Absorption And Routes Of Exposure

Absorption refers to uptake into the systemic circulation of an organism. Absorption occurs through three main routes of exposure:

• Ingestion: absorption through the lining of the gastrointestinal tract from food or other particles

• Inhalation: absorption through the lungs

• Dermal contact: absorption directly through the skin

Ingestion and inhalation are forms of intake. All three are mechanisms of uptake. The route of exposure determines how much of a toxin enters and how different organs are exposed. The toxicity of a substance depends on the route of exposure. For example, arsenic is more carcinogenic by inhalation than by ingestion, whereas vinyl chloride is the reverse. Asbestos danger from inhalation is well documented, but little evidence exists yet for its toxicity by ingestion.

Uptake by ingestion occurs via absorption through cell membranes lining the gastrointestinal tract. Most of the surface area of the gastrointestinal (GI) tract is associated with the villi of the small intestines. Thus, most neutral molecules will be absorbed there. Organic acids and bases, on the other hand, depend on pH relationships for their absorption. The pH of the stomach ranges from 1 to 3, and the intestines from 5 to 8. Thus, weak acids will be undissociated in the stomach and tend to be absorbed there. Conversely, weak bases will be ionized in the stomach and therefore unable to pass membrane barriers by passive transport. However, they can be absorbed in the intestines at the higher pH.

The pH relationships in the GI tract form a special mechanism for facilitating absorption of acids and bases. Because blood plasma has a pH close to neutral, weak acids will be mostly dissociated in it, and only a small fraction will be in the undissociated form. However, in the low pH environment of the stomach, weak acids will be mostly undis-sociated. The undissociated form, being uncharged, can pass through the membranes of the cells lining the stomach. After it crosses, it enters the bloodstream, where it become ionized due to the high pH. This keeps the concentration gradient high, maximizing the passive diffusion flux.

Figure 18.2 illustrates what is occurring in the case of benzoic acid. The concentration gradient of non-ionized acid is 100 — 1 = 99. If the driving force were based on the total concentration instead of the non-ionized concentration, the gradient would change sign (101 — 2513 = —2412). Benzoic acid would move from the blood into the stomach instead of the reverse. A similar situation occurs in the intestines, except in that case the pH of the lumen is higher than that of the blood. This facilitates absorption of weak bases by a similar mechanism.

Ingestion does not only involve food. Risk assessment for contaminated land sometimes must take into account the ingestion of soil or other solids by children. A typical assumption is that children eat 200 mg of soil per day.

The respiratory tract is the site of absorption by inhalation for gases, such as carbon monoxide, vapors of mercury, and high-vapor pressure liquids such as benzene

Stomach pH 2

Membrane

COO" COOH

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