ABSTRACT
The ability to detect manifestations of toxicity has evolved considerably in recent years. Traditional approaches evaluated toxicants associated with acute or chronic high-level exposure. Endpoints reflecting toxic damage focused on organ damage, cell death, and gross anatomical or histopathological changes. Functional endpoints such as behavior or immunocompetence were rarely evaluated. However, in many instances, these functional endpoints have proven to be more sensitive indicators of exposure or toxicity. This may be particularly relevant in situations where the manifestations of toxicity remain subclinical for extended periods of time. Noteworthy examples may include carcinogenesis or teratogenesis where the clinical syndromes may not be observed for months or years. Autoimmunity, hypersensitivity, and allergy are examples of immune dysfunction that may be triggered by immunotoxicants. Subtle functional alterations of the immune system may be useful to identify chemical exposure prior to gross anatomical or biochemical change. If functional disturbances are present without evidence of toxicity as identified by more classical testing, the existing threshold limit values or no effect levels for many xenobiotics may require reevaluation.
