Chronic dietary oncogenicity studies of indecainide in rats and mice

Chronic toxicity and oncogenicity studies of indecainide, an antiarrhythmic compound, were conducted in Fischer 344 rats and B6C3F1 mice at dietary concentrations of 0.0, 0.02, 0.04, or 0.08%. Sixty animals per sex per dose of each species were tested. The duration of compound administration was 2 years for both species. The average daily dose was 9.0, 18.0, or 37.0 mg/kg for rats and approximately 27.0, 53.0, or 113.0 mg/kg for mice. In rats, no biologically significant changes were seen with respect to mortality and clinical signs. Body weight gain and daily food consumption were significantly depressed in the 0.08% dose group males and 0.04 and 0.08% females. Treatment with indecainide had no toxicologically important effects on hematologic or clinical chemistry parameters or on organ weight values. Centrilobular fat deposition was present in the livers of males in the 0.04 and 0.08% dose groups. The incidence of benign and malignant tumors in the treated groups was not increased by treatment with indecainide. Survival of B6C3F1 mice was not significantly affected by exposure to indecainide. Mean body weight gain was slightly decreased throughout the study in mice receiving 0.02 or 0.04%, while mice receiving 0.08% indecainide had moderately decreased body weight gain. Treatment with indecainide had no toxicologically important effects on the hematologic or clinical chemistry parameters measured. No biologically important effects were observed in organ weight values. The incidence of non-neoplastic and neoplastic lesions was similar to those associated with aging in this strain and these were considered to be unrelated to drug treatment. Based on the findings in these studies, indecainide was not carcinogenic to either F344 rats or B6C3F1 mice at dietary concentrations of 0.02, 0.04, or 0.08% for 2 years.