Safety factors and establishment of acceptable daily intakes.

The acceptable daily intake (ADI) of food additives and other foreign compounds is derived usually by the application of a 100-fold safety factor to the 'no observable adverse effect' level in animal experiments. This safety factor is recognized as comprising two 10-fold factors to allow for possible differences between animals and humans, and for possible differences between individual humans. This paper reviews the adequacy of these safety factors in relation to published data on inter-species and inter-individual differences in both the kinetics and dynamics of foreign compounds. Although the 100-fold factor is reasonable, situations can be envisaged where the scientific data base indicates that considerably higher or lower factors would be more appropriate. A scheme is proposed that would allow structured flexibility to be available in the choice of safety factor to be used in the regulation of foreign compounds.