What are Endocrine Disrupting Chemicals?
Our endocrine system is extremely important. It is comprised of glands – the hypothalamus, thyroid, pituitary, adrenals, ovaries and testes – which produce hormones that act as chemical messengers in a multitude of complex interactions that drive the critical processes involved in reproduction, growth and development, the absorption of nutrients from food, the balance of blood glucose levels, and more. However, there are substances that threaten to topple this delicate balance, and they are all around us: in the air, in the water supply, and in our food, including the very first life-giving substances that we feed on as mammals.
They can play many tricks on our bodies, such as mimicking hormones, increasing or decreasing the production of certain hormones, transforming one hormone into another, interfering with hormone signaling, causing cells to die prematurely, or competing for nutrients. Endocrine disrupting chemicals, or EDCs, are chemical substances, either natural or manmade, that interfere with and alter the normal biosynthesis, metabolism or action of hormones. This deviation from homeostatic endocrine control consequently harms an individual life form, its offspring, or populations. (1) These chemicals are used in both industrial processes and personal products, including everything from children’s toys and appliances, to food packaging and skin care products. The following are a just few examples of EDCs and what they are capable of:
- Phthalates: chemicals used in soft plastics and perfume that cause anti-androgenic effects such as death-inducing signaling in testicular cells
- Atrazine: an herbicide used on corn crops which can turn male frogs into female frogs with viable eggs
- Polybrominated diphenyl ethers or PBDEs: used in fire retardants, they have contaminated people and wildlife, imitating thyroid activity and leading to lower IQ (2)
Hormone receptors bind with their corresponding hormones by fitting together like puzzle pieces. When molecules of EDCs that mimic the structure of these hormones are present, they will sometimes bind to the receptor instead of the body’s own hormones.
Why are EDCs a concern?
The issue of how EDCs are affecting our health and environment on a global scale has been a focus of great concern to international organizations, as well as scientific and public interest groups, including the U.N., the W.H.O., and the International Union of Pure and Applied Chemistry (IUPAC). The dangers of some EDCs are well-known, such as the cases of mercury, lead, perfluorinated chemicals, and arsenic. Research has led to significant advancement in our understanding of the harm that they cause, and many have been banned after being attributed to serious detrimental effects on humans and the environment. However, many of these chemicals that have been released in the form of fertilizers and herbicides are known to persist for decades in the water supply, soil, and food chain, and their build-up over time means even if their use were banned today, they would still be a concern for future generations. (3) The pesticide DDT is now banned in the US, but vapor containing it could travel from Mexico, where it is still used, and reach Minnesota in the form of rain. In fact, DDT has been found in humans and animals as far as the Arctic, where it has never actually been used. (4)
Though a direct causal link has not been established in humans for all of the harmful effects associated with EDCs, a wealth of laboratory testing has indeed demonstrated the adverse effects of various EDCs on the endocrine system of a range of animal species, including land mammals. Plausible links have been made between the presence of EDCs in the water and land, and the harmful effects seen on the reproduction, growth and development of local wildlife. Recent rises in reproductive disorders and diseases are believed to be related to the disturbance of the endocrine system by the use of EDCs, which have exploded in their use since the end of World War II. (5)
Bisphenol A – chemical structure and properties
“Endocrine disrupting chemicals” is a term that encompasses a wide spectrum of substances that vary greatly in structure and properties. As an example, we will investigate one of the most widely-used chemicals worldwide, and a subject of much debate currently: Bisphenol A, an organic synthetic compound commonly known as BPA. Belonging to the group of diphenylmethane derivatives and bisphenols with two hydroxyphenyl groups, BPA is a colorless solid that is soluble in organic solvents, but poorly soluble in water. (6)
Molecular Formula: C15H16O2
Molecular Weight: 228.28634 g/mol (6)
(Image credits, from left to right: myorganicchemistry.wikispaces.com/Bisphenol+A , pubchem.ncbi.nlm.nih.gov/compound/Bisphenol_A#section=3D-Conformer)
Synthesis of BPA
BPA is synthesized through the condensation of one unit of acetone (thus the "A" in its name) and two units of phenol. Then, hydrochloric acid or another strong acidic compound, like sulfonated polystyrene resin, is used to catalyze the two components, creating BPA molecules. (8)
Commercial uses of BPA
Six billion pounds of BPA are produced worldwide each year, and it is used primarily to make two classes of polymers: epoxy resins and polycarbonate. Polycarbonates, the end products of about 72% of BPA, are a group of thermoplastics that contain carbonate groups. (7) Polycarbonate is a very hard, nearly shatterproof, and extremely versatile material used to make a wide range everyday products such as water bottles, medical devices, eyeglasses, electronics, tupperware, CD and DVD cases, toys, playground and sporting equipment, and even dental sealants in children to prevent cavities. (7)(9)
To create polycarbonate, first Bisphenol A is reacted with sodium hydroxide, which deprotonates the hydroxyl groups of the Bisphenol A to produce the sodium salt of Bisphenol A.
(HOC6H4)2CMe2 + 2 NaOH → Na2(OC6H4)2CMe2 + 2 H2O
Next, the sodium salt of Bisphenol A, diphenoxide (Na2(OC6H4)2CMe2) is reacted with phosgene, or carbonyl chloride (COCl2) to produce a chloroformate, which subsequently is attacked by another phenoxide. The net reaction from the diphenoxide is:
Na2(OC6H4)2CMe2 + COCl2 → 1/n [OC(OC6H4)2CMe2]n + 2 NaCl
Alternatively, in a greener method that avoids the toxicity of working with phosgene (which was used in WWII as a chemical weapon), diphenyl carbonate (C13H10O3) can be used in a transesterification process: (7)
(HOC6H4)2CMe2 + (C6H5O)2CO → 1/n [OC(OC6H4)2CMe2]n + 2 C6H5OH
Epoxy resins made from BPA are used in the linings of food and beverage cans, including infant formula containers, and thermal paper used for receipts, as well as adhesives, paint additives, and flame retardants. Since it is an unstable polymer and is lipophilic, BPA molecules can leach into infant formula and other food products, especially when heated or in acidic conditions. (9)pubs.acs.org/cen/coverstory/89/8923cover2.html
Endocrine-disrupting activity of BPA
It is absolutely essential to evaluate the potentially harmful effects of a substance as pervasive as BPA, which has been detected in over 90% of human urine samples and has been shown to pass the placental barrier. (13) There is a large body of evidence to suggest that BPA may adversely affect physical, neurological, and behavioral development. It has been linked to a variety of reproductive problems and cancers, diabetes, obesity, early puberty, reduced cognitive abilities, behavioral changes in children and resistance to chemotherapy.(10) BPA is classified by the MeSH as a non-steroidal compound with estrogenic activity (6). BPA resembles and mimics the form of estrogen called endogenous 17beta-estradiol (E2), by binding to the estrogen receptor and modulating target expression (10).
Though it is often metabolized by the body, often less effectively in women than in men and even less effectively in children, (10) this fact alone does not mean that it is less harmful, or that it is only harmful in large doses, as has been purported. In fact, its metabolite, MBP, 4-methyl-2,4-bis(4-hydroxyphenl)pent-1-ene, is 1000-times stronger than BPA in its estrogenic effects. While BPA binds weakly to ER receptors, MBP binds strongly to both types of estrogen receptors (ER-alpha and ER-beta) and may change the activity of the cell, even displacing native or endogenous estradiol. (11) MBP is a longer compound than BPA, mimicking Estradiol better and binding more readily to the Estrogen receptor. Furthermore, a 2007 study showed that BPA binds strongly to the estrogen-related receptor γ (ERR-γ), which is found in high concentration in the placenta, accounting for its accumulation in this and other tissues where ERR-γ is present. (9)
Fetal exposure and reproductive system effects
When in a person’s life they are exposed to BPA is crucial to understanding any potential effects they may suffer even much later in life. The current consensus is that even minimal exposure to EDCs during certain key stages of development in fetuses and children can cause a range of problems, a causality which has been proven in many animal studies. Two studies, one with rats and one with humans, have shown that both active BPA and its inactive metabolite freely cross the placental barrier from mother to fetus, and that the fetus can break down the inactive form to its active, estrogenic form. (12) BPA has been detected in amniotic fluid, fat, blood, and breast milk. Even low levels of BPA are known to change the development of the mouse mammary gland, prostate, uterus and brain, and significantly alter the behavior of exposed mice and rats. In another study, female mice that were exposed to BPA as fetuses developed abnormalities of the ovaries, uterus and vagina, while other studies linked BPA to genetic abnormalities in eggs, an increased risk of mammary cancers, and early puberty in females. In male mice, effects included reduced sperm production and quality, and increased prostate size. (13) Behavioral and cognitive effects of BPA in male mice were reported in one study which concluded that female mice were not interested in mating with BPA-exposed male mice, and that “BPA-exposed males perform worse on spatial navigation tasks that assess their ability to find female partners in the wild.”(14) One human study correlated men with the highest levels of BPA to significantly lower sperm concentrations, and lower sperm motility, size and shape. (8) BPA exposure has also been associated with an increased risk of fertility disorders, including miscarriage and polycystic ovary disease. (13)
Safe at low doses?
Currently, the European Food Safety Authority considers current levels of BPA exposure to pose no health threats to people of any age. (17) According to the Environmental Protection Agency, people can safely be exposed to up to 50 µg of BPA per kg of body weight per day, the Tolerable Daily Intake (TDI) originally set in 1988 and widely debated by toxicologists and endocrinologists. (18) The Environmental Protection Agency´s approach to EDCs is the same approach as for other toxic compounds, which assumes a linear dose-dependent response to chemical exposures. They determine the lowest level at which there is an observed adverse effect, to arrive at an official reference dose—the daily human intake assumed to be safe, until proven otherwise. However, it is widely believed that the unique aspects of EDCs call for the need to incorporate even low-dose warnings into their risk assessment protocols. There are now more than 100 published peer-reviewed studies showing significant biological effects of low doses of BPA. (4)
The “wait-and-see” approach to EDC toxicity
The cumulative effects of long-term, low-dose exposure to BPA and other EDCs are still unknown. Meanwhile, synthetic chemical substances are deemed innocent until proven guilty; currently, no federal agency tests the toxicity of new materials before they are put on the market. The wait-and-see approach of the regulatory authorities means we may be sacrificing our health and that of future generations for the convenience of modern plastics and other products. A chemical can be used until it is proven to be harmful, not the other way around. According to the Chemical Hazard Data Availability Study, conducted by The EPA’s Office of Pollution Prevention and Toxics,
"of the 3,000 chemicals that the US imports or produces at more than 1 million lbs/yr, a new EPA analysis finds that 43% of these high production volume chemicals have no testing data on basic toxicity and only seven percent have a full set of basic test data. This lack of test data compromises the public’s right to know about the chemicals that are found in their environment, their homes, their workplace, and the products that they buy. Industry must do more to ensure that basic information is available on every high-production chemical they manufacture." (19)
Unfortunately, the practice seems to be to wait until there is overwhelming evidence, or until many people are affected in fatal or irrevocable ways by chemical substances, before they are investigated. The case of the synthetic estrogen DES in the 1950s and 1960s, and the alarming birth defects directly attributed to it, illustrates a particularly tragic example of what can happen. BPA has only been in use since 1957, and the history of EDCs so far often tells the story of a wide scale human experiment, of deadly chemical substances that we thought were safe until we learned better, in the hardest way possible.
The future of BPA and EDCs
At present, it seems it is up to the consumer to stay informed and decide what products to use, though it can be near impossible to successfully identify potentially harmful substances. For instance, many phthalates and other potential harmful EDCs are referred to as “fragrance,” a vague and misleading umbrella term. Some countries have established stricter limits on BPA in products for babies and children, including banning the use of BPA in baby bottles, and many manufacturers are voluntarily replacing BPA with substitutes in their products. Unfortunately, substitutes for BPA, including BPS, have proved to be harmful as well. (20)
Scientists, for their part, are currently faced with the challenge of establishing or disproving direct causality between BPA and its effects on humans, a task which involves many obstacles. First, it would be unethical to expose humans to high levels of potential toxins. Second, because BPA and other EDCs are ubiquitous, and have been found even in the most remote places on Earth, everyone is exposed to some degree, which means there is no control group to compare with. There are many factors at work, such as duration and frequency of exposure and dosage, as well as the methods in which different chemicals combine with each other, with other environmental toxins and with our own biochemistry. Furthermore, every individual possesses his or her own set of biological strengths and weaknesses, and predispositions and propensities toward disease. This presents a complex panorama that a narrow causal law for each substance could not possibly explain easily.
Like other environmental and health issues, the problems surrounding the mass use of EDCs is clearly one of global scale. It is imperative that professionals in the field of science, medicine, environmental issues, and public health, not to mention the plastics industry, stay abreast of current research, and that the legislation on the allowance of EDCs be adapted accordingly. The State of the Science of Endocrine Disrupting Chemicals (WHO/UNEP 2013), presented by the Inter-Organization Programme for the Sound Management of Chemicals (IOMC), is an extremely helpful and exhaustive report presenting important findings relevant to many fields.
How can I minimize my exposure to EDCs?
- Eliminate the use of pesticides and air fresheners in your garden and home.
- Soak non-organic fruits in a vinegar solution to remove pesticides
- Consume organic fruits and vegetables whenever possible, particularly thet welve most contaminated ones, the EWG´s “Dirty Dozen,” to avoid EDCs sprayed on produce in the form of pesticides and antifungals
- Use organic personal care and home cleaning products, including sunscreens, shampoos, soaps and detergents, makeup and skin care (Look for products without parabens, SLS, and phthalates) Consult the Environmental Working Group’s Skin Deep database of products for information on safety.
- Limit or eliminate consumption of foods packaged in cans, unless marked “BPA-free” Avoid buying products packaged in plastic. Instead choose foods that come in glass or waxed carton (Tetra Pak) packaging. Never heat foods in plastic containers.
- Don’t let children chew on soft plastic toys. (2)
For more information:
- The EWG’s “Deadly Dozen” most toxic EDCs and tips on how to minimize your exposure to them
- More information on sources of toxic chemicals in food and other products and how to avoid them
- Our Stolen Future: An excellent book on the history of EDCs, written for a general audience
- ”Why the US Leaves Deadly Chemicals on the Market” On legislation of EDCs in the US
- The State of the Science of Endocrine Disrupting Chemicals the 2013 WHO/UNEP document
- Documentaries on EDCs and other toxic chemicals and their effects on health:
- The Great Invasion
- The Human Experiment
- Endocrine Disrupting Chemicals: Science, Policy, and What You Can Do
11. Singleton DW et al; Mol Cell Endocrinol 221 (1-2): 47-55 (2004)
First image credit: Evan Kafka for Mother Jones (www.motherjones.com/environment/2014/03/tritan-certichem-eastman-bpa-free-plastic-safe)