Reference intervals for toxic metals: problems and prospects. Abraham J. Gitlitz memorial lecture

The problems of assigning reference values in laboratory medicine are particularly thorny in relation to metal concentrations in body fluids and tissues. Exposures to toxic metals are extremely variable, and a proper reference population and sampling strategy may be difficult to define. More importantly, current environmental exposures, especially to lead, methylmercury, and cadmium, may be associated with adverse effects. The question therefore arises of how to define and estimate an upper limit which provides a margin of safety. In addition, the relevance of a lower limit of the reference interval for non-essential metals may be questioned. Further, the levels of several toxic metals occurring in body fluids and tissues frequently appear to be considerably increased owing to anthropogenic exposures. Thus, reference intervals for "natural" metal concentrations would be of interest as a reflection of the levels to which Homo sapiens originally adapted. Limited information in this area is available. In addition, interpretation is sometimes hampered by possible laboratory contamination of samples and insufficient validity of metal determinations at low concentration levels. Major progress has been made during recent years, but the scientific basis for evaluating individual results of metal determinations in body fluids and tissues is still unsatisfactory.