Toxicology of mabuterol.
The acute, subacute and chronic toxicity of dl-1- (4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butyl-amino-ethanol hydrochloride (mabuterol), a new beta 2-selective adrenoceptor stimulant, was studied in mouse, rat, rabbit and dog. The acute oral LD50 was between 199.9 and 319.3 mg/kg in all four species used and did not differ significantly between the sexes. Intravenous LD50 was between 18.3 and 51.1 mg/kg (four species), i.p. between 60 and 78.3 mg/kg and s.c. between 113 and 125.7 mg/kg (mouse and rat only). In subacute and chronic studies in Wistar rats, mabuterol was dosed by gavage at 0, 10, 20, 40, 80 and 120 mg/kg for 1 month, and 0, 1, 2.5, 10 and 40 mg/kg for 3 (interim) and 6 months or in food at 0, 2.5, 10 and 40 mg/kg for 6 (interim) and 12 months. Beagle dogs were dosed by gelatine capsule with 0, 0.05, 0.5, 5 and 50 (25) mg/kg for 6 (interim) and 24 months. In rats, 1 and 2.5 mg/kg were well tolerated. At 10 mg/kg and above, irritability and hypersalivation were seen dependent on dose. Two males and one female given 120 mg/kg died from the test substance. In dogs, 0.05, 0.5 and 5 mg/kg were well tolerated. 50 mg/kg caused vomiting, diarrhoea, tonic-clonic convulsions and increased salivation. One male had to be killed because of severe convulsions. At term, 3 of 56 female rats of the one-year study had benign mesovarian leiomyomas. No other substance-related changes were discovered but all findings belonged to the spontaneous pathology of rat and dog, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001993:Bronchodilator Agents / Q000633:toxicity; D002214:Capsules; D002976:Clenbuterol / Q000031:analogs & derivatives / Q000633:toxicity*; D004285:Dogs; D004983:Ethanolamines / Q000633:toxicity*; D005260:Female; D005502:Food; D007441:Intubation, Gastrointestinal; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D002214:Capsules; D004983:Ethanolamines; C044573:mabuterol; D002976:Clenbuterol