Effects and possible mechanisms of per- and polyfluoroalkyl substances exposure on human thyroid function
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摘要: 全氟和多氟烷基化合物(per - and polyfluoroalkyl substances,PFASs)是一类人工合成的脂肪族化合物,广泛存在于环境介质中,对人类健康和环境具有潜在、持久性的危害,因此被认为是一种有机污染物(persistent organic pollutants,POPs)。大量实验室及人群流行病学研究表明,暴露于PFASs,不但会引起机体的各种毒性,且可导致甲状腺激素(thyroid hormone,TH)水平的改变,增加发生甲状腺功能减退的风险,进而引起发育迟滞、代谢紊乱等各种相应的临床症状。本文就几种长链、短链及新型PFASs,对PFASs在人体内的毒代动力学过程、PFASs暴露对甲状腺功能的影响及其可能的作用机制作一概述。
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关键词:
- 全氟和多氟烷基化合物 /
- 环境暴露 /
- 甲状腺激素 /
- 甲状腺功能减退
Abstract: Per- and polyfluoroalkyl substances (PFASs) are a class of synthetic aliphatic compounds, which are found widely in environmental media and are potentially and persistently hazardous to human health and the environment, thus being considered as persistent organic pollutants (POPs). Numerous experimental and population - based epidemiological studies have shown that exposure to PFASs not only causes various toxicities in the body, but also leads to changes in thyroid hormone (TH) level and increases the risk of hypothyroidism, which in turn causes various clinical symptoms such as developmental delays and metabolic disorders. In this paper, we describe the toxicokinetic processes of PFASs in humans, based on several long - chain, short - chain and emerging PFASs, and summarize effects and possible mechanisms of PFASs exposure on thyroid function. -
表 1 几种长链、短链及新型PFASs的基本信息
中文名称 英文名称 简称 类型 CAS号 分子式 相对分子质量 全氟丁酸 perfluorobutanoic acid PFBA 短链、新型 375-22-4 C4F7O2H 213.9 全氟辛酸 perfluorooctanoic acid PFOA 长链 335-67-1 C8F15O2H 413.93 全氟壬酸 perfluorononanoic acid PFNA 长链 375-95-1 C9F17O2H 464.08 全氟癸酸 perfluorodecanoic acid PFDA 长链 335-76-2 C10F19O2H 514.22 全氟十一酸 perfluoroundecanoic acid PFUdA 长链 2058-94-8 C11F21O2H 564.1 全氟十二酸 perfluorododecanoic acid PFDoA 长链 307-55-1 C12F23O2H 614.11 全氟丁基磺酸 perfluorobutanesulfonic acid PFBS 短链、新型 375-73-5 C4F9SO3H 299.92 全氟己基磺酸 perfluorohexanesulfonic acid PFHxS 短链、新型 355-46-4 C6F13SO3H 399.97 全氟辛基磺酸 perfluorooctanesulfonic acid PFOS 长链 1763-23-1 C8F17SO3H 499.99 -
[1] Lau C, Butenhoff JL, Rogers JM. The developmental toxicity of perfluoroalkyl acids and their derivatives[J]. Toxicology and Applied Pharmacology, 2004, 198(2): 231 – 241. doi: 10.1016/j.taap.2003.11.031 [2] Buck RC, Franklin J, Berger U, et al. Perfluoroalkyl and poly-fluoroalkyl substances in the environment: terminology, classifica-tion, and origins[J]. Integrated Environmental Assessment and Management, 2011, 7(4): 513 – 541. doi: 10.1002/ieam.258 [3] Sunderland EM, Hu XC, Dassuncao C, et al. A review of the pathways of human exposure to poly - and perfluoroalkyl substances (PFASs) and present understanding of health effects[J]. Journal of Exposure Science and Environmental Epidemiology, 2019, 29(2): 131 – 147. doi: 10.1038/s41370-018-0094-1 [4] Jensen AA, Leffers H. Emerging endocrine disrupters: perfluoroal-kylated substances[J]. International Journal of Andrology, 2008, 31(2): 161 – 169. doi: 10.1111/j.1365-2605.2008.00870.x [5] Jian JM, Chen D, Han FJ, et al. A short review on human exposure to and tissue distribution of per - and polyfluoroalkyl substances (PFASs)[J]. Science of the Total Environment, 2018, 636: 1058 – 1069. doi: 10.1016/j.scitotenv.2018.04.380 [6] Coperchini F, Awwad O, Rotondi M, et al. Thyroid disruption by perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA)[J]. Journal of Endocrinological Investigation, 2017, 40(2): 105 – 121. doi: 10.1007/s40618-016-0572-z [7] Fenton SE, Ducatman A, Boobis A, et al. Per - and polyfluoroalkyl substance toxicity and human health review: current state of know-ledge and strategies for informing future research[J]. Environmental Toxicology and Chemistry, 2021, 40(3): 606 – 630. doi: 10.1002/etc.4890 [8] Liew Z, Goudarzi H, Oulhote Y. Developmental exposures to perfluoroalkyl substances (PFASs): an update of associated health outcomes[J]. Current Environmental Health Reports, 2018, 5(1): 1 – 19. doi: 10.1007/s40572-018-0173-4 [9] Drover SSM, Villanger GD, Aase H, et al. Maternal thyroid function during pregnancy or neonatal thyroid function and attention deficit hyperactivity disorder[J]. Epidemiology, 2019, 30(1): 130 – 144. doi: 10.1097/EDE.0000000000000937 [10] Coperchini F, Croce L, Ricci G, et al. Thyroid disrupting effects of old and new generation PFAS[J]. Frontiers in Endocrinology, 2021, 11: 612320. doi: 10.3389/fendo.2020.612320 [11] Zhang WP, Pang SM, Lin ZQ, et al. Biotransformation of perfluoroalkyl acid precursors from various environmental systems: advances and perspectives[J]. Environmental Pollution, 2021, 272: 115908. doi: 10.1016/j.envpol.2020.115908 [12] United Nations Environment Programme. Stockholm convention on persistent organic pollutants (POPS)[EB/OL]. (2019 – 05 – 10).https://cil.nus.edu.sg/wp-content/uploads/2019/02/2001-Stockholm-Convention-on-Persistent-Organic-Pollutants-Annexes.pdf. [13] United States Environmental Protection Agency. EPA′s per- and polyfluoroalkyl substances (PFAS) action plan[R]. Washington: EPA, 2019. [14] Liang H, Wang ZL, Miao MH, et al. Prenatal exposure to perfluoroalkyl substances and thyroid hormone concentrations in cord plasma in a Chinese birth cohort[J]. Environmental Health, 2020, 19(1): 127. doi: 10.1186/s12940-020-00679-7 [15] Ballesteros V, Costa O, Iñiguez C, et al. Exposure to perfluoroalkyl substances and thyroid function in pregnant women and children: a systematic review of epidemiologic studies[J]. Environment Inter-national, 2017, 99: 15 – 28. doi: 10.1016/j.envint.2016.10.015 [16] 张静洁, 赵婷, 郑娟, 等.GB/T 29493.2 — 2021, 纺织染整助剂中有害物质的测定第2部分: 全氟化合 物 (PFCs) 的测定[S]. 北京: 中国标准出版社, 2021. [17] Poothong S, Papadopoulou E, Padilla-Sánchez JA, et al. Multiple pathways of human exposure to poly - and perfluoroalkyl substances (PFASs): from external exposure to human blood[J]. Environment International, 2020, 134: 105244. doi: 10.1016/j.envint.2019.105244 [18] Haug LS, Huber S, Becher G, et al. Characterisation of human exposure pathways to perfluorinated compounds – comparing exposure estimates with biomarkers of exposure[J]. Environment International, 2011, 37(4): 687 – 693. doi: 10.1016/j.envint.2011.01.011 [19] Schrenk D, Bignami M, Bodin L, et al. Risk to human health related to the presence of perfluoroalkyl substances in food[J]. EFSA Journal, 2020, 18(9): e06223. [20] De Silva AO, Armitage JM, Bruton TA, et al. PFAS exposure pathways for humans and wildlife: a synthesis of current know-ledge and key gaps in understanding[J]. Environmental Toxicology and Chemistry, 2021, 40(3): 631 – 657. doi: 10.1002/etc.4935 [21] Pérez F, Nadal M, Navarro-Ortega A, et al. Accumulation of per-fluoroalkyl substances in human tissues[J]. Environment International, 2013, 59: 354 – 362. doi: 10.1016/j.envint.2013.06.004 [22] Zheng P, Liu YX, An Q, et al. Prenatal and postnatal exposure to emerging and legacy per - /polyfluoroalkyl substances: levels and transfer in maternal serum, cord serum, and breast milk[J]. Science of the Total Environment, 2022, 812: 152446. doi: 10.1016/j.scitotenv.2021.152446 [23] Hu WY, Jones PD, DeCoen W, et al. Alterations in cell membrane properties caused by perfluorinated compounds[J]. Comparative Biochemistry and Physiology Part C:Toxicology and Pharmac-ology, 2003, 135(1): 77 – 88. doi: 10.1016/S1532-0456(03)00043-7 [24] Harada K, Inoue K, Morikawa A, et al. Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their species - specific excretion[J]. Environmental Research, 2005, 99(2): 253 – 261. doi: 10.1016/j.envres.2004.12.003 [25] Fujii Y, Niisoe T, Harada KH, et al. Toxicokinetics of perfluoroalkyl carboxylic acids with different carbon chain lengths in mice and humans[J]. Journal of Occupational Health, 2015, 57(1): 1 – 12. doi: 10.1539/joh.14-0136-OA [26] Zhang YF, Beesoon S, Zhu LY, et al. Biomonitoring of perfluoroalkyl acids in human urine and estimates of biological half-life[J]. Environmental Science and Technology, 2013, 47(18): 10619 – 10627. doi: 10.1021/es401905e [27] Han X, Nabb DL, Russell MH, et al. Renal elimination of perfluoro-carboxylates (PFCAs)[J]. Chemical Research in Toxicology, 2012, 25(1): 35 – 46. doi: 10.1021/tx200363w [28] Yang CH, Glover KP, Han X. Characterization of cellular uptake of perfluorooctanoate via organic anion - transporting polypeptide 1A2, organic anion transporter 4, and urate transporter 1 for their potential roles in mediating human renal reabsorption of perfluorocarboxylates[J]. Toxicological Sciences, 2010, 117(2): 294 – 302. doi: 10.1093/toxsci/kfq219 [29] Zhao W, Zitzow JD, Weaver Y, et al. Organic anion transporting polypeptides contribute to the disposition of perfluoroalkyl acids in humans and rats[J]. Toxicological Sciences, 2016, 156(1): 84 – 95. [30] Brent GA. Mechanisms of thyroid hormone action[J]. The Journal of Clinical Investigation, 2012, 122(9): 3035 – 3043. doi: 10.1172/JCI60047 [31] Ghassabian A, Trasande L. Disruption in thyroid signaling path-way: a mechanism for the effect of endocrine - disrupting chemicals on child neurodevelopment[J]. Frontiers in Endocrinology, 2018, 9: 204. doi: 10.3389/fendo.2018.00204 [32] Tsai MS, Lin CC, Chen MH, et al. Perfluoroalkyl substances and thyroid hormones in cord blood[J]. Environmental Pollution, 2017, 222: 543 – 548. doi: 10.1016/j.envpol.2016.11.027 [33] Aimuzi R, Luo K, Chen Q, et al. Perfluoroalkyl and polyfluoroalkyl substances and fetal thyroid hormone levels in umbilical cord blood among newborns by prelabor caesarean delivery[J]. Environment International, 2019, 130: 104929. doi: 10.1016/j.envint.2019.104929 [34] Berg V, Nøst TH, Pettersen RD, et al. Persistent organic pollutants and the association with maternal and infant thyroid homeostasis: a multipollutant assessment[J]. Environmental Health Perspectives, 2017, 125(1): 127 – 133. doi: 10.1289/EHP152 [35] Webster GM, Venners SA, Mattman A, et al. Associations between perfluoroalkyl acids (PFASs) and maternal thyroid hormones in early pregnancy: a population - based cohort study[J]. Environmental Research, 2014, 133: 338 – 347. doi: 10.1016/j.envres.2014.06.012 [36] Webster GM, Rauch SA, Marie NS, et al. Cross - sectional associations of serum perfluoroalkyl acids and thyroid hormones in U. S. adults: variation according to TPOAb and iodine status (NHANES 2007 – 2008)[J]. Environmental Health Perspectives, 2016, 124(7): 935 – 942. doi: 10.1289/ehp.1409589 [37] Boesen SAH, Long MH, Wielsøe M, et al. Exposure to perflouroalkyl acids and foetal and maternal thyroid status: a review[J]. Environmental Health, 2020, 19(1): 107. doi: 10.1186/s12940-020-00647-1 [38] Kim DH, Kim UJ, Kim HY, et al. Perfluoroalkyl substances in serum from South Korean infants with congenital hypothyroidism and shealthy infants – its relationship with thyroid hormones[J]. Environmental Research, 2016, 147: 399 – 404. doi: 10.1016/j.envres.2016.02.037 [39] Vieira VM, Hoffman K, Shin HM, et al. Perfluorooctanoic acid exposure and cancer outcomes in a contaminated community: a geographic analysis[J]. Environmental Health Perspectives, 2013, 121(3): 318 – 323. doi: 10.1289/ehp.1205829 [40] Berg V, Nøst TH, Hansen S, et al. Assessing the relationship between perfluoroalkyl substances, thyroid hormones and binding proteins in pregnant women; a longitudinal mixed effects approach[J]. Environment International, 2015, 77: 63 – 69. doi: 10.1016/j.envint.2015.01.007 [41] Conti A, Strazzeri C, Rhoden KJ. Perfluorooctane sulfonic acid, a persistent organic pollutant, inhibits iodide accumulation by thyroid follicular cells in vitro[J]. Molecular and Cellular Endocrinology, 2020, 515: 110922. doi: 10.1016/j.mce.2020.110922 [42] Song M, Kim YJ, Park YK, et al. Changes in thyroid peroxidase activity in response to various chemicals[J]. Journal of Environ-mental Monitoring, 2012, 14(8): 2121 – 2126. doi: 10.1039/c2em30106g [43] Boas M, Feldt-Rasmussen U, Main KM. Thyroid effects of endocrine disrupting chemicals[J]. Molecular and Cellular Endocrinology, 2012, 355(2): 240 – 248. doi: 10.1016/j.mce.2011.09.005 [44] Ren XM, Qin WP, Cao LY, et al. Binding interactions of perfluoroalkyl substances with thyroid hormone transport proteins and potential toxicological implications[J]. Toxicology, 2016, 366 – 367: 32 – 42. [45] Zhang J, Begum A, Brännström K, et al. Structure - based virtual screening protocol for in silico identification of potential thyroid disrupting chemicals targeting transthyretin[J]. Environmental Science and Technology, 2016, 50(21): 11984 – 11993. doi: 10.1021/acs.est.6b02771 [46] Weiss JM, Andersson PL, Lamoree MH, et al. Competitive binding of poly - and perfluorinated compounds to the thyroid hormone transport protein transthyretin[J]. Toxicological Sciences, 2009, 109(2): 206 – 216. doi: 10.1093/toxsci/kfp055 [47] Yu WG, Liu W, Jin YH. Effects of perfluorooctane sulfonate on rat thyroid hormone biosynthesis and metabolism[J]. Environmental Toxicology and Chemistry, 2009, 28(5): 990 – 996. doi: 10.1897/08-345.1 [48] Martin MT, Brennan RJ, Hu WY, et al. Toxicogenomic study of triazole fungicides and perfluoroalkyl acids in rat livers predicts toxicity and categorizes chemicals based on mechanisms of toxicity[J]. Toxicological Sciences, 2007, 97(2): 595 – 613. doi: 10.1093/toxsci/kfm065 [49] Yu WG, Liu W, Jin YH, et al. Prenatal and postnatal impact of perfluorooctane sulfonate (PFOS) on rat development: a cross-foster study on chemical burden and thyroid hormone system[J]. Environmental Science and Technology, 2009, 43(21): 8416 – 8422. doi: 10.1021/es901602d [50] Xin Y, Ren XM, Ruan T, et al. Chlorinated polyfluoroalkylether sulfonates exhibit similar binding potency and activity to thyroid hormone transport proteins and nuclear receptors as perfluorooc-tanesulfonate[J]. Environmental Science and Technology, 2018, 52(16): 9412 – 9418. doi: 10.1021/acs.est.8b01494 [51] Zhang SN, Guo XC, Lu SY, et al. Exposure to PFDoA causes disruption of the hypothalamus - pituitary - thyroid axis in zebrafish larvae[J]. Environmental Pollution, 2018, 235: 974 – 982. doi: 10.1016/j.envpol.2018.01.015 [52] Bjerregaard-Olesen C, Bach CC, Long MH, et al. Associations of fetal growth outcomes with measures of the combined xenoestrogenic activity of maternal serum perfluorinated alkyl acids in Danish pregnant women[J]. Environmental Health Perspectives, 2019, 127(1): 017006. doi: 10.1289/EHP1884 [53] Sonthithai P, Suriyo T, Thiantanawat A, et al. Perfluorinated chemicals, PFOS and PFOA, enhance the estrogenic effects of 17β - estradiol in T47D human breast cancer cells[J]. Journal of Applied Toxicology, 2016, 36(6): 790 – 801. doi: 10.1002/jat.3210 -