Chapter Six - Dose–Response for Essential Metals and the Evaluation of Mixed Exposures

Abstract

There is general recognition that a number of trace metals are essential for human health. For these essential trace metals (ETMs), there is a need for recommendations aimed at protection from deficiency at low dietary intakes and protection from toxicity at high intakes. Uncertainties in the evaluations forming the basis for the recommendations have in the past led to conflicting recommendations for some population subgroups. This chapter describes principles of evaluation using a balanced approach and applying methods to achieve adequate evaluations of information on adverse effects of deficiency as well as toxicity. Application of these principles intends to make it possible to define an acceptable range of oral intakes (AROIs). When intakes are in this range a great majority of the general population will suffer no adverse effects from deficiency or toxicity. The principles include the U-formed dose–response curve and the recognition that the AROI protects only approximately 95% of the general population. Persons with genetically determined special sensitivity may have needs for higher or lower intakes than those defined by the AROI. This chapter also deals with the joint action of ETMs, other metals, and some other nonmetallic food components. It summarizes a few gene–environment interactions for metal-related health effects and points out the potential importance of this relatively new research field. The chapter finally summarizes methods for evaluation of exposure to mixtures.