Assessment of Nongenotoxic Mechanisms in Carcinogenicity Test of Chemicals; Quinone, Quinone Imine, and Quinone Methide as Examples

Abstract Chemicals show carcinogenicity in rodent assays through genotoxic and nongenotoxic mechanisms. No threshold levels are defined for genotoxic carcinogens, and thus genotoxic carcinogens are tightly restricted. Nongenotoxic carcinogens often evoke tumorigenicity after chronic administration of high doses and show a threshold when testing multiple doses. However, verification of genotoxic and nongenotoxic carcinogens is not readily achievable in most cases. This is mainly because of overlapping of biological effects. Therefore, mechanistic support is of importance in the assessment of chemicals with tumorigenic potentials. From pathological and pharmaco (toxico) kinetic points of view, quinoids and precursors may be a category of genotoxicants different from those acting through a direct electrophilic reaction with DNA. Many food additives are capable of producing free radicals, and many food additives are able to act as free-radical scavengers. Free- and oxygen-radical scavenging mechanisms also function in the body, whereas such mechanisms are generally not present in tests of genotoxicity in vitro. Detailed investigations of in vivo pathological examinations and pharmaco (toxico) kinetic profiles on quinoid-related chemicals offer us clear assessments with regard to human safety.