Please use this identifier to cite or link to this item:
|Title:||Application of physiologically-based toxicokinetic modelling in oral-to-dermal extrapolation of threshold doses of cosmetic ingredients|
|Authors:||GAJEWSKA MONIKA; WORTH Andrew; URANI Chiara; BRIESEN Heiko; SCHRAMM Karl-Werner|
|Citation:||TOXICOLOGY LETTERS vol. 227 no. 3 p. 189-202|
|Publisher:||ELSEVIER IRELAND LTD|
|Type:||Articles in periodicals and books|
|Abstract:||The application of physiologically based toxicokinetic (PBTK) modelling in route-to-route (RtR) extrap-olation of three cosmetic ingredients: coumarin, hydroquinone and caffeine is shown in this study. In particular, the oral no-observed-adverse-effect-level (NOAEL) doses of these chemicals are extrapolated to their corresponding dermal values by comparing the internal concentrations resulting from oral and dermal exposure scenarios. The PBTK model structure has been constructed to give a good simulation performance of biochemical processes within the human body. The model parameters are calibrated basedon oral and dermal experimental data for the Caucasian population available in the literature. Particular attention is given to modelling the absorption stage (skin and gastrointestinal tract) in the form of several sub-compartments. This gives better model prediction results when compared to those of a PBTK model with a simpler structure of the absorption barrier. In addition, the role of quantitative structure–property relationships (QSPRs) in predicting skin penetration is evaluated for the three substances with a view to incorporating QSPR-predicted penetration parameters in the PBTK model when experimental values arelacking. Finally, PBTK modelling is used, first to extrapolate oral NOAEL doses derived from rat studiesto humans, and then to simulate internal systemic/liver concentrations – Area Under Curve (AUC) and peak concentration – resulting from specified dermal and oral exposure conditions. Based on these simulations, AUC-based dermal thresholds for the three case study compounds are derived and compared with the experimentally obtained oral threshold (NOAEL) values.|
|JRC Directorate:||Institute for Health and Consumer Protection Historical Collection|
Files in This Item:
There are no files associated with this item.
Items in repository are protected by copyright, with all rights reserved, unless otherwise indicated.