Environmental Health Criteria 228: PRINCIPLES AND METHODS FOR THE ASSESSMENT OF RISK FROM ESSENTIAL TRACE ELEMENTS.

The risk assessment approach described in this monograph applies only to essential trace elements (ETEs) involved in human health and not to non-essential elements. The monograph is designed to give methods that provide a framework for analysing the boundaries between deficient and excess oral intakes of ETEs. Application of the principles described in this monograph involves a multidisciplinary scientific assessment, using data on required nutritive intakes, deficiency and excess exposure. This monograph focusses on the concepts of the acceptable range of oral intake (AROI). The AROI is designed to limit deficient and excess intakes in healthy populations and is set for different age-sex groups and physiological states such as pregnancy and lactation. To facilitate comparisons, AROIs are discussed in relation to other risk assessment approaches. Homeostatic mechanisms involve regulation of absorption and excretion and tissue retention, which enable adaptation to varying nutrient intakes. These mechanisms provide for an optimal systemic supply for the performance of essential functions and must be considered in establishing an AROI. The impact of other factors, such as chemical form, dietary characteristics and interactions amongst ETEs, are also critical in determining the AROI for ETEs. When ETE intakes are above or below the boundaries of the AROI, the capacity of the homeostatic mechanisms is exceeded and the probability and severity of adverse effects increase. The homeostatic model was used to establish the AROI and is illustrated with examples and a series of theoretical curves. The process begins with the selection of the database for a particular ETE. A weight-of-evidence approach is then used for hazard identification, selecting relevant end-points of deficient and excess exposures. Next, the probability of risk and the severity of various effects are quantified and critical effects are selected. The AROI is then established by balancing end-points of comparable health significance. At this time, the exposure assessment is conducted. Finally, a risk characterization enumerating the strengths and weaknesses of the databases is performed, integrating the AROI and exposure assessment. [ABSTRACT FROM AUTHOR]