Providing a Theoretical Basis for Nanotoxicity Risk Analysis Departing from Traditional Physiologically-Based Pharmacokinetic (PBPK) Modeling
AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH SCHOOL OF ENGINEERING AND MANAGEMENT
Pagination or Media Count:
Novel properties of engineered nanoparticles that make them attractive may also present unique exposure risks. The traditional physiologically-based pharmacokinetic PBPK modeling assumption of instantaneous equilibration likely does not apply to nanoparticles. This simulation-based research begins with development of a model that includes di64256usion, active transport, and carrier mediated transport. Eigenvalue analysis was used to examine model behavior to focus future research. Results show that cellular transport processes greatly a64256ect biokinetics of nanoparticles. The new paradigm established by this research leverages traditional in vitro, in vivo, and PBPK modeling, but includes area under the curve to bridge animal testing results to humans. This allows assessment of risk and assists in setting appropriate exposure limits. The model provides critical understanding of nanoparticle biokinetics and allows estimation of total exposure. This e64256ort highlights future research needs and demonstrates how modeling can be used as a tool to advance nanoparticle risk assessment.