Biologically-based modeling insights in inhaled vapor absorption and dosimetry

The lung is a route of entry and also a target site for inhaled vapors, therefore, knowledge of the total absorbed dose and/or the dose absorbed in each airway during inhalation exposure is essential. Vapor absorption characteristics result primarily from the fact that vapors demonstrate equilibrium/saturation behavior in fluids. Thus, during inhalation exposures blood and airway tissue vapor concentrations increase to a steady state value and increase no further no matter how long the exposure. High tissue concentrations can be obtained with highly soluble vapors, thus solubility, as measured by blood:air partition coefficient, is a fundamentally important physical/chemical characteristic of vapors. While it is classically thought that vapor absorption occurs only in the alveoli it is now understood that this is not the case. Soluble vapors can be efficiently absorbed in the airways themselves and do not necessarily penetrate to the alveolar level. Such vapors are more likely to injure the proximal than distal airways because that is the site of the greatest delivered dose. There are substantial species differences in airway vapor absorption between laboratory animals and humans making interpretation of laboratory animal inhalation toxicity data difficult. Airway absorption is dependent on vapor solubility and is enhanced by local metabolism and/or direct reaction within airway tissues. Modern simulation models that incorporate terms for solubility, metabolism, and reaction rate accurately predict vapor absorption patterns in both animals and humans and have become essential tools for understanding the pharmacology and toxicology of airborne vapors.