Skip to main content
SpringerLink
Log in

Associations between paraben exposure, thyroid capacity, homeostasis and pituitary thyrotropic function in the general Taiwanese: Taiwan Environmental Survey for Toxicants (TEST) 2013

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ahmed J, Smethurst P (1980) Radioimmunoassay of thyroxine-binding globulin - evaluation of a kit and diagnostic application. Ann Clin Biochem 17:241–246

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Boas M, Feldt-Rasmussen U, Skakkebaek NE, Main KM (2006) Environmental chemicals and thyroid function. Eur J Endocrinol 154:599–611

    Article  CAS  Google Scholar 

  • Boas M, Main KM, Feldt-Rasmussen U (2009) Environmental chemicals and thyroid function: An update. Curr Opin Endocrinol 16:385–391

    Article  CAS  Google Scholar 

  • Brucker-Davis F (1998) Effects of environmental synthetic chemicals on thyroid function. Thyroid 8(9):827–856

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Casals-Casas C, Desvergne B (2011) Endocrine disruptors: From endocrine to metabolic disruption. Annu Rev Physiol 73:135–162

    Article  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  Google Scholar 

  • 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 developing standardized diagnostics and classification of non-thyroidal illness syndrome. BMC Endocr Disord 8:13

    Article  Google Scholar 

  • Dietrich JW, Landgrafe G, Fotiadou EH (2012) Tsh and thyrotropic agonists: Key actors in thyroid homeostasis. J Thyroid Res 2012:351864

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Franz VH (2007) Ratios: A short guide to confidence limits and proper use. ArXiv 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Rothman KJ (2021) The origin of modern epidemiology, the book. Eur J Epidemiol 36:763–765

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Schug TT, Janesick A, Blumberg B, Heindel JJ (2011) Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem 127:204–215

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Soni MG, Carabin IG, Burdock GA (2005) Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food Chem Toxicol 43:985–1015

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

Download references

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).

Author information

Authors and Affiliations

  1. National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan

    Po-Chin Huang, Yu-Jung Lin, Wan-Ting Chang & Hsin-I. Huang

  2. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

    Po-Chin Huang

  3. Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Po-Chin Huang

  4. Department of Safety, Health and Environmental Engineering, National United University, Miaoli, Taiwan

    Po-Chin Huang

  5. Department of Chemistry, Tunghai University, Taichung, Taiwan

    Hsin-Chang Chen

  6. Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang Ming Chiao Tung University, 155 Li-Nong Street, Sec. 2, Beitou, Taipei, 112, Taiwan

    Shih-Hao Leung & Jung-Wei Chang

  7. School of Public Health, National Defense Medical Center, Taipei, Taiwan

    Han-Bin Huang

Authors
  1. Po-Chin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hsin-Chang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shih-Hao Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu-Jung Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Han-Bin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wan-Ting Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hsin-I. Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jung-Wei Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to Jung-Wei Chang.

Ethics declarations

Ethics approval

The study was approved by the Research Ethics Committee of National Health Research Institutes and National Yang Ming Chiao Tung University (No. EC1020206 and No. YM109026E) of Taiwan.

Consent to participate

All donors involved in this study signed an informed consent form before the sample collection.

Consent for publication

The authors of this manuscript, titled Associations between Paraben Exposure, Thyroid Capacity, Homeostasis and Pituitary Thyrotropic Function in the General Taiwanese: Taiwan Environmental Survey for Toxicants (TEST) 2013, hereby provide their full consent for its publication in the Journal of Environmental Science and Pollution Research.

Competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Responsible Editor: Lotfi Aleya

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 111 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-023-31277-y

Keywords

Search

Navigation