[Reproductive and developmental toxicity studies of lactitol (NS-4) (4)--Perinatal and postnatal study in rats by oral administration].
A perinatal and postnatal 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 17 of pregnancy to day 21 after delivery. All pregnant rats per level were allowed to deliver naturally for postnatal examination of their offspring. The high dose caused diarrhea or soft stool in dams. The high dose suppressed the body weight of dams during the perinatal period. The food consumption of dams decreased in the intermediate and high dose groups. The water consumption of dams increased in the high dose group. The high dose caused enlargement of cecum and increase of weights of cecum in dams. The drug failed to affect the delivery of dams and gestation index. However, high dose caused prolongation of gestation period. Two dams in the high dose group failed to nurse their all newborns during early lactation. The drug did not affect the number of live newborns, birth index, external appearance, 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 the no-effect dose levels of lactitol are 0.7 g/kg for general toxicity in mother animals, 2.65 g/kg for reproductive function in mother animals, and 10 g/kg for their offspring.
Research Laboratories, Nippon Shinyaku Co. Ltd., Kyoto, Japan.
H
H
Ninomiya
K
K
Nishikawa
Y
Y
Ide
J
J
Kondo
K
K
Kishida
Y
Y
Yamashita
M
M
Watanabe
N
N
Sumi
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002432:Cecum / Q000187:drug effects / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D007774:Lactation / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013402:Sugar Alcohols / Q000008:administration & dosage / Q000633:toxicity*
D013402:Sugar Alcohols; C014635:lactitol