双酚类化合物对机体影响的研究进展

兰天; 段国珍; 刘娜; 樊光辉; 赵成周; 杨仕兵; 祁有朝

doi:10.13386/j.issn1002-0306.2022080072

双酚类化合物对机体影响的研究进展

doi: 10.13386/j.issn1002-0306.2022080072

兰天^{1, 2, 3, 4,},
段国珍²,
刘娜^{1, 3, 4},
樊光辉²,
赵成周³,
杨仕兵⁴,
祁有朝^{1, 2, 3, 4,*, ,}

1.
青海大学农牧学院，青海西宁 810016
2.
青海大学农林科学院，青海西宁 810016
3.
青海大学藏医学院，青海西宁 810016
4.
青海大学医学院，青海西宁 810016

基金项目: 青海省科技基础研究计划青年项目（2021-ZJ-962Q）；2020年度青海大学青年科研基金项目（2020-QNY-3）；县域创新试点县建设专项（2020-0407-NCC-0001）。

详细信息

作者简介:
兰天（1998−），女，硕士研究生，研究方向：药理学与毒理学，E-mial：1289495380@qq.com

通讯作者:
祁有朝（1990−），男，博士，副教授，研究方向：药理学与毒理学，E-mail：yaolixueyouchao@163.com

中图分类号: TS201.6
计量
- 文章访问数: 81
- HTML全文浏览量: 21
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2022-08-09
- 刊出日期: 2023-05-15

Research Progress on the Effects of Bisphenol Compounds on Human Beings and Animals

LAN Tian^{1, 2, 3, 4
,},
DUAN Guozhen²,
LIU Na^{1, 3, 4},
FAN Guanghui²,
ZHAO Chengzhou³,
YANG Shibing⁴,
QI Youchao^{1, 2, 3, 4,*
, ,}

1.
College of Agriculture and Animal Husbandry, Qinghai University, Xining 810016, China
2.
College of Agriculture and Forestry, Qinghai University, Xining 810016, China
3.
College of Tibetan Medicine, Qinghai University, Xining 810016, China
4.
College of Medical, Qinghai University, Xining 810016, China

摘要

摘要: 双酚类化合物（Bisphenol compounds，BPs）是合成高分子材料的重要原材料之一。目前，常见的双酚类化合物主要包括双酚A、双酚B、双酚F以及双酚AF等。现如今，双酚类化合物主要应用于塑料制品、食品包装、饮用水添加剂、海鲜等方面。大量的研究发现，双酚类化合物通过物理迁移、化学迁移、生物迁移途径侵入人类和动物体内，甚至在深海哺乳动物体内也检测到了该物质，从而影响了机体的生殖系统、神经系统、消化系统、心血管系统、行为、发育和代谢性疾病的发生发展。因此，双酚类化合物引起了更多的关注。因此，本文主要从BPs的分类、侵入机体的途径以及对机体的影响方面进行了综述，以期对BPs的进一步研究以及安全性和毒理学评价提供参考依据。
- 双酚类化合物 /
- 分类 /
- 侵入途径 /
- 机体影响 /
- 作用机制
Abstract: Bisphenol compounds (BPs) are one of the most significant raw materials, used in synthesizing high polymer materials. At present, common BPs mainly include bisphenol A, bisphenol B, bisphenol F, bisphenol AF and so on. Nowadays, BPs are principally applied in plastic products, the food packaging, drinking water additives, seafood and other fields. A large number of studies have found that BPs penetrate into human beings and animals by physical migration, chemical migration, biological migration and it even have been detected in deep-sea mammals, affecting the mechanisms of the reproductive system, central nervous system, digestive system, cardiovascular system, behavior, development, and metabolic diseases. Therefore, BPs have been attracting more attention. In the review, the classification, invasive pathway to foods of BPs, and its implication on human beings and animals are systematically reviewed, hoping to provide reference for the safety and toxicological evaluation of BPs.
- bisphenol compounds /
- classification /
- invasion pathways /
- effects on human beings and animals /
- mechanism

HTML全文

图 1 双酚类化合物的结构

Figure 1. Structure of BPs

下载: 全尺寸图片幻灯片

图 2 双酚类化合物入侵食品的途径

Figure 2. Invasion pathways of BPs into foods

下载: 全尺寸图片幻灯片

图 3 双酚类化合物对机体的作用

Figure 3. Effects of BPs on the human beings and animals

下载: 全尺寸图片幻灯片

图 4 BPs信号转导通路

Figure 4. Bisphenols signal transduction pathways

下载: 全尺寸图片幻灯片

表 1 双酚类化合物的结构与侵入方式

Table 1. Structure and invasion pathways of BPs

名称	分子式	分子结构	侵入方式	侵入途径	参考文献
双酚A（BPA） Bisphenol A	C₁₅H₁₆O₂		物理迁移化学迁移生物迁移	皮肤和粘膜消化道呼吸道	[13]
双酚B（BPB） Bisphenol B	C₁₆H₁₈O₂				[16−17]
双酚C（BPC） Bisphenol C	C₁₇H₂₀O₂				[25]
双酚E（BPE） Bisphenol E	C₁₄H₁₄O₂				[26]
双酚F（BPF） Bisphenol F	C₁₃H₁₂O₂				[27]
双酚P（BPP） Bisphenol P	C₂₄H₂₆O₂				[26]
双酚S（BPS） Bisphenol S	C₁₂H₁₀O₄S				[28]
双酚Z（BPZ） Bisphenol Z	C₁₈H₂₀O₂				[29]
双酚AF（BPAF） Bisphenol AF	C₁₅H₁₀F₆O₂				[23]
双酚AP（BPAP） Bisphenol AP	C₂₀H₁₈O₂				[30]
四溴双酚A（TBBPA） Tetrabromo bisphenol A	C₁₅H₁₂Br₄O₂				[31]
四氯双酚A（TCBPA） Tetrachloro bisphenol A	C₁₅H₁₂Cl₄O₂				[32]

下载: 导出CSV

表 2 BPs对生殖系统的影响

Table 2. Effects of BPs on the reproductive system

研究类型（模型）		BPs	浓度	影响	参考文献
体外	牛卵母细胞和精子	BPA，BPS，BPF	0.05 mg/mL	BPA处理：活性氧升高，重组人线粒体超氧化物歧化酶-2、谷胱甘肽过氧化物酶1、谷胱甘肽过氧化物酶4基因及蛋白表达降低；BPF、BPS处理：精子产量减少	[41]
体外	人类精子	BPA	0，10⁻³，10⁻²，10⁻¹，10，10³ nmol/L	精子活力、进行性运动和黄体酮诱导的顶体反应显着下降	[42]
体内	雄性大鼠	BPS	0.5，5，50 μg/L	精子活力、产量、附睾中精子数量减少；血浆睾酮、黄体生成素、卵泡刺激素浓度降低，雌二醇水平升高；睾丸中氧化应激水平升高	[43]
体内	成年雄性小鼠	BPA	5，50 mg/kg bw/day	生殖细胞比例异常、睾丸形态改变、精元干细胞功能特性丧失	[44]
体外	小鼠卵母细胞	BPA，BPF	5，25，50 μg/mL	纺锤体缩短，微管附着减少	[45]
体内	成年雄性大鼠	BPF	1，5，25，50 mg/kg/d	精子减少，睾丸激素分泌物水平降低	[46]
体内	雌性和雄性斑马鱼	BPB	0.001，0.01，0.1，1 mg/L	鱼卵数量减少，孵化率及存活率降低，生殖功能受损	[47]
体内	雌性和雄性斑马鱼	BPAF	0.05，0.25，1 mg/L	雄性斑马睾酮水平降低，鱼E2水平升高；雌性斑马鱼睾酮分泌增加	[48]

下载: 导出CSV

表 3 BPs对胚胎发育的影响

Table 3. Effects of BPs on embryonic development

BPs	模型	暴露浓度	结果	参考文献
BPAP	斑马鱼	200 μg/L	鱼卵孵化率降低、死亡率升高、卵黄囊水肿比例增高、心率降低、出现心脏环化障碍	[56]
BPA	热带非洲爪蟾	25，50，100 μmol/L	发育迟缓、胚孔异常闭合、尾部弯曲、心包水肿、体长缩短	[52]
BPABPSBPAFTMBPF	雏鸡胚胎	0.03，0.3，3，30 μmol/L	抑制体长及体重的增长，躯干四肢及器官发育畸形，胚胎存活率降低	[57]
BPABPSBPAF	胚胎干细胞	1，10 ng/mL	抑制胚胎干细胞分化	[58]
BPA	非洲爪蟾	1，10，20 μmol/L	严重畸形、行为能力受损、组织器官受损、诱导DNA损伤的凋亡	[59]

下载: 导出CSV

参考文献(90)

[1]	刘洪媛, 金静, 郭崔崔, 等. 环境样品中双酚类化合物的固相萃取研究进展[J]. 色谱,2021,39(8):835−844. [LIU H Y, JIN J, GUO C C, et al. Research progress of solid phase extraction of bisphenols in environmental samples[J]. Chromatograph,2021,39(8):835−844.
[2]	赵斌, 谭学蓉, 付瑜, 等. 基于QuEChERS的超高效液相色谱-串联质谱法快速测定果蔬中双酚类物质[J]. 分析化学,2022,50(5):810−821. [ZHAO B, TAN X R, FU Y, et al. Rapid determination of bisphenols in fruits and vegetables by ultra high-performance liquid chromatography-tandem mass spectrometry based on QuEChERS[J]. Analytical Chemistry,2022,50(5):810−821.
[3]	李明, 高文晖, 余建龙, 等. 双酚类化合物促进乳腺癌细胞增殖活性的研究[J]. 毒理学杂志,2021,35(3):179−183,192. [LI M, GAO W H, YU J L, et al. Study on the effect of bisphenols on the proliferation of breast cancer cells[J]. Journal of Toxicology,2021,35(3):179−183,192.
[4]	LEE H R, JEUNG E B, CHO M H, et al. Molecular mechanism(s) of endocrine-disrupting chemicals and their potent oestrogenicity in diverse cells and tissues that express oestrogen receptors[J]. Journal of Cellular and Molecular Medicine,2013,17(1):1−11. doi: 10.1111/j.1582-4934.2012.01649.x
[5]	COSTA E M, SPRITZER P M, HOHL A, et al. Effects of endocrine disruptors in the development of the female reproductive tract[J]. Arquivos Brasileiros de Endocrinologia e Metabologia,2014,58(2):153−161. doi: 10.1590/0004-2730000003031
[6]	WILLHITE C C, DASTON G P. Bisphenol exposure, hazard and regulation[J]. Toxicology,2019,425:152243. doi: 10.1016/j.tox.2019.152243
[7]	吴皓, 孙东, 蔡卓平, 等. 双酚A的内分泌干扰效应研究进展[J]. 生态科学,2017,36(3):200−206. [WU H, SUN D, CAI Z P, et al. Research progress on endocrine disrupting effect of bisphenol A[J]. Ecological Science,2017,36(3):200−206.
[8]	WINKLER J, LIU P, PHONG K, et al. Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome[J]. Proceedings of the National Academy of Sciences of the United States of America,2022,119(11):e2115308119. doi: 10.1073/pnas.2115308119
[9]	REED J M, SPINELLI P, FALCONE S, et al. Evaluating the effects of BPA and TBBPA exposure on pregnancy loss and maternal-fetal immune cells in mice[J]. Environmental Health Perspectives,2022,130(3):37010. doi: 10.1289/EHP10640
[10]	LIU J, LIAO M, HUANG R, et al. Perinatal combinational exposure to bisphenol a and a high-fat diet contributes to transgenerational dysregulation of cardiovascular and metabolic systems in mice[J]. Frontiers in Cell and Developmental Biology,2022,10:834346. doi: 10.3389/fcell.2022.834346
[11]	CHEN D, KANNAN K, TAN H, et al. Bisphenol analogues other than BPA: Environmental occurrence, human exposure, and toxicity-a review[J]. Environmental Science & Technology,2016,50(11):5438−5453.
[12]	VANDENBERG LN, HAUSER R, MARCUS M, et al. Human exposure to bisphenol A (BPA)[J]. Reproductive Toxicology,2007,24(2):139−77. doi: 10.1016/j.reprotox.2007.07.010
[13]	ZINCKE T. Mittheilungen aus dem chemischen laboratorium der universitat marburg[J]. Justus Liebigs Annalen der Chemie,1905,343:75−99. doi: 10.1002/jlac.19053430106
[14]	SABRY R, NGUYEN M, YOUNES S, et al. BPA and its analogs increase oxidative stress levels in in vitro cultured granulosa cells by altering anti-oxidant enzymes expression[J]. Molecular and Cellular Endocrinology,2022,545:111574. doi: 10.1016/j.mce.2022.111574
[15]	SERRA H, BEAUSOLEIL C, HABERT R, et al. Evidence for bisphenol B endocrine properties: Scientific and regulatory perspectives[J]. Environmental Health Perspectives,2019,127(10):106001. doi: 10.1289/EHP5200
[16]	CATENZA C J, FAROOQ A, SHUBEAR N S, et al. A targeted review on fate, occurrence, risk and health implications of bisphenol analogues[J]. Chemosphere,2021,268:129273. doi: 10.1016/j.chemosphere.2020.129273
[17]	WANG H, SONG S, SHAO M, et al. Determination of bisphenol analogues in food-contact plastics using diode array detector, charged aerosol detector and evaporative light-scattering detector[J]. Ecotoxicology and Environmental Safety,2019,186:109778. doi: 10.1016/j.ecoenv.2019.109778
[18]	杨倩, 刘建梅, 丁洁, 等. 双酚B对斑马鱼性别分化的影响及作用机制[J]. 生态毒理学报,2021,16(4):151−159. [YANG Q, LIU J M, DING J, et al. Effect and mechanism of bisphenol B on sex differentiation of zebrafish[J]. Journal of Ecotoxicology,2021,16(4):151−159.
[19]	LU S, YU Y, REN L, et al. Estimation of intake and uptake of bisphenols and triclosan from personal care products by dermal contact[J]. The Science of the Total Environment,2018,21:389−1396.
[20]	ROCHESTER J R, BOLDEN A L. Bisphenol S and F: A systematic review and comparison of the hormonal activity of bisphenol a substitutes[J]. Environmental Health Perspectives,2015,23(7):43−650.
[21]	KURUTO-NIWA R, NOZAWA R, MIYAKOSHI T, et al. Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives using a GFP expression system[J]. Environmental Toxicology and Pharmacology,2005,19(1):121−130. doi: 10.1016/j.etap.2004.05.009
[22]	李星, 王浩, 张文超, 等. 固相萃取-液相色谱-串联质谱法同时测定牛奶中双酚A、双酚F和双酚S[J]. 中国食品学报,2022,22(4):382−386. [LI X, WANG H, ZHANG W C, et al. Simultaneous determination of bisphenol A, bisphenol F and bisphenol S in milk by solid phase extraction-liquid chromatography-tandem mass spectrometry[J]. Chinese Journal of Food,2022,22(4):382−386.
[23]	MATSUSHIMA A, LIU X, OKADA H, et al. Bisphenol AF is a full agonist for the estrogen receptor ERalpha but a highly specific antagonist for ERbeta[J]. Environmental Health Perspectives,2010,118(9):1267−1272. doi: 10.1289/ehp.0901819
[24]	JI K, CHOI K. Endocrine disruption potentials of bisphenol A alternatives[J]. Korean Journal of Environmental Health Sciences,2013,39(1):1−18. doi: 10.5668/JEHS.2013.39.1.1
[25]	付国瑞, 鲁文嘉. 袋装液态乳中4种双酚类化合物的检测与分析[J]. 食品安全导刊,2018,197(6):153−156. [FU G R, LU W J. Detection and analysis of four bisphenols in bagged liquid milk[J]. Food Safety Guide,2018,197(6):153−156.
[26]	黄苑, 张维, 王瑞国, 等. 双酚类化合物污染现状和内分泌干扰效应研究进展[J]. 生态毒理学报,2022,17(1):1−27. [HUANG Y, ZHANG W, WANG R G, et al. Research progress on pollution status and endocrine disrupting effects of bisphenols[J]. Journal of Ecotoxicology,2022,17(1):1−27.
[27]	LAUREL P. Potential designated chemicals: p,p'-Bisphenols and diglycidyl ethers of p,p'-bisphenols[C]//Biomonitoring California Scientific Guidance Panel Meeting. Sacramento: Office of Environmental Health Hazard Assessment, 2012: 3
[28]	XUE J, KANNAN P, KUMOSANI T A, et al. Resin-based dental sealants as a source of human exposure to bisphenol analogues, bisphenol A diglycidyl ether, and its derivatives[J]. Environmental Research,2018,162:35−40. doi: 10.1016/j.envres.2017.12.011
[29]	BECERRA V, ODERMATT J. Interferences in the direct quantification of bisphenol S in paper by means of thermochemolysis[J]. Journal of Chromatography A,2013,1275:70−77. doi: 10.1016/j.chroma.2012.12.034
[30]	ZHANG L, FANG P, YANG L, et al. Rapid method for the separation and recovery of endocrine-disrupting compound bisphenol AP from wastewater[J]. Langmuir:The ACS Journal of Surfaces and Colloids,2013,29(12):3968−3975. doi: 10.1021/la304792m
[31]	ZHANG J, SHI J, GE H, et al. Tiered ecological risk assessment of nonylphenol and tetrabromobisphenol A in the surface waters of China based on the augmented species sensitivity distribution models[J]. Ecotoxicology and Environmental Safety,2022,236:113446. doi: 10.1016/j.ecoenv.2022.113446
[32]	YE G, CHEN Y, WANG H O, et al. Metabolomics approach reveals metabolic disorders and potential biomarkers associated with the developmental toxicity of tetrabromobisphenol A and tetrachlorobisphenol A[J]. Scientific Reports,2016,6:35257. doi: 10.1038/srep35257
[33]	杨丹, 李丹丹, 刘姗姗, 等. 双酚A对机体的影响及其作用机制[J]. 现代预防医学,2008(17):3280−3282,3287. [YANG D, LI D D, LIU S S, et al. Effect of bisphenol A on body and its mechanism[J]. Modern Preventive Medicine,2008(17):3280−3282,3287. doi: 10.3969/j.issn.1003-8507.2008.17.011
[34]	BHANDARI R K, VOM-SAAL F S, TILLITT D E. Transgenerational effects from early developmental exposures to bisphenol A or 17α-ethinylestradiol in medaka, Oryzias latipes[J]. Scientific Reports,2015,5:9303. doi: 10.1038/srep09303
[35]	BHANDARI R K, WANG X, SAAL F S V, et al. Transcriptome analysis of testis reveals the effects of developmental exposure to bisphenol a or 17α-ethinylestradiol in medaka (Oryzias latipes)[J]. Aquatic Toxicology,2020,225:105553. doi: 10.1016/j.aquatox.2020.105553
[36]	REZAEE-TAZANGI F, ZEIDOONI L, RAFIEE Z, et al. Taurine effects on Bisphenol A-induced oxidative stress in the mouse testicular mitochondria and sperm motility[J]. JBRA Assisted Reproduction,2020,24(4):428−435.
[37]	MARKEY C M, COOMBS M A, SONNENSCHEIN C, et al. Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs[J]. Evolution & Development,2003,5(1):67−75.
[38]	RICHTER C A, BIRNBAUM L S, FARABOLLINI F, et al. In vivo effects of bisphenol A in laboratory rodent studies[J]. Reproductive Toxicology,2007,24(2):199−224.
[39]	PIAZZA M J, URBANETZ A A. Environmental toxins and the impact of other endocrine disrupting chemicals in women's reproductive health[J]. JBRA Assisted Reproduction,2019,23(2):154−164.
[40]	XUE W, YAO X, TING G, et al. BPA modulates the WDR₅/TET₂ complex to regulate ERβ expression in eutopic endometrium and drives the development of endometriosis[J]. Environmental Pollution,2021,268(Pt B):115748.
[41]	NGUYEN M, SABRY R, DAVIS O S, et al. Effects of BPA, BPS, and BPF on oxidative stress and antioxidant enzyme expression in bovine oocytes and spermatozoa[J]. Genes,2022,13(1):142. doi: 10.3390/genes13010142
[42]	LI N, KANG H, PENG Z, et al. Physiologically detectable bisphenol A impairs human sperm functions by reducing protein-tyrosine phosphorylation[J]. Ecotoxicology and Environmental Safety,2021,221:112418. doi: 10.1016/j.ecoenv.2021.112418
[43]	ULLAH H, ULLAH F, REHMAN O, et al. Chronic exposure of bisphenol S (BPS) affect hypothalamic-pituitary-testicular activities in adult male rats: Possible in estrogenic mode of action[J]. Environmental Health and Preventive Medicine,2021,26(1):31. doi: 10.1186/s12199-021-00954-0
[44]	KARMAKAR P C, AHN J S, KIM Y H, et al. Paternal Exposure to bisphenol-A transgenerationally impairs testis morphology, germ cell associations, and stemness properties of mouse spermatogonial stem cells[J]. International Journal of Molecular Sciences,2020,21(15):5408. doi: 10.3390/ijms21155408
[45]	YANG L, BAUMANN C, DE-LA-FUENTE R, et al. Mechanisms underlying disruption of oocyte spindle stability by bisphenol compounds[J]. Reproduction,2020,159(4):383−396. doi: 10.1530/REP-19-0494
[46]	ULLAH A, PIRZADA M, AFSAR T, et al. Effect of bisphenol F, an analog of bisphenol A, on the reproductive functions of male rats[J]. Environmental Health and Preventive Medicine,2019,24(1):41. doi: 10.1186/s12199-019-0797-5
[47]	YANG Q, YANG X H, LIU J N, et al. Exposure to bisphenol b disrupts steroid hormone homeostasis and gene expression in the hypothalamic–pituitary–gonadal axis of zebrafish[J]. Water Air & Soil Pollution,2017,228(3):112.1−112.12.
[48]	YANG X, LIU Y, LI J, et al. Exposure to bisphenol AF disrupts sex hormone levels and vitellogenin expression in zebrafish[J]. Environmental Toxicology,2016,31(3):285−294. doi: 10.1002/tox.22043
[49]	谢军, 李小玲, 陈宏. 双酚A致体外培养大鼠胚胎发育毒性的时间-效应关系研究[J]. 实用预防医学,2010,17(8):1649−1651. [XIE J, LI X L, CHEN H, et al. Study on time-effect relationship of developmental toxicity of rat embryos induced by bisphenol A in vitro[J]. Practical Preventive Medicine,2010,17(8):1649−1651. doi: 10.3969/j.issn.1006-3110.2010.08.075
[50]	王连卿. 双酚A对小鼠早期胚胎体外发育的影响[D]. 哈尔滨: 东北农业大学, 2007 WANG L Q. Effect of bisphenol A on the development of early mouse embryos in vitro[D]. Harbin: Northeast Agricultural University, 2007.
[51]	裴新荣, 李勇, 龙鼎新, 等. 双酚A对小鼠早期胚胎发育毒性的体外实验研究[J]. 中国生育健康杂志,2003(1):34−37, 65. [PEI X R, LI Y, LONG D X, et al. Experimental study on the toxicity of bisphenol A on early embryonic development of mice in vitro[J]. Chinese Journal of Reproductive Health,2003(1):34−37, 65.
[52]	CHEN H, ZHONG K, ZHANG Y, et al. Bisphenol A interferes with redox balance and the Nrf2 signaling pathway in xenopus tropicalis during embryonic development[J]. Animals,2022,12(7):937. doi: 10.3390/ani12070937
[53]	MCCORMICK J M, PAIVA M S, HÄGGBLOM M M, et al. Embryonic exposure to tetrabromobisphenol A and its metabolites, bisphenol A and tetrabromobisphenol A dimethyl ether disrupts normal zebrafish (Danio rerio) development and matrix metalloproteinase expression[J]. Aquatic toxicology,2010,100(3):255−262. doi: 10.1016/j.aquatox.2010.07.019
[54]	王英红, 徐虹, 孔庆鑫, 等. 双酚S急性暴露对斑马鱼胚胎及子代胚胎发育的毒性效应[J]. 中国卫生检验杂志,2019,29(1):32−36. [WANG Y H, XU H, KONG Q X, et al. Toxic effects of acute exposure to bisphenol S on embryo and offspring embryo development of zebrafish[J]. Chinese Journal of Health Inspection,2019,29(1):32−36.
[55]	郭依晨, 韩静静, 严锐, 等. 双酚A胚胎期暴露对斑马鱼的发育毒性及运动行为的影响[J]. 毒理学杂志,2018,32(2):152−155. [GUO Y C, HAN J J, YAN R, et al. Effects of embryonic exposure to bisphenol A on developmental toxicity and exercise behavior of zebrafish[J]. Journal of Toxicology,2018,32(2):152−155. doi: 10.16421/j.cnki.1002-3127.2018.02.015
[56]	王宏烨, 曹诚, 刘益海, 等. 双酚AP对斑马鱼心脏发育毒性作用研究[J]. 环境科学与技术,2019,42(8):1−6. [WANG H B, CAO Y, LIU Y H, et al. Study on cardiac developmental toxicity of bisphenol AP on zebrafish[J]. Environmental science and technology,2019,42(8):1−6.
[57]	HARNETT K G, MOORE L G, CHIN A, et al. Teratogenicity and toxicity of the new BPA alternative TMBPF, and BPA, BPS, and BPAF in chick embryonic development[J]. Current research in Toxicology,2021,2:399−410. doi: 10.1016/j.crtox.2021.11.001
[58]	ZHOU R, XIA M, ZHANG L, et al. Individual and combined effects of BPA, BPS and BPAF on the cardiomyocyte differentiation of embryonic stem cells[J]. Ecotoxicology and Environmental Safety,2021,220:112366. doi: 10.1016/j.ecoenv.2021.112366
[59]	GE Y, REN F, CHEN L, et al. Bisphenol A exposure induces apoptosis and impairs early embryonic development in Xenopus laevis[J]. Environmental Pollution,2021,280:116901. doi: 10.1016/j.envpol.2021.116901
[60]	YANG Q, ZHU Z, LIU Q, et al. Adverse effects of bisphenol B exposure on the thyroid and nervous system in early life stages of zebrafish[J]. Comparative Biochemistry and Physiology. Toxicology & Ppharmacology:CBP,2021,250:109167.
[61]	LEE C T, HSIEH C F, WANG J Y. Bisphenol a Induces Autophagy Defects and AIF-Dependent Apoptosis via HO-1 and AMPK to Degenerate N_2a Neurons[J]. International Journal of Molecular Sciences,2021,22(20):10948. doi: 10.3390/ijms222010948
[62]	SAHOO P K, APARNA S, NAIK P K, et al. Bisphenol A exposure induces neurobehavioral deficits and neurodegeneration through induction of oxidative stress and activated caspase-3 expression in zebrafish brain[J]. Journal of Biochemical and Molecular Toxicology,2021,35(10):e22873.
[63]	KOIKE E, YANAGISAWA R, WIN-SHWE T T, et al. Exposure to low-dose bisphenol A during the juvenile period of development disrupts the immune system and aggravates allergic airway inflammation in mice[J]. International Journal of Immunopathology and Pharmacology,2018,32:1−14.
[64]	YOUN J Y, PARK H Y, LEE J W, et al. Evaluation of the immune response following exposure of mice to bisphenol A: induction of Th1 cytokine and prolactin by BPA exposure in the mouse spleen cells[J]. Archives of Pharmacal Research,2002,25(6):946−953. doi: 10.1007/BF02977018
[65]	LEE J, LIM K T. Plant-originated glycoprotein (36 kDa) suppresses interleukin-4 and -10 in bisphenol A-stimulated primary cultured mouse lymphocytes[J]. Drug and Chemical Toxicology,2010,33(4):421−429. doi: 10.3109/01480541003739229
[66]	SUGITA-KONISHI Y, SHIMURA S, NISHIKAWA T, et al. Effect of Bisphenol A on non-specific immunodefenses against non-pathogenicEscherichia coli[J]. Toxicology Letters,2003,136(3):217−227. doi: 10.1016/S0378-4274(02)00388-0
[67]	GOTO M, TAKANO-ISHIKAWA Y, ONO H, et al. Orally administered bisphenol A disturbed antigen specific immunoresponses in the naive condition[J]. Bioscience, Biotechnology, and Biochemistry,2007,71(9):2136−2143. doi: 10.1271/bbb.70004
[68]	ROY A, BAUER S M, LAWRENCE B P. Developmental exposure to bisphenol A modulates innate but not adaptive immune responses to influenza A virus infection[J]. PLoS One,2012,7(6):e38448. doi: 10.1371/journal.pone.0038448
[69]	FEITEIRO J, MARIANA M, GLÓRIA S, et al. Inhibition of L-type calcium channels by Bisphenol A in rat aorta smooth muscle[J]. The Journal of Toxicological Sciences,2018,43(10):579−586. doi: 10.2131/jts.43.579
[70]	BROWN A R, GREEN J M, MOREMAN J, et al. Cardiovascular effects and molecular mechanisms of bisphenol A and its metabolite MBP in zebrafish[J]. Environmental Science & Technology,2019,53(1):463−474.
[71]	PAL S, SARKAR K, NATH P P, et al. Bisphenol S impairs blood functions and induces cardiovascular risks in rats[J]. Toxicology Reports,2017,4:560−565. doi: 10.1016/j.toxrep.2017.10.006
[72]	ILOZUMBA M N, SHELVER W L, HONG C C, et al. Urinary concentrations of triclosan, bisphenol A, and brominated flame retardants and the association of triclosan with demographic characteristics and body fatness among women with newly diagnosed breast cancer[J]. International Journal of Environmental Research and Public Health,2022,19(8):4681. doi: 10.3390/ijerph19084681
[73]	ZHANG X, GUO N, JIN H, et al. Bisphenol A drives di(2-ethylhexyl) phthalate promoting thyroid tumorigenesis via regulating HDAC6/PTEN and c-MYC signaling[J]. Journal of hazardous materials,2022,425:127911. doi: 10.1016/j.jhazmat.2021.127911
[74]	龙子, 樊隽澍, 吴光源, 等. 低剂量双酚A通过调控PPARγ致小鼠糖脂代谢紊乱的研究[J]. 癌变·畸变·突变,2020,32(04):245−255. [LONG Z, FAN J S, WU G Y, et al. Low-dose bisphenol A regulates glucose and lipid metabolism disorder induced by PPARγ in mice[J]. Cancerous Aberration Mutation,2020,32(04):245−255.
[75]	MASUNO H, KIDANI T, SEKIYA K, et al. Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes[J]. Journal of Lipid Research,2002,43(5):676−684. doi: 10.1016/S0022-2275(20)30108-5
[76]	WADA K, SAKAMOTO H, NISHIKAWA K, et al. Life style-related diseases of the digestive system: endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome[J]. Journal of Pharmacological Sciences,2007,105(2):133−137. doi: 10.1254/jphs.FM0070034
[77]	SARGIS R M, JOHNSON D N, CHOUDHURY R A, et al. Environmental endocrine disruptors promote adipogenesis in the 3T3-L1 cell line through glucocorticoid receptor activation[J]. Obesity,2010,18(7):1283−1288. doi: 10.1038/oby.2009.419
[78]	HUC L, LEMARIÉ A, GUÉRAUD F, et al. Low concentrations of bisphenol A induce lipid accumulation mediated by the production of reactive oxygen species in the mitochondria of HepG₂ cells[J]. Toxicology in Vitro: An International Journal Published in Association with BIBRA,2012,26(5):709−717.
[79]	MOON M K, KIM M J, JUNG I K, et al. Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level[J]. Journal of Korean Medical Science,2012,27(6):644−652. doi: 10.3346/jkms.2012.27.6.644
[80]	HASSAN Z K, ELOBEID M A, VIRK P, et al. Bisphenol A induces hepatotoxicity through oxidative stress in rat model[J]. Oxidative Medicine and Cellular longevity,2012,2012:194829.
[81]	HYUN S A, KO M Y, JANG S, et al. Bisphenol-A impairs synaptic formation and function by RGS4-mediated negative regulation of BDNF/NTRK2 signaling in the cerebral cortex[J]. Disease Models & Mechanisms, 2022, 049177.
[82]	DONG P, YE G, TU X, et al. Roles of ERRα and TGF-β signaling in stemness enhancement induced by 1 µM bisphenol A exposure via human neural stem cells[J]. Experimental and Therapeutic Medicine,2022,23(2):164.
[83]	WU M, CONG Y, WANG K, et al. Bisphenol A impairs macrophages through inhibiting autophagy via AMPK/mTOR signaling pathway and inducing apoptosis[J]. Ecotoxicology and Environmental Safety,2022,234:113395. doi: 10.1016/j.ecoenv.2022.113395
[84]	LOUP B, POUMEROL E, JOUNEAU L, et al. BPA disrupts meiosis I in oogonia by acting on pathways including cell cycle regulation, meiosis initiation and spindle assembly[J]. Reproductive Toxicology,2022,111:166−177. doi: 10.1016/j.reprotox.2022.06.001
[85]	杨静. 双酚A及其类似物生物效应及构效关系研究[D]. 黄石: 湖北师范大学, 2021 YANG J. Study on biological effects and structure-activity relationship of bisphenol A and its analogues[D]. Huangshi: Hubei normal University, 2021.
[86]	KHAN N G, CORREIA J, ADIGA D, et al. A comprehensive review on the carcinogenic potential of bisphenol A:Clues and evidence[J]. Environmental Science and Pollution Research International, 2021, 28(16): 19643-19663.
[87]	TUDURÍ E, MARROQUI L, DOS SANTOS R S, et al. Timing of exposure and Bisphenol-A: Implications for diabetes development[J]. Frontiers in Endocrinology,2018,9:648. doi: 10.3389/fendo.2018.00648
[88]	VOM-SAAL F S, NAGEL S C, COE B L, et al. The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity[J]. Molecular and Cellular Endocrinology,2012,354(1−2):74−84. doi: 10.1016/j.mce.2012.01.001
[89]	SÁNCHEZ-GARRIDO M A, GARCÍA-GALIANO D, TENA-SEMPERE M. Early programming of reproductive health and fertility: Novel neuroendocrine mechanisms and implications in reproductive medicine[J]. Human Reproduction Update,2022,28(3):346−375. doi: 10.1093/humupd/dmac005
[90]	ACCONCIA F, PALLOTTINI V, MARINO M. Molecular mechanisms of action of BPA[J]. Dose-response:A Publication of International Hormesis Society,2015,13(4):1−9.