Re-Evaluating Acceptable Intake: A Comparative Study of N-Nitrosomorpholine and N-Nitroso Reboxetine Potency.

ABSTRACT: Establishing regulatory limits for Drug Substance-Related Impurities (NDSRIs) is challenging due to the limited genotoxicity and carcinogenicity data available for many of these impurities, often leading to conservative approaches. In this study, we evaluated the genotoxic potential of two structurally related nitrosamines: N-nitrosomorpholine (NMOR) and N-nitroso reboxetine. Compared to the well-studied NMOR, there is little toxicological information available for N-nitroso reboxetine. Currently, both compounds have an acceptable intake value of 127 ng/day, based on a read-across using the available carcinogenicity data of NMOR. While both compounds tested positive in a series of in vitro and in vivo assays, we found that the mutagenic potential of N-nitroso reboxetine was significantly l

SUBMITTER: Zhang S 

PROVIDER: S-EPMC11986803 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature