Hello to everyone!
The CPCA guideline mentions the following:
"Additionally, the potency categorization approach does not apply to N-nitrosamines where the N-nitroso group is attached to a nitrogen within a hetero aromatic ring (e.g., nitrosated indole)."
How is the AI of the above Nitrosamines calculated? Do we take the “worst case” 18ng/day?
Thank you in advance.
Nitrosated indoles, and similar compounds, I would argue are non-CoC due to an implausibility of forming a diazonium ion - and can thus be controlled to the general 1500 ng/day TTC. https://pubs.acs.org/doi/abs/10.1021/acs.oprd.3c00008
Research is ongoing as to how to categorize/assign potency for the other excluded categories, i.e. nitrosated amides/ureas/etc, which do form diazonium ions and can thus be more potent than the TTC; in the first instance I would use read-across for these if a suitable surrogate can be found.
Hi, @David
in your opinion, the read-across approach is applicable also to the active substances which do not form nitrosamines?
i.e. if the nitrosation of Irbesartan does not form the corresponding N-nitroso Irbesartan, but an oxime derivative:
Reaction of Irbesartan with Nitrous Acid Produces Irbesartan Oxime Derivatives, rather than N-Nitrosoirbesartan
could we reasonably assume that the same reaction should occur also for other sartans with a similar side chain, like Olmesartan Medoxomil?
[quote=“M.Louros, post:1, topic:8434, full:true”]
The CPCA guideline mentions the following:
"Additionally, the potency categorization approach does not apply to N-nitrosamines where the N-nitroso group is attached to a nitrogen within a hetero aromatic ring (e.g., nitrosated indole)."
How is the AI of the above Nitrosamines calculated? Do we take the “worst case” 18ng/day?
Thank you in advance.
