Uncertainties in the risk assessment of essential trace elements: The case of zinc

The U.S. Environmental Protection Agency (EPA) uses the Reference Dose (RfD) to evaluate the noncarcinogenic effects of chemicals. This methodology assumes a ''threshold'' concept, i.e., there is a level below which adverse effects will not occur. This theory has proven useful in the risk assessment and subsequent regulation of many chemicals. However, for the risk assessment of essential trace elements (ETEs), adjustments in the RfD methodology had to be made. These modifications were necessary to incorporate the fact that humans have certain nutritional requirements for ETEs, as noted in the Recommended Dietary Allowances (RDAs), in order to function properly. Since the RDAs for each ETE also vary with sex, age and physiological requirements, it was difficult to derive an RfD for an ETE that met the changing nutritional requirements of these different groups and still provided in a margin of safety at all stages. With zinc, this task was impossible. As a result, the RfD Work Group inserted a notation in the zinc RfD file that the RFD for zinc did not provide the RDA for infants, preadolescent children and, possibly, lactating women.