3-NOP: Mutagenicity and genotoxicity assessment

• Published in: Food and chemical toxicology Vol. 123; pp. 566 - 573
• Main Authors: Thiel, A., Schoenmakers, A.C.M., Verbaan, I.A.J., Chenal, E., Etheve, S., Beilstein, P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-01-2019
• Subjects: 3-NOP; Genotoxicity; Mutagenicity; Toxicity; 3-NOP; Mutagenicity; Toxicity; Genotoxicity
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2018.11.010

3-NOP (3-nitroxy-propanol) is a new development compound which reduces methane emission from ruminating animals. For registration purposes with emphasis on EU and North America data requirements, mutagenic and genotoxic potential was assessed following OECD protocols and respective guidance documents. 3-NOP mutagenicity and genotoxicity testing raised no flags with regard to these endpoints. In silico assessment of 3-NOP and its major plasma metabolite NOPA (3-nitroxy-propionic acid) were predicted negative with regard to the bacterial reverse mutation (Ames) test. Ames test, mouse lymphoma assay, in vitro micronucleus test, and the oral in vivo micronucleus test using rat bone marrow were all negative. Exposure of the rat bone marrow was verified by the presence of 3-NOP and its metabolites NOPA and HPA (3-hydroxy-propionic acid) a naturally occurring substance in mammals) in plasma following oral dosing. It is therefore concluded that 3-NOP and its metabolites pose no mutagenic and genotoxic potential.
•In silico, in vitro, and in vivo methods in a weight-of-evidence (WoE) assessment.•3-NOP and metabolites are not mutagenic.•3-NOP and metabolites are not genotoxic.