Endocrine Disruption

What Does Endocrine Disruption Mean?
  1. The Issue
  2. Opinions Differ
  3. What’s Next?
  4. References

The Issue

Our understanding of how endocrine disrupting chemicals (EDCs) interfere with hormones and other chemical signalers is growing rapidly. Once thought to primarily interfere with hormone receptors, we now know the culprits impact a wide range of signaling processes. They can interfere with hormone binding, transport, and production; gene expression; and a host of other cell regulatory mechanisms. These disruptions may affect the endocrine, immune and neural systems and may lead to developmental, reproductive, metabolic, brain, and behavior problems.

There is no doubt that the physical world, and a good portion of its human and animal life, is exposed to and contaminated with EDCs. Some are natural plant compounds called phytochemicals. Others are synthetic versions mostly released during human activities.

The long list of known and potential EDCs are found in:
  • water, soil, and air
  • plants
  • processed foods
  • pharmaceuticals
  • personal care products
  • household products
  • plastics
  • pesticides
  • industrial chemicals
  • humans and wildlife

Still, no simple conclusions about effects can be drawn. Even though exposure is widespread, we still don’t know the full extent of health risks and problems associated with EDCs.

Clearly, wildlife studies, laboratory experiments, and human experiences do provide evidence of health effects and intergenerational impacts from exposure to high concentrations of these ubiquitous substances. Male feminization, lower fertility, and other reproductive and developmental problems occur in a host of invertebrate species and wild fish, amphibians, reptiles, birds, and mammals.

Human impacts could be likely for certain individuals or populations in specific regions of the world. Attention has focused on health problems arising when EDCs interfere with estrogens, androgens, and other sex hormones and the thyroid hormones. These powerful messengers are key for proper functioning of the reproductive, immune, and central nervous systems. Health effects associated with EDCs include reproductive problems, such as reduced fertility, male and female reproductive tract abnormalities, and skewed male/female sex ratios; early puberty; brain and behavior problems; impaired immune functions; and various cancers.

Probably the most convincing evidence for human impacts comes from diethylstilbestrol (DES). DES, a strong synthetic estrogen banned since the 1970s, was given to pregnant women to prevent miscarriages. Years later, the grown daughters and sons of women who took the drug were having more reproductive problems and higher cancer rates than those not exposed to DES in the womb. Mice studies confirmed that DES caused the reproductive problems and certain cancers (including the rare rete-testicular cancer in males). More recent animal studies find granddaughters and sons may also be affected (CDC 2005).

Less clear, though, are impacts from daily, low level exposures to chemical mixtures.

Whether long-term exposure to low levels of EDCs causes health problems in adult wildlife and humans is still a question. Developing fetuses and embryos, whose growth and development is highly controlled by endocrine signals, may be the most vulnerable to and have the most lasting effects.

Many consensus statements issued and endorsed by scientists and scientific organizations echo this. The Wingspread statements, the Weybridge Report, and the Prague Declaration on Endocrine Disruption are examples.

The World Health Organization’s 2002 global report on endocrine disrupters also concluded that there is sufficient evidence of health effects from high-level exposure to EDCs in wildlife and weaker evidence for humans. Uncertainty from constant, low-level exposure “make understanding the potential effects posed by exposure to these chemicals an obvious international priority.”(IPCS 2002)

Opinions Differ

This heightened awareness - due to observed wildlife effects, increases in certain human endocrine diseases, and endocrine disruption seen in laboratory experiments - has raised global concern about EDCs. In response, governments (mainly European Union, the US, and Japan), international organizations, scientists, advocacy groups, policy makers, and individuals are backing efforts to understand, regulate, and educate about the contaminants.

But, many, including scientists, still disagree about the extent of detrimental health impacts of EDCs. What, if anything, should be done to reduce use and exposure? The debate continues, and opinions, it seems, fall into one of three camps:

  1. Some strongly believe that wildlife and laboratory evidence support that EDCs can cause - and may already have caused - health problems. Bans, screening/testing, and other immediate actions need to be taken to protect humans and wildlife
  2. Many believe there may be reason for concern but call for more research to clarify murky areas. A better understanding of how EDCs may impact the endocrine system will help identify the most harmful substances and lead to less human and wildlife exposure to these compounds.
  3. Others remain skeptical, believing that scientific data are inconclusive. Pointing to the lack of strong cause and effect evidence, they advocate more research and believe policy decisions should be put off until more is known about the subject.
How can such different opinions be represented when science is involved?
Cause and effect data are elusive with issues like EDCs because they involve complex biological systems, unclear exposure facts, and diverse health responses. In these cases, we use scientific, political, and public debate to weigh the evidence and decide how to deal with the potential effects.

What's Next?
All in all, EDCs are still largely an enigma. Unraveling the mysteries of how they interact with and influence endocrine, immune, neural and other systems in humans and wildlife requires more time, money, and research. In the long run, these efforts will pinpoint how EDCs interfere with signaling systems so we can fully understand their ultimate impact on reproduction, development, and health of individuals and populations.

Because of the likely health, social, and economic risks, some governments are taking action by gathering information, funding research initiatives, developing chemical screening and testing programs, and enacting new policies. US, Japan, and Europe are creating testing programs. The European Commission’s proposed Registration, Evaluation, and Authorisation of Chemicals (REACH)  is a comprehensive, precautionary-based approach to regulate chemicals. Several states and countries are banning or restricting use of convicted EDCs such as brominated flame retardants (PBDEs), plasticizers (phthalates), and pesticides. New ways to treat sewage and drinking water to lower or remove hormone-like substances are being developed.

Right now, there is still much to learn. For instance, there is a great need to better understand the basic gene expression, cell signal pathways, and chemical messengers that guide and regulate almost every bodily response. From there, it’s important to decipher EDCs unique modes of actions, quantify potency and dose, and clarify effects so we can identify vulnerable life stages and species. More data on human and wildlife exposure, including bioaccumulation, is also needed.

A broader approach can show if and how EDCs affect lesser studied processes and systems. These include nonsteroid hormones, enzymes, fat production and storage, immune responses, adrenal function, genetic controls such as methylation, and behavior and population effects (Guillette In Press; Tabb and Blumberg 2005).

Many questions remain unanswered and await further investigation. Some of these, as outlined in consensus statements, workshop reports, and other sources, include:

  • How do EDCs affect nonestrogen hormones, protein messengers, and other chemical regulators? Gene regulation and function?
  • Which EDC mechanisms, actions, and interactions pose the biggest threat?
  • Which animals are the most vulnerable: insects, fish, amphibians, reptiles, birds, or mammals (including humans)?
  • Which age will be the most vulnerable to potential effects: fetuses, newborns, children, adolescents, or adults? Are developing embryos more susceptible than adults, thus impacting future generations? How do we accurately measure toxicity and evaluate the risk of exposure at different ages?
  • How do EDCs impact communities and populations?
  • How are reproduction, disease, immune functions, cognition, and behavior affected?
  • Can wildlife, animal, and cell culture data be applied to humans, when it is clear that some EDCs have different effects in different animals?
  • How many compounds interfere with hormone signals? There is a great need for rapid and reliable testing systems.
  • What levels of exposure over what time frames will cause adverse effects? Does constant, low-level exposure cause reproductive, health, and behavioral problems? There is a need for more monitoring and biomarkers to evaluate human exposure since daily or lifetime exposure is unknown.
  • How do such things as length of exposure, dose, route of exposure (ingested, inhaled), age, and gender influence toxic effects?
  • How do profession, age, dose, diet, genetics, and other factors influence human susceptibility? How do mixtures of compounds react and interact with each other, hormones, and the endocrine and other body control systems? Are the effects additive or synergistic (greater than additive)? Do chemicals in a mixture cancel out each other's effects? Does exposure to a range of chemicals at a low dose have the same or greater effects as exposure to one chemical at a high dose?
  • Are exposure effects sequential? For example, does exposure to one chemical predispose, or make an animal more sensitive to, subsequent chemicals? In the case of diethylstilbestrol (DES), the drug predisposes animals to an altered response to endogenous estrogens that may contribute to the development of cancer.

  • CDC (Centers for Disease Control and Prevention). 2005. DES Update.
  • Guillette, LJ Jr. In Press (2006). Endocrine disrupting contaminants: Beyond the Dogma. Environmental Health Perspectives.
  • 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.
  • Tabb, MM and Blumberg B. 2005. New modes of action for endocrine disrupting chemicals. Molecular Endocrinology, doi:10.1210/me.2004-0513 (Online 21 July 2005).