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Title: Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract

Abstract

Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross-species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to ironmore » oxide nanoparticles, micro- and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat and human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles.« less

Authors:
 [1];  [2];  [3];  [4];  [4];  [4];  [5];  [6]; ORCiD logo [6]
  1. CIIT Centers for Health Research
  2. Applied Research Associates, Inc.
  3. Virginia Commonwealth University
  4. New York University
  5. BATTELLE COLUMBUS OFFICE
  6. BATTELLE (PACIFIC NW LAB)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1512452
Report Number(s):
PNNL-SA-109668
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Inhalation Toxicology
Additional Journal Information:
Journal Volume: 26; Journal Issue: 14
Country of Publication:
United States
Language:
English
Subject:
Lung deposition, nanosized particles, particle

Citation Formats

Asgharian, Bahman, Price, Owen, Oldham, M, Chen, Lung-Chi, Saunders, E L., Gordon, T, Mikheev, Vladimir B., Minard, Kevin R., and Teeguarden, Justin G. Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract. United States: N. p., 2014. Web. doi:10.3109/08958378.2014.935535.
Asgharian, Bahman, Price, Owen, Oldham, M, Chen, Lung-Chi, Saunders, E L., Gordon, T, Mikheev, Vladimir B., Minard, Kevin R., & Teeguarden, Justin G. Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract. United States. doi:10.3109/08958378.2014.935535.
Asgharian, Bahman, Price, Owen, Oldham, M, Chen, Lung-Chi, Saunders, E L., Gordon, T, Mikheev, Vladimir B., Minard, Kevin R., and Teeguarden, Justin G. Thu . "Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract". United States. doi:10.3109/08958378.2014.935535.
@article{osti_1512452,
title = {Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract},
author = {Asgharian, Bahman and Price, Owen and Oldham, M and Chen, Lung-Chi and Saunders, E L. and Gordon, T and Mikheev, Vladimir B. and Minard, Kevin R. and Teeguarden, Justin G.},
abstractNote = {Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross-species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro- and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat and human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles.},
doi = {10.3109/08958378.2014.935535},
journal = {Inhalation Toxicology},
number = 14,
volume = 26,
place = {United States},
year = {2014},
month = {11}
}

Works referenced in this record:

Inhaled aerosol particle dosimetry in mice: A review
journal, December 2010


Particokinetics In Vitro: Dosimetry Considerations for In Vitro Nanoparticle Toxicity Assessments
journal, November 2006

  • Teeguarden, Justin G.; Hinderliter, Paul M.; Orr, Galya
  • Toxicological Sciences, Vol. 95, Issue 2
  • DOI: 10.1093/toxsci/kfl165

Role of Cilia, Mucus, and Airway Surface Liquid in Mucociliary Dysfunction: Lessons from Mouse Models
journal, March 2008

  • Mall, Marcus A.
  • Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 21, Issue 1
  • DOI: 10.1089/jamp.2007.0659

Pulmonary response after exposure to inhaled nickel hydroxide nanoparticles: Short and long-term studies in mice
journal, December 2009


Aerosol Inhalation in the Rat Lung Part II: Theoretical Predictions of Particle Deposition Patterns
journal, January 1995


Computer Simulation of Inspiratory Airflow in All Regions of the F344 Rat Nasal Passages
journal, August 1997

  • Kimbell, J. S.; Godo, M. N.; Gross, E. A.
  • Toxicology and Applied Pharmacology, Vol. 145, Issue 2
  • DOI: 10.1006/taap.1997.8206

Anatomic Models of the tracheobronchial and pulmonary regions of the rat
journal, November 1979

  • Yeh, H. C.; Schum, G. M.; Duggan, M. T.
  • The Anatomical Record, Vol. 195, Issue 3
  • DOI: 10.1002/ar.1091950308

Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans
journal, November 2012


Use of Computational Fluid Dynamics Models for Dosimetry of Inhaled Gases in the Nasal Passages
journal, May 2001


Regional particle size dependent deposition of inhaled aerosols in rats and mice
journal, December 2011


Deposition of ultrafine aerosols in rat nasal molds
journal, November 1990


Comparative inhalation toxicity of nickel subsulfide to F344/N rats and B6C3F1 mice exposed for 12 days
journal, August 1987


Deposition and Clearance Models of Ni Compounds in the Mouse Lung and Comparisons with the Rat Models
journal, November 1999

  • Hsieh, T. H.; Yu, C. P.; Oberdorster, Gunter
  • Aerosol Science and Technology, Vol. 31, Issue 5
  • DOI: 10.1080/027868299304084

Particle inhalability curves for humans and small laboratory animals*1
journal, June 1995


Use of a Pharmacokinetic-Driven Computational Fluid Dynamics Model to Predict Nasal Extraction of Hydrogen Sulfide in Rats and Humans
journal, July 2006

  • Schroeter, J. D.; Kimbell, J. S.; Andersen, M. E.
  • Toxicological Sciences, Vol. 94, Issue 2
  • DOI: 10.1093/toxsci/kfl112

Comparison of Predicted and Experimentally Measured Aerosol Deposition Efficiency in BALB/C Mice in a New Nose-Only Exposure System
journal, September 2009

  • Oldham, Michael J.; Phalen, Robert F.; Budiman, Thomas
  • Aerosol Science and Technology, Vol. 43, Issue 10
  • DOI: 10.1080/02786820903082029

Toxicity Testing in the 21st Century: Bringing the Vision to Life
journal, December 2008

  • Andersen, Melvin E.; Krewski, Daniel
  • Toxicological Sciences, Vol. 107, Issue 2
  • DOI: 10.1093/toxsci/kfn255

Dosimetric Adjustments for Interspecies Extrapolation of Inhaled Poorly Soluble Particles (PSP)
journal, January 2005

  • Jarabek, Annie M.; Asgharian, Bahman; Miller, Frederick J.
  • Inhalation Toxicology, Vol. 17, Issue 7-8
  • DOI: 10.1080/08958370590929394

Comparison of Analytical and Numerical Particle Deposition Using Commercial CFD Packages: Impaction and Sedimentation
journal, January 2008

  • Robinson, Risa J.; Snyder, Pamela; Oldham, Michael J.
  • Inhalation Toxicology, Vol. 20, Issue 5
  • DOI: 10.1080/08958370701858435

Exact analysis of aerosol deposition during steady breathing
journal, September 1978


A Modeling Study of the Effect of Gravity on Airflow Distribution and Particle Deposition in the Lung
journal, January 2006

  • Asgharian, Bahman; Price, Owen; Oberdörster, Gunter
  • Inhalation Toxicology, Vol. 18, Issue 7
  • DOI: 10.1080/08958370600602009

Predicted Tracheobronchial and Pulmonary Deposition in a Murine Asthma Model
journal, January 2007

  • Oldham, Michael J.; Robinson, Risa J.
  • The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, Vol. 290, Issue 10
  • DOI: 10.1002/ar.20593

Pulmonary function assessment by whole-body plethysmography in restrained versus unrestrained mice
journal, January 2002


Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles
journal, July 2005

  • Oberdörster, Günter; Oberdörster, Eva; Oberdörster, Jan
  • Environmental Health Perspectives, Vol. 113, Issue 7
  • DOI: 10.1289/ehp.7339

Mucociliary clearance of insoluble particles from the tracheobronchial airways of the human lung
journal, June 2001


Empirical Equations for Nasal Deposition of Inhaled Particles in Small Laboratory Animals and Humans
journal, January 1993


Dosimetry Modeling of Inhaled Formaldehyde: Comparisons of Local Flux Predictions in the Rat, Monkey, and Human Nasal Passages
journal, November 2001

  • Kimbell, J. S.; Subramaniam, R. P.; Gross, E. A.
  • Toxicological Sciences, Vol. 64, Issue 1
  • DOI: 10.1093/toxsci/64.1.100

ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies
journal, January 2010

  • Hinderliter, Paul M.; Minard, Kevin R.; Orr, Galya
  • Particle and Fibre Toxicology, Vol. 7, Issue 1
  • DOI: 10.1186/1743-8977-7-36

A Multiple-Path Model of Fiber Deposition in the Rat Lung
journal, January 1998


Stochastic Morphometric Model of the Balb/c Mouse Lung
journal, July 2010

  • Madl, Pierre; Hofmann, Werner; Oldham, Michael J.
  • The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, Vol. 293, Issue 10
  • DOI: 10.1002/ar.21208

Deposition of fibers in the rat lung
journal, January 1989


A Multiple-Path Model of Particle Deposition in the Rat Lung
journal, November 1995


Deposition of Ultrafine (NANO) Particles in the Human Lung
journal, January 2007


Comparing Inhaled Ultrafine versus Fine Zinc Oxide Particles in Healthy Adults: A Human Inhalation Study
journal, May 2005

  • Beckett, William S.; Chalupa, David F.; Pauly-Brown, Andrea
  • American Journal of Respiratory and Critical Care Medicine, Vol. 171, Issue 10
  • DOI: 10.1164/rccm.200406-837OC

Particle Deposition in a Multiple-Path Model of the Human Lung
journal, January 2001

  • Asgharian, B.; Hofmann, W.; Bergmann, R.
  • Aerosol Science and Technology, Vol. 34, Issue 4
  • DOI: 10.1080/02786820119122

Inbred strain variation in lung function
journal, August 2002


Respiratory Deposition and Inhalability of Monodisperse Aerosols in Long-Evans Rats
journal, January 2003


Interindividual Variability in Nasal Filtration as a Function of Nasal Cavity Geometry
journal, June 2009

  • Garcia, Guilherme J. M.; Tewksbury, Earl W.; Wong, Brian A.
  • Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 22, Issue 2
  • DOI: 10.1089/jamp.2008.0713

Magnetic particle detection (MPD) for in-vitro dosimetry
journal, May 2013


Prediction of particle deposition in the human lung using realistic models of lung ventilation
journal, October 2006


Dosimetric Comparisons of Particle Deposition and Retention in Rats and Humans
journal, January 2005

  • Brown, James S.; Wilson, William E.; Grant, Lester D.
  • Inhalation Toxicology, Vol. 17, Issue 7-8
  • DOI: 10.1080/08958370590929475