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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
CRACK IT Challenge

DARTpaths: Mapping developmental and reproductive toxicity (DART) genes and pathways for cross-species comparison of toxic compound effects

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  • Replacement



Developmental and reproductive toxicity (DART) testing is required to assess the impact of new chemicals on adult fertility and embryo development. Currently, these tests use large numbers of animals, primarily rats and rabbits, and are expensive and time consuming. The relevance of the data generated to effects in humans is not always clear. DART is extremely complex involving many diverse biological processes and interconnected adverse outcome networks. There has been increasing interest in using cell-based, non-mammalian and computational approaches to improve the ability to predict chemicals with DART potential. This has coincided with the development of the Adverse Outcome Pathway (AOP) concept which links events caused by a chemical interaction at a molecular level, with adverse effects in an organism or population through a set of defined biochemical pathways. Combined with developments in molecular biology, -omics opportunities, high tech data-science and interconnectivity of databases, the potential to align these data sets to deliver reliable DART prediction can be realised.

The DARTpaths Challenge aims to develop an in silico platform that integrates information on the relationship between specific genes and physiological pathways with data on the effects of specific chemicals in a range of mammalian and non-mammalian species (from social amoeba, to fruit flies to rodents), including humans where data is available. The team led by Professor Raymond Pieters from the University of Applied Sciences Utrecht aims to develop a user-friendly platform that allows in silico prediction and evaluation of DART. This tool will also allow the selection of the most relevant non-mammalian assays for a list of DART relevant pathways.

Full details about this CRACK IT Challenge can be found on the CRACK IT website.