ENDOCRINE DISRUPTORS AND OTHER SCARY THINGS BY CANDICE DOUGLAS, MICHAEL MOORE and ROSALIND SCHOOF PTI Environmental Protecting the environment is a complex and often controversial issue. That is why the application of scientific principles and the appropriate use of scientific research are critical when evaluating real risks versus perceived risks from exposure to chemicals. The great apple scare of 1989 over the use of the pesticide Alar is a prime example of how misinterpreting scientific research can result in huge repercussions. The apple industry lost millions of dollars, Alar was banned and the apple growers filed a $200 million lawsuit against the organizations that initiated the scare. How estrogen influences organisms. When the dust finally settled, we learned that the scientific information used to support this huge scare was based on the inaccurate analyses of research on mice conducted in 1977. In addition, the analyses falsely interpreted animal results to predict human cancer risk. For the environment, the real tragedy is that Alar was banned and replaced with potentially more toxic chemicals. The Alar situation clearly demonstrates the importance of understanding and correctly interpreting scientific data when evaluating the effects of chemicals on human health and the environment. Today, environmental scientists and regulators, as well as the media and environmental groups are focusing significant attention and resources on "endocrine disruptors," chemicals suspected of interfering with the normal functioning of sex hormones in humans and wildlife. For example, certain synthetic chemicals mimic the action of the female hormone, estrogen, thus disrupting the normal functioning of sex hormones. Scientists refer to these synthetic chemicals as "xenoestrogens" (pronounced zee-no-estrogens). To avoid the mistakes made with the apple scare of 1989, it is important to take a balanced and logical approach to evaluating the potential risks associated with exposure to xenoestrogens. Xenoestrogens and hormones To determine potential risks associated with xenoestrogens, it is valuable to understand the role of estrogen in the body and how xenoestrogens can disrupt the endocrine system. In females, estrogen is produced in the ovaries and placenta and functions in the development and maintenance of secondary sex characteristics, maturation and cyclic activity of accessory sex organs, and, in general, regulates reproduction. In males, estrogen is produced in the testicles and is found in sperm; however, too much estrogen inhibits the growth of testes and the production of sperm. The physiological role of estrogen in males is unknown. The accompanying figure illustrates how the biological effects of estrogen are coordinated via a specific protein known as the estrogen receptor. Following transport into the nucleus of the cell, estrogen binds to the estrogen receptor. Two estrogen-bound receptors come together to form a complex. This complex binds with specific DNA sequences (known as estrogen response elements) located in the proximity of genes that are influenced by the presence of estrogen. Genes affected by the presence of estrogen may produce a new protein or cease the production of a protein. The altered expression of these genes leads to changes required for regulation of the reproductive system. Scientists are concerned that exposure to xenoestrogens may result in the inappropriate stimulation of the estrogenic pathway in both humans and wildlife, thus disrupting the endocrine system. A familiar example of endocrine disruption is the use of estrogen-containing birth control pills to prevent reproduction. A balanced approach In her recently published book entitled "Our Stolen Future," Dr. Theo Colborn hypothesizes that exposure to xenoestrogens may be related to reports of decreased sperm counts and increased incidence of breast cancer in humans. She discusses the possible negative effects associated with endocrine disruptors and identifies more than 50 chemicals that may act as endocrine disruptors. These chemicals include common pesticides, herbicides, insecticides, industrial chemicals (such as dioxin, mercury, and PCBs), and metals. Many of these chemicals are used in the production of numerous products that we, as consumers, use every day (e.g., plastics, detergents, lawn and garden chemicals). However, as with the great apple scare of 1989, there is considerable controversy among scientists surrounding the validity of the research used to support Dr. Colborn's hypotheses. For example, Dr. Alvin Paulsen, an endocrinologist and fertility expert at the University of Washington, recently published research results that show sperm counts for men in Seattle have not decreased during the last 21 years. Numerous additional studies have also cast serious doubts on the hypothesis that xenoestrogens have caused a decrease in human sperm counts. Scientists at PTI Environmental Services, a local environmental science consulting firm, confirm that industry is concerned with the issue of xenoestrogens. PTI is currently in the process of assisting its industrial clients in evaluating whether chemicals identified on Colborn's "hit-list" truly act as endocrine disruptors. Several of PTI's industrial clients have asked the firm to examine the methods used to identify chemicals as endocrine disruptors and to develop scientifically defensible positions regarding the status of specific chemicals as endocrine disruptors. Because so many of the chemicals that Colborn identified as potential endocrine disruptors are used widely in industrial processes, it is important for industry to be prepared and to take proactive measures. Scientists at PTI are suggesting to their industrial clients that they: Become actively involved in associations (such as the Chemical Manufacturers Association) to develop research programs on endocrine disruptors, to avoid poor risk management decisions like those made during the apple scare of 1989 Establish a proactive position and guide regulatory development so that any new regulations are based on sound science and adopt meaningful criteria Conduct initial screening tests on waste streams to identify if there may be a problem and then develop a strategy for handling the situation Develop scientifically sound positions that address whether a chemical is correctly classified as an endocrine disruptor Assess their company's potential liabilities related to endocrine disrupting chemicals and prepare and implement a consistent corporate-wide position. Obviously, the United States government and various regulating entities are keeping an eye on the endocrine disruptor research. To date, the activities of the government and regulating entities on this issue include the following: Officials at the National Institute of Environmental Health expect to fund approximately $3.3 million in extramural grants to study issues related to endocrine disruption EPA's Office of Research and Development plans to spend $5 million in 1996 on new research related to endocrine disruptors At a workshop sponsored by EPA in May 1996, a commitment was unanimously endorsed to develop a screening and testing plan by year's end to identify chemicals that disrupt the hormones and reproductive systems of humans and wildlife EPA is issuing two new reporting rules under Toxic Substance Control Act (TSCA) Section 4(A). These rules will regulate compounds based on their ability to cause endocrine disrupting effects and will require manufacturers and importers to submit data on production, exposure, and health and safety rules The Senate recently passed a bill amending the Safe Drinking Water Act to require EPA to initiate a screening and testing program for environmental estrogens within two years of its effective date The White House has launched a workgroup on hormone disruptors and is attempting to coordinate federal efforts through the Interagency Committee on Environment and Natural Resources. As scientists conduct more research and learn more about the effects of xenoestrogens on the endocrine system, we may find it necessary to ban some chemicals. For example, DDT is identified as a potential endocrine disruptor and this chemical was previously recognized as causing adverse reproductive effects. In her 1962 book, "Silent Spring," Rachel Carson warned the public of the adverse effects that DDT was having on the ecosystem, and society responded by restricting the use of DDT. Today, we find that animal populations that were in decline as a result of the use of DDT are now rebounding. We can see this response first hand with the increasing population of eagles in the Northwest. By developing a balanced approach that is based on appropriate scientific research, we are in a better position to make sound environmental management decisions that will protect our environment. In addition, we will avoid repeating situations like the apple scare of 1989 and implementing unnecessary or overly protective regulations. Candice R. Douglass is communications manager, Michael Moore, Ph.D., is a toxicologist and Rosalind Schoof, Ph.D., is a board-certified toxicologist and principal of PTI Environmental Services, Bellevue.