[Reproductive and developmental toxicity studies of lactitol (NS-4) (2)--Teratogenicity study in rats by oral...

A teratogenicity study of lactitol, a hepatic encephalopathy drug, was conducted in Sprague-Dawley rats. Female rats were given lactitol orally at dose levels of 0 (control), 0.7, 2.65 and 10 g/kg from day 7 to day 17 of pregnancy. Twenty-two female rats per dose level were sacrificed on day 20 of pregnancy for examination of their fetuses, and thirteen pregnant rats per dose level were allowed to deliver naturally for postnatal examination of their offspring. The high dose of lactitol caused diarrhea or soft stool in pregnant rats. The food consumption of female rats decreased in the intermediate and high dose groups. The water consumption of female rats increased in the high dose group. The drug failed to alter the body weight of female rats. The weights of cecum of dams increased in the intermediate and high dose group. The high dose caused enlargement of cecum in dams. The drug failed to alter the numbers of corpora lutea and implantations, fetal mortality, the number of live fetuses, body weight of live fetus, sex ratio, and external, visceral and skeletal development of fetuses. Lactitol did not affect the delivery of dams, the number of live newborns, birth index, external development, body weight, viability index, weaning index, and sex ratio of weanlings. Nor did lactitol have any adverse effect on the postnatal development of the first (F1) generation offspring, such as differentiation, emotionality, motor ability, learning ability or reproductive performance. Nor did lactitol have any adverse effect on the second (F2) generation offspring. The results show that no-effect dose levels of lactitol are 0.7 g/kg for general toxicity in mother animals, 10 g/kg for reproductive function in mother animals and their offspring.