Resolution of historically discordant Ames test negative/rodent carcinogenicity positive N-nitrosamines using a sensitive, OECD-aligned design.

ABSTRACT: The in vitro bacterial reverse mutation (Ames) test is crucial for evaluating the mutagenicity of pharmaceutical impurities. For N-nitrosamines (NAs) historical data indicated that for certain members of this chemical class, the outcomes of the Ames test did not correlate with their associated rodent carcinogenicity outcomes. This has resulted in negative outcomes in an OECD (Organization for Economic Cooperation and Development)-aligned Ames test alone (standard or enhanced) no longer being considered sufficient by regulatory authorities to assess potential carcinogenic risk of NAs if present as impurities in drug products. Consequently, extensive follow-up in vivo testing can be required to characterize the potential mutagenicity and genotoxic carcinogenicity of NA impurities (i.e. beyon

SUBMITTER: Thomas DN 

PROVIDER: S-EPMC12022218 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature