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Journal of Toxicology
Volume 2012 (2012), Article ID 359471, 11 pages
Review Article

Physiologically Based Toxicokinetic Modelling as a Tool to Support Risk Assessment: Three Case Studies

1Federal Institute for Risk Assessment, Max Dohrn Strasse 8-10, 10589 Berlin, Germany
2Institute for Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany

Received 10 October 2011; Revised 28 January 2012; Accepted 16 February 2012

Academic Editor: Jane C. Caldwell

Copyright © 2012 Hans Mielke and Ursula Gundert-Remy. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In this contribution we present three case studies of physiologically based toxicokinetic (PBTK) modelling in regulatory risk assessment. (1) Age-dependent lower enzyme expression in the newborn leads to bisphenol A (BPA) blood levels which are near the levels of the tolerated daily intake (TDI) at the oral exposure as calculated by EFSA. (2) Dermal exposure of BPA by receipts, car park tickets, and so forth, contribute to the exposure towards BPA. However, at the present levels of dermal exposure there is no risk for the adult. (3) Dermal exposure towards coumarin via cosmetic products leads to external exposures of two-fold the TDI. PBTK modeling helped to identify liver peak concentration as the metric for liver toxicity. After dermal exposure of twice the TDI, the liver peak concentration was lower than that present after oral exposure with the TDI dose. In the presented cases, PBTK modeling was useful to reach scientifically sound regulatory decisions.