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Title: Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals

Abstract

Rodents are routinely used in inhalation toxicology tests as human surrogates. However, in vitro dosimetry tests in rodent casts are still scarce due to small rodent airways and in vitro tests to quantify sub-regional dosimetry are still impractical. We hypothesized that for inertial particles whose deposition is dominated by airflow convection (Reynolds number) and particle inertia (Stokes number), the deposition should be similar among airway replicas of different scales if their Reynolds and Stokes numbers are kept the same. In this study, we aimed to (1) numerically test the hypothesis in three airway geometries: a USP induction port, a human nose model, and a Sprague-Dawley rat nose model, and (2) find the range of applicability of this hypothesis. Five variants of the USP and human nose models and three variants of the rat nose model were tested. Inhalation rates and particle sizes were scaled to match the Reynolds number and Stokes numbers. A low-Reynolds-number k–ω model was used to resolve the airflow and a Lagrangian tracking algorithm was used to simulate the particle transport and deposition. Statistical analysis of predicted doses was conducted using ANOVA. For normal inhalation rates and particle dia- meters ranging from 0.5 to 24 mm, themore » deposition differences between the life-size and scaled models are insignificant for all airway geometries considered (i.e., human nose, USP, and rat nose). Furthermore, the deposition patterns and exit particle profiles also look similar among scaled models. However, deposition rates and patterns start to deviate if inhalation rates are too low, or particle sizes are too large. For the rat nose, the threshold velocity was found to be 0.71 m/s and the threshold Froude number to be 50. Results of this study provide a theoretical foundation for sub-regional in vitro dosimetry tests in small animals and for interpretation of data from inter-species or intra-species with varying body sizes.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1373014
Report Number(s):
PNNL-SA-122330
Journal ID: ISSN 0021-8502; 400412000
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Aerosol Science; Journal Volume: 99; Journal Issue: C
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 54 ENVIRONMENTAL SCIENCES

Citation Formats

Xi, Jinxiang, Kim, JongWon, Si, Xiuhua A., Corley, Richard A., and Zhou, Yue. Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals. United States: N. p., 2016. Web. doi:10.1016/j.jaerosci.2016.01.013.
Xi, Jinxiang, Kim, JongWon, Si, Xiuhua A., Corley, Richard A., & Zhou, Yue. Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals. United States. doi:10.1016/j.jaerosci.2016.01.013.
Xi, Jinxiang, Kim, JongWon, Si, Xiuhua A., Corley, Richard A., and Zhou, Yue. 2016. "Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals". United States. doi:10.1016/j.jaerosci.2016.01.013.
@article{osti_1373014,
title = {Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals},
author = {Xi, Jinxiang and Kim, JongWon and Si, Xiuhua A. and Corley, Richard A. and Zhou, Yue},
abstractNote = {Rodents are routinely used in inhalation toxicology tests as human surrogates. However, in vitro dosimetry tests in rodent casts are still scarce due to small rodent airways and in vitro tests to quantify sub-regional dosimetry are still impractical. We hypothesized that for inertial particles whose deposition is dominated by airflow convection (Reynolds number) and particle inertia (Stokes number), the deposition should be similar among airway replicas of different scales if their Reynolds and Stokes numbers are kept the same. In this study, we aimed to (1) numerically test the hypothesis in three airway geometries: a USP induction port, a human nose model, and a Sprague-Dawley rat nose model, and (2) find the range of applicability of this hypothesis. Five variants of the USP and human nose models and three variants of the rat nose model were tested. Inhalation rates and particle sizes were scaled to match the Reynolds number and Stokes numbers. A low-Reynolds-number k–ω model was used to resolve the airflow and a Lagrangian tracking algorithm was used to simulate the particle transport and deposition. Statistical analysis of predicted doses was conducted using ANOVA. For normal inhalation rates and particle dia- meters ranging from 0.5 to 24 mm, the deposition differences between the life-size and scaled models are insignificant for all airway geometries considered (i.e., human nose, USP, and rat nose). Furthermore, the deposition patterns and exit particle profiles also look similar among scaled models. However, deposition rates and patterns start to deviate if inhalation rates are too low, or particle sizes are too large. For the rat nose, the threshold velocity was found to be 0.71 m/s and the threshold Froude number to be 50. Results of this study provide a theoretical foundation for sub-regional in vitro dosimetry tests in small animals and for interpretation of data from inter-species or intra-species with varying body sizes.},
doi = {10.1016/j.jaerosci.2016.01.013},
journal = {Journal of Aerosol Science},
number = C,
volume = 99,
place = {United States},
year = 2016,
month = 9
}
  • In order to estimate accurately an effective dose equivalent for exposures to radon daughters, knowledge of their deposition in the lung is required. However, the nose and mouth are effective filters for removing aerosol particles, especially in the range of sizes of {open_quotes}unattached{close_quotes} radon daughters. Therefore, it is equally important to have reliable data on deposition in this region of the respiratory tract. We will describe our work in studying nasal and oral deposition of {open_quotes}unattached{close_quotes} radon daughters in casts of these airways. Several hollow casts of adult and child nasal and oral airways were fabricated at The John Hopkinsmore » University from layers of Perspect{trademark} (an acrylic plastic). The shapes of the airway passages were obtained from nuclear magnetic resonance sectional images of healthy subjects. The casts were exposed to radon gas and daughters produced by flushing filtered air through a commercially available {sup 226}Ra source. The gas stream was drawn through a 1.4-L cylindrical tube to allow measurable growth of {sup 218}Po activity before it was passed through casts of both nasal passages or the oral cavity. The deposition of {open_quotes}unattached{close_quotes} {sup 218}Po was measured by comparing the activity collected on filters mounted in series and in parallel with a cast. Measurements were made at various flow rates (Q; 4 to 20 L min{sup -1}). The diffusion coefficient (D) of {sup 218}Po was measured each time the flow rate was changed, by replacing the cast with a stainless steel gauze screen and measuring the activity penetrating the screen. The measured diffusion coefficient ranged from 0.02 to 0.05 cm{sup 2} s{sup -1} and was found to vary with the residence time of {sup 218}Po in the growth tube. The deposition efficiency ({eta}) of {sup 218}Po measured in these casts ranged from 50 to 70%, and was similar to values we found previously, using casts of nasal and oral airways from cadavers.« less
  • Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditionsmore » using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.« less
  • Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathingmore » conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.« less
  • The deposition efficiencies of ultrafine aerosols and thoron progeny were measured in youth nasal replicas. Clear polyester-resin casts of the upper airways of 1.5-yr-old (Cast G), 2.5-yr-old (Cast H), and 4-yr-old (Cast I) children were used. These casts were constructed from series of coronal magnetic resonance images of healthy children. Total deposition was measured for monodisperse NaCl or Ag aerosols between 0.0046 and 0.20 {mu}m in diameter at inspiratory and expiratory flow rates of 3, 7, and 16 L min{sup -1} (covering a near normal range of breathing rates for children of different ages). Deposition efficiency decreased with increasing particlemore » size and flow rate, indicating that diffusion was the main deposition mechanism. Deposition efficiency also decreased with increasing age at a given flow rate and particle size. Based on information obtained and information on minute volumes for different age groups, we predicted nasal deposition in age groups ranging from 1.5- to 20-yr-old at resting breathing rates. Our results showed that the nasal deposition increases with decreasing age for a given particle size between 0.001 to 0.2 {mu}m. This information will be useful in deriving future population-wide models of respiratory tract dosimetry. 24 refs., 12 figs., 3 tabs.« less
  • The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 {mu}m particles in 10 human subjects and in our preliminary studies using 0.004-0.15 {mu}m particles in four adult volunteers. No oral deposition was reported in either of thesemore » studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 {mu}m with the nasal dimensions of each subject.« less