ABSTRACT
Traditional toxicological testing of additives in food has relied on dose exaggeration (relative to anticipated human exposure) via relevant routes of exposure to provide a qualitative characterization of the nature of adverse events that could arise as the result of exposure to chemical substances. This was often followed by a steppeddown, but still exaggerated multiple dose regimen suitable to the nature of the study (e.g., subacute through chronic oral testing, reproductive toxicity, developmental toxicity, and neurotoxicity) to attempt to characterize relationship between dose and toxicity, and identify exposures that do or do not cause adverse outcomes within the limits of detection of the assay (1-4). Dose-exaggeration studies provide an opportunity to evaluate the dose-response relationship, making it possible to estimate impacts outside the observable range of responses. In addition, the exaggerated dose can increase the frequency of observed toxicological effects and increase the likelihood of observing a rare event. The results of well-designed exaggerated dose studies on relatively few animals make it possible to predict potential toxicological effects in the general population. Over time, these studies have proven their utility for both qualitative and quantitative characterizations of toxicity and the estimate of risk to humans or other animals (5). The studies form the basis of the approach used by toxicologists and regulators in assessing the risk to humans (or other animal species) from unintended exposures, or for estimating safe exposure levels for intended or unavoidable exposures.
