[On the chronic toxicity of labetalol (AH-5158); a combined alpha-and beta-adrenoceptor-blocking agent (author's transl)].

Chronic toxicity and recovery tests of labetalol hydrochloride, alpha-and beta-adrenoceptor blocking agent, were carried out using male and female Wistar strain rats. The drug was orally administered at 50, 100 or 200 mg/kg/day for 9 months. In all the drug-treated groups, increase in salivation was observed from immediately after to 15 minutes after dosing through treatment period. Suppression of body weight gain was observed in male rats in the 200 mg/kg/day group. Food comsumption tended to be higher in all the drug-treated groups than in the control group. Similar trend was seen also in water comsumption, and increase in urine volume was noted in the groups treated with 100 and 200 mg/kg/day. In the serum biochemical examination, dose-dependent elevation in potassium level was noted in all drug-treated groups, but the values were within the range of physiological variation. In the 100 and 200 mg/kg/day groups, an increase was observed in the absolute heart weight and in its relative weight against body weight. Major abnormalities found in histopathological findings were; swelling of parenchymatous cells in liver and kidney, swelling of fibers and swelling or proliferation of interstitial cells in cardiac and skeletal muscles, and congestion in spleen. No notable abnormality was found in any examination item in the recovery test.