PRINCIPLES OF TOXICOLOGY

468 RISK ASSESSMENT
producing the effect, this is termed synergism. The special case in which one of the two chemicals has
no effect on its own, but nonetheless increases the toxicity of another, is termed potentiation.
There are a number of tests available to determine whether two chemicals interact in an additive,
subadditive (i.e., antagonistic), or supraadditive (i.e., synergistic) fashion. One of the most straightforward
is the construction of an isobologram (see Figure 18.8). Two chemicals are administered in
varying proportions, ranging from 100% chemical A to 100% chemical B. If the interaction between
the two chemicals follows dose addition, their responses will lie along a line that connects the response
for 100% chemical A to the response for 100% chemical B. If the responses to chemical combinations
are greater than would be predicted by dose addition, that is, if they lie above and to the right of the
dose-addition line, a synergistic effect can be inferred. On the other hand, responses below the line
and to the left indicate antagonism.
From a practical standpoint, interactions among chemicals are very difficult to deal with quantitatively
in a risk assessment. These interactions are seldom well characterized and can be dosedependent—synergism
or antagonism that occurs at one dose combination of the chemicals may not
occur at other dose combinations. Also, while tests exist to examine the nature of interactions between
two chemicals, as described in the paragraph above, interactions among multiple chemicals are much
more difficult to assess and characterize. Although the problem of addressing chemical interactions
has been recognized for some time, research to solve this problem is still in a relatively early stage of
development. Scientists are still struggling to identify circumstances where important interactions
might take place, and rigorous techniques for adjusting risk estimates to account for interactions do
not yet exist.
18.8 COMPARATIVE RISK ANALYSIS
For the purposes of this chapter, comparative risk analysis is a means of placing estimates of risk into
a larger context in order to provide risk managers and stakeholders with a better perspective for decision
making. Comparative risk analysis can also help nontechnical audiences understand the implications
of a risk assessment, particularly when findings are reported in unfamiliar quantitative jargon.
Furthermore, risk comparisons may be of value in setting priorities and allocating resources within
regulatory agencies. In response to many risk problems posed by chemical exposure, the following
questions might be asked, all of which should prompt the conduct of a comparative risk analysis:
(1) whether the receptors are exposed to the same chemical from other sources, (2) whether
exposure to the chemical also occurs from other environmental media, and (3) whether other
chemicals from the same sources pose additional risks to receptors. Several types of risk
comparisons are listed below.
1. Comparisons of magnitude such as equating a “one in one million” risk to the length of 1 inch
in 16 miles, 30 seconds in a year, or 1 drop in 16 gallons
2. Comparisons of risk posed by the same chemical from different sources
3. Comparisons of risk posed by different chemicals from the same source
4. Comparisons of risk posed by different chemicals for the same target organ
5. Comparisons of familiar versus less familiar risks
6. Comparisons of voluntary versus involuntary risks
7. Comparisons of natural versus anthropogenic or technologic risks
8. Comparisons of risks of the same magnitude posed by different risk factors
Just as risk comparisons can be of value, they can also hinder risk communication. For example,
inappropriate comparisons can be confusing and may serve to minimize risks that, in reality, deserve
serious consideration. To maximize the benefits of risk comparison and avoid its pitfalls, it is