Description:

Accurate health risk assessments of inhalation exposure to nanomaterials will require dosimetry models that account for interspecies differences in dose delivered to the respiratory tract. Mechanistic models offer the advantage to interspecies extrapolation that physicochemical properties of particles and species differences in ventilation, airway architecture and physiological parameters can be incorporated explicitly to describe inhaled dose. The objective of this research is to extend existing, verified mechanistic models of particle deposition in the respiratory tract of rats and humans to both cover the range of size for nanoparticles and nanotubes. Deposition mechanisms are described based on first principles and semi-empirically as required. Semi-empirical models of penetration from the upper respiratory tract (URT) can also be used to describe regional deposition fraction in the URT and could be extended to localized modeling. The approach includes model verification with experimental data obtained both in human and rat casts of the upper respiratory tract as well as in vivo studies of respiratory tract deposition.

URLs/Downloads:

Final Progress Report

2006 Progress Report

Record Details:

Record Type:PROJECT( ABSTRACT )

Start Date:11/15/2005

Completion Date:11/15/2007

Record ID: 143628

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Related Organizations:

Role :OWNER

Organization Name :THE HAMNER INSTITUTES

Mailing Address :6 Davis Drive
POB 12137

Citation :Research Triangle Park

State :NC

Zip Code :27709

Project Information:

Approach :

Manufactured nanoparticles and nanotubes will be obtained from manufacturers and generated in our laboratories. Deposition of nanomaterial will be measured in nasal casts of humans and rats. These data will allow calculation of the fraction of inhaled material that passes through the URT and enters the lower respiratory tract (LRT). Next, existing models of LRT deposition will be extended to include mechanisms for nanomaterial. For nanoparticles, existing models for fine and coarse particles will extended by accounting for the mechanisms of axial diffusion and mixing. This will address the previous inadequate treatment of dispersive effects in the existing models that has limited their applicability to nanosized particles. For nanotubes, deposition depends on nanotube orientation in the air. Net orientation of a cloud of nanotubes entering each airway will be found to calculate their deposition. A software package with a graphical-user interface will be developed to provide rapid computational capabilities to run simulations based on these models. A series of nose-only exposure events in Long-Evans rats will be conducted to measure regional and lobar deposition of nanoparticles in the respiratory tract. Deposition models will be verified in rats by comparing deposition predictions against measurements from nose-only exposures, and in humans by comparing the model predictions against available data in the literature.

Cost :$375,000.00

Research Component :Health Effects

Approach :

Manufactured nanoparticles and nanotubes will be obtained from manufacturers and generated in our laboratories. Deposition of nanomaterial will be measured in nasal casts of humans and rats. These data will allow calculation of the fraction of inhaled material that passes through the URT and enters the lower respiratory tract (LRT). Next, existing models of LRT deposition will be extended to include mechanisms for nanomaterial. For nanoparticles, existing models for fine and coarse particles will extended by accounting for the mechanisms of axial diffusion and mixing. This will address the previous inadequate treatment of dispersive effects in the existing models that has limited their applicability to nanosized particles. For nanotubes, deposition depends on nanotube orientation in the air. Net orientation of a cloud of nanotubes entering each airway will be found to calculate their deposition. A software package with a graphical-user interface will be developed to provide rapid computational capabilities to run simulations based on these models. A series of nose-only exposure events in Long-Evans rats will be conducted to measure regional and lobar deposition of nanoparticles in the respiratory tract. Deposition models will be verified in rats by comparing deposition predictions against measurements from nose-only exposures, and in humans by comparing the model predictions against available data in the literature.

Cost :$375,000.00

Research Component :Nanotechnology

Project IDs:

ID Code :R832531

Project type :EPA Grant