Development of In-silico Strategies To Advance the 3Rs in Toxicity Testing

Testing for developmental and reproduction toxicity (DART) hazard requires the use of large numbers of mammals (rats and rabbits), and leads to high costs for industry. Alternative test systems like amoeba’s, nematodes and zebrafish embryo’s are used with the aim to reduce the number of mammalian test animals. There is currently no overall systematic approach (to enable data mining or query ‘what if’ questions) to assess the species relevance, usefulness and applicability domain of the available model systems (conventional in vivo mammalian animal models and alternative nonmammalian systems) used to assess DART. Reliably linking data of specific genes with specific responses between organisms is essential to the development of reliable alternative non-mammalian DART test systems, as well as defining the applicability domains of these models.
In this project, a new model organism was introduced in a tool that establishes relationships between DART phenotypes and underlying molecular metabolic pathways. A process of downloading and updating data files was automated and a script was created for extracting orthologous genes from unprocessed files.