Development of a rat and human PBPK model for bromate and estimation of human equivalent concentrations in drinking...

A physiologically based pharmacokinetic (PBPK) model was developed to described uptake, disposition and clearance of bromate in the rat using published experimental data in rat. The rodent bromate model was extrapolated to human using species-specific physiological parameters and standard interspecies scaling of rate constants. The bromate model is kinetically linear (i.e. AUC and Cmax) across the range of drinking water concentrations used in the cancer bioassays (15 to 500 ppm). This is likely the result of the poor oral bioavailability of bromate due to high reduction rates in the intestinal tract. The bromate PBPK model was used to assess the human equivalent drinking water concentration (HEC) consistent with average plasma concentrations in the rodent bioassays. At drinking water concentrations <500 mg/L, the predicted HEC was two to three fold lower than the bioassay concentration and was dependent on the reported drinking water intake reported in the bioassay.