U.S. EPA uses the term reference dose (RfD) for safe human dose (SHD), which is defined as the no observed adverse effect level (NOAEL) divided by a set of uncertainty factors (UF) and safety factors (SF). U.S. FDA on the other hand uses the term acceptable daily intake (ADI) for this RfD or SHD. ADI values are also used by the World Health Organization (1962) to define the lifetime allowable daily intake of pesticide and food additive residues. The main differences between the two approaches are the ways in which the NOAEL, the UF, and the SF are determined and used. The UF and SF, that together typically amounting to 100- to 1,000-fold, are used to account for interspecies difference, intraspecies sensitivity, and data quality.

The concerns with adverse health effects also vary greatly among health statutes and hence among regulatory agencies. In the United States, for example, health statutes similar to the Clean Air Act require risk-based standards to protect human health by providing an ample margin of safety. Yet other health statutes like the Clean Water Act impose regulations that are based on the best available technology.

It is important to note that in reference to the chart provided in Slide 6, certain toxic agents like pesticides, asbestos, nuclear power are listed under the uncontrollable and not observable group. This group typically receives higher or highest priority in regulatory risk assessment, whereas smoking, handguns and other societal problems have lower priorities as they are put under the controllable and observable category.