Toxicology

Principles of Toxicology

The basic principle of toxicology is that the dose determines the poison. This principle was first set forth by the sixteenth-century Swiss physician Paracelsus (1493–1541), who pointed out, “What is there that is not a poison? All things are poison and nothing [is] without poison. Solely the dose determines that a thing is not a poison” (Klassen 1996, title page). Many substances that are essential for life will poison the body if taken in too large a dose. For [Page 1629]example, iron is an essential nutrient, but ingesting too much iron causes iron poisoning. Similarly, taking the recommended dosage of the pain killer acetaminophen usually relieves pain with no adverse affects. Acetaminophen is broken down in the liver into a number of metabolites, including one that is poisonous. This toxic metabolite is rapidly detoxified by being conjugated with glutathione, a chemical found within the liver cells. If more toxic metabolites are formed than there is glutathione available to detoxify it, the levels of toxic agent accumulates, damaging the liver cells. Exceeding the recommended dosage can cause liver damage.

Dosage is expressed as amount in milligrams of the substance per kilogram of body weight. If the same quantity of a substance is ingested by a child and by an adult, the child receives a much larger dose.

Dose-Response Curves

Dose-response curves graph the relationship between the dose administered and an observed adverse effect. In using dose-response curves, three assumptions are made: The observed response is assumed to be caused by the chemical administered, the response magnitude is related to the dose, and the toxic effect is expressed precisely and can be measured quantitatively.

The threshold dose is the minimum dose that causes an all-or-nothing response. A threshold is assumed to exist for all chemicals except carcinogens. The threshold concept allows toxicologists to set safe exposure limits. It is assumed that there is no safe level of exposure to a carcinogen. This no-threshold concept is subject to vigorous debate because of its implications for public policy.

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