Novel biomarker platform for a 3Rs approach to assessment of developmental and reproductive toxicity

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Any chemical that is released into the environment has the potential to be harmful, including those used in the agro-and petrochemical industries which form a significant percentage of the UK GDP. Current regulations stipulate that such compounds must be tested for their potential to cause harm to the developing foetus and to reproduction and so chemicals are routinely tested on rats and rabbits over one or two generations to determine any effects. This uses a large number of animals (at least 2500 per compound) and is not entirely predictive of effects in man. We aim to develop an alternative testing approach to identify compounds with a high risk of developmental and reproductive toxicity (DART) using non-verterbrate model organisms, the nematode worm (C. elegans) and social amoebae (Dictyostelium). This approach will provide a sensitive and robust assay system and the use of two organisms in combination increases the predictive power massively. We will establish a collection of reporters for different developmental events in both organisms, clustering into useful groups informative of particular developmental and reproductive processes. The system will be educated by testing on compounds known to cause, or not to cause, DART culminating in the development of a predictive medium throughput pipeline. Ultimately this will enable the elimination of potentially harmful chemicals early in product development, without testing on rats and rabbits.