Effects of in utero and lactational exposure to tamoxifen in SD rats.
Pregnant CD (SD) IGS rats were given tamoxifen (TMX) orally at doses of 0.12, 0.6, or 3 microg/kg/day from gestational day 6 to postnatal day 21, and the effects of TMX exposure on all offspring were examined 10 weeks after birth; the reproductive performance of the offspring was also evaluated. Although the body weights of the dams treated with TMX remained normal from gestational day 6 until the day of autopsy (postnatal day 21), three dams in the 3 microg/kg/day group died during the pregnancy or partum periods. These deaths were regarded as the toxicological effects of TMX. No changes were detected in the reproductive parameters of all the TMX groups except for a decrease in the number of newborns/live newborns in the 3 microg/kg/day group. No abnormal clinical signs, body weight change, ano-genital distance, vaginal opening, or organ weight changes were detected in any of TMX groups, but the day of preputial separation was prolonged in the male offspring of all TMX groups and cleft phallus was detected in the female offspring of the 0.6 and 3 microg/kg/day groups. No abnormalities were detected in the reproductive performance of the male and female offspring.
Yamasaki
Kanji
K
Chemicals Evaluation and Research Institute, 3-822, Ishii, Hita, Oita 877-0061, Japan. yamasaki-kanji@ceri.jp
Noda
Shuji
S
Muroi
Takako
T
Mitoma
Hideo
H
Takakura
Saori
S
Sakamoto
Satoko
S
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D005837:Genitalia, Male / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D007774:Lactation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000633:toxicity*; D013629:Tamoxifen / Q000008:administration & dosage* / Q000633:toxicity*
D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen