Development of a comprehensive test battery for neuroteratogenicity


Prof. Dr. Marcel Leist

Doerenkamp-Zbinden Chair for Alternative in vitro Methods

University of Konstanz, Germany

Less than 5% of the major industrial chemicals produced at high volumes (> 1000 tons/year) have been characterized for their potential hazard to fetal and neonatal brain development. Chemical-induced disturbances of nervous system development (= neuroteratogenicity) are well known for few compound (e.g. mercury, PCBs and toluene), and are therefore likely to occur for many others. Thus, there is an urgent need for test systems to identify such a hazard. Even for pesticides that have been tested, there is still a need to better understand and quantify the potential hazard, in order to provide the least dangerous products, in cases where overall human protection is not possible (e.g. in developing countries) (1). Animal-based testing cannot solve this problem due to high costs, lack of sufficient infrastructure and doubtful predictivity. Therefore, several initiatives have been started to generate in vitro test systems, and to assemble these in test batteries. In our project, which is based on pilot work initially funded by the EU FP7 project ESNATS (2), we optimize the design and assembly of such test batteries. A main objective is to define basic criteria for compound selection and characterization, for tiering of test steps, and for finding acceptance criteria and defining decision points. We use a library of 28 compounds for initial test runs to define such criteria, and to define interfaces for inclusion of additional information, chemicals and tests. The goal of the project is to publish the setup of a test battery design.



1. Krause KH, van Thriel C, De Sousa PA, Leist M, Hengstler JG. Monocrotophos in Gandaman village: India school lunch deaths and need for improved toxicity testing. Arch Toxicol. 2013 Oct;87(10):1877-81.

2. Leist M, Ringwald A, Kolde R, Bremer S, van Thriel C, Krause KH, Rahnenführer J, Sachinidis A, Hescheler J, Hengstler JG. Test systems of developmental toxicity: state-of-the art and future perspectives. Arch Toxicol. 2013 Dec;87(12):2037-42.