of sensitivities to toxic effects. The model described below accounts for the normal expected variability in sensitivity, but it excludes subpopulations with extreme and distinct vulnerabilities. Such subpopulations consist of individuals needing medical supervision; they are better served through the use of public health screening, product labeling, or other individualized health care strategies. Such populations may not be at negligible risk when their intakes reach the UL developed for the healthy population. The decision to treat identifiable vulnerable subgroups as distinct (not protected by the UL) is a matter of judgment and is discussed in the individual nutrient chapters, as applicable.

In the context of toxicity, the bioavailability of an ingested nutrient can be defined as its accessibility to normal metabolic and physiological processes. Bioavailability influences a nutrient’s beneficial effects at physiological levels of intake and also may affect the nature and severity of toxicity due to excessive intakes. The concentration and chemical form of the nutrient, the nutrition and health of the individual, and excretory losses all affect bioavailability. Bioavailability data for specific nutrients must be considered and incorporated into the risk assessment process.

Some nutrients may be less readily absorbed when part of a meal than when consumed separately. Supplemental forms of some nutrients may require special consideration if they have higher bioavailability since they may present a greater risk of producing adverse effects than equivalent amounts from the natural form found in food.

A diverse array of adverse health effects can occur as a result of the interaction of nutrients. The potential risks of adverse nutrient–nutrient interactions increase when there is an imbalance in the intake of two or more nutrients. Excessive intake of one nutrient may interfere with absorption, excretion, transport, storage, function, or metabolism of a second nutrient. Possible adverse nutrient–nutrient interactions are considered as a part of setting a UL. Nutrient–nutrient interactions may be considered either as a critical endpoint on which to base a UL, or as supportive evidence for a UL based on another endpoint.

In addition to nutrient interactions, other considerations have the potential to influence nutrient bioavailability, such as the nutritional status