Seasonal variations of several pharmaceutical residues in surface water and sewage treatment plants of Han River, Korea

SC IE N CE OF T H E TOT AL E N V I RO N ME N T 4 0 5 ( 2 00 8 ) 1 2 0–1 28

a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m

w w w. e l s e v i e r. c o m / l o c a t e / s c i t o t e n v

Seasonal variations of several pharmaceutical residues in surface water and sewage treatment plants of Han River, Korea Kyungho Choi a,⁎, Younghee Kim a , Jeongim Park b , Chan Koo Park c , MinYoung Kim c , Hyun Soo Kim d , Pangyi Kim d a

School of Public Health, Seoul National University, Seoul, Republic of Korea College of Natural Sciences, Soonchunhyang University, Asan, Republic of Korea c Seoul Research Institute of Health and Environment, Seoul, Republic of Korea d College of Natural Sciences, Yongin University, Yongin, Republic of Korea b

AR TIC LE I N FO

ABS TR ACT

Article history:

We collected influent and effluent samples from four sewage treatment plants (STPs) as well

Received 16 March 2008

as surface water samples in Han River of Seoul, Korea, in three sampling events representing

Received in revised form 3 June 2008

different flow conditions, i.e., April, June, and August, 2005, and analyzed for eleven

Accepted 6 June 2008

pharmaceuticals including acetaminophen, caffeine, carbamazepine, cimetidine, diltiazem,

Available online 6 August 2008

trimethoprim, and five sulfonamide antibiotics, using LC-MS-ESI. Pharmaceuticals of high annual production amount were detected in higher level in STP influents. Levels of

Keywords:

pharmaceutical residues in the influents were the highest for acetaminophen (average

Pharmaceuticals

27,089 ng/L), followed by caffeine (23,664 ng/L), cimetidine (8045 ng/L), and sulfamethoxazole

Influent

(523 ng/L). Levels of acetaminophen and caffeine in STP effluents were very low compared to

Effluent

the influent concentrations. However cimetidine was detected in relatively high levels even in

Seasonal variation

STP effluent samples. In effluent samples, cimetidine showed the highest level (5380 ng/L),

Hazard quotient

followed by caffeine (278 ng/L), sulfamethoxazole (193 ng/L), and carbamazepine (111 ng/L). The

Cimetidine

concentration of cimetidine was also the highest in surface water samples (average 281 ng/L), which is the highest level reported from surface water worldwide to our knowledge. Caffeine (268.7 ng/L), acetaminophen (34.8 ng/L), and sulfamethoxazole (26.9 ng/L) were also detected in relatively high levels. Levels of pharmaceuticals detected in surface water samples upstream STPs were generally very low compared to the downstream samples, suggesting that the STPs potentially be a major source of the test pharmaceuticals into Han River. The hazard quotients (HQs) were calculated for the test pharmaceuticals based on their occurrences in surface water, and no pharmaceutical resulted in HQ greater than one, suggesting that their potential environmental impact may be low. © 2008 Elsevier B.V. All rights reserved.

1.

Introduction

Pharmaceutical residues detected in surface water have prompted public concerns worldwide. Pharmaceutical com-

pounds are biologically active by design and hence might affect certain keystone species potentially leading to disturbance of ecosystem. Flaherty and Dodson (2005) reported that chronic exposure to certain pharmaceuticals could elicit changes in

Abbreviations: ATP, acetaminophen; CAF, caffeine; CBZ, carbamazepine; CTD, cimetidine; DTZ, diltiazem; SMX, sulfamethoxazole; TMP, trimethoprim; SCP, sulfachloropyridazine; STZ, sulfathiazole; SMZ, sulfamethazine; SDM, sulfadimethoxine. ⁎ Corresponding author. School of Public Health, Seoul National University, 28 Yunkeon Chongro Seoul 110-799, Republic of Korea. Fax: +82 2 745 9104. E-mail address: [email protected] (K. Choi). 0048-9697/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.scitotenv.2008.06.038

S CIE N CE OF T H E TOT AL E N V I RO N ME N T 4 0 5 ( 2 00 8 ) 1 2 0–1 28

sex ratio and fecundity of Daphnia magna. Mimeault et al. (2005) also demonstrated that environmental levels of gemfibrozil, a lipid regulator, bioaccumulated in goldfish (Carassius auratus) and reduced the level of plasma testosterone. In a 7-year whole-lake experiment in Canada, Kidd et al. (2007) demonstrated that low level chronic exposures to 17α-ethynylestradiol caused ultimately a near extinction of fathead minnow (Pimephales promelas) from the experimental lake, potentially through feminization of the male fish. Studies on environmental occurrences of pharmaceutical residues date back to 1970's in US (Hignite and Azarnoff, 1977), however it is only last decade that comprehensive environmental surveys have been conducted and their potential implications on ecosystem health have been rigorously studied (Fent et al., 2006; Jjemba, 2006; Kolpin et al., 2002). Most of the occurrence surveys for environmental pharmaceuticals were limited geographically in North America and Europe (Hilton and Thomas, 2003), with little work reported in Korea (Choi et al., 2008; Han et al., 2006; Park, 2006). Because the patterns and volumes of pharmaceutical use are different by country, the levels of pharmaceutical occurrence in the environment might be different in Korea. The present study was conducted to understand the occurrences of several major pharmaceuticals in Han River of Seoul, Korea, and evaluate their potential ecological risks. Han River, our study site, is one of the most important rivers in Korea, which runs through the heart of the Seoul, where about (a quarter) of the whole Korean population (approximately 10,297K) live. There are four sewage treatment plants (STPs) in Seoul, which receive mostly domestic wastewater and direct the effluent to Han River. Hence discharge of human pharmaceutical products through STPs to Han River is of potential concern (Park, 2006). Studies suggested that the levels of active pharmaceutical compounds could vary depending on the weather conditions (Choi et al., 2008; Kolpin et al., 2004), therefore we collected water samples in three different events to see variations in pharmaceutical occurrences by flow conditions. The occurrence data were compared with hazard information to estimate the potential ecological risks of the target compounds.

2.

Materials and methods

2.1.

Target pharmaceuticals

We chose eleven pharmaceuticals based on their frequent occurrences in other countries and ease of analyses. In addition, production amount in Korea was derived from Korea Pharmaceutical Manufacturers Association (2003) and employed for selection of target compounds. Cimetidine was chosen because this compound was ranked 6th in production amount in 2003 (Park, 2006). The target pharmaceuticals that were measured in the present study include acetaminophen, caffeine, carbamazepine, cimetidine, diltiazem, and five sulfonamide antibiotics, i.e., sulfamethoxazole, sulfachlorpyridazine, sulfathiazole, sulfamethazine, and sulfadimethoxine. Trimethoprim was also added because this antibiotic is commonly used with other sulfonamide antibiotics (López-Martínez et al., 2002).

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All pharmaceutical compounds were purchased from Sigma Aldrich (St. Louis, MO, USA). The structures and chemical formulas are shown in Table 1. Atrazine-d5 (C8H14ClN5-d5) was used as an internal standard. All the reagent and extraction solvent were an HPLC grade. Standard stock solutions were prepared with methanol (1 g/L), and were used for making standard solutions. Stock solutions were kept air-tight in a dark cooling room before use, but generally used immediately after preparation.

2.2.

Sampling and sample preparation

The mainstream Han River was selected as study area. As shown in Fig. 1, four municipal STPs within the Seoul city boundary, i.e., JungRang, TanCheon, NanJi, and SeoNam STPs, and four locations in mainstream Han River, i.e., JamSil, HanNam, MaPo, and HaengJu, were chosen for sampling (Fig. 1). From STPs, both influent and effluents were grabsampled. The mainstream Han River was also grab-sampled in three events of April, June, and August, 2005 to reflect different flow conditions of the River. Precipitation recorded in Seoul for ten days before each sampling event for April, June, and August was approximately 25, 3–17, and 120–146 mL, respectively (http://www.kmg.go.kr, Korea Meteorological Administration website). Average effluent flows for TanCheon, JungRang, SeoNam, and NanJi STPs are 892, 1515, 1729, and 887 m3/d, and all the STPs employ secondary treatment with activated sludge (Ministry of Environment, 2006). In Table 2, removal efficiencies of conventional water pollution parameters like biochemical oxygen demand, chemical oxygen demand, suspended solids, total nitrogen, and total phosphorus are summarized for each STP. Water samples were collected in glass bottles (3 L) that were pre-rinsed several times with deionized water in the laboratory, and rinsed with sample water on site. Water chemistries such as pH and water temperature were measured at the time of sampling. Samples, wrapped with aluminum foil, were shipped on ice and delivered to the laboratory within 8 h. Samples were stored in air-tight condition in dark cold room until the analyses but no longer than 2 wks.

2.3.

Sample treatment and analyses

2.3.1.

Solid-phase extraction (SPE)

The samples were filtered with ashless filter paper (5C, 110 mm) to eliminate the suspended matter. The filtration flow rate was approximately 20 min/L, meanwhile that of STP influent samples which contained more suspended matter was about 1 h/L. Atrazine-d5 was added as an internal standard to all water samples. After adding 10 g of Na2EDTA to each sample, the samples were diluted with methanol to 1.25 mg/L of Na2EDTA. Na2EDTA was added to improve sample recovery of test pharmaceuticals. The solid phase extraction procedure was performed using a 1 g HLB cartridge (Waters-Millford, MA, USA). Two cartridges were employed for extraction of each 1 L sample. The cartridges were preconditioned with 6 mL of methanol and 6 mL of distilled water. The samples were introduced to the cartridges at flow rates of 2 and 5 mL/min for sewage influent and other water samples, respectively. After sample loading, the solid phase was

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Molecular weight, formula, and LogKow of the test pharmaceuticals were gleaned from available literatures. Where applicable, units are shown in parenthesis. NA: amount manufactured is not available. Except for caffeine, all the pharmaceuticals with ‘NA' NA’ signs are produced in amounts less than 7000 kg per annum (Kim et al., 2007). Abbreviations- ATP: acetaminophen, CAF: caffeine, CBZ: carbamazepine, CTD: cimetidine, DTZ: diltiazem, SMX: sulfamethoxazole, TMP: trimethoprim, SCP: sulfacholoropyridazine, STZ: sulfathiazole, SMZ: sulfamethazine, SDM: sulfadimethoxine.

Anti-biotic 122-11-2 310.3 C12H14N4O4S 0.63 NA Anti-biotic 57-68-1 277.3 C13H15N3O2S 0.89 NA Anti-biotic 723-46-6 253.3 C10H11N3O3S 0.89 61,272 Anti-epileptic 298-46-4 236.3 C15H12N2O 2.45 9155 Application CAS no. Molecular weight (g/mol) Formula LogKow Amount manufactured (kg)

Analgesic 103-90-2 151.2 C8H9NO2 0.46 1,068,921

Stimulant 58-08-2 194.2 C8H10N4O2 0.01 NA

Antacid 51481-61-9 252.3 C10H16N6S 0.40 132,809

Anti-hypertensive 42399-41-7 414.5 C22H26N2O4S 2.79 9071

Anti-biotic 738-70-5 290.3 C14H18N4O3 0.91 13,553

Anti-biotic 80-32-0 284.7 C10H9ClN4O2S 0.31 NA

Anti-biotic 72-14-0 255.3 C9H9N3O2S2 0.89 NA

SDM SMX CBZ CAF ATP

Table 1 – Overview of the target pharmaceutical compounds

CTD

DTZ

TMP

SCP

STZ

SMZ

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washed with 10 mL of distilled water. Cartridges were allowed to dry for 30 min to remove excess water. The pharmaceuticals retained were eluted with 10 mL of methanol. Then the methanol extracts were evaporated to 500 µL using a nitrogen evaporator (N-EVAPRTM 112, Organomation Associates, Berlin, MA, USA) and 750 µL of the mobile phase A solution was added. The extracts were stored in amber vials.

2.3.2.

Chemical analyses

All samples were analyzed using a Mass Selective ZQ 2000 quadrupole mass analyzer (Waters, Milford, MA, USA) equipped with an electrospray ionization source and operated in the positive ion mode. The LC separations were performed on the Waters 2690 system (Waters, Milford, MA, USA) consisting of a binary pump, a vacuum degasser, and autosampler, and a thermostated column. Analytical operation condition for LC/ ESI/MS is summarized in Table 3. Sample aliquots were injected to a 3 µm, 4.6 × 100 mm Phenominex Luna C8 column (Phenominex, Torance, CA, USA). The mobile phase used in the chromatographic separation consisted of a binary mixture (A:B = 90/10, v/v) of solvents A (aqueous 10 mM ammonium formate with 0.3% formic acid (90%) and methanol (10%)) and B (10 mM ammonium formate with 0.5 formic acid in methanol) at a flow rate of 0.25 mL/min. The column oven temperature was set to 30 °C. The MS analyses were carried out in positive mode-electrospray ionization (ESI). Nitrogen was used as the desolvation and nebulizing gas at flow rates of 419 and 64 L/h, respectively. The source and desolvation temperatures were 150 and 400 °C, respectively. In order to achieve sensitive and selective detection of the analytes, the choice of precursor and product ions, and the cone voltage were optimized separately for each pharmaceutical.

2.4.

Calculation of hazard quotients

Hazard quotients of test pharmaceuticals were calculated from the measured environmental concentrations divided by the predicted no effect concentrations (PNECs) of the test pharmaceuticals. The PNECs are derived from the effect levels of the most sensitive test organism, obtained from the literature. Per European Commission recommendation (EC, 2003) an assessment factor of 1000 was applied to the lowest median effective concentration (EC50) value to account for long-term subchronic effects on other sensitive ecological receptors.

3.

Results and discussion

3.1.

Pharmaceutical levels in surface water of Han River

The levels of the pharmaceuticals in Han River are summarized in Table 4. Compounds such as cimetidine, caffeine, acetaminophen, and sulfamethoxazole were generally detected frequently in high levels. It is noteworthy that the occurrence levels of these pharmaceuticals at JamSil, a location upstream of the STPs were either under detection or quite low. This observation strongly suggested the contribution of STP effluents as a source for these compounds in the mainstream Han River. Cimetidine, an antacid, was detected up to 1338 ng/L in surface water. Average occurrence level for cimetidine was

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Fig. 1 – Sampling locations in Han River, Korea. Surface water sampling locations are indicated with open circles. From sewage treatment plants, both influent and effluent samples were collected and the locations of STPs are indicated with closed circles.

715 ng/L in April, and 350 ng/L in June, 2005, however during the high flow condition, the frequency of detection decreased notably. Cimetidine is one of the least reported pharmaceutical in other countries. Kolpin et al. (2002) detected cimetidine in 8 out of 84 stream water samples with median detected level of 74 ng/L (maximum 580 ng/L). In 2004 report, Kolpin et al. (2004) showed the levels of cimetidine varied by flow conditions in the surface water near cities in Iowa, USA. During low flow season they detected cimetidine in 9 out of 30 samples with the maximum level of detection at 338 ng/L. Under normal flow condition this compound was barely detected. Annual production amount of this antacid in Korea was 133 ton in 2003 (Kim et al., 2007), while only 160 ton of cimetidine was used in USA annually (Versteeg et al., 2005). Considering that the population and area of US are approximately 6 and 94 folds greater than those of Korea, it is evident that the use of this compound Table 2 – Removal efficiencies for conventional water pollution parameters and treatment capacities of each sewage treatment plant in Seoul STP (treatment capacity in million m3/day)

Type of water

BOD COD

TanCheon (1.10)

Influent Effluent Influent Effluent Influent Effluent Influent Effluent

150.9 10.7 134 12.8 111.3 10.3 123.3 11.1

JungRang (1.71) Nanji (1.00) SeoNam (2.00)

74.3 11.5 68.7 12.4 57.3 10.3 65 10.8

SS

111.9 6.0 101.5 6.0 101.8 3.6 121.6 5.5

is relatively greater among Koreans than US people. The concentration of cimetidine in Han River is the highest level reported worldwide (Schwab et al., 2005), to our knowledge. Relatively high levels of caffeine were detected in Han River. Except for the upstream JamSil, concentrations of caffeine remained relatively constant at three downstream locations at around 200 ng/L. The caffeine level detected in Han River is about two folds greater than that of US streams (n = 84, median 81 ng/L) (Kolpin et al., 2002), and slightly greater than that observed in German River Elbe (n = 7, average 126 ng/L) (Weigel et al., 2004). The frequency of detection in Han River was 92%, which is comparable to the maximum detection frequency (83%) in Iowa rivers (Kolpin et al., 2004). Level of caffeine in Han River did not show a seasonal variation. Caffeine is not only

Table 3 – Analytical operation conditions for LC/ESI/MS for the determination of the test pharmaceuticals Activity MS

T-N T-P

32.5 20.1 32.3 19.1 32.1 15.4 29.8 19.5

3.4 1.0 3.5 1.4 2.6 1.4 3.0 1.7

Units are in mg/L unless otherwise noted. BOD: biochemical oxygen demand, COD: chemical oxygen demand, SS: suspended solids, T-N: total nitrogen, T-P: total phosphorus.

LC

Condition Type Ion mode Source temperature (°C) Desolvation temperature (°C) Cone gas flow (L/h) Desolvation gas flow (L/h) LM resolution HM resolution Multiplier Run time (min) Column Flow (mL/min) Stop time (min) Column temperature (°C) Sample temperature (°C)

SIR ES+ 147–150 400–395 64 419 17.4 15.5 650–648 35 Luna C8 column (3 μm, 100 × 4.6 mm) 0.250 40 30 20

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HaengJu

MaPo

HanNam

Unit in ng/L. Method detection limit was 5 ng/L for acetaminophen, carbamazepine, diltiazem, and sulfamethoxazole; 10 ng/L for caffeine, trimethoprim, and sulfadimethoxine; 20 ng/L for cimetidine and sulfamethazine; and 30 ng/L for sulfachlorpyridazine and sulfathiazole. Han River flows in the direction from JamSil to HaengJu.

b 10 b 10 b 10 b 10 b 10 b 10 10 b 10 b 10 13 b 10 b 10 b 10 15 b 10 b10 25 15 b 10 11 b 10 b 10 26 b 10 6 b5 b5 13 36 82 19 41 21 31 33 21 b5 b5 b5 b5 b5 b5 b5 b5 b5 13 b5 b5 b20 b20 b20 1338 459 78 38 365 b20 769 233 b20 b10 12 37 250 246 373 256 295 148 250 37 115 JamSil

April, 2005 June, 2005 August, 2005 April, 2005 June, 2005 August, 2005 April, 2005 June, 2005 August, 2005 April, 2005 June, 2005 August, 2005

b5 b5 b5 6 5 127 69 12 26 94 19 31

b5 6 b5 b5 11 36 b5 10 6 6 8 6

Diltiazem Cimetidine Carbamazepine Caffeine Acetaminophen Sampling event Location

Table 4 – Levels of the test pharmaceuticals in the surface water in Han River, Korea by sampling season

Sulfamethoxazole

Trimethoprim

Sulfadimethoxine

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used as stimulant in medicine but also used in various food and beverage. In US, usage of caffeine in medicine was 182 ton for 2002, and this amount was thought to represent about 0.8% of the total US caffeine use (Williams, 2005). As suggested by a big difference of detection between the upstream and downstream locations, the source of this product in Han River appears to be through STP effluents. Acetaminophen was detected at on average 12–61 ng/L by flow condition, however seasonal pattern in detection levels was not observed. The acetaminophen levels in surface water were relatively lower than those reported in North America or in Europe. In US streams Kolpin et al. (2002) detected this pain reliever in 20 out of 84 samples and reported a median level of 110 ng/L with the maximum detection of 10,000 ng/L. Sulfamethoxazole was detected in downstream STPs in a range between 13 and 82 ng/L, which were similar to those reported for German surface water (Hirsch et al., 1999). Sulfamethoxazole or its metabolites, e.g., acetyl-sulfamethoxazole, have been detected in US and UK surface water samples in higher levels (Hilton and Thomas, 2003; Kolpin et al., 2002). Carbamazepine was also frequently detected in downstream Han River, but the levels of detection were around 6–36 ng/L, which are in similar range to the levels reported for near harbor and in rivers of Ontario, Canada, i.e., 2–80 ng/L (Metcalfe et al., 2003). The rest of the test compounds were not frequently detected in the surface water, potentially because of efficient removal in STPs, fast degradation in the ambient environment, or their relatively limited use in human medicine that could lead to low STP influent concentrations.

3.2.

Pharmaceutical levels in STP effluents in Han River

Concentrations of the test pharmaceuticals in the STP effluents are summarized in Table 5. Pharmaceutical levels in the effluents were generally greater than those detected in the surface water, except for acetaminophen. This observation deserves an attention. Because acetaminophen is characterized by rapid degradation (Richardson and Bowron, 1985), the level of acetaminophen in the surface water was expected to be much lower than that of effluent. Acetaminophen was detected in only two effluent samples out of 12, and the level of detection was b10 ng/L. Han et al. (2006), however detected acetaminophen using gas chromatography-mass spectrometry in 12 out of 14 effluent samples with an average of 60 ng/L, in a study conducted for the STPs of four cities in Korea. This discrepancy may be in part explained by different STPs being studied and also could be explained by difference in analytical method being employed. Cimetidine was detected in the highest levels among the test pharmaceuticals in all effluent samples except one. The average concentration of cimetidine detected in the effluents was 5380 ng/L. Caffeine was detected in all effluent samples. The level of caffeine in the effluent was the highest in the low flow season, i.e., in June (average of 503 ng/L). Samples collected in high flow condition contained the lowest level of caffeine. Metcalfe et al. reported b30 ng/L caffeine in the three Ontario STP effluents, but in another STP, they observed on average 677 ng/L (n = 3) (Metcalfe et al., 2003). In the present study, sulfamethoxazole was present in the STP effluents at 85–319 ng/L. These levels are lower than those detected in Germany (on average 400 ng/L with the maximum of 2000 ng/L)

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(Hirsch et al., 1999) or in UK (acetyl-sulfamethoxazole in a range between 690 and 2200 ng/L) (Hilton and Thomas, 2003). Carbamazepine was detected in all effluent samples collected in June and August, 2005, at around 140 ng/L. These levels are quite similar to the levels (7–126 ng/L) reported for the Ontario STPs effluent (Metcalfe et al., 2003).

production, acetaminophen is the highest production pharmaceutical among the test pharmaceuticals, followed by carbamazepine, cimetidine, diltiazem, sulfamethoxazole, and trimethoprom (Kim et al., 2007). The occurrence levels in the influents followed the same order.

3.4. 3.3.

Ecological risk of pharmaceuticals in Han River

Pharmaceutical levels in STPs

As shown in Table 5, among the test pharmaceuticals, acetaminophen, caffeine, and cimetidine were detected in the highest levels in the STP influents. In the influent samples, acetaminophen was detected on average 27.1 µg/L with the maximum at 56.9 µg/L. The level of acetaminophen in STP influents did not vary by season. Caffeine was also detected in influents in a range between 9.8 and 36.9 µg/L. As indicated in Fig. 2, however, the levels of acetaminophen and caffeine that were detected in STP effluents notably decreased. In contrast, decrease of cimetidine and sulfamethoxazole was relatively low in STP effluents. Since cimetidine was detected in both STP influents and effluents in high amount (2.6–17.7 µg/L with 100% detection rate in influents, and 3.1–7.8 µg/L with 92% detection rate in effluents), STP removal efficiency for this compound needs to be improved. The influent concentrations of pharmaceuticals tend to correlate with the annual production amount in Korea. Based on the information available for the amount of

The hazard quotient (HQ) for each test pharmaceutical was derived based on the measured levels of pharmaceuticals in the surface water, Han River. HQ implies potential chances of ecological impact, from which one can determine whether further evaluation may be required. The 95% upper confidence limits (UCLs) of the mean were calculated according to the appropriate distribution of the data, and were utilized to reflect more conservative exposure scenario. As indicated in Table 6, all the test pharmaceuticals resulted in HQs less than one, therefore suggesting that their tendency for potential environmental impact may be low. Kim et al. (2007) suggested that the HQs for sulfamethoxazole and acetaminophen should be greater than one, based on the predicted environmental concentrations estimated from the amount of manufacture in Korea. Compared to the predicted level, however, environmental levels of acetaminophen, for example, were approximately 500 folds lower. The reason for this discrepancy may be found from the high metabolic rate (Sweetman, 2002) and

Table 5 – Levels of the test pharmaceuticals in influent and effluent samples of the four sewage treatment plants in Han River, Korea by sampling season STP

Sampling event

TanCheon April, 2005 June, 2005 August, 2005 JungRang April, 2005 June, 2005 August, 2005 NanJi April, 2005 June, 2005 August, 2005 SeoNam April, 2005 June, 2005 August, 2005

Acetaminophen

Carbamazepine

Cimetidine

Diltiazem

Influent

Effluent

Influent

Effluent

Influent

Effluent

Influent

Effluent

Influent

Effluent

56,944 34,021 18,729 22,325 48,097 25,461 22,706 13,046 18,286 28,756 23,407 13,284

b5 b5 b5 b5 b5 b5 b5 9 b5 6 b5 b5

36,856 30,615 18,405 9750 33,821 21,070 18,706 14,313 24,436 20,750 29,491 25,758

688 873 148 19 508 135 75 431 33 169 201 53

13 201 203 b5 451 242 b5 156 223 6 283 29

6 115 108 b5 159 103 b5 155 120 6 141 195

9088 16,925 4982 10,081 17,651 2628 4669 5617 2165 5663 14,100 2968

7119 5182 5322 5381 5732 3272 3100 6,138 b20 7763 5654 4520

5 b5 b5 13 b5 b5 19 b5 b5 6 b5 b5

13 b5 b5 6 b5 b5 b5 b5 b5 b5 b5 b5

Sulfamethoxazole

TanCheon April, 2005 June, 2005 August, 2005 JungRang April, 2005 June, 2005 August, 2005 NanJi April, 2005 June, 2005 August, 2005 SeoNam April, 2005 June, 2005 August, 2005

Caffeine

Trimethoprim

Influent

Effluent

Influent

381 316 984 300 611 660 156 221 849 263 652 877

63 180 193 25 185 275 31 148 316 219 185 492

275 135 45 81 496 84 19 97 b 10 125 401 104

Effluent b10 87 b10 13 119 b10 b10 108 b10 31 110 174

Sulfachloropyridazine Influent b 30 b30 206 b30 b30 447 b30 b30 476 b30 b30 340

Effluent b 30 b 30 149 b 30 b 30 135 125 b 30 b 30 b 30 b 30 50

Sulfathiazole Influent b30 b30 b30 531 b30 b30 450 b30 b30 b30 b30 b30

Effluent b30 b30 b30 b30 b30 b30 b30 b30 b30 b30 b30 b30

Sulfadimethoxine Influent

Effluent

169 b 10 b 10 31 213 b 10 100 30 b 10 31 b 10 b 10

13 b 10 b 10 13 70 b 10 b 10 21 b 10 b 10 b 10 b 10

Unit in ng/L. Method detection limit was 5 ng/L for acetaminophen, carbamazepine, diltiazem, and sulfamethoxazole; 10 ng/L for caffeine, trimethoprim, and sulfadimethoxine; 20 ng/L for cimetidine and sulfamethazine; and 30 ng/L for sulfachlorpyridazine and sulfathiazole.

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Fig. 2 – Levels of test pharmaceuticals in the influent and effluent of four STPs in Han River, Korea, by sampling event. Black bars indicate levels in the influent, and gray bars indicate those detected in the effluent samples. Error bars show maximum levels detected. ATP: acetaminophen, CAF: caffeine, CBZ: carbamazepine, CTD: cimetidine, DTZ: diltiazem, SMX: sulfamethoxazole, TMP: trimethoprim, SCP: sulfachloropyridazine, STZ: sulfathiazole, SDM: sulfadimethoxine.

rapid degradation characteristics (Richardson and Bowron, 1985) of this pharmaceutical. The HQs calculated for test pharmaceuticals in Han River are not different from other studies which also suggested low

chance of ecological impact for many pharmaceuticals based on acute toxicity tests (Choi et al., 2008; Fent et al., 2006; Han et al., 2006). It may not be prudent, however, to preclude these physiologically active compounds from further study. The use of

Table 6 – Comparison of measured surface water concentrations of select pharmaceuticals with predicted no effect concentrations Substances

Toxicity PNEC (μg/L)

Acetaminophen Caffeine Carbamazepine Cimetidine Diltiazem Sulfamethoxazole Trimethoprim Sulfachlorpyridazine Sulfathiazole Sulfamethazine Sulfadimethoxine

9.2 151 31.6 271.3 8.2 0.146 120.7 26.4 85.4 158.8 204.5

Test endpoint 48 96 96 96 96 96 96 15 96 96 96

h D. magna immobility h P. promelas mortality h C. meneghiniana growth h D. magna immobility h D. magna immobility h S. capricornutum growth h D. magna immobility min V. fischeri florescence h D. magna immobility h D. magna immobility h D. magna immobility

Measured concentration (μg/L)

HQ based on

Reference

Mean

95% UCL

Distr

Mean concentration

95% UCL

Kuhn et al. (1989) Russom et al. (1997) Ferrari et al. (2004) Kim et al. (2007) Kim et al. (2007) Ferrari et al. (2004) Kim et al. (2007) Kim et al. (2007) Kim et al. (2007) Kim et al. (2007) Kim et al. (2007)

0.0348 0.1687 0.0078 0.274 NA 0.0257 0.0106 NA NA NA NA

0.0639 0.2338 0.0117 0.464 0.013 0.0371 0.0142 NA NA NA 0.013

LN N LN BS NA N BS NA NA NA NA

3.8E– 03 1.1E– 03 2.5E– 04 1.0E– 03 NA 1.8E– 01 8.8E– 05 NA NA NA NA

6.9E– 03 1.5E– 03 3.7E– 04 1.7E– 03 1.6E– 03 2.5E– 01 1.2E– 04 NA NA NA 6.4E– 05

95%UCL = 95% of upper confidence limit of the mean. LN = log normal distribution. N = normal distribution. BS = bootstrap result because of non-normal distribution. NA = not applicable.

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standard acute ecotoxicity data, which were the basis for derivation of PNECs in this study, may not be appropriate for assessing ecological risks of pharmaceuticals in the environment. There is a need for targeted ecotoxicological studies focusing on chronic subtle but ecologically meaningful environmental effects of pharmaceuticals and their metabolites individually or in mixture to fully understand potential impacts of these pharmaceuticals in the environment (Fent et al., 2006). Prioritizing future research efforts based on potential ecological risks is also important considering number of pharmaceuticals in use and limited socioeconomic resources (Ankley et al., 2007; Kostich and Lazorchak, 2008).

4.

Conclusions

In the current study, we collected water samples from STPs and mainstream Han River, Seoul, Korea, in three events representing medium, low, and high flow conditions, and analyzed for eleven major human pharmaceuticals using LC-MS-ESI. In the STP influents, acetaminophen (on average 27,089 ng/L), caffeine (23,664 ng/L), cimetidine (8045 ng/L), and sulfamethoxazole (523 ng/L) were detected in relatively higher levels. The pharmaceutical concentrations in the STP influents correlated well with the production amount of the pharmaceuticals in Korea. STP removal efficiencies appeared to be good for acetaminophen and caffeine, while relatively low for cimetidine. It was evident that the STPs were important source of discharge of these compounds into Han River: Surface water samples collected from upstream STPs generally were under detection levels or very low levels compared to the downstream samples. In the surface water, pharmaceuticals with higher occurrence levels include cimetidine (281 ng/L), caffeine (268.7 ng/L), acetaminophen (34.8 ng/L), and sulfamethoxazole (26.9 ng/L). The cimetidine level in the ambient Han River was the highest among the reported levels worldwide. The HQs calculated for all the test pharmaceuticals were less than one, suggesting that their potential for ecological impact may be low. It may be too early, however, to preclude these physiologically active compounds from further study because very little is known about the subtle but ecologically meaningful effects of this group of chemicals from long-term low-dose exposure.

Acknowledgement This work was supported by the Korea Research Foundation Grant (2005KRF-D00177).

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