Fantastic publication by Bringezu et al.
Salmonella typhimurium TA100 and TA1535 and E. coli WP2 uvrA are highly sensitive to detect the mutagenicity of short Alkyl-N-Nitrosamines in the Bacterial Reverse Mutation Test
Humans are exposed to low levels of N-nitrosamines via different sources. N-Nitrosamines have recently been detected as impurities in various marketed drugs and they are known mutagenic carcinogens belonging to the cohort of concern as referred to in the ICH M7 guideline. Despite their well-known mutagenic properties, there is ongoing discussion on the suitability of the bacterial reverse mutation assay and using induced rat liver S9 as the external source of metabolism to detect their mutagenic potential. Therefore, we have investigated the mutagenic potential of N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodipropylamine, and N-nitrosodibutylamine in vitro under various conditions. Our work showed that the bacterial reverse mutation assay applying plate incorporation or preincubation protocols and using [Salmonella typhimurium] strains TA100 and TA1535 and E. coli WP2 uvrA is suitable to predict the [mutagenicity] of n-nitrosamines in the presence of phenobarbital/β-naphthoflavone induced rat liver S9.