Use of biologic markers for toxic end-points in assessment of risks from exposure to chemicals.

Biologic markers are familiar tools for monitoring human absorption of, and reaction to, potentially toxic chemicals. The concept of applying biologic markers to the risk assessment process is a natural, but more recent, development and the principles remain to be fully elaborated. Biologic markers may be measurements of exposure, of effects, of genetic or induced sensitivity or of disease. The ideal biologic marker for risk assessment purposes is a quantitative measurement of a chemical, biochemical, functional or morphological change in the system that is initiated by a chemical and which results in pathologic change and overt toxicity. It follows that some understanding of the mechanism of toxicity and of dose-response relationships are pre-requisite for selection of suitable biologic markers for use in risk assessment. Where biologic markers for toxicity are common between mammalian species, extrapolation of data for quantitative risk assessment purposes becomes more reasonable. In the field of carcinogenesis, some DNA and protein adducts have been proposed as biologic markers for assessment of risk associated with exposure to genotoxic carcinogens. However, less progress is evident in relation to other toxic end-points including those for pulmonary, reproductive, immuno- and neuro-toxicity, despite intensive efforts.