Case Studies for CPCA Scoring

[Yosukemino]

I add the example of NTTP(7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo-[4,3- a]pyrazine) @David posted.

EMA Q&A Rev. 16 EMA/409815/2020 - MAJOR UPDATE

that is I believe the structure - it’s not nitroso-sitagliptin itself, rather the nitrosamine of an impurity of sitagliptin. It has been assigned a compound-specific limit of 37 ng/day by read-across from nitroso-1,2,3,6-tetrahydropyridine (with the aromatic group assumed to be comparable to the double bond there and the ‘arylic’ position like the allylic in NTHP), though by CPCA would have a limit of 100: (2,2) for H-count = 1 In a generic 6-membered ring = 2 Aromatic group at b-position ac…

The AI of NTTP and NNV(nitroso-varenicline) are both calculated from the AI of NTHP by the read-across method. Though NTTP has the activating feature, NNV has no activating feature. But the score of NNV is 2, the same as that of NTTP. It’s interesting.

The score of NNV: ((2,2) for H-count = 1, In a 7-membered ring = 1, Total2, limit 100 ng/day).