Xu Tiantian, Li Ping, Wu Siyu, Lei Lili, He Defu
Lab of Toxicology , School of Ecological and Environmental Sciences , East China Normal University , 500# DongChuang RD , Shanghai , 200241 , China . Email:
Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration , East China Normal University , Shanghai , 200241 , China.
Toxicol Res (Camb). 2016 Oct 26;6(1):63-72. doi: 10.1039/c6tx00306k. eCollection 2017 Jan 1.
Organophosphate flame retardants (PFRs) are a new class of flame retardants. The health risks of PFRs have received attention recently. However, little is known about the potential toxicity of PFRs on the nervous system. Herein, we evaluated the neurotoxic effects of two typical PFRs, tris(2-chloroethyl) phosphate (TCEP) and tris(2-chloropropyl) phosphate (TCPP), using . Median lethal concentrations of chronic exposure (3 d) were 1578 and 857 mg L for TCEP and TCPP, respectively. The sublethal dose of TCEP or TCPP significantly inhibited the body length and reduced the lifespans of nematodes. 500 mg L and above of TCEP/TCPP led to a significant decline in the locomotor frequency of body bending and head thrashing. Furthermore, their exposure reduced the crawling speed and the frequency of bending oscillation of nematodes. This indicates that TCEP/TCPP induces locomotor deficits, along with Parkinsonian-like movement impairment including bradykinesia and hypokinesia. Using transgenic worms, we found that TCEP/TCPP could induce down-expression of P and resulted in the degeneration of dopaminergic neurons, especially PDE neurons. Moreover, TCEP/TCPP induced over-expression of , which indicates the aggregation of α-synuclein in the process of degeneration. These findings suggest the neurotoxicity risks of organophosphorus flame retardants, which are associated with the locomotor deficits and dopaminergic degeneration.
有机磷酸酯类阻燃剂（PFRs）是一类新型阻燃剂。PFRs的健康风险近来受到关注。然而，人们对PFRs对神经系统的潜在毒性知之甚少。在此，我们使用……评估了两种典型的PFRs，磷酸三（2-氯乙基）酯（TCEP）和磷酸三（2-氯丙基）酯（TCPP）的神经毒性作用。慢性暴露（3天）的半数致死浓度，TCEP和TCPP分别为1578和857 mg/L。TCEP或TCPP的亚致死剂量显著抑制了线虫的体长并缩短了其寿命。500 mg/L及以上的TCEP/TCPP导致线虫身体弯曲和头部摆动的运动频率显著下降。此外，它们的暴露降低了线虫的爬行速度和弯曲振荡频率。这表明TCEP/TCPP会诱发运动功能障碍，以及类似帕金森病的运动损伤，包括运动迟缓及运动减少。利用转基因蠕虫，我们发现TCEP/TCPP可诱导P……的表达下调，并导致多巴胺能神经元，尤其是PDE神经元退化。此外，TCEP/TCPP诱导……的表达上调，这表明在退化过程中α-突触核蛋白发生了聚集。这些发现提示了有机磷阻燃剂的神经毒性风险，其与运动功能障碍和多巴胺能神经元退化有关。
