Endocrine Disruptors

The endocrine system is comprised of a number of glands in the body that do not have ducts and other similar structures. The endocrine system includes the ovaries; the testes; the thyroid, parathyroid, adrenal, and pituitary glands; the pineal body; the pancreas; as well as cells releasing hormones found in the gastrointestinal tract, kidney, heart and placenta. What distinguishes endocrine glands from other glands is that endocrine glands secrete certain chemicals called hormones and other glands produce other chemicals or fluids; for example, lacrimal glands secrete tears, salivary glands produce saliva, and sweat glands produce sweat.

Hormones (so-called "chemical messengers") produced by endocrine glands enter the capillaries (and lymph vessels) of the blood circulatory system. They travel through the bloodstream to specific "receptors" in target organs or systems where they can trigger their biological effects.

The endocrine system is important because it coordinates and regulates many essential body functions such as:

• Growth and maturation.
• Behaviour.
• Reproduction and embryo development.
• Production, use and storage of energy.
• Balance and maintenance of water and salt (electrolytes) in the body.
• Reaction to stimuli (e.g., fright, excitement).

Some examples of hormones secreted by the endocrine system are:

• ACTH (adrenocorticotrophic hormone) - produced by the pituitary gland to influence the release of corticosteroid hormones from the adrenal glands.
• ADH (anti-diuretic hormone, vasopressin) - produced by the pituitary gland to stimulate water reabsorption by the kidney tubules.
• Adrenaline (epinephrine) and noradrenaline (norepinephrine) - two hormones formed in the adrenal gland that help the body to react (e.g., flight or fight, body defense mechanisms) under stressful conditions (they can increase the heart rate, blood pressure, blood sugar levels, blood clotting rate).
• Estrogen - a female sex hormone produced by the ovaries.
• Testosterone - a male sex hormone produced by the testes, ovaries, and adrenal glands.
• Insulin - secreted by the pancreas and regulates the storage and use of carbohydrates in the body.
• Thyroid hormone - produced in the thyroid and influences the function of virtually every cell in the body (growth, development and metabolism).

Concerns have been raised over the possible roles of chemicals since many of the complex activities of the human body are controlled by the endocrine system. In addition, endocrine systems are present in most animals such as other mammals, non-mammalian vertebrates (e.g., birds, fish, amphibians, and reptiles) and invertebrates (e.g., insects, spiders, snails, crabs, lobsters, etc.).

The endocrine system controls many functions of the body, both immediate reactions and life-long functions. The hormones stabilize or balance functions in the normal body. In turn, the levels of hormones produced in the body are influenced by stimuli the body receives and are regulated by complex biological feedback systems. Any disruption to this balance can cause changes in the reproduction, development, growth, or behaviour that can affect that animal or human or their offspring or children.

Certain substances, both naturally-occurring and man-made, can affect the endocrine system. Some chemicals in plants (phytoestrogens) have estrogen-like effects. Certain drugs and environmental pollutants can either mimic or block actions of some hormones. When there is interference with the normal communication between the "messenger" hormone and the cell receptors, the chemical message is misinterpreted and an abnormal response is generated in the body.

Understanding the role of the endocrine system (and the hormones that they produce) in the normal functioning of the body gives us some indication of the types of problems that might occur when proper endocrine function is disrupted. Many of these organs influence each other's activities, producing very complex interactions and making the effect of the disruptors exceedingly difficult to identify or predict.

Substances can disrupt the normal function of endocrine systems in three different ways:

1. They can mimic a natural hormone and lock onto a receptor within the cell. The disruptor may give a signal stronger than the natural hormone, or a signal that occurs at the "wrong" time.
2. They can bind to a receptor within a cell and thus prevent the correct hormone from binding. The normal signal then fails to occur and the body fails to respond properly.
3. The disruptors can interfere or block the way natural hormones and receptors are made or controlled. This interference or blockage may occur only if relatively large doses of the substance are present.

If the endocrine disruptor stimulates or inhibits the endocrine system, then increased or decreased amounts of hormone may be produced. In some cases, even very small amounts of a disruptor may have a detectable effect. In addition, small amounts of different endocrine disruptor chemicals may have a cumulative effect.  In some cases the by-products of the chemicals may have greater harmful effect than the parent chemical.

The number of substances believed to act as endocrine disruptors is wide and varied, including both natural and synthetic materials. Concern arises because potential endocrine disruptors may be present in the environment at very low levels but still may be able to cause effects.

Many plants and animals produce substances that can have endocrine effects. Some of the substances are toxic but certain effects have proven beneficial in some circumstances. For example, some "endocrine disruptors" have been used to control fertility (birth control pills), to treat cancer (corticosteroids), and to treat psychiatric disorders and other medical conditions. Natural substances, such as sex hormones or phytoestrogens (plant chemicals having estrogen-like effects), can become concentrated in industrial, agricultural and municipal wastes. Exposure to these wastes may produce reactions in humans, wildlife, fish or birds.

Endocrine disruptors are found also in synthetic chemicals used as industrial solvents, lubricants, and their byproducts. These include polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), and dixons. Other examples of endocrine disruptors include bisphenol A (BPA) from plastics, dichlorodiphenyltrichloroethane (DDT) from pesticides, vinclozolin from fungizides, and diethylstilbestrol (DES) from pharmaceutical agents. Certain metals such as cadmium, mercury, arsenic, lead, manganese, and zinc also disrupt endocrine systems.

Many consumer products like cosmetics, personal care products and cleaners, (especially the fragranced products), contain complex mixtures of chemicals that have endocrine disruption properties.

Synthetic chemicals suspected as endocrine disruptors may reach humans and animals in a variety of ways. Some, such as pesticides, are released intentionally. Others are by-products of industrial processes and waste disposal - these include dioxins and PCBs - or are discharged from industrial or municipal treatment systems (See Table below)

Sources, category (type) and examples of substances that have been reported as potential endocrine disruptors include:

(Source: Endocrine Disruptors Update, 2000, Environment Canada, and Endocrine Disruptors and Asthma-Associated Chemicals in Consumer Products. R.E. Dodson, M. Nishioka, L.J. Standley, et all. (2012). « Environment Health Perspective ». Vol. 120, No. 7, pages 935-943)

The most prominent and well documented health concerns from exposure to endocrine disruptors are reproductive and developmental effects. Some of the disorders that have been seen in animal studies include oligospermia (low sperm count), testicular cancer, and prostate hyperplasia in adult males; vaginal adenocarcinoma, disorders of ovulation, breast cancer, and uterine fibroids in adult females. Disruption to thyroid functions, obesity, bone metabolism and diabetes are also linked to exposure endocrine disruptors.

Outcomes from occupational exposure of endocrine disruptors have been documented in limited studies. The table below summarizes some of these studies:

1. Endocrine Disruptors in the Workplace, Hair Spray, Folate Supplementation, and Risk of Hypospadias: Case-Control Study. G. Ormond et al. Environmental Health Perspectives. Vol. 117, no. 2 (February 2009)
2. Occupation and occupational exposure to endocrine disrupting chemicals in male breast cancer: a case-control study in Europe. S. Villeneuve et al. Occupational and Environmental Medicine. Vol. 67 (2010), p. 837-844
3. Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction. D. Li et al. Human Reproduction. Vol. 25, no. 2 (February 2010), p. 51-27
4. The effects of metals as endocrine disruptors. I. Iavicoli et al. Journal of Toxicological Environmental Health. Vol. 12, no. 3 (March 2009), p. 206-23
5. Effect of endocrine disruptor pesticides: A Review. W. Mnif et al. International Journal of Environmental Research and Public Health. Vol. 8, no. 6 (June 2011), p. 2265-2303
6. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case-control study. J.T. Brophy et al. Environmental Health. Vol. 11:87 (November 2012)
7. Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring. E Haraux, et all. International Journal of Environment Research and Public Health. Vol. 14, no. 1 (January 2017)
8. Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation: A European Meta-Analysis. L. Birks, et al. Environmental Health Perspectives. Vol. 124, no. 11 (November 2016). p. 1785-1793