ticular sequences, with a gene, that are mutated (Thilly et al., 1982). This capability may allow for the differentiation of the mutational changes that occur spontaneously in a person's cells from those gene changes that might be induced by environmental exposures (Marx, 1989).

Markers of exposure, because of their accessibility and relative ease of interpretation, have been used more often than have markers of effect. In a number of studies markers of exposure have been used to show internal doses of such substances as lead, TCE or its metabolites, or PCBs in serum. No direct studies on persons living near hazardous-waste or Superfund sites have thus far used more sophisticated cellular and biochemical markers, such as DNA or protein adducts, to assess exposure in epidemiologic studies. However, a number of studies have detected adducts to chemicals that may also be found at such sites (see discussion of Hemminki et al., 1990, below). No epidemiologic studies have been found involving hazardous-waste sites that use biologic markers of susceptibility.

For the most part, biologic markers have not been extensively used in epidemiologic studies of hazardous-waste sites because research has not yet linked cellular and molecular biochemical tests with specific disease risks and with other biologic markers (Heath, 1983). There appears to be no impetus for performing the preparatory studies necessary to take a marker at the laboratory development stage and adequately characterize it for use in field studies of waste-site populations. This latter use requires understanding of the natural history, persistence, background levels, variability, and confounding factors for candidate markers. Also, cost considerations may be pivotal, insofar as some of the techniques involve expensive and time-consuming instrumentation. New technologies will offer some exciting options, which will be discussed further in Report 2.

The Centers for Disease Control (CDC) and the Agency for Toxic Substances and Disease Registry (ATSDR) Subcommittee on Biomarkers of Organ Damage has assessed the potential of markers for use in screening populations near hazardous-waste sites (CDC/ATSDR, 1990). The subcommittee 's report discusses markers for the renal, hepatobiliary, and immune systems. It distinguishes tests that are performed routinely in clinical laboratories from those that are used in epidemiologic population studies. The criteria for the usefulness of markers will vary according to their purpose. The report concludes that the ideal marker should be relatively specific to a narrow range of toxicants and that it should be relatively absent or constant in unexposed controls. It should be possible to measure by minimally invasive means that are acceptable to the subject, and it should be inexpensive to



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