Update on genotoxicity and carcinogenicity testing of 472 marketed pharmaceuticals

• Published in: Mutation research. Reviews in mutation research 2009-03, Vol.681 (2-3), p.209-229
• Main Authors: Brambilla, Giovanni, Martelli, Antonietta
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carcinogenicity; Fundamental and applied biological sciences. Psychology; Genotoxicity; Marketed drugs; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair
• ISSN: 1383-5742; 1388-2139
• DOI: 10.1016/j.mrrev.2008.09.002

This survey is a compendium of genotoxicity and carcinogenicity information of 838 marketed drugs, whose expected clinical use is continuous for at least 6 months or intermittent over an extended period of time. Of these 838 drugs, 366 (43.7%) do not have retrievable genotoxicity or carcinogenicity data. The remaining 472 (56.3%) have at least one genotoxicity or carcinogenicity test result. Of the 449 drugs with at least one genotoxicity test result, 183 (40.8%) have at least one positive finding. Of the 338 drugs with at least one carcinogenicity test result, 160 (47.3%) have at least one positive result. Concerning the predictivity of genetic toxicology findings for long-term carcinogenesis assays, of the 315 drugs which have both genotoxicity and carcinogenicity data 116 (36.8%) are neither genotoxic nor carcinogenic, 50 (15.9%) are non-carcinogens which test positive in at least one genotoxicity assay, 75 (23.8%) are carcinogenic in at least one sex of mice or rats but test negative in genotoxicity assays, and 74 (23.5%) are both genotoxic and carcinogenic. Only 208 (24.8%) of the 838 drugs considered have all data required by current guidelines for testing of pharmaceuticals. However, it should be noted that a large fraction of the drugs considered were developed and marketed prior to the present regulatory climate. Although the laws do not require re-testing based on revised standards, in the absence of epidemiological studies excluding a carcinogenic risk to humans, a re-evalutation would be appropriate.