The potential environmental risks of pharmaceuticals in vietnamese aquatic systems case study of antibiotics and synthetic hormones

The potential environmental risks of pharmaceuticals in Vietnamese aquatic systems: case study of antibiotics and synthetic hormones Hoang Thi Thanh Thuy & Tuan Dinh Nguyen Environmental Science and Pollution Research ISSN 0944-1344 Volume 20 Number 11 Environ Sci Pollut Res (2013) 20:8132-8140 DOI 10.1007/s11356-013-2060-8 23 Your article is protected by copyright and all rights are held exclusively by SpringerVerlag Berlin Heidelberg This e-offprint is for personal use only and shall not be selfarchived in electronic repositories If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website The link must be accompanied by the following text: "The final publication is available at link.springer.com” 23 Author's personal copy Environ Sci Pollut Res (2013) 20:8132–8140 DOI 10.1007/s11356-013-2060-8 REVIEW ARTICLE The potential environmental risks of pharmaceuticals in Vietnamese aquatic systems: case study of antibiotics and synthetic hormones Hoang Thi Thanh Thuy & Tuan Dinh Nguyen Received: July 2013 / Accepted: August 2013 / Published online: 13 August 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract Presently, many pharmaceuticals are listed as emerging contaminants since they are considered to be great potential threats to environmental ecosystems These contaminants, thus, present significant research interest due to their extensive use and their physicochemical and toxicological properties This review discusses a whole range of findings that address various aspects of the usage, occurrence, and potentially environmental risks of pharmaceuticals released from various anthropogenic sources, with emphasis on the aquatic systems in Vietnam The published information and collected data on the usage and occurrence of antibiotics and synthetic hormone in effluents and aquatic systems of Vietnam is reported This is followed by a potential ecological risk assessment of these pollutants The extensive use of antibiotics and synthetic hormones in Vietnam could cause the discharge and accumulation of these contaminants in the aquatic systems and potentially poses serious risks for ecosystems Vietnam is known to have extensively used antibiotics and synthetic hormones, so these contaminants are inevitably detected in aquatic systems Thus, an appropriate monitoring program of these contaminants is urgently needed in order to mitigate their negative effects and protect the ecosystems Keywords Pharmaceuticals Antibiotics Synthetic hormones Aquatic systems Resistant bacteria Endocrine disruptors Background and purposes Pharmaceuticals comprise an array of products, including chemical formulations and multiple biological targets Responsible editor: Philippe Garrigues H T Thanh Thuy (*) : T D Nguyen Ho Chi Minh City University for Natural Resources and Environment, Ho Chi Minh City, Vietnam e-mail: hengthuy@yahoo.de Recently, a variety of pharmaceutical compounds have been detected in the environment as well as their potential negative ecological significance on nontarget species In particular, aquatic systems are highly susceptible to be at risk for potential contamination by various pharmaceutical products due to increasing human population density and intensive animal farming techniques For example, both human and veterinary antibiotics have been also discovered in various surface waters and, recently, studies showed that some of which have been linked to ecological impacts at trace concentrations (Sanderson et al 2003) The presence of antibiotic residues in different environmental compartments is a growing problem of unexpected consequences, i.e., appearance of resistant bacteria as occurring in the Escherichia coli crisis in Germany during 2011 or the decline of vulture population in India due to the bioaccumulation of diclofenac taken from carcasses of dead livestock (Ginebreda et al 2010) In addition, synthetic hormone 17α-ethinyl estradiol (EE2), which is a main composition of birth control pharmaceutical, is now collectively known as endocrine-disrupting compound, which could mimic natural hormones in the endocrine systems of animals (Kidd et al 2007) Therefore, reports of occurrence of pharmaceuticals (EE2 and antibiotics) in aquatic systems have raised substantial concern among the public and regulatory agencies The contamination due to the EE2 and pharmaceutical residues have been reported in effluents of wastewater treatment plants (WWTPs) (Gracia-Lor et al 2011; Gros et al 2006) and in rivers and lakes around the world (Kasprzyk-Hordern et al 2008; Kolpin et al 2002) However, the literature related with this topic in Vietnam remains scare As other developing countries, antibiotics and synthetic hormones are widely used in Vietnam In addition, most of the wastewater is not treated or only primary treated so that poses a negative impact on the environment Thus, the present review does focus on antibacterial agents including fluoroquinolones (FQs), tetracyclines (TCs), Author's personal copy Environ Sci Pollut Res (2013) 20:8132–8140 cephalosporins (CEPHs), and xenoestrogen 17α-ethinyl estradiol (EE2) because of their high consumption and their observed persistence in the aquatic environment The recent literature published on the topic of consumption, occurrence, and potential risks of these contaminants in Vietnamese aquatic systems will be cited and reviewed Usage of antibiotics and synthetic hormones Human pharmaceuticals Presently, there are no trusted data available about the total consumption for antibiotics in Vietnam According to the number of registered brands and unofficial information from pharmacies and hospitals, β-lactams, macrolides, and FQs are the most widely used types (Duong et al 2008) Another survey carried out with GARP-Vietnam, University of Oxford and Vietnamese Ministry of Health has shown high consumption of antibiotics in most hospitals in Vietnam, with an increased use of new generation and expensive antibiotics like carbapenems In general, CEPHs are the most common used antibiotics in all hospitals, followed by penicillins, macrolides, and quinolones (GARP-Vietnam 2010) The recent study by our group was conducted during April–May 2012 The interviews were based on an extensive questionnaire Altogether, 10 hospitals and 17 pharmacies were interviewed in the key economic zone of South Vietnam (Hochiminh City, Binh Duong and Dong Nai provinces) The results confirmed that FQs, TCs, and CEPHs are still widely used (Table 1) In addition, these antibiotics are also bestselling antibiotics in pharmacies This study has also revealed the extensive use of synthetic hormones in Vietnamese hospitals; follitropin, estrogens, and progesterone are frequently used In addition, the data from pharmacies indicated that many contraceptive medicines are sold The most popular synthetic hormones of these medicines are ethinyl estradiol, desogestrel, dydrogesterone, levonorgestrel, etc (Table 2) Veterinary pharmaceuticals Agriculture, including aquaculture, is an increasingly important economic sector in Vietnam and in which antibiotics are extensively used as growth promoters as well as for prophylaxis and treatment of infections For example, integrated agricultural operations, such as Vietnam’s common “vegetable, aquaculture, caged-animal” system, may present an increased risk of human exposure to antibiotics and antibiotic-resistant bacteria/genes (Suzuki and Hoa 2012) The other data indicate that 70 % of all pharmaceutical products used in the animal sector are antibiotics (National Agro-Forestry-Fisheries Quality Assurance Department 2009) The data reported from husbandry showed the consumption of antibiotics as follows: 8133 Table The frequency (%) of antibiotics using and selling in South Vietnam (based on a survey of 10 hospitals and 17 pharmacies) Group/substance Hospital Pharmacies Internal treatment External treatment Fluoroquinolones Ciprofloxacin Levofloxacin Norfloxacin Tetracyclines Doxycycline Tetracycline Oxytetracycline Cephalosporins Cefaclor Cefotaxime Cefoperazone Cefepime Cefazolin Cefdinir Ceftazidime Ceftriaxone Cephalexin Cefadroxil – – 40 40 10 90 90 40 100 100 47 50 30 – 100 60 30 100 88 – 20 70 50 30 30 10 10 20 90 20 50 10 20 10 0 90 10 94 41 12 – – – – 94 82 FQs, enrofloxacin (ENRO-7 %) and norfloxacin (NOR5 %) TCs, tetracycline (TC-4 %) More precisely, for Vietnamese shrimp farming, the most common antibiotics used can be divided into the following five groups: (1) FQs (ENRO, NOR, ciprofloxacin (CIP), and oxolinic acid (OXLA)), (2) sulfonamides (sulfamethoxazole, sulfadiazine), (3) TCs (oxytetracycline (OTC)), (4) diaminopyrimidines (trimethoprim, ormetoprim), and (5) unclassified (griseofulvin and rifampicin) (Thuy et al 2011) Occurrence in wastewater and aquatic system FQs Several studies have reported the occurrence of FQs in Vietnamese wastewaters as well as aquatic systems Duong et al (2008) have reported the maximum concentrations of the FQs (CIP) and NOR in aqueous grab samples from the hospital wastewater effluents varied from 10 to 15 μg/l (Table 3) Other FQs like levofloxacin (LEV), ofloxacin (OFL), and lomefloxacin were below the detection limit The levels of CIP and NOR in Vietnam were generally in the same order of magnitude as in Switzerland The removal of the analyzed FQs from the water stream during wastewater treatment was between 80 and 87 %, presumably mainly through sorption to Author's personal copy 8134 Environ Sci Pollut Res (2013) 20:8132–8140 Table Types of contraceptive hormones sold in South Vietnam No Commercial Active substance name Manufacturer Ciclomex Ethinyl Estradiol Diane 35 Drasperin Duphaston Ethinyl Estradiol Droprrenone, Ethinyl estradiol Dydrogesterone Genestron Levonorgestrel Marvelon Mercilon Mifestad Newchoice Desogestrel, Ethinyl estradiol Desogestrel, Ethinyl estradiol Mifepriston Levonorgestrel, Ethinyl Estradiol Levonorgestrel, Ethinyl estradiol Desogestrel, Ethinyl estradiol Lynestrenol Levonorgestrel Desogestrel, Ethinyl estradiol Ethinyl estradiol, Levonorgostrel Ethinyl estradiol, Levonorgostrel Laboratorios Recalcine S.A Chile Schering AG, Germany Laboratorios Recalcine S.A Chile Solvay Pharmaceuticals GmbH, Germany Laboratorios Recalcine S.A Chile Ampharco USA 10 Nordette 11 Novynette 12 Orgametril 13 Postinor 14 Regulon 15 Rigevidon 16 Triregol N.V Organon, Ireland Stada, Vietnam Nam ha, Vietnam Wyeth Medica, Ireland Gedeon Richter, Hungary N.V Organon Gedeon Richter, Hungary Gedeon Richter, Hungary Gedeon Richter, Hungary Consilient Health, England particulates These elimination rates are in agreement with the values reported in the literature Related with the shrimp culture, Le and Munekage (2004) have reported the occurrence of NOR at 0.06–6.06 mg/l in the water column and 6.51–2,615 mg/kg in the sediment of intensive ponds and improved extensive ponds OXLA could be detected in the water column at a concentration similar to that of NOR (0.01–2.5 mg/l), but not in the sediment The “water column concentration” indicates present inflow, while the “sediment concentration” indicates the value integrated over time (Takasu et al 2011) Thus, the presence of antibiotics in both samples suggests that the antibiotics are presently used and retained in the sediment Another study reported by Takasu et al (2011) showed that OFL/LEV and NOR were found to be major FQs in waters of Vietnam, including city canals, hospital wastewater, pig farm wastewater, and aquaculture sites This suggests that OFL/ LEV and NOR have been widely used for human and veterinary purposes OFL and NOR were confirmed as major environmental contaminants A recent decrease in drug application and/or dilution effects may explain the improved contamination situation in aquaculture settings The most recent study showed that CIP is still a commonly used FQ for shrimp larvae in Vietnam (Thuy and Loan 2012) In shrimp pond water samples, CIP concentrations varied from 0.35 to 1.23 μg/l At the outlet, the CIP levels ranged from 0.65 to 0.98 μg/l and 1.54–1.88 μg/kg in water and sediment samples, respectively TCs A recent study by Shimizu et al (2013) has shown that OTC was predominant in livestock wastewater The mean value of Vietnamese pig farm effluents was 175 ng/l The level of other tetracycline pharmaceuticals (TC and doxytetracycline (DOX)) was relatively low, almost below LOD and LOQ In the suburban and city canals as well as in Mekong delta, only OTC was detected, whereas TC and DOX were below the detection limit The geometric means of urban and suburban canal samples were and 45 ng/l, respectively In the Mekong delta, the concentrations of TC, DOX, and OTC were relatively low TC and DOX were not detected in all samples, and OTC was detected only at one site The dilution with non-contaminated river water has decreased the level of TCs in Mekong delta CEPHs This antibiotic group belongs to β-lactam antibiotics, which are widely used to treat bacterial infections of various organs (e.g., bovine mastitis, pneumonia, arthritis, etc.) In contrast to their high consumption, the data related with occurrence of CEPHs in Vietnamese effluent as well as receiving water bodies were not readily available EE2 The xenoestrogen EE2 is the major compound of the contraceptive pill and eventually gets excreted in urine Studies abroad have shown that the concentrations of EE2 in the environment are mostly lower than ng/l, whereas concentrations in the WWTP effluent can exceed 50 ng/l (Moschet 2009) Due to the higher persistence of EE2 in the WWTP, the concentrations of this pharmaceutical in the environment is analogous to concentrations of the natural estrogens, despite the fact that it is excreted in much smaller amounts However, no data related with this compound in effluent and aquatic system for Vietnam could be found Environmental fate of pharmaceuticals in aquatic system The detection of antibiotics like FQs and TCs in Vietnamese agricultural and hospital wastewater as listed in Table is probably due to the fact that these antibiotics are not fully absorbed either by target organisms and/or human beings This observation is consistent with previous studies showing excretion rates of 30–85 and 60–90 % for FQs and TCs, respectively (Table 4) In addition, due to the wide variation of antibiotic’s degradability, some of them still remain in treated wastewater and after that enter the receiving water bodies This is the case of FQs, which are frequently detected Author's personal copy Environ Sci Pollut Res (2013) 20:8132–8140 8135 Table Occurrences of antibiotics (μg/l or μg/kg) in Vietnam Substance Surface water Sediment Wastewater References FQs CIP 0.65–0.98 1.54.–1.88 Agricultural wastewater Shrimp larvae: 0.35–1.23 Hospital wastewater Raw: 1.1–10.9b; 25.8±8.1c Treated: 3.7±1.3c Thuy and Loan 2012 Duong et al 2008 NOR Surface layer: 60–6,060 Bottom layer: 80–4,040 6,510–2,616×103 Le and Munekage 2004 Hospital wastewater: Raw: b.d −15.2b; 6.8±1.1c Treated: 1.4±0.2 (c) OXLA OFL/LEV TCs DOX Surface layer: 10–2,500 Bottom layer: 10–2,310 City canal: 185–782 1,810–426.31×103 Le and Munekage 2004 Takasu et al 2011 b.d TTC b.d OTC Urban canal: b.d.−0.0053 (2/12)a Suburban canal: b.d.−0.216 (2/29)a River water: b.d.−0.004 (1/25)a a Duong et al 2008 Agricultural wastewater/sewage sludge b.d Sewage sludge: b.d.−0.3163 (1/7)a Agricultural wastewater Pig farm: 0.031–0.9 (5/14)a Aquaculture: b.d Shimizu et al 2013 Shimizu et al 2013 Number of detected samples/total samples b One grab samples of untreated water (duplicated analysis) c Hourly sampling and to a lesser extent of TCs The environmental fate of each pharmaceutical group can be summarized as follows: Table Excretion and removal rates for antibiotics and EE2 Group Excretion Removal rate (%) References rate (%) FQs 30–85 78–93 TCs 60–90 CEPHs 92.6 EE2 35 Lindberg et al 2005; Isidori et al 2005 Li and Zhang 2010; Watkinson et al 2009; Gulkowska et al 2008; Lindberg et al 2006; Lindberg et al 2005 Hirsch et al 1999; Isidori et al 2005 70–98 Li and Zhang 2010; Gulkowska et al 2008; Lindberg et al 2005 Harada et al 1976 95 Homem and Santos 2011 Johnson et al 2000 80–90 Baronti et al 2000; Layton et al 15.8–70.9 (MBR 2000; Yang et al 2012 without/with PAC) MBR membrane bioreactors and PAC powdered activated carbon FQs Previous studies have reported that FQs are insensitive to hydrolysis and increased temperatures but are degraded by UV light (Burhenne et al 1997; Ge et al 2010; Knapp et al 2005; Lai and Lin, 2009) For example, CIP—a frequently detected FQ—has a solubility of 35 g/l (Kümmerer 2009) In addition, laboratory tests confirmed that CIP biodegradation seems to be insignificant The calculated half-lives for CIP are about 25 days (Thuy et al 2012) However, the photodegradability of FQs is pH dependent, so it is probably one of the reasons why FQs are so frequently detected in pond water as well as surface water In addition, FQs are sensitive to sorption into soil and clay Giger et al (2003) and Golet et al (2002) have reported the persistence of FQs in sludge-treated soils several months after application FQs have also been found to adsorb onto sediments Córdova-Kreylos and Scow (2007) have measured the sorption of CIP in sediment samples from three Californian salt marshes Sediments were exposed to a CIP concentration gradient (0–200 mg/l) The correlation of sorption coefficients (log Kd) was positive with clay content (r2 =0.98) and negative with pH (r2 = 0.99) Author's personal copy 8136 TCs Some instability in aquatic systems could be demonstrated for some TCs (Halling-Sørensen 2000) In general, the hydrolysis rates for OTC increase as the pH deviates from pH and as temperature increases The half-lives of OTC vary due to differences in temperature, light intensity, and flow rate In addition, TCs are susceptible to photodegradation For example, Samuelsen (1989) has investigated the sensitivity of OTC towards light in seawater as well as in sediments This antibiotic proved to be stable in sediments rather than in seawater Oka et al (1989) have also reported that no other photodegradation process is known for this antimicrobial molecule Thus, TCs remain in the sediment for a long period, as shown by Lunestad and Goksøyr (1990) CEPHs The environmental fate and impacts of CEPHs are still unclear Jiang et al (2010) have studied the degradation of four CEPHs (cefradine, cefuroxime, ceftriaxone, and cefepime) from each generation in the surface water and sediment of Lake Xuanwu, China The CEPHs are degraded abiotically in the surface water in the dark with half-lives of 2.7–18.7 days, which are almost the same as that in sterilized surface water Under exposure to simulated sunlight, the half-lives of the CEPHs decrease significantly to 2.2–5.0 days, with the maximal decrease for ceftriaxone from 18.7 days in the dark to 4.1 days under light exposure Elimination rates of the CEPHs in oxic sediment (halflives of 0.8–3.1 days) are higher than in anoxic sediment (halflives of 1.1–4.1 days), mainly attributed to biodegradation Thus, it can be concluded that abiotic hydrolysis is the primary process for the elimination of cefradine, cefuroxime, and cefepime In the case of ceftriaxone, direct photolysis is the major degradation mechanism in the surface water of the lake In addition, biodegradation is responsible for the elimination of the CEPHs in the sediment (Jiang et al 2010) EE2 The synthetic hormone EE2 is excreted in urine and feces in a ratio of about 4:6 In the environment, this steroid hormone can be degraded in different ways This includes sorption, photolytic degradation, as well as microbial degradation There is a lot of literature dealing with sorption (e.g., Cirja et al 2007; Lee et al 2003), but less about photolytic degradation has been reported (e.g., Liu et al 2003; Zuo et al 2006) However, the most important process to eliminate this xenoestrogen is the microbial degradation Sorption and to minor extent photodegradation can also play a role in the elimination of EE2 in the aquatic system Hazards and risks Antibiotic resistance The concern regards the effect these antibiotics may have on aquatic systems after receiving effluents from various sources Environ Sci Pollut Res (2013) 20:8132–8140 The most obvious concern relates to how these antibiotics will affect the nontarget bacteria in the aquatic system, since the role of antibiotics are to kill bacteria Moreover, as mentioned before, most seriously negative effects on the aquatic ecosystems are not the only fear with antibiotics, but also the risk for the development of resistance amongst bacteria towards these compounds Such a resistance can evolve either through selective pressure on bacterial strains, mutation, or through the acquisition of new DNA from other resistant bacteria (Tenover 2006) The resistance can later spread to bacteria causing human diseases (Kumar et al 2005) Thus, it is necessary to mitigate unnecessary prescriptions of the drugs, especially for developing countries like Vietnam, where people already overuse antibiotics, often without prescriptions FQs Since FQs are not natural compounds, it is believed that bacteria not possess FQ resistance genes However, bacteria resistant to FQs can be found easily (Duong et al 2008; Takasu et al 2011) The reason for that is due to the long halflives in the environment, so FQs pose a selective pressure for environmental bacteria in the environment Previous studies have shown that FQs are relatively stable in water and sediment (Kümmerer 2009; Le and Munekage 2004), which might be due to sorption onto particulates (Lai and Lin 2009; Nowara et al 1997) A broad range of bacteria can acquire resistance to FQs including common bacteria (Escherichia coli), pathogenic bacteria (e.g., Acinetobacter), and aquatic bacteria (e.g., Brevundimonus) Proteobacteria and Actinobacteria are the major taxa of FQ-resistant bacteria, indicating that FQ-resistant bacteria are not limited to specific groups (Takasu et al 2011) In addition, Takasu et al (2011) have found that there is no relationship between the concentration of FQs in the environment and the rate of bacterial resistance Therefore, despite the lower level of contamination, the occurrence rate of FQ-resistant bacteria has been found to be higher in Vietnam than in Thailand (Takasu et al 2011) Thus, the aquatic environment is hypothesized to be a natural reservoir of FQ-resistant bacteria and resistance genes TCs The wide application as human and veterinary medicines has been accompanied by an increased frequency of TCs resistance (Akinbowale et al 2007; Gao et al 2012; Ryu et al 2012) Presently, more than 40 different tetracycline resistance determinants have been reported (Roberts 2005) In aquaculture ecosystems, several tetracycline resistance determinants tet(A)–tet(W) have been identified in fish pathogenic bacteria from a number of geographical locations and fish species (Akinbowale et al 2007; Gao et al 2012; Seyfried et al 2010) as well as amongst commensals (Ryu et al 2012) In addition, bacteria resistant to OTC, a TC derivative, have been reported in fish pathogens and environmental bacteria (Nonaka et al 2007) Park and Choi 2008 62.3 3.13 LC50 (48 h) (mortality) Kim et al 2009 Oxolinic acid EC50 (7 days) (population growth inhibition) LC50 (48 h) NOEC(21 days) reproduction NOEC (21 days) reproduction NOEC Wollenberger et al 2000 Isidori et al 2005 Park and Choi 2008 Yamashita et al 2006 Halling-Sørensen et al 2000 Ref 4.01 0.300 EC50 (72 h) (growth inhibition) EC50 (72 h) (growth inhibition) NOEC (growth inhibition) NOEC (96 h) growth inhibition Ecotoxicity Toxicological data endpoint Algae 20 Schlabach 2009 40 Ando et al 2007 150 Yamashita et al 2006 Ref PNEC (ng/l) Park and Choi 2008 0.05 EC50 (growth rate) HallingSørensen 2000 NOEC (growth Eguchi et al inhibition) 2004 182 Tetracycline 17α10 Ethinylestradiol Hormone 110.1 Oxytetracycline LOEC (21 days) (fertilization rate) LC50 (96 h) LC50 (48 h) (mortality) Chlortetracycline 78.9 Grung et al 2007 Pawlowski et al 2004 Nordic Council of Ministers 2012 44.8 0.2 EC50 (21 days) (reproduction) Ando et al 2007 PNEC (72 h) (reproduction) Yamashita et al 2006 0.09 0.183 EC50 (growth rate) HallingSørensen 2000 Lin et al 2008 Jones et al 2002; Lin et al 2008 21900 0.002 Jones et al 2002; Lin et al 2008 Jones et al 2002; Lin et al 2008 Jones et al 2002; Lin et al 2008 Jones et al 2002; Lin et al 2008 Jones et al 2002; Lin et al 2008 200 90 40 Cefotaxime Tetracyclines 1250 EC50 (48 h) (immobilization) Holten Lützhøft et al 1999 Cefazolin 225 16 Grung et al 2008 0.18 Cephalexin Cephalosporins Sarafloxacin NOEC (21 days) (reproduction) Golet et al 2002; Lin et al 2008 Golet et al 2002; Lin et al 2008 Golet et al 2002; Lin et al 2008 Ref Lowest PNEC 2500 0.38 Ofloxacin Norfloxacin Marbofloxacin LC50 (96 h) (mortality) 60 0.031 100 Halling-Sørensen et al 2000 Levofloxacin NOEC 100 Ecotoxicity Toxicological data endpoint Ecotoxicity Toxicological data endpoint Ref Crustacean Fish Ecotoxicological data (μg/l) Enrofloxacin Ciprofloxacin Fluoroquinolones Compound Table Toxicity data of pharmaceuticals Author's personal copy Environ Sci Pollut Res (2013) 20:8132–8140 8137 Author's personal copy 8138 Environ Sci Pollut Res (2013) 20:8132–8140 These finding are consistent with the study of Zhang et al (2009), which have indicated that among the TCs resistance genes, the tet(M) is one of the most widely distributed tetracycline resistance determinants The host range for the tet(M) covers 42 genera, and this gene continues to have the widest host range of any tet genes (Roberts 2005) Suzuki et al (2008) reported that the tet(M) has been also isolated in coastal aquaculture areas and sediments in Mekong River, Vietnam (PNECs) are calculated applying a safety factor The acute and chronic toxicity as well as lowest PNECs of studied pharmaceuticals were listed in Table It was found that the maximum levels of antibiotics (FQs and TCs) in Vietnamese aquatic system have exceeded the PNECs, which could lead to seriously negative impacts on the ecosystem CEPHs The potential resistance of Enterobacteriaceae family against the third generation of CEPHs has been reported by Arikan and Aygan (2009) The highest resistance is detected to the Ceftizoxime and the lowest one is to the Ceftriaxone in both sampling periods (October 2006–February 2007 and June–October 2007) Klebsiella pneumonia shows the highest resistance to all three antibiotics compared to the Enterobacter aerogenes and E coli Thus, it could be concluded that in spite of low concentrations in the aquatic system, the development of antibiotic resistance should be taken into account Presently, relatively little is known about the situation in developing countries like Vietnam, where the pharmaceutical market is rapidly growing Pharmaceuticals are widely used as human and veterinary medicines as well as animal feed additives Due to their relatively high excretion rate, ineffective removal, and improper disposal, the pharmaceuticals could enter into the aquatic system via many pathways such as hospital, domestic, and agricultural wastewaters In fact, a great variety of antibiotics have been detected in wastewater and even in surface water in Vietnam up to now Once entered into aquatic systems, the pharmaceuticals have been found to be rather persistent, which strengthened the assumption of them constituting a very high risk Thus, in conclusion, the results of this study underline the importance of the negative impacts of antibiotics and synthetic hormones in Vietnamese aquatic systems This also further emphasizes the need for appropriate monitoring program of these contaminants in order to mitigate their negative effects and protect the ecosystems Endocrine disruption effect As mentioned above, EE2 belongs to the endocrine disruptors, and the concentration levels known to have effects are extraordinarily low For example, effects due to EE2 have been documented at the sub-ppt level in surrounding water (i.e., 0.05 ng/l) (Larsen et al 2008) This means that if they exceed this level in the environment, it can lead to a misbalance of the endocrine system in animals Effects like feminization of male fish have already been observed near WWTP effluents, including decreased growth of the testes and vitellogenin (an egg yolk precursor protein) production in male fish which results in reduced reproduction Purdom et al (1994) for example have found that EE2 concentrations in the range of 1–10 ng/L (i.e., concentrations that have been observed in rivers) could induce vitellogenin production in male rainbow trout Toxicity data The selected pharmaceuticals are now known to pose considerable risks, and low concentrations are not related with low toxicity Presently, toxicity data of antibiotics is greatly needed for the understanding of their ecological impacts and the performance of environmental risk assessments Studies about the toxicity effects of antibiotics have been performed with aquatic organisms in recent years, including luminescent bacteria, algae, invertebrates, and fishes The toxic effects of antibiotics in aquatic environments can be expressed as median effective concentration or no observed effect concentration Based on toxicity data, the predicted no-effect concentrations Conclusions Acknowledgments The authors would like to thank Prof Lewis Hinchman and Dr Paul Truong for editing the English manuscript and two anonymous reviewers for comments 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REVIEW ARTICLE The potential environmental risks of pharmaceuticals in Vietnamese aquatic systems: case study of antibiotics and synthetic hormones Hoang Thi Thanh Thuy & Tuan Dinh Nguyen Received:... on the aquatic systems in Vietnam The published information and collected data on the usage and occurrence of antibiotics and synthetic hormone in effluents and aquatic systems of Vietnam is reported... a potential ecological risk assessment of these pollutants The extensive use of antibiotics and synthetic hormones in Vietnam could cause the discharge and accumulation of these contaminants in