Endocrine Disruption: An Introduction

Linda-Jo Schierow

Specialist in Environmental Policy

Eugene H. Buck

Senior Analyst in Natural Resources Policy Resources,
Science, and Industry Division

January 11, 2001

RS20778

Background

What are "endocrine disruptors"? Some scientists hypothesize that certain chemicals in the environment, the so-called "endocrine disruptors," 1 may harm wildlife, aquatic life, or human health by interfering with the action of reproductive and other hormones. 2 Evidence to support this hypothesis is generally accepted for some vertebrate animals, such as fish and alligators, exposed to high levels of some environmental contaminants, primarily in surface water, but is scanty for humans exposed to low levels of contaminants. Researchers are working to better define the range of potential effects, and to identify vulnerable animal species and chemicals with endocrine-disrupting potential. Attention has focused on certain chemicals that are ubiquitous at low levels in the air, surface water, and food, and at higher levels in many consumer products, including medical devices and baby toys. Chemicals of potential concern include a number of pesticides (e.g., DDT, lindane, and vinclozolin), medicinal drugs (especially synthetic hormones), and certain industrial compounds (e.g., phthalates, bisphenol A, polychlorinated biphenyls (PCBs), some dibenzodioxins, lead, methyl mercury, and organotins).

How did the hypothesis originate? Although at least one hearing was held in 1993 3 on the possible health effects of "estrogenic compounds," the endocrine disruptor hypothesis first came to widespread congressional attention in 1996, with the publication of the book Our Stolen Future. 4 It summarized studies by wildlife biologists, epidemiologists, and other scientists, and hypothesized a possible environmental cause, linking observed increases in deformities and population declines of amphibians, evidence of declining human fertility, and alleged increases in rates ofbreast, testicular, and prostate cancers, as well as endometriosis.

Conflicting Evidence

The hypothesized link between hormone function and chemical exposure is biologically plausible; there is clear evidence that some chemicals can disrupt hormonal processes in people and some wildlife, 5 especially if the chemical is directly administered or otherwise received in a concentrated dose during fetal or infant development. For example, it is well known that daughters born to women who took the drug diethylstilbestrol (DBS), a synthetic estrogen, early in their pregnancies between the mid 1940s and 1971, now have a greatly increased risk of vaginal cancer. 6 In addition, studies have documented a higher than normal incidence of genital tract abnormalities following in utero exposure to DES.7 More than 10 years after the 1980 poisoning of Lake Apopka in Florida by a pesticide spill, scientists found abnormal development of secondary sexual characteristics in alligators. 8 And laboratory experiments demonstrate the exquisite sensitivity of the reproductive system of mink to very low levels of PCBs.9 Moreover, the developmental, reproductive, and carcinogenic effects for which increased incidences have been reported in humans, are similar to effects on reproductive structure and function that have been observed in wildlife and fish exposed to endocrine disruptors. 10

Concern about possible hormone disruption also has been fueled by the limited information available about levels of exposure. Some potentially estrogenic substances are heavily used and, in some cases, released to the environment. For example, wastewater effluent from sewage treatment plants contains many potential endocrine disruptors, including synthetic hormones. Other potential endocrine disruptors are prevalent in certain foods, such as soy-based milk substitutes; soy beans contain phytoestrogens (e.g., genistein) at relatively high levels.

Another reason for possible concern is the high level of biological availability and activity (by design) of some pharmaceutical and agricultural chemicals with strong effects on the endocrine system. Synthetic hormones are an obvious example. Birth control compounds, synthetic estrogen for postmenopausal women, and synthetic thyroid hormone are three common contaminants of wastewater.

Of course, release does not necessarily imply persistent presence in the environment, or subsequent exposure to vulnerable populations of animals or people. Available data are reassuring, because known potential disruptors of endocrine function generally are present in the environment at very low levels. On the other hand, many are ubiquitous at these low levels, raising the question of possible additive or synergistic effects with continual exposure. 11 Foods and surface water often contain trace amounts of pesticides, and many consumer products contain low levels of endocrine modulators such as phthalates or bisphenol A.

However, plausible toxicity and potential exposure are not sufficient conditions to demonstrate significant public health or ecological risks. Unfortunately, for the most part, data do not exist to accurately assess potential environmental risks, and existing data offer support conflicting views. Thus, controversies swirl around such questions as the extent to which people generally are exposed to endocrine modulators, whether very low levels of exposure potentially could affect human health, and whether exposure to very low levels of chemicals in the environment currently is affecting reproduction, fetal development, or other hormone-dependent functions in animal or human populations. Nevertheless, a panel of convened by the National Academy of Sciences concluded -

Environmental [hormonally active agents] probably have contributed to declines in some wildlife populations, including fish and birds of the Great Lakes and juvenile alligators of Lake Apopka, and possibly to diseases and deformities in mink in the United States, river otters in Europe, and marine mammals in European waters. Such contaminants, along with inbreeding, might have contributed to the poor reproductive success of the endangered Florida panther and the increased embryonic mortality of the snapping turtle in the Great Lakes. 12

Those skeptical of the disruptor hypothesis argue that mammals have homeostatic mechanisms to moderate small fluctuations in hormone levels, so they are unlikely to be overwhelmed by low levels of environmental exposure. To the argument that low concentrations of several chemicals may additively exert influence on those exposed, skeptics counter that multiple disruptors are just as likely to compete, resulting in combined effects that are less than additive. Moreover, synergenicity between, disruptors has never been demonstrated. 13

On-going studies of developmental effects in rats have recently found effects on the reproductive organs from very low levels of exposure to DES and bisphenol-A, an ingredient m some plastic. Similarly, preliminary results indicate low-dose effects on the brain and immune system from genestein and nonylphenol (a chemical in detergents). The question remains whether those effects will adversely affect human health, however. 14 An expert workshop to evaluate the data on low-dose effects of endocrine disruptors recently concluded that such effects from estrogenic compounds have been clearly demonstrated, but the final report from the workshop is not expected until 2001. 15

Congressional and Administrative Attention

In 1996, Congress enacted amendments to federal pesticide and drinking water statutes that mandated screening of pesticides and drinking water contaminants for potential to disrupt the endocrine system. The Food Quality Protection Act (FQPA) Section 408(p) 16 directs EPA to require validated tests, not later than 3 years after August 3, 1996, of registered pesticide ingredients (both active and inert) for their potential to modulate endocrine systems. 17 The 1996 Safe Drinking Water Act Amendments (P.L. 104-182) authorize screening for endocrine disruption potential of contaminants found m sources of drinking water. 18 Actual screening of chemicals for toxic effects will be conducted by manufacturers of suspect chemicals. For substances found to have endocrine effects on humans, the laws authorize EPA to take appropriate action to protect public health under existing statutory authority. 19

To help implement the new provisions, EPA organized the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC). This committee of scientists, representing various chemical manufacturers and distributors, chemical users, public health advocates, environmentalists, and other stakeholder groups, assisted EPA in designing the chemical screening and testing program. The committee's recommendations, released October 5, 1998, were reviewed by a special peer review panel consisting of members of the FIFRA Science Advisory Panel and the independent Science Advisory Board. EPA relied heavily on EDSTAC recommendations in developing the Endocrine Disruptor Screening Program. 20 Although the program was designed and "established" in 1998, it is not in operation. EPA is still developing the methods that will be used to prioritize chemicals for screening and is attempting to validate the methods that will be used to test high-priority chemicals.

In addition to the EPA testing program, there are research programs on endocrine disruption in public health agencies of the federal government. The National Science and Technology Council's Committee on the Environment and Natural Resources formed an Endocrine Disruptor Working Group to coordinate the federal government's response to concerns about endocrine disruptors. 21

Legislative Issues

The 107th Congress may consider proposals to increase or decrease funding for the endocrine disruption screening program, or to expand its requirements to include additional chemicals or endocrine effects. For example, S. 1712 in the 106th Congress would have required screening of substances discharged into the nation's water. Congress appropriated $6.6millionforthe FY2000program, and $10.2 million in FY2001 (House Rept. 106-988). Several other legislative proposals in the 106th Congress (e.g., S. 1112, S. 1716, S. 2109, H.R. 1657, and H.R. 3275) would have expanded the reporting or regulatory requirements of other environmental statutes to cover chemicals with possible estrogenic or other hormonal effects. Such proposals may garner support if scientific evidence accumulates indicating significant adverse environmental or human health effects. On the other hand, on-going studies may not substantiate claims of adverse health or ecological effects of exposure to endocrine disruptors at environmental levels, and proposals for less research or regulation may result.

Footnotes

1 Some of these substances, such as the phytoestrogens which occur naturally in some plants, are similar in form and action to natural hormones; these are called "hormone mimics." The terms "environmental estrogen" and "xenoestrogen" are narrower, referring only to those chemicals that mimic the action of the female sex hormone estrogen. Other endocrine disruptors do not mimic, but otherwise modify the synthesis, secretion, transport, binding, action, or elimination of natural hormones. Some scientists prefer the more neutral but just as inclusive term "endocrine modulators" over the better known term "endocrine disruptors."

2 The endocrine system includes the glands (e.g., thyroid, pituitary gland, pancreas, ovaries, or testes) and their secretions (i.e., hormones), that are released directly into the body's circulatory system (rather than through ducts). The endocrine system controls blood sugar levels, blood pressure, metabolic rates, growth, development, aging, and reproduction.

3 U.S. House of Representatives, Committee on Energy and Commerce, Subcommittee on Health and the Environment. Health Effects of Estrogenic Pesticides. 103th Cong., 1st Sess., Oct. 21, 1993. Washington, DC: U.S. Govt. Print. Off. (1994) 185 p.

4 Colbum, Theo, Dianne Dumanoski, and John Peterson Myers. Our Stolen Future: Are We Threatening Our Fertility, Intelligence, and Survival? A Scientific Detective Story. New York: Penguin. (1996) 316 p.

5 Generally, scientists have studied effects in vertebrates, especially amphibians, freshwater fish, and mammals.

6 Herbst, A., H. Ulfelder, and D. Poskanzer. "Adenocarcinoma of the vagina: Association of maternal stilbestrol therapy with tumor appearance in young women," New England Journal of Medicine, v. 284, (1971) p. 878-881.

7 Mittendorf, R. Teratogen update: Carcinogenesis and teratogenesis associated with exposure to diethylstilbestrol(DES) in utero. Teratology,v.51,n.6, (1995) p. 435-445.

8 Guillette, L., T. Gross, D. Gross, A. Rooney, and H. Percival. "Gonadal steroidogenesis in vitro from juvenile alligators obtained from contaminated or control lakes," Environmental Health Perspectives, v. 103, n. 4, p. 31-36. (1995)

9 Golub, Man S., James M. Donald, and Joe A. Reyes. "Reproductive toxicity of commercial PCB mixtures: LOAELs and NOAELs from animal studies," Environmental Health Perspectives, v. 94, p. 245-253. (1991)

10 U.S. Environmental Protection Agency (1997). Special Report on Environmental Endocrine Disruption: An Effects Assessment and Analysis, EPA/630/R-96/012. p. 5.

11 National Academy of Sciences (1999). Hormonally Active Agents in the Environment, National Academy Press, Washington, DC.

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

12 National Academy of Sciences, p. 7.

13 McLachlan, J.A. "Synergistic effect of environmental estrogens: Report withdrawn" [retraction of Amold, S.F., D.M. Klotz, B.M. Collins, et al. In: Science, v. 277, p. 1489-1492. (1996)] Science, v. 277, p. 459-463 (1997)

14 That is, the effects observed are not known to be adverse. For example, at certain very low doses fetal exposure to bisphenol-A produces enlarged prostates in male rats.

15 Kaiser, Jocelyn. "Panel cautiously confirm low-dose effects," Science, v. 290, p. 695,697. (2000)

16 See §405 of P.L. 104-170, amending §408 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 346a).

17 The EPA Office of Science Coordination and Policy website describes the statutory authority for the Endocrine Disruptor Screening Program.
http://www.epa.gov/scipoly/oscpendo/

18 See §136 of P.L. 104-182, adding a new §1457 to the Safe Drinking Water Act (42 U.S.C. 300j-17).

19 Federal Food, Drug, and Cosmetic Act, as amended; 21 U.S.C. 346a(p)(6).

20 U.S. Environmental Protection Agency. "Environmental Protection Agency Endocrine Disruptor Screening Program, Report to Congress." August 2000. p. 5.

21 For more information about this group, see EPA's website on the Endocrine Disruptors Research Initiative. http://www.epa.gov/endocrine/