基于生物监测与分子对接的十溴联苯人体暴露与代谢排泄机制研究

Study on human exposure and metabolic excretion mechanism of decabromobiphenyl based on biological monitoring and molecular docking

摘要

通过结合环境监测与分子对接技术，系统评估了十溴联苯（decabromobiphenyl，BB-209）的暴露特征及人体代谢排泄机制。结果显示，BB-209在宿舍灰尘中占主导地位（占多溴联苯总量的91%，中位浓度：0.857ng/g）。在头发样本中，BB-209是主要蓄积同系物（最高浓度：16.04ng/g），在不同生活环境中无显著差异，表明存在持续暴露。在尿液样本中，低溴代同系物4，4'-二溴联苯（4，4'-dibromobiphenyl，BB-15）浓度增加，而BB-209因与巨蛋白（Megalin，LRP2）结合能强（-6.76kcal/mol）故排泄受限。分子对接结果显示，BB-209与细胞色素P450酶（cytochromeP450，CYP450）的结合能弱于2，2'，4，4'，5，5'-六溴联苯（2，2'，4，4'，5，5'-hexabromobiphenyl，BB-153），其结合自由能分别为-6.79kcal/mol和-7.27kcal/mol，证实其代谢惰性。与已禁止的类似污染物相比，BB-209在灰尘中的残留水平显著高于十氯联苯（decachlorobiphenyl，PCB-209），它在头发中的积累量达到十溴二苯醚（decabromodiphenyl ether，BDE-209）的21%。目前，BB-209尚未纳入《关于持久性有机污染物的斯德哥尔摩公约》（简称《斯德哥尔摩公约》）及我国的《重点管控新污染物清单》。本研究建议将头发监测作为评估BB-209暴露的有效工具，加强对电子产品中多溴联苯同系物的区分，为控制BB-209对人体的健康风险提供了科学依据。

Abstract

This study systematically evaluated the exposure characteristics and human metabolic excretion mechanisms of decabromobiphenyl (BB-209) by integrating environmental monitoring and molecular docking techniques. The results showed that BB-209 was predominant in dormitory dust, accounting for 91% of the total polybrominated biphenyls with a median concentration of 0.857ng/g. In hair samples, BB-209 was the major accumulated congener (maximum concentration: 16.04ng/g), and no significant difference was observed across different living environments, indicating ongoing exposure. Urine analysis revealed increased excretion of the low-brominated congener 4,4'-dibromobiphenyl (BB-15), whereas BB-209 excretion was limited due to its strong binding energy with Megalin (-6.76 kcal/mol). Molecular docking results demonstrated that BB-209 has a weaker binding affinity to CYP450 enzymes than 2,2',4,4',5,5'-hexabromobiphenyl (BB-153), with binding free energies of -6.79 kcal/mol and -7.27 kcal/mol, respectively, confirming its metabolic inertness. Compared with banned analogous pollutants, BB-209 exhibited significantly higher residual levels in dust than decachlorobiphenyl (PCB-209), and its accumulation in hair reached 21% of that of decabromodiphenyl ether (BDE-209). Currently, BB-209 has not been included in the Stockholm Convention on Persistent Organic Pollutants (Stockholm Convention) or China's List of Key Controlled New Pollutants. This study recommends hair monitoring as an effective tool for assessing BB-209 exposure and calls for enhanced differentiation of polybrominated biphenyl congeners in electronic products, thereby providing a scientific basis for controlling the health risks posed by BB-209 to humans.

关键词

十溴联苯（BB-209） / 人体生物监测 / 分子对接 / 暴露评估 / Megalin蛋白

Key words

Decabromobiphenyl (BB-209) / Human biomonitoring / Molecular docking / Exposure assessment / Megalin

参考文献

[1] Antonio Agudo, Pierluigi Cocco, Kristan J Aronson, et al. Polychlorinated biphenyls and polybrominated biphenyls [J]. IARC Monogr Eval Carcinog Risks Hum, 2016, 107: 9-500.

[2] Mehran Alaeea, Pedro Ariasb, Andreas Sjödin, et al. An overview of commercially used brominated flame retardants, their applications, their use patterns in different countries/regions and possible modes of release [J]. Environment International, 2003, 29(6): 683-689.

[3] 包峻松 . 人体血清中卤代阻燃剂暴露水平影响因素及健康效应的初步研究[D]. 北京: 中央民族大学, 2022.

[4] Stockholm convention on persistent organic pollutants [J]. Gefahrst Reinhalt Luft, 2015, 75(7—8): 264.

[5] CB/T 26572— 2011 电子电气产品中限用物质的限量要求[S]. 北京: 中华人民共和国国家质量监督检验检疫总局, 中国国家标准化管理委员会, 2011.

[6] GB 18584— 2024 家具中有害物质限量[S]. 北京: 国家市场监督管理总局,国家标准化管理委员会, 2024.

[7] Wang Shijie, Jin Jingxi, Guo Chen, et al. Previously identified and unidentified polybrominated biphenyl congeners in serum from people living in an electronic waste dismantling area in China [J]. Chemosphere, 2021, 279: 130478.

[8] 石银俊, 周衍霄, 朱国华, 等 . 同位素稀释气相色谱—高分辨质谱法测定土壤和沉积物中20种多溴联苯[J]. 环境化学, 2018, 37(9): 1994-2001.

[9] Zhao Gaofeng, Wang Zijian, Michael H Dong, et al. PBBs, PBDEs, and PCBs levels in hair of residents around e—waste disassembly sites in Zhejiang Province, China, and their potential sources [J]. Science of the Total Environment, 2008, 397(1): 46-57.

[10] Jin—Woo Jeon, Chul—Su Kim, Ho—Joong Kim, et al. Spatial distribution, source identification, and anthropogenic effects of brominated flame retardants in nationwide soil collected from South Korea [J]. Environmental Pollution (Barking, Essex : 1987), 2020(prepublish): 116026.

[11] Wang Maosung, Chen ShuijenHuang, Kuolin, et al. Determination of levels of persistent organic pollutants (PCDD/Fs, PBDD/Fs, PBDEs, PCBs, and PBBs) in atmosphere near a municipal solid waste incinerator [J]. Chemosphere, 2010, 80(10): 1220-1226.

[12] Angela A Peverly, Amina Salamova, Ronald A Hites . Air is still contaminated 40 years after the Michigan Chemical plant disaster in St. Louis, Michigan [J]. Environmental Science & Technology, 2014, 48(19): 11154-11160.

[13] Andreas Sjodin, Hakan Carlsson, Kaj Thuresson, et al. Flame retardants in indoor air at an electronics recycling plant and at other work environments [J]. Environmental Science & Technology, 2001, 35(3): 448-54.

[14] 董黎静, 戴玄吏, 滕加泉, 等 . DPX快速萃取程序升温大体积进样GC/MS法测定水中19种多溴联苯化合物[J]. 环境监控与预警, 2016, 8(4): 9-17, 66.

[15] Kebede K Kefenia, Jonathan O Okonkwoa, Ben M Botha . Concentrations of polybromobiphenyls and polybromodiphenyl ethers in home dust: Relevance to socio—economic status and human exposure rate [J]. Science of the Total Environment, 2014, 470—471: 1250-1256.

[16] Kingsley Kay . Polybrominated biphenyls (PBB) environmental contamination in Michigan, 1973—1976 [J]. Environmental Research, 1977, 13(1): 74-93.

[17] Robert B Hood, Metrecia L Terrell, Sarah Mardovich, et al. Polybrominated biphenyls (PBBs) and prevalence of autoimmune disorders among members of the Michigan PBB registry [J]. Environmental Research, 2023, 239(P1): 117312.

[18] Andreas Sjödin, Richard S Jones, Lee—Yang Wong, et al. Polybrominated diphenyl ethers and biphenyl in serum: Time trend study from the national health and nutrition examination survey for years 2005/06 through 2013/14 [J]. Environmental Science & Technology, 2019, 53(10): 6018-6024.

[19] Bao Junsong, Jin Hongli, Wang Ying, et al. New emerging polybromobiphenyls in serum of general population and their disruption on thyroid hormone receptor β1 [J]. Environment International, 2022, 166: 107390.

[20] Jiang Junjie, Li Tianwei, Wang Erde, et al. Polybrominated diphenyl ethers in dust, hair and urine: Exposure, excretion [J]. Chemosphere, 2024, 352: 141380.

[21] Wang Erde, Zhang Yan, Li Tianwei, et al. Dechlorane plus in dust, hair and urine: Exposure, excretion and level change [J]. Environmental Research, 2024, 262(P2): 119807.

[22] Gurusankar Saravanabhavan, Mike Walker, Mireille Guay, et al. Urinary excretion and daily intake rates of diethyl phthalate in the general Canadian population [J]. Science of the Total Environment, 2014, 500—501: 191-198.

[23] Frederik Lessmann, André Schütze, Tobias Weiss, et al. Metabolism and urinary excretion kinetics of di(2—ethylhexyl) terephthalate (DEHTP) in three male volunteers after oral dosage [J]. Archives of Toxicology, 2016, 90(7): 1659-1667.

[24] Erik I Christensen, Henrik Birn, Tina Storm, et al. Endocytic receptors in the renal proximal tubule [J]. Physiology (Bethesda, Md), 2012, 27(4): 223-236.

[25] Furge Laura Lowe, Guengerich F Peter . Cytochrome P450 enzymes in drug metabolism and chemical toxicology [J]. Biochemistry and Molecular Biology Education, 2006, 34(2): 66-74.

[26] Guengerich F Peter . Roles of individual human cytochrome P450 enzymes in drug metabolism [J]. Pharmacological Reviews, 2024, 76(6): 1104-1132.

[27] Wilson Maldonado—Rojas, Karen Rivera—Julio, Jesus Olivero—Verbel, et al. Mechanisms of interaction between persistent organic pollutants (POPs) and CYP2B6: An in silico approach [J]. Chemosphere, 2016, 159: 113-125.

[28] Golnoush Abbasi, Andreas M Buser, Anna Soehl, et al. Stocks and flows of PBDEs in products from use to waste in the U.S. and Canada from 1970 to 2020 [J]. Environmental Science & Technology, 2015, 49(3): 1521-1528.

[29] Barbara A Beckingham, Kerry Wischusen, Joanna P Walker . Phthalate exposure among U.S. college—aged women: Biomonitoring in an undergraduate student cohort (2016—2017) and trends from the National Health and Examination Survey (NHANES, 2005—2016) [J]. PloS One, 2022, 17(2): e0263578.

[30] Li Junqi, Dong Zheng, Wang Ying, et al. Human exposure to brominated flame retardants through dust in different indoor environments: Identifying the sources of concentration differences in hair from men and women [J]. Chemosphere, 2018, 205: 71-79.

[31] Li Junq, Dong Zheng, Wang Ying, et al. Different organophosphate flame retardant and metabolite concentrations in urine from male and female university students in Beijing and an assessment of exposure via indoor dust [J]. Environmental Toxicology and Chemistry, 2019, 38(4): 760-768.

[32] Chinemerem Ruth Ohoeo, Abiodun Olagoke Adeniji, Anthony Ifeanyi Okoh, et al. Polybrominated diphenyl ethers in the environmental systems:A review [J]. Journal of Environmental Health Science and Engineering, 2021, 19(1): 1-19.

[33] Wu Jing, Hu Jicheng, Wang Shijie, et al. Levels, sources, and potential human health risks of PCNs, PCDD/Fs, and PCBs in an industrial area of Shandong Province, China [J]. Chemosphere, 2018, 199: 382-389.

[34] Chitra Narayanan, Yevgen Nazarenko . In silico characterization of molecular interactions of aviation—derived pollutants with human proteins: Implications for occupational and public health [J]. Atmosphere, 2025, 16(8): 919.

[35] Wang Ruige, Lin Yaqi, Sun Ying, et al. Insight into the molecular recognition of human and polar bear pregnane X receptor by three organic pollutants using molecular docking and molecular dynamics simulations [J]. Environment International, 2024, 190: 108926.

基金资助

内蒙古工业大学战略性先导性科技项目-能源转型背景下的环境治理(DC2400003368)

内蒙古自治区自然科学基金(2025QN04023)