Abstract
BackgroundNose-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.MethodComputational 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.ResultsRegional deposition of nanoparticles in human and the rat olfactory was extremely low, with the highest deposition (< 3.5 and 8.1%) occurring for high diffusivity particles of 1.5 nm and 5 nm, respectively. Due to significant filtering of extremely small particles (< 2 nm) by abrupt sharp turns at front of the rat nose, only small fractions of the inhaled nanoparticles (in this range) reached rat olfactory than that in human (1.25 to 45%); however, for larger sizes (> 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 < 1.5 nm were filtered out by rat anterior nasal cavity, and therefore deposition in human olfactory region exceeded that in the rat model.ConclusionRegional deposition dose of inhaled nanoparticles in a human and rat olfactory region was governed by particle size and the breathing rate. Interspecies correlation was determined by combining the effect of deposition dosage, physical\\geometric features, and genetic differences. Developed empirical equations provided a tool to quantify inhaled nanoparticle dose in human and rat nasal olfactory regions, which lay the ground work for comprehensive interspecies correlation between the two species. Furthermore, this study contributes to the fields in toxicology, i.e., neurotoxicity evaluation and risk assessment of UFPs, in long-term and low-dose inhalation exposure scenarios.
Highlights
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
Regional deposition dose of inhaled nanoparticles in a human and rat olfactory region was governed by particle size and the breathing rate
Human and rat nasal and olfactory airway model comparison The human nasal olfactory is located in the superior main nasal passage, while for the rat it is predominantly located in the posterior half of the nasal cavity (Fig. 1a)
Summary
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 nasal olfactory is undoubtedly a critical junction where the time course and toxicant dose dependency might be inferred Neurological disorders, such as Parkinson’s and Alzheimer’s disease, are suspected to be related to long-term brain accumulation of toxicants, which may lead to a gradual progression and staged neurological responses [1]. In such a hypothesis, chronic low-dose exposure and prolonged brain accumulation of exogenous airborne ultrafine particles (UFPs) are critical to define the neurodegeneration. Particle transport via nose-to-brain route has attracted increased attention based on the findings that exogenous materials can bypass the BBB via the olfactory pathway. The findings suggested negative impact to human olfactory function and plausible toxicological mechanisms contributing to human cognitive impairment by environmental exposure to ambient pollutants via the olfactory pathway
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