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Mutagenicity of the C-nitroso analog of fenitrothion
Abstract:
The chemicals fenitrothion, nitroso fenitrothion, amino fenitrothion and 3-methyl-4-nitrophenol were tested for mutagenicity to Salmonella typhimurium strains TA98 and TA100, both in the presence and absence of rat liver S-9 mix. The strong mutagenicity of nitroso fenitrothion to both strains either in the presence or absence of S-9 mix contrasted with the observation that fenitrothion displayed no mutagenicity in these tester strains. The results suggest that the normal nitroreductases present in TA98 and TA100 cannot metabolize fenitrothion to a mutagenic metabolite. This inability of the tester strains to effect partial nitroreduction results in the failure of this screening system to predict the potential genotoxicity of this pesticide.
Insights
Nitroso fenitrothion is mutagenic, but fenitrothion is not detected as mutagenic in Salmonella strains. This indicates limitations in using these tester strains to predict the genotoxicity of fenitrothion.
Area of Science:
- Environmental toxicology
- Chemical mutagenesis
- Bacterial genetics
Background:
- Fenitrothion is an organophosphate insecticide widely used globally.
- Assessing the genotoxicity of pesticides is crucial for environmental and human health risk assessment.
- The Ames test using Salmonella typhimurium is a standard method for mutagenicity screening.
Purpose of the Study:
- To evaluate the mutagenicity of fenitrothion and its metabolites, including nitroso fenitrothion, amino fenitrothion, and 3-methyl-4-nitrophenol.
- To investigate the metabolic activation pathways of these chemicals in Salmonella typhimurium strains TA98 and TA100.
- To determine the efficacy of the Ames test in predicting the genotoxicity of fenitrothion.
Main Methods:
- Bacterial mutagenicity assays were performed using Salmonella typhimurium strains TA98 and TA100.
- Tests were conducted both in the presence and absence of rat liver S-9 mix to assess metabolic activation.
- The chemicals tested included fenitrothion, nitroso fenitrothion, amino fenitrothion, and 3-methyl-4-nitrophenol.
Main Results:
- Nitroso fenitrothion exhibited strong mutagenicity to both Salmonella strains, irrespective of S-9 mix presence.
- Fenitrothion itself did not display mutagenicity in either strain, with or without metabolic activation.
- The results suggest that Salmonella strains TA98 and TA100 lack the necessary nitroreductases to metabolize fenitrothion into a mutagenic form.
Conclusions:
- The standard Ames test may underestimate the genotoxic potential of fenitrothion due to the inability of tester strains to perform essential metabolic activation.
- Nitroso fenitrothion serves as a potent mutagen, highlighting the importance of considering its formation.
- Further research is needed to develop or utilize screening systems capable of accurately assessing the genotoxicity of pesticides like fenitrothion.