committee was charged to ''examine the occurrence, toxicologic data, mechanisms of action, and potential role of natural carcinogens in the causation of cancer (in humans), including relative risk comparisons with synthetic carcinogens and a consideration of anticarcinogens." In addition, the committee was charged to assess "the impact of these materials (natural carcinogens) on initiation, promotion, and progression of tumors." Further, the committee was charged to "focus on the toxicologic information available for natural substances" and to "develop a strategy for selecting additional natural substances for toxicological testing."

In this report, the "initiation, promotion, and progression" stages of carcinogenesis were considered from a mechanistic point of view. However, most of the available carcinogenicity data on the compounds that were reviewed do not provide precise information on the specific stage or stages of the multistage process of carcinogenesis at which these compounds act. Since the terms initiator, promoter, and progressor are especially difficult to apply to specific agents, particularly as they pertain to human carcinogenesis, the committee chose primarily to discuss agents as being genotoxic or nongenotoxic. The committee viewed its charge to address toxicologic issues as limited to cancer.

For this report, the committee adopted the definition of a carcinogen proposed by the International Agency for Research on Cancer (IARC). IARC defines a carcinogen as any agent, the exposure to which increases the incidence of malignant neoplasia. It is recognized that many factors can influence the process of tumor formation and that the application of this definition does not always identify the influence of high-dose levels of chemicals used in rodent testing, nor does it identify the uncertainties in extrapolating results from these rodent bioassays to much lower exposure/dose in humans. In this report, the term "exposure" means the amount of a synthetic or naturally occurring agent (including contaminants) ingested from the diet.

The number of naturally occurring chemicals present in the



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