Endocrine Disruptors

Characteristics

Fate and Transport in the Environment

Methods for Monitoring in the Environment

Methods for Measuring Human Exposure

Exposure Pathway

Strategies for Preventing or Controlling Exposure


PCBs - Harmful Effects

PCBs - Dose Response

Sites of Toxicity

Mechanisms of Toxicity

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What are endocrine disruptors?

The endocrine system is a complex communication system between chemical signals and their targets responsible for regulating internal functions of the body (for more info see http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookENDOCR.html). Any substance that alters the function of this system is termed an endocrine disruptor. Endocrine disruptors, commonly referred to as “Endocrine Disrupting Chemicals” (EDCs), can alter endocrine function by a variety of different mechanisms:

1. By mimicking the sex steroid hormones estrogen and androgen by binding to their natural receptors either as agonists or antagonists.
2. By altering the synthesis and breakdown of natural hormones.
3. By modifying the production and functioning of hormone receptors.

In general, compounds that mimic estrogens are termed environmental estrogens whereas compounds that block hormone action are termed anti-estrogens or anti-androgens (male sex hormone). Environmental estrogens have been the focus of the majority of research on endocrine disruptors. This includes, but is not limited to chemicals that mimic the female sex hormone estradiol-17b.

Chemical structures of EDCs
Interestingly, the chemical structures of natural hormones and environmental hormones are most often very different. It is not possible to determine whether a chemical is an endocrine disruptor or not by merely looking at its chemical structure. Because the structures of endocrine disruptors are so variable and unpredictable, they are sometimes synthesized unintentionally. A couple examples include the pesticide DDT and polychlorinated biphenyls (PCBs), both of which have estrogenic activity, but were originally synthesized for a completely unrelated purpose. The figure below demonstrates the structural diversity of chemicals in the environment reported to be estrogenic (1).

Sources of endocrine disruptors
Chemicals capable of acting as endocrine disruptors are ubiquitous in our environment. They can be found in:

  • The natural environment (air, water, soil)
  • Food products (soybeans, legumes, flax, yams, and clover)
  • Plants (phytoestrogens are chemicals naturally found in plants that can act as endocrine disruptors and are present in fruits, veggies, beans, and grasses)
  • Household products (breakdown products of detergents and associated surfactants, including nonylphenol and octylphenol)
  • Pesticides (o,p'-DDT, endosulfan, atrazine, nitrofen, and tributyl tin)
  • Plastics (bisphenol A, phthalates)
  • Pharmaceuticals (drug estrogens - birth control pills, DES, cimetidine)
  • Industrial chemicals (polychlorinated biphenyls (PCBs), dioxin and benzo(a)pyrene)
  • Byproducts of incineration, paper production, and fuel combustion.
  • Metals (cadmium, lead, mercury)

We are exposed to these various endocrine disruptors by eating and drinking them, breathing them, and using them whether at home or at work.

Human health effects of endocrine disruptors
There are many unknowns when it comes to determining the human health effects resulting from exposure to various endocrine disruptors. In fact, there is much controversy among professionals as to what the risks of exposure, if any, have on human health. However, mounting evidence based on lab based toxicology studies, field studies, status and trend studies, epidemiology, wildlife and lab animals, suggest that the threat to human health is real and that the same deleterious health effects seen in animals studied can be extrapolated to humans. For example, in vitro studies involving estrogen-responsive cells in the lab have discovered differences in response to estrogens depending on what type of plasticware they used (2). Another study in Florida observed reduced phallus size and altered estrogen to testosterone levels in alligators, which are speculated to have been the result of developmental exposure to environmental estrogens or anti-androgens (3). Evidence of possible human health effects from exposure to environmental estrogens stem from a paper that was published in 1992 suggesting decreased sperm counts and male reproductive capabilities over the past 50 years (4). A reanalysis of this study was performed more recently and similar results were found (5). Perhaps more well known is the link between the development of cancer and other reproductive health problems in sons and daughters of women who took DES while pregnant

Speculated human health effects include:

  • Reproductive Effects/Birth Defects
  • Cancer
  • Low sperm count/Sexual Dysfunction
  • Heart Disease
  • Cognitive Disorders
  • Sex Reversal
  • Premature puberty
  • Altered immune function

It is believed that timing of exposure is critical, especially in the case of developing fetuses and infants who may be the most vulnerable to the effects of environmental estrogens. However, what health effects are caused by what chemicals and in what doses at what time is still being debated. Bioaccumulation of chemicals within the body is also a legitimate concern.

Other Issues and Concerns
Assessing the human health risks of endocrine disruptors is a daunting task that is going to require much more research. There are many unanswered questions surrounding the debate on endocrine disruptors and human health effects. Questions regarding:

  • Chemical persistence in the environment
  • Fate and transport
  • Mechanisms of action in the human body
  • Doses that are harmful
  • Effects of bioaccumulation
  • Cumulative exposures and effects
  • Effects of age at exposure
  • Identifying specific health problems
  • The number of synthetic chemicals that can act like natural hormones
  • Effects of exposure to multiple chemicals (possible synergism)

Some researchers agree that there may be health effects, but only in extremely high doses that are unlikely to be encountered in one’s lifetime. Others believe that the data backing wildlife and laboratory studies on endocrine disruptors are very compelling and demonstrate a true risk to human health. Work that still needs to be done include:

  • Identifying compounds able to act as endocrine disruptors and then developing reliable and sensitive assays to test for them.
  • Ascertaining the health effects
  • Understanding the impact of age, dose, length of exposure, timing of exposure, and genetics has on health effects.
  • Learning more about the interactions between multiple synthetic chemicals and how they react in the body and the environment.

Because the endocrine system is vital to health, especially reproductive health and the maintenance of species, much effort is being placed into the research of chemicals that may disrupt this system. However, because there are so many unknowns about endocrine disruptors such as what chemicals are included, their persistence in the environment and their health effects, it is challenging to study them. John McLachlan, a researcher in this area writes, “As patterns begin to emerge in environmental endocrine science, recognition of similarities to those associated with evolution and development should provide insights to mechanisms and outcomes. Without pattern recognition, there is not the ability to predict, and without prediction there is not the possibility to prevent” (1).

References:

McLachlan J 2001 Environmental signaling: what embryos and evolution teach us about endocrine disrupting chemicals. Endocrine Reviews 22:319-341

Soto AM, Justicia H, Wray JW, Sonnenschein C 1991 p-Nonylphenol: an estrogenic xenobiotic released from “modified” polystyrene. Environ Health Perspect 92:167-173

Guillet Jr LJ et al. 1999 Plasma steroid concentrations and male phallus size in juvenile alligators from seven Florida lakes. Gen Comp Endocrinol 116:356-372

Carlsen et al. 1992 Evidence for decreasing quality of semen during last 50 years. Br Med J 305:609-613

Swan SH, Elkin EP, Fenster L 2000 The question of declining sperm density revisited: an analysis of 101 studies published 1934-1996. Environ Health Perspect. Oct; 108(10):961-6