Session: Parallel session 8 - Quantification

Contribution of Multiomics to Toxicology: Case Studies

A new paradigm has emerged in toxicology, moving towards a more mechanistic understanding of the mode of action (MOA) of chemicals for refining risk assessment. Such approach is expected to improve the classification and the prioritization of compounds, therefore reducing the use of animals in line with the 3R rules (Replacement, Reduction, Refinement). For this purpose, numerous human cell models representative of target organs can be used, from 2D cell lines to organoids. Efforts have been made to develop cell models with structural and physiological relevance as well as to mimic some pathologies. Using this broad range of cell models, multiomics enable to determine and quantify the fate and effects of compounds. In this context, we have studied the kinetic and concentration-responses of chemicals by the combination of proteomic and metabolomics analyses. Indeed, this methodology was applied to pesticides, bacterial toxins and mycotoxins, alone or in mixtures, on intestinal and liver cell models. Complex liver models mimicking steatotic liver disease associated with metabolic dysfunction (MASLD) were also used. Examples will be provided to illustrate how multiomics can highlight precise mechanisms such as targeted protein disruption or transcription factor activation, events based on the interaction of contaminants with their targets, thus in some cases enabling the potential development of remediation or toxicity-reducing strategies. We will also illustrate the key role of proteomic analyses of molecular interactions between proteins and contaminants in revealing their modes of action using in vitro and in vivo strategies.