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

1 23
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
The potential environmental risks of
pharmaceuticals in Vietnamese aquatic
systems: case study of antibiotics and
synthetic hormones
Hoang Thi Thanh Thuy & Tuan Dinh
Nguyen
1 23
Your article is protected by copyright and
all rights are held exclusively by Springer-
Verlag Berlin Heidelberg. This e-offprint is
for personal use only and shall not be self-
archived 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”.
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, thu s,
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 r eleased from various anthro pogenic sources,
with emphasis on the aquatic syste ms in Vietnam. The p ublish ed
information and c ollected data on t he usage and occu rrence of
antibiotics and s ynthetic hormone in effluents and a quatic sys-
tems of V ietnam is reported. This is followed by a potential
ecological risk assessment of these pollutants. The extensive
use of antibiotics and s ynthetic hormones in Vietnam could cause
the discharge and accumulation of these contaminants in the
aquatic s ystems and potentially poses serious risks for ecosys-
tems. Vietnam is known t o 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 ur gently needed in ord er to mitigate their
negative effects and prot ect the eco systems.
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 residu es

in different environmental compartments is a growing prob-
lem of unex pected consequences, i. e., ap pearance 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;Grosetal.2006)andin
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:
Environ Sci Pollut Res (2013) 20:8132–8140
DOI 10.1007/s11356-013-2060-8
Author's personal copy
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
Vi etnam. According to the number of registered brands
and unofficial information from pharmacies and hospitals,
β-lactams, macrolides, and FQs are the most w idely 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-Vietnam 2010).
The recent study by our grou p 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 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. (Table 2).
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’scommon“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 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 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
Tabl e 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
Ciprofloxacin 40 90 100
Levofloxacin 40 90 100
Norfloxacin 10 40 47
Tetracyclines
Doxycycline 50 100 100
Tetracycline 30 60 88
Oxytetracycline – 30 –
Cephalosporins

Cefaclor 20 50 94
Cefotaxime 70 10 41
Cefoperazone 50 0 12
Cefepime 30 20 6
Cefazolin 30 10 –
Cefdinir 10 0 –
Ceftazidime 10 0 –
Ceftriaxone 20 0 –
Cephalexin 90 90 94
Cefadroxil 20 10 82
Environ Sci Pollut Res (2013) 20:8132–8140 8133
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 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)showedthat
OFL/LEVand 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 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 tha t
OTC was predominant in l ivestock wastewater. The mean value
of V ietnamese pig farm effluents was 175 ng/l. The level of other
tetracycline pharmaceuticals ( TC and doxy tetracycline (DOX))
was relatively low, almost below LOD an d LOQ. In the su burban
and city canals a s well as in Mekong delta, only OTC was
detected, whereas TC and DOX were below th e 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 rive r w ater 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 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 (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
Tabl e 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
8134 Environ Sci Pollut Res (2013) 20:8132–8140
Author's personal copy
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;Geetal.2010; Knapp et al.
2005; Lai and Lin, 2009). For example, CIP—afrequently
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 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 (r
2
=0.98) and negative with pH (r
2

=
0.99).
Tabl e 3 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
Thuy and Loan 2012
Hospital wastewater
Raw: 1.1–10.9
b
;25.8±8.1
c
Duong et al . 2008
Treated: 3.7±1.3
c
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±1.1
c
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
OFL/LEV City canal: 185–782 Takasu et al. 2011
TCs
DOX b.d.
TTC b.d. Agricultural wastewater/sewage sludge
b.d.
Shimi zu et al. 2013
OTC Urban canal: b.d.−0.005
3
(2/12)
a
Sewage sludge: b.d.−0.316
3
(1/7)
a
Shimi zu 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
Tabl e 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;Lindbergetal.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 PA C powdered activated carbon
Environ Sci Pollut Res (2013) 20:8132–8140 8135
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)havealsoreportedthatnoother
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, C hina. T he CEPHs are degraded abiotically in the
surface water in the d ark with half-lives of 2 .7–18.7 days, which
are almost the same as that in sterilized surface water. Und er
exposure to si mulated s unlight, t he half-lives of the CEPHs
decrease significantly to 2. 2–5.0 days, with the maximal decrease
for ceftriaxone from 18.7 da ys i n the dark to 4.1 days under light
exposure. Elimination rates o f the C EPHs in oxic sediment (half-
lives of 0.8–3.1 days) are higher than in anoxic sediment (half-
lives of 1.1–4.1 days), mainly a ttributed to bio degradation. Thus,
it can be conc luded tha t abiotic hydrolysis is the primary process
for the elimination of cefradine, cefuroxime, and cefepime. In t he
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). Thu s, 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;Nowaraetal.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 ar e the ma jor 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).
8136 Environ Sci Pollut Res (2013) 20:8132–8140
Author's personal copy
Tabl e 5 Toxicity data of pharmaceuticals
Compound Ecotoxicological data (μg/l) Lowest PNEC
Fish Crustacean Algae PNEC
(ng/l)
Ref.
Ecotoxicity
data
Toxicological
endpoint
Ref. Ecotoxicity
data
Toxicological
endpoint
Ref. Ecotoxicity
data
Toxicological
endpoint
Ref.
Fluoroquinolones
Ciprofloxacin 100 NOEC Halling-Sørensen

et al. 2000
60 NOEC Halling-Sørensen
et al. 2000
20 Golet et al. 2002;
Lin et al. 2008
Enrofloxacin 5 NOEC(21 days)
reproduction
Park and Choi
2008
Levofloxacin 100 LC50 (96 h)
(mortality)
Kim et al. 2009 0.031 NOEC (21 days)
reproduction
Yamashita et al.
2006
0.300 NOEC (96 h)
growth
inhibition
Yamashita et al.
2006
Marbofloxacin 62.3 LC50 (48 h) Isidori et al. 2005
Norfloxacin 4.01 NOEC (growth
inhibition)
Ando et al. 2007 150 Golet et al. 2002 ;
Lin et al. 2008
Ofloxacin 3.13 EC50 (7 days) (population
growth inhibition)
Wollenber ger
et al. 2000
40 Golet et al. 2002;

Lin et al. 2008
Oxolinic acid 0.38 NOEC (21 days)
(reproduction)
Grung et al. 2008 0.18 EC50 (72 h)
(growth
inhibition)
Schlabach 2009
Sarafloxacin 16 EC50 (72 h)
(growth
inhibition)
Holten Lützhøft
et al. 1999
Cephalosporins
Cephalexin 2500 Jones et al. 2002;
Lin et al. 2008
Cefazolin 1250 Jones et al. 2002;
Lin et al. 2008
Cefotaxime 40 Jones et al.
2002;
Lin et al. 2008
Tetracyc lines
Chlortetracycline 78.9 LC50 (48 h)
(mortality)
Park and Choi 2008 225 EC50 (48 h)
(immobilization)
Park and Choi
2008
0.05 EC50 (growth rate) Halling-
Sørensen
2000

90 Jones et al. 2002;
Lin et al. 2008
Oxytetracycline 1 10.1 LC50 (48 h)
(mortality)
Nordic Council of
Ministers 2012
0.2 PNEC (72 h) (reproduction) Yamashita et al.
2006
0.183 NOEC (growth
inhibition)
Eguchi et al.
2004
200 Jones et al. 2002;
Lin et al. 2008
Tetracycline 1 82 LC50 (96 h) Pawlowski et al.
2004
44.8 EC50 (21 days)
(reproduction)
Ando et al. 2007 0.09 EC50 (growth rate ) Halling-
Sørensen
2000
21900 Jones et a l. 2002;
Lin et al. 2008
Hormone
17α-
Ethinylestradiol
10 LOEC (21 days)
(fertilization rate)
Grung et al. 2007 0.002 Lin et al. 2008
Environ Sci Pollut Res (2013) 20:8132–8140 8137

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 Table 5. 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.
References
Akinbowale OL, Peng H, Barton MD (2007) Diversity of tetracycline
resistance genes in bacteria from aquaculture sources in Australia. J
Appl Mic robiol 103:2016–2025
Ando T, Nagase H, Eguchi K, Hirooka T, Nakamura T, Miyamoto K et al
(2007) A novel method using cyanobacteria for ecotoxicity test of
veterinary antimicrobial agents. Environ Toxicol Chem 26(4):601–
606
Arikan B, Aygan A (2009) Resistance variations of third generation of
cephalosporins in some of the Enterobacteriaceae members in hos-

pital sewage. Int J Agric Biol 11:93–96
Baronti C, Curini R, D’Ascenzo G, Di Corcia A, Gentili A, Samperi R
(2000) Monitoring natural and synthetic estrogens at activated treat-
ment plants and in receiving river water. Environ Sci Techno l
34:5059–5066
Burhenne J, Ludwig M, Nikoloudis P, Spiteller M (1997) Photolytic
degradation of fluoroqu inolo ne carbo xylic acids in aqueous
solution. Part 1. Primary photoproducts and halflives. Environ Sci
Pollut Res 4(1) :10–15
8138 Environ Sci Pollut Res (2013) 20:8132–8140
Author's personal copy
Cirja M, Zuehlke S, Ivashechkin P, Hollender J, Schaffer A, Corvini PFX
(2007) Behavior of two differently radiolabelled 17 alpha-
ethinylestradiols continuously applied to a laboratory scale mem-
brane bioreactor with adapted industrial-activated sludge. Water Res
41:4403–4412
Córdova-Kreylos AL, Scow KM (2007) Effects of ciprofloxacin on salt
marsh sediment microbial communities. ISME J 1(7):585–595
Duong HA, Pham NH, Nguyen HT, Hoang TT, Pham HV, Pham VC,
Berg M, Giger W, Alder AC (2008) Occurrence, fate, and antibiotic
resistance of fluoroquinolone antibacterials in hospital wastewaters
in Hanoi, Vietnam. Chemosphere 72(6):968–973
Eguchi K, Nagase H, Ozawa M, Endoh YS, Got o K, Hirata K, Miyamoto
K, Yoshimura H (2004) Evaluation of antimicrobial agents for veter-
inary use in the ecotoxicity test using microalgae. Chemosphere
57:1733–1738
Gao P, Mao D, Luo Y, Wang L, Xu B, Xu L (2012) Occurrence of
sulphonamide and tetracycline-resistant bacteria and resistance
genes in aquaculture environment. Water Res 46:2355–2364
GARP-Vietnam (2010) Situation Analysis of Antibiotic Use and Resis-

tance in Vietnam. Project Report
Ge L, Chen J, Wei X, Zhang S, Qiao X, Cai X, Xie Q (2010) Aquatic
photochemistry of fluoroquinolone antibiotics: kinetics, pathways,
and multivariate effects of main water constituents. Environ Sci
Technol 44:2400–2405
Giger W, Alder AC, Golet EM, Kohler HPE, McArdell CS, Molnar E,
Siegrist H, Suter MJF (2003) Occurrence and fate of antibiotics as
trace contaminants in wastewater, sewage sludges, and surface
water. Chimia (Aarau) 57:485–491
Ginebreda A, Munoz I, de Alda ML, Brix R, Lopez-Doval J, Barcelo D
(2010) Environmental risk assessment of pharmaceuticals in rivers:
relationships between hazard indexes and aquatic macro inverte-
brate diversity indexes in the Llobregat River (NE Spain). Environ
Int 36:153–162
Golet EM, Alder AC, Giger W (2002) Environmental exposure and risk
assessment of fluoroquinolone antibacterial agents in wastewater
and river water of the Glatt Valley Watershed, Switzerland. Environ
Sci Technol 36:3645–3651
Gracia-Lor E, Sancho JV, Hernández F (2011) Multi-class determination
of around 50 pharmaceuticals, including 26 antibiotics, in environ-
mental and wastewater samples by ultra-high performance liquid
chromatography-tandem mass spectrometry. J Chromatogr A
1218:2264–2275
Gros M, Petrović M, Barceló D (2006) Development of a multi-residue
analytical methodology based on liquid chromatography–tandem
mass spectrometry (LC–MS/MS) for screening and trace level
determination of pharmaceuticals in surface and wast ewaters.
Ta lant a 70:67 8–690
Grung M, Heimstad ES, Moe M, Schlabach M, Svenson A, Thomas K,
Woldegiorgis A (2007) Human and Veterinary Pharmaceuticals,

Narcotics, and Personal Care Products in the Environment. Swedish
Environmental Research Institute
Grung M, Källqvist T, Sakshaug S, Skurtveit S, Thomas KV (2008)
Environmental assessment of Norwegian priority pharmaceuticals
based on the EMEA guideline. Ecotoxicol Environ Saf 71:328–340
Gulkowska A, Leung HW, So MK, Taniyasu S, Yamashita N, Yeung
LWY, Richardson BJ, Lei AP, Giesy JP, Lam PKS (2008) Removal
of antibiotics from wastewater by sewage treatment facilities in
Hong Kong and Shenzhen, China. Water Res 42:395–403
Halling-Sørensen B (2000) Algal toxicity of antibacterial agents used in
intensive farming. Chemosphere 40:731–739
Halling-Sørensen B, Holten Lützhøft HC, Andersen HR, Ingerslev F
(2000) Environmental risk assessment of antibiotics, comparison
of mecillinam, trimethoprim, and ciprofloxacin. J Antimicrob
Chemother 46(suppl 1):53–58
Harada Y, Matsubara S, Kakimoto M, Noto T, Nehashi T (1976)
Ceftezole, a new cephalosporin C derivative II. Distribution and
excretion in parenteral administration. J Antibiot 29(10):1071–1082
Hirsch R, Ternes T, Haberer K, Kratz KL (1999) Occurrence of antibi-
otics in the aquatic environment. Sci Total Environ 225:109–118
Holten Lützhøft HC, Halling-Sørensen B, Jørgensen SE (1999) Algal
toxicity of antibacterial agents applied in Danish farming. Arch
Environ Contam Toxicol 36:1–6
Homem V, Santos L (2011) Degradation and removal methods of antibi-
otics from aqueous matrices—A review. J Environ Manage
92:2304–2347
Isidori M, Lavorgna M, Nardelli A, Pascarella L, Parrella A (2005) Toxic
and genotoxic evaluation of six antibiotics on nontarget organisms.
Sci Total Environ 346:87–98
Jiang M, Wang L, Ji R (2010) Biotic and abiotic degradation of four

cephalosporin antibiotics in a lake surface water and sediment.
Chemosphere 80(11):1399–1405
Johnson AC, Belfroid A, Di Corcia A (2000) Estimating steroid estrogen
inputs into activated sludge treatment works and observations on
their removal from the effluent. Sci Total Environ 256:163–173
Jones OAH, Voulvoulis N, Lester JN (2002) Aquatic environmental
assessment of the top 25 English prescription pharmaceuticals.
Water Res 36:5013–5022
Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ (2008) The occurrence of
pharmaceuticals, personal care products, endocrine disruptors, and
illicit drugs in surface water in Sou th Wales, UK. Water Res
42:3498–3518
Kidd KA, Blanchfield PJ, Mill s KH, Palace VP, Evans RE ,
Lazorchak JM, Flick RW (2007) Collapse of a fish population
after e xposure to a synthetic e strogen. Proc Natl Acad Sci U S
A104:8897–8901
Kim JW, Ishibashi H, Yamauchi R, Ichikawa N, Takao Y, Hirano M,
Koga M, Arizono K (2009) Acute toxicity of pharmaceutical and
personal care products on freshwater crustacean (Thamnocephal us
platyurus) and fish (Oryzias latipes). J Toxicol Sci 34:227–232
Knapp CW, Cardoza LA, Hawes JN, Wellington EMH, Larive CK,
Graham DW (2005) Fate and effects of enrofloxacin in aquatic
systems under different light conditions. Environ Sci Technol
39:9140–9146
Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber
LB, Buxton HT (2002) Pharmaceuticals, hormones, and other or-
ganic wastewater contaminants in US streams, 1999–2000: a na-
tional reconnaissance. Environ Sci Technol 36:1202–1211
Kumar K, Gupta SC, Chander Y, Singh AK (2005) Antibiotic use in
agriculture and its impact on the terrestrial environment. Adv Agron

87:1–54
Kümmerer K (2009) Antibiotics in the aquatic environment—areview
-part I. Chemosphere 75:417–434
Lai HT, Lin JJ (2009) Degradation of oxolinic acid and flumequine in
aquaculture pond waters and sediments. Chemosphere 75:462–468
Larsen M, Hansen K, Henriksen P, Baatrup E (2008) Male zebrafish
(Danio rerio) courtship behavior resists the feminizing effects of
17α-ethinyloestradiol—morphological sexual characteristics do
not. Aquat Toxicol 87(4):234–244
Layton AC, Gregory BW, Seward JR, Schultz TW, Sayler GS (2000)
Mineralization of steroidal hormones by biosolids in wastewater
treatment systems in Tennessee USA. Environ Sci Technol
34(18):3925–3931
Le TX, Munekage Y (2004) Residues of selected antibiotics in water and
mud from shrimp ponds in mangrove areas in Vietnam. Mar Pollut
Bull 49:922
–929
Lee LS, Strock TJ, Sarmah AK, Rao PSC (2003) Sorption and dissipation
of testosterone, estrogens, and their primary transformation products
in soils and sediment. Environ Sci Technol 37(18):4098–4105
Environ Sci Pollut Res (2013) 20:8132–8140 8139
Author's personal copy
Li B, Zhang T (2010) Biodegradation and adsorption of antibiotics in the
activated sludge process. Environ Sci Technol 44:3468–3473
LinAYC,YuTH,LinCF(2008)Pharmaceuticalcontaminationin
residential, industrial, and ag ricultural waste streams: risk to
aqueous env ironments in Taiwan. Chemosp here 74(1):131–141
Lindberg RH, Wennberg P, Johansson MI, Tysklind M, Andersson BAV
(2005) Screening of human antibiotic substances and determination
of weekly mass flows in five sewage treatment plants in Sweden.

Environ Sci Technol 39(10):3421–3429
Lindberg RH, Olofsson U, Rendahl P, Johansson MI, Tyskli nd M, Andersson
BAV ( 2006) Behavior of fluoroquinolones and trimethoprim during
mechanical, chemical, and active sludge treatment of sewage wa ter and
digestion of sludge. Envi ron Sci T echnol 40:1042–1048
Liu B, Wu F, Deng N S (2003) UV-light induced photode gradation of 1 7
alpha-ethynylestradiol in aqueous solutions. J Haz Mat 98 (1–3):311 –
316
Lunestad BT, Goksøyr J (1990) Reduction in the antibacterial effect of
oxytetracycline in seawater by complex formation with magnesium
and calcium. Dis Aquat Organ 9:67–72
Moschet C (2009) Microbial degradation of steroid hormones in the
environment and technical systems. />aquaticchemistry/teaching/archive_past_lectures/term_paper_08_09/
HS08_CHRISTOPH_MOSCHET_rev_termpaper.pdf
National Agro-Forestry-Fisheries Quality Assurance Department (2009)
Monthly report of antibiotic residue in aquaculture. http://www.
nafiqad.gov.vn/d-chuong-trinh-giam-sat/a-duluong/ (in Vietnamese)
Nonaka L, Ikeno K, Suzuki S (2007) Distribution of tetracycline resis-
tance gene, tet(M), in Gram-positive and Gram-negative bacteria
isolated from sediment and seawater at a coastal aquaculture sites in
Japan. Microbes Environ 22:335–364
Nordic Council of Ministers (2012) PPCP Monitoring in the Nordic
Countries – Status Report
Nowara A, Burhenne J, Spiteller M (1997) Binding of fluoroquinolone
carboxylic acid derivatives to clay minerals. J Agric Food Chem
45:1459–1463
Oka H, Ikai Y, Kawamura N, Yamada M, Harada K, Ito S, Suzuki M
(1989) Photodecomposition products of tetracycline in aqueous
solution. J Agric Food Chem 37:226–231
Park S, Choi K (2008) Hazard assessment of commonly used agricultural

antibiotics on aquatic ecosystems. Ecotoxicology 17:526–538
Pawlowski S, van Aerle R, Tyler CR, Braunbeck T (2004) Effects of 17-
ethinylestradiol in a fathead minnow (Pimephales promelas) gonadal
recrudescence assay. Ecotoxicol Environ Saf 57:330–345
Purdom CE, Hardiman PA, Bye VVJ, Eno NC, Tyler CR, Sumpter JP
(1994) Estrogenic effects of effluents from sewage treatment works.
Chem Ecol 8(4):275–285
Roberts MC (2005) Update on acquired tetracycline resistance genes.
FEMS Microbiol Let t 245:195–203
Ryu SH, Park SG, Choi SM, Hwang YO, Ham HJ, Kim SU, Lee YK,
Kim MS, Park GY, Kim KS, Chae YZ (2012) Antimicrobial resis-
tance and resistance genes in Escherichia coli strains isolated from
commercial fish and seafood. Int J Food Microbiol 152:14–18
Samuelsen OB (1989) Degradation of oxytetracycline in seawater at two
different temper atures and ligh t int ensities and the pe rsistence o f
oxytetracycline in the sediment from a fish farm. A quaculture 83:7–16
Sanderson H, Johnson DJ, Wilson CJ, Brain RA, Solomon KR (2003)
Probabilistic hazard assessment of environmentally occurring phar-
maceutic als toxicity to fish, daphnids, and algae by ECOSAR
screening. Toxicol Lett 144:383–395
Schlabach M (2009) Environmental screening of selected organic com-
pounds. Swedish Environmental Research Institute
Seyfried EE, Newton RJ, Rubert KF IV, Pedersen JA, McMahon KD
(2010) Occurrence of tetracycline resistance genes in aquaculture
facilities with varying use of oxytetracycline. Microb Ecol 59:799–
807
Shimizu A, Takada H, Koike T, Takeshita A, Saha M, Rinawati NN,
Murata A, Suzuki T, Suzuki S, Chiem NH, Tuyen BC, Viet PH,
Siringan MA, Kwan C, Zakaria MP, Reungsang A (2013) Ubiqui-
tous occurrence of sulfonamides in tropical Asian waters. Sci Total

Environ 452–453:108–115
Suzuki S, Hoa PTP (2012) Distribution of quinolones, sulfonamides,
tetracyclines in aquatic environment and, antibiotic resistance in
Indochina. Front Microbiol 3:1–8
Suzuki S, Kobayashi T, Suehiro F, Tuyen BC, Tana TS (2008) High
occurrence rate of tetracycline (TC)-resistant bacteria and TC resis-
tance genes relates to microbial diversity in sediment of Mekong
river main waterway. Microbes Environ 23:149–152
Takasu H, Suzuki S, Reungsang A, Viet PH (2011) Fluoroquinolone (FQ)
contamination does not correlate with occurrence of FQ-resistant
bacteria in aquatic environments of Vietnam and Thailand. Microbes
Environ 26:135–143
Tenover FC (2006) Mechanisms of antimicrobial resistance in bacteria.
Am J Med 119(6):3–10
Thuy HTT, Loan TTC (2012) Antibiotic residues from shrimp farming in
coastal wetland. Nat Resour Environ 2(2012):61– 63 (in
Vietnamese)
Thuy HTT, Nga LP, Loan TTC (2011) Antibiotic contaminants in coastal
wetlands from Vietnamese shrimp farming. Environ Sci Pollut Res
18:835–841
Thuy HTT, Loan TTC, Nga LP, Quoc DP, Phuong TH (2012) Fate of
fluoroquinolone antibiotics in Vietnamese coastal wetland ecosys-
tem. Wetl Ecol Manag 20:399–408
Watkinson AJ, Murby EJ, Kolpin DW, Constanzo SD (2009) The occur-
rence of antibiotics in an urban watershed: from wastewater to
drinking water. Sci Total Environ 407:2711–2723
Wollenberger L, Halling-Sørensen B, Kusk KO (2000) Acute and chronic
toxicity of veterinary antibiotics to Daphnia magna. Chemosphere
40:723–730
Yamashita N, Yasojima M, Miyajima K, Suzuki Y, Tanaka H (2006)

Effects of antibacterial agents, levofloxacin and clarithromycin, on
aquatic organisms. Water Sci Technol 53:65–72
Yang W, Zhou H, Cicek N (2012) Removal mechanisms of 17β-estradiol
and 17α-ethinylestra diol in membrane bioreactors. Water Sci
Technol 66( 6):1263–1269
Zhang XX, Zhang T, Fang HH ( 2009) Antibiotic resistance
genes in water environment. A ppl Microbiol Biotechol
82:397–414
Zuo YG, Zhang K, Deng YW (2006) Occurrence and photochemical
degradation of 17 alpha ethinyl estradiol in Acushnet river estuary.
Chemosphere 63(9):1583–1590
8140 Environ Sci Pollut Res (2013) 20:8132–8140
Author's personal copy