Developmental circulatory failure caused by metabolites of organophosphorus flame retardants in zebrafish, Danio rerio
Developmental circulatory failure caused by metabolites of organophosphorus flame retardants in zebrafish, Danio rerio
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DOI：
10.1016/j.chemosphere.2019.125738
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发表时间：
2020-05-01
期刊：
影响因子：
8.8
通讯作者：
Kubota, Akira
中科院分区：
文献类型：
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作者：
Lee, Jae Seung;Morita, Yuri;Kubota, Akira
有机磷酸三酯在全球范围内用作阻燃剂和增塑剂的添加剂，作为多溴二苯醚的替代品。越来越多的证据表明人类接触有机磷阻燃剂 (OPFR) 并造成环境污染，因此需要对此类化学品进行充分的毒性评估。虽然已经报道了几种 OPFR 的发育毒性，但 OPFR 代谢物的发育影响仍有待了解。本研究旨在利用斑马鱼胚胎 (Danio rerio) 表征 OPFR 代谢物的发育效应。磷酸三苯酯 (TPHP) 及其两种代谢物，磷酸 3-羟基苯基二苯基酯和磷酸 4-羟基苯基二苯基酯，最能有效诱导心包水肿和主干血管血流量减少。其他 TPHP 代谢物，如磷酸二苯酯和磷酸 4-羟基苯基苯基酯，在浓度高达 30 μM 时，循环衰竭没有显着增加。三（1,3-二氯-2-丙基）磷酸盐在 30 μM 时显示出循环衰竭，但其代谢物双（1,3-二氯-2-丙基）磷酸盐却没有。磷酸三(2-氯乙基)酯及其代谢物磷酸双(2-氯乙基)酯均不会诱发循环衰竭。随着 OPFR 及其代谢物辛醇-水分配系数的增加，循环衰竭似乎会加剧，这表明这些化学物质造成的发育性循环衰竭可以通过其生物累积潜力来估计。本研究证明羟基化 TPHP 代谢物的发育循环障碍几乎与 TPHP 等效。二酯 OPFR 代谢物在本研究中使用的浓度下没有表现出重大的发育毒性。目前的结果为进一步了解 OPFR 及其代谢物毒性机制的异同奠定了基础。 (C) 2019 Elsevier Ltd. 保留所有权利。
Organophosphate triesters are used worldwide as additives in flame retardants and plasticizer as a replacement of polybrominated diphenyl ethers. Increasing evidence on human exposure to and environmental contamination with organophosphorus flame retardants (OPFRs) requires an adequate toxicity assessment for this class of chemicals. While developmental toxicity of several OPFRs has been reported, developmental effects of OPFR metabolites have still to be understood. The present study aimed at characterizing developmental effects of OPFR metabolites using zebrafish embryos (Danio rerio). Triphenyl phosphate (TPHP) and two of its metabolites, 3-hydroxylphenyl diphenyl phosphate and 4-hydroxylphenyl diphenyl phosphate, were most potent for inducing pericardial edema and reduction in blood flow in trunk vessels. Other TPHP metabolites, such as diphenyl phosphate and 4-hydroxylphenyl phenyl phosphate, showed no substantial increase in circulatory failure at concentrations up to 30 mu M. Tris (1,3-dichloro-2-propyl) phosphate showed circulatory failure at 30 mu M, but its metabolite bis(1,3-dichloro-2-propyl) phosphate did not. Neither tris(2-chloroethyl) phosphate nor its metabolite bis(2-chloroethyl) phosphate, induced circulatory failure. The circulatory failure appeared to be enhanced with the increase in the octanol-water partition coefficients of OPFRs and their metabolites, suggesting that developmental circulatory failure posed by these chemicals could be estimated by their bioaccumulative potential. The present study demonstrated developmental circulatory failure of hydroxylated TPHP metabolites, which was almost equipotent to TPHP. Diester OPFR metabolites showed no major developmental toxicity at the concentrations used in this study. The current results establish the foundation for further understanding the similarities and differences in the toxic mechanisms between OPFRs and their metabolites. (C) 2019 Elsevier Ltd. All rights reserved.