Introduction

EDCs are a heterogeneous group of exogenous chemicals or chemical mixtures that interfere with the action of hormones, causing a variety of medical disorders. Over the past 60 years, the number of EDCs has markedly increased. Modern life is associated with the daily use of multiple chemicals. Through air, water, and food, humans are regularly exposed to hundreds of EDCs [1-16].

The in utero or lifetime exposure to EDCs can be a significant component of the environmental origin of several medical conditions. Transgenerational effects are also observed with EDCs. The medical disorders caused by EDCs include diabetes, obesity, NAFLD, infertility, and cancers (non-exhaustive list) [1,3,4,8-15,17-40].

EDCs represent a threat for human health and a financial burden for the society [41]. By promoting public knowledge and initiating preventive measures, it is possible to minimize the deleterious consequences of EDCs for generations to come.

Characteristics of EDCs

In 2002, the International Programme on Chemical Safety belonging to the World Health Organization proposed the following definition for EDCs: “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.”

EDCs are mainly man-made chemicals but can also be found in plants or fungi. The number of man-made chemicals is over 140,000. According to the Endocrine Disruption Exchange, there are approximately 1,000 chemicals considered as EDCs. The sources of EDCs include phytoestrogens (e.g., genistein), industrial (e.g., dioxins and perchlorates), agricultural (e.g., organochlorines, organophosphates, and carbamates), residential (e.g., bisphenol A and phthalates), medical devices (e.g., bisphenol A and phthalates), and pharmaceutical (e.g., diethylstilbestrol and parabens) [1-17,21,23,25-28,30,33,34,36,37,41-43].

The EDCs are present in a variety of products including dust, soil, water, food, cosmetics, soaps, shampoos, toothpastes, plastic containers, toys, nicotine, and fertilizers (non-exhaustive list) (Figure 1). According to the United States (US) Environmental Protection Agency (EPA), each day, children ingest 60-100 mg of dust from indoor environment. Contamination from plastic packaging is a serious concern [6,7]. The worldwide plastic production is around 400 million metric tons per year with almost half coming from Asia (mainly from China) and approximately 40% used for packaging (especially for beverages and food). The United States of America (USA), Japan, the European Union (EU), and China are the world largest producers while the African and the Central and South American countries are the world smallest producers of plastic packaging waste per capita. In most cases, plastic packaging is thrown away within few minutes of its first use. Plastic pollution in water could more than double by 2030. Most plastics do not biodegrade and when discarded, can take up to thousands of years to decompose. In terms of food contamination, monosodium glutamate (flavor enhancer), genistein (soy-based foods), and high-fructose corn syrup (sweetener) are relevant contributors.

EDCs can travel very long distances in the air. They accumulate in the food chain and are ingested. Exposure to EDCs begins before birth, even before conception. Air, water, food, skin, vein, breast milk, and placenta represent different routes of exposure to EDCs [1-18,22,23,27,33,34,37,42,43]. It is common to be exposed simultaneously to several EDCs. This multiple exposure can create difficulties during the interpretation of the results of epidemiological studies [44].

Numerous EDCs can be detected in human body fluids

(e.g., blood and urine) and tissues (e.g., adipose tissue and liver). The majority of EDCs are highly lipophilic and stored in adipose tissue. Non-lipophilic EDCs are bound to albumin. Some EDCs have long half-lives (months or years, e.g., organochlorines) while others have short half-lives (minutes, hours, or days, e.g., bisphenol A) [1,10,11,14,18,20,28,43,44]. The liver metabolizes EDCs and may store lipophilic EDCs. Lipophilic EDCs are more resistant to degradation.

EDCs may interact with or activate hormone receptors (membrane and nuclear receptors), antagonize hormone receptors, alter hormone receptor expression, alter signal transduction in hormone-responsive cells, induce epigenetic modifications in hormone-producing or hormone-responsive cells [e.g., Deoxyribonucleic Acid (DNA) methylation and histone modifications], alter hormone synthesis, alter hormone transport across cell membranes, alter hormone distribution or circulating hormone levels, alter hormone metabolism or clearance, and alter fate of hormone-producing or hormone-responsive cells (Table 1) [1,3,4,8,10-15,17-19,21,24-26,28-30,34,36,43-45]. EDCs are active at very low doses and can have persistent effects [1,4,8,9,11,14,17].

Adverse Effects of EDCs

By altering the homeostatic systems through environmental or developmental exposures, EDCs have deleterious consequences for humans. A single EDC may be innocuous by itself but when combined with other EDCs, it may cause adverse effects (cocktail effects) [33]. No safe dose of EDC exposure can be established. Information on chronic low-dose exposure to EDCs is relatively limited.

The in utero or lifetime exposure to EDCs can be a significant component of the environmental origin of multiple medical conditions. The timing of exposure to EDCs has an important influence on the health consequences of EDCs. Pregnancy is a very sensitive window for EDCs exposure. Pregnant women can be exposed to multiple EDCs (e.g., bisphenol A, phthalates, parabens, and flame retardants) that are able to cross the placenta and affect the embryo/fetus. This exposure is associated with inflammatory cytokine levels in maternal circulation [16]. The oxidative stress caused by EDCs can be the mediator of several adverse health outcomes [46]. The Week 4 to Week 8 of the embryonic period is a sensitive and vulnerable window of organogenesis and any exposure to EDCs during that period can cause major congenital anomalies. The developing embryo/fetus and neonate are more sensitive than adults to the actions of EDCs (Figure 2) [1,4,8,11,14,16,18,2124,26,30,31,35,42,44-47]. The prenatal damage may lead to adverse consequences later in life (developmental origins of adult disease). There is also a possibility to induce heritable changes that are propagated through multiple generations without any new exposure (transgenerational inheritance) [1,11,21,23-26,30,45].

Endocrine glands are particular targets for EDCs and every endocrine axis may be affected [10]. Gender may play a role in the impact of EDCs [10,11,26,32]. The sexually dimorphic effects of EDCs are likely through interactions with sex hormone receptors.

The medical disorders caused by EDCs include diabetes, obesity, NAFLD, infertility, and cancers (non-exhaustive list) (Table 2) [1,3,4,8-15,17-40].

EDCs and Endocrinology/Metabolism

Diabetes

The incidence of diabetes has risen significantly over the last several decades and is expected to rise dramatically in the years to come [18,19,21,48]. The role of several EDCs in this rise has been extensively investigated. Prenatal and early-life exposures to EDCs can play a role in the development of type 1 diabetes [22]. EDCs with androgenic activity (e.g., bisphenol A) may interfere with β-cell function, impair insulin secretion (by accelerating insulitis), and cause type 1 diabetes (Figure 3) [19,22]. Several EDCs that cause obesity may promote the development of type 2 diabetes through weight gain and the resulting insulin resistance. Exposure to bisphenol A can cause insulin resistance and type 2 diabetes [19]. In the USA, the higher burden of diabetes in the vulnerable populations (e.g., Latinos, African Americans, and low-income individuals) may be partly due to a higher exposure of these populations to several EDCs [21,49]. The confirmation of the current findings on exposure to EDCs and risk of developing diabetes requires large prospective studies [1,4,8,11,12,18-22,49].

Obesity

Obesity is a worldwide pandemic responsible for increased morbidity/mortality and high cost for the society [50-52]. The current obesity pandemic cannot be fully explained by alterations in food intake and/or decrease in exercise. The important increase of the EDCs in the environment over the past few decades coincides with the obesity pandemic. Some EDCs called obesogens, impair the regulation of adipose tissue and food intake, reduce basal metabolic rate, and predispose to weight gain and obesity despite normal diet and exercise [1,3,4,9-14,20,23-31]. These EDCs can also cause resistance to weight loss in subjects on antiobesity diet and/or drug. Approximately 50 obesogens have been identified including monosodium glutamate, nicotine, bisphenol A, phthalates, parabens, and tributyltin (non-exhaustive list). Obesogens impact several tissues and organs including adipose tissue, brain, liver, stomach, and pancreas. At the level of adipose tissue, obesogens increase the number of adipocytes by activating the nuclear receptor signaling pathways critical for adipogenesis and increase storage of fat, leading to obesity (Figure 4) [2326,28-30]. Early-life exposure to obesogens can be responsible for overweight and obesity in children [14,31]. Transgenerational inheritance is also possible with some obesogens (e.g., bisphenol A and tributyltin) [23-26,30]. Since white adipose tissue is an important reservoir of lipophilic obesogens, a rapid weight loss, by increasing the plasma levels of lipophilic obesogens, may cause weight cycling (yo-yo effect).

NAFLD

NAFLD is a pandemic with a prevalence of approximately 25% among adult population worldwide. It is commonly associated with overweight and obesity [32,53,54]. The liver is an ideal target for persistent EDCs particularly because it metabolizes EDCs and stores lipophilic persistent EDCs. EDCs can promote NAFLD by interfering directly or indirectly with liver lipogenesis [11,32].

Reproductive System Disorders

EDCs can cause several disorders in the hypothalamicpituitary-gonadal axis including intersex variation (ambiguous genitalia), cryptorchidism (undescended testicles), hypospadias (abnormal opening of urethra), precocious puberty, polycystic ovary syndrome, endometriosis, uterine fibroids, and infertility [1,4,8-10,15,17,33-35,47,55]. In male subjects, the prenatal exposure to EDCs that have estrogenic and/or antiandrogenic activity (e.g., diethylstilbestrol, bisphenol A, and phthalates) may alter the secretion and/or action of the Leydig cell hormones (e.g., testosterone and insulin-like peptide 3) that regulate testicular descent, causing cryptorchidism in newborn [55]. In female subjects, the in utero exposure to diethylstilbestrol (given to millions of women 50-80 years ago to prevent miscarriage) had caused genital malformations, infertility, and vaginal adenocarcinoma while the exposed mothers had an increased risk of breast cancer [8,35]. Exposure to several EDCs during pregnancy is associated with increased risk of low birth weight in neonate [42].

EDCs and Oncology

The occurrence of several cancers can be promoted by exposure to some EDCs (e.g., dioxins, organochlorines, arsenic, cadmium, and diethylstilbestrol). These cancers include skin cancer, thyroid cancer, breast cancer, endometrial cancer, vaginal cancer, testicular cancer, prostate cancer, and lymphoma (nonexhaustive list) (Figure 5) [1,3,4,8-10,15,17,33-35,37-40].

EDCs and Dermatology

EDCs can induce skin diseases through direct contact or indirect systemic absorption. Several EDCs (e.g., dioxins, phthalates, parabens, and arsenic) can act directly on different skin cells (e.g., keratinocytes, sebocytes, melanocytes, stem cells, and fibroblasts) and be responsible for a variety of disorders including dermatitis, chloracne, hyperpigmentation, and aging (coarse wrinkles, irregular pigment spots, and elastosis) [37].

EDCs and Other Medical Specialties

Increased incidence of neuro-psychiatric (e.g., neurodevelopment disorders, anxiety), cardiovascular (e.g., hypertension and coronary heart disease), respiratory (e.g., asthma), renal (e.g., albuminuria), ocular (e.g., dry eye disease), and immunological (e.g., autoimmunity) disorders has been reported in association with exposure to EDCs [1,4,8,9,36,43,5660]. However, more robust epidemiological studies are needed before providing solid conclusions.

Preventive Strategies

EDCs represent a threat for human health and a financial burden for the society [41]. For a better understanding of the health risks related to EDCs it is important to conduct robust and welldesigned epidemiological studies [61]. The promotion of public knowledge and the initiation of preventive measures can minimize the deleterious consequences of EDCs for future generations. Several agencies (e.g., US EPA and European Food Safety Agency) are regulating the EDCs. Countries have differences in regulations, including differences between the USA and the EU. Countries that have significant heavy chemicals industry are less open to promote greener chemicals production [8,62,63].

Although exposure to EDCs cannot be entirely avoided in many situations, every effort should be made to minimize it [4,8]. It is particularly important to identify windows of sensitivity to reduce or avoid the exposure to EDCs (e.g., fetal and neonatal periods).

The following recommendations should be considered as a guidance (non-exhaustive list):

• Wash hands before preparing or consuming food.
• Use filtered water by installing a filter on the faucet to minimize phthalates intake.
• Consume low-fat low-meat fresh food (instead of processed and canned food) and organic produce to reduce the ingestion of EDCs, especially pesticides.
• Avoid beverages and foods stored in plastic containers. Replace plastics used in food preparation (e.g., for storing and for heating in microwave) with glass, ceramic, stainless steel, and bisphenol A-free products to reduce the intake of bisphenol A and phthalates. Keep water bottles cool to reduce bisphenol A leaching. Minimize the use of nonstick cookware. Throw away any scratched nonstick pans.
• Use organic, natural cosmetics. Prioritize makeup and perfume products that are free of phthalates, parabens, and triclosan. For sunscreens, mineral-based products containing zinc oxide or titanium dioxide as active ingredients should be preferred.
• Do not burn conventional candles and avoid air fresheners.

Several of the above recommendations are difficult to implement for practical and/or financial reasons.

Cost of EDCs

The annual cost of EDCs is around hundreds of billions of dollars. According to a relatively recent report, the cost of EDCsrelated medical disorders in the USA was $340 billion (2.33% of the gross domestic product), higher than in the EU where it was $217 billion (1.28% of the gross domestic product) [41]. Regulatory actions allowing the limitation of the most prevalent and hazardous EDCs could have significant economic benefits.

Conclusion

EDCs are a heterogeneous group of exogenous chemicals or chemical mixtures that interfere with the action of hormones. Through air, water, and food, humans are regularly exposed to hundreds of EDCs. The in utero or lifetime exposure to EDCs can be a significant component of the environmental origin of several medical conditions. The medical disorders caused by EDCs include diabetes, obesity, NAFLD, infertility, and cancers (non-exhaustive list). EDCs represent a threat for human health and a financial burden for the society. The promotion of public knowledge and the initiation of preventive measures can minimize the deleterious consequences of EDCs.

Figures

Tables

References

1. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, et al. (2015) EDC-2: The Endocrine Society’s second scientific statement on Endocrine-disrupting chemicals. Endocr Rev 36: E1-E150.
2. Schneider M, Pons JL, Labesse G, Bourguet W (2019) In silico predictions of endocrine disruptors properties. Endocrinology 160: 2709-2716.
3. Yang O, Kim HL, Weon JI, Seo YR (2015) Endocrine-disrupting chemicals: Review of toxicological mechanisms using molecular pathway analysis. J Cancer Prev 20: 12-24.
4. Hall JM, Greco CW (2020) Perturbation of nuclear hormone receptors by endocrine disrupting chemicals: Mechanisms and pathological consequences of exposure. Cells 9: 13.
5. Wong HL, Garthwaite DG, Ramwell CT, Brown CD (2019) Assessment of occupational exposure to pesticide mixtures with endocrinedisrupting activity. Environ Sci Pollut Res 26: 1642-1653.
6. Bang DY, Kyung M, Kim MJ, Jung BY, Cho MC, et al. (2012) Human risk assessment of endocrine-disrupting chemicals derived from plastic food containers. Compr Rev Food Sci Food Saf 11: 453-470.
7. Groh KJ, Backhaus T, Carney-Almroth B, Geueke B, Inostroza PA, et (2019) Overview of known plastic packaging-associated chemicals and their hazards. Sci Total Environ 651: 3253-3268.
8. Encarnacão T, Pais AACC, Campos MG, Burrows HD (2019) Endocrine disrupting chemicals: Impact on human health, wildlife and the environment. Sci Prog 102: 3-42.
9. Preda C, Ungureanu MC, Vulpoi C (2012) Endocrine disruptors in the environment and their impact on human health. Environ Eng Manag J 11: 1697-1706.
10. Lauretta R, Sansone A, Sansone M, Romanelli F, Appetecchia M (2019) Endocrine disrupting chemicals: Effects on endocrine glands. Front Endocrinol 10: 178.
11. Papalou O, Kandaraki EA, Papadakis G, Diamanti-Kandarakis E (2019) Endocrine disrupting chemicals: An occult mediator of metabolic disease. Front Endocrinol 10: 112.
12. Le Magueresse-Battistoni B, Labaronne E, Vidal H, Naville D (2017) Endocrine disrupting chemicals in mixture and obesity, diabetes and related metabolic disorders. World J Biol Chem 8: 108-119.
13. Kassotis CD, Stapleton HM (2019) Endocrine-mediated mechanisms of metabolic disruption and new approaches to examine the public health threat. Front Endocrinol 10: 39.
14. Yang C, Lee HK, Kong APS, Lim LL, Cai Z, et al. (2018) Early-life exposure to endocrine disrupting chemicals associates with childhood Ann Pediatr Endocrinol Metab 23: 182-195.
15. Jeng HA (2014) Exposure to endocrine disrupting chemicals and male reproductive health. Front Public Health 2: 55.
16. Kelley AS, Banker M, Goodrich JM, Dolinoy DC, Burant C, et al. (2019) Early pregnancy exposure to endocrine disrupting chemical mixtures are associated with inflammatory changes in maternal and neonatal Sci Rep 9: 5422.
17. La Merrill MA, Vandenberg LN, Smith MT, Goodson W, Browne P, et al. (2020) Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification. Nat Rev Endocrinol 16: 45-57.
18. Mimoto MS, Nadal A, Sargis RM (2017) Polluted pathways: Mechanisms of metabolic disruption by endocrine disrupting Curr Environ Health Rep 4: 208-222.
19. Sakkiah S, Wang T, Zou W, Wang Y, Pan B, et al. (2018) Endocrine disrupting chemicals mediated through binding androgen receptor are associated with diabetes mellitus. Int J Environ Res Public Health 15:
20. Lind PM, Lind L (2018) Endocrine-disrupting chemicals and risk of diabetes: An evidence-based review. Diabetologia 61: 1495-1502.
21. Sargis RM, Simmons RA (2019) Environmental neglect: Endocrine disruptors as underappreciated but potentially modifiable diabetes risk Diabetologia 62: 1811-1822.
22. Howard SG (2018) Developmental exposure to endocrine disrupting chemicals and type 1 diabetes mellitus. Front Endocrinol 9: 513.
23. Heindel JJ (2019) History of the obesogen field: Looking back to look Front Endocrinol 10: 14.
24. Chamorro-Garcia R, Blumberg B (2019) Current research approaches and challenges in the obesogen field. Front Endocrinol 10: 167.
25. Ribeiro CM, Beserra BTS, Silva NG, Lima CL, Rocha PRS, et al. (2020) Exposure to endocrine-disrupting chemicals and anthropometric measures of obesity: A systematic review and meta-analysis. BMJ Open 10: e033509.
26. Egusquiza RJ, Blumberg B (2020) Environmental obesogens and their impact on susceptibility to obesity: New mechanisms and chemicals. Endocrinology 161: 1-14.
27. van der Meer TP, van Faassen M, van Beek AP, Snieder H, Kema IP, et al. (2020) Exposure to endocrine disrupting chemicals in the Dutch general population is associated with adiposity-related traits. Sci Rep 10: 9311.
28. Griffin MD, Pereira SR, DeBari MK, Abbott RD (2020) Mechanisms of action, chemical characteristics, and model systems of obesogens. BMC Biomed Eng 2: 6.
29. Marraudino M, Bonaldo B, Farinetti A, Panzica GC, Ponti G, et al. (2019) Metabolism disrupting chemicals and alteration of neuroendocrine circuits controlling food intake and energy metabolism. Front Endocrinol 9: 766.
30. Lee MK, Blumberg B (2019) Transgenerational effects of obesogens. Basic Clin Pharmacol Toxicol 125 (Suppl 3): 44-57.
31. Agay-Shay K, Martinez D, Valvi D, Garcia-Esteban R, Basagaña X, et al. (2015) Exposure to endocrine-disrupting chemicals during pregnancy and weight at 7 years of age: A multi-pollutant approach. Environ Health Perspect 123: 1030-1037.
32. Deierlein AL, Rock S, Park S (2017) Persistent endocrine-disrupting chemicals and fatty liver disease. Curr Environ Health Rep 4: 439-449.
33. Bonde JP, Flachs EM, Rimborg S, Glazer CH, Giwercman A, et al. (2017) 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 23: 104-125.
34. Rehman S, Usman Z, Rehman S, AlDraihem M, Rehman N, et (2018) Endocrine disrupting chemicals and impact on male reproductive health. Transl Androl Urol 7: 490-503.
35. Reed CE, Fenton SE (2013) Exposure to diethylstilbestrol during sensitive life stages: A legacy of heritable health effects. Birth Defects Res C Embryo Today 99: 134-146.
36. Nowak K, Jabłońska E, Ratajczak-Wrona W (2019) Immunomodulatory effects of synthetic endocrine disrupting chemicals on the development and functions of human immune cells. Environ Int 125: 350-364.
37. Ju Q, Zouboulis CC (2016) Endocrine-disrupting chemicals and skin Rev Endocr Metab Disord 17: 449-457.
38. Del Pup L, Mantovani A, Cavaliere C, Facchini G, Luce A, et al. (2016) Carcinogenetic mechanisms of endocrine disruptors in female cancers (Review). Oncol Rep 36: 603-612.
39. Corti M, Lorenzetti S, Ubaldi A, Zilli R, Marcoccia D (2022) Endocrine disruptors and prostate cancer. Int J Mol Sci 23: 1216.
40. Costas L, Infante-Rivard C, Zock JP, Van Tongeren M, Boffetta P, et al. (2015) Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study. Br J Cancer 112: 1251-1256.
41. Attina TM, Hauser R, Sathyanarayana S, Hunt PA, Bourguignon JP, et (2016) Exposure to endocrine-disrupting chemicals in the USA: A population-based disease burden and cost analysis. Lancet Diabetes Endocrinol 4: 996-1003.
42. Birks L, Casas M, Garcia AM, Alexander J, Barros H, et al. (2016) Occupational exposure to endocrine-disrupting chemicals and birth weight and length of gestation: A European meta-analysis. Environ Health Perspect 124: 1785-1793.
43. Toft G, Høyer BB (2019) Prenatal exposure to endocrine-disrupting chemicals and child behavior. Curr Opin Endocr Metab Res 7: 43-48.
44. Lee DH, Jacobs Jr DR (2015) Methodological issues in human studies of endocrine disrupting chemicals. Rev Endocr Metab Disord 16: 289
45. Alavian-Ghavanini A, Rüegg J (2018) Understanding epigenetic effects of endocrine disrupting chemicals: From mechanisms to novel test methods. Basic Clin Pharmacol Toxicol 122: 38-45.
46. Neier K, Marchlewicz EH, Dolinoy DC, Padmanabhan V (2015) Assessing human health risk to endocrine disrupting chemicals: A focus on prenatal exposures and oxidative stress. Endocr Disruptors 3: e1069916.
47. Rich AL, Phipps LM, Tiwari S, Rudraraju H, Dokpesi PO (2016) The increasing prevalence in intersex variation from toxicological dysregulation in fetal reproductive tissue differentiation and development by endocrine-disrupting chemicals. Environ Health Insights 10: 163-171.
48. NCD Risk Factor Collaboration (2016) Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4 million participants. Lancet 387: 1513-1530.
49. Ruiz D, Becerra M, Jagai JS, Ard K, Sargis RM (2018) Disparities in environmental exposures to endocrine-disrupting chemicals and diabetes risk in vulnerable populations. Diabetes Care 41: 193-205.
50. GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. (2017) Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 377: 13-27.
51. Gadde KM, Martin CK, Berthoud HR, Heymsfield SB (2018) Obesity. Pathophysiology and management. J Am Coll Cardiol 71: 69-84.
52. Shephard RJ (2019) On determining how much obesity is costing HFJC 12: 80-116.
53. Mundi MS, Velapati S, Patel J, Kellogg TA, Abu Dayyeh BK, et al. (2020) Evolution of NAFLD and its management. Nutr Clin Pract 35: 72-84.
54. Heshmati HM (2021) Treatment of nonalcoholic fatty liver disease through changes in gut microbiome and intestinal epithelial barrier. In: Advances in Hepatology. Rodrigo L., Martins I.J., Guo X., and Qi X. (eds), IntechOpen, London, p. 139-159.
55. Fénichel P, Chevalier N, Lahlou N, Coquillard P, Wagner-Mahler K, et al. (2019) Endocrine disrupting chemicals interfere with Leydig cell hormone pathways during testicular descent in idiopathic Front Endocrinol 9: 786.
56. Schug TT, Blawas AM, Gray K, Heindel JJ, Lawler CP (2015) Elucidating the links between endocrine disruptors and neurodevelopment. Endocrinology 156: 1941-1951.
57. Migliaccio S, Bimonte VM, Besharat ZM, Sabato C, Lenzi A, et al. (2022) Environmental contaminants acting as endocrine disruptors modulate atherogenic processes: New risk factors for cardiovascular diseases in women? Biomolecules 12: 44.
58. Nunes-Silva A, Dittz D, Santana HS, Faria RA, Freitas KM, et al. (2018) The pollutant organotins leads to respiratory disease by inflammation: A mini-review. Front Endocrinol 8: 369.
59. Tadevosyan NS, Kirakosyan GV, Muradyan SA, Poghosyan SB, Khachatryan BG (2021) Relationship between respiratory morbidity and environmental exposure to organochlorine pesticides in Armenia. J Health Pollut 11: 1-10.
60. Pontelli RCN, Souza MCO, Fantucci MZ, de Andrade M, Rocha EM (2019) The role of endocrine disruptors in ocular surface diseases. Med Hypotheses 122: 157-164.
61. Ho V, Pelland-St-Pierre L, Gravel S, Bouchard MF, Verner MA, et (2022) Endocrine disruptors: Challenges and future directions in epidemiologic research. Environ Res 204: 111969.
62. Slama R, Bourguignon JP, Demeneix B, Ivell R, Panzica G, et al. (2016) Scientific issues relevant to setting regulatory criteria to identify endocrine-disrupting substances in the European Union. Environ Health Perspect 124: 1497-1503.
63. Michel C (2019) How to regulate endocrine disrupting chemicals? Feedback and future development. Curr Opin Endocr Metab Res 7: 21-25.