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Journal of Hazardous Materials 248– 249 (2013) 219– 227

Contents lists available at SciVerse ScienceDirect

Journal of Hazardous Materials

jou rn al h om epage: www.elsev ier .com/ loc ate / jhazmat

valuation of pharmaceuticals and personal care products with emphasis onnthelmintics in human sanitary waste, sewage, hospital wastewater, livestockastewater and receiving water

on-Jin Sima,b, Hee-Young Kima, Sung-Deuk Choic, Jung-Hwan Kwond, Jeong-Eun Oha,∗

Department of Civil and Environmental Engineering, Pusan National University, Busan 609-735, Republic of KoreaEnvironmental & Marine Evaluation Team, Korea Testing & Research Institute, Ulsan 681-802, Republic of KoreaSchool of Urban and Environmental Engineering, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of KoreaDivision of Environmental Science and Ecological Engineering, Korea University, Seoul 136-701, Republic of Korea

i g h l i g h t s

This study is about PPCPs in sewage, wastewater and receiving water.Few surveys have globally reported on anthelmintics in wastewater and surface water.This is the comprehensive study on anthelmintics in wastewater and water environment.We evaluated the characteristic patterns of various classes of PPCPs.This is the most comprehensive study worldwide.

r t i c l e i n f o

rticle history:eceived 26 July 2012eceived in revised form 1 January 2013ccepted 6 January 2013vailable online 11 January 2013

eywords:harmaceuticals and personal care

a b s t r a c t

We investigated 33 pharmaceuticals and personal care products (PPCPs) with emphasis on anthelminticsand their metabolites in human sanitary waste treatment plants (HTPs), sewage treatment plants (STPs),hospital wastewater treatment plants (HWTPs), livestock wastewater treatment plants (LWTPs), riverwater and seawater. PPCPs showed the characteristic specific occurrence patterns according to waste-water sources. The LWTPs and HTPs showed higher levels (maximum 3000 times in influents) ofanthelmintics than other wastewater treatment plants, indicating that livestock wastewater and humansanitary waste are one of principal sources of anthelmintics. Among anthelmintics, fenbendazole and

roductsnthelminticsuman sanitary wasteastewater

eceiving water

its metabolites are relatively high in the LWTPs, while human anthelmintics such as albendazole andflubendazole are most dominant in the HTPs, STPs and HWTPs. The occurrence pattern of fenbendazole’smetabolites in water was different from pharmacokinetics studies, showing the possibility of transfor-mation mechanism other than the metabolism in animal bodies by some processes unknown to us. Theriver water and seawater are generally affected by the point sources, but the distribution patterns in some

ly dif

receiving water are slight

. Introduction

During the last several decades, the production and usef pharmaceuticals and personal care products (PPCPs) havencreased rapidly with improved living standards. Too often, thesed PPCPs are discharged into the water environment, caus-

ng adverse impacts on humans and the aquatic ecosystem such

s endocrine disruption, renal failure and the emergence ofntibiotic-resistant bacteria [1–3]. Thus, PPCPs became an emerg-ng environmental concern worldwide. Earlier research on PPCPs

∗ Corresponding author. Tel.: +82 51 510 3513; fax: +82 51 514 9574.E-mail address: jeoh@pusan.ac.kr (J.-E. Oh).

304-3894/$ – see front matter © 2013 Elsevier B.V. All rights reserved.ttp://dx.doi.org/10.1016/j.jhazmat.2013.01.007

ferent from the effluent, indicating the influence of non-point sources.© 2013 Elsevier B.V. All rights reserved.

in public waterways had been concentrated to antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) in Europe and USAbecause of their relatively high usage frequencies [4–10]. Due togrowing concerns with PPCPs, the research interests have beenextended to more diverse categories of pharmaceuticals such as�-blockers, anthelmintics, synthetic hormones, illicit drugs as wellas their metabolites [11–14]. However, little has been reported onthe levels and the environmental fate of anthelmintics that havebeen discharged into the water environment.

Anthelmintic drugs are widely used for the treatment of gas-

trointestinal parasites in humans and animals [15]. More thanten different anthelmintics are commercially available, and alben-dazole, flubendazole, thiabendazole and fenbendazole are mostfrequently used amongst them [15,16]. Attentions have been paid

2 s Materials 248– 249 (2013) 219– 227

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Table 1Target compounds in this study.

Compound Acronym Compound Acronym

Anthelmintic AntibioticAlbendazole ABZ Lincomycin LINFlubendazole FLBZ Trimethoprim TMPThiabendazole TBZ Sulfathiazole STHFenbendazole FBZ Sulfamerazine SMROxfendazole FBZ-SO Sulfamethazine SMZFenbendazole sulfone FBZ-SO2

SulfamonomethoxineSMM

p-Hydroxyfenbendazole FBZ-OHSulfachloropyridazine

SCP

Amino fenbendazole FBZ-NH2 Sulfamethoxazole SMX�-Blocker N-acetyl

sulfamethoxazoleSMX-Ac

Atenolol ATN Sulfadimethoxine SDMMetoprolol MTP Non-steroidal

anti-inflammatory drugPropanolol PRP Acetaminophen ACT

Antibacterial agent Mefenamic acid MFNTriclosan TCS Ibuprofen IBP

Stimulant Diclofenac DCFCaffeine CAF Naproxen NPX

Anti-seizure Ketoprofen KTPCarbamazepine CBM Lipid regulator

20 W.-J. Sim et al. / Journal of Hazardou

n anthelmintics because of their resistance to biodegradationnd potential risks on non-target organisms in the environment17–20]. Anthelmintics might cause critical sub-lethal effects onrganisms like earthworms [20] and Oh et al. [19] have reportedhat ecological hazard quotients of fenbendazole, albendazole andubendazole are 2770, 9.7 and 4, respectively, based on acute tox-

city results using water fleas. According to hazard information andhe usage in Korea, fenbendazole was classified as priority groupseeding further investigations [21]. Similarly, fenbendazole andlbendazole were also assigned to top priority group in the UK22,23]. Although the concern with anthelmintics has increased,o our best knowledge, only two surveys have globally reported onhe distribution of anthelmintics in wastewater and surface water13,24]. Weiss et al. [24] have reported on the levels of flubendazolen seepage water of a manured area, and Van de Steene et al. [13]nvestigated flubendazole in wastewater and surface water. Exceptor flubendazole, other anthelmintics in water have not been stud-ed at all, despite the fact that many studies on anthelmintics inuman and animal bodies have been performed since the 1980s and

t is estimated that approximately 50% of the anthelmintics admin-stered are discharged into the public waterways [25]. In the case ofenbendazole, 44–50% of the dose is excreted unchanged throughhe feces, whereas other portion is mostly metabolized in the body25]. In general, pharmaceuticals absorbed in the bodies are trans-ormed into metabolites and excreted through the urine and feces.lbendazole and fenbendazole are transformed into the sulfox-

de form and, finally, metabolized into the sulfones [15,26,27].hus sulfoxidation is regarded as a major pathway of anthelminticetabolism. Besides the sulfone form, other types of anthelminticetabolites such as the amino- and hydroxyl-metabolites were

eported [25]. It is well-accepted that transformation products ofharmaceuticals are significant emerging water pollutants becausehey might hold biological activities [28–30].

In this study, we investigated eight anthelmintics including theetabolites in influents and effluents of sewage, human sanitaryaste (urine and feces), hospital wastewater, livestock wastewater

reatment plants and receiving water to understand their distribu-ion and fate in the aquatic environment. In the case of metabolites,enbendazole’s metabolites were selected because fenbendazoleas listed in the priority group for the ecosystem and humanealth and its metabolites were well-known compared to othernthelmintics. The influent and effluent samples from two humananitary waste treatment plants (HTPs), eight sewage treatmentlants (STPs), two hospital wastewater treatment plants (HWTPs)nd two livestock wastewater treatment plants (LWTPs) were col-ected for the evaluation of selected anthelmintics. In addition,he receiving water survey was also performed on river waternd seawater. Other 25 different PPCPs were additionally ana-yzed to compare them with the occurrence of anthelmintics in the

ater environment. The main aim of the study was to provide annderstanding of the fate and distribution characteristics of vari-us anthelmintics in the sources and water environment with therst comprehensive survey worldwide.

. Methods

.1. Sampling

The sampling locations surveyed in this study are presented inig. 1. Sampling sites are located in Ulsan and Busan, two large citiesith over one million inhabitants in Korea. Wastewater samples

ere collected from the influents (after grit remover) and effluents

final outlet) in two HTPs, eight STPs and two HWTPs using the4–48 h composite sampling method. STPs treat sewage includingousehold wastewater and others, while HTPs only treat human

Antipruritic Gemfibrozil GFBCrotamiton CTM Clofibric acid CFB

sanitary waste (urine and feces). The river (19 sites) and seawater(7 sites) samples were collected in Ulsan using the grab samplingmethod. In Ulsan, sampling was performed twice between June andOctober 2010. In Busan, the survey was carried out once in June2010. Two LWTPs are located in rural area near Nakdong River. Thesamples from LWTPs were collected twice between September andOctober, 2011. The information on the sampling sites is listed inTable S1 in Supplementary Material. All samples were collected inamber glass bottles and refrigerated immediately.

2.2. Sample preparation

In this study, 33 PPCPs were analyzed in human sanitarywaste, sewage, hospital wastewater, river and seawater sam-ples (Table 1). The target compounds consist of anthelmintics(8 compounds), antibiotics (10), NSAIDs (6), �-blockers (3), lipidregulators (2) and others (4). Fenbendazole sulfone (FBZ-SO2),p-hydroxyfenbendazole (FBZ-OH) and amino fenbendazole (FBZ-NH2) were kindly provided by Dr. Sung-Hwa Yoon (Ajou University,Suwon, Republic of Korea), and the other standards includingalbendazole (ABZ), thiabendazole (TBZ), flubendazole (FLBZ) andfenbendazole (FBZ) and oxfendazole (FBZ-SO) were purchased fromSigma–Aldrich (St. Louis, MO, USA), Dr. Ehrenstorfer (Augsburg,Germany) and CIL (Andover, MA, USA). The samples were extractedusing an automated solid-phase extraction (SPE) system (HorizonTechnology, Salem, NH, USA) with HLB® disks (Waters, Milford, MA,USA). Before extraction, all water samples were filtered with 1 �mglass fiber filters (Whatman, Maidstone, UK). The samples (100 mLof influents and 400 mL of effluents, river water and seawater)were spiked with 40 ng of disodium ethylenediamine tetra aceticacid dihydrate (Na2EDTA-2H2O) and 20 �L of internal standardssolution (sulfathiazole-d4 and 13C2-ibuprofen; 10 ng/�L). The SPEdisks were preconditioned with methyl tertiary butyl ether (MTBE),methanol and water, then the samples were loaded onto the disks.The preconditioned disks were washed with water and dried for20 min. The dried disks were eluted with 10% methanol/MTBE

and methanol. The experimental conditions of SPE are shown inTable S2 in Supplementary Material. The extracts were concen-trated to 1 mL using TurboVap LV (Caliper Life Sciences, Hopkinton,MA, USA).

W.-J. Sim et al. / Journal of Hazardous Materials 248– 249 (2013) 219– 227 221

locatio

2

pwQdpdpmrs

2

tTogwi1fiwtsn(

Fig. 1. Sampling

.3. Instrumental measurement

The final extracts were analyzed by liquid chromatogra-hy/tandem mass spectrometry (LC/MS/MS). All target compoundsere separated and quantified using a 1200 HPLC coupled to a 6460QQ (Agilent, Santa Clara, CA, USA). To obtain the best LC/MS/MSata, target compounds were classified into two groups (group A:ositive ion mode, group B: negative ion mode). Instrumental con-itions varied with analytical groups and the MS/MS analysis waserformed in the positive or negative electrospray ionization (ESI)ode. All analytes were identified and quantified using the multi-

eaction monitoring (MRM) mode. The instrumental conditions areummarized in Supplementary Material (Table S3 and S4).

.4. QA/QC

Calibration curves were drawn using six to eight standard solu-ions (0.01–5 �g/L) pretreated by the SPE method for the samples.he correlation coefficients (r2) of the calibration curves werever 0.99. For recovery tests of the extraction methods, all tar-et compounds and internal standards were spiked into deionizedater. Then, the test samples were analyzed using the analyt-

cal method. The recoveries of target PPCPs ranged from 50 to20%, except for lincomycin and atenolol (less than 50%). To con-rm the matrix effects and recovery, all target analytes (0.5 �g/L)ere spiked into the STP influent and river samples (n = 3, respec-

ively). The obtained accuracies of all analytes in the samples wereatisfactory (70–130%). Limits of quantification (LOQs) (signal-to-oise = 10) of target compounds ranged from 0.0001 to 0.0134 �g/LTable S5, Supplementary Material).

ns in this study.

2.5. Statistics analysis

A multivariate statistics analysis was performed using SPSS 19software (SPSS Inc., Chicago, IL, USA) to examine the correlationof anthelmintic distributions in the water samples. The objectsare samples, and the variables are normalized concentrations ofcompounds for the principal component analysis (PCA). The con-centrations of all anthelmintics were normalized by dividing by thesum of concentrations for each sample. The score plot from the PCAindicates the pattern of samples.

3. Results and discussion

3.1. Occurrence and fate of anthelmintics in HTPs, STPs, HWTPs,LWTPs and receiving water

3.1.1. Concentrations of anthelmintics in water systemTable 2 shows the concentrations of anthelmintics in the HTPs,

STPs, HWTPs, LWTPs and receiving water samples. In the influents,the LWTPs (3.28–535 �g/L) had the highest total concentrations,followed by the HTPs (7.18–56.4 �g/L), STPs (0.515–7.72 �g/L)and HWTPs (0.167–2.61 �g/L). This result indicates that live-stock wastewater and human sanitary waste are one of principalsources of anthelmintics into the environment. Unlike the influ-ents, the total concentrations in the HTP effluents (4.28–12.8 �g/L)were greater than those in the STPs (0.266–6.04 �g/L), LWTPs(0.274–2.21 �g/L) and HWTPs (0.110–0.586 �g/L). In the HTPs,

FLBZ (influents: 4.59–49.4 �g/L, effluents: 4.20–12.4 �g/L) had thehighest levels in all influent and effluent samples, followed by ABZ,TBZ and FBZ. Like FLBZ and ABZ, TBZ in the human sanitary wastepresented a high detection frequency of 100% because FLBZ and ABZ

222 W.-J. Sim et al. / Journal of Hazardous Materials 248– 249 (2013) 219– 227

Table 2Concentrations (�g/L) of anthelmintics in the wastewater and water samples.

Sample ABZ FLBZ TBZ FBZ FBZ-SO FBZ-SO2 FBZ-OH FBZ-NH2 Total

HTPs Influent Freq 3/3 3/3 3/3 1/3 0/3 0/3 0/3 0/3 3/3Mean a 3.75 20.0 0.029 0.002 ND ND ND ND 23.8Med a 3.15 6.07 0.042 – – – – – 7.79Min a 1.10 4.59 0.001 – – – – – 7.18Max a 6.99 49.4 0.045 – – – – – 56.4

Effluent Freq 3/3 3/3 3/3 1/3 0/3 0/3 0/3 0/3 3/3Mean 0.398 9.13 0.014 0.003 ND ND ND ND 9.55Med 0.335 10.8 0.020 – – – – – 11.6Min 0.080 4.20 0.001 – – – – – 4.28Max 0.777 12.4 0.020 – – – – – 12.8

STPs Influent Freq 13/13 13/13 4/13 6/13 4/13 3/13 5/13 7/13 13/13Mean 0.891 1.46 0.038 0.116 0.016 0.025 0.021 0.006 2.44Med 0.713 0.878 0.038 0.034 0.014 0.021 0.012 0.001 1.76Min 0.189 0.205 0.030 0.018 0.004 0.007 0.008 0.000 0.515Max 3.02 4.67 0.046 0.533 0.032 0.046 0.062 0.017 7.72

Effluent Freq 13/13 13/13 10/13 4/13 5/13 2/13 3/13 3/13 13/13Mean 0.114 1.14 0.013 0.013 0.019 0.021 0.004 0.001 1.28Med 0.036 0.401 0.011 0.015 0.007 0.021 0.004 0.001 0.461Min 0.011 0.237 0.000 0.001 0.001 0.004 0.003 0.000 0.266Max 0.594 5.63 0.035 0.021 0.067 0.037 0.006 0.001 6.04

HWTPs Influent Freq 2/3 3/3 0/3 1/3 2/3 0/3 0/3 0/3 3/3Mean 0.656 0.530 ND 0.025 0.015 ND ND ND 0.985Med 0.656 0.135 – – 0.015 – – – 0.180Min 0.098 0.061 – – 0.008 – – – 0.167Max 1.21 1.39 – – 0.021 – – – 2.61

Effluent Freq 3/3 3/3 2/3 1/3 2/3 0/3 0/3 0/3 3/3Mean 0.162 0.174 0.018 0.014 0.023 ND ND ND 0.369Med 0.147 0.222 0.018 – 0.023 – – – 0.429Min 0.042 0.051 0.018 – 0.003 – – – 0.110Max 0.298 0.251 0.019 – 0.042 – – – 0.568

LWTPs Influent Freq 0/4 4/4 2/4 4/4 4/4 4/4 2/4 4/4 4/4Mean ND 1.78 0.078 64.0 2.59 32.6 24.2 26.0 143Med – 0.857 0.078 6.83 0.441 0.501 1.71 4.60 16.8Min – 0.354 0.063 1.11 0.218 0.283 0.693 0.554 3.28Max – 5.059 0.093 241 9.27 96.9 92.7 94.1 535

Effluent Freq 2/4 4/4 2/4 4/4 4/4 4/4 2/4 4/4 4/4Mean 0.080 0.364 0.011 0.666 0.192 0.142 0.033 0.136 1.47Med 0.080 0.466 0.011 0.575 0.217 0.132 0.033 0.111 1.70Min 0.052 0.084 0.004 0.029 0.031 0.015 0.023 0.018 0.274Max 0.108 0.543 0.017 1.49 0.305 0.291 0.043 0.303 2.21

River Freq 29/38 35/38 28/38 18/38 11/38 8/38 13/38 21/38 38/38Mean 0.011 0.129 0.007 0.009 0.006 0.002 0.004 0.002 0.141Med 0.010 0.028 0.009 0.004 0.001 0.002 0.004 0.001 0.042Min 0.004 0.002 0.000 0.001 0.000 0.001 0.000 0.000 0.006Max 0.038 1.17 0.022 0.063 0.056 0.005 0.011 0.011 1.31

Seawater Freq 4/14 8/14 4/14 4/14 2/14 1/14 3/14 4/14 14/14Mean 0.008 0.013 0.009 0.001 0.000 0.001 0.001 0.002 0.013Med 0.008 0.009 0.009 0.001 0.000 – 0.002 0.001 0.010Min 0.004 0.002 0.009 0.001 0.000 – 0.001 0.000 0.001Max 0.010 0.034 0.009 0.002 0.001 – 0.002 0.006 0.042

F detec

aawbHttas1Siwtp

req: detection frequency, Med: median, Min: minimum, Max: maximum, ND: nota The values were calculated except for ND-data.

re most widely used for human anthelmintics and because TBZ islso widely used for humans as well as animals and plants. FBZas detected one time in the influent and effluent from one HTP,

ut FBZ’s metabolites were not detected in the HTP samples at all.owever, in the LWTPs, FBZ and its metabolites were found at rela-

ively high levels with high detection frequencies (93%) comparedo the other anthelmintics (54%), which reflects the wide use of FBZnd FBZ-SO for various livestock and pets [15,25–27]. For this rea-on, in the influents from the LWTPs, the levels of FBZ ranged from.11 to 241 �g/L, followed by FBZ-SO2, FBZ-NH2, FBZ-OH and FBZ-O. In the STPs, FLBZ, the human anthelmintic, was most dominant

n both influents (0.205–4.67 �g/L) and effluents (0.237–5.63 �g/L)

ith 100% of detection frequency. FBZ and its metabolites inhe STP had a relatively high detection frequency of 32% com-ared to the HTPs (7%), indicating the discharge of veterinary

ted (< LOQ)

anthelmintics from households (e.g., pets). In the HWTPs, FLBZ(influents: 0.061–1.39 �g/L, effluents: 0.051–0.251 �g/L) and ABZ(influents: 0.098–1.21 �g/L, effluents: 0.042–0.298 �g/L) showedrelatively high concentrations.

In the case of the receiving water, the river samples(0.006–1.31 �g/L) showed higher total concentrations ofanthelmintics than seawater (0.001–0.042 �g/L) likely due tohigher dilution in seawater samples. Fig. 2 shows the concen-trations of anthelmintics in the river water and seawater sitesinvestigated. Among the sampling sites, H4, T2, Y3 and S2 locateddownstream from the STPs or HTP showed the highest concen-

trations in each sampling catchment, indicating the influenceof effluents discharged from the STPs or HTP. Like the most ofwastewater samples except the LWTPs, FLBZ was dominant with ahigh frequency of detection (>90%) in the river water.

W.-J. Sim et al. / Journal of Hazardous Materials 248– 249 (2013) 219– 227 223

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3

twtc(bLdi5otih>c

Fig. 2. Total concentrations of anthelmintic

As described earlier, only two surveys of FLBZ have reportedn wastewater and surface water. According to Weiss et al. [24],he concentration of FLBZ ranged from 25 from 56 �g/L in seepageater of a manured area, and another study performed in Belgium

eported low levels of FLBZ in wastewater collected from fiveastewater treatment plants (WWTPs) (influents: max. 0.221 �g/L,

ffluents: max 0.215 �g/L) and 16 surface water samples (max..020 �g/L), which were comparable to the results of this study13]. For the other anthelmintic, no data was available for compar-son.

Earlier studies have identified that FBZ-SO, FBZ-SO2 and FBZ-OHre the major metabolites of FBZ in various animals, while FBZ-H2 is minor in their study on FBZ pharmacokinetics [15,25,26,31].owever, FBZ metabolites in this study showed different occur-

ence patterns. Overall, FBZ-SO2 and FBZ-OH had relatively highroportions as in the previous studies, and FBZ-NH2 also showed

dominant result. Especially, in the livestock wastewater, FBZ-H2 had 100% of detection frequency and concentrations similar toBZ-SO2 and FBZ-OH. In the sewage and receiving water, FBZ-NH2howed the highest detection frequency. FBZ-NH2 is a hydrolysisroduct of FBZ after the cleavage of the peptide bonding, whichay occur in the presence of aquatic microorganisms. Thus, the

igh frequency of FBZ-NH2 in the water samples may be due to theicrobial hydrolysis of FBZ although this process is not dominant

n mammals.

.1.2. Elimination rates of anthelmintics in treatment processesFig. 3 shows the elimination tendencies of anthelmintics in

he HTPs, STPs, HWTPs and LWTPs. In this study, the targetastewater plants employ the biological treatment processes as

he main system, except for one HWTP (HS1). HS1 consists ofhemical flocculation followed by activated carbon adsorptionTable S1, Supplementary Material). The main processes of STPs areased on the general activated sludge system, while the HTPs andWTPs have unique or complex biological processes (e.g., aerobicigestion, liquid corrosion, etc.), due to high organic loads of their

nfluents. ABZ in the STPs has significant removal tendencies (over0% except for one case), while others mostly showed insignificantr inconsistent removal patterns with a large variation. Among thearget anthelmintics, FLBZ’s removal rates have been investigated

n a previous study. Van de Steene et al. [13] reported that FLBZas insignificant elimination patterns with a large variation (<0 to90%), as in this study. Our result is similar to elimination efficien-ies of other pharmaceuticals in previous studies [32,33]. Except for

rious river and seawater samples collected.

some compounds (e.g., ACT and CAF), many pharmaceuticals, espe-cially antibiotics, show insignificant elimination patterns or have alarge variation in WWTPs.

3.2. Distribution patterns of anthelmintics in water environment

As shown in the score plot from the multivariate statistics(Fig. 4), the samples were divided into three groups (A, B and C).In group A, FLBZ and ABZ that are mostly used for humans hadthe largest proportion (92 ± 9%, over 70%), and all the samplesfrom the HTPs, STPs HWTPs and 69% of receiving water samplesbelonged to group A. More specifically, these samples in groupA were further divided into subgroups according to the sampletypes: group A1 (79% of effluent samples + 48% of receiving water)and group A2 (79% of influent samples + 21% of receiving water). Ingroup A1, FLBZ (mean proportion to total concentration ± standarddeviation: 88 ± 9%) was most dominant, followed by ABZ (7 ± 7%).For group A2, even though the dominant anthelmintics were thesame, the compositions were different: FLBZ (53 ± 13%) and ABZ(36 ± 15%). As described earlier, among the target anthelmintics,ABZ had the highest removal tendency, while FLBZ’s eliminationrates were insignificant in the HTPs, STPs and HWTPs. For thisreason, the proportions of ABZ decreased in the effluents comparedwith the influents, while FLBZ had the opposite result. In the caseof receiving water, among the total of 52 points, 36 samples wereclassified into group A. Especially, 25 receiving water sampleswere located in group A1, indicating the influence of the effluentsfrom the sources. Even though the effluents directly flow intothe water environment, some receiving water samples in groupA2 showed occurrence results different from the effluents. Thissuggests the possibility of untreated wastewater flowing into thereceiving water, which is similar to what was found in our previousstudy [33]. The various pharmaceuticals including NSAIDs andantibiotics were also surveyed in STPs and rivers. Most of the riversamples were grouped with the STP effluents, while some riversamples showed occurrence and distribution patterns similar toSTP influents, indicating the seepage of untreated wastewater intorivers. Unlike group A, in group B (13 receiving water points, whichis 25% of total receiving water), TBZ (41 ± 29%) had a relativelyhigher proportion, followed by ABZ (19 ± 18%), FBZ-OH (14 ± 27%),

FBZ (8 ± 15%) and FBZ-NH2 (6 ± 9%). As TBZ is used for plants aswell as humans and animals, the group B sites seem to be relatedwith its usage in non-point sources. The livestock wastewater andthree receiving water samples were classified as group C. In group

224 W.-J. Sim et al. / Journal of Hazardous Materials 248– 249 (2013) 219– 227

TPs (

C(tFo

3w

(fPAtafiidsicHt

Fig. 3. Elimination of anthelmintics in the HTPs, STPs and HW

, FBZ (36 ± 30%) was the most dominant, followed by FBZ-NH220 ± 28%), FBZ-SO2 (16 ± 29%) and FBZ-SO (10 ± 17%). In group C,he proportions (89 ± 15%) of veterinary drugs except for ABZ andLBZ were higher than those in group A. This suggests the possibilityf the contribution of non-point sources such as livestock farms.

.3. Occurrence characterization of PPCPs according toastewater sources

In our earlier studies, antibiotics and NSAIDs in various sourcessewage, wastewater from livestock, hospital and pharmaceuticalactories) were surveyed, and characteristic occurrence patterns ofPCPs depending on wastewater sources were identified [33,34].s an extension of our previous study, anthelmintics, �-blockers,

riclosan and crotaminton were added as new target compounds,nd the human sanitary waste was surveyed in this study for therst time. Table 3 lists the concentrations of each class of PPCPs

n the HTPs, STPs, HWTPs, LWTPs and receiving water, and theetailed concentrations of PPCPs except for anthelmintics in thistudy are summarized in Table S6 in Supplementary Material. In the

nfluents, the LWTPs (1385–5307 �g/L) showed the highest totaloncentrations of PPCPs, followed by the HTPs (168–498 �g/L),WTPs (79.5–466 �g/L) and STPs (23.2–124 �g/L). Fig. 5a shows

he fraction of PPCP groups according to sample types. The fraction

Fig. 4. Score plot from princip

+: not detected in the influent, but detected in the effluent).

was calculated by dividing the concentration of each PPCP groupby the total concentration. Although the fraction of PPCP groupswas slightly different among the influent samples from the HTPs,STPs and HWTPs, the influent wastewater samples related withhuman sources showed almost similar patterns as dominantoccurrence of antibiotics, NSAIDs and �-blockers (Fig. 5a). In theLWTP influents, antibiotics were dominant unlike other waste-water, while �-blockers were not detected. Although �-blockersare antiarrhythmic drugs for humans and animals, the livestockwastewater seems to have relatively low occurrence levels becausefew amounts are used for edible animals.

The concentrations of PPCPs in the influents were comparedwith their annual usage amounts in Korea. According to netproduct amounts of human pharmaceuticals in Korea, 2004,NSAIDs such as ACT (895,775 kg/year), IBP (143,398 kg/year), MFN(63,354 kg/year) and NPX (42,150 kg/year) were at the upper ranksin terms of production amounts. Among NSAIDs surveyed in thisstudy, IBP, NPX, ACT and NPX were dominant compounds in thehuman sanitary waste. In the STP influents, ACT and IBP showedhigher levels than other NSAIDs, and ACT was most dominant

in the hospital wastewater (Table S6 in Supplementary Mate-rial). Although the amounts of annual production do not correlatewell with the observed concentrations of PPCPs in wastewa-ter, the highly produced PPCPs were detected at relatively high

al component analysis.

W.-J. Sim et al. / Journal of Hazardous Materials 248– 249 (2013) 219– 227 225

Table 3Concentrations (�g/L) of PPCP groups in HTPs, STPs, HWTPs, LWTPs and receiving water.

Sample Antibiotics NSAIDs �-Blockers Anthelmintics Others Total

HTPs Influent Freq 3/3 3/3 3/3 3/3 3/3 3/3Mean a 106 48.8 98.6 23.8 17.8 295Med a 90.9 56.2 57.6 7.79 19.9 218Min a 57.5 25.0 41.9 7.18 13.3 168Max a 169 65.1 196 56.4 20.1 498

Effluent Freq 3/3 3/3 3/3 3/3 3/3 3/3Mean 21.1 0.826 0.204 9.55 4.42 36.1Med 8.00 0.791 0.177 11.6 5.55 22.0Min 2.28 0.596 0.028 4.28 0.576 13.8Max 53.0 1.09 0.406 12.8 7.14 72.5

STPs Influent Freq 13/13 13/13 13/13 13/13 13/13 13/13Mean 17.6 16.1 14.7 2.44 7.90 58.7Med 13.2 14.0 8.44 1.76 6.50 46.2Min 3.00 4.28 2.89 0.515 1.53 23.2Max 65.4 32.5 43.8 7.72 16.3 124

Effluent Freq 13/13 13/13 13/13 13/13 13/13 13/13Mean 14.6 0.593 4.41 1.28 0.502 21.4Med 6.03 0.510 4.16 0.461 0.345 12.4Min 0.763 0.151 0.724 0.266 0.047 3.49Max 95.3 1.35 13.8 6.04 1.65 105

HWTPs Influent Freq 3/3 3/3 3/3 3/3 3/3 3/3Mean 74.1 78.3 44.1 0.985 30.3 228Med 45.4 53.9 5.71 0.180 32.4 138Min 2.90 53.6 3.79 0.167 19.0 79.5Max 174 128 123 2.61 39.3 466

Effluent Freq 3/3 3/3 3/3 3/3 3/3 3/3Mean 18.8 9.47 4.64 0.369 10.4 43.7Med 13.5 10.3 2.07 0.429 14.1 45.9Min 7.01 2.10 1.62 0.110 0.812 12.1Max 35.9 16.1 10.2 0.568 16.4 73.2

LWTPs Influent Freq 4/4 3/4 0/4 4/4 4/4 4/4Mean 2395 923 ND 143 32.0 3262Med 1663 324 – 16.8 21.1 3178Min 1025 65.9 – 3.28 8.01 1385Max 5230 2378 – 535 77.9 5307

Effluent Freq 4/4 4/4 2/4 4/4 4/4 4/4Mean 153 0.331 0.125 1.47 4.97 160Med 13.0 0.268 0.125 1.70 2.76 22.8Min 1.53 0.030 0.008 0.274 0.410 2.39Max 586 0.758 0.242 2.21 14.0 593

River Freq 38/38 38/38 38/38 38/38 38/38 38/38Mean 0.349 0.189 0.207 0.141 0.130 1.02Med 0.117 0.074 0.054 0.042 0.063 0.570Min 0.019 0.007 0.000 0.006 0.012 0.084Max 2.74 2.65 1.95 1.31 0.568 5.98

Seawater Freq 14/14 14/14 14/14 14/14 14/14 14/14Mean 0.111 0.056 0.045 0.013 0.051 0.276Med 0.034 0.018 0.029 0.010 0.023 0.129Min 0.001 0.006 0.000 0.001 0.003 0.044Max 0.715 0.219 0.223 0.042 0.301 1.21

F detec

cTmai[tmSf(Etrp

req: detection frequency, Med: median, Min: minimum, Max: maximum, ND: not

a The values were calculated except for ND-data.

oncentrations in the influents from the HTPs, STPs and HWTPs.he annual production of LIN (8590 kg/year) for humans wasuch lower than those of ACT, IBP, MFN and NPX, but it was

lso dominantly detected in the HTPs, STPs and HWTPs, result-ng from its persistent property in the environment, unlike NSAIDs33]. As for veterinary pharmaceuticals, Kim et al. [21] reportedhe top 50 compounds based on sales amount of veterinary

edicine in Korea, 2005. Among target compounds in this study,TH (442,971 kg/year) and FBZ (356,187 kg/year) were dominant,ollowed by LIN (189,633 kg/year), TMP (109,310 kg/year), ACT103,276 kg/year), SMZ (98,659 kg/year) and SMX (70,969 kg/year).

xcept for TMP, these compounds had higher concentrations thanhe other PPCPs in the livestock wastewater, indicating a cor-elation between usage amounts and detection levels up to aoint.

ted (< LOQ)

In the effluents, more characteristic occurrence patterns ofPPCPs with the type of wastewater were observed than in theinfluents. The LWTPs showed the highest levels (2.39–593 �g/L),followed by the HTPs (13.8–72.5 �g/L), STPs (3.49–105 �g/L) andHWTPs (12.1–73.2 �g/L). Like the influent, the fraction of antibi-otics was dominant in all types of effluents, which are relatedwith the low removal efficiencies of antibiotics in the WWTPs,and especially, the fraction of antibiotics in the LWTP effluent waspredominant (over 95%). The next dominant group of PPCPs wasanthelmintics in human sanitary waste and �-blockers in the STPeffluents. In the effluents from the STPs and LWTPs, NSAIDs showed

lower fraction than the other PPCP groups, as they did in our pre-vious studies [33,34].

Because the wastewater directly affects the water environment,the daily load in the wastewater was calculated by multiplying the

226 W.-J. Sim et al. / Journal of Hazardous Materials 248– 249 (2013) 219– 227

of PP

ttlhtspt(rtcrsPt(uas

Fig. 5. Distribution of PPCPs according to sample types: (a) fraction

otal concentration and the volumetric flow rate (Fig. 5b). Unlikehe total concentration patterns, the STPs showed the greatest dailyoads of PPCPs in both influent and effluent samples because ofigher flow rates than the other sources (Table S1, Supplemen-ary Material), indicating again that the STPs are the most principalource of PPCPs discharged into the water environment, as in ourrevious study [34]. In the river samples, the total concentra-ions of PPCPs ranged from 0.084 to 5.98 �g/L, and the seawater0.044–1.21 �g/L) showed lower levels than the river water. Thisesult might be related to the dilution of river water in the coast. Inhe receiving water samples, antibiotics showed the highest con-entrations as was the case in the wastewater. Thus, most of theiver water and seawater seem to be affected by the point sourcesuch as HTPs, STPs and HWTPs. However, the fraction pattern ofPCP groups in the receiving water was slightly different fromhe STP effluent but similar to that in the STP and HWP influents

Fig. 5a), indicating the influence of non-point sources includingntreated sewage. As the sewage collection rate in Ulsan is 92.4%ccording to the Ministry of Environment of Korea, some untreatedewage might have discharged directly into the water environment.

CP groups, (b) daily loads in wastewater (bar: average, line: range).

4. Conclusions

In this study, the occurrence and distribution of PPCPs weresurveyed with emphasis on anthelmintics in the HTPs, STPs,HWTPs, LWTPs and receiving water. The livestock wastewater andhuman sanitary waste had relatively high total concentrations ofanthelmintics, indicating that livestock wastewater and humansanitary waste are the principal sources of anthelmintics to aquaticenvironment. Some river and seawater sites located downstreamfrom the sources showed the highest concentrations in each catch-ment, showing the contribution of effluent discharges from thesources. In all the influents and effluents except for the LWTPs,FLBZ and ABZ were predominant because they are the most widelyused human anthelmintics. In addition to anthelmintics, we alsoinvestigated 25 PPCPs such as antibiotics, NSAIDs and �-blockersin various wastewater types and observed the characteristic spe-

cific occurrence patterns of PPCPs according to wastewater sources.Especially, the livestock wastewater showed the antibiotic pre-dominant distribution pattern of PPCP groups, while antibiotics andthe other PPCP classes showed dominant patterns in the human

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W.-J. Sim et al. / Journal of Hazardou

anitary waste, sewage and hospital wastewater. Based on theseatterns, it was possible to trace the sources of PPCPs discharged

nto the receiving water, such as untreated non-point or treatedoint sources.

cknowledgements

We thank Dr. Sung-Hwa Yoon for providing metabolites of FBZ.his work was supported by the National Research Foundation oforea (NRF) grant funded by the Ministry of Education, Science andechnology (MEST) (No. 2009-0074454 & No. 2010-0006942).

ppendix A. Supplementary data

Supplementary data associated with this article can beound, in the online version, at http://dx.doi.org/10.1016/.jhazmat.2013.01.007.

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