FDA Revisiting the mutagenicity and genotoxicity of N-nitroso propranolol in bacterial and human in vitro assays

[Diego_HM]

Hi Nitrosamine exchange community,

I have recently came across to one very interesting paper around the mutagenicity and genotoxicity of N-nitroso-propanolol (NNP) with various methodologies performed by the FDA.

In summary, against “some” odds NNP is positive for bacterial mutation in the Ames test, damages DNA, induces MN and is mutagenic in human cells.

Revisiting the mutagenicity and genotoxicity of N-nitroso propranolol in bacterial and human in vitro assays - ScienceDirect

With this results I would say the “lol” nitrosamines would maybe get more complex to de-risk with just “in-vitro” and how for example this corresponds to EFPIA position for beta-blockers.

[Naiffer_Host]

In summary, we revisited the issue of NNP mutagenicity and genotoxicity using multiple
testing approaches. This study demonstrated that NNP is positive for bacterial mutation in the
Ames test and that hamster liver S9 is generally more effective than rat liver S9 in detecting the
mutagenicity of NNP in bacteria. NNP also damages DNA, induces MN, and is mutagenic in
human cells; and CYP2C19 appears to be the main human enzyme accounting for its
bioactivation. Our results provide novel information for the hazard identification and risk
assessment of NNP, and the types of experiments with expanded testing conditions utilized in
this study may also be useful for exploring and characterizing the mutagenicity and genotoxicity
of other nitrosamine and NDSRI drug impurities.