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

REVIEW ARTICLEThe potential environmental risks of pharmaceuticals in Vietnamese aquatic systems: case study of antibiotics and synthetic hormones Hoang Thi Thanh Thuy&Tuan Dinh Nguyen R

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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

pharmaceuticals in Vietnamese aquatic systems: case study of antibiotics and

synthetic hormones

Hoang Thi Thanh Thuy & Tuan Dinh Nguyen

1 23

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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: 1 July 2013 / Accepted: 1 August 2013 / Published online: 13 August 2013

# Springer-Verlag Berlin Heidelberg 2013

Abstract Presently, many pharmaceuticals are listed as

emerg-ing 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

sys-tems 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

ecosys-tems Vietnam is known to have extensively used antibiotics and

synthetic hormones, so these contaminants are inevitably

detect-ed 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

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 poten-tial 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 prob-lem 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 com-position of birth control pharmaceutical, is now collectively known as endocrine-disrupting compound, which could

mim-ic 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 con-tamination 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),

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

DOI 10.1007/s11356-013-2060-8

cephalosporins (CEPHs), and xenoestrogen 17α-ethinyl

es-tradiol (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

aquat-ic 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,

Univer-sity 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

anti-biotics like carbapenems In general, CEPHs are the most

common used antibiotics in all hospitals, followed by

penicil-lins, macrolides, and quinolones (GARP-Vietnam2010)

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 (Table1) In addition, these antibiotics are also

best-selling 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,

levonorges-trel, etc (Table2)

Veterinary pharmaceuticals Agriculture, including

aquacul-ture, is an increasingly important economic sector in Vietnam

and in which antibiotics are extensively used as growth

pro-moters 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

Hoa2012)

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

con-sumption of antibiotics as follows:

– FQs, enrofloxacin (ENRO-7 %) and norfloxacin

(NOR-5 %) – 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) un-classified (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 hos-pital wastewater effluents varied from 10 to 15μg/l (Table3) 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

Table 1 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

Tetracyclines

Cephalosporins

Author's personal copy

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

in-tensive ponds and improved exin-tensive 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

veter-inary purposes OFL and NOR were confirmed as major

environmental contaminants A recent decrease in drug

appli-cation and/or dilution effects may explain the improved

con-tamination situation in aquaculture settings

The most recent study showed that CIP is still a commonly used FQ for shrimp larvae in Vietnam (Thuy and Loan2012)

In shrimp pond water samples, CIP concentrations varied from 0.35 to 1.23μg/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

5 and 45 ng/l, respectively In the Mekong delta, the concentra-tions 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 toβ-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 re-ceiving water bodies were not readily available

EE2 The xenoestrogen EE2 is the major compound of the contraceptive pill and eventually gets excreted in urine Stud-ies abroad have shown that the concentrations of EE2 in the environment are mostly lower than 5 ng/l, whereas concen-trations 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 3 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 (Table4) 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

Table 2 Types of contraceptive hormones sold in South Vietnam

No Commercial

name

Active substance Manufacturer

1 Ciclomex Ethinyl Estradiol Laboratorios Recalcine S.A.

Chile

2 Diane 35 Ethinyl Estradiol Schering AG, Germany

3 Drasperin Droprrenone, Ethinyl

estradiol

Laboratorios Recalcine S.A.

Chile

4 Duphaston Dydrogesterone Solvay Pharmaceuticals

GmbH, Germany

5 Genestron Levonorgestrel Laboratorios Recalcine S.A.

Chile

6 Marvelon Desogestrel, Ethinyl

estradiol

Ampharco USA

7 Mercilon Desogestrel, Ethinyl

estradiol

N.V Organon, Ireland

8 Mifestad Mifepriston Stada, Vietnam

9 Newchoice Levonorgestrel,

Ethinyl Estradiol

Nam ha, Vietnam

10 Nordette Levonorgestrel,

Ethinyl estradiol

Wyeth Medica, Ireland

11 Novynette Desogestrel, Ethinyl

estradiol

Gedeon Richter, Hungary

12 Orgametril Lynestrenol N.V Organon

13 Postinor Levonorgestrel Gedeon Richter, Hungary

14 Regulon Desogestrel, Ethinyl

estradiol

Gedeon Richter, Hungary

15 Rigevidon Ethinyl estradiol,

Levonorgostrel

Gedeon Richter, Hungary

16 Triregol Ethinyl estradiol,

Levonorgostrel

Consilient Health, England

and to a lesser extent of TCs The environmental fate of each pharmaceutical group can be summarized as follows: 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 (Kümmerer2009) 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 sam-ples 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)

Table 3 Occurrences of antibiotics ( μg/l or μg/kg) in Vietnam

FQs

CIP 0.65 –0.98 1.54 –1.88 Agricultural wastewater

Shrimp larvae: 0.35 –1.23 Thuy and Loan2012 Hospital wastewater

Raw: 1.1 –10.9 b

; 25.8±8.1c

Duong et al 2008

Treated: 3.7±1.3c NOR

Surface layer: 60 –6,060 6,510 –2,616×10 3

Le and Munekage 2004

Bottom layer: 80 –4,040

Hospital wastewater:

Raw: b.d −15.2 b

; 6.8±1.1c

Duong et al 2008

Treated: 1.4±0.2(c) OXLA Surface layer: 10 –2,500 1,810 –426.31×10 3

Le and Munekage 2004

Bottom layer: 10 –2,310

TCs

DOX b.d.

b.d.

Shimizu et al 2013

OTC Urban canal: b.d −0.005 3

(2/12)a Sewage sludge: b.d −0.316 3

(1/7)a Shimizu et al 2013

Suburban canal: b.d −0.216 (2/29) a

Agricultural wastewater Pig farm: 0.031 –0.9 (5/14) a

River water: b.d −0.004 (1/25) a

Aquaculture: b.d.

a Number of detected samples/total samples

b

One grab samples of untreated water (duplicated analysis)

c

Hourly sampling

Table 4 Excretion and removal rates for antibiotics and EE2

Group Excretion

rate (%)

Removal rate (%) References

FQs 30–85 Lindberg et al 2005 ; Isidori

et al 2005

78–93 Li and Zhang 2010 ; Watkinson

et al 2009 ; Gulkowska et al.

2008 ; Lindberg et al 2006 ; Lindberg et al 2005

TCs 60–90 Hirsch et al 1999 ; Isidori et al.

2005

70–98 Li and Zhang 2010 ; Gulkowska

et al 2008 ; Lindberg et al.

2005

CEPHs 92.6 Harada et al 1976

95 Homem and Santos 2011

EE2 35 Johnson et al 2000

80–90 15.8–70.9 (MBR without/with PAC)

Baronti et al 2000 ; Layton et al.

2000 ; Yang et al 2012

MBR membrane bioreactors and PAC powdered activated carbon

Author's personal copy

TCs Some instability in aquatic systems could be

demonstrat-ed for some TCs (Halling-Sørensen 2000) In general, the

hydrolysis rates for OTC increase as the pH deviates from

pH 7 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

lives of 0.8–3.1 days) are higher than in anoxic sediment

(half-lives 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,

biodeg-radation 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

degra-dation 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

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 ecosys-tems 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 se-lective 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 peo-ple already overuse antibiotics, often without prescriptions FQs Since FQs are not natural compounds, it is believed that bacteria do not possess FQ resistance genes However, bacte-ria resistant to FQs can be found easily (Duong et al.2008; Takasu et al.2011) The reason for that is due to the long half-lives 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 sedi-ment (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 concen-tration of FQs in the environment and the rate of bacterial resistance Therefore, despite the lower level of contamina-tion, 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 de-terminants tet(A)–tet(W) have been identified in fish patho-genic 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)

P (n

Ecotoxicity data

growth inhibition

Halling-Sørensen 2000

Halling-Sørensen 2000

Hormone 17 α- Ethiny

Author's personal copy

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

tetra-cycline 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

CEPHs The potential resistance of Enterobacteriaceae

fam-ily 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

concentra-tions in the aquatic system, the development of antibiotic

resistance should be taken into account

Endocrine disruption effect

As mentioned above, EE2 belongs to the endocrine disruptors,

and the concentration levels known to have effects are

ex-traordinarily 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,

in-cluding 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

consid-erable 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

bac-teria, algae, invertebrates, and fishes The toxic effects of

antibiotics in aquatic environments can be expressed as

medi-an effective concentration or no observed effect concentration

Based on toxicity data, the predicted no-effect concentrations

(PNECs) are calculated applying a safety factor The acute and chronic toxicity as well as lowest PNECs of studied pharma-ceuticals were listed in Table5 It was found that the maxi-mum levels of antibiotics (FQs and TCs) in Vietnamese aquatic system have exceeded the PNECs, which could lead

to seriously negative impacts on the ecosystem

Conclusions 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 addi-tives 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

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 that greatly improved the manuscript This research was supported by the Ministry of Natural Resources and Environment, Project TNMT.04.30.

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