Researchers from the University of Oxford have created a new approach to reduce the use of thousands of animals used annually for assessing the developmental and reproductive toxicity (DART) potential of new chemicals. The CombiDART platform combines two non-vertebrate model systems (the nematode C. elegans and the social amoeba Dictyostelium discoideum) to rapidly assess compounds for DART, whilst also providing information on mechanism of action.
CombiDART developers are now seeking partners to help further develop and validate the platform to meet end user needs and encourage wider uptake of the approach. Potential partners should be able to provide compounds for validation, expertise in automation of screening and advice and guidance on how end users would prefer to adopt the screen (as an in-house screen, outsourced, etc.).
Establishing DART effects of new compounds is a regulatory requirement to assess the potential effects of chemicals on the developing foetus. These studies use large numbers of animals (up to 1,400 rats for extended tests), are expensive and time consuming. In addition, the relevance to humans of effects seen in these studies is not always clear and significant species differences exist. Molecular pathways in both C.elegans and Dictyostelium are well-conserved with mammals and both models have been used to study the mechanistic effects of compounds on molecular processes, especially development and reproduction. CombiDARTs combinatorial approach means that pathways absent in one organism can often be detected in the other, reducing false negative results as well as identifying organism-specific effects, reducing the risk of false positives.
Using CombiDART as an early screen to identify chemicals with high potential for mammalian DART will enable companies to remove from development compounds with undesirable profiles before these chemicals are tested in vertebrates. Each compound removed will reduce the number of animals used in regulatory DART assessments by approximately 2000.
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