Nasal Dosimetry of Inhaled Gases and Particles: Where Do Inhaled Agents Go in the Nose?

Abstract

The anatomical structure of the nasal passages differs significantly among species, affecting airflow and the transport of inhaled gases and particles throughout the respiratory tract. Since direct measurement of local nasal dose is often difficult, 3-dimensional, anatomically accurate, computational models of the rat, monkey, and human nasal passages were developed to estimate regional transport and dosimetry of inhaled material. The computational models predicted that during resting breathing, a larger portion of inspired air passed through olfactory-lined regions in the rat than in the monkey or human. The models also predicted that maximum wall mass flux (mass per surface area per time) of inhaled formaldehyde in the nonsquamous epithelium was highest in monkeys (anterior middle turbinate) and similar in rats and humans (dorsal medial meatus in the rat and mid-septum in the human, near the squamous/nonsquamous epithelial boundary in both species). For particles that are 5 μm in aerodynamic diameter, preliminary simulations at minute volume flow rates predicted nasal deposition efficiencies of 92%, 11% and 25% in the rat, monkey, and human, respectively, with more vestibular deposition in the rat than in the monkey or human. Estimates such as these can be used to test hypotheses about mechanisms of toxicity and supply species-specific information for risk assessment, thus reducing uncertainty in extrapolating animal data to humans.