The European ACuteTox project: a modern integrative in vitro approach to better prediction of acute toxicity.

ACuteTox (optimization and prevalidation of an in vitro test strategy for predicting human acute toxicity) is an integrated European Union project under the Sixth Framework Programme with the aim of demonstrating that animal tests for acute systemic toxicity currently used for regulatory purposes could be replaced by a combination of alternative assays. Validated alternative test methods are urgently required for safety toxicology testing of chemicals, cosmetics, and drugs.

Estimation of human blood LC50 values for use in modeling of in vitro-in vivo data of the ACuteTox project.

The main aim of the ACuteTox project, under EU 6th Framework programme, is to investigate whether animal toxicity tests for acute systemic toxicity could be replaced by a combination of alternative assays. Data for 97 reference chemicals was collected in the ACuteTox database (Acutoxbase), designed to handle invitro and invivo (human and animal) lodged data. The principal basis for demonstration of the applicability of invitro tests is the invitro-invivo modeling, by using statistical correlation between invitro IC50 molar values (the 50% inhibitory concentration for the endpoints measured) and human blood molar concentrations LC50 (50% lethal concentrations).

The integrated acute systemic toxicity project (ACuteTox) for the optimisation and validation of alternative in vitro tests.

The ACuteTox project is designed to replace animal testing for acute systemic toxicity, as is widely used today for regulatory purposes, by using in vitro and in silico alternatives. In spite of the fact that earlier studies on acute systemic toxicity demonstrated a good correlation between in vitro basal cytotoxicity data (the 50% inhibitory concentration [IC50]) in human cell lines and rodent LD50 values, and an even better correlation between IC50 values and human lethal blood concentrations, very few non-animal tests have been accepted for general use. Therefore, the aim of the ACuteTox project is to adapt new testing strategies, for example, the implementation of new endpoints and new cell systems for toxicity screening, organ-specific models, metabolism-dependent toxicity, tissue absorption, distribution and excretion, and computer-based prediction models.