In 1986, approximately 15 percent of adults in the United States consumed supplements that contained copper (Moss et al., 1989; see Table 2-2). Based on data from the Third National Health and Nutrition Examination Survey provided in Appendix Table C-16, the median dietary plus supplemental copper intake was similar to the intake from food alone. The mean intake of dietary and supplemental copper (1.3 to 2.2 mg/day) was approximately 0.3 to 0.5 mg/day greater for men and women than the mean intake from food (1.0 to 1.7 mg/day).
The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects for almost all individuals. Although members of the general population should be advised not to routinely exceed the UL, intake above the UL may be appropriate for investigation within well-controlled clinical trials. Clinical trials of doses above the UL should not be discouraged, as long as subjects participating in these trials have signed informed consent documents regarding possible toxicity and as long as these trials employ appropriate safety monitoring of trial subjects. In addition, the UL is not meant to apply to individuals who are receiving copper under medical supervision.
Reviews of the toxicity studies in experimental animals (ATSDR, 1990; EPA, 1987; IPCS, 1998; NRC, 1977) indicate that these studies are not useful for setting a UL for humans. Very few of these studies used chronic exposures, only one or two doses were used, and the reporting of experimental details and results was incomplete. In addition, some studies used routes of exposure that are not relevant to human intake (Toyokuni and Sagripanti, 1994). Finally, animal species vary markedly in their sensitivity to copper (Davis and Mertz, 1987); thus it is difficult to determine the most appropriate model in which to assess human toxicity to copper.
The long-term toxicity of copper is not well studied in humans, but it is rare in normal populations not having some hereditary defect in copper homeostasis (Olivares and Uauy, 1996). Copper homeostasis is affected by the interaction among zinc, copper, iron, and molybdenum. In addition, the level of dietary protein, interact-