Toxicology studies generally use multiple doses that span the expected range from where no effects would be observed to where clinical or histopathologic changes would be evident. The highest dose at which no overt toxicity occurs in a 90-day study (the maximum tolerated dose), is generally used to establish animal dosing levels for chronic assays that provide insight into potential latent effects, including cancer, reproductive or developmental toxicity, and immunotoxicity. These studies constitute the mainstays of toxicologic practice.³

In addition to animal studies, efforts to identify and understand the effects of environmental chemicals, drugs, and other agents on human populations have used epidemiologic studies to examine the relationship between a dose and the response to exposures. In contrast to animal studies, in which exposures are experimentally controlled, epidemiologic studies describe exposure with an estimate of error, and they assess the relationship between exposure and disease distribution in human populations. These studies operate under the assumption that many years of chemical exposures or simple passage of time may be required before disease expression can be detected.