Essentiality and toxicity of trace elements: Principles and methods for assessment of risk from human exposure to essential trace elements

Recommendations aimed at protecting the public from toxicity of essential elements have been developed separately from those recommendations aimed at protection from deficiency. Because of the uncertainties involved in evaluations, these recommendations have sometimes been in conflict, emphasizing the need for a new approach including a balanced consideration of nutritional as well as toxicological data.

In developing these new principles of evaluation, some basic concepts based on interindividual variability in sensitivity to deficiency and toxicity must be considered. Such variation translates into one interval of (low) daily intakes, at which there is risk of developing deficiency, and another interval of (high) dietary intakes, at which toxicity may occur. In most instances there is a third set of intakes in between, which represents the acceptable range of oral intakes (AROI) in which no adverse effects occur. It must be noted, however, that such a range cannot be found that protects all persons from adverse effects. Those persons with genetically determined sensitivity may require higher intakes to avoid deficiency, or lower intakes to avoid toxicity than those defined by AROI. AROI is defined as protecting 95% of an unselected human population from even minimal adverse effects of deficiency or toxicity. J. Trace Elem. Exp. Med. 13:141–153, 2000.