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Endocrine Disruptors

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  • 1.Endocrine DisruptorsA growing body of evidence suggests that numerous chemicals, both natural and man- made, may interfere with the endocrine system and produce adverse effects in laboratory animals, wildlife, and humans. Scientists often refer to these chemicals as endocrine disruptors. Endocrine disruption is an important public health concern that is What are endocrine disruptors? being addressed by the National Institute ofEndocrine disruptors are naturally occurring Environmental Health Sciences (NIEHS).compounds or man-made substances that may mimic or interfere with the function of hormones in the These chemicals are found in many of thebody. Endocrine disruptors may turn on, shut off, everyday products we use, including someor modify signals that hormones carry, which may plastic bottles and containers, liners of metal affect the normal functions of tissues and organs. food cans, detergents, flame retardants, food,Many of these substances have been linked with developmental, reproductive, neural, immune, and toys, cosmetics, and pesticides. Although other problems in wildlife and laboratory animals. limited scientific information is available on the potential adverse human health effects, Some research suggests that these substances are also concern arises because endocrine disrupting adversely affecting human health in similar ways, resulting in reduced fertility and increased incidences chemicals present in the environment at or progression of some diseases, including obesity, very low levels have been shown to have diabetes, endometriosis, and some cancers. adverse effects in wildlife species as well as in laboratory animals. The difficulty of assessing public health effects is increased by the fact that people are typically exposed to multipleThe endocrine system keeps our bodies endocrine disruptors simultaneously. in balance, maintaining homoestasis and guiding proper growth and development. NIEHS and the National Toxicology Program (NTP) support research to understand how these chemicals work, and to understand the These chemicals have also been referred to as effects they may have in various animal and endocrine modulators, environmental hormones, human populations, with the long term goaland endocrine active compounds. Environmental of developing prevention and intervention chemicals with estrogenic activity are probably the most well studied, however chemicals with anti- strategies to reduce any adverse effects. estrogen, androgen, anti-androgen, progesterone, or thyroid-like activity have also been identified.PO BOX 12233 Research Triangle Park, NC 27709 Phone: 919. 541.1919 http://www.niehs.nih.gov Printed on recycled paper. May 2010

2. What is the endocrine system and why is it important?What is NIEHS research telling us about The endocrine system is one of the bodys main endocrine disruptors? communication networks and is responsible forNIEHS has been a pioneer in conducting research controlling and coordinating numerous body on the health effects of endocrine disruptors functions. Hormones are first produced by thefor more than three decades, starting with the endocrine tissues, such as the ovaries, testes, adrenal, endocrine-disrupting effects of the pharmaceutical, pituitary, thyroid, and pancreas, and then secreted into diethylstilbestrol (DES). the blood to act as the bodys chemical messengersFrom the 1940s1970s, DES was used to treat women where they direct communication and coordinationwith high-risk pregnancies, with the mistaken belief among other tissues throughout the body.that it prevented miscarriage. In 1972, prenatal For example, hormones work with the nervousexposure to DES was linked to the development of system, reproductive system, kidneys, gut, liver,a rare form of vaginal cancer in daughters whose and fat to help maintain and control:mother received DES, and with numerous non-cancerous changes in both sons and daughters. Body energy levelsNIEHS researchers developed animal models of Reproduction DES exposure that successfully replicated and Growth and development predicted human health problems, and have been Internal balance of body systems, or homeostasis useful in studying the mechanisms involved in DES Response to surroundings, stress, and injury toxic effects.1 NIEHS researchers also showed thatthe effects of DES and other endocrine disruptors Endocrine disrupting chemicals may interfere withinvolved the estrogen receptor.2 the bodys own hormone signals because of their structure and activity.In addition to the fact that we now know thatendocrine disruptors are widely dispersed in ourenvironment, some other key points about exposure How are people exposed to endocrine disruptors?to endocrine disruptors have emerged. People may be exposed to endocrine disruptors through the food and beverages they consume, medicine they take, pesticides they apply, and cosmetics they use. So, exposures may be throughFour points about endocrine disruption: the diet, air, skin, and water. Low dose matters Some environmental endocrine disrupting Wide range of health effects chemicals, such as the pesticide DDT, dioxins, and Persistence of biological effects polychlorinated biphenyls (PCBs) used in electrical Ubiquitous exposure equipment, are highly persistent and slow to degrade in the environment making them potentially hazardous over an extended period of time.Exposures at low levels count.The bodys own normal endocrine signaling involvesvery small changes in hormone levels, yet we knowthese changes can have significant biological effects.This leads scientists to think that chemical exposures,even at low doses, can disrupt the bodys delicateendocrine system and lead to disease.In 2000, an independent panel of experts convenedby NIEHS and NTP found that there was credibleevidence that some hormone-like chemicals canaffect test animals bodily functions at very low levels well below the no effect levels determined bytraditional testing.3 3. Research from NIEHS investigators have shownthat the adverse effects of DES in mice can be passedto subsequent generations even though they werenot directly exposed. The increased susceptibilityfor tumors was seen in both the granddaughtersand grandsons of mice who were developmentallyexposed to DES.6 7 Mechanisms involved in thetransmission of disease were shown to involveepigenetic events that is altering gene functionwithout altering DNA sequence.8New research funded by NIEHS also found that Endocrine disrupting chemicals may impact a broadendocrine disruptors may affect not just the offspring range of health effects. of mothers exposed during pregnancy, but futureoffspring as well. The researchers found that several Although there is limited evidence to prove that endocrine disrupting chemicals caused fertility defects low-dose exposures are causing adverse human in male rats that were passed down to nearly every health effects, there is a large body of research in male in subsequent generations. This study suggests experimental animals and wildlife suggesting thatthat the compounds may have caused changes in endocrine disruptors may cause:the developing male germ cells, and that endocrine Reductions in male fertility and declines in the disruptors may be able to reprogram or change the numbers of males born. expression of genes without mutating DNA.9 The roleof environmental endocrine disrupting chemicals in Abnormalities in male reproductive organs. the transmission of disease from one generation to Female reproductive health issues, including another is of great research interest to NIEHS. fertility problems, early puberty, and early reproductive senescence. What are some current areas of Research NIEHSis pursuing? Increases in mammary, ovarian, and prostate cancers. Researchers are playing a lead role in uncoveringthe mechanisms of action of endocrine disruptors. Increases in immune and autoimmune diseases,Today, scientists are: and some neurodegenerative diseases. Developing new models and tools to better There are data showing that exposure to BPA, understand how endocrine disruptors work. as well as other endocrine disrupting chemicals with estrogenic activity, may have effects on obesity Developing high throughput assays to determine and diabetes. These data, while preliminary andwhich chemicals have endocrine disrupting activity. only in animals, indicate the potential for endocrine Examining the long-term effects of exposure to disrupting agents to have effects on other endocrinevarious endocrine disrupting compounds during systems not yet fully examined.development and on diseases later in life. Effects of endocrine disruptors may begin early and be persistent. Conducting epidemiological studies in humanpopulations. Research shows that endocrine disruptors may pose the greatest risk during prenatal and early postnatal Developing new assessments and biomarkers development when organ and neural systems areto determine exposure and toxicity levels developing. In animals, adverse consequences, such especially how mixtures of chemicals impact as subfertility, premature reproductive senescence,individuals. and cancer, are linked to early exposure, but they Developing intervention and prevention strategies. may not be apparent until much later in life.4 5 4. How do endocrine disruptors work? What are some examples of endocrine disruptors?From animal studies, researchers have learned A wide and varied range of substances are thought tomuch about the mechanisms through which cause endocrine disruption.endocrine disruptors influence the endocrineChemicals that are known endocrine disruptorssystem and alter hormonal functions.include diethylstilbestrol (the synethetic estrogenEndocrine disruptors can: DES), dioxin and dioxin-like compounds,polychlorinated biphenyls (PCBs), DDT, and some Mimic or partly mimic naturally occurringother pesticides.hormones in the body like estrogens(the female sex hormone), androgens (themale sex hormone), and thyroid hormones,potentially producing overstimulation. Bind to a receptor within a cell and blockthe endogenous hormone from binding.The normal signal then fails to occur and thebody fails to respond properly. Examples of Bisphenol A (BPA) is a chemical produced inchemicals that block or antagonize hormones large quantities for use primarily in the productionare anti-estrogens and anti-androgens.of polycarbonate plastics and epoxy resins. TheNTP Center for the Evaluation of Risks to Human Interfere or block the way natural hormones Reproduction completed a review of BPA inor their receptors are made or controlled, forSeptember 2008. The NTP expressed some concernexample, by altering their metabolism infor effects on the brain, behavior, and prostate glandthe liver.in fetuses, infants, and children at current humanexposures to bisphenol A. 10 Normal HormoneHormone Mimic Hormone BlockerDi(2-ethylhexyl) phthalate (DEHP) is a high Hormone Receptor production volume chemical used in themanufacture of a wide variety of consumer foodpackaging, some childrens products, and some Cell Nucleuspolyvinyl chloride (PVC) medical devices. In 2006,Cellular Response Cellular Response Cellular Response the NTP found that DEHP may pose a risk to humandevelopment, especially critically ill male infants.11 When absorbed in the body, an endocrine disruptor can decrease or increase normal hormone levels (left), mimic Phytoestrogens are naturally occurring substances the bodys natural hormones (middle), or alter the naturalin plants that have hormone-like activity. Examples production of hormones (right).of phytoestrogens are genistein and daidzein, whichcan be found in soy-derived products.1 Endocrinology. 2006. 147(6):S11-S17. 2 Developmental Biology. 2001. 238:224-238. 3 National Toxicology Programs Report of the Endocrine Disruptors Low-Dose Peer Review. 2001. 4 Environmental Health Perspectives. 1995. 103:83-87. 5 Endocrinology. 2006. 147(6):S11-S17. 6 Carcinogenesis. 2000. 21(7):1355-1363. 7 Carcinogenesis. 1998. 19:1655-1663. 8 Cancer Research. 2000. 60:235-237. 9 Science. 2005. 308(5727):1466-1469. 10 NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A. NIH Publication No. 08-5994. September 2008. 11 NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di(2-ethylhexyl) Phthalate (DEHP). NIH PublicationNo. 06-4476. November 2006.

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