Pharmaceuticals residues in selected tropical surface water bodies from Selangor (Malaysia): Occurrence and potential risk assessments

Science of the Total Environment 642 (2018) 230–240

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Pharmaceuticals residues in selected tropical surface water bodies from Selangor (Malaysia): Occurrence and potential risk assessments Sarva Mangala Praveena a,⁎, Siti Norashikin Mohamad Shaifuddin b, Syazwani Sukiman a, Fauzan Adzima Mohd Nasir a, Zanjabila Hanafi a, Norizah Kamarudin c, Tengku Hanidza Tengku Ismail d, Ahmad Zaharin Aris d a

Department of Environmental and Occupational Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia Department of Environmental Health and Safety, Faculty of Health Sciences, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia c Department of Forest Management, Faculty of Forestry, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia d Department of Environmental Sciences, Faculty of Environmental Studies, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia b

H I G H L I G H T S

G R A P H I C A L

A B S T R A C T

• Pharmaceutical residues have created new issues to human health and environment. • Ciprofloxacin concentrations were the highest in all the river samples. • Human risk assessment showed low health risk. • Ecotoxicological risk assessment indicated moderate risks.

a r t i c l e

i n f o

Article history: Received 26 March 2018 Received in revised form 24 May 2018 Accepted 5 June 2018 Available online xxxx Keywords: Pharmaceuticals Surface water ELISA Occurrence Potential risks

a b s t r a c t This study investigated the occurrence of nine pharmaceuticals (amoxicillin, caffeine, chloramphenicol, ciprofloxacin, dexamethasone, diclofenac, nitrofurazone, sulfamethoxazole, and triclosan) and to evaluate potential risks (human health and ecotoxicological) in Lui, Gombak and Selangor (Malaysia) rivers using commercial competitive Enzyme-Linked Immunosorbent Assay (ELISA) kit assays. Physicochemical properties of these rivers showed the surface samples belong to Class II of Malaysian National Water Quality Standards which requires conventional treatment before consumption. All the pharmaceuticals were detected in all three rivers except for triclosan, dexamethasone and diclofenac which were not detected in few of sampling locations in these three rivers. Highest pharmaceutical concentrations were detected in Gombak river in line of being as one of the most polluted rivers in Malaysia. Ciprofloxacin concentrations were detected in all the sampling locations with the highest at 299.88 ng/L. While triclosan, dexamethasone and diclofenac concentrations were not detected in a few of sampling locations in these three rivers. All these nine pharmaceuticals were within the levels reported previously in literature. Pharmaceutical production, wastewater treatment technologies and treated sewage effluent were found as the potential sources which can be related with pharmaceuticals occurrence in surface water samples. Potential human risk assessment showed low health risk except for ciprofloxacin and dexamethasone. Instead, ecotoxicological risk assessment indicated moderate risks were present for these rivers. Nevertheless, results confirmation using instrumental techniques is needed for higher degree of

⁎ Corresponding author at: Department of Environmental and Occupational Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia. E-mail address: [email protected] (S.M. Praveena).

https://doi.org/10.1016/j.scitotenv.2018.06.058 0048-9697/© 2018 Elsevier B.V. All rights reserved.

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specificity. It is crucial to continuously monitor the surface water bodies for pharmaceuticals using a costeffective prioritisation approach to assess sensitive sub-populations risk. © 2018 Elsevier B.V. All rights reserved.

1. Introduction Emerging contaminant such as pharmaceuticals has generated new issues and risk implications on water quality (X. Liu et al., 2017; Zhou et al., 2017). Generally, pharmaceuticals released into environment from sewage treatment plant effluent, improper disposal of expired pharmaceutical products, hospital waste, domestic sewage, manufacturing plants waste, runoffs from intensive agricultural operations, and excreta from both human and animals (Ahmed and Kasraian, 2002; Celiz et al., 2009; Jiskra and Hollender, 2013; Khetan and Collins, 2007; Patneedi and Prasadu, 2015; Puckowski et al., 2016; Sirés and Brillas, 2012; Wu et al., 2017). The continuous release of pharmaceutical residues into environment will be ultimately distributed to the aquatic environment and groundwater system via leaching and surface runoff. Pharmaceuticals are known to be stable with low biodegradation and high lipophilicity which tend to bioaccumulate in biological organisms and persistent in the environment. Pharmaceutical residues may also affect physiological functions in biological systems considering that they are potential as endocrine disrupters. Hence, the human health as well as the environment have been at risk mainly due to the pharmaceutical exposure, especially in the aquatic environment that receives treated wastewater effluent which will then be utilised as raw water for drinking water (Gavrilescu et al., 2015; Wu et al., 2015; Zeng et al., 2015). In relation to this, it should be acknowledged that low concentrations of pharmaceutical in the environment at micro-pollutant level give challenge to identification and quantification (Puckowski et al., 2016). Numerous detection methods such as the instrumental method can be applied in pharmaceutical quantification namely highperformance liquid chromatography (HPLC) and gas chromatography mass spectrometry (GCMS). However, there are several disadvantages to these methods such as high detection limit, high operating costs, high usage of chemicals, chemical waste disposal, and clean up involving large number of sample despite the fact that it has been widely applied in pharmaceutical detection involving environmental samples (Białk-Bielińska et al., 2016; Huo et al., 2007; Mohamed, 2015). On the other hand, non-instrumental methods via immunoassay technique are found to provide an alternative methodology that requires the use of specific combinations of antigen and antibody, which is deemed highly sensitive in pharmaceutical determination involving complex environmental matrixes such as surface and wastewater samples. Commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kits that adopt the immunoassay technique has been developed based on the selectivity and affinity of an antibody for its antigen which need to be performed based on certain validation steps. Currently, ELISA kits are used as a quantitative analysis tool in detecting pollutants that are not detected by other instruments such as LC-MS by broad crossreactivity of antibodies (Shelver and Smith, 2003; Aga et al., 2005; Bradley et al., 2014). ELISA kits are gaining ground because it involves simple sample preparation steps, reasonable cost, small sample volume usage, quick analysis time and the results are highly correlated with the results obtained from HPLC or GCMS (Fang et al., 2016; Huo et al., 2007). It should be noted that immunoassay technique is faced with several matrix effects, but it is often minimized by dilution or adjusting the medium in standard curve construction (Shelver et al., 2008). Meanwhile, Calisto et al. (2011) emphasized that ELISA kits are suitable for screening purposes in order to identify contaminated areas but instrumental techniques (e.g. GCMS, LC–MS/MS) are required to further analyse samples from specific areas. Previous studies have shown the capability of commercial ELISA kits for pollutant quantification in various

environmental samples, namely surface water, wastewater, and groundwater (Amitarani et al., 2002; Huo et al., 2007; Shelver et al., 2008; Calisto et al., 2011; Bahlmann et al., 2012; Bradley et al., 2014). Consumption of human pharmaceuticals especially to treat and control disease related to obesity is at the rise considering Malaysia has the highest number of overweight and obese people in Asia countries (Chan et al., 2017). In addition, veterinary pharmaceuticals usage to prevent, treat, and control illness as well as to promote animal growth in Malaysia is also increasing (Zakaria, 2017). In most cases, continuous exposure of pharmaceutical residue that are released in the form of excreta from human and animals, sewage treatment plant effluents, and improper pharmaceutical products disposal will eventually end up in aquatic environment and groundwater system. The raw water supply from aquatic environment which contains pharmaceuticals will then be treated and supplied as drinking water to residential areas. Moreover, human can be exposed to pharmaceutical residues in drinking water due to the limited capability of conventional drinking treatment systems. Contrasting to other developing countries in Asia, very limited data is available on environmental presence of pharmaceuticals in Malaysian surface water. Up to the present time, only a few of published studies reported the pharmaceutical concentrations found in surface waters of Malaysia (Al-Odaini et al., 2010; Al-Qaim et al., 2014). Findings from indicated that the presence of pharmaceutical residues in drinking water is due to the incompetency of conventional drinking water treatment plants in Malaysia in removing pharmaceuticals. Most of the published studies, however were more focused on pharmaceuticals by putting a very little emphasis on the risks associated with pharmaceutical residues present in the surface water samples. Apart from the high usage of pharmaceuticals in human health and animal livestock in Malaysia, pharmaceutical residue present in the surface water environment is crucial to be investigated for the purpose of filling the knowledge gap on environmental and human health risks associated with tropical climate of Southeast Asia. Moreover, quantitative findings including environmental and human health risks are vital in order to assess public health exposure, especially in the areas where surface water is used as the source of raw water specifically referring to people who are living downstream. The present study aims to demonstrate the potential and ability of ELISA kits in pharmaceutical screening for the purpose of providing new insights on the contamination status, particularly involving surface water. Lack of studies in Malaysia clearly reflects the need to investigate the physicochemical properties and pharmaceuticals (amoxicillin, caffeine, chloramphenicol, ciprofloxacin, dexamethasone, diclofenac, nitrofurazone, sulfamethoxazole, and triclosan) occurrence in the surface water samples obtained from Lui, Gombak, and Selangor rivers. Moreover, another purpose of this study was to assess human health and ecotoxicological risks associated with pharmaceutical residues pollution in the river waters investigated in this study. The present study acts as a pioneer in providing the quantitative findings of pharmaceutical pollution through ELISA kit assay utilization, including its risks to human health and environment. 2. Materials and method 2.1. Study area and surface water sampling Fig. 1 shows the sampling locations involving surface water samples collected from Lui, Selangor, and Gombak rivers. Supplementary 1 also provides detailed information of sampling locations from Lui, Selangor, and Gombak rivers. Lui and Selangor rivers are respectively located in

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Fig. 1. Surface water sampling locations involving Lui, Selangor and Gombak rivers.

the districts of Hulu Langat and Hulu Selangor, in the state of Selangor. The Gombak River is situated in the Federal Territory of Kuala Lumpur (Malaysia). These rivers receive high amount of rainfall due to its location in the tropical zone as well as the contribution of monsoons that occur during November–February and May–August every year (Nawaz et al., 2016). The Lui River is located on the upstream of Langat River with an area of 68.1 km2, including the basin length of 11.5 km with an average altitude of 354 m. It is important to note that this river serves as the main water catchment area that provides raw water supply for a total of 1.2 million people within the basin (Nawaz et al., 2016). Moreover, Lui River is located on a steep slope of 35% with high rain intensity especially during monsoon seasons. This river is also exposed to various anthropogenic activities due to the urbanization process, population settlements, and agricultural activities in the vicinity (Atan et al., 2017; Nawaz et al., 2016). The Selangor River is one of the important rivers that is located in the northern part of Selangor state (Malaysia), with a total length of about 60 km with an area of 1820 km2 (Kawasaki et al., 2016). The oil palm and rubber plantations constitute the major use of the land, including 10 pharmaceutical manufacturers located in Hulu Selangor along the Selangor river. Report by World Wildlife Fund (Malaysia) has identified major pollution sources along the Selangor river which include runoff from agriculture land, untreated industrial effluent, and domestic sewage (Ong, 2001). According to the Malaysian Water Academy (2017), Selangor River is the major water

supply of drinking water for the surrounding areas including Bukit Badong and Rantau Panjang, and a source of raw water intake for Sungai Tinggi Dam. The Gombak River is a tributary in the upper part of the Klang River which flows through Selangor and Kuala Lumpur with the length of 12 km and an area of 123.3 km2. The Gombak River is categorized as the most polluted tributary of Klang River due to industrial and domestic effluent discharges. This river has been affected by massive developmental schemes that have been implemented from 1995 to 2020. It is inevitable that the surface water quality has been degraded in parallel to the increase in the population density and urbanization rates that cover multiple townships located along this river (Faris, 2012; Ismail, 2011). For this study, surface water samples were collected in duplicates with pre-cleaned amber glass bottles. The amber bottles were rinsed twice with surface water prior to collecting the samples at a depth of 0.5 m below the water surface level. The amber glass bottles were rinsed with acid wash and methanol prior to surface water sampling, followed by oven drying to reduce interference possibilities (Guedes-Alonso et al., 2013). The surface samples were analysed in the next 24 h. The physico-chemical properties of surface water were measured in-situ during the sampling. Thermo Scientific pH 450 m was used to measure pH and temperature, while CyberScan COND 600 Series Conductivity meter was employed to measure conductivity, total dissolved solid, and oxidation/reduction potential, followed by the detection of turbidity using HACH 2100P Portable Turbidimeter in all the surface water samples.

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2.2. Sample extraction and ELISA kit analysis All surface water samples (100 mL) were filtered through a 0.45 μm Whatman membrane filter in order to remove impurities prior to sample extraction, followed by acidifying to pH 3 using sulphuric acid as suggested by Grabic et al. (2012). The filtered water samples were required to undergo solid phase extraction using HLB Oasis SPE cartridges containing 0.20 g of Oasis® HLB (30 μm) solid-phase material (Waters, Manchester, UK) which is packed into 6 mL cartridges. The cartridges were preconditioned with 5 mL methanol and 5 mL ultrapure water, whereas the samples were aspirated through SPE cartridges at the rate of approximately 5 mL/min. Next, the cartridges were washed using 5 mL ultrapure water containing 5% of methanol at a flow rate of approximately 1 mL/min and dried under vacuum for b1 min after the extraction of the samples. The cartridges were then extracted by eluting using two successive 2.5 mL aliquots of methanol, followed by 3 mL aliquots of ethyl acetate. In the final step of this process, the extracts were then evaporated to 2 mL under a gentle air stream and then analysed using ELISA kits. In the present study, pharmaceutical determination in extracted surface water samples were performed using commercial competitive ELISA kit. These selected commercial competitive ELISA kits offer quality of antibody reagents, which exhibits high degree of sensitivity and specificity for each specific pharmaceutical with simple and easily adapted analysis steps. The surface samples as well as the standards provided by the manufacturer were pipetted at a predetermined volume into different wells to enable it to be pre-coated with specific antibody for selected pharmaceutical. The wells were then incubated in the dark at room temperature for a certain period of time after adding the enzyme conjugate. The content in the wells were discarded, followed by three to four cycle washing step using wash solution. A predetermined volume of buffer substrate solution was added into each well and the plate was re-incubated in the dark at room temperature for a certain period of time. Finally, all the enzyme reaction in the plates was stopped by adding stop buffer containing sulphuric acid into each well after the incubation period for all the tested pharmaceuticals ended. The plates were read immediately after adding the stop buffer on a microplate spectrophotometer (Dynex MRX Revelation and Revelation TC 96 Well Microplate Reader) at 450 nm wavelength. The data was analysed using the Revelation Software (Version 4.25). 2.3. Quality assurance/quality control All the chemicals utilised in this study were of high purity purchased from J. T. Baker, Inc. The ultra-pure water was used in the preparation of all the solutions obtained from the purification of demineralized water in a Milli-Q system. All glasswares were cleaned by soaking in nitric acid and methanol overnight, washed with distilled water and dried in the oven. In this case, the reagent and procedural blanks for each sample were processed and handled similar to actual surface water samples. All surface water samples were analysed in duplicates. Environmental samples contain a variety of matrix constituents; hence, it is worrying that their complexity can eventually affect the performance of antibody or enzyme in ELISA kit analysis (Patrícia et al., 2013; Schneider et al., 2005). Water salinity has been found to be a potential interfering matrix effects in ELISA kit analysis (Calisto et al., 2011; Silva et al., 2013). However, ELISA kit performance in this study is not influenced by matrix effects considering that the water salinity is low (Calisto et al., 2011; Silva et al., 2013). A validation method was performed based on the criteria set by European Commission Decision 2002/657/EC by further focusing the linearity and recovery (European Commission, 2003). In this experiment, the linearity for each targeted pharmaceutical was constructed using the standards provided by ELISA kits at six levels (25–50,000 ng/ L). As presented in Supplementary 2, the calibration curves manage to be obtained through linear regression analysis of standard solutions which is carried out by plotting absorbance against

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pharmaceuticals concentration coefficient correlation values of N0.94. Recoveries for each pharmaceutical were also evaluated at low (0.025 ng/L) and high concentration (50 ng/L) of water samples, which is found to be in the range of 44.98% to 161.96%. According to the European Community (2015), the recovery rates within 45–160% are acceptable as long as it is within the working range of ELISA kits. 2.4. Data analysis and potential risks (human health and ecotoxicological) assessment The statistical analysis for the present study was performed using Statistical Package for the Social Sciences (SPSS), version 23.0. The descriptive statistics is used in to obtain the mean, minimum, maximum, and standard deviation values of the targeted pharmaceuticals. The human health risk assessment was performed to determine the potential risks of multiple pharmaceuticals in surface water, especially to the exposed population which is composed of adults and children. The hazard quotient of human health risk (HQHH) was assessed via human health risk assessment approach (Eq. (1)) for both adults and children, which was similarly applied by Gaffney et al. (2015) and Lin et al. (2016). Table 1 summarizes the values used in Eq. (2). In this study, the acceptable daily intake (ADI) values of targeted pharmaceuticals were adapted from several sources (e.g. European Medicines Agency, 2003; Schwab et al., 2005; Joint FAO/WHO Expert Committee on and Additives, 2006; GCC Standardization Organization, 2009; Lozano and Trujillo, 2012; Shanmugam et al., 2014; Australian Pesticide and Veterinary Medicines Authority, 2017) based on the lowest toxicological effects. HQHH ¼ Cs=DWEL

1

DWEL ¼ ðADI  BW  HQ Þ=ðDWI  AB  FOEÞ

2

where: Cs corresponds to pharmaceutical compound concentration found in surface water, DWEL is Drinking Water Equivalent Level, ADI is the acceptable daily intake (mg/kg day), BW is body weight for adults and children (kg), HQ is the Hazard Quotient, DWI is the Drinking Water Intake (L/day), AB is the gastrointestinal absorption rate, EF is exposure frequency (Table 1). However, the ADI values were absent for chloramphenicol and nitrofurazone, thus preventing the HQ for both pharmaceuticals to be computed. Nevertheless, it is important to note that Hazard Quotient value of b1 indicates an insignificant risk to human health, while HQ N1 suggest a likelihood of adverse effects to adults and children. The ecotoxicological risk assessment was applied to describe the toxicity level of different living organisms in surface water using hazard quotient (RQ) as shown in Eq. (3) that was previously applied by Lin et al. (2016) and Archana et al. (2017). The ecotoxicological risks were classified based on the criteria suggested by Stockholm County Council (2014). Hence, it should be noted that the RQ value b 0.1 indicates that the risk is insignificant, the RQ value between 0.1 and 1.0 is considered low, and the RQ value between 1 and 10 is considered moderate. The RQ value N 10 indicates that high potential ecological risk is suspected. RQ ¼ MEC=PNEC

3

where: MEC refers to pharmaceutical compound concentration found in surface water; PNEC corresponds to the Predicted No-Effect Concentrations (PNECs) referring to the toxicity reference value derived from literature (Supplementary 3).

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Table 1 Variable values used in potential human risk assessment. Symbols

Variables

Value

References

Cs ADI

Pharmaceuticals concentration in river Acceptable daily intake

Mean of pharmaceuticals concentration From literature

This study European Medicines Agency (2003), Schwab et al. (2005), Joint FAO/WHO Expert Committee on and Additives (2006), GCC Standardization Organization (2009), Lozano and Trujillo (2012); Shanmugam et al. (2014); Australian Pesticide and Veterinary Medicines Authority (2017)

BW

Body weight Adults Children Hazard Quotient Drinking water ingestion rate Gastrointestinal absorption rate Frequency Of exposure

61.57 kg 19.5 kg 1 1.996 L/day 1 365 days/365 days = 1

Ab Razak et al. (2015) Praveena and Omar (2017) Gaffney et al. (2015) Ab Razak et al. (2015) Gaffney et al. (2015) Gaffney et al. (2015)

HQ DWI AB FOE

3. Result and discussion 3.1. Physicochemical characteristics and pharmaceuticals concentration in surface water of Lui, Gombak, and Selangor rivers Table 2 summarizes the physicochemical characteristics of surface water at each sampling location in Lui, Selangor, and Gombak rivers. The pH values of the water are ranged from 6.15 to 7.01 with the temperature between 24.50 and 27.30 °C. Meanwhile, the total dissolved solid and turbidity are shown to be ranging from 36.11 to 304.33 ppm and turbidity 4.42 to 86.07 NTU, respectively. The water conductivity and oxidation/reduction potential values are recorded to be in the range of 36.89 to 310.53 μS and −30.17 to 69.06 mV, respectively. In general, the physicochemical characteristics of these surface water samples are classified as Class II under Malaysian National Water Quality Standards, which requires the water supply to be treated conventionally to ensure that it is safe for body contact (Zainudin, 2010). Table 3 shows pharmaceuticals concentrations found in Lui, Gombak, and Selangor rivers. Catchments in Gombak river recorded higher concentrations for most of the pharmaceuticals, compared to Lui and Selngor rivers. This is in agreement with the fact that Gombak river is one of the most polluted rivers in Malaysia primarily due to the effluents from industries, overflows from broken septic tanks pipelines, inefficient drainage system, domestic waste, and wastewater treatment effluents (Moorthy and Jeyabalan, 2011; Faris, 2012; Ismail

et al., 2014). In addition, there are several private hospitals, clinics, and medical analysis laboratories located near the Gombak River. It is undeniable that hospitals in Malaysia have developed their own wastewater/sewage treatment plants, while others hire subcontractors such as Radicare and Pantai Medivest to treat their waste. Diclofenac (non-steroidal anti-inflammatory drugs) was detected found in all the sampling locations of these three rivers. Mean diclofenac concentrations were recorded as 2.76 ng/L, 4.84 ng/L, and 4.30 ng/L in the Lui, Gombak, and Selangor rivers. This is not surprising considering that diclofenac is ranked as the top three drugs that are most commonly used in Malaysia in 2010 (Ministry of Health Malaysia, 2014). According to Khairuddin et al. (2017), non-steroidal anti-inflammatory drugs are the most inexpensive drug, which are commonly available in retail pharmacies and easily accessible by patients. Hence, this type of drug is often used as self-medication, but more likely can be abused and misused. The mean concentrations of ciprofloxacin were recorded as 112.40 ng/L, 267.20 ng/L, and 198.91 ng/L, respectively in the Lui, Gombak, and Selangor rivers. Ciprofloxacin has been listed as one of the five common antibacterial agents used in 2009 and 2010 that is utilised to treat upper respiratory tract infection (URTI) and urinary tract infection (UTI) (Ministry of Health Malaysia, 2014; Teng et al., 2011). Similarly, URTI has been reported as the most common infection cases (51%) in Malaysian hospitals, thus requiring the prescription of antibiotics and ciprofloxacin due to their excellent efficacy across a wide spectrum of infection with minimal side effects (Teng et al.,

Table 2 Physico-chemical properties of water samples collected from Lui, Gombak and Selangor rivers (n = 18). Location

Physico-chemical properties of river water samples pH

Temperature (°C)

Conductivity (μS)

Total dissolved solid (ppm)

Oxidation/reduction potential (mV)

Turbidity (NTU)

Lui River L1 L2 L3 L4 L5 L6

6.15 6.57 6.59 6.71 6.67 6.58

25.27 24.60 24.50 24.93 24.80 24.90

36.89 41.66 51.30 126.00 39.53 41.58

36.11 41.33 50.14 124.37 38.77 40.52

22.40 −2.03 −0.37 −11.67 −8.90 −3.20

4.42 7.94 8.05 8.57 9.54 10.10

Gombak River G1 G2 G3 G4 G5 G6

6.99 7.01 6.95 6.91 6.92 6.93

27.30 26.63 27.17 27.07 27.20 27.30

227.73 295.33 283.80 274.90 310.53 297.93

242.93 271.73 276.87 281.60 304.33 298.10

−29.03 −30.17 −27.30 −24.50 −24.87 −25.47

13.47 12.17 11.87 32.32 30.47 30.60

Selangor River S1 S2 S3 S4 S5 S6

6.73 5.75 5.56 6.04 6.60 6.47

26.70 25.90 25.90 27.23 27.00 26.93

60.35 54.74 69.06 66.96 51.30 66.88

58.99 53.44 70.32 66.36 48.29 69.08

0.90 50.43 69.06 32.53 9.33 8.83

56.50 84.57 60.13 82.50 86.07 79.27

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Table 3 Mean concentration of pharmaceuticals in the surface water samples. Locations

Concentration of compounds (ng/L) Amoxicillin

Caffeine

Chloramphenicol

Ciprofloxacin

Dexamethasone

Diclofenac

Nitrofurazone

Sulfamethoxazole

Triclosan

4.44 1.01 1.10 1.23 0.58 ND 1.39 ND 4.44 1.56

32.47 26.86 29.18 32.77 30.73 28.74 30.12 26.86 32.77 2.30

15.52 16.69 16.11 15.80 17.30 18.03 16.57 15.52 18.03 0.96

87.48 52.5 126.96 138.17 134.71 134.57 112.40 52.50 138.17 34.85

ND ND ND ND ND 0.11 0.02 ND 0.11 0.05

4.49 3.36 1.11 2.66 ND 4.92 2.76 ND 4.49 1.92

41.93 32.43 33.95 38.60 41.81 41.51 38.37 32.43 41.93 4.22

71.81 63.50 67.58 71.29 75.48 19.26 61.49 19.26 75.48 21.08

5.01 3.14 20.80 14.30 8.57 11.54 10.56 3.14 20.80 6.48

Gombak River G1 7.11 G2 7.17 G3 7.24 G4 7.72 G5 7.81 G6 7.66 Mean 7.45 Min 7.11 Max 7.81 SD 0.31

36.60 36.60 36.31 36.62 36.75 36.70 36.60 36.31 36.75 0.15

22.86 22.72 23.22 23.37 23.10 23.31 23.10 22.72 23.37 0.26

271.03 273.75 299.88 266.48 225.18 266.88 267.20 225.18 299.88 24.05

7.63 5.45 1.75 8.78 8.23 6.04 6.31 1.75 8.78 2.57

15.07 ND 2.14 4.77 3.36 3.69 4.84 ND 15.07 5.27

41.68 44.03 40.21 41.28 42.02 41.65 41.81 40.21 44.03 1.25

98.43 109.34 99.57 96.81 98.22 101.00 100.56 96.81 109.34 4.52

ND ND ND ND ND ND – – – –

Selangor River S1 2.52 S2 2.02 S3 1.75 S4 3.41 S5 6.07 S6 2.71 Mean 3.08 Min 1.75 Max 6.07 SD 1.58

25.50 31.82 16.27 18.26 35.43 27.25 25.76 16.27 35.43 7.47

22.67 21.80 22.97 24.35 21.48 24.04 22.88 21.48 24.35 1.16

157.59 143.75 227.70 258.53 165.59 240.30 198.91 143.75 258.53 48.90

2.21 ND ND ND ND 2.19 0.73 ND 2.21 1.13

4.63 3.13 1.02 1.53 ND 15.49 4.30 ND 15.49 5.72

43.06 42.57 43.10 41.97 41.57 43.61 42.65 41.57 43.61 0.76

99.96 84.31 109.22 86.67 84.80 114.24 96.53 84.31 114.24 13.20

ND ND ND ND ND ND – – – –

Lui River L1 L2 L3 L4 L5 L6 Mean Min Max SD

2004). Teng et al. (2001) indicated that about 46% antibiotic prescribing rate involves the government health clinics in Malaysia. It should be noted that sulfamethoxazole also belongs to the same therapeutical classes (antibiotics), and found to be in the range of 19.26 to 75.48 ng/L and 96.81 to 109.34 ng/L and 84.31 ng/L to 114.24 ng/L respectively in the Lui, Gombak, and Selangor rivers. However, it has been reported that the number of this combination drug in Malaysia healthcare system has been decreasing due to the side effects of sulphur component found in sulfamethoxazole (Ministry of Health Malaysia, 2014). Moreover, chloramphenicol concentrations were found in the range of 15.80 to 18.03 ng/L, 22.72 ng/L to 23.37 ng/L and 21.48 ng/L to 24.35 ng/L, respectively in the Lui, Gombak, and Selangor rivers. Chloramphenicol is the most common antibiotic agent used in ophthalmological treatment however it has been banned in Malaysia due to their physico-chemical properties and potential health risk (Ministry of Health Malaysia, 2017). Amoxicillin and nitrofurazone that belong to therapeutical classes of bacterial infections were detected in all three surface water samples. Amoxicillin was detected in the range of ND to 4.44 ng/L, 7.11 to 7.81 ng/L and 1.75 to 6.07 ng/L, respectively in the Lui, Gombak, and Selangor rivers. According to Ministry of Health Malaysia (2014), amoxicillin is the widely used antibacterial agent for both the public and private sectors in the Malaysian primary healthcare system in 2009 and 2010. This pharmaceutical compound is the most preferred because it is a safe choice for urinary tract infection treatment among pregnant women. However, since E. coli has been reported to be resistance to amoxicillin, alternative drugs such as cephalosporins and nitrofurantoin have replaced amoxicillin as the first line UTI treatment (Loh and Sivalingam, 2007). Nitrofurazone was detected in the range of 32.43 to 41.81 ng/L, 40.21 to 44.03 ng/L and 41.57 to 43.61 ng/L, respectively in the Lui, Gombak, and Selangor rivers. Similarly, the ban on nitrofurazone was linked to its toxicity and carcinogenic potential

to human (Department of Chemistry, 2016). The detection of chloramphenicol and nitrofurazone in surface water is still a major concern despite. It is believed that the presence of these two compounds was believed to be originated from illegal antibiotic usage in the aquaculture sector (Ng et al., 2014; Zainudin, 2010). Caffeine from psychoactive stimulant therapeutical class was detected in all water samples, in the range of 26.86 to 32.77 ng/L, 36.31 to 36.75 ng/L and 16.27 to 35.43 ng/L, respectively in the Lui, Gombak, and Selangor rivers. In regard to this, caffeine found in environmental sample including surface water can be linked to other medicines that is believed to boost the effects of certain analgesics in cough, cold, and headache (Al Qarni et al., 2016). Dexamethasone is detected at mean concentrations of 0.02 ng/L, 6.32 ng/L and 0.73 ng/L, respectively in the Lui, Gombak, and Selangor rivers. The Ministry of Health Malaysia (2014) reported that dexamethasone is the second most common used antiinflammatory therapeutical class drug due to its ability to treat allergies, blood, hormone, and immune system disorders in Malaysia. Dexamethasone is the main steroid choice among health practitioners for the purpose of surgical procedures, either in private or public sectors. Triclosan is only detected at mean concentration of 10.56 ng/L in Lui river. Triclosan is an antimicrobial agent that is utilised in medical field and most commonly found in personal care products such as toothpastes, shampoos, soaps, mouthwashes, and other cleaning supplies (Ali and Chew, 2015). The occurrence of these pharmaceuticals in the sampling locations of Lui, Gombak and Selangor rivers further suggests that it is most likely associated with large pharmaceuticals production including over-thecounter medications, prescription drug products, nutraceuticals, traditional medicines, and health supplements in all dosage forms (Hassali et al., 2009). The local industry pharmaceuticals production is about 30% in order to meet the local demand involving those who are mainly

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residing in this study area (Klang Valley). According to the Malaysian Investment Development Authority (2014), there has been growing effort from the Malaysian government in promoting biopharmaceuticals (biologics and vaccines and over-the-counter products) production through the Healthcare National Key Economic Area sector (Malaysian Investment Development Authority, 2014). According to the Ministry of Health Malaysia (2017), the total utilization of medicines in the country has raised by 31.4% from 433.47 DDD/1000 inhabitants/day to 569.55 DDD/1000 inhabitants/day. Hence, the increasing amount of local production and utilization of medicine may contribute to indiscriminate disposal. Insufficiently treatment of municipal wastewater discharge is identified as the major source that is responsible for surface water contamination. In relation to this, it is indicated that pharmaceutical removal efficacies in secondary treatments are low, hence can have impacts in aquatic environment including river water. Additionally, wastewater treatment plants have the tendency to transform the less toxic pharmaceutical metabolites from industries and municipal into a more toxic form, in which higher concentrations were detected along the outflow of the wastewater treatment plant (Li, 2014; H.-Q. Liu

et al., 2017; Wee and Aris, 2017). Pharmaceutical compounds will undergo the degradation process once it enters the aquatic environment, which mainly involves biodegradation by bacteria and abiotic (hydrolysis and photocatalytic degradation) which will reduce initial pharmaceutical concentrations in river water. On the other hand, the transformation process in river water will change pharmaceutical structure to new pharmaceutical compounds with different molecular mass. Moreover, the photolytic degradation due to continuous high amount of sunlight in tropical climate will change initial pharmaceutical molecule and decrease their pharmaceutical concentrations in tropical surface waters (Gaso-Sokac et al., 2017; Rivera-Jaimes et al., 2018). The concentrations of targeted pharmaceuticals in this study were compared with those reported in previous studies globally as presented in Table 4. In general, the targeted pharmaceuticals in the current study were found to be within the range reported by the literature on pharmaceutical present in surface water worldwide except for dexamethasone. Dexamethasone in tropical surface water of this study was found to be higher compared to the concentrations of surface water from temperate climate (Spain and Hungary). According to Archana et al. (2017),

Table 4 Comparison of pharmaceuticals concentrations in various rivers in the world. Pharmaceuticals

Location

Concentration (ng/L)

Reference

Amoxicillin

Lui River (Malaysia) Gombak River (Malaysia) Selangor River (Malaysia) Rivers in Australia Seine River (Paris) River Taff (United Kingdom) Lui River (Malaysia) Gombak River (Malaysia) Selangor River (Malaysia) Northern Antarctic Peninsula Region Dongjiang River Basin (China) Rivers in Spain Tennessee River (United States) Lui River (Malaysia) Gombak River (Malaysia) Selangor River (Malaysia) River Taff (United Kingdom) Beiyun River (China) Rivers in China Lui River (Malaysia) Gombak River (Malaysia) Selangor River (Malaysia) Rivers in Madrid Region (Spain) Rivers in Australia Lui River (Malaysia) Gombak River (Malaysia) Selangor River (Malaysia) Rivers in Spain Rivers in Hungary Lui River (Malaysia) Gombak River (Malaysia) Selangor River (Malaysia) Northern Antarctic Peninsula Region Rivers in Spain Rivers in Mexico Lui River (Malaysia) Gombak River (Malaysia) Selangor River (Malaysia) Lui River (Malaysia) Gombak River (Malaysia) Selangor River (Malaysia) Rivers in Madrid Region (Spain) Llobregat River (Spain) Rivers in Australia Rivers in Mexico Lui River (Malaysia) Gombak River (Malaysia) Selangor River (Malaysia) Turia River (Spain) Rivers in China Minnesota (US)

ND – 4.44 7.11–7.81 1.75–6.07 200 68 b10–622 26.86–32.77 36.31–36.75 16.27–35.43 b0.66–322.89 18.4–430.0 13.2–415.7 18.1–175.7 15.52–18.03 22.72–23.37 21.48–24.35 b2–15 bLOQ – 32.3 b3.38–28.36 52.50–138.17 225.18–299.88 143.75–258.53 b13–569 1300 ND – 0.11 1.75–8.78 ND – 2.21 ND b0.01–0.06 ND – 4.92 ND – 15.07 ND – 15.49 ND – 7761 89.53–176.78 258–1398 32.43–41.93 40.21–44.03 41.57–43.61 19.26–75.48 96.81–109.34 84.31–114.24 32–952 13–149 2000 76–722 3.14–20.80 ND ND 1 3.99–105 0.005–0.310

This study This study This study (Watkinson et al., 2009) (Tuc Dinh et al., 2011) (Kasprzyk-Hordern et al., 2008) This study This study This study (González-Alonso et al., 2017) (Yang et al., 2018) (Fernández et al., 2010) Conley et al. (2008) This study This study This study Kasprzyk-Hordern et al. (2008) (Dai et al., 2015) (Jiang et al., 2011) This study This study This study (Valcárcel et al., 2011) (Watkinson et al., 2009) This study This study This study (Gros et al., 2012) (Tölgyesi et al., 2010) This study This study This study (González-Alonso et al., 2017) (López-Serna et al., 2012) (Gaso-Sokac et al., 2017; Rivera-Jaimes et al., 2018) This study This study This study This study This study This study (Valcárcel et al., 2011) (Boleda et al., 2013) (Watkinson et al., 2009) (Gaso-Sokac et al., 2017; Rivera-Jaimes et al., 2018) This study This study This study (Carmona et al., 2014) (Yang et al., 2018) (Lyndall et al., 2017)

Caffeine

Chloramphenicol

Ciprofloxacin

Dexamethasone

Diclofenac

Nitrofurazone

Sulfamethoxazole

Triclosan

S.M. Praveena et al. / Science of the Total Environment 642 (2018) 230–240

pharmaceuticals are exhibited discordantly due to their different consumptions and exploitation in each country. Ministry of Health Malaysia (2017) states that the topical dexamethasone usage has been highly adopted in surgical procedure performed in both public and private healthcare facilities due to its ability to produce better results and be cost-effective despite the reduce in the overall use of dexamethasone in topical steroids. However, other pharmaceutical concentrations in surface water of Lui, Gombak, and Selangor rivers were found to be low compared to other studies worldwide. 3.2. Potential risks (human health and ecotoxicological) assessment for Lui, Gombak, and Selangor rivers The continuous release are predicted to cause long-lasting impacts due to their environmental persistence despite the low concentration and small fraction of pharmaceuticals released to the environment (Larsson, 2014). Fig. 2 presents the HQHH values representing potential human health risks for Lui, Gombak, and Selangor rivers. All the pharmaceutical compounds except for ciprofloxacin and dexamethasone have recorded to have HQHH value b 1. Ciprofloxacin has HQHH value N 1 for all the rivers, while dexamethasone shows HQHH value of N1 for Gombak and Selangor rivers in both adults and children. On top of that, children tend to show higher risks for all the targeted pharmaceuticals due to their lower body weight (Lin et al., 2016). Furthermore, ecotoxicological risks towards living organisms in surface water are estimated in all three rivers, whereby RQ values for all the pharmaceutical compounds have indicated that the ecotoxicological risk is within the moderate risks except for diclofenac as illustrated in Fig. 3. Hence, it can be implied that higher RQ values for diclofenac shows that the living organisms in surface water are at higher risk of being exposed. The potential human health and ecotoxicological risks have indicated threats in these rivers; however, these risks assessments were performed based on certain assumptions and data that are available in the literature. Meanwhile, the total pharmaceutical concentrations for potential human health risks obtained in this study compared with data obtained from literatures may lead to the overestimation of risks

237

in this study area. Moreover, bioavailability form of pollutant is considered more suitable to be incorporated in health risk assessment to ensure that accurate risks can be estimated for any type of population (Praveena et al., 2015). Similarly for ecotoxicological risks, lack of chronic toxicity data, large dataset of toxicity values for various organisms species available in the literature, and PNEC value calculated from acute toxicity data (EC50, LC50) have hindered accurate estimation of ecotoxicological risks to be achieved in this study area (Archana et al., 2017; Lin et al., 2016). Furthermore, studies by Acuña et al. (2004) and Aristi et al. (2015) showed that the dilution effects caused by rainfall and self-purification are believed to be among the processes that may be able to reduce total pharmaceutical concentrations along the river after being discharged from the wastewater treatment facilities. The reduction of total pharmaceutical concentrations is also possible through adsorption andphotolytic degradation processes in the river (Gaso-Sokac et al., 2017; Rivera-Utrilla et al., 2013). 4. Conclusion The present study has demonstrated the potential use of ELISA kit as a screening tool for pharmaceutical residues in surface water. The physicochemical characteristics indicated these surface water samples were in Class II of Malaysian Interim Water Quality Standards. Overall, all of selected pharmaceuticals compounds were detected along the Lui, Gombak, and Selangor rivers indicating that the continuous output of pharmaceuticals from large production of pharmaceuticals, increase of medicine consumption, wastewater treatment technology and treated sewage effluent are among the sources that lead to the presence of pharmaceutical residues along the surface waters. The potential human health risks showed that HQHH values were less than one except for ciprofloxacin and dexamethasone with HQHH between 1.521 and 41.36. On the other hand, the ecotoxicological risks determined using RQ values were found to be within the moderate risks except for diclofenac with RQ values N 30. It is recommended for these results to be validated using instrumental techniques such as GCMS and LC-MS/ MS.

Lui River

Gombak River

Selangor River

Fig. 2. Potential human health risks for Lui, Gombak and Selangor rivers.

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Fig. 3. Risk Quotient representing ecotoxicological risks for Lui, Gombak and Selangor rivers.

Acknowledgements We thank the Ministry of Higher Education (Malaysia) for funding this work under the Trans Research Grant Scheme (Grant number: 5535711) and Kurita Water and Environment Foundation (Grant number: 6389200). Special thanks and appreciation to Dr Ngah Zasmy A/l Unyah from Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi. org/10.1016/j.scitotenv.2018.06.058. References Ab Razak, N.H., Praveena, S.M., Aris, A.Z., Hashim, Z., 2015. Quality of Kelantan drinking water and knowledge, attitude and practice among the population of Pasir Mas, Malaysia. Public Health 131:103–111. https://doi.org/10.1016/j.puhe.2015.11.006. Acuña, V., Giorgi, A., Muñoz, I., Uehlinger, U., Sabater, S., 2004. Flow extremes and benthic organic matter shape the metabolism of a headwater Mediterranean stream. Freshw. Biol. 49:960–971. https://doi.org/10.1111/j.1365-2427.2004.01239.x. Aga, D.S., O'Connor, S., Ensley, S., Payero, J.O., Snow, D., Tarkalson, D., 2005. Determination of the persistence of tetracycline antibiotics and their degradates in manureamended soil using enzyme-linked immunosorbent assay and liquid chromatography-mass spectrometry. J. Agric. Food Chem. 53:7165–7171. https:// doi.org/10.1021/jf050415+. Ahmed, I., Kasraian, K., 2002. Pharmaceutical challenges in veterinary product development. Adv. Drug Deliv. Rev. https://doi.org/10.1016/S0169-409X(02)00074-1. Al Qarni, H., Collier, P., O'Keeffe, J., Akunna, J., 2016. Investigating the removal of some pharmaceutical compounds in hospital wastewater treatment plants operating in Saudi Arabia. Environ. Sci. Pollut. Res. 23:13003–13014. https://doi.org/10.1007/ s11356-016-6389-7. Ali, S.A., Chew, Y.W., 2015. FabV/triclosan is an antibiotic-free and cost-effective selection system for efficient maintenance of high and medium -copy number plasmids in Escherichia coli. PLoS One 10. https://doi.org/10.1371/journal.pone.0129547. Al-Odaini, N.A., Zakaria, M.P., Yaziz, M.I., Surif, S., 2010. Multi-residue analytical method for human pharmaceuticals and synthetic hormones in river water and sewage effluents by solid-phase extraction and liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 1217:6791–6806. https://doi.org/10.1016/j.chroma.2010.08.033. Al-Qaim, F.F., Abdullah, M.P., Othman, M.R., Latip, J., Zakaria, Z., 2014. Multi-residue analytical methodology-based liquid chromatography-time-of-flight-mass spectrometry for the analysis of pharmaceutical residues in surface water and effluents from sewage treatment plants and hospitals. J. Chromatogr. A 1345:139–153. https://doi.org/ 10.1016/j.chroma.2014.04.025. Amitarani, B.E., Pasha, A., Gowda, P., Nagendraprasad, T.R., Karanth, N.G.K., 2002. Comparison of ELISA and GC methods to detect DDT residues in water samples. Indian J. Biotechnol. 1, 292–297. Archana, G., Dhodapkar, R., Kumar, A., 2017. Ecotoxicological risk assessment and seasonal variation of some pharmaceuticals and personal care products in the sewage treatment plant and surface water bodies (lakes). Environ. Monit. Assess. 189. https://doi.org/10.1007/s10661-017-6148-3. Aristi, I., von Schiller, D., Arroita, M., Barceló, D., Ponsatí, L., García-Galán, M.J., Sabater, S., Elosegi, A., Acuña, V., 2015. Mixed effects of effluents from a wastewater treatment plant on river ecosystem metabolism: subsidy or stress? Freshw. Biol. 60: 1398–1410. https://doi.org/10.1111/fwb.12576. Atan, I., Muhamad Najmi, N.S., Samsudin, M.B., Jaafar, J., Ashaari, Y., Mohammad, S.N., Baki, A., 2017. Bivariate flood frequency analysis of Sungai Lui Catchment in Malaysia using Archimedean Copulas. Proceedings of The IIER International Conference, Marrakesh, Morocco, 13th–14th January. vol. 2017, pp. 5–9. Australian Pesticide and Veterinary Medicines Authority, 2017. Acceptable Daily Intakes (ADI) for Agricultural and Veterinary Chemicals Used in Food Producing Crops or Animals. Public Affairs and Communication Branch, Australian Pesticide and Veterinary Medicines Authority, Kingston, Australia.

Bahlmann, A., Carvalho, J.J., Weller, M.G., Panne, U., Schneider, R.J., 2012. Immunoassays as high-throughput tools: monitoring spatial and temporal variations of carbamazepine, caffeine and cetirizine in surface and wastewaters. Chemosphere 89:1278–1286. https://doi.org/10.1016/j.chemosphere.2012.05.020. Białk-Bielińska, A., Kumirska, J., Borecka, M., Caban, M., Paszkiewicz, M., Pazdro, K., Stepnowski, P., 2016. Selected analytical challenges in the determination of pharmaceuticals in drinking/marine waters and soil/sediment samples. J. Pharm. Biomed. Anal. 121:271–296. https://doi.org/10.1016/j.jpba.2016.01.016. Boleda, M.R., Galceran, M.T., Ventura, F., 2013. Validation and uncertainty estimation of a multiresidue method for pharmaceuticals in surface and treated waters by liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 1286:146–158. https://doi.org/10.1016/j.chroma.2013.02.077. Bradley, P.M., Barber, L.B., Duris, J.W., Foreman, W.T., Furlong, E.T., Hubbard, L.E., Hutchinson, K.J., Keefe, S.H., Kolpin, D.W., 2014. Riverbank filtration potential of pharmaceuticals in a wastewater-impacted stream. Environ. Pollut. 193:173–180. https:// doi.org/10.1016/j.envpol.2014.06.028. Calisto, V., Bahlmann, A., Schneider, R.J., Esteves, V.I., 2011. Application of an ELISA to the quantification of carbamazepine in ground, surface and wastewaters and validation with LC-MS/MS. Chemosphere 84:1708–1715. https://doi.org/10.1016/j. chemosphere.2011.04.072. Carmona, E., Andreu, V., Picó, Y., 2014. Occurrence of acidic pharmaceuticals and personal care products in Turia River Basin: from waste to drinking water. Sci. Total Environ. 484:53–63. https://doi.org/10.1016/j.scitotenv.2014.02.085. Celiz, M.D., Tso, J., Aga, D.S., 2009. Pharmaceutical metabolites in the environment: analytical challenges and ecological risks. Environ. Toxicol. Chem. https://doi.org/10.1897/ 09-173.1. Chan, Y.Y., Lim, K.K., Lim, K.H., Teh, C.H., Kee, C.C., Cheong, S.M., Khoo, Y.Y., Baharudin, A., Ling, M.Y., Omar, M.A., Ahmad, N.A., 2017. Physical activity and overweight/obesity among Malaysian adults: findings from the 2015 National Health and morbidity survey (NHMS). BMC Public Health 17:1–12. https://doi.org/10.1186/s12889-017-4772-z. Conley, J.M., Symes, S.J., Kindelberger, S.A., Richards, S.M., 2008. Rapid liquid chromatography–tandem mass spectrometry method for the determination of a broad mixture of pharmaceuticals in surface water. J. Chromatogr. A 1185, 206–215. Dai, G., Wang, B., Huang, J., Dong, R., Deng, S., Yu, G., 2015. Occurrence and source apportionment of pharmaceuticals and personal care products in the Beiyun River of Beijing, China. Chemosphere 119:1033–1039. https://doi.org/10.1016/j. chemosphere.2014.08.056. Department of Chemistry, M, 2016. Drug residue screening [WWW Document]. (URL). http://www.kimia.gov.my/v3/en/about-us/environment-health-division/drug-residue.html. European Commission, 2003. Commission Decision 2003/181/EC of 13 March 2003 Amending Decision 2002/657/EC as Regards the Setting of Minimum Required Performance Limits (MRPLs) for Certain Residues in Food of Animal Origin. Off. J. Eur. Union L71, pp. 17–18. European Community, 2015. Standard Validation Procedure For Biomarker Immunoassays. Version 4.1 Safer and Faster Evidence Based Translation. Innovative Medicines Initiative (IMI) Programme. European Medicines Agency, 2003. Committee for veterinary medicinal products. Diclofenac Summary Report. European Agency for the Evaluation of Medicinal Products Veterinary Medicines and Inspections, London, UK. Fang, T.Y., Praveena, S.M., deBurbure, C., Aris, A.Z., Ismail, S.N.S., Rasdi, I., 2016. Analytical techniques for steroid estrogens in water samples - a review. Chemosphere 165: 358–368. https://doi.org/10.1016/j.chemosphere.2016.09.051. Faris Gorashi, A.A., 2012. Prediction of water quality index using back propagation network algorithm. Case study: Gombak River. J. Eng. Sci. Technol. 7, 447–461. Fernández, C., González-Doncel, M., Pro, J., Carbonell, G., Tarazona, J.V., 2010. Occurrence of pharmaceutically active compounds in surface waters of the Henares-Jarama-Tajo river system (Madrid, Spain) and a potential risk characterization. Sci. Total Environ. 408:543–551. https://doi.org/10.1016/j.scitotenv.2009.10.009. Gaffney, V. de J., Almeida, C.M.M., Rodrigues, A., Ferreira, E., Benoliel, M.J., Cardoso, V.V., 2015. Occurrence of pharmaceuticals in a water supply system and related human health risk assessment. Water Res. 72, 199–208. Gaso-Sokac, D., Habuda-Stanic, M., Busic, V., Zobundzija, D., 2017. Occurrence of pharmaceuticals in surface water. Croat. J. Food Sci. Technol. 9:204–210. https://doi.org/ 10.17508/CJFST.2017.9.2.18. Gavrilescu, M., Demnerová, K., Aamand, J., Agathos, S., Fava, F., 2015. Emerging pollutants in the environment: present and future challenges in biomonitoring, ecological risks and bioremediation. New Biotechnol. 32:147–156. https://doi.org/10.1016/j. nbt.2014.01.001.

S.M. Praveena et al. / Science of the Total Environment 642 (2018) 230–240 GCC Standardization Organization, 2009. Maximum Residues Limits of Veterinary Drugs in Food. (GSO CAC/MRL 02:2009). https://www.google.com/url?sa=t&rct=j&q= &esrc=s&source=web&cd=1&cad=rja&uact=8&ved= 0ahUKEwivvMnglvDYAhWKNo8KHfrMAccQFggoMAA&url=https%3A%2F% 2Fmembers.wto.org%2Fcrnattachments%2F2014. González-Alonso, S., Merino, L.M., Esteban, S., López de Alda, M., Barceló, D., Durán, J.J., López-Martínez, J., Aceña, J., Pérez, S., Mastroianni, N., Silva, A., Catalá, M., Valcárcel, Y., 2017. Occurrence of pharmaceutical, recreational and psychotropic drug residues in surface water on the northern Antarctic Peninsula region. Environ. Pollut. 229: 241–254. https://doi.org/10.1016/j.envpol.2017.05.060. Grabic, R., Fick, J., Lindberg, R.H., Fedorova, G., Tysklind, M., 2012. Multi-residue method for trace level determination of pharmaceuticals in environmental samples using liquid chromatography coupled to triple quadrupole mass spectrometry. Talanta 100: 183–195. https://doi.org/10.1016/j.talanta.2012.08.032. Gros, M., Rodríguez-Mozaz, S., Barceló, D., 2012. Fast and comprehensive multi-residue analysis of a broad range of human and veterinary pharmaceuticals and some of their metabolites in surface and treated waters by ultra-high-performance liquid chromatography coupled to quadrupole-linear ion trap tandem. J. Chromatogr. A 1248:104–121. https://doi.org/10.1016/j.chroma.2012.05.084. Guedes-Alonso, R., Afonso-Olivares, C., Montesdeoca-Esponda, S., Sosa-Ferrera, Z., Santana-Rodríguez, J.J., 2013. An assessment of the concentrations of pharmaceutical compounds in wastewater treatment plants on the island of Gran Canaria (Spain). Springerplus 2:1–8. https://doi.org/10.1186/2193-1801-2-24. Hassali, M.A., Yuen, K.H., Ibrahim, M.I.M., Wong, J.W., Ng, B.H., Ho, D.S.S., 2009. Malaysian pharmaceutical industry: opportunities and challenges. J. Generic Med. 6:246–252. https://doi.org/10.1057/jgm.2009.12. Huo, S.M., Yang, H., Deng, A.P., 2007. Development and validation of a highly sensitive ELISA for the determination of pharmaceutical indomethacin in water samples. Talanta 73:380–386. https://doi.org/10.1016/j.talanta.2007.03.055. Ismail, Zubaidah, 2011. Monitoring and management issues of heavy metal pollution of Gombak River, Kuala Lumpur. Int. J. Phys. Sci. 6:7961–7968. https://doi.org/ 10.5897/IJPS11.764. Ismail, Z., Sulaiman, R., Karim, R., 2014. Evaluating trends of water quality index of selected Kelang river tributaries. Environ. Eng. Manag. J. 13, 61–72. Jiang, L., Hu, X., Yin, D., Zhang, H., Yu, Z., 2011. Occurrence, distribution and seasonal variation of antibiotics in the Huangpu River, Shanghai, China. Chemosphere 82: 822–828. https://doi.org/10.1016/j.chemosphere.2010.11.028. Jiskra, M., Hollender, J., 2013. Fate of the pharmaceutical diclofenac in the aquatic environment. Biogeochem. Pollut. Dyn. 1–16. Joint FAO/WHO Expert Committee on Additives, F, 2006. Evaluation Of Certain Veterinary Drug Residues In Food. (Sixty-sixth report of the Joint FAO/WHO Expert Committee on Food Additives). WHO technical report series No. 93. World Health Organization, Singapore. Kasprzyk-Hordern, B., Dinsdale, R.M., Guwy, A.J., 2008. The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK. Water Res. 42:3498–3518. https://doi.org/10.1016/j. watres.2008.04.026. Kawasaki, N., Kushairi, M.R.M., Nagao, N., Yusoff, F., Imai, A., 2016. Seasonal Changes of Nutrient Distributions along Selangor River, Malaysia. International Journal of Advances in Chemical Engineering & Biological Sciences 3, 113–116. Khairuddin, K.A., Jatau, A.I., Manan, M.M., Tiong, C.S., Chitneni, M., Abdullah, A.H., Mahalingam, S.R., Arshad, K., 2017. Identification of potential inhibitors against the human influenza a virus targeting the CPSF30 and RNA binding domains of the NS1 protein. Indian J. Pharm. Educ. Res. 51:156–161. https://doi.org/10.5530/ijper.5. Khetan, S.K., Collins, T.J., 2007. Human pharmaceuticals in the aquatic environment: a challenge to green chemisty. Chem. Rev. https://doi.org/10.1021/cr020441w. Larsson, D.G.J., 2014. Pollution from drug manufacturing: review and perspectives. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 369, 20130571. https://doi.org/10.1098/ rstb.2013.0571. Li, W.C., 2014. Occurence, sources, and fate fo pharmaceuticals in aquatic environment and soil. Environ. Pollut. 187:193–201. https://doi.org/10.1016/j.envpol.2014.01.015. Lin, T., Yu, S., Chen, W., 2016. Occurrence, removal and risk assessment of pharmaceutical and personal care products (PPCPs) in an advanced drinking water treatment plant (ADWTP) around Taihu Lake in China. Chemosphere 152:1–9. https://doi.org/ 10.1016/j.chemosphere.2016.02.109. Liu, H.-Q., Lam, J.C.W., Li, W.-W., Yu, H.-Q., Lam, P.K.S., 2017. Spatial distribution and removal performance of pharmaceuticals in municipal wastewater treatment plants in China. Sci. Total Environ. 586:1162–1169. https://doi.org/10.1016/j. scitotenv.2017.02.107. Liu, X., Yang, D., Zhou, Y., Zhang, J., Luo, L., Meng, S., Chen, S., Tan, M., Li, Z., Tang, L., 2017. Electrocatalytic properties of N-doped graphite felt in electro-Fenton process and degradation mechanism of levofloxacin. Chemosphere 182:306–315. https://doi. org/10.1016/j.chemosphere.2017.05.035. Loh, K.Y., Sivalingam, N., 2007. Urinary tract infections in pregnancy. Malaysian Fam. Physician 2:54–57. https://doi.org/10.1016/S0094-0143(05)70218-4. López-Serna, R., Postigo, C., Blanco, J., Pérez, S., Ginebreda, A., de Alda, M.L., Petrović, M., Munné, A., Barceló, D., 2012. Assessing the effects of tertiary treated wastewater reuse on the presence emerging contaminants in a Mediterranean river (Llobregat, NE Spain). Environ. Sci. Pollut. Res. 19:1000–1012. https://doi.org/10.1007/s11356011-0596-z. Lozano, María Constanza, Trujillo, M., 2012. Chemical residues in animal food products: an issue of public health. Public Health - Methodology, Environmental and Systems Issues. InTech (ISBN 978-953-51-0641-8). https://doi.org/10.5772/711. Lyndall, J., Barber, T., Mahaney, W., Bock, M., Capdevielle, M., 2017. Evaluation of triclosan in Minnesota lakes and rivers: part I – ecological risk assessment. Ecotoxicol. Environ. Saf. 142:578–587. https://doi.org/10.1016/j.ecoenv.2017.04.049.

239

Malaysian Investment Development Authority, 2014. Guide on Pharmaceutical Industry in Malaysia. Malaysian Investment Development Authority, Kuala Lumpur, Malaysia. Malaysian Water Academy, 2017. Operation of A Water Supply Dam. http://www.mwa. org.my/pdf/170516_DSM-for-MWA.pdf, Accessed date: 24 March 2018. Ministry of Health Malaysia, 2014. Malaysian Statistics on Medicines 2009 & 2010. Pharm. Serv. Div. Clin. Res. Cent. Minist. Heal., pp. 1–204. Ministry of Health Malaysia, 2017. Malaysian Statistics on Medicines 2011–2014. Pharmaceutical Services Division Ministry of Health Malaysia, Petaling Jaya, Malaysia. Mohamed, H.M., 2015. Green, environment-friendly, analytical tools give insights in pharmaceuticals and cosmetics analysis. TrAC Trends Anal. Chem. 66:176–192. https:// doi.org/10.1016/j.trac.2014.11.010. Moorthy, R., Jeyabalan, G., 2011. Environmental ethics in river water management. Am. J. Environ. Sci. 7:370–376. https://doi.org/10.3844/ajessp.2011.370.376. Nawaz, N., Harun, S., Othman, R., Arien, H., 2016. Rainfall runoff modeling by multilayer perceptron neural network for LUI river catchment. J. Technol. 78. Ng, K.H., Samuel, L., Kathleen, M.M., Leong, S.S., Felecia, C., 2014. Distribution and prevalence of chloramphenicol-resistance gene in Escherichia coli isolated from aquaculture and other environment. Int. Food Res. J. 21, 1321–1325. Ong, D.J., 2001. Land Use in the Selangor River: A Study on the Application and Strategy for Integrated River Basin Management. WWF Malaysia. Patneedi, C.B., Prasadu, K.D., 2015. Impact of pharmaceutical waste on human life and environment. Rasayan J. 8, 2008–2011. Patrícia, C., Lima, D.L.D., Schneider, R.J., Otero, M., Esteves, V.I., 2013. Development of ELISA methodologies for the direct determination of 17 b - estradiol and 17 a -ethinylestradiol in complex aqueous matrices. J. Environ. Manag. 124:121–127. https://doi.org/10.1016/j.jenvman.2013.03.041. Praveena, S.M., Omar, N.A., 2017. Heavy metal exposure from cooked rice grain ingestion and its potential health risks to humans from total and bioavailable forms analysis. Food Chem. 235:203–211. https://doi.org/10.1016/j.foodchem.2017.05.049. Praveena, S.M., Pradhan, B., Ismail, S.N.S., 2015. Spatial assessment of heavy metals in surface soil from Klang District (Malaysia): an example from a tropical environment. Hum. Ecol. Risk Assess. Int. J. 21:1980–2003. https://doi.org/10.1080/ 10807039.2015.1017872. Puckowski, A., Mioduszewska, K., Łukaszewicz, P., Borecka, M., Caban, M., Maszkowska, J., Stepnowski, P., 2016. Bioaccumulation and analytics of pharmaceutical residues in the environment: a review. J. Pharm. Biomed. Anal. 127:232–255. https://doi.org/ 10.1016/j.jpba.2016.02.049. Rivera-Jaimes, J.A., Postigo, C., Melgoza-Alemán, R.M., Aceña, J., Barceló, D., López de Alda, M., 2018. Study of pharmaceuticals in surface and wastewater from Cuernavaca, Morelos, Mexico: occurrence and environmental risk assessment. Sci. Total Environ. 613–614:1263–1274. https://doi.org/10.1016/j.scitotenv.2017.09.134. Rivera-Utrilla, J., Sánchez-Polo, M., Ferro-García, M.Á., Prados-Joya, G., OcampoPérez, R., 2013. Pharmaceuticals as emerging contaminants and their removal from water. A review. Chemosphere 93:1268–1287. https://doi.org/10.1016/j. chemosphere.2013.07.059. Schneider, C., Schöler, H.F., Schneider, R.J., 2005. Direct sub-ppt detection of the endocrine disruptor ethinylestradiol in water with a chemiluminescence enzyme-linked immunosorbent assay. Anal. Chim. Acta 551:92–97. https://doi.org/10.1016/j. aca.2005.07.018. Schwab, B.W., Hayes, E.P., Fiori, J.M., Mastrocco, F.J., Roden, N.M., Cragin, D., Meyerhoff, R.D., D'Aco, V.J., Anderson, P.D., 2005. Human pharmaceuticals in US surface waters: a human health risk assessment. Regul. Toxicol. Pharmacol. 42:296–312. https:// doi.org/10.1016/j.yrtph.2005.05.005. Shanmugam, G., Ramasamy, K., Selvaraj, K.K., Sampath, S., Ramaswamy, B.R., 2014. Triclosan in fresh water fish Gibelion catla from the Kaveri River, India, and its consumption risk assessment. Environ. Forensic 15:207–212. https://doi.org/ 10.1080/15275922.2014.930940. Shelver, W.L., Smith, D.J., 2003. Determination of ractopamine in cattle and sheep urine samples using an optical biosensor analysis: comparative study with HPLC and ELISA. J. Agric. Food Chem. 51:3715–3721. https://doi.org/10.1021/jf021175q. Shelver, W.L., Shappell, N.W., Franek, M., Rubio, F.R., 2008. ELISA for sulfonamides and its application for screening in water contamination. J. Agric. Food Chem. 56:6609–6615. https://doi.org/10.1021/jf800657u. Silva, D., Ponte, C.G.G., Hacker, M.A., Antas, P.R.Z., 2013. A whole blood assay as a simple, broad assessment of cytokines and chemokines to evaluate human immune responses to Mycobacterium tuberculosis antigens. Acta Trop. 127:75–81. https://doi. org/10.1016/j.actatropica.2013.04.002. Sirés, I., Brillas, E., 2012. Remediation of water pollution caused by pharmaceutical residues based on electrochemical separation and degradation technologies: a review. Environ. Int. https://doi.org/10.1016/j.envint.2011.07.012. Stockholm County Council, 2014. Environmentally classified pharmaceuticals 2014–2015. http://www.janusinfo.se/Global/Miljo_och_lakemedel/Miljobroschyr_2014_engelsk_ webb.pdf (1–54). Teng, C.L., Shajahan, Y., Khoo, E.M., Nurjahan, I., Leong, K.C., Yap, T.G., 2001. The management of upper respiratory tract infections. Med J Malaysia 56, 260–266 (quiz 267). Teng, C.L., Achike, F.I., Phua, K.L., Norhayati, Y., Nurjahan, M.I., Nor, A.H., Koh, C.N., 2004. General and URTI-specific antibiotic prescription rates in a Malaysian primary care setting. Int. J. Antimicrob. Agents 24:496–501. https://doi.org/10.1016/j. ijantimicag.2004.06.015. Teng, C.L., Tong, S.F., Khoo, E.M., Lee, V., Zailinawati, A.H., Mimi, O., Chen, W.S., Nordin, S., 2011. Antibiotics for URTI and UTI. Aust. Fam. Physician 40, 325–329. Tölgyesi, Á., Verebey, Z., Sharma, V.K., Kovacsics, L., Fekete, J., 2010. Simultaneous determination of corticosteroids, androgens, and progesterone in river water by liquid chromatography-tandem mass spectrometry. Chemosphere 78:972–979. https:// doi.org/10.1016/j.chemosphere.2009.12.025.

240

S.M. Praveena et al. / Science of the Total Environment 642 (2018) 230–240

Tuc Dinh, Q., Alliot, F., Moreau-Guigon, E., Eurin, J., Chevreuil, M., Labadie, P., 2011. Measurement of trace levels of antibiotics in river water using on-line enrichment and triple-quadrupole LC-MS/MS. Talanta 85:1238–1245. https://doi.org/10.1016/j. talanta.2011.05.013. Valcárcel, Y., González Alonso, S., Rodríguez-Gil, J.L., Gil, A., Catalá, M., 2011. Detection of pharmaceutically active compounds in the rivers and tap water of the Madrid Region (Spain) and potential ecotoxicological risk. Chemosphere 84:1336–1348. https://doi. org/10.1016/j.chemosphere.2011.05.014. Watkinson, A.J., Murby, E.J., Kolpin, D.W., Costanzo, S.D., 2009. The occurrence of antibiotics in an urban watershed: from wastewater to drinking water. Sci. Total Environ. 407:2711–2723. https://doi.org/10.1016/j.scitotenv.2008.11.059. Wee, S.Y., Aris, A.Z., 2017. Endocrine disrupting compounds in drinking water supply system and human health risk implication. Environ. Int. 106:207–233. https://doi.org/ 10.1016/j.envint.2017.05.004. Wu, H., Zeng, G., Liang, J., Guo, S., Dai, J., Lu, L., Wei, Z., Xu, P., Li, F., Yuan, Y., He, X., 2015. Effect of early dry season induced by the Three Gorges Dam on the soil microbial biomass and bacterial community structure in the Dongting Lake wetland. Ecol. Indic. 53:129–136. https://doi.org/10.1016/j.ecolind.2015.01.041. Wu, H., Lai, C., Zeng, G., Liang, J., Chen, J., Xu, J., Dai, J., Li, X., Liu, J., Chen, M., Lu, L., Hu, L., Wan, J., 2017. The interactions of composting and biochar and their implications for

soil amendment and pollution remediation: a review. Crit. Rev. Biotechnol. 37: 754–764. https://doi.org/10.1080/07388551.2016.1232696. Yang, Y.Y., Zhao, J.L., Liu, Y.S., Liu, W.R., Zhang, Q.Q., Yao, L., Hu, L.X., Zhang, J.N., Jiang, Y.X., Ying, G.G., 2018. Pharmaceuticals and personal care products (PPCPs) and artificial sweeteners (ASs) in surface and ground waters and their application as indication of wastewater contamination. Sci. Total Environ. 616–617:816–823. https://doi.org/ 10.1016/j.scitotenv.2017.10.241. Zainudin, Z., 2010. Benchmarking river water quality in Malaysia. Jurutera 2, 12–15. Zakaria, Marzuki, 2017. Use of antimicrobial agents in veterinary medicine in Malaysia. 2nd OIE Information Seminar for Praticing Veterinatians: Combating AMR (Kuala Lumpur, Malaysia). Zeng, G., Wu, H., Liang, J., Guo, S., Huang, L., Xu, P., Liu, Y., Yuan, Y., He, X., He, Y., 2015. Efficiency of biochar and compost (or composting) combined amendments for reducing Cd, Cu, Zn and Pb bioavailability, mobility and ecological risk in wetland soil. RSC Adv. 5:34541–34548. https://doi.org/10.1039/C5RA04834F. Zhou, Y., Liu, X., Xiang, Y., Wang, P., Zhang, J., Zhang, F., Wei, J., Luo, L., Lei, M., Tang, L., 2017. Modification of biochar derived from sawdust and its application in removal of tetracycline and copper from aqueous solution: adsorption mechanism and modelling. Bioresour. Technol. 245:266–273. https://doi.org/10.1016/j. biortech.2017.08.178.