Metabolism and disposition of [14C]-methylcyclosiloxanes in rats

Comparison of the low vs. high dose oral gavage administration of D4 and D5 demonstrated dose-dependent kinetic behavior. Data and modeling results suggest differences in metabolism between low and high dose administration indicating high dose administration results in or approaches non-linear saturated metabolism. These low dose data sets were used to refine the D4/D5 multi-route harmonized PBPK model to allow for a better description of the disposition and toxicokinetics of D4/D5 following oral exposure. With a refined oral uptake description, the model could be used in risk assessment to better define the internal dose of D4 and D5 following exposure to D4 and D5 via multiple routes.