Subchronic Studies of Thenyldiamine in Fischer 344 Rats

Abstract

Thenyldiamine, an antihistamine used extensively as a sleep aid, has not been adequately studied for subchronic or chronic toxicity. This report presents the results of subchronic studies of thenyldiamine in the rat. Fischer 344 rats were administered thenyldiamine hydrochloride in their feed at dose levels of 0, 250, 500, 1000, 2000, and 4000 ppm (calculated as free amine) for 14 days or at dose levels of 0, 125, 250, 500, 1000, and 2000 ppm for 90 days. There were no mortalities in either study. Except for decreased weight gain, no significant treatment-related toxicity was observed in the 14-day study. In the 90-day study, 500 ppm and 1000 ppm were the lowest doses responsible for causing a significant decrease in weight gain in females and males, respectively. Clinical signs, gross observations at necropsy, and organ weights in the 90-day study were not remarkable. Histologically, a treatment-related mild fatty change was found in the livers of male rats, but the effect was so mild as to make the significance questionable. Treatment-related changes were also observed in the parotid salivary glands, but the significance of these changes was also questionable in view of the variability of this gland and its recognized physiological responses to antihistamines.