13-Week oral toxicity study of captafol in F344/DuCrj rats.

Captafol fed at concentrations of 0, 0.075, 0.15, 0.3, and 0.6% to both sexes of F344 rats for 13 weeks produced dose-related decreases in body weight in males and females given 0.15% or higher concentrations. A dose-dependent decrease in urinary pH was observed in males receiving 0.3 or 0.6% and in females given 0.15% or higher concentrations of captafol. The 0.3 and 0.6% doses produced slight increases in leukocyte count and glutamic-pyruvic transaminase activity in females, along with a mild increase in alkaline phosphatase activity in the 0.6% case. The liver- and kidney-to-body weight ratios were increased in both male and female rats. Histopathological changes were observed in the forestomach, liver, and kidney. Squamous cell hyperplasia and edema accompanied by polynuclear leukocyte infiltration and dilation of vessels in the lamina propria were observed in the forestomach of both sexes given 0.15% or higher concentrations. Oval cell proliferation was apparent around Glisson's sheath in the livers of females given 0.3 and 0.6% captafol. Multifocal appearance of karyocytomegaly and tubular cell atypia in the proximal tubules of the kidney was found in the 0.3 and 0.6% groups of both sexes.