Dosimetry implications of upper tracheobronchial airway anatomy in two mouse varieties

Strain- and variety-related differences in responses of mice have been reported for a variety of inhaled particulate and gaseous materials. It is important to understand the potential contributions to such responses of differences in delivered doses to the respiratory tract as well as differences in biochemical processes. Deposition doses of inhaled particles are influenced by several factors, including airway anatomy, ventilation, and particle characteristics. Tracheobronchial airway morphometry for airway generations 1-6 of the BALB/c mouse was generated using replica lung casts prepared in situ. Measurements were performed on two groups: control and ovalbumin-sensitized male BALB/c mice. These measurements were compared with previously published airway morphometry of male B6C3F(1) mice. Sensitization did not significantly change measured airway dimensions in the BALB/c mouse. However, the two mouse varieties had significant differences in airway anatomy. The differences found in airway anatomy between mouse varieties correlated with differences in body length and chest circumference. Particle deposition predictions for both varieties of mice were performed for unit density spherical particles from 0.1 to 10 microm in diameter at two ventilation rates using a published aerosol dosimetry computer code. Particle deposition in the proximal tracheobronchial tree ranged up to 3 times greater for the BALB/c mouse for a 2 microm particle diameter and high ventilation rate. These differences in predicted particle deposition suggest that observed strain and variety differences in response to inhaled particulate matter may be in part due to differences in delivered doses to the respiratory tract.