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Katharina Brotzmann

Contact:

Centre for Organismal Studies

Abteilung Tierphysiologie / Entwicklungsbiologie

Im Neuenheimer Feld 504

Tel: +49-(0)6221/54-6254

Fax:: +49-(0)6221/54-6162

e-Mail: Brotzmann@uni-heidelberg.de

 

 
 

 

Dissertation title:

Danio rerio as model system for teratogenicity testing.

Short description:

In recent years there has been an increasing interest in switching from the “black box” animal-test systems to alternatives. Since 1981 the Organisation of Economic Co-operation and Development has been actively working towards increasing animal welfare and with the 2013 published OECD guideline 236 this quest has taken on new dimensions. This has led to a shift in the scientific community, which is now set on finding working alternatives such as human cell responses. With this in mind, the flagship programme EU-ToxRisk started in 2016, driving mechanism-based toxicology testing and risk assessment for the 21st century. Here, a consortium of 39 international partners are aiming to fundamentally change the concept of toxicology and the current tests used, hoping to develop animal-free chemical safety tests. The new methods used in this project will involve in silico, as well as in vitro tests with human relevance, aspiring to translate post-exposure molecular mechanisms into useful information for safety testing strategies. Among the cooperating partners are experts from field such as cell biology, -omics technologies, systems biology and computational modelling, in order to fully define the functional mechanisms between a given chemical substance and their toxic effects.

My research in this project focuses on the effect of valproic acid (VPA) and its metabolites. Since 1962 VPA is known for its anticonvulsive effects and has been used  as the most effective drug for epilepsy, bipolar disorders, mania and various forms of psychosis and addictive disorders since then, although the mechanism of this compound, as well as the potential toxicity of its metabolites is still largely unknown. Regarding the most prominent adverse effects (I.e. liver toxicity, spina bifida and causing behavioural changes in patients such as apathy, confusion and aggression), the zebrafish embryo has been chosen as model organism in order to better understand the compounds’ mechanisms and threats. Furthermore, the fact that VPA as well as most of its metabolites are water-soluble makes it even more interesting and necessary to address their impacts on organism and select modes of action, which are then used to create extrapolation schemes to support risk assessment and ecotoxicological reaearch. Zebrafish embryo tests have been conducted in the past and have shown a great insight into the understanding the mechanisms of toxicology and organism processes after exposure. The zebrafish system has been found to show very similar responses to chemical exposure as humans, making them great model organisms to work with when assessing toxicological and hazardous effects on the health status of humans.