Abstract
Several studies have suggested that some endocrine disruptors such as synthetic phenols, parabens and phthalates may disrupt thyroid hormone signaling and associated negative feed-backs with the central hypothalamic-pituitary-thyroid (HPT) axis. Therefore, we investigated urinary paraben and blood thyroid hormone levels in the Taiwanese population. Our sample comprised 264 adults (aged 18–97 years) and 75 minors (aged 7–17 years) from Taiwan Environmental Survey for Toxicants 2013. Urinary levels of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were assessed. Hormones of particular interest include: thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). We sought integrated parameters to describe the transfer of thyroid hormones in homeostatic models. The geometric mean urinary paraben levels of the adults were higher than those of the minors (adults vs. minors; MeP: 383 vs. 62.4 ng/mL; PrP: 109 vs. 8.00 ng/mL; EtP: 39.5 vs. 2.38 ng/mL, and BuP: 6.36 vs. 2.13 ng/mL). In the male adults, we discovered that 0.253% (p = 0.032), 0.256% (p = 0.041) and 0.257% (p = 0.037) decreases in the TSH, TSH/T4 and TSH/FreeT4 ratio was associated with 1% EtP increases, respectively. In the female minors, 0.093% (p = 0.044), 0.072% (p = 0.047) and 0.156 (p = 0.004) increases in the TSH ratios were associated with a 1% MeP, EtP and BuP increase, respectively. Moreover, 0.151% (p = 0.008) and 0.177% (p = 0.001) increases in TSH/T4 and TSH/free T4 ratios were associated with a BuP 1% increase, respectively. Finally, EtP was positively associated with SPINA-GT (β: 15.66, p = 0.036) in the male adults. By contrast, EtP were positively associated with Jostel’s TSH index and sTSHI (β: 0.072, p = 0.049; β: 0.107, p = 0.049) in the female minors. The Taiwanese population is commonly exposed to parabens, which can potentially lead to alteration of thyroid hormone homeostasis.
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References
Ahmed J, Smethurst P (1980) Radioimmunoassay of thyroxine-binding globulin - evaluation of a kit and diagnostic application. Ann Clin Biochem 17:241–246
Aker AM, Johns L, McElrath TF, Cantonwine DE, Mukherjee B, Meeker JD (2018) Associations between maternal phenol and paraben urinary biomarkers and maternal hormones during pregnancy: A repeated measures study. Environ Int 113:341–349
Aker AM, Watkins DJ, Johns LE, Ferguson KK, Soldin OP, Del Toro LVA, ... & Meeker JD (2016) Phenols and parabens in relation to reproductive and thyroid hormones in pregnant women. Environ Res 151:30–37
Andersen FA (2008) Final amended report on the safety assessment of methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben, and benzylparaben as used in cosmetic products. Int J Toxicol 27:1–82
Baker BH, Wu H, Laue HE, Boivin A, Gillet V, Langlois MF, Bellenger JP, Baccarelli AA, Takser L (2020) Methylparaben in meconium and risk of maternal thyroid dysfunction, adverse birth outcomes, and Attention-Deficit Hyperactivity Disorder (ADHD). Environ Int 139:105716. https://doi.org/10.1016/j.envint.2020.105716
Bernal J (2007) Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab 3(3):249–259
Boas M, Feldt-Rasmussen U, Skakkebaek NE, Main KM (2006) Environmental chemicals and thyroid function. Eur J Endocrinol 154:599–611
Boas M, Main KM, Feldt-Rasmussen U (2009) Environmental chemicals and thyroid function: An update. Curr Opin Endocrinol 16:385–391
Brucker-Davis F (1998) Effects of environmental synthetic chemicals on thyroid function. Thyroid 8(9):827–856
Burr WA, Evans SE, Lee J, Prince HP, Ramsden DB (1979) Ratio of thyroxine to thyroxine-binding globulin in the assessment of thyroid-function. Clin Endocrinol 11:333–342
Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL (2008) Urinary concentrations of triclosan in the U.S. Population: 2003–2004. Environ Health Perspect 116:303–307
Calafat AM, Ye X, Wong LY, Bishop AM, Needham LL (2010) Urinary concentrations of four parabens in the U.S. Population: Nhanes 2005–2006. Environ Health Perspect 118:679–685
Casals-Casas C, Desvergne B (2011) Endocrine disruptors: From endocrine to metabolic disruption. Annu Rev Physiol 73:135–162
Chen HC, Chang JW, Sun YC, Chang WT, Huang PC (2022) Determination of parabens, bisphenol a and its analogs, triclosan, and benzophenone-3 levels in human urine by isotope-dilution-uplc-ms/ms method followed by supported liquid extraction. Toxics 10(1):21
Coiffier O, Nakiwala D, Rolland M, Malatesta A, Lyon-Caen S, Chovelon B, ... & Philippat C (2023) Exposure to a mixture of non-persistent environmental chemicals and neonatal thyroid function in a cohort with improved exposure assessment. Environ Int 173:107840
Crisp TM, Clegg ED, Cooper RL, Wood WP, Anderson DG, Baetcke KP et al (1998) Environmental endocrine disruption: An effects assessment and analysis. Environ Health Persp 106:11–56
Dietrich JW, Mitzdorf U, Weitkunat R, Pickardt CR (1997) The pituitary-thyroid feed back control: Stability and oscillations in a new nonlinear model. J Endocrinol Invest 20:100
Dietrich JW (2002) Der hypophysen-schilddrüsen-regelkreis. Entwicklung und klinische anwendung eines nichtlinearen modells. Logos-Verlag, Berlin 188
Dietrich JW, Tesche A, Pickardt CR, Mitzdorf U (2004) Thyrotropic feedback control: Evidence for an additional ultrashort feedback loop from fractal analysis. Cybernet Syst 35:315–331
Dietrich JW, Stachon A, Antic B, Klein HH, Hering S (2008) The aqua-fontis study: Protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for develo** standardized diagnostics and classification of non-thyroidal illness syndrome. BMC Endocr Disord 8:13
Dietrich JW, Landgrafe G, Fotiadou EH (2012) Tsh and thyrotropic agonists: Key actors in thyroid homeostasis. J Thyroid Res 2012:351864
Dietrich JW, Landgrafe-Mende G, Wiora E, Chatzitomaris A, Klein HH, Midgley JE et al (2016) Calculated parameters of thyroid homeostasis: Emerging tools for differential diagnosis and clinical research. Front Endocrinol (lausanne) 7:57
Eriksson E, Andersen HR, Ledin A (2008) Substance flow analysis of parabens in Denmark complemented with a survey of presence and frequency in various commodities. J Hazard Mater 156:240–259
Franz VH (2007) Ratios: A short guide to confidence limits and proper use. Ar**v 0710.2024v1
Genuis SJ, Birkholz D, Curtis L (2013) Paraben levels in an urban community of Western Canada. International Scholarly Research Notices, 2013
Gogoi P, Kalita JC (2020) Effects of butylparaben exposure on thyroid peroxidase (tpo) and type 1 iodothyronine deiodinase (d1) in female wistar rats. Toxicology 443:152562
Hoermann R, Midgley JEM, Larisch R, Dietrich JW (2015) Homeostatic control of the thyroid-pituitary axis: Perspectives for diagnosis and treatment. Front Endocrinol 6:177
Hoermann R, Larisch R, Dietrich JW, Midgley JEM (2016) Derivation of a multivariate reference range for pituitary thyrotropin and thyroid hormones: Diagnostic efficiency compared with conventional single-reference method. Eur J Endocrinol 174:735–743
Huang HB, Pan WH, Chang JW, Chiang HC, Guo YL, Jaakkola JJ et al (2017) Does exposure to phthalates influence thyroid function and growth hormone homeostasis? The Taiwan environmental survey for toxicants (test) 2013. Environ Res 153:63–72
Huang PC, Waits A, Chen HC, Chang WT, Jaakkola JJK, Huang HB (2020) Mediating role of oxidative/nitrosative stress biomarkers in the associations between phthalate exposure and thyroid function in Taiwanese adults. Environ Int 140:105751
Huang PC, Tsai CH, Liang WY, Li SS, Huang HB, Kuo PL (2016) Early phthalates exposure in pregnant women is associated with alteration of thyroid hormones. PLoS One 11(7):e0159398
Huang PC, Chen HC, Chou WC, Lin HW, Chang WT, Chang JW (2022) Cumulative risk assessment and exposure characteristics of parabens in the general taiwanese using multiple hazard indices approaches. Sci Total Environ 843
Janjua NR, Mortensen GK, Andersson AM, Kongshoj B, Skakkebaek NE, Wulf HC (2007) Systemic uptake of diethyl phthalate, dibutyl phthalate, and butyl paraben following whole-body topical application and reproductive and thyroid hormone levels in humans. Environ Sci Technol 41:5564–5570
Jostel A, Ryder WD, Shalet SM (2009) The use of thyroid function tests in the diagnosis of hypopituitarism: Definition and evaluation of the tsh index. Clin Endocrinol 71:529–534
Koeppe ES, Ferguson KK, Colacino JA, Meeker JD (2013) Relationship between urinary triclosan and paraben concentrations and serum thyroid measures in nhanes 2007–2008. Sci Total Environ 445:299–305
Liang JF, Yang XX, Liu QS, Sun ZD, Ren ZH, Wang XY et al (2022) Assessment of thyroid endocrine disruption effects of parabens using in vivo, in vitro, and in silico approaches. Environ Sci Technol 56:460–469
Liu ML, Yi SJ, Chen PY, Chen M, Zhong WJ, Yang J et al (2019) Thyroid endocrine disruption effects of perfluoroalkyl phosphinic acids on zebrafish at early development. Sci Total Environ 676:290–297
Murk AJ, Rijntjes E, Blaauboer BJ, Clewell R, Crofton KM, Dingemans MML et al (2013) Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals. Toxicol in Vitro 27(4):1320–1346
Noyes PD, Friedman KP, Browne P, Haselman JT, Gilbert ME, Hornung MW et al (2019) Evaluating chemicals for thyroid disruption: Ppportunities and challenges with in vitro testing and adverse outcome pathway approaches. Environ Health Perspect 127(9):95001
Pan WH, Wu HJ, Yeh CJ, Chuang SY, Chang HY, Yeh NH et al (2011) Diet and health trends in Taiwan: Comparison of two nutrition and health surveys from 1993–1996 and 2005–2008. Asia Pac J Clin Nutr 20:238–250
Reichlin S, Utiger RD (1967) Regulation of the pituitary-thyroid axis in man: Relationship of tsh concentration to concentration of free and total thyroxine in plasma. J Clin Endocrinol Metab 27:251–255
Rothman KJ (2021) The origin of modern epidemiology, the book. Eur J Epidemiol 36:763–765
Schroeder HR, Johnson PK, Dean CL, Morris DL, Smith D, Refetoff S (1986) Homogeneous apoenzyme reactivation immunoassay for thyroxin-binding globulin in serum. Clin Chem 32:826–830
Schug TT, Janesick A, Blumberg B, Heindel JJ (2011) Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem 127:204–215
Shishiba Y, Umezu Y, Ohtsuki N (1983) Clinical-evaluation of free-thyroxine calculation from thyroxine and thyroxine binding globulin radioimmunoassays. Eur J Nucl Med 8:1–3
Smith KW, Braun JM, Williams PL, Ehrlich S, Correia KF, Calafat AM et al (2012) Predictors and variability of urinary paraben concentrations in men and women, including before and during pregnancy. Environ Health Perspect 120:1538–1543
Soni MG, Carabin IG, Burdock GA (2005) Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food Chem Toxicol 43:985–1015
Taha M, Marie AM, Ahmed-Farid OA (2020) Combined approaches for evaluation of xenoestrogen neural toxicity and thyroid dysfunction: Screening of oxido-nitrosative markers, DNA fragmentation, and biogenic amine degradation. J Biochem Mol Toxicol 34(9):e22521
Taylor PN, Lansdown A, Witczak J, Khan R, Rees A, Dayan CM, Okosieme O (2023) Age-related variation in thyroid function- a narrative review highlighting important implications for research and clinical practice. Thyroid Res 16(1):20
Taxvig C, Vinggaard AM, Hass U, Axelstad M, Boberg J, Hansen PR et al (2008) Do parabens have the ability to interfere with steroidogenesis? Toxicol Sci 106:206–213
Vo TT, Yoo YM, Choi KC, Jeung EB (2010) Potential estrogenic effect(s) of parabens at the prepubertal stage of a postnatal female rat model. Reprod Toxicol 29:306–316
Zoeller RT (2005) Environmental chemicals as thyroid hormone analogues: New studies indicate that thyroid hormone receptors are targets of industrial chemicals? Mol Cell Endocrinol 242(1–2):10–15
Zuo JL, Huo TB, Du X, Yang Q, Wu Q, Shen JZ et al (2021) The joint effect of parental exposure to microcystin-lr and polystyrene nanoplastics on the growth of zebrafish offspring. J Hazard Mater 410:124677
Acknowledgements
We would like to thank our research assistants for their assistance in data and specimen collection and sample pretreatment. We are also deeply grateful to the research collaboration of the Nutrition and Health Survey in Taiwan team, Prof. Pan Wen-Harn, Mr. Zheng Chen, and others, and for the support in sampling provided by the Health Promotion Administration, Ministry of Health and Welfare, Taiwan.
Funding
We would also like to extend thanks to the National Health Research Institutes for their financial support (Grant No.: EM-112-PP-11, EM-113-PP-11), and Ministry of Science and Technology Council (Grant No.: MOST 110–2314-B- 400–039, MOST 111–2314-B-400–013). This work was supported partially by the Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan and by Kaohsiung Medical University Research Center Grant (KMU-TC112A01-1).
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Po-Chin Huang conceived and designed the experiments. Hsin-Chang Chen, Shih-Hao Leung and Wan-Ting Chang performed the experiments. Jung-Wei Chang and Han-Bin Huang and Po-Chin Huang analyzed the data. Po-Chin Huang, Hsin-Chang Chen and Jung-Wei Chang contributed tools for reagents, materials, and analysis. Po-Chin Huang, and Jung-Wei Chang wrote the paper. Specimen collection as well as sample arrangement and preparations were managed by Yu-Jung Lin, Wan-Ting Chang, and Hsin-I Huang. Po-Chin Huang, Yu-Jung Lin, Han-Bin Huang and Jung-Wei Chang contributed to critical revision of the manuscript.
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Huang, PC., Chen, HC., Leung, SH. et al. Associations between paraben exposure, thyroid capacity, homeostasis and pituitary thyrotropic function in the general Taiwanese: Taiwan Environmental Survey for Toxicants (TEST) 2013. Environ Sci Pollut Res 31, 1288–1303 (2024). https://doi.org/10.1007/s11356-023-31277-y
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DOI: https://doi.org/10.1007/s11356-023-31277-y