SEVERITY OF EFFECT IN TOXICOLOGY

In toxicology, two types of dose-response curves are used (Eaton and Klaassen 1996). One type relates dose to the incidence of an effect in a group of subjects. For each subject in the group, the effect either occurs or does not occur (binary response). The second type of dose-response curve relates dose to the severity of response of an individual subject. The severity of response of a subject is "graded" according to objective or subjective criteria. Objective severity descriptors can be obtained by direct measurement (e.g., degree of cholinesterase inhibition by organophosphates). Subjective grading can be performed by an investigator, or in human experimentation, the subject might be asked to judge the severity of response. Examples of responses that often are subjectively graded are erythema and eye irritation. Toxicologists generally are referring to the second type of dose-response curve when discussing severity of effect.

Figure 4-1 illustrates the two types of dose-response curves and shows how more-and less-sensitive individuals are depicted in each type. To incorporate severity into an incidence dose-response curve, health effects would need to be categorized into discrete categories so that an individual could be classified as either showing that severity of effect or not. Figure 4-1A depicts that approach using three severity levels for coughing: mild, severe, and incapacitating. The proportion of individuals experiencing a given severity of coughing is plotted against dose. More-sensitive individuals are at the lower-left end of the curve for a specified severity of coughing, and less-sensitive individuals at the upper-right end of the curve. The curves are likely to be overlapping; some of the more-sensitive individuals might experience severe coughing at doses that only produce mild coughing in others.

For a severity dose-response curve (Figure 4-1B), severity of response is represented as a continuum. In this case, more-sensitive individuals are represented by curves starting at lower exposure concentrations, and the population is represented by a series of individual severity dose-response curves. The individual curves might be parallel (i.e., equal slopes), or the slope of the dose-response curves might be more steep for more-sensitive individuals. In either case, the severity of response in a sensitive individual would be greater than the severity of response in a normal individual at a given dose, as was shown for SO2 in Chapter 3. The proportion of the population experiencing a given



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