Toxicity due to excess and deficiency.

Customary approaches to setting safe upper levels for the intake of nutrients use, as critical events, adverse health that which, when adjusted using uncertainty factors (UF), produce values that, when they are applied to population risk analysis, along with dietary reference values that have been independently derived using a different approach by nutritionists, may provide narrow and unrealistic safe ranges of dietary intake. This study describes the evolving concept of the risk assessment of nutrients in which the critical events are based on homeostatic health effects that occur at the upper extreme of the physiological range of intakes. These events can be envisaged as markers of failing adaptation to high exposures and as heralds of potential later adverse events. Such markers may be associated with smaller and more easily characterized uncertainties than those applied to the more gross toxicological architectural, functional, or reproductive health effects used in standard toxicological risk assessment. The study also outlines the potential extension of this homeostatic model to the determination of safe lower limits of intake for essential nutrients and the identification, when homeostasis fails, of thresholds for inadequate intakes that can be adjusted by using uncertainty factors (UF) to derive adequate reference intakes.