TABLE 4.
Physiological and Biochemical Parameters Used in the Rat, Monkey, and Human CFD/PBPK Models
| Parameter | Rat | Monkey | Human | Source |
| Body weight (kg) | 0.315 | 1.3 | 72.0 | Rat and human from Schroeter et al. (2008); monkey from this study |
| Total ventilation (ml/min) | 434 | 907 | 13,800 | Twice the minute volume according to Schroeter et al. (2008) |
| Cardiac output (CO; ml/min) | 106 | 303 | 5921 | Brown et al. (1997) |
| Blood flow to nasal subepitheliuma | ||||
| %CO | 1 | 1 | 1 | Schroeter et al. (2008) |
| ml/cm3/s | 0.445 | 1.225 | 2.542 | |
| Blood flow to pharynx, larynx, trachea, bronchi, and bronchiole subepithelium | ||||
| %CO | 3.8 | 3.8 | 3.8 | Timchalk et al. (2001a); Brown et al. (1997) |
| ml/cm3/sec | 1.903 | 1.038 | 7.921 | |
| Acrolein-specific parameters | ||||
| Air diffusivity (cm2/s) | 0.105 | 0.105 | 0.105 | Schroeter et al. (2008) |
| Water diffusivity (cm2/s) | 1.22 × 10−5 | 1.22 × 10−5 | 1.22 × 10−5 | Schroeter et al. (2008) |
| Water:air partition coefficient | 88 | 88 | 88 | Schroeter et al. (2008) |
| K f (sec−1) | 0.05 | 0.02b | 0.02 | Schroeter et al. (2008) |
| K m (µg/l) | 0.5 | 0.5 | 0.5 | Schroeter et al. (2008) |
| VmaxC (µg/l/s)c | 573 | 375 | 112 | Recalculated in this study |
a Normalized blood flows used by Schroeter et al. (2008) to the volume of each regional subepithelial compartment (calculated from Tables 1–3) to account for different thickness along the airways beyond the nose.
b First-order metabolism in the monkey assumed to be equal to human.
c Normalized the saturable metabolism pathway Vmax from Schroeter et al. (2008) to the volume of each regional mucus+epithelium tissue compartment (calculated from Tables 1–3) to account for different thicknesses along the airways beyond the nose and re-scaled from the rat according to body weight and relative tissue volumes (see text). The resulting VmaxC, which is a tissue volume scalable Vmax, was recalibrated against the nasal extraction data of Morris (1996) and Struve et al. (2008) and was adjusted by a factor of 0.25 or 0.5 for airways beyond the nose (or mouth) corresponding to observations summarized by Franks (2005) of weak (pharynx, larynx, trachea, and main bronchi) or moderate (bronchioles) aldehyde dehydrogenase activities, respectively (see text).