The question of whether temporal equivalence can be established between test species and humans and be useful in the safety assessment of food additives has puzzled risk assessors throughout decades. The basic biological elements in any mammalian species, including humans, such as homeostasis, basal metabolism and body size/surface area, reproduction features, the timing of cellular proliferation, and aging and health as well as the relation between aging and the diet are essential in this discussion. It is concluded that exposure studies covering selected segments of the total lifetime of any animal species cannot replace lifetime studies in the same animal species in the routine safety testing of food additives, but they may in many cases turn out to become the pivotal study for the entire safety assessment.