Copper and human health: Biochemistry, genetics, and strategies for modeling dose-response relationships

Aw, Tar-Ching and Stern, Bonnie Ranson and Solioz, Marc and Krewski, Daniel and Aggett, Peter and Baker, Scott and Dourson, MIchael and Crump, Kenny and Haber, Lynne and Hertzberg, Rick and Keen, Carl and Meek, Bette and Rudenko, Larisa and Schoeny, Rita and Slob, Wout and Starr, Tom (2007) Copper and human health: Biochemistry, genetics, and strategies for modeling dose-response relationships. Journal of Toxicology and Environmental Health Part B-Critical Reviews, 10 (3). pp. 157-222. ISSN 1093-7404. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Copper (Cu) and its alloys are used extensively in domestic and industrial applications. Cu is also an essential element in mammalian nutrition. Since both copper deficiency and copper excess produce adverse health effects, the dose-response curve is U-shaped, although the precise form has not yet been well characterized. Many animal and human studies were conducted on copper to provide a rich database from which data suitable for modeling the dose-response relationship for copper may be extracted. Possible dose-response modeling strategies are considered in this review, including those based on the benchmark dose and categorical regression. The usefulness of biologically based dose-response modeling techniques in understanding copper toxicity was difficult to assess at this time since the mechanisms underlying copper-induced toxicity have yet to be fully elucidated. A dose-response modeling strategy for copper toxicity was proposed associated with both deficiency and excess. This modeling strategy was applied to multiple studies of copper-induced toxicity, standardized with respect to severity of adverse health outcomes and selected on the basis of criteria reflecting the quality and relevance of individual studies. The use of a comprehensive database on copper-induced toxicity is essential for dose-response modeling since there is insufficient information in any single study to adequately characterize copper dose-response relationships. The dose-response modeling strategy envisioned here is designed to determine whether the existing toxicity data for copper excess or deficiency may be effectively utilized in defining the limits of the homeostatic range in humans and other species. By considering alternative techniques for determining a point of departure and low-dose extrapolation ( including categorical regression, the benchmark dose, and identification of observed no-effect levels) this strategy will identify which techniques are most suitable for this purpose. This analysis also serves to identify areas in which additional data are needed to better define the characteristics of dose-response relationships for copper-induced toxicity in relation to excess or deficiency.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculties > Science Technology and Medical Studies > Kent Institute of Medicine and Health Sciences (KIMHS)
Depositing User: Stephen Holland
Date Deposited: 19 Dec 2007 18:56
Last Modified: 09 Apr 2014 10:10
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