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 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.

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 ∼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 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.

Keywords: Computational fluid dynamics simulations; nanoparticle toxicology; nasal filtration; neurotoxicity; olfactory epithelium; particle deposition; risk assessment; ultrafine aerosols.

Figure 1. Lateral view of computational models of the human nasal passages

Models 1A, 1B, and 1C represent the same nasal geometry, but with olfactory regions (dark gray) of different sizes. Model 2 represents the nasal anatomy of a different individual. It was used for validating our computational methods because several in vitro experiments and CFD simulations in the literature were based on this nasal geometry (see text for details).

Figure 2. Deposition efficiency of inhaled nanoparticles in a human nasal cavity model (Model 1A)

Symbols correspond to simulation results, while lines depict fitted curves.

Figure 3. Olfactory fraction of total nasal deposition in a human nasal cavity model (Model 1A)

Symbols correspond to simulation results, while lines depict fitted curves.

Figure 4. Olfactory deposition efficiency in a human nasal cavity model (Model 1A)

Symbols correspond to simulation results, while lines depict fitted curves.

Figure 5. Deposition patterns of 3-nm and 30-nm particles in the human nasal cavity for a 15 L/min inhalation rate

While 3-nm particles deposit preferentially in the anterior nose, 30-nm particles deposit more uniformly in the nasal passages. The atmospheric nanoparticle concentration was 160 μg/m³, which is the experimental atmospheric concentration in Oberdorster et al. (2004). Colormap scale: f_max = 1.3 × 10⁻⁶ μg/s.mm².

Figure 6. Dose of nanoparticles deposited in the human nasal cavity averaged along the perimeter of coronal cross sections and plotted as a function of the distance from the nostrils

The atmospheric nanoparticle concentration was 160 μg/m³, which is the experimental atmospheric concentration in Oberdorster et al. (2004). Curves are shown for airflow rates of 15L/min, and particles sizes of 3 nm and 30 nm.

Figure 7. Effect of varying the olfactory surface area on estimates of olfactory deposition

All models have the same geometry (Figure 1), except for variations in the olfactory surface area. (A) Olfactory deposition efficiency of 1–100 nm particles. (B) The ratio of olfactory deposition efficiency in Model 1B to olfactory deposition efficiency in Model 1A is approximately 0.50, which is the ratio between their olfactory surface areas. Similarly, the ratio of olfactory deposition efficiency in Model 1C to Model 1A is approximately 2.0, which is the ratio between their olfactory surface areas. The olfactory surface areas in Models 1A, 1B, and 1C are 11.2 cm², 5.6 cm², and 22.0 cm², respectively.

Figure 8. Total deposition efficiency of inhaled nanoparticles in the human nasal cavity (Model 2) for a 10 L/min steady-state inhalation rate

(A) In vivo and in vitro experimental data from the literature compared to our computational results. (B) Computational studies from the literature compared to our results. References: (Cheng et al., 1996; Cheng et al., 1995; Cheng et al., 1996; Ge et al., 2012; Ghalati et al., 2012; Kelly et al., 2004b; Shi et al., 2008; Swift et al., 1992; Xi & Longest, 2008; Zamankhan et al., 2006).

Figure 9. Nanoparticle deposition in the nasal cavity and olfactory region of humans and rats at rest (breathing rate = 15 L/min in humans and 0.58 L/min in rats)

(A) Total nasal deposition efficiency. (B) Olfactory deposition efficiency. (C) Rat-to-human ratio of nasal deposition efficiency and olfactory deposition efficiency. (D) Number of particles deposited in the olfactory region (olfactory dose) for an atmospheric concentration of 10,000 particles/cm³, assuming an uniform particle distribution in the 1–100nm range. Data for rats taken from Garcia and Kimbell (2009).