Animal cancer tests and cancer prevention.

The toxicological significance of exposures to synthetic chemicals is examined in the context of exposures to naturally occurring chemicals. We calculate that 99.99% (by weight) of the pesticides in the US diet are chemicals that plants produce to defend themselves (nature's pesticides). Only 52 of these natural pesticides have been tested in high-dose animal cancer tests, and 27 are rodent carcinogens; these 27 are shown to be present in many common foods. The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins (eg, dioxin) are compared to natural chemicals (eg, indole carbinol [in broccoli] and ethanol). The finding that, in high-dose tests, a high proportion of both natural and synthetic chemicals are carcinogens, mutagens, teratogens, and clastogens (30%-50% for each group) calls into question current efforts to use these tests to protect public health by regulating low doses of synthetic chemicals. The administration of chemicals at the maximum tolerated dose in standard animal cancer tests is postulated to increase cell division (mitogenesis), which in turn increases rates of mutagenesis and, thus, carcinogenesis. The animal data are consistent with this mechanism, because a high proportion--about 50%--of all chemicals tested (whether natural or synthetic) are indeed rodent carcinogens.(ABSTRACT TRUNCATED AT 250 WORDS)