Induction of gastrointestinal tumors in mice fed the fungicide folpet : possible mechanisms

Dietary administration of the fungicide folpet, N-(trichloromethylthio)phthalimide, to B6C3F1 mice at dose levels of 1,000, 5,000 and 10,000 ppm induced a dose-related appearance of duodenal atypical hyperplasia, adenomas and adenocarcinomas. The appearance in some of these animals of gastric papillomas and gastric squamous cell carcinomas was correlated in many instances to the presence of duodenal obstructions. It is suggested that the gastric lesions appeared subsequent to, and as an indirect result of, these partial lumenal duodenal obstructions. We suggest that the presence of duodenal obstructions is consistent with the notion that reflux of folpet, bile acids and pancreatic enzymes into the stomach may have acted to irritate and consequently stimulate local neoplastic proliferation. In addition, the duodenal obstructions may have resulted in delayed emptying time of the stomach contents with consequential stagnation. This would cause high concentrations of folpet to act locally on the gastric mucosa.