Toxicological evaluations of carcinogens and noncarcinogens: pros and cons of different approaches

Toxicological evaluations are performed to provide estimates of the safety/risk entailed in specified exposures to chemicals. This paper presents the two common approaches to toxicological evaluations. One of these assumes the presence of threshold doses. It involves determination of no-effect levels and extrapolation to acceptable daily intakes in man. This procedure has been widely and successfully used for noncarcinogens. For carcinogens, a number of mathematical models have been proposed for estimating the level of risk associated with a specified exposure level or the dose that is considered virtually safe, e.g., with a risk level of 10(-6). Variations of these major approaches are also outlined. Examples are included to indicate that a deficiency of significant biological data, such as an unexpected toxic effect and the marked influence of modifying factors, can invalidate a toxicological evaluation. It is also pointed out that such deficiencies cannot be overcome by any mathematical manipulation of the available dose-response data.