Search

Abstract Background Nose-to-brain transport of airborne ultrafine particles (UFPs) via the olfactory pathway has been verified as a possible route for particle translocation into the brain. The exact relationship between increased airborne toxicant exposure and neurological deterioration in the human central nervous system, is still unclear. However, the nasal olfactory is undoubtedly a critical junction where the time course and toxicant dose dependency might be inferred. Method Computational fluid-particle dynamics modeling of inhaled nanoparticles (1 to 100 nm) under low to moderate breathing conditions (5 to 14 L/min – human; and 0.14 to 0.40 L/min – rat) were performed in physiologically realistic human and rat nasal airways. The simulation emphasized olfactory deposition, and variations in airflow and particle flux caused by the inter-species airway geometry differences. Empirical equations were developed to predict regional deposition rates of inhaled nanoparticles on human and rat olfactory mucosa in sedentary breathing. Considering, breathing and geometric differences, quantified correlations between human and the rat olfactory deposition dose against a variety of metrics were proposed. Results Regional deposition of nanoparticles in human and the rat olfactory was extremely low, with the highest deposition ( 3 nm), significantly higher percentage of the inhaled nanoparticles reached rat nasal olfactory than that in human (2 to 32 folds). Taking into account the physical and geometric features between human and rat, the total deposition rate (#/min) and deposition rate per unit surface area (#/min/mm2) were comparable for particles> 3 nm. However, when body mass was considered, the normalized deposition rate (#/min/kg) in the rat olfactory region exceeded that in the human. Nanoparticles

Olfactory pathway, susceptible for direct translocation of inhaled nanoparticles into the brain, has been verified in a number of animal studies over past decades. In case of toxic substances, the extremely low dose strongly suggests a subclinical condition that prevents noticeable neurodegeneration until years after prolonged exposure. The exact mechanism, between elevated presence of toxic substances (e.g. heavy metals) and deteriorated neurofunction in human central nervous system, is still not clear; however, nasal olfactory, being portal of the entry for such a transport route, is undoubtedly a critical junction where hint to the time course and dose dependency might be inferred. Using a physiologically realistic nasal and upper airway replica, this study performed human inhalation simulations of nanoparticles (1–100 nm) under low to moderate breathing conditions (5–14 L/min). Emphasis is on olfactory deposition and the various factors contributing to the process. Details on airflow pattern and particle flux in nasal and olfactory were made visible through a 2D unwrapped surface mapping technique, and it was found out that airflow pattern, especially nasal wall shear had a remarkable correlation to particle movement and deposition at the ultrafine scale (< 1–2 nm). Olfactory deposition efficiency was found to be extremely low (< 3.5%), and showed distinctive variation in high diffusivity region when compared to that in the entire nasal cavity. The entrance profile of olfactory deposited particles was seen to be highly selective and unanimously originated from upper section of the nostril near nasal septum. Current study is of significant value to the understanding of human uptake of inhaled nanoparticles through olfactory pathway. [ABSTRACT FROM AUTHOR]