Have you been wondering what the talk about endocrine disruptors in the environment is about? Disruptions in the endocrine system and hormone levels it produces can lead to cancers and irregularities in the reproductive system. Some scientists propose that hormones can induce cancers by directly altering genetic material (DNA) or can induce cancers indirectly through cellular activities. Many researchers think that hormone imbalance can lead to increased rates of cancers and reduced fertility. Scientists are also developing genetic biomarkers for early detection of cancers, as well as new therapies and prevention
A variety of chemicals are known to disrupt the endocrine systems of animals in laboratory studies, and compelling evidence has accumulated that endocrine systems of certain fish and wildlife have been affected by chemical contaminants, resulting in developmental abnormalities and reproductive impairment. However, the relationship of human diseases of the endocrine system and exposure to environmental contaminants is poorly understood and scientifically controversial.
Because of the potentially serious consequences of human exposure to endocrine disrupting chemicals, Congress included specific language on endocrine disruption in the Food Quality Protection Act and amended Safe Drinking Water Act in 1996. The former mandated that EPA develop an endocrine disruptor screening program, whereas the latter authorizes EPA to screen endocrine disruptors found in drinking water sources.
Endocrine disruptors are chemicals which interfere with endocrine system function. An endocrine system is found in nearly all animals, including mammals, non-mammalian vertebrates (like fish, amphibians, reptiles, and birds), and invertebrates (like snails, lobsters, insects, and other species). The endocrine system consists of glands and the hormones they produce that guide the development, growth, reproduction, and behavior of human beings and animals. Some of the endocrine glands are the pituitary, thyroid, and adrenal glands, the female ovaries and male testes. Hormones are biochemicals, produced by endocrine glands, that travel through the bloodstream and cause responses in other parts of the body.
Many industrial and environmental chemicals mimic, antagonize or indirectly alter the activity of steroid hormones. Classes of herbicides, fungicides, insecticides, nematocides, and industrial chemicals, such as dioxins, polychlorinated biphenyls (PCBs) and other chlorinated chemicals, such as octylphenol or bisphenol A, may be weakly estrogenic, antiestrogenic, antiandrogenic, or may affect thyroid hormone functioning. These chemicals, known as "endocrine disruptors", may bind to estrogen or other hormone receptors, either imitating the action of the hormone or blocking its activity. By interfering with the normal functioning of receptors, these chemicals can perturb the growth and development in the exposed organism. Other chemicals, i.e. some phthalate esters, glycol ethers and "peroxisome proliferators," appear to be endocrine disruptors by indirectly altering steroid hormone activity at a post receptor site of action.
Many recently published studies indicate that various species of wildlife (birds, reptiles, etc.) have been exposed to endocrine-disrupting chemicals in their habitats and are showing signs of changes in reproductive function and behavior. Taken together, the wildlife data paint a picture of harmful pollution effects on natural habitats that may eventually lead to the decline of various species of animals. Morphological changes in sexual organs, changes in mating behavior and offspring rearing behaviors, smaller litter sizes, and evidence of declines in reproductive capacity all signal alarm for these affected animal populations.
In addition to these natural "sentinel type" studies there are also extensive studies using rodent models showing similar toxicity to the reproductive, immune and nervous systems as a result of prenatal exposures to endocrine disruptors such as tetrachlorodibenzo-p-dioxin (TCDD), Diethylstilbestrol (DES, an estrogenic therapeutic) and various pesticides and industrial chemicals.
Estrogens are a group of chemically similar hormones responsible for female sexual development; estrogen is produced mainly by the ovaries, but also by the adrenal glands. Androgens are substances, usually hormones, responsible for male sex characteristics. Testosterone, the sex hormone produced by the testicles, is an androgen. The thyroid gland secretes two main hormones, thyroxine and triiodothyronine, into the bloodstream. These hormones stimulate all the cells in the body.
Hormones can produce both positive and negative effects. For example, some types of breast cancer are exacerbated by estrogen, but studies also indicate that estrogen has a protective effect in combating heart disease and osteoporosis-related fractures in older women.
Disruption of this complex system can occur in various ways. For example, some chemicals may mimic a natural hormone,"fooling" the body into over-responding to the stimulus or responding at inappropriate times. Other chemicals may block the effects of a hormone in parts of the body normally sensitive to it. Still others may directly stimulate or inhibit the endocrine system, causing overproduction or underproduction of hormones. Certain drugs are used to intentionally cause some of these effects, such as birth control pills.
An example of the devastating consequences of exposure of developing animals, including humans, to endocrine disruptors is the case of the potent drug diethylstilbestrol (DES), a synthetic estrogen. Medical doctors prescribed DES to as many as five million pregnant women to block spontaneous abortion prior to DES being banned in the early 1970's. DES was prescribed in the mistaken belief that it would prevent miscarriage and promote fetal growth. It was discovered after the children went through puberty that DES affected the development of the reproductive system and caused vaginal cancer. Since then, Congress has improved how drugs and other chemicals are evaluated and regulated requiring that an endocrine disruptor screening program be established is a recent and significant step.
Polychlorinated biphenyl (PCBs) are synthetic lipid-like compounds once used as insulating materials in transformers and capacitors (banned in US in 1970s) that are persistent in the environment. Indeed, residues of these compounds can be measured in people around the world. Exposure currently is via eating contaminated fish. Jacobson (R01ES05843) has been following a population of children born to mothers who consumed large amounts of fish and thereby had exposure to PCBs during pregnancy. They measured PCB levels in umbilical cord blood and maternal blood and milk samples and correlated these values with behavior, achievement and reading mastery tests (when appropriate). They showed that in utero exposure to PCBs was associated with poorer short term memory during infancy and childhood and deficits in intellectual ability (6.2 deficits in IQ), short and long term memory and focused and sustained attention in school age children (to 11 yrs of age).
Since PCB exposure has been linked to reduced concentrations of thyroid hormones (needed to stimulate neuronal and glial proliferation and differentiation) the NIEHS is funding two epidemiological studies (Jacobson; R01ES08327 and Hertz-Picciotto; R01ES08316) to confirm and determine the role of thyroid hormone alterations in the PCB neurotoxicity. Similarly, Zoeller (R01ESO8333) and Peterson (R01ES06806) are using animal studies to examine the effects of PCB exposure during development. Zoeller has shown that PCBs can exert permanent effects on the thyroid hormones and brain development. Developmental exposure to a commercial mixture of PCBs causes elevation of serum thyroid hormones and a decrease in thyroid hormone receptor levels in the hippocampus, the area responsible for specific kinds of learning. This combination of animal- mechanistic studies with human epidemiologic studies should provide the data needed to protect the public health from this type of endocrine disruptors.
Bisphenol A, one of the top 50 chemicals produced in the U.S. (71.6 billion pounds) is a monomer utilized in the manufacture of epoxy resins that are used to line metal food and drink cans as well as in dental sealants. Studies by Adler (R01ES08301), vom Saal (R01ES08293) and Murray (R01ES08314) have shown that bisphenol A also has weak estrogenic activity in vitro and in animal studies. Vom Saal has shown that Bisphenol A at maternal doses of 2 or 20 g/kg, in the range of human exposures, stimulated enlargement of the prostates (20-30%) of male mice, an effect that persisted into adulthood. The public health significance of these data is that the enlarged prostates may lead to prostate cancer - a form of a cancer that has been increasing in the human population.
The Bisphenol A exposure during development also significantly reduced daily sperm production per gram of adult testis, increased preputial gland weight, all of which could affect fertility. Of additional importance is that these effects occurred at low relevant concentrations, i.e. concentrations that humans could be exposed to, and are concentrations that are orders of magnitude lower than the NOEL (no observed effect level) estimated for bisphenol A from typical high dose toxicity studies. Thus, vom Saal has shown that testing of endocrine disrupting chemicals must be done over a wide range of concentrations down to relevant exposure paradigms and not only high doses with linear extrapolation to low relevant doses.
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 harmful effects like reproductive and developmental defects and certain cancers. EPA has banned PCB's, dieldrin, DDT, chlordane, aldrin, kepone, mirex, endrin, and toxaphene. Organochlorine pesticides still registered for use in the United States 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 the Endocrine Disruptor Screening Program.
Endocrine Disruptors Research Initiative, U.S. EPA Office of Research and Development, and its "Related Sites" page
Food Quality Protection Act (FQPA), U.S. EPA Office of Pesticide Programs
Hormonally Active Agents in the Environment, a report from the National Academy of Sciences
National Institute of Environmental Health Sciences, Endocrine Disruptors (Use the search function to locate additional items at this site)
Office of Science and Technology Policy (Scroll down for information on Endocrine Disruptors)
Organization for Economic and Cooperative Development (OECD) Endocrine Disrupters Assessment Activities
Review of the EPA's Proposed Environmental Endocrine Disruptor Screening Program Science Advisory Board Report. EPA Document No. EPA-SAB-ED-99-013, July 1999. (PDF File)
Science Policy Council Interim Position On Environmental Endocrine Disruption. EPA Document No. EPA/630/R-96/012, February 1997.