Between a rock and a hard place: methods for setting dietary allowances and exposure limits for essential minerals

For each essential trace element, there are two ranges of intake associated with adverse health effects: intakes that are too low and can lead to nutritional deficits and intakes that are too high and can lead to toxicity. Between these two ranges, there is a range of safe and adequate intakes that is compatible with good health; the challenge is to define that range quantitatively. The exposure limit for toxicity traditionally has been determined by dividing a "no-observed-adverse-effect level," often from studies in experimental animals, by a series of uncertainty factors. Dietary allowances to meet nutritional requirements, on the other hand, have been based primarily on data in humans. Uncertainty, variability and limitations in the data base tend to increase estimates of nutritional requirements and decrease estimated toxic exposure limits, driving the values closer together. Chromium (III) and zinc are contrasting cases. Other factors, such as bioavailability, selection of the critical effect and interactions also can play important roles. Close coordination between the nutrition and toxicology communities, as envisioned in the NRC Food and Nutrition Board initiative on Dietary Reference Intakes, is essential in establishing acceptable ranges of intake for trace elements.