@conudel will probably take this live, but my perspective is that there are at least two categories to consider - as discussed elsewhere (Ponting & Foster), the original CoC was simply NN=O, so that captures lots of compoundsโฆ
to briefly summarise that paper and other work:
- N-nitrosoureas/amides/carbamates: Mostly mutagenic and some exemplars are potent carcinogens. However, much less likely to form (Schlingemann et al) and if they do form no metabolic activation required so current Ames test concerns not so significant - but equally metabolism-derived SAR, such as that that underpins the CPCA, is not applicable - so even if these were part of the current regulatory focus, a different CPCA-like approach would be needed
- N-nitrosated aromatic systems, such as N-nitrosoindoles: Can be mutagenic via an alternative mechanism, but not CoC-potent - normal M7 control
- Nitrosated heterosubstituted amines: Can be mutagenic via an alternative mechanism, but not CoC-potent - normal M7 control
- Nitrosated primary amines: probably unstable
For clarity in discussing these, Iโve tended to push the use of nitrosamine specifically to mean nitrosated secondary amines (nitrogen must be singly bonded to exactly two carbon atoms, those carbon atoms may not be formally multiply bonded to a heteroatom (unless that bond is part of an aromatic system, e.g. a 2-pyridyl group), and used the terms listed above for the other N-nitroso compounds.