Olfactory deposition of inhaled nanoparticles in humans

Abstract

Context 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. Objectives This manuscript aims to (1) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (2) compare the olfactory dose in humans with our earlier dose estimates for rats. Materials and 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 approximately 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. Discussion and conclusion 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 due to their larger minute volume. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles.

Developmental neurotoxicity of inhaled ambient ultrafine particle air pollution: Parallels with neuropathological and behavioral features of autism and other neurodevelopmental disorders

“…One cited limitation of rodent models of inhaled air pollution has been that rodents, unlike humans, are obligate nose-breathers and thus dosing to mouse results in higher exposures relative to humans. However, this may be a minimal or negligent concern according to a recent study based on computational modeling using an anatomically accurate model of the human nasal cavity that found that the olfactory dose per unit surface area is actually estimated to be higher in humans for 1-7 nm particles based on the larger inhalation rates of humans [196]. The latter is of particular note as emphasized in a recent editorial [197], given the presence in fly ash and car exhaust of a significant fraction of particles below 10 nm, often overlooked because of measurement difficulty [198].…”

Consideration of the respiratory cycle asymmetry in the numerical modeling of the submicron particles deposition in the human nasal cavity

“…8B from [4], supplemented by our curve. In this figure, three curves reflect the results obtained for [4][5][6], the remaining four represent calculations for different original models. In four papers [4][5][6][7], the Euler approach was used to calculate particle motion, the others [8,9] and our work used the Lagrange approach.…”

“…5 comparisons of our results with the calculated [14] and experimental [15] data are presented for the d mathematical and experimental models based on the same MRI scans, which were used in [4][5][6]. Our calculations were carried out for the model shown in Fig.…”

“…The figure is an analogue of Fig. 8B from [4], supplemented by our curve. In this figure, three curves reflect the results obtained for [4][5][6], the remaining four represent calculations for different original models.…”

“…In four papers [4][5][6][7], the Euler approach was used to calculate particle motion, the others [8,9] and our work used the Lagrange approach. Following the authors of [4], we can recognize the comparison as quite good.…”