Einfluss zellulärer Transportprozesse auf die Biokonzentration von Umweltchemikalien
In my PhD thesis project I address the question: How do cellular transport proteins influence the actual dose of environmental chemicals in an organism through active transport? Chemicals in the environment can accumulate in tissues of organisms. This is called “bioconcentration”. If a chemical has a high potential to bioconcentrate it can be more deleterious to an organism. Therefore, information on the bioconcentration potential of a chemical is necessary for determining its human and environmental health risiks and needs to be obtained, as for instance regulated by the REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) framework of the European Union. For determining bioconcentration of a chemical animal experiments need to be carried out. A way to avoid the animal experiments could be to use computer models that predict bioconcentration of a chemical. However, current models generally provide inaccurate predictions, because they do not take into account biological processes that are important for the uptake of a chemical by an organism. Thus, organisms are protected by an “active barrier” that determine if a chemical can enter the organism or not. Consideration of these biological processes will help to improve computer models. Information on interaction of chemicals with important biological processes influencing the bioconcentration can also be obtained with animal-free in vitro tests. Within my PhD work I develop an in vitro test for determining interaction of chemicals with active cellular transport proteins that constitute an important component of the “active barrier” of an organism against chemicals. Eventually, this test may be part of a tool kit of “intelligent testing” that comprises in vitro tests and a computer model. This tool kit may contribute to the 3 Rs (reduce – refine – replace) of animal tests and make animal tests obsolete.
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