Toxicology of micronutrients: adverse effects and uncertainty.

The establishment of safe upper intake levels for micronutrients must consider the intake-response relations for both deficiency and toxicity. Limited data are available on the toxicities of most micronutrients, and few studies that meet the criteria considered essential for the risk assessment of other chemicals in food, such as pesticides and food additives, have been performed. In some cases, the application of large uncertainty factors, which are used to establish the amount of a chemical that would be safe for daily intake throughout life, could result in nutritionally inadequate intakes of micronutrients. As a consequence, lower than normal uncertainty factors have been applied to determine safe or tolerable intakes of many micronutrients. There is no clear scientific rationale, on the basis of the metabolism and elimination of micronutrients or the nature of the adverse effects reported for high intakes, for the use of reduced uncertainty factors for micronutrient toxicity. A review of recent evaluations of selected vitamins and minerals shows little consistency in the application of uncertainty factors by different advisory groups, such as the Institute of Medicine in the United States and the Scientific Committee on Foods in the European Union. It is apparent that, in some cases, the uncertainty factor applied was selected largely to give a result that is compatible with nutritional requirements; therefore, the uncertainty factor represented part of risk management rather than hazard characterization. The usual risk assessment procedures for chemicals in food should be revised for micronutrients, so that the risks associated with intakes that are too low and too high are considered equally as part of a risk-benefit analysis.