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For some nutrients, the range between the upper and lower limits may be extremely narrow and even overlap, which creates difficulties when setting safety margins. A new approach for estimating optimal intakes, taking into account several health biomarkers, has been developed and applied to selenium, but at present there are insufficient data to extend this technique to other micronutrients. The existing methods for deriving reference values for Cu and Fe are described. For Cu, there are no sensitive biomarkers of status or health relating to marginal deficiency or toxicity, despite the well-characterised genetic disorders of Menkes and Wilson's disease which, if untreated, lead to lethal deficiency and overload, respectively. For Fe, the wide variation in bioavailability confounds the relationship between intake and status and complicates risk\u2013benefit analysis. As with Cu, health effects associated with deficiency or toxicity are not easy to quantify, therefore status is the most accessible variable for risk\u2013benefit analysis. Serum ferritin reflects Fe stores but is affected by infection\/inflammation, and therefore additional biomarkers are generally employed to measure and assess Fe status. Characterising the relationship between health and dietary intake is problematic for both these trace elements due to the confounding effects of bioavailability, inadequate biomarkers of status and a lack of sensitive and specific biomarkers for health outcomes.<\/jats:p>","DOI":"10.1017\/s0029665110003873","type":"journal-article","created":{"date-parts":[[2010,9,22]],"date-time":"2010-09-22T13:15:24Z","timestamp":1285161324000},"page":"1-9","source":"Crossref","is-referenced-by-count":11,"title":["Risk\u2013benefit analysis of mineral intakes: case studies on copper and iron"],"prefix":"10.1017","volume":"70","author":[{"given":"Susan J.","family":"Fairweather-Tait","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda J.","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Collings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2010,9,22]]},"reference":[{"key":"S0029665110003873_ref069","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/81.4.814"},{"key":"S0029665110003873_ref053","unstructured":"53. 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