New Approaches in Chemical Risk Assessment

Rapid advances in scientific knowledge and challenges with respect to the reliability of animal testing have resulted in a paradigm shift in toxicology where new approaches are being developed. The core of these new approaches to chemical risk assessment includes (high-throughput) in vitro toxicity screening that forms an efficient way to identify potential biological targets of chemicals and adverse outcome pathways. Yet, relying on in vitro results only may misrepresent the in vivo situation as in vivo kinetics (i.e. absorption, distribution, metabolism and excretion) of the chemicals are not accounted for in the in vitro assays. Key to new approaches in chemical risk assessment is therefore to also integrate the in vitro data with kinetic information to extrapolate the results to the in vivo situation. Several approaches exist, varying from comparing the results with human plasma data, or applying reverse dosimetry by combining in vitro toxicity results with simple (steady-state) kinetic models or more complex physiologically based pharmacokinetic (PBPK) models, to obtain in vivo equivalent oral dose levels. Within this lecture the work of the  ILSI expert group on the exploitation of ToxCast data will be presented. This expert group explores opportunities to understand better how these new data and methods may be used in the safety risk assessment for foods.