Faqi A S, Dalsenter P R, Merker H J, Chahoud I
Institut für Klinische Pharmakologie und Toxikologie, Freie Universität, Berlin, Germany.
Toxicol Appl Pharmacol. 1998 Jun;150(2):383-92. doi: 10.1006/taap.1998.8433.
The effects of low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the reproductive system of male offspring rats were examined. The dams were treated subcutaneously 2 weeks prior to mating and throughout mating, pregnancy, and lactation. They received an initial loading dose of 25, 60, or 300 ng TCDD/kg body wt, followed by a weekly maintenance dose of 5, 12, or 60 ng TCCD/kg body wt (TCDD 25/5, TCDD 60/12, and TCDD 300/60). Three dams per group were killed on Gestation Day 21 and the fetuses were removed. The concentration of TCDD in the maternal liver and fat was measured. After birth, developmental landmarks in male rats were monitored. At weaning, the concentration of TCDD in the offspring liver and testis was determined. Effects on male reproduction were studied on Postnatal Days (PND) 70 and 170. At weaning, the concentration of TCDD in the offspring liver was 0.24, 0.39, and 1.78 ng/g in the TCDD 25/5, TCDD 60/12, and TCDD 300/60 groups, respectively. In the testes, the concentration of TCDD was 0.25 ng/g in the TCDD 25/5 and TCDD 60/12 groups and 0.28 ng/g in the TCDD 300/60 group. The number of sperm per cauda epididymis was reduced in TCDD groups at puberty and at adulthood. Daily sperm production was permanently decreased as was the sperm transit rate in the TCDD-exposed male rats, thus increasing the time required by the sperm to pass through the cauda epididymis. Moreover, the male rats of the TCDD groups showed an increased number of abnormal sperm when investigated at adulthood. Similarly, mounting and intromission latencies were significantly increased in the TCDD 25/5 and TCDD 300/60 groups. In the highest dose group, serum testosterone concentration was decreased at adulthood. Likewise, in this dose group permanent changes including pyknotic nuclei and the occurrence of cell debris in the lumen were revealed. The lowest adverse effect level and the no observed effect level can be estimated to be substantially lower than the estimated daily dose of the lowest dose which is 0.8 ng/kg body wt/day. Sperm parameters were more susceptible than the other end points investigated. However, the question as to whether such doses exposed throughout gestation and lactation induce subtle changes in humans remains to be determined.
研究了低剂量2,3,7,8 - 四氯二苯并 - p - 二恶英（TCDD）对雄性后代大鼠生殖系统的影响。在交配前2周及整个交配、怀孕和哺乳期，对母鼠进行皮下注射。它们接受25、60或300 ng TCDD/kg体重的初始负荷剂量，随后每周接受5、12或60 ng TCCD/kg体重的维持剂量（TCDD 25/5、TCDD 60/12和TCDD 300/60）。每组三只母鼠在妊娠第21天处死，取出胎儿。测量母鼠肝脏和脂肪中TCDD的浓度。出生后，监测雄性大鼠的发育标志。断奶时，测定后代肝脏和睾丸中TCDD的浓度。在出生后第70天和170天研究对雄性生殖的影响。断奶时，TCDD 25/5、TCDD 60/12和TCDD 300/60组后代肝脏中TCDD的浓度分别为0.24、0.39和1.78 ng/g。在睾丸中，TCDD 25/5和TCDD 60/12组TCDD的浓度为0.25 ng/g，TCDD 300/60组为0.28 ng/g。青春期和成年期，TCDD组附睾尾精子数量减少。TCDD暴露的雄性大鼠每日精子生成永久减少，精子转运速率也降低，从而增加了精子通过附睾尾所需的时间。此外，成年期研究发现，TCDD组雄性大鼠异常精子数量增加。同样，TCDD 25/5和TCDD 300/60组的爬跨潜伏期和插入潜伏期显著增加。在最高剂量组，成年期血清睾酮浓度降低。同样，在该剂量组中发现了包括核固缩和管腔内细胞碎片出现等永久性变化。最低不良反应水平和未观察到效应水平估计远低于最低剂量的估计每日剂量0.8 ng/kg体重/天。精子参数比所研究的其他终点更敏感。然而，在整个妊娠期和哺乳期暴露于这样的剂量是否会在人类中引起细微变化，仍有待确定。
