Is the PentaBDE replacement, tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC12 cells.
Is the PentaBDE replacement, tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC12 cells.
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DOI：
10.1016/j.taap.2011.01.005
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发表时间：
2011-11-01
影响因子：
3.8
通讯作者：
Stapleton HM
中科院分区：
文献类型：
--
作者：
Dishaw LV;Powers CM;Ryde IT;Roberts SC;Seidler FJ;Slotkin TA;Stapleton HM
有机磷酸盐阻燃剂（OPFR）被用作2004年淘汰的商用五溴二苯醚混合物的替代品。OPFR在环境中普遍存在，在住宅灰尘中检测到高浓度，表明人类广泛接触。OPFR在结构上类似于神经毒性有机磷农药，引起了人们对人类接触和毒性的担忧。本研究评价了三（1，3-二氯-2-丙基）磷酸酯（TDCPP）的神经毒性，并与有机磷农药毒死蜱（CPF）（一种已知的发育神经毒物）进行了比较。我们还测试了三种结构相似的OPFR的神经毒性，即三（2-氯乙基）磷酸酯（TCEP）、三（1-氯丙基）磷酸酯（TCPP）和三（1，3-二溴丙基）磷酸酯（TDBPP），以及五溴二苯醚的主要成分2，2 ′，4，4 ′-四溴二苯醚（BDE-47）。使用未分化和分化的PC 12细胞，DNA合成，氧化应激，分化成多巴胺能或胆碱能神经表型，细胞数量，细胞生长和神经突起生长的变化进行了评估。TDCPP显示出浓度依赖性神经毒性，其作用通常等于或大于等摩尔浓度的CPF。TDCPP抑制DNA合成，所有OPFR减少细胞数量，并改变神经分化。虽然TDCPP升高氧化应激，但对细胞活力或生长没有不利影响。TDCPP和TDBPP促进分化为两种神经元表型，而TCEP和TCPP促进胆碱能表型。BDE-47对细胞数量、细胞生长或神经突生长没有影响。我们的研究结果表明，不同的OPFR对神经分化表现出不同的影响，这表明多种毒性机制的参与。此外，这些数据表明，OPFR可能会影响神经发育与类似或更大的效力相比，已知的和可疑的神经毒物。
Organophosphate flame retardants (OPFRs) are used as replacements for the commercial PentaBDE mixture that was phased out in 2004. OPFRs are ubiquitous in the environment and detected at high concentrations in residential dust, suggesting widespread human exposure. OPFRs are structurally similar to neurotoxic organophosphate pesticides, raising concerns about exposure and toxicity to humans. This study evaluated the neurotoxicity of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) compared to the organophosphate pesticide, chlorpyrifos (CPF), a known developmental neurotoxicant. We also tested the neurotoxicity of three structurally similar OPFRs, tris (2-chloroethyl) phosphate (TCEP), tris (1-chloropropyl) phosphate (TCPP), and tris (1,3-dibromopropyl) phosphate (TDBPP), and 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), a major component of PentaBDE. Using undifferentiated and differentiating PC12 cells, changes in DNA synthesis, oxidative stress, differentiation into dopaminergic or cholinergic neurophenotypes, cell number, cell growth and neurite growth were assessed. TDCPP displayed concentration-dependent neurotoxicity, often with effects equivalent to or greater than equimolar concentrations of CPF. TDCPP inhibited DNA synthesis, and all OPFRs decreased cell number, and altered neurodifferentiation. Although TDCPP elevated oxidative stress, there was no adverse effect on cell viability or growth. TDCPP and TDBPP promoted differentiation into both neuronal phenotypes, while TCEP and TCPP promoted only the cholinergic phenotype. BDE-47 had no effect on cell number, cell growth or neurite growth. Our results demonstrate that different OPFRs show divergent effects on neurodifferentiation, suggesting the participation of multiple mechanisms of toxicity. Additionally, these data suggest that OPFRs may affect neurodevelopment with similar or greater potency compared to known and suspected neurotoxicants.
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影响因子：
10.4
作者：
Herbstman JB;Sjödin A;Kurzon M;Lederman SA;Jones RS;Rauh V;Needham LL;Tang D;Niedzwiecki M;Wang RY;Perera F
通讯作者：
Perera F
影响因子：
11.4
作者：
Johnson, Paula I.;Stapleton, Heather M.;Slodin, Andreas;Meeker, John D.
通讯作者：
Meeker, John D.
影响因子：
56.9
作者：
BLUM, A;GOLD, MD;THENOT, JP
通讯作者：
THENOT, JP
影响因子：
3.8
作者：
Dingemans, Milou M. L.;van den Berg, Martin;Westerink, Remco H. S.
通讯作者：
Westerink, Remco H. S.
影响因子：
10.4
作者：
Harley KG;Marks AR;Chevrier J;Bradman A;Sjödin A;Eskenazi B
通讯作者：
Eskenazi B