. "3 A Model for the Development of Tolerable Upper Intake Levels." Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: The National Academies Press, 1997.
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DRI DIETARY REFERENCE INTAKES FOR Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride
that account for interspecies and intraspecies differences in response to the hazardous effects of substances and to account for other uncertainties (WHO, 1987). These factors are used to make inferences about the threshold dose of substances for members of a large and diverse human population from data on adverse effects obtained in epidemiological or experimental studies. These factors are applied consistently when data of specific types and quality are available. They are typically used to derive acceptable daily intakes for food additives and other substances for which data on adverse effects are considered sufficient to meet minimum standards of quality and completeness (FAO/WHO, 1982). These adopted or recognized factors have sometimes been coupled with other factors to compensate for deficiencies in the available data and other uncertainties regarding data.
The UL is generally based on a no-observed-adverse-effect level (NOAEL) that is identified for a specific circumstance in the hazard identification and dose-response assessment steps of the risk assessment. The NOAEL is the highest intake (or experimental dose) of a nutrient at which no adverse effects have been observed in the individuals studied. If there are no adequate data demonstrating a NOAEL, then a lowest-observed-adverse-effect level (LOAEL) may be used. A LOAEL is the lowest intake (or experimental dose) at which an adverse effect has been identified. The derivation of a UL from a NOAEL (or LOAEL) involves a series of choices about what factors should be used to deal with uncertainties. Uncertainty factors (UFs) are attempts both to deal with gaps in data (for example, lack of data on humans or lack of adequate data demonstrating a NOAEL) and with incomplete knowledge regarding the inferences required (for example, the expected variability in response within the human population). The problems of both data and inference uncertainties arise in all steps of the risk assessment. A discussion of options available for dealing with these uncertainties is presented below and in greater detail in Appendix C.
A UL is not, in itself, a description of human risk. It is derived by application of the hazard identification and dose-response evaluation steps (Steps 1 and 2) of the risk assessment model. To determine whether exposed populations are at risk requires an exposure assessment (Step 3, evaluation of their intakes of the nutrient) and a determination of the fractions of those populations, if any, whose intakes exceed the UL (for example, those whose intakes exceed the estimated threshold for toxicity). In the exposure assessment and risk characterization steps (Steps 3 and 4; described in the respective chapters for each nutrient), the ninety-fifth percentile in-