Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 EDCs represent a health threat that should not be underestimated when dealing with human pregnancy. They could impact on human fertility, fetal development and pregnancy success. + 1167 word(s) 1167 2020-06-16 11:43:39 |
2 format change Meta information modification 1167 2020-06-18 04:08:46 | |
3 format correct -6 word(s) 1161 2020-10-27 09:55:22 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Rolfo, A.; Nuzzo, A.M.; De Amicis, R.; Moretti, L.; Bertoli, S.; Leone, A. Endocrine Disrupting Chemicals. Encyclopedia. Available online: https://encyclopedia.pub/entry/1119 (accessed on 28 March 2024).
Rolfo A, Nuzzo AM, De Amicis R, Moretti L, Bertoli S, Leone A. Endocrine Disrupting Chemicals. Encyclopedia. Available at: https://encyclopedia.pub/entry/1119. Accessed March 28, 2024.
Rolfo, Alessandro, Anna Maria Nuzzo, Ramona De Amicis, Laura Moretti, Simona Bertoli, Alessandro Leone. "Endocrine Disrupting Chemicals" Encyclopedia, https://encyclopedia.pub/entry/1119 (accessed March 28, 2024).
Rolfo, A., Nuzzo, A.M., De Amicis, R., Moretti, L., Bertoli, S., & Leone, A. (2020, June 17). Endocrine Disrupting Chemicals. In Encyclopedia. https://encyclopedia.pub/entry/1119
Rolfo, Alessandro, et al. "Endocrine Disrupting Chemicals." Encyclopedia. Web. 17 June, 2020.
Endocrine Disrupting Chemicals
Edit

Endocrine-disrupting chemicals (EDCs) are exogenous substances able to mimic or to interfere with the endocrine system, thus altering key biological processes such as organ development, reproduction, immunity, metabolism and behavior. High concentrations of EDCs are found in several everyday products including plastic bottles and food containers and they could be easily absorbed by dietary intake. In recent years, considerable interest has been raised regarding the biological effects of EDCs, particularly Bisphenol A (BPA) and phthalates, on human pregnancy and fetal development. Several evidence obtained on in vitro and animal models as well as by epidemiologic and population studies strongly indicated that endocrine disruptors could negatively impact fetal and placental health by interfering with the embryonic developing epigenome, thus establishing disease paths into adulthood. Moreover, EDCs could cause and/or contribute to the onset of severe gestational conditions as Preeclampsia (PE), Fetal Growth Restriction (FGR) and gestational diabetes in pregnancy, as well as obesity, diabetes and cardiovascular complications in reproductive age. Therefore, despite contrasting data being present in the literature, endocrine disruptors must be considered as a therapeutic target. Future actions aimed at reducing or eliminating EDC exposure during the perinatal period are mandatory to guarantee pregnancy success and preserve fetal and adult health.

Endocrine-disrupting chemicals Bisphenol A Phthalates Pregnancy Reproductive Health Obesity Diabetes Fetal Programming Pregnancy-related disorders

1. Introduction

According to the World Health Organization (WHO), an endocrine disruptor is “an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub) populations”[1].

Endocrine Disrupting Chemicals (EDCs) disrupt endocrine functions mainly by mimicking natural hormones like estrogens, androgens or thyroid hormones. Moreover, they could alter hormones’ metabolism, thus blocking and antagonizing their interaction with the specific membrane and/or intra-cellular receptors[2]. Almost 800 chemicals are suspected to interfere with endocrine functions[3]. For example, dioxins are a byproduct in herbicide production, paper bleaching or in waste burning, while perchlorate is a secondary product of aerospace, weapon and pharmaceutical industries frequently found in drinking water[4][5]. Other EDCs are perfluoroalkyl and polyfluoroalkyl (PFAS), used in industrial applications as firefighting foams and non-stick pans[6]. Phytoestrogens are natural endocrine disruptors occurring in plants that have hormone-like activity, such as genistein and daidzein, that are in soy products like tofu or soy milk[7]. Of particular interest are BPA and phthalates, widely investigated as “obesogenic” factors that could interfere with pregnancy physiology and fetal development, thus being a leading cause of reproductive disorders[3]. Fresh meat, fish and vegetables which are not packed in plastic have a low concentration of BPA and phthalates[8], while ready-to-eat and fast food products stored in plastic bags and cans are a major exposure source to these EDCs[9][10].

BPA is an industrial chemical obtained from condensation between phenol and acetone that has been used to produce plastics and resins since the 1960s. It is considered the first synthetic estrogen produced, although it does not possess a steroid structure since it does not include the phenanthrene nucleus[11]. BPA is found in polycarbonate plastics that are commonly used in containers to store food, beverages and other goods. It is also present in epoxy resins used to coat metal products as food cans, bottle tops and water supply lines. Indeed, it is very easy to be exposed to BPA, and since 2011 the European Union prohibited BPA use at least in polycarbonate baby bottles. BPA was recently removed from many consumer products, being replaced by its structural analogs Bisphenol-S (BPS) and Bisphenol-F (BPF). Nevertheless, BPS and BPF have detrimental effects similar to BPA, such as cytotoxicity, genotoxicity, reproductive toxicity, dioxin-like effects and neurotoxicity. Moreover, it has been shown that BPS and BPF exhibit estrogenic and/or anti-androgenic activities similar to or even greater than those of BPA[12][13]. While studies investigating BPS and BPF metabolism are lacking, BPA is absorbed by the digestive tract and, to a lesser extent, by the skin through direct contact[14]. After ingestion, BPA is metabolized by the intestinal microbiota and by the liver, mainly by glucuronidation and, to a lesser extent, sulfation, resulting in the production of BPA monoglucuronide (BPA-G) and BPA sulphate (BPA-S), with BPA-G being the main BPA metabolite in humans[15]. The majority of BPA is metabolized to BPA-G via the Uridine 5′-diphospho-glucuronosyltransferase (UGT) system. Studies on the fetal expression of UGT enzymes responsible for BPA glucuronidation detected no to low enzyme activity during the prenatal period[16]. Nevertheless, the human fetus is exposed to high BPA concentrations, since BPA-G and BPA-S are deconjugated and thus converted back to BPA in the placenta[17].

BPA is well known for its estrogenic activity exerted through the activation of the Estrogen Receptor (ER), with a stronger affinity for ERβ than for ERα, whereas BPA-G did not show ER-mediated estrogenic activity[18], but it exerted pro-inflammatory effects via the competitive inhibition of PPAR-γ signaling[19].

Phthalates are diesters of phthalic acid classified into high- and low-molecular-weight ones. The first category includes several compounds that are largely adopted to increase plastic flexibility and durability. Among them, the most commonly employed additive is di (2-ethylhexyl) phthalate (DEHP). Low-molecular-weight phthalates, like diethyl phthalate (DEP), are mainly used in personal care products and cosmetics, but they could be also found in pesticides and in food packaging[20]. Exposure to DEHP is reflected by the presence of its metabolites in urine, such as mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate, mono (2-ethyl-5-carboxypentyl) phthalate and mono(2-ethyl-5-oxohexyl) phthalate, whereas the main urinary metabolite of DEP is mono-ethyl phthalate (MEP). Remarkably, the bioactivity of phthalate metabolites is superior to that of the original substance[15].

2. Risk factors

BPA and phthalates are therefore widely present in everyday life due to the considerable volume of plastic produced[21]. They could be released at room temperature but heating facilitates their leaking out, resulting in massive food and beverage contamination[22]. For example, in polycarbonate (PC) bottles, high temperatures stimulate BPA migration into water by promoting hydrolysis and/or wall permeability[23], with a temperature that influences BPA migration more than heating time[24]. Table 1 summarizes the most important EDCs known to be disease risk factors.

Table 1. Endocrine-disrupting chemicals (EDCs) most relevant to human health.

EDC

Metabolites

Exposure Sources

Bisphenol[9]
Bisphenol A (BPA)
Bisphenol S (BPS)
Bisphenol F (BPF)
Bisphenol B (BPB)

[25]
BPA glucuronide (BPA-G)
BPA sulfate (BPA-S)

Synthetic[9]
Food packaging;
Thermal receipts;
Plastic dinnerware;
Polycarbonate plastic;
Epoxy resins;
Dental sealants;

High-Molecular-Weight Phathalate[9]
Di(2-ethylhexyl) phthalate (DEHP)

[9]
Mono(2-ethyl-5-hydroxyhexyl) phthalate; mEHHP
Mono(2-ethylhexyl) phthalate; mEHP
Mono(2-ethyl-5-oxohexyl) phthalate; mEOHP
Mono(2-ethyl-5-carboxypentyl) phthalate; mECPP

Synthetic[9]
Food packaging and processing;
Pharmaceutical coatings;
PVC plastics;
Building materials;
Medical devices;

Low-Molecular-Weight Phathalate[9]
Diethyl phthalate (DEP)

[9]
Monoethyl phthalate; mEP

Synthetic[9]
Fragrant PCPs:|
perfumes/colognes;
deodorants;
soaps,
shampoos
lotions;

Persistent Organic Pollutants (POPs)
Dichlorodiphenyltrichloroethane (DDT)[26]
Dioxins (PCDD, PCDF)[4]

chlorodiphenyldichloroethylene (DDE)

Synthetic
Pesticides; [26]
Insecticide;
Combustion; [4]
Incineration;
Waste burning;
Paper bleaching;

Polycyclic Aromatic Hydrocarbons (PAHs)[26]
polybrominated diphenyl ethers (PBDEs)
polychlorinated biphenyls (PCBs)
brominated flame retardants (BFRs)

 

Synthetic[26]
 Combustion processes;
Building materials;
Electronics furniture;
Hydraulic fluids;

Perfluorinated Alkylated Substances (PFAS)[6]
Perfluoroalkyl
Polyfluoroalkyl

 

Synthetic[6]
Personal care products:
Polishes and Paints;

Non-stick cookware;
Fire-fighting foams;

Phytoestrogens[7]
Isoflavonoids (Genistein, Daidzein)

 

Natural[7]
Soy beans and other legumes

References

  1. World Health Organization (WHO). Global Assessment of the State-Of-The-Science of Endocrine Disruptors. Available online: https://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/ (accessed on 21 April 2020)
  2. Claude Monneret; What is an endocrine disruptor?. Comptes Rendus. Biologies 2017, 340, 403-405, 10.1016/j.crvi.2017.07.004.
  3. Tiziana Filardi; Francesca Panimolle; Andrea Lenzi; Susanna Morano; Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications. Nutrients 2020, 12, 525, 10.3390/nu12020525.
  4. Ashok K Rathoure; Dioxins: source, origin and toxicity assessment. Biodiversity International Journal 2018, 2, 310-314, 10.15406/bij.2018.02.00079.
  5. Maricel V. Maffini; Leonardo Trasande; Thomas G. Neltner; Perchlorate and Diet: Human Exposures, Risks, and Mitigation Strategies. Current Environmental Health Reports 2016, 3, 107-117, 10.1007/s40572-016-0090-3.
  6. Andres Cardenas; Russ Hauser; Diane R. Gold; Ken Kleinman; Marie-France Hivert; Abby F. Fleisch; Pi-I D. Lin; Antonia M. Calafat; Thomas F. Webster; Edward S. Horton; et al.Emily Oken Association of Perfluoroalkyl and Polyfluoroalkyl Substances With Adiposity.. JAMA Network Open 2018, 1, e181493-e181493, 10.1001/jamanetworkopen.2018.1493.
  7. Heather B. Patisaul; Wendy Jefferson; The pros and cons of phytoestrogens. Frontiers in Neuroendocrinology 2010, 31, 400-419, 10.1016/j.yfrne.2010.03.003.
  8. Tine Fierens; Mirja Van Holderbeke; Hanny Willems; S. De Henauw; I. Sioen; Transfer of eight phthalates through the milk chain — A case study. Environment International 2013, 51, 1-7, 10.1016/j.envint.2012.10.002.
  9. Diana C Pacyga; Sheela Sathyanarayana; Rita S Strakovsky; Dietary Predictors of Phthalate and Bisphenol Exposures in Pregnant Women.. Advances in Nutrition: An International Review Journal 2019, 10, 803-815, 10.1093/advances/nmz029.
  10. Ami R. Zota; Cassandra A. Phillips; Susanna D. Mitro; Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003–2010. Environmental Health Perspectives 2016, 124, 1521-1528, 10.1289/ehp.1510803.
  11. Darja Gramec Skledar; Lucija Peterlin Mašič; Bisphenol A and its analogs: Do their metabolites have endocrine activity?. Environmental Toxicology and Pharmacology 2016, 47, 182-199, 10.1016/j.etap.2016.09.014.
  12. Erin Ihde; Stacy Zamudio; Ji Meng Loh; Yalin Zhu; John Woytanowski; Lawrence Rosen; Min Liu; Brian Buckley; Application of a novel mass spectrometric (MS) method to examine exposure to Bisphenol-A and common substitutes in a maternal fetal cohort. Human and Ecological Risk Assessment: An International Journal 2017, 24, 331-346, 10.1080/10807039.2017.1381831.
  13. Da Chen; Kurunthachalam Kannan; Hongli Tan; Zhengui Zheng; Yong-Lai Feng; Yan Wu; Margaret Widelka; Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity—A Review. Environmental Science & Technology 2016, 50, 5438-5453, 10.1021/acs.est.5b05387.
  14. Frank Toner; Graham Allan; Stephen S. Dimond; John M. Waechter; Dieter Beyer; In vitro percutaneous absorption and metabolism of Bisphenol A (BPA) through fresh human skin. Toxicology in Vitro 2018, 47, 147-155, 10.1016/j.tiv.2017.11.002.
  15. Wojciech Żwierełło; Agnieszka Maruszewska; Marta Skórka-Majewicz; Marta Goschorska; Irena Baranowska-Bosiacka; Karolina Dec; Daniel Styburski; Anna Nowakowska; Izabela Gutowska; The influence of polyphenols on metabolic disorders caused by compounds released from plastics - Review.. Chemosphere 2019, 240, 124901, 10.1016/j.chemosphere.2019.124901.
  16. Ronald N. Hines; The ontogeny of drug metabolism enzymes and implications for adverse drug events. Pharmacology & Therapeutics 2008, 118, 250-267, 10.1016/j.pharmthera.2008.02.005.
  17. Cheri L. Stowell; Kevin K. Barvian; Peter C.M. Young; Robert M. Bigsby; Dawn E. Verdugo; Carolyn R. Bertozzi; Theodore S. Widlanski; A Role for Sulfation-Desulfation in the Uptake of Bisphenol A into Breast Tumor Cells. Chemistry & Biology 2006, 13, 891-897, 10.1016/j.chembiol.2006.06.016.
  18. J B Matthews; K Twomey; T R Zacharewski; In vitro and in vivo interactions of bisphenol A and its metabolite, bisphenol A glucuronide, with estrogen receptors alpha and beta.. Chemical Research in Toxicology 2001, 14, 149–157.
  19. Saba Rehman; Zeenat Usman; Sabeen Rehman; Moneera Aldraihem; Noor Rehman; Ibraheem Rehman; Gulfam Ahmad; Endocrine disrupting chemicals and impact on male reproductive health. Translational Andrology and Urology 2018, 7, 490-503, 10.21037/tau.2018.05.17.
  20. Yu Wang; Hongkai Zhu; Kurunthachalam Kannan; A Review of Biomonitoring of Phthalate Exposures.. Toxics 2019, 7, 21, 10.3390/toxics7020021.
  21. Hanne Frederiksen; Martin Blomberg Jensen; N Jørgensen; Henriette Boye Kyhl; Steffen Husby; Niels E Skakkebæk; Katharina M. Main; Anders Juul; Anna-Maria Andersson; N. E. Skakkebaek; et al. Human urinary excretion of non-persistent environmental chemicals: an overview of Danish data collected between 2006 and 2012. REPRODUCTION 2014, 147, 555-565, 10.1530/rep-13-0522.
  22. Cao Li; Jia Xu; Dan Chen; YuXiu Xiao; Detection of phthalates migration from disposable tablewares to drinking water using hexafluoroisopropanol-induced catanionic surfactant coacervate extraction.. Journal of Pharmaceutical Analysis 2016, 6, 292-299, 10.1016/j.jpha.2016.04.002.
  23. Aschberger, K.; Castello, P.; Hoekstra, E.; Karakitsios, S.; Munn, S.; Pakalin, S.; Sarigiannis, D.; Bisphenol A and baby bottles: Challenges and perspectives. Luxemb. Publ. Off. Eur. Union 2010, 10, 5–50.
  24. Simona Bertoli; Alessandro Leone; Alberto Battezzati; Human Bisphenol A Exposure and the “Diabesity Phenotype”. Dose-Response 2015, 13, 13, 10.1177/1559325815599173.
  25. Roy Gerona; Janet Pan; Ami R. Zota; Jackie M. Schwartz; M. Friesen; Julia Taylor; Patricia A Hunt; Tracey J. Woodruff; Direct measurement of Bisphenol A (BPA), BPA glucuronide and BPA sulfate in a diverse and low-income population of pregnant women reveals high exposure, with potential implications for previous exposure estimates: a cross-sectional study. Environmental Health 2016, 15, 50, 10.1186/s12940-016-0131-2.
  26. Xiuting Li; Yan Gao; Jun Wang; Guixiang Ji; Yan Lu; Dandan Yang; Huan-Xi Shen; Qiu Dong; Liping Pan; Hang Xiao; et al.Baoli Zhu Exposure to environmental endocrine disruptors and human health. Journal of Public Health and Emergency 2017, 1, 8-8, 10.21037/jphe.2016.12.09.
More
Information
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , , , , ,
View Times: 875
Revisions: 3 times (View History)
Update Date: 27 Oct 2020
1000/1000