Hello, good day!
Could you help me please?
Appendix 2 of EMA/451665/2023, mentions the following:
The carcinogenic potency categorization method applies to N-nitrosamines that have:
- A carbon atom on both sides of the N-nitroso group and where the carbon is not directly linked by a double bond to a heteroatom (i.e. N-nitrosamides, N-nitrosoureas, N-nitrosoguanidines and other related structures are excluded).
In addition, the potency categorization method does not apply to N-nitrosamines:
- Where the N-nitroso group is attached to a nitrogen within a heteroaromatic ring (e.g. nitrosated indole).
These limitations are due to the fact that these subclasses of N-nitroso compounds are not expected to follow the α-hydroxylation metabolic activation pathway, which is believed to be responsible for the highly potent mutagenic and carcinogenic activity of nitrosamines.
That said, does this mean that nitrosamines that do not meet these characteristics may not be considered for future confirmatory testing?
For example, the following molecule:
