Yamasaki Kanji, Noda Shuji, Muroi Takako, Mitoma Hideo, Takakura Saori, Sakamoto Satoko
Chemicals Evaluation and Research Institute, 3-822, Ishii, Hita, Oita 877-0061, Japan.
Toxicology. 2005 Apr 1;209(1):47-54. doi: 10.1016/j.tox.2004.12.004. Epub 2005 Jan 6.
Pregnant CD(SD) IGS rats were given flutamide (FLUT) orally at doses of 0.4, 2, or 10 mg/kg/day from gestational day 6 to postnatal day (PND) 20, and the effects of FLUT exposure on male offspring were examined 10 weeks after birth, and compared to the effects in offspring treated after weaning and in offspring untreated after weaning. Although the body weight of the dams treated with FLUT remained normal, two dams in the 10 mg/kg/day group were killed because of abnormal parturition periods and loss of all the pups. The number of stillborns and dead newborns at birth was significantly higher in the 10 mg/kg/day group than in the control groups. No abnormalities in the reproductive parameters of the other dams treated with FLUT were detected. The body weights of the male offspring in each group remained normal from birth until the end of the study. The ano-genital distance was significantly shortened in 2 and 10 mg/kg/day groups. Changes in the organ weights and gross findings were detected in the 2 and/or 10 mg/kg/day groups with or without the continuous administration of FLUT after weaning; these changes were more appreciable in groups treated with FLUT after weaning than in groups untreated after weaning. The prolongation of preputial separation was observed in the 0.4 and 2 mg/kg/day groups treated with FLUT after weaning, but this change was not detected in the same dose groups untreated after weaning. The testosterone levels were higher in the 10 mg/kg/day group treated with FLUT after weaning. The present data demonstrated that the endocrine-mediated effects on rats were more appreciable in offspring treated with FLUT after weaning than in offspring untreated after weaning.
妊娠的CD(SD) IGS大鼠从妊娠第6天至出生后第20天，每天按0.4、2或10 mg/kg的剂量口服氟他胺(FLUT)，在出生10周后检查FLUT暴露对雄性后代的影响，并与断奶后治疗的后代和断奶后未治疗的后代的影响进行比较。尽管用FLUT治疗的母鼠体重保持正常，但10 mg/kg/天组的两只母鼠因分娩期异常和所有幼崽死亡而被处死。10 mg/kg/天组出生时的死产和新生死亡数量显著高于对照组。未检测到用FLUT治疗的其他母鼠生殖参数有异常。每组雄性后代的体重从出生到研究结束都保持正常。2和10 mg/kg/天组的肛门与生殖器距离显著缩短。在2和/或10 mg/kg/天组中，无论断奶后是否持续给予FLUT，均检测到器官重量和大体检查结果的变化；断奶后用FLUT治疗的组比断奶后未治疗的组这些变化更明显。断奶后用FLUT治疗的0.4和2 mg/kg/天组观察到包皮分离延长，但断奶后未治疗的相同剂量组未检测到这种变化。断奶后用FLUT治疗的10 mg/kg/天组睾酮水平较高。目前的数据表明，内分泌介导的对大鼠的影响在断奶后用FLUT治疗的后代中比在断奶后未治疗的后代中更明显。
