Essentiality and Toxicity in Copper Health Risk Assessment: Overview, Update and Regulatory Considerations

Copper (Cu), an essential element required as a cofactor and/or structural component of numerous metalloenzymes, is uniquely positioned as a case study for issues associated with the essential metals health risk assessment, because of its extensive database. Essential elements pose distinct challenges when establishing regulatory guidelines because too little as well as too much intake can produce adverse health consequences and the dose-response curve is roughly U-shaped. Thus, conventional health risk assessment paradigms do not apply to essential elements; the dose-response assessment needs to define an acceptable range of oral intake (AROI) which prevents deficiency by meeting nutritional requirements while avoiding toxicity due to high intakes. The conceptual framework for this type of risk assessment includes consideration of biological processes that are unique to essential elements—homeostasis, basal and normative nutritional requirements, bioavailability, and nutrient–nutrient interactions. In th...