Subchronic Studies of Pyrilamine in B6C3F1 Mice

Abstract

The purpose of this study was to determine the effects of subchronic exposure to the antihistamine pyrilamine maleate and to establish dosage levels to use in a 2-year chronic study. A 14-day repeated-dose study in male and female B6C3F1 mice at dietary levels of pyrilamine (as the free base) of 0, 196, 392, 783, 1563, or 3122 ppm revealed no influence on body weight gain and resulted in no deaths, nor abnormal clinical or gross necropsy observations. Parotid gland cell necrosis was more apparent in high-dosage groups than in controls of either gender. Male and female B6C3F1 mice also were administered pyrilamine for 90 days at dietary concentrations of 0, 375, 750, 1500, 3000, or 6000 ppm. Weight gain was markedly suppressed in the 6000 ppm group, but less so at 1500 and 3000 ppm. Parotid gland cell necrosis was apparent in males receiving 750 ppm pyrilamine and above and in females at 1500 ppm and above. Cytomegaly was noted in the parotid glands of both sexes at midlevel dosages but not in control, low-dosage, or high-dosage animals. It was concluded that 1500 ppm pyrilamine would not be life-threatening to B6C3F1 mice in a chronic study.