Lack of induction of nuclear aberrations by captan in mouse duodenum

The fungicide, captan, is known to induce point mutations in vitro. In extremely high doses, technical grade captan leads to duodenal tumors in mice. In short-term in vivo assays for genotoxicity, equivocal results have been obtained with captan. In this study, the genotoxicity of captan was studied in vivo in the proximal small intestine of the mouse, the site of its oncogenicity. Orally administered captan up to 4,000 mg/kg body weight failed to induce a response in the small intestine nuclear aberration assay in a wide range of doses under a variety of experimental conditions, including pretreatment of animals with L-buthionine-S, R-sulfoximine (an inhibitor of glutathione biosynthesis). 1,2,3,6-Tetrahydrophthalimide and bis (trichloromethyl)disulfide, two compounds that have been identified as impurities in technical grade captan, also failed to produce positive results in this assay.