DETECTIVE as part of the SEURAT-1 cluster

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  • SEURAT Research Cluster & coordination action COACH

In 2009 the Health Programme of DG Research defined a long-term target, the Safety Evaluation Ultimately Replacing Animal Testing (SEURAT) with a five years goal, the development of a strategy to replace repeated dose systemic toxicity testing. Based on the knowledge achieved in previous projects, this research initiative will develop the "building blocks" for "SEURAT" through the funding of six integrating projects :

 

 

SCR&Tox, “Stem Cells for Relevant Efficient Extended and Normalized Toxicology”

HeMiBio, “Hepatic Microfluidic Bioreactor”

DETECTIVE, “Detection of endpoints and biomarkers of repeated dose toxicity using in vitro systems”

COSMOS, “Integrated In Silico Models for the Prediction of Human Repeated Dose Toxicity of COSMetics to Optimise Safety”

NOTOX, “Predicting long-term toxic effects using computer models based onsystems characterization of organotypic cultures “

ToxBank, “Supporting Integrated Data Analysis and Servicing of Alternative Testing Methods in Toxicology”

The integration of the individual projects (building blocks) will be supported by the Coordination Action “COACH”. The Research Cluster has been set up to develop a novel “human safety assessment strategy” in an integrated approach targeting repeated dose toxicity. The goal is the integration of the technologies developed and data generated in the different building blocks in order to understand how complementary novel approaches can be used to devise an overall strategy for reaching the ultimate long-term goal of replacing current repeated dose systemic toxicity testing in human safety assessment. The success of this initiative will depend on a close and structured interaction across all the building blocks that foster the realisation of synergistic effects.

A key task in the SEURAT initiative was the identification of organs that could be targeted during in vivo systemic toxicity testing by cosmetic  ingredients as well as the potential modes of toxicological action involved. This information is crucial for the selection of compounds to be tested in all projects under the SEURAT cluster, including DETECTIVE. Indeed, in the initial phase of DETECTIVE, in vitro systems are optimized and selected using a set of chemicals with clear-cut toxicological properties, mainly pharmaceuticals, while in the later phase, the developed experimental systems will be challenged with a number of cosmetic ingredients as a proof-of-principle exercise. In order to establish a toxicological link between the chemicals used in both phases of the project, it was thus of utmost importance to find out which organs and potential types of toxicity could be of relevance for cosmetic ingredients. This task was dealt with by DETECTIVE partner 5 (VUB-Belgium), using a self-generated electronic databank of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. This information has been embedded in a scientific manuscript that will be published in the journal Archives of Toxicology and is considered as valuable input for the ToxBank consortium, responsible for overall compound selection within the SEURAT project cluster.