Written by Dr. Sanjana V.B Bhms,dbrm,cdn

Founder & medical director of siahmsr wellness.in

All rights reserved with siahmsr digital healthcare[siahmsr wellness]

Reviewed by SIAHMSR medical team.

Overview

  Endocrine-disrupting chemicals (EDCs) are substances reaching your body from various sources such as environment, food products, personal care products etc. and interfere with the normal function of the endocrine system and hormones. These substances can be natural as well as man-made.

Many chemicals have endocrine-disrupting properties, including bisphenol A, organochlorines, polybrominated flame retardants, alkylphenols, and phthalates. Most often contact with these chemicals may occur through diet, air, skin, and water. Endocrine-disrupting chemicals (EDCs) have significant impacts on biological systems.

  Of late, EDCs are discussed unprecedently due to their link with various health issues such as infertility, nervous system & respiratory system diseases, cardiovascular diseases etc. Studies point out that EDCs are closely connected with obesity, diabetes, learning disabilities, endometriosis and various types of cancers.

EDCs are found in almost all products of our day to day lives, including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones.

Different types of EDCs

  There are various types of endocrine disruptors and their mechanism of action also vary in your body. Some EDCs can function as "hormone mimics" and the body misinterpret them as hormones and as a result problems in the functions of your body happen.

A few other EDCs block natural hormonal functions in the body. Hormones have specific functions to do in human body and any imbalance or dysfunction can upset the body in multiple ways. Another group of EDCs can affect the level of hormones in your blood as they can affect the production, breaking down, or storage of hormones. Furthermore, other EDCs can change the sensitivity of the body to different hormones.

 It is impossible to avoid or prevent EDCs in your life and environment, however their impact can be considerably reduced by deliberate avoidance of those substances which can act as an endocrine disruptor.

Common types of endocrine disrupting chemicals [ EDCs]

  EDCs can affect your body and health adversely as their sources are multiple and myriad. According to the Endocrine Society, there are nearly 85,000 human-made chemicals in the world, and 1,000 or more of these substances can work as endocrine disruptors, based on their unique properties. Some of the common endocrine disrupting chemical are listed below:

•   Industrial chemicals and pesticides

 Some common examples for pesticides are DDT, Chlorpyrifos, Atrazine, 2, 4-D, Glyphosate. These can contaminate water and food sources and reaching the food chain, these chemicals cause detrimental impact to human health.

Perchlorate is a colorless salt manufactured and used as an industrial chemical to make rockets, explosives, and fireworks, which can be found in some groundwater and can cause health hazards.

•  Household chemicals

  Lead, Phthalates, Cadmium are a few toxic chemicals reaching from household items of children. Bisphenol A (BPA), Phthalates, Phenol are found in plastics and food storage materials. Bisphenol A (BPA) is used to make polycarbonate plastics and epoxy resins. It is used in manufacturing, food packaging, toys, and other applications. BPA resins may be found in the lining of some canned foods and beverages.

Phthalates are a large group of compounds used as liquid plasticizers. They are found in some food packaging, cosmetics, fragrances, children’s toys, and medical device tubing. Cosmetics containing phthalates include nail polish, hair spray, aftershave lotion, cleanser, and shampoo.

•  Fabrics treated with flame retardants

•  Cosmetics

  Cosmetics such as lotions, products with fragrance, and anti-bacterial soaps etc. contain these EDCs mostly. Triclosan is an ingredient that was previously added to some antimicrobial and personal care products, like liquid body wash and soaps which can be an endocrine disruptor chemical.

•  Processed foods

•  Soy-based products

    The phyto estrogens in soy products can mimic estrogen  hormone in women of reproductive age group and act as an endocrine disruptor.

•  Industrial solvents and lubricants contain Polychlorinated biphenyls (PCBs) and Dioxins. Also Brominated Flame Retardants, PCBs found in building materials are endocrine disruptors.

(PCBs) were used to make electrical equipment, such as transformers, and are in hydraulic fluids, heat transfer fluids, lubricants, and plasticizers. PCBs were mass-produced globally until they were banned in 1979.

Impact of Endocrine disrupting chemicals on human health

Most of the studies regarding the adverse effects of EDCs on human health requires cutting edge research to confirm them. However, it has been found that EDCs impact health in numerous ways. They can cause:

•          Neurological and behavioral changes

•          Difficulty with stress response.

•          Impact on metabolism

•          Obesity and type 2 diabetes

•          Interfere with thyroid function

•          Infertility

Some classes of EDCs (DDT, BPA, phthalates, PCBs, others) can affect reproductive health by mimicking or blocking the effects of male and female sex hormones

•          Affect growth and development

•          High exposures to EDCs during gestation can lead to low-birth weight in infants and developmental problems.

•          Disrupted sexual development

•          Low immunity

•          Cancer

Exposure to estrogen or androgen mimicking EDCs can promote breast and prostate cancer growth and/or interfere with hormonal cancer therapy

Impact of EDCs on fetuses and children

High exposure to endocrine disrupting chemicals during gestation or pregnancy can have adverse impact on foetus causing developmental delays and numerous other problems in children as they grow over the years.

EDCs and their properties, actions in human body

An EDC may have both estrogenic and anti-androgenic or have estrogenic and progesterone properties.

EDCs can also act through genomic and non-genomic mechanisms. Genomic responses are delayed and require several hours to become established.

EDCs act by modulating the endogenous steroid hormone metabolism, nuclear receptor coactivators (NCOAs), and proteasome-targeted degradation of endogenous hormones.

The mechanisms of EDCs involve divergent pathways including estrogenic, androgenic, thyroid, peroxisome proliferator-activated receptor γ (PPARγ), retinoid, and other nuclear receptors. Endocrine-disrupting chemicals are thought to act primarily through NRs including ERs, ARs, PRs, TRs, and others.

   An organochlorine pesticide (methoxychlor) has been reported to cause estrogenic action by binding to estrogen receptor α (ERα) and estrogen receptor β (ERβ) subtypes .

In addition to receptor interference, EDCs can also interfere with enzyme action involved in steroidogenesis. Phthalates and such plasticizers exert anti-androgenic activity by disrupting steroidogenesis in the H295R assay.

 It has been reported that some EDCs inhibit 5-α reductase that converts testosterone to dihydrotestosterone . Thus, EDCs can affect hormone receptor expression. It has been reported that BPA alters the epigenome and causes the malregulation of steroid receptors .

Mutations or subtle modifications of gene expression induce the transgenerational effects of EDCs. It is still unclear how EDC exposure during early development leads to phenotypic changes that manifest as diseases much later in life or even in the next generation .

Some EDCs such as BPA and alkylphenols exert endoplasmic reticulum (ER) stress. The exact mechanism of how EDCs cause endoplasmic reticulum stress still needs to be studied.

Research by NIEHS on endocrine disrupting chemicals

 NIEHS has been conducting research on the health effects of endocrine disruptors for over three decades. Although EDCs cause a significant public health concern, the exact mechanism between EDCs and diseases remain unclear. These studies have helped in better understanding of health impacts of EDCs.

This project was started with the endocrine-disrupting effects of the drug diethylstilbestrol (DES). From 1940s through 1970s, DES was used to treat women with high-risk pregnancies, with the mistaken belief that it prevented miscarriage. In 1972, prenatal exposure to DES was linked to the development of a rare form of vaginal cancer in daughters whose mothers took DES, and with numerous noncancerous changes in both sons and daughters.

 NIEHS experiments on the drug DES successfully replicated and predicted health problems associated with the drug.

NIEHS was involved in developing a consensus statement in 2019 on the key characteristics of endocrine-disrupting chemicals, which provides a framework to help scientists evaluate potential endocrine disruptors[2].

Role of EDCs in endometriosis

Endometriosis is an estrogen hormone dependent disease associated with multiple causes. However, some evidences are there to suggest an association between phthalate esters, bisphenol A, organochlorinated environmental pollutants and the prevalence of endometriosis in women [3].

Role of EDCs in increasing the risk for breast cancer & other diseases

 EDC exposures may potentially increase the risk of breast cancer. As majority of EDCs are highly persistent in the environment and  are bio-accumulative, it is essential to assess the long-term impacts of EDC exposures.

 It is recommended that well-designed exposure assessments of potential EDCs in food and food packing are necessary and their potential link to breast cancer development need to be carefully evaluated. This may contribute  for subsequent EDC policy making and regulations [4].

EDCs that have estrogenic properties, such as alkylphenol, BPA, and phthalates, could induce precocious puberty [9].

A significant reduction in serum estradiol and thyroxine concentration, a significant delay in the date of vaginal opening, disruption in the length of the estrous cycle, and a decrease of corpora lutea were observed resulting from long-term exposure to parabens.

Clinical and experimental data also indicate that exposure to EDCs affects fertility by interfering with including folliculogenesis, steroidogenesis, ovulation, fertilization, and gestation, which means EDCs disrupt ovarian function and fertility.

Numerous studies have suggested that exposure to EDCs may increase the incidence of uterine fibroids by promoting estrogen-dependent hyperplasia of the myometrium, endometriosis, premature ovarian failure, and polycystic ovary syndrome (PCOS).

In addition, exposure to EDCs during early gestation disrupts intrauterine implantation and uterine reception, leading to implantation failure.

Other clinical studies have shown that BPA exposure is linked to the risk of insulin resistance and type 2 diabetes mellitus (T2D) in women of reproductive age, including pregnant women

EDCs can also promote nonalcoholic fatty liver disease (NAFLD) by increasing free fatty acid (FFA) uptake, increasing lipogenesis, decreasing triglyceride exportation via very low-density lipoprotein(VLDL), and/or decreasing FFA β-oxidation.

EDCs affect thyroid function in multiple ways, including hormone biosynthesis, transport, metabolism, and TR activity . Thus, clinical and animal studies have suggested that EDC exposure could impair thyroid signaling during development and be associated with neurological deficits .

Clinical studies have proven that exposure to polybrominated diphenyl ethers (PBDEs) is associated with hypothyroidism . Another brominated flame retardant, 2,4,6-tribromophenol (TBP), can disrupt thyroid hormone homeostasis and the presence of TBP influenced thyroid actions as regulators of gene expression.

The risk of these agents interfering with neural development by disrupting the thyroid hormone signaling axis needs to be considered.

Phthalates -an important endocrine disrupting chemical & its impact

  Phthalates are chemicals that are used in a variety of consumer products including cosmetic and personal care products such as hair care products (hair sprays, mousses, and gels), deodorants (including antiperspirants), nail polishes, lotions (body lotions and body creams), skin cleansers, and baby products (oils, lotions, shampoos and diaper creams).

   According to studies diethyl phthalate (DEP), dimethyl phthalate (DMP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) were detected mostly in these products. Diethyl phthalate was the most frequently detected phthalate. Dermal exposure to phthalates in infant, toddler and female adult was estimated [5].

  A number of human biomonitoring studies on the monoesters of phthalates has highlighted the large extent of humans exposure to various phthalates [6].

  The United States and the European Union are currently regulating several phthalates including DEHP and DnBP in children's products, and similar action is underway in Canada (EC, 2009b).

The European Union has banned DnBP and DEHP for use in cosmetic and personal care products in the European market (SCCP, 2007), both are classified in the European Union as category 2 substances to reproduction; that means substances which can impair fertility, or if they cause developmental toxicity in humans.

References

1.        Endocrine Society."Endocrine-Disrupting Chemicals (EDCs) | Endocrine Society." Endocrine.org, Endocrine Society, 2 February 2024, https://www.endocrine.org/patient-engagement/endocrine-library/edcs

2.        https://pubmed.ncbi.nlm.nih.gov/31719706/

3.        https://pubmed.ncbi.nlm.nih.gov/32903210/

4.        https://pubmed.ncbi.nlm.nih.gov/33819127/

5. https://www.sciencedirect.com/science/article/abs/pii/S0013935111000284

6.        (Blount et al., 2000, CDC [Centers for Disease Control and Prevention], 2005, Calafat and McKee, 2006, Koch et al., 2005, Wittassek and Angerer, 2008).

7. https://pubmed.ncbi.nlm.nih.gov/21899826

8. https://www.mdpi.com/1422-0067/24/6/5342

9. https://pubmed.ncbi.nlm.nih.gov/36612336/