DETECTIVE is part of an integrated research strategy towards the replacement of animal testing set up by the European Commission (EC) within the FP7 Health Programme and supported by the Cosmetics Europe – The Personal Care Association, previously European Cosmetics Association (Colipa). Within this collaborative project, 15 partners address the development of biomarkers of long-term toxicity in human target cells.
DETECTIVE is one of the six research projects funded under the SEURAT-1 cluster umbrella. Emphasis will be put on the systematic exploitation of a battery of complementary functional and “-omics” readouts, including high content and high throughput screening platforms to identify and investigate human biomarkers in cellular models for repeated dose in vitro testing. While functional parameters give more insights into the effects of toxicants on specific cell functions of interest, “-omics” techniques will deliver data on the entire cellular situation at the molecular level. Importantly, DETECTIVE will perform for the first time an in-depth investigation of repeated dose effects on epigenetics and microRNA expression thus exploring whether such analyses deepen our understanding of toxic modes of action.
Upon combination and subsequent integration of the various readouts, biomarkers of optimal predictivity for human long-term toxicity in vitro can be obtained. Based on integrative statistical analysis, systematic verification and correlation with in vivo data, the most relevant, highly specific, sensitive and predictive biomarkers will be selected.
DETECTIVE concentrates on hepatoxic and cardiotoxic, and – to a smaller extent – nephrotoxic effects representing three target organs of repeated dose toxicity. Ultimately, developed concepts will also be applicable to other organs or organ systems affected by systemic toxicants such as the nervous system. Furthermore, it is expected that DETECTIVE will be able to define human toxicity pathways relevant for all organs.
In 2009 the Health Programme of DG Research defined a long-term target, the Safety Evaluation Ultimately Replacing Animal Testing (SEURAT-1) with a five years goal, the development of a strategy to replace repeated dose systemic toxicity testing.