title: Modeling the in vivo case with in vitro nanotoxicity data.
abstract: As more in vitro nanotoxicity data appear in the literature, these findings must be translated to in vivo effects to define nanoparticle exposure risk. Physiologically based pharmacokinetic (PBPK) modeling has played a significant role in guiding and validating in vivo studies for molecular chemical exposure and can develop as a significant tool in guiding similar nanotoxicity studies. This study models the population dynamics of a single cell type within a specific tissue. It is the first attempt to model the in vitro effects of a nanoparticle exposure, in this case aluminum (80 nm) and its impact on a population of rat alveolar macrophages (Wagner et al. 2007, J. Phys. Chem. B 111:7353-7359). The model demonstrates how in vitro data can be used within a simulation setting of in vivo cell dynamics and suggests that PBPK models should be developed quickly to interpret nanotoxicity data, guide in vivo study design, and accelerate nanoparticle risk assessment.
authors.affiliation: Air Force Institute of Technology, Wright-Patterson Air Force Base, Ohio 45433, USA. Michael.Shelley@afit.edu
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shelley
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wagner
authors.forename: Saber M
authors.initials: SM
authors.lastname: Hussain
authors.forename: Charles
authors.initials: C
authors.lastname: Bleckmann
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000633:toxicity*; D008954:Models, Biological; D010316:Particle Size; D011237:Predictive Value of Tests; D051381:Rats
chemical_list: D000535:Aluminum