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Spatial visualization of theoretical nanoparticle deposition in the human respiratory tract.

ABSTRACT: BACKGROUND:Although nanoparticles and their hazardous effects on human health are well elucidated meanwhile, inhalation and distribution of these materials in the human respiratory tract still represent partly enigmatic phenomena. Main objective of the present study was the detailed description of a mathematical method, with the help of which spatial distributions of nanoparticles deposited in the tracheobronchial tree may be visualized appropriately. METHODS:The technique is founded on a stochastic model of the bronchial network, within which inhaled particles follow individual, randomly selected trajectories. The lengths of these random paths depend on the airway-specific deposition probabilities calculated for the particles and the duration of the breath cycle. Positions of the deposited material were determined by computation of the exact lengths of individual particle trajectories and the orientation of single path segments within a Cartesian coordinate system, where the z-direction corresponds with the trachea. For a better quantification of the particle distribution and its eventual comparison with experimental data particle coordinates were fitted into a voxel grid [1 voxel = (0.467 cm)(3)]. Particle deposition is chiefly controlled by diffusive processes, whereas deposition mechanisms associated with inertia or gravity play a subordinate role. RESULTS:Deposition patterns were visualized for particles with sizes of 1, 10, and 100 nm. As clearly demonstrated by the results obtained from the modeling procedure, under normal breathing conditions 1-nm particles tend to deposit in the upper airways, whilst 10- and 100-nm particles are preferably accumulated in the airways of the central and peripheral lung. The particle dose deposited in the extrathoracic and thoracic airways within one breath cycle significantly declines with increasing particle size. CONCLUSIONS:Based on the predictions presented in this study possible consequences of nanoparticle inhalation to the health of subjects increasingly exposed to these airborne materials were discussed.

SUBMITTER: Sturm R

PROVIDER: S-EPMC4691007 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Spatial visualization of theoretical nanoparticle deposition in the human respiratory tract.

Sturm Robert R

Annals of translational medicine 20151201 21

<h4>Background</h4>Although nanoparticles and their hazardous effects on human health are well elucidated meanwhile, inhalation and distribution of these materials in the human respiratory tract still represent partly enigmatic phenomena. Main objective of the present study was the detailed description of a mathematical method, with the help of which spatial distributions of nanoparticles deposited in the tracheobronchial tree may be visualized appropriately.<h4>Methods</h4>The technique is foun ...[more]

PMID: 26734636

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Project description:BackgroundThe increased production of nanomaterials has caused a corresponding increase in concern about human exposures in consumer and occupational settings. Studies in rodents have evaluated dose-response relationships following respiratory tract (RT) delivery of nanoparticles (NPs) in order to identify potential hazards. However, these studies often use bolus methods that deliver NPs at high dose rates that do not reflect real world exposures and do not measure the actual deposited dose of NPs. We hypothesize that the delivered dose rate is a key determinant of the inflammatory response in the RT when the deposited dose is constant.MethodsF-344 rats were exposed to the same deposited doses of titanium dioxide (TiO?) NPs by single or repeated high dose rate intratracheal instillation or low dose rate whole body aerosol inhalation. Controls were exposed to saline or filtered air. Bronchoalveolar lavage fluid (BALF) neutrophils, biochemical parameters and inflammatory mediator release were quantified 4, 8, and 24 hr and 7 days after exposure.ResultsAlthough the initial lung burdens of TiO? were the same between the two methods, instillation resulted in greater short term retention than inhalation. There was a statistically significant increase in BALF neutrophils at 4, 8 and 24 hr after the single high dose TiO? instillation compared to saline controls and to TiO? inhalation, whereas TiO? inhalation resulted in a modest, yet significant, increase in BALF neutrophils 24 hr after exposure. The acute inflammatory response following instillation was driven primarily by monocyte chemoattractant protein-1 and macrophage inflammatory protein-2, mainly within the lung. Increases in heme oxygenase-1 in the lung were also higher following instillation than inhalation. TiO? inhalation resulted in few time dependent changes in the inflammatory mediator release. The single low dose and repeated exposure scenarios had similar BALF cellular and mediator response trends, although the responses for single exposures were more robust.ConclusionsHigh dose rate NP delivery elicits significantly greater inflammation compared to low dose rate delivery. Although high dose rate methods can be used for quantitative ranking of NP hazards, these data caution against their use for quantitative risk assessment.

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Spatial visualization of theoretical nanoparticle deposition in the human respiratory tract.

Publications

Spatial visualization of theoretical nanoparticle deposition in the human respiratory tract.

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