Coplanar PCBs Health Effects in the Rat: Dose-Effect Relationships and Reproductive Toxicity Endopoint

(1)在妊娠第15天（GD 15）单次注射10或100 μg/kg的PCB 126可显著延迟子代的阴道开口（VO）。相比之下，每天暴露于PCB 126仅在3 μg/kg/天的剂量下延迟VO，尽管在1 μg/kg/天组中PCB 126直到绒毛膜促性腺激素（CG）15的累积剂量估计远大于10 μg/kg。此外，虽然单次注射PCB 126减少了黄体（CL）数量，但每日暴露于1μg/kg/day并没有改变它。这些发现表明，与GD 15单次注射相比，每日暴露PCB 126可能会减少PCB 126对雌性后代的影响。(2)采用半定量RT-PCR方法研究Co-PCBs对大鼠肝细胞色素P450酶（CYP 1A 1）、1A 2和2B 1/2 mRNA表达的影响。在子宫内暴露于PCB 126（3μg/kg）或PCB 169（30 μg/kg）可诱导雄性和雌性后代肝脏中CYP 1A 1和CYP 1A 2 mRNA表达水平。妊娠大鼠暴露于PCB 126（30 μg/kg）或PCB 169（30 μg/kg）可诱导胎盘CYP 1A 1、CYP 1A 2和CYP 2B 1/2 mRNA表达水平。(1)采用微量双向电泳技术，对出生后1、3、6、15周龄的大鼠在胚胎期暴露于PCB 126或PCB 169后血浆中的蛋白质进行了分析。在出生前暴露于Co-PCBs的6周龄和15周龄大鼠中观察了Co-PCBs暴露对血浆中补体成分（C3和C4）的影响。当从Co-PCB对活体的影响方面考虑生殖和发育毒性作为终点时，估计非活性量为1 μg/kg。(4)结果还表明，在胎生期暴露和新生儿的牛奶介导的暴露影响肝脏中的CYP 1A 1，CYP 1A 2和CYP 2B 1/2 mRNA的表达和血浆中蛋白质的补体系统的动态变化。

(1) Single injection of 10 or 100 μg/kg of PCB 126 on gestation day (GD) 15 to the dams delayed vaginal opening (VO) of their offspring significantly. In contrast, daily exposure to PCB 126 delayed VO only at a dose of 3 μg/kg/day, although cumulative doses of PCB 126 until chorionic gonandotropin (CG) 15 in the 1 μg/kg/day-group were estimated as much larger than 10 μg/kg. In addition, while a single injection of PCB 126 reduced the number of corpus lutea (CL), daily exposure to 1μg/kg/day did not alter it. These findings indicate that daily exposure may diminish effects of PCB 126 on female offspring as compared to single injection on GD 15. (2) The effects of Co-PCBs on CYP1A1, CYP1A2 and CYP2B1/2 mRNA expression were investigated by semi quantitative RT-PCR analysis in rats. In utero exposure to PCB126 (3μg/kg) or PCB169 (30 μg/kg) induced CYP1A1 and CYP1A2 mRNA expression levels in the liver of both male and female offspring. Exposure to PCB126 (30 μg/kg) or PCB169 (30 μg/kg) to pregnant rats induced CYP1A1, CYP1A2 and CYP2B1/2 mRNA expression levels in the placenta. (1) Proteins in the plasma of the (1-, 3-, 6-, and 15-week-old) rats, which were exposed to PCB126 or PCB169 in the viviparous phase, were analyzed by micro 2-dimensional electrophoresis. The influence of exposure to Co-PCBs on complement components (C3 and C4) in the plasma was observed in the 6- and 15-week-old rats, which were prenatally exposed to Co-PCBs. When toxicity for reproduction and development was considered from the aspect of the influence of Co-PCBs on a living body as an end point, the inactive amount was estimated to be 1 μg/kg. (4) It was also revealed that the exposure in the viviparous phase and milk-mediated exposure of neonates influenced expression of CYP1A1, CYP1A2, and CYP2B1/2 mRNA in the liver and dynamic changes in the complement system of proteins in the plasma.