Determining a Reference Dose (RfD) for Zinc. J. M. Donohue, C. O. Abernathy, and R. E. Cantilli, U.S. Environmental Protection Agency (EPA). Mail Code 4304, 401 M Street, SW, Washington DC 20460
Zinc is an essential micronutrient that can have adverse effects when exposure exceeds dietary needs. The EPA has established a RfD for zinc based on its effects on copper absorption and erythrocyte superoxide dismutase activity. Decreases of serum copper were noted in both males and females consuming 50 mg/day zinc in the form of dietary supplements for periods of 6 to 12 weeks. Parallel decreases in superoxide dismutase activity potentially weaken physiological defenses against free radical oxygen. Data on the long-term effects of zinc supplements of copper homeostasis are not available, but case study data support long-term adverse effects of supplemental zinc (50 to 200 mg/day) on copper bioavailability. Based on these data, 60 mg/ day zinc (50 mg/day of a zinc supplement plus approximately 10 mg in the diet) is a minimal LOAEL for effects on human health. Using standard EPA risk assessment practices, a RfD of 0.3 mg/kg/day can be derived which provides adequate zinc to meet nutritional needs for all age/sex groups except infants and children, and possibly lactating women, while protecting susceptible adults from potential adverse effects. Support for the zinc RfD is provided by data that indicate possible adverse effects of zinc supplementation (50 to 300 mg/day) on serum high density lipoprotein concentrations (a risk factor for cardiovascular disease). Adverse effects of short term zinc supplementation of serum magnesium and iron concentrations have also been reported.