Many chemicals, both man-made and naturally occuring, can elicit a carcinogenic response either as a mutagenic response in vitro or as a frank tumor in vivo. In both instances emphasis has been placed historically on the dose which elicits the response. When the carcinogenic response is related to the pharmacokinetics of the carcinogen taking into account the dose, the frequency of dosing, andthe relative half lives of the carcinogen, its reactive metabolites and any modified macromolecules, a narrow plateau level of modified macro-molecules is found in specific responsive tissues or species of animals. This plateau threshold concept for carcinogen as defined by the pharmacokinetics, has been evaluated for both chloroform and aflatoxin. The carcinogenic risk associated with plateaus can be evaluated experimentally, and perhaps can be evaluated today with the available data at hand.
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