Safety assessments of chemicals with thresholded effects.

Toxicological evaluation of chemicals with thresholded effects involves the estimation of their acceptable daily intakes (ADI). The following steps are involved in the evaluation: judging the completeness of the available chemical and biological data, determination of the no-effect level (NEL), selection of an appropriate safety factor, and extrapolation of the NEL to the ADI using the selected safety factor. The relative insignificance of the sample size on the NEL, the advantages of body weight (compared to the body surface) as a basis for interspecies extrapolation, the size of the safety factor as a function of the nature of the toxic effects, and the multiplicity of the toxicological investigations, in addition to the conventional short-term and long-term toxicity studies, are described. In addition, the possible inadvisability of overemphasizing the importance of dose-response relationship at the expense of in-depth, relevant studies is discussed.