National Drinking Water Clearinghouse
West Virginia University
PO Box 6893
Morgantown, WV
26506-6893


They're in the Water They Make Fish Change Sex
Endocrine Disruptors-What are they doing to you?



by Kathy Jesperson
On Tap Associate Editor
kjespers@wvu.edu


Scientists have been documenting a series of strange situations lately. In certain places around the world, fish have spontaneously changed sexes. The sexual organs of male alligators in Florida have failed to develop to a mature size. And the thyroid glands of Great Lakes salmon have enlarged.

Other peculiar phenomena began cropping up as well: bald eagles have failed to reproduce, male panthers have almost no testosterone, and about seven percent of male tadpoles have developed ovaries. Something must be terribly wrong.

Scientists have found that certain chemicals disrupt the endocrine systems of wildlife. Nearly all animals have an endocrine system, including mammals; non-mammalian vertebrates, such as fish, amphibians, reptiles, and birds; and invertebrates, such as snails, lobsters, insects, and other species.

Because humans also have an endocrine system, these findings have led scientists to ask a serious question: If these chemicals disrupt the endocrine systems in wildlife, what are they doing to humans

Many scientists argue that if these chemicals affect wildlife, it must follow that they also affect humans. Critics argue that there is no proof that these chemicals affect humans in any way. However, many scientists point out that there’s no sense in waiting around for a generation of hermaphrodites to encourage the U.S. Environmental Protection Agency (EPA) to move ahead with its research. It’s time to get moving now.

While the EPA already regulates some chemicals thought to be endocrine disruptors, the agency has really only begun to research how many potential endocrine disruptors there are. And because this is only the beginning, it may take a long time before a complete list of these chemicals is available. In the meantime, it’s a good idea to learn as much as possible about what is in our drinking water supplies and how these substances affect our health.

Chemicals, such as pesticides, fertilizers, fuel additives, and detergents, are spread through the environment in a variety of ways, such as exhaust, spills, and waste discharges. In the case of many agricultural products, they are intentionally released.

Because of this constant chemical supply to the environment, many substances can and do drain or leach into source water supplies. Fish and other aquatic life live in the water, animals drink it, and a lot of it finds its way to the local drinking water treatment system.

What is an endocrine system?
The endocrine system consists of glands, hormones, and receptors. Endocrine glands include the hypothalamus, pineal, pituitary, thyroid, parathyroid, thymus, adrenal, ovaries, prostate, and testes.

The pituitary gland acts as the control center, telling the other glands when to send their signals and how much hormone to send. The pituitary gets its cues from the hypothalamus, which acts as a regulator, telling the pituitary to increase hormone production or to slow it down and shut it off. These messages travel back and forth continuously throughout all parts of an organism, keeping everything balanced and coordinated.

The glands produce hormones, such as adrenocorticotropic hormone (ACTH), corticosteroid, adrenaline, estrogen, testosterone, androgen, insulin, triiodothyronine, and thyroxin.

Hormones are involved in just about every biological function. They are better known as the body’s chemical messengers because they travel through the bloodstream and cause responses in other parts of the body. The amount of hormone that an animal’s body produces depends upon the stimuli that its body receives. They also can work at astonishingly low concentrations—in parts per billion or even trillion.

Hormones regulate:
• reproduction and embryo development,
• growth and maturation,
• energy production, use, and storage,
• electrolytes—the balance and maintenance of water and salt,
• reaction to stimuli, such as fright and excitement, and
• behavior of human beings and animals.

Receptors, which are in the cells of various target organs and tissues, recognize and respond to the hormones. Receptors are a part of a complex biological feedback system that regulates the response. Any disruption to the balance can cause changes to take place in these reactions.

What are endocrine disruptors?

Endocrine disruptors are synthetic or naturally occurring chemicals that interfere with the balance of normal hormone functions in animals, including humans. This imbalance can cause various abnormalities of the reproductive system, such as the feminization of males and the masculinization of females. Among other abnormalities, they also can cause enlargement of the thyroid gland, birth defects, behavioral changes, depressed immune systems, and an increased vulnerability to disease.

An endocrine disrupting chemical can affect the endocrine system of an organism in a number of ways, but they typically affect animals in three specific ways. They can mimic, block, or trigger a hormone response.

Chemicals that mimic respond like normal hormones inside the body. A good example of a mimicking endocrine disruptor is the potent drug diethylstilbestrol (DES), a synthetic estrogen. Doctors prescribed DES to as many as five million pregnant women to block spontaneous abortion prior to DES being banned in the early 1970s.

When doctors first began prescribing DES, they believed that it would prevent miscarriage and promote fetal growth. However, researchers discovered that after the children went through puberty, DES affected the development of the reproductive system of the daughters of the mothers given DES, and it caused vaginal cancer. In addition, these women have an increased risk of developing endometriosis.

Sons born to mothers given DES have an increased frequency of undescended testes, congenital birth defects, hypospadia, and decreased adult sperm count.

A second group of disruptors are hormone blockers. These interfere with how naturally occurring hormones function. Blockers bind to the same protein receptors as the real hormone but do not stimulate any action. They sit in the way of the natural hormone and prevent it from sending its message.

An example of a blocker is how DDE (a metabolic breakdown product of the pesticide DDT) blocked action of testosterone in male alligators in Lake Apopka, Florida, which led to undersized penises. Testosterone, a male hormone, is needed for proper reproductive development.

Triggers are the third category of disruptors. They attach to protein receptors, then trigger an abnormal response in the cell. These triggers cause growth at the wrong time, an alteration of metabolism, or synthesis of a different product. The best-known triggers are dioxin and dioxin-like chemicals. Dioxin acts through a hormone-like process to initiate entirely new responses.

What kinds of substances can be endocrine disruptors?
The number of substances believed to be 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 harmful effects.

Many plants and animals produce substances that can have endocrine effects. Some of the substances are toxic but others have proven beneficial in certain circumstances. For example, some endocrine disruptors have been used to control fertility (birth control pills), to treat cancer (corticosteroids), 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.

Where are endocrine disruptors found and what are examples?

Synthetic chemicals suspected as endocrine disruptors may reach humans and animals in a variety of ways. Some, such as pesticides, are used to treat food crops and can leach into groundwater supplies. Others are by-products of industrial processes and waste disposal—these include dioxins and PCBs—or are discharged from industrial or municipal treatment systems.

The pesticides include chlorinated organic chemicals such as DDT, toxaphene, and kepone. Industrial compounds include PCBs, phenol, and dioxins. Their most common characteristics include persistence in the environment and in organisms and solubility in fats, rather that water.

What are the health effects?
Wildlife offers the greatest evidence of the health effects of endocrine disruptors. However, some researchers point out that the human endocrine system is so similar to that in wildlife that they must conclude that humans have been affected as well.

Some of the suspected effects in humans are declining sperm counts; climbing rates of breast, testicular, and prostate cancer; and the increasing incidence of childhood hyperactivity and learning disorders.

Developing embryos and the very young are thought to be at the greatest risk because hormone activity guides the growth of a baby’s nervous and immune systems and programs organs and tissues, such as the liver, blood, kidneys, and muscles, so they will function properly. During early development, this regulation of growth and development is critical for a child.

According to In Harm’s Way, a report linking home-cleaning and industrial chemicals to developmental disabilities, including behavioral and learning disabilities, these chemicals are toxic to the developing child and can lead to hyperactivity, attention deficit disorder, lower intelligence, and motor skill impairment.

Among the chemicals evaluated in this groundbreaking study are

• lead, mercury, cadmium, and manganese;
• pesticides;
• dioxins and PCBs;
• solvents used in gasoline, paints, glues, and cleaning solutions; and
• nicotine and alcohol.

The report found that the blood chemistry of more than 80 percent of adults and 90 percent of children in the U. S. contains residues of one or more harmful pesticides.

“The urgency of this issue is underscored by the fact that between five and 10 percent of school children in America have learning disabilities and at least an equivalent amount have ADHD (attention deficit hyperactivity disorder),” said Dr. Ted Schettler, one of the report’s co-authors.

Other recent studies also link endocrine disruptors to developmental disabilities. For example, according to a study recounted in the August 2001 issue of the Journal of Occupational and Environmental Medicine, even low levels of ammonium perchlorate in drinking water may negatively affect fetuses and newborns.

The study reported that perchlorate—a chemical that is used in the manufacture of rockets, missiles, and fireworks, among other products—may be the reason behind higher-than-normal thyroid stimulating hormone (TSH) levels, which points to hypothyroidism, identified in some newborns in Arizona. And because perchlorate crosses the placenta, it has the potential to cause hypothyroidism in fetuses.

Thyroid hormone is essential for normal neurological function and development. Thyroid hormone deficiencies during fetal development or early infancy can lead to mental retardation, hearing loss, and speech problems. Children with thyroid deficiencies, even those with normal IQs, can have language comprehension problems, impaired learning and memory, and hyperactive behavior.

According to the Magic Foundation for Children’s Growth, clinical hypothyroidism is marked by a deficiency in the secretion of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). These hormones regulate metabolism and, in children, growth.

A child with hypothyroidism may have an enlarged thyroid gland, also known as a goiter. But more likely, the child will fail to grow, particularly in height. At the time of birth, however, the symptoms and signs of hypothyroidism are minimal or absent. But the foundation warns: “the lack of adequate thyroid hormone from birth until approximately two years of age is associated with varying degrees of permanent mental retardation.”

Dr. Ross Brechner, lead author of the study and chief of the Arizona Department of Health Services, found that mothers who drink water with detectable levels of perchlorate gave birth to babies with elevated levels of thyroid stimulating hormone (TSH), an indicator of the thyroid disorder known as hypothyroidism.

Scientists with the Arizona Department of Health Services’ Bureau of Health Statistics compared newborn screening data for 1,542 infants born in Yuma and Flagstaff between 1994 and 1997. Researchers chose these cities because Yuma draws all of its drinking water from the Colorado River below Lake Mead, which is contaminated by the rocket fuel ingredient, while Flagstaff does not use any water from the Colorado River. Also, the cities are comparable in size and socioeconomic status, and conventional water treatment plants serve both communities.

The study found that infants born in Yuma had significantly higher levels of hormones that stimulate the thyroid than those born in Flagstaff. This is indicative of thyroid disorder and hypothyroidism.

“(This study)suggests that even low-level perchlorate contamination of drinking water may be associated with adverse health effects in neonates and highlights the need for both further study and control of human low-level perchlorate exposure,” noted the study’s authors.

As much as 1,000 parts per billion (ppb) of perchlorate have been detected in the Las Vegas Wash, which feeds Lake Mead and the Colorado River. The chemical also has been detected in the river below the lake, which provides water to approximately 20 million people.

Currently, California is the only state that has a standard for perchlorate, which is set at 18 ppb. In 1999, the perchlorate level in Yuma’s treated water was 6ppb; the chemical was not detected in Flagstaff’s water.

These worrying trends are increasing. And the health of men, women, and children are increasingly at risk.


Worrying Trends in Male Health
Testicular cancer
Testicular cancer has increased by 55 percent between 1979 and 1991 in England and Wales. In 1991, these countries reported 1,137 new testicular-cancer cases. Since testicular cancer is mainly a disease of young men, the increased age of the population is not a reason for the increase of this cancer (as it is with many other cancers). It is thought that testicular cancer is initiated early in life, before birth.

Most researchers currently believe that testicular cancer results mainly from problems occurring during the development of testes while the individual is developing in the mother’s womb. These same researchers also hypothesize that hormone-disrupting chemicals are the cause of the increase.

Rates of increase measured in other countries include: an increase of 300 percent between 1945 and 1990 in Denmark and an annual increase of 2.3 percent in the Baltic countries. It is clear that rates of increase and incidence vary between different countries, with Finland having among the lowest incidence in Europe; men in Finland also seem to have the highest sperm counts in Europe.

Declining sperm counts

Many studies in recent years have suggested that sperm counts have reduced in the last 40 or so years. A major re-analysis of results from many studies concluded that sperm counts in Europe and the U.S. have been declining, with sperm counts in Europe having declined at 3.1 million per milliliter a year over the period 1971–1990.

One worrying trend that shows up in some studies is a correlation between year of birth and sperm count, with those born most recently having the lowest sperm counts.

A study of the sperm counts of Scottish men has shown that men born in the 1970s are producing 24 percent fewer sperm than are men born in the 1950s. However, a smaller study published at the same time suggests that sperm count has not declined in specimens collected in Toulouse, France, between 1977 and 1992. This is in contrast to earlier research in Paris, which did show a reduction; the authors suggest that this difference may be due to environmental differences.

Some recent studies have found even more startling results. A 2002 University of Missouri study found that men of lower economic status who live in rural Missouri have lower sperm counts than those of higher economic status who live in urban areas of the state, as well as men who live in other areas of the nation.

Researchers found that fertile men from Missouri’s Boone County have a mean sperm count of approximately 59 million per milliliter, compared to 103 million for men in New York, 99 million for men in Minnesota, and 81 million in Los Angeles. The Missouri men also tended to have much less vigorous sperm.

The study hypothesized that farms make up more than half of Boone County, so there may be a correlation between use of chemical fertilizers, herbicides, or pesticides and the results of the study.

Reproductive abnormalities
The reproductive abnormalities cryptorchidism (undescended testes) and hypospadias (urethra opening on the underside of the penis) may also be increasing, but the data on cryptorchidism is very limited, and on hypospadias there are problems of definition. However, clear increases in cryptorchidism have been observed in England, and increases in incidence of hypospadias have been observed in many countries. The incidence of hypospadias in Finland is lower than in other Scandinavian countries.

Are fewer male babies being born?
The ratio of male to female births has declined during the last 20–40 years in Denmark, the Netherlands, Sweden, Germany, Norway, Finland, Canada, and the U.S.; fewer male babies are being born than would normally be expected. It is not clear why this is happening, though environmental pollution and hormone-disrupting chemicals have been suggested as possible causes.

This hypothesis is supported by data from Seveso, Italy, where an industrial accident released large amounts of dioxin. In the eight years after the accident, 12 daughters and no sons were born to nine couples with the highest dioxin exposure.

Worrying Trends in Female Health
Breast cancer

Breast cancer incidence estimates show a one percent increase per year since the 1940s in the U.S., and a 50 percent increase in Denmark between 1945 and 1980. It has also increased in the United Kingdom over the last few decades. Research has suggested a link between breast cancer and exposure to hormone disrupting chemicals such as DDT, dioxin, and polychlorinated biphenyls (PCBs).

Early puberty
Research is suggesting that girls in the U.S. are now entering puberty earlier than has been found previously. The potential role of chemicals in this change is supported by a study, which compared the onset of puberty in children with differing levels of two persistent synthetic chemicals, PCBs and DDE in their mothers while they were pregnant.

Girls whose mothers had the highest levels, and who were therefore exposed to the highest amounts of DDE and PCBs in the womb, entered puberty 11 months earlier than girls with lower exposures. The onset of puberty in boys was not affected. Other studies have shown that girls who enter puberty earlier are at increased risk of breast cancer.

What is EPA doing?
Although regulatory policy concerning endocrine disruptors is still evolving, EPA has already taken regulatory action on some chemicals of concern through its pesticide and toxic substances programs.

Organochlorine compounds, such as PCBs and chlorinated pesticides, have long been problematic in the environment for a number of reasons, and many of them (such as DDT) induce endocrine activity. The term organochlorine refers to chemical compounds that have a chlorinated hydrocarbon structure, that is, they are formed from atoms of hydrogen, carbon, and chlorine.

Although their effect may be much weaker than the body’s natural hormones (like estrogens, androgens, and thyroid hormones), they are nonetheless suspected of disrupting the endocrine system, resulting in the aforementioned harmful effects like reproductive and developmental defects and certain cancers.

EPA has banned PCBs, dieldrin, DDT, chlordane, aldrin, kepone, mirex, endrin, and toxaphene. Organochlorine pesticides still registered for use in the U.S. include endosulfan, lindane, methoxychlor, dicofol, dienochlor, and heptachlor. However, their use is very restricted, and most are scheduled for priority pesticide re-registration review. They will likely be among the first compounds to be screened in EPA’s Endocrine Disruptor Screening Program.

This program will focus on providing methods and procedures to detect and characterize endocrine activity of pesticides, commercial chemicals, and environmental contaminants. The Safe Drinking Water Act of 1996 now authorizes EPA to screen for endocrine disruptors in drinking water sources.

For more information about this program or to obtain EPA’s latest information about endocrine disruptors, visit the agency’s Web site at www.epa.
gov/scipoly/oscpendo. Or call the Safe Drinking Water Hotline at (800) 426-4791.

Regulated Chemicals Known to Cause Endocrine Dysfunction


References

The Associated Press. 2002. “Sperm Quality Low in Farming Region.” “Study Finds Sperm Quality, Count Low in Farming Region; Researchers Cite Agricultural Chemicals.”

Chiffriller, Margaret. 2002. “Breast Cancer and the West Nile Virus.” Breastcancer.about.com/library/weekly/aa081400a.htm?terms=pesticide.

ExtoxNet. 2002. “Questions About Endocrine Disruptors.” ace.orst.edu/info/extoxnet/faqs/pesticide/endocrine.htm.

Keith, Lawrence H. 2002. “Protecting Children’s Health. Preventing Exposure to Endocrine Disruptors—A Teaching Aid.” Instant Refernce Sources, Inc. www.instantref.com.

Natural Resources Defense Council. 2002. “Toxic Chemicals and Health: Endocrine Disruptors.” www.nrdc.org/health/effects/qendoc.asp.

Porter, Warren P., James W. Jaeger, and Ian H. Carlson. 1999. “Endocrine, immune, and behavioral effects of aldicarb (carbamate) atrazine (triazine), and nitrate (fertilizer) mixtures at groundwater concentrations.” Toxicology and Industrial Health.

Schettler, Ted, Jill Stein, Fay Reich, Maria Valenti. 2000. In Harm’s Way, Toxic Threats to Child Development. Cambridge, MA: Greater Boston Physicians for Social Responsibility.

Shomon, Mary. 2002. “Pesticides Targeting West Nile-Carrying Mosquitos May be a Thyroid Danger.” Thyroid.about.com/library/weekly/aa072600a.htm?terms=pesticide.

U.S. Environmental Protection Agency. 2002. “Endocrine Disruptor Screening Program Web site.” Endocrine Disruptors. www.epa.gov/scipoly/oscpendo/index.htm

U.S. Environmental Protection Agency. 1998. Endocrine Disruptor Screening and Testing Advisory Committee Final Report. www.epa.gov.

Warhurst, A. Michael. 2000. “Introduction to Hormone Disrupting Chemicals.” Website.lineone.net/~mwarhurst/chemicals.html.

Why Files. 2002. “Endocrine Disruptors, Crossed wires? EPA tackles hormone disruptors.” Whyfiles.org/045env_hormone/main1.html

World Wildlife Fund Canada. 1997. “Reducing Your Risk.” Wwf.ca/satellite/reduce-risk/.

About The Author
Kathy Jesperson has been writing technical articles for the National Environmental Services Center for more than 10 years. Her background in biological science really helps when she writes articles about the health effects of certain drinking water contaminants.