Spec. Issue 2006 - Article Summary

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AcuteTox – optimating and pre-validation of an in vitro test strategy for predicting human acute toxicity

Cecilia Clemedson1, Bas Blaauboer2, José Castell3, Pilar Prieto4, Leila Risteli 5,
Joan-Albert Vericat 6 and Albrecht Wendel7

1Expertrådet Environmental Competence AB, Sollentuna, Sweden; 2Institute for Risk Assessment Sciences, Utrecht University,
The Netherlands; 3University Hospital La Fe, Valencia, Spain; 4ECVAM, Institute for Health and Consumer Protection, Joint
Research Center, European Commission, Ispra (Va), Italy; 5Research and Innovation Services, University of Oulu, Finland;
6NeuroPharma S.A., Preclinical Development, Tres Cantos, Spain; 7Biochemical Pharmacology, University of Konstanz, Germany

ACuteTox is an integrated project under the EU-FP6 with the aim to develop a simple and robust in vitro testing strategy for prediction of human acute systemic toxicity, which could replace animal tests used for regulatory purposes. Studies show good correlation of over 70% between in vitro basal cytotoxicity and rodent LD50 values or human lethal blood concentrations. However, a number of discrepancies occur which result in misclassification. ACuteTox aims to identify factors that can eliminate these misclassifications. The outliers in the in vitro/in vivo correlation will be evaluated in order to introduce further parameters (ADE, metabolism and organ specificity), which might improve the correlation. Integration of alerts and correctors in a prediction algorithm, together with implementation of medium throughput approaches, would allow establishment of a new testing strategy to better predict toxic classification.

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