Handbook of Solvents - George Wypych - ChemTech - Ventech!

15.2.1 Use of breath monitoring 1083
mixed venous blood. These are the prevailing conditions when breath monitoring takes
place after the end of the exposure 17 and therefore, samples of alveolar air after exposure
should reflect concentrations in mixed venous blood. During exposure, however, alveolar
air should reflect concentrations in arterial blood. Solvent concentrations in arterial and venous
blood diverge even more with physical exertion.
To summarize, the uptake of solvent vapors through inhalation will depend on the following
factors: 3
1. Pulmonary ventilation, i.e., the rate at which fresh air (and solvent vapor) enters the
lungs. This is determined by the metabolic rate and therefore depends on physical exertion.
The concentration in alveolar air approaches that in inhaled air when the physical exertion is
great. When exertion is low, the alveolar air concentration approaches the concentration in
mixed venous blood.
2. Diffusion of the solvent vapor through the gas-blood interface. According to Fick’s
2nd law, the rate of diffusion through the interface depends on the concentration gradient
across the tissue membrane. Therefore, the concentration of the vapor leaving the lungs depends
on the amount of vapor entering the alveoli, on the solubility in blood (blood/gas partition
coefficient) and on the flow rate of the blood through the lungs. For lipophilic
chemicals, such as organic solvents that readily cross cellular membranes, diffusion is not
the rate-limiting factor. 18
3. The solubility of the vapor in the blood. The higher the blood/gas partition coefficient,
the more rapidly the vapor will diffuse into the blood, until equilibrium is achieved.
At equilibrium the net diffusion between blood and air ceases, but the concentrations in air
and blood may still be different. A highly soluble vapor will therefore demonstrate a lower
alveolar air concentration relative to the inhaled air concentration during exposure, and a
higher alveolar concentration relative to the inhaled air concentration after exposure.
4. The circulation of the blood through the lungs and tissues. This depends on the cardiac
output and therefore, on physical exertion. For a soluble vapor, high exertion moves
blood faster, increasing uptake.
5. The diffusion of the vapor through the tissue membranes, which depends on membrane
permeability and is governed by Fick’s law, as discussed in #2 above.
6. The solubility of the solvent vapor in the tissue. This reflects the tissue/blood partition
coefficient of the solvent vapor and depends largely on the lipid composition of the particular
tissue. Lipophilic vapors will exhibit high solubility in tissues with high fat content,
freeing blood of vapors and increasing uptake.
Substances that are not well metabolized are eliminated primarily through the lungs 3
and to a lesser extent through the kidneys. During elimination through the lungs the same
physiological principles apply in a reverse sequence.
15.2.1.4 Types of exhaled air samples
Samples obtained from even a single breath may contain different concentrations of the solvent
vapor of interest depending on the way the sample was collected. This is a result of the
non-homogeneity of the exhaled air discussed previously. Figure 15.2.1.2 depicts a concentration
curve of a solvent in exhaled air. When measurement takes place in an environment
free of that solvent, the first part of the exhalation, corresponding to air in the anatomical
dead space, will be solvent-free (Phase 1). Then the solvent concentration curve rises
sharply reflecting exhalation of air from the respiratory zone of the lungs (Phase 2). This
phase is followed by a slowly increasing plateau, indicating an alveolar steady state (Phase
3). The level of this plateau depends on the preceding ventilatory state of the subject, being
higher for a hypoventilating subject and lower for a hyperventilating subject. 6 Sample col-