Mechanistic Dosimetry Models of Nanomaterial Deposition in the Respiratory TractEPA Grant Number: R832531
Title: Mechanistic Dosimetry Models of Nanomaterial Deposition in the Respiratory Tract
Investigators: Asgharian, Bahman , Wong, Brian A.
Institution: The Hamner Institutes
EPA Project Officer: Carleton, James N
Project Period: November 15, 2005 through November 15, 2007
Project Amount: $375,000
RFA: Exploratory Research: Nanotechnology Research Grants Investigating Environmental and Human Health Effects of Manufactured Nanomaterials: A Joint Research Solicitation - EPA, NSF, NIOSH (2005) RFA Text | Recipients Lists
Research Category: Health , Safer Chemicals , Health Effects , Nanotechnology
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.
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.
This effort will result in mechanistic dosimetry models to predict the localized deposition of inhaled nanomaterial in the respiratory tract of rats and humans. Specific products include:
- Deposition measurements of nanosized particle in casts of human and rat nasal URT airways
- Semi-empirical relationships to predict nanomaterial deposition in the URT airways
- Respiratory tract deposition models of nanoparticles and nanotubes in humans and rats
- Measurements of regional and lobar deposition of nanomaterial in the heads and lungs of rats
- A user-friendly software package to implement models and provide rapid simulation capability