Limits of metabolic tolerance to copper and biological basis for present recommendations and regulations

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Abstract
Acute copper toxicity is infrequent in humans. The evidence for chronic toxicity is derived principally from patients with Wilson disease and cases of infantile cirrhosis that were related to excessive copper intakes. The evaluation of the safety of a nutrient requires toxicologic studies to determine the limits of safe exposure. The acceptable daily intake (ADI) is calculated by determining the highest no-observed-adverse-effect level (NOAEL). When it is not possible to identify the NOAEL, the lowest observed-adverse-effect level (LOAEL) may be used. For the calculation of human ADI, the NOAEL or LOAEL obtained is divided by an arbitrary safety factor to provide an adequate margin of security. Drinking water standards have been adopted by the United States, the European Community, the World Health Organization, and other countries. The upper limits of copper concentration in water are based on organoleptic considerations and on debatable toxicity information. Given the importance of copper as an essential mineral for human health, it is conceivable that this and other essential minerals with health significance should be approached differently from nonessential minerals.