Subchronic Studies of Tripelennamine in B6C3F1 Mice

Abstract

The subchronic toxicity of tripelennamine hydrochloride was determined to provide data for selecting dose levels for a 2-year study in mice. Male and female B6C3F1 mice were administered the drug in their feed at dose levels of 0, 150, 300, 600, 1200, and 2400 ppm (calculated as free amine) for 14 days or 0, 300, 600, 1200, 2400, and 4800 ppm for 90 days. Little toxicity was observed in the 14-day study. In the 90-day study, final body weights of males and females of the 4800 ppm groups were reduced 14% and 4%, respectively. Clinical observations and necropsy findings were unremarkable in the 90-day study. Decreased heart weight/brain weight ratios in males and increased liver weight/brain weight ratios in females were seen at dose levels as low as 600 ppm. Histologically, changes consisting of cytomegaly, karyomegaly, and cytoplasmic vacuolization of the liver, mild to severe cytomegaly and necrosis of parotid salivary gland acinar cells, and a mild degree of vacuolar degeneration of the bronchial epithelium of the lung were observed. The results indicate that an oral dose level of 2000 ppm tripelennamine would not be life-shortening in male or female B6C3F, mice in a 2-year study.