Uptake and effects of dioxin like compounds in fish : in vitro in vivo and cross species extrapolation using physiologically based toxicokinetic models

• Main Author: Brinkmann, Markus
• Other Authors: Hollert, Henner, Oehlmann, Jörg
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Publikationsserver der RWTH Aachen University 2016
• Subjects: info:eu-repo/classification/ddc/570; Biowissenschaften; Biologie; dioxins; dioxin-like compounds; PCDD/Fs; PCBs; in vitro-in vivo extrapolation; toxicokinetic models; PBTK; PBPK; sediment re-suspension; Rainbow trout; common roach; European eel; Zebrafish; transcriptomics
• Online Access: https://publications.rwth-aachen.de/record/540579; https://publications.rwth-aachen.de/search?p=id:%22RWTH-2015-05952%22

The past decades have witnessed an unparalleled interest of the public and of the scientific community in dioxins and dioxin-like compounds (DLCs) such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), as well as dioxin-like polychlorinated biphenyls (dl-PCBs). DLCs belong to the group of persistent organic pollutants, which are characterised by low environmental degradation rates and environmental half-lives ranging from months to decades. In the water column, the strong adsorption of DLCs to suspended solids renders the sediment a long-term sink for, and potential secondary source of, pollution. Although DLC emissions have decreased substantially because of international efforts, they are still re-distributed in the environment by poorly understood processes. DLCs biomagnify in higher trophic levels of the aquatic food web due to their lipophilic character and can thus still pose a considerable risk to humans, e.g. via consumption of contaminated fish. Whether sediment-bound DLCs are also available to fish through non-dietary routes, e.g. during the re-suspension of sediments, is a contentious issue. Consequently, no sediment-based environmental quality standards (EQSs) for DLCs exist, despite their legal requirement by European directives such as the water framework directive (WFD) and the environmental quality standards directive (EQSD). DLCs are known to cause a plethora of acute and chronic toxic effects in humans and wildlife, including neuro-, immuno-, and hepatotoxic effects; they can also affect reproduction and increase the risk for specific cancers. All DLCs share planar structural properties and thus show high binding affinities for the cytosolic aryl hydrocarbon receptor (AhR). Many of the toxic effects associated with DLCs are believed to be mediated by AhR activation.Conventional chemical analyses of DLCs using high resolution gas chromatography and high resolution mass spectrometry are costly and require highly specialised personnel. It is evident that ...