[Genotoxicity of carcinogenic substances in humans and animals]

To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the I.A.R.C. Monographs for their carcinogenic effects in human and animals and for the activity in short-term tests. The prevalence of genotoxic carcinogens on four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and of agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 149) was determined. A high prevalence in the order of 80 to 90% of genotoxic carcinogens was found in each of the groups 1, 2A and 2B, which were also shown to be multi-species/multi-tissues carcinogens. Neither the prevalence of genotoxic carcinogens nor the distribution of carcinogenic potency in rodents reveal any specific characteristics of the human carcinogens in group 1 that differentiates them from agents in groups 2A and 2B or from many in group 3. This suggests that substances in group 2A and 2B and possibly several in group 3, are carcinogenic to humans. These results indicate that (a) an agent with unknown carcinogenic potential showing sufficient evidence of activity in in vitro/in vivo genotoxicity assays (involving as endpoints DNA damage, chromosomal/mutational damage) may represent a hazard to humans; and (b) an agent showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity by rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens.