title: Olfactory deposition of inhaled nanoparticles in humans.
abstract: BACKGROUND
  Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.
  
  
  OBJECTIVE
  This article aims to (i) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (ii) compare the olfactory dose in humans with our earlier dose estimates for rats.
  
  
  METHODS
  An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1-100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature.
  
  
  RESULTS
  In humans, olfactory dose of inhaled nanoparticles is highest for 1-2 nm particles with ∼1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles.
  
  
  CONCLUSIONS
  Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans in the 1--7 nm size range due to the larger inhalation rate in humans. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles.
authors.affiliation: Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin , Milwaukee, WI , USA .
authors.forename: Guilherme J M
authors.initials: GJ
authors.lastname: Garcia
authors.forename: Jeffry D
authors.initials: JD
authors.lastname: Schroeter
authors.forename: Julia S
authors.initials: JS
authors.lastname: Kimbell
mesh_terms: D000328:Adult; D000818:Animals; D003198:Computer Simulation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D057446:Hydrodynamics; D019570:Inhalation Exposure; D008297:Male; D008875:Middle Aged; D008953:Models, Anatomic; D053758:Nanoparticles / Q000737:chemistry*; D009296:Nasal Cavity / Q000187:drug effects / Q000378:metabolism; D009666:Nose; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000378:metabolism; D010316:Particle Size; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results
keywords: Computational fluid dynamics simulations; nanoparticle toxicology; nasal filtration; neurotoxicity; olfactory epithelium; particle deposition; risk assessment; ultrafine aerosols