BDE No 99
(Synonyms: 2,2',4,4',5-五溴联苯醚, 2,2′,4,4′,5-PentaBDE) 目录号 : GC18657
BDE No 99 是在人体体液和脂肪饮食中检测到的主要多溴联苯醚 (PBDE) 同系物。
Cas No.:60348-60-9
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Human and mouse neural progenitor cells |
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Preparation Method |
Human mouse neural progenitor cells (NPCs) were differentiated with DMSO or increasing concentrations of BDE No 99 for 5 days. oligodendrocyte lineage cells were immunocytochemically stained with an antibody against O4 and nuclei were counterstained with Hoechst 33258. Viability was measured with the Alamar-Blue assay two hours prior fixation. |
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Reaction Conditions |
0.01 - 20µM BDE No 99 for 5 days. |
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Applications |
BDE No 99 reduces NPC differentiation to the oligodendrocyte (O4+ cells) lineage. BDE No 99 reduced human and murine O4+ cell formation in a concentration-dependent manner with human NPCs being 7-times more sensitive towards BDE No 99 exposure than their murine counterparts. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6J conventional(CV) mice, C57BL/6J germ-free (GN) mice |
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Preparation Method |
CV and GN mice were randomly allocated for the treatment of vehicle (corn oil, 10 ml/kg), or BDE No 99 via oral gavage once daily for 4 days. Livers were collected 24 hours after the last dosing on the fifth day and immediately frozen in liquid nitrogen. The mRNAs of phase-I drug-metabolizing enzymes Cyp1a2 , Cyp2b10, and Cyp3a11 were quantified in livers of CV mice using RT-qPCR. |
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Dosage form |
10, 100 μmol/kg BDE No 99, oral gavage |
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Applications |
Many Cyp2 family members (such as Cyp2a5, Cyp2b10, Cyp2c37, Cyp2c50, Cyp2c54, and Cyp2c55) are upregulated by BDE No 99 in livers of both CV and GF mice, with a much greater fold change observed in GF conditions. |
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References: [1]. Dach K, Bendt F, et al. BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action. Sci Rep. 2017 Mar 20;7:44861. [2]. Li CY, Lee S, et al. Novel Interactions between Gut Microbiome and Host Drug-Processing Genes Modify the Hepatic Metabolism of the Environmental Chemicals Polybrominated Diphenyl Ethers. Drug Metab Dispos. 2017 Nov;45(11):1197-1214. |
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BDE No 99 is the predominant Polybrominated diphenyl ethers(PBDE) congeners detected in human fluid and fatty diet. PBDEs are persistent and bio-accumulative in the environment.[1].
BDE No 99 reduced human and murine oligodendrocyte lineage (O4+) cell formation in a concentration-dependent manner (IC50 1.9?μM and 13.6?μM, respectively and IC20 0.9?μM and 6.9?μM, respectively) with human NPCs being 7-times more sensitive towards BDE No 99 exposure than their murine counterparts. BDE No 99 reduced generation of human and mouse O4+ cells, but there is no indication for BDE No 99 interfering with cellular TH signaling during O4+ cell formation. BDE No 99 reduced hMBP expression due to oligodendrocyte reduction, but concentrations that did not affect the number of mouse O4+ cells inhibited TH-induced mMog transcription by a yet unknown mechanism[2]
BDE No 99 increased unconjugated bile acids(BAs) in the serum, liver, small large intestinal contents(SIC) and large intestinal contents(LIC) of conventional mice. BDE No 99 profoundly decreased the alpha diversity of gut microbiome and differentially regulated 45 bacterial species. BDE No 99 downregulated enzymes and transporters involved in BA metabolism, in a gut microbiome-dependent manner[3]
References:
[1]. Frederiksen M, Vorkamp K, et al. Human internal and external exposure to PBDEs--a review of levels and sources. Int J Hyg Environ Health. 2009 Mar;212(2):109-34.
[2]. Dach K, Bendt F, et al. BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action. Sci Rep. 2017 Mar 20;7:44861.
[3]. Li CY, Dempsey JL, et al. PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice. Drug Metab Dispos. 2018 Aug;46(8):1226-1240.
BDE No 99 是在人体体液和脂肪饮食中检测到的主要多溴联苯醚 (PBDE) 同系物。 PBDEs 在环境中具有持久性和生物蓄积性。[1]。
BDE No 99 以浓度依赖性方式减少人和鼠少突胶质细胞谱系 (O4+) 细胞形成（IC50 分别为 1.9μM 和 13.6μM，IC20 分别为 0.9μM 和 6.9μM），人类 NPC 的数量是其 7 倍对 BDE No 99 的暴露比他们的小鼠对应物更敏感。 BDE No 99 减少了人和小鼠 O4+ 细胞的生成，但没有迹象表明 BDE No 99 在 O4+ 细胞形成过程中干扰细胞 TH 信号传导。 BDE No 99 由于少突胶质细胞减少而降低了 hMBP 表达，但不影响小鼠 O4+ 细胞数量的浓度通过未知机制抑制了 TH 诱导的 mMog 转录[2]
BDE No 99 增加了常规小鼠血清、肝脏、小肠内容物 (SIC) 和大肠内容物 (LIC) 中的未结合胆汁酸 (BA)。 BDE No 99 显着降低了肠道微生物组的 alpha 多样性，并对 45 种细菌进行了差异调节。 BDE No 99 以肠道微生物组依赖性方式下调参与 BA 代谢的酶和转运体[3]
| Cas No. | 60348-60-9 | SDF | |
| 别名 | 2,2',4,4',5-五溴联苯醚, 2,2′,4,4′,5-PentaBDE | ||
| 化学名 | 1,2,4-Tribromo-5-(2,4-dibromophenoxy)benzene | ||
| Canonical SMILES | BrC1=C(OC2=CC(Br)=C(Br)C=C2Br)C=CC(Br)=C1 | ||
| 分子式 | C12H5Br5O | 分子量 | 564.69 |
| 溶解度 | 50 μg/mL in isooctane | 储存条件 | Store at 2-8°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7709 mL | 8.8544 mL | 17.7088 mL |
| 5 mM | 0.3542 mL | 1.7709 mL | 3.5418 mL |
| 10 mM | 0.1771 mL | 0.8854 mL | 1.7709 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
BDE-99, but not BDE-47, is a transient aryl hydrocarbon receptor agonist in zebrafish liver cells
Toxicol Appl Pharmacol2016 Aug 15;305:203-215.PMID: 27343407DOI: 10.1016/j.taap.2016.06.023
Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting chemicals that affect the environment and the health of humans and wildlife. In this study, the zebrafish liver (ZFL) cell line was used in vitro to investigate two major PBDE contaminants: 2, 2', 4, 4', 5-pentabromodiphenyl ether (BDE-99) and 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47). BDE-99 was found to significantly induce cytochrome P450 (CYP1A), uridine diphosphate glucuronosyl transferase 1 family a, b (ugt1ab), 7-ethoxyresorufin-O-deethylase activity and an aryl hydrocarbon receptor (Ahr) dependent xenobiotic response element luciferase reporter system, confirming the Ahr-mediated activation of CYP1A by BDE-99. The time-course effect indicated that the role of BDE-99 in Ahr-mediated signaling is likely to be transient and highly dependent on the ability of BDE-99 to induce CYP1A and ugt1ab, and presumably its metabolism. BDE-99 also exhibited a significant dose-response effect on a developed zebrafish pregnane X receptor luciferase reporter gene system. However, the other abundant contaminant under study, BDE-47, did not exhibit the above effects. Together, these results indicated that the molecular mechanism of PBDEs induced in ZFL cells is a chemically specific process that differs between members of the PBDE family. CYP1A induction derived by BDE-99 warrants further risk assessment as the humans, wildlife and environment are exposed to a complex mixture including dioxin-like compounds and carcinogenic compounds.
Developmental exposure to BDE-99 hinders cerebrovascular growth and disturbs vascular barrier formation in zebrafish larvae
Aquat Toxicol2019 Sep;214:105224.PMID: 31255847DOI: 10.1016/j.aquatox.2019.105224
Polybrominated diphenyl ethers (PBDEs) are distributed throughout the environment. Despite a moratorium on their use, concentrations of PBDEs in the atmosphere and in residential environments remain high due to their persistence. The environmental health risks remain concerning and one of the major adverse effects is neurodevelopmental toxicity. However, the early response and effects of PBDEs exposure on the developing brain remain unknown. In the present study, we investigated the impacts of 2,2',4,4',5-pentabrominated diphenyl ether (BDE-99) on vascular growth and vascular barrier function with an emphasis on cerebral blood vessels, in the early life stages, using a zebrafish model. No general toxicity was observed in exposing zebrafish larvae to 0-0.5 μM BDE-99 at 72 hpf. BDE-99 exposure resulted in neither general toxicity nor pronounced developmental impairment in somatic blood vessels, including intersegmental vessels (ISV) and common cardinal veins (CCV). Meanwhile, both 0.05 μM and 0.5 μM of BDE-99 reduced cerebrovascular density as well as down-regulation of VEGFA and VEGFR2 in the head. In addition, BDE-99 exposure increased vascular leakage, both in cerebral and truncal vasculature at 72 hpf. The accentuated vascular permeability was observed in the head. The mRNA levels of genes encoding tight junction molecules decreased in the BDE-99-exposed larvae, and more robust reductions in Cldn5, Zo1 and Jam were detected in the head than in the trunk. Moreover, proinflammatory factors including TNF-α, IL-1β and ICAM-1 were induced, and the expression of neurodevelopment-related genes was suppressed in the head following BDE-99 exposure. Taken together, these results reveal that developmental exposure to BDE-99 impedes cerebrovascular growth and disturbs vascular barrier formation. The cerebral vasculature in developing zebrafish, a more sensitive target for BDE-99, may be a promising tool for the assessment of the early neurodevelopmental effects due to PBDEs exposure.
BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action
Sci Rep2017 Mar 20;7:44861.PMID: 28317842DOI: 10.1038/srep44861
Polybrominated diphenyl ethers (PBDEs) are bioaccumulating flame retardants causing developmental neurotoxicity (DNT) in humans and rodents. Their DNT effects are suspected to involve thyroid hormone (TH) signaling disruption. Here, we tested the hypothesis whether disturbance of neural progenitor cell (NPC) differentiation into the oligodendrocyte lineage (O4+ cells) by BDE-99 involves disruption of TH action in human and mouse (h,m)NPCs. Therefore, we quantified differentiation of NPCs into O4+ cells and measured their maturation via expression of myelin-associated genes (hMBP, mMog) in presence and absence of TH and/or BDE-99. T3 promoted O4+ cell differentiation in mouse, but not hNPCs, and induced hMBP/mMog gene expression in both species. BDE-99 reduced generation of human and mouse O4+ cells, but there is no indication for BDE-99 interfering with cellular TH signaling during O4+ cell formation. BDE-99 reduced hMBP expression due to oligodendrocyte reduction, but concentrations that did not affect the number of mouse O4+ cells inhibited TH-induced mMog transcription by a yet unknown mechanism. In addition, ascorbic acid antagonized only the BDE-99-dependent loss of human, not mouse, O4+ cells by a mechanism probably independent of reactive oxygen species. These data point to species-specific modes of action of BDE-99 on h/mNPC development into the oligodendrocyte lineage.
Hepatic microsomal metabolism of BDE-47 and BDE-99 by lesser snow geese and Japanese quail
Chemosphere2017 Sep;182:559-566.PMID: 28525869DOI: 10.1016/j.chemosphere.2017.05.027
In the present study, we investigated the oxidative biotransformation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) by liver microsomes from wild lesser snow geese (Chen caerulescens caerulescens) and domesticated Japanese quail (Coturnix japonica). Formation of hydroxy-metabolites was analyzed using an ultra-high performance liquid chromatography-tandem mass spectrometry-based method. Incubation of BDE-47 with avian liver microsomes produced sixteen hydroxy-metabolites, eight of which were identified using authentic standards. The major metabolites formed by liver microsomes from individual lesser snow geese were 4-hydroxy-2,2',3,4'-tetrabromodiphenyl ether (4-OH-BDE-42), 3-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (3-OH-BDE-47), and 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether (4'-OH-BDE-49). By comparison, 4-OH-BDE-42 and 4'-OH-BDE-49, but not 3-OH-BDE-47, were major metabolites of Japanese quail liver microsomes. Unidentified metabolites included monohydroxy- and dihydroxy-tetrabromodiphenyl ethers. Incubation of BDE-99 with avian liver microsomes produced seventeen hydroxy-metabolites, twelve of which were identified using authentic standards. The major metabolites formed by lesser snow goose liver microsomes were 2,4,5-tribromophenol, 3-OH-BDE-47, 4'-OH-BDE-49, 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether (4-OH-BDE-90), and 5'-hydroxy-2,2',4,4',5-pentabromodiphenyl ether (5'-OH-BDE-99). By comparison, the major metabolites produced by liver microsomes from Japanese quail included 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) and 2-hydroxy-2',3,4,4',5-pentabromodiphenyl ether (2-OH-BDE-123), but not 3-OH-BDE-47. Unidentified metabolites consisted of monohydroxy-pentabromodiphenyl ethers, monohydroxy-tetrabromodiphenyl ethers and dihydroxy-tetrabromodiphenyl ethers. Another difference between the two species was that formation rates of BDE-47 and BDE-99 metabolites were greater with liver microsomes from male than female Japanese quail, but a sex difference was not observed with lesser snow geese.
Toxicity of BDE-47, BDE-99 and BDE-153 on swimming behavior of the unicellular marine microalgae Platymonas subcordiformis and implications for seawater quality assessment
Ecotoxicol Environ Saf2019 Jun 15;174:408-416.PMID: 30851538DOI: 10.1016/j.ecoenv.2019.02.050
Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants, have been extensively applied and eventually leached into the surrounding environment. Marine microalgae are not only the dominant primary producers of marine ecosystem, but also food source for aquaculture. PBDEs have been found to remarkably inhibit growth, photosynthesis and metabolism of marine microalgae. However, whether they also affect swimming behavior of marine motile microalgae remains unknown. We chose BDE-47, BDE-99 and BDE-153 as model PBDEs, and the unicellular marine green flagellate, Platymonas subcordiformis, as test organism to figure out this issue. After two-hour exposure, motile cells proportion (MOT), swimming velocity (VCL, VAP and VSL), and swimming pattern (LIN and STR) of P. subcordiformis were measured via computer assisted cell movement tracking. Results suggest that the three PBDEs not only reduced motile cells proportion and swimming velocity, but also altered swimming pattern. BDE-47 was more toxic than BDE-99, followed by BDE-153, indicating their toxicity decreased as bromination degree increases. Swimming ability of P. subcordiformis was even completely arrested when BDE-47 and BDE-99 at 32 μg/L. The impairment of swimming ability by PBDEs might thereby hinder growth and survival of marine microalgae, and subsequently threaten marine ecosystem and aquaculture industry. More importantly, this study implies that marine microalgae swimming behavior test is more efficiency and sensitive than traditional marine microalgal bioassays, like growth and photosynthesis tests. We suggest that although future work is needed, swimming behavior analysis of P. subcordiformis with MOT, VCL and VAP as endpoints can be developed as a low-cost, convenient, fast, reliable and sensitive method for seawater quality assessment.