Overview of upper respiratory tract vapor uptake studies.

This review is aimed at highlighting toxicologically relevant physiological and biochemical factors that influence the delivery of inhaled vapors to nasal tissues. Numerous experiments in rodents have shown that vapor uptake efficiencies are dependent on vapor solubility (as measured by blood:air partition coefficient) and inspiratory flow rate. Nasal tissues are rich in xenobiotic metabolizing enzymes, and it has been shown experimentally through the use of metabolic inhibitors that inspired vapors are metabolized in nasal tissue and that this process serves to enhance inspired vapor uptake efficiency in that site. Metabolism-based species differences in vapor uptake have been observed among rodent species. Concentration-dependent changes in vapor uptake have also been observed and related to saturation of local metabolic pathways at high exposure concentrations. Therefore, appropriate consideration of local metabolism is necessary for comprehensive high- to low-dose or species extrapolations of nasal toxicity data. Recent studies have provided evidence of sensory nerve-mediated reflex responses that alter nasal vascular function and may alter nasal inspired vapor dosimetric relationships. In toto, these studies also indicate the need to define uptake behavior for a vapor of interest over a wide range of exposure concentrations due to the possibility of nonlinear metabolism kinetics or the induction of nasal reflex and/or toxic responses. Such data are required for the formulation of a robust nasal dosimetry model.