Safer chemicals using less animals: kick-off of the European ONTOX project
Mathieu Vinken, Emilio Benfenati, François Busquet, José Vicente Castell, Djork-Arné Clevert, Theo M. C. M. de Kok, Hubert A. A. M. Dirven, Ellen Fritsche, Liesbet Geris, Rafael Gozalbes, Thomas Härtung, Danyel G. J. Jennen, Ramiro Jover, Helena Kanďárová, Nynke I. Kramer, Cyrille A. M. Krul, Thomas H. Luechtefeld, Rosalinde Masereeuw, Erwin Roggen, Stephan Schaller · Toxicology · 2021
century toxicity testing and next generation risk assessment. ONTOX will deliver a generic strategy to create new approach methodologies (NAMs) in order to predict systemic repeated dose toxicity effects that, upon combination with tailored exposure assessment, will enable human risk assessment. For proof-of-concept purposes, focus is put on NAMs addressing adversities in the liver, kidneys and developing brain induced by a variety of chemicals. The NAMs each consist of a computational system based on artificial intelligence and are fed by biological, toxicological, chemical and kinetic data. Data are consecutively integrated in physiological maps, quantitative adverse outcome pathway networks and ontology frameworks. Supported by artificial intelligence, data gaps are identified and are filled by targeted in vitro and in silico testing. ONTOX is anticipated to have a deep and long-lasting impact at many levels, in particular by consolidating Europe's world-leading position regarding the development, exploitation, regulation and application of animal-free methods for human risk assessment of chemicals.