[Chronic toxicity study of ranitidine hydrochloride orally administered in rats]

Chronic toxicity of ranitidine hydrochloride, a new histamine H2-receptor antagonist, was studied using Sprague Dawley rats. Ranitidine was administered orally at dose levels of 30, 100, 300 and 1000 mg/kg/day for 26 or 53 weeks. In the 1000 mg/kg/day group, ten of 31 females died showing acute toxic signs. In the survived animals of this dose group, changes were observed, such as salivation, depression of body weight gain, increase in water consumption, increase in urinary Na and K excretion, increase in serum albumin content, increase in weights of the liver, kidneys and heart. Main histopathological findings were as follows: centrolobular or midzonal fat deposition in liver, increase in s-ER in hepatocytes, increase in foamy cells in lung and some slight degenerative changes occasionally seen in renal tubules. In the 300 mg/kg/day group, the changes similar to those in the 1000 mg/kg/day group were observed, however, the degree of these changes was more moderate. All of the above-mentioned findings were demonstrated to be reversible in recovery period for 8 weeks. In the 100 and 30 mg/kg/day groups, no remarkable changes were observed in both sexes. It was concluded that the maximum nontoxic dose of ranitidine hydrochloride was 100 mg/kg/day in male and female rats.