Optimizing the detection of N-nitrosamine mutagenicity in the Ames test

• Published in: Regulatory toxicology and pharmacology Vol. 153; p. 105709
• Main Authors: Heflich, Robert H., Bishop, Michelle E., Mittelstaedt, Roberta A., Yan, Jian, Guerrero, Sharon K., Sims, Audrey M., Mitchell, Kamela, Moore, Nyosha, Li, Xilin, Mei, Nan, Elespuru, Rosalie K., King, Sruthi T., Keire, David A., Kruhlak, Naomi L., Dorsam, Robert T., Raw, Andre S., Davis Bruno, Karen L., McGovern, Timothy J., Atrakchi, Aisar H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.11.2024
• Subjects: Acceptable intake limit; Activation, Metabolic; Ames test; Animals; Carcinogenic potency categorization approach; Cricetinae; Drug Contamination; Drug impurities; Escherichia coli - drug effects; Escherichia coli - genetics; Hamster liver S9; Liver - drug effects; Liver - metabolism; Male; Mutagenicity dose-response ranking; Mutagenicity Tests - methods; Mutagens - toxicity; Nitrosamine drug substance-related impurities; Nitrosamines - toxicity; Preincubation; Rat liver S9; Rats; Salmonella typhimurium - drug effects; Salmonella typhimurium - genetics; Small-molecule N-Nitrosamines; Drug impurities; Nitrosamine drug substance-related impurities; Hamster liver S9; Ames test; Mutagenicity dose-response ranking; Acceptable intake limit; Carcinogenic potency categorization approach; Preincubation; Rat liver S9; Small-molecule N-Nitrosamines

Accurately determining the mutagenicity of small-molecule N-nitrosamine drug impurities and nitrosamine drug substance-related impurities (NDSRIs) is critical to identifying mutagenic and cancer hazards. In the current study we have evaluated several approaches for enhancing assay sensitivity for ev...