Keynote comment: nitrosatable drugs, cancer, and guidelines for genotoxicity

Guidelines for genotoxicity testing of pharmaceuticals1 establish that specific protocol modifications or additional tests are necessary for the best possible detection of genotoxicity of compounds with specific structural alerts. However, they do not show the need for doing adequate tests in order to assess whether a nitrosatable drug could undergo endogenous nitrosation to a genotoxic-carcinogenic N-nitroso compound. No assessment of such a possibility was found in more than 200 investigators' brochures on theoretically nitrosatable drugs from the past 6 years that we examined as members of various ethics committees. The omission of assessing the possible risk of drug nitrosation to human beings is difficult to justify.