Learning

Endocrine Disrupting Chemicals
  1. Signaling to Communicate
  2. Endocrine Disrupters
  3. Altered States
  4. An Incomplete Story
  5. How we got here
  6. References

Signaling to Communicate

bee on flowerI say hello. You say hi back. We’ve just used word signals to communicate. In this simple example, a sender (me) sends a verbal message or signal (hello) that conveys information to a receiver (you), who responds back to the signal with another signal (hi).

But, a loud noise or being far apart can interfere with the signal and possibly disrupt the communication. If that happens, the received message could be normal, garbled, or not gotten at all, leading to either no reply or an altered response, such as “What?”

CAPTION: Plants use colorful, scented flowers as signals to attract pollinators like this bee. CREDIT: By Jack Dykinga, Agricultural Research Service, USDA

In the natural world, signaling between and within organisms is universal and essential. Organisms signal to other organisms with sounds, sights, and smells. Words, colors, body posture, and pheromones are examples. These types of signals generally convey messages outwardly between people or among creatures.

Within an organism, unseen electrical and chemical signals dominate. The pulses and molecules facilitate communication inside a cell, between cells, and among organs and body systems. In people and vertebrate animals, the endocrine, nervous, and immune systems use chemical messengers, such as hormones and enzymes, to regulate body function, control behavior, and integrate hormone, brain, immune, and other body systems.



Endocrine Disrupters

plane spraying fieldA bevy of synthetic chemicals and natural plant compounds, as well as some physical factors, such as light and low oxygen, can also interact with these natural chemical-signaling systems. The endocrine system, with its complex network of glands, hormones, and cell receptors, is especially prone to their influences.

Compounds that interfere with natural hormone functions have many names: environmental estrogens, xenoestrogens, endocrine disrupters, endocrine modulators, and environmental hormones, to name the most common. Although all researchers do not accept one specific term, endocrine disrupters (EDs) and endocrine disrupting chemicals (EDCs) are probably used most widely.

CAPTION: Pesticides are applied to crops to control insects and weeds. In this case, an insecticide bait targeting western corn rootworms is sprayed on soybeans in Illinois. CREDIT: By Ken Hammond, Agricultural Research Service, USDA

EDCs differ in origin, size, potency, chemical life cycle, amount, and effects. Many are chemicals produced for specific purposes and are used in pesticides, plastics, cosmetics, electrical transformers and other products. Other substances are generated as a byproduct during manufacturing or are breakdown products of some other chemical. Some, like diethylstilbestrol (DES) and ethinylestradiol, are synthetic drugs, while others are natural plant compounds called phytoestrogens.




Altered States

Normally, hormones released from glands signal target cells to start and stop complex chemical relays that control development, reproduction, and internal functions. The foreign EDs, though, can interfere in a number of ways and send unintended messages. Like the loud noise or distance that disrupted our hello message, EDs can mess with and possibly alter biological signals.

They can do this in several ways. EDs can bind to hormone receptors where they can mimic, block, or otherwise influence normal hormone actions. The altered signal can cause proper or improper responses with similar, none, weaker, stronger, or totally different effects than natural hormones. Substances can also act indirectly by altering how natural hormones, their receptors, or their protein carriers are made, used, and broken apart.

But, a chemical may have more than one action. Some interlopers may interfere in only one way; others can interact in multiple ways. For example, p,p’-DDE, a derivative of the pesticide DDT, can weakly mimic estrogen and block out androgens, producing an overall feminizing effect.




An Incomplete Story

alfa alfa rootsTo date, most is known about how EDs interfere with one or a combination of steroid hormones (the estrogens, androgens, progestins, and corticoids) and thyroid hormones, including thyroxine. Within this group, attention has focused on the so-called environmental estrogens – the synthetic and plant compounds that affect the natural estrogen hormones, particularly the potent and widespread estradiol, which regulates reproduction. A wide range of invertebrates (coral, lobster, snails, and starfish) and all the vertebrates produce estradiol (Cheek et al. 1998). Altering this hormone could affect a large section of the Earth’s organisms.

CAPTION: Rhizobium bacteria (shown as fluorescent green) make their home inside the tiny root hairs of an alfalfa root (magnified 100X). CREDIT: Jennifer Fox, PhD

Lesser known, but just as important, are substances that interfere with thyroid and androgen hormones. Antiandrogens, like the fungicide vinclozolin, produce males with malformed organs and female characteristics. Opposite effects are seen in fish exposed to the growth steroid trenbolone and plant steroid compounds found in pulp and paper mill effluent. Both masculanize, producing females with male attributes.

But, other hormone signals and body systems, such as the peptide hormones, may also be vulnerable. These less studied interactions influence most body regulatory processes, including appetite, immunity, brain functions, and metabolism. Physical factors, such as low oxygen conditions, can influence hormones, too. Light and electromagnetic fields may contribute to certain cancers by altering performance of the hormone melatonin, which controls human hormone production and sleep (Blask et al. 2005).

EDCs can also interrupt signaling between organisms, but again, effects are not fully understood. Legume plants, such as beans and soybeans, rely on special bacteria living in their roots to provide needed nitrogen. To recruit the bacteria to their roots, plants release chemicals into the soil that can bind to the bacteria’s receptors and initiate the gene expression necessary to find its way to the plant. Chemicals, such as DDT and the herbicide 2,4-D, can block signaling to various degrees, hampering recruitment of the essential partners (Fox 2004; Fox et al. 2004).

Although most are weaker than natural hormones, some EDCs have been associated with reproductive and developmental problems in wildlife and laboratory animals. Many of the indicted chemicals have distinct effects in different species and organs and at different developmental stages. Quantity, potency, mixes, and inappropriate timing, such as exposure to developing fetuses, growing infants, and young children whose rapidly growing bodies depend on endocrine signals, are important factors that dictate the type and degree of known effects, including cancer, deformities, and reproductive problems.

Because they are everywhere, wildlife and humans face a constant barrage of toxic chemicals. Air, water, dust, and animals carry EDCs to every continent. Exposure occurs in every stage of life, from development in egg or womb to adulthood, and any number of sources, including food, air, water, soil, household products, breast milk, and the womb.

How much is too much? We still do not know. Although EDCs can affect wildlife, the human health risks that may be associated with these mostly low-level yet constant exposures are still largely unknown and highly controversial.




How we got here
estradiolThe idea that naturally occurring chemicals can alter hormone function and affect health is an old one. Human cultures from antiquity to the present sought remedies and drugs from plants they knew had the power to heal or hurt. Some of these plants, such as mold, clover, fruits, and legumes (soy), contain estrogen-like chemicals. The mimics can cause infertility and other reproductive problems as well as impede or encourage disease in domestic animals and humans.

CAPTION: Many plant compounds can mimic effects of 17-beta-estradiol, the most potent and widespread natural estrogen hormone in humans and animals. CREDIT: ChemIDPlus, National Library of Medicine

 

A newer notion is that certain synthetic chemicals can also interact with chemical messaging systems, whether or not they were made for that purpose. Some not meant to be endocrine active were later found to act like hormones. For example, a 1938 study verified that the synthetic bisphenol A, synthesized decades earlier, could mimic estrogens (Dodds and Lawson 1936, 1938).

Others were always intended to exploit natural systems. For instance, drugs in birth control pills simulate natural estrogens and progestins. Many pesticides developed to kill insects, weeds and other pests intentionally target hormone, immune, and other essential signaling systems. For this reason, it should not be surprising that certain toxic compounds can also affect the systems in wildlife and humans.

In the United States, production and use of synthetic organic chemicals began in earnest in the 1940s World War II era and climbed steadily throughout the second half of the century. Production topped more than 400 billion pounds annually in the late 1990s. Today, compounds used as pesticides, drugs, food and product additives, and industrial chemicals (solvents, lubricants) number more than 80,000.

By the early 1960s, concern was already growing about the rapid and unrestricted use of chemicals. The synthetic compounds, especially the insecticide DDT, were contaminating water, soil, wildlife, and even humans possibly causing severe health problems (egg shell thinning, cancer, die offs) in wildlife, asserted Rachel Carson in her book Silent Spring. The problems were especially pronounced in top-of-the-food-chain predatory species that eat other contaminated animals and concentrate the chemicals.

Although it was not yet clear that many of the substances were hormonally active, evidence gradually accumulated. For one, Australian farmers reported infertility, reproductive abnormalities, and even death in sheep grazing on clover and cows eating moldy feed. Estrogen-like compounds (phytoestrogens) were to blame.

alligatorFor another, similar reproductive problems were recognized in wildlife, laboratory animals, and humans during the following three decades. Eggshell thinning in eagles and sea gull breeding troubles, which both contributed to plummeting bird populations in the Great Lakes region, were linked to feminizing effects from DDT exposure.

CAPTION: Fish, birds, alligators, and other wildlife provided some of the first evidence for endocrine disrupting effects. CREDIT: Susan Middleton © California Academy of Sciences

Bill and bone deformities, bizarre reproductive behavior, and dying chicks plagued gulls and other water birds. In Florida, researchers investigating declining alligator populations discovered males with small phalluses and female-like hormone levels in heavily contaminated lakes. In the laboratory, mice exposed to the artificial estrogen DES before birth developed uterine deformities and rare forms of vaginal cancer as adults, similar to patterns seen in adult women. Fish living below sewage treatment plants in England were found with skewed hormone levels, female egg protein in males, and both male and female gonad tissues (intersex). In laboratory tests, plastics and product additives tested positive as estrogenic substances.

By the 1990s, evidence for the underlying, unifying theme of endocrine disruption was growing. And word about it was getting out. A cadre of scientists, brought together by researcher Theo Colborn, gathered in Racine, Wisconsin, for the first Wingspread conference in 1991. The result was a unified consensus statement asserting that synthetic chemicals could interfere with hormones of animals, and possibly people. Fetuses and the young were at the greatest risk for disease, abnormalities, and reproductive problems that were already manifesting in wildlife (Wingspread Statement 1991).

Then, books (Our Stolen Future, Hormonal Chaos), Web sites (e.hormone), government reports, and more consensus statements from workshops and conferences roused political and public interest (Colborn et al. 1996; Krimsky 2002). In response, governments convened expert panels to investigate risks from EDs and develop testing and screening programs (EDSTAC 1998). The sheer magnitude of the job, though, is daunting and most have made little progress towards testing the compounds.

Several hormonally active chemicals have been restricted since Rachel Carson’s first warnings. For instance, by the 1980s, the US and Europe had banned or reduced use of many of the most persistent chemicals, such as the insecticide DDT and the industrial PCBs. But, the chemicals’ widespread presence and long-lasting effects linger today because the persistent organic pollutants (POPs) degrade slowly, accumulate in fat, and are still produced and used in some parts of the world. The Stockholm Convention, signed by a majority of world countries and ratified in 2002, is an effort to control what’s considered the worst of the worst (Stockholm Convention on POPs Web site).

Less long-lived chemicals with endocrine disrupting potential infiltrate a vast array of everyday products. Many occur at low levels in products we all use. Bisphenol A is added to plastic water bottles, food can linings, and dental sealants. The ubiquitous phthalates keep plastics in baby toys and medical devices soft and flexible and are added to an enormous number of products including cosmetics, drugs, pesticides, and paints. Polybrominated diphenyl ethers (PBDEs) retard fire and are widely used in foams and plastics. Europe has successfully limited use of certain phthalates and PBDEs and California is trying to do the same.

However, not everyone agrees that vast numbers of synthetic chemicals - some banned, others still widely made and used - pose long-term reproductive, developmental, and other health effects in wildlife and humans. Even one of the most comprehensive reports to date, the 2003 global assessment of endocrine disruptors, called for more research after finding health effects in wildlife exposed to high amounts but less clear evidence for human health effects (IPCS 2002).




References
  • Blask DE, Brainard GC, Dauchy RT, Hanifin JP, Davidson LK, Krause JA, Sauer LA, Rivera-Bermudez MA, Dubocovich ML, Jasser SA, Lynch DT, Rollag MD, and Zalatan F. 2005. Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats. Cancer Research 65:11174-11184.
  • Carson, RL. 1962. Silent Spring.
  • Cheek AO, Vonier PM, Oberdorster E. Burow BC and McLachlan JA. 1998. Environmental signaling: A biological context for endocrine disruption. Environmental Health Perspectives 106(Supp. 1):5-10.
  • Colborn,T, Dumanoski D, and Myers, JP. 1996. Our Stolen Future. New York: Penguin Books.
  • Dodds EC and Lawson W. 1936. Synthetic estrogenic agents without the phenanthrene nucleus. Nature 137:996.
  • Dodds EC and Lawson W. 1938. Molecular structure in relation to oestrogenic activity. Compounds without a phenanthrene nucleus. Proceedings of the Royal Society. London B. 125:222-232.
  • EDSTAC (Endocrine Disruptor Screening and Testing Advisory Committee) Final Report. 1998. Vols. 1-2. Washington, DC: US Environmental Protection Agency. Available: http://europa.eu.int/comm/environment/endocrine/index_en.htm
  • Fox JE, Starcevic M, Jones PE, Burow ME, and McLachlan JA. 2004. Phytoestrogen signaling and symbiotic gene activation are disrupted by endocrine-disrupting chemicals. Environmental Health Perspectives 112(6):672-677.
  • Fox JE. 2004. Chemical communication threatened by endocrine-disrupting chemicals. Environmental Health Perspectives. 112(6):648-653.
  • IPCS (International Programme on Chemical Safety). 2002. Global Assessment of the State-of-the-Science of Endocrine Disruptors. WHO/PCS/EDC/02.2. Eds. Damstra T, Barlow S, Bergman A, Kavlock R, and Van Der Kraak G. Geneva, Switzerland: World Health Organization. Available: http://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/. Accessed 28 November 2005.
  • Krimsky, S. 2002. Hormonal Chaos: The Scientific and Social Origins of the Environmental Endocrine Hypothesis. Baltimore: Johns Hopkins University Press.
  • Stockholm Convention on POPs Web site. Available: http://www.pops.int/. Accessed 27 January 2006.
  • Wingspread Consensus Statement. 1991. Available: http://www.johnsonfdn.org/spring96/wildlife.html