ing specific health outcomes. A variety of health outcomes associated with trichloroethylene is discussed in Chapters 3 to 8. At least three levels of health outcomes should be considered in assessing the human health risks associated with exposure to trichloroethylene: biomarkers of effects and susceptibility, morbidity, and mortality.

Few known susceptibility biomarkers specific to trichloroethylene have been assessed in humans. In the case of liver toxicity (see Chapter 4), incipient effects on the liver could be measured by changes in liver enzymes in the serum, although significant toxicity would have to be present for these measurements to be useful. Assessment of immune function may have a place in assessing adverse effects of trichloroethylene (see Chapter 8), but this outcome is nonspecific (Iavicoli et al. 2005). Human studies on proteinuria and other early markers of kidney toxicity are important (see Chapter 3). However, none of these potential biomarkers is specific to trichloroethylene.

High occupational or accidental exposure to trichloroethylene can produce toxicity, in particular, liver and central nervous system effects. The public-health review process focuses on more subtle effects resulting from exposures to lower concentrations. These morbidity outcomes can be in the form of cancer and noncancer outcomes. Many nonfatal, noncancer health end points are poorly measured and the few studies are difficult to interpret, mostly because current health monitoring systems are not set up to easily link health outcome data to exposure. On the other hand, cancer incidence is enumerated much more accurately by tumor registries, which usually have high diagnostic accuracy (histologic assessment of tumor location and tumor type). Alternatively, histologically confirmed cases of cancer (except for nonmelanotic skin cancer) can be identified through records in hospital pathology departments, which may be useful in two ways. First, they provide the cases for case-control studies, the method of choice to assess rare tumors, such as childhood cancers. Second, they match cohorts to tumor registries where the cohort members reside.

Mortality is readily identified from death certificates, which are collected routinely on a jurisdictional basis (e.g., state or province) and collated nationally. This outcome has the advantage of having complete national coverage but diagnostic accuracy is reduced because the attending physicians who fill out the certificates usually do not have the benefit of histologic diagnosis or autopsy findings. Most cohort studies rely on mortality data for risk assessment. It must be recognized that diagnostic accuracy from death certificates varies by the specific diagnosis (Brenner and Gefeller 1993).

Disease classification systems are also periodically revised, adding to diagnostic inconsistency (Irons 1992). The issue of changes in diagnostic coding systems is illustrated for the classification of lymphatic and hemato-



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