health effect. When evidence for such adverse interactions is available, it is considered in establishing a nutrient's UL.
Concept
Like all chemical agents, nutrients can produce adverse health effects if intakes from any combination of food, water, nutrient supplements, and pharmacologic agents are excessive. Some lower level of nutrient intake will ordinarily pose no likelihood (or risk) of adverse health effects in normal individuals even if the level is above that associated with any benefit. It is not possible to identify a single "risk-free" intake level for a nutrient that can be applied with certainty to all members of a population. However, it is possible to develop intake levels that are unlikely to pose risk of adverse health effects to most members of the general population, including sensitive individuals. For some nutrients or food components these intake levels may, however, pose a risk to subpopulations with extreme or distinct vulnerabilities.
Model for the Derivation of Tolerable Upper Intake Levels
The possibility that the methodology used to derive ULs might be reduced to a mathematical model that could be generically applied to all nutrients was considered. Such a model might have several potential advantages, including ease of application and assurance of consistent treatment of all nutrients. It was concluded, however, that the current state of scientific understanding of toxic phenomena in general, and nutrient toxicity in particular, is insufficient to support the development of such a model. Scientific information regarding various adverse effects and their relationships to intake levels varies greatly among nutrients and depends on the nature, comprehensiveness, and quality of available data. The uncertainties associated with the unavoidable problem of extrapolating from the circumstances under which data are developed (for example, in the laboratory or clinic) to other circumstances (for example, to the healthy population) adds to the complexity.
Given the current state of knowledge, any attempt to capture in a mathematical model all the information and scientific judgments that must be made to reach conclusions regarding ULs would not be consistent with contemporary risk assessment practices. Instead, the model for the derivation of ULs consists of a set of scientific factors that always should be considered explicitly. The framework under which these factors are organized is called risk assessment. Risk assessment (NRC, 1983, 1994) is a systematic means of evaluating the probability of occurrence of adverse health effects in humans from excess exposure to an environmental agent (in this case, a nutrient or food component) (FAO/WHO, 1995; Health Canada, 1993). The hallmark of risk
