Uncertainties in a pharmacokinetic modeling for inorganic arsenic

This paper presents a pharmacokinetic modeling of inorganic arsenic deposition in rodents for a short-term exposure by the oral route. The work involves (i) the development of a physiologically-based pharmacokinetic (PBPK) model, and (ii) the uncertainty analysis of the model. Efforts on the development of a PBPK: model are directed towards the prediction of the kinetic behavior of inorganic arsenic in the body, including tissue and blood concentrations, and especially, the urinary excretion of arsenic and its methylated metabolites. However, large uncertainties are associated with predictions from the model. Some of this uncertainties derives from the uncertainties about model inputs. In order to assess how model predictions are affected by the uncertainties of model inputs, the study performs a quantative uncertainty analysis in conjuction with the developed PBPK model. This approach provides a clear advantage in understanding the kinetic behavior of a chemical and its metabolites in the body for assessing risks associated with inorganic arsenic exposures.