PBPK modeling, a tool for low-dose toxicology and individual effect assesment

TOXI 28

Peter J. van Bladeren, peter.van-bladeren@rdls.nestle.com, Nestle Research Centre, Lausanne, Switzerland and Ivonne MCM. Rietjens, ivonne.rietjens@wur.nl, Department of Toxicology, University of Wageningen, Wageningen, Netherlands.
Toxicology is a science studying the interaction of chemicals with living organisms.Traditionally focus is on the adverse effects resulting from this interaction. Huge advances have been made in toxicology, not only in explaining mechanisms and assessing hazards and risks, but also in using the outcome of studies to obtain deeper insight into the functioning of living cells and organisms. The current major challenges for toxicologists are i) the understanding and prediction of the effects of low doses of chemicals such as e.g., the case for non-nutritive dietary constituents, and ii) the existence and determination of thresholds for these effects. An extremely valuable tool for the translation of mechanistic insight into an understanding of low-dose effects is Physiologically-Based PharmacoKinetic and/or PharmacoDynamic Modelling. This allows prediction of levels of the relevant metabolites in target organs and cells. Moreover, the consequences of species differences and interindividual differences can be taken into account. Thus, knowledge of both genetic and phenotypic differences can lead to individual effect assesment. Depending on the circumstances, this effect may be adverse but also beneficial.