Développement de séquences d’événements aboutissant à l’hépatotoxicité et modèles in vitro associés

National audienceIn accordance with the United States National Research Council [NRC (2007)] recommendations for research into new pathways likely to help determine the mode of action of the environmental substances responsible for their toxicity, the objective of this work is to assess the possibility of applying these recommendations and to assess how their consideration might lead to revising or completing current practices for hazard identification during health risk assessments. Better knowledge of mechanisms of action, at both the cellular and molecular levels, should enable us to define the early response associated with a battery of (in vitro) tests and with some types of biomarkers. In particular, the development of models such as in vitro human cells or in silico (computational) approaches might make this possible. This new approach is illustrated here by a target organ, the liver: we inventory its diseases and map the mode of action of environmental pollutants. This methodology could thus allow us to describe the relevant pathways of hepatotoxicity, in association with xenobiotic exposure and, in particular, the early predictive features of different types of liver damage