Roles Of Sar In Cancer Risk Assessment

In the absence of adequate epidemiologic data and based on the findings that virtually all known human carcinogens are also rodent carcinogens, data from lifetime exposure animal bioassays are primarily used for identifying chemical substances that may be associated with carcinogenic effects in humans. However, the high cost of testing, the large number of animals used in 2-year rodent bioassays, and the huge number of chemicals for which carcinogenicity data do not exist have made it impractical and inhibitory to test each of the thousands of existing chemicals for carcinogenicity. Meanwhile, government health regulatory agencies are under increasing mandate to screen large lists of existing chemicals in commerce and the environment for carcinogenic and other toxicologic effects. Structure-activity relationship is serving an increasingly important role in the risk assessment process as the first line approach in hazard identification, prioritizing chemicals for testing, designing test strategies, identifying research needs, and providing mechanistic insight to support risk assessment and regulatory decision-making. The general approach for assessment of potential human carcinogens is depicted in Figure 3. Some examples that illustrate the roles of SAR in the cancer risk assessment process of existing and premanufactured chemicals under various regulatory statutes of the U.S. Environmental Protection Agency (EPA) are presented below.

1. To obtain data necessary for the EPA to assess and manage the risk of hazardous air pollutants (HAPs) regulated under the Clean Air Act, SAR was used as one of the criteria to select seven of the 21 HAPs for testing of carcinoge-nicity (43).

2. Currently, EPA is using SAR in the prioritization process of selecting representative chemicals from a list of 215 disinfection by-products (DBP) detected in drinking water for potential future carcinogenicity testing (44).

Structure-activity relationships (SAR)

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