[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (2). Study for effects on pre- and postnatal development in rats, including maternal function].

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.