Reference values for the study of low doses of metals.

The role of biological monitoring (BM) in the prevention of exposure to toxic metals has currently acquired considerable importance. However, in the near future the usefulness of BM in occupational medicine could be reduced by the fact that exposure to toxic substances will progressively decrease and consequently problems of comprehension will occur. BM can maintain its importance in the prevention field if sensitivity and specificity of the biological indicators (BI) are increased and if this activity is specifically directed towards groups of subjects. To achieve this last goal, one of the problems which must be solved is the identification of "reference values" (RV) which define the BI levels in the general population not occupationally or environmentally exposed to the toxic substance under study. It is necessary to "refer" to these values in order to compare the data obtained in a population which is presumed to be exposed. In this presentation, the example of blood cadmium is used in order to discuss the criteria required to identify RV. Herein the data of a personal case list are reported, particularly the variables which must be considered when selecting subjects to form "reference groups". Conversely, the possibility of obtaining RV through meta-analysis studies, pooling the results published in international literature, are evaluated.