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Liver Damage. Liver damage in humans is observed almost exclusively in patients with Wilson’s disease and children with Indian childhood cirrhosis (ICC) and idiopathic copper toxicosis (ICT). ICC and ICT have been associated with high copper intakes. However, familial relationships and genetic factors are required for the expression of liver toxicity from high levels of copper intake (Joshi et al., 1987; Kishore and Prasad, 1993; Pandit and Bhave, 1996; Tanner, 1998). The rarity of ICT and ICC outside of Germany and India and the lack of liver damage noted in children in the United States exposed to levels of copper between 8.5 and 8.8 mg/L in drinking water support the hypothesis that copper is only one factor required for the expression of these diseases (Scheinberg and Sternlieb, 1994).

Further evidence of an underlying hereditary defect in copper homeostasis in ICC comes from Kishore and Prasad (1993). These authors found that one-third of the ICC cases examined have α-1-antitrypsin deficiency. In view of the weight of evidence supporting a genetic basis for the liver damage in Wilson’s disease, ICC, and ICT, it is not appropriate to use data from such populations to develop a UL for copper in populations with normal copper homeostatic mechanisms.

Pratt and coworkers (1985) reported no evidence of liver damage or gastrointestinal effects in a double-blind study of seven subjects given 10 mg/day of copper gluconate for a period of 12 weeks. Although from a small study, these results are consistent with the safe upper level of intake of 10 to 12 mg/day of copper proposed by the World Health Organization (WHO, 1996) and the International Programme on Chemical Safety (IPCS, 1998). At higher doses, acute liver failure was reported in one subject, who had no known genetic defect in copper homeostasis, after consuming 30 mg/day of copper from supplements for 2 years, followed by 60 mg/day for an additional but unspecified period of time (O’Donohue et al., 1993).

Other Systemic Effects. Little evidence indicates that chronic exposure to copper results in systemic effects other than liver damage. No association between the level of copper intake and spontaneous abortions has been found, and data are inadequate to assess the reproductive or developmental effects of copper in humans (IPCS, 1998). Also, there is little convincing evidence that copper is causally associated with the development of cancer in humans.

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