[Reproductive and developmental toxicity study of prednisolone farnesylate (PNF)--study of subcutaneous administration of PNF during the perinatal and lactation periods in rats].
The effects of Prednisolone farnesylate (PNF), a newly synthesized corticosteroid, administrated during the perinatal and postnatal periods were studied in Sprague-Dawley rats. This compound was injected subcutaneously to female rats at dose levels of 0(control), 0.05, 0.5 and 5 mg/kg/day, once a day, for the period from day 17 of pregnancy to day 21 after parturition. Twenty-two to 25 dams in each dose 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 0.5 and 5 mg/kg, decreased body weight gains, atrophy of the thymus and retention of the substance at the injected site were noted. However, general signs, food consumption, parturition, lactation and nursing behaviors were not affected by the administration of PNF. 2. 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 0.05 mg/kg/day, 5 mg/kg/day or more and 5 mg/kg/day or more, respectively, under the experimental conditions of this study. Moreover, the F2 fetuses are not affected by doses up to 5 mg/kg/day of PNF.
Taniguchi
H
H
Kyudo Laboratory of Safety Assessment, Kyudo Co., Ltd., Saga, Japan.
Araki
E
E
Nagai
M
M
Masaki
K
K
Mizoguchi
S
S
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; D007279:Injections, Subcutaneous; D007774:Lactation / Q000187:drug effects*; D008297:Male; D008431:Maternal-Fetal Exchange; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*
C080069:prednisolone farnesylate; D005204:Farnesol; D011239:Prednisolone