Derivation of mass transfer coefficients for transient uptake and tissue disposition of soluble and reactive vapors in lung airways.

Evaluation of vapor uptake by lung airways and subsequent dose to lung tissues provides the bridge connecting exposure episode to biological response. Respiratory vapor absorption depends on chemical properties of the inhaled material, including solubility, diffusivity, and metabolism/reactivity in lung tissues. Inter-dependent losses in the air and tissue phases require simultaneous calculation of vapor concentration in both phases. Previous models of lung vapor uptake assumed steady state, one-way transport into tissues with first-order clearance. A new approach to calculating lung dosimetry is proposed in which an overall mass transfer coefficient for vapor transport across the air-tissue interface is derived using air-phase mass transfer coefficients and analytical expressions for tissue-phase mass transfer coefficients describing unsteady transport by diffusion, first-order, and saturable pathways. Feasibility of the use of mass transfer coefficients was shown by calculating transient concentration levels of inhaled formaldehyde in the human tracheal airway and surrounding tissue. Formaldehyde tracheal air concentration and wall-flux declined throughout the breathing cycle. After the inhalation period, peak tissue concentration moved from the air-tissue interface into the tissue due to desorption into the air and continued diffusional transport across the tissue layer. While model predictions were performed for formaldehyde, which serves as a model of physiologically relevant, highly reactive vapors, the model is equally applicable to other soluble and reactive compounds.