[Reproductive and developmental toxicity studies of FUT-187. (V)--Perinatal and postnatal study in rats with oral administration of FUT-187].
FUT-187 was given orally at 20, 120 and 720 mg/kg to female rats during the perinatal and postnatal periods and the effect on dams and offspring were evaluated. One dam during the terminal period of gestation and 3 dams after delivery in the 720 mg/kg group died due to FUT-187. In dams, an increased pancreas weight in the 20 mg/kg or more groups, temporary salivation after dosing in the 120 mg/kg or more groups, and a depression of body weight gain and decreased food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In offspring, postnatal death rate in the 720 mg/kg group tended to increased. Decreased body weight gain and delayed appearance of abdominal hair and descent of testis in the 720 mg/kg group were statistically significant in comparison with controls. There were no treatment-related abnormalities in visceral examination, organ weight, skeletal examination, sensory function, behavioral function, learning ability or reproductive function. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for dams, and 120 mg/kg for reproductive performance of dams and offspring development.
Furuhashi
T
T
NRI Life Science, Kanagawa, Japan.
Uehara
M
M
Takei
A
A
Kurihara
H
H
Yoshida
R
R
Maruden
A
A
Shimamura
K
K
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*
D007093:Imidazoles; C058875:sepimostate mesilate