Pharmaceutical Removal Synergy Between Biological-Wageningen University and Research 426133

Pharmaceutical Removal:
Synergy between Biological and Chemical Processes
for Wastewater Treatment
Henrik Arnoud de Wilt

Thesis committee
Promotor
Prof. Dr H.H.M. Rijnaarts
Professor of Environmental Technology
Wageningen University & Research
Co-promotor
Dr A.A.M. Langenhoff
Associate Professor, Sub-department of Environmental Technology
Wageningen University & Research
Other members
Prof. Dr L.E.M. Vet, Wageningen University & Research
Prof. Dr F. Omil, University of Santiago de Compostela, Spain
Dr C.H.M. Hofman-Caris, KWR Watercycle Research Institute, Nieuwegein
Dr P.M.F. van der Maas, Waterlaboratorium Noord, Glimmen
This research was conducted under auspices of the Graduate School for Socio-
Economic and Natural Sciences of the Environment (SENSE)
Pharmaceutical Removal:
Synergy between Biological and Chemical Processes
for Wastewater Treatment
Thesis
submitted in fulfilment of the requirements for the degree of doctor
at Wageningen University
by the authority of the Rector Magnificus
Prof. Dr A.P.J. Mol,
in the presence of the
Thesis Committee appointed by the Academic Board
to be defended in public
on Friday 2 February 2018
at 4 p.m. in the Aula.
Pharmaceutical Removal: Synergy between Biological and Chemical Processes for
Wastewater Treatment,
208 pages.
PhD thesis, Wageningen University, Wageningen, the Netherlands (2018)

With references, with summaries in English, Dutch and Russian
ISBN: 978-94-6343-721-9
DOI: 10.18174/426133
Моим самым близким и любимым Данюхе, Давидушке и Машеньке
Voor mijn naaste en geliefde Daniël, Davíd en Masha

Contents
Summary 1
Chapter 1 7
General introduction
Chapter 2 31
Sorption and biodegradation of pharmaceuticals
under different redox conditions
Chapter 3 57
Mild photocatalytic pre-treatment: improved biological degradation
of degradable and otherwise recalcitrant pharmaceuticals
Chapter 4 75
Enhanced pharmaceutical removal from water
in a three step bio-ozone-bio process
Chapter 5 99
Micropollutant removal in an algal treatment system
fed with source separated wastewater streams
Chapter 6 125
General discussion - Synergy between biological and chemical processes;
towards lower pharmaceutical emissions
Bibliography 153
Nomenclature 179
Samenvatting 181
Резюме 187
Acknowledgement 193
Curriculum Vitae 197

Summary
Pharmaceuticals are used worldwide at increasing consumption rates which are
Summary
not expected to decrease on short time horizons. Large quantities of administrated
pharmaceuticals are excreted unaltered or as metabolites via faeces or urine and end-
Pharmaceuticals are used worldwide at increasing consumption rates which are
up via the toilet and sewer system at the wastewater treatment plant.
not expected to decrease on short time horizons. Large quantities of administrated
Conventional wastewater treatment plants employing activated sludge
pharmaceuticals are excreted unaltered or as metabolites via faeces or urine and end-
treatment are designed to remove bulk constituents, like organic matter, nitrogen
up via the toilet and sewer system at the wastewater treatment plant.
and phosphorous, which are present at concentrations of milligrams per litre. These
Conventional wastewater treatment plants employing activated sludge
treatment plants were not designed for removing the broad spectrum of
treatment are designed to remove bulk constituents, like organic matter, nitrogen
pharmaceuticals comprising thousands of highly complex molecules present in
and phosphorous, which are present at concentrations of milligrams per litre. These
wastewater. These compounds, found at low concentrations of nanograms to
treatment plants were not designed for removing the broad spectrum of
micrograms per litre, are therefore generally only poorly removed. The biodegradable
pharmaceuticals comprising thousands of highly complex molecules present in
pharmaceuticals that are removed are rather transformed than mineralized. As a
wastewater. These compounds, found at low concentrations of nanograms to
matter of fact, countless pharmaceuticals or their human metabolites and
micrograms per litre, are therefore generally only poorly removed. The biodegradable
transformation products are discharged into the environment.
pharmaceuticals that are removed are rather transformed than mineralized. As a
The presence of these insidious compounds in the environment are one of the
matter of fact, countless pharmaceuticals or their human metabolites and
main challenges humanity is facing as they jeopardise the aquatic environment and
transformation products are discharged into the environment.
human health. Adverse effects on the aquatic ecosystem like the feminization of fish
The presence of these insidious compounds in the environment are one of the
are well reported and threaten the entire ecosystem. Intake waters for drinking water
main challenges humanity is facing as they jeopardise the aquatic environment and
production were found to contain high pharmaceutical concentrations emitted by
human health. Adverse effects on the aquatic ecosystem like the feminization of fish
wastewater effluents posing risks to the public health in case drinking water is poorly
are well reported and threaten the entire ecosystem. Intake waters for drinking water
treated. The presence of pharmaceuticals hampers the reuse of wastewater effluents
production were found to contain high pharmaceutical concentrations emitted by
whereas worldwide water scarcity problems could partially be solved by effluent
wastewater effluents posing risks to the public health in case drinking water is poorly
reuse. Hence, there is a strong motivation to remove pharmaceuticals before they
treated. The presence of pharmaceuticals hampers the reuse of wastewater effluents
enter the aquatic environment.
whereas worldwide water scarcity problems could partially be solved by effluent
Being a main hub in the water cycle, wastewater treatment plants are the most
reuse. Hence, there is a strong motivation to remove pharmaceuticals before they
optimal place to raise barriers against pharmaceuticals before they are discharged.
enter the aquatic environment.
Various biological and chemical processes have been studied for their capacities to
Being a main hub in the water cycle, wastewater treatment plants are the most
remove pharmaceuticals of which some have been locally implemented. Nevertheless,
optimal place to raise barriers against pharmaceuticals before they are discharged.
these processes show either insufficient pharmaceutical removal or are considered
Various biological and chemical processes have been studied for their capacities to
costly and unsustainable. Thus, there is a lack of cost-effective pharmaceutical
remove pharmaceuticals of which some have been locally implemented. Nevertheless,
1
these processes show either insufficient pharmaceutical removal or are considered
costly and unsustainable. Thus, there is a lack of cost-effective pharmaceutical
1
treatment processes. Therefore, this dissertation investigates different processes for
the cost-effective removal of pharmaceuticals to be applied in wastewater treatment,
with a focus on the synergy between biological and chemical treatment processes for
treatment processes. Therefore, this dissertation investigates different processes for
an enhanced pharmaceutical removal (Chapter 1).
the cost-effective removal of pharmaceuticals to be applied in wastewater treatment,
The low costs associated to biological treatment increases its implementation
with a focus on the synergy between biological and chemical treatment processes for
potential and favours the research on biological processes. Among the various
an enhanced pharmaceutical removal (Chapter 1).
parameters affecting biological processes, redox conditions are considered one of the
The low costs associated to biological treatment increases its implementation
most important parameters. In batch and column experiments employing constructed
potential and favours the research on biological processes. Among the various
wetland sediments aerobic, sulfate reducing and methanogenic redox conditions were
parameters affecting biological processes, redox conditions are considered one of the
most favourable for pharmaceutical removal (Chapter 2). In contrast, micro-
most important parameters. In batch and column experiments employing constructed
aerophilic and nitrate reducing conditions were less effective. Biodegradation and
wetland sediments aerobic, sulfate reducing and methanogenic redox conditions were
sorption contributed to the observed removal and both were influenced by the applied
most favourable for pharmaceutical removal (Chapter 2). In contrast, micro-
redox conditions. Saturation of sorption sites for propranolol, i.e. the compound with
aerophilic and nitrate reducing conditions were less effective. Biodegradation and
the highest sorption coefficient among the investigated pharmaceuticals, was found
sorption contributed to the observed removal and both were influenced by the applied
to occur after 300 pore volume changes under most favourable redox conditions. This
redox conditions. Saturation of sorption sites for propranolol, i.e. the compound with
suggests that in biological filtration applications sorption of pharmaceuticals is of
the highest sorption coefficient among the investigated pharmaceuticals, was found
minor importance compared to biodegradation. The persistence of biorecalcitrant
to occur after 300 pore volume changes under most favourable redox conditions. This
pharmaceuticals such as carbamazepine towards biodegradation and sorption under
suggests that in biological filtration applications sorption of pharmaceuticals is of
all redox conditions stresses the shortcoming of biological treatment and indicates the
minor importance compared to biodegradation. The persistence of biorecalcitrant
need for additional treatment processes.
pharmaceuticals such as carbamazepine towards biodegradation and sorption under
Mild UV-LED TiO2 photocatalysis combined with subsequent biological
all redox conditions stresses the shortcoming of biological treatment and indicates the
treatment demonstrated improved pharmaceutical removal over single photocatalysis
need for additional treatment processes.
or biological treatment (Chapter 3). Mild photocatalytic treatment removed three out
Mild UV-LED TiO2 photocatalysis combined with subsequent biological
of the nine studied pharmaceuticals. Interestingly, the biodegradation of four
treatment demonstrated improved pharmaceutical removal over single photocatalysis
pharmaceuticals enhanced after mild photocatalytic pre-treatment, even though only
or biological treatment (Chapter 3). Mild photocatalytic treatment removed three out
one of them was targeted by photocatalysis. In addition, biodegradation of diclofenac,
of the nine studied pharmaceuticals. Interestingly, the biodegradation of four
which persisted during single process biological treatment, was observed after mild
pharmaceuticals enhanced after mild photocatalytic pre-treatment, even though only
photocatalytic pre-treatment. Based on the literature it is postulated that
one of them was targeted by photocatalysis. In addition, biodegradation of diclofenac,
intermediates formed during mild photocatalysis enhanced the biodegradation of
which persisted during single process biological treatment, was observed after mild
pharmaceuticals by the activation of enzymatic systems responsible for initial attack
photocatalytic pre-treatment. Based on the literature it is postulated that
of organic molecules.
intermediates formed during mild photocatalysis enhanced the biodegradation of
pharmaceuticals by the activation of enzymatic systems responsible for initial attack
of organic molecules.
2
2
Summary
The presence of ozone scavengers in wastewater effluent like organic carbon,

reduce the effectiveness of ozonation for the oxidation of pharmaceuticals.Summary
Elevated
total organic carbon (TOC) concentrations, such as the 17.3 mg TOC/L present in the
The presence of ozone scavengers in wastewater effluent like organic carbon,
investigated effluent, consequently demand high absolute ozone inputs for
reduce the effectiveness of ozonation for the oxidation of pharmaceuticals. Elevated
pharmaceutical removal, thus reducing the cost-effectiveness of ozonation. A three
total organic carbon (TOC) concentrations, such as the 17.3 mg TOC/L present in the
step bio-ozone-bio process (BO3B) consisting of two identical trickling filters utilizing
investigated effluent, consequently demand high absolute ozone inputs for
sand as biomass carriers and an ozone reactor was therefore designed (Chapter 4).
pharmaceutical removal, thus reducing the cost-effectiveness of ozonation. A three
Various hydraulic retention times (HRTs) and ozone doses were investigated aiming
step bio-ozone-bio process (BO3B) consisting of two identical trickling filters utilizing
at a cost-effective pharmaceutical removal from wastewater effluent. At an HRT of
sand as biomass carriers and an ozone reactor was therefore designed (Chapter 4).
1.5 hours a 38% TOC removal was found over the first biological reactor, thereby
Various hydraulic retention times (HRTs) and ozone doses were investigated aiming
proportionally reducing the ozone demand in the subsequent ozone reactor. Enhanced
at a cost-effective pharmaceutical removal from wastewater effluent. At an HRT of
pharmaceutical removal was observed over the first biological reactor compared to
1.5 hours a 38% TOC removal was found over the first biological reactor, thereby
conventional wastewater treatment, despite of the short HRT and low amount of
proportionally reducing the ozone demand in the subsequent ozone reactor. Enhanced
biomass in the BO3B system. Even pharmaceuticals known to be moderately
pharmaceutical removal was observed over the first biological reactor compared to
biodegradable such as sulfamethoxazole were effectively biodegraded. At ozone doses
conventional wastewater treatment, despite of the short HRT and low amount of
down to 0.2 g O3/g TOC an effective removal of biorecalcitrant pharmaceuticals such
biomass in the BO3B system. Even pharmaceuticals known to be moderately
as carbamazepine was found. The 17% TOC removal over the last biological reactor
biodegradable such as sulfamethoxazole were effectively biodegraded. At ozone doses
demonstrated the removal of transformation products formed during ozonation.
down to 0.2 g O3/g TOC an effective removal of biorecalcitrant pharmaceuticals such
Simultaneous nutrient recovery and pharmaceutical removal was found in algal
as carbamazepine was found. The 17% TOC removal over the last biological reactor
photobioreactors running on anaerobically treated black water or urine (Chapter 5).
demonstrated the removal of transformation products formed during ozonation.
Algae, known to take up nitrogen and phosphorus from these highly concentrated
Simultaneous nutrient recovery and pharmaceutical removal was found in algal
source separated wastewater streams, demonstrated to contribute to the
photobioreactors running on anaerobically treated black water or urine (Chapter 5).
pharmaceutical removal observed in the algal photobioreactors. Control experiments
Algae, known to take up nitrogen and phosphorus from these highly concentrated
revealed that algae, bacteria and light contributed to the pharmaceutical removal.
source separated wastewater streams, demonstrated to contribute to the
Pharmaceuticals susceptible to photolysis such as diclofenac were photodegraded,
pharmaceutical removal observed in the algal photobioreactors. Control experiments
whereas paracetamol and metoprolol were removed by a combination of
revealed that algae, bacteria and light contributed to the pharmaceutical removal.
biodegradation and photodegradation. The sorption of pharmaceuticals to algal
Pharmaceuticals susceptible to photolysis such as diclofenac were photodegraded,
biomass was limited which favours the use of harvested algal biomass as fertilizer in
whereas paracetamol and metoprolol were removed by a combination of
agriculture over for instance direct urine application.
biodegradation and photodegradation. The sorption of pharmaceuticals to algal
The outcomes of this dissertation provide insight into the limitations of single
biomass was limited which favours the use of harvested algal biomass as fertilizer in
biological and chemical processes for pharmaceutical removal and illuminate the
agriculture over for instance direct urine application.
importance of combinations of complementary processes to overcome single process
The outcomes of this dissertation provide insight into the limitations of single
biological and chemical processes for pharmaceutical removal and illuminate the
3
importance of combinations of complementary processes to overcome single process
3
disadvantages (Chapter 6). Site-specific conditions such as wastewater composition
dictate which combination is locally most favourable as there is no universal cost-
effective combination of processes. Implementation should therefore rather focus on
disadvantages (Chapter 6). Site-specific conditions such as wastewater composition
tailor-made combinations as there is a wide arsenal of biological and chemical
dictate which combination is locally most favourable as there is no universal cost-
treatment processes available. To further improve the cost-effectiveness of combined
effective combination of processes. Implementation should therefore rather focus on
processes future research should focus on underlying removal mechanisms including
tailor-made combinations as there is a wide arsenal of biological and chemical
the enzymatic pathways of pharmaceutical degradation and transformation product
treatment processes available. To further improve the cost-effectiveness of combined
formation and removal.
processes future research should focus on underlying removal mechanisms including
For the studied removal processes in this dissertation an outlook on further
the enzymatic pathways of pharmaceutical degradation and transformation product
research and upscaling is presented. The BO3B process and the algal treatment
formation and removal.
system are ready to be tested on a pilot scale. Especially the upscaling potential of
For the studied removal processes in this dissertation an outlook on further
the BO3B system is high as on lab-scale it was successfully tested for almost a year
research and upscaling is presented. The BO3B process and the algal treatment
on real wastewater. During this period high pharmaceutical removal efficiencies were
system are ready to be tested on a pilot scale. Especially the upscaling potential of
achieved in a cost-effective manner. Upscaling should mainly focus on the operation
the BO3B system is high as on lab-scale it was successfully tested for almost a year
of the biological reactors as they make the BO3B process cost-effective. The algal
on real wastewater. During this period high pharmaceutical removal efficiencies were
treatment system is currently tested on pilot scale. A focus on the removal of a broad
achieved in a cost-effective manner. Upscaling should mainly focus on the operation
suite of micropollutants is recommended for pilot scale testing. The combination of
of the biological reactors as they make the BO3B process cost-effective. The algal
photocatalysis and biodegradation requires further lab-scale research as TiO2
treatment system is currently tested on pilot scale. A focus on the removal of a broad
immobilization is needed to make the system more sustainable and the system was
suite of micropollutants is recommended for pilot scale testing. The combination of
only tested on a clean matrix.
photocatalysis and biodegradation requires further lab-scale research as TiO2
Obtained knowledge of the past decades stresses the importance of effect
immobilization is needed to make the system more sustainable and the system was
based removal strategies as most studies, including this dissertation, primarily rely
only tested on a clean matrix.
on chemical parameters such as individual pharmaceutical concentrations,
Obtained knowledge of the past decades stresses the importance of effect
overlooking the effects of pharmaceuticals on for instance the aquatic environment.
based removal strategies as most studies, including this dissertation, primarily rely
Source separation based sanitation systems enabling cost-effective pharmaceutical
on chemical parameters such as individual pharmaceutical concentrations,
removal and interventions at earlier stages in the chain from pharmaceutical
overlooking the effects of pharmaceuticals on for instance the aquatic environment.
manufacturing to drinking water production reducing the need for end-of-pipe
Source separation based sanitation systems enabling cost-effective pharmaceutical
solutions are highly recommended solutions to reduce pharmaceutical emission into
removal and interventions at earlier stages in the chain from pharmaceutical
the environment. Moreover, stricter legislation regarding the regulation of
manufacturing to drinking water production reducing the need for end-of-pipe
pharmaceutical concentrations in the effluent is recommended.
solutions are highly recommended solutions to reduce pharmaceutical emission into
The results of this dissertation provide further understanding of combining
the environment. Moreover, stricter legislation regarding the regulation of
biological and chemical treatment processes for pharmaceutical removal and is
pharmaceutical concentrations in the effluent is recommended.
The results of this dissertation provide further understanding of combining
4
biological and chemical treatment processes for pharmaceutical removal and is
4
Summary
thereby one of the many steps to be taken to prevent the wastewater related
Summary
emissions of pharmaceuticals and other contaminants jeopardizing the environment
and the public health.
thereby one of the many steps to be taken to prevent the wastewater related
emissions of pharmaceuticals and other contaminants jeopardizing the environment
and the public health.
5
Chapter 1
1.1 Pharmaceuticals in the water cycle

1.1.1 Occurrence
Human pharmaceuticals comprise a wide group of various organic compounds
1.1 Pharmaceuticals in the water cycle
intended to treat human illness and diseases. They are mostly synthetically
1.1.1 Occurrence
manufactured and are therefore considered xenobiotic. Pharmaceuticals are being
Human pharmaceuticals comprise a wide group of various organic compounds
used worldwide, though usage of type and quantity differs per country [138]. Around
intended to treat human illness and diseases. They are mostly synthetically
3000 different medical substances are used in the European Union [85]. In 2007 the
manufactured and are therefore considered xenobiotic. Pharmaceuticals are being
estimated human consumption of pharmaceuticals in the Netherlands totalled 1.273
used worldwide, though usage of type and quantity differs per country [138]. Around
metric tonnes, which equals approximately 78 gram per capita per year. By then a
3000 different medical substances are used in the European Union [85]. In 2007 the
consumption increase of 17% was expected by 2020 due to aging of the population,
estimated human consumption of pharmaceuticals in the Netherlands totalled 1.273
while for 2050 an increase of 37% was predicted [283]. However, more recent data
metric tonnes, which equals approximately 78 gram per capita per year. By then a
shows an higher realised increase in Dutch pharmaceutical consumption. Expressed
consumption increase of 17% was expected by 2020 due to aging of the population,
as daily standard doses the consumption of pharmaceuticals in the Netherlands grew
while for 2050 an increase of 37% was predicted [283]. However, more recent data
per year by 2.6%, 2.9%, 2.5%, 1.1% and 6.4% in 2015, 2014, 2013, 2012 and 2011
shows an higher realised increase in Dutch pharmaceutical consumption. Expressed
respectively [249, 250].
as daily standard doses the consumption of pharmaceuticals in the Netherlands grew
Consumed pharmaceuticals are mainly excreted via urine and faeces [60].
per year by 2.6%, 2.9%, 2.5%, 1.1% and 6.4% in 2015, 2014, 2013, 2012 and 2011
After excretion, human pharmaceuticals end up in wastewater and are transported to
respectively [249, 250].
wastewater treatment plants (WWTPs) [85, 129, 139]. Conventional WWTPs are
Consumed pharmaceuticals are mainly excreted via urine and faeces [60].
commonly designed for the removal of bulk organic matter, nitrogen and phosphorus
After excretion, human pharmaceuticals end up in wastewater and are transported to
but not for pharmaceutical removal. Although some pharmaceuticals are removed
wastewater treatment plants (WWTPs) [85, 129, 139]. Conventional WWTPs are
during wastewater treatment, numerous pharmaceuticals are ineffectively removed
commonly designed for the removal of bulk organic matter, nitrogen and phosphorus
and are discharged with the WWTP effluent [65, 287]. Hence, wide ranges of
but not for pharmaceutical removal. Although some pharmaceuticals are removed
numerous pharmaceuticals at ng/L up to low µg/L concentrations have been
during wastewater treatment, numerous pharmaceuticals are ineffectively removed
measured in wastewater effluents and in surface waters [196] Moreover, low
and are discharged with the WWTP effluent [65, 287]. Hence, wide ranges of
concentrations up to 0.1 µg/L of pharmaceuticals are also detected in various drinking
numerous pharmaceuticals at ng/L up to low µg/L concentrations have been
water sources [286, 288]. Pharmaceuticals were only detected in the water cycle over
measured in wastewater effluents and in surface waters [196] Moreover, low
the last decades as only recently analytical techniques allowed the detection of these
concentrations up to 0.1 µg/L of pharmaceuticals are also detected in various drinking
compounds in aqueous environments at low concentrations [262].
water sources [286, 288]. Pharmaceuticals were only detected in the water cycle over
the last decades as only recently analytical techniques allowed the detection of these
compounds in aqueous environments at low concentrations [262].
8
Chapter 1
Chapter 1
Figure 1.1 Pathways of pharmaceuticals and other micropollutants from production to

drinking water (Figure from [22]).
Figure 1.1 Pathways of pharmaceuticals and other micropollutants from production to

1.1.2 Fate
drinking water (Figure from [22]).
Effluents of WWTPs treating merely wastewater from households are identified
as the main source of pharmaceuticals entering the environment [128]. Besides
1.1.2 Fate
administration and excretion of pharmaceuticals, unused and expired
Effluents of WWTPs treating merely wastewater from households are identified
pharmaceuticals are also disposed down household drains. In a German survey 18%
as the main source of pharmaceuticals entering the environment [128]. Besides
of the respondents said they flushed outdated pharmaceuticals down the drain [95].
administration and excretion of pharmaceuticals, unused and expired
In a U.S. study only 23% of the respondents reported to return expired
pharmaceuticals are also disposed down household drains. In a German survey 18%
pharmaceuticals to the pharmacy, whereas more than 50% had flushed
of the respondents said they flushed outdated pharmaceuticals down the drain [95].
pharmaceuticals through the toilet [236]. In addition to households, hospitals,
In a U.S. study only 23% of the respondents reported to return expired
agriculture and livestock and industries are also recognised as sources of
pharmaceuticals to the pharmacy, whereas more than 50% had flushed
pharmaceuticals entering the environment (Figure 1.1). Hospital wastewaters contain
pharmaceuticals through the toilet [236]. In addition to households, hospitals,
high concentrations of pharmaceuticals [94]. However, due to the relatively small size
agriculture and livestock and industries are also recognised as sources of
pharmaceuticals entering the environment (Figure 1.1). Hospital wastewaters contain
9
high concentrations of pharmaceuticals [94]. However, due to the relatively small size
9
of this stream it is typically diluted by a factor 100 in the sewer system before it
enters the WWTPs [137]. In addition, some hospitals have their own tailor made
wastewater treatment plant aiming at low pharmaceutical emissions to the sewer
of this stream it is typically diluted by a factor 100 in the sewer system before it
system [204]. Both the dilution of wastewater in the sewer system and treatment by
enters the WWTPs [137]. In addition, some hospitals have their own tailor made
some individual hospitals explains why less than 15% of the total pharmaceutical load
wastewater treatment plant aiming at low pharmaceutical emissions to the sewer
fed to WWTPs is estimated to originate from hospitals [147].
system [204]. Both the dilution of wastewater in the sewer system and treatment by
Pharmaceutical use in agriculture and livestock mainly concerns the use of
some individual hospitals explains why less than 15% of the total pharmaceutical load
antibiotics. Sim et al. [240] compared WWTPs treating domestic, hospital, livestock
fed to WWTPs is estimated to originate from hospitals [147].
and industrial wastewater in Korea and found highest total pharmaceutical
Pharmaceutical use in agriculture and livestock mainly concerns the use of
concentrations in the influents of livestock WWTPs. Although livestock WWTPs had
antibiotics. Sim et al. [240] compared WWTPs treating domestic, hospital, livestock
the highest pharmaceutical influent concentrations, municipal WWTPs were found the
and industrial wastewater in Korea and found highest total pharmaceutical
principal source of pharmaceuticals to the aquatic environment as their disposed loads
concentrations in the influents of livestock WWTPs. Although livestock WWTPs had
were highest. Nevertheless, these findings might be different for other countries.
the highest pharmaceutical influent concentrations, municipal WWTPs were found the
Pharmaceutical producing industries in Europe and North America are assumed to
principal source of pharmaceuticals to the aquatic environment as their disposed loads
have minimal pharmaceutical emissions into the environment due to good
were highest. Nevertheless, these findings might be different for other countries.
manufacturing practice regulations [51, 304]. However, no data is available to verify
Pharmaceutical producing industries in Europe and North America are assumed to
this assumption [139]. In the effluent of an Indian WWTP serving pharmaceutical
have minimal pharmaceutical emissions into the environment due to good
manufacturers elevated concentrations of the antibiotic ciprofloxacin up to 31 mg/L
manufacturing practice regulations [51, 304]. However, no data is available to verify
and high concentrations of numerous other pharmaceuticals have been detected.
this assumption [139]. In the effluent of an Indian WWTP serving pharmaceutical
These concentrations exceed toxic levels to various organisms by multiple orders of
manufacturers elevated concentrations of the antibiotic ciprofloxacin up to 31 mg/L
magnitude [146]. Similar findings were reported for a manufacturer of the antibiotic
and high concentrations of numerous other pharmaceuticals have been detected.
oxytetracycline in China which was found in WWTP effluent at concentrations up to
These concentrations exceed toxic levels to various organisms by multiple orders of
19 mg/L [153].
magnitude [146]. Similar findings were reported for a manufacturer of the antibiotic
oxytetracycline in China which was found in WWTP effluent at concentrations up to
1.1.3 Characteristics
19 mg/L [153].
Pharmaceuticals cover a broad range of compounds with chemically complex
structures and many different chemical and physical properties (Table 1.1).
1.1.3 Characteristics
Pharmaceuticals are typically polar or charged compounds and thereby hydrophilic
Pharmaceuticals cover a broad range of compounds with chemically complex
[139, 260]. Many of them contain acidic groups which favours speciation of the
structures and many different chemical and physical properties (Table 1.1).
compound [77]. Polar compounds mostly dissolve well in water and are therefore
Pharmaceuticals are typically polar or charged compounds and thereby hydrophilic
easily dispersed in aquatic environments. The spread of hydrophobic pharmaceuticals
[139, 260]. Many of them contain acidic groups which favours speciation of the
compound [77]. Polar compounds mostly dissolve well in water and are therefore
easily dispersed
10 in aquatic environments. The spread of hydrophobic pharmaceuticals
10
Chapter 1
in aquatic environments is relatively limited and much slower as they tend to

Chapter 1
accumulate in the fatty tissues of organisms [114].
Metabolic processes in the human body can alter the pharmaceutical into
in aquatic environments is relatively limited and much slower as they tend to
metabolites before excretion (Figure 1.2). After excretion further transformation of
accumulate in the fatty tissues of organisms [114].
the pharmaceutical or its metabolites can take place in wastewater treatment plants
Metabolic processes in the human body can alter the pharmaceutical into
and the environment resulting in countless transformation products. Some of the
metabolites before excretion (Figure 1.2). After excretion further transformation of
products formed during specific treatment are known to exhibit higher toxicity levels
the pharmaceutical or its metabolites can take place in wastewater treatment plants
compared to the original compounds [118].
and the environment resulting in countless transformation products. Some of the
products formed during specific treatment are known to exhibit higher toxicity levels
compared to the original compounds [118].
I
Figure 1.2 Transformation pathways of pharmaceuticals (adapted from [139]).
Figure 1.2 Transformation pathways of pharmaceuticals (adapted from [139]).
11
11
Table 1.1 Pharmaceuticals studied in this dissertation; their therapeutic function, chemical structure and physico-chemical properties.
Water
Removal during
Therapeutic pKaa Log Kowb solubility
Pharmaceutical Chemical structure wastewater
function [15, 191] [15, 191] (mg/mL)
treatment [164]
[121, 191]
12
Atenolol Beta-blocker 9.4 0.2 955 Moderate
Atorvastatin Lipid regulator 4.3 4.2 0.1
Caffeine Stimulant 10.4 -0.1 21.6 High
Carbamazepine Anti-epileptic 13.9 2.5 0.01 Low
Diclofenac Anti-inflammatory 4.2 4.5 0.002 Low
Fluoxetine Anti-depressant 10.1 4.1 33

Gemfibrozil Lipid Regulator 4.7 4.8 0.008 High
Ibuprofen Anti-inflammatory 4.9 4.0 0.01 High
Metoprolol Beta-blocker 9.6 1.9 47 Low
Naproxen Anti-inflammatory 4.2 3.2 0.016 High
Paracetamol Pain killer 9.4 0.5 0.1
Propranolol Beta-blocker 9.4 3.5 1.72
Sulfamethoxazole Antibiotic 5.7 0.9 0.01 Moderate
Trimethoprim Antibiotic 7.1 0.9 0.4 Moderate
13
a - pKa: dissociation constant; b - Log Kow: octanol-water partitioning coefficient.
I
1.2 Effects of pharmaceuticals in the water cycle

1.2.1 Environmental effects
Improved analytics of the last two decades allowed the detection of
pharmaceuticals in various matrices and enabled investigations into the fate and
ecological effects of these compounds [196, 262, 283]. Though the fate of
pharmaceuticals, i.e. pathways of pharmaceuticals through the environment, is
now relatively well known, the actual ecological effects in the environment are still
poorly understood [85, 139, 190, 315]. Effects of numerous individual
pharmaceuticals on specific test organisms like bacteria, algae, daphnia and other
aquatic organisms are well studied, but limited studies report the effects of
pharmaceutical mixtures in the environment [287]. The number of
pharmaceuticals emitted into the environment is world-wide still increasing and
this is not expected to change in the near future.
Due to the enormous variety in types of pharmaceuticals used and emitted,
exposure to organisms in the environment concerns predominantly mixtures rather
than to individual compounds. Although concentrations of individual compounds in
water and soils are often non-toxic, exposure to these mixtures could result in a
synergistic toxicity, thus leading to high risks [233]. Brian et al. [34] studied the
effects on fish of exposure to a mixture of estrogenic compounds. They found
estrogenic compounds to act together in an additive manner imposing fish toxicity
at concentrations of which the individual compounds did not induce a response.
Similarly, Cleuvers [50] demonstrated elevated toxicity for a mixture of anti-
inflammatory drugs over the toxicity of the individual compounds which could be
explained by the principle of concentration-addition.
Also for mixtures of compounds with different modes of toxic action, additive
toxic effects were found compared to the individual compounds [5]. Thus, the
presence of numerous individual pharmaceuticals in wastewater could result in
risks for the aquatic environment near the effluent discharge areas of the WWTPs
[77, 141, 325]. The variety among the broad array of individual pharmaceuticals
results in that different modes of toxic action and multiple toxicological end-points
need to be accounted for to determine actual toxicities [85]. For instance, Guler
and Ford [98] discovered behavioural changes resulting in increased predation
risks for the marine amphipod Echinogammarus marinus when exposed to the
14
Chapter 1
anti-depressant fluoxetine at environmentally relevant concentrations. Decreased

activity of the benthic invertebrate Gammarus pulex was found at ibuprofen and
fluoxetine concentrations of 10-100 ng/L [63]. Kidney, liver and gill cell alterations
were observed in rainbow trout (Oncorhynchus mykiss) exposed to 1 µg/L
concentrations of diclofenac [274].
Acute toxicity tests with standard testing organisms like daphnia, algae and
bacteria revealed that the lowest observed effect concentrations (LOEC) are about
two orders of magnitude higher than concentrations found in WWTP effluents.
However, for other specific organisms LOEC of individual compounds were found
at typical WWTP effluent concentrations, e.g. diclofenac for fish, and propranolol
and fluoxetine for zooplankton and benthic organisms [85]. I
All above mentioned toxicity studies were conducted at laboratory scale.
Translating results of laboratory toxicity tests to the real aquatic environment is
complicated since there seems not to be a single assessment factor which can be
applied for all aquatic species and for all pharmaceuticals. Moreover, laboratory
tests mostly focus on acute toxic effects rather than on chronic toxicity [57]. In
their review on ecotoxicology of pharmaceuticals Fent, et al. [85] state that only
little is known about long term effects and chronic toxicity to aquatic organisms.
Moreover, limited studies report the actual impact of pharmaceuticals on the
aquatic environment as the presence of other potential ecological stress
compounds (such as pesticides, personal care products, industrial additives, etc.)
complicates parsing out the actual contribution of pharmaceuticals.
Various authors therefore handle a more pragmatic approach and study the
ecological effects of WWTP effluent discharge into the aquatic environment without
unravelling the contributions of individual compounds. Field studies on river
systems receiving WWTP effluents have shown endocrine-disruptive effects
resulting in intersex rainbow darters (Etheostoma caeruleum) [259, 270].
Moreover, discharge of various anti-depressants by WWTPs resulted in the
bioaccumulation of these compounds in the brain, liver, muscle and gonads of
various fish species in the Niagara River and are hypothesized to affect the
biological diversity [17].
The abovementioned lab-scale and field studies demonstrate that the
current understanding of the actual acute and chronic effects of pharmaceuticals
mixtures on the environment is incomprehensive and inconclusive. Further
15
research is required to elucidate especially the potentially harmful long term

ecological effects of pharmaceutical mixtures on the aquatic environment at
environmentally relevant concentrations, i.e. to assess LOECs of pharmaceutical
mixtures for aquatic biota networks in the environment.
1.2.2 Effects on human health

Pharmaceuticals have been detected in various sources of drinking water
and thereby pose a potential risk to human health [32]. Touraud et al. [273]
concluded in 2011 that there was no consensus among scientists on what risks
pharmaceuticals actually pose to human health as their reviewed studies often
reported uncertainties and the toxicity of mixture effects on human health is
difficult to quantify. Even in very recent studies, utilizing an extensive
environmental monitoring dataset with a large number of pharmaceuticals for the
human health risk assessment of pharmaceutical mixtures in drinking water, no
complete risk overview can be given [113]. Moreover, there are no institutionalized
risk assessment methods for the presence of pharmaceuticals in drinking water
[273]. Therefore methods using indirect exposure, based on predicted
environmental concentrations, and human pharmacology and toxicology data of
pharmaceuticals have been applied to assess the toxicological effects of drinking
water or fish consumption on human health.
For various individual or groups of pharmaceuticals no appreciable human
health risks have been found [25, 58, 59, 122, 226, 252]. Thus, to date there is
no direct science based reason for concern as there are no clear indications of
adverse effects on human health. However, unlike ecological and aquatic organism
studies, studies on the effects of low levels of wide ranges of chemicals on human
health are hampered by the impossibility to do controlled exposure experiments
with populations. Therefore, it cannot yet be excluded that adverse human health
effects exist due to a continuous exposure to low levels of a wide range of
chemicals. A recent meta-analysis showed that between 1973 and 2011 the sperm
count of Western men expressed as sperm concentration and total sperm count
reduced by 52% and 59%, respectively [152]. The authors state that these
findings are plausibly associated to multiple environmental influences such as
exposure to chemicals. The implications of reduced sperm count go beyond fertility
and reproduction concerns as they also pose serious public health, societal and
16
Chapter 1
economical related problems. For this and other reasons, drinking water
companies often imply the precautionary principle or a so called “clean source”
strategy and policy: they give high value to the image of their water products
which is related to the quality of the water resources they use and the perception
of drinking water consumers [113, 242]. Thus, drinking water companies strive for
use of water resources that are free from unnatural organic components, such as
pesticides, pharmaceuticals and other compounds, and this is a strong “society-
driven” motivation for considering measures to remove pharmaceuticals from
WWTP effluents.
The situation is different for the presence of a specific group of
pharmaceuticals, namely antibiotics, in wastewater and in water resource systems I
used for drinking water that are affected by WWTP effluents. For these compounds
environmental exposure raises human and animal health concerns due to the
proven development of clinically relevant antibiotic-resistant bacteria [41, 48]. The
extent of natural bacterial populations that have acquired resistance to these
antibiotics (often used as life-saving medicines) is increasing [31, 168]. This may
cause yet also unknown human health risks via exposure of humans to these
antibiotic-resistant bacteria through the natural environment, via crops and live-
stock food products or via poorly disinfected drinking water.
1.2.3 Need for measures

The abovementioned concerns regarding widespread and continuous
emissions of mixtures of pharmaceuticals at low concentrations through WWTP
effluents to the aquatic environment is suspected to cause –largely unknown-
acute and/or chronic toxicity effects in aquatic populations. As mentioned above,
to date there are no direct science based reasons concerning acute risks to human
health regarding pharmaceutical emissions. Nevertheless, there are multiple
reasons as mentioned above which stress the need to remove these insidious
compounds quickly after they enter the water cycle. Thus, from an environmental
and human health related perspective to reduce the possible risks pharmaceuticals
pose, there are strong motivations to conduct further research on ways to reduce
pharmaceutical emissions, i.e. by prevention and technological removal measures
like the further treatment of WWTP effluents.
17
1.3 Legislation
From a legislative perspective first steps have been taken concerning the
presence of pharmaceuticals in the water cycle. To date, the most progressive
policies have been implemented in Switzerland. In the early 2000s the issue of
micropollutants entered the Swiss political agenda [184]. Actions were taken from
2009 onwards when the Swiss Federal Office for the Environment proposed
revisions to the nationwide Swiss Waters Protection Ordinance with respect to
micropollutants (including pharmaceuticals). In 2016 a revised Waters Protection
Act passed both Swiss parliamentary chambers and came into force. Thereafter
the implementation of the revised Waters Protection Ordinance was started, which
is currently in progress. In brief, the Waters Protection Ordinance foresees the
upgrade of large size WWTPs (>100 000 population equivalents (PE)) and
moderate size WWTPs (10 000 - 100 000 PE) which discharge into streams with
minute dilution or those being used for drinking water extraction. In practice this
implies that approximately 50% of the Swiss wastewater will undergo advanced
post-treatment as about 100 out of 800 WWTPs will be upgraded [232]. With the
upgrade, WWTPs have to meet an 80% removal efficiency of 5 compounds from a
list of 12 micropollutants (11 pharmaceuticals and 1 biocide). Individual Cantons
are free in their choice for the 5 compounds they monitor and every 5 years the
list of 12 compounds is subject to change. The upgrade concerns the investment
costs of about 1.2 billion CHF and additional operational costs of 130 million CHF
per year. As the polluter pays principle is practiced [184] the Swiss inhabitants are
charged an additional 9 CHF per person per year for the next 25 years [232].
Although to date there are no discharge regulation for pharmaceuticals in
the European Union, an European wide water policy started already in the year
2000 [22]. This “Water Framework Directive” and its regulations concern the
prioritization of potentially harmful substances (amongst other pharmaceuticals)
and has already been extended with several directives and amendments. In the
Directive 2013/39/EU for the first time a pharmaceutical (diclofenac) and a
synthetic hormone (17-alpha-ethinylestradiol) were added to the so called ‘watch
list’. This watch list comprises of potentially hazardous compounds for which it is
recommended that monitoring and treatment solutions should receive extra
attention with the objective to protect the aquatic environment and the human
18
Chapter 1
health. Recently three antibiotics (azithromycin, clarithromycin and erythromycin)

were added to the watch list via an amendment (Decision 2015/495/EU).
To the best of my knowledge no policies and regulation have been
implemented in other countries. Although there is a raise in scientific attention for
micropollutants in various countries, this is commonly not reflected in implemented
policies. For instance the current environmental quality standard for surface water
in China do not mention pharmaceuticals [185]. Similarly Singapore, Japan New
Zealand and Australia have no specific legislation for the discharge of
pharmaceuticals to the environment even though their water acts aim at reducing
risks for human health [203]. Likewise, the primary objective of the United States
Federal Clean Water Act is “to restore and maintain the chemical, physical and I
biological integrity of U.S. waters”, but the Act doesn’t include legislation on the
monitoring or discharge of pharmaceuticals, and the Safe Drinking Water Act does
neither.
1.4 Pharmaceutical removal

1.4.1 Current (biological) treatment
WWTPs have a crucial role in the emissions of pharmaceuticals to surface
waters [14, 125]. Moreover, they are one of the few main hubs in the entire water
cycle. Hence, WWTPs are an ideal spot to prevent pharmaceutical emissions into
the environment. Despite pharmaceutical removal is currently not a design
parameter for WWTPs, various researchers have reported the removal of
pharmaceuticals in WWTPs, indicating the potential of biological treatment [124,
190, 238]. In general, high variations in pharmaceutical elimination efficiencies
are found among different WWTPs which are typically linked to the WWTP design
[47]. This suggests that pharmaceutical treatment can possibly improve when
pharmaceutical removal would be regarded as a design parameter. Various WWTP
characteristics and design parameters have therefore been studied to gain a better
understanding of the underlying pharmaceutical removal mechanisms. Removal
rates seem to depend on treatment plant configurations and parameters like
biological nitrogen removal, diversity of the microbial community, hydraulic
retention time, sludge retention time and the use of biofilm carriers [47, 49, 81,
82, 123, 124, 241]. Moreover, redox conditions are also found to affect the
19
pharmaceutical removal [247]. Most pharmaceuticals are best degraded under

aerobic conditions while others might need anoxic or anaerobic redox conditions
[36, 83, 105]. Besides the design of a WWTP the characteristics of individual
pharmaceuticals largely influences their fate during water treatment [312]. Within
a given WWTP some pharmaceuticals are generally marginally removed (<5%)
while others show removal percentages of over 95% [37, 287]. For instance,
aspirin, estradiol, ibuprofen, and paracetamol are known to be effectively
biodegraded during wastewater treatment, while crotamiton, diazepam and
diclofenac are typically not eliminated [125]. In general, biodegradation and
sorption are the mechanisms controlling pharmaceutical removal during biological
wastewater treatment [267]. The biodegradability and sorption behaviour of an
individual pharmaceutical largely depends on its chemical structure and physico-
chemical properties. The great variety in observed removal mechanisms can
therefore be explained by the broad array of chemical structures and physico-
chemical properties of the pharmaceuticals (Table 1.1).
1.4.2 Room for improvement within biological treatment

The influence of the compound characteristics and the effect of the type of
treatment plant configuration suggests that a variety of treatment conditions and
processes with different modes of action might be needed for realising effective
pharmaceutical removal. WWTPs could be upgraded or extended with additional
treatment steps to reduce pharmaceutical emissions. On the one hand, this may
be achieved by improving or extending current biological process. I hypothesize
that this can be achieved by for instance the implementation of more diverse redox
gradients over a treatment plant, oligotrophic zones for specific pharmaceutical
degrading biomass, retention of specific biomass, non-continuous feeding (e.g.
feed-famine regimes), longer hydraulic retention times, use of other biomass than
activated sludge (e.g. fungi or algae). On the other hand, non-biological treatment
processes can be applied for a better pharmaceutical removal.
1.4.3 Chemical treatment

Chemical treatment processes like advanced oxidation processes (AOPs)
making use of photolysis, photocatalysis, ozone, hydrogen peroxide or Fenton
20
Chapter 1
process, or sorptive processes like activated carbon (AC) addition or filtration can
effectively eliminate pharmaceuticals [1, 164, 262]. Most chemical treatment
processes originate from drinking water treatment, however they have also been
successfully applied in wastewater treatment as a post-treatment step [109, 197,
264, 293, 303, 329]. AOPs rely on the direct or indirect oxidation of a compound
[225]. Oxidative processes like ozonation typically break down compounds into
smaller fragments, but do not completely mineralize compounds into CO2 and H2O
[293]. Moreover, in a complex matrix like wastewater ozone will not only react
with the target compounds (e.g. pharmaceuticals) but also with other matrix
constituents. This reduces the process efficiency and results in the formation of
countless by-products which possibly expose a higher toxicity than the I
pharmaceuticals treated [208]. Ozonation is therefore often combined with a
subsequent AC filtration step [90, 134, 218]. Though AOPs can effectively remove
pharmaceuticals they require high energy and/or chemical inputs. Sorptive
processes like AC filtration rely on the interaction of a sorbate (e.g. a
pharmaceutical) with a sorbent like AC. These systems do not transform sorbates
but bind them onto the AC sorbent [198]. High pharmaceutical removal efficiencies
can be obtained by AC filtration, however removal efficiencies decrease over time
due to saturation of the AC and not all pharmaceuticals are effectively removed
[96]. Once the sorbent is saturated it should be replaced or regenerated as non-
regularly regenerated filters demonstrate low to nil pharmaceutical removal [244].
Disposal of saturated sorbent only shifts the problem, e.g. to landfilling, whereas
regeneration requires high energy inputs. In summary, a possible solution to
prevent pharmaceuticals entering the environment could be the upgrade of WWTPs
supplemented with chemical treatment. Until now these processes have
demonstrated higher removal efficiencies compared to biological treatment [164,
222, 287]. Although chemical treatment processes are promising for
pharmaceutical removal the wide scale implementation is hampered by some
major issues. They require high energy, chemical or material inputs which all
translate into high operational costs and are not environmentally sustainable.
Moreover, these processes often result in the formation numerous unknown by-
products which possibly jeopardise the receiving aquatic environment to a greater
extent than the compounds removed.
21
1.4.4 Combined treatment

Biological and chemical treatment processes for pharmaceutical removal
both have their downsides and limitations, e.g. incomplete pharmaceutical
removal, high energy and chemical inputs, high operational costs, environmental
unsustainability. A combination of complementary treatment processes, abating
the limitations of individual processes, could therefore be a versatile alternative.
Scott and Ollis [235] reviewed the literature on combined biological and chemical
treatment processes for the removal of organic contaminants from water and
concluded that combined process can have advantages over single processes.
When economical, physical and technological strengths and limitations of individual
processes are recognized, the synergy of complementary processes can be used
to design a cost-effective combination of processes.
In theory, avoiding the limitations and using the strengths of two different
types of processes and to create synergy could be the combination of biological
treatment and ozonation. The first is a cheap process but incapable of effectively
removing all individual pharmaceuticals, e.g. clofibric acid and bezafibrate are
known to be well removed, whereas diclofenac and carbamazepine are reported to
be very poorly removed [124]. On the contrary, ozonation has high operational
cost and results in by-product formation, for instance it hardly removes clofibric
acid and bezafibrate, but effectively oxidises diclofenac and carbamazepine [264].
In addition, biological treatment can possibly be used to remove the harmful
ozonation by-products as they are typically biodegradable [243].
In practice, various combinations of processes have already been studied
and applied for the removal of organic contaminants from water. Though these
studies often report enhanced removal efficiencies compared to single processes,
they merely focus on a single compound often in model (simple) matrices rather
than on a mixture of compounds in a complex matrix like wastewater [46, 80, 93,
107, 201, 297, 313]. Concerning the removal of a broad array of pharmaceuticals
from wastewater, Hofman-Caris, et al. [109] found that anion exchange followed
by UV/H2O2 treatment was a versatile combination of two chemical treatment
processes. Biological activated carbon filtration, a combination of biological
treatment and activated carbon filtration, was proven to effectively remove
pharmaceuticals and reduce toxicity from WWTP effluents [217]. Ozonation
followed by biological activated carbon filtration of WWTP effluent showed even
22
Chapter 1
higher pharmaceutical removal [218]. Sand-filtration followed by ozonation of a

secondary clarified effluent effectively removed estrogenicity, whereas sand-
filtration only or sand-filtration followed by a moving-bed bioreactor were less
effective [99]. Oller, et al. [198] reviewed the combination of AOPs and biological
treatment for wastewaters containing pharmaceuticals. They concluded that
photocatalysis, ozonation and ultrasound oxidation were well studied and typically
result in an increased biodegradability and a decreased toxicity. Moreover, they
concluded that the potential of combinations of AOPs and biological treatment is
still under exploited since not many cost-effective combinations of chemical and
biological treatment are available.
I
1.5 Knowledge gaps and research opportunities
The need to prevent pharmaceutical emissions into the environment for the
abovementioned reasons related to ecological risks and human health, stresses
the necessity for versatile treatment processes to eliminate pharmaceuticals from
wastewater. As the research on pharmaceutical removal only started some
decades ago [263] combined with the wide variety in possible treatment processes
[164], there are still numerous knowledge gaps on the fundamental and practical
aspects of pharmaceutical removal. These knowledge gaps concern pressing
questions on single treatment processes as well as on the combination of
treatment processes.
Taking into consideration that current WWTPs merely use biological
treatment processes, this suggests that if biological pharmaceutical removal can
be improved it would potentially be the most sustainable and cost-effective
solution. First, within biological treatment, redox conditions are regarded as one
of the key parameters in biological conversions [306]. Though the most prevalent
redox conditions in biological processes at WWTPs (aerobic and anaerobic) are well
studied [36, 83, 247], there is limited information on how specific redox conditions
influence biodegradation and sorption behaviour of pharmaceuticals, which are
regarded as the most important removal mechanisms during biological treatment.
Second, the type and presence of organisms utilized in biological treatment
is of great importance. Typical biological processes at WWTPs make use of
activated sludge, which is in essence a diverse microbial population consisting of
mainly bacteria which are loosely bound in a settable floc. As raw wastewater
23
contains multiple orders of magnitude more easy biodegradable compounds than

pharmaceuticals, it is likely that organisms degrading complex substrates, such as
pharmaceuticals, are easily outcompeted. Providing oligotrophic environments
with minimal substrate competition is therefore hypothesized to be an effective
strategy to enrich for pharmaceutical degrading microorganisms. Moreover,
pharmaceuticals are typically present in the ng/L to µg/L range, these low
substrate levels only support minimal microbial growth, therefore retention of
organisms is of great importance to successfully operate biological treatment
processes.
In addition to the commonly used microbial populations in wastewater
treatment, also other organisms can be employed for the typical objectives of a
WWTP. One of the other organisms capable of wastewater treatment are green
microalgae. These phototropic organisms are therefore utilized in some
wastewater treatment configurations [3, 61, 100, 110]. Algal treatment is well
studied for the effective removal and recovery of nutrients from highly
concentrated wastewater streams like black water or urine [276, 285]. Little is
known however, whether algae are capable of removing the high concentrations
of pharmaceuticals which are also present in those streams [36, 157]. Moreover,
as the recovered nutrients present in the algal biomass are potentially used as
fertilizer in agriculture it is of great importance to known whether pharmaceuticals
sorb onto the algal biomass to prevent their introduction into the food chain.
As long as biological treatment does not form an adequate barrier against
the majority of the pharmaceuticals present in sewage, further research is also
needed on other treatment processes or combinations of them. As described
above, combinations of complementary processes are found to have beneficial
effects over single processes and therefore have a great potential to reduce
pharmaceutical loads into the environment. Nonetheless, there is still a lack of
sustainable and cost-effective combined treatment options which motivates the
further investigation into these treatment processes.
The work on algal treatment processes for wastewater treatment typically
utilize photobioreactors to cultivate the algae [276, 285]. These reactors are
illuminated to support algae growth, however the influence of illumination in
photobioreactors on pharmaceutical removal is not well studied whereas it is
known that photolysis in the natural environment can degrade pharmaceuticals
24
Chapter 1
[140, 143]. As various removal mechanisms like algal degradation, microbial

degradation, sorption to biomass and photolysis occur concurrently in
photobioreactors, this provides an unique opportunity to study the synergy
between biological and chemical treatment processes.
Photocatalysis and biodegradation are known complementary processes for
the removal of various organic contaminants such as quinolone, pyridine and
pesticides from water [297, 311, 322, 323]. For a limited number of individual
pharmaceuticals this combination has been studied [93, 201, 307], but for
pharmaceutical mixtures the effectiveness of the combined treatment remains
unknown. Moreover, photocatalytic processes commonly require considerable
amounts of energy inputs and are thereby not very sustainable. Hence, it is of I
great importance to improve the resource efficiency, e.g. in an energy efficient
combination with biological treatment, before this treatment process can find its
way to large scale application in wastewater treatment.
Ozonation and biological treatment is a potentially versatile combination of
treatment processes for the removal of pharmaceuticals. Ozonation followed by
biological treatment is well established in drinking water treatment [212, 293], but
to a lesser extend in wastewater treatment [111, 329]. On the one hand, this is
mainly due to the current absence of pharmaceutical removal requirements during
wastewater treatment, whereas drinking water production requirements are much
more strict. On the other hand, the composition of wastewater is highly different
than drinking water sources like surface- or groundwater. Compared to matrices
of drinking water sources, wastewater matrices (influent and effluent) typically
consist of higher concentrations of a wide array of matrix constituents like organic
matter, nutrients, trace elements and other chemicals such as pharmaceuticals,
personal care products and pesticides. As ozonation targets multiple matrix
constituents others than pharmaceuticals, post-treatment by ozonation is not very
resource-efficient for the specific removal of pharmaceuticals. Most of the studies
that investigated ozonation as tertiary WWTP step reported relatively low amounts
of matrix constituents [111, 117, 329]. Matrices however, are known to be
different at each individual treatment plant (e.g. due to different ‘clients’) and can
also vary per geographical region (e.g. due to local water hardness and
background natural organic matter). Getting a more comprehensive and local
(Dutch) understanding of the versatility of this treatment is therefore of scientific
25
interest and can help decision makers in implementation of treatment processes.

A well-studied aspect of ozonation in drinking water production is the formation of
ozonation by-products. These are of concern as they potentially increase toxicity
[118]. For ozonation in wastewater treatment toxicity aspects are studied to a
lesser extent. Thus, besides increasing the resource efficiency, trapping or
transforming the possibly harmful by-products is of great importance. Both issues
motivate further research on the combination of ozonation and biological
treatment and challenge researchers to come up with innovative ideas how to
overcome the issues.
In summary, there are still many knowledge gaps on how to enhance
pharmaceutical removal by single and/or combined treatment processes.
Inherently, this shows the potential of research opportunities to improve single
processes and to search for synergetic combinations of processes.
1.6 Objective of this dissertation

To prevent future pharmaceutical emissions into the environment, adequate
measures for the removal of pharmaceuticals from WWTP effluents need to be
developed. Development of wide scale implementation of such measures is
hampered by the fact that known biological and chemical removal processes result
in incomplete removal, and that insufficient insight exists in the functioning and
effectiveness of processes used in the synergetic use of combined treatment
processes. Therefore, the objective of this dissertation is to contribute to a better
understanding and the further development of treatment processes for the
removal of pharmaceuticals from wastewater.
1.7 Scope and outline of this dissertation

This dissertation focuses on the research opportunities on single and
combined processes for pharmaceutical removal. The experimental work of this
dissertation aims at a better understanding of specific aspects of biological
treatment processes, like the effect of redox conditions and the type of involved
microorganisms, and the interaction between biological and chemical removal
processes. Moreover, combinations of treatment processes were developed for a
better pharmaceutical removal. Among the broad spectrum of pharmaceuticals a
26
Chapter 1
limited amount was selected for the experimental work of this dissertation.
Selection criteria were; consumption, occurrence in wastewater, physico-chemical
properties and removal efficiencies during biological treatment. The selected
pharmaceuticals are among the most sold in the Netherlands [283] and commonly
found in wastewater [287]. Furthermore, they cover a wide range of physico-
chemical properties and their reported removal efficiencies in WWTPs range from
high to low removal [164].
The influence of specific redox conditions on the biological removal of
pharmaceuticals is elucidated in Chapter 2 with a focus on the influence of redox
conditions on biodegradation and sorption behaviour.
In Chapter 3 we describe the combination of a mild photocatalytic treatment I
process and a subsequent biological treatment process for a resource-efficient
pharmaceutical treatment.
In Chapter 4 we present a three-step biological-ozone-biological process
combining the strengths of biological treatment and ozonation with the aim to
minimize the energy input and hydraulic retention time, while effectively removing
pharmaceuticals and their associated toxicity.
In Chapter 5 we focus on the removal of pharmaceuticals by algae in
alternative sanitation systems. We investigated the effectiveness of an algal
photobioreactor for the simultaneous removal of nutrients and pharmaceuticals.
Finally, in Chapter 6 findings and outcomes of the presented work in this
dissertation are synthesized and reflected. An outlook on single and combined
treatment processes for pharmaceutical removal is given, including the
identification of current knowledge gaps and recommendations for further research
and the scale up of the processes studied in this dissertation. Attention is paid to
the developments in analytical chemistry, including metabolite and transformation
product identification, and the need for effect based removal strategies. Moreover,
developments in other fields such as restrictive discharge legislation, the role and
awareness of other actors in the pharmaceutical chain and the benefits of
alternative sanitation systems are discussed as environmental problem solving
generally requires a multidisciplinary approach. All together, the synergy between
biological and chemical treatment processes and developments in legislation,
awareness of other actors and benefits of alternative sanitation systems can be a
boost towards lower pharmaceutical emissions into the environment.
27
29
Chapter 2
Sorption and biodegradation of pharmaceuticals under
different redox conditions
A modified version of this chapter has been published as
Arnoud de Wilt*, Yujie He*, Nora Sutton, Alette Langenhoff and Huub Rijnaarts.
Sorption and biodegradation of six pharmaceutically active compounds under four different
redox conditions. Chemosphere, 193 (2018) 811-819
* Equally contributing authors
Influence of redox conditions on biodegradation and sorption
Abstract
This study explored the removal of six pharmaceuticals in lab-scale
experiments with sediments under four redox conditions, namely aerobic, nitrate
reducing, sulfate reducing, and methanogenic conditions using batch and column
set-ups. Redox conditions were found to influence pharmaceutical removal by
sorption and biodegradation. The most optimal pharmaceutical removal was
observed at the outer ranges of the redox spectrum, i.e. either aerobic or deeply
anaerobic (sulfate reducing and methanogenic conditions), whereas nitrate
reducing conditions were found least effective for pharmaceuticals biodegradation
and sorption. For instance, sorption coefficient Kd values for metoprolol in column
experiments were 90, 65, 42 and 11 L/kg for sulfate reducing, methanogenic,
aerobic and nitrate reducing conditions, respectively. For the same conditions Kd
values for propranolol were 101, 94, 55 and 55 L/kg, respectively. As expected,
biodegradation efficiencies were highest under aerobic conditions, showing >99%
removal of caffeine and naproxen, but no removal for propranolol and
carbamazepine. The adaptive capacity of sediment was demonstrated by pre-
exposure to pharmaceuticals leading to improved pharmaceutical biodegradation.
The results of this study indicate the necessity to combine diverse redox
conditions, including aerobic conditions, for maximizing pharmaceutical removal
by sorption and biodegradation. Furthermore, our findings stress the need for
additional treatment measures as recalcitrant pharmaceuticals are not effectively
removed under any redox condition.
Keywords
Pharmaceuticals; Redox conditions; Sorption; Biodegradation; Sediment
32
Chapter 2
2.1 Introduction
Pharmaceuticals were developed to target specific human physiological
pathways [180]. After consumption, residual pharmaceuticals or/and their
metabolites are excreted from human bodies into sewage systems. Conventional
wastewater treatment plants (WWTPs) are not specifically designed for removing
pharmaceuticals [230]. Therefore, pharmaceuticals that are not completely
removed are discharged to the aquatic environment and may even reach drinking
water intakes [40]. In this context, efficient post-treatment technologies for
removing pharmaceuticals are needed and emerging.
Biological technologies are robust and attractive as post-treatment
processes. However, processes involved in biotechnological systems are more
complex and require a proper understanding to come to a robust design and
operation. In most biological technologies, both sorption and biodegradation play
II
an important role in removing organic contaminants. It is well known that organic
matter, temperature and pH affect sorption of organic contaminants [183],
however the effect of redox conditions (electron acceptors) on sorption behaviour
on organic contaminants is less known. On the contrary for biodegradation, specific
electron acceptors select for specific microbial communities with different targeted
functions, and thereby strongly influence the biological removal of organic
contaminants [84]. For example, transformation of sulfamethoxazole was reported
to strongly depend on the occurrence of nitrate reducing conditions and be
sensitive to the concentration of nitrate [21].
Although redox conditions are identified as one of the controlling factors for
biodegrading pharmaceuticals, the reported dependencies of removal processes
on redox conditions vary significantly for specific pharmaceuticals for various
reasons. Firstly, most of the previous works only study the removal efficiencies of
pharmaceuticals under oxic and anoxic conditions without identifying the dominant
terminal electron acceptor [309, 330]. Secondly, results reported for
pharmaceutical biodegradation in terms of redox effects are often contradictory.
For example, sulfamethoxazole (SMX) was proven to be more rapidly eliminated
under anoxic conditions than under aerobic conditions in bank filtration in the work
of Heberer et al. [106], while Baumgarten et al. [24] concluded that SMX was
more rapidly removed under aerobic conditions compared to anoxic conditions.
Conkle et al. [53] concluded that degradation of carbamazepine (CBZ) was
33
enhanced under aerobic conditions as compared to anaerobic conditions in

sediment collected from three types of wetlands; in contrast, Hai et al. [101]
reported that CBZ showed degradation only in an anoxic environment instead of
under oxic conditions in a membrane bioreactor. Furthermore, the various studies
that report the effects of redox conditions on pharmaceutical removal are difficult
to compare as they use different reactor setups, different concentrations and
different compounds.
Thus, there is a significant knowledge gap on comparative effects of redox
conditions on removal of pharmaceuticals in biotechnological systems. To get a
more comprehensive understanding of the influence of selected redox conditions
on specific pharmaceutical removal via sorption and biodegradation, it is necessary
to investigate this in defined experimental setups varying the applied redox
conditions. Therefore, the objective of this study is to elucidate the influence of
redox conditions on removal mechanisms of six pharmaceuticals applying four
specific conditions of the wide redox spectrum. Batch and column systems were
used for controlled biological tests under aerobic, nitrate reducing, sulfate
reducing, and methanogenic conditions. The results of this study give insight into
understanding the influence of redox conditions on pharmaceutical removal in
biotechnological systems.
2.2 Materials and Methods

2.2.1 Chemicals and regents
Pharmaceuticals metoprolol (MET), caffeine (CAF), propranolol (PRO),
carbamazepine (CBZ), naproxen (NAP), ibuprofen (IBP) were purchased from
Sigma-Aldrich (U.S.). Details of the pharmaceutical stock solution, other chemicals
used and physio-chemical properties of pharmaceuticals are given in Text S2.1
and Table S2.1.
2.2.2 Experimental setup

2.2.2.1 Sediment
Sediment of constructed wetlands (CWs) at WWTPs Hapert and Land van
Cuijk (both in the Netherlands) was collected as a solid phase of the batch and
column systems. In addition, the sediments contain microorganisms that serve as
34
Chapter 2
a natural inoculant of the biologically active laboratory systems. CWs at both

facilities have received WWTP effluent for several years. Sediment dry matter (DM)
and organic matter (OM) content were determined gravimetrically after drying at
105 °C following combustion at 550 °C.
The aerobic column was inoculated with upper layer sediment (0-5 cm) with
an OM content of 6.2 g OM/kg DM. Sediment at a depth of 10-20 cm below the
surface level with an OM content of 16.2 g OM/kg DM was collected to inoculate
the anaerobic columns. A mixture of upper, deeper layer, and rhizosphere
sediment was used for batch experiments containing 19 g OM/kg DM.
Concentrations of the six pharmaceuticals varied from 0 to 777 ng/g in CW
sediment [104].
2.2.2.2 Batch experiments

Four different media were used to enrich dominant bacteria in different
II
redox conditions. Media were prepared according to previous works for aerobic
(Table S2.2), nitrate reducing [79], sulfate reducing [145], and methanogenic
conditions [112]. The ionic strength of media was calculated by OLI Studio
Analyzer 9.2 software. In each batch bottle, 120 mL medium was mixed with 15 g
wet sediment as inoculum. Batches were spiked with a mixture of six
pharmaceuticals at 1 mg/L each. For analytical reasons the spiking concentration
is far above the environmental relevant concentrations of pharmaceuticals, as also
been applied in previous works [2, 119]. The gas phase of each bottle was filled
with either atmospheric air for aerobic conditions or CO2/N2 (20/80, v/v) for
anaerobic conditions. Among the four redox conditions, no extra carbon source
was added except for the pharmaceuticals. Abiotic controls contained 1.3 g/L of
sodium azide in aerobic batch bottles and 0.3 g/L of mercury chloride in anaerobic
bottles to supress microbial activity.
The aerobic batch experiment lasted for six weeks and the anaerobic batch
lasted for three months. Samples of week 0 were collected the day after spiking
to ensure a homogeneous distribution of pharmaceuticals. In order to determine
the role of microbial adaptation, mixed pharmaceuticals were re-spiked three times
in the aerobic batches (biotic and abiotic) for enrichment after week 6. Batch
bottles were incubated on a shaker (120 rpm) at 20°C. Batch bottles were
incubated in the dark during the experiment to prevent photolysis. Compared to
35
the spiked pharmaceutical levels, the initial pharmaceutical concentrations in the

sediment were minute and thus desorption of the initial pharmaceuticals to the
liquid phase is negligible. Sorption coefficient Kd was calculated from the abiotic
controls as the ratio of the pharmaceuticals concentration in the sediment phase
and in the water phase at equilibrium. The concentrations of sorbed
pharmaceuticals were calculated from the measured water phase concentrations
based on mass balance.
2.2.2.3 Column experiments

Column experiments were conducted in four continuous-fed upflow soil
columns (Figure 2.1). Identical to the batch experiments, aerobic, nitrate reducing,
sulfate reducing and methanogenic conditions were tested. Cylindrical glass
columns (0.23 L) were packed with sediment containing 292 g DM and 230 g DM
for respectively aerobic and anaerobic experiments. Sediment was retained in the
columns by sintered glass filters (pore size 40-100 μm). The packed sediment was
circularly homogenised biweekly, while keeping sediment layers at their depths in
the columns. This is needed to prevent bypass flows through the columns. Columns
were fed with medium at a flow rate of 9.8±0.4 mL/h, resulting in a hydraulic
retention time of 8.2±0.3 h. For each redox condition, specific media were
prepared (Table S2.2), which contained about 100 μg/L pharmaceuticals during
the experiment of 110 days. Prior to the experiment columns were run two weeks
on media without pharmaceuticals to allow redox conditioning. Columns and media
were kept in the dark during the experiment to prevent photolysis.
Influent and effluent grab samples were collected for chemical analysis
within 24 hours from each other per time point. Pharmaceutical removal was
calculated based on effluent concentrations per time point over the averaged
influent concentration of the entire experiment to deal with fluctuations in the
influent concentration. Sorption parameter values (specific sorption coefficient Kd)
were determined for sorptive pharmaceuticals by calculating the retardation factor
from the time point when the effluent pharmaceutical concentration reached fifty
percent of the influent concentration.
36
Chapter 2
Effluent
Aerobic column Sampling points
Nitrate reducing column
Sulfate reducing column
Methanogenic column
N2 /
CO 2
Sampling II
points
Air
Sulfate
Nitrate + Sulfide
Medium + Medium + Sulfide
Pharmaceuticals Pharmaceuticals
Figure 2.1 Experimental set-up of the column experiments.
2.2.3 Sample collection and analysis

Liquid samples were taken from batch media and column influents and
effluents for pharmaceutical measurements. Samples collected from batch bottles
were centrifuged at 10 000 rpm for 10 min and stored at -20 °C prior to analysis.
Before analysis liquid samples of column experiments were pre-treated by solid
phase extraction (SPE) to allow the detection of low concentrations in column
effluents. Oasis HLB SPE cartridges (6 cc/60 mg, Waters, U.S.) were pre-
37
conditioned with 5 mL methanol and equilibrated with 5 mL buffered deionized

water (10 μL buffer/mL, pH=10, Merck, Germany). Cartridges were loaded with 3
mL and 9 mL for influent and effluent samples, respectively. Loaded cartridges
were washed with 5 mL buffered deionized water and eluted with 10 mL 25%
NH4OH: methanol (8/92, v/v). Eluates were evaporated till dryness under a gentle
nitrogen flow. Samples were reconstituted in 1 mL 3.6% methanol. Prior to SPE,
10,11-dihydrocarbamazepine was spiked to samples as an internal standard.
Pharmaceutical analysis was conducted on a liquid chromatograph with a
diode array detector as described by He et al. [103]. Quantification was based on
the internal standard and external calibration standards. SPE recoveries for all
compounds in all samples were within 85-115% and thereby valid for
quantification.
Concentrations of nitrite, nitrate, and sulfate were measured by ion
chromatography. Before measurement, samples were filtered using a 0.45 μm
cellulose filter (VWR, U.S.) and diluted five times with MilliQ water. A Dionex ICS-
2100 IC system (Thermo, U.S.) was used for analysis. The system was equipped
with an anion exchange column (Dionex, IonPac AS19, 4×250 mm), where the
anions were separated using a hydroxide gradient. The eluent was made
automatically using the eluent generator configured with a KOH cartridge (Dionex
P/N 058900) and deionized water as the carrier. Detection was done by a DS6
Heated conductivity cell.
Oxygen and methane from the headspace of batches were analysed on a
gas chromatograph. The instrument (GC-2010, Shimadzu, Japan) contained a
parallel combination column: Porabond Q (50 m x 0.53 mm; 10 µm) and Molsieve
5A (25 m x 0.53 mm; 50 µm). The carrier gas was helium and operated at 0.95
bar. Column temperature was 80°C, detector temperature was 150°C, and
injection temperature was 120°C. Pressure in the batch was measured by a digital
pressure meter (GMH 3151, Greisinger) for calculating gas volume. In the aerobic
column dissolved oxygen was measured by optical oxygen meter Fibox 3 trace
(PreSens, Germany) fixed near the outlet of the column. For methanogenic column
experiments, dissolved methane in liquid effluent samples was turned into gaseous
methane as described by Zhang et al. [319] and analysed by GC as described
above.
38
Chapter 2
2.3 Results
2.3.1 Redox conditions
Consumption of electron acceptors and accumulation of respiration products
were observed in all batches and columns (Figure S2.1). Under aerobic conditions,
O2 consumption was observed. Nitrate and sulfate consumption were detected
under nitrate and sulfate reducing conditions, respectively. Production of CH4 was
observed under methanogenic conditions. These results indicated that the desired
redox conditions were achieved.
2.3.2 Removal of pharmaceuticals

2.3.2.1 Batch systems
Outcomes from abiotic controls are used to characterize the sorption
capacity of the used sediment for targeted pharmaceuticals. In general, a high II
sorption capacity of CW sediment was found for NAP, CAF, PRO, and MET while
CBZ and IBP were much less sorbed (Table 2.1). Sorption of pharmaceuticals
under aerobic conditions were not used to compare with anaerobic conditions, as
the sorption did not achieve equilibrium under aerobic conditions while it did under
anaerobic condition due to the longer cultivation. When comparing pharmaceutical
sorption under different anaerobic redox conditions, nitrate reducing conditions
showed lower sorption capacity for MET, NAP, and CAF compared to sulfate
reducing and methanogenic conditions.
Biodegradation in batches was determined by comparing biotic and abiotic
removal efficiencies. Under aerobic conditions, MET, CAF, NAP and IBP were almost
completely removed within 6 weeks, which was mainly contributed to
biodegradation as sorption only contributed to less than 30% (Table 2.1). In
comparison, PRO and CBZ were poorly biodegraded considering their similar biotic
and abiotic removal. Under anaerobic conditions, only CAF was readily biodegraded
under nitrate and sulfate reducing conditions. Removal of CAF under methanogenic
conditions was mainly caused by sorption (Table 2.1). Similarly, the observed
removal of PRO, NAP, and MET was a result of their high sorption rather than
biodegradation. Under all anaerobic conditions IBP and CBZ were poorly removed
in the biotic and abiotic batches.
39
To determine the role of microbial adaptation, the aerobic inoculum in

batches was enriched to select for pharmaceutical removal by re-spiking
pharmaceuticals. During the first six weeks, NAP and IBP were approximately 60-
70% removed within one week and complete removal was reached at week 3
(Figure 2.2). After re-spiking, complete removal of NAP and IBP was reached within
one week. This was mainly contributed to biodegradation as sorption almost
achieved saturation after re-spiking (Figure S2.2). Therefore, microbial adaptation
by pre-exposure did accelerate the biodegradation of NAP and IBP. Half-lives of
NAP and IBP were 1.0 and 1.8 days, respectively; half removal of MET and CAF
reached less than 1 day (Figure S2.3).
Table 2.1 Biotic and abiotic removal (%) of pharmaceuticals in batches under different
redox conditions: 6 weeks cultivation under aerobic conditions; 3 months cultivation under
anaerobic redox conditions.
Redox condition Type PRO MET CAF NAP IBP CBZ
Biotic 81 95 100 100 96 43
Aerobic
Abiotic 55 29 27 15 25 22
Biotic 55 -9a 94 14 -9 -14
Nitrate reducing
Abiotic 77 -32 27 26 25 28
Biotic n.d.b 56 95 94 -1 -16
Sulfate reducing
Abiotic n.d. 60 48 93 -5 24
Biotic 66 52 95 94 5 3
Methanogenic
Abiotic 67 32 85 87 -3 22
a - Negative removal might be caused by analytical deviation; b - Not determined as the
PRO concentration under sulfate reducing conditions was accidently very low (0.05 mg/L),
which is close to the detection limit.
40
Chapter 2
120
Re-spike
100
80
Removal (%)
60
40
Naproxen
Ibuprofen
20
0
0 7 21 42
424646 77 84 89 95 105
Time (day)
II
Figure 2.2 Removal of naproxen and ibuprofen under aerobic condition with re-spike of
pharmaceuticals at day 46, 84, and 95.
2.3.2.2 Column systems

Different removal patterns were observed for individual pharmaceuticals in
columns among the tested redox conditions (Figure 2.3). Main removal
mechanisms were interpreted based on the observed removal patterns. Sorption
was indicated to be a dominating removal process when initial pharmaceutical
removal was followed by breakthrough of that compound. Biodegradation was
identified by the presence of a lag phase, significant removal and absence of
subsequent breakthrough behaviour. IBP and CBZ for which no significant sorption
or biodegradation was observed in any of the columns were classified as persistent
(Figure 2.3).
Significant removal (>95%) of PRO and MET followed by compound
breakthrough was apparent under all redox conditions (Figure 2.3). Therefore,
sorption was identified to be their dominant removal mechanism. Sorption of PRO
and MET appears to be affected by the applied redox conditions. Methanogenic and
sulfate reducing conditions indicated better sorption compared to aerobic and
nitrate reducing conditions for PRO and MET. Especially the removal of MET under
nitrate reducing conditions was limited compared to the other anaerobic redox
conditions whereas the sediment was identical.
41
CAF appeared initially to be removed by sorption in each column (65-99%)

(Figure 2.3). However, the sorption capacity of the sediment towards CAF was low
compared to PRO and MET as breakthrough behaviour was observed after day 4
in all columns. Under all redox conditions, biodegradation of CAF took place after
a lag phase: under aerobic and nitrate reducing conditions the lag phase lasted 27
days, while only after 67 days an increase in removal was found in the sulfate
reducing and methanogenic columns.
a) PRO b) MET c) CAF

100
50
0
Removal (%)
-50
0 20 40 60 80 100 120 0 20 40 60 80 100 120 0 20 40 60 80 100 120
d) NAP e) IBP f) CBZ

100
50
-50
0 20 40 60 80 100 120 0 20 40 60 80 100 120 0 20 40 60 80 100 120
Time (day)
Aerobic Nitrate reducing Sulfate reducing Methanogenic
Figure 2.3 Removal of pharmaceuticals under different redox conditions in continuous

flow-through columns: a) PRO; b) MET; c) CAF; d) NAP; e) IBP; f) CBZ. Negative removals
are due to temporal fluctuations in influent concentrations.
42
Chapter 2
The removal of NAP showed significant differences among the tested redox
conditions. Complete NAP removal (>99%) was achieved in the aerobic column
after a lag phase of 27 days. The presence of the lag phase followed by the
continuously high removal indicates that biodegradation was the main removal
mechanisms for NAP under aerobic conditions. Insignificant NAP removal (<25%)
was observed under nitrate reducing conditions (Figure 2.3). In the sulfate
reducing and methanogenic columns, a constant NAP removal throughout the
experiment of around 80% was found. This phenomenon could not be attributed
to sorption, as there was neither breakthrough of NAP nor a constant complete
NAP removal. Chemical NAP removal by the reactor medium was also excluded as
demonstrated in a separate test. Therefore most likely biodegradation is the main
removal mechanism for NAP under sulfate reducing and methanogenic conditions.
Why the removal did not improve over time, as would be expected due to the
II
growth of more specialized NAP degrading microorganisms in a biological system,
is not fully understood.
2.4 Discussion
2.4.1 Sorption of pharmaceuticals
In both batches and columns, stronger sorption was indicated for PRO, MET
and CAF while CBZ and IBP showed no significant sorption. NAP was highly sorbed
in batches under sulfate reducing and methanogenic conditions but not in columns.
Values of pharmaceutical sorption coefficient Kd were calculated for batch systems
under all anaerobic conditions. In columns the breakthrough behaviour of PRO,
MET and CAF allowed the calculation of the retardation factor and Kd. All these Kd
values were compared to literature data on sorption behaviour of target
pharmaceuticals in soils and sediments (Figure 2.4). Kd values found in this study
are in accordance with reported literature values, except for MET in columns. Like
coefficients from literature, we also demonstrate that PRO, CAF and MET sorbed
more readily than NAP, CBZ, and IBP (median, Figure 2.4).
43
1200
800 Batch-Nitrate reducing
300 Batch-Sulfate reducing
Sorption coefficient Kd (L/kg)
Batch-Methanogenic
Column-Aerobic
250
Column-Nitrate reducing
Column-Sulfate reducing
200 Column-Methanogenic
150
100
50
0
PRO MET CAF NAP IBP CBZ
Figure 2.4 Comparison of sorption coefficients Kd between this study and literature [23,
53, 68, 70, 159, 166, 170, 219, 231, 296, 308, 310, 320, 324]. For literature values of
PRO, MET, CAF, NAP, IBP and CBZ, n= 12, 7, 6, 15, 19, and 8, respectively. The box plot
shows the values found in literature in maximum, third quartile, median, first quartile, and
minimum. The squares, triangles, crosses and circles represent the values for the different
redox conditions in batch (no filling) and column (filled).
Sorption of pharmaceuticals was reported to depend on their physico-

chemical properties, such as hydrophobicity and molecular charge [35]. In this
study, we found that pharmaceutical sorption by the sediment is more related to
the molecular charge of pharmaceuticals than their hydrophobicity. To characterize
the hydrophobicity, the apparent partitioning coefficient Log Dow (Table S2.1) was
applied to modify the octanol-water partition coefficients Log Kow with pH [149].
However, pharmaceutical sorption did not correlate with Log Dow (Figure S2.4).
Based on pKa values (Table S2.1) and the pH range in our study (pH = 6.8-7.5),
CBZ has no charge, IBP and NAP are negatively charged, while the other three
pharmaceuticals are positively charged. Most sediment matrix components are
negatively charged [166, 310]. This likely explains why the cationic
pharmaceuticals (CAF, PRO, MET) showed a stronger tendency to sorb compared
to anionic (IBP) and neutral species (CBZ). The high sorption of anionic NAP in
batches might be caused by the OM present in the sediment. Similar results were
44
Chapter 2
found by Martínez-Hernández, et al. [166]. These authors observed that sorption

onto the inorganic surface of sediment was the predominant sorption mechanism
for all positively and negatively charged pharmaceuticals examined with the
exception of NAP, which was partitioned to OM instead. The higher OM content in
batches in this study might explain its higher sorption compared to the columns.
The variety among the reported Kd values per pharmaceutical in literature
(Figure 2.4) are hypothesized to be related to the different experimental
conditions, e.g. different soils and sediments [2]. By the unique experimental
design of this study, we showed a strong influence of the redox conditions on the
experimentally determined Kd values (Figure 2.4). Anaerobic column experiments
were inoculated with the same inoculum. Similarly, all anaerobic batches were
inoculated with the same sediment. However, different pharmaceutical sorption
coefficients were found under different anaerobic redox conditions in both batches
II
and columns (Figure 2.4). Sorption of NAP in batches was found to be lowest under
nitrate reducing conditions and highest under sulfate reducing conditions. A similar
phenomenon was found for PRO sorption in columns and MET sorption in both
systems that followed the order nitrate reducing < methanogenic < sulfate
reducing conditions. In both systems, sorption of CAF followed the order nitrate
reducing < sulfate reducing < methanogenic conditions.
The sorption differences under various anaerobic redox conditions could not
be explained by the characteristics of the media we applied, such as ionic strength.
Among all pharmaceuticals investigated in batches, only CAF sorption showed to
be inversely correlated to ionic strength with 149.5, 108.1 and 63.8 mmol/L under
nitrate reducing, sulfate reducing and methanogenic conditions, respectively.
However, the correlation identified for CAF in batches was not observed in
columns, where ionic strength are similar under three anaerobic conditions (50.4,
69.3, and 42.6 mmol/L under nitrate reducing, sulfate reducing and methanogenic
conditions, respectively). Overall, among all factors influencing sorption behaviour,
redox conditions and molecular charge are found to dictate sorption behaviour in
this study.
Sorption coefficients Kd of MET and CAF under different redox conditions
correlated between batches and columns (Figure 2.5), which indicates a
consistency among the two experimental systems. However, the Kd variations
between pharmaceuticals seem to be influenced by the experimental system, as
45
the sorption coefficients of individual pharmaceuticals were not distributed along

the 1:1 line (Figure 2.5). Batch experiments are commonly conducted to predict
the sorption behaviour of target compounds in continuous systems, however our
results demonstrate a high system dependency of the determined Kd values, which
hampers the direct translation of Kd from batch to continuous systems. Thus, our
data show that a variability in experimentally determined Kd values per
pharmaceutical can be introduced by differences in redox conditions and in
experimental system. As the effect of redox conditions and experimental system
on sorption behaviour of pharmaceuticals is rarely described before, further studies
need to be conducted to understand the underlying mechanisms.
120
Kd in columns (L/kg)
90
1:1 line
Propranolol
60
Metoprolol
Caffeine
30
0
0 30 60 90 120
Kd in batches (L/kg)
Figure 2.5 Linear relationship of sorption coefficients between batch and column
experiments under different anaerobic redox conditions.
Sorption coefficients Kd in our column study show that breakthrough is

expected in sediment based applications. For the most sorptive pharmaceutical,
PRO in this study, saturation of sediment sorption sites occurred after
approximately 300 pore volumes under sulfate reducing conditions. Ramil et al.
[213] demonstrated that sorption isotherms of PRO and MET to river and stream
sediments are linear between 2-200 μg/L. For linear sorption behaviour retardation
factors are independent on the pharmaceutical concentration. Thus, reflecting on
sediment based applications treating pharmaceuticals in WWTP effluents that are
generally in the same concentration range, the sorption capacity of sorptive
46
Chapter 2
pharmaceuticals like PRO will reach saturation after approximately 300 pore
volumes.
2.4.2 Biodegradation of pharmaceuticals

Aerobic batch and column experiments both demonstrated an effective CAF
and NAP biodegradation. Their significant biodegradation is consistent with their
biodegradation in soil columns reported by Kim et al. [130]. Additionally, in
batches IBP and MET were biodegraded, whereas in columns no significant IBP
removal was observed and MET was removed by sorption. The poor removal of
IBP is contrary to what other authors reported [144], most probably due to
insufficient oxygen throughout the entire aerobic column. The applied hydraulic
retention time of 8 hours is in a similar range of 3-18 hours for which IBP removal
is reported [81], and seems therefore long enough. Zwiener and Frimmel [330]
II
concluded that IBP is primarily degraded under aerobic conditions and poorly in
the absence of oxygen in biofilm reactors. Throughout our experiment, no
dissolved oxygen (DO) was found in the aerobic column effluent as it was
completely consumed in the column. Hence, it is assumed that competition for DO
resulted in micro-aerophilic conditions with a too low DO concentration to support
aerobic IBP biodegradation. MET was biodegraded and sorbed in batches whereas
sorption was the only removal mechanisms in columns. Similar to IBP removal in
column, a low DO concentration resulting in micro-aerophilic conditions might be
a limiting factor in MET biodegradation in column which was also observed by
Radke and Maier [211].
Anaerobic batch and column experiments both demonstrated an effective
CAF biodegradation. To our knowledge, there is a lack of studies on CAF
biodegradation under anaerobic conditions in sediment. Among the anaerobic
conditions, NAP biodegradation was observed in the sulfate reducing and
methanogenic columns. In sulfate reducing and methanogenic batches NAP
biodegradation could not be confirmed, as NAP removal was mainly ascribed to
sorption. In accordance with the literature, PRO and CBZ were not effectively
biodegraded under any redox condition in both batch and column experiments [83,
207, 211].
In our study using well-defined redox conditions, batch and column
experiments independently showed that biodegradation of pharmaceuticals was
47
influenced by the applied redox conditions (Table 2.2). Most optimal

pharmaceutical biodegradation was observed at the outer ranges of the redox
spectrum, i.e. either aerobic or deeply anaerobic (sulfate reducing and
methanogenic conditions), with fastest removal by biodegradation under aerobic
conditions. In batch experiments, NAP, MET and IBP were readily biodegradable
under aerobic conditions while they were recalcitrant under all anaerobic
conditions. A similar conclusion was identified for IBP biodegradation by Conkle et
al. [53]. Half-lives of IBP were 7-19 days or >7 months under aerobic or anaerobic
conditions, respectively.
Intermediate redox conditions like the micro-aerophilic and nitrate reducing
conditions, which are often found in groundwater systems [26, 72, 169], appear
not suitable for maximized biodegradation of a wide range of pharmaceuticals.
According to previous research on anaerobic biodegradation of fuel hydrocarbons
which also contain aromatic rings like pharmaceuticals, nitrate and sulfate
appeared to be the most preferred electron acceptors for degrading toluene,
ethylbenzene and xylenes [254]. Nevertheless, in our study NAP was poorly
biodegraded under nitrate reducing conditions in the column, while it was
effectively biodegraded under the other two anaerobic redox conditions.
Table 2.2 Biodegradation of pharmaceuticals under the tested redox conditions in batch
and column. Biodegradation observed (+), no biodegradation observed (-).
Aerobic Nitrate reducing Sulfate reducing Methanogenic
Pharmaceutical
Batch Column Batch Column Batch Column Batch Column
PRO - - - - - - - -
MET + - - - - - - -
CAF + + + + + + - +
NAP + + - - - + - +
IBP + - - - - - - -
CBZ - - - - - - - -
Biodegradation of pharmaceuticals is hypothesized to be limited in the

natural environment as oxygen is typically absent in soils and sediments [195].
Thus, maximizing biodegradation of the complete suite of pharmaceuticals present
in surface and wastewater should include aerobic conditions possibly combined
with deeply anaerobic redox conditions (i.e. to save WWTP aeration costs), and is
inadequate under micro-aerophilic and nitrate reducing conditions. In engineered
48
Chapter 2
sediment based systems such as CWs, we therefore recommend to include aerobic

conditions and deeply anaerobic conditions.
Pre-exposure to pharmaceuticals can improve the biodegradation capacity
of sediments towards pharmaceuticals. Batch experiments in this work showed a
better removal for IBP, NAP, CAF and MET, compared to half-life times reported in
literature [53, 161, 320]. The improved removal can be explained by the exposure
of the sediments to pharmaceuticals prior to the laboratory scale experiments.
Sediments used in this study were collected from CWs receiving secondary
effluents of WWTPs and were in operation for more than 15 years. We detected
the target pharmaceuticals in the CW influents in the range of 59-6492 ng/L (Table
S2.3) demonstrating that the sediments have been exposed to pharmaceuticals.
Adaptation of microorganisms to compounds can significantly improve
biodegradation rates [245]. Especially for microbes capable of degrading
II
micropollutants, pre-exposure to the compounds can enhance their biodegradation
ability [42, 172]. Enrichment experiments by re-spiking pharmaceuticals in batch
further improved the biodegradation rates of IBP and NAP. Thus, the significance
of microbial growth by pre-exposure to pharmaceutical resulting in enhanced
biodegradation was further confirmed.
Pharmaceuticals demonstrating low to no removal by sorption and
biodegradation under all redox conditions even after re-exposure, like CBZ, require
additional treatment. In natural environments photo-oxidation has been reported
to target pharmaceuticals in surface waters [140]. However, this is restricted to a
limited number of pharmaceuticals [143] and photo-oxidation is typically not
relevant in soil-sediment systems. Hence, in addition to sorption and
biodegradation, other technologies such as advanced oxidation processes are
needed in WWTPs to remove recalcitrant pharmaceuticals from treated effluents
before they enter the natural environment.
Conclusions
In conclusion, our results show that pharmaceutical removal is influenced
by the applied redox conditions via both sorption and biodegradation. Therefore
this study provides insights into the importance of redox conditions in developing
and designing biological techniques for pharmaceutical treatment. Sorption
behaviour among different pharmaceuticals is influenced by the applied redox
49
conditions and the molecular charge of pharmaceuticals. Hydrophobicity of

pharmaceuticals and ionic strength did not have an effect on pharmaceutical
sorption in this study. Highest sorption coefficient Kd values are found under
sulfate reducing and methanogenic conditions. Additionally, our study indicate a
high variability in experimentally determined Kd values per pharmaceutical in
different experimental system, i.e. batch and column systems. Most optimal
pharmaceutical biodegradation is observed at the outer ranges of the redox
spectrum, i.e. either aerobic or deeply anaerobic (sulfate reducing and
methanogenic conditions), instead of the intermediate redox conditions like micro-
aerophilic and nitrate reducing conditions. Fastest pharmaceutical biodegradation
is observed under aerobic conditions. From practical perspective, saturation of the
sediment sorption capacity in sediment based applications treating
pharmaceuticals is expected within approximately 300 pore volumes for the most
sorptive compounds in this study.
To increase removal efficiencies for a number pharmaceuticals, several strategies
are recommended: adapt and enrich biomass by pre-exposure to pharmaceuticals
in bioactive soil, sediment or other porous media filters; combine aerobic
conditions with deeply anaerobic redox conditions in biotechnological systems; add
advanced oxidation processes in WWTPs for removal of recalcitrant
pharmaceuticals.
Acknowledgement
We thank Yang Jiang and Linda Verweij for their support during the
experiments. Support provided by China Scholarship Council for the research of
Yujie He at Wageningen University is kindly acknowledged.
50
Chapter 2
Supplementary Information
Table S2.1 Physico-chemical properties of target pharmaceutically active compounds
Pharmaceutical Chemical structure pKaa Log Kowb Log Kocc Log Dowd
Propranolol 9.42 3.48 3.45 1.06
Metoprolol 9.67 1.88 2.10 -0.79
Caffeine 10.4 -0.07 1 -3.47
II
Naproxen 4.15 3.18 2.54 0.33
Ibuprofen 4.91 3.97 2.60 1.88
Carbamazepine 13.9 2.45 3.588 -4.45
a - pKa: dissociation constant; b - Log Kow: octanol-water partition coefficient; c - Log Doc:
soil organic carbon-water partitioning coefficient; d - Log Dow is the pH dependent Log Kow,
calculated at pH=7. Data from [71, 278].
51
Table S2.2 Medium composition for all columns and aerobic batches, adjusted from [162].
Concentration in
Reactor Compounds
medium (mg/L)
NH4Cl 1020
Macro nutrients Aerobic batches and
CaCl2.2H2O 48
all columns
MgSO4.7H2O 54
Aerobic batches and Na2HPO4 433

pH buffer
all columns NaH2PO4 234
FeCl2.4H2O 1.2
CoCl2.6H2O 1.2
MnCl2.4H2O 0.3
CuCl2.2H2O 0.018
ZnCl2 0.03
Aerobic batches and HBO3 0.03

Trace elements
all columns (NH4)6Mo7O24.4H2O 0.05
Na2SeO3.5H2O 0.06
NiCl2.6H2O 0.03
EDTA (tripex 2) 0.6
HCl 36% 0.0006
Resazurin 0.3
Nitrate reducing
NaNO3 850
columns
Redox specific NaSO4 1190
Sulfate reducing
compounds
columns Na2S.9H2O 120
Methanogenic columns Na2S.9H2O 120

Note: aerobic column medium was 60-80% oxygen saturated, other column media were
flushed with N2 and did not contain oxygen.
Table S2.3 Concentration of pharmaceuticals (ng/L) in the influent of the constructed

wetland where the sediment inoculum was collected (average ± deviation, n=2).
Pharmaceutical PRO MET CAF NAP IBP CBZ
Concentration 58±10 1426±35 118±22 180±17 6492±261 204±7
52
Chapter 2
A 1,8
1,6
O2 (mmol)
1,4
1,2
0 2 4 6 8 10 12
Time (day)
B 0,5 2000
methanogenic nitrate sulfate
NO3-/SO42- (mg/L)
0,4
1500
CH4 (mmol)
0,3
1000
0,2
500
0,1
0,0 0 II
0 2 4 6 8 10 12 14
Time (week)
C Influent NO3 in nitrate reducing column

2000 Effluent NO3 in nitrate reducing column
NO3-/SO42- (mg/L)
1750 Influent SO4 in sulfate reducing column

1500 Effluent SO4 in sulfate reducing column
1250
1000
750
500
250
0
0 10 20 30 40 50 60 70 80 90 100 110
Time (day)
12
D
9
CH4 (mg/L)
0
0 10 20 30 40 50 60 70 80 90 100 110
Time (day)
Figure S2.1 Concentrations of electron acceptors and reaction products. A) O2

concentration in aerobic batch experiment; B) CH4, NO3-, and SO42- concentrations in
anaerobic batch experiment; C) influent and effluent NO3- and SO42- concentrations in
nitrate and sulfate columns; D) effluent CH4 concentration in the methanogenic column.
53
100
80 MET CAF PRO

Abiotic removal (%)
CBZ NAP IBP

60
40
20
0
0 2 4 6 8 10 12
-20
Time (day)
Figure S2.2 Abiotic removal of pharmaceuticals after re-spiking under aerobic conditions.
MET CAF PRO CBZ NAP IBP
120
re-spike
100
80
Remioval (%)
60
40
20
-20
0 7 21 4246 77 84 89 95 105
Time (day)
Figure S2.3 Removal of pharmaceuticals under aerobic conditions. Pharmaceuticals were
re-spiked three times at day 46, 84, and 95.
54
Chapter 2
1.0
NAP
B-S
B-M
CAF
CBZ
IBP
log Dow
B-N
MET
PRO C-S
C-M
C-N II
C-A
-1.0
-1.0 1.0
Figure S2.4 Principle component analysis of the relationship between Log Dow of
pharmaceuticals and their Kd under the applied redox conditions. B-N, B-S, and B-M
represent nitrate reducing, sulfate reducing, and methanogenic conditions in batches; C-
A, C-N, C-S, and C-M represent aerobic, nitrate reducing, sulfate reducing, and
methanogenic conditions in columns. The eigenvalues of the first and second canonical axis
are 0.56 and 0.39. The intersection angles between arrows represent their correlations, in
which a more acute intersection angle means stronger correlations. The results show that
Lod Dow of pharmaceuticals is not correlated with the Kd value under any applied redox
conditions.
55
Chapter 3
Mild photocatalytic pre-treatment:
improved biological degradation of degradable
and otherwise recalcitrant pharmaceuticals
A modified version of this chapter has been submitted as
Arnoud de Wilt, Maricor Arlos, Mark Servos, Huub Rijnaarts,

Alette Langenhoff and Wayne Parker. Mild photocatalytic pre-treatment: improved
biological degradation of degradable and otherwise recalcitrant pharmaceuticals.
Combined mild photocatalysis and biodegradation
Abstract
Pharmaceuticals in the environment are of great concern as they jeopardise
the aquatic environment and pose potential risks to human health. This stresses
the need for technologies to remove pharmaceuticals before they enter the
environment. Single processes for pharmaceutical removal are often found
ineffective and resource intensive. In this study the combination of photocatalysis
and biodegradation was investigated for the removal of nine selected
pharmaceuticals. We designed a combined process consisting of a resource
efficient mild photocatalysis and a subsequent biological treatment which was
compared to the single processes of intensive photocatalysis and biological
treatment. During the UV-TiO2 based mild and intensive photocatalysis
atorvastatin, atenolol and fluoxetine were effectively removed. The biological
treatment after mild photocatalytic pre-treatment removed diclofenac effectively
while it persisted during the single biological treatment. Moreover, the
biodegradation of atorvastatin, caffeine, gemfibrozil and ibuprofen was enhanced
after mild photocatalytic pre-treatment compared to single biological treatment.
The enhanced biodegradation of those pharmaceuticals was most probably
triggered by the biodegradation of photocatalytic products. Biodegradation was the
predominant removal mechanism and sorption was of minor importance during
biological treatment as shown by abiotic controls. These findings show that mild
photocatalysis followed by biological treatment is an effective and resource
efficient combination for pharmaceutical removal.
Keywords
Photocatalysis; Biodegradation; Pharmaceuticals; Pre-treatment; Combined
treatment
58
Chapter 3
3.1 Introduction
The occurrence of pharmaceuticals in the aquatic environment has become
a worldwide environmental concern [233]. After administration, pharmaceuticals
largely end up in excreta and are transported via sewage to municipal wastewater
treatment plants (WWTPs). WWTPs are commonly designed for cost-effective
removal of bulk organic matter, nitrogen and phosphorus and typically make use
of biological treatment processes. There are limitations regarding the removal of
pharmaceuticals in biological treatment processes currently employed at WWTPs
as pharmaceuticals are often incompletely removed [124, 287]. Advanced
oxidation processes (AOPs) making use of photocatalysis, ozone, or hydrogen
peroxide (the latter often in combination with Fenton’s Reagent), can effectively
eliminate pharmaceuticals [164]. The main advantage of AOPs is the complete
oxidation of organic contaminants in a wide variety of applications [132]. However,
AOPs have disadvantages over biological processes. AOPs require either
continuous energy and/or chemical inputs that are significantly higher than those
required for biological processes. Toxic by-products can be formed during AOP III
treatment which can be more toxic than the parent compounds [118].
Furthermore, the various AOP reaction mechanisms are mostly non-specific,
targeting not only the compounds of concern but also other compounds present in
the matrix thereby reducing the elimination efficiency of AOPs for target
compounds such as pharmaceuticals [187].
Using the strengths of AOP and biodegradation in a combined technology
could possibly result in better overall pharmaceutical removal. Scott and Ollis
[235] concluded in their review of technologies for the removal of organic
contaminants in water that two-step treatment technologies combining chemical
and biological processes can have advantages over single processes. The benefits
of employing a combination of processes can be obtained for wastewaters
containing: 1) recalcitrant compounds; 2) biodegradable wastes with small
amounts of recalcitrant compounds; 3) inhibitory compounds; and 4) intermediate
dead-end products [235].
In the field of water and soil contamination, this principle has been studied
and applied to demonstrate the advantages of combined processes for the removal
of various contaminants [80, 115, 313, 314]. A sequential combination of
photocatalytic and biological treatment processes doubled 2,4,6-trinitrotoluene
59
(TNT) mineralisation as compared to biological treatment alone, whereas no TNT

mineralisation was observed for the single photocatalytic process [107].
Furthermore, the combined treatment resulted in more soluble and polar
transformation products when compared to the single processes. For quinoline
removal, the maximum specific growth rate increased by 15% and the inhibition
constant doubled when changing from biodegradation only to sequential coupled
photocatalysis and biodegradation [311]. Photocatalytic pre-treatment that
reduced COD by 8-10%, enhanced the subsequent biodegradation of the dye
intermediate H-acid [186]. Chun and Yizhong [46] demonstrated the advantage of
combining photocatalysis with biodegradation for wastewater containing non-
biodegradable azo dyes. The biodegradability of the wastewater indicated by the
BOD5/COD ratio was enhanced from nil to 0.75, after a 20- to 30-minute
photocatalytic oxidation. In soil remediation, combining chemical oxidation using
Fenton’s reagent with biodegradation, removed diesel more effectively than
applying single processes [258].
Specifically for micropollutant removal the combination of chemical and
biological removal has received less attention. Positive effects on the
biodegradation of the widely applied antibiotic tetracycline were found after pre-
treatment by ozonation [93] and photocatalysis [307]. In the study of Gómez-
Pacheco, et al. [93] tetracycline in the influent inactivated the microbial population
of biological waste water treatment, whereas AOP pre-oxidation resulted in 100%
mineralisable TOC and stable biological treatment. Biodegradation and
mineralization of the broad-spectrum antibiotic sulfadiazine could be accelerated
by 35 and 71%, respectively, when intimately coupled to photocatalysis [201].
Also for the pesticide 2,4,6-trichlorophenol a faster removal was found for
sequentially and intimately coupled photocatalysis and biodegradation compared
to the single processes [297]. Complete degradation and detoxification of the
herbicide atrazine was obtained by photocatalytic pre-treatment followed by
biodegradation. The single photocatalytic treatment resulted in complete atrazine
removal but inefficiently mineralized and detoxified the transformation products
[44].
The main aim of the current study was to gain insight into the influence of
AOP pre-treatment on the subsequent biodegradation of pharmaceutical
compounds, as there are only few reports describing this in literature. Since AOP
60
Chapter 3
processes are generally energy and/or chemically intensive, we developed a mild

photocatalysis method requiring low energy input. The removal of nine commonly
detected pharmaceuticals in wastewater was studied by combining this mild
photocatalysis method and biodegradation in batch experiments. The
pharmaceuticals were selected as representative compounds for various classes of
pharmaceuticals and were applied in a mixture in the treated water. The
combination of mild photocatalysis followed by biodegradation was tested and the
pharmaceutical removal was compared to removal in the single processes of
intensive photocatalysis and biodegradation.

3.2.1 Chemicals
A pharmaceutical stock solution that contained 9 compounds (Table 3.1):
atenolol, atorvastatin, caffeine, carbamazepine, diclofenac, fluoxetine, gemfibrozil,
ibuprofen and naproxen was employed. The stock solution (2 g/L) was prepared
in HPLC grade methanol and stored at -20°C. Powdered TiO2, commercially III
available as P25 (99.7% purity, Sigma-Aldrich, Canada) was used for the
photocatalytic experiments. Suppliers for all other reagents and chemicals used in
this study are described in detail elsewhere [14].
61
Table 3.1 Chemical structure and therapeutic function of the studied pharmaceuticals
Atenolol Atorvastatin Caffeine
Beta-blocker Lipid regulator Stimulant
Carbamazepine Diclofenac Fluoxetine
Anti-epileptic Anti-inflammatory Anti-depressant
Gemfibrozil Ibuprofen Naproxen
Lipid Regulator Anti-inflammatory Anti-inflammatory
3.2.2 Experimental set-up

Figure 3.1 displays the three experimental protocols that were studied: 1)
intensive photocatalytic treatment (IP); 2) single process biological treatment (B);
and 3) mild photocatalytic pre-treatment followed by biological treatment (MP+B).
62
Chapter 3
Figure 3.1 Experimental protocols, 1) intensive photocatalytic treatment (IP), 2) single

process biological treatment (B) and 3) mild photocatalytic pre-treatment followed by
biological treatment (MP+B).
3.2.2.1 Photocatalytic experiments

Batch photocatalytic experiments were performed with the set-up described III
by Arlos, et al. [15]. Beakers (650 mL) wrapped in aluminium foil containing 600
mL of ultrapure water were amended with TiO2 suspension to a final concentration
of 0.5 g/L. The batches were spiked with 150 µL of the pharmaceutical stock
solution to obtain concentrations of 500 µg/L (6 mM methanol). Prior to light
exposure the batches were equilibrated for 30 minutes in the dark. For intensive
photocatalytic experiments 2 mL samples were taken directly before the lamps
were activated and after 15, 30, 45, 60 and 120 minutes of illumination. In the
separately performed mild photocatalytic experiments, samples were taken
directly before illumination and after 15 and 30 minutes of illumination. The
contents of the beakers after 30 minutes of light exposure in the mild
photocatalytic experiments were centrifuged (3500 rpm, 30 minutes) and filtered
(0.45 µm, Supor-450 membrane filter, Pall Life Sciences, Canada). Thereafter,
samples for pharmaceutical analysis were taken and this solution was further used
in biological experiments. Dark control experiments without illumination were
performed for 120 minutes to assess non-photocatalytic pharmaceutical removal.
63
3.2.2.2 Biological experiments

Aerobic batch experiments were performed in 200 mL amber flasks, closed
with cotton-wool stoppers. Three types of batches were prepared: 1) B protocol;
2) MP+B protocol; and 3) abiotic controls. The MP+B batches were filled with the
solution obtained after the mild photocatalytic experiments. The B and abiotic
control batches were filled with demineralised water and spiked with 50 µL of
pharmaceutical stock solution to obtain initial concentrations of 500 µg/L. All
batches were amended with macro-nutrients, trace elements and pH buffer as
described in Chapter 2. Biomass obtained from four locations around Waterloo,
Canada (secondary sludge of Elmira WWTP, river sediment of Heidelberg creek,
sand of polishing filter of Galt WWTP and Rotating Biological Contactor sludge of
WWTP Foxboro) was used to inoculate batches until final concentrations of 49.4 g
TSS/L and 5.5 g VSS/L. TSS and VSS were determined according to standard
methods [8]. Batch experiments were performed in triplicate and incubated at
room temperature on a shaker plate. Abiotic controls were initially amended with
0.5 mM NaN3 to supress biological activity and closed with a rubber stopper.
However, oxygen consumption in the abiotic batches could not be fully suppressed,
showing that biologic activity was insufficiently inhibited. Additional NaN3 spikes of
0.5 mM on days 8, 12 and 13, 0.75 mM on day 14 and 1 mM on days 15 and 17
were added and did not completely supress oxygen consumption. Ternes et al.
[266] reported that 30 minutes after spiking the sorption equilibrium for
pharmaceuticals was reached in batch experiments with 2.4 g VSS/L of secondary
sludge. Similarly, Martínez-Hernández et al. [167] achieved sorption equilibrium
of pharmaceuticals after 12 hours in batch experiments containing 250 g soil/L.
Hence, due to this fast sorption equilibrium only the abiotic results of day 1 were
used to assess sorption behaviour in this study. Samples (5 mL) of the biotic
batches were taken on day 0,1,3,7,14 and 21, directly frozen and stored at -10°C
prior to pharmaceutical analysis. Replicate batches were tested for outliers
according to ANCOVA statistical model (significance <0.05) in which we considered
time as a covariate. The testing criterion was the difference in pharmaceutical
removal (C/C0) between replicates. The same ANCOVA model was used to test for
differences in removal (C/C0) over time in the biological experiments of the B and
MP+B protocols.
64
Chapter 3
3.2.3 Pharmaceutical analysis

Samples from the AOP experiments were directly centrifuged for 45 minutes
at 3500 rpm to separate the liquid phase and TiO2. After thawing the samples from
the biological experiments were centrifuged for 10 minutes at 3500 rpm.
Thereafter, the supernatants were extracted by solid phase extraction (SPE) and
analysed by LC-MS/MS according to the procedure described by Arlos, et al. [15]
but only using 2 mL sample instead of 4 mL was used for SPE in this study.
3.3 Results and Discussion

3.3.1 Photocatalysis
3.3.1.1 Intensive photocatalysis (IP protocol)
Experimental results of the illuminated batches and controls were compared
to assess the contribution of photocatalysis to pharmaceutical removal. The results
of the control experiments revealed that non-photocatalytic removal processes
contributed little (<25%) to the pharmaceutical removal in our AOP experiments,
as has been reported in the literature [15]. By contrast significant removals III
(>80%) of atorvastatin, atenolol and fluoxetine were observed in intensive
photocatalytic (IP) experiments after 2 hours (Figure 3.2a). The other tested
compounds were less susceptible to photocatalysis and were removed by less than
40%. Photocatalytic degradation of organic compounds has been described by
Langmuir-Hinshelwood kinetics [229]. A simplified model can be used for low
�
compound concentrations (<mg/L) and denoted as ln( ) = −�� in which C/C0 (µg/L
�0
/ µg/L) is the actual pharmaceutical concentration divided by the initial

pharmaceutical concentration, k (min-1) is the apparent first-order reaction rate
constant, and t (min) is time. The pharmaceutical concentrations in this study were
in the µg/L range, therefore the dilute system condition was believed to apply and
reaction rate constants were calculated according to the abovementioned
equation. For atorvastatin, atenolol and fluoxetine the calculated rate constants
(R2 >0.99%) were 41.5, 29.0 and 15.4 x 10-3 min-1, respectively. These results
agreed with the findings of the experimental work and the literature reviewed by
Arlos, et al. [15] on photocatalytic degradation of pharmaceuticals. Their reported
rate constants for atorvastatin, atenolol and fluoxetine ranged between 13.4-68.8,
7.4-14.5 and 8.4-40.8 x 10-3 min-1, respectively. Thus, atenolol was removed at a
65
higher rate in our study. The rate constants of the other pharmaceuticals did not
exceed 4.8 x 10-3 min-1 (R2 <0.88). Similarly, Arlos, et al. [15] found low rate
constants (<8.7 x 10-3 min-1) to no degradation for naproxen, ibuprofen and
carbamazepine.
Atenolol Atorvastatin Caffeine Carbamazepine Diclofenac

Fluoxetine Gemfibrozil Ibuprofen Naproxen
1.50
a) b)
1.25 Atenolol
Atorvastatin
1.00 Caffeine
Removal C/C0
0.75 Diclofenac
Fluoxetine
0.50
Gemfibrozil
Ibuprofen
0.25
Naproxen
0.00
0 15 30 45 60 120 0 15 30
Time (minutes) Time (minutes)

Figure 3.2 Pharmaceutical removal (C/C0) during photocatalysis of a) IP protocol and b)
MP+B protocol. Error bars represent standard deviations between triplicates.
3.3.1.2 Mild photocatalysis (MP+B protocol)

For the MP+B photocatalytic experiments the illumination time was chosen
based on the outcomes of the IP experiments. The illumination time was selected
to provide (1) substantial removal of photocatalytic degradable compounds and
(2) sufficient remaining compound concentrations to study biodegradation.
Therefore 30 minutes illumination was selected for the resource-efficient mild
photocatalytic experiments as substantial removal (>50%) was achieved at 75%
less energy input than the IP tests. Further, the remaining pharmaceutical
concentrations were sufficiently high after 30 minutes of illumination to allow for
assessment of pharmaceutical removal in the subsequent biological experiments.
During the mild photocatalysis substantial removals of atorvastatin (75%),
atenolol (50%) and fluoxetine (35%) were observed, while the other
66
Chapter 3
pharmaceuticals showed low removal (<5%) (Figure 3.2b). The photocatalysis

results in the MP+B test were in good accordance with the findings of the IP
protocol, as the same compounds were removed (atorvastatin, atenolol and
fluoxetine) at similar removal rates (<20% difference between the two tests). This
indicates the robustness of the photocatalysis process for pharmaceutical removal.
3.3.2 Biological treatment

3.3.2.1 Single process biological treatment (B protocol)
The B protocol was employed to assess the biodegradability of the target
pharmaceuticals (Figure 3.3). The ANCOVA testing revealed a significant outlier in
atin
the B protocol results when the pharmaceutical removals (C/C0) in the individual
replicates were compared and therefore the outlier bottle results were not included
ac in the trend analysis. From Figure 3.3, it can be seen that significant removal
e
(>80%) of seven pharmaceuticals was observed in the first 21 days of the B
zil
protocol testing. Diclofenac and carbamazepine were recalcitrant towards
n
biodegradation as after 21 days they were reduced by less than 50% and 40%,
n III
respectively. These results were in agreement with previous reports of their fate
during biological treatment [7, 287]. In addition, to parse out the removal
mechanisms of individual pharmaceuticals abiotic (Table 3.2) and biotic (Figure
3.3) batches were compared in more detail.
The concentrations of caffeine, ibuprofen, naproxen and atorvastatin were
reduced significantly (>99%) within 7, 7, 14 and 21 days, respectively. Partial
gemfibrozil removal (80%) was found after 21 days. These findings agree with
those of Luo, et al. [164] who reviewed the fate of pharmaceuticals in wastewater
treatment and classified caffeine, ibuprofen, gemfibrozil and naproxen as “highly
removed (>70%)”. The findings for atorvastatin correspond well with those of
Golovko et al. [92] where an average of 93% atorvastatin removal was observed
on a yearly basis in a Czech WWTP. It was concluded that biodegradation was the
prevalent removal mechanism for caffeine, ibuprofen, gemfibrozil, atorvastatin
and naproxen in our experiments as during the first day their concentrations in the
abiotic batches decreased by only 18-34% (Table 3.2).
67
500 Atenolol Atorvastatin Caffeine

400
B protocol
300
MP+B protocol
200
100
0
0 7 14 21 0 7 14 21 0 7 14 21
500 Carbamazepine Diclofenac Fluoxetine
Concentration (g/l)
400
300
200
100
0
0 7 14 21 0 7 14 21 0 7 14 21
500 Gemfibrozil Ibuprofen Naproxen
400
300
200
100
0
0 7 14 21 0 7 14 21 0 7 14 21
Time (days)
Figure 3.3 Pharmaceutical concentrations in biological treatment experiments, B protocol
(red spheres) and MP+B protocol (blue triangles).
Fluoxetine concentrations decreased rapidly in both the biotic and abiotic

batches (Table 3.2, Figure 3.3) indicating that sorption was the main removal
process. In samples taken on day 0, the fluoxetine concentrations were found to
be less than the spiking concentrations (>25%) in both the biotic and abiotic
batches. After 1 day, fluoxetine removal in the biotic and abiotic batches was 75%
and 84%, respectively and by day 3 over 99% removal was observed in both
batches. These findings correspond well with lab-scale experiments of Pomiès et
al. [206] who concluded that sorption was the only removal mechanism for
fluoxetine.
68
Chapter 3
Table 3.2 Pharmaceutical removal (C/C0) after 1 day in the abiotic experiments.
Carbamazepine
Atorvastatin
Gemfibrozil
Fluoxetine
Diclofenac
Ibuprofen
Naproxen
Caffeine
Atenolol
Pharmaceutical
Abiotic removal 53% 31% 18% 9% 25% 84% 24% 23% 34%
The atenolol concentrations at day 1 were reduced by 53% in the abiotic

batches as compared to 44% in the biotic batches (Table 3.2, Figure 3.3),
suggesting sorption was initially the major removal mechanism. Thereafter
biodegradation became the predominant removal mechanism as higher removals
were observed in the biotic batches. In the literature, biodegradation has been
reported to be the predominant removal mechanism of atenolol in wastewater
treatment, whereas sorption to activated sludge has been found to be low [176,
206]. The low sorption coefficients reported in the literature were contrary to the
initial atenolol removal observed in the abiotic batches of this study. The differing III
sorption behaviour might be explained by the inoculum mixture used in this study
as the creek sediment likely contained a significant clay fraction (not measured).
Kodešová et al. [135] found a positive correlation between clay content and
atenolol sorption which was driven by cationic exchange between negatively
charged clay particles and positively charged atenolol at neutral pH.
3.3.2.2 Biological treatment after mild photocatalysis

(MP+B protocol)
High pharmaceutical removals (>99%) were observed after 21 days in the
biological experiments of the MP+B protocol (Figure 3.3). Only carbamazepine was
incompletely removed (65%) by the end of the experiments. The initial
concentrations of atorvastatin, and atenolol were lower compared to the B protocol
due to their photocatalytic degradation during pre-treatment. The low initial
fluoxetine concentration was attributed to removal during photocatalysis and rapid
sorption to the inoculum as observed in the B protocol. Moreover, approximately
50% of the fluoxetine was lost during the centrifugation and filtration steps that
were carried out between the photocatalytic and biodegradation experiments. The
predominant removal mechanisms were considered to be similar in these tests as
69
in the B protocol; sorption for fluoxetine, sorption and biodegradation for atenolol
and biodegradation for the other pharmaceuticals.
Significantly faster removal was found for atorvastatin, caffeine, diclofenac,
gemfibrozil and ibuprofen in the biological experiments of the MP+B protocol as
compared to the B protocol. Results of the ANCOVA are provided in Table S3.1.
Out of these pharmaceuticals, only atorvastatin was partially eliminated (75%)
during mild photocatalytic pre-treatment. The enhanced atorvastatin removal may
have been due to a co-substrate effect as reported by other authors. Yan, et al.
[311] found faster quinoline removal during biological treatment after photolytic
pre-treatment. They suggested this could result from quinoline and its photolysis
products being simultaneously biodegraded and thereby both contributing to
biomass growth. Further, enhanced biodegradation induced by photolysis products
was demonstrated for sulfadiazine by Pan, et al. [201], 2,4,6-trichlorophenol by
Wang, et al. [297] and for pyridine by Zhang, et al. [323]. These authors reported
that biodegradation of the main photolysis product generated intracellular electron
carriers that initiated the initial mono-oxygenation reaction for biodegradation of
target compounds. In sunlit surface water two photolysis products of atorvastatin
were found, one as a result of N-dealkylation, the other formed by
photonucleophilic aromatic substitution of the F atom by OH [143]. Similar to the
2,4,6-trichlorophenol photolysis the dehalogenation of atorvastatin could indicate
the formation of a more readily biodegradable product.
Enhanced biological removal of caffeine, diclofenac, gemfibrozil and
ibuprofen was observed after pre-treatment, even though they were not
significantly removed during mild photocatalysis. Contrary to the B protocol results
in which diclofenac was classified as recalcitrant, biological removal of diclofenac
was found in the MP+B protocol. At day 21 more than 99% removal of diclofenac
was observed, whereas only 50% was removed in the B protocol. In addition,
caffeine and ibuprofen were removed within 3 days as compared to 7 days in the
B protocol while gemfibrozil removal at day 7 was 95% compared to 50% in the B
protocol. Like atorvastatin, it is hypothesized that the enhanced biodegradation of
caffeine, diclofenac, gemfibrozil and ibuprofen was triggered by the presence of
photocatalytic products. Although none of these pharmaceuticals was effectively
removed during mild photocatalysis, the products formed during photocatalytic
removal of atenolol, atorvastatin and fluoxetine may have enhanced their
70
Chapter 3
biodegradation. By contrast, pre-treatment did not improve the removal of

naproxen in subsequent biodegradation testing while naproxen was effectively
biodegraded in the B protocol.
The molecular structures of the pharmaceuticals (Table 3.1) were compared
to assess whether there was a relationship between structure and the biological
removal responses observed after pre-treatment. A carboxyl group is present in
atorvastatin, diclofenac, gemfibrozil and ibuprofen but also in naproxen. Caffeine
is the only pharmaceutical without a phenyl ring, yet not the only one exhibiting
enhanced biodegradation. Atorvastatin, caffeine, gemfibrozil and ibuprofen have
methyl groups, as does naproxen, whereas diclofenac does not have it. In
particular, the response of naproxen after pre-treatment was elucidated as it
behaved differently than the other pharmaceuticals that displayed enhanced
removal. As ibuprofen removal is well described in the literature and its structure
has many commonalities with naproxen, their reported degradation pathways were
compared. Naproxen was the only pharmaceutical in this study that contained an
ether group. Ether cleavage, hydroxylation and aromatic ring cleavage are known
III
naproxen degradation pathways [209, 239, 302, 326], and occur mostly co-
metabolically [209, 302]. The reported ibuprofen degradation pathways are
hydroxylation, dealkylation followed by hydroxylation, demethylation followed by
O-hydroxylation and demethylation followed by dehydrogenation [30]. Hence, the
literature reveals a limited overlap in the broad and complex array of
transformation pathways for naproxen and ibuprofen. Moreover, co-metabolic
processes appear to be important for naproxen removal. These factors could
possibly explain why naproxen removal was not enhanced after the mild
photocatalytic pre-treatment. Overall, no clear relation was found between the
chemical structure and biodegradation responses of the pharmaceuticals after pre-
treatment.
Atenolol and carbamazepine removal efficiencies were similar in the
biological experiments conducted for the B and MP+B protocols. Atenolol sorption
to clay particles was hypothesized to explain the lack of difference observed in
removal efficiency between the two protocols, indicating that photocatalytic pre-
treatment did not affect atenolol sorption. The similar removal of carbamazepine
with or without photocatalytic pre-treatment was attributed to the general
persistence of carbamazepine towards biodegradation, as observed in many
71
previous studies [164, 287]. We could not test the differences in fluoxetine
removal efficiencies as it was substantially removed during filtration prior to the
biological experiments of the MP+B protocol.
In summary, mild photocatalytic pre-treatment with a subsequent biological
treatment was found to be an effective combination of processes to improve the
removal of pharmaceuticals. Scott and Ollis [235] indicated that choosing
complementary processes is a key design priority in order to benefit from
synergistic effects. In this study, the recalcitrance of diclofenac towards
biodegradation was overcome by pre-treatment. Furthermore, biodegradable
pharmaceuticals like atorvastatin, caffeine, gemfibrozil and ibuprofen were
biodegraded at a higher rate compared to biological treatment without pre-
treatment. Hence, our study demonstrates that mild photocatalytic pre-treatment
and biodegradation are complementary processes and their synergy can result in
a better pharmaceutical removal compared to the single processes.
3.4 Conclusions
Sequentially combined mild photocatalysis and biological treatment
effectively removed 8 out of 9 studied pharmaceuticals. The biological degradation
of 5 pharmaceuticals improved after mild photocatalytic pre-treatment in a
subsequent biological treatment of which only atorvastatin was removed during
mild photocatalysis. Biodegradation of the atorvastatin photocatalytic degradation
products most probably triggered the enhanced atorvastatin biodegradation by
initiation of mono-oxygenation reactions. Caffeine, diclofenac, gemfibrozil and
ibuprofen were not susceptible to photocatalysis, however their biodegradation
efficiency enhanced after mild photocatalytic pre-treatment. During intensive and
mild photocatalysis 3 out of 9 pharmaceuticals were removed, atenolol,
atorvastatin and fluoxetine. We hypothesize that their photocatalytic products
resulted in the enhanced biodegradation of caffeine, diclofenac, gemfibrozil and
ibuprofen. Similar observed photocatalytic rate constants of the separately
performed intensive and mild photocatalytic experiments indicate the process
robustness of photocatalysis for pharmaceuticals removal. Biodegradation was the
predominant removal mechanism in biological experiments for most
pharmaceuticals, whereas fluoxetine was removed by sorption to the inoculum and
atenolol by both sorption and biodegradation. Carbamazepine was recalcitrant
72
Chapter 3
towards photocatalysis and biodegradation. Overall, mild photocatalysis followed

by biological treatment is an effective and resource efficient combination,
achieving a substantial reduction of energy input for the photocatalysis and an
enhanced biodegradation of biodegradable and recalcitrant pharmaceuticals
susceptible and non-susceptible to photocatalysis.
Acknowledgement
We would like to thank Leslie Bragg for her support on the analytical work
and Robert Liang for providing the experimental setup and the P25 powder. We
kindly acknowledge financial support from the Association Canada Studies the
Netherlands and the Knowledge-to-Knowledge project within the Partners in
Business Water and Soil Canada cluster.
Table S3.1 Significance output of the ANCOVA statistical model in which we considered III
time as a covariate. Results are the significances of the difference in pharmaceutical
removal (C/C0) per compound between the single process biological experiments (B
protocol) and the mild photocatalytic pre-treated biological experiments (MP+B protocol).
A significance of <0.05 was considered significant (highlighted in green).
Carbamazepine
Atorvastatin
Gemfibrozil
Fluoxetine
Diclofenac
Ibuprofen
Naproxen
Caffeine
Atenolol
Pharmaceutical
Significance 0.219 0.011 0.044 0.250 0.002 n.d. 0.008 0.024 0.184
n.d. – not determined because too few data points available due to rapid sorption
73
Chapter 4
Enhanced pharmaceutical removal from water
in a three step bio-ozone-bio process
A modified version of this chapter has been submitted as
Arnoud de Wilt, Koen van Gijn, Tom Verhoek, Amber Vergnes, Mirit Hoek,
Huub Rijnaarts and Alette Langenhoff. Enhanced pharmaceutical removal
from water in a three step bio-ozone-bio process
A three-step Bio-Ozone-Bio process
Abstract
Individual treatment processes like biological treatment or ozonation have
their limitations for the removal of pharmaceuticals from secondary clarified
effluents with high total organic carbon (TOC) concentrations (i.e. 17 mg/L). These
limitations can be overcome by combining these two processes for a cost-effective
pharmaceutical removal. A three-step biological-ozone-biological (BO3B)
treatment process was therefore designed for the enhanced pharmaceutical
removal from wastewater effluent. The first biological step removed 38% of ozone
scavenging TOC, thus proportionally reducing the absolute ozone input for the
subsequent ozonation. Complementariness between biological and ozone
treatment, i.e. targeting different pharmaceuticals, resulted in cost-effective
pharmaceutical removal by the overall BO3B process. At a low ozone dose of 0.2 g
O3/g TOC and an HRT of 1.46 hours in the biological reactors, the removal of 8 out
of 9 pharmaceuticals exceeded 85%, except for metoprolol (60%). Testing various
ozone doses and HRTs revealed that pharmaceuticals were ineffectively removed
at 0.1 g O3/g TOC and an HRT of 0.3 hours. At HRTs of 0.47 and 1.46 hours easily
and moderately biodegradable pharmaceuticals such as caffeine, gemfibrozil,
ibuprofen, naproxen and sulfamethoxazole were over 95% removed by biological
treatment. The biorecalcitrant carbamazepine was completely ozonated at a dose
of 0.4 g O3/g TOC. Ozonation products are likely biodegraded in the last biological
reactor as a 17% TOC removal was found. No appreciable acute toxicity towards
D. magna, P. subcapitata and V. fischeri was found after exposure to the influents
and effluents of the individual BO3B reactors. The BO3B process is estimated to
increase wastewater treatment costs by 15%, whereas the yearly tariff per
population equivalent in the Netherlands is estimated to increase by less than
10%. Overall, the BO3B process is a cost-effective treatment process for the
removal of pharmaceuticals from secondary clarified effluents.
Keywords
Biodegradation; Ozonation; Combined treatment; Pharmaceuticals; Wastewater
76
Chapter 4
4.1 Introduction
Human consumption of pharmaceuticals has increased in the past years and
is expected to rise even more due to the growing world population and increased
average age [283]. After administration pharmaceuticals are excreted and
disposed into the sewer [85]. This results in elevated pharmaceutical
concentrations in wastewater, as is illustrated by measurements of numerous
studies over the past decades [188, 228]. Many pharmaceuticals are persistent in
conventional wastewater treatment plants (WWTPs) [222, 287]. Pharmaceutical
levels in WWTP effluents jeopardize the aquatic environment [77, 85, 141, 325]
and reach drinking water resources [188]. As a result, they end up in the water
cycle, and this stresses the need for their removal from WWTP effluents.
Ozone treatment has been studied for pharmaceutical removal [164].
Ozonation is an effective technique to oxidize pharmaceuticals [116]. Ozone
targets electrophilic compounds that contain double bonds, aromatic structures or
amine groups which are often found in the chemical structure of pharmaceuticals
[193]. Ozonation leads to shorter and more oxidized products which are not further
broken down by ozone, but are more susceptible to biodegradation [243]. High
removal rates can be obtained by ozonation, but process efficiency reduces when
other compounds than the pollutants of interest are present [187]. WWTP effluents IV
contain orders of magnitudes more harmless organic matter than residual
pharmaceutical concentrations, both being oxidized by ozone, resulting in
degradation processes competition for ozone. The biodegradability of recalcitrant
compounds typically increases after ozonation [6]. However, toxic by-products can
be formed during ozonation [118], resulting in the need of a subsequent treatment
step after ozonation [222]. Activated carbon (AC) is a commonly proposed post-
ozone treatment step as it effectively removes organic compounds from water
through adsorption and does not generate toxic by-products [134]. A costly
downside of AC is the regeneration or replacement of AC when saturated.
An alternative or addition to physical-chemical techniques is biological
treatment, i.e. employing microorganisms to degrade pharmaceuticals. In general,
biological treatment requires low energy and chemical inputs. However, complex
molecules like pharmaceuticals present at low concentrations are challenging to
biodegrade [164]. For many pharmaceuticals insufficient degradation rates result
in incomplete removal in biological processes applied at WWTPs [124]. Moreover,
77
specific micropollutant degrading microorganisms are easily outcompeted by other

microorganisms that depend on easily degradable substrates present at higher
concentrations [155].
Combining biological and ozone treatment can be an alternative set of
processes for enhanced pharmaceutical removal. Combinations of biological
processes with advanced oxidation processes, including ozonation, are known to
have beneficial effects over single process technologies [235]. Effective
degradation and mineralisation of the degradation products was achieved in a
combined ozone-biological process for the widely prescribed antibiotic tetracycline
[93]. Biodegradation and mineralisation of the antibiotic sulfadiazine were
accelerated by UV-photolysis pre-treatment by 35 and 71%, respectively, [201].
In the study presented here, the capacities of biological and ozone
treatment processes are combined for pharmaceutical removal in a post-treatment
process at the WWTP. A three-step biological-ozone-biological (BO3B) treatment
process is designed to investigate the process removal efficiency. Applied ozone
dose and the hydraulic retention time (HRT) of the bioreactors are the studied key-
parameters to adjust the process performance. The aim of this study is therefore
to test the influence of the applied ozone dose and HRT on the BO3B process
performance. Both chemical and toxicological parameters are used to assess the
BO3B process efficiency. An optimal combination of biological and ozone treatment
is hypothesized to result in a cost-effective BO3B process to remove
pharmaceuticals and the toxicity they impose at minimal energy input.

4.2.1 Feed solution and inoculum
Secondary clarified effluent was obtained from WWTP Bennekom
(Bennekom, the Netherlands) as feed solution for the experimental work. WWTP
Bennekom has a carrousel configuration, is operated with biological nitrogen and
phosphate removal and has a capacity to treat 20 000 population equivalents. Two
batches of effluent were taken during the experiment. The effluent had an average
total organic carbon (TOC) concentration of 17.3±3.3 mg/L and a pH of 7.6±0.2,
other effluent characteristics are given in Tables S4.1 and S4.2. Inocula from three
locations were taken and mixed. The inoculum mixture consisted of MBR sludge
78
Chapter 4
from a hospital wastewater treatment facility (Pharmafilter, Reinier de

Graafziekenhuis, Delft, the Netherlands), primary and secondary sludge of WWTP
Bath (Bath, the Netherlands) treating a mixture of industrial and domestic
wastewater, and biomass from the BioGAC polishing step of WWTP Horstermeer
(One-Step filter, Nederhorst den Berg, the Netherlands).
4.2.2 Chemicals
The pharmaceutical stock solution was prepared in HPLC grade methanol
and consisted of caffeine, carbamazepine, diclofenac, gemfibrozil, ibuprofen,
metoprolol, naproxen, sulfamethoxazole and trimethoprim. To avoid the influence
of methanol on the experiments, spikes of the stock solution were evaporated till
dryness under a gentle nitrogen stream whereafter secondary clarified effluent was
added to obtain the feed solution with a pharmaceutical concentration of
approximately 200 µg/L.
4.2.3 Experimental setup BO3B process

The experimental setup, consisting of a biological reactor (BR1), an ozone
reactor (O3R) and a second biological reactor (BR2), were operated in series
(Figure 4.1). An adaptation period of 5 months was applied for the physical and IV
biological stabilization of the BO3B process before various process parameters were
tested. Thereafter different ozone doses in O3R and HRTs of the bioreactors were
studied during a 5-month experimental period. HRTs of respectively 1.46, 0.47
and 0.3 hours were tested by changing the flow rate. Four ozone doses were tested
by varying the ozone concentration in the injected gas mixture, 0.1, 0.2, 0.4 and
0.5 g O3/g TOC. Each time a parameter was changed the BO3B process was
operated for 4-7 days before samples were taken and new settings were applied.
79
Ozone Off-gas
Feed
TOC TOC
BR1 BR2
O3 products
O3R
Settler
Air
Air
Effluent
Wash-out
Figure 4.1 Schematic of the experimental set-up. BR1 represents the first biological
reactor, O3R the ozone reactor and BR2 the second biological reactor.
4.2.3.1 Biological reactors BR1 and BR2

Two identical lab-scale reactors (BR1 and BR2) were operated in continuous
mode. Sand with a diameter of 1.2-1.6 mm was obtained from a drinking water
treatment plant sandfilter (Vitens, de Meern, the Netherlands) and functioned as
the carrier material in the reactors. Sand and the inoculum mixture were mixed
and formed the filter bed of the reactors. BR1 and BR2 were inoculated with 2.8
and 3.3 kg of filter bed material, respectively, the effective reactor volume was
approximately 1,4 L. The initial dry matter (DM) and organic matter (OM) content
of the filter bed was 749.5 g DM/kg and 38.0 g OM/kg, respectively. After wash-
out of surplus filter bed material during the adaptation period these contents
decreased to 734.9 g DM/kg and 30.8 g OM/kg at 23 weeks of operation. Reactors
were fed from the top by continuous dripping.
80
Chapter 4
The influent was dispersed evenly over the filter bed surface by a fine porous
plate placed on top of the filter bed. Effluent was discharged at the bottom of the
reactors. A net with marbles on the bottom retained the filter bed. BR1 was
operated with a subsequent 1.5 L settler, preventing washed-out biomass to enter
the O3R. BR1 was fed with the feed solution as described in section 4.2.1, BR2 with
the effluent of the O3R. In both reactors aerobic conditions were obtained by a
counter-current air flow. Fluorescein was used in a conservative tracer pulse test
to determine the HRT. Fluorescein concentrations in the effluent were analysed at
a frequency of 10 seconds.
4.2.3.2 Ozone reactor O3R

A glass-column ozone reactor (inner Ø 3.6 cm, height 216 cm) with an
effective liquid volume of 1.6 L operated in a counter-current mode was
continuously fed with effluent of BR1. A gaseous ozone/air mixture was injected
at the bottom of the column though a diffuser to create fine bubbles. An air flow
of 1 L/h was used to generate ozone (Ozon Netech NT-BT 2G) and continuously
analysed (Ozone analyser BMT 964) before injection into the reactor. Ozone in the
reactor off-gas was measured by a spectrophotometer (KRATOS Spectroflow 783
UV/Vis Absorbance Detector model 9000-7831, path length=6 mm, λ=254) and IV
residual ozone in the liquid effluent by the indigo method [18]. In both streams
ozone was not detected during the experiment. The applied ozone dose was
expressed as g O3/g TOC.
4.2.4 Nutrient limitation experiments

Batch experiments were performed to investigate whether the BO3B process
was nutrient limited. Two series of duplicate serum bottles (250 mL) were fed with
150 mL feed solution and inoculated with 3.7 g of BR1 filter bed material. The filter
bed material was taken after 25 weeks of reactor operation. One series of batches
was amended with a mixture of macro nutrients and trace elements (Chapter 2).
The aerobic batches were closed with cotton-wool stoppers, incubated at 20°C on
a shaker plate and sampled at 0, 46, 53, 69, 77 and 94 hours.
81
4.2.5 Analytical methods

4.2.5.1 Pharmaceuticals
Liquid samples for pharmaceutical analysis were taken from the influents
and effluents of the reactors and batch experiments. Samples were directly
centrifuged at 3620 g, after which the supernatant was frozen and stored at -10°C
prior to extraction. Pharmaceuticals were extracted by SPE and analysed by LC-
DAD according to the procedure described in Chapter 2.
4.2.5.2 TOC
Liquid samples for TOC determination were taken from the influents and
effluents of the reactors and batch experiments and analysed on a Shimadzu TNM-
L ROHS TOC-L. TOC was calculated as the difference between Total Carbon (TC)
and Inorganic Carbon (IC). IC samples were acidified to pH 2 to convert inorganic
carbonates into CO2. CO2 was converted from the liquid phase to the gas phase by
sparging synthetic air (80% N2, 20% O2, 0% CO2) and analysed by a non-
dispersive infra-red (NDIR) detector. The carbon in the TC samples was burned at
720°C and converted into gaseous CO2 where after it was analysed on the NDIR
detector.
4.2.5.3 Toxicity assays

Standardized bioassays on three trophic levels involving Daphnia magna,
Pseudokirchneriella subcapitata and Vibrio fischeri were conducted as they have
been widely used for determining toxic effects of pharmaceuticals in wastewater
[75, 76, 88]. The aquatic bioassays to test for acute toxicity were conducted on
the feed solution and effluents of each BO3B treatment step operated at an ozone
dose of 0.2 g O3/g TOC and an HRT of 1.46 hours. D. magna immobilization was
determined with the Daphtoxkit F™ magna tests (MicroBioTests Inc.) according to
the ISO Standard 6341. D. magna immobilization was studied after 48 hour
exposure. P. subcapitata growth inhibition and toxicity towards V. fischeri were
tested according to the methods described by He, et al. [103] but using K2Cr2O7
as positive control to validate the protocol for the P. subcapitata assay.
82
Chapter 4

4.3.1 General performance
Nutrient removal, pH changes and wash-out of the filter bed were
investigated to assess the general performance of the biological reactors.
Consistent with the prevailing aerobic conditions in BR1, ammonium and nitrite
were completely nitrified to nitrate. No further conversion of nitrate was found
over O3R and BR2. Phosphate concentrations were halved over the BO3B process,
which mainly occurred in BR1. No remarkable changes in pH were found as the pH
in the effluents of BR1, O3R and BR2 was 7.7, 8.1 and 7.7, respectively. Because
of nutrient and trace element limitation concerns in the feed solution, the effect of
nutrient and trace element addition was studied in batch experiments. Results of
the batches amended with a nutrient and trace element solution did not
demonstrate a higher TOC or pharmaceutical removal efficiency (data not shown).
Pharmaceutical removal patterns and rates were identical between batches with
or without the additional nutrients and trace elements. This showed that the feed
solution (i.e. the secondary clarified effluent) contained sufficient nutrients and
trace elements to support biological TOC and pharmaceutical removal. During the
adaptation period of 5 months inclination of the filter bed by several centimetres
and wash-out of surplus particulate OM was observed. Initially the OM content of IV
BR1 was 50.7 g OM/kg DM, whereas this was reduced to 41.8 g OM/kg DM after
the adaptation period. Thereafter, no appreciable wash-out was observed during
the 5 month experimental period. No major changes in the TOC and
pharmaceutical removal efficiency of BR1 were observed during the adaptation
period. This implies that the biomass was well adapted to pharmaceuticals and no
noticeable further adaptation occurred. Incidental clogging of major flow paths
affecting the reactor hydraulics was observed throughout the entire 10 months of
operation. In most cases the clogging was overcome by the reactor itself by water
build-up after which new flow paths were formed.
83
4.3.2 The BO3B process

We designed the BO3B process as a cost-effective alternative to direct
ozonation for the removal of pharmaceuticals from WWTP effluents. As
implementation of ozone treatment is often associated with high operational costs,
the BO3B process aims at reducing ozone inputs. A key parameter determining the
cost-effectiveness of ozonation is the OM concentration, i.e. TOC or dissolved
organic carbon (DOC), as it reacts with ozone and OH radicals and thereby
decreases the removal efficiency of target compounds [295]. Hence, Lee et al.
[150] found that the removal of pharmaceuticals by ozonation was consistent
when the ozone dose was normalized to the OM concentration in the liquid (i.e., g
O3/g DOC) for various WWTP effluents with different origins. Direct ozonation of
the feed solution used in this study, containing a moderately high OM
concentration of 17.3±3.3 mg TOC/L, would require relatively high absolute ozone
doses. Therefore we aimed at TOC removal in the first biological treatment step
(BR1). At the most intensively studied HRT of 1.46 hours a TOC elimination of
38±4% was observed over BR1. Thus, by applying a TOC normalized ozone dose,
the absolute ozone dose in the subsequent O3R could be proportionally reduced,
thereby increasing the cost-effectiveness of O3R to remove the present
pharmaceuticals. In comparison, studies on post-treatment by ozonation of Swiss,
Japanese and U.S. wastewaters used feed solutions with lower OM concentrations;
7.0-7.7 [117], 2.9-4.2 [193], 4.2-6.0 [111], 2.4-4.8 [329] and 4.7-7.1 mg DOC/L
[150]. However, for other wastewaters originating from the U.S., Australia and
Germany, moderate to high OM concentrations are found, 6.6-10.3 mg TOC/L
[298] and 15-26.4 [150] and 23.0 mg DOC/L [265]. This demonstrates the high
variety in wastewater matrices and indicates that the benefit of biological OM
removal prior to ozonation is not limited to this study only. The TOC removal over
O3R was 6%. However, the average TOC removal at ozone doses ranging from
0.1-0.5 g O3/g TOC was 13±6% and did not correlated with the ozone dose. This
low and unsteady TOC removal during ozonation is also found by others [20]. The
average TOC removal over BR2 was 17±3%, which is a result of the increased
biodegradability after ozonation [243].
84
Chapter 4
4.3.3 Pharmaceutical removal in the BO3B process
100
80
60
Removal (%)
40
20
BR1 O3R BR2

-20
e
e
en
il
c
en
im
le
lo
z
na
in
in
zo
ro
po
pr
x
f
ep
fe
ro
ro
fe
fib
xa
ho
ro
af
up
az
lo
ap
em
ho
et
C
et
ic
Ib
m
N
M
im
D
et
G
ba
Tr
ar
lfa
C
Su
Figure 4.2 Pharmaceutical removal over the BO3B process at an ozone dose of 0.2 g O3/g IV
TOC and an HRT of 1.46 hours.
Pharmaceutical removal over the BO3B process operated at an ozone dose

and HRT of respectively 0.2 g O3/g TOC and 1.46 hours is depicted in Figure 4.2.
In general, pharmaceuticals were effectively removed over the three step process
displaying removal efficiencies of >60% to complete removal. Compounds known
to be susceptible towards biodegradation such as caffeine, gemfibrozil, ibuprofen
and naproxen were well removed (>95%) in the first bioreactor (BR1). Of the
moderately biodegradable compounds sulfamethoxazole was efficiently removed
(>99%), whereas metoprolol and trimethoprim were only partially removed during
biological treatment, respectively 32% and 42%. Unsurprisingly, the recalcitrant
compounds carbamazepine and diclofenac showed limited removal in BR1 (<14%).
Carbamazepine, diclofenac and trimethoprim were targeted by ozonation in the
subsequent O3R, demonstrating removal efficiencies of 77%, 80% and 49%,
respectively. The other compounds were removed by <10%. The small remaining
85
fractions of diclofenac and trimethoprim after ozonation were completely removed

during the second biological treatment step (BR2), whereas metoprolol was poorly
removed (21%). In addition, a slight increase (4%) in the carbamazepine
concentration was found after BR2 which could indicate carbamazepine production.
Back-transformation of conjugated metabolites to the parent compound is found
for carbamazepine during biological treatment [210, 291]. Back-transformation of
ozonation products is to our knowledge not described in the literature, thus no firm
explanation could be found for this slightly increased carbamazepine
concentration.
The pharmaceutical removal patterns of this study were compared to the
literature on biological treatment and ozonation. BR1 and BR2 were qualitatively
compared to conventional activated sludge (CAS) systems, as they were inoculated
with biomass derived from CAS systems. Taking into account that there is a high
variance in reported removal efficiencies of individual compounds among various
studies, removal efficiencies of caffeine, ibuprofen and naproxen in CAS processes
are generally above 75% [65, 164, 241, 287]. This corresponds well with the fate
of these pharmaceuticals in BR1 of this work. Similar to the moderate removal of
metoprolol and the low removal of carbamazepine and diclofenac in BR1, reported
removal efficiencies are typically around 40% and below 35%, respectively. In
contrast, gemfibrozil, sulfamethoxazole and trimethoprim are relatively well
removed in this work compared to their reported removal efficiencies in the
literature of approximately 60%, 50% and 30%, respectively [65, 164, 241, 287].
Especially the removal of gemfibrozil and sulfamethoxazole in BR1 was high
(>99%). Biodegradation is the predominant removal mechanisms in biological
treatment [7]. Therefore, the biodegradation rates in our study were higher
compared to CAS systems, since we employed a lower HRT, a lower amount of
biomass and higher pharmaceutical concentrations. For other biological treatment
systems, e.g. sand-filters, elevated removal efficiencies for individual
pharmaceuticals have been observed compared to CAS systems [91, 217]. A better
removal in a sand-filter than in CAS systems was found by Reungoat, et al. [217]
for i.a. trimethoprim. Nevertheless, in that sand-filter the removal efficiencies of
caffeine, gemfibrozil, metoprolol and sulfamethoxazole were low, ~30%, ~50%,
<10%, no removal, respectively, compared to CAS systems and BR1 of this work.
Correspondingly, Göbel, et al. [91] found a high (74%) trimethoprim removal
86
Chapter 4
during sand filtration, however no effective elimination was found for

sulfamethoxazole and other antibiotics. In sand filtration and activated sludge
treatment aerobic conditions were found to correlate positively to pharmaceutical
removal [7, 91, 171]. Surprisingly, the compounds for which better anaerobic
removal is reported such as trimethoprim and sulfamethoxazole were well
removed in BR1. Hence, the observed pharmaceutical removal suggested that BR1
was an effective barrier to biodegradable compounds.
The effective oxidation of diclofenac, carbamazepine and trimethoprim
during ozone treatment at 0.2 g O3/g TOC and an HRT of 1.46 hours is in good
agreement with their high reported ozonation rate constants (kO3) of 6.8, 3 and
2.7 x 105 M-1 s-1, respectively [329]. The limited metoprolol removal during
ozonation corresponds well with its moderate kO3 of 2 x 103 M-1 s-1. The results of
this work are in accordance with the work on ozonation of secondary clarified
effluent by Hollender, et al. [111]. Similarly, this can be attributed to the high
ozonation rate constants, the neutral pH and the absence of ozone scavengers like
nitrite (<0.05 mg/L). Although the removal efficiency decreased at lower ozone
doses for most of their tested compounds, diclofenac, carbamazepine and
trimethoprim were well removed (>95%) at 0.40 g O3/g DOC. At this dose
metoprolol removal was approximately 60%, whereas it was effectively removed IV
(>95%) at 1.16 g O3/g DOC. The observed removal by ozonation is typically a
result of the breakdown of pharmaceuticals into smaller oxidized products rather
than mineralisation [243]. For example, the formation of different quinazoline-
containing products during carbamazepine ozonation [178]. Therefore
considerable amounts of ozonation products will enter BR2.
87
4.3.4 Effect of ozone dose

A B
100
80
60
Removal (%)
40
20
-20
C D
100
80
60
Removal (%)
40
20
0
BR1 O3R BR2
-20
lfa a lol
fib c
ro n
fib c
lfa Na lol
up il
ho le
ro n
lo e
Tr oxa n
ho le
lo e
up il
az ne
az ne
Tr oxa n
im
im
Ib roz
Ib roz
em a
em a
D pin
M rofe
D pin
M rofe
h xe
h xe
im zo
im zo
po
po
G fen
G fen
pr
pr
i
i
ba ffe
ba ffe
m pro
m pro
e
e
ar Ca
ar Ca
et
et
et
et
ic
ic
m
m
N
et
et
C
C
Su
Su
Figure 4.3 Pharmaceutical removal over the BO3B process at an HRT of 1.46 hours and
ozone doses of (A) 0.1, (B) 0.2, (C) 0.4 and (D) 0.5 g O3/g TOC.
Pharmaceutical removal over the BO3B process at ozone doses varying from
0.1-0.5 g O3/g TOC at an HRT of 1.46 hours is depicted in Figure 4.3. The
recalcitrance of carbamazepine towards biodegradation and its high ozonation rate
constant (>105 M-1 s-1) allows this compound to be used as indicator for the O3R
performance at different ozone doses. At ozone doses of 0.4 and 0.5 g O3/g TOC
carbamazepine was completely removed over the BOB process, which was mainly
88
Chapter 4
contributed to ozonation. Incomplete removal of ~90% and ~75% was found for
ozone doses of 0.2 and 0.1 g O3/g TOC, respectively. These results are in good
accordance with Lee, et al. [150], who reported a carbamazepine removal by
ozonation of ~55%, 55-90% and >99% at ozone doses of 0.1, 0.25 and 0.5 g
O3/g DOC, respectively. For the other pharmaceuticals a complete removal was
obtained even at the lowest ozone doses, except for trimethoprim, even though
BR1 performed poorly in that testing campaign. Thus, ozonation effectively
contributed to the pharmaceutical removal in the BO3B process at an ozone dose
of 0.1 g O3/g TOC (e.g. >99% diclofenac and >40% carbamazepine removal). This
is better than the <30% pharmaceutical removal at an ozone dose of 0.1 g O3/g
DOC reported by Reungoat et al. [216] which can possibly be explained by the
difference in using DOC or TOC to normalize the ozone dose as the amount of DOC
is smaller than the amount of TOC. In general, the removal of diclofenac,
metoprolol and trimethoprim was unsteady over BR1 and O3R in the different test
campaigns. Although their biodegradability is typically reported as moderate or
low [65, 164, 241, 287], these compounds were effectively biodegraded during
some of our test campaigns. In all cases, the combination of BR1 and O3R
effectively removed diclofenac, independently of the applied ozone dose.
Metoprolol is less susceptible to ozonation and unsteadily removed in O3R when IV
BR1 showed low removal (i.e. at 0.1 and 0.2 g O3/g TOC). The low metoprolol
removal by ozonation is similar to the findings of Hollender, Zimmermann et al.
(2009) who found ~90% and ~60% metoprolol removal at 0.62 and 0.40 g O3/g
DOC, respectively. Trimethoprim removal did not correlate well with the applied
ozone dose. At the intermediate ozone doses it was removed by ozonation,
whereas it was not removed at highest and lowest ozone doses. Regarding the
reported high trimethoprim ozonation rate constant (>105 M-1 s-1) removal at 0.5
g O3/g TOC was expected. No other explanation than a possible analytical error at
the highest ozone dose could be found to explain this finding. Ozonation of
bromide-containing water can lead to the formation of bromate, which is suspected
to be carcinogenic to humans [292]. In our study bromide was not found above
the detection limit (5 µg/L) in any of the samples. Hence, no toxic effects of
bromate is expected as drinking water standards are 10 µg/L. These findings are
in good accordance with the low bromide concentrations detected in drinking water
intake of typically <25 μg/L [294].
89
4.3.5 Effect of HRT

A B C
100
80
60
Removal (%)
40
20
0
BR1 O3R BR2
-20
et f e n
im
az e
lfa ap lol
em ac
up l
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lfa ap n
az e
em ac
n
Ib ozil
im
ro n
ic ne
lfa Na lol
az ne
fib c
up il
Tr oxa n
e
lo e
im
ho le
I b oz i
Ib roz
em a
in
et oxe
D pin
l
in
et oxe
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M rofe
h xe
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D pin
im zo
im zo
im zo
po
pr
G fen
po
G fen
pr
G fen
pr
i
ba affe
o
fe
ep
ba ffe
ro
r
r
fib
Tr oxa
e
fib
r
Tr xa
e
ho
ro
r
r
ar Caf
r
up
lo
ar Ca
et
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et
et
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h
m
N
m
m
N
M
D
et
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m
m
ar
C
C
Su
Su
Su
Figure 4.4 Pharmaceutical removal over the BO3B process at an ozone dose of 0.2 g O3/g
TOC and HRTs of 0.3 (A), 0.47 (B) and 1.46 (C) hours.
Pharmaceutical removal over the BO3B process at varying HRTs from 0.3-
1.46 hours at an ozone dose of 0.2 g O3/g TOC is depicted in Figure 4.4. The easily
biodegradable pharmaceuticals caffeine, ibuprofen and naproxen were used to
assess the influence of HRT on the BO3B process pharmaceutical removal. At HRTs
of 0.47 and 1.46 hours the removal of these and most other compounds is highly
similar, resulting in an efficient removal. Only metoprolol behaved different as it
was better removed at an HRT of 0.47 hours. This agrees well with the results of
the ozone dose tests (Figure 4.3) in which the biological removal of metoprolol
was unsteady over the different test campaigns. Similarly, trimethoprim removal
over BR1 also fluctuated. In contrast to metoprolol, trimethoprim was effectively
removed in O3R and BR2. The limited biological removal of caffeine, ibuprofen and
naproxen at an HRT of 0.3 hours compared to the longer HRTs suggests that 0.3
hours is too short for an effective biological treatment. Matamoros, et al. [171]
reported a similar trend of decreasing pharmaceutical removal efficiencies at
increasing hydraulic loading rates for a sand-filter. At a loading rate of 70 mm day-
1
, corresponding to an HRT of 4-6 hours, caffeine, diclofenac, ibuprofen and
naproxen were removed at 98, 76, 90 and 80%, respectively. However, at a
loading rate of 160 mm day-1 the removal efficiencies decreased to approximately
66, 58, 50 and 54%, respectively. Assuming a linear relation for the sand-filter
90
Chapter 4
between hydraulic loading rate and HRT, whereby these results can be
quantitatively compared to those at the HRT of 1.46 hours of this study, this
suggest that the pharmaceutical removal of BR1 was relatively high. Escolà Casas
and Bester [78] studied and reviewed diclofenac removal in various sand-filters
(i.e. slow and fast filtration) and found HRT related reaction rate constants k
��
(ln = � × ��) of 0.004, 0.04, 0.37 and 1.92 hours-1 at HRTs of 5.7, 9.01, 0.108
��
and 0.13 hours, respectively. The HRT related reaction rate constants of diclofenac
in this study are 0.10, 0.96 and 0.59 hours-1 at HRTs of 1.46, 0.47 and 0.3 hours,
respectively, and thereby at the higher end compared to the reported rate
constants by Escolà Casas and Bester [78]. An HRT based rate constant calculation
is a simplification of reality, neglecting heterogeneity aspects of filter beds such as
redox, substrate and biomass gradients. However, the high variety among
reported rates suggests that the difference between studies (e.g. inoculation of
the sand-filter, type of wastewater and operational conditions) justifies the
comparison of HRT based rate constants. In the literature oxygen or biomass levels
are reported to be rate limiting in sand-filters [78, 171]. In this study an overdose
of oxygen was supplied and a surplus of well-adapted biomass was present at
inoculation resulting in the wash out of biomass. Therefore, it is hypothesized that
the contact time between biomass and pharmaceuticals is the rate limiting factor. IV
Even though the pharmaceutical removal over BR1 was limited at an HRT of 0.3
hours, the removal over the entire BO3B process was similar at the three HRTs.
Remaining fractions of pharmaceuticals were effectively ozonated in O3R resulting
in a complete removal of most pharmaceuticals except for carbamazepine (~80%)
and trimethoprim (~50%). TOC removal over BR1 reduced from 38%, to 31% to
19% at HRTs of 1.46, 0.47 and 0.3 hours, respectively. Similarly, Matamoros, et
al. [171] found a decrease in TSS and BOD5 at decreasing HRTs.
91
4.3.6 Lowest ozone dose and lowest HRT

100
80
60
Removal (%)
40
20
BR1 O3R BR2

-20
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Figure 4.5 Pharmaceutical removal over the BO3B process at an ozone dose of 0.1 g O3/g
TOC and an HRT of 0.3 hours.
The pharmaceutical removal at an ozone dose of 0.1 g O3/g TOC and an HRT
of 0.3 hours is depicted in Figure 4.5. A complete pharmaceutical removal is
achieved, except for carbamazepine and trimethoprim. The pharmaceutical
removal over BR1 in this campaign is higher compared to the HRT of 0.3 hours at
an ozone dose of 0.2 g O3/g TOC (Figure 4.4). This can be explained by the
incidental changes in the outflow regime due to clogging of the BR1 filter bed.
Especially at short HRTs this hydraulic behaviour can locally strongly influence the
pharmaceutical removal in the reactor. Therefore an HRT longer than 0.3 hours is
recommended to achieve a continuous and high pharmaceutical removal. At an
HRT of 0.3 hours the pharmaceutical removal over O3R was low. The low removal
of carbamazepine is in the same range as its low removal over O3R at an ozone
dose of 0.1 g O3/g TOC at an HRT of 1.46 hours (Figure 4.3). The ineffective
ozonation of pharmaceuticals that are recalcitrant towards biological treatment,
such as carbamazepine, indicates that an ozone dose of 0.1 g O3/g TOC is too low
for the effective removal of a broad pallet of pharmaceuticals and therefore higher
doses are recommended for full scale implementation.
92
Chapter 4
4.3.7 Toxicity
The pharmaceutical removal during the campaign in which toxicity was
tested is depicted in Figure S4.1. Although the pharmaceutical concentrations in
the BO3B influent in this study were above environmental relevant concentrations,
no significant inhibition was found for D. magna, P. subcapitata and V. fischeri in
the toxicity bioassays (Figure S4.2-S4.4). The bioassays with P. subcapitata and
V. fischeri demonstrated the highest toxicity, however inhibition did not exceed
25% and showed no significant difference between effluent samples of the
individual steps of the BO3B process. This is contrary to the increased toxicity
towards D. magna, P. subcapitata and V. fischeri found after ozonation of other
pharmaceuticals such as ketoprofen [118]. However, this can be explained by the
high concentrations (>mg/L) applied in that study compared to this study. Kaiser
et al. [127] found that transformation products after biological treatment of
carbamazepine can be more toxic for V. fischeri than carbamazepine. As
carbamazepine persisted in BR1 it is unlikely that many transformation products
were formed resulting in low observed toxicities in this study. The three applied
bioassays test for acute toxicity towards the test organisms. This limits an in-depth
toxicological evaluation as chronic toxicity such as genotoxic effects are not studied
in these bioassays. For instance, bio-transformation products of carbamazepine IV
were found to have a higher genotoxicity potential than carbamazepine, however
these products were effectively removed during ozonation [33]. Although the low
observed acute toxic effects hampered the evaluation of individual BO3B process
steps in toxicity reduction, the combination of ozonation with a subsequent
biological treatment (i.e. sand filtration) was found to effectively reduce toxicity
[248]. Nevertheless, further ecotoxicological investigations are recommended as
pharmaceuticals and their transformation products formed during biological and
ozone treatment can pose diverse ecotoxicological risks [164].
4.3.8 Costs and energy demand

Depending on the energy price and the system requirements, production
costs of ozone are reported to be 0.8 - 1.6 €/kg O3, which represents 20-40% of
the total costs for large scale ozonation installations [265]. The BO3B process
operated at an ozone dose of 0.2 g O3/g TOC and HRT of 1.46 hours effectively
removed pharmaceuticals in this study. Moreover, 38% TOC removal was achieved
93
during biological treatment prior to ozonation (i.e. BR1). Therefore the costs for
ozone production in the BO3B process are <0.004 €/m3 considering a secondary
clarified effluent with an average TOC concentration of 17.3 mg/L. Thereby the
total costs for ozonation (investment and operational costs) are estimated to be
<0.03 €/m3. The investment and operational costs for biological pre- and post-
treatment (i.e. BR1 and BR2, respectively) are hypothesized to be smaller or equal
to the costs for ozonation as the operational costs of sand-filters is known to be
low. The total costs for additional treatment by the BO3B process are therefore
estimated to be <0.06 €/m3. These costs are on the lower end of the costs
estimated by Joss, et al. [125], who reported the additional investment and
operational costs for ozonation and post-filtration to be 0.05 – 0.15 €/m3
depending on the WWTP size and DOC concentration. According to the Dutch Water
Authorities, the investment and operational costs for conventional wastewater
treatment (excluding sewer transport costs) in the Netherlands are 0.45 €/m3
[280]. Thus, the additional costs for BO3B treatment are less than 15% of the total
treatment costs. In addition, the yearly average wastewater treatment tariff is
€55.69 per population equivalent [280]. Based on the <0.06 €/m3 for BO3B
treatment the yearly additional costs are estimated to be <5 € per population
equivalent, which corresponds to a less than 10% tariff increase. The energy
requirements for ozone production are approximately 15 and 35 kWh/kg O3 when
manufactured from oxygen and air, respectively [89]. Hence, the energy demand
is about 0.03 - 0.07 kWh/m3. Together with the energy demand of pumps and
other equipment the total demand is estimated to be 0.1 – 0.15 kWh/m3, which
corresponds well with literature estimations of 0.1 – 0.3 kWh/m3 [125]. The energy
demand for conventional wastewater treatment in the Netherlands is about 0.39
kWh/m3 of which 0.17 kWh/m3 is needed for aeration [280]. Post-treatment by a
BO3B process would therefore increase the energy consumption by approximately
25-38%. Overall, this study demonstrates that even for secondary clarified
effluents with high TOC levels ozonation can be a cost-effective treatment process
when combined with biological pre- and post- treatment steps, i.e. the BO3B
process. Therefore, BO3B treatment is found an effective process for the reduction
of emission of potentially harmful compounds into the aquatic environment.
94
Chapter 4
4.4 Conclusions
The combination of biological treatment and ozonation in the designed
three-step BO3B process is found an effective treatment process for the removal
of pharmaceuticals from secondary clarified effluent with high TOC concentrations.
Ozonation and biological treatment are complementary processes targeting
different pharmaceuticals. Pharmaceutical removal over the BO3B process
exceeded 85%, except for metoprolol (60%), at a low ozone dose of 0.2 g O3/g
TOC and an HRT of 1.46 hours in the biological reactors. Carbamazepine that
persisted during biological treatment was completely ozonated at increased ozone
doses of 0.4 g O3/g TOC, whereas at a dose of 0.1 g O3/g TOC it showed low
removal (<40%). Easily and moderately biodegradable pharmaceuticals such as
caffeine, gemfibrozil, ibuprofen, naproxen and sulfamethoxazole were >95%
removed by biological treatment at HRTs of 0.47 and 1.46 hours. At the lowest
tested HRT of 0.3 hours these pharmaceuticals were incompletely removed (35%-
95%). The input of absolute amounts of ozone was effectively reduced by the
elimination of TOC over the first biological step, i.e. BR1. At HRTs of 1.46, 0.47
and 0.3 hours a decrease in TOC concentration was found over BR1of respectively
38%, 31% and 19%, resulting in a proportional reduction of ozone in the
subsequent ozone reactor, i.e. O3R. No appreciable acute toxicity towards D. IV
magna, P. subcapitata and V. fischeri was found after exposure to the influents
and effluents of the individual BO3B reactors. However, further ecotoxicological
investigations are suggested. The secondary clarified effluent contains sufficient
nutrients and trace elements to support biological pharmaceutical removal. Costs
associated to BO3B treatment are estimated to increase the current treatment
costs for conventional wastewater treatment by 15%, whereas the yearly tariff per
population equivalent in a country like the Netherlands is estimated to increase by
less than 10%. The energy demand for wastewater treatment is expected to
increase by 25-38%. Overall, the BO3B process is a cost-effective treatment
process for the removal of pharmaceuticals from secondary clarified effluents.
Acknowledgement
We would like to thank Lilian Prinsen for her practical support.
95
Table S4.1 Concentrations (mg/L) of the ionic constituents from the WWTP Bennekom
secondary clarified effluent.
F- Cl- NO2- NO3- NH4+ SO24- PO43- Br-
Batch 1 0.14 260.4 n.d. 5.98 0.08 6.65 1.62 n.d.
Batch 2 0.08 60.2 0.53 4.50 4.70 3.32 1.01 n.d.
n.d. – not detected, NO2- detection limit is <50 µg/L, Br detection limit is 5 µg/L. Anions
-
were analysed on an Ion Chromatograph (Dionex ICS 2100, Dionex IonPac AS17, 4 x 2505
mm). An injection volume of 10 μL was used with a constant flow of 1 mL / minute and
the following flow program: 10 minutes at 5 mM KOH, in 15 minutes a linear increase to
30 mM KOH, 3 minutes on 30 mM KOH and back to 5 mM KOH in 2 minutes. Samples were
diluted 10 times. Measurements were performed in triplicate, stated values are the
average. Ammonium was analysed by Hach Lange kits LCK 303 and 304.
Table S4.2 Average concentrations (mg/L) and standard deviations of the carbon fractions
in the feed solution of the BO3B process over the 5-month experimental period.
Total carbon Total inorganic carbon Total organic carbon
48.5±9.1 31.2±6.3 17.3±3.3
140
120
100
80
Removal (%)
60
40
20
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-40
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Figure S4.1 Pharmaceutical removal over the BO3B process during the toxicity tests at an
ozone dose of 0.2 g O3/g TOC and an HRT of 1.46 hours.
96
Chapter 4
100
80
% inhibition
60
40
20
0
Figure S4.2 Toxicity towards V. fischeri of the feed water (Infl.), first biological reactor
(BR1), ozone reactor (O3R) and second biological reactor (BR2). Columns represent the
average toxicity (n=6), error bars represent standard deviations.
100
% growth inhibition
80
60
40
20
0
Figure S4.3 Toxicity towards P. subcapitata of the feed water (Infl.), first biological reactor
IV
100
% immobilized
80
60
40
20
0
Figure S4.4 Toxicity towards D. magna of the feed water (Infl.), first biological reactor
97
Chapter 5
Micropollutant removal in an algal treatment system
fed with source separated wastewater streams
This chapter has been published as
Arnoud de Wilt, Andrii Butkovskyi, Kanjana Tuantet, Lucia Hernandez

Leal, Tânia Vasconcelos Fernandes, Alette Langenhoff and Grietje
Zeeman. Micropollutant Removal in an Algal Treatment System Fed with
Source Separated Wastewater Streams. Journal of Hazardous Materials,
304 (2016) 84–92
Treatment in an algal photobioreactor
Abstract
Micropollutant removal in an algal treatment system fed with source
separated wastewater streams was studied. Batch experiments with the
microalgae Chlorella sorokiniana grown on urine, anaerobically treated black water
and synthetic urine were performed to assess the removal of six spiked
pharmaceuticals (diclofenac, ibuprofen, paracetamol, metoprolol, carbamazepine
and trimethoprim). Additionally, incorporation of these pharmaceuticals and three
estrogens (estrone, 17β-estradiol and ethinylestradiol) into algal biomass was
studied. Biodegradation and photolysis led to 60 – 100% removal of diclofenac,
ibuprofen, paracetamol and metoprolol. Removal of carbamazepine and
trimethoprim was incomplete and did not exceed 30% and 60%, respectively.
Sorption to algal biomass accounted for less than 20% of the micropollutant
removal. Furthermore, the presence of micropollutants did not inhibit C.
sorokiniana growth at applied concentrations. Algal treatment systems allow
simultaneous removal of micropollutants and recovery of nutrients from source
separated wastewater. Nutrient rich algal biomass can be harvested and applied
as fertilizer in agriculture, as lower input of micropollutants to soil is achieved when
algal biomass is applied as fertilizer instead of urine.
Keywords
Micropollutants; Wastewater; Algae; Source separation; Pharmaceuticals
100
Chapter 5
5.1 Introduction
The global increase of population and consequent shortage of natural
resources causes increasing interest in mining of commodities present in waste
streams, such as the domestic wastewater, which is a potential source of energy,
organic matter and nutrients [199, 289].
The use of algae in wastewater treatment is promising for their high nutrient
recovery capacity. Algae have demonstrated simultaneous removal of nitrogen and
phosphorus from domestic wastewater down to very low concentrations of 2.2
mg/L and 0.15 mg/L, respectively, by uptake of the nutrients into their cells [28].
High biomass yields can be achieved when growing algae heterotrophically in the
presence of ammonia and nitrate [131]. Harvested algal biomass is a potential
source for production of fertilizer and bioenergy [38, 179, 205, 224].
Source separated collection of toilet wastewater makes recovery of organic
matter and nutrients economically feasible because of their high concentration in
a relatively small volume [316]. This volume is less than 30% of the total volume
of domestic wastewater when conventional toilets are used, and even less than
5% when vacuum toilets are used due to the reduced volume of flush water [268].
It contains 38% of organic matter, 88% of nitrogen and 68% of phosphorus of the
domestic wastewater [136]. Toilet wastewater, comprising of urine, faeces, toilet
paper and flush water, can be collected either as a single stream, called black
water, or as two separate streams, urine (yellow water) and faeces (brown water)
[200]. Most of the organic matter comes from faeces, while nutrients are mainly
V
present in urine [136]. Treatment of black water in an up-flow anaerobic sludge
blanket (UASB) reactor allows conversion of organic matter into biogas [317].
Numerous techniques are available to remove nitrogen and phosphorus from the
nutrient rich anaerobically treated black water (AnBW) or urine. However, most of
these techniques are characterized by nutrient removal rather than by nutrient
recovery [261, 284]. Techniques that allow nutrient recovery like struvite or
calcium phosphate precipitation often have the drawback that they cannot
adequately recover nitrogen and phosphorus simultaneously [179, 269, 317].
According to the stoichiometry of the process only 3% of nitrogen can be recovered
from source-separated urine by struvite precipitation while phosphorus can be
almost completely recovered [175]. Thus, an algal treatment system might be
more suitable, and can be used instead for nutrients recovery from AnBW or urine
101
(Figure 5.1) as it is one of the few techniques demonstrating simultaneous nitrogen

and phosphorus recovery.
Tuantet, et al. [276] showed that 85% of phosphorus and 90% of nitrogen
are recovered from urine by incorporation into algal biomass. Vasconcelos
Fernandes, et al. [285] also showed high recovery of nitrogen (74%) and
phosphorus (98%) from AnBW, when growing Chlorella sorokiniana in batch [86].
The algal biomass, enriched with nutrients, can be used as fertilizer [277].
Figure 5.1 Two options of algal treatment system utilization for treatment of source
separated wastewater streams.
In addition to carbon and nutrients, black water contains pathogens and

organic micropollutants. Lienert, et al. [157] investigated excretory routes of 212
pharmaceuticals, and showed that nearly two thirds of them are excreted with
urine, while the rest are excreted with faeces.
Micropollutants are insufficiently removed during anaerobic treatment of
black water and end up in the AnBW [62]. Thus, successful treatment of AnBW or
urine should provide adequate removal of micropollutants before the treated
102
Chapter 5
effluent is discharged or reused. Shi et al. [237] showed that natural and synthetic
estrogens can be effectively removed in algae-based wastewater treatment
systems. However, little is known about the removal of pharmaceuticals by algae.
The quality of the algal biomass, grown on AnBW or urine, is also a focus for
research, because algae can potentially accumulate persistent organic
micropollutants [54]. The presence of micropollutants in algal biomass grown on
AnBW or urine can hinder the possibilities for biomass utilization as fertilizer and
needs to be addressed [158, 301].
The aim of this study is to assess micropollutant removal and sorption to
biomass in an algal treatment system with AnBW and urine used as growth media.
Six pharmaceuticals (ibuprofen, diclofenac, paracetamol, trimethoprim, metoprolol
and carbamazepine) and three estrogens (estrone (E1), estradiol (E2), and
ethinylestradiol (EE2)) were studied, with the estrogens determined in algal
biomass only. The possibilities for reuse of algal biomass in agriculture are further
discussed. Additionally, the inhibiting effect of elevated concentrations of
micropollutants on algae growth is presented.

5.2.1 Micropollutants
Ibuprofen, diclofenac, metoprolol, trimethoprim, paracetamol, fenoprofen,
diaveridine, dihydrocarbamazepine, trimethoprim-d9, estrone, 17β-estradiol,
V
ethinylestradiol and 17β-estradiol-d3 were purchased from Sigma-Aldrich
(Germany). Carbamazepine was purchased from Fagron (the Netherlands). The
standard and spiking solutions of the compounds were prepared in methanol. The
chosen pharmaceuticals represent different therapeutic groups and are widely
used in large quantities in Europe and North America. Most of them are persistent,
as they are not readily degradable in municipal wastewater treatment plants,
except for paracetamol [124]. The studied compounds also cover a wide range of
physical-chemical properties and biodegradability.
103
5.2.2 Inoculum and media

C. sorokiniana CCAP211/8K was obtained from the Culture Collection of
Algae and Protozoa (Oban, UK). Algae were pre-cultivated in an incubator at 35°C
in 250 mL shake flasks containing 100 mL M8a medium [133], enriched air with
3% CO2 (v/v) and continuous average irradiation of 80 µmol m-2 s-1. Male urine
was collected from waterless urinals at the sub-department of Environmental
Technology, Wageningen University, the Netherlands. Urine was diluted six times
with demi water to support equal biomass growth in all batches. Urine was stored
at 4°C prior to the start of the experiments. AnBW was collected from a UASB
reactor operated at 25°C and HRT of 37 days treating black water from 60
households in Sneek, The Netherlands. AnBW was diluted three times to support
equal biomass growth in all batches and was stored at 4°C prior to the
experiments. Urea-based synthetic urine was prepared to mimic non-hydrolysed
urine and consisted of (in 1L) 600 mg urea (CO(NH2)2), 56 mg K2SO4, 110 mg
K2HPO4, 30 mg Na2HPO4.2H2O, 320 mg NaCl, 21.2 mg CaCl2.2H2O and 73.8 mg
MgSO4.7H2O. M8a medium was used as a reference medium for biomass growth
in urine and AnBW [133]. M8a medium was diluted two times to support equal
biomass growth in all batches. Dilutions to support equal biomass growth for all
media were based on preliminary experiments. Composition of all media is shown
in Table 5.1.
All media were filtered over Whatman® Ashless, Grade 589/1 paper filters
with pore size Ø 12-25 µm. Iron and micronutrients were added to the diluted
urine, synthetic urine and diluted AnBW to obtain final concentrations of 160 μM
EDTA ferric sodium salt, 100 μM Na2EDTA.2H2O, 0.5 μM H3BO3, 33 μM MnCl2.4H2O,
5.5 μM ZnSO4.7H2O and 3.7 μM CuSO4.5H2O. At the beginning of the experiment
all media were buffered with 75 mM Hepes at pH 7.0. During the experiment the
pH was manually controlled with 2M HCl or 2M NaOH at pH 7.0.
Table 5.1 Composition of urine, AnBW, synthetic urine and M8a medium.
PO4-P Ptotal NH4-N Ntotal
Medium Dilution factor
(mg/L) (mg/L) (mg/L) (mg/L)
Urine 6 24.7 25.2 540 854
AnBW 3 24.5 24.7 235 236
Synthetic Urine - 21.2 305
M8a medium 2 107.7 257
104
Chapter 5
5.2.3 Experimental set-up

Batch experiments were performed in 500 mL sterilized Erlenmeyer flasks,
closed with sterile cotton-wool stoppers. The flasks were filled with 300 mL
medium, inoculated with 1.66 x 105 cell/mL C. sorokiniana, and spiked with a
solution of micropollutants in a final concentration of 100-350 μg/L (Table S5.1).
Spiking of micropollutants was necessary to obtain sufficient LC-MS response
(>100 times higher than the limit of quantification). After spiking, the
concentrations of the pharmaceuticals were in the same order of magnitude as the
maximal concentrations reported in AnBW and source-separated urine (Table
S5.1). Batch experiments were performed at ten different conditions, with each
condition performed in triplicate (Table 5.2). Batches without algal inoculum were
started one month later to prevent cross-contamination from other batches in the
incubator. All batches were run until the algal growth curves reached the stationary
phase.
Batches were incubated at 35°C (Infors HT® Multitron incubator) with a
continuous average illumination of 68 µmol m-2 s-1. The incubator headspace was
enriched with 3% CO2 (v/v) and humidity controlled at 75%. Batches were
continuously shaken and randomized daily for equal light distribution. Abiotic
batches were set up to test the non-biological micropollutant removal. Biological
activity was supressed in the abiotic batches by addition of 0.2 g/L NaN3. Liquid
samples of 3 mL were taken from each replicate at intervals during the 31 day
incubation period to monitor biomass growth. Duplicate samples of 5 mL were V
taken from each replicate for micropollutant analysis on day 0, 1, 3, 10, 17, 23
and 31.
105
Table 5.2 Overview of the batch experiments (each variation reproduced in triplicate).
Medium Algae MP NaN3 Comments
M8a medium + - - Unlimited algal growth
Urine + - - Algal growth in urine
AnBW + - - Algal growth in AnBW
Synthetic urine + + - MP removal in synthetic urine with algae
Urine + + - MP removal in urine with algae
AnBW + + - MP removal in AnBW with algae
Urine - + - MP removal in urine without algae
AnBW - + - MP removal in AnBW without algae
Urine - + + MP removal in urine at abiotic conditions
AnBW - + + MP removal in AnBW at abiotic conditions
MP - Micropollutants
5.2.4 Biomass growth determination

Chlorophyll-a concentrations were measured with a Phyto-PAM (Heinz Walz
GmbH, Germany). Chlorophyll-a concentrations provide an estimate of the amount
of algal biomass. As a measure of actual versus optimal algae growth, chlorophyll-
a results are presented as relative concentrations compared to M8a (Cx/Cmax_M8a)
regarding M8a as the most optimal growth medium for algae in this experiment.
The optical density at 750 nm (OD750) was used as a non-specific indicator
of microbial biomass growth. OD750 was determined by spectrometry analyses
(Heλios UV, Unicam, UK). The measured OD750 values of the batches were
corrected for initial OD750 values of the media.
Dry weight was measured before and after the experiment. Samples were
filtered over pre-washed 0.2 μm glass microfiber filters (GF/F filter, Whatman Plc.,
UK) and dried overnight at 60°C. The filters were cooled to room temperature in
a desiccator prior to the weighing. Dry weight produced during the experiment was
calculated as the difference between dry weight measured at the last and first day
of the experiment.
5.2.5 Nutrient analysis

The concentrations of nitrogen and phosphorus were measured with Hach
Lange test kits in the batches at the beginning and end of the experiment (N total –
LCK338, NH4-N – LCK303, NO2-N – LCK342, NO3-N – LCK340, Ptotal – LCK350 and
PO4-P – LCK350). Mg2+ was measured with Inductively Coupled Plasma Optical
106
Chapter 5
Emission Spectrometer (ICP-OES, Perkin-Elmer Optima 5000 DV) at the end of the
experiment.
The samples for nutrients analysis were centrifuged at 3400 rpm for 10
minutes and filtered through <2 µm pore size paper filter. Nitrogen removal is
presented as the difference between Ntotal at the beginning and NH4+-N at the end
of the experiment, as NO2-N and NO3-N were not found in the batches at the end
of the experiment. Absolute phosphorus removal is presented as the difference
between initial and final PO4-P concentrations. Relative nitrogen and phosphorus
removal is presented as Cx/C0.
5.2.6 Micropollutant analysis

Samples for micropollutant analysis were centrifuged at 3400 rpm for 10
minutes directly after sampling for separation of liquid phase from suspended
matter, which represents algal biomass. Liquid samples and solid pellets were
stored separately at -20ºC until analysis. Liquid samples were directly injected
onto the LC-MS/MS. Solid pellets were mixed in 5 mL of acetonitrile and sonicated
during 20 minutes for micropollutant extraction. The extract was separated from
the solids by centrifugation. For pharmaceuticals analysis 2 mL of extract was
evaporated till dryness in the vacuum chamber under a gentle nitrogen stream.
The precipitate was dissolved in methanol, then diluted with milliQ in a ratio 9:1
and injected into the column. For estrogen analysis 1 mL of extract was evaporated
till dryness. The precipitate was dissolved in 50 µL of 0.1 M Na2CO3 solution and
V
50 µL of dansyl chloride solution in dried acetone and incubated at 60ºC during 10
minutes according to the modified method of Anari et al. [9]. 0.2 mL of acetonitrile
and 0.2 mL of milliQ were added to the extract after incubation before injection to
the column.
Analysis of micropollutants was performed by LC-MS/MS consisting of
Agilent 1200 HPLC with Agilent 6410 triple quadruple MS/MS operated with Agilent
Masshunter software. A Phenomenex Kinetex Phenyl-Hexyl column (100x2.1 mm,
100 Å pore size) was used for separation of pharmaceuticals, and a Phenomenex
Gemini Phenyl-Hexyl column (150x3.0 mm, 110 Å pore size) was used for
separation of estrogens. The injection volumes, composition of elution solvents,
elution gradients and mobile phase flows are presented in Table S5.2. The MS/MS
was working in multiple reaction monitoring (MRM) mode. The temperature of
107
electrospray ionization source was 320°C with nitrogen used as a collision gas. The
nebulizer pressure was 50 psi and a capillary voltage 4000 V. The retention times,
monitored ions and MS parameters of the studied compounds are presented in
Table S5.3.
The internal standards were spiked to liquid samples prior to injection and
to solid samples prior to extraction (Table S5.1). The samples for calibration curves
(7-point calibration for liquid samples and 8-point calibration for solid samples)
were prepared in triplicates separately for liquid and solid samples by dissolution
of analytes in milliQ. Calibration samples were treated in the same way as liquid
and solid samples. The precision of the method was determined as a relative
standard deviation between triplicate measurements and was below 15% for each
analysed concentration. For recovery determination analytes were spiked to the
liquid samples taken on day 0 and to the solid samples (Table S5.4). Recoveries
were determined as the ratio of the measured amount of an analyte in a spiked
sample minus the measured background amount of an analyte in a sample divided
by the spiked amount of an analyte. A signal-to-noise ratio (S/N) of three was
used to estimate limits of detection and signal-to-noise ratio of ten was used for
estimate limits of quantification (Table S5.5).
108
Chapter 5
A
1,0
M8a
Relative Chlorophyll-a level
Synt. Urine + MP
0,8
AnBW
(Cx / Cmax_M8a)
AnBW + MP
0,6
Urine
Urine + MP
0,4
0,2
0,0
0 5 10 15 20 25 30
Time (days)
B
14
M8a
12
Synt. Urine + MP
AnBW
10
AnBW + MP
V
Optical density at 750 nm
8 Urine
Urine + MP
6
(-)
0
0 5 10 15 20 25 30
Time (days)
Figure 5.2 Chlorophyll-a levels (A), expressed concentration divided over maximal
concentration in M8a medium and optical densities at 750 nm (B). Error bars represent
standard deviations between triplicates
109

5.3.1 Algae growth and nutrient removal
Algal biomass growth, presented as chlorophyll-a (Figure 5.2a), and non-
specific biomass growth, presented as OD750 (Figure 5.2b), and dry weight (Figure
5.3) were determined in all batches to assess possible toxic effects of spiked
micropollutants on algae. During the first week of the experiment all inoculated
batches displayed a similar increase in chlorophyll-a and OD750, except for the
more pronounced increase in OD750 in spiked AnBW. The similarities in biomass
growth up to day 14, regardless of the medium, confirmed the absence of acute
toxic effects of the spiked micropollutants to C. sorokiniana. Experiments were
stopped when no further algae growth was expected. Urine batches were incubated
for 23 days, all other batches for 31 days. Final chlorophyll-a levels, OD750 and dry
weights were similar between spiked and non-spiked inoculated AnBW, spiked and
non-spiked inoculated urine and synthetic urine and M8a medium, except for OD750
in AnBW. The final OD750 in the non-spiked AnBW was 33% higher than in the
spiked AnBW. However, chlorophyll-a levels and dry weights in these batches were
similar. Apparently the spiked micropollutants were not toxic for C. sorokiniana at
the applied concentrations (~100-350 µg/L) within the timeframe of the
experiment.
7
6
Dry solids (g/L)
5
4
3
2
1
0
M8a Urine AnBW Synt. Urine + AnBW + Urine + AnBW + Urine + AnBW +
Urine + MP MP MP MP MP - MP-
MP abiotic abiotic algae algae
Figure 5.3 Dry weight of the algal biomass grown on the different media. Error bars
represent standard deviations between triplicates; MP – Micropollutants.
Chlorophyll-a was not present in abiotic batches and non-inoculated

batches, confirming the absence of algal biomass in these batches. Abiotic and
non-inoculated batches showed a maximal OD750 of 0.5 and dry weight of 0.7 g/L
110
Chapter 5
only, most likely due to the presence of bacteria, fine particles and precipitate
formation in the form of struvite, calcium phosphate, or other precipitates during
the experiment [279]. Average OD750 in non-inoculated and abiotic batches was
more than an order of magnitude lower than in inoculated urine. As optical density
is proportional to bacterial density throughout the bacterial growth phase no
noticeable bacterial growth occurred in the non-inoculated and abiotic batches
[189].
Despite no difference observed between growth of algae in spiked and non-
spiked batches, differences in biomass growth parameters were found between
the media used in the experiments (Figure 5.2, Figure 5.3). Depletion of essential
nutrients in the media was investigated as the possible reason of the observed
differences. Nitrogen and phosphorus were completely removed in AnBW and
synthetic urine at the end of the experiment (Figure 5.4). Complete nitrogen
removal is in accordance with other studies on nutrient removal by algae [276,
285].
Nitrogen Phosphorous
100%
Nutrient removal (%)
80%
60%
40%
V
20%
0%
M8a Synt. Urine + AnBW AnBW + MP Urine Urine + MP
MP
Figure 5.4 Nitrogen (red bars) and phosphorus (blue bars) removal in the inoculated
batches at the end of the experiment (23 days for urine batches and 31 days for other
batches); MP – Micropollutants.
111
Molar N:P ratios in AnBW and synthetic urine in this study were 21:1 and
32:1 respectively, which is above the average N:P ratio in algal biomass (16:1),
also known as Redfield ratio [214]. However, both nutrients were depleted in
AnBW and synthetic urine, whereas only phosphorus depletion was expected based
on the Redfield ratio. Tuantet, et al. [276] and Vasconcelos Fernandes, et al. [285]
found N:P ratios of 15:1 to 33:1 in C. sorokiniana biomass grown on human urine
and AnBW, showing similar deviations of actual N:P ratios from the Redfield ratio.
The N:P ratios reported by Tuantet, et al. [276] and Vasconcelos Fernandes, et al.
[285] evince the possibility of simultaneous nitrogen and phosphorus depletion
observed in this experiment .
Growth on M8a medium was nitrogen limited. Batches with M8a medium
showed the highest absolute phosphorus removal but lowest removal efficiency
(25%). This was expected as the molar N:P ratio in the medium was only 5:1
which is much lower than the Redfield ratio (16:1).
Algal biomass growth on urine was not limited by nitrogen or phosphorus.
Both nutrients were still present in urine at the end of the experiment, while the
absolute nitrogen removal was two times higher than in the other batches.
However, growth of algal biomass on urine was already lower than that on AnBW
and synthetic urine on day 14. Tuantet et al. [275] demonstrated that magnesium
(Mg2+) deficiency in urine can limit algae growth. Dry weight magnesium content
in Chlorella sp. ranges between 0.36% and 0.8% [86] indicating the required initial
Mg2+ concentrations in the medium equal to 6.5 – 20 mg/L based on their biomass
densities of 2.5 and 1.8 g/L, respectively. Literature reports Mg2+ concentrations
of 77 mg/L [279], 119 mg/L [86] and 145 mg/L [163] in fresh urine and 0 to 11.1
mg/L [175], 0.14 to 0.77 mg/L [276] and 1 mg/L [279] in hydrolysed urine. About
60% of the urine was hydrolysed by the beginning of the experiment. Moreover,
prior to pH controlling and buffering the pH in the collected urine was 9.1.
Hypothesized is that due to the hydrolysis and high pH most of Mg 2+ precipitated
and thus became unavailable for uptake by algal cells. This assumption is
confirmed by measurements of magnesium concentrations, giving 16.8±0.6 mg/L
Mg2+ in AnBW and 0.9±0.4 mg/L Mg2+ in urine by the end of the experiment.
Therefore Mg2+ deficiency limited further algae growth and nutrients removal in
the inoculated urine batches.
112
Chapter 5
5.3.2 Micropollutant removal

The removal of spiked pharmaceuticals from the liquid phase in batches with
and without algal inoculum and in abiotic batches is presented as the relative
concentration (Cx/C0) (Figure 5.5).
Diclofenac removal (40% to 60%) was observed in all batches. As the
removal was similar in all batches, including the abiotic ones, it is most likely
attributed to phototransformation. Indeed, direct photolysis plays an important
role for removal of diclofenac [140], while biodegradation of diclofenac in
wastewater treatment systems is insignificant [321].
Ibuprofen removal was observed in all batches, with a higher removal in
AnBW as growth medium. Indirect photodegradation in the presence of
photosensitizers, such as dissolved organic matter (DOM) is a possible pathway of
ibuprofen removal [160]. Canonica et al. [39] showed that the rate of indirect
photolysis can vary depending on the DOM species used as sensitizer, thus, the
faster removal of ibuprofen in AnBW could be explained by better photosensitizing
properties of DOM species present in AnBW compared to other used media.
Paracetamol was rapidly removed in all batches, except for the urine under abiotic
conditions. Paracetamol is a readily biodegradable compound, as indicated by a
reported biodegradation constant kbio >102 L gss-1 day-1 [124]. Additionally, De
Laurentiis et al. [64] reported that direct photolysis is an important mechanism of
paracetamol removal in surface waters. Both mechanisms could have been
involved in the paracetamol removal in this study, because the compound was V
removed in the inoculated batches and abiotic AnBW. However, no sound
explanation for the absence of paracetamol removal in abiotic urine batches was
found.
Complete removal of metoprolol was achieved in batches with algae grown
on synthetic urine and AnBW. Approximately 70% of this compound was removed
in the non-inoculated batches with AnBW. Lower removal was observed in the
urine batches. However, high standard deviations in the urine batches did not allow
to conclude on the extent of metoprolol removal in urine. Biotransformation was
the dominant mechanism responsible for the removal of metoprolol, as no removal
was observed in the abiotic batches. The removal of carbamazepine did not exceed
10% except for the batch with algae grown on AnBW, where it reached 30%. Low
removal of carbamazepine is consistent with the data of other researchers, who
113
showed that carbamazepine is stable towards biodegradation under aerobic

conditions and phototransformation [11, 321].
Trimethoprim removal did not exceed 40%, except for the batch with algae
grown on AnBW, where removal reached 60%. It is consistent with findings of
Suarez et al. [255], who reported high resistance of trimethoprim to biological
removal in aerobic conditions. Removal of trimethoprim in the abiotic batches
reached 20% indicating that photolysis, apart from biotransformation, is a possible
mechanism of trimethoprim removal in urine and AnBW, as was also demonstrated
in previous studies [227].
The observed removal of paracetamol, ibuprofen, metoprolol,
carbamazepine and trimethoprim correlates with published aerobic
biodegradability of these compounds [124, 256]. Algae did contribute to the
removal of metoprolol, as a higher removal was observed in batches inoculated
with algae compared to the non-inoculated batches. This is explained by
mixotrophic nature of microalgae, including Chlorella species, and their ability to
degrade micropollutants [257]. However, removal of the other micropollutants was
neither enhanced nor decreased in the presence of algae. Therefore
biotransformation of these micropollutants was possibly attributed to activity of
natural present microorganisms in AnBW and urine.
In addition to biotransformation, photolysis appears to be a major removal
mechanism in algal treatment systems. Unlike most other biological treatment
processes, the algal treatment systems use illumination for biomass growth, which
increases the removal of the light-sensitive micropollutants. For example, removal
of diclofenac and metoprolol in a conventional sewage treatment plant (STP)
operated at SRTs of 10 days is less than 25%, as reported by Radjenović, et al.
[210]. Removal of these compounds in the algal treatment system studied in the
present paper is higher, e.g. 40-60% removal of diclofenac and complete removal
of metoprolol [210]. Removal of paracetamol (99%), ibuprofen (99%),
trimethoprim (40-60%) and carbamazepine (30%) is similar to that reported for
STP (99%, 99%, 40% and <30%, respectively) [210, 321]. Hence algal
wastewater treatment systems are at least as good as conventional STPs with
respect to pharmaceutical removal. Removal of micropollutants and recovery of
nutrients could be also expected in microalgal biofilms treating the effluent of STP,
as described by Boelee, et al. [28].
114
Chapter 5
A B
1,4 1,4
Diclofenac Ibuprofen
1,2 1,2
1 1
0,8 0,8
Cx/C0
0,6 0,6
0,4 0,4
0,2 0,2
0 0
0 5 10 15 20 25 30 0 5 10 15 20 25 30
C D
1,4 1,4
Paracetamol Metoprolol
1,2 1,2
1 1
0,8 0,8
Cx/C0
0,6 0,6
0,4 0,4
0,2 0,2
0 0
0 5 10 15 20 25 30 0 5 10 15 20 25 30
E F
1,4 1,4
Carbamazepine Trimethoprim
1,2 1,2
1 1
V
0,8 0,8
Cx/C0
0,6 0,6
0,4 0,4
0,2 0,2
0 0
0 5 10 15 20 25 30 0 5 10 15 20 25 30
Time (days) Time (days)
Figure 5.5 Pharmaceuticals removal from liquid phase, expressed as triplicate averaged
concentration divided over concentration at the beginning of the experiment (C x/C0) Error
bars represent standard deviations between triplicates; MP – Micropollutants.
115
The potential of more intensively illuminate algal treatment systems with respect
to higher micropollutant removal is therefore an interesting topic for further
research.
The concentrations of spiked micropollutants in suspended matter at the
end of the experiment of the batches with AnBW and urine were compared (Table
5.3). Diclofenac, trimethoprim, carbamazepine and ethinylestradiol were adsorbed
to the suspended matter in both growth media. Natural estrogens and metoprolol
were only adsorbed to the suspended matter in the batches with urine. Ibuprofen
and paracetamol were not detected in suspended matter.
According to the data (Table 5.3), only limited sorption of the studied
pharmaceuticals to the suspended matter was observed. The results are
comparable with the previous studies of Lai et al. [142], who showed that only 6%
of estrogens were adsorbed to algal biomass and of Hirooka et al. [108], who
observed no accumulation of bisphenol A in algal cells. Concentration limits for
pharmaceuticals and hormones in organic fertilizers do not exist yet, which makes
it impossible to assess the feasibility of application of algae as fertilizer from a
legislative point of view. However, the environmental impact of algae applied as
fertilizer can be assessed by the model, developed by Rieß [220] and extended by
Hammer and Clemens [102].
Table 5.3 Sorption of micropollutants to suspended matter.

% adsorbed (of initial % adsorbed (of
Concentration, ug/g
Compound concentration) removed amount)
urine AnBW urine AnBW urine AnBW
Diclofenac 2.9 ± 1.5 1.4 ± 0.6 7.5 5.5 15.6 9.1
Ibuprofen <LOD <LOD <0.5 <0.6 <0.5 <0.6
Paracetamol <LOD <LOD <0.1 <0.1 <0.1 <0.1
Metoprolol 0.2 ± 0.1 <LOD 0.4 <0.1 0.8 <0.1
Trimethoprim 0.7 ± 0.4 1.2 ± 0.4 1.1 3.7 3.8 7.6
Carbamazepine 0.9 ± 0.4 1.2 ± 0.5 2.6 5.0 12.3 16.7
Estrone 10.2 ± 2.5 <LOD n.d. n.d. n.d. n.d.
β-estradiol 0.1 ± 0.1 <LOD n.d. n.d. n.d. n.d.
Ethinylestradiol 2.5 ± 1.4 0.2 ± 0.1 n.d. n.d. n.d. n.d.
n.d. – not detected
116
Chapter 5
The model assumes that a certain input of nutrients to the agricultural soil
(N – 170 kg ha-1 year-1, P – 26.4 kg ha-1 year-1, K – 132.8 kg ha-1 year-1) is required
for crop production. To prevent over fertilization, the application of organic
fertilizers is limited by the nutrient concentration. The nutrient with the lowest
fertilizing demand will determine the application rate. According to the elemental
composition of biomass (C H1.75±0.02 O0.42±0.04 N0.15±0.02 P0.008±0.003
Mg0.002±0.0003) [276], C. sorokiniana contains in weight percentages 9.2% of
nitrogen and 1% of phosphorus. Nitrogen is the limiting nutrient with 1.9 ton ha-1
year-1 of algal biomass required to meet the nitrogen demand. If algal biomass
from this study would be applied as fertilizer, the annual input of micropollutants
is 0.0055 kg ha-1 diclofenac, 0.0017 kg ha-1 carbamazepine, 0.01938 kg ha-1
estrone and 0.0048 kg ha-1 ethinylestradiol. These values are considerably lower
than the annual input of diclofenac (2.9 kg ha-1), carbamazepine (26.6 kg ha-1),
estrone (0.275 kg ha-1) and comparable to the annual input of ethinylestradiol
(0.0025 kg ha-1) predicted from direct application of raw urine as a fertilizer [102].
Thus, agricultural application of algal biomass, grown on urine or AnBW is
preferred over direct application of urine to achieve lower inputs of micropollutants
to soil.
Biomass grown on AnBW contains lower concentrations of micropollutants
than biomass grown in urine, as shown in this study. This is probably due to the
low biomass yield in the urine batches as a result of the low Mg 2+ content in the
hydrolysed urine. Unless the urine is freshly collected and used for microalgae V
growth, addition of Mg2+ directly to the microalgae culture would be a relatively
simple option. The nutrient ratio in AnBW is favourable for algal growth.
Additionally, micropollutants can be removed during the anaerobic treatment
process, reducing their loads for the algal treatment system and, potentially,
sorption to the algal biomass. For example, trimethoprim is stable under aerobic
conditions, while being removed during anaerobic treatment [62].
117
5.4 Conclusions
Our results show that the tested micropollutants did not inhibit C.
sorokiniana growth at spiked concentrations (100-350 µg/L). In our batches,
ibuprofen and diclofenac were photolytically removed, whereas the combination of
photolysis and biodegradation was responsible for the removal of metoprolol and
paracetamol. Carbamazepine and trimethoprim were recalcitrant towards both
biodegradation and photolysis. Algae enhanced metoprolol removal, but did not
enhance nor constrain removal of the other micropollutants. Removal of
metoprolol and diclofenac in the studied algal treatment system is higher than in
the conventional STP with a SRT of 10 days showing the removal potential of algae
based systems. Sorption to the algal biomass accounted for <20% of the removed
micropollutants, showing that the use of algal biomass grown on urine or AnBW as
fertilizer introduces less micropollutants to soil compared to the direct application
of urine. Therefore algal treatment systems have a potential to remove
micropollutants while simultaneously closing the cycle of nutrients in a safer way.
Acknowledgements
This research was partially funded by the Algobioloop project allocated to
NIOO-KNAW and partners (ETE-WUR, BPE-WUR, DeSaH BV and Waterboard Vallei
and Veluwe) by Innowator-RVO. This work was performed in the cooperation
framework of Wetsus, Centre of Excellence for Sustainable Water Technology
(www.wetsus.nl). Wetsus is cofunded by the Dutch Ministry of Economic Affairs
and Ministry of Infrastructure and Environment, the European Union Regional
Development Fund, the Province of Fryslân, and the Northern Netherlands
Provinces. The authors would like to thank the participants of the research theme
“Separation at Source” for the fruitful discussions and their financial support. The
authors would like to thank Ton van der Zande and Xinan Li for their contribution
to the experimental part of the study.
118
Chapter 5
Table S5.1 Measured initial concentrations (µg/L) of the studied pharmaceuticals in the
batches after spiking.
Measured initial Maximal reported Maximal reported
Compound
concentrations (C0) concentrations in AnBW concentrations in urine
Ibuprofen 317 ± 33 456 [62] 794 [271]
Diclofenac 147 ± 9 59.1 [62] 72 [27]
Carbamazepine 117 ± 17 6.2 [62] 29 [271]
Metoprolol 181 ± 62 91.4 [36] n.f.*
Paracetamol 337 ± 23 602 [62] n.f.*
Trimethoprim 202 ± 30 2.1 [62] 1300 [27]
n.f. – data not found
119
Table S5.2 Composition of mobile phases and elution gradient programs for LC separation
of the studied micropollutants.
Mobile phases
Pharmaceuticals (positive electrospray ionization): 2.5 l H2O + 1.5 mL
CH2O2 + 0.5 mL C4HF7O2 + 30 mg C2H2O4
Mobile Pharmaceuticals (negative electrospray ionization): 2.5 l H2O + 0.75 mL
phase A CH2O2 + 1.5 mL NH3
Estrogens (positive electrospray ionization): 2.5 l H2O + 1 mL CH2O2
+ 1 mL NH3
Pharmaceuticals (positive electrospray ionization): C2H3N + 0.1% CH2O2
Mobile
Pharmaceuticals (negative electrospray ionization): C2H3N
phase B
Estrogens (positive electrospray ionization): C2H3N
Gradient elution programs
Pharmaceuticals Pharmaceuticals Estrogens
(positive electrospray (negative electrospray (positive electrospray
ionization)a ionization)b ionization)c
Mobile Mobile Mobile
Time, Pump, Time Pump, Time Pump,
phase B, phase B, phase B,
min ml/min (min) ml/min (min) ml/min
% % %
0.0 2 0.35 0.0 5 0.35 0.0 10 0.5
1.0 2 0.35 1.0 5 0.35 2.0 10 0.5
8.0 100 0.35 7.0 100 0.35 3.0 75 0.5
9.0 100 0.35 9.0 100 0.35 8.0 75 0.5
9.5 2 0.35 9.5 5 0.35 8.5 100 0.5
15.0 2 0.35 15.0 5 0.35 11.0 100 0.5
11.1 10 0.5
15.0 10 0.5
a - injection volume 3 µL; b - injection volume 10 µL; c- injection volume 2 µL
120
Table
Table
S5.3
S5.3
Retention
Retention
times
times
(RT),
(RT),
monitored
monitored
ions,
ions,
MS MS
parameters
parameters
andand
internal
internal
standards,
standards,
usedused
for correction
for correction
of peak
of peak
areas
areas
of the
of the
studied
studied
micropollutants.
micropollutants.
RT RT Fragmentor
Fragmentor Collision
Collision Corresponding
Corresponding
internal
internalIonization
Ionization
Compound
Compound Precursor
Precursor
ion ion Product
Product
ion ion
(min)
(min) voltage
voltage
(V) (V) energy
energy
(eV)(eV) standard
standard mode
mode
Analysed
Analysed
pharmaceuticals
pharmaceuticals
Ibuprofen
Ibuprofen 7.347.34 205.0
205.0 161.0
161.0 80 80 0 0 Fenoprofen
Fenoprofen Negative
Negative
Diclofenac
Diclofenac 7.367.36 294.0
294.0 250.0
250.0 80 80 5 5 Fenoprofen
Fenoprofen Negative
Negative
Carbamazepine
Carbamazepine 6.876.87 237.2
237.2 194.2
194.2 155155 16 16 Dihydrocarbmazepine
Dihydrocarbmazepine Positive
Positive
Metoprolol
Metoprolol 6.216.21 268.2
268.2 191.1
191.1 80 80 15 15 Diaveridine
Diaveridine Positive
Positive
Paracetamol
Paracetamol 3.103.10 152.1
152.1 109.9
109.9 90 90 13 13 Diaveridine
Diaveridine Positive
Positive
Trimethoprim
Trimethoprim 5.965.96 291.1
291.1 261.1
261.1 160160 25 25 Trimethoprim-d9
Trimethoprim-d9 Positive
Positive
a a
Estrone
Estrone 10.17
10.17 504.2
504.2 171.1
171.1 200200 40 40 β-Estradiol-d3
β-Estradiol-d3 Positive
Positive
a a
β-Estradiol
β-Estradiol 9.469.46 506.2
506.2 171.1
171.1 200200 40 40 β-Estradiol-d3
Positive
a a
Ethinylestradiol
Ethinylestradiol 9.659.65 530.2
530.2 171.1
171.1 200200 40 40 β-Estradiol-d3
Positive
Internal
Internal
standards
standards
Fenoprofen
Fenoprofen 7.237.23 241.0
241.0 197.0
197.0 80 80 0 0
Diaveridine
Diaveridine 5.895.89 261.2
261.2 245.2
245.2 155155 16 16
Dihydrocarbmazepine
Dihydrocarbmazepine 6.916.91 239.2
239.2 194.2
194.2 160160 22 22
Trimethoprim-d9
Trimethoprim-d9 5.925.92 300.0
300.0 280.0
280.0 145145 26 26
a a
β-Estradiol-d3
β-Estradiol-d3 9.449.44 509.2
509.2 171.1
171.1 200200 40 40
a - dansylated
a - dansylated
forms
forms
121
121
V
Table S5.4ainRecoveries
Treatment of the studied micropollutants in liquid samples (in %).
an algal photobioreactor
Medium content
Compound
Table S5.4a Recoveries
Synthetic Urine micropollutants
of the studied AnBW in liquid samples (in %).
Urine AnBW
urine + + + Urine AnBW
Medium content (abiotic) (abiotic)
algae algae algae
Ibuprofen
Compound 89.8
Synthetic 96.8
Urine 96.8
AnBW 95.0 92.0 94.9 92.6
Urine AnBW
Diclofenac 113.3+
urine 119.8
+ 102.4
+ 111.9
Urine 111.9
AnBW 103.6 116.4
(abiotic) (abiotic)
Carbamazepine 94.1
algae 100.2
algae 71.1
algae 108.1 109.6 114.9 115.7
Metoprolol
Ibuprofen 105.8
89.8 81.9
96.8 109.1
96.8 92.0
95.0 80.0
92.0 148.4
94.9 103.2
92.6
Paracetamol
Diclofenac 85.7
113.3 79.8
119.8 75.1
102.4 85.8
111.9 100.9
111.9 86.8
103.6 98.0
116.4
Trimethoprim
Carbamazepine 73.9
94.1 66.3
100.2 67.7
71.1 74.4
108.1 71.7
109.6 92.1
114.9 83.7
115.7
Metoprolol 105.8 81.9 109.1 92.0 80.0 148.4 103.2
Paracetamol 85.7 79.8 75.1 85.8 100.9 86.8 98.0
Table S5.4b Recoveries
Trimethoprim 73.9of the studied
66.3 micropollutants
67.7 in solid71.7
74.4 samples (in %).
92.1 83.7
Medium content
Compound
Table S5.4b Recoveries
Synthetic Urine
of the studied AnBW in solid samples (in %).
micropollutants
urine + + +
Medium content
algae algae algae
Ibuprofen
Compound 110.0
Synthetic 101.2
Urine 98.4
AnBW
Diclofenac 73.6+
urine 80.0
+ 80.1
+
Carbamazepine 126.0
algae 120.0
algae 131.9
algae
Metoprolol
Ibuprofen 120.2
110.0 125.3
101.2 112.4
98.4
Paracetamol
Diclofenac 136.4
73.6 127.4
80.0 161.6
80.1
Trimethoprim
Carbamazepine 174.4
126.0 123.2
120.0 137.2
131.9
Estrone
Metoprolol 113.3
120.2 116.0
125.3 110.1
112.4
Β-Estradiol
Paracetamol 105.8
136.4 129.3
127.4 99.7
161.6
Ethinylestradiol
Trimethoprim 103.9
174.4 167.3
123.2 114.2
137.2
Estrone 113.3 116.0 110.1
Β-Estradiol 105.8 129.3 99.7
Ethinylestradiol 103.9 167.3 114.2
122
122
Chapter 5
Table S5.5 Limits of detection and quantification of the studied micropollutants in liquid
Chapter 5
samples (in µg/L) and in solid samples (µg/g).
Limits of detection Limits of quantification

Table S5.5 Limits of detection and quantification of the studied micropollutants in liquid
Compound
Liquid
samples (in µg/L) and phase,
in solid Solid phase,
samples (µg/g). Liquid phase, Solid phase,
µg/L µg/g µg/L µg/g
Limits of detection Limits of quantification
Ibuprofen 0.25 0.29 0.84 0.96
Compound
Diclofenac 0.05
Liquid phase, 0.01
Solid phase, 0.15
Liquid phase, 0.03
Solid phase,
Carbamazepine 0.41
µg/L 0.13
µg/g 1.36
µg/L 0.42
µg/g
Metoprolol
Ibuprofen 0.26
0.25 0.03
0.29 0.87
0.84 0.09
0.96
Paracetamol
Diclofenac 0.48
0.05 0.03
0.01 1.59
0.15 0.10
0.03
Trimethoprim
Carbamazepine 0.35
0.41 0.07
0.13 1.17
1.36 0.24
0.42
Estrone
Metoprolol n.d.
0.26 0.01
0.03 n.d.
0.87 0.02
0.09
Estradiol
Paracetamol n.d.
0.48 0.00
0.03 n.d.
1.59 0.01
0.10
Ethinylestradiol
Trimethoprim n.d.
0.35 0.00
0.07 n.d.
1.17 0.01
0.24
Estrone n.d. 0.01 n.d. 0.02
Estradiol n.d. 0.00 n.d. 0.01
Ethinylestradiol n.d. 0.00 n.d. 0.01
123
123
Chapter 6
General discussion
Synergy between biological and chemical processes;

towards lower pharmaceutical emissions
General discussion; towards lower pharmaceutical emissions
6.1 Thediscussion;
General need fortowards
safe water
lower pharmaceutical emissions
Worldwide drinking water supply systems are under increasing pressure as

water scarcity, climate change, population growth, demographic changes and
6.1 The need for safe water
urbanization challenges the provision of safe drinking water [305]. Limited
Worldwide drinking water supply systems are under increasing pressure as
accessibility to safe drinking water is on the political agendas globally already for
water scarcity, climate change, population growth, demographic changes and
several decades. As a result, the seventh goal of the United Nations Millennium
urbanization challenges the provision of safe drinking water [305]. Limited
Development Goals (MDG) established in 2000 aims at reducing the proportion of the
accessibility to safe drinking water is on the political agendas globally already for
world’s population without sustainable access to safe water by 2015 [281]. Although
several decades. As a result, the seventh goal of the United Nations Millennium
big steps were made during these 15 years, by 2015 still 2.1 billion people did not
Development Goals (MDG) established in 2000 aims at reducing the proportion of the
have access to “safely managed drinking water services” which is defined as drinking
world’s population without sustainable access to safe water by 2015 [281]. Although
water from an improved water source that is located on premises, available when
big steps were made during these 15 years, by 2015 still 2.1 billion people did not
needed, and free from faecal and priority chemical contamination [305]. Of these
have access to “safely managed drinking water services” which is defined as drinking
people, 1.3 billion had access to basic drinking water services (i.e. improved drinking
water from an improved water source that is located on premises, available when
water availability within a round trip of 30 minutes), the other 844 million people even
needed, and free from faecal and priority chemical contamination [305]. Of these
lacked basic drinking water services. Because of the inaccessibility to clean drinking
people, 1.3 billion had access to basic drinking water services (i.e. improved drinking
water the United Nations Sustainable Development Goals established in 2015 included
water availability within a round trip of 30 minutes), the other 844 million people even
the following targets on water quality; 6.1 “By 2030, achieve universal and equitable
lacked basic drinking water services. Because of the inaccessibility to clean drinking
access to safe and affordable drinking water for all” and 6.3 “By 2030, improve water
water the United Nations Sustainable Development Goals established in 2015 included
quality by reducing pollution, eliminating dumping and minimizing release of
the following targets on water quality; 6.1 “By 2030, achieve universal and equitable
hazardous chemicals and materials, halving the proportion of untreated wastewater
access to safe and affordable drinking water for all” and 6.3 “By 2030, improve water
and substantially increasing recycling and safe reuse globally” [282]. The increasing
quality by reducing pollution, eliminating dumping and minimizing release of
pressure on safe drinking water supply is a worldwide problem, not only affecting
hazardous chemicals and materials, halving the proportion of untreated wastewater
developing countries. For instance, droughts over the past 16 years in the southern
and substantially increasing recycling and safe reuse globally” [282]. The increasing
states of the U.S. caused historically low water levels in the Colorado river leading to
pressure on safe drinking water supply is a worldwide problem, not only affecting
water scarcity and thereby a high pressure on the drinking water supply [13].
developing countries. For instance, droughts over the past 16 years in the southern
An important strategy to overcome issues regarding drinking water supply is
states of the U.S. caused historically low water levels in the Colorado river leading to
the reuse of wastewater for water recovery [305]. The reuse of WWTP effluents for
water scarcity and thereby a high pressure on the drinking water supply [13].
drinking water production is already practiced over 50 years in many countries [69].
An important strategy to overcome issues regarding drinking water supply is
In most cases this concerns an indirect reuse, applying a natural system such as a
the reuse of wastewater for water recovery [305]. The reuse of WWTP effluents for
groundwater aquifer for additional treatment, retention and dilution with other water
drinking water production is already practiced over 50 years in many countries [69].
streams between the WWTP effluent and drinking water intake. However, over the
In most cases this concerns an indirect reuse, applying a natural system such as a
groundwater aquifer for additional treatment, retention and dilution with other water
126
streams between the WWTP effluent and drinking water intake. However, over the
126
Chapter 6
past decade the direct reuse of WWTP effluent for drinking water productionChapter
has also
6
been applied. Especially in the U.S., Southern Africa and Singapore multiple projects
have started applying the direct reuse for drinking water production as additional
past decade the direct reuse of WWTP effluent for drinking water production has also
treatment processes are able to eliminate contaminants to drinking water inlet
been applied. Especially in the U.S., Southern Africa and Singapore multiple projects
standards [69, 148]. Nevertheless, there is an ongoing debate regarding the public
have started applying the direct reuse for drinking water production as additional
health, treatment of emerging contaminants, monitoring, costs and maintenance
treatment processes are able to eliminate contaminants to drinking water inlet
aspects of direct reuse [69]. In addition to the reuse for drinking water purposes,
standards [69, 148]. Nevertheless, there is an ongoing debate regarding the public
reuse of WWTP effluents for other purposes such as irrigation, industrial application,
health, treatment of emerging contaminants, monitoring, costs and maintenance
urban uses and environmental purposes like flow restoration have also been
aspects of direct reuse [69]. In addition to the reuse for drinking water purposes,
extensively studied [202]. Even in countries like the Netherlands where droughts and
reuse of WWTP effluents for other purposes such as irrigation, industrial application,
water scarcity are no major issues the debate of using non-traditional drinking water
urban uses and environmental purposes like flow restoration have also been
sources is conducted as costs for drinking water production increase due to
extensively studied [202]. Even in countries like the Netherlands where droughts and
environmental issues such as pollution and salinization of aquifers [253].
water scarcity are no major issues the debate of using non-traditional drinking water
The presence of numerous micropollutants is one of the main issues when reuse
sources is conducted as costs for drinking water production increase due to
of WWTP effluent for other purposes is considered [305]. Among the broad suite of
environmental issues such as pollution and salinization of aquifers [253].
micropollutants covering pharmaceuticals, pesticides, herbicides, personal care
The presence of numerous micropollutants is one of the main issues when reuse
products, hormones and many others contaminants, the focus of this dissertation is
of WWTP effluent for other purposes is considered [305]. Among the broad suite of
only on pharmaceuticals. Chapter 1 describes the effects which pharmaceuticals can
micropollutants covering pharmaceuticals, pesticides, herbicides, personal care
have on the environment and human health when discharged to surface waters as
products, hormones and many others contaminants, the focus of this dissertation is
currently practiced. Both the (direct) reuse and the discharge to surface waters of
only on pharmaceuticals. Chapter 1 describes the effects which pharmaceuticals can
WWTP effluents motivate the elimination of pharmaceuticals and other
have on the environment and human health when discharged to surface waters as
micropollutants at the WWTP and call for immediate action. Different treatment
currently practiced. Both the (direct) reuse and the discharge to surface waters of
processes for the removal of pharmaceuticals are therefore presented in this
WWTP effluents motivate the elimination of pharmaceuticals and other
dissertation. In this chapter these processes are further discussed with respect to
micropollutants at the WWTP and call for immediate action. Different treatment
their functioning and how they can contribute to a strategy towards a safer water
VI
processes for the removal of pharmaceuticals are therefore presented in this
reuse or discharge. The parameters and processes identified for the research
dissertation. In this chapter these processes are further discussed with respect to
presented in this dissertation are presented in Table 6.1 were.
their functioning and how they can contribute to a strategy towards a safer water
reuse or discharge. The parameters and processes identified for the research
presented in this dissertation are presented in Table 6.1 were.
127
127
Table 6.1
General Overview oftowards
discussion; the parameters and processes studied
lower pharmaceutical for pharmaceutical removal in
emissions
the chapters of this dissertation.
Parameter/Process Chapter 2 Chapter 3 Chapter 4 Chapter 5
Table 6.1 Overview
Biological of the parameters and processes studied for pharmaceutical removal in
treatment
the chapters of this dissertation.
Redox conditions X
Parameter/Process Chapter 2 Chapter 3 Chapter 4 Chapter 5
Mixed inoculum X X
Biological treatment
TOC removal X
Redox conditions
Real wastewater X X X
MixedAlgae
inoculum X X X
TOC removal X
Chemical treatment
Real wastewater X X
UV-LED TiO2
Algae X X
photocatalysis
Chemical treatment
Ozonation X
Photolysis
UV-LED TiO2 X
X
photocatalysis
Ozonation X
6.2 Pharmaceutical removal by biological treatment
Photolysis X
Conventional WWTPs are not designed for pharmaceutical elimination and
optimization of the current treatment processes or extension with other treatment
6.2 Pharmaceutical removal by biological treatment
processes is needed to obtain an improved pharmaceutical removal. WWTPs typically
Conventional WWTPs are not designed for pharmaceutical elimination and
employ biological processes for bulk organic matter, nitrogen and phosphorous
optimization of the current treatment processes or extension with other treatment
removal as they are regarded robust and more cost-effective compared to other
processes is needed to obtain an improved pharmaceutical removal. WWTPs typically
treatment processes. Based on these arguments biological treatment for
employ biological processes for bulk organic matter, nitrogen and phosphorous
pharmaceutical removal is therefore desired. Multiple factors and parameters
removal as they are regarded robust and more cost-effective compared to other
influence the biological removal processes in wastewater treatment of which many
treatment processes. Based on these arguments biological treatment for
cannot be adjusted as they relate to the incoming wastewater, e.g. amounts of
pharmaceutical removal is therefore desired. Multiple factors and parameters
organic matter, nutrients, trace elements, toxins, etc. Others can be used to steer
influence the biological removal processes in wastewater treatment of which many
the process performance, e.g. hydraulic and solid retention times, redox conditions,
cannot be adjusted as they relate to the incoming wastewater, e.g. amounts of
type of biomass, biomass attachment, substrate dosage and substrate availability in
organic matter, nutrients, trace elements, toxins, etc. Others can be used to steer
individual treatment steps. The influence of redox conditions, the effect of
the process performance, e.g. hydraulic and solid retention times, redox conditions,
biodegradable substrates and the application of alternative microorganisms is
type of biomass, biomass attachment, substrate dosage and substrate availability in
elucidated in this dissertation and further elaborated and discussed in this section.
individual treatment steps. The influence of redox conditions, the effect of
biodegradable substrates and the application of alternative microorganisms is
elucidated in this dissertation and further elaborated and discussed in this section.
128
128
Chapter 6
6.2.1 Influence of redox conditions Chapter 6

The influence of redox conditions is of great importance for any biological
conversion. In Chapter 2 we demonstrated that aerobic conditions exert the most
6.2.1 Influence of redox conditions
optimal biological removal of pharmaceuticals. However, under deeply anaerobic
The influence of redox conditions is of great importance for any biological
conditions, i.e. sulfate reducing or methanogenic conditions, we also found high
conversion. In Chapter 2 we demonstrated that aerobic conditions exert the most
pharmaceutical removal. Intermediate redox conditions like micro-aerophilic and
optimal biological removal of pharmaceuticals. However, under deeply anaerobic
nitrate reducing conditions were less effective. In general aerobic conditions are
conditions, i.e. sulfate reducing or methanogenic conditions, we also found high
reported in the literature to be most favourable for the biodegradation of a wide
pharmaceutical removal. Intermediate redox conditions like micro-aerophilic and
variety of pharmaceuticals [7, 26, 83, 215, 247]. However, some individual
nitrate reducing conditions were less effective. In general aerobic conditions are
pharmaceuticals are better degraded under a specific redox condition. For instance,
reported in the literature to be most favourable for the biodegradation of a wide
sulfamethoxazole was better removed under micro-aerophilic conditions compared to
variety of pharmaceuticals [7, 26, 83, 215, 247]. However, some individual
fully aerobic and anoxic/aerobic cycling [247]. Moreover, sulfamethoxazole and
pharmaceuticals are better degraded under a specific redox condition. For instance,
trimethoprim were better removed under methanogenic conditions compared to
sulfamethoxazole was better removed under micro-aerophilic conditions compared to
aerobic conditions [7] and venlafaxine, diatrizoate and tramadol were better removed
fully aerobic and anoxic/aerobic cycling [247]. Moreover, sulfamethoxazole and
under iron reducing, sulfate reducing and methanogenic conditions compared to
trimethoprim were better removed under methanogenic conditions compared to
aerobic conditions [83]. This suggests that a biological process covering a redox
aerobic conditions [7] and venlafaxine, diatrizoate and tramadol were better removed
gradient from aerobic to methanogenic conditions has advantages over a single redox
under iron reducing, sulfate reducing and methanogenic conditions compared to
condition which is therefore recommended for all biological processes aiming at
aerobic conditions [83]. This suggests that a biological process covering a redox
pharmaceutical removal.
gradient from aerobic to methanogenic conditions has advantages over a single redox
condition which is therefore recommended for all biological processes aiming at
6.2.2 Effects of biodegradable substrates
The presence of easily biodegradable substrates in high concentrations is
hypothesized to negatively influence the pharmaceutical removal (Chapter 1). In
6.2.2 Effects of biodegradable substrates
Chapter 4 a relatively high pharmaceutical removal was observed in the investigated
The presence of easily biodegradable substrates in high concentrations is VI
biological reactor of the BO3B process compared to the literature on pharmaceutical
hypothesized to negatively influence the pharmaceutical removal (Chapter 1). In
removal in WWTPs. In comparison with WWTPs the applied HRT in our system was
Chapter 4 a relatively high pharmaceutical removal was observed in the investigated
short and biomass levels were low, which would suggest a low pharmaceutical
biological reactor of the BO3B process compared to the literature on pharmaceutical
removal. However, the observed removal was high which is most likely related to the
removal in WWTPs. In comparison with WWTPs the applied HRT in our system was
difference in organic matter (OM) concentration and composition of the feed solutions
short and biomass levels were low, which would suggest a low pharmaceutical
as the BO3B process was running on secondary clarified effluent. Whereas raw
removal. However, the observed removal was high which is most likely related to the
wastewater entering WWTPs contains high amounts of OM (80-260 mg TOC/L) with
difference in organic matter (OM) concentration and composition of the feed solutions
as the BO3B process was running on secondary clarified effluent. Whereas raw
129
wastewater entering WWTPs contains high amounts of OM (80-260 mg TOC/L) with
129
a high BOD/TOC
General ratio
discussion; (1.2-2.0),
towards lowerthe secondary effluent
pharmaceutical is typically low in OM (<20
emissions
mg TOC/L) and less biodegradable (BOD/TOC 0.2-0.5) as OM removal (i.e. BOD
removal) is one of the main objectives of wastewater treatment [261]. The negative
a high BOD/TOC ratio (1.2-2.0), the secondary effluent is typically low in OM (<20
influence of OM on the pharmaceutical removal is also described in other studies. In
mg TOC/L) and less biodegradable (BOD/TOC 0.2-0.5) as OM removal (i.e. BOD
column experiments mimicking managed aquifer recharge (MAR) systems the
removal) is one of the main objectives of wastewater treatment [261]. The negative
removal of pharmaceuticals enhanced at lower biodegradable organic matter (BOM)
influence of OM on the pharmaceutical removal is also described in other studies. In
concentrations, i.e. biodegradable dissolved organic carbon concentrations of 0.69
column experiments mimicking managed aquifer recharge (MAR) systems the
mg/L versus 1.55 mg/L [155]. A higher microbial density at increasing ratios of BOM
removal of pharmaceuticals enhanced at lower biodegradable organic matter (BOM)
over OM was reported, whereas both the microbial diversity and the metabolic
concentrations, i.e. biodegradable dissolved organic carbon concentrations of 0.69
capability of the microorganisms to degrade pharmaceuticals declined. Moreover, at
mg/L versus 1.55 mg/L [155]. A higher microbial density at increasing ratios of BOM
low compared to high OM levels higher microbial diversities and lower microbial
over OM was reported, whereas both the microbial diversity and the metabolic
densities were found in field and laboratory scale MAR systems, demonstrating that
capability of the microorganisms to degrade pharmaceuticals declined. Moreover, at
high substrate levels limit the capacity of a microbiome to degrade a broad array of
low compared to high OM levels higher microbial diversities and lower microbial
compounds [154]. Additionally, in MAR systems the biological removal of
densities were found in field and laboratory scale MAR systems, demonstrating that
pharmaceuticals could be linked to co-metabolism rather than to direct substrate
high substrate levels limit the capacity of a microbiome to degrade a broad array of
utilization by comparing the pharmaceutical removal in a pre-exposed microbial
compounds [154]. Additionally, in MAR systems the biological removal of
community to a unexposed community [4]. The authors found a similar
pharmaceuticals could be linked to co-metabolism rather than to direct substrate
pharmaceutical removal in pre-exposed and unexposed microbial communities,
utilization by comparing the pharmaceutical removal in a pre-exposed microbial
suggesting that microbial adaptation to pharmaceuticals did not occur. Hence, the
community to a unexposed community [4]. The authors found a similar
utilization of pharmaceuticals as primary substrate is unlikely which is further
pharmaceutical removal in pre-exposed and unexposed microbial communities,
supported by the high concentration difference between pharmaceuticals and other
suggesting that microbial adaptation to pharmaceuticals did not occur. Hence, the
substrates in MAR systems. Instead of adaptation, the capacity for pharmaceutical
utilization of pharmaceuticals as primary substrate is unlikely which is further
degradation is dictated by other factors which influence the microbial community such
supported by the high concentration difference between pharmaceuticals and other
as the composition and concentration of primary substrates [4]. In most
substrates in MAR systems. Instead of adaptation, the capacity for pharmaceutical
environments primary substrates are present in higher concentrations than
degradation is dictated by other factors which influence the microbial community such
pharmaceuticals, e.g. raw wastewater, primary clarified effluent, secondary clarified
as the composition and concentration of primary substrates [4]. In most
effluent, surface water and groundwater, most likely favouring co-metabolic
environments primary substrates are present in higher concentrations than
degradation. Similarly, the work presented in Chapter 3 showed that photocatalytic
pharmaceuticals, e.g. raw wastewater, primary clarified effluent, secondary clarified
products enhanced the subsequent biodegradation of atorvastatin, caffeine,
effluent, surface water and groundwater, most likely favouring co-metabolic
diclofenac, gemfibrozil and ibuprofen. Based on the literature it was postulated that
degradation. Similarly, the work presented in Chapter 3 showed that photocatalytic
biodegradation of photocatalytic products generated intracellular electron carriers
products enhanced the subsequent biodegradation of atorvastatin, caffeine,
diclofenac, gemfibrozil and ibuprofen. Based on the literature it was postulated that
130
biodegradation of photocatalytic products generated intracellular electron carriers
130
Chapter 6
that initiated the initial mono-oxygenation reaction for biodegradation of the

Chapter 6
pharmaceuticals, suggesting that co-metabolisms was highly important. In contrast,
adaptation to pharmaceuticals was found in Chapter 2 as pharmaceutical removal in
that initiated the initial mono-oxygenation reaction for biodegradation of the
batch experiments enhanced after re-spiking pharmaceuticals. Pharmaceuticals
pharmaceuticals, suggesting that co-metabolisms was highly important. In contrast,
dissolved in methanol were added multiple times without the addition of other OM
adaptation to pharmaceuticals was found in Chapter 2 as pharmaceutical removal in
sources. As every re-spike contained the same ratio of pharmaceuticals to methanol
batch experiments enhanced after re-spiking pharmaceuticals. Pharmaceuticals
the observed increase in removal efficiency could be related to adaptation or to an
dissolved in methanol were added multiple times without the addition of other OM
increase of pharmaceutical degrading biomass. Hence, the role of microbial
sources. As every re-spike contained the same ratio of pharmaceuticals to methanol
adaptation and co-metabolic degradation in the biological removal of pharmaceuticals
the observed increase in removal efficiency could be related to adaptation or to an
remains ambiguous. Likely, the microbial adaptation differs per individual
increase of pharmaceutical degrading biomass. Hence, the role of microbial
pharmaceutical as was also found for non-pharmaceutical contaminants by Spain and
adaptation and co-metabolic degradation in the biological removal of pharmaceuticals
Van Veld [246]. In their study on pre-exposed and unexposed microbial communities
remains ambiguous. Likely, the microbial adaptation differs per individual
adaptation was found towards 2,4-dichlorophenoxyacetic acid and p-nitrophenol,
pharmaceutical as was also found for non-pharmaceutical contaminants by Spain and
whereas no adaptation was found to trifluralin and p-cresol was well degraded in both
Van Veld [246]. In their study on pre-exposed and unexposed microbial communities
communities. Moreover, the contaminant concentration during pre-exposure was
adaptation was found towards 2,4-dichlorophenoxyacetic acid and p-nitrophenol,
found to affect the adaptation, e.g. lower concentrations p-nitrophenol were needed
whereas no adaptation was found to trifluralin and p-cresol was well degraded in both
to achieve adaptation than for methyl parathion [245]. These findings on
communities. Moreover, the contaminant concentration during pre-exposure was
pharmaceuticals and non-pharmaceutical contaminants stress the need for additional
found to affect the adaptation, e.g. lower concentrations p-nitrophenol were needed
research as adaptation can potentially enhance the biodegradation in real
to achieve adaptation than for methyl parathion [245]. These findings on
applications. Therefore further investigations should focus on the functioning of
pharmaceuticals and non-pharmaceutical contaminants stress the need for additional
microbial adaptation and unravel the parameters that steer the adaptation which can
research as adaptation can potentially enhance the biodegradation in real
be used in application.
applications. Therefore further investigations should focus on the functioning of
microbial adaptation and unravel the parameters that steer the adaptation which can
6.2.3 Algae and fungi
be used in application. VI
Biological processes for treatment of various contaminants reported in the
literature mainly concern the utilization of bacteria, e.g. wastewater treatment with
6.2.3 Algae and fungi
activated sludge, anaerobic sludge digestion, in-situ soil remediation and sand
Biological processes for treatment of various contaminants reported in the
filtration in drinking water production. However, also other microorganisms such as
literature mainly concern the utilization of bacteria, e.g. wastewater treatment with
algae or fungi are known for their capacities to degrade or take up various
activated sludge, anaerobic sludge digestion, in-situ soil remediation and sand
contaminants [66, 74, 87, 192]. The use of algal wastewater treatment processes is
filtration in drinking water production. However, also other microorganisms such as
of increasing interest as they provide a clean effluent, and enable resource recovery
algae or fungi are known for their capacities to degrade or take up various
contaminants [66, 74, 87, 192]. The use of algal wastewater treatment processes is
131
of increasing interest as they provide a clean effluent, and enable resource recovery
131
in the form
General of fertilizer,
discussion; protein-rich
towards feed or biofuel
lower pharmaceutical via the harvested algal biomass
emissions
[55]. Most studies focus on the resource recovery by algae, whereas the removal of
pharmaceuticals which are also present in those systems is only limitedly studied.
in the form of fertilizer, protein-rich feed or biofuel via the harvested algal biomass
Chapter 5 describes an algal treatment process for the simultaneous removal of
[55]. Most studies focus on the resource recovery by algae, whereas the removal of
nitrogen and phosphorus and pharmaceuticals in an alternative sanitation system. It
pharmaceuticals which are also present in those systems is only limitedly studied.
was found that algae contributed to the removal of pharmaceuticals while also
Chapter 5 describes an algal treatment process for the simultaneous removal of
recovering nitrogen and phosphate from the wastewater. For instance, metoprolol
nitrogen and phosphorus and pharmaceuticals in an alternative sanitation system. It
removal enhanced in the presence of algae. Sorption and uptake of pharmaceuticals
was found that algae contributed to the removal of pharmaceuticals while also
by algae was limited and was hypothesized be safe for the application of algal biomass
recovering nitrogen and phosphate from the wastewater. For instance, metoprolol
as fertilizer. The photobioreactor in which the algae were cultivated had a positive
removal enhanced in the presence of algae. Sorption and uptake of pharmaceuticals
effect on the pharmaceutical removal as compounds susceptible to photolysis such as
by algae was limited and was hypothesized be safe for the application of algal biomass
diclofenac were effectively removed by photodegradation. Moreover, the naturally
as fertilizer. The photobioreactor in which the algae were cultivated had a positive
present microbes in the wastewater also contributed to the pharmaceutical removal.
effect on the pharmaceutical removal as compounds susceptible to photolysis such as
Hence, a synergy was found in the combination of algal-, microbial- and
diclofenac were effectively removed by photodegradation. Moreover, the naturally
photodegradation for the removal of pharmaceuticals. Similarly, Matamoros et al.
present microbes in the wastewater also contributed to the pharmaceutical removal.
[174] also concluded that algae contributed to the removal of pharmaceuticals from
Hence, a synergy was found in the combination of algal-, microbial- and
wastewater as the presence of algae enhanced ibuprofen and caffeine removal.
photodegradation for the removal of pharmaceuticals. Similarly, Matamoros et al.
Moreover, they did not found uptake of pharmaceuticals by the algae. In an outdoor
[174] also concluded that algae contributed to the removal of pharmaceuticals from
pilot scale algal treatment plant an effective pharmaceutical removal and a
wastewater as the presence of algae enhanced ibuprofen and caffeine removal.
subsequent reduction in hazard quotient were found when operated in a warm
Moreover, they did not found uptake of pharmaceuticals by the algae. In an outdoor
(25±1°C) and cold season (13±1°C) [173]. Nevertheless, this was achieved at HRTs
pilot scale algal treatment plant an effective pharmaceutical removal and a
of 4 and 8 days and a reactor of depth of 0.3 cm to allow sunlight penetration into
subsequent reduction in hazard quotient were found when operated in a warm
the reactor. Hence, these HRTs and reactor depths exhibit a large surface footprint
(25±1°C) and cold season (13±1°C) [173]. Nevertheless, this was achieved at HRTs
and are thereby unrealistic design parameters for densely populated countries like
of 4 and 8 days and a reactor of depth of 0.3 cm to allow sunlight penetration into
the Netherlands where available land is scarce and costly. Moreover, algal treatment
the reactor. Hence, these HRTs and reactor depths exhibit a large surface footprint
systems require light input and moderate to high temperatures for algae growth.
and are thereby unrealistic design parameters for densely populated countries like
Climate conditions in the Netherlands were found unsuitable for WWTP effluent post-
the Netherlands where available land is scarce and costly. Moreover, algal treatment
treatment by algal biofilm reactors as solar irradiance levels and temperatures were
systems require light input and moderate to high temperatures for algae growth.
not high enough to support sufficient algal biomass growth [29]. Therefore outdoor
Climate conditions in the Netherlands were found unsuitable for WWTP effluent post-
solar based algal reactors for resource recovery and pharmaceutical removal are
treatment by algal biofilm reactors as solar irradiance levels and temperatures were
hypothesized not to be a feasible treatment option in the Netherlands. However, for
not high enough to support sufficient algal biomass growth [29]. Therefore outdoor
solar based algal reactors for resource recovery and pharmaceutical removal are
132
hypothesized not to be a feasible treatment option in the Netherlands. However, for
132
Chapter 6
locations at lower latitudes (e.g. in Spain), for events like festivals or campsites during
Chapter 6
summer in the Netherlands when irradiation and temperatures are higher or for
systems running on artificial light sources like LED-UV systems in temperature
locations at lower latitudes (e.g. in Spain), for events like festivals or campsites during
controlled greenhouses an algae based process might be a versatile treatment
summer in the Netherlands when irradiation and temperatures are higher or for
system. The continuous improvements of LED irradiation suggest that LED based algal
systems running on artificial light sources like LED-UV systems in temperature
treatment systems, preferably combined with solar irradiance, can become a cost-
controlled greenhouses an algae based process might be a versatile treatment
effective wastewater treatment process. Further research is recommended to focus
system. The continuous improvements of LED irradiation suggest that LED based algal
on the technical and financial feasibility of LED based algal treatment systems in
treatment systems, preferably combined with solar irradiance, can become a cost-
greenhouses for the cost-effective recovery of nutrients and simultaneous
effective wastewater treatment process. Further research is recommended to focus
pharmaceutical removal from wastewater. Moreover, research has to include a much
on the technical and financial feasibility of LED based algal treatment systems in
wider pallet of pharmaceuticals and toxicity assessment of the effluent as both are
greenhouses for the cost-effective recovery of nutrients and simultaneous
currently limitedly understood.
pharmaceutical removal from wastewater. Moreover, research has to include a much
Among the various fungi species used in biological treatment processes, white-
wider pallet of pharmaceuticals and toxicity assessment of the effluent as both are
rot fungi and their enzymes have been well studied for the removal of pharmaceuticals
currently limitedly understood.
[56]. These organisms have a ligninolytic enzymatic system allowing them to produce
Among the various fungi species used in biological treatment processes, white-
extracellular enzymes which can target various contaminants in a non-specific and
rot fungi and their enzymes have been well studied for the removal of pharmaceuticals
radical based manner [45]. Their ability to produce strong oxidants like peroxide
[56]. These organisms have a ligninolytic enzymatic system allowing them to produce
effectively targets compounds that persist in other biological treatment processes
extracellular enzymes which can target various contaminants in a non-specific and
such as the recalcitrant pharmaceutical carbamazepine [223]. Although white-rot
radical based manner [45]. Their ability to produce strong oxidants like peroxide
fungi are promising for pharmaceutical removal, issues related to the contamination
effectively targets compounds that persist in other biological treatment processes
of the reactors, and thereby the competition with other microorganism suppressing
such as the recalcitrant pharmaceutical carbamazepine [223]. Although white-rot
the fungi, have been identified when culturing them under non-sterile conditions using
fungi are promising for pharmaceutical removal, issues related to the contamination
real wastewater [19, 156]. This might be one of the reasons why implementation of
of the reactors, and thereby the competition with other microorganism suppressing
fungal based technologies in domestic wastewater treatment is limited.
the fungi, have been identified when culturing them under non-sterile conditions using VI
real wastewater [19, 156]. This might be one of the reasons why implementation of
6.2.4 Opportunities in biological treatment
fungal based technologies in domestic wastewater treatment is limited.
Multiple biological processes and the parameters influencing these processes
have been studied for the removal of pharmaceuticals. Findings of these studies have
6.2.4 Opportunities in biological treatment
resulted in a better understanding of biological treatment processes and relevant
Multiple biological processes and the parameters influencing these processes
aspects for the design and operation of them. Nevertheless none of them, nor a
have been studied for the removal of pharmaceuticals. Findings of these studies have
combination of them, has been found adequate to achieve a complete removal of the
resulted in a better understanding of biological treatment processes and relevant
aspects for the design and operation of them. Nevertheless none of them, nor a
combination of them, has been found adequate to achieve a complete removal of 133
the
133
pharmaceuticals typically
General discussion; towardsfound in pharmaceutical
lower wastewater [1,emissions
83, 164, 222]. Similarly, in this
dissertation (Chapters 2-5) it was demonstrated that biological processes do not form
an effective barrier against all pharmaceuticals. Large molecules typically persist
pharmaceuticals typically found in wastewater [1, 83, 164, 222]. Similarly, in this
during biological treatment, whereas intermediate or small size molecules are easily
dissertation (Chapters 2-5) it was demonstrated that biological processes do not form
biodegraded or even mineralized [165]. In combination with additional treatment
an effective barrier against all pharmaceuticals. Large molecules typically persist
steps targeting large molecules, biological removal might therefore be a versatile
during biological treatment, whereas intermediate or small size molecules are easily
treatment process. Reflecting on the outcomes of this dissertation several
biodegraded or even mineralized [165]. In combination with additional treatment
recommendations are given regarding the design and operation of biological
steps targeting large molecules, biological removal might therefore be a versatile
processes when biological treatment is considered for pharmaceutical removal.
treatment process. Reflecting on the outcomes of this dissertation several
Concerning bacterial based processes, it is recommended to incorporate multiple
recommendations are given regarding the design and operation of biological
redox stages, including fully aerobic and methanogenic conditions, to create niches
processes when biological treatment is considered for pharmaceutical removal.
for a diverse microbial community targeting a wide spectrum of pharmaceuticals. In
Concerning bacterial based processes, it is recommended to incorporate multiple
addition, pharmaceutical removal can be best accomplished under oligotrophic
redox stages, including fully aerobic and methanogenic conditions, to create niches
conditions, i.e. in a post-treatment step where primary substrate levels are low. In
for a diverse microbial community targeting a wide spectrum of pharmaceuticals. In
case of sub-optimal performance of the secondary treatment and clarification, a two-
addition, pharmaceutical removal can be best accomplished under oligotrophic
step process might be desired to remove primary substrates in the first and
conditions, i.e. in a post-treatment step where primary substrate levels are low. In
pharmaceuticals in the second step. When irradiance levels and temperatures allow a
case of sub-optimal performance of the secondary treatment and clarification, a two-
cost-effective algae growth, algal treatment systems are recommended as they form
step process might be desired to remove primary substrates in the first and
a barrier against multiple pharmaceuticals and provide opportunities for resource
pharmaceuticals in the second step. When irradiance levels and temperatures allow a
recovery. However, algal treatment systems have their limitations regarding
cost-effective algae growth, algal treatment systems are recommended as they form
pharmaceutical removal. For a safe direct reused or discharge effluents of algal
a barrier against multiple pharmaceuticals and provide opportunities for resource
treatment systems the non-removed pharmaceuticals should therefore be additionally
recovery. However, algal treatment systems have their limitations regarding
treated by other treatment processes. Therefore it is recommended for future
pharmaceutical removal. For a safe direct reused or discharge effluents of algal
research focusing on sustainable water treatment to employ algal treatment systems
treatment systems the non-removed pharmaceuticals should therefore be additionally
in combination with other processes for the efficient resource-recovery and a safe
treated by other treatment processes. Therefore it is recommended for future
effluent production.
research focusing on sustainable water treatment to employ algal treatment systems
Research on biological removal processes is ongoing and will continue,
in combination with other processes for the efficient resource-recovery and a safe
nevertheless it is questionable with the obtained knowledge of the past decades
effluent production.
whether it can be expected that a biological process will remove the highly complex
Research on biological removal processes is ongoing and will continue,
mixture of structurally diverse pharmaceuticals. Considering that pharmaceuticals are
nevertheless it is questionable with the obtained knowledge of the past decades
only part of the micropollutants which are currently detected in wastewater the entire
whether it can be expected that a biological process will remove the highly complex
mixture of structurally diverse pharmaceuticals. Considering that pharmaceuticals are
134of the micropollutants which are currently detected in wastewater the entire
only part
134
Chapter 6
load of harmful compounds at low concentrations is much higher which further6

Chapter
complicates an adequate elimination of all of these insidious compounds. Nonetheless,
biological processes can be part of a broader treatment system for the cost-effective
load of harmful compounds at low concentrations is much higher which further
removal of micropollutants which justifies the further investigation and understanding
complicates an adequate elimination of all of these insidious compounds. Nonetheless,
into biological processes. Research opportunities lie, amongst others, in the further
biological processes can be part of a broader treatment system for the cost-effective
unravelling of metabolic pathways of pharmaceutical degradation. A better
removal of micropollutants which justifies the further investigation and understanding
understanding of degradation pathways can result in the further optimization of
into biological processes. Research opportunities lie, amongst others, in the further
biological processes by steering for specific conditions favouring enzymatic systems
unravelling of metabolic pathways of pharmaceutical degradation. A better
involved in pharmaceutical degradation. Moreover, insight in the diversity of involved
understanding of degradation pathways can result in the further optimization of
metabolic pathways can indicate to what extend different enzymatic systems are
biological processes by steering for specific conditions favouring enzymatic systems
needed for the degradation of a broad spectrum of pharmaceuticals. This can be
involved in pharmaceutical degradation. Moreover, insight in the diversity of involved
useful for the design of a comparted biological treatment, creating optimal conditions
metabolic pathways can indicate to what extend different enzymatic systems are
for specific metabolic pathways in each compartment to target specific
needed for the degradation of a broad spectrum of pharmaceuticals. This can be
pharmaceuticals. First steps have been made in the field of understanding the
useful for the design of a comparted biological treatment, creating optimal conditions
metabolic pathways involved in pharmaceutical degradation [97, 182, 299, 300]. Yet,
for specific metabolic pathways in each compartment to target specific
to date, there is still a limited understanding of all enzymatic processes involved in
pharmaceuticals. First steps have been made in the field of understanding the
pharmaceutical degradation. Although research suggests that biological
metabolic pathways involved in pharmaceutical degradation [97, 182, 299, 300]. Yet,
pharmaceutical removal follows co-metabolic degradation pathways conclusive
to date, there is still a limited understanding of all enzymatic processes involved in
enzymatic evidence to confirm this is still lacking [4].
pharmaceutical degradation. Although research suggests that biological
pharmaceutical removal follows co-metabolic degradation pathways conclusive
6.3 Pharmaceutical
enzymatic removal
evidence to confirm by
this is chemical
still treatment
lacking [4].
Chemical treatment processes involving ozonation, photolysis, photocatalysis,
hydrogen peroxide, chlorination, Fenton’s reagent, electrolysis, ultrasound, ionising
6.3 Pharmaceutical removal by chemical treatment
radiation, microwaves and pulsed plasma have been applied for drinking water
Chemical treatment processes involving ozonation, photolysis, photocatalysis, VI
treatment, industrial wastewater treatment as well as in domestic wastewater
hydrogen peroxide, chlorination, Fenton’s reagent, electrolysis, ultrasound, ionising
treatment [52, 264].
radiation, microwaves and pulsed plasma have been applied for drinking water
In drinking water sources numerous contaminants and matrix constituents are
treatment, industrial wastewater treatment as well as in domestic wastewater
present at very low (ng/L) and low (mg/L) concentrations, respectively [264]. Hence,
treatment [52, 264].
the production of drinking water free of contaminants and low in matrix constituents
In drinking water sources numerous contaminants and matrix constituents are
favours one or more generic treatment steps. Industrial wastewaters typically contain
present at very low (ng/L) and low (mg/L) concentrations, respectively [264]. Hence,
the production of drinking water free of contaminants and low in matrix constituents
favours one or more generic treatment steps. Industrial wastewaters typically contain
135
135
a limiteddiscussion;
General number oftowards
contaminants present at high
lower pharmaceutical concentrations (g/L) in simple
emissions
matrices which eases a tailor made design of effective treatment processes [165].
In contrast, domestic WWTP effluents comprise a highly diverse mixture of
a limited number of contaminants present at high concentrations (g/L) in simple
matrix constituents typically present at orders of magnitude higher concentrations
matrices which eases a tailor made design of effective treatment processes [165].
compared to contaminants like pharmaceuticals. Moreover, WWTP effluent
In contrast, domestic WWTP effluents comprise a highly diverse mixture of
contaminants cover an array of structurally different compounds. Chemical treatment
matrix constituents typically present at orders of magnitude higher concentrations
processes effectively oxidize large molecules into smaller intermediates, however full
compared to contaminants like pharmaceuticals. Moreover, WWTP effluent
mineralization in the chemical treatment is often cost-intensive and thereby
contaminants cover an array of structurally different compounds. Chemical treatment
undesired. Therefore, combining chemical and biological processes for a complete
processes effectively oxidize large molecules into smaller intermediates, however full
mineralisation can be a favourable approach [165]. Even though chemical treatment
mineralization in the chemical treatment is often cost-intensive and thereby
processes can be highly effective for the removal of waterborne contaminants, the
undesired. Therefore, combining chemical and biological processes for a complete
ratio between matrix and contaminant concentrations and the diversity in
mineralisation can be a favourable approach [165]. Even though chemical treatment
contaminant chemical structures complicates the design of cost-effective and
processes can be highly effective for the removal of waterborne contaminants, the
sustainable treatment processes. Processes targeting specific contaminants do not
ratio between matrix and contaminant concentrations and the diversity in
provide the removal of a broad spectrum of contaminants, whereas more generic
contaminant chemical structures complicates the design of cost-effective and
processes inevitably result in the reaction with matrix constituents reducing the
sustainable treatment processes. Processes targeting specific contaminants do not
removal efficiency for target contaminants. As a result, each individual situation
provide the removal of a broad spectrum of contaminants, whereas more generic
therefore requires the assessment of the most adequate and cost-effective treatment
processes inevitably result in the reaction with matrix constituents reducing the
system.
removal efficiency for target contaminants. As a result, each individual situation
Recently, chemical treatment processes of a more generic character like
therefore requires the assessment of the most adequate and cost-effective treatment
ozonation and AC filtration have been well studied and locally implemented at WWTPs
system.
in post-treatment steps for pharmaceutical removal [73]. First results of their full
Recently, chemical treatment processes of a more generic character like
scale implementation indicate that these processes can result in the effective removal
ozonation and AC filtration have been well studied and locally implemented at WWTPs
of pharmaceuticals. Nevertheless, ozonation still raises concerns on the formation of
in post-treatment steps for pharmaceutical removal [73]. First results of their full
potentially toxic transformation products, whereas AC filtration requires the
scale implementation indicate that these processes can result in the effective removal
regeneration or replacement of the AC questioning the sustainability and cost-
of pharmaceuticals. Nevertheless, ozonation still raises concerns on the formation of
effectiveness of the process. In addition, a one to one translation of these results to
potentially toxic transformation products, whereas AC filtration requires the
other places is hampered by differences in local raw wastewater qualities and the site-
regeneration or replacement of the AC questioning the sustainability and cost-
specific performance of primary and secondary treatment processes. For example,
effectiveness of the process. In addition, a one to one translation of these results to
OM concentrations in secondary clarified effluents from individual Swiss, Japanese
other places is hampered by differences in local raw wastewater qualities and the site-
and U.S. WWTPs are two to ten times lower compared to those from individual
specific performance of primary and secondary treatment processes. For example,
OM concentrations in secondary clarified effluents from individual Swiss, Japanese
136WWTPs are two to ten times lower compared to those from individual
and U.S.
136
Chapter 6
Australian, German, U.S. and Dutch WWTPs (Chapter 4) [109, 111, 117, Chapter
150, 193,
6
265, 298, 329]. At high OM concentrations or in the presence of specific molecular
size OM fractions, pharmaceutical removal efficiencies in ozonation or AC filtration
Australian, German, U.S. and Dutch WWTPs (Chapter 4) [109, 111, 117, 150, 193,
drastically decrease [151, 327]. An investigated solution to overcome this problem is
265, 298, 329]. At high OM concentrations or in the presence of specific molecular
the combination of pre-ozonation followed by AC filtration in which the incoming OM
size OM fractions, pharmaceutical removal efficiencies in ozonation or AC filtration
is partially converted by ozonation into smaller molecule sizes which only limitedly
drastically decrease [151, 327]. An investigated solution to overcome this problem is
compete with pharmaceuticals for AC sorption sites [218, 328]. This is however a
the combination of pre-ozonation followed by AC filtration in which the incoming OM
resource intensive and costly treatment and might not be the most sustainable
is partially converted by ozonation into smaller molecule sizes which only limitedly
combination of processes.
compete with pharmaceuticals for AC sorption sites [218, 328]. This is however a
In other chemical processes employing oxidants such as hydrogen peroxide or
resource intensive and costly treatment and might not be the most sustainable
Fenton’s reagent for pharmaceutical removal OM matter is also known to reduce
combination of processes.
process efficiencies since it acts as an oxidant scavenger [22]. This suggests that pre-
In other chemical processes employing oxidants such as hydrogen peroxide or
treatment processes targeting OM removal could be of great interest as they increase
Fenton’s reagent for pharmaceutical removal OM matter is also known to reduce
chemical treatment of pharmaceuticals. Some pre-treatment processes have been
process efficiencies since it acts as an oxidant scavenger [22]. This suggests that pre-
investigated like the use of anion exchange. This process effectively removed the OM
treatment processes targeting OM removal could be of great interest as they increase
humic acid fraction of a WWTP effluent and resulted in an 84% lower energy demand
chemical treatment of pharmaceuticals. Some pre-treatment processes have been
for the subsequent UV/H2O2 treatment process aiming at pharmaceutical removal
investigated like the use of anion exchange. This process effectively removed the OM
[109]. Nevertheless, the costs associated to the combination of anion exchange and
humic acid fraction of a WWTP effluent and resulted in an 84% lower energy demand
subsequent UV/H2O2 treatment are relatively high as they increase the wastewater
for the subsequent UV/H2O2 treatment process aiming at pharmaceutical removal
treatment costs by approximately 75% [280]. Overall, there is a need for more cost-
[109]. Nevertheless, the costs associated to the combination of anion exchange and
effective and sustainable treatment processes including combinations of chemical and
subsequent UV/H2O2 treatment are relatively high as they increase the wastewater
biological processes, as currently there are only a few available for wastewater
treatment costs by approximately 75% [280]. Overall, there is a need for more cost-
treatment [198].
effective and sustainable treatment processes including combinations of chemical and
biological processes, as currently there are only a few available for wastewater VI
6.4 Synergy
treatment [198].between biological and chemical treatment processes
for pharmaceutical removal
Multiple combinations
6.4 Synergy of biological
between biological andand chemical treatment
chemical treatment processes have
processes
been demonstrated to be advantageous over single processes [120, 235]. In
for pharmaceutical removal
industries this concept is well introduced as combined process are used to treat
Multiple combinations of biological and chemical treatment processes have
textile, paper mill, winery, distillery and olive mill wastewaters [198]. The capacity of
been demonstrated to be advantageous over single processes [120, 235]. In
chemical treatment processes targeting non-biodegradable compounds to increase
industries this concept is well introduced as combined process are used to treat
textile, paper mill, winery, distillery and olive mill wastewaters [198]. The capacity of
137
chemical treatment processes targeting non-biodegradable compounds to increase
137
their biodegradability
General by forlower
discussion; towards instance a strong oxidant
pharmaceutical attack is the most known
emissions
combination. Chemical treatment is effective for oxidation of large molecules into
smaller intermediates, but not for full mineralization, whereas biological treatment
their biodegradability by for instance a strong oxidant attack is the most known
can effectively degrade and mineralize intermediate and small size molecules [165].
combination. Chemical treatment is effective for oxidation of large molecules into
The tipping point after which further chemical treatment is no more attractive and
smaller intermediates, but not for full mineralization, whereas biological treatment
biological treatment performs better is depicted in Figure 6.1. Moreover, as biological
can effectively degrade and mineralize intermediate and small size molecules [165].
treatment is generally cheaper and more sustainable than chemical treatment, the
The tipping point after which further chemical treatment is no more attractive and
latter is typically used as a short pre-treatment increasing the biodegradability and
biological treatment performs better is depicted in Figure 6.1. Moreover, as biological
reducing the overall treatment costs [52]. Although in industries the combination of
treatment is generally cheaper and more sustainable than chemical treatment, the
biological and chemical treatment processes is well introduced [198], it is only
latter is typically used as a short pre-treatment increasing the biodegradability and
limitedly applied in wastewater treatment. Chapters 3, 4 and 5 of this dissertation
reducing the overall treatment costs [52]. Although in industries the combination of
describe combinations of biological and chemical processes for pharmaceutical
biological and chemical treatment processes is well introduced [198], it is only
removal from wastewater with a focus on an unique combination in each chapter. The
limitedly applied in wastewater treatment. Chapters 3, 4 and 5 of this dissertation
studied combinations are further discussed in this section.
describe combinations of biological and chemical processes for pharmaceutical
removal from wastewater with a focus on an unique combination in each chapter. The
studied combinations are further discussed in this section.
Figure 6.1 The concept of combined chemical and biological treatment (adapted from [165])
Figure 6.1 The concept of combined chemical and biological treatment (adapted from [165])
138
138
Chapter 6
6.4.1 Chemical pre-treatment for enhanced biological pharmaceutical

Chapter 6
removal
Photocatalysis utilizing TiO2 to catalyse the reaction of UV-light with organic
6.4.1 Chemical pre-treatment for enhanced biological pharmaceutical
contaminants is a well-known treatment process and widely employed in diverse
removal
water treatment systems [52, 103, 126]. Sunlight based TiO2 photocatalytic
Photocatalysis utilizing TiO2 to catalyse the reaction of UV-light with organic
processes have been successfully demonstrated, but are limitedly applied compared
contaminants is a well-known treatment process and widely employed in diverse
to systems using UV-lamps as the UV content of solar irradiation reaching the earth
water treatment systems [52, 103, 126]. Sunlight based TiO2 photocatalytic
surface is only 3-5% [10, 22]. The use of UV-LED as alternative to traditional energy
processes have been successfully demonstrated, but are limitedly applied compared
intensive UV-lamps has greatly increased the process resource efficiency [194].
to systems using UV-lamps as the UV content of solar irradiation reaching the earth
Furthermore, the ongoing research on immobilized forms of TiO2 is hypothesized to
surface is only 3-5% [10, 22]. The use of UV-LED as alternative to traditional energy
further improve the sustainability and cost-effectiveness of TiO2 photocatalysis [16].
intensive UV-lamps has greatly increased the process resource efficiency [194].
Successful removal of pharmaceuticals from wastewater by TiO2 photocatalysis is
Furthermore, the ongoing research on immobilized forms of TiO2 is hypothesized to
reported, however the type and concentration of TiO2 and the process reaction time
further improve the sustainability and cost-effectiveness of TiO2 photocatalysis [16].
highly influence the degree of removal, i.e. good removal is achieved at high TiO2
Successful removal of pharmaceuticals from wastewater by TiO2 photocatalysis is
levels and long irradiation times [272]. Moreover, TiO2 photocatalytic pharmaceutical
reported, however the type and concentration of TiO2 and the process reaction time
removal is associated to the formation of toxic transformation products. These
highly influence the degree of removal, i.e. good removal is achieved at high TiO2
undesirable aspects can hamper the implementation of this promising technology, but
levels and long irradiation times [272]. Moreover, TiO2 photocatalytic pharmaceutical
can possibly be overcome when combining photocatalysis with biodegradation.
removal is associated to the formation of toxic transformation products. These
Chapter 3 therefore describes a mild photocatalytic TiO2 process followed by
undesirable aspects can hamper the implementation of this promising technology, but
biological treatment for pharmaceutical removal as a resource efficient alternative to
can possibly be overcome when combining photocatalysis with biodegradation.
single TiO2 photocatalysis. Similar to the literature, a selection of pharmaceuticals
Chapter 3 therefore describes a mild photocatalytic TiO2 process followed by
was removed by the employed photocatalysis whereas other persisted [15].
biological treatment for pharmaceutical removal as a resource efficient alternative to
Unexpectedly, in the subsequent biological treatment the degradation of atorvastatin,
single TiO2 photocatalysis. Similar to the literature, a selection of pharmaceuticals
caffeine, gemfibrozil and ibuprofen enhanced after photocatalytic pre-treatment, even
was removed by the employed photocatalysis whereas other persisted [15]. VI
though most of them were not targeted by photocatalysis. In addition, the
Unexpectedly, in the subsequent biological treatment the degradation of atorvastatin,
biodegradation of diclofenac was observed after photocatalytic pre-treatment
caffeine, gemfibrozil and ibuprofen enhanced after photocatalytic pre-treatment, even
whereas it persisted in biological control experiments without pre-treatment. Based
though most of them were not targeted by photocatalysis. In addition, the
on the literature on photocatalytic products and biodegradation pathways it was
biodegradation of diclofenac was observed after photocatalytic pre-treatment
postulated that intermediates formed during photocatalysis stimulated the
whereas it persisted in biological control experiments without pre-treatment. Based
biodegradation of pharmaceuticals. Hence, besides the benefits of combining chemical
on the literature on photocatalytic products and biodegradation pathways it was
pre-treatment with biological treatment for cost-effective mineralization of large
postulated that intermediates formed during photocatalysis stimulated the
biodegradation of pharmaceuticals. Hence, besides the benefits of combining chemical
139
pre-treatment with biological treatment for cost-effective mineralization of large
139
molecules it can betowards

General discussion; stated lower
that the biological treatment
pharmaceutical emissionsof pharmaceuticals also
benefits from the presence of photocatalytic products for the enhanced
biodegradation of parent compounds, i.e. pharmaceuticals. Next to the ongoing
molecules it can be stated that the biological treatment of pharmaceuticals also
advancements on TiO2 immobilization and UV-LED application, employing a mild
benefits from the presence of photocatalytic products for the enhanced
photocatalysis with subsequent biological treatment further increases the
biodegradation of parent compounds, i.e. pharmaceuticals. Next to the ongoing
sustainability. Overall, the enhanced biodegradation and improved sustainability are
advancements on TiO2 immobilization and UV-LED application, employing a mild
expected to stimulate the implementation of this combined treatment process. It
photocatalysis with subsequent biological treatment further increases the
should be noted that our findings were obtained using a clean matrix and powdered
sustainability. Overall, the enhanced biodegradation and improved sustainability are
TiO2, therefore further research on real WWTP effluents and using immobilized TiO2
expected to stimulate the implementation of this combined treatment process. It
is strongly recommended. Moreover, the toxicity of the final effluent should be
should be noted that our findings were obtained using a clean matrix and powdered
carefully assessed albeit potentially toxic photocatalytic products will most likely be
TiO2, therefore further research on real WWTP effluents and using immobilized TiO2
removed during the biological treatment.
is strongly recommended. Moreover, the toxicity of the final effluent should be
carefully assessed albeit potentially toxic photocatalytic products will most likely be
6.4.2 Biological pre-treatment for enhanced chemical pharmaceutical
removed during the biological treatment.
removal
The strong oxidative power of ozone towards a broad spectrum of
6.4.2 Biological pre-treatment for enhanced chemical pharmaceutical
micropollutants including pharmaceuticals is well studied and locally implemented as
removal
post-treatment in wastewater treatment [73]. Equal to the approach of combining
The strong oxidative power of ozone towards a broad spectrum of
chemical treatment followed by biological treatment used in industries, ozonation is
micropollutants including pharmaceuticals is well studied and locally implemented as
followed by sand-filtration for the initial chemical oxidative of large molecules and the
post-treatment in wastewater treatment [73]. Equal to the approach of combining
subsequent biodegradation for their further degradation or even mineralization [111,
chemical treatment followed by biological treatment used in industries, ozonation is
165]. This is an effective strategy when concentrations of matrix constituents like OM,
followed by sand-filtration for the initial chemical oxidative of large molecules and the
nitrite or other compounds competing for ozone with the target contaminants are
subsequent biodegradation for their further degradation or even mineralization [111,
present at minute levels. In case matrix composition and concentration are in
165]. This is an effective strategy when concentrations of matrix constituents like OM,
competition with contaminants for ozone other strategies should be employed. A
nitrite or other compounds competing for ozone with the target contaminants are
three-step design was therefore presented in Chapter 4 incorporating biological
present at minute levels. In case matrix composition and concentration are in
treatment, ozonation and biological treatment as the investigated secondary clarified
competition with contaminants for ozone other strategies should be employed. A
effluent comprised relatively high OM levels, i.e. 17 mg TOC/L. These OM levels
three-step design was therefore presented in Chapter 4 incorporating biological
required an opposing paradigm to the industrial design scheme where chemical
treatment, ozonation and biological treatment as the investigated secondary clarified
treatment supports the biological treatment. In the proposed BO3B design biological
effluent comprised relatively high OM levels, i.e. 17 mg TOC/L. These OM levels
pre-treatment facilitates the ozone treatment by removing matrix constituents that
required an opposing paradigm to the industrial design scheme where chemical
treatment supports the biological treatment. In the proposed BO3B design biological
140
pre-treatment facilitates the ozone treatment by removing matrix constituents that
140
Chapter 6
scavenge the ozone reaction with biorecalcitrant pharmaceuticals prior toChapter

entering
6
the ozone reactor. As 38% TOC removal was accomplished during biological pre-
treatment, this design allowed a minimal ozone input. The BO3B process effectively
scavenge the ozone reaction with biorecalcitrant pharmaceuticals prior to entering
removed biodegradable and biorecalcitrant pharmaceuticals, as the removal
the ozone reactor. As 38% TOC removal was accomplished during biological pre-
mechanisms of biological treatment and ozonation targeted different
treatment, this design allowed a minimal ozone input. The BO3B process effectively
pharmaceuticals. Finally, the ozonation transformation products are biodegraded in
removed biodegradable and biorecalcitrant pharmaceuticals, as the removal
the last biological treatment step before being discharged into the environment.
mechanisms of biological treatment and ozonation targeted different
Although the BO3B design incorporates three reactors, the estimated costs are low
pharmaceuticals. Finally, the ozonation transformation products are biodegraded in
and would increase the costs for current treatment by less than 15%. The BO 3B
the last biological treatment step before being discharged into the environment.
process is therefore a versatile alternative combination of treatment processes
Although the BO3B design incorporates three reactors, the estimated costs are low
compared to combinations such as ozonation and AC filtration which have been
and would increase the costs for current treatment by less than 15%. The BO 3B
demonstrated to effectively remove pharmaceuticals [218]. However, the
process is therefore a versatile alternative combination of treatment processes
combination of biological treatment with ozonation instead of AC filtration with
compared to combinations such as ozonation and AC filtration which have been
ozonation makes the process more sustainable as no regeneration or replacement of
demonstrated to effectively remove pharmaceuticals [218]. However, the
AC is needed and cost associated to biological treatment are generally lower than
combination of biological treatment with ozonation instead of AC filtration with
those for AC filtration.
ozonation makes the process more sustainable as no regeneration or replacement of
AC is needed and cost associated to biological treatment are generally lower than
6.4.3 Simultaneous biological and chemical treatment for
those for AC filtration.
pharmaceutical removal
Chemical treatment processes applied for the removal of organic compounds
6.4.3 Simultaneous biological and chemical treatment for
also exhibit disinfection properties. In drinking water production disinfection is one of
pharmaceutical removal
the main reasons why chemical processes are employed [242, 294]. As disinfection
Chemical treatment processes applied for the removal of organic compounds
has negative effects on microorganisms applied in biological treatment, there are only
also exhibit disinfection properties. In drinking water production disinfection is one of
a few examples of versatile combinations of simultaneous biological and chemical
the main reasons why chemical processes are employed [242, 294]. As disinfection VI
treatment processes. A well-known combination are algal treatment systems, such as
has negative effects on microorganisms applied in biological treatment, there are only
the photobioreactors investigated in Chapter 5. Treatment systems employing algae
a few examples of versatile combinations of simultaneous biological and chemical
are a combination of chemical and biological processes as the metabolism of algae
treatment processes. A well-known combination are algal treatment systems, such as
requires photons, i.e. light. Thus, photodegradation and biodegradation can occur
the photobioreactors investigated in Chapter 5. Treatment systems employing algae
simultaneously. We observed effective removal by photodegradation alone or in
are a combination of chemical and biological processes as the metabolism of algae
combination with biodegradation of pharmaceuticals such as diclofenac and
requires photons, i.e. light. Thus, photodegradation and biodegradation can occur
metoprolol, respectively. Although the findings of the investigated combination are
simultaneously. We observed effective removal by photodegradation alone or in
combination with biodegradation of pharmaceuticals such as diclofenac and
metoprolol, respectively. Although the findings of the investigated combination 141
are
141
promising,
General major drawbacks
discussion; have pharmaceutical
towards lower been identified.emissions
For instance, only a selection of
pharmaceuticals can be effectively removed by photolysis as not all compounds are
susceptible to photolysis, or at an insignificant rate for application in wastewater
promising, major drawbacks have been identified. For instance, only a selection of
treatment [12, 140, 143, 160]. General applicability of photolytic processes is also
pharmaceuticals can be effectively removed by photolysis as not all compounds are
hampered by the differences in wastewaters as matrix constituents like OM, nitrate
susceptible to photolysis, or at an insignificant rate for application in wastewater
and bicarbonate influence the photolysis of pharmaceuticals in different ways
treatment [12, 140, 143, 160]. General applicability of photolytic processes is also
requiring a site-specific evaluation of the photolytic efficiency [143]. This might
hampered by the differences in wastewaters as matrix constituents like OM, nitrate
explain why Matamoros, et al. [174] did not observe photodegradation of ibuprofen
and bicarbonate influence the photolysis of pharmaceuticals in different ways
in their algal photobioreactor running on primary clarified wastewater whereas in
requiring a site-specific evaluation of the photolytic efficiency [143]. This might
Chapter 5 we found that in anaerobically treated black water ibuprofen was
explain why Matamoros, et al. [174] did not observe photodegradation of ibuprofen
photodegraded. Irradiance intensities are also highly important as they influence the
in their algal photobioreactor running on primary clarified wastewater whereas in
photodegradation efficiency of pharmaceuticals [12]. Hence, solar based systems will
Chapter 5 we found that in anaerobically treated black water ibuprofen was
perform poorly at higher latitudes indicating the need of artificial irradiance.
photodegraded. Irradiance intensities are also highly important as they influence the
Although photolytic and biological pharmaceutical removal are complementary
photodegradation efficiency of pharmaceuticals [12]. Hence, solar based systems will
processes for pharmaceutical removal, they do not target all pharmaceuticals.
perform poorly at higher latitudes indicating the need of artificial irradiance.
Biorecalcitrant and photorecalcitrant pharmaceuticals, such as carbamazepine,
Although photolytic and biological pharmaceutical removal are complementary
persist in algal treatment processes. Hence, algal treatment processes exhibit great
processes for pharmaceutical removal, they do not target all pharmaceuticals.
benefits with respect to resource recovery, and for that purpose should be considered
Biorecalcitrant and photorecalcitrant pharmaceuticals, such as carbamazepine,
in wastewater treatment. While they can recover nutrients and remove
persist in algal treatment processes. Hence, algal treatment processes exhibit great
pharmaceuticals simultaneously, additional treatment is required for a full
benefits with respect to resource recovery, and for that purpose should be considered
in wastewater treatment. While they can recover nutrients and remove
Another well-studied combination of simultaneous biological and chemical
pharmaceuticals simultaneously, additional treatment is required for a full
processes is the intimately coupled photocatalysis and biodegradation [307]. Carriers
with an photocatalytic outer surface and attached microorganisms inside the carrier
Another well-studied combination of simultaneous biological and chemical
have demonstrated an effective removal of contaminants like the antibiotic
processes is the intimately coupled photocatalysis and biodegradation [307]. Carriers
tetracycline. The main advantage of this combination is the close distance between
with an photocatalytic outer surface and attached microorganisms inside the carrier
the reactive photocatalytic surface and the microorganisms which facilitates the
have demonstrated an effective removal of contaminants like the antibiotic
instant biodegradation of formed photocatalytic products. To date, this combination
tetracycline. The main advantage of this combination is the close distance between
is mainly tested on lab-scale, therefore it is unknown how effective this process will
the reactive photocatalytic surface and the microorganisms which facilitates the
be on full-scale running on real wastewater.
instant biodegradation of formed photocatalytic products. To date, this combination
is mainly tested on lab-scale, therefore it is unknown how effective this process will
be on full-scale running on real wastewater.
142
142
Chapter 6
6.5 Outlook, opportunities for lower pharmaceutical emissions

Chapter 6
The ongoing contamination of worldwide freshwater bodies by countless
micropollutants, including pharmaceuticals, jeopardizing the environment and human
6.5 Outlook, opportunities for lower pharmaceutical emissions
health is one of the main challenges humanity is facing [233]. Discharge of treated
The ongoing contamination of worldwide freshwater bodies by countless
and untreated domestic wastewater is one of the major micropollutant sources as
micropollutants, including pharmaceuticals, jeopardizing the environment and human
micropollutants are ineffectively removed during conventional wastewater treatment
health is one of the main challenges humanity is facing [233]. Discharge of treated
[234]. This dissertation and research by others has demonstrated the capacity of
and untreated domestic wastewater is one of the major micropollutant sources as
various treatment processes to remove pharmaceuticals from wastewater minimizing
micropollutants are ineffectively removed during conventional wastewater treatment
the further contamination of worldwide freshwater bodies. The use of complementary
[234]. This dissertation and research by others has demonstrated the capacity of
biological and chemical treatment processes has been found highly effective as major
various treatment processes to remove pharmaceuticals from wastewater minimizing
disadvantages of single processes like resource intensiveness or transformation
the further contamination of worldwide freshwater bodies. The use of complementary
product discharge can be tackled by combined treatment processes. A clear outcome
biological and chemical treatment processes has been found highly effective as major
of this dissertation is the inability of single processes for the cost-effectively removal
disadvantages of single processes like resource intensiveness or transformation
of a broad array of structurally highly different molecules in a complex matrix like
product discharge can be tackled by combined treatment processes. A clear outcome
wastewater effluent. Both biological processes and chemical processes have their
of this dissertation is the inability of single processes for the cost-effectively removal
limitations in targeting specific pharmaceuticals and are therefore recommended to
of a broad array of structurally highly different molecules in a complex matrix like
be combined to form an adequate barrier against micropollutants like
wastewater effluent. Both biological processes and chemical processes have their
pharmaceuticals.
limitations in targeting specific pharmaceuticals and are therefore recommended to
be combined to form an adequate barrier against micropollutants like
Table 6.2 Synergy between biological and chemical processes for pharmaceutical removal
pharmaceuticals.
Process combination Synergy Chapter
Table
Mild 6.2 Synergy
UV-LED TiO2 between biological Enhanced
Biological and chemical processes for
biodegradation of pharmaceutical
biodegradable removal
3
photocatalysis treatment and otherwise recalcitrant pharmaceuticals
Process combination Synergy Chapter
Biological Reduced ozone input by biological TOC
Mildtreatment
UV-LED TiO2 Ozonation
Biological Enhanced biodegradation
removal of biodegradable
4 VI
3
photocatalysis treatment and otherwise recalcitrant pharmaceuticals
Biological
Ozonation
Biological Biological removal
Reduced ozone of ozonation
input products
by biological TOC 4
treatment
Ozonation 4
treatment removal
Algal photobioreactor:
Single reactor system with multiple
Biological
Simultaneous photolysis and 5
Ozonation Biological removalremoval
pharmaceutical of ozonation products
mechanisms 4
treatment
biological treatment
Algal photobioreactor:
Single reactor system with multiple
Simultaneous photolysis and 5
pharmaceutical removal mechanisms
biological treatment
143
143
Different
General combinations
discussion; of biological
towards lower and chemical
pharmaceutical treatment processes have
emissions
been investigated in this dissertation. Synergy was found for all the studied
combinations, though the way this synergy was expressed differed per combination
Different combinations of biological and chemical treatment processes have
(Table 6.2). Mild photocatalytic pre-treatment was found to enhance the subsequent
been investigated in this dissertation. Synergy was found for all the studied
biological treatment, even for pharmaceuticals that were not targeted by
combinations, though the way this synergy was expressed differed per combination
photocatalysis. Biological pre-treatment removing ozone scavenging OM increased
(Table 6.2). Mild photocatalytic pre-treatment was found to enhance the subsequent
the cost-effectiveness of ozonation for pharmaceutical removal where after potentially
biological treatment, even for pharmaceuticals that were not targeted by
toxic ozonation products were biodegraded during subsequent biological treatment.
photocatalysis. Biological pre-treatment removing ozone scavenging OM increased
Simultaneously photodegradation and biodegradation in algal photobioreactors
the cost-effectiveness of ozonation for pharmaceutical removal where after potentially
demonstrated that in this specific case biological and chemical treatment can also be
toxic ozonation products were biodegraded during subsequent biological treatment.
integrated into a single reactor. Complementariness was found in all the studied
Simultaneously photodegradation and biodegradation in algal photobioreactors
combinations increasing the spectrum of targeted pharmaceuticals and the cost-
demonstrated that in this specific case biological and chemical treatment can also be
effectiveness of the combination compared to single processes. Based on these results
integrated into a single reactor. Complementariness was found in all the studied
and the literature on combined treatment processes for various contaminants it is
combinations increasing the spectrum of targeted pharmaceuticals and the cost-
postulated that other combinations than the three studied in this dissertation can be
effectiveness of the combination compared to single processes. Based on these results
cost-effective for the removal of pharmaceuticals. Moreover, the differences among
and the literature on combined treatment processes for various contaminants it is
the synergies found in the studies presented in this dissertation suggest that there
postulated that other combinations than the three studied in this dissertation can be
may be even a wider range of synergy when other combinations of biological and
cost-effective for the removal of pharmaceuticals. Moreover, the differences among
chemical processes are included. Therefore it is recommended to further study
the synergies found in the studies presented in this dissertation suggest that there
combined treatment processes to identify optimal solutions for the wide suite of
may be even a wider range of synergy when other combinations of biological and
wastewater effluents to be treated.
chemical processes are included. Therefore it is recommended to further study
The worldwide variety among raw wastewater compositions and treatment
combined treatment processes to identify optimal solutions for the wide suite of
plant configurations which both affect the effluent quality, complicates the design and
wastewater effluents to be treated.
development of a robust universal treatment process for pharmaceutical removal.
The worldwide variety among raw wastewater compositions and treatment
Rather, there should be a focus on site-specific solutions as there is a wide arsenal of
plant configurations which both affect the effluent quality, complicates the design and
biological and chemical treatment processes available. A better understanding of
development of a robust universal treatment process for pharmaceutical removal.
underlying process mechanisms is required to further improve and extend the
Rather, there should be a focus on site-specific solutions as there is a wide arsenal of
selection of process combinations enabling the design of tailor made treatment
biological and chemical treatment processes available. A better understanding of
processes for locations where the currently known combinations are not cost-
underlying process mechanisms is required to further improve and extend the
effective. Therefore, further research is recommended on understanding and
selection of process combinations enabling the design of tailor made treatment
processes for locations where the currently known combinations are not cost-
effective. Therefore, further research is recommended on understanding and
144
144
Chapter 6
improving biological and chemical treatment processes and the synergy when
Chapter 6
combining processes, as mentioned earlier in this chapter.
For locations where the wastewater effluent composition is well known, e.g.
improving biological and chemical treatment processes and the synergy when
the WWTP of Bennekom studied in this dissertation, investigated combinations can
combining processes, as mentioned earlier in this chapter.
be scaled up towards pilot installations. Upscaling of the BO3B treatment process and
For locations where the wastewater effluent composition is well known, e.g.
the algal treatment process is viable as lab-scale systems were successfully tested on
the WWTP of Bennekom studied in this dissertation, investigated combinations can
real wastewater. Moreover, the BO3B process was successfully run in a continuous
be scaled up towards pilot installations. Upscaling of the BO3B treatment process and
set-up for almost one year. In addition, the BO3B process performs better than other
the algal treatment process is viable as lab-scale systems were successfully tested on
combinations for estimated costs and sustainability aspects [109, 125]. Hence, the
real wastewater. Moreover, the BO3B process was successfully run in a continuous
promising results motivate the upscaling of this combined treatment process,
set-up for almost one year. In addition, the BO3B process performs better than other
especially with respect to the energy savings for ozonation by TOC removal in a
combinations for estimated costs and sustainability aspects [109, 125]. Hence, the
biological pre-treatment. Main points of attention concern the design and operation
promising results motivate the upscaling of this combined treatment process,
of the biological reactors for the removal of TOC, pharmaceuticals and transformation
especially with respect to the energy savings for ozonation by TOC removal in a
products. Full-scale sand-filters are regularly back-flushed to prevent clogging,
biological pre-treatment. Main points of attention concern the design and operation
however, the lab-scale reactors used in this dissertation were not regularly back
of the biological reactors for the removal of TOC, pharmaceuticals and transformation
flushed to prevent the wash-out of specific TOC and pharmaceutical degrading
products. Full-scale sand-filters are regularly back-flushed to prevent clogging,
microorganisms. Thus, on pilot-scale the need for regular back flushing should be well
however, the lab-scale reactors used in this dissertation were not regularly back
evaluated or performed in a manner that valuable biomass will not be flushed out.
flushed to prevent the wash-out of specific TOC and pharmaceutical degrading
Moreover, the lab-scale reactors were operated with a counter current air flow to
microorganisms. Thus, on pilot-scale the need for regular back flushing should be well
achieve fully aerobic conditions favouring the pharmaceutical degradation and to
evaluated or performed in a manner that valuable biomass will not be flushed out.
prevent clogging of the reactors. For larger scale reactors it might be more challenging
Moreover, the lab-scale reactors were operated with a counter current air flow to
to obtain fully aerobic conditions in a cost-efficient way and this aspect requires
achieve fully aerobic conditions favouring the pharmaceutical degradation and to
attention during the reactor design. Ozonation on full-scale is already applied for
prevent clogging of the reactors. For larger scale reactors it might be more challenging
pharmaceutical removal, and experiences from these projects can be used for a BO3B
to obtain fully aerobic conditions in a cost-efficient way and this aspect requires
pilot. Furthermore, a broader array of contaminants should be studied in a pilot plant,
VI
attention during the reactor design. Ozonation on full-scale is already applied for
including non-pharmaceutical micropollutants, to assess the effectiveness of the BO3B
pharmaceutical removal, and experiences from these projects can be used for a BO3B
process for numerous compounds at real WWTP effluent concentrations. Lastly,
pilot. Furthermore, a broader array of contaminants should be studied in a pilot plant,
bioassays with D. magna, P. subcapitata and V. fischeri showed no acute toxic effects
including non-pharmaceutical micropollutants, to assess the effectiveness of the BO3B
when exposed to the BO3B process effluent, however these assays cannot be regarded
process for numerous compounds at real WWTP effluent concentrations. Lastly,
as a full toxicological assessment. Chronic toxicity assays and specific toxicity assays,
bioassays with D. magna, P. subcapitata and V. fischeri showed no acute toxic effects
when exposed to the BO3B process effluent, however these assays cannot be regarded
as a full toxicological assessment. Chronic toxicity assays and specific toxicity assays,
145
145
e.g. genotoxicity
General or towards
discussion; carcinogenicity assessment, should
lower pharmaceutical therefore be conducted to
emissions
obtain a better understanding of the toxicity potential of the BO3B process effluent.
The algal treatment process is currently being up scaled at the NIOO building
e.g. genotoxicity or carcinogenicity assessment, should therefore be conducted to
(Wageningen, the Netherlands). By means of vacuum toilets a concentrated black
obtain a better understanding of the toxicity potential of the BO3B process effluent.
water stream is collected separately from the other wastewater streams and
The algal treatment process is currently being up scaled at the NIOO building
anaerobically digested after which it is fed into the algal treatment system. In tubular
(Wageningen, the Netherlands). By means of vacuum toilets a concentrated black
algal reactors located in a greenhouse the resource recovery, i.e. algae growth and
water stream is collected separately from the other wastewater streams and
harvesting, is further studied on pilot-scale. When the resource recovery on pilot scale
anaerobically digested after which it is fed into the algal treatment system. In tubular
will be successful, further investigations into the removal of pharmaceuticals is highly
algal reactors located in a greenhouse the resource recovery, i.e. algae growth and
recommended as these will be present in high concentrations due to the separate
harvesting, is further studied on pilot-scale. When the resource recovery on pilot scale
collection of the black water.
will be successful, further investigations into the removal of pharmaceuticals is highly
Pharmaceutical removal by the combination of photocatalysis and
recommended as these will be present in high concentrations due to the separate
biodegradation was only investigated in a clean matrix and therefore requires further
collection of the black water.
lab-scale testing with real wastewater before upscaling. Next to the effects of matrix
Pharmaceutical removal by the combination of photocatalysis and
constituents on the pharmaceutical removal the immobilization or recovery of TiO2
biodegradation was only investigated in a clean matrix and therefore requires further
should be investigated as the current process with powdered TiO2 is not sustainable.
lab-scale testing with real wastewater before upscaling. Next to the effects of matrix
Various methods to immobilize TiO2 have been developed, each with its own
constituents on the pharmaceutical removal the immobilization or recovery of TiO2
characteristics like isoelectric point which do influence the photocatalysis of for
should be investigated as the current process with powdered TiO2 is not sustainable.
instance pharmaceuticals [15]. Understanding the correlation between different TiO2
Various methods to immobilize TiO2 have been developed, each with its own
immobilization methods and the removal of pharmaceuticals in a subsequent
characteristics like isoelectric point which do influence the photocatalysis of for
biological treatment process is therefore highly relevant.
instance pharmaceuticals [15]. Understanding the correlation between different TiO2
The BO3B process seems the most versatile treatment process for
immobilization methods and the removal of pharmaceuticals in a subsequent
implementation on a short horizon taking into account the observed synergies
biological treatment process is therefore highly relevant.
between the investigated biological and chemical processes and the upscaling
The BO3B process seems the most versatile treatment process for
potential. Especially for wastewater effluents with relatively high OM concentrations
implementation on a short horizon taking into account the observed synergies
the complementariness between biological treatment and ozonation seems most
between the investigated biological and chemical processes and the upscaling
useful for application, like for instance at WWTP Bennekom.
potential. Especially for wastewater effluents with relatively high OM concentrations
The detection and identification of numerous pharmaceuticals in wastewater
the complementariness between biological treatment and ozonation seems most
only revealed the tip of the iceberg as it is already know that in the human body, in
useful for application, like for instance at WWTP Bennekom.
the sewer and during wastewater treatment countless metabolites and transformation
The detection and identification of numerous pharmaceuticals in wastewater
products can be formed. Indications that some of these compounds might be more
only revealed the tip of the iceberg as it is already know that in the human body, in
the sewer and during wastewater treatment countless metabolites and transformation
146can be formed. Indications that some of these compounds might be more
products
146
Chapter 6
harmful than the parent compounds, i.e. the consumed pharmaceuticals, implies that
Chapter 6
further research on this topic is needed. Understanding the behaviour, fate, effects
and treatability of pharmaceuticals took an enormous effort of the scientific
harmful than the parent compounds, i.e. the consumed pharmaceuticals, implies that
community over the last decades and is still ongoing. Hence, fully understanding the
further research on this topic is needed. Understanding the behaviour, fate, effects
role and impact of metabolites and transformation products is even more challenging
and treatability of pharmaceuticals took an enormous effort of the scientific
and is expected to provide numerous research needs to be addressed over the coming
community over the last decades and is still ongoing. Hence, fully understanding the
decades. In addition to pharmaceuticals high numbers of other micropollutants are
role and impact of metabolites and transformation products is even more challenging
also present in wastewater and should be taken into account in future research on
and is expected to provide numerous research needs to be addressed over the coming
the design of removal processes [234]. Moreover, non-chemical contamination like
decades. In addition to pharmaceuticals high numbers of other micropollutants are
antibiotic resistant genes and bacteria can pose a serious threat to public health and
also present in wastewater and should be taken into account in future research on
should therefore also be studied [41, 48]. Ideally, the disinfection properties of
the design of removal processes [234]. Moreover, non-chemical contamination like
chemical treatment processes can be applied to target micropollutant and antibiotic
antibiotic resistant genes and bacteria can pose a serious threat to public health and
resistant genes and bacteria, for example, as ozonation employed for micropollutant
should therefore also be studied [41, 48]. Ideally, the disinfection properties of
removal also demonstrated disinfection of secondary clarified effluent [20].
chemical treatment processes can be applied to target micropollutant and antibiotic
Pharmaceuticals are only one group of all the different waterborne
resistant genes and bacteria, for example, as ozonation employed for micropollutant
contaminants discharged with the effluent. Future research should therefore mainly
removal also demonstrated disinfection of secondary clarified effluent [20].
focus on effect based removal strategies as the final goal of wastewater treatment
Pharmaceuticals are only one group of all the different waterborne
processes is to provide a safe effluent posing none or minimal effects to the
contaminants discharged with the effluent. Future research should therefore mainly
subsequent compartments of the water cycle. Advanced analytical methods at leading
focus on effect based removal strategies as the final goal of wastewater treatment
institutes on micropollutant research can detect and quantify over 300 different
processes is to provide a safe effluent posing none or minimal effects to the
micropollutants present in aqueous matrices in a single run [177]. Even though this
subsequent compartments of the water cycle. Advanced analytical methods at leading
is a great achievement and the amount of detectable compounds will most likely even
institutes on micropollutant research can detect and quantify over 300 different
further increase, these methods do not provide an accurate assessment of the risk of
micropollutants present in aqueous matrices in a single run [177]. Even though this
the tested sample, i.e. the posed toxicity of the sample constituents mixture towards
is a great achievement and the amount of detectable compounds will most likely even
the ecosystem or humans [208]. Development of comprehensive and practically
VI
further increase, these methods do not provide an accurate assessment of the risk of
applicable assays to screen for toxicological effects, especially for chronic effects, is
the tested sample, i.e. the posed toxicity of the sample constituents mixture towards
therefore highly needed. Going beyond the performance assessment of treatment
the ecosystem or humans [208]. Development of comprehensive and practically
processes based on chemical parameters, effect based removal strategies
applicable assays to screen for toxicological effects, especially for chronic effects, is
incorporating in vivo and in vitro bioassays can provide a better insight in the obtained
therefore highly needed. Going beyond the performance assessment of treatment
removal efficiency.
processes based on chemical parameters, effect based removal strategies
incorporating in vivo and in vitro bioassays can provide a better insight in the obtained
removal efficiency.
147
147
It discussion;
General is difficult towards
to value thepharmaceutical
lower environmentalemissions
and public health benefits for
diminished pharmaceutical emissions via wastewater effluents, especially as the
chronic effects of exposure to mixtures of pharmaceuticals at low concentrations are
It is difficult to value the environmental and public health benefits for
so far limitedly understood. Conducting a thorough cost-benefit analysis is therefore
diminished pharmaceutical emissions via wastewater effluents, especially as the
very difficult, or even impossible. Nevertheless, indications that pharmaceuticals can
chronic effects of exposure to mixtures of pharmaceuticals at low concentrations are
severely affect the aquatic ecosystem and the worldwide need for wastewater reuse
so far limitedly understood. Conducting a thorough cost-benefit analysis is therefore
motivates investments to mitigate the problem of effluent pharmaceutical emissions.
very difficult, or even impossible. Nevertheless, indications that pharmaceuticals can
Estimated costs for the BO3B process implementation would result in increased
severely affect the aquatic ecosystem and the worldwide need for wastewater reuse
wastewater treatment costs of 15% for the Netherlands. Expressed per population
motivates investments to mitigate the problem of effluent pharmaceutical emissions.
equivalent this is around €5 per year, which is small compared to the yearly tariff for
Estimated costs for the BO3B process implementation would result in increased
wastewater treatment of €55 per population equivalent. Moreover, this increase is
wastewater treatment costs of 15% for the Netherlands. Expressed per population
only 0.014% of the Dutch average yearly spendable income [43]. Similarly, estimated
equivalent this is around €5 per year, which is small compared to the yearly tariff for
tariff increases of additional pharmaceutical removal processes in the literature are
wastewater treatment of €55 per population equivalent. Moreover, this increase is
€5-20 per person per year and only 0.1% per person for primary energy consumption
only 0.014% of the Dutch average yearly spendable income [43]. Similarly, estimated
[125]. Deciding to wait for a detailed cost-benefit analysis further jeopardizes the
tariff increases of additional pharmaceutical removal processes in the literature are
environment and the public health. The unknown risks and the limited costs
€5-20 per person per year and only 0.1% per person for primary energy consumption
associated to additional wastewater treatment processes for pharmaceutical removal
[125]. Deciding to wait for a detailed cost-benefit analysis further jeopardizes the
costs therefore justify their implementation.
environment and the public health. The unknown risks and the limited costs
Interventions at other stages in the chain from pharmaceutical manufacturing
associated to additional wastewater treatment processes for pharmaceutical removal
to drinking water treatment can be undertaken rather than the end-of-pipe solutions
costs therefore justify their implementation.
which are the focus of this dissertation and most literature. On the one hand, WWTPs
Interventions at other stages in the chain from pharmaceutical manufacturing
are a main hub in the water cycle which motivates effective end-of-pipe solutions as
to drinking water treatment can be undertaken rather than the end-of-pipe solutions
they can safeguard the next compartments in the water cycle such as surface, ground
which are the focus of this dissertation and most literature. On the one hand, WWTPs
and drinking water. On the other hand, measures taken at earlier stages in the
are a main hub in the water cycle which motivates effective end-of-pipe solutions as
pharmaceutical chain can positively influence subsequent stages reducing the overall
they can safeguard the next compartments in the water cycle such as surface, ground
impact. Initiated by the Dutch national government and the wastewater and drinking
and drinking water. On the other hand, measures taken at earlier stages in the
water authorities in the Netherlands, a chain-approach is formulated aiming at
pharmaceutical chain can positively influence subsequent stages reducing the overall
increased awareness of all chain-actors and when possible facilitating interventions
impact. Initiated by the Dutch national government and the wastewater and drinking
to reduce the negative impacts on subsequent [221, 290]. For example, in the
water authorities in the Netherlands, a chain-approach is formulated aiming at
province of Flevoland, the Netherlands, pharmacists and family doctors were informed
increased awareness of all chain-actors and when possible facilitating interventions
by the local water authorities on the treatability and environmental impact of
to reduce the negative impacts on subsequent [221, 290]. For example, in the
province of Flevoland, the Netherlands, pharmacists and family doctors were informed
by the148
local water authorities on the treatability and environmental impact of
148
Chapter 6
pharmaceuticals [181]. They agreed that in case there are biodegradable alternatives
Chapter 6
available to prescribe these over non-biodegradable pharmaceuticals, thereby
reducing the pharmaceutical loads into the environment. A successful experiment was
pharmaceuticals [181]. They agreed that in case there are biodegradable alternatives
performed In the hospital of Deventer by distributing urine collection bags to patients
available to prescribe these over non-biodegradable pharmaceuticals, thereby
who ingested contrast media for X-ray scanning [67]. Contrast media are known to
reducing the pharmaceutical loads into the environment. A successful experiment was
persist during wastewater treatment which favours their separate collection and
performed In the hospital of Deventer by distributing urine collection bags to patients
treatment. Patients were asked to collect their urine during 24 hours after ingestion
who ingested contrast media for X-ray scanning [67]. Contrast media are known to
and dispose the bags with the municipal solid waste. After collection this waste is
persist during wastewater treatment which favours their separate collection and
incinerated whereby the contrast media are effectively eliminated. Another aspect of
treatment. Patients were asked to collect their urine during 24 hours after ingestion
the Dutch chain approach is the support of Green Pharmacy, i.e. the development of
and dispose the bags with the municipal solid waste. After collection this waste is
degradable pharmaceuticals. Moreover, the chain approach aims at implementing the
incinerated whereby the contrast media are effectively eliminated. Another aspect of
environmental effect based assessment during the regulatory approval of
the Dutch chain approach is the support of Green Pharmacy, i.e. the development of
pharmaceuticals. Raising awareness among the general public on the proper disposal
degradable pharmaceuticals. Moreover, the chain approach aims at implementing the
of pharmaceuticals and the environmental and human health related effects of
environmental effect based assessment during the regulatory approval of
pharmaceuticals is also included in the chain approach. Even though the removal of
pharmaceuticals. Raising awareness among the general public on the proper disposal
pharmaceuticals at WWTPs will most likely remain the main stage in the entire
of pharmaceuticals and the environmental and human health related effects of
pharmaceutical chain, improvements at earlier stages like the examples mentioned
pharmaceuticals is also included in the chain approach. Even though the removal of
above can significantly impact the quantity and quality of the loads entering WWTPs
pharmaceuticals at WWTPs will most likely remain the main stage in the entire
and contribute to reduced emissions to the environment and are therefore strongly
pharmaceutical chain, improvements at earlier stages like the examples mentioned
recommended.
above can significantly impact the quantity and quality of the loads entering WWTPs
Switzerland is to date the only example where the discharge of micropollutants
and contribute to reduced emissions to the environment and are therefore strongly
including pharmaceuticals is restricted by legislation which forces the monitoring and
recommended.
80% removal of 5 out of 12 micropollutants [232]. Also for other countries, like the
Switzerland is to date the only example where the discharge of micropollutants
Netherlands, stricter legislation on WWTP effluent quality is required to manage the
including pharmaceuticals is restricted by legislation which forces the monitoring and
discharge of pharmaceuticals and other contaminants into the environment. The
VI
80% removal of 5 out of 12 micropollutants [232]. Also for other countries, like the
current knowledge on the negative effects and possible risks of mixtures of discharged
Netherlands, stricter legislation on WWTP effluent quality is required to manage the
contaminants on the environment and the public health motivates the implementation
discharge of pharmaceuticals and other contaminants into the environment. The
of the precautionary principle. By this policy makers can enforce more restrictive
current knowledge on the negative effects and possible risks of mixtures of discharged
discharge regulations as without further legislation implementation of additional
contaminants on the environment and the public health motivates the implementation
treatment processes is expected to be minimal.
of the precautionary principle. By this policy makers can enforce more restrictive
discharge regulations as without further legislation implementation of additional
treatment processes is expected to be minimal.
149
149
Indiscussion;
General a wider perspective, alternative
towards lower sanitation
pharmaceutical systems should be seriously
emissions
considered as the current wastewater collection and treatment systems are not
optimal for resource recovery, water usage minimization and pharmaceutical
In a wider perspective, alternative sanitation systems should be seriously
removal. Alternative sanitation systems such as the decentralised sanitation and
considered as the current wastewater collection and treatment systems are not
reuse concept are based on separation at source principles which promote the
optimal for resource recovery, water usage minimization and pharmaceutical
separation of individual wastewater streams, their specific treatment and the use of
removal. Alternative sanitation systems such as the decentralised sanitation and
cost-effective wastewater collection systems [136, 200]. On neighbourhood and office
reuse concept are based on separation at source principles which promote the
building scale this concept has been locally implemented and demonstrated to be a
separation of individual wastewater streams, their specific treatment and the use of
sustainable alternative allowing resource recovery and the demand minimization of
cost-effective wastewater collection systems [136, 200]. On neighbourhood and office
precious drinking water for toilet flushing [251, 285, 318]. This concept offers
building scale this concept has been locally implemented and demonstrated to be a
opportunities for a more cost-effective removal of pharmaceuticals as by the use of
sustainable alternative allowing resource recovery and the demand minimization of
vacuum toilets a highly concentrated black water stream is obtained with much higher
precious drinking water for toilet flushing [251, 285, 318]. This concept offers
pharmaceutical concentrations compared to conventional centralised systems [62].
opportunities for a more cost-effective removal of pharmaceuticals as by the use of
Although the design of most alternative sanitation systems aims at resource recovery
vacuum toilets a highly concentrated black water stream is obtained with much higher
and water demand minimization, a better pharmaceutical removal has been observed
pharmaceutical concentrations compared to conventional centralised systems [62].
in such an alternative sanitation full scale system than in conventional WWTPs [36].
Although the design of most alternative sanitation systems aims at resource recovery
Additional treatment steps aiming specifically at pharmaceuticals is postulated to be
and water demand minimization, a better pharmaceutical removal has been observed
more cost-effective than similar steps at conventional WWTPs as the high
in such an alternative sanitation full scale system than in conventional WWTPs [36].
pharmaceutical concentration and the low flow rate of the black water stream ease
Additional treatment steps aiming specifically at pharmaceuticals is postulated to be
the specific targeting of pharmaceuticals. The large-scale implementation of
more cost-effective than similar steps at conventional WWTPs as the high
alternative sanitation systems requires a willingness to innovate of the main actors
pharmaceutical concentration and the low flow rate of the black water stream ease
regarding legislative and construction aspects of sanitation systems, i.e.
the specific targeting of pharmaceuticals. The large-scale implementation of
municipalities, water boards and construction companies. The rigorously different way
alternative sanitation systems requires a willingness to innovate of the main actors
of wastewater collection in alternative sanitation systems, i.e. two streams of which
regarding legislative and construction aspects of sanitation systems, i.e.
one collected by vacuum, requires the costly replacement of the current sewer
municipalities, water boards and construction companies. The rigorously different way
infrastructure. The limited willingness to innovate and the high replacement costs of
of wastewater collection in alternative sanitation systems, i.e. two streams of which
conventional sewers hamper the rapid implementation of alternative sanitation
one collected by vacuum, requires the costly replacement of the current sewer
systems. However, for new to build neighbourhoods and offices this concept offers
infrastructure. The limited willingness to innovate and the high replacement costs of
serious advantages over the conventional gravitational sewer and wastewater
conventional sewers hamper the rapid implementation of alternative sanitation
treatment system, including benefits for pharmaceutical removal, and is therefore
systems. However, for new to build neighbourhoods and offices this concept offers
strongly recommended.
serious advantages over the conventional gravitational sewer and wastewater
treatment system, including benefits for pharmaceutical removal, and is therefore
150
strongly recommended.
150
Chapter 6
Knowing that pharmaceuticals are only one of the contaminants jeopardising

Chapter 6
freshwater bodies, a more general approach towards all chemical and non-chemical
contaminants including other micropollutants like hormones, pesticides and personal
Knowing that pharmaceuticals are only one of the contaminants jeopardising
care products and antibiotic resistant bacteria and genes should be applied. Hence,
freshwater bodies, a more general approach towards all chemical and non-chemical
well-designed treatment systems targeting multiple contaminants can prevent the
contaminants including other micropollutants like hormones, pesticides and personal
costly implementation of additional treatment processes for each individual type of
care products and antibiotic resistant bacteria and genes should be applied. Hence,
contaminant. Only with a broader scope going beyond pharmaceuticals the further
well-designed treatment systems targeting multiple contaminants can prevent the
contamination of the environment by effluent emissions can be prevented. The
costly implementation of additional treatment processes for each individual type of
current indications that numerous contaminants pose adverse effects to the
contaminant. Only with a broader scope going beyond pharmaceuticals the further
environment and human health demands an immediate action. The lack of legislation
contamination of the environment by effluent emissions can be prevented. The
should not be used as an excuse to wait, but calls upon the responsibility of water
current indications that numerous contaminants pose adverse effects to the
authorities and other stakeholders to act now. As long as chronic effects on the
environment and human health demands an immediate action. The lack of legislation
environment and public health are insufficiently understood the precautionary
should not be used as an excuse to wait, but calls upon the responsibility of water
principle should be applied to strive for the safe reuse of wastewater effluent and the
authorities and other stakeholders to act now. As long as chronic effects on the
harmless discharge into the environment. For the implementation of the
environment and public health are insufficiently understood the precautionary
precautionary principle, combined biological and chemical treatment processes are
principle should be applied to strive for the safe reuse of wastewater effluent and the
foreseen to play a crucial role in the cost-effective removal of contaminants from
harmless discharge into the environment. For the implementation of the
wastewater effluents.
precautionary principle, combined biological and chemical treatment processes are
foreseen to play a crucial role in the cost-effective removal of contaminants from
wastewater effluents.
VI
151
151
152
152
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pharmaceuticals by pollutant
UV/H2O2,inWater
the environment, J. Environ.
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5876-5888.
(2014) 157-161.
304. World Health Organization Good manufacturing practices for pharmaceutical products:
303. Wols
main B.A., Hofman-Caris
principles, in, 2014.C.H.M., Harmsen D.J.H., Beerendonk E.F. Degradation of 40
selected pharmaceuticals by UV/H2O2, Water Res., 47 (2013) 5876-5888.
305. World Health Organization Factsheet Drinking-Water, in, 2017.
304. World Health Organization Good manufacturing practices for pharmaceutical products:
306. Wu H.,
main Zhang J.,in,Ngo
principles, H.H., Guo W., Hu Z., Liang S., Fan J., Liu H. A review on the
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594-601.
306.
307. Wu H.,H.,
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Zou D., ZhouH.H., Guo W.,
D., Dong S., Hu
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Rittmann J., Liu H. A review
Enhancing on the
degradation
and mineralization
sustainability of tetracycline
of constructed using
wetlands for intimately
wastewater coupledDesign
treatment: photocatalysis and
and operation,
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Eng. J., 316 (2017) 7-14.
307.
308. Xiong H., Zou
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Degradation Wang J., Rittmann
adsorption B.E. Enhancing
of selected degradation
pharmaceuticals and
and mineralization
personal of (PPCPs)
care products tetracycline using intimately
in agricultural coupled photocatalysis
soils, Chemosphere, and
77 (2009) 1299-
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1305. (ICPB), Chem. Eng. J., 316 (2017) 7-14.
308.
309. Xu
XueJ., WuWu
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K., Huang X., Zhou andH.,
adsorption
Tsuno H.,ofTanaka
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Elimination and fate
personal
of selectedcare products (PPCPs)
micro-organic in agricultural
pollutants soils,anaerobic/anoxic/aerobic
in a full-scale Chemosphere, 77 (2009)process
1299-
combined with membrane bioreactor for municipal wastewater reclamation, Water
1305.
Res., 44 (2010) 5999-6010.
309. Xue W., Wu C., Xiao K., Huang X., Zhou H., Tsuno H., Tanaka H. Elimination and fate
310. of selected H.,
Yamamoto micro-organic
Nakamura Y., pollutants
Moriguchi in S.,
a full-scale
Nakamura anaerobic/anoxic/aerobic
Y., Honda Y., Tamura I.,process
Hirata
combined
Y., Hayashi withA.,membrane
Sekizawabioreactor for municipal
J. Persistence wastewater reclamation,
and partitioning Water
of eight selected
pharmaceuticals
Res., in the aquatic environment: Laboratory photolysis, biodegradation,
44 (2010) 5999-6010.
and sorption experiments, Water Res., 43 (2009) 351-362.
310. Yamamoto H., Nakamura Y., Moriguchi S., Nakamura Y., Honda Y., Tamura I., Hirata
311. Y., Hayashi
Yan N., Chang A., Sekizawa
L., Gan L., ZhangJ. Y.,Persistence and B.E.
Liu R., Rittmann partitioning of eight
UV photolysis selected
for accelerated
pharmaceuticals in the aquatic
quinoline biodegradation environment: Appl.
and mineralization, Laboratory photolysis,
Microbiol. biodegradation,
Biotechnol., 97 (2013)
and sorption experiments, Water Res., 43 (2009) 351-362.
10555-10561.
311. Yan N., Chang L., Gan L., Zhang Y., Liu R., Rittmann B.E. UV photolysis for accelerated
quinoline biodegradation and mineralization, Appl. Microbiol. Biotechnol., 97 (2013)
10555-10561. 175
175
312. Yang Y., Ok Y.S., Kim K.-H., Kwon E.E., Tsang Y.F. Occurrences and removal of
pharmaceuticals and personal care products (PPCPs) in drinking water and
water/sewage treatment plants: A review, Sci. Total Environ., 596 (2017) 303-320.
313.
312. Ye L., Y.,
Yang YouOk
H.,Y.S.,
Yao J.,
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H. Water
Kwon treatment technologies
E.E., Tsang for perchlorate:
Y.F. Occurrences A review,
and removal of
Desalination, 298 (2012)
pharmaceuticals 1-12.
and personal care products (PPCPs) in drinking water and
water/sewage treatment plants: A review, Sci. Total Environ., 596 (2017) 303-320.
314. Yeung A.T., Gu Y.-Y. A review on techniques to enhance electrochemical remediation
313. of contaminated
Ye soils,
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treatment 11-29.for perchlorate: A review,
technologies
Desalination, 298 (2012) 1-12.
315. Yu Y.Y., Huang Q.X., Wang Z.F., Zhang K., Tang C.M., Cui J.L., Feng J.L., Peng X.Z.
314. Occurrence
Yeung andY.-Y.
A.T., Gu behavior of on
A review pharmaceuticals, steroid electrochemical
techniques to enhance hormones, and remediation
endocrine-
disrupting
of personal
contaminated care
soils, productsMater.,
J. Hazard. in wastewater
195 (2011)and11-29.
the recipient river water of the
Pearl River Delta, South China, J. Environ. Monit., 13 (2011) 871-878.
315. Yu Y.Y., Huang Q.X., Wang Z.F., Zhang K., Tang C.M., Cui J.L., Feng J.L., Peng X.Z.
316. Zeeman G., Lettinga
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and behavior role of anaerobic digestion
pharmaceuticals, steroidofhormones,
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317.
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of anaerobic L., de Graaff M., Abu-Ghunmi
of domestic sewage inL., Mels
closing
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the water andB.,nutrient
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cycle Buisman C., van
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317. Zeeman G., Kujawa K., de Mes T., Hernandez L., de Graaff M., Abu-Ghunmi L., Mels
318. Zeeman
A., G., Kujawa-Roeleveld
Meulman B., Temmink H., BuismanK. Resource recovery
C., van Lier J., from source
Lettinga separatedtreatment
G. Anaerobic domestic
waste(water)
as streams;
a core technology forfull scale results,
energy, Water
nutrients Sci. Technol.,
and water recovery64 (2011)
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source-separated
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319. Zhang L., Hendrickx T.L.G., Kampman C., Temmink H., Zeeman G. Co-digestion to
318. support low
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associated
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pretreatment in agricultural
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560-566.
321.
320. Zhang Y.,
T., Geißen
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Sun N., C. Carbamazepine and diclofenac:
Y., Chen H. Sorption Removalofinwastewater-
and degradation wastewater
treatment plants
associated and occurrence
pharmaceuticals andin personal
water bodies,
careChemosphere, 73 (2008) 1151-1161.
products in agricultural soils and
sediment, Water Sci. Technol., 68 (2013) 991-998.
322. Zhang Y., Sun X., Chen L., Rittmann B.E. Integrated photocatalytic-biological reactor
321. for accelerated
Zhang 2,4,6-trichlorophenol
Y., Geißen degradation
S.U., Gal C. Carbamazepine andand mineralization,
diclofenac: RemovalBiodegradation,
in wastewater
23 (2012) plants
treatment 189-198.
and occurrence in water bodies, Chemosphere, 73 (2008) 1151-1161.
323.
322. Y., Sun
Zhang Y., Chang L., Yan
X., Chen N., Tang B.E.
L., Rittmann Y., Integrated
Liu R., Rittmann B.E. UV photolysis
photocatalytic-biological for
reactor
accelerating
for pyridine
accelerated biodegradation, degradation
2,4,6-trichlorophenol Environ. Sci.and
Technol., 48 (2014)Biodegradation,
mineralization, 649-655.
23 (2012) 189-198.
324. Zhang Y., Price G.W., Jamieson R., Burton D., Khosravi K. Sorption and desorption of
323. selectedY.,
Zhang non-steroidal
Chang L., anti-inflammatory
Yan N., Tang Y., drugs in an
Liu R., agricultural
Rittmann B.E. loam-textured
UV photolysis soil,
for
Chemosphere,
accelerating 174 (2017)
pyridine 628-637. Environ. Sci. Technol., 48 (2014) 649-655.
biodegradation,
325.
324. Zhao D.,
Zhang Y.,Zhu
PriceC., Sun Jamieson
G.W., S., Yu H.,R.,
Zhang L., D.,
Burton PanKhosravi
W., Zhang X., Yu H.,and
K. Sorption Gudesorption
J., Cheng S.
of
Toxicity of
selected pharmaceutical
non-steroidal wastewater on drugs
anti-inflammatory male reproductive system
in an agricultural of Mus musculus,
loam-textured soil,
Toxicol. Ind. Health,
Chemosphere, 23 (2007)
174 (2017) 47-54.
628-637.
325. Zhao D., Zhu C., Sun S., Yu H., Zhang L., Pan W., Zhang X., Yu H., Gu J., Cheng S.
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Toxicol. Ind. Health, 23 (2007) 47-54.
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178
Nomenclature
AnBW Anaerobically treated Black Water
AOP
Nomenclature
Advanced Oxidation Process
BOD Biological Oxygen Demand
AnBW Anaerobically treated Black Water
BOM Biodegradable Organic Matter
AOP Advanced Oxidation Process
BO3B Biological–Ozone–Biological
BOD Biological Oxygen Demand
CAF Caffeine
BOM Biodegradable Organic Matter
CAS Conventional Activated Sludge
BO3B Biological–Ozone–Biological
CBZ Carbamazepine
CAF Caffeine
COD Chemical Oxygen Demand
CAS Conventional Activated Sludge
CW Constructed Wetland
CBZ Carbamazepine
DAD Diode Array Detector
COD Chemical Oxygen Demand
DOC Dissolved Organic Carbon
CW Constructed Wetland
DOM Dissolved Organic Matter
DAD Diode Array Detector
DM Dry Matter
DOC Dissolved Organic Carbon
HRT Hydraulic Retention Time
DOM Dissolved Organic Matter
IBP Ibuprofen
DM Dry Matter
LC Liquid Chromatograph
HRT Hydraulic Retention Time
MET Metoprolol
IBP Ibuprofen
MS Mass Spectrometer
LC Liquid Chromatograph
NAP Naproxen
MET Metoprolol
OM Organic Matter
MS Mass Spectrometer
PRO Propranolol
NAP Naproxen
SPE Solid Phase Extraction
OM Organic Matter
TiO2 Titanium dioxide
PRO Propranolol
TOC Total Organic Carbon
SPE Solid Phase Extraction
UV Ultraviolet
TiO2 Titanium dioxide
WWTP Wastewater Treatment Plant
TOC Total Organic Carbon
UV Ultraviolet
WWTP Wastewater Treatment Plant
179
179
180
180
Samenvatting
Wereldwijd worden in toenemende mate geneesmiddelen geconsumeerd, en
Samenvatting
de verwachting is dat dit op de korte termijn niet afneemt. Enkele uren tot dagen na
inname van geneesmiddelen scheidt het menselijk lichaam deze uit via urine of
Wereldwijd worden in toenemende mate geneesmiddelen geconsumeerd, en
ontlasting. Door geavanceerde afvoermechanismen in het menselijk lichaam worden
de verwachting is dat dit op de korte termijn niet afneemt. Enkele uren tot dagen na
geneesmiddelen (gedeeltelijk) uitgescheden als zogenoemde metabolieten, d.w.z. in
inname van geneesmiddelen scheidt het menselijk lichaam deze uit via urine of
een andere moleculaire vorm dan het originele geneesmiddel. Geneesmiddelen en
ontlasting. Door geavanceerde afvoermechanismen in het menselijk lichaam worden
metabolieten komen via het toilet en het riool uiteindelijk in de
geneesmiddelen (gedeeltelijk) uitgescheden als zogenoemde metabolieten, d.w.z. in
rioolwaterzuiveringsinstallatie terecht.
een andere moleculaire vorm dan het originele geneesmiddel. Geneesmiddelen en
Huidige rioolwaterzuiveringsinstallaties, gebruikmakend van actief slib, zijn
metabolieten komen via het toilet en het riool uiteindelijk in de
ontworpen om bulkverontreinigingen, zoals organisch materiaal, stikstof en fosfaat,
rioolwaterzuiveringsinstallatie terecht.
te verwijderen. Deze installaties zijn echter niet ontworpen op het verwijderen van
Huidige rioolwaterzuiveringsinstallaties, gebruikmakend van actief slib, zijn
het brede spectrum aan geneesmiddelen dat in het afvalwater aanwezig is. Deze
ontworpen om bulkverontreinigingen, zoals organisch materiaal, stikstof en fosfaat,
groep stoffen met zeer uiteenlopende en complexe moleculaire structuren, aanwezig
te verwijderen. Deze installaties zijn echter niet ontworpen op het verwijderen van
in nano- tot microgrammen per liter, wordt daardoor doorgaans slechts minimaal
het brede spectrum aan geneesmiddelen dat in het afvalwater aanwezig is. Deze
verwijderd. De geneesmiddelen waarvan wel biologische afbraak wordt waargenomen
groep stoffen met zeer uiteenlopende en complexe moleculaire structuren, aanwezig
worden in de regel niet gemineraliseerd tot CO2 en H2O, maar enkel omgezet tot
in nano- tot microgrammen per liter, wordt daardoor doorgaans slechts minimaal
transformatieproduct met een licht veranderde structuur ten opzichte van het
verwijderd. De geneesmiddelen waarvan wel biologische afbraak wordt waargenomen
originele geneesmiddel. Dit resulteert in de emissie van ontelbare geneesmiddelen,
worden in de regel niet gemineraliseerd tot CO2 en H2O, maar enkel omgezet tot
metabolieten en transformatieproducten naar het milieu.
transformatieproduct met een licht veranderde structuur ten opzichte van het
De aanwezigheid van deze potentieel gevaarlijke stoffen in het milieu is een
originele geneesmiddel. Dit resulteert in de emissie van ontelbare geneesmiddelen,
van de grote uitdagingen van deze tijd omdat ze een serieuze bedreiging vormen voor
metabolieten en transformatieproducten naar het milieu.
de kwaliteit van het aquatisch milieu en de volksgezondheid. Negatieve gevolgen
De aanwezigheid van deze potentieel gevaarlijke stoffen in het milieu is een
zoals de vervrouwelijking van vissen zijn goed beschreven in literatuur en vormen
van de grote uitdagingen van deze tijd omdat ze een serieuze bedreiging vormen voor
een bedreiging voor het gehele ecosysteem. Aanzienlijke concentraties aan
de kwaliteit van het aquatisch milieu en de volksgezondheid. Negatieve gevolgen
geneesmiddelen in drinkwaterbronnen afkomstig van rioolwaterzuiveringsinstallaties
zoals de vervrouwelijking van vissen zijn goed beschreven in literatuur en vormen
vormen een gevaar voor de volksgezondheid indien drinkwater niet voldoende
een bedreiging voor het gehele ecosysteem. Aanzienlijke concentraties aan
gezuiverd wordt. Daarnaast belemmert de aanwezigheid van geneesmiddelen het
geneesmiddelen in drinkwaterbronnen afkomstig van rioolwaterzuiveringsinstallaties
hergebruik van afvalwater, terwijl wereldwijde waterschaarste juist gedeeltelijk
vormen een gevaar voor de volksgezondheid indien drinkwater niet voldoende
opgelost zou kunnen worden door hergebruik van afvalwater. De opsomming van de
gezuiverd wordt. Daarnaast belemmert de aanwezigheid van geneesmiddelen het
hergebruik van afvalwater, terwijl wereldwijde waterschaarste juist gedeeltelijk
181
opgelost zou kunnen worden door hergebruik van afvalwater. De opsomming van de
181
hierboven beschreven negatieve aspecten motiveert de verwijdering van
geneesmiddelen uit afvalwater voordat deze het aquatisch milieu bereiken.
Als een van de hoofdschakels in de waterketen zijn
hierboven beschreven negatieve aspecten motiveert de verwijdering van
rioolwaterzuiveringsinstallaties een optimale locatie voor een barrière tegen
geneesmiddelen uit afvalwater voordat deze het aquatisch milieu bereiken.
geneesmiddelenemissies naar het milieu. Meerdere biologische en chemische
Als een van de hoofdschakels in de waterketen zijn
processen zijn bestudeerd voor de verwijdering van geneesmiddelen, waarvan
rioolwaterzuiveringsinstallaties een optimale locatie voor een barrière tegen
sommige reeds lokaal geïmplementeerd zijn. Desalniettemin tonen veel van deze
geneesmiddelenemissies naar het milieu. Meerdere biologische en chemische
processen een onvolledige verwijdering van geneesmiddelen of worden ze
processen zijn bestudeerd voor de verwijdering van geneesmiddelen, waarvan
gekenmerkt door hoge kosten en lage duurzaamheid. Oftewel, er is een tekort aan
sommige reeds lokaal geïmplementeerd zijn. Desalniettemin tonen veel van deze
kost-effectieve processen voor geneesmiddelenverwijdering. Deze dissertatie gaat
processen een onvolledige verwijdering van geneesmiddelen of worden ze
daarom in op verschillende processen voor de kost-effectieve verwijdering van
gekenmerkt door hoge kosten en lage duurzaamheid. Oftewel, er is een tekort aan
geneesmiddelen uit afvalwater met een focus op de synergie tussen biologische en
kost-effectieve processen voor geneesmiddelenverwijdering. Deze dissertatie gaat
chemische zuiveringsprocessen voor een verbeterde geneesmiddelen verwijdering
daarom in op verschillende processen voor de kost-effectieve verwijdering van
(Hoofdstuk 1).
geneesmiddelen uit afvalwater met een focus op de synergie tussen biologische en
De doorgaans lage kosten voor biologische zuiveringsprocessen begunstigen
chemische zuiveringsprocessen voor een verbeterde geneesmiddelen verwijdering
de toekomstige implementatie ervan en stimuleren het onderzoek ernaar. Van alle
(Hoofdstuk 1).
parameters die invloed hebben op de werking van biologische processen worden
De doorgaans lage kosten voor biologische zuiveringsprocessen begunstigen
redox-condities gezien als een van de belangrijkste. Uit batch- en kolomexperimenten
de toekomstige implementatie ervan en stimuleren het onderzoek ernaar. Van alle
met sediment van helofytenfilters is gebleken dat geneesmiddelen het best worden
parameters die invloed hebben op de werking van biologische processen worden
verwijderd onder aërobe, d.w.z. zuurstofrijke, sulfaat reducerende en methanogene
redox-condities gezien als een van de belangrijkste. Uit batch- en kolomexperimenten
condities (Hoofdstuk 2). Microaërofiele en nitraat reducerende condities zijn minder
met sediment van helofytenfilters is gebleken dat geneesmiddelen het best worden
effectief. Biologische afbraak en sorptie aan sediment zijn geïdentificeerd als
verwijderd onder aërobe, d.w.z. zuurstofrijke, sulfaat reducerende en methanogene
onderliggende verwijderingsmechanismen van geneesmiddelen en worden beide
condities (Hoofdstuk 2). Microaërofiele en nitraat reducerende condities zijn minder
beïnvloed door de heersende redox-condities. Van de onderzochte geneesmiddelen
effectief. Biologische afbraak en sorptie aan sediment zijn geïdentificeerd als
vertoonde propranolol de hoogste sorptiecoëfficiënt. Voor propranolol vond onder de
onderliggende verwijderingsmechanismen van geneesmiddelen en worden beide
meest optimale redox-conditie verzadiging van de sediment sorptieplekken plaats na
beïnvloed door de heersende redox-condities. Van de onderzochte geneesmiddelen
300 porie volumewisselingen. Dit toont aan dat in biologische filtratieprocessen
vertoonde propranolol de hoogste sorptiecoëfficiënt. Voor propranolol vond onder de
geneesmiddelenverwijdering middels sorptie aan sediment slechts een minimale rol
meest optimale redox-conditie verzadiging van de sediment sorptieplekken plaats na
speelt ten opzichte van biodegradatie. De persistentie van biorecalitrante
300 porie volumewisselingen. Dit toont aan dat in biologische filtratieprocessen
geneesmiddelen zoals carbamazepine in biologische zuiveringsprocessen benadrukt
geneesmiddelenverwijdering middels sorptie aan sediment slechts een minimale rol
de onvolkomenheid van deze processen en onderschrijft de noodzaak voor additionele
speelt ten opzichte van biodegradatie. De persistentie van biorecalitrante
niet-biologische zuiveringsstappen.
geneesmiddelen zoals carbamazepine in biologische zuiveringsprocessen benadrukt
182
de onvolkomenheid van deze processen en onderschrijft de noodzaak voor additionele
niet-biologische zuiveringsstappen.
182
Samenvatting
Milde UV-LED TiO2 fotokatalyse gecombineerd met een nageschakeld biologisch

Samenvatting
zuiveringsproces toonde een verbeterde geneesmiddelenverwijdering ten opzichte
van beide afzonderlijke processen (Hoofdstuk 3). Drie van de negen onderzochte
Milde UV-LED TiO2 fotokatalyse gecombineerd met een nageschakeld biologisch
geneesmiddelen werden verwijderd door milde fotokatalyse. Vier geneesmiddelen
zuiveringsproces toonde een verbeterde geneesmiddelenverwijdering ten opzichte
vertoonden een verbeterde geneesmiddelenverwijdering tijdens biologische zuivering
van beide afzonderlijke processen (Hoofdstuk 3). Drie van de negen onderzochte
na milde fotokatalytische voorbehandeling. Verrassend genoeg, was slechts één van
geneesmiddelen werden verwijderd door milde fotokatalyse. Vier geneesmiddelen
deze vier geneesmiddelen verwijderd gedurende milde fotokatalyse. Bovendien werd
vertoonden een verbeterde geneesmiddelenverwijdering tijdens biologische zuivering
diclofenac biologisch afgebroken na voorbehandeling terwijl er zonder
na milde fotokatalytische voorbehandeling. Verrassend genoeg, was slechts één van
voorbehandeling geen afbraak plaats vond. Afgaande op literatuur is gepostuleerd
deze vier geneesmiddelen verwijderd gedurende milde fotokatalyse. Bovendien werd
dat afbraakproducten van de drie door milde fotokatalyse verwijderde
diclofenac biologisch afgebroken na voorbehandeling terwijl er zonder
geneesmiddelen hebben geleid tot de activering van enzymatische systemen die
voorbehandeling geen afbraak plaats vond. Afgaande op literatuur is gepostuleerd
betrokken zijn bij de initiële reacties voor de biodegradatie van organische moleculen.
dat afbraakproducten van de drie door milde fotokatalyse verwijderde
Naast geneesmiddelen zijn er talrijke andere (onschadelijke) organische
geneesmiddelen hebben geleid tot de activering van enzymatische systemen die
stoffen aanwezigheid in rioolwaterzuivering effluent. In het geval ozonisatie wordt
betrokken zijn bij de initiële reacties voor de biodegradatie van organische moleculen.
toegepast als additioneel zuiveringsproces voor geneesmiddelenverwijdering, vangen
Naast geneesmiddelen zijn er talrijke andere (onschadelijke) organische
deze stoffen een grote fractie van het ozon af waarmee de ozonisatie van
stoffen aanwezigheid in rioolwaterzuivering effluent. In het geval ozonisatie wordt
geneesmiddelen sterk in effectiviteit reduceert. Hoge totale organisch
toegepast als additioneel zuiveringsproces voor geneesmiddelenverwijdering, vangen
koolstofconcentraties (TOC), zoals 17,3 mg TOC/L in het voor deze studie
deze stoffen een grote fractie van het ozon af waarmee de ozonisatie van
onderzochte afvalwater, resulteren derhalve in een hoog ozonverbruik waardoor de
geneesmiddelen sterk in effectiviteit reduceert. Hoge totale organisch
kost-effectiviteit van ozonisatie afneemt. Om die reden is een bio-ozon-bio-proces
koolstofconcentraties (TOC), zoals 17,3 mg TOC/L in het voor deze studie
(BO3B) bestaande uit twee identieke druppelfilters met zand als dragermateriaal en
onderzochte afvalwater, resulteren derhalve in een hoog ozonverbruik waardoor de
een ozonreactor ontworpen (Hoofdstuk 4). Met als doel het ontwikkelen van een kost-
kost-effectiviteit van ozonisatie afneemt. Om die reden is een bio-ozon-bio-proces
effectieve zuivering zijn verschillende hydraulische verblijftijden en ozondoseringen
(BO3B) bestaande uit twee identieke druppelfilters met zand als dragermateriaal en
onderzocht. Over de eerste biologische zuiveringsstap is bij een relatief korte
een ozonreactor ontworpen (Hoofdstuk 4). Met als doel het ontwikkelen van een kost-
verblijftijd van 1,5 uur een TOC-verwijdering van 38% behaald, waardoor het ozon
effectieve zuivering zijn verschillende hydraulische verblijftijden en ozondoseringen
verbruik in de daaropvolgende ozonisatiestap evenredig verlaagd kon worden.
onderzocht. Over de eerste biologische zuiveringsstap is bij een relatief korte
Vergeleken met het actief-slibproces, zoals toegepast in huidige
verblijftijd van 1,5 uur een TOC-verwijdering van 38% behaald, waardoor het ozon
rioolwaterzuiveringsinstallaties, presteerde de eerste biologische zuiveringsstap van
verbruik in de daaropvolgende ozonisatiestap evenredig verlaagd kon worden.
het BO3B proces beter op geneesmiddelenverwijdering, ondanks de lage verblijftijd
Vergeleken met het actief-slibproces, zoals toegepast in huidige
en lage biomassaconcentratie. Zelfs enkele moeilijk afbreekbare geneesmiddelen
rioolwaterzuiveringsinstallaties, presteerde de eerste biologische zuiveringsstap van
zoals sulfamethoxazol werden biologisch verwijderd. Met een lage ozondosis van 0.02
het BO3B proces beter op geneesmiddelenverwijdering, ondanks de lage verblijftijd
g O3/g TOC werden in de ozonisatiestap biorecalcitrante geneesmiddelen zoals
en lage biomassaconcentratie. Zelfs enkele moeilijk afbreekbare geneesmiddelen
183
zoals sulfamethoxazol werden biologisch verwijderd. Met een lage ozondosis van 0.02
g O3/g TOC werden in de ozonisatiestap biorecalcitrante geneesmiddelen zoals
183
carbamazepine effectief verwijderd. De 17% TOC-verwijdering over de laatste
biologische zuiveringsstap is vermoedelijk toe te schrijven aan de biologische
verwijdering van ozonisatie producten.
carbamazepine effectief verwijderd. De 17% TOC-verwijdering over de laatste
In algen-fotobioreactoren is het gelukt om uit anaëroob behandeld zwart water
biologische zuiveringsstap is vermoedelijk toe te schrijven aan de biologische
en uit pure urine geneesmiddelenverwijdering en nutriënten terugwinning gelijktijdig
verwijdering van ozonisatie producten.
te bewerkstelligen (Hoofdstuk 5). Uit literatuur is bekend dat algen in staat zijn
In algen-fotobioreactoren is het gelukt om uit anaëroob behandeld zwart water
stikstof en fosfor op te nemen uit brongescheiden afvalwaterstromen. Uit onze
en uit pure urine geneesmiddelenverwijdering en nutriënten terugwinning gelijktijdig
experimenten blijkt dat ze daarnaast ook bijdragen aan geneesmiddelenverwijdering
te bewerkstelligen (Hoofdstuk 5). Uit literatuur is bekend dat algen in staat zijn
uit afvalwater. Controle-experimenten toonden aan dat zowel algen, bacteriën als ook
stikstof en fosfor op te nemen uit brongescheiden afvalwaterstromen. Uit onze
de belichting van de reactor bijdragen aan de geneesmiddelenverwijdering in de
experimenten blijkt dat ze daarnaast ook bijdragen aan geneesmiddelenverwijdering
algen-fotobioreactoren. Geneesmiddelen die vatbaar zijn voor licht zoals diclofenac
uit afvalwater. Controle-experimenten toonden aan dat zowel algen, bacteriën als ook
werden verwijderd middels fotolyse, terwijl andere, zoals paracetamol en metoprolol,
de belichting van de reactor bijdragen aan de geneesmiddelenverwijdering in de
door een combinatie van fotolyse en biodegradatie verwijderd werden. Sorptie van
algen-fotobioreactoren. Geneesmiddelen die vatbaar zijn voor licht zoals diclofenac
geneesmiddelen aan algen bleek minimaal waardoor het gebruik van deze
werden verwijderd middels fotolyse, terwijl andere, zoals paracetamol en metoprolol,
nutriëntrijke biomassastroom als meststof voordelen heeft over bemesting met urine.
door een combinatie van fotolyse en biodegradatie verwijderd werden. Sorptie van
De bevindingen van deze dissertatie geven inzicht in de tekortkomingen van
geneesmiddelen aan algen bleek minimaal waardoor het gebruik van deze
individuele biologische en chemische processen voor geneesmiddelenverwijdering uit
nutriëntrijke biomassastroom als meststof voordelen heeft over bemesting met urine.
afvalwater, en benadrukken de waarde van combinaties van complementaire
De bevindingen van deze dissertatie geven inzicht in de tekortkomingen van
processen waarbij de nadelen van individuele processen wordt overstegen (Hoofdstuk
individuele biologische en chemische processen voor geneesmiddelenverwijdering uit
6). Omdat er geen universele kost-effectieve combinatie van processen bestaat,
afvalwater, en benadrukken de waarde van combinaties van complementaire
bepalen locatiespecifieke omstandigheden zoals de afvalwatercompositie welke
processen waarbij de nadelen van individuele processen wordt overstegen (Hoofdstuk
combinatie lokaal het meest effectief is. De implementatie van aanvullende
6). Omdat er geen universele kost-effectieve combinatie van processen bestaat,
zuiveringsstappen dient daarom uit te gaan van op maat gemaakte combinaties.
bepalen locatiespecifieke omstandigheden zoals de afvalwatercompositie welke
Hierbij kan worden geput uit het reeds bestaande arsenaal aan biologische en
combinatie lokaal het meest effectief is. De implementatie van aanvullende
chemische processen voor afvalwaterzuivering en eventuele nog te ontwikkelen
zuiveringsstappen dient daarom uit te gaan van op maat gemaakte combinaties.
processen. Om de kost-effectiviteit van combinatieprocessen verder te verbeteren zal
Hierbij kan worden geput uit het reeds bestaande arsenaal aan biologische en
toekomstig onderzoek moeten focussen op de onderliggende
chemische processen voor afvalwaterzuivering en eventuele nog te ontwikkelen
verwijderingsmechanismen, waaronder de enzymatische routes waarlangs
processen. Om de kost-effectiviteit van combinatieprocessen verder te verbeteren zal
geneesmiddelen verwijderd worden en de formatie en afbraak van
toekomstig onderzoek moeten focussen op de onderliggende
transformatieproducten.
verwijderingsmechanismen, waaronder de enzymatische routes waarlangs
Voor de in deze dissertatie bestudeerde verwijderingsprocessen is een
geneesmiddelen verwijderd worden en de formatie en afbraak van
vooruitzicht geschetst betreffende vervolgonderzoek en opschaling. Het BO3B-proces
transformatieproducten.
184 de in deze dissertatie bestudeerde verwijderingsprocessen is een
Voor
vooruitzicht geschetst betreffende vervolgonderzoek en opschaling. Het BO3B-proces
184
Samenvatting
en het zuiveringsproces met algen zijn rijp om op pilot-schaal getest te worden.

Samenvatting
Voornamelijk de potentie van het BO3B-proces is hoog omdat dit reeds een jaar lang
succesvol op werkelijk afvalwater is getest. Gedurende deze periode is op kost-
en het zuiveringsproces met algen zijn rijp om op pilot-schaal getest te worden.
effectieve wijze een hoog verwijderingsrendement bereikt. Opschaling zou zich
Voornamelijk de potentie van het BO3B-proces is hoog omdat dit reeds een jaar lang
voornamelijk moeten richten op het bedrijven van de biologische zuiveringsstappen,
succesvol op werkelijk afvalwater is getest. Gedurende deze periode is op kost-
omdat deze de hoge kosten van het ozonisatieproces reduceren.
effectieve wijze een hoog verwijderingsrendement bereikt. Opschaling zou zich
Het zuiveringsproces met algen wordt momenteel bestudeerd op pilot-schaal.
voornamelijk moeten richten op het bedrijven van de biologische zuiveringsstappen,
Hiervoor wordt aanbevolen, net als voor andere vervolgonderzoeken, naast
omdat deze de hoge kosten van het ozonisatieproces reduceren.
geneesmiddelen ook andere microverontreinigingen te bestuderen. De combinatie
Het zuiveringsproces met algen wordt momenteel bestudeerd op pilot-schaal.
van fotokatalyse en biologische zuivering vereist verder laboratoriumonderzoek,
Hiervoor wordt aanbevolen, net als voor andere vervolgonderzoeken, naast
omdat deze combinatie enkel op een schone watermatrix getest is. Daarnaast dient
geneesmiddelen ook andere microverontreinigingen te bestuderen. De combinatie
er voor de verduurzaming van het proces naar TiO2-immobilisatie gekeken te worden.
van fotokatalyse en biologische zuivering vereist verder laboratoriumonderzoek,
Vergaarde kennis van de afgelopen decennia onderstreept het belang van
omdat deze combinatie enkel op een schone watermatrix getest is. Daarnaast dient
effect-gebaseerde verwijderingsstrategieën en dient te worden meegenomen in
er voor de verduurzaming van het proces naar TiO2-immobilisatie gekeken te worden.
toekomstig onderzoek en implementatie. De meeste studies echter, inclusief deze
Vergaarde kennis van de afgelopen decennia onderstreept het belang van
dissertatie, zijn voornamelijk gestoeld op chemische parameters zoals
effect-gebaseerde verwijderingsstrategieën en dient te worden meegenomen in
geneesmiddelen concentraties en gaan daardoor voorbij aan de effecten van de
toekomstig onderzoek en implementatie. De meeste studies echter, inclusief deze
onderzochte stoffen op het aquatische milieu.
dissertatie, zijn voornamelijk gestoeld op chemische parameters zoals
Interventies in de geneesmiddelenketen van farmaceutische industrie tot
geneesmiddelen concentraties en gaan daardoor voorbij aan de effecten van de
drinkwaterproductie waarmee end-of-pipe-oplossingen minder nodig zijn, evenals de
onderzochte stoffen op het aquatische milieu.
implementatie van striktere wet- en regelgeving omtrent het voorkomen van
Interventies in de geneesmiddelenketen van farmaceutische industrie tot
geneesmiddelenemissies, worden beide sterk aanbevolen om de
drinkwaterproductie waarmee end-of-pipe-oplossingen minder nodig zijn, evenals de
geneesmiddelenemissies naar het milieu te verminderen. Daarnaast wordt ook het
implementatie van striktere wet- en regelgeving omtrent het voorkomen van
realiseren van brongescheiden sanitatiesystemen aanbevolen, waarmee in
geneesmiddelenemissies, worden beide sterk aanbevolen om de
vergelijking tot gemengde afvalwaterstromen een kost-effectievere
geneesmiddelenemissies naar het milieu te verminderen. Daarnaast wordt ook het
geneesmiddelenverwijdering kan worden bewerkstelligd.
realiseren van brongescheiden sanitatiesystemen aanbevolen, waarmee in
Afsluitend kan gesteld worden dat de bevindingen beschreven in deze
vergelijking tot gemengde afvalwaterstromen een kost-effectievere
dissertatie aanvullend inzicht geven in het combineren van biologische en chemische
geneesmiddelenverwijdering kan worden bewerkstelligd.
processen ten behoeve van verregaande geneesmiddelenverwijdering uit afvalwater
Afsluitend kan gesteld worden dat de bevindingen beschreven in deze
en daarbij onderdeel uitmaken van een groter geheel aan handelingen die
dissertatie aanvullend inzicht geven in het combineren van biologische en chemische
noodzakelijk zijn ter voorkoming van verdere bedreiging die geneesmiddelenemissies
processen ten behoeve van verregaande geneesmiddelenverwijdering uit afvalwater
vormen voor mens en milieu.
en daarbij onderdeel uitmaken van een groter geheel aan handelingen die
185
noodzakelijk zijn ter voorkoming van verdere bedreiging die geneesmiddelenemissies
vormen voor mens en milieu.
185
186
186
Резюме
Резюме
Употребление лекарственных препаратов растет повсеместно и тенденции
к снижению их использования в ближайшем будущем не предвидится. Спустя
несколько часов, а то и дней, после приема медикаментов человеческий организм
Употребление лекарственных препаратов растет повсеместно и тенденции
выводит их с мочой или фекалиями. Но благодаря совершенным «механизмам
к снижению их использования в ближайшем будущем не предвидится. Спустя
дренажа» человека, фармацевтические препараты частично выделяются, в виде
несколько часов, а то и дней, после приема медикаментов человеческий организм
метаболитов (то есть в другой молекулярной форме, чем исходный препарат).
выводит их с мочой или фекалиями. Но благодаря совершенным «механизмам
Через туалет и канализацию медикаменты и метаболиты попадают на пункты
дренажа» человека, фармацевтические препараты частично выделяются, в виде
очистки сточных вод.
метаболитов (то есть в другой молекулярной форме, чем исходный препарат).
Нынешние очистные сооружения, работающие на базе активного ила,
Через туалет и канализацию медикаменты и метаболиты попадают на пункты
предназначены для удаления стандартных, объемных загрязнений, таких как
очистки сточных вод.
органика, азот и фосфат. Концентрация этих веществ в сточных водах
Нынешние очистные сооружения, работающие на базе активного ила,
исчисляется миллиграммами на литр. Однако современные установки не
предназначены для удаления стандартных, объемных загрязнений, таких как
рассчитаны на удаление широкого спектра фармацевтических продуктов,
органика, азот и фосфат. Концентрация этих веществ в сточных водах
присутствующих в сточных водах. Таким образом, эта группа соединений,
исчисляется миллиграммами на литр. Однако современные установки не
выраженная разнообразными и сложными молекулярными структурами и
рассчитаны на удаление широкого спектра фармацевтических продуктов,
присутствующая в нано-микрограммах в литре жидкости, удаляется минимально.
присутствующих в сточных водах. Таким образом, эта группа соединений,
Кроме того, те лекарственные средства, у которых наблюдается биодеградация
выраженная разнообразными и сложными молекулярными структурами и
(биологический распад), как правило, не минерализуются в СО2 и Н2О, а лишь
присутствующая в нано-микрограммах в литре жидкости, удаляется минимально.
преобразуются в продукт трансформации со слегка отличающейся от исходного
Кроме того, те лекарственные средства, у которых наблюдается биодеградация
лекарственного препарата химической структурой. Таким образом, в
(биологический распад), как правило, не минерализуются в СО2 и Н2О, а лишь
окружающую среду попадает бесчисленное количество медицинских препаратов,
преобразуются в продукт трансформации со слегка отличающейся от исходного
метаболитов и продуктов трансформации.
лекарственного препарата химической структурой. Таким образом, в
Присутствие этих потенциально опасных веществ в окружающей среде
окружающую среду попадает бесчисленное количество медицинских препаратов,
является одной из главных проблем нашего времени, поскольку они реально
метаболитов и продуктов трансформации.
угрожают качеству состояния водной среды и, как следствие, здоровью
Присутствие этих потенциально опасных веществ в окружающей среде
человечества. Отрицательные последствия этих процессов, такие как, например,
является одной из главных проблем нашего времени, поскольку они реально
феминизация рыб (развитие у особи мужского пола вторичных половых
угрожают качеству состояния водной среды и, как следствие, здоровью
признаков, характерных для женской особи), также представляют угрозу для
человечества. Отрицательные последствия этих процессов, такие как, например,
всей экосистемы. Оказалось, что источники питьевой воды, уже содержат
феминизация рыб (развитие у особи мужского пола вторичных половых
признаков, характерных для женской особи), также представляют угрозу 187
для
всей экосистемы. Оказалось, что источники питьевой воды, уже содержат
187
высокие концентрации фармацевтических веществ, которые выделяются в
экосистему очистными сооружениями. Вода, производимая подобными
источниками и очищенная ненадлежащим образом, создает реальную опасность
высокие концентрации фармацевтических веществ, которые выделяются в
для здоровья населения. В связи с этим, присутствие фармацевтических
экосистему очистными сооружениями. Вода, производимая подобными
препаратов в сточных водах препятствует их повторному использованию, в то
источниками и очищенная ненадлежащим образом, создает реальную опасность
время как глобальная нехватка воды на планете могла бы быть частично решена
для здоровья населения. В связи с этим, присутствие фармацевтических
именно путем повторного использования сточных вод. Перечисленные выше
препаратов в сточных водах препятствует их повторному использованию, в то
негативные аспекты мотивируют на удаление медикаментов из сточных вод,
время как глобальная нехватка воды на планете могла бы быть частично решена
прежде чем они достигнут водной среды.
именно путем повторного использования сточных вод. Перечисленные выше
Будучи одним из главных звеньев водной цепи, очистные сооружения
негативные аспекты мотивируют на удаление медикаментов из сточных вод,
являются оптимальным местом для перехвата фармацевтических препаратов до
прежде чем они достигнут водной среды.
их попадания в окружающую среду. Уже изучен ряд биологических и химических
Будучи одним из главных звеньев водной цепи, очистные сооружения
процессов удаления медицинских средств, часть из них уже применяется. Тем не
являются оптимальным местом для перехвата фармацевтических препаратов до
менее, многие из этих методов либо не способны удалять медицинские препараты
их попадания в окружающую среду. Уже изучен ряд биологических и химических
полностью, либо являются дорогостоящими и недолговечными. Иными словами,
процессов удаления медицинских средств, часть из них уже применяется. Тем не
сегодня существует реальная нехватка доступных, с экономической точки
менее, многие из этих методов либо не способны удалять медицинские препараты
зрения, и эффективных процессов удаления фармацевтических препаратов.
полностью, либо являются дорогостоящими и недолговечными. Иными словами,
Поэтому данная диссертация посвящена исследованию различных процессов
сегодня существует реальная нехватка доступных, с экономической точки
рентабельного удаления медицинских средств из сточных вод. В работе был
зрения, и эффективных процессов удаления фармацевтических препаратов.
сделан акцент на синергизм биологических и химических процессов очистки для
Поэтому данная диссертация посвящена исследованию различных процессов
улучшенного удаления лекарственных препаратов (глава 1).
рентабельного удаления медицинских средств из сточных вод. В работе был
В целом же низкая стоимость биологических процессов очистки сточных
сделан акцент на синергизм биологических и химических процессов очистки для
вод способствует их внедрению в будущем и стимулирует их исследования. Среди
улучшенного удаления лекарственных препаратов (глава 1).
различных параметров, влияющих на биологические процессы, окислительно-
В целом же низкая стоимость биологических процессов очистки сточных
восстановительные условия считаются одними из наиболее важных. Из batch и
вод способствует их внедрению в будущем и стимулирует их исследования. Среди
колоночных экспериментов, с использованием искусственных болот, стало
различных параметров, влияющих на биологические процессы, окислительно-
понятно, что удаление фармацевтических препаратов проходило наиболее
восстановительные условия считаются одними из наиболее важных. Из batch и
эффективно в аэробных, сульфатно-восстановительных и метаногенных
колоночных экспериментов, с использованием искусственных болот, стало
условиях (глава 2). В то время как, микроаэрофильные и нитрат-
понятно, что удаление фармацевтических препаратов проходило наиболее
восстановительные условия оказались менее эффективными. Биодеградация и
эффективно в аэробных, сульфатно-восстановительных и метаногенных
сорбция были идентифицированы как основные механизмы удаления
условиях (глава 2). В то время как, микроаэрофильные и нитрат-
лекарственных препаратов. Также было установлено, что эффективность этих
восстановительные условия оказались менее эффективными. Биодеградация и
188 были
сорбция идентифицированы как основные механизмы удаления
лекарственных препаратов. Также было установлено, что эффективность этих
188
Резюме
двух процессов (биодеградации и сорбции) зависит от

окислительно-
Резюме
восстановительных условий (redox). Из всех исследуемых лекарственных
средств, пропранолол показал самый высокий коэффициент сорбции. Было также
двух процессов (биодеградации и сорбции) зависит от окислительно-
обнаружено, что насыщение сорбционных участков пропранолом происходит
восстановительных условий (redox). Из всех исследуемых лекарственных
после 300-кратного изменения объема пор при наиболее благоприятных
средств, пропранолол показал самый высокий коэффициент сорбции. Было также
окислительно-восстановительных условиях. Это говорит о том, что в процессах
обнаружено, что насыщение сорбционных участков пропранолом происходит
биологической фильтрации сорбция фармацевтических препаратов имеет
после 300-кратного изменения объема пор при наиболее благоприятных
второстепенное значение по сравнению с биодеградацией. Устойчивость био-
окислительно-восстановительных условиях. Это говорит о том, что в процессах
рекальцитрантов, таких как карбамазепин, к процессам биологической очистки
биологической фильтрации сорбция фармацевтических препаратов имеет
подчеркивает их несовершенство и указывает на необходимость в
второстепенное значение по сравнению с биодеградацией. Устойчивость био-
дополнительных небиологических этапах очистки.
рекальцитрантов, таких как карбамазепин, к процессам биологической очистки
Так мягкий фотокатализ в присутствии УФ-светодиода и TiO2 в сочетании с
подчеркивает их несовершенство и указывает на необходимость в
последующей биологической обработкой продемонстрировал улучшенное
дополнительных небиологических этапах очистки.
удаление лекарственных средств по сравнению с этими же процессами,
Так мягкий фотокатализ в присутствии УФ-светодиода и TiO2 в сочетании с
проведенными по отдельности (глава 3). Три из девяти исследуемых
последующей биологической обработкой продемонстрировал улучшенное
фармацевтических препаратов были частично удалены путем мягкой
удаление лекарственных средств по сравнению с этими же процессами,
фотокаталитической обработки. Биодеградация четырех других медицинских
проведенными по отдельности (глава 3). Три из девяти исследуемых
препаратов также улучшилась после мягкой предварительной обработки
фармацевтических препаратов были частично удалены путем мягкой
фотокатализом. И лишь один из этих четырех препаратов был частично удален
фотокаталитической обработки. Биодеградация четырех других медицинских
во время легкого фотокатализа. Кроме того, мягкая предварительная
препаратов также улучшилась после мягкой предварительной обработки
фотокаталитическая обработка способствовала биодеградированию
фотокатализом. И лишь один из этих четырех препаратов был частично удален
диклофенака, который продемонстрировал устойчивость к однократной
во время легкого фотокатализа. Кроме того, мягкая предварительная
биологической обработке. Также выдвинуто предположение, что продукты
фотокаталитическая обработка способствовала биодеградированию
распада трех медицинских препаратов, удаляемые мягким фотокатализом,
диклофенака, который продемонстрировал устойчивость к однократной
приводят к активации биологических систем, участвующих в первоначальных
биологической обработке. Также выдвинуто предположение, что продукты
реакциях биодеградации органических молекул.
распада трех медицинских препаратов, удаляемые мягким фотокатализом,
Наряду с фармацевтическими препаратами в сточных водах также
приводят к активации биологических систем, участвующих в первоначальных
присутствует множество безвредных органических веществ. В этом случае, в
реакциях биодеградации органических молекул.
качестве дополнительного процесса очистки сточных вод, используется их
Наряду с фармацевтическими препаратами в сточных водах также
озонирование. Однако эти органические вещества захватывают большую часть
присутствует множество безвредных органических веществ. В этом случае, в
самого озона, что значительно снижает эффективность этого процесса. Высокие
качестве дополнительного процесса очистки сточных вод, используется их
концентрации общего органического углерода (ООУ) (17,3 мг ООУ/литр) в
озонирование. Однако эти органические вещества захватывают большую часть
189
самого озона, что значительно снижает эффективность этого процесса. Высокие
концентрации общего органического углерода (ООУ) (17,3 мг ООУ/литр) в
189
сточных водах, используемых для данного исследования, требуют ввода больших
доз озона, что снижает экономическую эффективность озонирования. Поэтому в
рамках исследования был разработан трехступенчатый био-озоно-биопроцесс
сточных водах, используемых для данного исследования, требуют ввода больших
(BO3B), включающий озоновый реактор и два одинаковых фильтра с насадкой,
доз озона, что снижает экономическую эффективность озонирования. Поэтому в
использующих песок в качестве носителей биомассы (глава 4). В целях
рамках исследования был разработан трехступенчатый био-озоно-биопроцесс
разработки рентабельной системы очистки были исследованы различные
(BO3B), включающий озоновый реактор и два одинаковых фильтра с насадкой,
времена гидравлического удержания (ВГУ) и дозы озона. Первый биологический
использующих песок в качестве носителей биомассы (глава 4). В целях
реактор удалял 38% ООУ при ВГУ в 1,5 часа, что пропорционально уменьшало
разработки рентабельной системы очистки были исследованы различные
потребность в озоне в последующем озоновом реакторе. Улучшенное удаление
времена гидравлического удержания (ВГУ) и дозы озона. Первый биологический
фармацевтических препаратов по сравнению с обычной очисткой сточных вод
реактор удалял 38% ООУ при ВГУ в 1,5 часа, что пропорционально уменьшало
наблюдалось в первом биологическом реакторе, несмотря на короткое ВГУ и
потребность в озоне в последующем озоновом реакторе. Улучшенное удаление
низкое количество биомассы в системе BO3B. Эффективная биодеградация была
фармацевтических препаратов по сравнению с обычной очисткой сточных вод
продемонстрирована даже для таких трудноразлагаемых лекарственных средств,
наблюдалось в первом биологическом реакторе, несмотря на короткое ВГУ и
как сульфаметоксазол. Био-рекальцитранты, такие как карбамазепин,
низкое количество биомассы в системе BO3B. Эффективная биодеградация была
эффективно удалялись при низких дозах озона (до 0,2 г O3/г ООУ). Удаление 17%
продемонстрирована даже для таких трудноразлагаемых лекарственных средств,
ООУ в последнем биологическом реакторе свидетельствовало об удалении
как сульфаметоксазол. Био-рекальцитранты, такие как карбамазепин,
продуктов трансформации, образовавшихся во время озонирования.
эффективно удалялись при низких дозах озона (до 0,2 г O3/г ООУ). Удаление 17%
Одновременное извлечение биогенов и удаление фармацевтических
ООУ в последнем биологическом реакторе свидетельствовало об удалении
препаратов было обнаружено в фотобиореакторах с культивацией водорослей,
продуктов трансформации, образовавшихся во время озонирования.
работающих на анаэробно обработанной черной воде или моче (глава 5). Было
Одновременное извлечение биогенов и удаление фармацевтических
обнаружено, что водоросли, которые, как известно, способны поглощать азот и
препаратов было обнаружено в фотобиореакторах с культивацией водорослей,
фосфор из этих высококонцентрированных источников сточных вод, также
работающих на анаэробно обработанной черной воде или моче (глава 5). Было
способствовали удалению из них фармацевтических препаратов. Контрольные
обнаружено, что водоросли, которые, как известно, способны поглощать азот и
эксперименты еще раз подтвердили факт содействия водорослей, бактерий и
фосфор из этих высококонцентрированных источников сточных вод, также
света в удалении фармацевтических препаратов. Нужно также отметить
способствовали удалению из них фармацевтических препаратов. Контрольные
поведение медицинских препаратов, оказавшихся чувствительными к фотолизу.
эксперименты еще раз подтвердили факт содействия водорослей, бактерий и
Так, например, диклофенак, после применения этой химической реакции,
света в удалении фармацевтических препаратов. Нужно также отметить
фотодеградировал, тогда как парацетамол и метопролол удалились лишь при
поведение медицинских препаратов, оказавшихся чувствительными к фотолизу.
комбинирование био- и фото- деградаций. Сорбция фармацевтических
Так, например, диклофенак, после применения этой химической реакции,
препаратов для водорослей оказалась минимальной, что позволяет
фотодеградировал, тогда как парацетамол и метопролол удалились лишь при
рекомендовать использование этой богатой питательными веществами биомассы
комбинирование био- и фото- деградаций. Сорбция фармацевтических
препаратов для водорослей оказалась минимальной, что позволяет
190
рекомендовать использование этой богатой питательными веществами биомассы
190
Резюме
в качестве удобрения, поскольку она имеет большие преимущества Резюме

перед
применением для таких же целей мочи.
Таким образом, результаты данной работы дают представление о
в качестве удобрения, поскольку она имеет большие преимущества перед
недостатках отдельно проведенных биологических и химических процессов
применением для таких же целей мочи.
удаления фармацевтических препаратов из сточных вод и подчеркивают
Таким образом, результаты данной работы дают представление о
ценность их комбинирования (глава 6). Специфические для каждой конкретной
недостатках отдельно проведенных биологических и химических процессов
ситуации условия, такие как, например состав сточных вод, определяют, какая
удаления фармацевтических препаратов из сточных вод и подчеркивают
комбинация процессов будет наиболее выгодна в данном случае, поскольку
ценность их комбинирования (глава 6). Специфические для каждой конкретной
универсальной экономически-эффективной комбинации процессов не
ситуации условия, такие как, например состав сточных вод, определяют, какая
существует. Поэтому внедрение дополнительных этапов очистки должно быть
комбинация процессов будет наиболее выгодна в данном случае, поскольку
сосредоточено на поиске индивидуальных комбинаций для каждого конкретного
универсальной экономически-эффективной комбинации процессов не
случая. Для дальнейшего повышения рентабельности комбинированных
существует. Поэтому внедрение дополнительных этапов очистки должно быть
процессов будущие исследователи должны сосредоточить свое внимание на
сосредоточено на поиске индивидуальных комбинаций для каждого конкретного
основных механизмах удаления, включая ферментативные пути деградации
случая. Для дальнейшего повышения рентабельности комбинированных
фармацевтических препаратов, а также образование и удаление продуктов
процессов будущие исследователи должны сосредоточить свое внимание на
трансформации.
основных механизмах удаления, включая ферментативные пути деградации
Изученные и описанные в этой диссертации процессы очистки
фармацевтических препаратов, а также образование и удаление продуктов
представляют собой прекрасную перспективу для дальнейших исследований и
трансформации.
укрепления opschaling (увеличения масштабов процессов). Так, например,
Изученные и описанные в этой диссертации процессы очистки
процесс BO3B и система очистки при помощи водорослей проведены в рамках
представляют собой прекрасную перспективу для дальнейших исследований и
пилотного проекта и готовы к последующим изучениям и экспериментам. Нужно
укрепления opschaling (увеличения масштабов процессов). Так, например,
отметить, что система BO3B была успешно протестирована в лабораторных
процесс BO3B и система очистки при помощи водорослей проведены в рамках
условиях на реальных сточных водах в течение года и продемонстрировала
пилотного проекта и готовы к последующим изучениям и экспериментам. Нужно
высокую эффективность удаления фармацевтических препаратов и оказалась
отметить, что система BO3B была успешно протестирована в лабораторных
экономически доступным способом.
условиях на реальных сточных водах в течение года и продемонстрировала
Будущим исследователям также необходимо сфокусироваться на работе
высокую эффективность удаления фармацевтических препаратов и оказалась
биологических реакторов, поскольку именно они способствуют рентабельности
экономически доступным способом.
процесса BO3B, и на удалении широкого спектра микрозагрязнений. Комбинация
Будущим исследователям также необходимо сфокусироваться на работе
фотокатализа и биодеградации также требует дальнейших лабораторных
биологических реакторов, поскольку именно они способствуют рентабельности
исследований, поскольку для улучшения устойчивости системы должен быть
процесса BO3B, и на удалении широкого спектра микрозагрязнений. Комбинация
решен вопрос иммобилизации TiO2; к тому же, данная система была проверена
фотокатализа и биодеградации также требует дальнейших лабораторных
только на чистой матрице.
исследований, поскольку для улучшения устойчивости системы должен быть
191
решен вопрос иммобилизации TiO2; к тому же, данная система была проверена
только на чистой матрице.
191
Знания, полученные в течение последних десятилетий, подчеркивают
важность усовершенствования стратегий очистки и нацелены на конечный
эффект. Исследования же, проведенные в рамках этой диссертации, обращены
Знания, полученные в течение последних десятилетий, подчеркивают
на оптимизацию химических показателей, таких как концентрации отдельных
важность усовершенствования стратегий очистки и нацелены на конечный
фармацевтических препаратов, и не учитывают конечный эффект этих
эффект. Исследования же, проведенные в рамках этой диссертации, обращены
препаратов, например, на водную среду. Системы санитарии (source separation),
на оптимизацию химических показателей, таких как концентрации отдельных
работающие на разделении сточных вод на выходе «из дома», позволяют
фармацевтических препаратов, и не учитывают конечный эффект этих
перехватить и экономически-эффективно удалить фармацевтические препараты
препаратов, например, на водную среду. Системы санитарии (source separation),
еще на ранних этапах очистки сточных вод. Кроме того, source separation
работающие на разделении сточных вод на выходе «из дома», позволяют
уменьшают потребность в очистке в конце технологического цикла, а также
перехватить и экономически-эффективно удалить фармацевтические препараты
являются настоятельно рекомендуемыми для повсеместного внедрения. Более
еще на ранних этапах очистки сточных вод. Кроме того, source separation
того, необходимо ужесточить законодательство, регулирующее концентрацию
уменьшают потребность в очистке в конце технологического цикла, а также
выбросов фармацевтических препаратов в сточные воды.
являются настоятельно рекомендуемыми для повсеместного внедрения. Более
В заключение хотелось бы отметить, что результаты, полученные в данной
того, необходимо ужесточить законодательство, регулирующее концентрацию
диссертации, способствуют лучшему пониманию сочетания процессов
выбросов фармацевтических препаратов в сточные воды.
биологической и химической очистки сточных вод от фармацевтического
В заключение хотелось бы отметить, что результаты, полученные в данной
загрязнения. А также являются набором шагов, которые необходимо предпринять
диссертации, способствуют лучшему пониманию сочетания процессов
для предотвращения дальнейших выбросов фармацевтических препаратов и
биологической и химической очистки сточных вод от фармацевтического
других загрязнителей, реально угрожающих окружающей среде и здоровью
загрязнения. А также являются набором шагов, которые необходимо предпринять
населения.
для предотвращения дальнейших выбросов фармацевтических препаратов и
других загрязнителей, реально угрожающих окружающей среде и здоровью
населения.
192
192
Acknowledgement
Acknowledgement
Like in nature, the local environment plays a crucial role in the success of
Acknowledgement
communities and individuals. Being a very happy individual, I would like to express
Like in nature, the local environment plays a crucial role in the success of
my gratitude for having worked in a very nice environment at the sub-department of
Like
communities in and
nature, the local
individuals. environment
Being a very happyplaysindividual,
a crucialI role wouldin like
the to
success
expressof
Environmental Technology. Populated with a diverse community of specialists, team-
communities
my gratitudeand individuals.
for having worked Being
in a avery
very happy
nice individual,
environment at Ithe
would like to express
sub-department of
players, critical thinkers and beer-drinkers the department houses an excellent
myEnvironmental Technology. Populated with a diverse community of specialists, team-of
gratitude for having worked in a very nice environment at the sub-department
atmosphere to flourish in both the scientific and personal direction. Credits therefore
Environmental
players, critical Technology.
thinkers and Populated with a diverse
beer-drinkers communityhouses
the department of specialists, team-
an excellent
to the chairmen Cees and Huub who manage to maintain this environment, but equal
players, critical
atmosphere thinkers
to flourish and the
in both beer-drinkers
scientific andthe department
personal houses
direction. Creditsan therefore
excellent
credits to all those colleagues who contribute(d) to this pleasant working place. As I
atmosphere
to the chairmen to flourish
Cees and in both
Huubthe who scientific
manageand personalthis
to maintain direction. Creditsbut
environment, therefore
equal
know that I will fail to name everybody of the department and considering that real
tocredits
the chairmen
to all those Cees and Huubwho
colleagues whocontribute(d)
manage to maintain this environment,
to this pleasant working place.but equal
As I
interaction is much more important than being mentioned on paper like in this
credits to allI those
know that will failcolleagues who contribute(d)
to name everybody to this pleasant
of the department working place.
and considering As I
that real
dissertation, I would like to thank ALL colleagues A LOT for the great time at the
interaction
know that I willis much
fail tomore
nameimportant
everybodythan of thebeing mentioned
department andonconsidering
paper like thatin this
real
department.
dissertation,
interaction is Imuch
wouldmore like to thank ALLthan
important colleagues A LOT for the
being mentioned on great
paper time
like at
in the
this
Success is not only dictated by the local environment, also the interaction
department. I would like to thank ALL colleagues A LOT for the great time at the
dissertation,
between individuals highly contribute to the success of individuals and thereby of the
Success is not only dictated by the local environment, also the interaction
department.
community.
between I would highly
individuals like tocontributes
thank two to individuals in of
particular for theirthereby
symbiotic
Success is not only dictated by thethe success
local individuals
environment, also and
the interactionof
interaction that
the community. highly
I would contributed
like to
to thank to the
two success of
individuals our local pharma-community.
inindividuals
particular for
between individuals highly contribute the success of andtheir symbiotic
thereby of the
Alette,
interaction starting
that highly together
contributed at the
to department
the success at
of exactly
our local the same date,
pharma-community. you were
community. I would like to thank two individuals in particular for their symbiotic
a symbiont since day one.
Alette, I wasat very happy that after our fruitful collaboration
date, you during
interaction thatstarting
highly together
contributed the department
to the success at of exactly
our local the same
pharma-community. were
my MSc thesis
a symbiont you
day had
one. theI wastrust in me thatto become ouryour PhD candidate during
in the
Alette,since
starting together atvery
the happy
departmentafter at exactly fruitful collaboration
the same date, you were
undiscovered
my MSc thesis fieldyou
of pharmaceutical
had the trust in removal.
me to As in a true
become yoursymbiosis I think we
PhD candidate in have
the
a symbiont since day one. I was very happy that after our fruitful collaboration during
learned and achieved a lot in our (scientific)work and I am very
undiscovered field of pharmaceutical removal. As in a true symbiosis I think we have pleased that most
my MSc thesis you had the trust in me to become your PhD candidate in the
likely thisand
learned symbiosis
achievedwilla not
lot end
in oursoon as I have theand
(scientific)work feeling
I am that
very there is way
pleased more
that mostwe
undiscovered field of pharmaceutical removal. As in a true symbiosis I think we have
can achieve.
likely Thank you
this symbiosis will for
not providing
end soon as meI oceans
have the offeeling
freedom thatwhile
therealso being
is way moresuchwea
learned and achieved a lot in our (scientific)work and I am very pleased that most
good mentor to
can achieve. me,you
Thank including your critical
for providing reflection
me oceans on ourwhile
of freedom workalsoandbeing
on me suchasaa
likely this symbiosis will not end soon as I have the feeling that there is way more we
good mentor
person. ThoughtoI me, including
am not that fond yourofcritical reflection
gardening, sewing on and
our reading
work and on me
e-mail at 7asAM,
a
can achieve. Thank you for providing me oceans of freedom while also being such a
I person. Though
admire your I am not
enormous thatand
drive fonddedication
of gardening, sewing
for the andin
aspects reading
life youe-mail at 7 AM,
find important.
good mentor to me, including your critical reflection on our work and on me as a
I admire
This your enormous
was very drive and
well expressed duringdedication
your timefor the
off, aspects
I highlyinappreciated
life you find important.
the contact
person. Though I am not that fond of gardening, sewing and reading e-mail at 7 AM,
This was very well expressed during your time off, I highly
we had in those months and truly believe that your dedication to work helped appreciated the contact
you to
I admire your enormous drive and dedication for the aspects in life you find important.
we had in those months and truly believe that your dedication
recover. Next to your dedication, the interest you show in a person beyond the work to work helped you to
This was very well expressed during your time off, I highly appreciated the contact
recover. Next to your dedication, the interest you show in a person beyond the work
we had in those months and truly believe that your dedication to work helped you to
193
recover. Next to your dedication, the interest you show in a person beyond the work
193
193
related interest makes you a pleasant person to work with and is a quality that
definitely improves the collaboration with others.
Huub, being a good motivator and a practically oriented person, I am very
related interest makes you a pleasant person to work with and is a quality that
thankful for our symbiosis. You kept the overview of our project and especially
definitely improves the collaboration with others.
contributed a lot by putting our work in a broader context during manuscript (re-
Huub, being a good motivator and a practically oriented person, I am very
)writing. I have learned a lot from your managing, networking and negotiation skills
thankful for our symbiosis. You kept the overview of our project and especially
and admire your capacity to convince others in an honest, but well thought out way,
contributed a lot by putting our work in a broader context during manuscript (re-
of the importance of our work while not being an annoying pushy salesperson. I am
)writing. I have learned a lot from your managing, networking and negotiation skills
happy that most likely we will continue to work together in the nearby future and
and admire your capacity to convince others in an honest, but well thought out way,
would like to note that looking at our department with its current size, research and
of the importance of our work while not being an annoying pushy salesperson. I am
personnel diversity and the wonderful and healthy state it is in, you can be very proud
happy that most likely we will continue to work together in the nearby future and
of yourself.
would like to note that looking at our department with its current size, research and
As an unidentified, but difficult to culture, multilingual sub-species, the civilians
personnel diversity and the wonderful and healthy state it is in, you can be very proud
occupying room 1.087 during the period 2013-2017 are kindly acknowledged for the
of yourself.
distraction of my PhD work they offered me, their great sense of humour, the in-
As an unidentified, but difficult to culture, multilingual sub-species, the civilians
depth discussions on environmental-political-craziness and the meaning of life, and
occupying room 1.087 during the period 2013-2017 are kindly acknowledged for the
the talks about cows and calves. Without you girls and guys my PhD work would have
distraction of my PhD work they offered me, their great sense of humour, the in-
been much more boring, and I know yours would be as well ;-) Apologies for the
depth discussions on environmental-political-craziness and the meaning of life, and
delay in your work caused by my distractivity, but I am pretty sure that all of you will
the talks about cows and calves. Without you girls and guys my PhD work would have
make it (or already made it) as room 1.087 is simply the best!
been much more boring, and I know yours would be as well ;-) Apologies for the
Yujie and Wenbo, thank you for being my partners in pharma-crime, it was
delay in your work caused by my distractivity, but I am pretty sure that all of you will
productive, interesting and fun working with you. The Chinese-Dutch food we cooked
make it (or already made it) as room 1.087 is simply the best!
and consumed together leaves some good memories. I would also like to thank the
Yujie and Wenbo, thank you for being my partners in pharma-crime, it was
people that contributed to this dissertation outside of our department; Tânia for
productive, interesting and fun working with you. The Chinese-Dutch food we cooked
bringing me in contact with microalgae, Lucia for the support to Andrii and me with
and consumed together leaves some good memories. I would also like to thank the
manuscript writing and Marco at Rikilt and Ton at Wetsus for the analytical
people that contributed to this dissertation outside of our department; Tânia for
contributions to our work.
bringing me in contact with microalgae, Lucia for the support to Andrii and me with
As not only the local but also macro environment is of great importance in
manuscript writing and Marco at Rikilt and Ton at Wetsus for the analytical
successfulness, I would like to acknowledge some people at the other side of the
contributions to our work.
Atlantic Ocean in the magnificent country called Canada. Many credits to Wayne
As not only the local but also macro environment is of great importance in
offering my family and me the opportunity to come to Waterloo. Thanks to Julia and
successfulness, I would like to acknowledge some people at the other side of the
Wayne for your warm welcome and for the work- and personal related wisdom you
Atlantic Ocean in the magnificent country called Canada. Many credits to Wayne
194
offering my family and me the opportunity to come to Waterloo. Thanks to Julia and
Wayne for your warm welcome and for the work- and personal related wisdom you
194
Acknowledgement
shared with us. Maricor, Leslie, Mark, Mark, Mark and Terry thanks for the great
Acknowledgement
cooperation, your time and patience and the pleasant contact we had. Tom thanks
for everything you shared with me and introducing me to local Canadian beers, I hope
shared with us. Maricor, Leslie, Mark, Mark, Mark and Terry thanks for the great
all is well with you and your family.
cooperation, your time and patience and the pleasant contact we had. Tom thanks
LeAF collega’s, vooropgesteld Marjo waaraan ik mijn aanstelling bij LeAF te
for everything you shared with me and introducing me to local Canadian beers, I hope
danken heb, hartelijk dank dat jullie mij hebben opgenomen in jullie fantastische
all is well with you and your family.
team van humorrijke wereldverbeteraars. Jullie enthousiasme en de interesse voor
LeAF collega’s, vooropgesteld Marjo waaraan ik mijn aanstelling bij LeAF te
de werkinhoud alsook in de mens die schuilgaat in iedere collega waardeer ik enorm.
danken heb, hartelijk dank dat jullie mij hebben opgenomen in jullie fantastische
Jan, Tiemen en Iemke, met jullie diverse achtergronden en persoonlijkheden is het
team van humorrijke wereldverbeteraars. Jullie enthousiasme en de interesse voor
heel prettig opboksen tegen conservatieve ambtenaren om deze het Nieuwe
de werkinhoud alsook in de mens die schuilgaat in iedere collega waardeer ik enorm.
Sanitatie-licht te laten zien. Ook al zal het nog jaren duren eerdat Nieuwe Sanitatie
Jan, Tiemen en Iemke, met jullie diverse achtergronden en persoonlijkheden is het
conventionele sanitatie wordt, er is hoop, of in LeAF termen er is ‘een stip op de
heel prettig opboksen tegen conservatieve ambtenaren om deze het Nieuwe
horizon’. Els en Kasia, het samenwerken aan de verwijdering van
Sanitatie-licht te laten zien. Ook al zal het nog jaren duren eerdat Nieuwe Sanitatie
microverontreiniging op praktijkschaal is een hele fijne aanvulling geweest op het lab-
conventionele sanitatie wordt, er is hoop, of in LeAF termen er is ‘een stip op de
schaal niveau waarop ik voor mijn promotie werkte. Met plezier hoop ik nog veel met
horizon’. Els en Kasia, het samenwerken aan de verwijdering van
jullie allemaal, ook met LeAF dames Darja, Judith, Miriam, Anita, Marjo en Grietje,
microverontreiniging op praktijkschaal is een hele fijne aanvulling geweest op het lab-
samen te blijven werken.
schaal niveau waarop ik voor mijn promotie werkte. Met plezier hoop ik nog veel met
I would also thank some people who might not be aware of this dissertation
jullie allemaal, ook met LeAF dames Darja, Judith, Miriam, Anita, Marjo en Grietje,
but did contribution to it. First, but not least, Юрий Алексеевич Гагарин (Yuri
samen te blijven werken.
Alekseyevich Gagarin), I saw you every day at the office. Your admirable
I would also thank some people who might not be aware of this dissertation
achievements have greatly inspired me. Your accompanying slogan Мужеству, труду,
but did contribution to it. First, but not least, Юрий Алексеевич Гагарин (Yuri
разуму, Советского народа слава (Courage, work, reason, for people's glory) has
Alekseyevich Gagarin), I saw you every day at the office. Your admirable
distinctly improved my Russian reading skills. Our relationship will not end soon as I
achievements have greatly inspired me. Your accompanying slogan Мужеству, труду,
will not delete you in the nearby future as my desktop background. Second, this
разуму, Советского народа слава (Courage, work, reason, for people's glory) has
dissertation profited from the symbiosis between art and science. Matching with the
distinctly improved my Russian reading skills. Our relationship will not end soon as I
combined processes approach for enhanced pharmaceutical removal, the combination
will not delete you in the nearby future as my desktop background. Second, this
of music and science improved the outcome of this dissertation. Therefore thanks to
dissertation profited from the symbiosis between art and science. Matching with the
all the artists of the Thunderdome Hardcore 100 album and to Sepultura for their
combined processes approach for enhanced pharmaceutical removal, the combination
Schizophrenia album as both helped to keep up my brain activity and typing speed.
of music and science improved the outcome of this dissertation. Therefore thanks to
Дорогие мои родственники, спасибо за ваш вклад в исследование и
all the artists of the Thunderdome Hardcore 100 album and to Sepultura for their
написание моей диссертации. Ваша поддержка и восхищение моей работой,
Schizophrenia album as both helped to keep up my brain activity and typing speed.
которую я, к сожалению, не смог вам хорошо объяснить, очень помогли мне. Вы
Дорогие мои родственники, спасибо за ваш вклад в исследование и
195
написание моей диссертации. Ваша поддержка и восхищение моей работой,
которую я, к сожалению, не смог вам хорошо объяснить, очень помогли мне. Вы
195
заставили меня почувствовать, что я делаю все правильно — и для себя и для
своей семьи. Еще раз спасибо, за все хорошее, и надеюсь, что мы еще долго и
часто будем встречаться.
заставили меня почувствовать, что я делаю все правильно — и для себя и для
Lieve familie en vrienden, dank voor jullie betrokkenheid, ieder op zijn/haar
своей семьи. Еще раз спасибо, за все хорошее, и надеюсь, что мы еще долго и
eigen wijze, bij de totstandkoming van deze dissertatie. Vooral de geweldige steun in
часто будем встречаться.
velerlei vormen die wij als gezin van jullie krijgen wordt enorm gewaardeerd. Mijn
Lieve familie en vrienden, dank voor jullie betrokkenheid, ieder op zijn/haar
dank is groot voor diegene die mij geholpen hebben te worden wie ik ben. Berte en
eigen wijze, bij de totstandkoming van deze dissertatie. Vooral de geweldige steun in
Marius, jullie in het bijzonder, hebben mij vertrouwen, sturing en ruimte gegeven
velerlei vormen die wij als gezin van jullie krijgen wordt enorm gewaardeerd. Mijn
waardoor ik een gelukkig mens ben geworden. Ondanks dat ik de dank hiervoor
dank is groot voor diegene die mij geholpen hebben te worden wie ik ben. Berte en
onvoldoende vaak uit spreek, wil ik jullie hier enorm voor bedanken en hoop ik ook
Marius, jullie in het bijzonder, hebben mij vertrouwen, sturing en ruimte gegeven
nog veel voor jullie te kunnen betekenen.
waardoor ik een gelukkig mens ben geworden. Ondanks dat ik de dank hiervoor
Allerliefste Daniël en Davíd, helaas hebben jullie nog weinig weet van de
onvoldoende vaak uit spreek, wil ik jullie hier enorm voor bedanken en hoop ik ook
materie waar papa zich de afgelopen jaren mee bezig heeft gehouden, maar een tipje
nog veel voor jullie te kunnen betekenen.
van de sluier; milieutechnologie is supertof. Zonder het jullie op te dringen komt er
Allerliefste Daniël en Davíd, helaas hebben jullie nog weinig weet van de
zeker een dag dat ik jullie haarfijn uitleg wat het effect van ozonisatie op
materie waar papa zich de afgelopen jaren mee bezig heeft gehouden, maar een tipje
carbamazepine is, en waarom milde fotokatalyse biodegradatie stimuleert. Weet dat
van de sluier; milieutechnologie is supertof. Zonder het jullie op te dringen komt er
mama en papa heel erg blij met jullie zijn en wij enorm veel van jullie houden. Zorg
zeker een dag dat ik jullie haarfijn uitleg wat het effect van ozonisatie op
goed voor elkaar, maak veel plezier in jullie levens en vergeet niet samen te spelen
carbamazepine is, en waarom milde fotokatalyse biodegradatie stimuleert. Weet dat
en samen te delen.
mama en papa heel erg blij met jullie zijn en wij enorm veel van jullie houden. Zorg
Моя любимая бубочка, если я должен поблагодарить кого-то за поддержку,
goed voor elkaar, maak veel plezier in jullie levens en vergeet niet samen te spelen
которую я получил во время моей аспирантуры, то это тебя. Этот период не
en samen te delen.
всегда был самым легким, с всеми делами, которые я хотел сделать, но я очень
Моя любимая бубочка, если я должен поблагодарить кого-то за поддержку,
благодарен, что ты дала мне много свободы для действий. Надеюсь, мы будем
которую я получил во время моей аспирантуры, то это тебя. Этот период не
пожинать плоды вместе. Ты замечательная жена и супер мама для наших
всегда был самым легким, с всеми делами, которые я хотел сделать, но я очень
прекрасных мальчиков. Ты не знаешь, как я счастлив с тобой. Скоро наши
благодарен, что ты дала мне много свободы для действий. Надеюсь, мы будем
мальчики подрастут, и наступит время, когда ты тоже сможешь позаботиться о
пожинать плоды вместе. Ты замечательная жена и супер мама для наших
себе. Не сомневайся в себе, больше уверенности, ты просто молодец! Я надеюсь,
прекрасных мальчиков. Ты не знаешь, как я счастлив с тобой. Скоро наши
что солнце будет долго сиять в наших сердцах, и я уверен, что у нас будет еще
мальчики подрастут, и наступит время, когда ты тоже сможешь позаботиться о
много хороших, красивых и счастливых моментов. С большой любовью и верой в
себе. Не сомневайся в себе, больше уверенности, ты просто молодец! Я надеюсь,
тебя, нежно целую, твой вонючка.
что солнце будет долго сиять в наших сердцах, и я уверен, что у нас будет еще
много хороших, красивых и счастливых моментов. С большой любовью и верой в
тебя, нежно целую, твой вонючка.
196
196
Curriculum vitae
Henrik Arnoud de Wilt was born on September 10th, 1987 in Utrecht, the
Curriculum vitae
Netherlands. In 2006 he finished his secondary education with a VWO beta-profile
diploma at the Stichtse Vrije School in Zeist, after which he started his Bachelor’s
Henrik Arnoud de Wilt was born on September 10th, 1987 in Utrecht, the
study Milieukunde with a specialisation in Milieutechnologie at Wageningen University.
Netherlands. In 2006 he finished his secondary education with a VWO beta-profile
Arnoud completed his Bachelor’s Degree at the sub-department of Environmental
diploma at the Stichtse Vrije School in Zeist, after which he started his Bachelor’s
Technology in 2009, with a thesis on the feasibility of plant power technology on
study Milieukunde with a specialisation in Milieutechnologie at Wageningen University.
green roofs. After graduation, he was employed by DeSaH and worked on the
Arnoud completed his Bachelor’s Degree at the sub-department of Environmental
construction and operation of a novel sanitation system including decentralised
Technology in 2009, with a thesis on the feasibility of plant power technology on
wastewater treatment at an Olympic boarding school in Crimea, Ukraine. In 2011 he
green roofs. After graduation, he was employed by DeSaH and worked on the
returned to the Netherlands to start his
construction and operation of a novel sanitation system including decentralised
Master’s study Environmental Sciences at
wastewater treatment at an Olympic boarding school in Crimea, Ukraine. In 2011 he
Wageningen University, with a
returned to the Netherlands to start his
specialisation in Environmental Technology.
Master’s study Environmental Sciences at
During his studies Arnoud continued to
Wageningen University, with a
remotely work part-time for DeSaH on the
specialisation in Environmental Technology.
project in Ukraine. He graduated in 2013
During his studies Arnoud continued to
with a thesis at the sub-department of
remotely work part-time for DeSaH on the
Environmental Technology on the biological
project in Ukraine. He graduated in 2013
removal of pharmaceuticals from domestic
with a thesis at the sub-department of
wastewater and an internship at the
Environmental Technology on the biological
Netherlands Institute of Ecology on removal of pharmaceuticals from source
removal of pharmaceuticals from domestic
separated wastewater by algae. Under supervision of Dr Alette Langenhoff and Prof.
wastewater and an internship at the
Dr Huub Rijnaarts Arnoud started a PhD in 2013 on the removal of pharmaceuticals
Netherlands Institute of Ecology on removal of pharmaceuticals from source
from wastewater at the sub-department of Environmental Technology of the
separated wastewater by algae. Under supervision of Dr Alette Langenhoff and Prof.
Wageningen University. In 2016, parallel to his PhD, he started to work part-time for
Dr Huub Rijnaarts Arnoud started a PhD in 2013 on the removal of pharmaceuticals
LeAF as a consultant on new sanitation and micropollutant removal. He will continue
from wastewater at the sub-department of Environmental Technology of the
his career in the field of micropollutant removal from wastewater at Royal
Wageningen University. In 2016, parallel to his PhD, he started to work part-time for
HaskoningDHV, while continuing his work for LeAF.
LeAF as a consultant on new sanitation and micropollutant removal. He will continue
his career in the field of micropollutant removal from wastewater at Royal
HaskoningDHV, while continuing his work for LeAF. 197
197
Netherlands Research School for the
Socio-Economic and Natural Sciences of the Environment
D I P L O M A
For specialised PhD training
The Netherlands Research School for the

Socio-Economic and Natural Sciences of the Environment
(SENSE) declares that

born on 10 September 1987 in Utrecht, The Netherlands
has successfully fulfilled all requirements of the

Educational Programme of SENSE.
Wageningen, 2 February 2018
the Chairman of the SENSE board the SENSE Director of Education
Prof. dr. Huub Rijnaarts Dr. Ad van Dommelen
The SENSE Research School has been accredited by the Royal Netherlands Academy of Arts and Sciences (KNAW)
The SENSE Research School declares that Mr Henrik Arnoud de Wilt has successfully fulfilled
all requirements of the Educational PhD Programme of SENSE with a
work load of 35 EC, including the following activities:
SENSE PhD Courses

o Environmental research in context (2014)
o Research in context activity: ‘Preparing and organizing scientific and social Alumni Day:
50 years Environmental Technology’ (2015)
o Advanced Course on Environmental Biotechnology (2015)
o Stable Isotope applications in Microbiology and Environmental Studies (2017)
Other PhD and Advanced MSc Courses

o Communication with the Media and the General Public, Wageningen University (2014)
o Competence Assessment, Wageningen University (2014)
o Voice Matters-Voice and Presentation Skills Training, Wageningen University (2015)
o Project and Time Management, Wageningen University (2015)
o Teaching and supervising Thesis students, Wageningen University (2015)
External training at a foreign research institute

o International Collaborative Research, University of Waterloo, Canada (2015)
o PhD study trip to Tsinghua University, Chinese Academy of Sciences, Tongji University
and etc. China (2016)
Management and Didactic Skills Training

o Supervising six MSc students (2013-2017)
o Supervising two BSc students (2016-2017)
o Assisting practicals of the MSc courses ‘water treatment’ (2013-2016), ‘Introduction
environmental technology’ (2013-2016) and Environmental project studies’ (2014)
Oral Presentations
o Pharmaceutical removal by algae grown on source separated wastewater. 9th IWA
Micropol & Ecohazard Conference, 22-25 November 2015, Singapore
o Nabehandeling van geneesmiddelen; 3-staps Bio-Ozon-Bio systeem. Kennisdag
Geneesmiddelen, 1 December 2016, Wageningen, The Netherlands
o Pharmaceutical removal in a Bio-Ozone-Bio process. 10th Micropol & Ecohazard
Conference, 17-20 September 2017, Vienna, Austria
SENSE Coordinator PhD Education
Dr. Monique Gulickx

Financial support from Wageningen University for the research of this dissertation is
gratefully acknowledged.
Financial support from Wageningen University for printing this dissertation is

gratefully acknowledged.

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Pharmaceutical Removal:

Synergy between Biological and Chemical Processes

for Wastewater Treatment

Henrik Arnoud de Wilt

Synergy between Biological and Chemical Processes

for Wastewater Treatment

Henrik Arnoud de Wilt

PhD thesis, Wageningen University, Wageningen, the Netherlands (2018)

Voor mijn naaste en geliefde Daniël, Davíd en Masha

Curriculum Vitae 197

The presence of ozone scavengers in wastewater effluent like organic carbon,

1.1 Pharmaceuticals in the water cycle

Figure 1.1 Pathways of pharmaceuticals and other micropollutants from production to

Figure 1.1 Pathways of pharmaceuticals and other micropollutants from production to

in aquatic environments is relatively limited and much slower as they tend to

Figure 1.2 Transformation pathways of pharmaceuticals (adapted from [139]).

Figure 1.2 Transformation pathways of pharmaceuticals (adapted from [139]).

Atorvastatin Lipid regulator 4.3 4.2 0.1

Caffeine Stimulant 10.4 -0.1 21.6 High

Carbamazepine Anti-epileptic 13.9 2.5 0.01 Low

Diclofenac Anti-inflammatory 4.2 4.5 0.002 Low

Fluoxetine Anti-depressant 10.1 4.1 33

Ibuprofen Anti-inflammatory 4.9 4.0 0.01 High

Metoprolol Beta-blocker 9.6 1.9 47 Low

Naproxen Anti-inflammatory 4.2 3.2 0.016 High

Paracetamol Pain killer 9.4 0.5 0.1

Propranolol Beta-blocker 9.4 3.5 1.72

Sulfamethoxazole Antibiotic 5.7 0.9 0.01 Moderate

Trimethoprim Antibiotic 7.1 0.9 0.4 Moderate

1.2 Effects of pharmaceuticals in the water cycle

anti-depressant fluoxetine at environmentally relevant concentrations. Decreased

research is required to elucidate especially the potentially harmful long term

1.2.2 Effects on human health

1.2.3 Need for measures

health. Recently three antibiotics (azithromycin, clarithromycin and erythromycin)

1.4 Pharmaceutical removal

pharmaceutical removal [247]. Most pharmaceuticals are best degraded under

1.4.2 Room for improvement within biological treatment

1.4.3 Chemical treatment

1.4.4 Combined treatment

higher pharmaceutical removal [218]. Sand-filtration followed by ozonation of a

contains multiple orders of magnitude more easy biodegradable compounds than

[140, 143]. As various removal mechanisms like algal degradation, microbial

interest and can help decision makers in implementation of treatment processes.

1.6 Objective of this dissertation

1.7 Scope and outline of this dissertation

A modified version of this chapter has been published as

enhanced under aerobic conditions as compared to anaerobic conditions in

2.2 Materials and Methods

2.2.2 Experimental setup

a natural inoculant of the biologically active laboratory systems. CWs at both

2.2.2.2 Batch experiments

the spiked pharmaceutical levels, the initial pharmaceutical concentrations in the

2.2.2.3 Column experiments

Nitrate reducing column

Sulfate reducing column

Figure 2.1 Experimental set-up of the column experiments.

2.2.3 Sample collection and analysis

conditioned with 5 mL methanol and equilibrated with 5 mL buffered deionized

2.3.2 Removal of pharmaceuticals

To determine the role of microbial adaptation, the aerobic inoculum in

2.3.2.2 Column systems

CAF appeared initially to be removed by sorption in each column (65-99%)