Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish
Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish
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DOI：
10.1093/toxsci/kfy173
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发表时间：
2018-10-01
影响因子：
3.8
通讯作者：
Levin, Edward D.
中科院分区：
文献类型：
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作者：
Glazer, Lilah;Hawkey, Andrew B.;Levin, Edward D.
随着较老的溴化阻燃剂(BFR)因发育过程中的神经毒性而被逐步淘汰，一种较新的阻燃剂被引入，即有机磷阻燃剂(OPFR)。目前，人们对OPFR暴露的潜在发育神经毒性或行为后果知之甚少。我们的目的是利用斑马鱼模型来表征4种广泛使用的OPFR对终生神经行为的影响。将斑马鱼胚胎暴露于0.1%DMSO(溶剂对照)，或以下处理之一：异丙基苯基磷酸盐(0.003，0.03，0.1，0.3mM)；丁基苯基二苯基磷酸盐(0.003，0.03，0.3，3mU)；2-乙基己基二苯基磷酸盐(0.03，0.3，1mU)；在第6天，测试幼虫在黑暗和光照交替条件下的活动能力。最后，在5-7个月大的时候，暴露的鱼和对照组进行了一系列的行为测试，以评估情绪功能、感觉运动反应、社会互动和捕食者逃避。这些测试显示，在所有受试化合物中，幼虫运动能力改变的短期影响具有化学特异性，而在IPP、BPDP或EHDP暴露后，成年幼虫焦虑相关行为的长期损害。我们的结果表明，OPFR可能不是逐步淘汰的BFR的安全替代品，可能会在整个寿命周期内造成行为影响。进一步的研究应该评估对哺乳动物实验模型和人类的风险。
As the older class of brominated flame retardants (BFRs) are phased out of commercial use because of findings of neurotoxicity with developmental exposure, a newer class of flame retardants have been introduced, the organophosphate flame retardants (OPFRs). Presently, little is known about the potential for developmental neurotoxicity or the behavioral consequences of OPFR exposure. Our aim was to characterize the life-long neurobehavioral effects of 4 widely used OPFRs using the zebrafish model. Zebrafish embryos were exposed to 0.1% DMSO (vehicle control); or one of the following treatments; isopropylated phenyl phosphate (IPP) (0.01, 0.03, 0.1, 0.3 mu M); butylphenyl diphenyl phosphate (BPDP) (0.003, 0.03, 0.3, 3 mu M); 2-ethylhexyl diphenyl phosphate (EHDP) (0.03, 0.3, 1 mu M); isodecyl diphenyl phosphate (IDDP) (0.1, 0.3,1, 10 mu M) from 0- to 5-days postfertilization. On Day 6, the larvae were tested for motility under alternating dark and light conditions. Finally, at 5-7 months of age the exposed fish and controls were tested on a battery of behavioral tests to assess emotional function, sensorimotor response, social interaction and predator evasion. These tests showed chemical-specific short-term effects of altered motility in larvae in all of the tested compounds, and long-term impairment of anxiety-related behavior in adults following IPP, BPDP, or EHDP exposures. Our results show that OPFRs may not be a safe alternative to the phased-out BFRs and may cause behavioral impacts throughout the lifespan. Further research should evaluate the risk to mammalian experimental models and humans.