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including sensitive individuals—when the nutrient is consumed over long periods of time. In other words, the UL is the highest usual intake level of a nutrient that poses no risk of adverse effects. In some cases subpopulations with extreme and distinct vulnerabilities may be at risk with intakes at or even below the UL.1 The process used to set the UL considers the intakes from all sources: food, water, nutrient supplements, and pharmacological agents, although in some cases the UL may apply only to specific sources.

The dose-response assessment, which concludes with an estimate of the UL, is built upon three toxicological concepts commonly used in assessing the risk of exposures to chemical substances: no-observed-adverse-effect level (NOAEL), lowest-observed-adverse-effect level (LOAEL), and uncertainty factor (UF). These are defined as:

  • NOAEL is the highest continuing intake of a nutrient at which no adverse effects have been observed in the individuals or groups studied. In some cases it may be derived from experimental studies in animals. When the available data are not sufficient to reveal the NOAEL, it is necessary to rely on a LOAEL.

  • LOAEL is the lowest continuing intake at which an adverse effect has been identified. For some nutrients, it may be derived from experimental studies in animals.

  • UFs are applied to the NOAEL, and if necessary to the LOAEL, in an attempt to address both gaps in data and incomplete knowledge regarding the inferences required (e.g., the expected variability in response within the population, or extrapolation from experimental animal to human data).

Scientific judgments are used to assign UFs for each of the specific sources of uncertainty associated with the data available for a nutrient. A composite UF for that nutrient is derived by multiplying the assigned UFs. Larger UFs are applied when animal data are used rather than human data, and in instances where the consequence of overconsumption is serious disease. A UF used to estimate a UL from a LOAEL will be larger than one used if a NOAEL is available. UFs established when this document was written are presented in Table 6-1; they range from 1 (expressing great confidence in the NOAEL) to 36 (reflecting extrapolation from experimental animal to human data and from a LOAEL to a NOAEL and other limitations in the data).


In this case, the subpopulations are identified and discussed in the individual chapters of the DRI nutrient reports (IOM, 1997, 1998b, 2000).

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