. "Steps in the Development of the Tolerable Upper Intake Level." Dietary Reference Intakes: A Risk Assessment Model for Establishing Upper Intake Levels for Nutrients. Washington, DC: The National Academies Press, 1998.
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Theoretical description of health effects of a nutrient as a function of level of intake. The Tolerable Upper Intake Level (UL) at point A is the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population. At intakes above the UL, the risk of adverse effects increases.
the general population (see Appendix B). Applying a UF to a NOAEL (or LOAEL) results in a value for the derived UL that is less than the experimentally derived NOAEL, unless the UF is 1.0. The larger the uncertainty, the larger the UF and the smaller the UL. This is consistent with the ultimate goal of the risk assessment: to provide an estimate of a level of intake that will protect the health of the healthy population (Mertz et al., 1994).
Although several reports describe the underlying basis for UFs (Dourson and Stara, 1983; Zielhuis and van der Kreek, 1979), the strength of the evidence supporting the use of a specific UF will vary. Because the imprecision of the UFs is a major limitation of risk assessment approaches, considerable leeway must be allowed for the application of scientific judgment in making the final determination. Since data are generally available regarding intakes of nutrients and food components in human populations, the data on nutrient toxicity may not be subject to the same uncertainties as with nonessential chemical agents, resulting in UFs for nutrients and food components typically less than 10. They are lower with higher quality data and when the adverse effects are extremely mild and reversible.
In general, when determining a UF, the following potential sources of uncertainty are considered and combined into the final UF:
Interindividual variation in sensitivity. Small UFs (close to 1) are used to represent this source of uncertainty if it is judged that little population variability is expected for the adverse effect, and larger factors (close to 10) are used if variability is expected to be great (NRC, 1994).