Questions about Endocrine Disruptors

Here are some of the most frequently asked questions about the endocrine system and endocrine disruptors:

The endocrine system is composed of ductless glands that secret hormones into the blood stream to act at distant sites. Together with the nervous system, the endocrine system is responsible for the integration of many different processes which allow complicated organisms to function as a unit (maintain homeostasis). What does the endocrine system look like?

Hormones can be proteins, polypeptides, amino acids, or steroids. The most well known hormones are the sex steroids estrogen, produced in the ovaries, and testosterone, produced in the testes. Estrogen and testosterone are also produced in the adrenal glands of both sexes. Other hormones include thyroxin, produced in the thyroid, and insulin, produced in the pancreas. The pituitary and hypothalamus in the brain release a variety of hormones that affect other organs, including the sex glands.

From the blood, hormones interact with cells by binding to special proteins called receptors. The binding is specific, like a key in a lock. When enough binding sites are occupied, then a message is passed on to the target cell nucleus unmasking genetic information which results in physiological reactions ultimately responsible for stimulating or regulating proper metabolism, development, growth, reproduction, and behavior. For example, in women estrogen works in this way to control the menstrual cycle, and in men testosterone controls sperm production. Hormones are released into the blood in very small amounts. Their levels are controlled by the rate of release, and the rate of degradation, usually by the liver or kidneys. Timing of hormone release is often critical for normal function. This is especially true during fetal development. Precise hormone control is important, as too much or too little at the wrong time can result in dysfunction of one or several body systems.

In laboratory studies, glands can be removed or hormones can be administered to study the effect on animals, such as rats or mice. Human diseases or inherited disorders, which involve hormone imbalance, are studied to better understand the resulting dysfunction and to develop treatments. For example, it is known that men produce small amounts of estrogen and women produce small amounts of testosterone. Too much estrogen in a man results in female characteristics such as enlarged breasts. Too much testosterone in a woman results in male characteristics such as facial hair. Hormone imbalance can be life threatening, as with insulin and diabetes. Estrogen imbalance has been implicated in certain forms of breast cancer.

There are chemical substances, sometimes called environmental estrogens, both from natural sources and man made, that if present in the body at the right concentration and at the right time, can adversely effect hormone balance or disrupt normal function in the organs that hormones regulate (modulate?). By EPA’s working definition, endocrine disruptors "interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body that are responsible for the maintenance of homeostasis (normal cell metabolism), reproduction, development, and/or behavior." Many endocrine disruptors are thought to mimic hormones. They have chemical properties similar to hormones that allows binding to hormone specific receptors on the cells of target organs. However, endocrine disruptor chemistry varies greatly, as does potency -- the effectiveness in binding and "turning on" the response. Most endocrine disruptors have very low potency as their chemistry is significantly different from the hormones they mimic. Lower potency means that a greater amount of endocrine disruptor is required to elicit the same response of the hormone they mimic. In addition to potency, the potential for a hormone-like effect depends on dose. For all known endocrine disruptors there is some dose, below which there will be no effect. At doses slightly above this threshold some endocrine disruptors elicit a beneficial effect, whereas at higher doses the effect is adverse (harmful). Please see EXTOXNET FAQs Endocrine Disruptors - Phytoestrogens.

Drugs have been specifically designed to treat hormone imbalance in humans. Diethylstilbesterol (DES), a drug with strong estrogenic properties administered to pregnant women until 1971 to prevent miscarriages, is a tragic example. Female children of mothers who took DES during pregnancy have a higher incidence of certain forms of ovarian and vaginal cancer. However, there are many drugs that mimic or otherwise affect hormone balance which are important to modern medicine. Other man made chemicals, with unintentional hormone-like activity include: pesticides such as DDT, vinclozolin, endosulfan, toxaphene, dieldrin, and DBCP, and industrial chemicals and byproducts such as polychlorinated biphenyls (PCBs), dioxins, and phenols. Some of these phenols are breakdown products of surfactants, found in soaps and detergents. Also implicated are heavy metals, plastics, cosmetics, textiles, paints, lubricants. Sewage treatment effluent may contain a variety of natural and man made endocrine disruptors, including natural hormones from animal and human waste.

Currently, there are no standard tests to determine if a chemical is an endocrine disruptor. However, both the Clean Water Act and the Food Quality Protection Act require the EPA to develop test methods by 1999. As many endocrine disruptors are thought to affect sex hormone function, and therefore reproduction, the findings in multigeneration animal studies, currently required for pesticide registration by EPA, can provide strong evidence of the potential for endocrine disruption.

There are natural chemicals in plants that have hormone-like activity. These chemicals, mostly phytoestrogens, are found in high levels in broccoli, cauliflower, soybeans, carrots, oats, rice, onions, legumes, apples, potatoes, beer, and coffee. Most phytoestrogens have weak activity (low potency) and people who consume diets rich in these substances may have a reduced risk of developing some hormone related diseases. However, the actual health risk or benefit of a diet rich in plant hormones is largely unknown. Some researchers argue that dietary consumption of plant hormones dwarfs the potential exposure from man made sources. Please see EXTOXNET -Phytoestrogens.

Most scientists do not believe that hormones cause or initiate cancer, but some hormones may promote cancer growth. This promotion may result in cancer that appears at a younger age than expected, or in a cancer that grows at a faster rate. These findings suggest that chemicals that act like hormones may also promote cancers. In women, estrogen is thought to play a role in the promotion of some forms of breast cancer. Based on a single epidemiological study, the presence of DDE, a metabolite of DDT, has been associated with increased risk of breast cancer. However, more recent studies provide strong evidence that there is no relationship between DDE exposure and breast cancer. Other studies suggest that specific phytoestrogens and certain PCBs and dioxins can block estrogen from promoting some forms of breast cancer. Please see EXTOXNET TIB - Carcinogenesis.

Recent studies of wildlife, including alligators, birds, and fish, have investigated the relationship between chemical exposure and reproductive problems. Many of these studies have shown that exposure to high doses can result in malformed reproductive organs, consistent with sex hormone imbalance at a critical stage of fetal development. Studies where very high doses of dioxin were fed directly to pregnant rats show effects on sexual development, sperm production, and sexual behavior in male pups. Directly feeding very high doses of DDT to rats has also shown adverse effects on sexual development. The dramatic results of these high dose studies has lead to speculation by toxicologists that the risk to reproductive success, associated with exposure to much lower levels of some chemicals in the environment, may be unacceptable.

In humans, a recent epidemiology study suggesting that sperm counts have declined by almost 50% over the past 50 years, and that this decline is associated with increased exposure to synthethic chemicals, has made the headlines. Other epidemiologists who have examined the same data do not reach this conclusion. Direct evidence of chemical effects on male fertility has been demonstrated in the study of workers involved in the manufacture of the older pesticides dibromochloropropane and leptophos (neither currently registered in the US). Again, such direct evidence is the result of exposure to very high doses.

The number of chemicals that have been implicated as potential endocrine disruptors is substantial. There are many opportunities for exposure to these chemicals, both singly and as mixtures, albeit usually at very low levels. There are a variety of adverse health effects related to endocrine system dysfunction. This is not surprising, as the basic function of the endocrine system, in addition to controlling sex characteristics and reproductive functions and responding to perceived hostility (adrenaline release), is to maintain homeostasis (even keel) among the diverse functions of the body. Of specific concern is that a single relatively small dose at the right time during pregnancy can effect the fetus in ways that will not show until adulthood, and may impact the next generation due to decreased reproductive success. Also of concern is that these chemicals have been implicated in the increased incidence of certain cancers, including breast cancer.

So what is the risk? What is known with an acceptable degree of certainty is that high doses of some of these chemicals can cause adverse health effects in humans and animals. As the adverse health effects observed in these studies are biologically plausible there is reason for concern. Significant research and biological plausibility also support that responses to endocrine disruptors are dose/potency related: there is a no-effect threshold. In addition, low doses of some substances may result in beneficial effects. Current information on likely levels of exposure does not indicate a significant risk of adverse health effects to humans or wildlife. However, EPA has identified "Hot Spots" where adverse effects to wildlife have been observed. Human epidemiology studies which have examined the relationship between the manufacture and use of endocrine disruptors and health effects are far from conclusive. However, as the findings in these studies do not allow the identification and contribution of all risk factors, endocrine disruptors cannot be ruled out. Consequently, EPA and other federal and state agencies will continue to provide substantial funding for research to better understand the risks posed by endocrine disruptors.

Here are some very informative external links that pertain to the endocrine system and endocrine disruptors:

Extoxnet FAQHome
Extoxnet Pesticides

This Page prepared by the EXTOXNET FAQ Team. , January 1998