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Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention

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Abstract

Endocrine Disrupting Chemicals (EDCs) are a global problem for environmental and human health. They are defined as “an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action”. It is estimated that there are about 1000 chemicals with endocrine-acting properties. EDCs comprise pesticides, fungicides, industrial chemicals, plasticizers, nonylphenols, metals, pharmaceutical agents and phytoestrogens. Human exposure to EDCs mainly occurs by ingestion and to some extent by inhalation and dermal uptake. Most EDCs are lipophilic and bioaccumulate in the adipose tissue, thus they have a very long half-life in the body. It is difficult to assess the full impact of human exposure to EDCs because adverse effects develop latently and manifest at later ages, and in some people do not present. Timing of exposure is of importance. Developing fetus and neonates are the most vulnerable to endocrine disruption. EDCs may interfere with synthesis, action and metabolism of sex steroid hormones that in turn cause developmental and fertility problems, infertility and hormone-sensitive cancers in women and men. Some EDCs exert obesogenic effects that result in disturbance in energy homeostasis. Interference with hypothalamo-pituitary-thyroid and adrenal axes has also been reported. In this review, potential EDCs, their effects and mechanisms of action, epidemiological studies to analyze their effects on human health, bio-detection and chemical identification methods, difficulties in extrapolating experimental findings and studying endocrine disruptors in humans and recommendations for endocrinologists, individuals and policy makers will be discussed in view of the relevant literature.

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Abbreviations

AR:

Androgen Receptor

AHR:

Aryl Hydrocarbon Receptor

BPA:

Bisphenol A

BMI:

Body Mass Index

DDT:

Dichlorodiphenyltrichloroethane

EDCs:

Endocrine Disrupting Chemicals

EPA:

Environmental Protection Agency

ER:

Estrogen Receptor

GH:

Growth Hormone

HPA:

Hypothalamo-Pituitary-Adrenal

ISNT:

In Situ Nick Translation

OCPs:

Organochlorinated Pesticides

OVX:

Ovariectomized

PPAR γ::

Peroxisome Proliferator-Activated Receptor γ

POPs:

Persistent Organochlorine Pollutants

PI3K :

Phosphatidylinositol 3 Kinase

PCBs:

Polychlorinated Biphenyls

COMET:

Single Cell Gel Electrophoresis Assay

NIS:

Sodium-Iodide Symporter Channel

SCSA:

Sperm Chromatin Structure Assay

TUNEL:

Terminal Transferase dUTP Nick End Labeling

TCDD:

Tetrachlorodibenzo-p-Dioxin

T4:

Thyroxine

T3:

Triiodothyronine

T2D:

Type 2 Diabetes

References

  1. Colborn T, Clement C. Wingspread Consensus Statement. Chemically-induced Alterations in Sexual and Functional Development: The Wildlife/human Connection. Princeton Scientific Publishing Company; 1992. p. 1–8.

  2. Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, et al. Endocrine-disrupting chemicals and public health protection: a statement of principles from the Endocrine Society. Endocrinology. 2012;153(9):4097–110. https://doi.org/10.1210/en.2012-1422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Gore AC. Environmental toxicant effects on neuroendocrine function. Endocrine. 2001;14(2):235–46. https://doi.org/10.1385/endo:14:2:235.

    Article  CAS  PubMed  Google Scholar 

  4. Carpenter DO. Effects of Persistent and Bioactive Organic Pollutants on Human Health. Wiley; 2013.

  5. McKinlay R, Plant JA, Bell JN, Voulvoulis N. Endocrine disrupting pesticides: implications for risk assessment. Environ Int. 2008;34(2):168–83. https://doi.org/10.1016/j.envint.2007.07.013.

    Article  CAS  PubMed  Google Scholar 

  6. Safe SH. Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment. Crit Rev Toxicol. 1994;24(2):87–149. https://doi.org/10.3109/10408449409049308.

    Article  CAS  PubMed  Google Scholar 

  7. Carpenter DO. Polychlorinated biphenyls (PCBs): routes of exposure and effects on human health. Rev Environ Health. 2006;21(1):1–23.

    Article  CAS  Google Scholar 

  8. Yilmaz B, Seyran AD, Sandal S, Aydin M, Colakoglu N, Kocer M, et al. Modulatory effects of Aroclors 1221 and 1254 on bone turnover and vertebral histology in intact and ovariectomized rats. Toxicol Lett. 2006;166(3):276–84. https://doi.org/10.1016/j.toxlet.2006.08.003.

    Article  CAS  PubMed  Google Scholar 

  9. Kutlu S, Colakoglu N, Halifeoglu I, Sandal S, Seyran AD, Aydin M, et al. Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats. Cell Biochem Funct. 2007;25(2):167–72. https://doi.org/10.1002/cbf.1289.

    Article  CAS  PubMed  Google Scholar 

  10. Yilmaz B, Sandal S, Carpenter DO. PCB 9 exposure induces endothelial cell death while increasing intracellular calcium and ROS levels. Environ Toxicol. 2012;27(3):185–91. https://doi.org/10.1002/tox.20676.

    Article  CAS  PubMed  Google Scholar 

  11. Bansal A, Henao-Mejia J, Simmons RA. Immune system: an emerging player in mediating effects of endocrine disruptors on metabolic health. Endocrinology. 2018;159(1):32–45. https://doi.org/10.1210/en.2017-00882.

    Article  CAS  PubMed  Google Scholar 

  12. Davis DL, Bradlow HL, Wolff M, Woodruff T, Hoel DG, Anton-Culver H. Medical hypothesis: xenoestrogens as preventable causes of breast cancer. Environ Health Perspect. 1993;101(5):372–7. https://doi.org/10.1289/ehp.93101372.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Uslu U, Sandal S, Cumbul A, Yildiz S, Aydin M, Yilmaz B. Evaluation of estrogenic effects of polychlorinated biphenyls and organochlorinated pesticides using immature rat uterotrophic assay. Hum Exp Toxicol. 2013;32(5):476–82. https://doi.org/10.1177/0960327112472999.

    Article  CAS  PubMed  Google Scholar 

  14. Marty MS, O'Connor JC. Key learnings from the endocrine disruptor screening program (EDSP) tier 1 rodent uterotrophic and Hershberger assays. Birth Defects Res B Dev Reprod Toxicol. 2014;101(1):63–79. https://doi.org/10.1002/bdrb.21098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rachon D. Endocrine disrupting chemicals (EDCs) and female cancer: informing the patients. Rev Endocr Metab Disord. 2015;16(4):359–64. https://doi.org/10.1007/s11154-016-9332-9.

    Article  CAS  PubMed  Google Scholar 

  16. Pinto CL, Mansouri K, Judson R, Browne P. Prediction of estrogenic bioactivity of environmental chemical metabolites. Chem Res Toxicol. 2016;29(9):1410–27. https://doi.org/10.1021/acs.chemrestox.6b00079.

    Article  CAS  PubMed  Google Scholar 

  17. Giulivo M. Lopez de Alda M, Capri E, Barcelo D. human exposure to endocrine disrupting compounds: their role in reproductive systems, metabolic syndrome and breast cancer. A review. Environ Res. 2016;151:251–64. https://doi.org/10.1016/j.envres.2016.07.011.

    Article  CAS  PubMed  Google Scholar 

  18. Morgan M, Deoraj A, Felty Q, Roy D. Environmental estrogen-like endocrine disrupting chemicals and breast cancer. Mol Cell Endocrinol. 2017;457:89–102. https://doi.org/10.1016/j.mce.2016.10.003.

    Article  CAS  PubMed  Google Scholar 

  19. Lymperi S, Giwercman A. Endocrine disruptors and testicular function. Metabolism. 2018;86:79–90. https://doi.org/10.1016/j.metabol.2018.03.022.

    Article  CAS  PubMed  Google Scholar 

  20. Fudvoye J, Bourguignon JP, Parent AS. Endocrine-disrupting chemicals and human growth and maturation: a focus on early critical windows of exposure. Vitam Horm. 2014;94:1–25. https://doi.org/10.1016/b978-0-12-800095-3.00001-8.

    Article  CAS  PubMed  Google Scholar 

  21. Beszterda M, Franski R. Endocrine disruptor compounds in environment: as a danger for children health. Pediatr Endocrinol Diabetes Metab. 2018;24(2):88–95. https://doi.org/10.18544/pedm-24.02.0107.

    Article  PubMed  Google Scholar 

  22. Greenspan LC, Lee MM. Endocrine disrupters and pubertal timing. Curr Opin Endocrinol Diabetes Obes. 2018;25(1):49–54. https://doi.org/10.1097/med.0000000000000377.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jacobsen PR, Christiansen S, Boberg J, Nellemann C, Hass U. Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats. Int J Androl. 2010;33(2):434–42. https://doi.org/10.1111/j.1365-2605.2009.01046.x.

    Article  CAS  PubMed  Google Scholar 

  24. Song WH, Mohamed EA, Pang WK, Kang KH, Ryu DY, Rahman MS, et al. Effect of endocrine disruptors on the ratio of X and Y chromosome-bearing live spermatozoa. Reprod Toxicol. 2018;82:10–7. https://doi.org/10.1016/j.reprotox.2018.09.002.

    Article  CAS  PubMed  Google Scholar 

  25. Kilic N, Sandal S, Colakoglu N, Kutlu S, Seyran A, Yilmaz B. Endocrine disruptive effects of polychlorinated biphenyls on the thyroid gland in female rats. Tohoku J Exp Med. 2005;206(4):327–32. https://doi.org/10.1620/tjem.206.327.

    Article  CAS  PubMed  Google Scholar 

  26. Calsolaro V, Pasqualetti G, Niccolai F, Caraccio N, Monzani F. Thyroid disrupting chemicals. Int J Mol Sci. 2017;18(12). https://doi.org/10.3390/ijms18122583.

  27. Li ZM, Hernandez-Moreno D, Main KM, Skakkebaek NE, Kiviranta H, Toppari J, et al. Association of in Utero Persistent Organic Pollutant Exposure with Placental Thyroid Hormones. Endocrinology. 2018;159(10):3473–81. https://doi.org/10.1210/en.2018-00542.

    Article  CAS  PubMed  Google Scholar 

  28. Sharpe RM, Drake AJ. Obesogens and obesity - an alternative view? Obesity (Silver Spring). 2013;21(6):1081–3. https://doi.org/10.1002/oby.20373.

    Article  Google Scholar 

  29. Darbre PD. Endocrine disruptors and obesity. Curr Obes Rep. 2017;6(1):18–27. https://doi.org/10.1007/s13679-017-0240-4.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Agas D, Sabbieti MG, Marchetti L. Endocrine disruptors and bone metabolism. Arch Toxicol. 2013;87(4):735–51. https://doi.org/10.1007/s00204-012-0988-y.

    Article  CAS  PubMed  Google Scholar 

  31. Carpenter DO, Sly PD. Environmental chemicals as endocrine disruptors. Rev Environ Health. 2016;31(4):399. https://doi.org/10.1515/reveh-2016-0064.

    Article  PubMed  Google Scholar 

  32. Gore AC, Crews D, Doan LL, La Merill M, Patisaul H, Zota A. Introduction to endocrine disrupting chemicals (EDCs). 2014. www.endocrine.org/~/media/endosociety/files/advocacy-and-outreach/important-documents/introduction-to-endocrine-disrupting-chemicals.pdf. Accessed July, 30 2019.

  33. Stockholm convention on persistent organic pollutants 2001. http://chm.pops.int/Portals/0/Repository/convention_text/UNEP-POPS-COP-CONVTEXT-FULL.English.PDF. Accessed June, 06 2019.

  34. The new POPs under the Stockholm Convention. Secretariat of the Stockholm Convention 2014. http://chm.pops.int/TheConvention/ThePOPs/TheNewPOPs/tabid/2511/Default.aspx. Accessed June, 06 2019.

  35. Nadal M, Domingo JL. Sources of Human Exposure. In: Carpenter DO, editor. Effects of Persistent and Bioactive Organic Pollutants on Human Health. Wiley; 2013. p. 8–25.

  36. Sandal S, Yilmaz B, Carpenter DO. Genotoxic effects of PCB 52 and PCB 77 on cultured human peripheral lymphocytes. Mutat Res. 2008;654(1):88–92. https://doi.org/10.1016/j.mrgentox.2008.05.005.

    Article  CAS  PubMed  Google Scholar 

  37. Pessah IN, Lein PJ, Seegal RF, Sagiv SK. Neurotoxicity of polychlorinated biphenyls and related organohalogens. Acta Neuropathol. 2019. https://doi.org/10.1007/s00401-019-01978-1.

  38. Yilmaz B, Sandal S, Chen CH, Carpenter DO. Effects of PCB 52 and PCB 77 on cell viability, [Ca(2+)](i) levels and membrane fluidity in mouse thymocytes. Toxicology. 2006;217(2–3):184–93. https://doi.org/10.1016/j.tox.2005.09.008.

    Article  CAS  PubMed  Google Scholar 

  39. Sandal S, Yilmaz B, Chen CH, Carpenter DO. Comparative effects of technical toxaphene, 2,5-dichloro-3-biphenylol and octabromodiphenylether on cell viability, [Ca2+]i levels and membrane fluidity in mouse thymocytes. Toxicol Lett. 2004;151(3):417–28. https://doi.org/10.1016/j.toxlet.2004.03.006.

    Article  CAS  PubMed  Google Scholar 

  40. Sandal S, Yilmaz B, Godekmerdan A, Kelestimur H, Carpenter DO. Effects of PCBs 52 and 77 on Th1/Th2 balance in mouse thymocyte cell cultures. Immunopharmacol Immunotoxicol. 2005;27(4):601–13. https://doi.org/10.1080/08923970500418752.

    Article  CAS  PubMed  Google Scholar 

  41. Ozcan M, Yilmaz B, King WM, Carpenter DO. Hippocampal long-term potentiation (LTP) is reduced by a coplanar PCB congener. Neurotoxicology. 2004;25(6):981–8. https://doi.org/10.1016/j.neuro.2004.03.014.

    Article  CAS  PubMed  Google Scholar 

  42. Hombach-Klonisch S, Pocar P, Kauffold J, Klonisch T. Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase-immortalized epithelial cell line of the porcine oviduct (TERT-OPEC). Toxicol Sci. 2006;90(2):519–28. https://doi.org/10.1093/toxsci/kfj102.

    Article  CAS  PubMed  Google Scholar 

  43. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, et al. EDC-2: the Endocrine Society's second scientific statement on endocrine-disrupting chemicals. Endocr Rev. 2015;36(6):E1–e150. https://doi.org/10.1210/er.2015-1010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ozturk MA, Kelestimur F, Kurtoglu S, Guven K, Arslan D. Anticholinesterase poisoning in Turkey - clinical, laboratory and radiologic evaluation of 269 cases. Hum Exp Toxicol. 1990;9(5):273–9. https://doi.org/10.1177/096032719000900503.

    Article  CAS  PubMed  Google Scholar 

  45. Guven M, Bayram F, Unluhizarci K, Kelestimur F. Endocrine changes in patients with acute organophosphate poisoning. Hum Exp Toxicol. 1999;18(10):598–601. https://doi.org/10.1191/096032799678839419.

    Article  CAS  PubMed  Google Scholar 

  46. Rattan S, Zhou C, Chiang C, Mahalingam S, Brehm E, Flaws JA. Exposure to endocrine disruptors during adulthood: consequences for female fertility. J Endocrinol. 2017;233(3):R109–r29. https://doi.org/10.1530/joe-17-0023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sandal S, Yilmaz B. Genotoxic effects of chlorpyrifos, cypermethrin, endosulfan and 2,4-D on human peripheral lymphocytes cultured from smokers and nonsmokers. Environ Toxicol. 2011;26(5):433–42. https://doi.org/10.1002/tox.20569.

    Article  CAS  PubMed  Google Scholar 

  48. Sereda B, Bouwman H, Kylin H. Comparing water, bovine milk, and indoor residual spraying as possible sources of DDT and pyrethroid residues in breast milk. J Toxicol Environ Health A. 2009;72(13):842–51. https://doi.org/10.1080/15287390902800447.

    Article  CAS  PubMed  Google Scholar 

  49. Langer P, Ukropec J, Kocan A, Drobna B, Radikova Z, Huckova M, et al. Obesogenic and diabetogenic impact of high organochlorine levels (HCB, p,p'-DDE, PCBs) on inhabitants in the highly polluted eastern Slovakia. Endocr Regul. 2014;48(1):17–24.

    Article  CAS  Google Scholar 

  50. Luo D, Pu Y, Tian H, Wu W, Sun X, Zhou T, et al. Association of in utero exposure to organochlorine pesticides with thyroid hormone levels in cord blood of newborns. Environ Pollut. 2017;231(Pt 1):78–86. https://doi.org/10.1016/j.envpol.2017.07.091.

    Article  CAS  PubMed  Google Scholar 

  51. Yucra S, Rubio J, Gasco M, Gonzales C, Steenland K, Gonzales GF. Semen quality and reproductive sex hormone levels in Peruvian pesticide sprayers. Int J Occup Environ Health. 2006;12(4):355–61. https://doi.org/10.1179/oeh.2006.12.4.355.

    Article  CAS  PubMed  Google Scholar 

  52. Mehrpour O, Karrari P, Zamani N, Tsatsakis AM, Abdollahi M. Occupational exposure to pesticides and consequences on male semen and fertility: a review. Toxicol Lett. 2014;230(2):146–56. https://doi.org/10.1016/j.toxlet.2014.01.029.

    Article  CAS  PubMed  Google Scholar 

  53. Zeng F, Lerro C, Lavoue J, Huang H, Siemiatycki J, Zhao N, et al. Occupational exposure to pesticides and other biocides and risk of thyroid cancer. Occup Environ Med. 2017;74(7):502–10. https://doi.org/10.1136/oemed-2016-103931.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Lee DH, Steffes MW, Sjodin A, Jones RS, Needham LL, Jacobs DR Jr. Low dose organochlorine pesticides and polychlorinated biphenyls predict obesity, dyslipidemia, and insulin resistance among people free of diabetes. PLoS One. 2011;6(1):e15977. https://doi.org/10.1371/journal.pone.0015977.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Collet SH, Picard-Hagen N, Lacroix MZ, Puel S, Viguie C, Bousquet-Melou A, et al. Allometric scaling for predicting human clearance of bisphenol a. Toxicol Appl Pharmacol. 2015;284(3):323–9. https://doi.org/10.1016/j.taap.2015.02.024.

    Article  CAS  PubMed  Google Scholar 

  56. Thayer KA, Doerge DR, Hunt D, Schurman SH, Twaddle NC, Churchwell MI, et al. Pharmacokinetics of bisphenol a in humans following a single oral administration. Environ Int. 2015;83:107–15. https://doi.org/10.1016/j.envint.2015.06.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Usman A, Ahmad M. From BPA to its analogues: is it a safe journey? Chemosphere. 2016;158:131–42. https://doi.org/10.1016/j.chemosphere.2016.05.070.

    Article  CAS  PubMed  Google Scholar 

  58. Liao C, Kannan K. A survey of bisphenol a and other bisphenol analogues in foodstuffs from nine cities in China. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2014;31(2):319–29. https://doi.org/10.1080/19440049.2013.868611.

    Article  CAS  PubMed  Google Scholar 

  59. Careghini A, Mastorgio AF, Saponaro S, Sezenna E. Bisphenol a, nonylphenols, benzophenones, and benzotriazoles in soils, groundwater, surface water, sediments, and food: a review. Environ Sci Pollut Res Int. 2015;22(8):5711–41. https://doi.org/10.1007/s11356-014-3974-5.

    Article  CAS  PubMed  Google Scholar 

  60. Paschoalini AL, Savassi LA, Arantes FP, Rizzo E, Bazzoli N. Heavy metals accumulation and endocrine disruption in Prochilodus argenteus from a polluted neotropical river. Ecotoxicol Environ Saf. 2019;169:539–50. https://doi.org/10.1016/j.ecoenv.2018.11.047.

    Article  CAS  PubMed  Google Scholar 

  61. Welfinger-Smith G, Minholz JL, Byrne S, Waghiyi V, Gologergen J, Kava J, et al. Organochlorine and metal contaminants in traditional foods from St. Lawrence Island, Alaska. J Toxicol Environ Health A. 2011;74(18):1195–214. https://doi.org/10.1080/15287394.2011.590099.

    Article  CAS  PubMed  Google Scholar 

  62. De Toni L, Tisato F, Seraglia R, Roverso M, Gandin V, Marzano C, et al. Phthalates and heavy metals as endocrine disruptors in food: a study on pre-packed coffee products. Toxicol Rep. 2017;4:234–9. https://doi.org/10.1016/j.toxrep.2017.05.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pirard C, Compere S, Firquet K, Charlier C. The current environmental levels of endocrine disruptors (mercury, cadmium, organochlorine pesticides and PCBs) in a Belgian adult population and their predictors of exposure. Int J Hyg Environ Health. 2018;221(2):211–22. https://doi.org/10.1016/j.ijheh.2017.10.010.

    Article  CAS  PubMed  Google Scholar 

  64. Cornelis C, D'Hollander W, Roosens L, Covaci A, Smolders R, Van Den Heuvel R, et al. First assessment of population exposure to perfluorinated compounds in Flanders, Belgium. Chemosphere. 2012;86(3):308–14. https://doi.org/10.1016/j.chemosphere.2011.10.034.

    Article  CAS  PubMed  Google Scholar 

  65. Perello G, Gomez-Catalan J, Castell V, Llobet JM, Domingo JL. Assessment of the temporal trend of the dietary exposure to PCDD/Fs and PCBs in Catalonia, over Spain: health risks. Food Chem Toxicol. 2012;50(2):399–408. https://doi.org/10.1016/j.fct.2011.06.077.

    Article  CAS  PubMed  Google Scholar 

  66. Chapin RE, Adams J, Boekelheide K, Gray LE Jr, Hayward SW, Lees PS, et al. NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol a. Birth Defects Res B Dev Reprod Toxicol. 2008;83(3):157–395. https://doi.org/10.1002/bdrb.20147.

    Article  CAS  PubMed  Google Scholar 

  67. Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. Exposure of the U.S. population to bisphenol a and 4-tertiary-octylphenol: 2003-2004. Environ Health Perspect. 2008;116(1):39–44. https://doi.org/10.1289/ehp.10753.

    Article  CAS  PubMed  Google Scholar 

  68. Volkel W, Colnot T, Csanady GA, Filser JG, Dekant W. Metabolism and kinetics of bisphenol a in humans at low doses following oral administration. Chem Res Toxicol. 2002;15(10):1281–7.

    Article  Google Scholar 

  69. Tasdemir Y, Salihoglu G, Salihoglu NK, Birgul A. Air-soil exchange of PCBs: seasonal variations in levels and fluxes with influence of equilibrium conditions. Environ Pollut. 2012;169:90–7. https://doi.org/10.1016/j.envpol.2012.05.022.

    Article  CAS  PubMed  Google Scholar 

  70. Sonne C, Dyck M, Riget FF, Beck Jensen JE, Hyldstrup L, Letcher RJ, et al. Penile density and globally used chemicals in Canadian and Greenland polar bears. Environ Res. 2015;137:287–91. https://doi.org/10.1016/j.envres.2014.12.026.

    Article  CAS  PubMed  Google Scholar 

  71. Brown TM, Macdonald RW, Muir DCG, Letcher RJ. The distribution and trends of persistent organic pollutants and mercury in marine mammals from Canada's eastern Arctic. Sci Total Environ. 2018;618:500–17. https://doi.org/10.1016/j.scitotenv.2017.11.052.

    Article  CAS  PubMed  Google Scholar 

  72. Lourencetti C, Grimalt JO, Marco E, Fernandez P, Font-Ribera L, Villanueva CM, et al. Trihalomethanes in chlorine and bromine disinfected swimming pools: air-water distributions and human exposure. Environ Int. 2012;45:59–67. https://doi.org/10.1016/j.envint.2012.03.009.

    Article  CAS  PubMed  Google Scholar 

  73. Weschler CJ, Nazaroff WW. Dermal uptake of organic vapors commonly found in indoor air. Environ Sci Technol. 2014;48(2):1230–7. https://doi.org/10.1021/es405490a.

    Article  CAS  PubMed  Google Scholar 

  74. Yilmaz B, Gilmore D, Wilson CA. Inhibition of the preovulatory LH surge in the rat by central noradrenergic mediation: involvement of an anaesthetic (urethane) and opioid receptor agonists. Biogenic Amines. 1996;12:423–35.

    CAS  Google Scholar 

  75. Yilmaz B, Gilmore DP, Wilson CA. Effects of DPDPE (a specific delta-opioid receptor agonist) and naloxone on hypothalamic monoamine concentrations during the pre-ovulatory LH surge in the rat. Eur J Endocrinol. 1998;139(5):546–51.

    Article  CAS  Google Scholar 

  76. Safe S. Endocrine disruptors and falling sperm counts: lessons learned or not! Asian J Androl. 2013;15(2):191–4. https://doi.org/10.1038/aja.2012.87.

    Article  PubMed  Google Scholar 

  77. Yesildaglar N, Yildirim G, Attar R, Karateke A, Ficicioglu C, Yilmaz B. Exposure to industrially polluted water resulted in regressed endometriotic lesions and enhanced adhesion formation in a rat endometriosis model: a preliminary study. Fertil Steril. 2010;93(5):1722–4. https://doi.org/10.1016/j.fertnstert.2009.09.028.

    Article  CAS  PubMed  Google Scholar 

  78. Sifakis S, Androutsopoulos VP, Tsatsakis AM, Spandidos DA. Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems. Environ Toxicol Pharmacol. 2017;51:56–70. https://doi.org/10.1016/j.etap.2017.02.024.

    Article  CAS  PubMed  Google Scholar 

  79. Mrema EJ, Rubino FM, Brambilla G, Moretto A, Tsatsakis AM, Colosio C. Persistent organochlorinated pesticides and mechanisms of their toxicity. Toxicology. 2013;307:74–88. https://doi.org/10.1016/j.tox.2012.11.015.

    Article  CAS  PubMed  Google Scholar 

  80. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S. Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000;58(4):852–8.

    Article  CAS  Google Scholar 

  81. Senthilkumaran B. Pesticide- and sex steroid analogue-induced endocrine disruption differentially targets hypothalamo-hypophyseal-gonadal system during gametogenesis in teleosts - a review. Gen Comp Endocrinol. 2015;219:136–42. https://doi.org/10.1016/j.ygcen.2015.01.010.

    Article  CAS  PubMed  Google Scholar 

  82. Bloom MS, Mok-Lin E, Fujimoto VY. Bisphenol a and ovarian steroidogenesis. Fertil Steril. 2016;106(4):857–63. https://doi.org/10.1016/j.fertnstert.2016.08.021.

    Article  CAS  PubMed  Google Scholar 

  83. Le Fol V, Ait-Aissa S, Sonavane M, Porcher JM, Balaguer P, Cravedi JP, et al. In vitro and in vivo estrogenic activity of BPA, BPF and BPS in zebrafish-specific assays. Ecotoxicol Environ Saf. 2017;142:150–6. https://doi.org/10.1016/j.ecoenv.2017.04.009.

    Article  CAS  PubMed  Google Scholar 

  84. Foster PM. Mode of action: impaired fetal leydig cell function - effects on male reproductive development produced by certain phthalate esters. Crit Rev Toxicol. 2005;35(8–9):713–9.

    Article  CAS  Google Scholar 

  85. Fisher JS. Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome. Reproduction. 2004;127(3):305–15. https://doi.org/10.1530/rep.1.00025.

    Article  CAS  PubMed  Google Scholar 

  86. Skinner MK, Manikkam M, Guerrero-Bosagna C. Epigenetic transgenerational actions of endocrine disruptors. Reprod Toxicol. 2011;31(3):337–43. https://doi.org/10.1016/j.reprotox.2010.10.012.

    Article  CAS  PubMed  Google Scholar 

  87. Karman BN, Basavarajappa MS, Hannon P, Flaws JA. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia. Toxicol Appl Pharmacol. 2012;264(1):1–12. https://doi.org/10.1016/j.taap.2012.07.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Harvey CN, Chen JC, Bagnell CA, Uzumcu M. Methoxychlor and its metabolite HPTE inhibit cAMP production and expression of estrogen receptors alpha and beta in the rat granulosa cell in vitro. Reprod Toxicol. 2015;51:72–8. https://doi.org/10.1016/j.reprotox.2014.12.001.

    Article  CAS  PubMed  Google Scholar 

  89. Zachow R, Uzumcu M. The methoxychlor metabolite, 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane, inhibits steroidogenesis in rat ovarian granulosa cells in vitro. Reprod Toxicol. 2006;22(4):659–65. https://doi.org/10.1016/j.reprotox.2006.04.018.

    Article  CAS  PubMed  Google Scholar 

  90. Lee SG, Kim JY, Chung JY, Kim YJ, Park JE, Oh S, et al. Bisphenol a exposure during adulthood causes augmentation of follicular atresia and luteal regression by decreasing 17beta-estradiol synthesis via downregulation of aromatase in rat ovary. Environ Health Perspect. 2013;121(6):663–9. https://doi.org/10.1289/ehp.1205823.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Souter I, Smith KW, Dimitriadis I, Ehrlich S, Williams PL, Calafat AM, et al. The association of bisphenol-a urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments. Reprod Toxicol. 2013;42:224–31. https://doi.org/10.1016/j.reprotox.2013.09.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Kandaraki E, Chatzigeorgiou A, Livadas S, Palioura E, Economou F, Koutsilieris M, et al. Endocrine disruptors and polycystic ovary syndrome (PCOS): elevated serum levels of bisphenol a in women with PCOS. J Clin Endocrinol Metab. 2011;96(3):E480–4. https://doi.org/10.1210/jc.2010-1658.

    Article  CAS  PubMed  Google Scholar 

  93. Ehrlich S, Williams PL, Missmer SA, Flaws JA, Berry KF, Calafat AM, et al. Urinary bisphenol a concentrations and implantation failure among women undergoing in vitro fertilization. Environ Health Perspect. 2012;120(7):978–83. https://doi.org/10.1289/ehp.1104307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Sugiura-Ogasawara M, Ozaki Y, Sonta S, Makino T, Suzumori K. Exposure to bisphenol a is associated with recurrent miscarriage. Hum Reprod. 2005;20(8):2325–9. https://doi.org/10.1093/humrep/deh888.

    Article  CAS  PubMed  Google Scholar 

  95. Philippat C, Mortamais M, Chevrier C, Petit C, Calafat AM, Ye X, et al. Exposure to phthalates and phenols during pregnancy and offspring size at birth. Environ Health Perspect. 2012;120(3):464–70. https://doi.org/10.1289/ehp.1103634.

    Article  CAS  PubMed  Google Scholar 

  96. Philippat C, Nakiwala D, Calafat AM, Botton J, De Agostini M, Heude B, et al. Prenatal exposure to nonpersistent endocrine disruptors and behavior in boys at 3 and 5 years. Environ Health Perspect. 2017;125(9):097014. https://doi.org/10.1289/ehp1314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Yilmaz B, Kutlu S, Canpolat S, Sandal S, Ayar A, Mogulkoc R, et al. Effects of paint thinner exposure on serum LH, FSH and testosterone levels and hypothalamic catecholamine contents in the male rat. Biol Pharm Bull. 2001;24(2):163–6. https://doi.org/10.1248/bpb.24.163.

    Article  CAS  PubMed  Google Scholar 

  98. Yilmaz B, Canpolat S, Sandal S, Akpolat N, Kutlu S, Ilhan N, et al. Paint thinner exposure inhibits testosterone synthesis and secretion in a reversible manner in the rat. Reprod Toxicol. 2006;22(4):791–6. https://doi.org/10.1016/j.reprotox.2006.08.002.

    Article  CAS  PubMed  Google Scholar 

  99. Bonde JP, Flachs EM, Rimborg S, Glazer CH, Giwercman A, Ramlau-Hansen CH, et al. The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis. Hum Reprod Update. 2016;23(1):104–25. https://doi.org/10.1093/humupd/dmw036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Joensen UN, Jorgensen N, Thyssen JP, Szecsi PB, Stender S, Petersen JH, et al. Urinary excretion of phenols, parabens and benzophenones in young men: associations to reproductive hormones and semen quality are modified by mutations in the Filaggrin gene. Environ Int. 2018;121(Pt 1):365–74. https://doi.org/10.1016/j.envint.2018.09.020.

    Article  CAS  PubMed  Google Scholar 

  101. Jensen TK, Carlsen E, Jorgensen N, Berthelsen JG, Keiding N, Christensen K, et al. Poor semen quality may contribute to recent decline in fertility rates. Hum Reprod. 2002;17(6):1437–40. https://doi.org/10.1093/humrep/17.6.1437.

    Article  PubMed  Google Scholar 

  102. Jorgensen N, Joensen UN, Jensen TK, Jensen MB, Almstrup K, Olesen IA et al. Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men. BMJ Open. 2012;2(4). doi:https://doi.org/10.1136/bmjopen-2012-000990.

  103. Petersen MS, Halling J, Jorgensen N, Nielsen F, Grandjean P, Jensen TK et al. Reproductive Function in a Population of Young Faroese Men with Elevated Exposure to Polychlorinated Biphenyls (PCBs) and Perfluorinated Alkylate Substances (PFAS). Int J Environ Res Public Health. 2018;15(9). doi:https://doi.org/10.3390/ijerph15091880.

  104. Hauser R. Urinary phthalate metabolites and semen quality: a review of a potential biomarker of susceptibility. Int J Androl. 2008;31(2):112–7. https://doi.org/10.1111/j.1365-2605.2007.00844.x.

    Article  CAS  PubMed  Google Scholar 

  105. Mendiola J, Jorgensen N, Andersson AM, Calafat AM, Ye X, Redmon JB, et al. Are environmental levels of bisphenol a associated with reproductive function in fertile men? Environ Health Perspect. 2010;118(9):1286–91. https://doi.org/10.1289/ehp.1002037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Mendiola J, Moreno JM, Roca M, Vergara-Juarez N, Martinez-Garcia MJ, Garcia-Sanchez A, et al. Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: a pilot study. Environ Health. 2011;10(1):6. https://doi.org/10.1186/1476-069x-10-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Nordkap L, Joensen UN, Blomberg Jensen M, Jorgensen N. Regional differences and temporal trends in male reproductive health disorders: semen quality may be a sensitive marker of environmental exposures. Mol Cell Endocrinol. 2012;355(2):221–30. https://doi.org/10.1016/j.mce.2011.05.048.

    Article  CAS  PubMed  Google Scholar 

  108. Ho SM, Tang WY. Belmonte de Frausto J, Prins GS. Developmental exposure to estradiol and bisphenol a increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer Res. 2006;66(11):5624–32. https://doi.org/10.1158/0008-5472.can-06-0516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Kogevinas M. Human health effects of dioxins: cancer, reproductive and endocrine system effects. Hum Reprod Update. 2001;7(3):331–9. https://doi.org/10.1093/humupd/7.3.331.

    Article  CAS  PubMed  Google Scholar 

  110. Meldrum DR, Morris MA, Gambone JC. Obesity pandemic: causes, consequences, and solutions-but do we have the will? Fertil Steril. 2017;107(4):833–9. https://doi.org/10.1016/j.fertnstert.2017.02.104.

    Article  PubMed  Google Scholar 

  111. Baudrand R, Goodarzi MO, Vaidya A, Underwood PC, Williams JS, Jeunemaitre X, et al. A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics. Metabolism. 2015;64(12):1674–81. https://doi.org/10.1016/j.metabol.2015.09.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Muscogiuri G, Barrea L, Laudisio D, Savastano S, Colao A. Obesogenic endocrine disruptors and obesity: myths and truths. Arch Toxicol. 2017;91(11):3469–75. https://doi.org/10.1007/s00204-017-2071-1.

    Article  CAS  PubMed  Google Scholar 

  113. Heindel JJ, Newbold R, Schug TT. Endocrine disruptors and obesity. Nat Rev Endocrinol. 2015;11(11):653–61. https://doi.org/10.1038/nrendo.2015.163.

    Article  CAS  PubMed  Google Scholar 

  114. Janesick A, Blumberg B. Minireview: PPARgamma as the target of obesogens. J Steroid Biochem Mol Biol. 2011;127(1–2):4–8. https://doi.org/10.1016/j.jsbmb.2011.01.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Watt J, Schlezinger JJ. Structurally-diverse, PPARgamma-activating environmental toxicants induce adipogenesis and suppress osteogenesis in bone marrow mesenchymal stromal cells. Toxicology. 2015;331:66–77. https://doi.org/10.1016/j.tox.2015.03.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994;79(7):1147–56. https://doi.org/10.1016/0092-8674(94)90006-x.

    Article  CAS  PubMed  Google Scholar 

  117. Bertuloso BD, Podratz PL, Merlo E, de Araujo JF, Lima LC, de Miguel EC, et al. Tributyltin chloride leads to adiposity and impairs metabolic functions in the rat liver and pancreas. Toxicol Lett. 2015;235(1):45–59. https://doi.org/10.1016/j.toxlet.2015.03.009.

    Article  CAS  PubMed  Google Scholar 

  118. Li X, Pham HT, Janesick AS, Blumberg B. Triflumizole is an obesogen in mice that acts through peroxisome proliferator activated receptor gamma (PPARgamma). Environ Health Perspect. 2012;120(12):1720–6. https://doi.org/10.1289/ehp.1205383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Ariemma F, D'Esposito V, Liguoro D, Oriente F, Cabaro S, Liotti A, et al. Low-dose Bisphenol-a impairs Adipogenesis and generates dysfunctional 3T3-L1 adipocytes. PLoS One. 2016;11(3):e0150762. https://doi.org/10.1371/journal.pone.0150762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Maloney EK, Waxman DJ. Trans-activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals. Toxicol Appl Pharmacol. 1999;161(2):209–18. https://doi.org/10.1006/taap.1999.8809.

    Article  CAS  PubMed  Google Scholar 

  121. Stahlhut RW, van Wijngaarden E, Dye TD, Cook S, Swan SH. Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ Health Perspect. 2007;115(6):876–82. https://doi.org/10.1289/ehp.9882.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Harley KG, Berger K, Rauch S, Kogut K, Claus Henn B, Calafat AM, et al. Association of prenatal urinary phthalate metabolite concentrations and childhood BMI and obesity. Pediatr Res. 2017;82(3):405–15. https://doi.org/10.1038/pr.2017.112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Yang C, Kong APS, Cai Z, Chung ACK. Persistent organic pollutants as risk factors for obesity and diabetes. Curr Diab Rep. 2017;17(12):132. https://doi.org/10.1007/s11892-017-0966-0.

    Article  CAS  PubMed  Google Scholar 

  124. Lee DH, Lee IK, Porta M, Steffes M, Jacobs DR Jr. Relationship between serum concentrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: results from the National Health and nutrition examination survey 1999-2002. Diabetologia. 2007;50(9):1841–51. https://doi.org/10.1007/s00125-007-0755-4.

    Article  CAS  PubMed  Google Scholar 

  125. Salihovic S, Ganna A, Fall T, Broeckling CD, Prenni JE, van Bavel B et al. The metabolic fingerprint of p,p'-DDE and HCB exposure in humans. Environ Int 2016;88:60–66. doi:https://doi.org/10.1016/j.envint.2015.12.015.

  126. Law J, Bloor I, Budge H, Symonds ME. The influence of sex steroids on adipose tissue growth and function. Horm Mol Biol Clin Invest. 2014;19(1):13–24. https://doi.org/10.1515/hmbci-2014-0015.

    Article  CAS  Google Scholar 

  127. Newbold RR, Padilla-Banks E, Jefferson WN. Environmental estrogens and obesity. Mol Cell Endocrinol. 2009;304(1–2):84–9. https://doi.org/10.1016/j.mce.2009.02.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Williams G. Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-alpha and GPER signalling. Mol Cell Endocrinol. 2012;351(2):269–78. https://doi.org/10.1016/j.mce.2011.12.017.

    Article  CAS  PubMed  Google Scholar 

  129. Luo JJ, Su DS, Xie SL, Liu Y, Liu P, Yang XJ, et al. Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish. FASEB J. 2018;32(5):2814–26. https://doi.org/10.1096/fj.201701171R.

    Article  PubMed  Google Scholar 

  130. Arsenescu V, Arsenescu RI, King V, Swanson H, Cassis LA. Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. Environ Health Perspect. 2008;116(6):761–8. https://doi.org/10.1289/ehp.10554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Moyer BJ, Rojas IY, Kerley-Hamilton JS, Nemani KV, Trask HW, Ringelberg CS, et al. Obesity and fatty liver are prevented by inhibition of the aryl hydrocarbon receptor in both female and male mice. Nutr Res. 2017;44:38–50. https://doi.org/10.1016/j.nutres.2017.06.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Nadal A, Quesada I, Tuduri E, Nogueiras R, Alonso-Magdalena P. Endocrine-disrupting chemicals and the regulation of energy balance. Nat Rev Endocrinol. 2017;13(9):536–46. https://doi.org/10.1038/nrendo.2017.51.

    Article  CAS  PubMed  Google Scholar 

  133. Farinetti A, Marraudino M, Ponti G, Panzica G, Gotti S. Chronic treatment with tributyltin induces sexually dimorphic alterations in the hypothalamic POMC system of adult mice. Cell Tissue Res. 2018;374(3):587–94. https://doi.org/10.1007/s00441-018-2896-9.

    Article  CAS  PubMed  Google Scholar 

  134. Ronn M, Lind L, Orberg J, Kullberg J, Soderberg S, Larsson A, et al. Bisphenol a is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans. Chemosphere. 2014;112:42–8. https://doi.org/10.1016/j.chemosphere.2014.03.042.

    Article  CAS  PubMed  Google Scholar 

  135. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, et al. Dynamics of fat cell turnover in humans. Nature. 2008;453(7196):783–7. https://doi.org/10.1038/nature06902.

    Article  CAS  PubMed  Google Scholar 

  136. Janesick AS, Blumberg B. Obesogens: an emerging threat to public health. Am J Obstet Gynecol. 2016;214(5):559–65. https://doi.org/10.1016/j.ajog.2016.01.182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest. 2006;116(7):1802–12. https://doi.org/10.1172/jci29103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Lind PM, Lind L. Endocrine-disrupting chemicals and risk of diabetes: an evidence-based review. Diabetologia. 2018;61(7):1495–502. https://doi.org/10.1007/s00125-018-4621-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Marroqui L, Tuduri E, Alonso-Magdalena P, Quesada I, Nadal A, Dos Santos RS. Mitochondria as target of endocrine-disrupting chemicals: implications for type 2 diabetes. J Endocrinol. 2018;239(2):R27–r45. https://doi.org/10.1530/joe-18-0362.

    Article  CAS  PubMed  Google Scholar 

  140. Ruiz D, Becerra M, Jagai JS, Ard K, Sargis RM. Disparities in environmental exposures to endocrine-disrupting chemicals and diabetes risk in vulnerable populations. Diabetes Care. 2018;41(1):193–205. https://doi.org/10.2337/dc16-2765.

    Article  CAS  PubMed  Google Scholar 

  141. Silverstone AE, Rosenbaum PF, Weinstock RS, Bartell SM, Foushee HR, Shelton C, et al. Polychlorinated biphenyl (PCB) exposure and diabetes: results from the Anniston community health survey. Environ Health Perspect. 2012;120(5):727–32. https://doi.org/10.1289/ehp.1104247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Wang SL, Tsai PC, Yang CY, Guo YL. Increased risk of diabetes and polychlorinated biphenyls and dioxins: a 24-year follow-up study of the Yucheng cohort. Diabetes Care. 2008;31(8):1574–9. https://doi.org/10.2337/dc07-2449.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Wu H, Bertrand KA, Choi AL, Hu FB, Laden F, Grandjean P, et al. Persistent organic pollutants and type 2 diabetes: a prospective analysis in the nurses' health study and meta-analysis. Environ Health Perspect. 2013;121(2):153–61. https://doi.org/10.1289/ehp.1205248.

    Article  CAS  PubMed  Google Scholar 

  144. Zong G, Valvi D, Coull B, Goen T, Hu FB, Nielsen F, et al. Persistent organic pollutants and risk of type 2 diabetes: a prospective investigation among middle-aged women in Nurses' health study II. Environ Int. 2018;114:334–42. https://doi.org/10.1016/j.envint.2017.12.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Song Y, Chou EL, Baecker A, You NC, Song Y, Sun Q, et al. Endocrine-disrupting chemicals, risk of type 2 diabetes, and diabetes-related metabolic traits: a systematic review and meta-analysis. J Diabetes. 2016;8(4):516–32. https://doi.org/10.1111/1753-0407.12325.

    Article  CAS  PubMed  Google Scholar 

  146. Kerger BD, Scott PK, Pavuk M, Gough M, Paustenbach DJ. Re-analysis of ranch hand study supports reverse causation hypothesis between dioxin and diabetes. Crit Rev Toxicol. 2012;42(8):669–87. https://doi.org/10.3109/10408444.2012.694095.

    Article  CAS  PubMed  Google Scholar 

  147. Taylor KW, Novak RF, Anderson HA, Birnbaum LS, Blystone C, Devito M, et al. Evaluation of the association between persistent organic pollutants (POPs) and diabetes in epidemiological studies: a national toxicology program workshop review. Environ Health Perspect. 2013;121(7):774–83. https://doi.org/10.1289/ehp.1205502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Cardenas A, Gold DR, Hauser R, Kleinman KP, Hivert MF, Calafat AM, et al. Plasma concentrations of per- and Polyfluoroalkyl substances at baseline and associations with glycemic indicators and diabetes incidence among high-risk adults in the diabetes prevention program trial. Environ Health Perspect. 2017;125(10):107001. https://doi.org/10.1289/ehp1612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Garcia-Arevalo M, Alonso-Magdalena P, Rebelo Dos Santos J, Quesada I, Carneiro EM, Nadal A. Exposure to bisphenol-a during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice. PLoS One. 2014;9(6):e100214. https://doi.org/10.1371/journal.pone.0100214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Moon MK, Jeong IK, Jung Oh T, Ahn HY, Kim HH, Park YJ, et al. Long-term oral exposure to bisphenol a induces glucose intolerance and insulin resistance. J Endocrinol. 2015;226(1):35–42. https://doi.org/10.1530/joe-14-0714.

    Article  CAS  PubMed  Google Scholar 

  151. Lee YM, Ha CM, Kim SA, Thoudam T, Yoon YR, Kim DJ, et al. Low-dose persistent organic pollutants impair insulin secretory function of pancreatic beta-cells: human and in vitro evidence. Diabetes. 2017;66(10):2669–80. https://doi.org/10.2337/db17-0188.

    Article  CAS  PubMed  Google Scholar 

  152. Chang KC, Hsu CC, Liu SH, Su CC, Yen CC, Lee MJ, et al. Cadmium induces apoptosis in pancreatic beta-cells through a mitochondria-dependent pathway: the role of oxidative stress-mediated c-Jun N-terminal kinase activation. PLoS One. 2013;8(2):e54374. https://doi.org/10.1371/journal.pone.0054374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Rovira-Llopis S, Banuls C, Diaz-Morales N, Hernandez-Mijares A, Rocha M, Victor VM. Mitochondrial dynamics in type 2 diabetes: pathophysiological implications. Redox Biol. 2017;11:637–45. https://doi.org/10.1016/j.redox.2017.01.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Sebastian D, Hernandez-Alvarez MI, Segales J, Sorianello E, Munoz JP, Sala D, et al. Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc Natl Acad Sci U S A. 2012;109(14):5523–8. https://doi.org/10.1073/pnas.1108220109.

    Article  PubMed  PubMed Central  Google Scholar 

  155. Yamada S, Asanagi M, Hirata N, Itagaki H, Sekino Y, Kanda Y. Tributyltin induces mitochondrial fission through Mfn1 degradation in human induced pluripotent stem cells. Toxicol in Vitro. 2016;34:257–63. https://doi.org/10.1016/j.tiv.2016.04.013.

    Article  CAS  PubMed  Google Scholar 

  156. Harvey PW. Adrenocortical endocrine disruption. J Steroid Biochem Mol Biol. 2016;155(Pt B):199–206. https://doi.org/10.1016/j.jsbmb.2014.10.009.

    Article  CAS  PubMed  Google Scholar 

  157. Martinez-Arguelles DB, Papadopoulos V. Mechanisms mediating environmental chemical-induced endocrine disruption in the adrenal gland. Front Endocrinol (Lausanne). 2015;6:29. https://doi.org/10.3389/fendo.2015.00029.

    Article  Google Scholar 

  158. Lauretta R, Sansone A, Sansone M, Romanelli F, Appetecchia M. Endocrine disrupting chemicals: effects on endocrine glands. Front Endocrinol (Lausanne). 2019;10:178. https://doi.org/10.3389/fendo.2019.00178.

    Article  Google Scholar 

  159. Hampl R, Kubatova J, Starka L. Steroids and endocrine disruptors - history, recent state of art and open questions. J Steroid Biochem Mol Biol. 2016;155(Pt B):217–23. https://doi.org/10.1016/j.jsbmb.2014.04.013.

    Article  CAS  PubMed  Google Scholar 

  160. Foster WG, Mertineit C, Yagminas A, McMahon A, Lecavalier P. The effects of hexachlorobenzene on circulating levels of adrenal steroids in the ovariectomized rat. J Biochem Toxicol. 1995;10(3):129–35.

    Article  CAS  Google Scholar 

  161. Araki A, Miyashita C, Mitsui T, Goudarzi H, Mizutani F, Chisaki Y, et al. Prenatal organochlorine pesticide exposure and the disruption of steroids and reproductive hormones in cord blood: the Hokkaido study. Environ Int. 2018;110:1–13. https://doi.org/10.1016/j.envint.2017.10.006.

    Article  CAS  PubMed  Google Scholar 

  162. Sargis RM, Heindel JJ, Padmanabhan V. Interventions to address environmental metabolism-disrupting chemicals: changing the narrative to empower action to restore metabolic health. Front Endocrinol (Lausanne). 2019;10:33. https://doi.org/10.3389/fendo.2019.00033.

    Article  Google Scholar 

  163. Mughal BB, Fini JB, Demeneix BA. Thyroid-disrupting chemicals and brain development: an update. Endocr Connect. 2018;7(4):R160–r86. https://doi.org/10.1530/ec-18-0029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Carvalho DP, Dupuy C. Thyroid hormone biosynthesis and release. Mol Cell Endocrinol. 2017;458:6–15. https://doi.org/10.1016/j.mce.2017.01.038.

    Article  CAS  PubMed  Google Scholar 

  165. Ghassabian A, Trasande L. Disruption in thyroid signaling pathway: a mechanism for the effect of endocrine-disrupting chemicals on child neurodevelopment. Front Endocrinol (Lausanne). 2018;9:204. https://doi.org/10.3389/fendo.2018.00204.

    Article  Google Scholar 

  166. Santos-Silva AP, Andrade MN, Pereira-Rodrigues P, Paiva-Melo FD, Soares P, Graceli JB, et al. Frontiers in endocrine disruption: impacts of organotin on the hypothalamus-pituitary-thyroid axis. Mol Cell Endocrinol. 2018;460:246–57. https://doi.org/10.1016/j.mce.2017.07.038.

    Article  CAS  PubMed  Google Scholar 

  167. Preau L, Fini JB, Morvan-Dubois G, Demeneix B. Thyroid hormone signaling during early neurogenesis and its significance as a vulnerable window for endocrine disruption. Biochim Biophys Acta. 2015;1849(2):112–21. https://doi.org/10.1016/j.bbagrm.2014.06.015.

    Article  CAS  PubMed  Google Scholar 

  168. Armstrong D. Implications of thyroid hormone signaling through the Phosphoinositide-3 kinase for xenobiotic disruption of human health. In: Gore AC, editor. Endocrine-disrupting chemicals: from basic research to clinical practice. Totowa: Humana Press; 2007. p. 193–202.

    Chapter  Google Scholar 

  169. Leung AM, Pearce EN, Braverman LE. Environmental perchlorate exposure: potential adverse thyroid effects. Curr Opin Endocrinol Diabetes Obes. 2014;21(5):372–6. https://doi.org/10.1097/med.0000000000000090.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Braverman LE, He X, Pino S, Cross M, Magnani B, Lamm SH, et al. The effect of perchlorate, thiocyanate, and nitrate on thyroid function in workers exposed to perchlorate long-term. J Clin Endocrinol Metab. 2005;90(2):700–6. https://doi.org/10.1210/jc.2004-1821.

    Article  CAS  PubMed  Google Scholar 

  171. Charatcharoenwitthaya N, Ongphiphadhanakul B, Pearce EN, Somprasit C, Chanthasenanont A, He X, et al. The association between perchlorate and thiocyanate exposure and thyroid function in first-trimester pregnant Thai women. J Clin Endocrinol Metab. 2014;99(7):2365–71. https://doi.org/10.1210/jc.2013-3986.

    Article  CAS  PubMed  Google Scholar 

  172. Knight BA, Shields BM, He X, Pearce EN, Braverman LE, Sturley R, et al. Effect of perchlorate and thiocyanate exposure on thyroid function of pregnant women from south-West England: a cohort study. Thyroid Res. 2018;11:9. https://doi.org/10.1186/s13044-018-0053-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. McKinney JD, Waller CL. Polychlorinated biphenyls as hormonally active structural analogues. Environ Health Perspect. 1994;102(3):290–7. https://doi.org/10.1289/ehp.94102290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Ulbrich B, Stahlmann R. Developmental toxicity of polychlorinated biphenyls (PCBs): a systematic review of experimental data. Arch Toxicol. 2004;78(5):252–68. https://doi.org/10.1007/s00204-003-0519-y.

    Article  CAS  PubMed  Google Scholar 

  175. Kato Y, Ikushiro S, Haraguchi K, Yamazaki T, Ito Y, Suzuki H, et al. A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats. Toxicol Sci. 2004;81(2):309–15. https://doi.org/10.1093/toxsci/kfh225.

    Article  CAS  PubMed  Google Scholar 

  176. Collins WT Jr, Capen CC. Fine structural lesions and hormonal alterations in thyroid glands of perinatal rats exposed in utero and by the milk to polychlorinated biphenyls. Am J Pathol. 1980;99(1):125–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Khan MA, Hansen LG. Ortho-substituted polychlorinated biphenyl (PCB) congeners (95 or 101) decrease pituitary response to thyrotropin releasing hormone. Toxicol Lett. 2003;144(2):173–82.

    Article  CAS  Google Scholar 

  178. Chauhan KR, Kodavanti PR, McKinney JD. Assessing the role of ortho-substitution on polychlorinated biphenyl binding to transthyretin, a thyroxine transport protein. Toxicol Appl Pharmacol. 2000;162(1):10–21. https://doi.org/10.1006/taap.1999.8826.

    Article  CAS  PubMed  Google Scholar 

  179. Carpenter DO. Exposure to and health effects of volatile PCBs. Rev Environ Health. 2015;30(2):81–92. https://doi.org/10.1515/reveh-2014-0074.

    Article  CAS  PubMed  Google Scholar 

  180. Schantz SL, Widholm JJ. Cognitive effects of endocrine-disrupting chemicals in animals. Environ Health Perspect. 2001;109(12):1197–206. https://doi.org/10.1289/ehp.011091197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Gilbert ME, Rovet J, Chen Z, Koibuchi N. Developmental thyroid hormone disruption: prevalence, environmental contaminants and neurodevelopmental consequences. Neurotoxicology. 2012;33(4):842–52. https://doi.org/10.1016/j.neuro.2011.11.005.

    Article  PubMed  Google Scholar 

  182. Gruppetta M, Mercieca C, Vassallo J. Prevalence and incidence of pituitary adenomas: a population based study in Malta. Pituitary. 2013;16(4):545–53. https://doi.org/10.1007/s11102-012-0454-0.

    Article  PubMed  Google Scholar 

  183. Cannavo S, Ferrau F, Ragonese M, Curto L, Torre ML, Magistri M, et al. Increased prevalence of acromegaly in a highly polluted area. Eur J Endocrinol. 2010;163(4):509–13. https://doi.org/10.1530/eje-10-0465.

    Article  CAS  PubMed  Google Scholar 

  184. Fortunati N, Guaraldi F, Zunino V, Penner F, D'Angelo V, Zenga F, et al. Effects of environmental pollutants on signaling pathways in rat pituitary GH3 adenoma cells. Environ Res. 2017;158:660–8. https://doi.org/10.1016/j.envres.2017.07.015.

    Article  CAS  PubMed  Google Scholar 

  185. Dietrich C, Kaina B. The aryl hydrocarbon receptor (AhR) in the regulation of cell-cell contact and tumor growth. Carcinogenesis. 2010;31(8):1319–28. https://doi.org/10.1093/carcin/bgq028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Cannavo S, Ragonese M, Puglisi S, Romeo PD, Torre ML, Alibrandi A, et al. Acromegaly is more severe in patients with AHR or AIP gene variants living in highly polluted areas. J Clin Endocrinol Metab. 2016;101(4):1872–9. https://doi.org/10.1210/jc.2015-4191.

    Article  CAS  PubMed  Google Scholar 

  187. Cannavo S, Trimarchi F, Ferrau F. Acromegaly, genetic variants of the aryl hydrocarbon receptor pathway and environmental burden. Mol Cell Endocrinol. 2017;457:81–8. https://doi.org/10.1016/j.mce.2016.12.019.

    Article  CAS  PubMed  Google Scholar 

  188. Shelby MD, Newbold RR, Tully DB, Chae K, Davis VL. Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays. Environ Health Perspect. 1996;104(12):1296–300. https://doi.org/10.1289/ehp.961041296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. OECD. Test No. 440: Uterotrophic Bioassay in Rodents. 2007. https://www.oecd-ilibrary.org/content/publication/9789264067417-en. Accessed July, 30 2019.

  190. Denslow ND, Chow MC, Kroll KJ, Green L. Vitellogenin as a biomarker of exposure for estrogen or estrogen mimics. Ecotoxicology. 1999;8(5):385–98. https://doi.org/10.1023/A:1008986522208.

    Article  CAS  Google Scholar 

  191. Heppell SA, Denslow ND, Folmar LC, Sullivan CV. Universal assay of vitellogenin as a biomarker for environmental estrogens. Environ Health Perspect. 1995;103(Suppl 7):9–15. https://doi.org/10.1289/ehp.95103s79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Matozzo V, Gagne F, Marin MG, Ricciardi F, Blaise C. Vitellogenin as a biomarker of exposure to estrogenic compounds in aquatic invertebrates: a review. Environ Int. 2008;34(4):531–45. https://doi.org/10.1016/j.envint.2007.09.008.

    Article  CAS  PubMed  Google Scholar 

  193. Arcaro KF, Gierthy JF. Assessing modulation of estrogenic activity of environmental and pharmaceutical compounds using MCF-7 focus assay. Methods Mol Biol. 2001;176:341–51. https://doi.org/10.1385/1-59259-115-9:341.

    Article  CAS  PubMed  Google Scholar 

  194. Ssempebwa J, Carpenter D, Yilmaz B, DeCaprio A, O'Hehir D, Arcaro K. Waste crankcase oil: an environmental contaminant with potential to modulate estrogenic responses. J Toxicol Environ Health A. 2004;67(14):1081–94. https://doi.org/10.1080/15287390490452308.

    Article  CAS  PubMed  Google Scholar 

  195. Bistan M, Podgorelec M, Marinšek Logar R, Tišler T. Yeast estrogen screen assay as a tool for detecting estrogenic activity in water bodies. Food Technol Biotechnol. 2012;50(4):427–33.

    CAS  Google Scholar 

  196. Routledge E, Sheahan D, Desbrow C, Brighty G, Waldock M, Sumpter J. Identification of estrogenic chemicals in STW effluent. 2. In vivo responses in trout and roach. Environ Sci Technol. 1998;32(11):1559–65.

    Article  CAS  Google Scholar 

  197. Naylor LH. Reporter gene technology: the future looks bright. Biochem Pharmacol. 1999;58(5):749–57. https://doi.org/10.1016/s0006-2952(99)00096-9.

    Article  CAS  PubMed  Google Scholar 

  198. Balaguer P, Boussioux AM, Demirpence E, Nicolas JC. Reporter cell lines are useful tools for monitoring biological activity of nuclear receptor ligands. Luminescence. 2001;16(2):153–8. https://doi.org/10.1002/bio.630.

    Article  CAS  PubMed  Google Scholar 

  199. Denison MS, Soshilov AA, He G, DeGroot DE, Zhao B. Exactly the same but different: promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. Toxicol Sci. 2011;124(1):1–22. https://doi.org/10.1093/toxsci/kfr218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. EU. Methods of sampling and analysis for the official control of levels of dioxins, dioxin- like PCBs and non-dioxin-like PCBs in certain foodstuffs and repealing Regulation (EC) No 1883/2006, 252/2012 (2012).

  201. EPA. Endocrine Disruptor Screening Program: Hershberger Assay OCSPP Guideline 890.1400 Standard Evaluation Procedure (SEP). In: Agency UEP, editor. Washington, DC2011.

  202. Mughal BB, Demeneix BA, Fini JB. Evaluating thyroid disrupting chemicals in vivo using Xenopus laevis. Methods Mol Biol. 1801;2018:183–92. https://doi.org/10.1007/978-1-4939-7902-8_15.

    Article  CAS  Google Scholar 

  203. Turque N, Palmier K, Le Mevel S, Alliot C, Demeneix BA. A rapid, physiologic protocol for testing transcriptional effects of thyroid-disrupting agents in premetamorphic Xenopus tadpoles. Environ Health Perspect. 2005;113(11):1588–93. https://doi.org/10.1289/ehp.7992.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Storey NM, Gentile S, Ullah H, Russo A, Muessel M, Erxleben C, et al. Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone. Proc Natl Acad Sci U S A. 2006;103(13):5197–201. https://doi.org/10.1073/pnas.0600089103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Pereira-Fernandes A, Demaegdt H, Vandermeiren K, Hectors TL, Jorens PG, Blust R, et al. Evaluation of a screening system for obesogenic compounds: screening of endocrine disrupting compounds and evaluation of the PPAR dependency of the effect. PLoS One. 2013;8(10):e77481. https://doi.org/10.1371/journal.pone.0077481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Casals-Casas C, Desvergne B. Endocrine disruptors: from endocrine to metabolic disruption. Annu Rev Physiol. 2011;73:135–62. https://doi.org/10.1146/annurev-physiol-012110-142200.

    Article  CAS  PubMed  Google Scholar 

  207. Pereira-Fernandes A, Vanparys C, Vergauwen L, Knapen D, Jorens PG, Blust R. Toxicogenomics in the 3T3-L1 cell line, a new approach for screening of obesogenic compounds. Toxicol Sci. 2014;140(2):352–63. https://doi.org/10.1093/toxsci/kfu092.

    Article  CAS  PubMed  Google Scholar 

  208. Odermatt A, Strajhar P, Engeli RT. Disruption of steroidogenesis: cell models for mechanistic investigations and as screening tools. J Steroid Biochem Mol Biol. 2016;158:9–21. https://doi.org/10.1016/j.jsbmb.2016.01.009.

    Article  CAS  PubMed  Google Scholar 

  209. Ahmed KEM, Froysa HG, Karlsen OA, Blaser N, Zimmer KE, Berntsen HF, et al. Effects of defined mixtures of POPs and endocrine disruptors on the steroid metabolome of the human H295R adrenocortical cell line. Chemosphere. 2019;218:328–39. https://doi.org/10.1016/j.chemosphere.2018.11.057.

    Article  CAS  PubMed  Google Scholar 

  210. Lee HB, Schwab TL, Sigafoos AN, Gauerke JL, Krug RG 2nd, Serres MR, et al. Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response. Genes Brain Behav. 2019;18(2):e12549. https://doi.org/10.1111/gbb.12549.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Huda Bhuiyan MN, Kang H, Kim JH, Kim S, Kho Y, Choi K. Endocrine disruption by several aniline derivatives and related mechanisms in a human adrenal H295R cell line and adult male zebrafish. Ecotoxicol Environ Saf. 2019;180:326–32. https://doi.org/10.1016/j.ecoenv.2019.05.003.

    Article  CAS  PubMed  Google Scholar 

  212. Tug N, Sandal S, Ozelgun B, Yilmaz B. Correlation of spermiogram profiles with DNA damage in sperm cells of infertile men: a comet assay study. Gynecol Endocrinol. 2011;27(1):49–54. https://doi.org/10.3109/09513590.2010.487598.

    Article  CAS  PubMed  Google Scholar 

  213. Yilmaz B, Sandal S, Ayvaci H, Tug N, Vitrinel A. Genotoxicity profiles in exfoliated human mammary cells recovered from lactating mothers in Istanbul; relationship with demographic and dietary factors. Mutat Res. 2012;749(1–2):17–22. https://doi.org/10.1016/j.mrgentox.2012.06.011.

    Article  CAS  PubMed  Google Scholar 

  214. Browne EP, Dinc SE, Punska EC, Agus S, Vitrinel A, Erdag GC, et al. Promoter methylation in epithelial-enriched and epithelial-depleted cell populations isolated from breast milk. J Hum Lact. 2014;30(4):450–7. https://doi.org/10.1177/0890334414548224.

    Article  PubMed  Google Scholar 

  215. Messerlian C, Martinez RM, Hauser R, Baccarelli AA. 'Omics' and endocrine-disrupting chemicals - new paths forward. Nat Rev Endocrinol. 2017;13(12):740–8. https://doi.org/10.1038/nrendo.2017.81.

    Article  CAS  PubMed  Google Scholar 

  216. Welshons WV, Nagel SC. Vom Saal FS. Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol a at levels of human exposure. Endocrinology. 2006;147(6 Suppl):S56–69. https://doi.org/10.1210/en.2005-1159.

    Article  CAS  PubMed  Google Scholar 

  217. Bunay J, Larriba E, Patino-Garcia D, Cruz-Fernandes L, Castaneda-Zegarra S, Rodriguez-Fernandez M, et al. Editor's highlight: differential effects of exposure to single versus a mixture of endocrine-disrupting chemicals on Steroidogenesis pathway in mouse testes. Toxicol Sci. 2018;161(1):76–86. https://doi.org/10.1093/toxsci/kfx200.

    Article  CAS  PubMed  Google Scholar 

  218. Kelce WR, Stone CR, Laws SC, Gray LE, Kemppainen JA, Wilson EM. Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist. Nature. 1995;375(6532):581–5. https://doi.org/10.1038/375581a0.

    Article  CAS  PubMed  Google Scholar 

  219. Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N, et al. Thyroid hormone action is disrupted by bisphenol a as an antagonist. J Clin Endocrinol Metab. 2002;87(11):5185–90. https://doi.org/10.1210/jc.2002-020209.

    Article  CAS  PubMed  Google Scholar 

  220. EU. Maximum levels for dioxins, dioxin-like PCBs and non dioxin-like PCBs in foodstuffs, 1259/2011 (2011).

  221. EU. EU legislation on Maximum Residue Levels. https://ec.europa.eu/food/plant/pesticides/max_residue_levels/eu_rules_en. Accessed July, 30 2019.

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Acknowledgments

This work was supported by grant TUBITAK 113S155 from the Scientific and Technological Research Council of Turkey (to Bayram Yilmaz).

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey

    Bayram Yilmaz

  2. Department of Internal Medicine, Faculty of Medicine, Yeditepe University, Istanbul, Turkey

    Hakan Terekeci

  3. Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey

    Suleyman Sandal

  4. Department of Endocrinology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey

    Fahrettin Kelestimur

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  1. Bayram Yilmaz
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Correspondence to Fahrettin Kelestimur.

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Yilmaz, B., Terekeci, H., Sandal, S. et al. Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention. Rev Endocr Metab Disord 21, 127–147 (2020). https://doi.org/10.1007/s11154-019-09521-z

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