A physiologically based pharmacokinetic model of inorganic arsenic.

This study presents a physiologically based pharmacokinetic model of inorganic arsenic disposition in humans. The model focuses on short-term exposures by the oral route. The model considers the four circulating species (AsIII, AsV, and two metabolites, i.e., monomethylarsenic (MMA) and dimethylarsenic (DMA)) in tissue groups. The model also provides for the reduction of AsV to AsIII via chemical reaction with tissue glutathione and the subsequent transformation of AsIII into two metabolites (MMA and DMA) based on the experimental observations. Effort on the development of the model is directed toward the prediction of the kinetic behavior of inorganic arsenic in the body, following environmental exposure at ambient water concentrations, including tissue and blood concentrations, and especially urinary excretion of arsenic and its methylated metabolites. While it is difficult to estimate some of parameters used in the model at this time, the current model assumptions and predictions seem to be consistent with the experimental observations found in the literature. Therefore, the current model, when more fully developed, is expected to provide insight into the behavior of inorganic arsenic and its methylated metabolites within the body and may help increase the understanding of risk assessment issues associated with inorganic arsenic in drinking water. Copyright 1999 Academic Press.