Purpose: SETAC is a professional society with worldwide membership from academia, government, business, and nongovernmental organizations. TIPs provide a credible and balanced scientific discussion of important environmental issues.
Endocrine Disruptors and Modulators
What is an endocrine disruptor and an endocrine modulator?
Humans and wildlife must regulate how their bodies function to remain healthy in an ever-changing environment. They do this through a complicated exchange between their nervous and endocrine systems. The endocrine systems in humans and wildlife are similar in that they are made up of internal glands that manufacture and secrete hormones. Hormones are chemical messengers that move internally, start or stop various functions, and are important in determining sleep/wake cycles, stimulating or stopping growth, or regulating blood pressure. Some of the most familiar hormones in humans or wildlife are those that help determine male and female gender, as well as control the onset of puberty, maturation, and reproduction. An endocrine disruptor is a chemical substance that interferes with, or has adverse effects on, the production, distribution, or function of these same hormones. Clearly, interference with or damage of hormones could have major impacts on the health and reproductive system of humans and wildlife, although not all of the changes would necessarily be detrimental. Sometimes these chemical substances are termed endocrine modulators to differentiate the more subtle changes they elicit, compared to substances that disrupt the endocrine system and cause more dramatic effects.
What is the endocrine disruption hypothesis?
Synthetic, and some naturally occurring, chemical substances in the environment are disrupting the normal functions of the endocrine system and its hormones in humans and wildlife.
This hypothesis first received significant attention in the 1980’s but has been discussed much more widely in the public press during the past five years. Development of female characteristics in males has been observed in colony-nesting seabirds from a few areas and is thought by some to be caused by continued exposure to residues of the chemical pesticide DDT. The impacted birds may not mate or nest readily, and if this occurs on a widespread basis, wildlife populations might decline. Similar scenarios of chemical exposure and accumulation have been put forward to explain apparent changes in human sperm quality and quantity or increases in some types of breast, prostate, and testicular cancers. However, whether environmental chemicals are responsible for these changes is controversial, because there are many other factors that influence fertility and cancer rates in humans.
How do chemicals interfere with hormones?
There are a number of ways in which synthetic or naturally occurring chemical substances can affect the endocrine system. A chemical may harm the glands that make hormones, either by killing the cells or by making them nonfunctional so no hormones are produced. Sometimes, a chemical might mimic a hormone so the body thinks that it has too much of that hormone. Then the body can overreact, either prematurely shutting down its own hormone production or producing an exaggerated response. Chemicals producing this exaggerated response are called agonists. In contrast, antagonists are chemicals that confuse the body so either it doesn’t respond correctly or does so only in a limited way. In other cases, chemicals might cause hormones to be degraded faster than usual, so that they are unable to perform their intended function adequately. Regardless of the situation, having too much or too little of the hormones it needs may cause the endocrine system to function inappropriately.
What are potential endocrine-disrupting chemicals?
Endocrine-disrupting chemicals may be either synthetic (man-made) or naturally occurring substances. Examples of synthetic chemical substances that potentially could disrupt the endocrine system are chlorinated pesticides (such as DDT and its related compounds) and similar substances like PCBs. Likewise, dioxins and other similar chemicals may be endocrine disruptors. Alkylphenols and phthalates are industrial chemicals used to make detergents, and they may affect the endocrine system at certain doses. In nature, plants such as soybeans, carrots, and grains produce phytoestrogens that can mimic certain hormones. As wood is processed to make paper and pulp, the effluents from this process can contain some of these same phytoestrogens.
In contrast, some chemicals also are used therapeutically as human and wildlife contraceptives and for important human hormone replacement therapies. These are primarily synthetic forms of reproductive hormones that are used for birth control, treatment of osteoporosis, and to reduce the potential for heart attacks. However, these beneficial chemicals might cause problems to fishes and wildlife as they are discarded or excreted and become part of municipal or industrial effluents entering the environment. Estradiol is an important hormone for regulating reproductive systems and it, too, is found in the environment, where it may lead to changes in the endocrine function of fishes and other aquatic organisms.
What is the evidence for environmental endocrine disruptors?
Humans: In the late 1940s and in the 1950s, some pregnant women received prescriptions for diethylstilbestrol (DES), a synthetic hormone that reduced the chance of miscarriage. There were no apparent side effects in these women, but their children experienced serious reproductive abnormalities upon maturation. In women, these included cancer, endometriosis, and breast cancer, and men experienced undescended testicles. While DES is not a chemical of environmental concern, it illustrates two important points:
- Embryos and fetuses can be more sensitive to the impacts of chemicals than children or adults; and
- The ultimate effects of endocrine disruption might not be seen until later in life or even until the next generation.
Some studies have suggested that human sperm counts may have been decreasing during the past several decades. While there is no direct evidence that environmental chemicals have caused this and some scientists argue that the studies were flawed, the possibility remains that endocrine disruptors could be the cause. Likewise, increasing numbers of breast, prostate, and other cancers may be related to endocrine disruption but no clear linkage has yet been established.
Wildlife: Wildlife may be exposed to endocrine disruptors in their natural environments. In addition to the cases of feminization of sea birds, alligators in Lake Apopka, Florida, are thought to have been affected by these types of chemical substances. Alligators living in the lake were exposed to DDT following a spill from a nearby chemical plant in 1980. Scientists subsequently found that the alligators had problems reproducing properly, because of changes in male reproductive organs. Fishes, snails, and other aquatic life appear to be affected by endocrine disruptors as well. Marine snails exposed to tributyl tin, a component of antifouling paint used on boats, experienced changes in their reproductive organs. Trout from the Great Lakes and other areas contaminated with PCBs and dioxins did not develop properly, while various fishes that lived near some sewage treatment outfalls became feminized or hermaphrodites (i.e. having both male and female reproductive organs).
These examples indicate that environmental contaminants have the potential to interfere with the proper functioning of hormones in humans and wildlife. However, it is not yet clear whether exposures to the often low concentrations of these chemical substances in the environment are sufficient to result in harmful effects.
What questions remain?
Despite the uncertainty about whether low-concentration environmental exposures are harmful, strong evidence exists today that some wildlife species in highly contaminated locations exhibit abnormal behavior, development, and reproduction, which may be caused by exposure to endocrine-disrupting chemicals. The DES case suggests that detrimental effects also are possible in humans, given a sufficient amount of exposure at an early stage of development. Building on considerable basic knowledge of animal and plant biology, the scientific community currently is expending considerable effort to find and document clear cause-and-effect linkages between low-concentration exposure to chemicals and significant changes in biological systems. Although there are no clear-cut examples of endocrine disruption in humans as a result of exposure to environmental contaminants, concerns over wildlife health remain high. In an effort to reduce potential future risk to humans and wildlife, efforts are now underway to develop new methods and techniques for screening new chemicals and some existing chemicals for endocrine-disruption properties. Currently, SETAC members are involved in all aspects of the endocrine disruption/modulation issue, from conducting fundamental toxicological research, to applying risk assessment methodologies to evaluate potential impacts, to explaining the science to the public, regulators, industry, and nongovernmental organizations. SETAC has been and will continue to be one of the important forums for scientific discussions about endocrine disruption and modulation.
Where is there more information about endocrine disruptors?
Several workshops over the past few years have produced summaries of what is known about endocrine disruptors. These include the following:
DeFur PL, M Crane, C Ingersoll, and L Tattersfield, eds. Endocrine Disruption in Invertebrates: Endocrinology, Testing, and Assessment. SETAC, Pensacola, FL. 1999.
Di Giulio RT and DE Tillitt. Reproductive and Developmental Effects of Contaminants in Oviparous Vertebrates. SETAC, Pensacola, FL. 1999.
European Commission. Proceedings of European Workshop on the Impact of Endocrine Disruptors on Human Health and Wildlife. (EUR 17549). 1996.
Kendall RJ, RL Dickerson, WA Suk, and JP Giesy, eds. Principles and Processes for Evaluating Endocrine Modulation in Wildlife. SETAC, Pensacola, FL. 1998.
National Academy of Sciences. Hormonally Active Agents in the Environment.
National Academy Press, Washington, DC. 2000.
Rolland RM, M Gilbertson, and RE Peterson, eds. Chemically-induced Alterations in the Functional Development and Reproduction of Fishes. SETAC, Pensacola, FL. 1997.
Tattersfield L, et al. Endocrine Modulators and Wildlife: Assessment and Testing. SETAC Europe, Brussels, Belgium. 1997.
US Environmental Protection Agency. Special Report on Endocrine Disruption: An Effects Assessment Analysis. (EPA/630/R-96/012). 1997.
US Environmental Protection Agency Science Advisory Board. Review of the EPA’s Proposed Environmental Endocrine Disruptor Screening Program. EPA/SAB EC-99-013. 1999.
Other TIPs are available free of charge from the SETAC offices and at www.setac.org
Ecological Risk Assessment, 1997
Sound Science, 1999
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Society of Environmental Toxicology and Chemistry (SETAC). 2000. Endocrine Disruptors and Modulators Technical Issue Paper. Pensacola, FL, USA.
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