[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (3). Teratogenicity study in rabbits].
Teratogenicity of sodium N[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied. ONO-5046.Na was injected intravenously at doses of 0, 7.5, 15 and 30 mg/kg/day to pregnant Kbl: NZW rabbits from day 6 to day 18 of pregnancy. All female rabbits were sacrificed on day 29 of pregnancy and their fetuses were examined. There were no clinical signs or death attributable to ONO-5046.Na. One dam in the control group and 3 dams in the 30 mg/kg/day group aborted. Body weight gain in the 15 and 20 mg/kg/day groups and food intake in the 30 mg/kg/day group were decreased during the administration period. These changes had recovered by the end of the study. Kidney weight was increased in the 30 mg/kg/day group. There were no effects of ONO-5046.Na in necropsy findings at cesarean section in dams at any dose levels. Developmental toxicity of ONO-5046.Na was not found at any dose levels. From these results, it is considered that the NOAEL of ONO-5046.Na is 7.5 mg/kg/day for pregnant animals and 30 mg/kg/day for fetuses.
Nishimura
T
T
Fukui Institute for Safety Research, ONO Pharmaceutical Co., Ltd., Japan.
Nakagawa
Y
Y
Sakai
M
M
Sugai
S
S
Chihara
N
N
Shirakawa
R
R
Sakamoto
T
T
Ikeda
Y
Y
Itagaki
I
I
Ozeki
Y
Y
Shinomiya
K
K
Fujita
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D007275:Injections, Intravenous; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D013449:Sulfonamides / Q000008:administration & dosage / Q000633:toxicity*
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine