ABSTRACT
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comprehensible and concise manner on such a broad topic, it is necessary to provide some definitions and assumptions that were used to narrow the subject area covered. To begin with, the tide of the chapter contains some terms that are open to interpretation and hence should be defined. “Natural” in the context of this chapter will include all compounds that are found in the food supply, exclusive of synthetic compounds that are either intentionally added or incidentally found in food. This would exclude many synthetic direct and indirect food additives, pesticides, animal drug residues, and most of the so-called environmentally persistent chemicals, such as DDT. Hence, “naturally occurring” includes all nonsynthetic substances that occur through nonanthropogenic activity (i.e., plant-or fungi-derived con taminants) and those that are formed endogenously in the food as a result of natural chemical procesess caused by some type of human activity (i.e., cooking). “Orally active” is used in the context of carcinogenesis and excludes the consideration of all compounds that are bereft of evidence of carcinogenic activity via the oral route of administration. Hence, there are many compounds which may be found in food that have carcinogenic activity upon some parenteral route of administration, such as inhalation (e.g., acetaldehyde), but either lack carcinogenic activity upon oral administration or have not been so tested. Since carcinogenic metabolic pathways are so heavily dependent on the route of administration, oral exposure is the only relevant route for food. Given that cancer formation is a multifactorial, multistage process, defining the term “carcinogen” is not so straightforward. For the purposes of this chapter, a rather simple definition was employed. A “carcinogen” is any solitary compound (i.e., not a mixture or physicochemically unidentified substances), exposure to which is capable of increasing the incidence of either benign or malignant neoplasm. Excluded from consid eration are all the “co-carcinogens”, “promoters”, and other amplifiers of the carcinogenic process. For example, certain macro-components of the diet such as alcohol and certain fats are excluded, as well as naturally occurring trace compounds that can occur in the diet, such as the diterpene esters from certain plants. Additionally, compounds that are known to exert their carcinogenic action via a secondary mechanism (i.e., nongenotoxic carcinogens), such as hormone disruptors (e.g., phytoestrogens and thioureas), are also excluded from consid eration. In general, effects of nongenotoxic carcinogens occur at high doses, above some threshold level that exceeds human exposure. Finally, somewhat arbitrarily, certain inorganic ions and compounds that are thought to produce cancer in humans (e.g., arsenic) are excluded from consideration.
