Hello，everyone！
I would like to ask: What is the basis for EMA’s revision of the limit for N-Nitroso-N-desmethyl-diphenhydramine from 18 ng/day to 100 ng/day? Where can I find the relevant supporting documentation?
based on EMA’s justification/note: Limit derived using structure-activity-relationship (SAR)/read-across approach using the TD50 of NNK as point of departure.
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While EMA has changed the limit for N-Nitroso-desmethyl-diphenhydramine to 100 ng/day, FDA still sticks to the old limit. How do you expect the chances that FDA will adpot the EMA limit? For countries outside EU/US, do you have experience which countries rely on the EMA limit and for which countries the FDA limit is the reference?
I also was curious whether FDA would move the AI limit to 100 ng/day under this rationale. It seems as though other structurally similar NDSRIs have been granted this AI limit under the NNK SAR/read-across rationale. Also was curious if one could argue this revision for others such as N-nitroso-N-desmethylchlorpheniramine?
FDA is using CPCA Cat 1 for the limit of 26.5 ng/day… I guess both are justifiable