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Thermal baths as sources of pharmaceutical and illicit drug contamination

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  • Geographical Institute Research Centre for Astronomy and Earth Sciences
  • Research Centre for Astronomy and Earth Sciences
  • Research Centre for Astronomy and Earth Sciences

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Despite the fact that there are tens of thousands of thermal baths in existence, knowledge about the occurrence of pharmaceutically active compounds (PhACs) in untreated thermal wastewater is very limited. Because used thermal water is typically legally discharged into surface waters without any treatment, the effluent poses environmental risks for the receiving water bodies. The aim of this study was to show the occurrence patterns and spatiotemporal characteristics of 111 PhACs in thermal wastewater. Six thermal water outflows of different thermal baths were tested in different seasons in the Budapest metropolitan region (Hungary), and diurnal analysis was performed. After solid-phase extraction, the samples were analysed and quantified by coupling supercritical fluid chromatography and mass spectrometry to perform simultaneous multi-residue drug analysis. The results confirm that water discharge pipes directly transport pharmaceuticals into surface water bodies; 34 PhACs were measured to be over the limit of quantification at least once, and 21 of them were found in more than one water sample. The local anaesthetic drug lidocaine, antiepileptic carbamazepine, analgesic derivative tramadol and illicit drug cocaine were detected in more than half of the samples. Caffeine, metoprolol and bisoprolol (cardiovascular drugs), benzoylecgonine (cocaine metabolite), diclofenac (NSAID), citalopram (antidepressant) and certain types of hormones also have a significant frequency of 30-50%. However, the occurrence and concentrations of PhACs vary according to the season and number/types of visitors. As demonstrated by the diurnal fluctuation, drug contamination of thermal waters can significantly vary, even for similar types of baths; furthermore, the quantity and types of some pollutants rapidly change in the discharged thermal wastewater.
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RESEARCH ARTICLE
Thermal baths as sources of pharmaceutical and illicit
drug contamination
Gergely Jakab
1,2,3
&Zoltán Szalai
1,2
&Gábor Michal
1,7
&Marianna Ringer
1
&Tibor Filep
1
&Lili Szabó
1,2
&
Gábor Maász
4
&Zsolt Pirger
4
&Árpád Ferincz
5
&Ádám Staszny
5
&Péter Dobosy
6
&Attila Csaba Kondor
1
Received: 13 July 2019 /Accepted: 25 September 2019
#The Author(s) 2019
Abstract
Despite the fact that there are tens of thousands of thermal baths in existence, knowledge about the occurrence of pharmaceu-
tically active compounds (PhACs) in untreated thermal wastewater is very limited. Because used thermal water is typically
legally discharged into surface waters without any treatment, the effluent poses environmental risks for the receiving water
bodies. The aim of this study was to show the occurrence patterns and spatiotemporal characteristics of 111 PhACs in thermal
wastewater. Six thermal water outflows of different thermal baths were tested in different seasons in the Budapest metropolitan
region (Hungary), and diurnal analysis was performed.After solid-phase extraction, the samples were analysed and quantified by
coupling supercritical fluid chromatography and mass spectrometry to perform simultaneous multi-residue drug analysis. The
results confirm that water discharge pipes directly transport pharmaceuticals into surface water bodies; 34 PhACs were measured
to be over the limit of quantification at least once, and 21 of them were found in more than one water sample. The local
anaesthetic drug lidocaine, antiepileptic carbamazepine, analgesic derivative tramadol and illicit drug cocaine were detected in
more than half of the samples. Caffeine, metoprolol and bisoprolol (cardiovascular drugs), benzoylecgonine (cocaine metabolite),
diclofenac (NSAID), citalopram (antidepressant) and certain types of hormones also have a significant frequency of 30-50%.
However, the occurrence and concentrations of PhACs vary according to the season and number/types of visitors. As demon-
strated by the diurnal fluctuation, drug contamination of thermal waters can significantly vary, even for similar types of baths;
furthermore, the quantity and types of some pollutants rapidly change in the discharged thermal wastewater.
Keywords Discharged thermal wastewater (DTWW) .Surface water contamination .Pharmaceutically active compounds
(PhACs) .Tourism
Introduction
Surface waters are polluted by pharmaceutically active com-
pounds (PhACs), which are regarded as widespread contam-
inants (Aus der Beek et al. 2016;DaughtonandTernes1999;
Deo 2014; Kümmerer 2008; Li et al. 2019). The negative
impact of certain PhACs, such as endocrine-disrupting
chemicals (e.g. hormones), antidepressants, sedatives, anaes-
thetics, recreational substances or illicit drugs, on aquatic eco-
systems has been proven in laboratories and in nature
(Bókony et al. 2018; Capaldo et al. 2018; Maász et al. 2017;
Martin et al. 2017). This problem is exacerbated by the fact
that some of the more persistent and slowly decomposing
agents reach the drinking water supply (Leung et al. 2014;
Tröger et al. 2018) and are absorbed by plants through irriga-
tion (Malchi et al. 2014; Margenat et al. 2019). These PhACs
consequently appear in the human food chain (Carter et al.
2014), even though their concentration is rather low.
Highlights
Bath outflows directly transport pharmaceuticals into surface water
bodies
Six thermal outflows were tested for 111 pharmaceuticals and drugs
Occurrence and concentration of substances is rather visitor related
Due to the flow through water treatment pharmaceuticals changes
rapidly
High biological activity may play a crucial role in pharmaceutical
occurrence
Gergely Jakab and Zoltán Szalai are equally credited authors.
Responsible Editor: Ester Heath
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s11356-019-06633-6) contains supplementary
material, which is available to authorized users.
*Attila Csaba Kondor
kondor.attila@csfk.mta.hu
Extended author information available on the last page of the article
https://doi.org/10.1007/s11356-019-06633-6
Environmental Science and Pollution Research (2020) 27:399410
/Published online: 2 December 2019
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The European Union has referred to the Water Framework
Directive to establish a watchlist of the most important con-
taminants that need to be monitored. The list was last updated
in 2018, and it includes several PhACs, as among others
oestrone (E1), 17β-estradiol (E2), 17α-ethinylestradiol
(EE2), diclofenac and macrolides (EU 2018), the sources of
which will have to be identified, monitored and screened un-
der more scrutiny in the future (Castiglioni et al. 2018;
Könemann et al. 2018).
In addition to communal sewage (Kasprzyk-Hordern et al.
2008; König et al. 2017; Roberts and Thomas 2006), PhACs
can contaminate the environment via other legal sources, such
as grey waters used for irrigation (Etchepare and van der Hoek
2015; Lees et al. 2016). Thermal spa water that has been
discharged into natural waters is also considered to be a legal
source of contamination. Thermal water used for bathing, un-
like that utilized for purposes of energetics, must not be
reinjected into the aquifer because of the presence of bacteria
and other contaminants, therefore it is typically discharged
into surface receivers. Although, in general, used thermal wa-
ter is known to have a potentially harmful environmental im-
pact (e.g. heat and salt load; Benz et al. 2017; Farsang et al.
2015;Kissetal.2013), little remains to be known about the
level of their pharmaceutical contamination, as there are few
reports on PhAC contamination of used thermal water-
sourced surface water. A related test was carried out by Avar
et al. (2016a,b);it revealed the existence ofEE2 (0.52 ng L
1
)
and other hormones (drospirenone, levonorgestrel, progester-
one; 1.26-2.28 ng L
1
) in the Hévíz-Páhoki Canal, which is
fed by Lake Hévíz, one of the largest thermal lakes in the
world. Additionally, the findings of Mackuľak et al. (2014,
2016) in the spa town of Pieštany, Slovakia indicate that a
higher than average presence of illicit drugs and anaesthetics
(e.g. tramadol) should be expected.
The global utilization of thermal water is increasing in co-
incidence with increasing health and wellness tourism (Smith
and Puczkó 2014). Figures released by the Global Wellness
Institute show the extent to which the thermal mineral springs
industry contributes to the more than 4.2 trillion USD well-
ness economy, with approximately 34,000 establishments;
this industry slightly overlaps the more generalized spa indus-
try, which has 150,000 establishments (Global Wellness
Economy Monitor 2018). Thermal spas that use water from
hot springs or drilled wells can be found in nearly 130 coun-
tries. Several thousand establishments discharge untreated
thermal water into natural receivers, thereby harming the vul-
nerable ecosystem.
Earlier research has proven that a significant amount of
PhACs enter swimming pool water during use. Most of this
contamination is the result of unhygienic behaviour (e.g. uri-
nation, defecation, gargling, vomiting) or the rinsing of
chemicals (e.g. creams, plasters) off of the skin (Ekowati
et al. 2016;Fantuzzietal.2018; Lindsay et al. 2017). Other
bodily fluids, such as perspiration due to warm water, can also
play an important role (Kanan and Karanfil 2011; Keuten et al.
2014). To date, PhAC monitoring has mainly been performed
using the water of swimming pools with water recirculation
technology, and where the water is disinfected with chlorine
and undergoes further treatment before being partially
discharged into the communal sewage system; thus, this
water does not reach natural waters directly. Ekowati et al.
(2016) sampled 17 Catalonian pools, and 10 of the 32 moni-
tored PhACs exceeded the limit of quantification (LOQ) val-
ue; particularly, carbamazepine was found to be ubiquitous
(27 of 51 water samples). Fantuzzi et al. (2018) tested the
occurrence of illicit drugs; they found some of their metabo-
lites and 48 pharmaceuticals in 10 indoor swimming pools in
Italy. They also found 11 of the 48 monitored PhACs; regard-
ing illicit drugs, only cocaine and its metabolites were identi-
fied in nine swimming pools.
Disinfection and chlorination in swimming pools help to
keep certain pharmaceutical substances (e.g. naproxen, acet-
aminophen; Weng et al. 2014) at an undetectable level; how-
ever, the reactive chlorine may induce the creation of metab-
olites that can be more toxic than the original compound (Judd
and Bullock 2003; Kanan and Karanfil 2011;Richardsonetal.
2010; Teo et al. 2016; Yue et al. 2016). Alternatively, water
recirculation technology can also influence the amount of cer-
tain PhACs, as some of the water remains in the system for
longer time periods, i.e. up to a few weeks, therefore allowing
chlorine-resistant compounds to accumulate (Ekowati et al.
2016; Fantuzzi et al. 2018). In the case of swimming pools,
the incoming tap water may already be contaminated by
PhACs (Suppes et al. 2017). However, in the case of thermal
spas, the filling water is typically sourced from hundreds of
metres underground, is above 30 °C, has high mineral content
and is free from anthropogenic contamination. Thus, to pre-
serve its therapeutic effects, the water cannot be diluted with
municipal water and cooled, and it cannot be disinfected like
the water of swimming pools, therefore, there is a larger
amount and variety of active microbial life in thermal water
as compared to treated water. The high biological activity can
breakdown organic molecules (even PhACs), and a number of
metabolites can be created (Szuróczki et al. 2016). Thermal
pools typically have a filling and draining system, or an in-
stantaneous system. The used thermal water is continuously
and directly discharged into natural waters without any further
treatment; this means that the PhACs that it may contain are
also discharged into natural waters (Farsang et al. 2015;Kim
1999). In countries in temperate and cold zones, where most
thermal spas can be found, spa use is more seasonal than
swimming pool use, and this impacts the potential contamina-
tion of the outflowing water (CP 2015, Ferrante et al. 2018,
Duro and Turrión-Prats 2019). Tourist influx in the summer
causes the number of visitors to increase, and can also pro-
foundly impact contamination levels. Based on statistics the
Environ Sci Pollut Res (2020) 27:399410
400
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types of winter and summer visitors significantly differ
(Csapó and Marton 2017). Tourists from abroad are overrep-
resented in summer visitors, whereas the ratio of elderly locals
is higher during the winter (HCSO 2017). Thus, it is necessary
to determinethe effectsof wellness and therapeutic tourism on
PhAC loads in thermal spas.
Hungary, particularly its capital, Budapest, has a number of
thermal spas, some of which are internationally renown (Erfurt-
Cooper and Cooper 2009). In terms of the number of thermal
springs and the overall industry, the country has a high global
ranking (Global Wellness Economy Monitor 2018; Michalkó
and Rácz 2010). Although there are risks attributed to the pres-
ence of PhACs and illicit drugs in surface waters, and there are
many thermal bath outflows all over the world, the contribution
of thermal spas has not yet been investigated. Therefore, in this
study, the concentrations of PhACs in discharged thermal
wastewater (DTWW) were investigated by using Hungarian
examples. The analysis summarized in this paper was per-
formed within the framework of a 3-year-long research project
supported by the Hungarian government that examined PhAC
contamination in the Budapest metropolitan region.
The aim of the study was i) to determine which PhACs can
be detected in DTWW; ii) to determine if the levels of PhACs
differ between the internationally recognized spas frequented
by tourists (international baths), and the baths that mainly
attract local inhabitants (local baths); iii) to determine if the
above-mentioned differences vary according to the season;
and iv) to determine if the levels of PhACs in internationally
recognized baths fluctuate within one single day in the high-
tourist season.
Materials and methods
Sampling properties
Water samples were collected from the open-ended water dis-
charge pipes of six Hungarian thermal baths in and around
Budapest from which effluent is directly transported to surface
waters. Each of these baths have drilled thermal wells, and the
sampled water outflows were located 10-20 m from the baths.
In this study, the baths were blindly marked as A through F.
Spas A, B and C are located in the central part of Budapest;
their number of visitors exceeds 300,000 per year. They are
open to tourists throughout the entire year, and, in addition to
the pools with certified therapeutic water, they also offer cold-
water pools for recreational purposes. Spas D, E and F are
located in the outskirts and suburbs of Budapest. They are also
open throughout the entire year, and, like Spas A-C, they have
pools with therapeutic water, and cold-water pools. However,
these spas are smaller, and receive 150,000-300,000 visitors
per year (HCSO 2017). The thermal pools of the sampled spas
are visited by more than 100 people in a single day in the
winter, at the larger spas, the number of thermal pool users
exceeds 1000 people per day in summer.
The sampled water pipes directly transport the used thermal
water collected from the thermal pools to surface waters. The
water from the discharge pipes is not directly related to the
nominal capacity of thermal wells, and some thermal spas
have more than one water outflow. The volume of the
DTWW significantly fluctuates; specifically, at peak times, it
is typically 100-200 L min
1
, which can vary depending on
the operations of the bath. The fluctuation of the temperature
of the effluent was minimal (28-35 °C), regardless of the sea-
son or the establishment;this is because the water temperature
of the pools designated for therapeutic purposes ranges from
30 to 35 °C, and the water is directly transported to the water
discharge pipe without any further dilution or cooling.
Overall, the water chemistry-related parameters (pH, conduc-
tivity, mineral content) of the sampled water were consistent
with the official data on the certified thermal waters, as pro-
vided by each of the spas; therefore, the volume of non-
thermal-pool water in outflow pipes, such as water sourced
from non-thermal pools, was, with one exception, negligible
at the time of sampling.
To examine seasonal fluctuation, the samples were collect-
ed in the off-season (15 February 2018, Thursday), pre-season
(10 June 2018, Sunday) and main tourist season (26
July 2018, Thursday), this corresponds to 6 spas × 1 sample
× 3 seasons = 18 samples. The sampling was always per-
formed between the time period of 13:00 and 16:00, as the
contaminated thermal water was presumed to be passing
through the discharge pipes by this time because of the filling
and draining system. However, the off-season sample from
Spa B was corrupted during laboratory preparations, causing
the measured values to be unreliable; therefore, they were not
used in the analysis. Thus, 17 water samples were used in the
seasonal analysis. To examine diurnal PhAC content fluctua-
tion in the DTWW, Spas A and B were sampled every 3-4 h. It
was not feasible to sample Spas A and B on the same day
because of logistical problems, namely - parallel with diurnal
monitoring at Spa A - other spas were also sampled.
Therefore, diurnal samples were obtained from Spa B during
a large-scale international music festival. Because the admis-
sion fee to the festival included free access to the spa, there
was a large number of foreign visitors. A total of seven (26
July 2018, Thursday, 6-24 h) and four (12 August 2018,
Sunday, 8-20 h) samples were collected from Spas A and B,
respectively; note that an (unplanned) additional sample was
obtained from Spa A because the composition of the
discharged water was visibly observed to suddenly change.
Thus, diurnal fluctuations were analysed as based on 12 sam-
ples from two locations. Spa B has two thermal water out-
flows, and the water from the other discharge pipe is used
by a different institution for heating and irrigation; therefore,
the sampled outdoor outflow was not always operating at full
Environ Sci Pollut Res (2020) 27:399410 401
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capacity. Consequently, four samples were collected per day,
at times when the output water pressure was high for longer
periods of time.
All samples (2.5 L for PhACs) were collected in amber
silanised glass bottles with Teflon faced caps (Thermo
Fisher Scientific) as grab samples and transported to the lab-
oratory in a darkcooler filled with ice within 4 h.The samples
were stored in a dark environment at 4 °C and extracted within
20 h, thereby, the sample was fully prepared within 24 h from
the sampling. The evaporated samples were stored at 80 °C
and analysed within 30 days.
The water was sampled at the joint, open-ended water dis-
charge pipes of the selected thermal spas; thus, the samples
reflect all the thermal water pools of each spa. The differences
between the pools, and those caused by the water recirculation
and/or filling and draining technology, were not considered;
this is because this study focused on the contamination level
of the water entering the surface water. The samples collected to
measure the levels of organic PhACs were preserved in formic
acid at a pH level below 2.0. To determine the basic
hydrochemical properties, 0.5 L of water was collected in a
sterile glass container. To assess carbon and nitrogen content,
50 ml of each sample was collectedandpreservedinformic
acid at a pH level below 2.0. To determine the heavy metal
content, 15 mL of water was collected in a centrifuge tube;
then, the sample was filtered by using a 0.45-μm PVA filter,
and nitric acid was added until the pH level decreased to below
2.0. The temperature, conductivity and redox potential of the
outflowing water were simultaneously measured as each sam-
ple was collected. All of these variables were also measured in
the laboratory, Table S1 provides the corresponding values.
Evaluation of hydrochemical properties
Dissolved carbon and nitrogen content was determined with a
MULTI N/C 3100 type, Analytik Jena AG made TOC/TN
instrument. The concentration of cations (ammonium, calci-
um, magnesium, sodium, potassium) and anions (fluoride,
chloride, sulphite, bromide, nitrite, nitrate) was established
with the help of a dual channel Dionex ICS 5000+ ion chro-
matograph. The nitrate and phosphate content of water sam-
ples was measured with a HACH DR/2000 type spectropho-
tometer, and its heavy metal content with a PlasmaQuant MS
Elite, Analytik Jena, Jena, Germany (ICP-MS) mass
spectrometer.
PhAC analysis
Details of the sample preparation process and setup for anal-
ysis have been previously reported (Maasz et al. 2019). To
summarize, the water samples were acidified with formic acid
and spiked with corresponding mass-labelled internal standard
to the sample quantification and compensation the matrix
effect and chemical losses during the sample preparation.
Due to the relatively low concentration, analytes in the filtered
samples were isolated using solid-phase extraction applying
Strata X-CW cartridges (33 μm, 200 mg 6 mL
1
, #8B-S035-
FCH, Phenomenex) and then eluted with ammonium
hydroxide-acetonitrile solution by AutoTrace 280 automatic
SPE system (Thermo Scientific). The sample was fully pre-
pared within 24 h from the sampling. The evaporated (by
nitrogen gas stream) eluates were reconstituted with acetoni-
trile and transferred to vials within30 days. Derivatization (by
dansyl-chloride) of steroid agents was performed to reach the
appropriate sensitivity. The selected PhACs were analysed
and quantified using supercritical fluid chromatography
(ACQUITY UPC2 system, Waters) coupled with tandem
mass spectrometry (MS) (Xevo TQ-S Triple Quadrupole,
Waters). Data were recorded in three technical replicates by
MassLynx software (V4.1 SCN950) and evaluated by
TargetLynx XS software. Separation of compounds was per-
formed on a 3.0 mm × 100.0 mm, 1.7 μm particle size,
ACQUITY UPC2 BEH analytical column (#186007607,
Waters). The MS measurement was performed in positive
ion mode. The electrospray ionization source was operated
at a spray voltage of 3 kV in both positive and negative ion
modes, and at a cone voltage of 30 V. MS/MS experiments
were performed by applying the multiple-reaction monitoring
method with an isolation window of 0.4 m/z. The observed
ions (mass in m/z) were accepted and quantified if the follow-
ing variables were within their respective limits: MS1 mass,
retention time, MS2 masses, fragmentation pattern and IS cor-
rection. Method characteristics, LOD, LOQ and validation
values are listed in Table S2.
The samples were used to identify 111 PhACs, including
pharmaceutical derivatives, illicit drugs and alkaloids such as
cocaine and caffeine. The agents to be analysed were deter-
mined based on Hungarian consumption data and the toxico-
logical effect profile. The PhACs were categorized into the
following nine groups for analysis: 1) antidepressants, 2) an-
tiepileptics, 3) anxiolytics, 4) cardiovascular drugs, 5) hor-
mones and derivatives, 6) stimulants, psychedelics, hallucino-
gens and their metabolites, 7) nonsteroidal anti-inflammatory
drugs (NSAIDs), 8) anaesthetics and analgesics, 9) other (in-
cluding alkaloids, such as caffeine). The groups can be direct-
ly compared to the classification systems described in the
relevant literature on PhAC contamination of swimming pools
(e.g. Fantuzzi et al. 2018).
Results and discussion
General results
Thirty-four of the monitored 111 PhACs were found to exceed
their respective LOQ value at least once in one of the water
Environ Sci Pollut Res (2020) 27:399410
402
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samples (Table S3); additionally, 21 of the PhACs were de-
tected in more than one sample. There are significant differ-
ences in the frequency of occurrence and concentration levels
of the detected PhACs (Table 1).
Theophylline was found to have the highest absolute con-
centration (max = 7184 ng L
1
); however, those were frequent
only at a rate of 20%. The average concentration of caffeine,
i.e. the most common stimulant, exceeded 1000 ng L
1
.Itis
present in various food items and health supplements (e.g.
coffee, energy drinks) as a natural component, and is not re-
lated to the consumption of pharmaceuticals; however, it can
be an indicator that the spa water has been contaminated by
urine and/or other bodily fluids (Teo et al. 2016). As was
observed with two antiepileptics (carbamazepine and
lamotrigine), three types of hormones (E1, EE2 and testoster-
one) and the illicit drug cocaine, lidocaine (anaesthetic) and
diclofenac (NSAID) the latter is an agent of several non-
prescription drugs, were found to have an average concentra-
tion above 10 ng L
1
. Note that, whether a PhAC is prescrip-
tion or non-prescription does not impact the frequency of its
occurrence in the samples. For some active substances (e.g.
carbamazepine, diclofenac, cocaine), the results were
Table 1 Concentrations of all PhACs found to exceed their LOQ value (MIN: measured minimum value, MAX: measured maximum value, Mean:
average of the measured values >LOQ)
PhACs Pharmacological classification Frequency of occurrence LOQ MIN MAX Mean
Number % ng L
1
lidocaine anaesthetics 22 79 0.10 0.81 132.86 29.84
tramadol analgesics 16 57 0.10 0.22 14.96 2.11
carbamazepine antiepileptics 17 61 0.10 0.17 188.57 32.13
lamotrigine antiepileptics 6 21 5.00 18.49 96.59 54.07
bupropion antidepressants 1 4 0.50 na 1.16 na
citalopram antidepressants 11 39 0.10 0.10 3.26 1.56
tiapride antidepressants 1 4 0.10 na 0.25 na
trazodone antidepressants 1 4 0.05 na 0.21 na
alprazolam anxiolytics 1 4 0.10 na 0.54 na
cinolazepam anxiolytics 1 4 0.10 na 0.36 na
betaxolol cardiovascular drugs 1 4 0.50 1.12 1.12 0.00
bisoprolol cardiovascular drugs 10 36 0.50 0.74 13.27 3.48
metoprolol cardiovascular drugs 9 32 0.10 0.60 9.54 4.07
perindopril cardiovascular drugs 4 14 0.10 0.24 0.89 0.52
propafenone cardiovascular drugs 2 7 0.50 0.91 1.55 1.23
verapamil cardiovascular drugs 1 4 0.05 na 0.56 na
benzoylecgonine stimulants (metabolite) 9 32 0.10 0.67 6.47 2.93
cocaine stimulants 15 54 0.05 0.14 194.02 30.33
ketamine hallucinogenic drugs 1 4 0.50 na 57.00 na
norketamine hallucinogenic drugs 1 4 5.00 na 10.37 na
oestrone hormones 12 43 0.05 0.10 112.59 12.03
17α-estradiol hormones 10 36 0.05 0.05 39.48 4.42
17β-estradiol hormones 1 4 0.05 na 5.60 na
estriol hormones 7 25 0.05 0.07 2.09 0.58
17α-etynylestradiol hormones 13 46 0.05 0.64 98.33 17.22
testosterone hormones 7 25 0.50 0.61 97.31 22.51
progesterone hormones 9 32 0.50 0.51 10.24 2.98
levonorgestrel hormones 3 10 1.00 1.06 8.19 3.70
drospirenone hormones 1 4 1.00 na 1.84 na
paracetamol NSAIDs 1 4 20.00 na 76.10 na
diclofenac NSAIDs 12 43 0.50 1.61 57.59 24.33
theophylline other (alkaloids) 6 21 10.00 59.43 7184.16 3308.93
caffeine other (alkaloids) 9 32 10.00 484.96 2061.43 1347.20
papaverine other (alkaloids) 1 4 0.10 na 1.36 na
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generally consistent with what was expected as based on the
results for swimming pools or different types of polluted wa-
ters frequented by tourists; however, until this study, most of
the above-mentioned PhACs had not been measured in bath-
ing waters.It should be noted that 17α-estradiol (aE2) and E2,
which are generally detected in all types of environmental
monitoring assessments (Aus der Beek et al. 2016), were de-
tected, but the frequency of detection of the former was much
higher in the sampled thermal spa water.
These findings can be used to compare the proportions of
the different groups of PhACs (Fig. 1). Although hormones
were the most frequent, the occurrence of hallucinogenic
drugs was also higher than their ratio within then monitored
111 PhACs. The increased proportion of antiepileptics (e.g.
carbamazepine, lamotrigine) is also significant; conversely,
the proportion of antidepressants decreased in the found and
frequent groups. Moreover, as with swimming pool water
(Ekowati et al. 2016; Fantuzzi et al. 2018), this group of
PhACs, particularly carbamazepine, was most frequently
found in thermal spa water. In contrast, anxiolytics and anaes-
thetics were not observed in high concentrations, although
some of their representative compounds, such as tramadol
and lidocaine, were detected in many of the samples. The
latter two PhACs were also found to be highly persistent, as
reported by Bollmann et al. (2016), Wood et al. (2017),
Malchi et al. (2014) and López-García et al. (2018). It should
be noted that neither the occurrence or concentration of
PhACs was found to be related to the chemical properties of
the spa water (Table S1). This also suggests that PhAC content
is independent of the water source, and that the analysed
PhACs are chemically stable enough to not interact with the
high solute components of the thermal water.
Regarding the PhACs that were detected only once, Spa B,
which is very popular with foreign visitors, exhibited the
highest rate of occurrence of single detection (four of six
samples). These PhACs include antidepressants (trazodone),
NSAIDs (paracetamol) and hallucinogenic drugs (ketamine
and norketamine). Accordingly, the lowest occurrence (three
of 10 samples) was found at Spa A, which also has a high
number of domestic and international visitors; one antidepres-
sant (bupropion) and two cardiovascular drugs (betaxolol, ve-
rapamil) were detected only once there. Alternatively, one
antidepressant (tiapride) and one anxiolytic (cinolazepam)
were found to be unique agents in three samples from Spa
C. For the local spas, there was no single occurrence at Spa
D, and, in the case of Spas E and F, the single-occurrence
PhACs were in the group termed other, e.g. papaverine
and anxiolytics (alprazolam, cinolazepam). Although there
were single occurrences of antidepressants at all of the inter-
national baths, this was not the case for any of the local spas.
Note that the above-mentioned PhACs were not included in
further analysis since they were only found in one sample.
Seasonal and geographical analysis
Seasonal analysis of the 17 samples collected from all out-
flows revealed hormones to be the most prevalent group in
the summer. Of the eight detected hormones, only testosterone
was found to occur in every season; hormones related to con-
traceptives were detected in all of the summer samples (Fig. 2,
Table S3). This is consistent with the empirical fact that young
women tend to visit thermal baths more often during their
summer holiday (HCSO 2017).
Alternatively, drugs used for the treatment of cardiovascu-
lar disorders (e.g. bisoprolol, metoprolol, perindopril) were
most prevalent in the tourism off-season. Two of the four
cardiovascular PhACs were not detected in the high-tourist
season, and the remaining two were only found in a few sam-
ples. As a hypothesis, this may indicate that older generations
Fig. 1 PhACs compositions in
the Monitored (all 111 PhACs);
Found (detected in at least one
sample, >LOQ) and Frequent
(detectedinmorethanone
sample > LOQ) groups
Environ Sci Pollut Res (2020) 27:399410
404
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
prefer to visit thermal spas in the off-season, as it was also
reported by Löke et al. (2018).
Various PhACs, such as the anaesthetics tramadol and li-
docaine, were found in most of the water samples, regardless
of the season. The possible reasons for the high proportion and
persistence of antiepileptics have been discussed above. It
should be noted that the absence of lamotrigine in the summer
samples was unexpected. This phenomenon cannot be ex-
plained using the currently available results; thus, its interpre-
tation necessitates further investigation. As was observed in
the results from swimming pools in Italy (Fantuzzi et al.
2018), in this study, cocaine was detected in every season;
furthermore, it was found in every sample in the pre-season.
This finding indicates that cocaine consumption is also wide-
spread among the local population, as Thomas et al. (2012)
and Mackulak et al. (2016) have also revealed. However, the
absolute peaks were observed in the summer at spas
frequented by tourists (Table S3).
Regarding geographical variation, research has shown that,
as compared to spas mainly visited by the locals, nearly all
PhACs occur more frequently at international thermal spas with-
in the city centre, and that the average concentrations of the
detected PhACs are higher, especially in the cases of cocaine
and certain hormones. The exceptions are the two forms of
oestrogen and the cardiovascular drug propafenone, which oc-
cur more frequently at spas located outside of the city (Fig. 3).
Diurnal analysis
Eight water samples were collected for Spa A diurnal analysis,
and only 15 of the 111 possible PhACs were detected (Fig. 4).
It should be noted that nearly half of the identified PhACs
were hormones, and that the occurrence (and non-
occurrence) of many other agents were atypical.
EE2 was identified at high concentrations (average:
23.1 ng L
1
), and with a wide range (4-98 ng L
1
,inseven
of the eight samples (coefficient of variation, CV = 140%).
The oestrogens were found to dynamically fluctuate,
exhibiting no apparent patterns. Different types of hormones
(testosterone, progesterone, levonorgestrel) were only occa-
sionally measured at low concentrations.
Of the anaesthetics, lidocaine was dominant in terms of fre-
quency and concentration. Nevertheless, the concentration of
this substance relevantly fluctuated (CV = 130%), and it was
absent in three samples, indicating fast water replacement.
Additionally, the steadily high concentration of EE2 indicates
persistent contamination throughout the entire day. It is also
noteworthy that the typically frequently detected carbamaze-
pine (Aus der Beek et al. 2016; Heberer 2002) was detected
only once (in the afternoon sample), and that the concentration
of diclofenac was found to be zero. Although they were detect-
ed in only three samples, alkaloids were found to have the
highest concentration, i.e. >1 μgL
1
in each case; this also
indicates fast water replacement and no accumulation.
Additionally, although cocaine was detected in only two of
the eight samples, its metabolite (benzoylecgonine) was present
in five samples.
Regarding daily distribution, an absolute peak was found in
the number of PhACs measured in sample of 15:00 at Spa A,
when nine PhACs were found. The next highest peaks oc-
curred in the noon and midnight samples. The 9:00 sample,
and the sample containing the murky water observed at 18:30
(according to general water chemistry, this sample was due to
pool rinsing), were found to have the fewest PhACs, even
though both samples also contained lidocaine and EE2.
Regarding the diurnal analysis for Spa B, which has inter-
national visitors, of the 15 PhACs that were found, only one-
third of them were hormones (Fig. 5). Some of the detected
hormones were also found at Spa A (e.g. E1, E2, estriol);
however, the summer diurnal analysis for Spa B did not yield
EE2; furthermore, it was only detected once at Spa B (26
July 2018). Although several types of hormones were found,
their concentrations were not high; specifically, with the ex-
ception of the testosterone measured in one sample, all
Fig. 2 Seasonal occurrence
frequency of the detected drugs
(%); A.epi: antiepilepticum;
A.dep: antidepressants;
Cardiovascular: cardiovascular
drugs; Anaesth: anaesthetics and
analgesics; NSAIDs: nonsteroidal
anti-inflammatory drugs;
Hallucin: stimulants,
hallucinogens and their
metabolites
Environ Sci Pollut Res (2020) 27:399410 405
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
hormones remained below 1 ng L
1
. Additionally, only the
concentration of E1 was stable, as the concentrations of the
other hormones fluctuated throughout the day; specifically,
their occurrence was inconsistent.
The concentrations of the anti-inflammatory drug
diclofenac and anaesthetic lidocaine were found to be high
(typically >10 ng L
1
), moreover, the time of day did not
relevantly affect the concentrations of these compounds
(CV = 40% and 30%, respectively). Because there was no
accumulation, the persistent presence of these compounds in-
dicates continuous and largely invariable levels of contamina-
tion. The concentration of the antiepileptic drug carbamaze-
pine (CV = 14%) was also found to be high and very stable;
specifically, the concentration was considerably higher
(36.1ngL
1
) than the swimming-pool-water average
(1.1 ng L
1
) measured by Fantuzzi et al. (2018). Although
Fantuzzi et al. (2018) detected carbamazepine metabolites at
concentrations up to 62 ng L
1
, their accumulation resulting
from water recirculation should be taken into account. Thus,
the persistently high concentration as a result of continuous
contamination is rather relevant. Additionally, although it
fluctuated (CV = 63%), the concentration of cocaine was
found to be the highest; furthermore, the concentration
remained high throughout the day. The concentration of co-
caine measured at Spa B within a single day (46-194 ng L
1
,
average: 104.2 ng L
1
) was found to be higher, by two orders
of magnitude, than the corresponding swimming pool mea-
surement by Fantuzzi et al. (2018) (average: 1.29 ng L
1
), and
the average ofthe data used forgeographicalanalysis (4.8 and
1.3 ng L
1
for international and local spas, respectively). It
should be noted that, although the cocaine metabolite
benzoylecgonine was detected in several samples from Spa
A under the condition of low cocaine occurrence, this metab-
olite was not detected at Spa B. This is unexpected, as
Fig. 4 Diurnal fluctuation of
PhAC concentrations in the
DTWW outflow of Spa A on 26
July 2018; A.epi: antiepilepticum;
A.dep: antidepressants;
Anaesthetics: anaesthetics and
analgesics; Hallucinogen:
stimulants, hallucinogens and
their metabolites
Fig. 3 Geographical-based
frequency variation of the
detected PhACs (%) of all
seasons; A.epi: antiepilepticum;
A.dep: antidepressants;
Cardiovascular: cardiovascular
drugs; Anaesth: anaesthetics and
analgesics; NSAIDs: nonsteroidal
anti-inflammatory drugs;
Hallucin: stimulants,
hallucinogens and their
metabolites
Environ Sci Pollut Res (2020) 27:399410
406
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
benzoylecgonine is much more stable than cocaine and the
concentration of the former is generally higher (McCall et al.
2016; Thiebault et al. 2019). The background of this finding
has been unknown yet, presumably, some other sources of
cocaine (other than human metabolism) might have been pres-
ent in the thermal water of Spa B.
Regarding daily fluctuation, the number and concentrations
of PhACs were found to reach their peak in the early afternoon.
Weng et al. (2014)andTeoetal.(2016) reported that caffeine
could be a good indicator of urination and other types of excre-
ment in swimming pools because it was consistently present at
a high concentration, which was related to the number of visi-
tors. However, this theory is not fully supported by the findings
of this study; although one sample was found to have a high
concentration of caffeine, it wasabsentinfourofthesamples
(note: eight total samples). This supports the view that the mea-
surements from swimming pools with strongly chlorinated wa-
ter and water recirculation systems can only be indirectly com-
paredtothermalspasystems.
Analysing all of the samples (off-season, pre-season, main
season and diurnal monitoring) from the two international
spas, which are similar in size and target the same type of
visitors, revealed that the frequency and concentration of car-
bamazepine are constantly low at Spa A, unlike those at Spa
B. However, as compared to Spa B, the frequent occurrence of
hormones and constant presence and high concentration of
EE2 at Spa A are relevant.
Conclusions
The findings of this study reveal that significant amounts of
PhACs enter thermal waters through the human body of vis-
itors, and are then directly transported to surface waters. The
measured concentrations indicate that thermal spas are not the
main sources of contamination even though the emission of
PhACs can still be relevant. The study itself, and the interpre-
tation of the results, have some constraints. For example, the
exact number, age and type (local inhabitants vs. tourists) of
visitors who used the thermal pools during periods of sample
collection are unknown. Furthermore, no previous studies, to
which the results of this study can be compared, could be
found. Nevertheless, our results can facilitate accurate assess-
ment of the environmental pollution caused by DTWW, they
also suggest the following:
&The concentrations and frequency of occurrence of
PhACs contaminating the environment could be seasonal
and dependent on the type of visitors.
&Many types of visitors use illicit drugs, as they were de-
tected at international and local spas. However, although
the concentrations of these PhACs increased at the time of
an international music festival, there was no sudden
change in the concentrations of other substances.
&As compared to the corresponding swimming pool mea-
surements, PhACs remain in thermal pools for shorter
periods of time, and at lower concentrations, because of
the different filling and draining water treatment process-
es; furthermore, the types of PhACs can significantly
change within a few hours in a thermal pool. Thus, the
sampling time at thermal spas can be a critical determining
factor. However, the concentrations of carbamazepine,
diclofenac and cocaine, which are usually ubiquitous and
very harmful to the environment, were negligible at one of
the sampled spas, whereas the occurrence and concentra-
tions of certain hormones were extremely high.
&Because the treatment and discharge technology and the
type of visitorsare not sufficient to justify such significant
differences, it is likely that different microbial composi-
tions and activity levels are contributing factors.
&Further research is required to better support the develop-
ment of environmental risk reduction procedures.
Fig. 5 Diurnal fluctuation of
various PhAC concentrations in
the thermal water discharged from
Spa B on 12 August 2018; A.dep:
antidepressants; A.epi:
antiepilepticum; Anaesth:
anaesthetics and analgesics;
NSAIDs: nonsteroidal anti-
inflammatory drugs; Halluc:
stimulants, hallucinogens and
their metabolites; Cardiovasc:
cardiovascular drugs
Environ Sci Pollut Res (2020) 27:399410 407
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Acknowledgments Open access funding provided by MTA Research
Centre for Astronomy and Earth Sciences (MTA CSFK). The research
was supported by National Research, Development and Innovation
Office (NKFIH), Hungary. Identification number: NVKP_16-1-2016-
0003.
Compliance with ethical standards
Declaration of interest The authors declare that they have no known
competing financial interests or personal relationship that could have
appeared to influence the results presented in this paper.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a link
to the Creative Commons license, and indicate if changes were made.
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Gergely Jakab
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&Zoltán Szalai
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&Gábor Michal
1,7
&Marianna Ringer
1
&Tibor Filep
1
&Lili Szabó
1,2
&Gábor Maász
4
&
Zsolt Pirger
4
&Árpád Ferincz
5
&Ádám Staszny
5
&Péter Dobosy
6
&Attila Csaba Kondor
1
1
Geographical Institute, Research Centre for Astronomy and Earth
Sciences, Hungarian Academy of Sciences, Budaörsi út 45,
Budapest H-1112, Hungary
2
Department of Environmental and Landscape Geography, Eötvös
Loránd University, Pázmány Péter sétány 1/C, Budapest H-1117,
Hungary
3
Institute of Geography and Geoinformatics, University of Miskolc,
Egyetemváros, Miskolc H-3515, Hungary
4
MTA-Centre for Ecological Research, Balaton Limnological
Institute, Klebelsberg Kuno u. 3., Tihany H-8237, Hungary
5
Department of Aquaculture, Szent István University, Páter K. u. 1,
GödöllőH-2100, Hungary
6
MTA-Centre for Ecological Research, Danube Research Institute,
Karolina út 29, Budapest H-1113, Hungary
7
Corvinus University of Budapest, Főm tér 8, Budapest H-1093,
Hungary
Environ Sci Pollut Res (2020) 27:399410
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... In this research, 26 small streams were sampled at 75 sampling sites ( Fig. 1; Fig. S1). The sampling frame was part of a larger research program aimed at exploring the PhACs contamination and its environmental and human risks of surface water (including the river Danube), groundwater, and drinking water in the Budapest metropolitan area (Kondor et al., 2021(Kondor et al., , 2020Staszny et al., 2021). The average water discharge of the sampled perennial streams ranged from 0.01 m 3 ·s -1 to 0.46 m 3 ·s -1 , but the average water flow of 19 streams did not reach 0.10 m 3 ·s -1 (Table S1) (RBMPH, 2015). ...
... Twenty-one sampling sites were located above WWTP discharges, from which thirty-five samples were collected. The outflows of the largest WWTPs of Budapest, which are responsible for 80% of the discharged wastewater in this region, flow directly into the Danube River (Kondor et al., 2020); thus, they were not covered by this study. ...
... One hundred and eleven PhACs with various physicochemical characteristics (Table S4) and seven heavy metals in both the aqueous and sediment phases were examined. The details of the applied water sampling methods, preparation processes, instrumental analytical approaches, validation parameters of measured PhACs, and data evaluation have been published in previous studies (Kondor et al., 2020;Maasz et al., 2019). Briefly, water sampling for strong anion and cation analyses was conducted by collecting a 500 mL water sample in a brown borosilicate glass container. ...
Article
Full-text available
Small streams are crucial but vulnerable elements of ecological networks. To better understand the occurrence of pharmaceutically active compounds (PhACs) in streams, this study focused on the occurrence, distribution, and environmental risk of 111 PhACs and 7 trace elements based on a total of 141 water and sediment samples from small streams located in the urbanizing region of Budapest, Hungary. Eighty-one PhACs were detected in the aqueous phase, whereas sixty-two compounds were detected in the sediment. Carbamazepine (CBZ) was the most frequently identified PhAC in water, and was found in 91.5% of all samples. However, the highest concentrations were measured for lamotrigine (344.8 μg·L⁻¹) and caffeine (221.4 μg·L⁻¹). Lidocaine was the most frequently occurring PhAC in sediment (73.8%), but the maximum concentrations were detected for CBZ (395.9 ng·g⁻¹) and tiapride (187.7 ng·g⁻¹). In both water and sediment, more PhACs were found downstream of the wastewater treatment plants (WWTPs) than in the samples not affected by treated wastewater, even though no relationship was observed between the total amount of treated wastewater and the number of detected PhACs. The PhAC concentrations were also independent of the distance from the WWTP effluents. PhAC-polluted samples were detected upstream of the WWTPs, thereby suggesting the relevance of diffuse emissions in addition to WWTP outlets. The most frequently detected PhACs in the sediment were usually also present in the water samples collected at the same place and time. The varying concentrations of PhACs and the fluctuating water–sediment properties resulted in a lack of correlation between the general chemical properties and the concentrations of PhACs, which makes it difficult to predict PhAC contamination and risks in urbanized small streams. The environmental risk assessment indicated that diclofenac had the highest risk in the sampling area.
... We chose the nominal concentration of 30 ng/L EE2 for two reasons. First, this value is environmentally realistic; for example, the average EE2 concentration in ponds, lakes and rivers is a few ng/L (Avar et al., 2016;Mina et al., 2018;Rechsteiner et al., 2020), but higher concentrations up to 98.33 ng/L occur at point sources of pollution (Jakab et al., 2020). Also, in a previous study (Bókony et al., 2018) we found EE2 in the sediment of a pond where agile frogs breed. ...
... A notable difference is that previous studies showing female-biased sex ratios in response to EE2 in amphibians either exposed individuals throughout their entire larval development and/or used doses much higher than the environmentally realistic concentrations Gyllenhammar et al., 2009;Hogan et al., 2008;Mackenzie et al., 2003;Pettersson and Berg, 2007;Tompsett et al., 2013Tompsett et al., , 2012. Our treatments were ecologically relevant in terms of both magnitude and duration, as EE2 typically occurs in surface waters in the ng/L concentration range and its presence is usually not constant, possibly due to photolysis and adsorption to suspended solids and sediment (Avar et al., 2016;Bhandari et al., 2015;Jakab et al., 2020;National Center for Biotechnology Information, 2020). Therefore, our findings suggest that population persistence in the agile frog (and other species with similar sensitivities) is threatened more by climate change than by xenoestrogens. ...
Article
Anthropogenic environmental change poses a special threat to species in which genetic sex determination can be overwritten by the thermal and chemical environment. Endocrine disrupting chemicals as well as extreme temperatures can induce sex reversal in such species, with potentially wide-ranging consequences for fitness, demography, population viability and evolution. Despite accumulating evidence suggesting that chemical and thermal effects may interact in ecological contexts, little is known about their combined effects on sex reversal. Here we assessed the simultaneous effects of high temperature (female-to-male sex-reversing agent) and 17α-ethinylestradiol (EE2), a widespread xenoestrogen (male-to-female sex-reversing agent), on sexual development and fitness-related traits in agile frogs (Rana dalmatina). We exposed tadpoles to a six-days heat wave (30 °C) and/or an ecologically relevant concentration of EE2 (30 ng/L) in one of three consecutive larval periods, and diagnosed sex reversals two months after metamorphosis using species-specific markers for genetic sexing. We found that high temperature induced female-to-male sex reversal, decreased survival, delayed metamorphosis, decreased body mass at metamorphosis, and increased the proportion of animals that had no fat bodies, while EE2 had no effect on these traits. Simultaneous exposure to heat and EE2 had non-additive effects on juvenile body mass, which were dependent on treatment timing and further complicated by a negative effect of sex reversal on body mass. These results show that environmentally relevant exposure to EE2 does not diminish the female-to-male sex-reversing effects of high temperature. Instead, our findings on growth suggest that climate change and chemical pollution may have complex consequences for individual fitness and population persistence in species with environment-sensitive sex determination.
... Titrimetry and spectrophotometry were applied to measure total hardness, alkalinity, phosphate, and nitrite concentrations. Additional properties are presented by Jakab et al. [2]. ...
... The electrospray ionization was provided by a spray voltage of 3 kV in both ion modes. All MS/MS measurements were completed in multiple-reaction-monitoring mode, more details are presented by Jakab et al. [2] and Maasz et al. [3]. The observed ions (mass in m/z) were accepted and quantified if they met the following criteria: retention time, proper MS1 mass, MS2 masses, IS correction, and fragmentation pattern. ...
Article
Full-text available
The present dataset provides data on the pharmaceutically active compounds (PhACs) concentrations measured in the Danube and the drinking water abstraction wells (DWAW) in the Budapest region. Grab samples were collected during five periods. One hundred and seven water samples from the Danube and ninety water samples from the relevant DWAWs were analyzed to quantify physical-chemical parameters, trace element concentrations, and one hundred and eleven PhACs, including pharmaceutical derivatives, illicit drugs, and alkaloids. The ion concentrations were measured using dual channel ion chromatography, spectrophotometric and titrimetric methods, and inductively coupled plasma mass spectrometry. PhACs concentrations were measured after solid-phase extraction applying supercritical fluid chromatography coupled with tandem mass spectrometry. Fifty-two PhACs were quantified in the Danube, and ten PhACs were present in >80% of the samples. Whereas thirty-two PhACs were quantified in the DWAWs. The present dataset is useful for further comparisons and meta-analyses.
... CECs have been identified in groundwater and surface water, in treated municipal and industrial wastewaters, and even in drinking water (Bolong et al., 2009;Coadou et al., 2017;Montagner et al., 2019;Tröger et al., 2018). New groups of compounds have also been reported as potential substances classified as emerging contaminants: halogenated methanesulfonic acids (MSAs) such as chloro-, bromo-, or iodo-methanesulfonic acids (Zahn et al., 2016); microplastics (MPs) (Wright & Kelly, 2017); flame retardants including tetrabromobisphenol A (TBBPA) (Ballesteros-Gómez et al., 2017); compounds used in ultraviolet (UV) filters and sun creams such as ethylhexyl dimethylaminobenzoate and benzocaine Tsui et al., 2017); contrast agents used in computed tomography such as those containing gadolinium (Rogowska et al., 2018); pharmaceutical substances such as lidocaine (Jakab et al., 2020); and even drugs such as cocaine and its metabolites identified in pool waters (Fantuzzi et al., 2018). ...
Article
Full-text available
The scientific data review shows that advanced oxidation processes based on the hydroxyl or sulfate radicals are of great interest among the currently conventional water and wastewater treatment methods. Different advanced treatment processes such as photocatalysis, Fenton’s reagent, ozonation, and persulfate-based processes were investigated to degrade contaminants of emerging concern (CECs) such as pesticides, personal care products, pharmaceuticals, disinfectants, dyes, and estrogenic substances. This article presents a general overview of visible light–driven advanced oxidation processes for the removal of chlorfenvinphos (organophosphorus insecticide), methylene blue (azo dye), and diclofenac (non-steroidal anti-inflammatory drug). The following visible light–driven treatment methods were reviewed: photocatalysis, sulfate radical oxidation, and photoelectrocatalysis. Visible light, among other sources of energy, is a renewable energy source and an excellent substitute for ultraviolet radiation used in advanced oxidation processes. It creates a high application potential for solar-assisted advanced oxidation processes in water and wastewater technology. Despite numerous publications of advanced oxidation processes (AOPs), more extensive research is needed to investigate the mechanisms of contaminant degradation in the presence of visible light. Therefore, this paper provides an important source of information on the degradation mechanism of emerging contaminants. An important aspect in the work is the analysis of process parameters affecting the degradation process. The initial concentration of CECs, pH, reaction time, and catalyst dosage are discussed and analyzed. Based on a comprehensive survey of previous studies, opportunities for applications of AOPs are presented, highlighting the need for further efforts to address dominant barriers to knowledge acquisition.
... The matter that few of the more tenacious and slowly decomposing components outreach the drinking water source and are captivated by plants over irrigation has worsened this issue. These PhACs, thus, give the impression in the human food chain, surprisingly yet their quantity is low [28]. ...
Chapter
In recent years, the pharmaceutical field has significantly achieved magnificent progress owing to the necessities of human health and life; however, it also led to drastic environmental issues. The existence of pharmaceuticals in water bodies, which could cause adverse effects on human beings and environment, rose up distress worldwide. The pharmaceutical components found in water bodies have mainly two origins: manufacturing procedures in pharmaceutical industry and common usage of pharmaceutics. The essence of pharmaceutical wastewater (PWW) is intricate, including large amount of organic matter, high salt, microbial toxicity, and non-biodegradable. In sight of water scarcity means, it is essential to figure out and expand techniques for pharmaceutics derived wastewater in water management. Nevertheless, numerous treatment methods have been established to serve pharmaceutical wastewater including biological treatments, membrane technologies, hybrid technologies, advanced oxidation processes, absorption methods, etc. Recently, metal organic frameworks (MOFs), metallic ions clusters linked with organic bridging linkers, have been utilized in number of uses such as storage, separation, sensing, catalysis, adsorption, and many others. The viability of MOFs toward wastewater treatment (WWT) for various pollutants is fundamentally because of the extreme porosity, discrete pore structure, and superficial modification. This chapter highlights the origin and treatment of pharmaceutical wastewaters via the utilization of MOFs and their hybrid systems. A brief perception of the future work in the field has also been discussed.
... PhAC quantitative analysis was conducted via supercritical fluid chromatography coupled with tandem mass spectrometry (SFC-MS/ MS). The details of the applied sample preparation processes and instrumental analytical approaches with validation parameters of measured PhACs and data evaluation have been published in previous studies [43,53,54]. The parameters of the method, limit of detection (LOD), limit of quantification (LOQ), and validation values are listed in Table S1. ...
Article
Full-text available
The presence of pharmaceutically active compounds (PhACs) in drinking waters might pose a serious threat to human health worldwide. Therefore, this study sought to measure PhACs in Danube-derived tap water from the Budapest metropolitan region (Hungary), and to compare the results of those measured in the bank filtrate after which a human health risk assessment (based on human risk quotient [hRQ]) was conducted for the detected PhACs. A total of 108 samples were collected from 21 sampling sites throughout 6 sampling campaigns. Our study screened for 102 PhACs, of which 19 were detected in the persistently chlorinated tap water samples. PhAC concentrations were much lower than previously assumed based on the contamination of raw water resources. The total mean concentration of the analyzed PhACs exceeded 30 ng L⁻¹ only at 5 sites. Moreover, the frequency of occurrence (FRO) of the 6 most common compounds (carbamazepine, lamotrigine, lidocaine, benzoylecgonine, tramadol, and cinolazepam) reached 50 % at 4 sites. The most frequent PhAC was carbamazepine (FRO = 53.7 %), the risk level of all PhACs investigated was negligible (hRQ<1) with carbamazepine having the highest hRQs (hRQMAX = 0.007; hRQMEAN = 0.001). Tap water provided lower PhAC concentrations farther from the water abstraction wells and treatment stations along the Danube. The travel time between the drinking water wells and taps with other factors, such as the varying microbiological pattern and the deposits in the supply system influence the PhAC concentrations. Based on the risk assessment, all investigated PhACs pose a negligible risk to consumers in the investigated urban area.
Article
The uncontrolled or continuous release of effluents from wastewater treatment plants leads to the omnipresence of pharmaceutical active compounds (PhACs) in the aquatic media. Today, this is a confirmed problem becoming a main subject of twin public and scientific concerns. However, still little information is available about the long-term impacts of these PhACs on aquatic organisms. In this review, efforts were made to reveal correlation between the occurrence in the environment, ecotoxicological and health risks of different PhACs via toxicological evaluation by zebrafish (Danio rerio). This animal model served as a bioindicator for any health impacts after the exposure to these contaminants and to better understand the responses in relation to human diseases. This review paper focused on the calculation of Risk Quotients (RQs) of 34 PhACs based on environmental and ecotoxicological data available in the literature and prediction from the ECOSAR V2.2 software. To the best of the authors’ knowledge, this is the first report on the risk assessment of PhACs by the two different methods as mentioned above. RQs showed greater difference in potential environmental risks of the PhACs. These differences in risk values underline the importance of environmental and experimental factors in exposure conditions and the interpretation of RQ values. While the results showed high risk to Danio rerio of the majority of PhACs, risk qualification of the others varied between moderate to insignifiant. Further research is needed to assess pharmaceutical hazards when present in wastewater before discharge and monitor the effectiveness of treatment processes. The recent new advances in the morphological assessment of toxicant-exposed zebrafish larvae for the determination of test compounds effects on the developmental endpoints were also discussed. This review emphasizes the need for strict regulations on the release of PhACs into environmental media in order to minimize their toxicity to aquatic organisms.
Article
For quite of time, supercritical fluid chromatography (SFC) is expected to make a big revolution in separation technologies. The technique is well known for developing fast and ultrafast high efficiency separation, improving the analytical method greenness. The evolution of SFC technologies (i.e., instrumentations, stationary phases) have shifted dramatically trends in SFC application from the chiral and pharmaceutical analysis toward new diverse application fields including drugs and bioactive compounds, metabolomics, environment, and food science analysis. Moreover, the applications have been greatly expanded toward the analysis of polar and very polar metabolites, resulting in certain successes. This review focuses on the most of SFC related studies during 2020 – 2021, covering the new development of SFC technologies, recent trends in application and method developments, and more importantly discusses the upcoming perspective regarding the art of supercritical fluid separation.
Article
Full-text available
Background In recent years, there are growing concerns about pharmaceutically active compounds (PhACs) in natural ecosystems. These compounds have been found in natural waters and in fish tissues worldwide. Regarding their growing distribution and abundance, it is becoming clear that traditionally used risk assessment methodologies and ecotoxicological studies have limitations in several respects. In our study a new, combined approach of environmental impact assesment of PhACs has been used. Methods In this study, the constant watercourses of the suburban region of the Hungarian capital (Budapest) were sampled, and the body shape and scale shape of three fish species (roach Rutilus rutilus , chub Squalius cephalus , gibel carp Carassius gibelio ) found in these waters were analyzed, based on landmark-based geometric morphometric methods. Possible connections were made between the differences in body shape and scale shape, and abiotic environmental variables (local- and landscape-scale) and measured PhACs. Results Significant connections were found between shape and PhACs concentrations in several cases. Despite the relatively large number of compounds (54) detected, citalopram, propranolol, codeine and trimetazidine significantly affected only fish body and scale shape, based on their concentrations. These four PhACs were shown to be high (citalopram), medium (propranolol and codeine), and low (trimetazidine) risk levels during the environmental risk assessment, which were based on Risk Quotient calculation. Furthermore, seven PhACs (diclofenac, Estrone (E1), tramadol, caffeine 17α-Ethinylestradiol (EE2), 17α-Estradiol (aE2), Estriol (E3)) were also categorized with a high risk level. However, our morphological studies indicated that only citalopram was found to affect fish phenotype amongst the PhACs posing high risk. Therefore, our results revealed that the output of (traditional) environmental/ecological risk assessment based on ecotoxicological data of different aquatic organisms not necessarily show consistency with a “real-life” situation; furthermore, the morphological investigations may also be a good sub-lethal endpoint in ecotoxicological assessments.
Article
Full-text available
Pharmaceuticals and personal care products (PPCPs) are abundantly used by people, and some of them are excreted unaltered or as metabolites through urine, with the sewage being the most important source to their release to the environment. These compounds are in almost all types of water (wastewater, surface water, groundwater, etc.) at concentrations ranging from ng/L to µg/L. The isolation and concentration of the PPCPs from water achieves the appropriate sensitivity. This step is mostly based on solid-phase extraction (SPE) but also includes other approaches (dispersive liquid-liquid microextraction (DLLME), buckypaper, SPE using multicartridges, etc.). In this review article, we aim to discuss the procedures employed to extract PPCPs from any type of water sample prior to their determination via an instrumental analytical technique. Furthermore, we put forward not only the merits of the different methods available but also a number of inconsistencies, divergences, weaknesses and disadvantages of the procedures found in literature, as well as the systems proposed to overcome them and to improve the methodology. Environmental applications of the developed techniques are also discussed. The pressing need for new analytical innovations, emerging trends and future prospects was also considered.
Article
Full-text available
The temporal dynamics of the wastewater influent loads of 25 drug target residues (DTR, both pharmaceuticals and illicit drugs) was assessed during 84 consecutive days. This monitoring scale enables longer temporal patterns than weekday/weekend patterns to be explored. In this study, we focus on day to day variations and the potential statistical correlation of each DTR analyzed in order to better understand the potential forcings that lead to the load variation of DTRs (alone or in clusters). The weekly patterns based on the weekly loads of DTRs were also analyzed and the impact of social and meteorological events on their variations was investigated. Two cold events occurred during the monitoring period and were associated with the highest loads of analgesics and non-steroidal anti-inflammatory drugs, as well as the lowest loads of stimulants. During the Easter holidays, a significant decrease in some year-long medication as well as analgesics was found, consistent with the demographic decrease within the catchment during this period. Lastly, a good correlation between the academic calendar and the loads of stimulants was found, emphasizing the overrepresentation of students in the consumption of recreational drugs. This study furnishes new insights in order to better understand the variations in DTR loads in wastewater influents, beyond the weekday/weekend pattern and the seasonal effect. Further investigations remain necessary, especially a real-time monitoring of the population figures within the catchment in order to improve our understanding of these results.
Article
Full-text available
The present analysis was carried out at one of the most important medical tourism service providers, the Hévíz Spa and St. Andrew Hospital for Rheumatic Diseases. The institution provides spa services in two locations: in the medicinal lake of Hévíz and in the 7 pools of the pool spa. The present research carried out a single cross-sectional survey of the service quality and consumer satisfaction both in the lake and in the pool bath. Altogether 300 consumers were surveyed between 27 February and 31 March 2017. The questionnaire included the double list of questions of the SERVQUAL method, about performance and importance of various factors. The customers of the two service locations significantly differ: while the customers of the medicinal lake are mainly guests paying for themselves, 70% of the customers in the pool bath are patients supported by the National Health Insurance Fund. The results of the survey (with 4.64 as the average grade of quality on a 5 – point scale) reflects the high service quality of the spa. Although the difference between the guests and the patients in the evaluation of the importance of various quality factors was not proven, there is a tendency of different ranking of the importance factors and the service quality factors (i.e. reliability, assurance, empathy, responsiveness, tangibles). The graphical representation of the values and importance made it possible to identify the quality factors that require urgent improvement, in order to provide better service quality for both the patients and the guests. Analysis of variance proved that the patients supported by the National Health Insurance Fund were more satisfied at both locations than guests paying for themselves. The high level of patient satisfaction is a very useful fact for the Hévíz Spa, because the level of satisfaction positively affects recommendations. This positive word of mouth promotion is highly valuable considering the fact, that the legislation in Hungary does not allow the promotion of health services.
Article
Tourism seasonality is generally seen as a problem for most of the main destinations in the world, particularly from the point of view of sustainability. Despite its importance, no reasonably homogeneous international measurement of seasonality is yet available on the global scale. Using the best World Tourism Organization (UNWTO) data, the paper uses the coefficient of variation, over the period 2008–2013 and for the main destinations, as a measure of tourism seasonality. In addition to the descriptive results, the paper includes a mixed effects panel data model, which allows us to investigate some reasonable main global determinants of seasonality. The results may be summarized as follows. Firstly, the world seasonality shows an inverted U pattern. Secondly, the highest (and increasing) seasonality is concentrated in the Mediterranean countries. Lastly, in terms of empirical determinants, geographical location, and the income of the major markets of origin are globally significant variables.
Article
Recent studies have proven that vegetables cultivated in peri-urban areas are exposed to a greater concentration of organic microcontaminants (OMCs) and trace elements (TEs) than those grown in rural areas. In this study, the occurrence and human health risk of chemical contaminants (16 TEs and 33 OMCs) in edible parts of lettuce, tomato, cauliflower, and broad beans from two farm fields in the peri-urban area of the city of Barcelona and one rural site outside the peri-urban area were assessed. The concentration of TEs and OMCs (on fresh weight basis) ranged from non-detectable to 17.4 mg/kg and from non-detectable to 256 μg/kg, respectively. Tomato fruits showed the highest concentration of TEs and OMCs. Principal component analysis indicated that the occurrence of chemical contaminants in vegetables depended on the commodity rather than the location (peri-urban vs rural). Risk assessment using hazardous quotient (HQ) and threshold of toxicological concern (TTC) approaches showed that the risk for the consumption of target vegetables in the peri-urban area was low and similar to that observed for the rural site. Total HQ values for TEs were always below 1, and a minimum consumption of 150 g/day for children and 380 g/day for adults is required to reach the TTC due to the presence of pesticides. Further studies are needed to estimate the combined effect of TEs and OMCs on human health. Keywords: Emerging contaminants, Trace elements, Pesticides, Vegetables, Risk assessment, Human exposure
Article
Pharmaceuticals have become “persistent” pollutants in the aquatic environment, due to their wide usage in daily life and their continuous release into the aquatic environment. Hence, prioritization and ranking lists are required to screen for target compounds as part of risk assessments. A ranking system based on three criteria, such as occurrence, exposure potential and ecological effects, was developed in this study for specific application to China. A total of 100 pharmaceuticals were selected as candidates based on the ranking system and available consumption data. These pharmaceuticals have been previously reported by wastewater treatment plants (WWTPs) in China. 13 pharmaceuticals were classified as priority pharmaceuticals, among which diclofenac, erythromycin, and penicillin G were highly prioritized. Due to their abuse, antibiotics contributed a majority to the priority pharmaceuticals among all therapeutic classes, indicating that antibiotics should be considered based on their behaviors in WWTPs. The pharmaceuticals ranking list achieved good applicability and will help to establish a focus for future monitoring and management of pharmaceuticals. It will also provide an important basis for both ecological risk assessment and pollution control of pharmaceuticals in the aquatic environment.
Article
The presence of illicit drugs in the aquatic environment represents a new potential risk for aquatic organisms, due to their constant exposure to substances with strong pharmacological activity. Currently, little is known about the ecological effects of illicit drugs. The aim of this study was to evaluate the influence of environmental concentrations of cocaine, an illicit drug widespread in surface waters, on the skeletal muscle of the European eel (Anguilla anguilla). The skeletal muscle of silver eels exposed to 20 ng L-1 of cocaine for 50 days were compared to control, vehicle control and two post-exposure recovery groups (3 and 10 days after interruption of cocaine). The eels general health, the morphology of the skeletal muscle and several parameters indicative of the skeletal muscle physiology were evaluated, namely the muscle whole protein profile, marker of the expression levels of the main muscle proteins; cytochrome oxidase activity, markers of oxidative metabolism; caspase-3, marker of apoptosis activation; serum levels of creatine kinase, lactate dehydrogenase and aspartate aminotransferase, markers of skeletal muscle damages. Cocaine-exposed eels appeared hyperactive but they showed the same general health status as the other groups. In contrast, their skeletal muscle showed evidence of serious injury, including muscle breakdown and swelling, similar to that typical of rhabdomyolysis. These changes were still present 10 days after the interruption of cocaine exposure. In fact, with the exception of the expression levels of the main muscle proteins, which remained unchanged, all the other parameters examined showed alterations that persisted for at least 10 days after the interruption of cocaine exposure. This study shows that even low environmental concentrations of cocaine cause severe damage to the morphology and physiology of the skeletal muscle of the silver eel, confirming the harmful impact of cocaine in the environment that potentially affects the survival of this species.
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The occurrence of illicit drugs (cocaine, opioids, amphetamines and cannabis derivatives), some of their metab-olites and 48 pharmaceuticals, was investigated in pool and source waters in ten Italian indoor swimming pools. The samples were analyzed by highperformance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS), after solid phase extraction (SPE). Cocaine and its metabolites were found in nine swimming pools, at concentrations from 0.3 to 4.2 ng/L for cocaine, 1.1 to 48.7 ng/L for norcocaine, 0.7 to 21.4 ng/L for benzoylecgonine and 0.1 to 7.3 ng/L for norbenzoylecgonine. Opioids, amphetamines and cannabis derivatives were never detected. The most frequent pharmaceuticals were anti-inflammatory drugs: ibuprofen was found in all the pool waters, with a maximum 197 ng/L and ketoprofen was detected in 9/10 samples (maximum 127 ng/L). Among anticonvulsants, carbamazepine and its metabolite, 10,11-dihydro-10,11dihydroxycarbamazepine, were frequent in swimming pool water (8/10 samples) at concentrations up to 62 ng/L. The cardiovascular drug valsartan was also found frequently (8/10 samples), but at lower concentrations (up to 9 ng/L). Other pharmaceuticals were detected occasionally and at lower concentrations (atenolol, enalapril, paracetamol, hydroclorothiazide, irbesartan and dehydro-erythromycin). Carbamazepine, irbesartan and dehydroerythromycin were detected at very low levels (up to 5 ng/L) in only one of the four source water samples. A quantitative risk assessment showed that the health risk for humans to these substance in swimming pool waters was generally negligible, even for vulnerable subpopulations such as children and adolescents.
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Many chemical pollutants have endocrine disrupting effects which can cause lifelong reproductive abnormalities in animals. Amphibians are the most threatened group of vertebrates, but there is little information on the nature and quantity of pollutants occurring in typical amphibian breeding habitats and on the reproductive capacities of amphibian populations inhabiting polluted areas. In this study we investigated the occurrence and concentrations of endocrine disrupting chemicals in the water and sediment of under-studied amphibian breeding habitats in natural, agricultural and urbanized landscapes. Also, we captured reproductively active common toads (Bufo bufo) from these habitats and let them spawn in a ‘common garden’ to assess among-population differences in reproductive capacity. Across 12 ponds, we detected 41 out of the 133 contaminants we screened for, with unusually high concentrations of glyphosate and carbamazepine. Levels of polycyclic aromatic hydrocarbons, nonylphenol and bisphenol-A increased with urban land use, whereas levels of organochlorine and triazine pesticides and sex hormones increased with agricultural land use. Toads from all habitats had high fecundity, fertilization rate and offspring viability, but the F1 generation originating from agricultural and urban ponds had reduced development rates and lower body mass both as larvae and as juveniles. Females with small clutch mass produced thicker jelly coat around their eggs if they originated from agricultural and urban ponds compared with natural ponds. These results suggest that the observed pollution levels did not compromise reproductive potential in toads, but individual fitness and population viability may be reduced in anthropogenically influenced habitats, perhaps due to transgenerational effects and/or costs of tolerance to chemical contaminants.