Issues in biochemical applications to risk assessment: when can lymphocytes be used as surrogate markers?

Abstract

The use of surrogate markers requires validation in humans. The validation is generally considered to consist of two processes. One is sensitivity and one is specificity. Sensitivity might be defined as the ability to adequately detect the nature of the chemical exposure of a given individual. When sensitivity is high, the occurrence of false negatives is low. Specificity reflects our ability to correctly classify individuals who are not exposed or who do not exhibit an adverse health effect. When specificity is high, false positives are low. One approach that might be used in the development of surrogate markers requires the availability-of adequate animal or cellular models for the toxic effects characteristic of the chemical being studied. In our opinion, the validation of surrogate markers is not possible without such in r?ro or in vitro models. Validation requires characterization of the markers in that animal model throughout the time course of the disease process. It is then necessary to determine which of those markers can be determined noninvasively. And finally, this information must be applied to the human condition following either environmental, occupational, or medical exposures. For the purpose of discussion, there are several different kinds of surrogate markers that have been used. These are listed in Table 1 and will be briefly summarized (] 7).