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

任何排放到环境中的化学品都有可能是有害的，包括那些用于农业和石化行业的化学品，这些行业占英国GDP的很大比例。目前的法规规定，必须测试这些化合物是否有可能对发育中的胎儿和生殖造成伤害，因此，在一到两代人的时间里，化学物质会定期在老鼠和兔子身上进行测试，以确定是否有影响。这使用了大量的动物(每种化合物至少2500只)，并不能完全预测对人类的影响。我们的目标是开发一种替代测试方法，利用非脊椎动物模式生物线虫(C.elegans)和社会阿米巴(Dictyostelius)来鉴定具有高发育和生殖毒性(DART)风险的化合物。这种方法将提供一个灵敏和稳健的检测系统，两种生物的结合使用将大大提高预测能力。我们将建立两个生物体中不同发育事件的记者集合，将其归类为有用的小组，提供特定发育和生殖过程的信息。该系统将通过测试已知会导致或不会导致DART的化合物来进行培训，最终开发出一种可预测的中等输量管道。最终，这将能够在产品开发的早期消除潜在的有害化学物质，而不需要在老鼠和兔子身上进行测试。

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.