Evaluation of 4-methylimidazole, in the Ames/Salmonella test using induced rodent liver and lung S9

Environmental and Molecular Mutagenesis
Carol Beevers, Richard H Adamson

Abstract

4-methylimidazole (4-MeI) is formed by the interaction of ammonia with reducing sugars and low levels have been identified as a by-product in coffee, soy sauce, wine, dark beers, soft drinks, and caramel colors. The 4-MeI has been reported to induce alveolar/bronchiolar tumors in mice but not rats. Its mechanism of action is unlikely to be due to genotoxicity as 4-MeI does not induce mutation in Salmonella typhimurium and does not induce micronuclei in rodent peripheral erythrocytes or bone marrow cells. However, the question of whether genetically reactive intermediates could be formed via lung-specific metabolism has not previously been addressed. The 4-MeI was tested for its ability to induce mutation in five standard Ames strains of S. typhimurium using induced rat (F344/N) and mouse (B6C3F1) liver and lung S9 as a source of exogenous metabolism. The chemicals were tested in an OECD 471-compliant bacterial reverse mutation assay, using both plate-incorporation and pre-incubation methodologies, together with 10% S-9 metabolic activation. No induction of mutation (as measured by an increase in revertant colonies) was observed and it was concluded that 4-MeI was not mutagenic in S. typhimurium using either rodent liver or lung...Continue Reading

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Citations

Nov 9, 2016·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Takeshi Morita, Chikako Uneyama
Feb 1, 2017·Drug and Chemical Toxicology·Rima Celik, Mehmet Topaktas
Aug 4, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·David BrusickMarisa O Rihner
Jun 27, 2021·Regulatory Toxicology and Pharmacology : RTP·Susan J BorghoffGrace A Chappell

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