Subchronic Studies of Tripelennamine in Fischer 344 Rats

Abstract

The purpose of this study was to determine the subchronic toxicity of the antihistamine tripelennamine and to allow selection of appropriate doses for chronic studies. Male and female Fischer 344 rats were administered tripelennamine hydrochloride in the feed at dose levels of 0, 300, 600, 1200, 2400, and 6000 ppm (as the free amine) for 14 days or at dose levels of 0, 150, 300, 600, 1200, and 2400 ppm for 90 days. In the 14-day study, all of the animals in the 6000 ppm groups died. All others survived until killed. Final body weights of treated groups were reduced from 3% to 25%. Cytoplasmic vacuolization of the liver was observed. In the 90-day study, a dose-dependent reduction in body weight gain was produced by tripelennamine, with a 10% reduction in final body weight occurring between 300 and 600 ppm. Reductions in various organ weights were found to be correlated with reduced final body weights. Tripelennamine produced cytoplasmic vacuolization or fatty change in the liver, cytomegaly and granular basophilic cytoplasm in the parotid salivary gland, and vacuolar degeneration of the bronchial epithelium of the lung. Based on the results of this study, it was determined that 400 ppm tripelennamine administered ad libitum in the feed to both male and female Fischer 344 rats would be an appropriate highest dose for a 2-year carcinogenicity study.