1-methyl-4-nitrosopiperazine can also be consider. Moreover EMA and Health Canada has published limit for 1-methyl-4-nitrosopiperazine.
Health Canada limit: 96.0 ng/day while EMA limit: 26.5 ng/day
Please note that is based on my subjective opinion (It can be subjected to correction)- Not published value. Still in the process of evaluation. Conservatively that is the least value that can be defended considering all piperazine based nitrosamines.
Read across from TriMNP will give an AI of 153 ng/day. TriMNP is the most potent nitroso-piperazine in the LCDB and it has robust carcinogenicity data, so it should be accepted as a valid surrogate for other nitroso-piperazines such as nitroso-ciprofloxacin.
Thanks @conudel. Agree to some extent. It looks like the most potent among all N-nitroso piperazines is 1-methyl-4-nitrosopiperazine. There is difference between 1,2,6-trimethyl-4-nitrosopiperazine and 1-methyl-4-nitrosopiperazine in terms of carcinogenicity.
Structurally 1-methyl-4-nitrosopiperazine looks more closer to N-nitroso Ciprofloxacin.
with absence of beta methyl substituents.
The MW difference should also be accounted for when doing a read across. You’re expecting the functional groups to contribute to the toxicity, not the MW generically.
Let me explain better. Don’t worry about the MW when identifying the closest surrogate. Sure, steric hinderances, etc. should be accounted for, but the last step in the process is:
AI (surrogate) * MW (molecule of interest) / MW (surrogate)
Dear @jason.brown. I Understand what you are referring to. Definitely one should not worry about MW for finding analogue because for NDSRI it is tough.
In regard to Molecular weight correction with respect to AI- could you please let me know does agency accepting such approaches.