Subchronic Studies of Triprolidine in Fischer 344 Rats

Abstract

Triprolidine, used extensively as an antihistamine, was studied for subchronic toxicity by administration as an admixture in the diet to male and female Fischer 344 rats at dosage levels of 0, 156, 312, 625, 1250, and 2500 parts per million (ppm) for 14 days and in a second study at 0, 250, 500, 1000, 2000, and 4000 ppm for 90 days. In the 14-day study, the only sign of toxicity observed either clinically or histologically was a reduction of final body weights (less than 10%) of both male and female rats in the 2500 ppm dosage group associated with reduced food consumption. In the 90-day study, final body weights were reduced, compared to controls, at the higher dosage levels with 4000 ppm resulting in a 20% and 13.4% reduction in males and females, respectively. Target organs were identified as the liver with hepatic fatty change and the parotid salivary gland, which exhibited treatment-related cytoplasmic alterations of the acinar cells. Males were more susceptible than females to both of these effects. These results indicate that rats would tolerate 2000 ppm triprolidine in a 2-year chronic bioassay without significant shortening of life span.