Rice D C
Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Protection Branch, Health Canada, Ottawa, Ontario.
Neurotoxicol Teratol. 1999 Jan-Feb;21(1):59-69. doi: 10.1016/s0892-0362(98)00031-2.
There is evidence that polychlorinated biphenyl (PCB) congeners have differential effects on endpoints of neurotoxicity depending on their chemical structure: specifically, that ortho-substituted congeners are neurotoxic whereas coplanar (dioxin-like) congeners are relatively inactive in producing neurotoxic effects. The effects of the coplanar congener 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on developmental endpoints, hematology, serum biochemistry, and performance on a spatial delayed alternation task were assessed in Long-Evans rats. Dams were dosed with 0, 0.25, or 1.0 microg/kg/day Monday to Friday beginning 5 weeks before and continuing through gestation and lactation. The first 2-week breeding period produced 10, 8, and 13 litters in the three dose groups, respectively. Breeding females from the control and low-dose group that did not conceive were rebred after 76 days of dosing, producing 7 and 6 litters, respectively. Reduction in weight gain from birth to weaning at 21 days of age (DOA) was observed in both dose groups of Cohort 1 but not in Cohort 2. Males in Cohort 1 exhibited a slight decrease in anogenital distance normalized for weight. Changes in hematological and some serum biochemical parameters were observed in the pups at DOA 21 and/or 60. PCB 126 was detected in fat sampled at both DOA 21 and 60. PCB 126 was not detected in brain samples at 60 DOA in any group; analysis of Cohort 2 at DOA 21 revealed levels in the treated group about 1/100 of those in fat. On the spatial delayed alternation task, there was no convincing evidence for impairment as a result of PCB exposure, as assessed by overall accuracy of performance and measures of perseverative and other types of inappropriate responding. These data provide further evidence for the lack of neurotoxicity of dioxin-like PCB congeners. However, assessment of performance on additional behavioral indices is required before definitive conclusions may be drawn.
有证据表明,多氯联苯(PCB)同系物根据其化学结构对神经毒性终点具有不同影响:具体而言,邻位取代的同系物具有神经毒性,而共平面(二噁英类)同系物在产生神经毒性作用方面相对不活跃。在Long-Evans大鼠中评估了共平面同系物3,3',4,4',5-五氯联苯(PCB 126)对发育终点、血液学、血清生物化学以及空间延迟交替任务表现的影响。从妊娠前5周开始至妊娠和哺乳期,母鼠于周一至周五按0、0.25或1.0微克/千克/天的剂量给药。在三个剂量组中,第一个为期2周的繁殖期分别产生了10窝、8窝和13窝幼崽。对照组和低剂量组中未受孕的繁殖雌性在给药76天后再次繁殖,分别产生了7窝和6窝幼崽。在第1组的两个剂量组中均观察到从出生到21日龄断奶时体重增加减少,但在第2组中未观察到。第1组中的雄性大鼠经体重标准化后的肛门生殖器距离略有减小。在21日龄和/或60日龄时,幼崽的血液学和一些血清生化参数发生了变化。在21日龄和60日龄采集的脂肪样本中均检测到了PCB 126。在任何组中,60日龄时脑样本中均未检测到PCB 126;对21日龄第2组的分析显示,处理组中的水平约为脂肪中水平的1/100。在空间延迟交替任务中,根据表现的总体准确性以及持续性和其他类型不适当反应的测量,没有令人信服的证据表明PCB暴露会导致损害。这些数据为二噁英类PCB同系物缺乏神经毒性提供了进一步证据。然而,在得出明确结论之前,需要对其他行为指标的表现进行评估。