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Deposition of Nanoparticles in the Human Respiratory Tract

Chiu-sen Wang and S. K. Friedlander. Chemical and Biomolecular Engineering, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095

Nanoparticles commonly occur in ambient air as well as in the workplaces where nanomaterials are manufactured. Rapid development of nanotechnologies in recent years has raised increasing concern about the health risk of nanomaterials. Toxicological studies indicate that, for the same total particle mass, nanoparticles administered to the lungs of rodents give rise to a greater inflammatory response than larger particles (Oberdörster, 2001). The enhanced toxicity is apparently associated with the larger surface area provided by nanoparticles that come into contact with lung fluids and cells. A likely cause for inflammation is the oxidative stress resulting from free radicals generated at the surfaces of nanoparticles (MacNee and Donaldson, 2003). In addition, surface area is a key factor that determines the quantity of toxic gaseous species adsorbed on a particle. Other toxicological studies have shown that nanometer-sized particulate pollutants can induce mitochondrial damage (Li et al., 2003). It also appears that nanoparticles deposited in the pulmonary region largely escape engulfing by alveolar macrophages and thereby have higher probabilities to enter interstitial spaces. The link between inhalation exposures and responses is the dose of particles specific to target tissues. To reach a target tissue in an individual, particles in ambient air or workplaces have to go through a sequence of steps including entry through the nose or mouth, transport through the respiratory tract, and deposition on airway surfaces. Once deposited, insoluble particles can be translocated from sites of deposition to other sites, while soluble particles can be either completely dissolved at sites of deposition or translocated. Inhaled particles deposit on airway surfaces by several mechanisms. For nanoparticles, the dominant mechanisms of deposition are convective Brownian diffusion during the inspiratory phase and Brownian motion during the short pause between the inspiratory and expiratory phases. Because the incoming air is, in general, heated and humidified during its passage through the nasal cavity, larynx and trachea, thermophoresis and diffusiophoresis also play an important role in the deposition of nanoparticles. The human respiratory tract consists of three distinct regions connected in series: the head airways, the tracheobronchial tree, and the alveolar region. The sequential nature of these three regions gives rise to the filtration effect: particles have a chance to enter a downstream region only if they have not deposited in an upstream region. The rate of deposition in each region depends on aerosol properties, airway structure and physiological factors. Calculations indicate that, while a substantial fraction of inhaled nanoparticles deposit in each of the three regions, local deposition rates vary markedly from site to site in each region. Furthermore, particles deposited in different regions are dissolved or removed from the airway surfaces at different rates. The response to a specific toxicant also varies from region to region. Local deposition rates are therefore needed for estimating tissue doses of inhaled particles. Ambient nanoparticle aerosols, which mostly originate from vehicular emissions and photochemical reactions in the atmosphere, generally consist of chain aggregates, compact solid particles and liquid droplets. Studies on the morphological properties of nanoparticles in Los Angeles aerosol show that the fraction of ambient particles with aggregate structure is 60% for particles with aerodynamic diameter between 50 and 75 nm and 38% for particles between 75 and 120 nm (Xiong and Friedlander, 2001). The size distribution of nanoparticle aerosols is usually determined using the Scanning Mobility Particle Sizer (SMPS) system. The instrument classifies particles according to electrical mobility and is commonly calibrated for spherical particles. In consequence data obtained from the instrument cannot directly provide the surface area and volume distributions for nanoparticle aggregates. Recently Lall and Friedlander (2006) have developed a method capable of relating the surface area and volume of a nanoparticle chain aggregate to the electrical mobility diameter measured with an SMPS system. The analysis takes into account the friction coefficient and charging efficiency of chain aggregates, under the assumption that the primary particles composing the aggregates are at least one order of magnitude smaller than the mean free path of the surrounding gas. Their calculations indicate that a chain aggregate with random orientation has a somewhat smaller surface area and a much smaller volume than a mobility equivalent sphere. Rates of particle deposition in the respiratory tract can be calculated using a number of computational schemes described in the books by ICRP (International Commission on Radiological Protection, 1994), NCRP (National Council on Radiation Protection and Measurements, 1997), and Wang (2005). In this presentation, an improved computational scheme is described which takes into consideration the effects of aggregate structure, thermophoresis and diffusiophoresis on deposition. Expressions for aggregate friction coefficient are used in calculations for the aggregate volume (or mass) in a given mobility diameter range and diffusional deposition from the same mobility diameter range. The improved computational scheme is therefore capable of relating the data obtained from an SMPS system to deposition in the respiratory tract.


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