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Influence of Route of Exposure

The route of exposure is an important factor that can affect the concentration of the toxicant (or its' metabolites) at any specific location within the blood or lymph.  This can be important since the degree of biotransformation, storage, and elimination (and thus toxicity) can be influenced by the time course and path taken by the chemical as it moves through the body.  For example, if a chemical goes to the liver before going to other parts of the body, much of it may be biotransformed quickly.  In this case, the blood levels of the toxicant "downstream" may be diminished or eliminated.  This can dramatically affect its potential toxicity.

This is exactly what often happens with toxicants that are absorbed through the gastrointestinal tract. The absorbed toxicants that enter the vascular system of the gastrointestinal tract are carried by the blood directly to the liver by the portal system. This is also true for those rare drugs that are administered by intraperitoneal injection.  Blood from most of the peritoneum also enters the portal system and goes immediately to the liver.  Blood from the liver then flows to the heart and then on to the lung, before going to other organs.  Thus, toxicants entering from the GI tract or peritoneum are immediately subject to biotransformation or excretion by the liver and elimination by the lung.  This is often referred to as the "first pass effect."  For example, first-pass biotransformation of the drug propranolol (cardiac depressant) is about 70% when given orally.  Thus, the blood level is only about 30% of that of a comparable dose administered intravenously.

Toxicants that are absorbed through the lung or skin enter the blood and go directly to the heart and systemic circulation.  The toxicant is thus distributed to various organs of the body before it goes to the liver, and not subject to this first-pass effect.  The same is true for intravenously or intramuscularly injected drugs.

A toxicant that enters the lymph of the intestinal tract will not go to the liver first but will slowly enter the systemic circulation.  The proportion of a toxicant moving by lymph is much smaller than that transported by the blood.

The blood level of a toxicant not only depends on the site of absorption but also the rate of biotransformation and excretion.  Some chemicals are rapidly biotransformed and excreted whereas others are slowly biotransformed and excreted.

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