Nishimura T, Chihara N, Sugai S, Sakamoto T, Shirakawa R, Nakagawa Y, Ikeda Y, Aze Y, Ozeki Y, Shinomiya K, Fujita T
Fukui Institute for Safety Research, ONO Pharmaceutical Co., Ltd., Japan.
J Toxicol Sci. 1998 Jul;23 Suppl 3:515-29. doi: 10.2131/jts.23.supplementiii_515.
Prenatal and postnatal toxicity of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied in Sprague-Dawley (SD) rats. ONO-5046.Na was injected intravenously at doses of 0, 18.75, 37.5 and 75 mg/kg/day to pregnant rats from day 7 of pregnancy to day 20 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. No adverse effects on dams were observed in clinical signs, body weight change, food consumption, pregnant, delivery or lactating performances. ONO-5046.Na did not affect the postnatal development of offspring, including birth index, survival index, physical and functional development, motor activity, emotionality, learning ability and reproductive performance. From these results, it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for dams and their offspring.
在斯普拉格-道利（SD）大鼠中研究了新型人中性粒细胞弹性蛋白酶抑制剂N-[2-[4-(2,2-二甲基丙酰氧基)苯基磺酰氨基]苯甲酰基]氨基乙酸钠四水合物（ONO-5046.Na）的产前和产后毒性。从妊娠第7天至产后第20天，以0、18.75、37.5和75mg/kg/天的剂量对怀孕大鼠静脉注射ONO-5046.Na。所有怀孕大鼠均自然分娩，以便对其后代进行产后检查。在临床体征、体重变化、食物消耗、怀孕、分娩或哺乳表现方面，未观察到对母鼠有任何不良影响。ONO-5046.Na不影响后代的产后发育，包括出生指数、存活指数、身体和功能发育、运动活动、情绪、学习能力和生殖性能。根据这些结果，认为ONO-5046.Na对母鼠及其后代的无观察到有害作用水平（NOAEL）为75mg/kg/天。
