Genotoxicity and carcinogenicity studies of analgesics, anti-inflammatory drugs and antipyretics

This survey is a compendium of genotoxicity and carcinogenicity information of analgesics, anti-inflammatory drugs and antipyretics. Data from 120 drugs were collected; 109 of them are still in the market. Of these 120 drugs, 58 (48.3%) do not have retrievable genotoxicity or carcinogenicity data. The remaining 62 (51.7%) have at least one genotoxicity or carcinogenicity test result. Of these 62 drugs, 31 have at least one positive finding: 26 tested positive in at least one genotoxicity assay, 13 in at least one carcinogenicity assay, and 8 gave a positive result in both at least one genotoxicity assay and at least one carcinogenicity assay. In terms of correlation between results of the various genotoxicity assays and absence of carcinogenic activity in mice and/or rats or in other species, 12 of 23 non–carcinogenic drugs tested positive in at least one of the various genotoxicity assay systems. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 35 drugs have both genotoxicity and carcinogenicity data: 11 of them (31.4%) were neither genotoxic nor carcinogenic, 4 (11.4%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 12 (34.3%) tested positive in at least one genotoxicity assay but were non-carcinogenic, and 8 (22,9%) gave a positive response in at least one genotoxicity assay and in at least one carcinogenicity assay. Only 22 (18.3%) of the 120 drugs considered have all data required by current guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior the present regulatory climate.