title: Clearance concepts applied to the metabolism of inhaled vapors in tissues lining the nasal cavity.
abstract: Some inhaled vapors are metabolized by tissues in the nasal cavity or carried away in nasal venous blood after diffusing from the lumen through the nasal epithelial tissues. These processes remove chemical from the airstream. Clearance (volume/time) is the volumetric airflow from which chemical would have to be completely removed to account for the net loss. We present here a steady-state analysis of a series of physiologically based clearance-extraction (PBCE) models for nasal clearance of inhaled vapors, consisting of one, two, three, or four subcompartments. A two-compartment model is the simplest representation of tissues in the nasal cavity, with an air and a tissue compartment. The three-compartment model had air, mucus, and tissue phases. The four-compartment model included both epithelial and submucosal tissues in addition to the air and mucus compartments. For the two-, three-, and four-compartment models, the airstream clearance (Cl(sys)) equation has a common form. Cl(sys) = Cl(tot)H(m:a)PA(gas)Q divided by Cl(tot)H(m:a)(Q + PA(gas)) + PA(gas)Q. In this equation, Cl(tot) is the total tissue clearance, PA(gas) is the gas-phase diffusional clearance, Q is the airflow, and H(muc:a) is the mucus air partition coefficient. Cl(tot) varies in complexity for the different models since it encompasses tissue diffusion, tissue clearance due to metabolism, and blood flow. A physiologically based clearance-extraction (PBCE) model for the whole nose with three nasal tissue regions, each containing a four-compartment tissue stack, was used to simulate nasal uptake of three vapors-acetone, methyl methacrylate (MMA), and vinyl acetate (VA)-to show the dependence of clearance on different parameters for specific compounds. Acetone is not metabolized in the nose, MMA is metabolized at a moderate rate by nasal tissues, and VA is metabolized at a high rate in mucus and tissues. Equations derived from steady-state analyses show the importance of the specific biochemical and physiological parameters for clearance of each of these chemicals and permit calculation of airstream clearance from simple algebraic relationships.
authors.affiliation: K. S. Crump Group, Inc., ICF Consulting, Inc., Research Triangle Park, North Carolina 27709, USA. manders@cvmbs.colostate.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Andersen
authors.forename: R
authors.initials: R
authors.lastname: Sarangapani
mesh_terms: D000096:Acetone / Q000493:pharmacokinetics; D000465:Algorithms; D019570:Inhalation Exposure; D020366:Methylmethacrylate / Q000493:pharmacokinetics; D008954:Models, Biological; D009079:Mucociliary Clearance / Q000502:physiology*; D009093:Mucus / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism*; D012997:Solvents / Q000493:pharmacokinetics; D014753:Vinyl Compounds / Q000493:pharmacokinetics
chemical_list: D012997:Solvents; D014753:Vinyl Compounds; D000096:Acetone; D020366:Methylmethacrylate; C011566:vinyl acetate