The human body is the most complex and highly organized multicellular structure that evolution has forged over the time period of six million years. The human endocrine system is one of the many physiological and anatomical changes that our body has gone through to accomplish the specific functions necessary for sustaining life. This system is a network of nine glands, including the pineal, hypothalamus, pituitary, thyroid, parathyroid, thymus, pancreas, adrenal gland, testes (male), and ovaries (female). The endocrine system controls body processes through the production, secretion, and regulation of hormones, which serve as a chemical messenger functioning in cellular and organ activity and, ultimately, maintaining the body’s homeostasis.
The Human Endocrine System.
Several chemicals that are also considered ingenious human discoveries are not completely safe for our own health. Endocrine disruptors, also known as endocrine-disrupting chemicals (EDCs), are a class of exogenous (grown outside an organism) substances that alter several functions of the endocrine system and have the potential to cause adverse health effects in an intact organism, its progeny, or sub-populations. There are numerous ways by which the EDCs can affect our endocrine system, including the increase in production of certain hormones, decrease in the production of hormones, mimicking hormones, changing one hormone to another, interfering with cell signaling, causing premature death of cells, competing with essential nutrients, binding to essential hormones, etc. In general, endocrine disruptors have the potential to derail any essential body function that involves hormones. Significant advances in research into endocrine-disrupting chemicals (EDCs) and their health effects have elevated concerns in recent years about these chemicals among several international scientific and health organizations. Through the efforts of several large-scale monitoring programs, the most prevalent EDCs in the human population are fairly well known. Here are some examples of endocrine disruptors that humans may come across in their daily life.
1. Bisphenol A (BPA)
Bisphenol A is a plastic chemical with the formula ({CH}_{3})_{2}{C}({C}_{6}{H}_{4}{O}_{6})_{2}. First synthesized in 1891, bisphenol A came into use as a synthetic estrogen in the 1930s. Later, chemists discovered that combined with phosgene (World War I toxic gas) and other compounds, BPA yielded a clear polycarbonate plastic suitable for the production of several daily life objects such as shatter-resistant headlights, eyeglass lenses, DVDs, and baby bottles. In 2003, Patricia Hunt, a reproductive biologist at Washington State University in Pullman, and her colleagues found that BPA was leaching out of the plastic cages that were housing female mice. Further studies on female mice revealed that it was hosting several health abnormalities. In recent years dozens of scientists around the globe have linked BPA to myriad health effects. BPA is a known endocrine disruptor, and numerous studies have found that laboratory animals exposed to low levels of it have elevated rates of diabetes, mammary and prostate cancers, decreased sperm count, reproductive problems, early puberty, obesity, and neurological problems. Although experts debate whether mice make good models for human effects, the core of the argument over BPA is theoretical and lacks experimental results. A 2004 report from the Harvard Center for Risk Analysis found “no consistent affirmative evidence for low-dose BPA effects.”
2. Atrazine
Atrazine is one of the most extensively used herbicides in modern agriculture. It is mainly used to stop the pre- and post-emergence of broadleaf and grassy weeds in crops such as sorghum, maize, sugarcane, lupins, pine, and eucalypt plantations, and triazine-tolerant canola. Atrazine has been a suspected teratogen (an agent or factor which causes malformation of an embryo), with some studies also relating it to the cause of demasculinization in male northern leopard frogs even at the exposure of very low concentrations. A September 2003 review by the Agency for Toxic Substances and Disease Registry (ATSDR) stated that one of the primary ways that atrazine can affect a person’s health is by altering the way that the reproductive system works. Studies of couples living on farms that use atrazine for weed control were found to have an increase in the risk of preterm delivery; however, these studies were difficult to interpret because most of the farmers were men who may have been exposed to several types of pesticides. Atrazine has also been linked to breast tumors, delayed puberty, and prostate inflammation in animals, and some research has also linked it to prostate cancer in people.
3. Dioxins
Dioxins are one of the many persistent environmental pollutants that are produced as a by-product 0f several industrial processes and natural processes such as volcanic eruptions and forest fires. Although the formation of dioxins is local, they are found throughout the world in the environment. The highest levels of these compounds are found in soils, sediments, and food, especially in dairy products, meat, and fish. Very low levels are found in plants, water, and air. When dioxins enter the food chain, they are stored in animal fats, which accounts for the 90% exposure of dioxins to human beings. Dioxins can stay in the human body for a long time as they are stable chemicals that do not break down easily. Concerns about dioxin’s presence in the human food chain have been raised because of its cancer-promoting, immunomodulating, and teratogenic effects in rodents. The lipophilic nature of dioxins results in their increased concentrations in the fat of animal and fish products, and their excretion via milk secretion in dairy cattle could lead to relatively high dioxin contamination in high-fat dairy products. Chloracne, an acne-like medical condition, was described as the first disease associated with exposure to dioxins in 1897. In 1930, it was again observed as an occupational hazard among the pesticide workers and among workers who manufactured industrial chemicals called PCBs (Perchlorinated Biphenyls). Chloracne produces skin eruptions, cysts, and pustules like a very bad case of teenage acne; except that the sores can occur all over the body, and in serious cases it can last for many years. Despite numerous epidemiological studies, dioxin has not been conclusively determined to be problematic for humans. Certain management practices, such as trimming the fat from meat, consuming low-fat dairy products, and simply cooking food properly, can substantially decrease exposure to dioxin compounds. The International Agency for Research on Cancer (IARC), part of the World Health Organization, published their research into dioxins and furans and announced on February 14, 1997, that the most potent dioxins, 2,3,7,8-TCDD (Tetrachlorodibenzodioxin), is now considered a Group 1 carcinogen.
4. Perchlorates
The term perchlorate refers to a negatively charged group of atoms consisting of a center chlorine atom attached to four oxygen atoms, {ClO}^{-}_{4}. Perchlorates usually form inorganic ionic compounds with a positively charged group such as ammonium or an alkali or alkaline earth metal. They form naturally in the upper atmosphere and then precipitates along with the rain. Although they can exist as both solid and liquid, most of the perchlorates are readily soluble in water, and therefore, they can easily move from soil to groundwaters by a process called leaching. Perchlorates are usually stable but show explosive characteristics when exposed to heat. In particular, this makes ammonium perchlorate vividly functional in rocket motors, fireworks, flares, gunpowder, and explosives. Other uses of perchlorates include temporary adhesives, electrolysis baths, batteries, airbags, drying agents, etching agents, cleaning agents and bleach, and oxygen generating systems. Perchlorates are known to remain unreacted in the environment for long periods of time; however, there are evidence that microorganisms found in soil and water may eventually reduce perchlorate to other substances. The primary human exposure to perchlorates occurs through food and drinking water. For instance, perchlorate is left behind when water containing perchlorate is used to irrigate plants evaporates. Also, cows may eat fodder containing perchlorate and pass them on in their milk. Some of the low-level exposure can also occur from several daily use products including bleach, bottled water, and tobacco products; even some nutritional supplements (vitamins and minerals) have been found to contain perchlorates. Once entered into the bloodstream, perchlorates can reach almost any body part and affect them. A few internal organs, for example, the thyroid, breast tissue, and salivary glands can take up relatively large amounts of perchlorate from the bloodstream. The main target organ for perchlorate toxicity in humans is the thyroid gland. Perchlorate has been shown to partially inhibit the thyroid’s uptake of iodine and affect the secretion of thyroid hormone that regulates certain body functions.
5. Phthalates
Phthalates, also known as plasticizers, are the chemical compounds used to make plastic more flexible and harder to break. In chemical terms, they are esters of phthalic acid ({C}_{6}{H}_{4}({CO}_{2}{H})_{2}). In the industrial sector, phthalates are widely used as they are very good solvents for other materials. They are used in hundreds of products, such as vinyl flooring, adhesives, detergents, lubricating oils, automotive plastics, plastic clothes (raincoats), and personal-care products (soaps, shampoos, hair sprays, and nail polishes), with the majority of applications in polyvinyl plastic products manufacturing. This makes the probability of human exposure to phthalates very likely. Several studies on phthalate toxicity have shown potentially adverse health effects, including disruptions in sex hormone production, interference with sexual development in infants, and changes in sexual behavior in adults. Depending on the levels of exposure, phthalates have been linked to reduced anogenital distance, the behavior of infant boys, decreased sexual desire and satisfaction in women, and malformed genital development in rodents. While phthalates is a huge class of chemicals and not every chemical in the class has been studied, those which have been shown to have negative health impacts are butyl benzyl phthalate (BBzP), dibutyl phthalate (DnBP), di-2-Ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), di-butyl phthalate (DBP), benzyl butyl phthalate (BBP), diisobutyl phthalate (DiBP), diisononyl phthalate (DiNP), di-n-octyl phthalate (DnOP), dipentyl phthalate (DPP), di-isobutyl phthalate (DiBP), di-isononyl phthalate (DiNP), di-n-octyl phthalate (DnOP), di-isohexyl phthalate, dicyclohexyl phthalate (DcHP), and di-isoheptyl phthalate. Early research also shows phthalate exposure may be associated with diabetes and insulin resistance, breast cancer, obesity, metabolic disorders, and immune functions.
6. Per- and Polyfluoroalkyl Substances (PFAS)
Per- and polyfluoroalkyl substances are a group of synthetic organofluorine chemical compounds that contain multiple fluorine atoms attached to an alkyl hydrocarbon chain. Since they take a significant amount of time to decompose in the environment and even inside the human body, PFAS are also famous by the name “forever chemicals.” They are used in the manufacturing of several products such as non-stick cookware, water-repellent clothing, stain-resistant fabrics and carpets, several cosmetics, firefighting foams, and products that resist grease. The most common PFAS that are studied extensively as endocrine disruptors are perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). Although the level of PFAS present in the environment can not be determined with absolute certainty, they can be found anywhere in the air, soil, and water, including sources of drinking water. People are most likely exposed to PFOA by drinking from contaminated water sources, and possibly by using products that contain PFOAs. Workers in the perfluorochemical industry can be exposed to greater amounts of PFOA than people in the general population. PFAS contamination has the potential to affect the growth, learning, and behavior of infants and older children. It can lower the chance of women getting pregnant and can increase the risk of cancer. Over time, scientists have lowered the standard levels of PFAS in daily use products; however, these limits are not legally enforceable. Scientists are also working on enhanced plasma technologies to break the C-F bonds present in PFOAs and PFOS so that the risk of drinking water contamination can be eliminated.
7. Phytoestrogens
Phytoestrogens are plant-derived nonsteroidal compounds that are found in many food items, particularly in soy. They are also known as “dietary estrogens” due to their structural similarity to the primary female sex hormone, 17‐β‐oestradiol (E2). This structural similarity to E2 enables phytoestrogens to cause antiestrogenic effects by binding to the estrogen receptors. These effects were first noticed a century ago in Western Australia when sheep grazing on isoflavone‐rich red clover fields showed fertility problems. In the last two decades, isoflavones (phytoestrogens) derived from soy have received significant attention because of the so-called “Japanese Phenomenon” connected to the lower incidence of specific chronic diseases in the Japanese compared with the Western population due to a higher intake of soy foods from early life onwards. This discovery is supported by the fact that after changing their eating habits, the prevalence of breast cancer in daughters of migrated Japanese Americans became comparable to that of Caucasian Americans. In contrast to these adverse health effects, various beneficial health effects have also been ascribed to phytoestrogens, such as a lowered risk of menopausal symptoms like hot flushes and osteoporosis. As a result, the debate over whether phytoestrogens are useful or hazardous to human health remains unsettled and the answer is likely to be influenced by factors such as age, health, and the presence or absence of specific gut bacteria.
8. Obesogens
Over the last two decades, the incidence of obesity and associated metabolic syndrome diseases has risen dramatically, becoming a global concern. The root cause associated with these problems is believed to be increased caloric intake and decreased physical activity. The recent studies, however, give an alternating viewpoint that highlights the possible involvement of foreign chemical compounds called obesogens, which disrupt the normal development and balance of lipid metabolism. Obesogens may be functionally defined as chemicals that negatively alter lipid homeostasis and fat storage mechanism, change metabolic setpoints, disrupt energy balance, or modify the regulation of appetite and satiety to promote fat accumulation and obesity. Obesity is closely linked to several diseases including insulin resistance, dyslipidemia, and hypertension, all of which are prominent risk factors for the development of type 2 diabetes and cardiovascular disease. Although until now data have been inadequate, there are some implied mechanisms of action by which obesogens affect our body.
- They can alter the action of metabolic sensors by mimicking the metabolic ligands to either block or upregulate hormone receptors.
- They can alter the ratio of sex hormones leading to changes in their control of lipid balance and dysregulating sex steroid synthesis. This, in turn, can produce proadipogenic effects; although, the nature of the effects may depend critically on the timing of exposure and the sex of the exposed individual.
- Another important class of obesogens interacts with central mechanisms that coordinate the whole-body response to daily nutritional fluctuations. The control over appetite exerted by the hypothalamic-pituitary-adrenal (H-P-A) axis plays a critical role to prevent hyperphagia and regulate energy homeostasis. Obesogens also have the potential to create changes in the central integration of energy balance including the regulation of appetite and satiety in the brain and the reprogramming of metabolic setpoints.
9. Triclosan
Triclosan (TCS, 2,4.4 ′ -trichloro-2 ′ -hydroxy-diphenyl ether) is a biphenyl compound linked together by oxygen as an ether. It is a necessary ingredient in several personal care products because of its remarkable antibacterial properties. Despite its benefits, there are several non-co9nclusive but strongly convinced studies that assert triclosan as ad toxic and a potential EDC. Humans are exposed to triclosan through several products including toothpaste, mouthwashes, deodorant, antibacterial soaps, antiperspirants and deodorants, cosmetics, and antiseptics. TCS is also present in several other consumer products such as trash bags, clothes, bedding, toys, and kitchen utensils. Once incorporated by the human body, triclosan is metabolized primarily through conjugation reactions into glucuronide and sulfate conjugates that are excreted in feces and urine. Pharmacokinetic studies demonstrate that triclosan sulfate and glucuronide may be formed in the liver at approximately equal rates at the environmentally relevant concentration of 1 to 5 microMolar. Exposure to triclosan is linked to several human health effects including abnormal thyroid signaling, weakening of the immune system, uncontrolled cell growth, developmental and reproductive issues, etc. Children exposed to these antibacterial products at an early age have an increased chance of developing allergies, asthma, and eczema.