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Endocrine-disrupting chemicals (EDCs): a global problem for environmental and human health

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There is increasing evidence from epidemiologic studies, case studies, and complementary animal and cell-based models that endocrine-disrupting chemicals (EDCs) can have effects on human health. According to the World Health Organization (WHO)/International Programme on Chemical Safety (IPCS), EDCs are “exogenous substances or mixtures that alter function(s) of the endocrine system and consequently cause adverse health effects in an intact organism, or its progeny, or (sub) populations”[1].

While EDCs exist naturally in soy, legumes, and other plant-based products, their major source results from industrial processes. EDCs are found in air, water, and soil, as well as in numerous household products and medical devices, and have thus become ubiquitous in our environment. As with other environmental contaminants, EDCs can cross the placenta and have now been implicated in the developmental origin of diseases such as obesity and diabetes. Epidemiologic data suggest that the rise in diabetes, cancer, and infertility in the past two to three decades could be attributable, at least in part, to in utero exposure to EDCs.

In a report published in The Lancet Diabetes & Endocrinology, Dr Trasande and his team show that the annual healthcare cost and lost earnings in the U.S. that can be attributed to low-level daily exposure to endocrine-disrupting chemicals exceeds $340 billion. This is equivalent to more than 2.3 per cent of the U.S. gross domestic product.


EDCs: a heterogeneous group of agents

It is estimated that there are about 1’000 chemicals with endocrine-acting properties. EDCs comprise pesticides, fungicides, industrial chemicals, plasticisers, 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.

Endocrine-disrupting chemicals (EDCs) encompass a heterogeneous group of agents that can be classified as plant-derived, industrial chemicals, manufactured households and consumables, medical supplies, and pharmaceuticals. Some EDCs are included in more than one category:

  • Plant-derived (phytoestrogens) – Enriched in flaxseed, nuts, soy products, cereals, breads, and legumes (genistein, daidzein);
  • Industrial chemicals – Pesticides, flame retardants (per- and polyfluoroalkyl substances [PFAS chemicals]), combustion products (polycyclic aromatic hydrocarbons [PAHs], dioxins), lubricants (polychlorinated biphenyls [PCBs]);
  • Household, personal care, and consumable items – Cosmetics, sunscreens, toys, food and beverage packaging materials, contaminated food, contaminated groundwater, tobacco products, tea tree and lavender oils, benzophenone-3 and oxybenzone, bisphenol A (BPA), phthalates, perchlorate, dioxins;
  • Medical supplies – Intravenous tubing, gloves, bags (BPA, phthalates);
  • Pharmaceuticals – Natural and synthetic steroids (diethylstilbestrol [DES], estradiol)


EDC-related
disorders

Sufficient clinical and experimental data exist to indicate that both prenatal and prepubertal effects of EDCs are manifested in male and female children in the form of premature thelarche and precocious puberty (females) and gynaecomastia with exposure to topical agents in preadolescent males. Prenatal exposure to EDCs, particularly diethylstilboestrol (DES) and bisphenol A (BPA), is associated with human female reproductive malformations, as well as cysts, adenomas, and carcinomas in reproductive tissues. Data from vertebrate experimental animals and humans provide compelling evidence that early exposure to multiple classes of EDCs may result in human reproductive deformities. This is substantiated by the reproductive malformations seen in DES sons. Clinical data indicate that postnatal exposure to dichlorodiphenyltrichloroethane (DDT)-containing pesticides and the plasticiser BPA is associated with significant decreases in sperm quality. This is a significant public health issue given that numerous regions of the world still use pesticides containing DDT, and BPA is abundant worldwide in thousands of daily household and medical products.

The available clinical and experimental evidence indicates that in utero exposure to EDCs increases the risk for breast and possibly testicular cancer later in life. Occupational exposure to EDCs is also associated with an elevated incidence of prostate cancer.

Human exposure to multiple EDCs (BPA and phthalates) is associated with a greater incidence of obesity and insulin resistance. BPA is also strongly linked to the development of cardiovascular disease, including hypertension in children and adults, coronary artery disease, and possible chronic kidney disease later in life. EDC exposure in utero is a risk factor for autism spectrum disorders (ASD) and lower intelligence quotient (IQ) in children. There is sufficient correlative evidence in humans to advise that EDC exposure be minimised during pregnancy, breastfeeding, and early in childhood because of the risk of these agents interfering with brain development either directly or by disrupting the thyroid hormone signalling axis.


An urgent need to improve the knowledge and education related to EDCs

A strategy for the prevention of exposures to EDCs is urgently needed. This will require different strategies at the level of individual capacity and beyond, by developing and implementing recommendations towards the protection of individuals and prevention strategies by policymakers and local governors. Education programs in schools and hospitals (especially in toxicology, endocrinology, paediatric and maternity clinics) will be helpful to improve the general understanding of EDCs and the consequences of exposure to such pollutants, especially in early life. The majority of health professionals (general doctors, specialist doctors, dentists, physiotherapists, chiropodists, psychologists, nurses, etc.) receive no initial training at all on endocrine disruptors but could have to answer questions on the subject from patients. Chemical risks in general, and those associated with the substitution of dangerous substances in particular, are too rarely an innovation factor or a factor integrated into innovations. They should be taken into account from the design stage by industrial sectors.

To meet this challenge, scientists and health professionals must benefit from solid training. The Master of Advanced Studies in Toxicology provides a whole module on molecular endocrinology. This exhaustive course covers a variety of topics related to EDCs such as hormonology and endocrine receptors, fertility and reproductions, endocrine disruptors and chronobiology, hormone-dependent cancer and metabolic disease given by recognised experts in the field. The Master of Advanced Studies in Toxicology is a comprehensive educational program recognised by national and international professional bodies as a postgraduate academic qualification in toxicology. The programme fulfils the demand for qualified toxicologists in industry, academia and regulatory bodies with the appropriate knowledge, experience, and professional qualification.

In addition to EDCs, other topics of major concern such as the impact of pollutants on the environment, food safety and occupational health, are also covered in the Master of Advanced Studies in Toxicology.

References

  • Attina TM, Hauser R, Sathyanarayana S, Hunt PA et al. Exposure to endocrine-disrupting chemicals in the USA: a population-based disease burden and cost analysis. Lancet Diabetes Endocrinol. 2016 Dec;4(12):996-1003. doi: 10.1016/S2213-8587(16)30275-3. Epub 2016 Oct 17. PMID: 27765541.
  • Gore et al. EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals 2015, Endocrine Rev 36, E1-E150. doi: 10.1210/er.2015-1010.
  • Yilmaz B, Terekeci H, Sandal S, Kelestimur F. Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention. Rev Endocr Metab Disord. 2020 Mar;21(1):127-147. doi: 10.1007/s11154-019-09521-z. PMID: 31792807.
  • Svingen T. Endocrine Disruptors in a New Era of Predictive Toxicology and Dealing With the "More is Different" Challenge. Front Toxicol. 2022 Apr 27;4:900479. doi: 10.3389/ftox.2022.900479. PMID: 35573277; PMCID: PMC9091552.
  • Second National strategy on endocrine disruptors 2019-2022 action plan. Accessed May 2022.
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