Subchronic Studies of Pyrilamine in Fischer 344 Rats

Abstract

This study was designed to determine the subchronic effects of the antihistamine, pyrilamine maleate, and to establish dose levels for a 2-year chronic study. Six male and six female F344 rats received dietary pyrilamine concentrations of 0, 392, 783, 1563, 3122, or 6276 ppm (as the free base) for 14 days. Only weight gain suppression was noted, at 3122 and 6276 ppm, especially in males. When 12 male and 12 female F344 rats were fed pyrilamine for 90 days at 0, 750, 1500, 3000, 6000, or 12,000 ppm, weight gain was suppressed and organ/body weight ratios often were higher than in controls at 3000 ppm and above. Heart/brain and thymus/brain ratios were decreased at 3000 ppm and above in males and at 6000 or 12,000 ppm in females. All rats receiving 6000 or 12,000 ppm pyrilamine exhibited severe diffuse parenchymal cell cytomegaly in the parotid salivary glands with a dose-related decrease in severity and prevalence at lower concentrations. Hepatocellular vacuolization, present only in males, increased in severity with dose, starting at 750 ppm. The severity of liver fatty metamorphosis increased with dose at the three low doses but was less apparent and/or disappeared at 6000 and 12,000 ppm. It was concluded that 3000 ppm pyrilamine would not be life threatening to F344 rats in a chronic study.