Pharmaceutical and personal care product contamination: a global scenario

Pharmaceutical and personal care product contamination: a global scenario

2

Vipin Chandra Kalia Department of Chemical Engineering, Konkuk University, Seoul, Republic of Korea

2.1

Introduction

Waste generation is an inherent process associated with the utilization of diverse products by human beings for their survival and sustenance. Wastes are viewed as a nuisance because the efforts needed to manage them are enormous. However, the organic matter component of these wastes can be exploited through a range of mechanisms, which can turn them into valuable resources. In nature, a unique mechanism operates such that no single organism can completely metabolize the complex organic matter. This paradox allows the intervention of diversity of organisms, whereby they all survive by using the metabolic products in a sequential manner. Plants, animals, and humans live in association with microbes, some of which are viewed as beneficial whereas others prove to be harmful. The harmful diseaselike scenario causes the use of bioactive molecules to break this relation and relieve human beings from pain and misery. Another factor which adds to this trouble is the harsh environmental pollutants, which also cause some damage to human health. These latent troublemakers are the pharmaceutical and personal care products (PPCPs), which include antimicrobial agents, hormones, synthetic musks, flushing of illegal drugs and pharmaceuticals. The persistent nature of these compounds is becoming a threat to the environment and human health, which extends from surface water, sludge, sewage, sediments, soil, aquatic bodies, treatment plants, wildlife, and humans. The need is to gauge their potential ecological and health risks and develop technologies to control them and create awareness among people on the disposal of unwanted pharmaceuticals. Human beings use a wide range of pharmaceuticals, which are used in order to improve health and to prevent and/or treat diseases of humans and animals. These products primarily are medicines, nutritional supplements, and drugs. Personal care products (PCPs), on the other hand, include those that help to enhance the quality of life by cleaning and adorning our bodies. These PCPs include a range of items such as shampoos, detergents, lotions, moisturizers, insect repellents, cosmetics,

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology. DOI: https://doi.org/10.1016/B978-0-12-816189-0.00002-0 © 2019 Elsevier Inc. All rights reserved.

28

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

antibacterial soaps, odorants, and sunscreens (Yang and Toor, 2015). The human contribution of PPCPs includes fecal matter, washings in the sinks and baths and outside the homes, the contaminants released by the pharmaceutical companies, hospitals, clinics, antibiotics, steroids. The PPCPs are discharged into the sewage system and the wastewater so generated needs to be treated before being released into the environment (Kinney et al., 2006; Aydin and Talini, 2013; Blair et al., 2013a,b; Tewari et al., 2013).

2.2

Distribution of pharmaceutical and personal care products in the environment

2.2.1 Europe 2.2.1.1 United Kingdom The initial studies on the analysis of PPCPs in river Lee, UK, were conducted more than three decades ago (Table 2.1). The concentrations of 25 different pharmaceutical products—tetracycline, erythromycin, sulfmethoxazole, theophylline, and dextropropoxyphene—were reported to be in the range of 1 μg/L (Richardson and Bowron, 1985). The presence of diverse pharmaceutical compounds (1) diclofenac, (2) acetylsulfamethoxazole, (3) erythromycin, (4) trimethoprim, (5) propranolol, and (6) mefenamic acid was found in water samples representing effluents and downstream surface waters (Hilton and Thomas, 2003). Different rivers in the United Kingdom such as Thames, Tees, Tyne, Belfast Lough, Tees, and Mersey were reported to contain sufficiently high quantities of trimethoprim, clotrimazole, clofibric acid, tamoxifen, mefenamic acid, ibuprofen, diclofenac, propranolol, and dextropropoxyphene (Thomas and Hilton, 2004). Investigations of water samples from the effluent and surface waters form sewage treatment plants (STPs) from five different places in the United Kingdom: (1) East Hyde, (2) Great Billing, (3) Corby, (4v) Ryemeads, and (5) Harpenden, were carried out for the presence of 10 pharmaceuticals. A few compounds could be detected with frequency of (1) 74% 100% such as dextropropoxyphene (74%, 195 ng/L), mefenamic acid (81%, 133 ng/ L), ibuprofen (84%, 3086 ng/L), diclofenac (86%, 424 ng/L), and propranolol (100%, 76 ng/L); (2) 33% 65% such as trimethoprim (65%, 70 ng/L), acetylsulfamethoxazole (33%, 50 ng/L), erythromycin (44%, 10 ng/L); and (3) 4% 9% such as sulfamethoxazole (9%, ,50 ng/L) and tamoxifen (4%, ,10 ng/L) (Ashton et al., 2004). Similarly, clotrimazole was detected with a frequency of 59% at a concentration of up to 22 ng/L in wastewater effluent and surface waters of River Tyne (Roberts and Thomas, 2006). River Taff and River Ely (South Wales, UK) were reported to have been contaminated with drugs, medicines, and endocrine disruptors as a result of the release of effluent of the treated wastewater (Kasprzyk-Hordern et al., 2008). This study revealed the diversity of compounds which are acting as contaminants: (1) antiepileptic drugs [carbamazepine (CBZ) and gabapentin], (2) antibacterial drugs (amoxicillin, trimethoprim, and erythromycin), (3) antianalgesics

Table 2.1 Pharmaceutical and personal care product contamination in diverse geographical environments Pharmaceutical and personal care product

Country

References

Compound

Concentration

Acetaminophen

34.8 ng/L 1890 mg/L 05 41 μg/L

Han River, South Korea United States Spain

Choi et al. (2008) Fram and Belitz (2011) Gros et al. (2010)

,50 ng/L 261 ng/L 313 ng/L 1360 ng/L 4700 ng/L 24 ng/g

United Kingdom Thailand

Ashton et al. (2004) Tewari et al. (2013)

Guadalquivir, Ebro, Jucar, and Llobregat rivers, Spain United Kingdom

Osorio et al. (2016)

Acetaminophen, ibuprofen, naproxen, ketoprofen, salicylic acid and diclofenac Acetylsulfamethoxazole Acetylsalicylic acid

Azithromycin Amitriptyline Atenolol Atenolol, carbamazepine, fluoxetine, gemfibrozil, antilipidemic, meprobamate, phenytoin, sulfamethoxazole, triclosan, bisphenol A Bisphenol A Caffeine

206 66 ng/L (I E) 68.0% reduction nd 690 ng/L 0.82 42 mg/L

2500 ng/L 268.7 ng/L 23,778 1744 ng/L (I E) 92.6% reduction 7.21 μg/kg

Mankyung River, South Korea United States

Baker and Kasprzyk-Hordern (2013) Kim et al. (2009) Benotti et al. (2009)

United States Han River, South Korea United Kingdom

Lapworth et al. (2012) Choi et al. (2008) Baker and Kasprzyk-Hordern (2013)

Guadiamar River in Seville, Spain

Martı´n et al. (2010) (Continued)

Table 2.1 (Continued) Pharmaceutical and personal care product Compound

Carbamazepine

References

Thailand United States United States United States United States Germany

Tewari et al. (2013) Wu et al. (2009) Fram and Belitz (2011) Whitacre (2011) Lapworth et al. (2012) Ferrari et al. (2004)

Mankyung River, South Korea WWTPs, near Fu-Hsing River, China United States United States

Kim et al. (2009) Lin et al. (2005)

Concentration 307 2250 ng/L 4.2 mg/L 290 mg/L 4900 ng/L 9800 ng/L 6.3 1.1 μg/L (I E) 82.5% reduction nd 595 ng/L 420 ng/L 5000 ng/L 420 mg/L

Cimetidine Clarithromycin Clofibric acid

Country

1.2 mg/L 7100 ng/L 281 ng/L nd 443 ng/L 1 9 ng/L

104 109 ng/L (I), 95 102 ng/L (E) 1.6 0.55 μg/L (I E) 65.6% reduction

United States United States Han River, South Korea Mankyung River, South Korea Lakes (the Greifensee, the Sempachersee, and the Zurichsee) Switzerland Northern Taiwan Germany

Lapworth et al. (2012) Miller and Meek (2006); Fram and Belitz (2011) Wu et al. (2009) Whitacre (2011) Choi et al. (2008) Kim et al. (2009) Buser et al. (1998a)

Fang et al. (2012) Ferrari et al. (2004)

Codeine

Codeine, ketoprofen, naproxen, diclofenac, and indomethacin Dextropropoxyphene Diclofenac

Dihydrocodeine

Dilantin Ephedrine Erythromycin

1255 372 ng/L (I E) 70.35% reduction 12 ng/g 214 mg/L 25 900 ng/L to 1 7 μg/L 10 ng/L to 1 μg/L 195 ng/L 152 185 ng/L (I), 100 131 ng/L (E) 2.1 1.2 μg/L (I E) 42.8% reduction 424 ng/L 1 12 ng/L 11 310 ng/L 46 mg/L 121 ng/L Up to 5040 ng/L 226 118 ng/L (I E) 47.78% reduction 22 mg/L 476 35 ng/L (I E) 92.64% reduction nd 137 ng/L ,10 ng/L

United Kingdom

Baker and Kasprzyk-Hordern (2013)

Guadalquivir, Ebro, Jucar, and Llobregat rivers, Spain United States Spain

Osorio et al. (2016)

Spain United Kingdom Northern Taiwan

Gros et al. (2010) Ashton et al. (2004) Fang et al. (2012)

Germany

Ferrari et al. (2004)

United Kingdom River Aabach, Switzerland River Aabach Lake Greifensee, Switzerland United States United States United States United Kingdom

Ashton et al. (2004) Buser et al. (1998b) Buser et al. (1998b)

United States United Kingdom

Miller and Meek (2006) Baker and Kasprzyk-Hordern (2013) Kim et al. (2009) Ashton et al. (2004)

Mankyung River, South Korea United Kingdom

Fram and Belitz (2011) Gros et al. (2010)

Miller and Meek (2006) Lapworth et al. (2012) Whitacre (2011) Baker and Kasprzyk-Hordern (2013)

(Continued)

Table 2.1 (Continued) Pharmaceutical and personal care product Compound

Concentration

Fluconazole Gemfibrozil

nd 111 ng/L 6 ng/g

Gemfibrozil metoprolol, atenolol, sulfamethoxazole, propranolol, and carbamazepine Hydrochlorothiazide

0.16 1.18 μg/L

Ibuprofen

3 ng/g nd 414 ng/L 724 2200 ng/L (I), 552 1600 ng/L (E) 30 ng/L 3086 ng/L 3 mg/L (I) 8 ng/L 13 ng/g

Ifenprodil Indomethacin

702 ng/L 2.8 mg/L Up to 1200 ng/L 1500 ng/L nd 35.4 ng/L nd 33.5 ng/L

Country

References

Mankyung River, South Korea Guadalquivir, Ebro, Jucar, and Llobregat rivers, Spain Hoje River, Sweden

Kim et al. (2009) Osorio et al. (2016)

Guadalquivir, Ebro, Jucar, and Llobregat rivers, Spain Mankyung River, South Korea Northern Taiwan

Osorio et al. (2016)

WWTPs, near Fu-Hsing River, China United Kingdom River and lakes, Switzerland River and lakes, Switzerland Guadalquivir, Ebro, Jucar, and Llobregat rivers, Spain Thailand United States United States United States Mankyung River, South Korea Mankyung River, South Korea

Lin et al. (2005)

Bendz et al. (2005)

Kim et al. (2009) Fang et al. (2012)

Ashton et al. (2004) Buser et al. (1999) Buser et al. (1999) Osorio et al. (2016) Tewari et al. (2013) Wu et al. (2009) Whitacre (2011) Lapworth et al. (2012) Kim et al. (2009) Kim et al. (2009)

Ketoprofen Levofloxacin Mefenamic acid

Morphine Naproxen

128 184 ng/L (I), 68 128 ng/L (E) nd 87.4 ng/L nd 326 ng/L 133 ng/L 251 ng/L 371 59 ng/L (I E) 84.1% reduction 170 ng/L 11.2 μg/kg

Nicotine

Nortramadol

Propranolol

3919 85 ng/L (I E) 97.8% reduction 397 144 ng/L (I E) 36.27% reduction nd 40.1 ng/L 76 ng/L 3.37 μg/kg

Salicylic acid

1.1 6.5 μg/L 9.49 μg/kg

Sertraline and citalopram

Between 10 and 100 200 ng/L 0.12 and 0.72 μg/L

Northern Taiwan

Fang et al. (2012)

Mankyung River, South Korea Mankyung River, South Korea United Kingdom Thailand United Kingdom

Kim et al. (2009) Kim et al. (2009) Ashton et al. (2004) Tewari et al. (2013) Baker and Kasprzyk-Hordern (2013) Lin et al. (2005)

WWTPs, near Fu-Hsing River, China Guadiamar River in Seville, Spain United Kingdom

Martı´n et al. (2010) Baker and Kasprzyk-Hordern (2013)

United Kingdom

Baker and Kasprzyk-Hordern (2013)

Mankyung River, South Korea United Kingdom Guadiamar River in Seville, Spain Denmark Guadiamar River in Seville, Spain Spain

Kim et al. (2009) Ashton et al. (2004) Martı´n et al. (2010)

Denmark

Christensen et al. (2009)

Christensen et al. (2009) Martı´n et al. (2010) Gros et al. (2010)

(Continued)

Table 2.1 (Continued) Pharmaceutical and personal care product Compound

Concentration

Sulfamethoxazole

26.9 ng/L 2.0 0.48 μg/L (I E) 76.0% reduction ,50 ng/L 252 ng/L Up to 1900 ng/L ,10 ng/L 6 ng/g

Tamoxifen Tetracyclines Tramadol

Trimethoprim Trimethoprim and sulfamethoxazole Paraxanthine 1,7-Dimethylxanthine

17α-Ethinylestradiol Beta-blockers, diuretics, antihypertensive enalapril, and histamine H2 receptor antagonists Norfloxacin, trimethoprim, ciprofloxacin, and ofloxacin

1122 738 ng/L (I E) 34.22% reduction 70 ng/L 18 70 mg/L 1.8 mg/L 120 mg/L 20,400 1219 ng/L (I E) 94.0% reduction 48.1 μg/kg High

High

I, Influent; E, effluent values in /g and /kg pertain to sediments.

Country

References

Han River, South Korea Germany

Choi et al. (2008) Ferrari et al. (2004)

United Kingdom United States United States United Kingdom Guadalquivir, Ebro, Jucar, and Llobregat rivers, Spain United Kingdom

Ashton et al. (2004) Lapworth et al. (2012) Whitacre (2011) Ashton et al. (2004) Osorio et al. (2016)

United Kingdom United States United States United States United Kingdom

Ashton et al. (2004) Fram and Belitz (2011) Wu et al. (2009) Fram and Belitz (2011) Baker and Kasprzyk-Hordern (2013)

Guadiamar River in Seville, Spain Spain

Martı´n et al. (2010) Gros et al. (2010)

Denmark

Christensen et al. (2009)

Baker and Kasprzyk-Hordern (2013)

Pharmaceutical and personal care product contamination: a global scenario

35

and antiinflammatory (codeine, diclofenac, ibuprofen, paracetamol, naproxen, and tramadol), and (4) PPCPs (CBZ, codeine, erythromycin, gabapentin, and valsartan). They also reported the presence of detectable quantities of illicit drugs: cocaine, amphetamine, and benzoylecgonine (1 39 g/day) (Kasprzyk-Hordern et al., 2008). PPCPs such as diclofenac, indomethacin, sulfamethoxazole, propranolol, and CBZ (highest concentration of up to 2336 ng/L), as contaminants, were also detected at a high frequency in water samples taken from River Ouse and influents of wastewater treatment plants (WWTPs) (Zhou et al., 2009). In another study, around 28 glucocorticoids were observed to be present in the range of 30 850 ng/L in the River Thames (Kugathas et al., 2012). A few WWTPs in England were also checked for the presence of medicines and drugs in their inlet and treated waters outlet. The following pharmaceuticals were detected in the water samples at different concentrations [influent and effluent (median, ng/L) respectively]: (1) caffeine (23,778 and 1744 ng/L), (2) 1,7-dimethylxanthine (20,400 and 1219 ng/L), (3) nicotine (3919 and 85 ng/L), (4) codeine (1255 and 372 ng/L), (5) tramadol (1122 and 738 ng/L), (6) ephedrine (476 and 35 ng/L), (7) nortramadol (397 and 144 ng/L), (8) morphine (371 and 59 ng/L), (9) dihydrocodeine (226 and 118 ng/L), and (10) amitriptyline (206 and 66 ng/L), respectively (Baker and Kasprzyk-Hordern, 2013). It reflected the variation in the effect of treatment on the degradation of different compounds, which showed around 34% to as high as 97.8% differences in the inlet and outlet concentrations. In another study conducted on samples from STP near the River Medway, UK, the concentrations of different compounds were as follows: CBZ (53 265 ng/L), meclofenamic acid (28 176 ng/L), propranolol (8 35 ng/L), indomethacin (6 28 ng/L), thioridazine (6 22 ng/L), meso-biliverdin (3 11 ng/L), and tamoxifen (2 8 ng/L) (Zhou and Broodbank, 2014).

2.2.1.2 Germany Pharmaceuticals belonging to diverse categories, represented by antiepileptic drugs, beta-blockers, antiphlogistics, psychiatric drugs, β2-sympathomimetics, and lipid regulators, were detected in domestic effluents and traced down in the stream and river waters in Germany (Table 2.1). Among these different compounds, the major contamination was due to the lipid regulator “bezafibrate” and CBZ, present in a concentration up to 3.5 and up to 6.3 μg/L, respectively (Ternes, 1998). A commonly used medicine, ibuprofen, was reported to get metabolized in WWTPs in Germany, as evident from the influent concentration of 3.5 μg/L and that of the effluent being 0.3 μg/L (Huppert et al., 1998). Investigations into STPs and river waters revealed the presence of around 6 μg/L of different metabolites arising from antibiotics—sulfamethoxazole, roxithromycin, and erythromycin (Hirsch et al., 1999). Sediment samples obtained from the Wickerbach creek, Frankfurt, Germany, were reported to contain a wide range of compounds: (1) antibiotics: trimethoprim sulfamethazine, erythromycin, roxithromycin, clarithromycin, sulfadiazine, and sulfamethoxazole; (2) pharmaceuticals and their metabolites—naproxen, ketoprofen, indomethacin, 2-hydroxy-ibuprofen, ibuprofen, gemfibrozil, fenoprofen, diclofenac, and clofibric acid; and (3) parasiticide ivermectin (Lo¨ffler and Ternes, 2003).

36

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

A detailed analysis of the pharmaceuticals in the effluent and surface water showed a reduction in their concentrations: 82.5% in the case of CBZ (6.3 1.1 μg/ L), 76.0% for sulfamethoxazole (2 0.48 μg/L), 65.6% for clofibric acid (1.6 0.55 μg/L), and 42.85% for diclofenac (2.1 1.2 μg/L); however, there was accumulation of propranolol from 0.29 to 0.59 μg/L (Ferrari et al., 2004). The occurrence of lipid regulators, antibiotics, and medicines such as ibuprofen, diclofenac, and CBZ in the range of 20 140 μg/L was reported from water samples taken from River Elbe (Wiegel et al., 2004). Racing the metabolic products of triclosan, that is, triclosan-methyl in STPs and surface water of the River Ruhr in Germany reflected minor differences of the two compounds in different water samples, which were between 0.3 and 10 ng/L (Bester, 2005).

2.2.1.3 Switzerland Lakes in Switzerland—the Greifensee, the Sempachersee, and the Zurichsee—were reported to be contaminated with 1 9 ng/L of clofibric acid (Buser et al., 1998a). A detailed analysis of the metabolic degradation of diclofenac in different rivers and lakes revealed that it varies from one sampling site to another, and by large it was in the range of 1 12 ng/L. River Aabach which is connected to Lake Greifensee contained a high concentration of diclofenac, ranging from 11 to 310 ng/L (Buser et al., 1998b). The presence and distribution of ibuprofen in samples collected from lakes, rivers, North Sea, WWTPs of Uster, Pfaffikon, and Gossau were quite high at 3 mg/L in the influent, whereas in the river and lakes, it was quite low at 8 ng/L (Buser et al., 1999).

2.2.1.4 Sweden The persistence of pharmaceuticals such as gemfibrozil metoprolol, atenolol, sulfamethoxazole, propranolol, and CBZ in the Hoje River waters was in the range of 0.16 1.18 μg/L (Bendz et al., 2005).

2.2.1.5 Finland The presence of pharmaceuticals in Eastern Finland water bodies—River Rakkolanjoki and Lake Haapajarvi—was found to be affected by the seasonal variations. The detected levels of the 15 drugs and medicine were in the range of nil to 556 ng/L. However, out of 15 different compounds, CBZ was always detected independently of the season (Meierjohann et al., 2016).

2.2.1.6 Italy Therapeutic chemical agents, such as clarithromycin, lincomycin, bezafibrate, erythromycin, furosemide, and atenolol, were detected to be present in the range of 0.1 250 ng/L in samples collected in the Italian Rivers Po and Lambro, northern Italy (Calamari et al., 2003). In the area spanning the Po Valley, northern Italy, the canal waters were checked before and after the treatment of

Pharmaceutical and personal care product contamination: a global scenario

37

wastewater. The water is generally used for irrigation hence an environmental risk assessment with respect to the presence of PPCPs was done (Al Aukidy et al., 2012). Pharmaceuticals which were always present in the influents and effluents were: (i) antibiotics - ciprofloxacin, azithromycin, roxithromycin, metronidazole, and clarithromycin, (ii) antihypertensive - hydrochlorothiazide, (iii) analgesic - diclofenac, (iv) the beta-blockers - sotalol, atenolol, and metoprolol (the psychiatric drug) - carbamazepine, and the antidiabetic - glibenclamide. The treatment of wastewater was quite effective as revealed by the reduced concentrations of different compound including antibiotics such as azithromycin, clarithromycin, and sulfamethoxazole (Al Aukidy et al., 2012).

2.2.1.7 Spain The presence of PPCPs was recorded in the surface waters of the rivers, Ebro and Llobregat, in Catalonia region and wastewaters. Here, benzophenone-3 was present in the highest concentration of 7 ng/L (Pedrouzo et al., 2009). Another report on the analysis of PPCPs in the Ebro River basin showed that among the 77 different compounds, salicylic acid, tamoxifen, sulfadiazine, clarithromycin, CBZ, and propranolol were present in almost all the sites. The metabolite -10,11-epoxicarbamazepine of CBZ was detected to be at a high concentration of 1667 ng/L in the Zadorra River (Pedrouzo et al., 2009). Another study carried over a period of 3 years at 4 different time points of effluents from WWTPs situated at 7 locations along the Ebro River Basin was based on 73 pharmaceuticals belonging to a variety of medicinal groups (Gros et al., 2010). The major observation of the study was that treatment plants are not sufficient to completely degrade the PCPPs. The potential hazards of the PPCPs: (1) analgesics and antiinflammatory compounds—ketoprofen, mefenamic acid, naproxen, indomethacin, diclofenac, ibuprofen, salicylic acid, acetaminophen, phenylbutazone, codeline, phenazone, propyphenazone; (2) lipid regulators and cholesterol-lowering statin drugs—fenofibrate, gemfibrozil, mevastatin, bezafibrate, clofibric acid, pravastatin, atorvastatin; (3) psychiatric drugs—paroxetine, fluoxetine, diazepam, lorazepam, CBZ; (4) histamines; (5) antibiotics; (6) beta-blockers, etc.—to surface and effluent wastewaters were estimated using a wide range of organisms such as fish, algae, and daphnids. The overall analysis indicated that this process is efficient; however, longer retention periods can prove more effective (Gros et al., 2010). Nonsteroidal antiinflammatory drugs (NSAIDs) such as ketoprofen, ibuprofen, naproxen, acetaminophen, salicylic acid, and diclofenac and analgesics were present in the highest concentrations from 18 to 41 μg/L in the influent and 5 μg/L in the effluent. Analgesics such as codeine were present in low amounts. The values of different PPCPs in influent wastewaters, ketoprofen, naproxen, diclofenac, salicylic acid and indomethacin, ranged from as low as 25 900 ng/L to 1 7 μg/L. In the treated wastewater, the overall concentration of these compounds was reduced down to 10 ng/L to 1 μg/L for codeine, diclofenac, ketoprofen, ibuprofen, and naproxen, whereas for salicylic acid, it varied between 10 and 100 200 ng/L. On the contrary, diuretics, beta-blockers, antihypertensive, histamine H2 receptor

38

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

antagonists, and enalapril were observed to be present in high overall concentrations (Gros et al., 2010). Pharmaceutical compounds were detected in the compost, sewage sludge, and sediments in samples collected from the Guadiamar River in Seville, Spain. The major compounds were propranolol (3.37 μg/kg), caffeine (7.21 μg/kg), salicylic acid (9.49 μg/kg), naproxen (11.2 μg/kg), and 17α-ethinylestradiol (48.1 μg/kg) (Martı´n et al., 2010). Samples collected from the sediments of Iberian River basins (Guadalquivir, Ebro, Jucar and Llobregat) in Spain were found to contain (1) azithromycin (24 ng/g), (2) ibuprofen (13 ng/g), (3) codeine (12 ng/g), (4) and (5) tetracyclines and gemfibrozil (6 ng/g), and (6) hydrochlorothiazide (3 ng/g) (Osorio et al., 2016).

2.2.1.8 Portugal A survey of water samples from more than 100 rivers spread over 27 European countries showed that certain pharmaceuticals such as CBZ caffeine and benzotriazole were quite persistent and were detected with high frequency and at high concentrations as well (Loos et al., 2009). Pharmaceutical compounds largely NSAIDs were reported to be present in the range of 0.05 100 μg/L in the influent, whereas their values varied up to in the influent and up to 50 μg/L in the discharge from the different WWTPs. The concentration of musks was 11.5 μg/L in the influent waters, which got lowered down to 0.9 μg/L in the discharge (Salgado et al., 2010).

2.2.1.9 Hungary Water and sediments collected from river Danube flowing through Budapest, Hungary, were found to be contaminated with pharmaceuticals such as ketoprofen, naproxen, diclofenac, and ibuprofen. In the water samples, the concentration of ketoprofen was quite low, whereas 8 50 ng/L of ibuprofen, 2 30 ng/L of naproxen, and 7 90 ng/L of diclofenac were detected. On the other hand, sediments were found to contain 2 20 ng/g of naproxen and 5 38 ng/g of diclofenac (Varga et al., 2010).

2.2.1.10 Denmark The discharge of pharmaceuticals in water bodies poses a great risk to aquatic organisms. Twenty-two human-used pharmaceuticals, especially those with high volume and high ecotoxicity, were checked in the effluents discharged from STPs. These contaminants belonged to nine different therapeutic groups (1) betablockers—sotalol, metoprolol, atenolol, propranolol; (2) lipid modifying agent— simvastatin; (3) diuretic such as furosemide; (4) antibiotics—norfloxacin, trimethoprim, ofloxacin, ciprofloxacin; (5) antiinflammatories—ibuprofen, ketoprofen, diclofenac, naproxen; (6) anxiolytics—oxazepam, diazepam; (7) analgesic such as paracetamol; (8) antiepileptic—CBZ, and (9) inhibitors of serotonin reuptake— sertraline, paroxetine, fluoxetine, and citalopram (Christensen et al., 2009). Here, ecotoxicological studies were conducted using established tests with bacteria,

Pharmaceutical and personal care product contamination: a global scenario

39

algae, fish, crustaceans, and rotifers, whereas chronic effects were done by employing fish and crustacean. The concentrations of beta-blockers in STP effluents were earlier reported to vary from 1.1 to 6.5 μg/L. In this specific study, propranolol showed the highest levels of acute and chronic toxicity. Among serotonin reuptake inhibitors, sertraline and citalopram are among those with highest concentrations of 0.12 and 0.72 μg/L, respectively. Antibiotics used against infections by pathogens—norfloxacin, trimethoprim, ciprofloxacin, and ofloxacin—were found in the highest concentrations in the effluents of STPs (Christensen et al., 2009).

2.2.2 Asia 2.2.2.1 China A study to estimate the distribution of pharmaceuticals ketoprofen, diclofenac, CBZ, naproxen ibuprofen, and clofibric acid as contaminants in groundwater, FuHsing River water, WWTPs, and tap water was conducted in China (Table 2.1). Tap water and groundwater were not found to contain any of these compounds. Naproxen was found at concentration of 30 ng/L in river water sample, whereas sample of effluent from WWTP showed the presence of ibuprofen, naproxen, and CBZ up to 30, 170, and 420 ng/L, respectively (Lin et al., 2005). Analysis of water samples form and the Pearl River in South China and Victoria Harbour, Hong Kong, for antibiotics revealed that seawater contained them below the detection limits, whereas in river water, most of the compounds were in the range of 11 67 ng/L, whereas amoxicillin was present in high concentrations: 66 460 ng/L (Xu et al., 2007). Pearl River Delta at Guangzhou, South China, was contaminated with 65 ng/L of estrogenic hormone, estrone, whereas pharmaceutical compounds such as clofibric acid, ibuprofen, and salicylic acid were detected frequently in water samples at a concentration of 248, 1417, and 2098 ng/L, respectively (Peng et al., 2008). The concentration levels of estrogens: (1) β-estradiol 17-valerate, (2) 17α-ethynylestradiol, (3) estrone, (4) β-estradiol, (5) estriol, and (6) diethylstilbestrol, in the samples taken from different rivers flowing through Tianjin area, China, were reported to be in the range of 0.98 51.6 ng/g of sediment (Lei et al., 2009). Study to estimate the occurrence of contamination due to antibiotics in municipal sewage and Nanming River flowing through Guiyang city, China, showed them to be present in high concentrations: (1) tetracycline (0.7 65.2 μg/L), (2) oxytetracycline (0.2 5.7 μg/L), and (3) chloramphenicol (5.8 47.4 μg/L) (Liu et al., 2009). Antibiotics used in the veterinary section for protecting animals from infections and diseases were found to contaminate soil, manure, groundwater, and vegetables. It was found that the transmission of antibiotics occurs through irrigation water in Tianjin, China. Analytes such as pefloxacin, ofloxacin, chlortetracycline, sulfadoxine, lincomycin, tetracycline, sulfamethoxazole, chloramphenicol, and sulfachloropyridazine were present in vegetable samples in the range of 0.1 and 532 μg/kg (Hu et al., 2010). Sediment samples collected from Pearl River, China,

40

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

were found to contain a diversity of antibiotics belonging to different classes: (1) tetracyclines, (2) fluoroquinolones, (3) macrolides, and (4) sulfonamides, in high concentration of 1560 μg/kg (Yang et al., 2010). Sediments of three Chinese rivers Yellow, Hai, and Liao in Northern China were found to contain antibiotics such as macrolides tetracycline, fluoroquinolones, and sulfonamides. The most contaminated among the three rivers were the samples collected from Hai River. The trends of distribution of antibiotics such as oxytetracycline, ciprofloxacin, ofloxacin, and norfloxacin were as follows: in concentrations up to 652, 653, 1290, and 5770 ng/g, respectively (Zhou et al., 2011). The occurrence and distribution of antibiotics such as macrolide antibiotics sulfonamide, tetracycline, and quinolones in the Haihe River Basin, China, were found to be routed through usage for veterinary purposes such as for fish ponds and swine farms at concentrations in the range of 0.12 47 μg/L (Luo et al., 2011). The distribution of antibiotics in sediments, water, sediments, aquatic animals, and plants from Baiyangdian Lake, China, revealed quinolones in the sediments and sulfonamides in lake water as the dominant antibiotics at concentrations of 65.5 1166 μg/kg and 0.86 1563 ng/L, respectively (Li et al., 2012). Pharmaceutically active compounds such as CBZ, E2, EE2, erythromycin, propranolol, roxithromycin, ibuprofen, and diclofenac were detected in the sediment samples and surface water in Taihu Lake, China, with concentrations ranging from 0.78 to 42.5 ng/L dry weight and 8.74 to 118 ng/L, respectively (Xie et al., 2015). Assessment of risk due to distribution and occurrence of pharmaceutical compounds in the Dongting Lake, China, showed that the most frequently detected ones were caffeine, CBZ, diclofenac, N,N-diethyl-meta-toluamide (DEET), ibuprofen, fluoxetine, and mefenamic acid. Their concentrations were in the range of 2.0 and 80.8 ng/L (Ma et al., 2016).

2.2.2.2 Taiwan The level of contamination and distribution of pharmaceutical residues in coastal seawater and the effluents of WWTP in Northern Taiwan were reported showing a change of 5% 40% in the effluent. The reported concentration of (1) ketoprofen, (2) ibuprofen, (3) diclofenac, and (4) clofibric acid in the (1) influent was 128 184, 724 2200, 152 185, 104 109 ng/L, and (2) effluent 68 128, 552 1600, 100 131, and 95 102 ng/L, respectively (Fang et al., 2012).

2.2.2.3 Korea The presence of antibiotics, hormones, and different pharmaceutical compounds was also found to be present in the water samples taken from Youngsan River, the Nakdong River, and the Han River flowing through South Korea (Kim et al., 2007). Residues of pharmaceutical such as sulfamethoxazole, acetaminophen, caffeine, cimetidine were detected in the surface water of the Han River, Korea, to be 26.9, 34.8, 268.7, and 281 ng/L, respectively (Choi et al., 2008). In another study on Mankyung River, South Korea, several pharmaceuticals were detected from

Pharmaceutical and personal care product contamination: a global scenario

41

negligible to different concentrations: atenolol (690 ng/L), clarithromycin (443 ng/ L), CBZ (595 ng/L), erythromycin (137 ng/L), fluconazole (111 ng/L), ibuprofen (414 ng/L), ifenprodil (35.4 ng/L), indomethacin (33.5 ng/L), levofloxacin (87.4 ng/ L), mefenamic acid (326 ng/L), and propranolol (40.1 ng/L) (Kim et al., 2009). A study to find out the distribution of pharmaceuticals in influent samples of WWTPs located near river basins in South Korea was found to contain CBZ, caffeine, and NSAIDs, as dominant contaminants among wastewater contaminated with products from hospitals, pharmaceutical manufacturers, households, and livestock farms (Sim et al., 2011).

2.2.2.4 Japan Water samples collected from Tokyo Bay and Tama River, Japan, were found to contain synthetic musks—musk xylene in all the 74 samples and musk ketone in 80% of them (Yamagishi et al., 1983). In Tamagawa River, antimicrobials such as trimethoprim, sulfapyridine, sulfamethoxazole, erythromycin-H2O, roxithromycin, azithromycin, and clarithromycin were reported to be present in 4 448 ng/L (Managaki et al., 2007).

2.2.2.5 Vietnam The distribution of antimicrobials—trimethoprim, sulfamethazine, sulfamethoxazole, and erythromycin-H2O—was found to be in the range of 7 360 ng/L in the Mekong Delta, Vietnam (Managaki et al., 2007).

2.2.2.6 Thailand Ecological impact of pharmaceuticals in the aquatic environment has been evaluated for their potential risks and ecological consequences. Samples of water collected from canals, WWTPs, and Chao Phraya River (Bangkok, Thailand) were monitored for the presence of 14 pharmaceutical products including trimethoprim, sulfathiazole, roxithromycin, ibuprofen, sulfamethoxazole, atenolol, ciprofloxacin, acetaminophen, sulfamethazine, naproxen, mefenamic acid, diclofenac, caffeine, and acetylsalicylic acid. The concentration of the residues of these PCPs in the influents to the WWTPs varied considerably: (1) acetylsalicylic acid 4.7 μg/L, (2) caffeine 2.25 μg/L, and (3) ibuprofen 0.7 μg/L. On the other hand, high concentrations in effluents were recorded as (1) caffeine 0.3 μg/L, (2) acetylsalicylic acid 0.26 μg/L, and (3) mefenamic acid 0.25 μg/L. Acetylsalicylic acid was found to be present in high concentration: (1) 1.36 μg/L in canals and (2) 0.31 μg/L in the river water. Pharmaceuticals—sulfamethazine, roxithromycin, and sulfamethoxazole— passed through the WWTPs without getting degraded. Hazard quotients estimated for compound such as mefenamic acid, ciprofloxacin, acetylsalicylic acid, ciprofloxacin, and diclofenac were estimated to be hazardous implying potential ecological risks (Tewari et al., 2013).

42

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

2.2.2.7 India Effluent from WWTP of a drug manufacturing company in Patancheru, Hyderabad, India, was reported to contain very high levels of pharmaceuticals, that is, up to 31 mg ciprofloxacin/L (Larsson et al., 2007). From the same area, highly contaminated samples were reported from drinking, surface and groundwater, which contained 1.2 mg/L of cetirizine and 6.5 mg/L of ciprofloxacin as major ones (Fick et al., 2009). A detailed analysis carried out for assessing the ecotoxicological risk caused by pharmaceutical compounds such as antimicrobial, preservatives, and antiepileptics samples collected from sediments and surface water of three Indian rivers: Vellar, Tamiraparani, and Kaveri, revealed that antimicrobial triclosan was present in all the samples at concentrations of 32.1, 46.9, and 85.3 ng/g, respectively (Ramaswamy et al., 2011).

2.2.3 United States Residues of PPCPs evaluated in the waters in the United States were found to be anticonvulsant, antibiotics, flame retardants, antiinflammatory, plasticizer, and stimulants (Table 2.1). A report on the presence of estrogenic hormones in the effluents of municipal WWTPs in California, and surface water from a wetland which was receiving this treated water, that is, from the Colorado River and the Sacramento River delta, revealed 0.6 and 1.9 ng/L of 17α-ethinylestradiol (EE2) and 17β-estradiol (E2), respectively. On the other hand, the respective values for these compounds were .0.05 and 0.08 ng/L (Huang and Sedlak, 2001). A survey done in 2002 revealed the presence of the chemicals, which are used as major components of PPCPs such as antibiotics, stimulants, opioid analgesic, analgesic, antiinflammatory drugs, plasticizers, sterol, hormone, and fire retardant. The concentration of analgesic, plasticizers, and sterol was very high in the range of 10 150 g/L, where others were present in relatively low concentrations, ranging from 19 to 6000 mg/L. The concentrations of contaminants were generally well below the drinking water health advisories, drinking water guidelines, or criteria set for aquatic life (Kolpin et al., 2002). Accumulation of pharmaceuticals at .0.1 ng/ g such as slective serotonin reuptake inhibitors (SSRI) sertraline and fluoxetine in the fish was collected from streams of North Texas, USA (Brooks et al., 2005). An evaluation of contamination due to antibiotics being present in the discharge from East Aurora and Holland, New York, revealed 0.04 0.07 μg/L concentration of clindamycin, sulfamethoxazole, and ciprofloxacin (Batt et al., 2006). A wide range of compounds released as residues of PPCPs in groundwater have been reported quite frequently. Another study, which was carried out by analyzing groundwater from 38 sites, reported the presence of (1) 22 mg/L of dilantin (a component of antiepileptic drugs) and (2) 46 mg/L of diclofenac (used as antiinflammatory drug), and a high quantity of CBZ anticonvulsant at a concentration of 420 mg/L (Miller and Meek, 2006). Analysis of water from River Mississippi in New Orleans, Louisiana, was found to be contaminated by PPCPs such as (1) (2) estrone and 17β-estradiol (,1 5 ng/L), (3) ibuprofen (,1 34 ng/L), (4) caffeine (,1 38 ng/L),

Pharmaceutical and personal care product contamination: a global scenario

43

(5) naproxen (,1 135 ng/L), (6) bisphenol A (,1 147 ng/L), (7) clofibric acid (3 27 ng/L), (8) triclosan (9 26 ng/L), (9) acetaminophen (25 65 ng/L), and (10) CBZ (43 114 ng/L) (Zhang et al., 2007). Pharmaceuticals such as CBZ, diltiazem, diphenhydramine, and norfluoxetine were found to be present in the range of 0.66 5.14 ng/g in the muscles of fish from Pecan Creek, Denton County Texas, USA (Ramirez et al., 2007). Distribution of antibiotics and hormones in the river Choptank in Maryland was reported to be 0.005 0.007 μg/L for sulfadimethoxine and sulfamethoxazole (Arikan et al., 2008). Compounds such as sulfamethoxazole, monoethoxylate, bisphenol A, 4-octylphenol, and tri(2-chloroethyl) phosphate, which are used to prepare antibiotic, detergent metabolite, fire retardant, and plasticizer, were detected in a nation-wide survey of groundwater from 47 sites (Barnes et al., 2008). Surface and groundwater were reported with a frequency of 12% 59%, which represented chemicals used as sterol, metabolites of caffeine and nicotine, anticonvulsant, plasticizer, and fire retardant (Focazio et al., 2008). A comprehensive survey based on finished drinking water samples from 18 different sites provided greater insights to the chemicals which may act as contaminants (Benotti et al., 2009). Here, chemicals used for preparing items of daily life such as atenolol used as beta-blockers, CBZ as anticonvulsant, fluoxetine as antidepressant, gemfibrozil as antilipidemic, meprobamate as antianxiety, phenytoin as anticonvulsant, sulfamethoxazole as antibiotic, triclosan as antibacterial, and bisphenol A as a plasticizer. The concentrations of these compounds varied from 0.82 to 42 mg/L (Benotti et al., 2009). PPCPs such as galaxolide (300 2100 ng/L) and tonalide (21 290 ng/L) were reported to be accumulating in fish in rivers which received discharge from WWTPs in different places in the United States: Illinois, Texas, Florida, Arizona, and Pennsylvania. The other pharmaceuticals found to be present in liver and fillets included CBZ, diphenhydramine, diltiazem, fluoxetine, gemfibrozil, norfluoxetine, and sertraline (Ramirez et al., 2009). The impact of effluentdominated streams was determined by analyzing their presence in white sucker fish (Catostomus commersoni) neural tissue. Sertraline, fluoxetine, and their metabolic products were the major compounds present in low concentrations of 0.1 6 ng/g (Schultz et al., 2010). A large-scale groundwater survey based on 1231 sites had some very interesting information for waste managers (Fram and Belitz, 2011). The variation in compounds released in to groundwater was quite wide: (1) 18 70 mg/L of antibiotics such as trimethoprim and sulfamethoxazole, (2) 120 mg/L of caffeine metabolite (p-xanthine), (3) 214 mg/L of opioid analgesic (codeine), (4) 290 mg/L of stimulant (caffeine), (5) 420 mg/L of anticonvulsant (CBZ), and (6) 1890 mg/L of analgesic (acetaminophen) (Fram and Belitz, 2011). Many drugs, antibiotics, and medicines are found in surface and groundwaters: (1) caffeine 9800 ng/L, (2) CBZ 5000 ng/L, (3) bisphenol A 2500 ng/L, (4) ibuprofen 1500 ng/L, (5) sulfamethoxazole 252 ng/ L, and (6) diclofenac 121 ng/L (Lapworth et al., 2012). These contaminants are also found to be present in streams, surface water, and regular drinking water: (1) caffeine 4.9 μg/L, (2) CBZ up to 7.1 μg/L, (3) ibuprofen up to 1.2 μg/L, (4) sulfamethoxazole up to 1.9 μg/L, and (5) diclofenac up to 5.04 μg/L (Whitacre, 2011). In groundwater, the range of different compounds varied quite considerably: caffeine

44

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

(13% 83%), CBZ (1.2% 42%), sulfamethoxazole (10% 24%), ibuprofen (nil 7%), and bisphenol A (8% 59%) (Lapworth et al., 2012). Monitoring of the wastewater treated in two WWTPs before being discharged into Charleston Harbor, South Carolina, for PPCPs including 11 different hormones revealed that the highest concentrations were recorded for ibuprofen, caffeine, and acetaminophen, whereas triclocarban and triclosan were present in relatively lower concentrations. The surface water in the Charleston Harbor was found to contain acetaminophen, cotinine, and caffeine in 22%, 33%, and 98% of the samples, respectively (Hedgespeth et al., 2012). The distribution of PPCPs in sediment samples obtained from rivers Grindstone, Sauk, Mississippi, South Fork of the Crow and creeks Center, Okabena and lakes such as Shagawa, Superior, and Pepin in Minnesota was reported to contain 822 ng/g of triclocarban in freshwater sediments (Venkatesan et al., 2012). PPCPs and alkylphenols analyses from mussels, sediments, and surface waters in an urban estuary at San Francisco Bay, California, where discharge from municipal and industrial wastewater outfalls showed 14 ng/g of DEET in mussels, 33 ng/g of triclocarban in sediment, and 92 ng/L of valsartan in surface water (Klosterhaus et al., 2013). PCPs and two alkylphenol surfactants were found in fish fillets streams in Texas. Different samples were found in the following concentration ranges (ng/g): (1) triclosan, 17 31, (2) tonalide, 26 97, (3) benzophenone, 37 90, and (4) galaxolide, 234 970 (Mottaleb et al., 2013). Bull sharks (Carcharhinus leucas) inhabiting the Caloosahatchee River were found to have accumulated 0.10 6.25 ng/g of the following compounds: venlafaxine, sertraline, fluvoxamine, fluoxetine, paroxetine, citalopram, and 17α-ethinylestradiol (Gelsleichter and Szabo, 2013). Pharmaceuticals, perfluorosurfactants, and other organic wastewater compounds in analysis of public drinking from water wells located in a shallow sand and gravel aquifer in Cape Cod, Massachusetts, USA, showed that the most frequently detected pharmaceuticals were including the anticonvulsant phenytoin, CBZ, and sulfamethoxazole, at concentrations ranging from 66 to 113 ng/L (Schaider et al., 2014). Sediments samples collected from the Alafia River in Florida were reported to contain from nil to 33 ng/g of ephedrine, lidocaine, caffeine, diphenhydramine, CBZ, nicotine, trimethoprim, and acetaminophen (Yang et al., 2015). Samples taken from Zumbro River watershed, Minnesota, were found to contain different PPCPs at high frequency (72% 99%) and at concentrations ranging from 3.3 to 29 ng/L, such as (1) acetaminophen (3.3 ng/L), (2) trimethoprim (5.9 ng/L), (3) metolachlor (10 ng/L), (4) caffeine (17 ng/L), and (5) atrazine (29 ng/L) (Fairbairn et al., 2016). Drugs prescribed and others which have not been prescribed for treating diseases affecting humans and animals find their way to the rivers and streams around the world. The pharmaceutical drugs have been reported to be detected from such water bodies in Europe and the United States (Ternes et al., 2001; Kolpin et al., 2002). The concentration of PCPPs and the risks associated with them were evaluated in the effluent of the WWTPs at varying distances from the lake. Lake Michigan is among the top 10 lakes in terms of its volume and area (Beeton, 2002). Fifty-four PPCPs and hormones present in surface water and sediment samples were analyzed at six different time points spread over a period of 2 years. PPCPs frequently

Pharmaceutical and personal care product contamination: a global scenario

45

detected in Lake Michigan were triclosan, caffeine, sulfamethoxazole, and metformin. PPCPs were detected in samples collected from sites which were up to 3.2 km away. An assessment of ecological risk was found to be in the medium or high level, indicating a significant threat (Blair et al., 2013a).

2.2.4 Canada A study conducted on the effluent collected from STPs in Canada revealed the presence of acidic and neutral drugs (Table 2.1). In this study, CBZ along with lipid regulators such as gemfibrate and bezafibrate were present in high concentrations of up to as 2.3 μg/L (Metcalfe et al., 2003a). The origin of these contaminants is generally through the STPs and surface waters near them. Chemical analysis was done of water samples taken from lower Great Lakes, Lake Erie and Lake Ontario, STPs in Windsor, and sites near Hamilton Harbour, western Lake Ontario, in Ontario, Canada. Antiepileptic drug CBZ and acidic drugs were found to be present at distances, which were up to 500 m away from the treatment plants. Drugs could not be detected in certain locations; however, others such as ketoprofen, CBZ, fenoprofen, and clofibric acid were reported from samples taken from near Lake Erie and Niagara River. Neutral and acidic drugs in surface waters in effluents of certain STPs and the discharge into the Little River were at the same levels. Caffeine and cotinine, the antibiotic trimethoprim, and antidepressant fluoxetine were the most frequently detected compounds in STP effluents and surface waters. Drug atorvastatin, which is used to regulate lipids, was also detected in the effluent and surface water (Metcalfe et al., 2003b). Analysis of receiving water and municipal wastewaters on the coastal region of Vancouver Island, British Columbia, revealed the presence of acidic drugs salicylic acid, naproxen, ibuprofen, and caffeine (Verenitch et al., 2006). Investigations into the contamination caused by pharmaceuticals in agricultural landscape area near the western Lake Erie basin revealed the presence of paraxanthine, CBZ, and caffeine in 56% 88% of the samples. The concentration of different compounds varied from 1.2 mg/L of CBZ, 1.8 mg/L of paraxanthine, 2.8 mg/L of ibuprofen, to 4.2 mg/L of Caffeine. There were no such chemicals in the soil sediments. The origin of these pharmaceutical products was linked to the septic systems which were present around the agricultural fields (Wu et al., 2009).

2.2.5 South America Polar drugs residues were found to be present as contaminants in sewage and natural waters flowing through Rio de Janeiro, Brazil (Table 2.1). This is a major source of drinking water which was found to contain 0.01 0.06 μg/L of naproxen, diclofenac, and clofibric acid (Stumpf et al., 1999). In an attempt to evaluate the possibility of using wastewater for agricultural purposes in Tula Valley in Mexico, it was found that the wastewater contained potential endocrine disruptors and pharmaceuticals (ng/L): ibuprofen 742 1406, diclofenac 2052 4824, and naproxen 7267 13,589 ng/L. In contrast, pharmaceuticals such as ketoprofen, clofibric acid,

46

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

and gemfibrozil were present in negligible concentrations (Gibson et al., 2010). Influent and effluent samples from WWTPs situated at Penha and Ilha do Governador, Rio de Janeiro, were found to contain high concentrations of ibuprofen (Ferreira, 2014a). Psychiatric pharmaceuticals such as diazepam, clonazepam, and bromazepam were detected in surface water samples from Guandu River, Rio de Janeiro, at concentrations ranging from 42 to 335 ng/L (Ferreira, 2014b).

2.2.6 Australia and New Zealand Triclosan was detected up to 75 ng/L in surface waters collected from five rivers, where effluent from WWTPs was discharged (Table 2.1). Six different antibiotics were reported from waterways of South-East Queensland. Here, cephalexin, the most prescribed antibiotic in Australia, was found to be present in a high quantity of 2000 ng/L (Costanzo et al., 2005). Samples collected from WWTPs in Australia were found to be contaminated with antimicrobial compound triclosan: 23 343 ng/ L in the treated water and 0.09 16.79 mg/kg in the solids (Ying and Kookana, 2007). The presence of antibiotics was detected in the effluent generated by different hospitals, WWTPs, rivers, and drinking water catchment areas of South-East Queensland, Australia. The concentrations of antibiotics in the (1) hospital effluent was up to 14.5 μg/L, (2) influent and effluent of WWTP were up to 64 and 3.4 μg/ L, respectively, and (3) river water showed up to 2 μg/L. However, the drinking water samples didn’t show any of the antibiotics (Watkinson et al., 2009). CBZ was reported from samples of sediments collected from Mackreath Creek and Scott Creek in Australia (Williams and Kookana, 2010). A nation-wide survey conducted in Australia and New Zealand revealed the presence of PPCPs in marine sediments, river systems, and sewage sludge. River waters were frequently detected to contain pharmaceuticals such as (1) CBZ 682 ng/L, (2) salicylic acid 1530 ng/L, (3) caffeine 3770 ng/L, and (4) paracetamol 7150 ng/L (Scott et al., 2014). Acetaminophen at 7.7 ng/g and naproxen at 5.5 ng/g were detected from the estuarine areas near Auckland, New Zealand (Stewart et al., 2014).

2.2.7 Africa Very few studies have been conducted in this continent on the contamination due to PPCPs (Table 2.1). In a study conducted in analyzing PPCPs in Nairobi River, Kenya, among the 10 compounds which were checked, the most prevalent were antiepileptic, antiinflammatory, and analgesics at the rate of about 30 35 μg/L, whereas antimalarial drugs and antibiotics were detected at 25 30 and 25 30 μg/L and the antivirals were found to be at low concentrations of 10 15 μg/L (K’oreje et al., 2012). Pharmaceutical compounds were checked in a dam along the River Umgeni River and its surface water, which is a major source of water in KwaZuluNatal, South Africa. The compounds were present with a high frequency of 100% in the different sample of surface water tested for caffeine, nalidixic acid, ibuprofen, tetracycline, chloramphenicol, atenolol, acetaminophen, diclofenac, erythromycin, and sulfamethoxazole. Caffeine was detected at a high concentration of 61 μg/

Pharmaceutical and personal care product contamination: a global scenario

47

L, whereas nalidixic acid was at 31 μg/L. Treatment plants were effective in achieving 43% 94% reduction in the pharmaceutical compounds (Agunbiade and Moodley, 2014). A study to detect the presence of metabolites of pharmaceutical compounds in water and sediment samples of Msunduzi River, KwaZulu-Natal, South Africa revealed that the concentration of ibuprofen was at 85 and 117 μg/L in surface water and wastewater, respectively. Similarly, antibiotics were present in lower concentrations of .10 and 34.5 μg/L in surface water and wastewater, respectively (Matongo et al., 2015). An analysis of the trends in the presence of contaminants on the aquatic environments of Tanzania showed that amoxicillin along with drugs used for treating malaria such as lumefantrine and artemether were present in the range of 3 32 μg/L (Miraji et al., 2016). Antibiotics and antiretroviral drugs were reported to be present in water samples collected from the Nairobi River Basin, Kenya. Here, concentrations of different compounds were as follows (μg/L): ciprofloxacin 0.5, trimethoprim 2.6, nevirapine 4.8, lamivudine 5.4, zidovudine 7.7, and sulfamethoxazole 13.8 (Ngumba et al., 2016). Water samples representing groundwater and surface water collected from the pharmaceutical industrial area of Sango Ota, Ogun State, in Nigeria revealed the presence of ciprofloxacin paracetamol, chloroquine, and diclofenac at concentrations ranging from 1 to 17 μg/L (Olaitan et al., 2014). Further efforts to establish the quantum of pharmaceuticals and their impact on the environment, a campaign was launched in Lagos, Nigeria. The residues found in sewage sludge and surface waters included ibuprofen up to 8.8 μg/L, whereas diclofenac up to 1100 μg/kg dry weight was detected in sewage sludge (Olarinmoye et al., 2016). Sediment samples gathered from Msunduzi River, KwaZulu-Natal, of South Africa were checked for the presence of acidic pharmaceuticals. Aspirin was reported to be present in the range of 212 427 ng/g, whereas ibuprofen was in the range of 5 11 ng/g, ketoprofen and diclofenac ranged from 7 to 57 and 57 to 309 ng/g, respectively (Agunbiade and Moodley, 2016). In another study, sediments from the same river were reported to be at a high concentration of 659 ng/g (Matongo et al., 2015).

2.2.8 Impact of pharmaceutical and personal care products on health of aquatic organisms Effect of PPCPs on the health of animals and humans has been evaluated quite frequently; however, the real impact is still not clear. There is an inflow of emerging contaminants which are found to persist for longer periods of time in surface waters. Although WWTPs are known to be helpful in removing easily biodegradable compounds, however, PCPPs are not easy to remove. PPCPs used for treating human beings are not always completely degraded during the sewage treatment and may thus contaminate the water bodies. Thus the risk can be high if a large amount of treated sewage wastewater is discharged in to slow flowing water bodies (Ternes et al., 2002; Stackelberg et al., 2004). The real impact of PCPPs on the environment and health human is difficult to evaluate because most of the time they get diluted. However, compounds such as hormones may show their impact easily on the

48

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

aquatic organisms which may affect their reproduction and development even at very low concentrations (Vajda et al., 2008). Sex change in fish due to low concentrations up to few ng/L has been reported due to estrogens—estradiol, estrone, and ethinylestradiol (Jobling et al., 2003; Vajda et al., 2008). Hormonal contraceptives 17α-ethinylestradiol at 2 10 ng/L resulted in inducing synthesis of vitellogenin (generally found only in females) in male Gobiocypris rarus, Oryzias latipes, and Danio rerio (Ma et al., 2005; Zha et al., 2007; Xu et al., 2008). PPCPs present in the effluents of WWTPs have deleterious effects on the reproductive system of aquatic organisms. It was largely because of the accumulation of estrogenic contaminants especially in fish. It consequently resulted in the production of vitellogenin, which could be the cause for the feminization of wild fish (Gibson et al., 2005). Natural and synthetic ED compounds in the water and the living beings in a coastal lagoon in Venice were detected in concentrations up to 211 ng/L and 289 μg/kg dry weight, respectively. Samples taken from Mediterranean mussel (Mytilus galloprovincialis) were found to possess 7.2 240 ng/g in dry weight of 17α-ethinylestradiol and nonylphenol (Pojana et al., 2007). Exposure to pharmaceutical compound levonorgestrel present in the sewage effluents resulted in its accumulation in the blood of rainbow trout at concentrations of 8.5 12 ng/mL (Fick et al., 2010). Tonalide and galaxolide were reported to get accumulated at concentrations 5.5 and 81 ng/g wet weight in bream and tilapia fish from Rhine River, Germany, respectively (Subedi et al., 2011). A survey of the food items present in the local market was found to contain residues of pharmaceuticals items in liver and kidney of lamb, veal, pork, and chicken muscle. The most frequently detected compounds were the antibacterial such as pyrimethamine and florfenicol and hormones such as 17β-estradiol and estrone (Azzouz et al., 2011). A dramatic toxicity caused by livestock exposed to diclofenac was reported from Pakistan by the catastrophic decline in the population of vultures which fed on them. The concentrations in the range of 0.051 0.643 μg/g were found in the kidneys of all 25 vultures which were found to have died due to complete renal failure (Oaks et al., 2004). A wide range of antibiotics were detected in most of the (1) fish species: loach yellow catfish (Pelteobagrus fulvidraco), (Misgurnus anguillicaudatus), topmouth gudgeon (Pseudorasbora parva); (2) crustacean species such as crab (Eriocheir sinensis), river snail (Viviparus), shrimps (Macrobrachium nipponense), and lobster (Palinuridae); and (3) hydrophytes (aquatic plants) such as Hydrocharis dubia, Ceratophyllum demersum, and Salvinia natans collected in Baiyangdian Lake, China. The concentrations of antibiotics in the crustaceans were 129, 253, and 1769 μg/kg, respectively (Li et al., 2012). The presence of antibiotic ciprofloxacin (as high as 795 μg/kg) was also reported in the aquatic plant Echinodorus amazonicus in a simulated microcosmos (Chen et al., 2007; Zhang et al., 2009). Wild species of fish such as carp, crucian carp, and silvery minnow from Dianchi Lake in Southern China were reported to accumulate steroid estrogens up to 11.3 ng/g dry weight. Estrogen accumulation was highest in the liver, which was followed by gills and muscle (Liu et al., 2011). In the aquaculture conditions prevailing Pearl River delta, South China, accumulation of fluoroquinolones in

Pharmaceutical and personal care product contamination: a global scenario

49

Lutjanus argentimaculatus from Hailing Island, Sparus macrocephalus from Dapeng’ao, and Siganus fuscescens from Hailing island was detected up to concentrations of 5, 133, and 255 ng/g wet weight, respectively. Liver was found to have higher concentrations of fluoroquinolones than in muscle tissue. However, both the tissues were found to contain norfloxacin in concentrations higher than those of enrofloxacin and ciprofloxacin (He et al., 2012). There have been studies which showed that benzodiazepines affect fish behavior and their feeding rate, especially when it has been well established that waters worldwide contain a cocktail of different pharmaceutical products (Boxall et al., 2012; Verlicchi et al., 2012). An assessment of the pharmaceuticals, which remain active even after passing through the WWTPs, can cause harm to the aquatic organisms. Benzodiazepine anxiolytic drug oxazepam was even reported to modify the behavior of and feeding rate of wild European perch (Perca fluviatilis). Water carrying drugs even at dilute concentrations of 1.8 μg/L showed an increase in activity, reduction in sociality, and higher feeding rate. It can thus be envisaged that such anxiolytic drugs can lead to changes in the behavior of animals which consequently are likely to affect the ecology and evolution as well (Brodin et al., 2013). Antifungal and antibacterial agents are used while preparing toothpastes, deodorants, and soaps. Triclosan is a major component to make these products effective as cleaning agents. This compound and its metabolic products (e.g., triclocarban) have been reported to be harmful to aquatic living beings (Ishibashi et al., 2004; Dussault et al., 2008; Tamura et al., 2013). In a test study, it was found out that these two compounds can be toxic at different concentrations to different aquatic organisms: 4 35 μg/L for green algae exposed for 72 hours, 7 230 μg/L for daphnia exposed for 48 hours, and 45 340 μg/L for fish exposed for 96 hours, were sufficient to kill at least 50% of the test population (Tamura et al., 2013). Aquatic animals such as mussel, clam, and oyster, present in the Ebro delta, Spain, revealed the presence of psychiatric drug venlafaxine and the antibiotic azithromycin with high frequency. Their concentrations were found to be 3.0 ng/g in oysters and 2.7 ng/g in mussels (Alvarez-Mun˜oz et al., 2015). Persistence of PPCPs in natural freshwater resources has been reported quite often (Kasprzyk-Hordern et al., 2009; Bahlmann et al., 2014; Petrie et al., 2014; Blair et al., 2015). Efforts were made to evaluate the removal of PPCPs including those which have the potential to act as endocrine disruptors, via WWTP following trickling filter beds and activated sludge procedures. Raw sewage was found to contain PPCPs in high loads of up to 10 kg/day. Of the two methods used for WW treatment, trickling filter beds resulted in around 70% removal of 55 PPCPs involved in this study. On the other hand, activated sludge proved effective in achieving up to 85% removal (Kasprzyk-Hordern et al., 2009). Wastewater samples from a different location in two countries, Portugal and Germany, were evaluated for the presence of CBZ and its metabolites. Wastewater samples (effluent and influent) from WWTP analyzed using liquid-chromatography tandem mass spectrometry revealed that the most persistent compounds were (1) 3-hydroxy-CBZ, (2) 10,11-dihydro-10-hydroxy-CBZ (3) 10,11-dihydro-10,11-dihydroxy-CBZ (DiOHCBZ), (10-OH-CBZ), (4) 10,11-epoxy-10,11-dihydro-CBZ, (5) 2-hydroxy-CBZ,

50

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

and their concentrations in the influent and effluent were almost similar. 10-OHCBZ, DiOH-CBZ, and CBZ were found to be present in high concentrations ranging from 1.1 to 5 μg/L. Other pharmaceuticals such as oxcarbazepine and the metabolites: (1) 4-hydroxy-CBZ (4-OH-CBZ), (2) 1-hydroxy-CBZ (1-OH-CBZ), and (3) 9-hydroxymethyl-10-carbamoylacridan were also detectable (Bahlmann et al., 2014). Using activated sludge-based WWTP seems to be inefficient in removing (PPCPs) from wastewater. Out of 57 hormones and PPCPs evaluated in this WWTP, 48 were detected as soluble, whereas 29 were found absorbed to solids. It was realized that certain highly biodegradable PPCPs don’t degrade below a threshold level (Blair et al., 2015). The study carried out to analyze the fate of 55 different compounds passing through the WWTP revealed the presence of 41 of them in the effluent, 40 of them were present in environmental waters which were upstream and downstream of the WWTP. Around 28% of them were found to be removed by approximately 50%, whereas 18% of them were degraded only to around 25%. Three illicit drugs (1) cocaine, (2) mephedrone, and (3) methamphetamine were detected in the ranges of 27 147, 35 120, and 270 450, respectively. Certain of these compounds: (1) ibuprofen, (2) naproxen, (3) diclofenac, and (4) CBZ have an ability to disrupt the endocrine system (Archer et al., 2017). The major issue with the use of PPCPs is their potential to prove toxic even to nontarget organisms (Ebele et al., 2017). An antidepressant is fluoxetine, which is used to target the serotonin 5-hydroxytryptamine (5-HT) signaling pathway. Since this compound has great significance on aquatic organisms, any change in its metabolism is likely to have an adverse effect on reproduction, locomotion in mussels even at very low concentrations (Franzellitti et al., 2013; Ford and Fong, 2016). The presence of PPCPs especially those which are likely to adversely influence the endocrine system in aquatic animals is a worry for the aquaculture industry. Quite a few PPCPs especially consumer products have been classified as endocrine disruptors: (1) naturally occurring mycotoxins and phytoestrogens, and (2) synthetic—diethylstilbestrol and bisphenol A (Wielogo´rska et al., 2015). These compounds in isolation may not elicit any adverse response; however, together, they may prove highly toxic (Cleuvers, 2003). Combination of two different therapeutic drugs such as (1) the antiepileptic drug e CBZ and the lipid-lowering agent clofibric acid affected Daphnia magna in a drastic manner (Thorpe et al., 2001), (2) 4-tert-nonylphenol and estradiol behaved in additive or synergistic manner leading to the production of vitellogenin in juvenile rainbow trout. Effect of diclofenac at a concentration of 5 50 μg/L affected the gill integrity, kidney, and a few immune parameters in the brown trout—a salmonid species found in rivers in Germany (Hoeger et al., 2005). Exposing freshwater fish Leuciscus cephalus to 17β-estradiol resulted in a significant increase in plasma vitellogenin (Flammarion et al., 2000). Goldfish (Carassius auratus) exposed to gemfibrozil led to the reduction of plasma testosterone by more than 50% after a period of 14 days of treatment (Mimeault et al., 2005). Another risk with the persistence of PPCPs in water is the possibility of bacteria developing resistance to antibiotics. In fact, antibiotics used extensively to keep animals healthy and treating human infections has already been shown to be responsible for the emergence of antibiotic-resistant microbes (Davies et al., 2006;

Pharmaceutical and personal care product contamination: a global scenario

51

WHO, 2015). Effluents of a WWTP in Australia were found to contain a diverse range of antibiotics: erythromycin, ampicillin, tetracycline, trimethoprim, ciprofloxacin, and trimethoprim/sulfamethoxazole. Bacterial strains occurring in the WWTP were reported to have enhanced antibiotic resistance (Costanzo et al., 2005). Similar observations were reported also due to antibiotic causing contamination in aquatic bodies (Novo et al., 2013) and toxicity due to antibiotic ciprofloxacin was reported on green algae (Halling-Sørensen et al., 2000). A feed additive (oxolinic acid) used in fish farms was reported to prove toxic to D. magna. Similarly, fluoroquinolone antibiotics (lumequine, enrofloxacin, lomefloxacin, ciprofloxacin, and ofloxacin) were found to be toxic against aquatic organisms: (1) duckweed (Microcystis aeruginosa), (2) the green alga (Lemna minor), (3) the cyanobacterium, (4) the crustacean (Pseudokirchneriella subcapitata), D. magna, fathead minnow (Pimephales promelas) (Robinson et al., 2005). It has been observed that the presence of PPCPs in aquatic systems can prove toxic even to nontarget organisms leading to abnormal growth and development (Wilkinson et al., 2016). In addition, there have been cases, such as in certain rotifers, microcrustaceans, and algae, where acetylated or photodegraded products of the sulfapyridine and naproxen turned out to be more toxic than the parent compound (Isidori et al., 2005; Garcı´a-Gala´n et al., 2012). A change in physiological conditions such as pH or accumulation of metals in biofilms also causes enhanced toxicity, for example, due to antibiotics fluoroquinolones and tetracyclines (Zhang et al., 2012).

2.2.9 Opinion WWTPs are expected to provide a solution for the discharge of relatively clean waters. However, as revealed above through a large number of studies, most PPCPs get diluted but don’t get metabolized. It may be desirable to introduce microbes which can specifically target certain components of PPCPs and clean the environment (Deshmukh et al., 2016; Dwivedi et al., 2018).

Acknowledgments This work was supported by Brain Pool grant (NRF-2018H1D3A2001746) by National Research Foundation of Korea (NRF) to work at Konkuk University.

References Agunbiade, F.O., Moodley, B., 2016. Occurrence and distribution pattern of acidic pharmaceuticals in surface water, wastewater, and sediment of the Msunduzi River, KwazuluNatal, South Africa. Environ. Toxicol. Chem. 35, 36 46. Agunbiade, F.O., Moodley, B., 2014. Pharmaceuticals as emerging organic contaminants in Umgeni River water system, KwaZulu-Natal, South Africa. Environ. Monit. Assess. 186, 7273 7291.

52

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

Al Aukidy, M., Verlicchi, P., Jelic, A., Petrovic, M., Barcelo`, D., 2012. Monitoring release of pharmaceutical compounds: occurrence and environmental risk assessment of two WWTP effluents and their receiving bodies in the Po Valley, Italy. Sci. Total Environ. 438, 15 25. Alvarez-Mun˜oz, D., Huerta, B., Fernandez-Tejedor, M., Rodrı´guez-Mozaz, S., Barcelo´, D., 2015. Multi-residue method for the analysis of pharmaceuticals and some of their metabolites in bivalves. Talanta 136, 174 182. Archer, E., Petrie, B., Kasprzyk-Hordern, B., Wolfaardt, G.M., 2017. The fate of pharmaceuticals and personal care products (PPCPs), endocrine disrupting contaminants (EDCs), metabolites and illicit drugs in a WWTW and environmental waters. Chemosphere 174, 437 446. Arikan, O.A., Rice, C., Codling, E., 2008. Occurrence of antibiotics and hormones in a major agricultural watershed. Desalination 226, 121 133. Ashton, D., Hilton, M., Thomas, K.V., 2004. Investigating the environmental transport of human pharmaceuticals to streams in the United Kingdom. Sci. Total Environ. 333, 167 184. Aydin, E., Talini, I., 2013. Analysis, occurrence and fate of commonly used pharmaceuticals and hormones in the Buyukcekmece Watershed, Turkey. Chemosphere 90, 2004 2012. Azzouz, A., Souhail, B., Ballesteros, E., 2011. Determination of residual pharmaceuticals in edible animal tissues by continuous solid-phase extraction and gas chromatographymass spectrometry. Talanta 84, 820 828. Bahlmann, A., Brack, W., Schneider, R.J., Krauss, M., 2014. Carbamazepine and its metabolites in wastewater: analytical pitfalls and occurrence in Germany and Portugal. Water Res. 57, 104 114. Baker, D.R., Kasprzyk-Hordern, B., 2013. Spatial and temporal occurrence of pharmaceuticals and illicit drugs in the aqueous environment and during wastewater treatment: new developments. Sci. Total Environ. 454-455, 442 456. Barnes, K.K., Kolpin, D.W., Furlong, E.T., Zaugg, S.D., Meyer, M.T., Barber, L.B., 2008. A national reconnaissance of pharmaceuticals and other organic wastewater contaminants in the United States I) Groundwater. Sci. Total Environ. 402, 192 200. Batt, A.L., Bruce, I.B., Aga, D.S., 2006. Evaluating the vulnerability of surface waters to antibiotic contamination from varying wastewater treatment plant discharges. Environ. Pollut. 142, 295 302. Beeton, A.M., 2002. Large freshwater lakes: present state, trends, and future. Environ. Conserv. 29, 21 38. Bendz, D., Paxe´us, N.A., Ginn, T.R., Loge, F.J., 2005. Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Ho¨je River in Sweden. J. Hazard. Mater. 122, 195 204. Benotti, M.J., Trenholm, R.A., Vanderford, B.J., Holady, J.C., Stanford, B.D., Snyder, S.A., 2009. Pharmaceuticals and endocrine disrupting compounds in US drinking water. Environ. Sci. Technol. 43, 597 603. Bester, K., 2005. Fate of triclosan and triclosan-methyl in sewage treatment plants and surface waters. Arch. Environ. Contam. Toxicol. 49, 9 17. Blair, B., Crago, J.P., Hedman, C.J., Klaper, R.D., 2013a. Pharmaceuticals and personal care products in the Great Lakes above concentrations of environmental concern. Chemosphere 93, 2116 2123. Blair, B., Nikolaus, A., Hedman, C., Klaper, R., Grundl, T., 2015. Evaluating the degradation, sorption, and negative mass balances of pharmaceuticals and personal care products during wastewater treatment. Chemosphere 134, 395 401.

Pharmaceutical and personal care product contamination: a global scenario

53

Blair, B.D., Crago, J.P., Hedman, C., Treguer, R.J.F., Magruder, C., Royer, L.S., et al., 2013b. Evaluation of a model for the removal of pharmaceuticals, personal care products, and hormones from wastewater. Sci. Total Environ. 444, 515 521. Boxall, A.B., Rudd, M.A., Brooks, B.W., Caldwell, D.J., Choi, K., Hickmann, S., et al., 2012. Pharmaceuticals and personal care products in the environment: what are the big questions? Environ. Health Perspect. 120, 1221 1229. Brodin, T., Fick, J., Jonsson, M., Klaminder, J., 2013. Dilute concentrations of a psychiatric drug alter behavior of fish from natural populations. Science 339, 814 815. Brooks, B.W., Chambliss, C.K., Stanley, J.K., Ramirez, A., Banks, K.E., Johnson, R.D., et al., 2005. Determination of select antidepressants in fish from an effluent dominated stream. Environ. Toxicol. Chem. 24, 464 469. Buser, H.-R., Mu¨ller, M.D., Theobald, N., 1998a. Occurrence of the pharmaceutical drug clofibric acid and the herbicide mecoprop in various Swiss lakes and in the Northsea. Environ. Sci. Technol. 32, 188 192. Buser, H.-R., Poiger, T., Mu¨ller, M.D., 1998b. Occurrence and fate of the pharmaceutical drug diclofenac in surface Waters: rapid photodegradation in a lake. Environ. Sci. Technol. 32, 3449 3456. Buser, H.-R., Poiger, T., Mu¨ller, M.D., 1999. Occurrence and environmental behavior of the chiral pharmaceutical drug ibuprofen in surface waters and in wastewater. Environ. Sci. Technol. 33, 2529 2535. Calamari, D., Zuccato, E., Castiglioni, S., Bagnati, R., Fanelli, R., 2003. Strategic survey of therapeutic drugs in the rivers Po and Lambro in northern Italy. Environ. Sci. Technol. 37, 1241 1248. Chen, J.F., Zhou, X.Z., Nie, X.P., Jiang, T.J., 2007. Fate of Ciprofloxacin in a simulated micro-cosmos system by different exposure ways. Shengtai Xuebao/Acta Ecol. Sin. 27, 5300 5307. Choi, K., Kim, Y., Park, J., Park, C.K., Kim, M., Kim, H.S., et al., 2008. Seasonal variations of several pharmaceutical residues in surface water and sewage treatment plants of Han River, Korea. Sci. Total Environ. 405, 120 128. Christensen, A.M., Markussen, B., Baun, A., Halling-Sorensen, B., 2009. Probabilistic environmental risk characterization of pharmaceuticals in sewage treatment plant discharges. Chemosphere 77, 351 358. Cleuvers, M., 2003. Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicol. Lett. 142, 185 194. Costanzo, S.D., Murby, J., Bates, J., 2005. Ecosystem response to antibiotics entering the aquatic environment. Mar. Pollut. Bull. 51, 218 223. Davies, J., Spiegelman, G.B., Yim, G., 2006. The world of sub-inhibitory antibiotic concentrations. Curr. Opin. Microbiol. 9, 445 453. Deshmukh, R., Khardenavis, A.A., Purohit, H.J., 2016. Diverse metabolic capacities of fungi for bioremediation. Indian J. Microbiol. 56, 247 264. Dussault, E`.B., Balakrishnan, V.K., Sverko, E., Solomon, K.R., Sibley, P.K., 2008. Toxicity of human pharmaceuticals and personal care products to benthic invertebrates. Environ. Toxicol. Chem. 27, 425 432. Dwivedi, K., Rudrashetti, A.P., Chakrabarti, T., Pandey, R.A., 2018. Transformation products of carbamazepine (CBZ) after ozonation and their toxicity evaluation using Pseudomonas sp. strain KSH-1 in aqueous matrices. Indian J. Microbiol. 58, 193 200. Ebele, A.J., Abdallah, M.A.E., Harrad, S., 2017. Pharmaceuticals and personal care products (PPCPs) in the freshwater aquatic environment. Emerg. Contam. 3, 1 16.

54

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

Fairbairn, D.J., Karpuzcu, M.E., Arnold, W.A., Barber, B.L., Kaufenberg, E.F., Koskinen, W. C., et al., 2016. Sources and transport of contaminants of emerging concern: a two-year study of occurrence and spatiotemporal variation in a mixed land use watershed. Sci. Total Environ. 551-552, 605 613. Fang, T.-H., Nan, F.-H., Chin, T.-S., Feng, H.-M., 2012. The occurrence and distribution of pharmaceutical compounds in the effluents of a major sewage treatment plant in Northern Taiwan and the receiving coastal waters. Mar. Pollut. Bull. 64, 1435 1444. Ferrari, B., Mons, R., Vollat, B., Fraysse, B., Paxe´us, N., Giudice, R.L., et al., 2004. Environmental risk assessment of six human pharmaceuticals: are the current environmental risk assessment procedures sufficient for the protection of the aquatic environment? Environ. Toxicol. Chem. 23, 1344 1354. Ferreira, A.P., 2014a. Identification quantification ibuprofen conventional wastewater treatment plants Rio de Janeiro, Brazil their discharge to the aquatic environment. J. Adv. Biol. 4, 305. Ferreira, A.P., 2014b. Environmental investigation of psychiatric pharmaceuticals: Guandu River, Rio de Janeiro state, Southeast Brazil. J. Chem. Health Risk 4, 25 32. Fick, J., So¨derstro¨m, H., Lindberg, R.H., Phan, C., Tysklind, M., Larsson, D.G.J., 2009. Contamination of surface, ground, and drinking water from pharmaceutical production. Environ. Toxicol. Chem. 28, 2522 2527. Fick, J., Lindberg, R.H., Parkkonen, J., Arvidsson, B., Tysklind, M., Larsson, D.G.J., 2010. Therapeutic levels of levonorgestrel detected in blood plasma of fish: results from screening rainbow trout exposed to treated sewage effluents. Environ. Sci. Technol. 44, 2661 2666. Flammarion, P., Brion, F., Babut, M., Garric, J., Migeon, B., Noury, P., et al., 2000. Induction of fish vitellogenin and alterations in testicular structure: preliminary results of estrogenic effects in chub (Leuciscus cephalus). Ecotoxicology 9, 127 135. Focazio, M.J., Kolpin, D.W., Barnes, K.K., Furlong, E.T., Meyer, M.T., Zaugg, S.D., et al., 2008. A national reconnaissance for pharmaceuticals and other organic wastewater contaminants in the United States—II) untreated drinking water sources. Sci. Total Environ. 402, 201 216. Ford, A.T., Fong, P.P., 2016. The effects of antidepressants appear to be rapid and at environmentally relevant concentrations. Environ. Toxicol. Chem. 35, 794 798. Fram, M.S., Belitz, K., 2011. Occurrence and concentrations of pharmaceutical compounds in groundwater used for public drinking-water supply in California. Sci. Total Environ. 409, 3409 3417. Franzellitti, S., Buratti, S., Valbonesi, P., Fabbri, E., 2013. The mode of action (MOA) approach reveals interactive effects of environmental pharmaceuticals on Mytilus galloprovincialis. Aquat. Toxicol. 140-141, 249 256. Garcı´a-Gala´n, M.J., Gonza´lez Blanco, S., Lo´pez Rolda´n, R., Dı´az-Cruz, S., Barcelo´, D., 2012. Ecotoxicity evaluation and removal of sulfonamides and their acetylated metabolites during conventional wastewater treatment. Sci. Total Environ. 437, 403 412. Gelsleichter, J., Szabo, N.J., 2013. Uptake of human pharmaceuticals in bull sharks (Carcharhinus leucas) inhabiting a wastewater-impacted river. Sci. Total Environ. 456457, 196 201. Gibson, R., Smith, M.D., Spary, C.J., Tyler, C.R., Hill, E.M., 2005. Mixtures of estrogenic contaminants in bile of fish exposed to wastewater treatment works effluents. Environ. Sci. Technol. 39, 2461 2471. Gibson, R., Duran-Alvarez, J.C., Estrada, K.L., Chavez, A., Jimenez Cisneros, B., 2010. Accumulation and leaching potential of some pharmaceuticals and potential endocrine

Pharmaceutical and personal care product contamination: a global scenario

55

disruptors in soils irrigated with wastewater in the Tula Valley, Mexico. Chemosphere 81, 1437 1445. Gros, M., Petrovic, M., Ginebreda, A., Barcelo, D., 2010. Removal of pharmaceuticals during wastewater treatment and environmental risk assessment using hazard indexes. Environ. Int. 36, 15 26. Halling-Sørensen, B., Lu¨tzhøft, H.-C.H., Andersen, H.R., Ingerslev, F., 2000. Environmental risk assessment of antibiotics: comparison of mecillinam, trimethoprim and ciprofloxacin. J. Antimicrob. Chemother. 46, 53 58. He, X., Wang, Z., Nie, X., Yang, Y., Pan, D., Leung, A.O.W., et al., 2012. Residues of fluoroquinolones in marine aquaculture environment of the Pearl River delta, South China. Environ. Geochem. Health 34, 323 335. Hedgespeth, M.L., Sapozhnikova, Y., Pennington, P., Clum, A., Fairey, A., Wirth, E., 2012. Pharmaceuticals and personal care products (PPCPS) in treated wastewater discharges into Charleston Harbor, South Carolina. Sci. Total Environ. 437, 1 9. Hilton, M.J., Thomas, K.V., 2003. Determination of selected human pharmaceutical compounds in effluent and surface water samples by high-performance liquid chromatography electrospray tandem mass spectrometry. J. Chromatogr. A 1015, 129 141. Hirsch, R., Ternes, T., Haberer, K., Kratz, K.-L., 1999. Occurrence of antibiotics in the aquatic environment. Sci. Total Environ. 225, 109 118. Hoeger, B., Ko¨llner, B., Dietrich, D.R., Hitzfeld, B., 2005. Water-borne diclofenac affects kidney and gill integrity and selected immune parameters in brown trout (Salmo trutta f. fario). Aquat. Toxicol. 75, 53 64. Hu, X., Zhou, Q., Luo, Y., 2010. Occurrence and source analysis of typical veterinary antibiotics in manure, soil, vegetables and groundwater from organic vegetable bases, northern China. Environ. Pollut. 158, 2992 2998. Huang, C.H., Sedlak, D.L., 2001. Analysis of estrogenic hormones in municipal wastewater effluent and surface water using enzyme-linked immunosorbent assay and gas chromatography/tandem mass spectrometry. Environ. Toxicol. Chem. 20, 133 139. Huppert, N., Wu¨rtele, M., Hahn, H.H., 1998. Determination of the plasticizer butylbenzenesulfonamide and the pharmaceutical Ibuprofen in wastewater using solid phase microextraction (SPME). Fresenius’ J. Anal. Chem. 362, 529 536. Ishibashi, H., Matsumura, N., Hirano, M., Matsuoka, M., Shiratsuchi, H., Ishibashi, Y., et al., 2004. Effects of triclosan on the early life stages and reproduction of Medaka Oryzias latipes and induction of hepatic vitellogenin. Aquat. Toxicol. 67, 167 179. Isidori, M., Lavorgna, M., Nardelli, A., Parrella, A., Previtera, L., Rubino, M., 2005. Ecotoxicity of naproxen and its phototransformation products. Sci. Total Environ. 348, 93 101. Jobling, S., Casey, D., Rodgers-Gray, T., Oehlmann, J., Schulte-Oehlmann, U., Pawlowski, S., et al., 2003. Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent. Aquat. Toxicol. 65, 205 220. K’oreje, K.O., Demeestere, K., De Wispelaere, P., Vergeynst, L., Dewulf, J., Van Langenhove, H., 2012. From multi-residue screening to target analysis of pharmaceuticals in water: development of a new approach based on magnetic sector mass spectrometry and application in the Nairobi River basin, Kenya. Sci. Total Environ. 437, 153 164. 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. Kasprzyk-Hordern, B., Dinsdale, R.M., Guwy, A.J., 2009. The removal of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs during wastewater treatment and its impact on the quality of receiving waters. Water Res. 43, 363 380.

56

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

Kim, J.-W., Jang, H.-S., Kim, J.-G., Ishibashi, H., Hirano, M., Nasu, K., et al., 2009. Occurrence of pharmaceutical and personal care products (PPCPs) in surface water from Mankyung River, South Korea. J. Health Sci. 55, 249 258. Kim, S.D., Cho, J., Kim, I.S., Vanderford, B.J., Snyder, S.A., 2007. Occurrence and removal of pharmaceuticals and endocrine disruptors in South Korean surface, drinking, and waste waters. Water Res. 41, 1013 1021. Kinney, C.A., Furlong, E.T., Werner, S.L., Cahill, J.D., 2006. Presence and distribution of wastewater-derived pharmaceuticals in soil irrigated with reclaimed water. Environ. Toxicol. Chem. 25, 317 326. Klosterhaus, S.L., Grace, R., Hamilton, M.C., Yee, D., 2013. Method validation and reconnaissance of pharmaceuticals, personal care products, and alkylphenols in surface waters, sediments, and mussels in an urban estuary. Environ. Int. 54, 92 99. Kolpin, D.W., Furlong, E.T., Meyer, M.T., Thurman, E.M., Zaugg, S.D., Barber, L.B., et al., 2002. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999 2000: a National Reconnaissance. Environ. Sci. Technol. 36, 1202 1211. Kugathas, S., Williams, R.J., Sumpter, J.P., 2012. Prediction of environmental concentrations of glucocorticoids: the River Thames, UK, as an example. Environ. Int. 40, 15 23. Lapworth, D.J., Baran, N., Stuart, M.E., Ward, R.S., 2012. Emerging organic contaminants in groundwater: a review of sources, fate and occurrence. Environ. Pollut. 163, 287 303. Larsson, D.G.J., De Pedro, C., Paxeus, N., 2007. Effluent from drug manufactures contains extremely high levels of pharmaceuticals. J. Hazard. Mater. 148, 751 755. Lei, B., Huang, S., Zhou, Y., Wang, D., Wang, Z., 2009. Levels of six estrogens in water and sediment from three rivers in Tianjin area, China. Chemosphere 76, 36 42. Li, W., Shi, Y., Gao, L., Liu, J., Cai, Y., 2012. Occurrence of antibiotics in water, sediments, aquatic plants, and animals from Baiyangdian Lake in North China. Chemosphere 89, 1307 1315. Lin, W.-C., Chen, H.-C., Ding, W.-H., 2005. Determination of pharmaceutical residues in waters by solid-phase extraction and large-volume on-line derivatization with gas chromatography-mass spectrometry. J. Chromatogr. A 1065, 279 285. Liu, H., Zhang, G., Liu, C.Q., Li, L., Xiang, M., 2009. The occurrence of chloramphenicol and tetracyclines in municipal sewage and the Nanming River, Guiyang City, China. J. Environ. Monit. 2009 (2009), 1199 1205. Liu, J., Wang, R., Huang, B., Lin, C., Wang, Y., Pan, X., 2011. Distribution and bioaccumulation of steroidal and phenolic endocrine disrupting chemicals in wild fish species from Dianchi Lake, China. Environ. Pollut. 159, 2815 2822. Lo¨ffler, D., Ternes, T.A., 2003. Determination of acidic pharmaceuticals, antibiotics and ivermectin in river sediment using liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 1021, 133 144. Loos, R., Gawlik, B.M., Locoro, G., Rimaviciute, E., Contini, S., Bidoglio, G., 2009. EU wide survey of polar organic persistent pollutants in European river waters. Environ. Pollut. 157, 561 568. Luo, Y., Xu, L., Rysz, M., Wang, Y., Zhang, H., Alvarez, P.J.J., 2011. Occurrence and transport of tetracycline, sulfonamide, quinolone, and macrolide antibiotics in the Haihe River basin, China. Environ. Sci. Technol. 45, 1827 1833. Ma, R., Wang, B., Lu, S., Zhang, Y., Yin, L., Huang, J., et al., 2016. Characterization of pharmaceutically active compounds in Dongting Lake, China: occurrence, chiral profiling and environmental risk. Sci. Total Environ. 557-558, 268 275.

Pharmaceutical and personal care product contamination: a global scenario

57

Ma, T., Wan, X., Huang, Q., Wang, Z., Liu, J., 2005. Biomarker responses and reproductive toxicity of the effluent from a Chinese large sewage treatment plant in Japanese medaka (Oryzias latipes). Chemosphere 59, 281 288. Managaki, S., Murata, A., Takada, H., Tuyen, B.C., Chiem, N.H., 2007. Distribution of macrolides, sulfonamides, and trimethoprim in tropical waters: ubiquitous occurrence of veterinary antibiotics in the Mekong delta. Environ. Sci. Technol. 41, 8004 8010. Martı´n, J., Santos, J.L., Aparicio, I., Alonso, E., 2010. Multi-residue method for the analysis of pharmaceutical compounds in sewage sludge, compost and sediments by sonicationassisted extraction and LC determination. J. Sep. Sci. 33, 1760 1766. Matongo, S., Birungi, G., Moodley, B., Ndungu, P., 2015. Pharmaceutical residues in water and sediment of Msunduzi River, KwaZulu-Natal, South Africa. Chemosphere 134, 133 140. Meierjohann, A., Brozinski, J.-M., Kronberg, L., 2016. Seasonal variation of pharmaceutical concentrations in a river/lake system in Eastern Finland. Environ. Sci. Process Impacts 18, 342 349. Metcalfe, C.D., Koenig, B.G., Bennie, D.T., Servos, M., Ternes, T.A., Hirsch, R., 2003a. Occurrence of neutral and acidic drugs in the effluents of Canadian sewage treatment plants. Environ. Toxicol. Chem. 22, 2872 2880. Metcalfe, C.D., Miao, X.S., Koenig, B.G., Struger, J., 2003b. Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada. Environ. Toxicol. Chem. 22, 2881 2889. Miller, K.J., Meek, J., 2006. Helena Valley ground water: pharmaceuticals, personal care products, endocrine disruptors (PPCPs) and microbial indicators of fecal contamination. Montana Bureau of Mines and Geology, Open File Report. 532. Available from: http:// www.mbmg.mtech.edu/pdf-open-files/mbmg532-helenavalley.pdf. Mimeault, C., Woodhouse, A.J., Miao, X.S., Metcalfe, C.D., Moon, T.W., Trudeau, V.L., 2005. The human lipid regulator, gemfibrozil bioconcentrates and reduces testosterone in the goldfish, Carassius auratus. Aquat. Toxicol. 73, 44 54. Miraji, H., Othman, O.C., Ngassapa, F.N., Mureithi, E.W., 2016. Research trends in emerging contaminants on the aquatic environments of Tanzania. Scientifica (Cairo) 2016, 3769690. Mottaleb, M.A., Usenko, S., O’donnell, J.G., Ramirez, A.J., Brooks, B.W., Chambliss, C.K., 2013. Gas chromatography mass spectrometry screening methods for select UV filters, synthetic musks, alkylphenols, an antimicrobial agent, and an insect repellent in fish. J. Chromatogr. A 1216, 815 823. Ngumba, E., Gachanja, A., Tuhkanen, T., 2016. Occurrence of selected antibiotics and antiretroviral drugs in Nairobi River Basin, Kenya. Sci. Total Environ. 539, 206 213. Novo, A., Andre, S., Viana, P., Nunes, O.C., Manaia, C.M., 2013. Antibiotic resistance, antimicrobial residues and bacterial community composition in urban wastewater. Water Res. 47, 1875 1887. Oaks, J.L., Gilbert, M., Virani, M.Z., Watson, R.T., Meteyer, C.U., Rideout, B.A., et al., 2004. Diclofenac residues as the cause of vulture population decline in Pakistan. Nature 427, 630 633. Olaitan, O.J., Anyakora, C., Bamiro, T., Tella, A.T., 2014. Determination of pharmaceutical compounds in surface and underground water by solid phase extraction-liquid chromatography. J. Environ. Chem. Excotoxicol. 6, 20 26. Olarinmoye, O., Bakare, A., Ugwumba, O., Hein, A., 2016. Quantification of pharmaceutical residues in wastewater impacted surface waters and sewage sludge from Lagos, Nigeria. J. Environ. Chem. Excotoxicol. 8, 14 24.

58

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

WHO, 2015. Antibiotic Resistance: Multi-Country Public Awareness Survey. In: Organisation, W.H. (Ed.), World Health Organisation. Available from:http://apps.who. int/medicinedocs/documents/s22245en/s22245en.pdf Osorio, V., Larran˜aga, A., Acen˜a, J., Pe´rez, S., Barcelo´, D., 2016. Concentration and risk of pharmaceuticals in freshwater systems are related to the population density and the livestock units in Iberian Rivers. Sci. Total Environ. 540, 267 277. Pedrouzo, M., Borrull, F., Marce, R.M., Pocurull, E., 2009. Ultra-high-performance liquid chromatography tandem mass spectrometry for determining the presence of eleven personal care products in surface and wastewaters. J. Chromatogr. A 1216, 6994 7000. Peng, X., Yu, Y., Tang, C., Tan, J., Huang, Q., Wang, Z., 2008. Occurrence of steroid estrogens, endocrine-disrupting phenols, and acid pharmaceutical residues in urban riverine water of the Pearl River Delta, South China. Sci. Total Environ. 397, 158 166. Petrie, B., Barden, R., Kasprzyk-Hordern, B., 2014. A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring. Water Res. 72, 3 27. Pojana, G., Gomiero, A., Jonkers, N., Marcomini, A., 2007. Natural and synthetic endocrine disrupting compounds (EDCs) in water, sediment and biota of a coastal lagoon. Environ. Int. 33, 929 936. Ramaswamy, B.R., Shanmugam, G., Velu, G., Rengarajan, B., Larsson, D.G.J., 2011. GCMS analysis and ecotoxicological risk assessment of triclosan, carbamazepine and parabens in Indian rivers. J. Hazard. Mater. 186, 1586 1593. Ramirez, A.J., Mottaleb, M.A., Brooks, B.W., Chambliss, C.K., 2007. Analysis of pharmaceuticals in fish using liquid chromatography-tandem mass spectrometry. Anal. Chem. 79, 3155 3163. Ramirez, A.J., Brain, R.A., Usenko, S., Mottaleb, M.A., O’donnell, J.G., Stahl, L.L., et al., 2009. Occurrence of pharmaceuticals and personal care products in fish: results of a national pilot study in the United States. Environ. Toxicol. Chem. 28, 2587 2597. Richardson, M.L., Bowron, J.M., 1985. The fate of pharmaceutical chemicals in the aquatic environment. J. Pharm. Pharmacol. 37, 1 12. Roberts, P.H., Thomas, K.V., 2006. The occurrence of selected pharmaceuticals in wastewater effluent and surface waters of the lower Tyne catchment. Sci. Total Environ. 356, 143 153. Robinson, A.A., Belden, J.B., Lydy, M.J., 2005. Toxicity of fluoroquinolone antibiotics to aquatic organisms. Environ. Toxicol. Chem. 24, 423 430. Salgado, R., Noronha, J.P., Oehmen, A., Carvalho, G., Reis, M.A.M., 2010. Analysis of 65 pharmaceuticals and personal care products in 5 wastewater treatment plants in Portugal using a simplified analytical methodology. Water Sci. Technol. 62, 2862 2871. Schaider, L.A., Rudel, R.A., Ackerman, J.M., Dunagan, S.C., Brody, J.G., 2014. Pharmaceuticals, perfluorosurfactants, and other organic wastewater compounds in public drinking water wells in a shallow sand and gravel aquifer. Sci. Total Environ. 468469, 384 393. Schultz, M.M., Furlong, E.T., Kolpin, D.W., Werner, S.L., Schoenfuss, H.L., Barber, L.B., et al., 2010. Antidepressant pharmaceuticals in two U.S. Effluent-impacted streams: occurrence and fate in water and sediment, and selective uptake in fish neural tissue. Environ. Sci. Technol. 44, 1918 1925. Scott, P.D., Bartkow, M., Blockwell, S.J., Coleman, H.M., Khan, S.J., Lim, R., et al., 2014. A national survey of trace organic contaminants in Australian rivers. J. Environ. Qual. 43, 1702 1712.

Pharmaceutical and personal care product contamination: a global scenario

59

Sim, W.J., Lee, J.W., Lee, E.S., Shin, S.K., Hwang, S.R., Oh, J.E., 2011. Occurrence and distribution of pharmaceuticals in wastewater from households, livestock farms, hospitals and pharmaceutical manufactures. Chemosphere 82, 179 186. Stackelberg, P.E., Furlong, E.T., Meyer, M.T., Zaugg, S.D., Henderson, A.K., Reissman, D. B., 2004. Persistence of pharmaceutical compounds and other organic wastewater contaminants in a conventional drinking-water treatment plant. Sci. Total Environ. 329, 99 113. Stewart, M., Olsen, G., Hickey, C.W., Ferreira, B., Jeli´c, A., Petrovi´c, M., et al., 2014. A survey of emerging contaminants in the estuarine receiving environment around Auckland, New Zealand. Sci. Total Environ. 468-469, 202 210. Stumpf, M., Ternes, T.A., Wilken, R.-D., Silvana Vianna, R., Baumann, W., 1999. Polar drug residues in sewage and natural waters in the state of Rio de Janeiro, Brazil. Sci. Total Environ. 225, 135 141. Subedi, B., Mottaleb, M.A., Chambliss, C.K., Usenko, S., 2011. Simultaneous analysis of select pharmaceuticals and personal care products in fish tissue using pressurized liquid extraction combined with silica gel cleanup. J. Chromatogr. A 1218, 6278 6284. Tamura, I., Kagota, K., Yasuda, Y., Yoneda, S., Morita, J., Nakada, N., et al., 2013. Ecotoxicity and screening level ecotoxicological risk assessment of five antimicrobial agents: triclosan, triclocarban, resorcinol, phenoxyethanol and p-thymol. J. Appl. Toxicol. 33, 1222 1229. Ternes, T., Bonerz, M., Schmidt, T., 2001. Determination of neutral pharmaceuticals in wastewater and rivers by liquid chromatography-electrospray tandem mass spectrometry. J. Chromatogr. A 938, 175 185. Ternes, T.A., 1998. Occurrence of drugs in German sewage treatment plants and rivers. Water Res. 32, 3245 3260. Ternes, T.A., Meisenheimer, M., McDowell, D., Sacher, F., Brauch Jr., H., et al., 2002. Removal of pharmaceuticals during drinking water treatment. Environ. Sci. Technol. 36, 3855 3863. Tewari, S., Jindal, R., Kho, Y.L., Eo, S., Choi, K., 2013. Major pharmaceutical residues in wastewater treatment plants and receiving waters in Bangkok, Thailand, and associated ecological risks. Chemosphere 91, 697 704. Thomas, K.V., Hilton, M.J., 2004. The occurrence of selected human pharmaceutical compounds in UK estuaries. Mar. Pollut. Bull. 49, 436 444. Thorpe, K.L., Hutchinson, T.H., Hetheridge, M.J., Scholze, M., Sumpter, J.P., Tyler, C.R., 2001. Assessing the biological potency of binary mixtures of environmental estrogens using vitellogenin induction in juvenile rainbow trout (Oncorhynchus mykiss). Environ. Sci. Technol. 35, 2476 2481. Vajda, A.M., Barber, L.B., Gray, J.L., Lopez, E.M., Woodling, J.D., Norris, D.O., 2008. Reproductive disruption in fish downstream from an estrogenic wastewater effluent. Environ. Sci. Technol. 42, 3407 3414. Varga, M., Dobor, J., Helenkar, A., Jurecska, L., Yao, J., Za´ray, G., 2010. Investigation of acidic pharmaceuticals in river water and sediment by microwave-assisted extraction and gas chromatography mass spectrometry. Microchem. J. 95, 353 358. Venkatesan, A.K., Pycke, B.F.G., Barber, L.B., Lee, K.E., Halden, R.U., 2012. Occurrence of triclosan, triclocarban, and its lesser chlorinated congeners in Minnesota freshwater sediments collected near wastewater treatment plants. J. Hazard. Mater. 229-230, 29 35. Verenitch, S.S., Lowe, C.J., Mazumder, A., 2006. Determination of acidic drugs and caffeine in municipal wastewaters and receiving waters by gas chromatography ion trap tandem mass spectrometry. J. Chromatogr. A 1116, 193 203.

60

Pharmaceuticals and Personal Care Products: Waste Management and Treatment Technology

Verlicchi, P., Al Aukidy, M., Zambello, E., 2012. Occurrence of pharmaceutical compounds in urban wastewater: removal, mass load and environmental risk after a secondary treatment—a review. Sci. Total Environ. 429, 123 155. 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. Whitacre, D.M., 2011. Reviews of Environmental Contamination and Toxicology., 202. Springer, pp. 79 84. Wiegel, S., Aulinger, A., Brockmeyer, R., Harms, H., Lo¨ffler, J., Reincke, H., et al., 2004. Pharmaceuticals in the river Elbe and its tributaries. Chemosphere 57, 107 126. Wielogo´rska, E., Elliott, C.T., Danaher, M., Chevallier, O., Connolly, L., 2015. Validation of an ultrahigh performance liquid chromatography-tandem mass spectrometry method for detection and quantitation of 19 endocrine disruptors in milk. Food Control 48, 48 55. Wilkinson, J.L., Hooda, P.S., Barker, J., Barton, S., Swinden, J., 2016. Ecotoxic pharmaceuticals, personal care products, and other emerging contaminants: a review of environmental, receptor-mediated, developmental, and epigenetic toxicity with discussion of proposed toxicity to humans. Crit. Rev. Environ. Sci. Technol. 46, 336 381. Williams, M., Kookana, R., 2010. Isotopic exchangeability as a measure of the available fraction of the human pharmaceutical carbamazepine in river sediment. Sci. Total Environ. 407, 2711 2723. Wu, C.X., Witter, J.D., Spongberg, A.L., Czajkowski, K.P., 2009. Occurrence of selected pharmaceuticals in an agricultural landscape, western Lake Erie basin. Water Res. 43, 3407 3416. Xie, Z., Lu, G., Liu, J., Yan, Z., Ma, B., Zhang, Z., et al., 2015. Occurrence, bioaccumulation, and trophic magnification of pharmaceutically active compounds in Taihu Lake, China. Chemosphere 138, 140 147. Xu, H., Yang, J., Wang, Y., Jiang, Q., Chen, H., Song, H., 2008. Exposure to 17α-ethynylestradiol impairs reproductive functions of both male and female zebrafish (Danio rerio). Aquat. Toxicol. 88, 1 8. Xu, W.H., Zhang, G., Zou, S.C., Li, X.D., Liu, Y.C., 2007. Determination of selected antibiotics in the Victoria Harbour and the Pearl River, South China using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Environ. Pollut. 145, 672 679. Yamagishi, T., Miyazaki, T., Horii, S., Akiyama, K., 1983. Synthetic musk residues in biota and water from Tama River and Tokyo Bay (Japan). Arch. Environ. Contam. Toxicol. 12, 83 89. Yang, J.F., Ying, G.G., Zhao, J.L., Tao, R., Su, H.C., Chen, F., 2010. Simultaneous determination of four classes of antibiotics in sediments of the Pearl Rivers using RRLC-MS/ MS. Sci. Total Environ. 408, 3424 3432. Yang, Y.-Y., Toor, G.S., 2015. Contaminants in the Urban Environment: Pharmaceuticals and Personal Care Products (PPCPs) Part 2. p. SL420. http://edis.ifas.ufl.edu/ss633. Yang, Y.Y., Toor, G.S., Williams, C.F., 2015. Pharmaceuticals and organochlorine pesticides in sediments of an urban river in Florida, USA. J. Soils Sediments 15, 993 1004. Ying, G.G., Kookana, R.S., 2007. Triclosan in wastewaters and biosolids from Australian wastewater treatment plants. Environ. Int. 33, 199 205. Zha, J., Wang, Z., Wang, N., Ingersoll, C., 2007. Histological alternation and vitellogenin induction in adult rare minnow (Gobiocypris rarus) after exposure to ethynylestradiol and nonylphenol. Chemosphere 66, 488 495.

Pharmaceutical and personal care product contamination: a global scenario

61

Zhang, C.Y., Zhou, X.Z., Chen, J., Nie, X.P., 2009. Dynamics and fate of ciprofloxacin in a simulated aquatic system. J. Ecol. Rural Environ. 25, 73 78. Zhang, S., Zhang, Q., Darisaw, S., Ehie, O., Wang, G., 2007. Simultaneous quantification of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and pharmaceuticals and personal care products (PPCPs) in Mississippi river water, in New Orleans, Louisiana, USA. Chemosphere 66, 1057 1069. Zhang, Y., Cai, X., Lang, X., Qiao, X., Li, X., Chen, J., 2012. Insights into aquatic toxicities of the antibiotics oxytetracycline and ciprofloxacin in the presence of metal: complexation versus mixture. Environ. Pollut. 166, 48 56. Zhou, J., Broodbank, N., 2014. Sediment-water interactions of pharmaceutical residues in the river environment. Water Res. 48, 61 70. Zhou, J.L., Zhang, Z.L., Banks, E., Grover, D., Jiang, J.Q., 2009. Pharmaceutical residues in wastewater treatment works effluents and their impact on receiving river water. J. Hazard. Mater. 166, 655 661. Zhou, L.J., Ying, G.G., Zhao, J.L., Yang, J.F., Wang, L., Yang, B., et al., 2011. Trends in the occurrence of human and veterinary antibiotics in the sediments of the Yellow River, Hai River and Liao River in northern China. Environ. Pollut. 159, 1877 1885.

Further reading Lo´pez-Serna, R., Petrovi´c, M., Barcelo´, D., 2012. Occurrence and distribution of multiclass pharmaceuticals and their active metabolites and transformation products in the Ebro River basin (NE Spain). Sci. Total Environ. 440, 280 289.