Establishing and Applying Key Events in Support of MOA

This section will build upon the overview information presented in Ihe previous sections to lay out for known rodent carcinogens, what specific information is required, and how it is used to establish an MOA in animals and its relevance to humans. Specific examples are provided also for illustrating the appUcation of the framework approach leading to risk charactoization. 

Is the Weight of Evidence Sufficient to Establish the MOA in Animals The following information is used as a guide for evaluating each hypothesized carcinogenic MOA (ERA 2005 Meek et al. 2003) and is, in a sense, a corollary to the queries that were presented in the framework ovCTview above. 

The particular approach presented by Preston and Williams (2005) was for DNA-reactive carcinogens, although as shown here it is readily adaptable to non-DNA-reactive chemicals. The framework is the description of key events for tumor development and is shown in Table 13.2. There is an essential temporal sequence 

TABLE 13.2. Key Events for Tumor Development DNA-Reactive MOAs 

Exposure of target cells (e.g., stem cells) to ultimate DNA-reactive and mutagenic species in some cases this requires metabolism. 

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