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would be detected with historical use. Similarly, carcinogenic effects are not inconsistent with the historical use information since they would not be expected to be detected if they did occur.

The prototype integrative evaluation process showed that with so many different types of information to process and consider, it is useful to note what is certain and focus on uncertainties. As explained in Chapter 10, causal model diagrams may be useful to visually illustrate what is known and where data gaps exist. In doing so, they can help focus thinking and information searching on remaining questions (as made more obvious by missing or weak linkage arrows). A causal model on the relationship between chaparral and liver effects is presented in Figure 11-1 as an example of the diagram’s value. A solid arched arrow illustrates a relationship between chaparral ingestion and adverse liver effects in humans, independent of knowledge about hazards that may be associated with NDGA. Another pathway between chaparral and liver effects is based on the relationship between chaparral and NDGA and knowledge of how chemical structures like NDGA can be metabolized into quinones that subsequently result in adverse liver effects. A related substance with this effect is acetaminophen.

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