Thresholds in Chemical Carcinogenesis

Abstract

This review deals with the controversial subject of thresholds in chemical carcinogenesis. It is essential to consider this subject in relation to a number of other matters which have a direct bearing on it. These include the use of the maximum tolerated dose (MTD) in animal bioassays. These are at times excessive and not consistent with the definition of the MTD. Many bioassays are carried out at only one or two doses so that reliable dose-response curves and hence a threshold cannot be established. In addition, laboratory animal bioassays even at the lowest doses used are frequently above those encountered in the environment by several orders of magnitude. The various biochemical and biologic events which a xenobiotic is subjected to in vivo are described in more detail in relation to threshold. Also, dose-dependent alterations in metabolic pathways are reviewed for vinyl chloride and 1, 4-dioxane. The value of examining the muta-genidty and cardnogenidty of activated carcinogenic intermediates is examined using a series of chloroalkene epoxides as intermediates. The interdisciplinary approaches that need to be used in risk assessment, which is required by federal regulatory agencies, are pointed out. It is concluded that thresholds do exist for some chemical carcinogens.