Endocrine Disruptors: A Quiet Threat to health

In the past few decades, many scientists and public health officials have raised the alarm about a new kind of pollution that affects the endocrine system of humans and wildlife. As we learn more about the role of the endocrine system in regulating almost every major process in our bodies, subtle changes to the system caused by low-level environmental contamination are appearing increasingly significant to our health. This article explains some of the basic tenets of endocrine disruption and underlines the connection between the health of our rivers and the health of the human and wildlife populations that they sustain.

 Report by Benjamin Lemmond

 

 “ The possibility of an environmental influence on the hormonal control in organisms is scientifically indisputable … [The] potential effects on humans and on nature are so tremendous that there is a need for immediate clarification. ”


The German Environmental Agency Workshop Report: Endocrinally Active Chemicals in the Environment, March 1995, Berlin
 


Warning Signs

In 2003, researchers from the USGS investigating a fish kill on the Potomac River discovered a bizarre problem in some of the River's male small-mouth bass: male fish were showing signs of developing female biological characteristics, including the development of female sex organs and production of eggs. In 2004, numerous reports of this phenomena of 'intersex' fish emerged regarding white sucker fish in Boulder Creek, CO; soon after, reports came in from across the country of intersex fish in the Mississippi River, the Rio Grande, Columbia River Basin, Yukon River Basin, the Colorado River, the Apalachicola–Flint–Chattahoochee, the Savannah, and the Pee Dee. And even before the phenomena was observed in the United States, intersex fish had already been found in the UK, Germany, Spain, France, Belgium, and Denmark.

So what is happening to these fish? And how did this strange phenomena become so common? 

Extensive studies of these fish, and the rivers that they live in, have revealed that low levels of certain chemicals found in treated wastewater, stormwater runoff, and even permitted discharges into the river, are causing disturbances in the hormonal systems in wildlife. This system, which is also known as the endocrine system, regulates numerous individual biological processes, including reproduction, brain function, and the immune system in wildlife and humans. Many synthetic plastics, detergents, pharmaceuticals, pesticides, and industrial chemicals are included in this category of pollutants known as "endocrine disruptors".

The effects of these chemicals on the reproductive health of male fish has led to fertility declines, abnormal mating behavior, and the collapse of some local populations. Recently, scientists discovered that these chemicals also caused a reduction in levels of hepcidin, a hormone that is suspected to help fish, frogs, and mammals resist microbial infection. This discovery helped explain how the intersex phenomena might be related to the widespread, unexplained fish kills in some of these rivers. Recently, the PBS series ‘Frontline’ produced an excellent documentary on some of the pollution issues facing major waterways. The link between endocrine disruption and the decline in the Potomac’s small mouth bass population is featured in one section ('Chapter 5') of the film, which you can watch online here

Fish are not the only animals threatened by endocrine disruptors. Endocrine disruptors have also been implicated in patterns of birth defects, hatching failures, and population declines in many bird, reptile, amphibian and invertebrate species around the world. Additional information on the effects of endocrine disruptors on wildlife species can be found at the Fish & Wildlife Service page onAmphibian Declines, the USGS Page on intersex fish, or a page summarizing new studies related to endocrine disruptors in wildlife.

Humans, too, are at risk of adverse health effects from endocrine disruption. Our environment provides us with steady exposure to endocrine disruptors, at levels ranging from reasonably insignificant to potentially serious. Developing fetuses are most at risk, since the long-term fate of one's physical and mental characteristics are heavily influenced by hormone-mediated signals during this stage of development. Small differences in hormone activity in pregnant mothers and the developing fetus have serious implications for health.

There is much debate over what amount of these chemicals, exactly, our bodies can tolerate without experiencing negative health consequences. And unfortunately, there are still many missing pieces of information that prevent us from managing the health risks of these chemicals with our regulatory system's standard approach to managing chemical hazards. This approach requires the development of a set of formulas that can describe the likely effects of a given exposure (more information on this process can be found in the Terms and Concepts page).

Yet there is considerable evidence that suggests that the potential consequences of our current exposures to endocrine disruptors are significant enough to warrant a different approach to managing risk: prevent exposure to chemicals that are likely to be harmful and pose a significant threat, even if it is not yet possible to say exactly how much harm a given amount of the chemical will cause. This "precautionary" approach may be ideal from a public health perspective, but it runs in to trouble when other elements are considered - namely, the economic incentives to allow these substances to flow through our markets unregulated. Many known endocrine disruptors are the cornerstones of major industries, as described briefly in the table below.

 

Chemical
Health Effects:
Amount Produced/Used
Detected in Humans?
Bisphenol-A, BPA: Polycarbonate plastic (water bottles, CDs, cups), dental fillings, canned food (can lining)
Estrogenic: can increase risk of certain cancers, birth defects, and developmental abnormalities
6-7 billion lbs produced each year (globally)
Found in more than 93% of U.S. population
Phthalates: Plastic additives used in car interiors, soft vinyl toys, hospital tubing, perfumes Anti-androgenic: increased risk of birth defects in males, also linked to obesity and improper insulin regulation
approx. 11 billion lbs/year (globally)
Found in >75% of general U.S.  population
 Triclosan: antibiotic used in antibacterial soaps, toothpaste, mouthwash, deodorant Anti-androgenic: linked to testicular dysgenesis and reduced sperm production
>1 million lbs/year (in the U.S.)
Found in 74.6% of general U.S. population
 Pesticides, Herbicides, Fungicides
vary by chemical
1.12 trillion lbs/year (in the U.S.)

In 2005, 21.4 million pounds of pesticides that are "known to cause reproductive toxicity" and  28.4 million pounds of pesticides that are "known to cause cancer" were used in the state of California alone.
Varies by chemical. Some banned pesticides are still found universally (hexachlorobenzene, banned in 1966, is found in 99.9% of current U.S. population over 12).


As the evidence emerges over the dangers of even low doses of these chemicals, we realize that there have been several overlooked opportunities in decades past to act on what we knew about the dangers of endocrine disruptors.


Lessons from the Past

 

From 1938 to 1971, millions of pregnant mothers were given a synthetic estrogen called diethylstilbestrol (DES) to reduce the chance of miscarriage. Later, it became apparent that the daughters of DES-treated mothers had an elevated risk of breast and vaginal cancer, due to the effects of DES on their development in utero.  This experience, though tragic, taught us much about the serious consequences of human exposure to endocrine disruptors. The studies of the impact of DES showed that the effects of endocrine disruption can have serious trans-generational implications for health. We also learned that a synthetic estrogen is capable of producing cancer, and that organisms in key stages of development are uniquely sensitive to endocrine disruption.

At the same time that the evidence indicting DES in causing thousands of cancers began to emerge, vast quantities of another chemical similar to DES were being synthesized to feed the world's skyrocketing demand for plastic products. Bisphenol-A is the monomer used to make polycarbonate, a kind of sturdy plastic used in CD's, plastic foodware (including baby bottles and reusable water bottles), toys, food cans (as a lining), and many other products. However, although the BPA polymer (polycarbonate) is a stable and safe material, there are always traces of BPA in the finished product, since the process of polymerization is never 100% complete. The un-polymerized BPA that remains in the finished product can slowly leach out of the polymer matrix and into the food or water inside the container. This process is accelerated when the polycarbonate plastic is heated. In this way, most humans in industrialized societies are exposed to BPA almost every day. And even though BPA is metabolized quickly by the body, it still appears in the majority of blood samples in the US population (more than 93% of blood samples in the latest national biomonitoring survey conducted by the CDC). This suggests that human exposure to BPA is continuous and comes from sources in our environment with which we have regular contact.

The properties of Bisphenol-A that qualify it as an endocrine disruptor - namely, the fact that it mimics natural estrogen in the body - had in fact been known for decades before it was used as a plastic. In the 1930's, BPA was promoted, along with DES, as a candidate for hormone therapy due to its estrogenic properties. However, BPA was found to be less potent than DES, and therefore it was not used as a pharmaceutical. 

Today, more than 6 billion pounds of BPA are produced each year and made in to products destined for contact with our food and water, despite numerous studies showing adverse effects at doses within the range of human environmental exposures. The plastics industry fervently denies  the conclusions of these studies. The debate over regulating BPA is one of the most prominent issues regarding the hazards of endocrine disruptors today. Many states and cities are attempting to ban the chemical from products such as baby bottles (so far a ban has been passed in only one state, Minnesota).

Another important moment in the history of our knowledge of endocrine disruption came in the early 90’s, when scientists discovered that synthetic pesticides dumped into Lake Apopka in Florida were disrupting the endocrine systems of alligators, fish, and other aquatic species, causing birth deformities, abnormal mating behavior, and population declines in some species. Pesticides have long been implicated in negative health effects of so-called "non-target" species, such as birds. The findings in Lake Apopka showed the danger of these chemicals to aquatic wildlife. These studies show that many pesticides can disrupt the endocrine system of wildlife exposed to pesticides in their environment, even though pesticides are generally far less potent than natural hormones or some other synthetic chemicals like BPA.

Pesticides are intentionally designed to harm living organisms. While we are told that pesticides are safe when used for their intended application, the unintended effects of these chemicals on so-called "non target" organisms are not as well accounted for. The risk to the human population from pesticide exposure remains unclear, but we do know that we are exposed to pesticides on a regular basis, and that there is more and more evidence that suggests that these chemicals can be harmful to sensitive members of the population at very low levels.

A recent article in the New York Times reported that as many as 33 million Americans have been exposed to atrazine, a commonly used herbicide, in their drinking water. In many towns, citizens were not warned of spikes in the concentration of atrazine in their water above the federal heath standard of 3 parts per billion in drinking water. However, most of the agricultural chemicals found in drinking water have no health standard for drinking water. Recent research has shown that atrazine and other pesticides (including glyphosate-based pesticides such as Roundup) can have negative health consequences at lower levels than previously thought, levels which may be significant to sensitive groups such as pregnant women. Atrazine has been associated with birth defects and low birth weights in rural areas of the United States, at concentrations in water as low as 0.1 parts per billion.

In the decades since the "green revolution" unleashed a relentless demand for pesticides, hundreds of pesticides have been banned due to newly-discovered health consequences, including endocrine disruption. Yet many pesticides that have been banned for decades are still detected in human tissue, animals, and even human amniotic fluid at levels that concern many scientists and public health officials.

 

How Can Endocrine Disruptors Harm Us?

The endocrine system is the system in our bodies that coordinates important biological changes such as growth and development, sexual maturation, brain function, and our immune and metabolic systems. This system is able to control all of these processes simultaneously by using chemicals called hormones. Hormones are the chemical 'messengers' produced by the endocrine glands (thyroid, adrenal, pancreas, testes, and ovaries) in response to specific stimuli. For example, insulin is released by the pancreas when high amounts of glucose (sugar) are present in the blood. Other hormones, such as those involved in the onset of puberty, respond to more complex stimuli such as body mass, social factors, and physical environment.

Once released, hormones are transported through the bloodstream in extremely small quantities to a target organ or tissue. The hormones are then recognized by certain hormone receptors on cells in the body that translate hormone signals into a biological response. Other hormones may be released to regulate the initial hormone, a process known as a "feedback loop" (more information on feedback loops). This auto-regulatory system ensures that precise levels of many hormones are maintained in the bloodstream. In this way, the endocrine system allows the organism to change its structure and develop new capabilities in response to the appropriate environmental stimuli. This ability is a critical survival mechanism for vertebrates and invertebrates in all parts of the biosphere.

The basic tenet of endocrine disruption is that certain chemicals can directly or indirectly interfere with certain events normally controlled by hormones or any other function of the endocrine system, such as hormone production, transport, metabolism or elimination.

Many endocrine disruptors are structurally similar to natural hormones and may bind to the same receptors, triggering the same response that would be caused by the natural hormone. However, since these responses are caused by environmental chemicals and not ordered by the organism’s own endocrine system, the unintended endocrine activity can produce untimely or unhealthy effects. In laboratory animals, exposure to estrogen-like substances such as Bisphenol-A, at doses well within the range of human exposures (including levels measured in fetal blood) has caused early mammary gland development, early sexual maturation, disruption of estrous cycle in females, decreased sperm production and fertility in males, and decreases in immune function and antioxidant enzyme function. These effects in laboratory animals are similar to some of the conditions in humans suspected to be influenced by endocrine disrupting chemicals like BPA. Endocrine disruptors can also suppress the function of natural hormones by occupying a hormone receptor without triggering a response, rendering those hormone receptors incapable of receiving the body’s own hormone signals.

In addition to receptor interference, endocrine disruption can occur in other stages of hormone synthesis, transport, or breakdown, or can be a result of toxicity to a gland involved in hormone production, transport, or excretion. For example, the thyroid gland is a common target of many environmental endocrine disruptors such as PCBs, and the resulting thyroid damage can disrupt the function of the processes regulated by thyroid hormones, such fetal neurodevelopment. Endocrine disruptors often affect more than one organ or tissue, making the prediction of the effects of exposure to an endocrine disruptor very complex and difficult to model.

The extensive (and still growing) list of chemicals that are known to target the endocrine system includes numerous persistent organic pollutants (PCBs, organochlorine pesticides, dioxins/furans), plastics and plastic additives (Bisphenol-A, phthalates, flame retardants), agricultural and household pesticides, herbicides and fungicides, antibiotics such as triclosan (used in antibacterial hand soaps), growth hormones used in animal production, heavy metals such as mercury, and even some common cleaning agents. Natural and synthetic hormones (such as the birth control hormone) can also disrupt the endocrine system when other organisms are unintentionally exposed. For a list of chemicals and the research showing their endocrine-disrupting activity, check out the list compiled by an endocrine disruption research and advocacy group, "Our Stolen Future".

The effects of one chemical are often compounded by additive or synergistic interaction with other endocrine disruptors in the body (see Terms and Concepts page). This phenomena contributes to the overall lack of regulation of EDCs, since it tends to make quantifying risk – a standard precursor to regulation – much more complex.

Despite the difficulty of predicting the exact relationship between exposure and effect, there are many individual pieces of evidence that, altogether, suggest that a problem is already occurring in humans. Many epidemiological studies have found correlations between low-level drinking water contamination by pesticides and herbicides and birth abnormalities. Other studies with laboratory animals have suggested that exposures to chemicals such as BPA and phthalates at concentrations within the range of human exposure (including fetal exposure)can cause severe adverse health effects. Many epidemiological studies have correlated exposure to phthalates and risk of obesity and diabetes. Unexplained increases in breast cancer, prostate cancer, genital deformities in males, and earlier onset of puberty in females in recent decades have raised the concern about the role of endocrine disruptors in these health trends. The research and advocacy group "Our Stolen Future" has compiled a review of recent studies on the effects of endocrine disruptors in humans, which can be found here. A list of studies related to endocrine disruptors and human health can also be found on the Links and Sources page of this report.

 

How does exposure to endocrine disruptors occur?

Almost all living organisms on the planet are currently exposed to a mixture of several of these chemicals in their environment. The most common routes of exposure is through food and water - either because the food or water has come in contact with these chemicals or because the food itself contained an endocrine disrupting chemical. Most food - especially meat, eggs, and dairy products - contain detectable levels of certain endocrine disrupting chemicals such as PCBs, DDT, and dioxin, which resist environmental degradation and accumulate in the food chain (a phenomena known as "bioaccumulation").  A recent report from the United States Geological Survey (USGS) found mercury, which is an endocrine disruptor, in every fish sampled from 291 U.S. streams, including streams in unpopulated, remote areas. Some of the highest concentrations of mercury were found in North and South Carolina. Mercury deposition from coal fired power plants, which are abundant in this region, is a major contributor to the mercury found in our waters. For more on this recent study, you can read the Department of the Interior’s press release or visit the USGS site for the study.

Exposures to these chemicals from the ambient environment (air and water) are especially significant for wildlife -  for example, fish who swim in water containing several endocrine disrupting chemicals. Organisms that live in water are especially vulnerable to endocrine disruptors, since their environment is the receiving end for much of our pollution – agricultural runoff, stormwater and sewage from cities, and industrial pollution are all regularly dumped into rivers and streams. As a result, most of these chemicals are commonly found in streams, rivers, oceans, and to a lesser extent, groundwater and drinking water. Numerous species of fish, birds, marine mammals, reptiles, insects, and amphibians routinely show biologically significant levels of some endocrine disruptors in tissue and blood samples.

Though it is less significant than other routes of exposure, human exposure to these chemicals in the ambient environment does occur. Some chemicals, such as phthalates, can volatilize into the air and be inhaled (that "new car smell" is, in fact, the smell of phthalates off-gassing from your dashboard); additionally, phthalates are often used in fragrance and cosmetic products. Triclosan, an antibiotic often used in hand soaps, can be absorbed through the skin as well as by ingestion/musosal absorption from certain dental hygiene products (toothpaste, mouthwash) containing triclosan. Pesticides (and many other chemicals) may linger in household dust, clothes (especially of farm workers) and be absorbed through skin or ingested. Many endocrine disruptors are also commonly detected in drinking water, though our exposure to the same chemicals via interaction with synthetic materials (especially polycarbonate and vinyl plastics) and ingestion of chemicals in our food remains, by far, the most significant route of human exposure to endocrine disruptors.

 

 

 


 
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