. "3 A Model for the Development of Tolerable Upper Intake Levels." Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: The National Academies Press, 2001.
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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
Consideration of Variability in Sensitivity
The risk assessment model outlined in this chapter is consistent with classical risk assessment approaches in that it must consider variability in the sensitivity of individuals to adverse effects of nutrients or food components. A discussion of how variability is dealt with in the context of nutritional risk assessment follows.
Physiological changes and common conditions associated with growth and maturation that occur during an individual’s lifespan may influence sensitivity to nutrient toxicity. For example, sensitivity increases with declines in lean body mass and with declines in renal and liver function that occur with aging; sensitivity changes in direct relation to intestinal absorption or intestinal synthesis of nutrients; in the newborn infant sensitivity is also increased because of rapid brain growth and limited ability to secrete or biotransform toxicants; and sensitivity increases with decreases in the rate of metabolism of nutrients. During pregnancy, the increase in total body water and glomerular filtration results in lower blood levels of water-soluble vitamins dose for dose and therefore results in reduced susceptibility to potential adverse effects. However, in the unborn fetus this may be offset by active placental transfer, accumulation of certain nutrients in the amniotic fluid, and rapid development of the brain. Examples of life stage groups that may differ in terms of nutritional needs and toxicological sensitivity include infants and children, the elderly, and women during pregnancy and lactation.
Even within relatively homogeneous life stage groups, there is a range of sensitivities to toxic effects. The model described below accounts for normally expected variability in sensitivity but excludes subpopulations with extreme and distinct vulnerabilities. Such subpopulations consist of individuals needing medical supervision; they are better served through the use of public health screening, product labeling, or other individualized health care strategies. Such populations may not be at negligible risk when their intakes reach the UL developed for the healthy population. The decision to treat identifiable vulnerable subgroups as distinct (not protected by the UL) is a matter of judgment and is discussed in individual nutrient chapters, as applicable.
In the context of toxicity, the bioavailability of an ingested nutrient can be defined as its accessibility to normal metabolic and phys-