PRINCIPLES UNDERLYING DOSE SELECTION FOR, AND EXTRAPOLATION FROM, THECARCINOGEN BIOASSAY - DOSE INFLUENCES MECHANISM

The purpose of the bioassay is not to simply find chemicals that can b e labeled as carcinogens. On the contrary, the overall goal is to prov ide a reasonable assessment of the possible hazard that a chemical mig ht pose to people under realistic conditions of exposure. This paper f ocuses upon the doses commonly used in the bioassay within the context that dose influences mechanism and, over a wide range of doses, mecha nism changes with changing dose. Thus, a carcinogenic effect observed at a high dose is not necessarily expected to occur at lower doses. A variety of examples are provided to illustrate the points that (a) any high dose, no matter how high, that permits test animals to live long enough to develop tumors is not an appropriate criterion for defining an acceptable high dose to employ in a carcinogen bioassay; and (b) e mphasis should be placed upon research that may discern probable thres holds for the carcinogenic effect of chemicals, especially nongenotoxi c chemicals. (C) 1995 Academic Press, Inc.