Roy T S, Andrews J E, Seidler F J, Slotkin T A
Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Teratology. 1998 Aug;58(2):62-8. doi: 10.1002/(SICI)1096-9926(199808)58:2<62::AID-TERA7>3.0.CO;2-2.
Chlorpyrifos is used increasingly as a pesticide in place of more toxic alternatives such as parathion. Although chlorpyrifos is not a potent dysmorphogen, recent reports that fetal or infant exposures may exceed acceptable limits have raised concern about the potentially more subtle effects on brain development. In the current study, whole rat embryo culture was used to study the effects of chlorpyrifos at the neural tube stage of development. On embryonic day 9.5, embryos were exposed to 0.5, 5, or 50 micrograms/ml of chlorpyrifos. After 48 hr (embryonic day 11.5), embryos were examined for dysmorphogenesis and were then processed for light microscopic examination of the neuroepithelium. Examination of 1-micron-thick toluidine blue-stained sections of the forebrain and hindbrain region revealed reduced and altered mitotic figures, with dispersion and disorientation of the mitotic layer. In addition, cytotoxicity was evidenced by cytoplasmic vacuolation, enlargement of intercellular spaces, and the presence of a significant number of apoptotic cells. These alterations were evident even at the lowest concentration of chlorpyrifos, which produced no dysmorphogenesis. The effects were intensified at higher concentrations, which were just at the threshold for dysmorphogenesis; the neuroepithelial abnormalities, however, were still present in embryos that were not dysmorphogenic. Our results in rat embryo culture support the idea that chlorpyrifos specifically targets brain development at low concentrations, indicating the need to reevaluate the safety of this compound for exposure in vivo.
毒死蜱作为一种杀虫剂，正越来越多地被用于替代毒性更强的替代品，如对硫磷。尽管毒死蜱不是一种强效的致畸剂，但最近有报道称胎儿或婴儿接触毒死蜱的量可能超过可接受限度，这引发了人们对其对大脑发育潜在更细微影响的担忧。在当前的研究中，采用全大鼠胚胎培养来研究毒死蜱在神经管发育阶段的影响。在胚胎第9.5天，将胚胎暴露于0.5、5或50微克/毫升的毒死蜱中。48小时后（胚胎第11.5天），检查胚胎是否存在畸形发生，然后对其进行处理以用于神经上皮的光学显微镜检查。对前脑和后脑区域1微米厚的甲苯胺蓝染色切片检查发现，有丝分裂细胞数量减少且形态改变，有丝分裂层分散且排列紊乱。此外，细胞毒性表现为细胞质空泡化、细胞间隙增大以及大量凋亡细胞的存在。即使在未产生畸形的毒死蜱最低浓度下，这些改变也很明显。在较高浓度下（刚好处于畸形发生的阈值）这些影响会加剧；然而，在未致畸的胚胎中神经上皮异常仍然存在。我们在大鼠胚胎培养中的结果支持这样一种观点，即毒死蜱在低浓度下会特异性地影响大脑发育，这表明有必要重新评估该化合物在体内暴露的安全性。
