Effects of a daily feeding-restriction on the reproductive and development toxicity parameters in female rats.
On the assumption of that the oral administration of an acid-unstable test compound into the empty stomach could enhance the systemic exposure to the test compound, the non-pregnant and pregnant rats had free access to the diet only for five hours per day. Female rats under the restricted feeding for a period of 21 days took diet at two thirds of the daily food-intake by the control animals, and lost their weight more than 10%. The vaginal smear test in these animals revealed a prolonged estrous cycle and diestrous period over four days. On the other hand, the restricted feeding from Day 0 to Day 17 of gestation suppressed the weight gain of pregnant animals but did not cause any significant influence upon the litter data, incidence of external anomalies or fetal skeletal development. The restricted feeding from Day 0 of gestation to Day 7 of lactation seriously disturbed the nursing behavior and the growth of offspring. These results suggested that the dosing method under the above-mentioned restricted feeding might be applicable to the teratology study but could not be applied to the fertility study nor to the peri- and post-natal study.
Kawaguchi
T
T
Department of Drug Safety Research, Eisai Co., Ltd., Kawashima Industrial Park, Gifu, Japan.
Matsubara
Y
Y
Okada
F
F
Okuda
Y
Y
Niwa
N
N
Yamatsu
K
K
Igarashi
T
T
D000014:Abnormalities, Drug-Induced / Q000378:metabolism*; D000818:Animals; D004435:Eating; D005314:Embryonic and Fetal Development; D004971:Estrus; D005260:Female; D005298:Fertility; D007743:Labor, Obstetric; D007774:Lactation; D051379:Mice; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013997:Time Factors; D014116:Toxicology / Q000379:methods