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Background

The ACuteTox project represents the first attempt to create an integrated testing strategy based solely on in vitro and in silico methods, with the purpose of replacing animal testing for predicting human acute oral systemic toxicity and classification of chemicals into the different EU Classification, Labelling and Packaging (CLP) and GHS toxicity classes. At present a large number of in vitro models for acute toxicity testing are available. Studies, such as the Register of Cytotoxicity and the NICEATM/ECVAM Validation Study of In Vitro Cytotoxicity Test Methods, have shown good correlation between in vitro basal cytotoxicity data and rodent LD50 values. In addition, the MEIC (Multicenter Evaluation of In Vitro Cytotoxicity) programme showed a good correlation (around 70%) between in vitro basal cytotoxicity data and human lethal blood concentrations. This means, however, that when using the existing in vitro tests, a certain number of misclassifications will occur. ACuteTox aimed to identify factors that could optimise the in vitro-in vivo correlation for acute systemic toxicity.

Project objectives

The main objectives of the project included the compilation, evaluation and generation of high quality in vitro and in vivo data on a set of reference chemicals for comparative analyses, and the identification of factors that influence the correlation between in vitro (concentration) and in vivo (dose) toxicity, particularly taking into consideration biokinetics, metabolism and organ toxicity (liver, central nervous system, kidney). Moreover, innovative tools (e.g. cytomics) and new cellular systems for anticipating animal and human toxicity were explored. The overview of project activities and interaction between the different work packages is presented in Fig. 1(Workplan Project Structure.pdf). Ultimately, the goal was to design a simple, robust and reliable in vitro test strategy amendable for robotic testing, associated with the prediction models for acute oral toxicity.