The nonclinical branch of regulatory pharmacology has traditionally relied on the sensitivity and specificity of regulatorily recommended bioassays. Nonetheless, any predictive testing (e.g., safety pharmacology) with less than 100% sensitivity or 100% specificity is significantly prone to deliver false (negative or positive) results (outcomes discordant to the clinical gold standard). It was recently suggested that the statistics-based and regulatory pertinent “predictive values approach” (PVA) might help to reach a more predictive use of preclinical testing data. To resolve the associated probabilities of carcinogenicity to humans, the PVA was applied to 37 pharmaceuticals (bearing inadequate epidemiological evidence of carcinogenicity but) identifiable as unequivocal mutagens. According to current knowledge, a 98.9% (or more) probability of carcinogenicity to humans was reckoned for those 37 genotoxic drugs. Accordingly, these pharmaceutical drugs might be scientifically and regulatorily regarded as “carcinogenic to humans.” In the USA, European Union, or Canada, the great majority of these 37 pharmaceuticals are currently authorized for medical use in humans. From this appraisal results, the following is suggested 1) for the pharmaceuticals listed in this report, to include significant carcinogenicity warnings in the prescribing information; 2) to conduct pharmacoepidemiology studies or risk-benefit analyses (as warranted), and 3) based on the respective risk-benefit analyses, to re-evaluate the authorization of hydralazine and phenoxybenzamine as antihypertensives, oxcarbazepine as an anticonvulsant, and phenazopyridine as a urinary tract antimicrobial or analgesic. For those four latter drugs (e.g., phenoxybenzamine), a 99.5% probability of carcinogenicity to humans was estimated.
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