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Toxicity pathways in zebrafish cell lines : an ecotoxicological perspective on ”toxicity testing in the 21st century”

Lungu-Mitea, Sebastian (2020). Toxicity pathways in zebrafish cell lines : an ecotoxicological perspective on ”toxicity testing in the 21st century”. Diss. (sammanfattning/summary) Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880
ISBN 978-91-7760-656-7
eISBN 978-91-7760- 657-4
[Doctoral thesis]

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Abstract

Standard toxicological in vivo testing has been challenged as the procedures are time-consuming, expensive, and require a large number of animals; given the number of problematic chemicals. Novel toxicological frameworks, such as "toxicity testing in the 21st century", proposed the use of "new approach methods" (in vitro and in silico techniques), that can be applied in high-throughput setups and would allow for the testing of a large number of compounds. However, such new approach methods need to be designed and evaluated first. Especially within ecotoxicology, the coverage of species-specific bioanalytical tools, e.g. for fish, is rather scarce. Currently, mainly in vitro assays of mammalian and bacterial origin are used. This thesis outlines how to design and scrutinise fish transient reporter gene assays. We have established transient reporter gene assays in permanent zebrafish fibroblasts and hepatocytes of the oxidative stress response and the xenobiotic metabolism toxicity pathways. We identified non-specific effects caused by transient transfection itself and suggested preventive strategies. Further, we identified toxicity pathways' cross-talk as a significant driver of uncertainty in regards to the assessment of receptor-mediated toxicity. Additionally, we evaluated the correlation between cytotoxicity in cultured zebrafish cells and the acute toxicity observed in zebrafish embryos. When using chemical distribution models to derive bioavailable concentrations, we observed a good positive correlation between the two test systems. The results advocate an intensified use of fish in vitro assays in integrated testing strategies. Conclusively, new approach methods, as developed and applied in this thesis, show great potential in future toxicity testing and environmental monitoring.

Authors/Creators:Lungu-Mitea, Sebastian
Title:Toxicity pathways in zebrafish cell lines : an ecotoxicological perspective on ”toxicity testing in the 21st century”
Year of publishing :2020
Number:2020:69
Number of Pages:87
Publisher:Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-7760-656-7
ISBN for electronic version:978-91-7760- 657-4
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Article category:Other scientific
Version:Published version
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Pharmacology and Toxicology
Keywords:toxicity pathways, Tox21, 3Rs, reporter gene assays, cytotoxicity assays, mass-balance modelling, cross-talk, AOP
URN:NBN:urn:nbn:se:slu:epsilon-p-108711
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-108711
ID Code:18700
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:19 Nov 2020 13:04
Metadata Last Modified:20 Nov 2020 11:28

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