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Published on: May 12, 2019
Folpet-induced short term cytotoxic and proliferative changes in the mouse duodenum
Elliot Gordon1, Samuel M Cohen, Pramila Singh
1Elliot Gordon Consulting, LLC, Princeton Junction, NJ, USA. ebgfox@comcast.net
Toxicology Mechanisms and Methods
|October 25, 2011
Summary
Folpet, an agricultural fungicide, causes tumors in mice by damaging the duodenum. These early toxic effects and subsequent cell regeneration are reversible, suggesting a non-DNA reactive mechanism for folpet carcinogenicity.
Area of Science:
- Toxicology
- Gastroenterology
- Carcinogenesis
Background:
- Folpet is an agricultural fungicide known to induce tumors in the mouse gastrointestinal tract.
- Tumor formation in the duodenum has a dietary threshold of approximately 1000 ppm.
Purpose of the Study:
- To investigate the early histological changes in the mouse duodenum induced by folpet.
- To evaluate the reversibility of these folpet-induced changes.
Main Methods:
- Mice were fed a diet containing 6000 ppm folpet for 28 days.
- Histological and macroscopic changes were assessed during treatment and after a 17-day recovery period.
Main Results:
- Macroscopic and microscopic duodenal and forestomach changes were observed, including hyperplasia and inflammation.
- These changes showed a reduction in severity and incidence during the recovery period, indicating reversibility.
- Early histological changes suggest a non-DNA reactive mode of action involving cytotoxicity and regenerative proliferation.
Conclusions:
- Folpet-induced duodenal tumors in mice appear to result from cytotoxicity leading to regenerative proliferation, rather than direct DNA interaction.
- Exposure levels below those causing cytotoxicity are unlikely to lead to tumor formation.
