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@PHDTHESIS{DiPaolo:673445,
author = {Di Paolo, Carolina},
othercontributors = {Hollert, Henner and Brack, Werner and Silvestre, Frederic},
title = {{M}echanism-specific toxicity bioassays for water quality
assessment and effect-directed analysis},
school = {RWTH Aachen University},
type = {Dissertation},
address = {Aachen},
reportid = {RWTH-2016-08695},
pages = {1 Online-Ressource (xxvi, 273 Seiten) : Illustrationen,
Diagramme, Karten},
year = {2016},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University; Dissertation, RWTH Aachen University, 2016},
abstract = {Biological assays have been applied to investigate
freshwater quality for more than a century, and the public
awareness of the threats of aquatic pollution has motivated
advances in water quality regulations. In Europe, such a
scenario led to the establishment of the Water Framework
Directive (WFD) as a unified and harmonised framework for
water protection, with the main objective to achieve a good
water ecological and chemical status. Despite the recognized
relevance of bioassays by scientists and national
authorities, until now they are not recommended for direct
application in the WFD monitoring activities. A reason for
that is that there are remaining research questions that
need further clarification before bioassays are integrated
in water quality monitoring.The EDA-EMERGE Marie Curie
Initial Training Network, in which context the present
thesis was developed, was set up to investigate and answer
some of these questions. The project aimed at the
assessment, monitoring and management of water quality in
European river basins through different approaches,
including the investigation and development of new
effect-directed analysis (EDA) methods for the
identification of toxicants in surface waters. For that, new
bioanalytical, chemical and hyphenated methods were
developed. In this thesis, mechanism-specific bioassays were
newly developed, advanced or adapted for the assessment of
emerging pollutants or water samples, and as guiding tools
in EDA investigations. The research questions guiding this
thesis were: (i) How can mechanism-specific bioassays
adequately be integrated into EDA?; (ii) How to advance
aquatic relevant mechanism-specific bioassays?; (iii) Are
mechanism-specific bioassays able to properly evaluate
emerging pollutants as single compounds and as mixtures?;
and (iv) How to efficiently apply bioassay battery
approaches and what are their benefits for the water quality
assessment? In order to answer these questions, the overall
objectives of this thesis were: (1) To adapt bioassay
protocols and develop respective testing strategies for
application as guiding tools in EDA studies; (2) To develop
aquatic relevant mechanism-specific bioassays utilizing
zebrafish early life stages and zebrafish liver cell lines;
(3) To evaluate the effects of emerging pollutants as single
chemicals and as mixtures on aquatic organisms and in vitro
bioassays; and (4) To apply and evaluate bioassays and
bioassay battery approaches to investigate water sample
extracts and emerging aquatic pollutants. These objectives
were explored in complementary studies focusing on bioassay
development and adaptation, followed by the application of
bioassays to evaluate diverse aquatic pollutants and water
samples, and ultimately leading to a comprehensive
multi-organism and multi-mechanism aquatic toxicity
assessment approach. In parallel, other activities were
developed in the context of the project, including an
intensive training in EDA-related methods and a joint
monitoring study for evaluating water samples from different
European river basins in bioassays and chemicals
analysis.Initially, a literature review provided an overview
of EDA investigations that applied bioassays with zebrafish
as guiding tools, with mechanism-specific bioassays being
identified as particularly useful for EDA investigations.
Subsequently, mechanism-specific assays with zebrafish
models were developed in the context of this thesis. One
study focused on the development of a new method to evaluate
chronic, delayed toxicity using zebrafish early life stages,
which also identified early endpoints that can potentially
predict later effects. Another study developed protocols to
evaluate micronucleus occurrence in a zebrafish liver cell
line and zebrafish larvae as a robust genotoxicity endpoint,
and applied the methods to investigate genotoxic compounds.
Further, the effects of neuroactive and neurotoxic compounds
on the behavioural response of zebrafish larvae following a
light-dark transition stimulus were also investigated.
Additionally, antiandrogenicity and the induction of the p53
protein pathway were assessed by using respective reporter
gene cell-based assays. A testing strategy utilizing the p53
assay and a bioassay for cell viability assessment was
applied to investigate genotoxic compounds as single
exposures and mixtures. Antiandrogenicity assessment of
surface water samples identified a particularly active
sample, which was selected for a follow-up EDA
investigation. Since only a limited sample volume was left,
downscaled methods of dosing and exposure procedures had to
be developed and validated using model (anti)androgenic
compounds. Afterwards, the developed tools were applied in
the EDA study. Finally, an interlaboratory study involving
different collaborating partners was organized within this
PhD project. A basic bioassay battery containing
organism-level and in vitro mechanism-specific assays was
applied to investigate a pristine water extract spiked with
emerging pollutants as single chemicals or mixtures. This
study is expected to support and promote the use of a basic
bioassay battery for water quality monitoring.In summary,
this thesis developed new and improved existing bioassays
and bioassay testing strategies for future
mechanism-specific toxicity investigations of aquatic
emerging pollutants, chemical mixtures or water samples; or
as guiding tools in effect-directed analysis.},
cin = {162420 / 160000},
ddc = {570},
cid = {$I:(DE-82)162420_20140620$ / $I:(DE-82)160000_20140620$},
pnm = {EDA-EMERGE - Innovative biodiagnosis meets chemical
structure elucidation – Novel tools in effect directed
analysis to support the identification and monitoring of
emerging toxicants on a European scale (290100)},
pid = {G:(EU-Grant)290100},
typ = {PUB:(DE-HGF)11},
urn = {urn:nbn:de:hbz:82-rwth-2016-086955},
url = {https://publications.rwth-aachen.de/record/673445},
}
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