reported in any previous paper.
Sewage treatment plays an important role in removing
contaminants from reclaimed water. Several papers have
reported the efficiency of removal of EDCs and pharmaceu-
ticals during sewage treatment and their removal mechan-
isms (Ternes, 1998; Carballa et al., 2004). The studies indicated
that physico-chemical properties, especially hydrophobicity,
and biodegradability control the efficiency of removal of EDCs
and pharmaceuticals. However, large variability in removal
efficiency was reported for some pharmaceuticals (e.g., Clara
et al., 2005; Tauxe-Wuersch et al., 2005), implying that factors
other than compound-specific properties affect removal
efficiency. In these contexts, studying the efficiencies of
removal of a wide range of pharmaceuticals and EDCs in
various sewage treatment plants (STPs) in real-world condi-
tions is important to generalizing our knowledge of the
mechanisms of removal of these compounds.
Thus, the present study had the following purposes: (1) To
identify the concentrations of a wide range of pharmaceu-
ticals and EDCs in influents and effluents at municipal STPs
in Tokyo. (2) To determine the efficiencies of removal of the
pharmaceuticals and EDCs during primary and secondary
treatments and the mechanisms of removal.
2.Materials and methods
2.1. Sampling and STPs surveyed
Twenty-four-hour composite samples of plant influent and
secondary effluent were taken from five municipal STPs in
Tokyo in December 2001, April, May, July, August, November
2002, and February 2003. All the plants use primary and
secondary treatment with activated sludge. Information on
the individual plants and on the individual sampling events is
summarized in Table 1 and Table S1 in Supplementary data,
The samples were transported cool to the laboratory, and
filtered through pre-baked glass fiber filters (Whatman).
Filtrates were stored at 51C until solid-phase extraction
(SPE) (normally 24h after filtration). Before storage, part of
the filtrates was acidified with 4M HCl to pH 2, and the rest
was stored without any pH adjustment.
2.2. Extraction and purification
Chemical structures and physico-chemical properties of the
pharmaceuticals and EDCs are listed in Table S2 in Supple-
mentary data. Pharmaceuticals were categorized into three
groups according to their functional groups and purified by
different processes. Compounds having a carboxylic group
(carboxylic pharmaceuticals) are aspirin, ibuprofen, fenopro-
fen, naproxen, mefenamic acid, and ketoprofen. Compounds
having a hydroxy group (phenolic pharmaceuticals) are
thymol and triclosan. Compounds having an amide group
(amide pharmaceuticals) are diethyltoluamide, crotamiton,
propyphenazone, and carbamazepine.
The carboxylic pharmaceuticals were extracted with a SPE
cartridge (Sep-Pak Environmental tC18 plus, Waters; 900mg
resin weight) under acidic condition (pH ¼ 2). The cartridges
had been previously washed with hexane, dichloromethane
(DCM), methanol (MeOH), and distilled water. One liter of
filtrate was passed through the cartridge at a flow rate of
15mL/min. The compounds retained on the cartridge were
eluted with 20mL of MeOH. The eluents were methylated
with BF3/MeOH (10% [w/w] boron trifluoride in MeOH,
Supelco, Tokyo) for 5h at 801C. Methylated derivatives were
liquid–liquid-extracted with n-hexane and purified by 5%
H2O-deactivated silica gel column chromatography (Nakada
et al., 2004). The column (1cm?9cm) was eluted with 20mL
of hexane/DCM (75:25; v/v), 40mL of DCM, and 30mL of DCM/
acetone (70:30; v/v). Naproxen, fenoprofen, and mefenamic
acid were eluted in the DCM fraction, while aspirin and
ketoprofen were eluted in both the DCM and DCM/acetone
fractions. The eluents were evaporated to dryness and re-
dissolved in 50–1000mL of injection internal standard solution
(IIS, 1mg/mL naphthalene-d8, anthracene-d10, p-terphenyl-d14,
benz[a]anthracene-d12and perylene-d12in isooctane) for gas
chromatograph-mass spectrometer (GC-MS) analysis.
The phenolic and amide pharmaceuticals were extracted
(pH ¼ 6–8). The other conditions of the extraction and
purification were the same as for the carboxylic pharmaceu-
ticals described above. In the purification procedure using the
5% H2O-deactivated silica gel column, the phenolic pharma-
ceuticals (thymol and triclosan) were eluted in the DCM
fraction, while the amide pharmaceuticals were eluted in the
DCM/acetone fraction. The DCM/acetone fraction was re-
duced in volume, supplemented with IIS solution, and
directly subjected to GC-MS analysis. Phenolic pharmaceu-
ticals in the DCM fraction were derivatized to acetates with
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Table 1 – Operational parameters for the sewage treatment plants (STPs) surveyed
Plant IDPopulation servedAveraged flow (m3/d) Retention time
Hydraulic (h)Solids (d)
pyridine and acetic anhydride before GC-MS analysis. Acyla-
tion was performed according to Isobe et al. (2002). Acetates
were extracted with hexane, concentrated to dryness, and
redissolved in 50–1000mL of the IIS isooctane solution for GC-
Phenolic EDCs (nonylphenol: NP; octylphenol: OP; and
bisphenol A: BPA) and natural estrogens (estrone: E1, 17b-
estradiol: E2, and estriol: E3) were extracted and purified
according to the method described in our previous paper
(Nakada et al., 2004). The EDCs were derivatized to acetates as
above and then subjected to GC-MS analysis.
2.3. Instrumental analysis
The pharmaceuticals and EDCs were quantified by a GC-MS
(Agilent Technology, Tokyo, Japan, HP5973 with HP6890). An
HP-5 MS (Agilent Technology, Tokyo, Japan) capillary column
(30m, 0.25mm i.d., 0.25mm film thickness) was used with
helium as the carrier gas at 100kPa. GC-MS operating
conditions were 70eV ionization potential with the MS
interface at 3101C. The injection port was maintained at
3001C, and the sample was injected in splitless mode.
For the analysis of all the pharmaceuticals, the column was
maintained at 701C for the first 1min, then heated to 1801C at
201C/min, then to 2501C at 61C/min, then to 3101C at 301C/
min, where it was maintained for 5min. For the analysis of AP
acetates, the column was maintained at 701C for the first
2min, then heated to 1801C at 301C/min, then to 2001C at
21C/min, then to 3101C at 301C/min, where it was maintained
for 10min. For the analysis of acetates of BPA, E1, E2, and E3,
the column was maintained at 701C for the first 1min, then
heated to 2001C at 201C/min, then to 2601C at 51C/min, then
to 3101C at 301C/min, where it was maintained for 10min.
Target compounds were measured according to the quanti-
fication ions listed in Table S2 (Supplementary data) in
selected ion monitoring mode. Calibration curves for the
pharmaceuticals were drawn with five points ranging from
0.1 to 2ppm. No recovery correction was made for the
pharmaceuticals. Details of quantification of EDCs by GC-MS
are described elsewhere (Isobe et al., 2001; Nakada et al.,
2004). Recovery corrections were made for alkylphenols, BPA,
E1, E2, and E3 using recoveries of the corresponding
surrogates listed in Table S3.
Reproducibility was determined by four replicate analyses of
the STP effluents. Relative standard deviations of concentra-
tions of the target compounds were less than 15% (Table S4 in
Supplementary data). Recovery by the whole analytical
procedure was checked through triplicate analysis of STP
effluents in which standard mixtures were spiked. The
standard mixtures containing individual target compounds
of 250–500ng dissolved in 50–100mL of acetone were spiked
into the STP effluents in the glass tank during SPE. Recoveries
of the target compounds proved to be more than 70% except
for aspirin (33%) and thymol (56%). The concentrations of
pharmaceuticals were not corrected by the recoveries, while
EDC concentrations were corrected by the recovery of the
corresponding surrogates described above. Procedural blanks
for pharmaceuticals and EDCs through the entire procedure
were determined with every set of samples (usually four)
analyzed. Limits of quantification were defined as three times
the procedure blank value, or three times the noise level of
the base line on the chromatograms if no peaks were detected
in the procedural blank. Limits of quantifications normally
found during the study are listed in Table S4.
3. Results and discussion
wastewater influents and secondary effluents in Tokyo
Occurrence of pharmaceuticals and EDCs in
Fig. 1(a) and Table S5 show concentrations of the pharma-
ceuticals and EDCs in the STP influents. Aspirin had the
highest concentrations, ranging from 470 to 19400ng/L
(average: 732077003ng/L, n ¼ 16), among the pharmaceuti-
cals analyzed. Because of the low recovery of aspirin during
the analytical process (33%), this value might be under-
(6697212ng/L), and triclosan (5117243ng/L) followed. This
study is the first to report the occurrence of crotamiton in
sewage. Crotamiton is an antipruritic drug that is applied to
the skin, so some proportion of it is likely to be washed off the
skin to domestic wastewater. The concentration range of
ibuprofen (381–1130ng/L) was 1 order of magnitude lower
than those reported in Switzerland (Tauxe-Wuersch et al.,
2005), Finland (Lindqvist et al., 2005), Sweden (Bendz et al.,
2005), and Spain (Carballa et al., 2004). Triclosan concentra-
tions also were 1 order of magnitude lower than those
reported in the USA (McAvoy et al., 2002) and the UK
(Sabaliunas et al., 2003). These lower values might be due to
a lower usage of ibuprofen and triclosan in Japan. The per-
capita consumption rate of ibuprofen in Japan is estimated to
be 0.78g/person/year (Table 2). This is 1 order of magnitude
lower than rates calculated for Switzerland (Tauxe-Wuersch
et al., 2005) and Finland (Lindqvist et al., 2005). Diethyltolua-
mide showed a wider range of concentrations, from 20 to
1820ng/L (503ng/L on average). The lowest concentrations of
diethyltoluamide (20–53ng/L) were recorded during winter
(February 2003). This is probably due to less application of this
insect repellent during cold weather. Thymol, naproxen,
ketoprofen, and carbamazepine showed the third highest
concentration ranges (tens to hundreds of ng/L). Ketoprofen
concentrations were of the same order as those in Germany
(Heberer, 2002), Sweden (Bendz et al., 2005), Switzerland
(Tauxe-Wuersch et al., 2005), and Finland (Lindqvist et al.,
2005). Concentrations of naproxen were again 1 order of
magnitude lower than those reported in Sweden (Bendz et al.,
2005), Finland (Lindqvist et al., 2005), and Spain (Carballa et
al., 2004). A possible explanation for the lower naproxen
concentration is less usage of the pharmaceutical in Japan.
The per-capita consumption rate of naproxen was estimated
at 0.2–0.3g/person/day (Table 2) and was 1 order of magnitude
lower than rate calculated for Europe (Lindqvist et al., 2005).
Propyphenazone and fenoprofen showed the lowest concen-
trations (i.e., o100ng/L) among the pharmaceuticals ana-
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The concentrations of 11 pharmaceuticals in 16 influent
samples seasonally collected from the five STPs were
compared mutually. Positive correlations (r40.6) were ob-
served for 11 pairs of pharmaceuticals among 55 pairs. The
details are listed in Table S6. Among anti-inflammatory drugs,
higher correlations were generally observed, probably be-
cause these drugs generally used at the same time of the year.
Interestingly, a good correlation was observed between
diethyltoluamide and triclosan.
Among the EDCs, NP showed the highest concentrations,
followed by BPA and OP (Fig. 1(a)). These concentrations were
comparable to those in a nationwide survey in Japan (Tanaka
et al., 2003) and in Europe (Clara et al., 2005). The concentra-
tions of natural estrogens, especially E2, detected in this
study are comparable to those reported from Europe (Ternes
et al., 1999; Clara et al., 2005).
Using figures for total sales (Ministry of Health, Labor and
Welfare of Japan, 2002) and the unit prices of the drugs
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Table 2 – Estimated sales and per-capita consumptions and predicted concentrations of pharmaceuticals in influents of
STPs surveyed in Japan in 2002
influents of STPsb
Measured concentration in
influents of STPs surveyed
(n ¼ 16)
aCalculated from the sales data dividing by the population of Japan (127 million).
bCalculated from the per-capita consumption and total serviced population and discharging sewage volume of all STP surveyed (Table 1) with
correction by the excretion as parent compound.
cObtained from the Statistical Yearbook of Pharmaceutical Industry Productions Trends by Ministry of Health, Labour and Welfare (2002).
dObtained from the package inserts for each pharmaceutical.
eReferred from literature (Roberts et al., 1996 and The Pharmaceutical Society of Great Britain, 1979).
fCalculated from sales based on the Statistical Yearbook of Pharmaceutical Industry Productions Trends by Ministry (Ministry of Health, 2002)
and unit price of individual pharmaceuticals.
1 10 100 1000 10000 100000
0.11 10 100 1000
Fig. 1 – Concentrations of the pharmaceuticals and EDCs in sewage influents (a) and secondary effluents (b) in Tokyo.
containing the target pharmaceuticals, the contents of the
pharmaceuticals in individual drugs indicated on the package
inserts, which is obligated by the Japanese Pharmaceutical
Affairs Law to be enclosed with every drug, and the total
population of Japan (127 million), we calculated per-capita
consumption of the pharmaceuticals (Table 2). Furthermore,
we combined excretion rates as parent compounds for the
individual compounds indicated on the package inserts or in
Roberts et al. (1996) and the pharmaceutical codex (The
Pharmaceutical Society of Great Britain, 1979), the population
in each catchment, and the volumes of STP influents (Table 1)
with the per-capita consumption amounts of the pharma-
ceuticals to calculate their predicted environmental concen-
trations in STP influents (PECinfs, Table 2). PECinfs of
ibuprofen, ketoprofen, naproxen, and carbamazepine are
comparable to those observed in the influents (Table 2). The
PECinfof aspirin was 1 order of magnitude lower than the
measured concentrations in the influents. Underestimation
of excretion rate of aspirin or of sales of the drug and disposal
of the drug without taking could be responsible for the lower
estimate of PECinf. These comparisons, however, demonstrate
the potential utility of numerical prediction based on data
from civil authorities to estimate the concentrations of
pharmaceuticals in sewage and the associated risks.
Concentrations of the target pharmaceuticals and EDCs in
secondary effluents are illustrated in Fig. 1(b). Detailed data
are listed in Table S7. Crotamiton was the most abundant
among the pharmaceuticals, with concentration range from
245 to 968ng/L. Diethyltoluamide, triclosan, mefenamic acid,
aspirin, naproxen, carbamazepine, and ketoprofen were the
second most abundant pharmaceuticals, with concentrations
of tens to hundreds of ng/L. Ibuprofen showed a wide range of
concentrations (i.e., ng/L to hundreds of ng/L), but these
concentrations were again similar to or 1 order of magnitude
lower than those reported in Europe and the USA (Ternes,
1998; Gross et al., 2004; Glassmeyer et al., 2005; Tauxe-
Wuersch et al., 2005). Thymol and fenoprofen showed the
lowest concentrations (i.e., sub-ng/L to a few ng/L).
The EDC concentrations in the secondary effluents (Fig. 1(b)
and Table S7) were consistent with concentrations that we
previously reported for these chemicals in secondary effluent
from STPs in Tokyo (Nakada et al., 2004). The concentrations
of alkylphenols were similar to or up to 3 orders of magnitude
lower than those reported in the USA and Europe (Snyder
et al., 1999; Ko ¨rner et al., 2000). On the other hand, the
concentrations of estrogens were comparable to those
reported in the other countries (Ternes et al., 1999; Servos
et al., 2005).
Removal of pharmaceuticals and EDCs during
Using the concentrations of the pharmaceuticals and EDCs in
the influents and the corresponding secondary effluents, we
calculated their removal efficiencies during primary and
secondary treatment (Table S8, Fig. 2). Among the acidic
pharmaceuticals, aspirin and ibuprofen were removed most
efficiently, at over 90%, whereas ketoprofen and naproxen
had low removal efficiencies, ?45% on average, with large
variability (0% to ?80%). Microbial and chemical degradation,
including conversion to salicylic acid, is the likely mechanism
of removal of aspirin. The high efficiencies of removal of
ibuprofen are consistent with the results reported from STPs
in Europe (Ternes, 1998; Paxeus, 2004; Lindqvist et al., 2005;
Tauxe-Wuersch et al., 2005). The efficient removal of ibupro-
fen is ascribed to biodegradation (Paxeus, 2004). However,
lower efficiencies of removal of ibuprofen (?30%) were
reported at several STPs with shorter solid retention time
(SRT; Tauxe-Wuersch et al., 2005) and hydraulic retention
time (Clara et al., 2005). Tauxe-Wuersch et al. (2005) defined a
critical value for the SRT (at 101C) to remove ibuprofen from
the influent as about 5 days. Higher efficiencies of removal by
STPs in Tokyo are probably due to longer SRT (?5 days) and
hydraulic retention time (?9h). Fenoprofen had relatively
high efficiencies of removal (85% on average), although it
showed large variability (65–95%). The lower removal efficien-
cies for ketoprofen and naproxen can be partly ascribed to
their less hydrophobic nature (logKowE3). Also, their persis-
tence under microbial attack (Boyd et al., 2005) could be
responsible. Low efficiency of removal of naproxen was
reported from STPs in Germany (66%, Ternes, 1998) and in
Spain (40–55%, Carballa et al., 2004), although higher removal
(55–98%) was reported from STPs in Finland (Lindqvist et al.,
2005). Large variability in ketoprofen removal was also
reported from STPs in the other studies (e.g., 51–100%,
Lindqvist et al., 2005).
Among the phenolic pharmaceuticals, thymol had a high
removal efficiency (?95%), but triclosan had a lower removal
efficiency (?70% on average) (Fig. 2). Thymol probably
volatilizes during sewage treatment because of its relatively
high vapor pressure (i.e., 0.0022mm Hg). Triclosan showed a
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-7000 10 20 30 40 50 60 70 80 90 100
Removal Efficiency (%)
Fig. 2 – Removal efficiencies of pharmaceuticals and EDCs
during primary+secondary treatments in sewage treatment
plants in Tokyo.
wide range of removal (45–93%). The variability is similar to
those observed in five EU countries (Paxeus, 2004).
Amide-type pharmaceuticals (diethyltoluamide, propyphe-
nazone, carbamazepine, and crotamiton) were not efficiently
removed (Fig. 2): average removal efficiencies were lower than
45%. Their poor removal is partly due to their hydrophilic
nature (logKow o3) and chemical stability. Their removal
efficiencies varied widely. In several cases, concentrations of
crotamiton, propyphenazone, and carbamazepine in the
secondary effluents were higher than those in corresponding
influents. This can be explained by breakdown of conjugates
of the pharmaceuticals. No significant removal of carbama-
zepine during secondary sewage treatment was reported
from STPs in Europe (Ternes, 1998; Clara et al., 2004a,b;
Paxeus, 2004). Owing to its persistent nature, carbamazepine
has been proposed as a molecular marker of sewage (Clara et
al., 2004b). Our results confirmed the utility of carbamazepine
as a molecular marker.
Furthermore, we propose crotamiton as a more powerful
molecular marker of sewage effluent on account of its low
removal during secondary treatment and its higher abun-
dance in secondary effluent (hundreds of ng/L) than carba-
mazepine (tens of ng/L). Crotamiton also had less variability
in its concentrations in sewage influents and effluents, with
relative standard deviations of concentrations of 40% and
35%, respectively, which are lower than those for carbama-
zepine (94% and 74%). Negligible sorption of crotamiton to soil
was confirmed by a soil column experiment in which
secondary effluents were percolated through 50-cm soil
column (Shinohara et al., in press). All these features indicate
that crotamiton meets the criteria of anthropogenic molecu-
lar markers (Takada and Eganhouse, 1998). Therefore, it can
be used to track the transport pathway of wastewater in
groundwater and in coastal environments and to estimate the
dilution of wastewater in coastal waters. Because crotamiton
is discharged to sewage together with pharmaceuticals and
personal care products and it can be transported in aquatic
systems conservatively, crotamiton can be used as a con-
servative surrogate to study the removal processes of the
other pharmaceuticals and personal care products.
Natural estrogens were removed efficiently: 86% for E1, 90%
for E2, and 100% for E3 on average. The removal of natural
estrogens in Tokyo seems to be at least as efficient as those
reported in Spain (Carballa et al., 2004) and Canada (Servos et
al., 2005). The removal of E1 was somewhat lower than those
of the other estrogens. This could be caused by conversion of
E2 to E1 in the treatment process, as other researchers
suggested (Ternes et al., 1999), or by cleavage of estrogen
conjugates (Carballa et al., 2004). NP and OP had relatively
lower removal rates (61–75% and 32–65%, respectively) than
those in our previous study (93% for NP and 84% for OP, Isobe
et al., 2001) and in the other studies (e.g., 88% for NP; Bennie et
al., 1998). The lower efficiency of the removal of alkylphenols
in the present study is probably due to the analysis of only the
dissolved phase. The generation of alkylphenols through
degradation of alkylphenolethoxylates during secondary
treatment could also contribute to the lower removal of
alkylphenols. On the other hand, BPA was removed almost
completely (492%). Because BPA is relatively less hydropho-
bic (logKow¼ 3.32; Table S2), the high removal efficiency is not
attributable to adsorption to solids, but to aerobic biodegra-
dation during secondary treatment.
Aspirin, crotamiton, ibuprofen, triclosan, and diethyltolua-
mide were the most abundant pharmaceuticals in untreated
wastewater. During primary+secondary treatment, aspirin,
ibuprofen, and thymol were removed efficiently (490%
efficiency). On the other hand, amide-type pharmaceuticals
(e.g., crotamiton and carbamazepine), ketoprofen, and na-
proxen showed poor removal during secondary treatment
(o50% efficiency), which is probably due to their lower
hydrophobicity (logKowo3.2). Crotamiton was most abundant
in the effluent and was demonstrated to be a suitable
molecular marker owing to its persistent nature. Currently
we are studying the distribution and behaviors of the various
pharmaceuticals in receiving waters (rivers and the adjacent
costal zone). For such studies, crotamiton can be used as a
conservative molecular marker.
The present research has been conducted as a part of a Core
Research for Evolutional Science and Technology (CREST)
entitled ‘‘Risk-based Management of Self-regulated Urban
Water Recycle and Reuse System’’ headed by Prof. Furumai in
‘‘Hydrological Modeling and Water Resources System’’ sup-
ported by Japan Science and Technology Agency. This study
was also supported by Grant-in-Aid from the Ministry of
Education and Culture of Japan (Project no. 15510044, no.
16360263). We thank the Bureau of Sewerage Tokyo Metropo-
litan Government for their cooperation in collecting sewage
effluent samples. Several graduates and undergraduates in
LOG provided welcome assistance with fieldwork.
Appendix A. Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.watres.2006.06.039.
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