SaferWorldbyDesign Webinar: From mouse to zebrafish embryo – An alternative to mammalian teratogenicity tests?

In the assessment of e.g. pharmaceuticals, teratogenicity tests are mandatory. Usually, these are performed in mammals, which is a particular challenge from an animal welfare perspective and leads to a great need for the development of alternative test systems. In this context, the zebrafish (Danio rerio) embryo has received increasing attention as a non-protected vertebrate in vivo model. To assess its suitability as an alternative to mammalian tests, the correlation between (1) effects of valproic acid and nine of its analogues in zebrafish embryos and (2) their known neurodevelopmental effects in mice was analyzed. All effects were assessed, and particular care was given to endpoints putatively related to neurodevelopmental toxicity. In the results, a standard evaluation of lethal and sublethal toxicity merely indicated a correlation of 40 % with in vivo mouse data, whereas a detailed assessment of selected effects resulted in a correspondence of 75 %. A differential evaluation of endpoints specific to selected modes-of-action thus documents a significant increase in the predictive power of the zebrafish embryo model for mammalian teratogenicity.

Acknowledgment (GA, art. 38.1.2): This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 681002.

Presenter: Katharina Brotzmann (Aquatic Ecology and Toxicology, Centre for Organismal Studies (COS), University of Heidelberg)

Dr. Brotzmann graduated in biology and Germanic philology and completed her Ph.D. in the Aquatic Ecology and Toxicology Group at the Centre for Organismal Studies, University of Heidelberg (Germany). Her recent research focused on pharmaceutical-induced liver and neurotoxic effects in the zebrafish (Danio rerio) embryo and the evaluation of this vertebrate model organism as an alternative to mammalian testing for toxicological hazard and risk assessment. She gained extensive experience with acute toxicity tests, histopathology, (confocal laser scanning) microscopy, structure-activity relationship analysis, toxicokinetics and transcriptomics. In her current research within the project PharmaSea (http://www.waterjpi.eu/joint-calls/joint-call-2020-aquaticpollutants/aquaticpollutants-rdi-funded-projects-booklet/pharmasea), she investigates the presence, behavior, and risk associated with active pharmaceutical ingredients (APIs) in marine ecosystems.