Thermal baths as sources of pharmaceutical and illicit drug contamination

Abstract

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.

Full text

RESEARCH ARTICLE
Thermal baths as sources of pharmaceutical and illicit
drug contamination
Gergely Jakab
1,2,3
&Zoltán Szalai
1,2
&Gábor Michalkó
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) 27:399–410
/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 Piešt’any, 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) 27:399–410
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) 27:399–410 401
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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
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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) 27:399–410
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 Mackul’ak 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) 27:399–410 405
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) 27:399–410
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) 27:399–410 407
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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Affiliations
Gergely Jakab
1,2,3
&Zoltán Szalai
1,2
&Gábor Michalkó
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, Fővám tér 8, Budapest H-1093,
Hungary
Environ Sci Pollut Res (2020) 27:399–410
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