Calciu C, Chan H M, Kubow S
School of Dietetics and Human Nutrition, Macdonald Campus of McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
Toxicology. 1997 Dec 26;124(2):153-62. doi: 10.1016/s0300-483x(97)00145-5.
The presence of persistent organic pollutants, including the pesticide toxaphene has been reported even in remote regions such as the Arctic and is becoming a health concern. The technical mixture of toxaphene contains over 800 different congeners. The numbers of prevalent congeners, however, decrease along the food chain. About 20 major congeners are found in fish, eight in marine mammals and only two major ones in human, 2-exo,3-endo,5-exo,6-endo,8,8,10,10-octachlorobornane (T2) and 2-exo,3-endo,5-exo,6-endo,8,8,9,10,10-nonachlorobornane (T12). Embryotoxicity of these individual congeners is not known, as previous studies focused on the toxaphene technical mixture. We studied the relative dysmorphogenic activity of toxaphene technical mixture and individual congeners (T2 and T12) using rat embryo culture. Explanted embryos (0-2 somites) were treated for 48 h with concentrations of 0 (DMSO 0.01%), 100, 1000 and 5000 ng/ml of either (a) toxaphene technical mixture; (b) T2; (c) T12; or (d) a 50:50 mixture of T2 and T12. The treatment period corresponds to gestational days (GD) 10-12, a period within the critical time of morphogenesis and organogenesis. Both the technical mixture and the two individual congeners had a significant adverse effects on the total morphological score, somite number, head and crown rump length and the central nervous system scores of embryos. All treatments caused a high incidence of central nervous system defects. The T2 and T12 congeners differed in their spectrum of abnormalities as exposure to T2 caused limb and flexion defects which were not observed with the T12 congener. Differences were also observed in the type of toxicity and the target sites between the technical mixture and the congeners. T2 showed a more potent adverse effect on the morphological score as compared to the technical mixture. Both T2 and T12 were less inhibitory on growth than the technical mixture as indicated by crown-rump length but they showed a stronger inhibitory effect on otic system development. The mixture of T2 + T12 showed a synergistic effect on decreasing crown-rump and head length. Conversely, the combination of T2 and T12 inhibited the strong adverse effect of the individual congeners on otic development. The results suggest environmentally predominant toxaphene congeners can have organ specific embryotoxic effects not predicted by the toxaphene technical mixture.
据报道，即使在北极等偏远地区也存在包括农药毒杀芬在内的持久性有机污染物，这正成为一个健康问题。毒杀芬的工业混合物包含800多种不同的同系物。然而，常见同系物的数量沿食物链递减。在鱼类中发现约20种主要同系物，在海洋哺乳动物中发现8种，而在人类中仅发现两种主要同系物，即2-外向，3-内向，5-外向，6-内向，8,8,10,10-八氯冰片烷（T2）和2-外向，3-内向，5-外向，6-内向，8,8,9,10,10-九氯冰片烷（T12）。由于先前的研究集中在毒杀芬工业混合物上，这些单个同系物的胚胎毒性尚不清楚。我们使用大鼠胚胎培养研究了毒杀芬工业混合物以及单个同系物（T2和T12）的相对致畸活性。将移出的胚胎（0-2体节）用浓度为0（二甲基亚砜0.01%）、100、1000和5000 ng/ml的以下物质处理48小时：（a）毒杀芬工业混合物；（b）T2；（c）T12；或（d）T2和T12的50:50混合物。处理期对应于妊娠第10-12天，这是形态发生和器官发生关键时期内的一个阶段。工业混合物以及两种单个同系物对胚胎的总形态评分、体节数、头臀长度和中枢神经系统评分均有显著不良影响。所有处理均导致中枢神经系统缺陷的高发生率。T2和T12同系物在异常谱方面存在差异，因为暴露于T2会导致肢体和屈曲缺陷，而T12同系物未观察到这些缺陷。在工业混合物和同系物之间的毒性类型和靶位点也观察到差异。与工业混合物相比，T2对形态评分显示出更强的不良影响。如头臀长度所示，T2和T12对生长的抑制作用均小于工业混合物，但它们对耳系统发育显示出更强的抑制作用。T2 + T12混合物在降低头臀和头部长度方面显示出协同作用。相反，T2和T12的组合抑制了单个同系物对耳发育的强烈不良影响。结果表明，环境中占主导地位的毒杀芬同系物可产生毒杀芬工业混合物未预测到的器官特异性胚胎毒性作用。
