used in this chapter to illustrate EPA's approach to health effects that involve noncancer end points. They constitute the first completed noncancer risk-assessment guidelines in a series that EPA plans to issue.
The first of the two questions typically considered in the assessment of chemical toxicity concerns the types of toxic effects that the chemical can cause. Can it damage the liver, the kidney, the lung, or the reproductive system? Can it cause birth defects, neurotoxic effects, or cancer? This type of hazard information is obtained principally through studies in groups of people who happen to be exposed to the chemical (epidemiologic studies) and through controlled laboratory experiments involving various animal species. Several other types of experimental data can also be used to assist in identifying the toxic hazards of a chemical.
Epidemiologic studies clearly provide the most relevant kind of information for hazard identification, simply because they involve observations of human beings, not laboratory animals. That obvious and substantial advantage is offset to various degrees by the difficulties associated with obtaining and interpreting epidemiologic information. It is often not possible to identify appropriate populations for study or to obtain the necessary medical information on the health status of individuals in them. Information on the magnitude and duration of chemical exposure, especially that experienced in the distant past, is often available in only qualitative or semiquantitative form (e.g., the number of years worked at low, medium, and high exposure). Identifying other factors that might influence the health status of a population is often not possible. Epidemiologic studies are not controlled experiments. The investigator identifies an exposure situation and attempts to identify appropriate ''control" groups (i.e., unexposed parallel populations), but the ease with which this can be accomplished is largely beyond the investigator's control. For those and several other reasons, it is difficult or impossible to identify cause-effect relationships clearly with epidemiologic methods (OSTP, 1985).
It is rare that convincing causal relationships are identified with a single study. Epidemiologists usually weigh the results from several studies, ideally involving different populations and investigative methods, to determine whether there is a consistent pattern of responses among them. Some of the other factors that are often considered are the strength of the statistical association between a particular disease and exposure to the suspect chemical; whether the risk of the disease increases with increasing exposure to the suspect agent; and the degree to which other possible causative factors can be ruled out. Epidemiologists