Principles of Toxicology
The discipline of toxicology
considers the adverse effects of chemicals, including drugs, and other agents,
such as biological toxins and radiation, on biological systems. Toxicity
associated with drug action can gener-ally be characterized as either an extension
of the ther-apeutic effect, such as the fatal central nervous system (CNS)
depression that may follow a barbiturate over-dose, or as an effect that is
unrelated to the therapeutic effect, such as the liver damage that may result
from an acetaminophen overdose.
The target organ for the
expression of xenobiotic toxicity is not necessarily the tissue or organ in
which the drug produces its therapeutic effect, nor is it neces-sarily the
tissue that has the highest concentration of the agent. For example, lead
accumulates in bone but produces no toxicity there; certain chlorinated
pesti-cides accumulate in adipose tissue but produce no local adverse effects.
Drugs such as acetaminophen cause necrosis in the centrilobular portion of the
liver at a site of the monooxygenase enzymes that bioactivate the analgesic.
It is necessary to
distinguish between the intrinsic toxicity of a chemical and the hazard it
poses. While a chemical may have high intrinsic toxicity, it may pose little or
no hazard if exposure is low. In contrast, a rela-tively nontoxic chemical may
be quite hazardous if ex-posure is large or the route of exposure is not