The Derivation of a Measure for a Long-Term Exposure from a Short-Term Exposure PBPK Model. Donghan Yu, KAERI, P.O. Box 105, Taejon, KOREA, 305-600
The use of complex physiologically-based pharmacokinetic (PBPK) models has been widely accepted for mechanistic understanding of dose-response assessment. Its principal advantage over current simple scaling by the body weight or surface area in extrapolating species is quite obvious. However, developing a such full dynamic model for a long-term exposure may be hard since the carcinogenic process requires the information about detailed mechanisms and the large amounts of pharmacokinetic parameters. From the practical point of view, a simple way, i.e., the derivation of a single measure from a short-term exposure model, may provide a promising direction for a long-term risk assessment. For this study, the short-term exposure model for inorganic arsenic previously developed by the author has been examined for different time patterns of dose administration. The basic assumption is that the risk due to oral exposure should depend only on the area-under-curve (AUC) of the internal dose time series. Specifically, the AUC of certain species including metabolites in a selected tissue group is determined. The simulations have been performed for repeating low oral exposures per 8 hour interval and 4 hour interval. For each case, the simulation has also incorporated the uncertainty of input parameters in the model. The results indicate that the certain AUCs may be used for a relevant measure for purposes of predicting the long-term risk for inorganic arsenic. Efforts on the development of a such measure are directed towards the prediction of the integral effect due to internal about detailed mechanisms and the large amounts of pharmacokinetic parameters. From the practical point of view, a simple way, i.e., the derivation of a single measure from a short-term exposure model, may provide a promising direction for a long-term risk assessment. For this study, the short-term exposure model for inorganic arsenic previously developed by the author has been examined for different time patterns of doset . . . . . . [RiskWorld Note: Submitted abstract incomplete]