Deposition of inhaled nanoparticles in the rat nasal passages: Dose to the olfactory region

Abstract

In vivo experiments have shown that nanoparticles depositing in the rat olfactory region can translocate to the brain via the olfactory nerve. Quantitative predictions of the dose delivered by inhalation to the olfactory region are needed to clarify this route of exposure and to evaluate the dose-response effects of exposure to toxic nanoparticles. Previous in vivo and in vitro studies quantified the percentage of inhaled nanoparticles that deposit in the rat nasal passages, but olfactory dose was not determined. The dose to specific nasal epithelium types is expected to vary with inhalation rate and particle size. The purpose of this investigation, therefore, was to develop estimates of nanoparticle deposition in the nasal and, more specifically, olfactory regions of the rat. A three-dimensional, anatomically accurate, computational fluid dynamics (CFD) model of the rat nasal passages was employed to simulate inhaled airflow and to calculate nasal deposition efficiency. Particle sizes from 1 to 100 nm and airflow rates of 288, 432, and 576 ml/min (1, 1.5, and 2 times the estimated resting minute volume) were simulated. The simulations predicted that olfactory deposition is maximum at 6–9% of inhaled material for 3- to 4-nm particles. The spatial distribution of deposited particles was predicted to change significantly with particle size, with 3-nm particles depositing mostly in the anterior nose, while 30-nm particles were more uniformly distributed throughout the nasal passages.

Keywords:

• CFD simulation
• epithelial map
• nasal filtration
• nanoparticle toxicology
• olfactory epithelium
• particle deposition
• rat nose
• risk assessment

Acknowledgements

We are grateful to Dr. Eileen Kuempel (National Institute for Occupational Safety and Health) for providing the original concept for this study. We thank Dr. Kai Zhao (Monell Chemical Senses Center) and Dr. Kevin Minard (Pacific Northwest National Laboratory) for providing the surface area and volume of their computational models of the rat nose. We also thank Dr. Kambiz Nazridoust (The Hamner Institutes) for his help with Fluent software and Elizabeth Gross (The Hamner Institutes) for her assistance on rat histology and anatomy. In addition, we are grateful to Dr. Jeffry Schroeter (The Hamner Institutes) and Dr. Bahman Asgharian (The Hamner Institutes) for their careful review of this article.

Note on MPPD software

The functional relationships describing how nasal and olfactory deposition vary with particle size in the rat [Eqs. (1), (2) and (3); Table 2] have been implemented in the software Multiple-Path Particle Deposition Model (MPPD). The MPPD software is copyrighted by The Hamner Institutes for Health Sciences (formerly CIIT Centers for Health Research) and RIVM (National Institute for Public Health and the Environment, the Netherlands), but it is provided free in the United States with the condition that users cite The Hamner and RIVM in any publications using dosimetry predictions obtained in MPPD. The software can be obtained by contacting Dr. Bahman Asgharian ([email protected]).

Declaration of interest: Funding for this work was provided by the American Chemistry Council and by the National Institute for Occupational Safety and Health through Requisition #000HCCEE-2006-36673. The authors alone are responsible for the content and writing of the article.