[Toxicology of carteolol]

Studies of the acute toxicity of 5-(3-tert-butylamino-2-hydroxy-propoxy)-3, 4-dihydro-2(1H)-quinolinone hydrochloride (carteolol hydrochloride, Endak, Endak mite) in various species by different modes of administration revealed comparatively slight necropsy and histological changes despite characteristic clinical features of poisoning, There were only minor discrepancies in LD50 between the different species, and no sex differences were observed. The LD50 was 2000-4000 times the therapeutic dose. Death is thought to be due to excessive enhancement of the pharmacological action of the sympathomimetic component with extreme abnormalities of blood distribution and interference with cardiac and lung function. In subchronic and chronic toxicity tests in rats no effects due to the drug were demonstrable for doses of up to 150 mg/kg. In dogs the highest dose free from side-effects was between 3 and 30 mg/kg. Above 10 times the therapeutic dose there was some increase in brown adipose tissue, but this is not thought to be of any pathological significance. No teratogenic effects were detected in experiments on mice, rats and rabbits, and no embryotoxic or fetotoxic activity was seen except for doses high enough to produce toxic effects in the mother animals. No carcinogenic properties were identified. Tests for mutagenic effects (S. typhimurium, E. coli, cytogenetic studies in rats, dominant lethal test) yielded negative results.