Reproductive and developmental toxicity studies of lactitol (NS-4) (1)--Fertility study in rats by oral administration

Abstract

A study of fertility and fetal development was conducted in Sprague-Dawley rats. Male rats were given lactitol, a hepatic encephalopathy drug, orally from 63 days before mating to the end of mating period. Female rats were given from 14 days before mating to day 7 of pregnancy. The dose levels for both males and females were 0 (control), 0.7, 2.65 and 10 g/kg. The females were sacrificed on day 20 of pregnancy for examination of their fetuses. The decrease in food consumption in either male or female was observed in the intermediate and high dose groups. The high dose caused soft stool, diarrhea and increase in water consumption in either male or female. Moreover, the high dose caused salivation and suppression of body weight gain in male. In the pathological examination, the enlargement of cecum were observed in male of the intermediate and high dose groups. The increase in cecum weight were observed in male in all lactitol groups, and in female of the high dose group. Lactitol did not affect on copulation and fertility indexes in either male or female rats. Lactitol failed to affect on estrous cycle in female rats, and number of corpora lutea, implantations and preimplantation egg losses. In the fetal examination, lactitol did not affect on the development of live fetuses. The results show that no-effect dose levels of lactitol are less than 0.7 g/kg in male rats and 0.7 g/kg in female rats for general toxicity, and 10 g/kg for reproductive function in parent animals and fetuses.