The use of physiologically based models to integrate diverse data sets and reduce uncertainty in the prediction of @entity13756 and XXXX kinetics across life stages and species.

@entity1 @entity8789 @entity6893 @entity13756 @entity35
The effects of @entity13756 on the incorporation of @entity6893 into @entity8789 have been studied for more than 40 years in many species and under varying exposure conditions. Nevertheless, the database for this drinking water contaminant is still incomplete, particularly with regard to @entity1 developmental risk. A method for integrating the available data and forming meaningful conclusions for risk assessment is needed. To this end, an initial suite of physiologically based pharmacokinetic (PBPK) models has been developed, which incorporates physiological data for the relevant species and life stages and kinetic data for @entity13756 and @entity6893 , as well as the interaction between the two anions. The validated models successfully describe @entity13756 -induced inhibition of thyroid @entity6893 uptake and @entity13756 and @entity6893 kinetics in the male, pregnant, lactating, fetal, and neonatal @entity35 and the adult @entity1 . The relationships of model-predicted internal dose metrics and kinetic parameters allow a direct comparison of internal dose metrics across life stages in @entity35 and @entity1 . By incorporating all the available data, these models provide a framework for species and life stage extrapolation where the lack of specific data sets would otherwise limit predictive capability. This paper demonstrates two approaches for calculating life stage-specific equivalent doses in a risk assessment for @entity13756 : the direct combination of validated model predictions, and the development of preliminary PBPK models for the @entity1 -sensitive populations based on the relationship of the parameters in the validated @entity35 and @entity1 models. Either approach can be used to perform the needed dosimetry. However, the second approach provides the advantage of a preliminary @entity1 life stage-specific PBPK model that can be used for identification of key data gaps and estimation of uncertainty.
