MANIFESTATIONS OF TOXICITY Organ Toxicity

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 generally be characterized as either an extension of the therapeutic effect, such as the fatal central nervous system (CNS) depression that may follow a barbiturate overdose, or as an effect that is unrelated to the therapeutic effect, such as the liver damage that may result from an acetaminophen overdose. This chapter focuses on the tissue response associated with the latter type of drug toxicity and on the toxicities associated with several important classes of nontherapeutic agents. 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 necessarily the tissue that has the highest concentration of the agent. For example, lead accumulates in bone but produces no toxicity there; certain chlorinated pesticides 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 relatively nontoxic chemical may be quite hazardous if exposure is large or the route of exposure is not physiological. MANIFESTATIONS OF TOXICITY