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@PHDTHESIS{Gundlach:840423,
author = {Gundlach, Michael},
othercontributors = {Hollert, Henner and Schäffer, Andreas},
title = {{N}euroactive psychotropic drugs in aquatic systems and the
co-treatment of non-target organisms},
school = {RWTH Aachen University},
type = {Dissertation},
address = {Aachen},
publisher = {RWTH Aachen University},
reportid = {RWTH-2022-01249},
pages = {1 Online-Ressource : Illustrationen, Diagramme},
year = {2021},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University 2022; Dissertation, RWTH Aachen University, 2021},
abstract = {The focus on the analysis of the major consequences of
human impact on Earth for different ecosystems has been
constantly changing over the last centuries. A brief
overview of the current situation reveals the drastic
consequences of climate change and the loss of different
species for life on earth and shows how much humans are
changing their environment. A serious but much less visible
environmental problem is the contamination of freshwater
systems by micropollutants, as the resulting consequences
cause massive damage at aquatic species communities and have
negative impacts on human health due to the closely
connected circular systems. Micropollutants are an
inhomogeneous group of various microparticles and chemicals
that deteriorate the quality of drinking water and which can
only be insufficiently eliminated by conventional
purification methods. One group of micropollutants whose
concentration in the environment has been steadily
increasing are human psychotropic drugs. Increasing stress
in different life areas is one reason for mental illnesses
like depressions and burnout, which leads to an annual
increase in the development and use of neuroactive
pharmaceuticals. These substances finally enter the aquatic
environment through excretion or incorrect disposal and
cause ecological changes in the structure of the ecosystems.
The European Medicines Agency has formulated a guideline to
counteract these consequences, which clearly defines a
two-stage procedure for testing the environmental hazard of
active pharmaceutical ingredients. However, this system
operates on the principle that not all pharmaceuticals need
to pass through both stages and that only OECD and
ISO-validated standard tests may be used for data generation
in the selection of biological test methods. This approach
has clear limitations in the effect analysis of neuroactive
substances because they are designed to trigger a specific
effect at a specific concentration range in the nervous
system. The effects that occur at the molecular and
physiological levels could not uniformly be measured by
general standard test methods and many problems caused by
these substances could not be quantified completely. This
problem has not yet been sufficiently investigated for the
mixtures of these substances that always occur in the
environment. A tiered approach was used to investigate the
pure substance mirtazapine, artificially prepared mixtures
of various neuroactive substances, and native samples from
hospital wastewater. The swimming behavior of zebrafish
embryos, showed a decreased activity of more than 45 $\%$
for mirtazapine concentrations of more than 1 mg/L compared
to the control groups. In comparison, the swimming activity
of Daphnia magna increased concentration-dependently for the
measured concentrations from 0.1 – 200 µg/L mirtazapine.
Sedative effects on the swimming behavior of zebrafish
embryos could be measured in the more complex samples that
were artificially produced as well as in the native
environmental samples. The activity decreases were also
measurable for substance combinations with complementary
modes of action. At gene regulatory level, increases of
8-fold were measured compared to the control group for genes
of the serotonin- and dopamine-systems (slc17a6a, slc2a2,
slc6a3a). The analysis of native hospital wastewater samples
was carried out in an interdisciplinary cooperation i.e.
with the Psychiatry Department of the University Hospital
Aachen and the Environmental Research Center in Leipzig. The
results show a decreased activity for the swimming behavior
of zebrafish embryos in relation to the concentration of the
recovered neuropharmaceuticals. Activity decreases were
measured at the beginning of the day and in the early
afternoon. At the gene level, an increase in genes i.e. of
the serotonin system could be measured. The behavioral
effects can probably be attributed to an overload of the
central neural system, which is responsible for the
coordination of the movements. The central objective of this
work was the development of a tiered test approach on
different biological levels to improve the environmental
risk assessment for neuroactive substances. Therefore,
different quantification methods on physiological level and
various ways of quantification these effects on cellular and
molecular level are tested and improved. Finally, the
results should help to set up recommendations on regulatory
level for a better protection of aquatic non-target
organisms against these substances in the future.},
cin = {162710 / 160000 / 162420},
ddc = {570},
cid = {$I:(DE-82)162710_20140620$ / $I:(DE-82)160000_20140620$ /
$I:(DE-82)162420_20140620$},
typ = {PUB:(DE-HGF)11},
doi = {10.18154/RWTH-2022-01249},
url = {https://publications.rwth-aachen.de/record/840423},
}
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