Environmental estrogens

The United States Environmental Protection Agency (EPA ) defines an environmental endocrine disruptor—the term the Agency uses for environmental estrogens—as "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body that are responsible for the maintenance of homeostasis , reproduction, development, and/or behavior." Dr. Theo Colborn, a zoologist and senior scientist with the World Wildlife Fund , and the person most credited with raising national awareness of the issue, describes these chemicals as "hand-me-down poisons" that are passed from mothers to offspring and may be linked to a wide range of adverse effects, including low sperm counts, infertility, genital deformities, breast and prostate cancer , neurological disorders in children such as hyperactivity and attention deficits, and developmental and reproductive disorders in wildlife . Colborn discusses these effects in her 1996 book, Our Stolen Future —co-authored with Dianne Dumanoski and John Peterson Myers—which asks: "Are we threatening our fertility, intelligence, and survival?" Some other names used for the same class of chemicals are hormone disruptors, estrogen mimics, endocrine disrupting chemicals, and endocrine modulators.

While EPA takes the position that it is "aware of and concerned" about data indicating that exposure to Environmental endocrine disruptors may cause adverse impacts on human health and the environment , the Agency at present does not consider endocrine disruption to be "an adverse endpoint per se." Rather, it is "a mode or mechanism of action potentially leading to other outcomes"—such as the health effects Colborn described drawing from extensive research of numerous scientists—but, in EPA's view, the link to human health effects remains an unproven hypothesis. For Colborn and a significant number of other scientists, however, enough is known to support prompt and far-reaching action to reduce exposures from these chemicals and myriad products that are manufactured using them. Foods, plastic packaging, and pesticides are among the sources of exposure Colborn raises concerns about in her book.

Ultimately, the environmental estrogens issue is about whether these chemicals are present in the environment at high enough levels to disrupt the normal functioning of wildlife and human endocrine systems and thereby cause harmful effects. The endocrine system is one of at least three important regulatory systems in humans and other animals (the nervous and immune systems are the other two) and includes such endocrine glands as the pituitary, thyroid, pancreas, adrenal, and the male and female gonads, or testes and ovaries. These glands secrete hormones into the bloodstream where they travel in very small concentrations and bind to specific sites called "cell receptors" in target tissues and organs. The hormones affect development, reproduction, and other bodily functions. The term "endocrine disruptors" includes not only estrogens but also antiandrogens and other agents that act on the endocrine system.

The question of whether environmental endocrine disruptors may be causing effects in humans has arisen over the past decade based on a growing body of evidence about effects in wildlife exposed to dichlorodiphenyl-trichlorethane (DDT), polychlorinated biphenyls (PCBs), and other chemicals. For instance, field studies have proven that tributyltin (TBT), which is used as an antifouling paint on ships, can cause "imposex" in female snails, which are now commonly found with male genitalia, including a penis and vas deferens, the sperm-transporting tube. TBT has also been shown to cause decreased egg production by the periwinkle (Littorina littorea ). As early as 1985, concerns arose among scientists and the public in the United Kingdom over the effects of synthetic estrogens from birth control pills entering rivers, a concern that was heightened when anglers reported catching fish with both male and female characteristics. Other studies have found Great Lakes salmon to invariably have thyroids that were abnormal in appearance, even when there were no overt goiters. Herring gulls (Larus argentatus ) throughout the Great Lakes have also been found with enlarged thyroids. In the case of the salmon and gulls, no agent has been determined to be causing these effects. But other studies have linked DDT exposure in the Great Lakes to eggshell thinning and breakage among bald eagles and other birds. In Lake Apopka, Florida, male alligators (Alligator mississippiensis ) exposed to a mixture of dicofol, DDT, and dichlorodiphenyldichloroethylene (DDE) have been "demasculinized," with phalluses one-half to one-fourth the normal size. Red-eared turtles (Trachemys scripta ) in the lake have also been demasculinized. One 1988 study reported that four of 15 female black bears (Ursus americanus ) and one of four female brown bears (Ursus arctos ) had, to varying degrees, male sex organs. These and nearly 300 other peer-reviewed studies have led EPA—in conjunction with the multi-agency White House Committee on Environment and Natural Resources—to develop a "framework for plan ning" and an extensive research agenda to answer questions about the effects of endocrine disruptors. The goal is to better understand the potential effects of such chemicals on human beings before implementing regulatory actions.

The federal research agenda has been evolving through a series of workshops. As early as 1979, the National Institute of Environmental Health Sciences (NIEHS), based in Research Triangle Park, North Carolina, held an "Estrogens in the Environment" conference to evaluate the chemical properties and diverse structures among environmental estrogens. NIEHS held a second conference in 1985 that addressed numerous potential toxicological and biological effects from exposure to these chemicals. NIEHS's third conference, held in 1994, focused on detrimental effects in wildlife. At an April 1995 EPA-sponsored workshop on "Research Needs for the Risk Assessment of Health and Environmental Effects of Endocrine Disruptors," a number of critical research questions were discussed: What do we know about the carcinogenic effects of endocrine-disrupting agents in humans and wildlife? What are the research needs in this area, including the highest priority research needs? Similar questions were discussed for reproductive effects, neurological effects, immunological effects, and a variety of risk assessment issues. Drawing on the preceding conferences and workshops, in February 1997 EPA issued a Special Report on Environmental Endocrine Disruption: An Effects Assessment and Analysis that recommended key research needs to better understand how environmental endocrine disruptors may be causing the variety of specific effects in human beings and wildlife hypothesized by some scientists. For instance, male reproductive research should include tests that evaluate both the quantity and quality of sperm produced. Furthermore, when testing the endocrine-disrupting potential of chemicals, it is important to test for both estrogenic and antiandrogenic activity because new data suggest that it is possible the latter—antiandrogenic activity—not estrogenic activity, is causing male reproductive effects. In the area of ecological research, EPA's special report highlighted the need for research on such issues as what chemicals or class of chemicals can be considered genuine endocrine disruptors and what dose is needed to cause an effect.

Even before environmental estrogens received a place on the federal environmental agenda as a priority concern, Colborn and other scientists first met in July 1991 in Racine, Wisconsin, to discuss their misgivings about the prevalence of estrogenic chemicals in the environment. From that meeting came the landmark "Wingspread Consensus Statement" of 21 leading researchers. The statement asserted that the scientists were certain that a large number of human-made chemicals that have been released into the environment, as well as a few natural ones, "have the potential to disrupt the endocrine system of animals, including humans," and that many wildlife populations are already affected by these chemicals. Furthermore, the scientists expressed certainty that the effects may be entirely different in the embryo, fetus, or perinatal organisms than in the adult; that effects are more often manifested in offspring than in exposed parents; that the timing of exposure in the developing organism is crucial; and that, while embryonic development is the critical exposure period, "obvious manifestations may not occur until maturity." Besides these and other "certain" conclusions, the scientists estimated with confidence that "some of the developmental impairments reported in humans today are seen in adult offspring of parents exposed to synthetic hormone disruptors (agonists and antagonists) released in the environment" and that "unless the environmental load of synthetic hormone disruptors is abated and controlled, large scale dysfunction at the population level is possible." The Wingspread Statement included numerous other consensus views on what models predict and the judgment of the group on the need for much greater research and a comprehensive inventory of these chemicals.

The Food Quality Protection Act of 1996 (FQPA) and the Safe Drinking Water Act Amendments of 1996 require EPA to develop a screening program to determine whether pesticides or other substances cause effects in humans similar to effects produced by naturally occurring estrogens and other endocrine effects. The FQPA requires pesticide registrants to test their products for such effects and submit reports, and it requires that registrations be suspended if registrants fail to comply. Besides the EPA screening program, the United Nations Environment Programme is pursuing a multinational effort to manage "persistent organic pollutants," including DDT and PCBs, which, though banned in the United States, are still used elsewhere and can persist in the environment and be transported long-distance. In February 1997, Illinois became the first state to issue a strategy for endocrine disruptors that requires every Illinois EPA program to assess its current activities affecting these chemicals and to begin monitoring a list of known, probable, and suspected chemicals in case further action is needed in the future.

[David Clarke ]

RESOURCES

BOOKS

Colborn, T., D. Dumanoski, and J. P. Myers. Our Stolen Future. New York: Penguin Books, 1996.

"Estrogens in the Environment." Environmental Health Perspectives Supplements 3, supplement 7. North Carolina: Research Triangle Park, 1995.

National Science and Technology Council. Committee on Environment and Natural Resources. The Health and Ecological Effects of Endocrine Disrupting Chemicals, A Framework for Planning. Washington, D.C., 1996.

U.S. Environmental Protection Agency. Special Report on Environmental Endocrine Disruption: An Effects Assessment and Analysis. (EPA/630/R-96/012). Washington, D.C.: GPO, 1997.