Hi everyone,
I wasn’t able to attend SOT, but I have seen an abstract for a poster called “Mutagenicity and Genotoxicity of Twelve Nitrosamine Drug Substance-Related Impurities in Human TK6 Cells: Correlation with Enhanced Ames Test” which sounds really interesting.
Does anyone know if there are any papers around linked to this abstract?
Any other interesting developments on nitrosamines discussed?
There is a large number of exciting poster and presentations by the FDA
2024_nctr_sot_presentations_508.pdf (283.5 KB)
Xiaoqing Guo (DGMT). Abstract Number: 3094, Poster Board Number: P198. Title: “In vitro mutagenicity assessment of N-nitrosodimethylamine in 2D and 3D HepaRG cell cultures using High-Fidelity sequencing”
Xilin Li (DGMT). Abstract Number: 3090, Poster Board Number: P194. Title: “Mutagenicity and Genotoxicity of Twelve Nitrosamine Drug Substance-Related Impurities in Human TK6 Cells: Correlation with Enhanced Ames Test”
Tao Chen (DGMT). Abstract Number: 3091, Poster Board Number: P195. Title: “Application of Duplex Sequencing to Evaluate Mutagenicity of Aristolochic Acid and Methapyrilene in Fisher 344 Rats”
Robert Heflich (DGMT). Abstract Number: 1210. Title: “FDA N-nitrosamine drug impurity project” (Also participating in a panel discussion after presentations: Carcinogenic potency assessment and other hot topics for regulation of N-nitrosamines: a panel discussion)
A big shot out to our FDA colleagues who have been kind to share the posters from the recent SOT …
Xiaoqing Guo: In vitro mutagenicity assessment of N-nitrosodimethylamine in 2D and 3D HepaRGcell cultures using High-Fidelity sequencing
2024 SOT Carol NDMA HiFi.pdf (758.1 KB)
Xilin Li (DGMT). “Mutagenicity and Genotoxicity of Twelve Nitrosamine Drug Substance-Related Impurities in Human TK6 Cells: Correlation with Enhanced Ames Test”
SOT2024 upload.pdf (621.3 KB)
Many thanks @Naiffer_Host for posting these, and for everyone at the FDA for providing them.
I believe that the publication for the work in the first poster is here, for people who want to delve into much more detail:
The second poster is very interesting, on several fronts. It is good to see a human based alternative to the AMES test, and that the data so far correlates between the two different test methods. The poster has raised a few questions in my mind:
where the FDA have tested nitrosamines and they are negative by both the AMES test and the new test, will the FDA be publishing these findings and updating the daily limits appropriately?
the negative result for Phenylephrine is a surprise (to the authors of the poster as well), as under the current CPCA assessment it should be category 2, and have a limit of 100ng/day. Structurally it is similar to other NDSRIs tested, that were positive. Is this caused by the OH group present within Phenylephrine? Does this give indications for potential updates to the CPCA?
