Das Projekt "Short-term in vitro assays for long-term toxicity (PREDICTOMICS)" wird vom Umweltbundesamt gefördert und von Bayer AG durchgeführt. The development of new pharmaceutical compounds will be more efficient if human relevant toxicology information early in the selection process is available. While acute toxicity can be reasonably detected during the early preclinical stages of drug development, long-term toxicity is more difficult to predict, relying almost exclusively on animal experiments Animal experimentation of this kind is expensive and time consuming, raises ethical issues and do not necessarily represent a toxicological relevance to man. This project address the urgent need to develop in vitro based systems which are capable of predicting long term toxicity in humans. The major objectives of this project are:1)To develop advanced cell culture systems which as best possible represents the human liver and kidney in vivo. This will be achieved using combined strategies namely:co-cultures of resident cell types,targeted cell transformation,stem cell technology and new developments in organotypic cell culture (i.e. perfusion cultures and 3D cultures).2)To identify specific early mechanistic markers of toxin induced cell alterations by using integrated genomic,proteomic and cytomic analysis.3)To establish and prevalidate a screening platform (cell systems together with analysis tools) which is unambiguously predictive of toxin induced chronic renal and hepatic disease.This proposal is unique in it's mechanistic integration of the three levels of cellular dynamics (genome, proteome and cytome) together with advanced cell culture technology to detect early events of cellular injury. Only with such an integrated approach will in vitro techniques ever be applicable to predicting chronic toxicity in man. This project,if successful will(1) contribute to the replacement of animal testing in drug development, (2) increase ... Prime Contractor: Fundacion Hospital Universitario 'La Fe', Experimental Hepatology Unit, Research Center; Valencia; Espana.
Das Projekt "Optimisation and pre-validation of an in vitro test strategy for predicting human acute toxicity (A-CUTE-TOX)" wird vom Umweltbundesamt gefördert und von Fraunhofer-Institut für Toxikologie und Experimentelle Medizin (ITEM) durchgeführt. Validated alternative test methods are urgently required for safety toxicology of drugs, chemicals and cosmetics. Both REACH and 7th amendment of Cosmetics Directive call for the broad replacement of animal experiments on a short-term. While some animal tests for topical toxicity have been successfully replaced one by one by alternative methods, systemic toxicities require new test strategies in order to achive an adequate safety level. The aim of A-Cute-Tox is to develop a simple and robust in vitro t esting strategy for prediction of human acute systemic toxicity, which could replace the animal acute toxicity tests used today. The involvement of ECVAM in the project management and that of regulators (such as ECB) guarantees of the follow-up. The Scie ntific objectives of the project are: 1. Compilation, critical evaluation and generation of high quality in vitro and in vivo data for comparative analysis. 2. Identifying factors (ADE, metabolism and organ specificity) that influence the correlation betwe en in vitro toxicity (concentration) and in vivo toxicity (dosage), and to define an algorithm that accounts for this. 3. Explore innovative tools and cellular systems to identify new end-points and strategies to better anticipate animal and human toxicit y. 4. To design a simple, robost and reliable in vitro test strategy amenable for robotic testing, associated with the prediction model for acute toxicity. The project will develop the concepts required to compose testing strategies via the continuous imp lementation of novel in vitro and in silico alternatives. The approach requires the dimensions of a transnational Integrated Project, involving prominent toxicity research groups in the EU, close monitoring by and input from the regulatory community and p rofessional managerial steering. In return, it offers the realistic opportunity to achive a substantial reduction of animal experiments in acute systemic toxicity assessments. Prime Contractor: University of Oulu, Administration, Research and Innovation Services; Oulu; Suomi/Finland.