PRINCIPLES OF TOXICOLOGY - Biology East Borneo

468 RISK ASSESSMENTproducing the effect, this is termed synergism. The special case in which one of the two chemicals hasno 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 straightforwardis the construction of an isobologram (see Figure 18.8). Two chemicals are administered invarying proportions, ranging from 100% chemical A to 100% chemical B. If the interaction betweenthe two chemicals follows dose addition, their responses will lie along a line that connects the responsefor 100% chemical A to the response for 100% chemical B. If the responses to chemical combinationsare greater than would be predicted by dose addition, that is, if they lie above and to the right of thedose-addition line, a synergistic effect can be inferred. On the other hand, responses below the lineand to the left indicate antagonism.From a practical standpoint, interactions among chemicals are very difficult to deal with quantitativelyin a risk assessment. These interactions are seldom well characterized and can be dosedependent—synergismor antagonism that occurs at one dose combination of the chemicals may notoccur at other dose combinations. Also, while tests exist to examine the nature of interactions betweentwo chemicals, as described in the paragraph above, interactions among multiple chemicals are muchmore difficult to assess and characterize. Although the problem of addressing chemical interactionshas been recognized for some time, research to solve this problem is still in a relatively early stage ofdevelopment. Scientists are still struggling to identify circumstances where important interactionsmight take place, and rigorous techniques for adjusting risk estimates to account for interactions donot yet exist.18.8 COMPARATIVE RISK ANALYSISFor the purposes of this chapter, comparative risk analysis is a means of placing estimates of risk intoa larger context in order to provide risk managers and stakeholders with a better perspective for decisionmaking. Comparative risk analysis can also help nontechnical audiences understand the implicationsof 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 withinregulatory agencies. In response to many risk problems posed by chemical exposure, the followingquestions 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) whetherexposure to the chemical also occurs from other environmental media, and (3) whether otherchemicals from the same sources pose additional risks to receptors. Several types of riskcomparisons are listed below.1. Comparisons of magnitude such as equating a “one in one million” risk to the length of 1 inchin 16 miles, 30 seconds in a year, or 1 drop in 16 gallons2. Comparisons of risk posed by the same chemical from different sources3. Comparisons of risk posed by different chemicals from the same source4. Comparisons of risk posed by different chemicals for the same target organ5. Comparisons of familiar versus less familiar risks6. Comparisons of voluntary versus involuntary risks7. Comparisons of natural versus anthropogenic or technologic risks8. Comparisons of risks of the same magnitude posed by different risk factorsJust 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, deserveserious consideration. To maximize the benefits of risk comparison and avoid its pitfalls, it is