Abstract:
BACKGROUND : Cerium dioxide nanoparticles (nanoceria) are increasingly being used in a variety
of products as catalysts, coatings, and polishing agents. Furthermore, their antioxidant properties
make nanoceria potential candidates for biomedical applications. To predict and avoid toxicity,
information about their biokinetics is essential. A useful tool to explore such associations
between exposure and internal target dose is physiologically based pharmacokinetic (PBPK)
modeling. The aim of this study was to test the appropriateness of our previously published
PBPK model developed for intravenous (IV) administration when applied to various sizes of
nanoceria and to exposure routes relevant for humans.
METHODS : Experimental biokinetic data on nanoceria (obtained from various exposure routes,
sizes, coatings, doses, and tissues sampled) in rats were collected from the literature and also
obtained from the researchers. The PBPK model was first calibrated and validated against IV
data for 30 nm citrate coated ceria and then recalibrated for 5 nm ceria. Finally, the model was
modified and tested against inhalation, intratracheal (IT) instillation, and oral nanoceria data.
RESULTS : The PBPK model adequately described nanoceria time courses in various tissues for
5 nm ceria given IV. The time courses of 30 nm ceria were reasonably well predicted for liver
and spleen, whereas the biokinetics in other tissues were not well captured. For the inhalation,
IT instillation, and oral exposure routes, re-optimization was difficult due to low absorption and,
hence, low and variable nanoceria tissue levels. Moreover, the nanoceria properties and exposure
conditions varied widely among the inhalation, IT instillation, and oral studies, making it difficult
to assess the importance of different factors.
CONCLUSION : Overall, our modeling efforts suggest that nanoceria biokinetics depend largely
on the exposure route and dose.
