[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (1). Single-dose intravenous toxicity studies in rats and dogs].
Single-dose toxicity studies of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, were conducted in Sprague-Dawley (SD) rats and beagle dogs. The rats of both sexes were administered ONO-5046.Na intravenously at a single dose of 150, 300 or 450 mg/kg. The male dogs were also given ONO-5046.Na at a single dose of 75 or 150 mg/kg. In the rat study, hypoactivity, bradypnea and paleness of limbs and pinna were observed at doses of 300 mg/kg and above. In particular, one of six female rats in the 450 mg/kg group showed clonic convulsion and died. In surviving animals, those signs disappeared within 3 hr after administration. No effect on body weight gain was seen in either group. Necropsy findings showed a slight foamy fluid in the bronchus, hemorrhage at the right knee joint muscle, tendon and lung in a dead animal. In the dog study, no effects on clinical signs, body weight, food consumption and blood biochemistry were seen in any animals of the 75 and 150 mg/kg groups. It is concluded that the approximate lethal doses are 450 mg/kg in rats and 150 mg/kg and above in dogs.
Fukui Institute for Safety Research, ONO Pharmaceutical Co., Ltd., Japan.
H
H
Yanagi
K
K
Yamaguchi
K
K
Shimizu
Y
Y
Shichino
K
K
Nishiyama
H
H
Mori
K
K
Shinomiya
H
H
Ueda
Y
Y
Suzuki
H
H
Yonezawa
T
T
Fujita
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D004285:Dogs; D004435:Eating / Q000187:drug effects; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D007275:Injections, Intravenous; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007928:Lethal Dose 50; D008168:Lung / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D013449:Sulfonamides / Q000008:administration & dosage / Q000633:toxicity*
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005998:Glycine