level of total chronic daily intake of a nutrient judged to be likely to pose no risk of adverse health effects to the most sensitive members of the healthy population. It is developed by applying the model described. The term tolerable is chosen because it connotes a level of intake that can, with high probability, be tolerated biologically by individuals, but it does not imply acceptability of that level in any other sense. Particularly, it should not be inferred that nutrient intakes greater than the RDA are recommended as being beneficial to an individual. The term adverse effect is defined as any significant alteration in the structure or function of the human organism (Klaassen et al., 1986) or any impairment of a physiologically important function, in accordance with the definition set by the joint World Health Organization, Food and Agriculture Organization of the United Nations, and International Atomic Energy Agency (WHO/FAO/IAEA) Expert Consultation in Trace Elements in Human Nutrition and Health (WHO, 1996).

A MODEL FOR 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. (A fuller discussion of this problem is set forth in the section on “Risk Assessment and Food Safety”.) Scientific information regarding various adverse effects and their relationships to intake levels varies greatly among nutrients, depending on the nature, comprehensiveness, and quality of available data and 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). 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.

An appropriate model for the derivation of ULs consists, then, not of a mathematical formula, but rather a set of scientific factors that always should be considered explicitly. The framework under



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