PNNL

Abstract

Abstract Context: Computational fluid dynamics (CFD) simulations of airflows coupled with physiologically based pharmacokinetic (PBPK) modeling of respiratory tissue doses of airborne materials have traditionally used either steady-state inhalation or a sinusoidal approximation of the breathing cycle for airflow simulations despite their differences from normal breathing patterns. Objective: Evaluate the impact of realistic breathing patterns, including sniffing, on predicted nasal tissue concentrations of a reactive vapor that targets the nose in rats as a case study. Materials and methods: Whole-body plethysmography measurements from a free-breathing rat were used to produce profiles of normal breathing, sniffing and combinations of both as flow inputs to CFD/PBPK simulations of acetaldehyde exposure. Results: For the normal measured ventilation profile, modest reductions in time- and tissue depth-dependent areas under the curve (AUC) acetaldehyde concentrations were predicted in the wet squamous, respiratory and transitional epithelium along the main airflow path, while corresponding increases were predicted in the olfactory epithelium, especially the most distal regions of the ethmoid turbinates, versus the idealized profile. The higher amplitude/frequency sniffing profile produced greater AUC increases over the idealized profile in the olfactory epithelium, especially in the posterior region. Conclusions: The differences in tissue AUCs at known lesion-forming regions for acetaldehyde between normal and idealized profiles were minimal, suggesting that sinusoidal profiles may be used for this chemical and exposure concentration. However, depending upon the chemical, exposure system and concentration and the time spent sniffing, the use of realistic breathing profiles, including sniffing, could become an important modulator for local tissue dose predictions.