EMA Nitrosamine Q&A Rev13 published

Dear All,

In this revision, the AI limit for new six nitrosamines are included. Some of them are higher than 1.5 microgram per day. It’s helpful for read across calculation.


I’ll update our AI table in the community. Thank you

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NPYR and NDELA are included to serve as points of departure for derivation of other AIs by SAR and read across. They may be used for some NDSRIs in the future.



I’m glad to see the evolution and clarity of the Q(SAR) approach taken

Nitroso Nebivolol looks more similar to NDELA.
It is very helpful.

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Can anybody hep how 78000 ng/day derived for N-nitroso Diphenylamine (CAS RN 86-30-6).
EMA states that “Limit based on the most sensitive TD50 derived from the most robust TD50 dataset from carcinogenic potency database (CPDB) applying the lower boundary of the 99% CI for the TD50 estimate (TD50L01)”

Interested to know where does TD50 of 78 mg/kg/day came from?

This may be considered best surrogate for Nebivolol

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I am working on FDC (Fixed Dose Combination) say Drug X+ Drug Y. MDD (Maximum Daily Dose) of Drug Y as per literature is 450 mg but for my FDC MDD of Drug Y is 210 mg. Can you plz. explain which MDD should be used to determine NDSRI for drug Y.

The limitation was calculated form this POD

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@desaimayur78 MDD as per Fixed dose combination should be considered i.e. 210 mg of drug Y

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