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Endocrine Disruptors
Over the past decade, a growing    shown to have adverse effects        Some scientists think these
For example, hormones work         How do Endocrine                    such as Bisphenol A are
with the nervous system,   ...
are genistein and daidzein         disruptors for more than            • Conducting epidemiological
which can be found in ...
Exposures at Low Levels                                      disrupting agents to have                                    ...
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Endocrine Disruptors


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Endocrine Disruptors

  1. 1. Endocrine Disruptors Over the past decade, a growing shown to have adverse effects Some scientists think these body of evidence suggests in wildlife species, as well as chemicals also are adversely that numerous chemicals, in laboratory animals at these affecting human health in both natural and man-made, low levels. similar ways resulting in may interfere with the endocrine The difficulty of assessing public declined fertility and increased system and produce adverse health effects is increased by incidences or progression of effects in humans, wildlife, the fact that people are typically some diseases including fish or birds. Scientists often exposed to multiple endocrine endometriosis and cancers. refer to these chemicals as disruptors simultaneously. These chemicals have also “endocrine disruptors.” The National Institute of been referred to as endocrine These chemicals are found in Environmental Health Sciences modulators, environmental many of the everyday products (NIEHS) and the National hormones, and endocrine active we use including some plastic Toxicology Program (NTP) compounds. Environmental bottles, metal food cans, support research to understand chemicals with estrogenic how these chemicals work activity are probably the most and to understand the effects well studied however chemicals that they may have in various with anti-estrogen, androgen, animal and human populations anti-androgen, progesterone, with the long term goals of or thyroid-like activity have also developing prevention and been identified. intervention strategies to reduce any adverse effects. What is the Endocrine System and Why is it Important? What are Endocrine Disruptors? The endocrine system is one of Endocrine disruptors are the body’s main communication naturally occurring compounds networks and is responsible for or man-made chemicals that controlling and coordinating detergents, flame retardants, may interfere with the numerous body functions. food, toys, cosmetics, and production or activity of Hormones are first produced pesticides. Although limited hormones of the endocrine by the endocrine tissues, such scientific information is system leading to adverse as the ovaries, testes, pituitary, available on the potential health effects. Many of thyroid and pancreas, and then adverse human health effects, these chemicals have been secreted into the blood to act as concern arises because endocrine linked with developmental, the body’s chemical messengers disrupting chemicals while reproductive, neural, immune, where they direct communication present in the environment at and other problems in wildlife and coordination among other very low levels, have been and laboratory animals. tissues throughout the body. PO BOX 12233 Research Triangle Park, NC 27709 Phone: 919.541.3345 June 2006
  2. 2. For example, hormones work How do Endocrine such as Bisphenol A are with the nervous system, Disruptors work? suspected endocrine disruptors reproductive system, kidneys, From animal studies, researchers based on animal studies. gut, liver and fat to help have learned much about the Bisphenol A (BPA) is a man- maintain and control: mechanisms through which made chemical that can leach • body energy levels endocrine disruptors influence out of plastic products when • reproduction the endocrine system and alter heated. BPA is used in the hormonal functions. manufacture of polycarbonate • growth and development plastics, often used for food and • internal balance of body Endocrine disruptors can: beverage containers, and epoxy systems, called homeostasis • mimic or partly mimic naturally resins found in dental sealants. • responses to surroundings, occurring hormones in the body like estrogens (the female Bisphenol A (BPA) stress, and injury sex hormone) and androgens Endocrine disrupting chemicals (the male sex hormone) and may interfere with the body’s thyroid hormones, potentially own hormone signals because producing overstimulation OH OH of their structure and activity. • bind to a receptor within a Some endocrine disruptors cell and block the endogenous occur among a group of Hormone hormone from binding. chemicals referred to as Hormone The normal signal then fails phthalates, a class of chemicals Receptor that soften and increase the to occur and the body fails to respond properly. Examples flexibility of polyvinyl chloride of chemicals that block or plastics. An example of a antagonize hormones are anti- phthalate is a compound called Cell estrogens or anti-androgens. Di (2-ethylhexyl) phthalate Nucleus (DEHP). DEHP is a high • interfere or block the way production volume chemical natural hormones or their Hormone used in the manufacture of Mimic receptors are made or a wide variety of consumer controlled, for example by products, such as building blocking their metabolism products, car products, clothing, in the liver. food packaging, some children’s What are some examples products and some polyvinyl of Endocrine Disruptors? chloride medical devices. Recently, an independent panel A wide and varied range of of experts assembled by the substances are thought to National Toxicology Program Hormone cause endocrine disruption. (NTP) found that DEHP Blocker Chemicals that are known may pose a risk to human endocrine disruptors include development, especially for diethylstilbesterol (the drug critically ill male infants.1 DES), dioxin and dioxin like compounds, PCBs, DDT, Phytoestrogens are naturally and some other pesticides. occurring substances in plants Some chemicals, particularly that have hormone-like activity. pesticides and plasticizers, Examples of phytoestrogens
  3. 3. are genistein and daidzein disruptors for more than • Conducting epidemiological which can be found in soy three decades starting with studies in human populations derived products. the endocrine disrupting • Developing new assessment effects of the pharmaceutical and biomarkers to determine To specifically evaluate the effects that chemicals have diethylstilbestrol (DES). exposure and toxicity levels, on human reproduction, the From the 1940s -1970s, DES was especially how mixtures of National Toxicology Program used to treat women with high chemicals impact individuals (NTP) developed The Center risk pregnancies with the • Developing intervention and for the Evaluation of Risks to mistaken belief that it prevented prevention strategies Human Reproduction (CERHR). miscarriage. In 1972, prenatal This center has evaluated the exposure to DES was linked Some examples of findings in endocrine disruptor effects with the development of a rare important research areas are of seven phthalates and the form of vaginal cancer in the provided below. phytoestrogen genistein found DES-daughters, and with Developmental Exposures in soy infant formulas.2 numerous non-cancerous changes in both sons and Research shows that endocrine How are People Exposed to daughters. NIEHS researchers disruptors may pose the Endocrine Disruptors? greatest risk during prenatal developed animal models of People may be exposed to DES exposure that successfully and early postnatal development endocrine disruptors through replicated and predicted human when organ and neural systems the food and beverages they health problems and have are developing. In animals, consume, medicine they take, been useful in studying the adverse consequences, such and cosmetics they use. mechanisms involved in DES- as subfertility, premature toxic effects.3 NIEHS researchers reproductive senescence and also showed the effects of DES cancer are linked to early and other endocrine disruptors exposure, but they may not involved the estrogen receptor be apparent until much later protein mechanism.4 Researchers in life.5 are playing a lead role in Researchers supported by uncovering the mechanisms of NIEHS at the University of action of endocrine disruptors Cincinnati and the University of Illinois found that animals So, exposures may be Today, scientists are: exposed to low doses of the through the diet, air, and skin. • Developing new models and natural human estrogen Some environmental endocrine tools to better understand how estradiol, or the environmental disrupting chemicals, such as endocrine disruptors work estrogen bisphenol A (BPA), DDT, are highly persistent during fetal development and and slow to degrade in the • Developing high throughput estradiol as adults were more environment making them assays to determine which likely to develop a precursor of potentially hazardous over chemicals have endocrine prostate cancer than those who an extended period of time. disrupting activity were not exposed. This suggests What Is NIEHS Research • Examining the long-term that exposure to environmental Telling Us About effects of exposure to and natural estrogens during Endocrine Disruptors? various endocrine disrupting fetal development could affect The NIEHS has been a pioneer compounds during the way prostate genes behave, in conducting research on the development, and on disease and may lead to higher rates of health effects of endocrine and dysfunction later in life prostate disease during aging.6
  4. 4. Exposures at Low Levels disrupting agents to have New research funded by the effects on other endocrine NIEHS also found that endocrine In 2000, an independent panel of systems not yet fully examined. disruptors may affect not just experts convened by the NIEHS Transgenerational Effects the offspring of mothers and the National Toxicology exposed during pregnancy, Program (NTP) found that there There is some evidence that but future offspring as well. was “credible evidence” that endocrine disruptors may The researchers found that two some hormone-like chemicals not only impact the individual endocrine disrupting chemicals, can affect test animals’ bodily directly exposed, but also caused fertility defects in male functions at very low levels - future generations. rats that were passed down to well below the “no effect” Research from NIEHS nearly every male in subsequent levels determined by traditional investigators have shown generations. This study suggests testing.7 Although, there is little that the adverse effects of that the two compounds may evidence to prove that low-dose DES in mice can be passed to have caused changes in the exposures are causing adverse subsequent generations even developing male germ cells human health effects, there though they were not directly and that endocrine disruptors is a large body of research in exposed. The increased may be able to reprogram or experimental animals and susceptibility for tumors was change the expression of genes wildlife suggesting that endocrine seen in both the granddaughters without mutating DNA.10 disruptors may cause: and grandsons of mice who The role of environmental • reductions in male fertility were developmentally exposed endocrine disrupting chemicals and declines in the numbers to DES.8 Mechanisms involved in the transmission of disease of males born in the transmission of disease from one generation to another • abnormalities in male were shown to involve is of great research interest to reproductive organs epigenetic events.9 the NIEHS. • female reproductive diseases including fertility problems, early puberty, and early reproductive senescence • increases in mammary, ovarian, and prostate cancers There are data showing that exposure to Bisphenol A as well as other endocrine disrupting chemicals with estrogenic activity may have effects on obesity and diabetes. These data while preliminary and only in animals indicate the potential for endocrine 1 NTP Brief on the Potential Human Reproductive and Developmental Effects of Di (2-ethylhexyl) Phthalate (DEHP). Draft, May 2006. 2 CERHR website. 3 Endocrinology 147 (6) Supplement S11-S17, 2006. 4 Developmental Biology. 2001. 238:224-238. 5 Environmental Health Perspectives 103:83-87, 1995. Endocrinology 147 (6) Supplement S11-S17, 2006. 6 Cancer Research. 2006 Jun 1;66(11):5624-32. 7 National Toxicology Program’s Report of the Endocrine Disruptors Low-Dose Peer Review, 2001. 8 Carcinogenesis. 2000 Jul;21(7):1355-63. Carcinogenesis 19; 1655-1663. 9 Cancer Research 2000 60-235-237. 10 Science 3 June 20. Vol. 308. no. 5727, pp. 1466 - 1469.