[Reproductive and developmental toxicity study of prednisolone farnesylate (PNF)--study by subcutaneous administration of PNF during the period of fetal organogenesis in rats].
A teratogenicity study of Prednisolone farnesylate (PNF), a newly synthesized corticosteroid, was conducted in Sprague-Dawley rats. This compound was administrated subcutaneously to female rats at dose levels of 0(control), 1, 5 and 25 mg/kg/day, once a day, for 11 days from day 7 to day 17 of pregnancy. In each dose group, 26 or 27 dams were killed on day 20 of pregnancy to examine their fetuses. The remaining 14 or 15 dams of each group were allowed to litter naturally, and observations were made on the postnatal growth and development of their offspring. 1. In the dams treated at doses of 1 mg/kg or more, decreased body weight gains and food consumption and retention of the substance at the injected site were noted. However, general signs, parturition, lactation and nursing behaviors were not affected by the administration of PNF. 2. In the F1 fetuses, no embryonic or fetal lethal effect, fetal retardation and teratogenic effect were noted. 3. In the F1 newborns, the postnatal growth, development, responses, behaviors, learning ability and reproductive ability were not influenced. Additionally, no embryonic or fetal abnormalities of their fetuses (F2) were detected. From these results, the no-effect dose levels of PNF on the parental general states, the parental reproductive ability and those of the F1 offspring are thought to be less than 1 mg/kg/day, 25 mg/kg/day and 25 mg/kg/day, respectively, under the experimental conditions of this study. Moreover, the F2 fetuses are not affected by doses up to 25 mg/kg/day of PNF.
Taniguchi
H
H
Kyudo Laboratory of Safety Assessment, Kyudo Co., Ltd., Saga, Japan.
Himeno
Y
Y
Chono
M
M
Araki
E
E
Nakamura
M
M
Tsuji
M
M
Tanaka
H
H
Shinomiya
M
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005204:Farnesol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*
C080069:prednisolone farnesylate; D005204:Farnesol; D011239:Prednisolone