Update on genotoxicity and carcinogenicity testing of 472 marketed pharmaceuticals.
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.
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Viale Benedetto XV 2, I-16132 Genoa, Italy. Electronic address: amartell@unige.it.
Giovanni
G
Brambilla
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Viale Benedetto XV 2, I-16132 Genoa, Italy.
Antonietta
A
Martelli
D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000032:analysis; D040541:Marketing; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D051381:Rats
D002273:Carcinogens; D004364:Pharmaceutical Preparations