Physiologically based toxicokinetic modelling as a tool to assess target organ XXXX in route-to-route extrapolation--the case of @entity1524 .

@entity1 @entity137 @entity1524 @entity35 @entity99
@entity1524 ( @entity1524 ) is occurring in food, and is also used in cosmetics. In order to perform a risk assessment for both oral and dermal exposure, we applied a physiologically based approach to model kinetics in @entity1 by simulating both routes of exposure. The concentration-time profile in liver revealed a higher peak concentration (C(max-hep)) for the oral when compared to the dermal route. The area under the concentration-time curve in the liver (AUC(hep)) was found the same for both routes if the same extent of absorption is assumed. Dose response information from published @entity35 studies were used to identify the metric relevant for liver @entity137 . Liver exposure levels resulting from doses and durations as outlined in the studies were simulated in a @entity35 model. We obtained 31 data pairs of C(max-hep) and AUC(hep). @entity99 was observed at doses which resulted in simulated C(max-hep) values exceeding a certain liver concentration whereas we could not identify a clear cut off value of AUC(hep). Our findings support the notion that liver @entity137 of @entity1524 in @entity35 is related to C(max-hep) rather than to AUC(hep). If these findings can be transferred to the situation in @entity1 , the result demonstrates that route specific differences in organ peak concentrations have to be considered when performing route-to-route extrapolation.
