Table 2.
Mutagenicity and genotoxicity evaluation of ten nitrosamine drug substance-related impurities (NDSRIs).
| NDSRIs | Mutation |
MN |
Comet |
γH2A.X |
|||||
|---|---|---|---|---|---|---|---|---|---|
| Enhanced Amesa | TK/HPRT b | TK6 no S9b | TK6 + 2 % hamster S9b | 2D HepaRG | 3D HepaRG | 2D HepaRG | 3D HepaRG | 3D HepaRG | |
|
| |||||||||
| N-nitroso-duloxetine | + | + | + | + | + | + | + | + | + |
| N-nitroso-fluoxetine | + | + | + | + | + | + | + | + | + |
| N-nitroso-lorcaserin | + | + | − | + | − | + | + | + | + |
| N-nitroso-nortriptyline | + | + | + | + | + | + | + | + | + |
| N-nitroso-varenicline | + | + | − | + | − | + | + | + | + |
| N-nitroso-diclofenac | − | − | + | − | − | − | − | − | − |
| N-nitroso-folic acid | − | N/A | N/A | N/A | − | − | − | − | −c |
| N-nitroso-paroxetine | − | − | − | − | − | − | − | − | − |
| N-nitroso-desvaleryl-valsartan | − | − | − | − | − | − | − | − | − |
| N-nitroso-desvaleryl-valsartan methyl ester | − | − | + | − | − | − | − | − | −c |
a
The Ames responses were obtained from Heflich et al. (2024).
b
The responses in TK6 cells were obtained from Li et al. (2024).
c
Positive/equivocal when 3D spheroids were exposed to NDSRIs with hEGF for 72 h (Fig. 4).