Abstract
Endocrine disrupting chemicals (EDCs) include a variety of chemicals with different structures. Disruption of the complicated endocrine system by these chemicals has been suspected to affect the health of wildlife and humans. Exposure to EDCs has been linked to malformations of the genital tract, alterations in reproduction, some cancers in the reproductive organs, and changes in neurodevelopment and behavior for several decades even though the evidence from experimental or human studies is not completely consistent. On the other hand, the growing body of recent evidence has strongly suggested that EDCs may contribute to the development of obesity and obesity-related metabolic dysfunctions like type 2 diabetes. EDCs may be involved in the pathogenesis of various chronic diseases, particularly obesity-related diseases, which have increased with industrialization. However, the complicated characteristics of EDCs like non-linear dose-response relationships and mixture effects hamper researchers from obtaining consistent results from experimental or human studies. More basic and clinical studies should be performed in order to understand the health effects of EDCs, including the effects on the epigenome, developmental programming, transgenerational effects, and crosstalk among endocrine systems and metabolic and immune systems. Also, researchers need to keep in mind that traditional approaches may not be satisfactory in studying the health effects of EDCs. Considering the complexity of EDCs, a precautionary approach should be applied to the field of EDCs. Any effort to decrease exposure to EDCs would be beneficial in the prevention and control of various diseases.
References
1. Kavlock RJ, Daston GP, DeRosa C, Fenner-Crisp P, Gray LE, Kaattari S, Lucier G, Luster M, Mac MJ, Maczka C, Miller R, Moore J, Rolland R, Scott G, Sheehan DM, Sinks T, Tilson HA. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. Environ Health Perspect. 1996. 104:Suppl 4. 715–740.
2. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev. 2009. 30:293–342.
3. Kretschmer XC, Baldwin WS. CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005. 155:111–128.
4. Myers JP, Zoeller RT, vom Saal FS. A clash of old and new scientific concepts in toxicity, with important implications for public health. Environ Health Perspect. 2009. 117:1652–1655.
5. Welshons WV, Thayer KA, Judy BM, Taylor JA, Curran EM, vom Saal FS. Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Environ Health Perspect. 2003. 111:994–1006.
6. Medlock KL, Lyttle CR, Kelepouris N, Newman ED, Sheehan DM. Estradiol down-regulation of the rat uterine estrogen receptor. Proc Soc Exp Biol Med. 1991. 196:293–300.
7. Rajapakse N, Silva E, Kortenkamp A. Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action. Environ Health Perspect. 2002. 110:917–921.
8. Vandenberg LN, Maffini MV, Sonnenschein C, Rubin BS, Soto AM. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev. 2009. 30:75–95.
9. Sohoni P, Sumpter JP. Several environmental oestrogens are also anti-androgens. J Endocrinol. 1998. 158:327–339.
10. Markey CM, Rubin BS, Soto AM, Sonnenschein C. Endocrine disruptors: from wingspread to environmental developmental biology. J Steroid Biochem Mol Biol. 2002. 83:235–244.
11. Cooper RL, Kavlock RJ. Endocrine disruptors and reproductive development: a weight-of-evidence overview. J Endocrinol. 1997. 152:159–166.
12. Marselos M, Tomatis L. Diethylstilboestrol: II, pharmacology, toxicology and carcinogenicity in experimental animals. Eur J Cancer. 1992. 29A:149–155.
13. Grün F, Blumberg B. Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology. 2006. 147:6 Suppl. S50–S55.
14. Baillie-Hamilton PF. Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med. 2002. 8:185–192.
15. Newbold RR, Padilla-Banks E, Snyder RJ, Phillips TM, Jefferson WN. Developmental exposure to endocrine disruptors and the obesity epidemic. Reprod Toxicol. 2007. 23:290–296.
16. Ruzzin J, Petersen R, Meugnier E, Madsen L, Lock EJ, Lillefosse H, Ma T, Pesenti S, Sonne SB, Marstrand TT, Malde MK, Du ZY, Chavey C, Fajas L, Lundebye AK, Brand CL, Vidal H, Kristiansen K, Frøyland L. Persistent organic pollutant exposure leads to insulin resistance syndrome. Environ Health Perspect. 2010. 118:465–471.
17. Lim S, Ahn SY, Song IC, Chung MH, Jang HC, Park KS, Lee KU, Pak YK, Lee HK. Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance. PLoS One. 2009. 4:e5186.
18. Lee DH, Lind L, Jacobs DR Jr, Salihovic S, van Bavel B, Lind PM. Associations of persistent organic pollutants with abdominal obesity in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Environ Int. 2012. 40:170–178.
19. 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:e15977.
20. Alonso-Magdalena P, Quesada I, Nadal A. Endocrine disruptors in the etiology of type 2 diabetes mellitus. Nat Rev Endocrinol. 2011. 7:346–353.
21. Hectors TL, Vanparys C, van der Ven K, Martens GA, Jorens PG, Van Gaal LF, Covaci A, De Coen W, Blust R. Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt beta cell function. Diabetologia. 2011. 54:1273–1290.
22. Lee DH, Lee IK, Song K, Steffes M, Toscano W, Baker BA, Jacobs DR Jr. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002. Diabetes Care. 2006. 29:1638–1644.
24. Lee DH, Lee IK, Jin SH, Steffes M, Jacobs DR Jr. Association between serum concentrations of persistent organic pollutants and insulin resistance among nondiabetic adults: results from the National Health and Nutrition Examination Survey 1999-2002. Diabetes Care. 2007. 30:622–628.
25. 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 Nut-rition Examination Survey 1999-2002. Diabetologia. 2007. 50:1841–1851.
26. Lee DH, Lind PM, Jacobs DR Jr, Salihovic S, van Bavel B, Lind L. Polychlorinated biphenyls and organochlorine pesticides in plasma predict development of type 2 diabetes in the elderly: the prospective investigation of the vasculature in Uppsala Seniors (PIVUS) study. Diabetes Care. 2011. 34:1778–1784.
27. Lee DH, Steffes MW, Sjodin A, Jones RS, Needham LL, Jacobs DR Jr. Low dose of some persistent organic pollutants predicts type 2 diabetes: a nested case-control study. Environ Health Perspect. 2010. 118:1235–1242.