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Endocrine disruptor

Endocrine disruptor

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Endocrine disruptors are chemicals that interfere with endocrine (or hormone system) in animals, including humans. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders. Specifically, they are known to cause learning disabilities, severe attention deficit disorder, cognitive and brain development problems, deformations of the body (including limbs); sexual development problems, feminizing of males or masculine effects on females, etc. Any system in the body controlled by hormones, can be derailed by hormone disruptors. The critical period of development for most organisms is between the transition from a fertilized egg, into a fully formed infant. As the cells begin to grow and differentiate, there are critical balances of hormones and protein changes that must occur. Therefore, a dose of disrupting chemicals can do substantial damage to a developing fetus (baby). Whereas, the same dose may not significantly affect adult mothers. For a more scientific explanation, see below:

Endocrine disruptors are substances that "interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s in the body that are responsible for development, behavior, fertility, and maintenance of homeostasis (normal cell metabolism)." They are sometimes also referred to as hormonally active agents, endocrine disrupting chemicals, or endocrine disrupting compounds (EDCs).

EDC studies have shown that endocrine disruptors can cause adverse biological
Biological process
A biological process is a process of a living organism. Biological processes are made up of any number of chemical reactions or other events that results in a transformation....

 effects in animals, and low-level exposures also cause similar effects in human beings.
The term endocrine disruptor is often used as synonym for xenohormone
Xenohormone
Xenohormones are a group of either naturally occurring or artificially created compounds showing hormone-like properties. A type of endocrine disruptor, the most commonly occurring xenohormones are xenoestrogens, compounds that share the same chemical properties as estrogen...

 although the later can mean any naturally occurring or artificially produced compound showing hormone-like properties (usually binding to certain hormonal receptors).

History of the field of endocrine disruption


The term endocrine disruptor was coined at the Wingspread Conference Centre in Wisconsin, in 1991. One of the early papers on the phenomenon was by Theo Colborn in 1993. In this paper, she stated that environmental chemicals disrupt the development of the endocrine system, and that effects of exposure during development are often permanent.
Although the endocrine disruption has been disputed by some, work sessions from 1992 to 1999 have generated consensus statements from scientists regarding the hazard from endocrine disruptors, particularly in wildlife and also in humans. The Endocrine Society
The Endocrine Society
The Endocrine Society is a professional, international medical organization in the field of endocrinology and metabolism, founded in 1916 as The Association for the Study of Internal Secretions. The official name of the organization was changed to The Endocrine Society on January 1, 1952. It is a...

 released a scientific statement outlining mechanisms and effects of endocrine disruptors on “male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology,” and showing how experimental and epidemiological studies converge with human clinical observations “to implicate EDCs as a significant concern to public health.” The statement noted that it is difficult to show that endocrine disruptors cause human diseases, and it recommended that the precautionary principle
Precautionary principle
The precautionary principle or precautionary approach states that if an action or policy has a suspected risk of causing harm to the public or to the environment, in the absence of scientific consensus that the action or policy is harmful, the burden of proof that it is not harmful falls on those...

 should be followed. A concurrent statement expresses policy concerns.

Endocrine disrupting compounds encompass a variety of chemical classes, including drugs, pesticides, compounds used in the plastics industry and in consumer products, industrial by-products and pollutants, and even some naturally produced botanical chemicals. Some are pervasive and widely dispersed in the environment and may bio-accumulate. Some are persistent organic pollutants (POP's), and can be transported long distances across national boundaries and have been found in virtually all regions of the world, and may even concentrate near the North Pole, due to weather patterns and cold conditions. Others are rapidly degraded in the environment or human body or may be present for only short periods of time. Health effects attributed to endocrine disrupting compounds include a range of reproductive problems (reduced fertility, male and female reproductive tract abnormalities, and skewed male/female sex ratio
Sex ratio
Sex ratio is the ratio of males to females in a population. The primary sex ratio is the ratio at the time of conception, secondary sex ratio is the ratio at time of birth, and tertiary sex ratio is the ratio of mature organisms....

s, loss of fetus, menstrual problems); changes in hormone levels; early puberty; brain and behavior problems; impaired immune functions; and various cancers.
One example of the consequences of the exposure of developing animals, including humans, to hormonally active agents is the case of the drug diethylstilbestrol
Diethylstilbestrol
Diethylstilbestrol is a synthetic nonsteroidal estrogen that was first synthesized in 1938. Human exposure to DES occurred through diverse sources, such as dietary ingestion from supplemented cattle feed and medical treatment for certain conditions, including breast and prostate cancers...

 (DES), a non-steroidal estrogen and not an environmental pollutant. Prior to its ban in the early 1970s, doctors prescribed DES to as many as five million pregnant women to block spontaneous abortion, an off-label use
Off-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...

 of this medication prior to 1947. It was discovered after the children went through puberty that DES affected the development of the reproductive system and caused vaginal cancer
Vaginal cancer
Vaginal cancer is any type of cancer that forms in the tissues of the vagina. Primary vaginal cancer is rare in the general population of women and is usually a squamous carcinoma. Metastases are more common. Vaginal cancer occurs more often in women over age 50, but can occur at any age, even in...

. The relevance of the DES saga to the risks of exposure to endocrine disruptors is questionable, as the doses involved are much higher in these individuals than in those due to environmental exposures.

Aquatic
Aquatic
Aquatic means relating to water; living in or near water or taking place in waterAquatic may also refer to:* Aquatic animal, either vertebrate or invertebrate, which lives in water for most or all of its life...

 life subjected to endocrine disruptors in an urban effluent have experienced decreased levels of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 and increased feminization.

Endocrine system



Endocrine systems are found in most varieties of animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...

s. The endocrine system consists of gland
Gland
A gland is an organ in an animal's body that synthesizes a substance for release of substances such as hormones or breast milk, often into the bloodstream or into cavities inside the body or its outer surface .- Types :...

s that secrete hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s, and receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 that detect and react to the hormones.

Hormones travel throughout the body and act as chemical messengers. Hormones interface with cells that contain matching receptors in or on their surfaces. The hormone binds with the receptor, much like a key would fit into a lock. The endocrine system regulates adjustments through slower internal processes, using hormones as messengers. The endocrine system secretes hormones in response to environmental stimuli and to orchestrate developmental and reproductive changes. The adjustments brought on by the endocrine system are biochemical, changing the cell's internal and external chemistry to bring about a long term change in the body. These systems work together to maintain the proper functioning of the body through its entire life cycle. Sex steroids such as estrogens and androgens, as well as thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...

 hormones, are subject to feedback
Feedback
Feedback describes the situation when output from an event or phenomenon in the past will influence an occurrence or occurrences of the same Feedback describes the situation when output from (or information about the result of) an event or phenomenon in the past will influence an occurrence or...

 regulation, which tends to limit the sensitivity of these glands.

Hormones work at very small doses (part per billion ranges). Endocrine disruption can thereby also occur from low-dose exposure to exogenous hormones or hormonally active chemicals that can interfere with receptors for other hormonally mediated processes. Furthermore, since endogenous
Endogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

 hormones are already present in the body in biologically active concentrations, additional exposure to relatively small amounts of exogenous
Exogenous
Exogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....

 hormonally active substances can disrupt the proper functioning of the body's endocrine system. Thus, an endocrine disruptor can elicit adverse effects at much lower doses than a toxicity, acting through a different mechanism.

The timing of exposure is also critical. Most critical stages of development occur in utero, where the fertilized egg divides, rapidly developing every structure of a fully formed baby, including much of the wiring in the brain. Interfering with the hormonal communication in utero can have profound effects both structurally and toward brain development. Depending on the stage of reproductive development, interference with hormonal signaling can result in irreversible effects not seen in adults exposed to the same dose for the same length of time. Experiments with animals have identified critical developmental time points in utero and days after birth when exposure to chemicals that interfere with or mimic hormones have adverse effects that persist into adulthood. Disruption of thyroid function early in development may be the cause of abnormal sexual development in both males and females early motor development impairment, and learning disabilities.

There are studies of cell cultures, laboratory animals, wildlife, and accidentally exposed humans that show that environmental chemicals cause a wide range of reproductive, developmental, growth, and behavior effects, and so while "endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real." While compounds that produce estrogenic, androgenic, antiandrogenic, and antithyroid actions have been studied, less is known about interactions with other hormones.

The interrelationship between exposures to chemicals and health effects are rather complex. It is hard to definitively link a particular chemical with a specific health effect, and exposed adults may not show any ill effects. But, fetuses and embryos, whose growth and development are highly controlled by the endocrine system, are more vulnerable to exposure and may suffer overt or subtle lifelong health and/or reproductive abnormalities. Prebirth exposure, in some cases, can lead to permanent alterations and adult diseases.

Some in the scientific community are concerned that exposure to endocrine disruptors in the womb or early in life may be associated with neurodevelopmental disorders including reduced IQ, ADHD, and autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...

. Certain cancers and uterine abnormalities in women are associated with exposure to DES in the womb due to DES
DES
-Computing:* Data Encryption Standard* DirectShow Editing Services, an Application Programming Interface-Medical:* Diethylstilbestrol, a synthetic estrogen and the origin of the phrase "DES daughter"* DES gene, which encodes the Desmin protein...

 used as a medical treatment.

In another case, phthalates in pregnant women’s urine was linked to subtle, but specific, genital changes in their male infants – a shorter, more female-like anogenital distance
Anogenital distance
Anogenital distance is the distance from the anus to the genitalia, the base of the penis or vagina. It is considered medically significant for a number of reasons, in both humans and animals. It is regulated by dihydrotestosterone, which can be disrupted by phthalates common in plastics...

 and associated incomplete descent of testes and a smaller scrotum and penis. The science behind this study has been questioned by phthalate industry consultants. As of June 2008, there are only five studies of anogenital distance in humans, and one researcher has stated "Whether AGD measures in humans relate to clinically important outcomes, however, remains to be determined, as does its utility as a measure of androgen action in epidemiologic studies."

Dose-response controversy


One major objection to the theory of endocrine disruptors is the dosage effect. There is a large gap between high exposures seen in a laboratory experiment versus the relatively low levels found in the environment. Critics argue that dose-response relationship
Dose-response relationship
The dose-response relationship, or exposure-response relationship, describes the change in effect on an organism caused by differing levels of exposure to a stressor after a certain exposure time...

 data suggest that the amounts of the chemicals actually in the environment are too low to cause an effect. A consensus statement by the Learning and Development Disabilities Initiative rebuts this criticism arguing that "The very low-dose effects of endocrine disruptors can not be predicted from high-dose studies, which contradicts the standard 'dose makes the poison' rule of toxicology. Nontraditional dose-response curves are referred to as nonmonotonic dose response curves." Furthermore, endocrine disrupting effects have been noted in animals exposed to environmentally relevant levels of some chemicals. For example, researchers have found that a common flame retardant
Flame retardant
Flame retardants are chemicals used in thermoplastics, thermosets, textiles and coatings that inhibit or resist the spread of fire. These can be separated into several different classes of chemicals:...

, PBDE
PBDE
Polybrominated diphenyl ethers or PBDE, are organobromine compounds that are used as flame retardants. Like other brominated flame retardants, PBDEs have been used in a wide array of products, including building materials, electronics, furnishings, motor vehicles, airplanes, plastics,...

-47, affects the reproductive system and thyroid gland of female rats in doses of the order of those to which humans are exposed.

The dosage objection could also be overcome if low concentrations of different endocrine disruptors were synergistic, which was asserted in a paper by Arnold. This paper was published in Science
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....

 in June 1996, and was one reason for the passage of the Food Quality Protection Act
Food Quality Protection Act
The Food Quality Protection Act , or H.R.1627, was passed unanimously by Congress in 1996 and was signed into law by former U.S. President Bill Clinton on August 3, 1996...

 of 1996. The results could not be confirmed with the same and alternative methodologies, and the original paper was retracted, with Arnold found to have committed scientific misconduct by the United States Office of Research Integrity
United States Office of Research Integrity
The Office of Research Integrity is one of the bodies concerned with research integrity in the United States. It was created when the Office of Scientific Integrity in the National Institutes of Health and the Office of Scientific Integrity Review in the Office of the Assistant Secretary for...

. Subsequent papers by other authors demonstrated that low concentrations of endocrine disruptors can have synergistic effects in amphibians, but it is not clear that this is an effect mediated through the endocrine system.

The conventional relationship (more exposure equals higher risk) has been challenged by some studying endocrine disruptors. For example, it has been claimed that Tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...

 and some phthalates
Phthalates
Phthalates , or phthalate esters, are esters of phthalic acid and are mainly used as plasticizers . They are used primarily to soften polyvinyl chloride...

 have fundamentally different (and harmful) effects on the body at low doses than at high doses.

Routes of exposure


Food is a major mechanism by which people are exposed to pollutants. Diet is thought to account for up to 90% of a person's PCB and DDT body burden. In a study of 32 different common food products from three grocery stores in Dallas, fish and other animal products were found to be contaminated with PBDE. Since these compounds are fat soluble, it is likely they are accumulating from the environment in the fatty tissue of animals we eat. Some suspect fish consumption is a major source of many environmental contaminates. Indeed, both wild and farmed salmon from all over the world have been shown to contain a variety of man-made organic compounds.

With the increase in household products containing pollutants and the decrease in the quality of building ventilation, indoor air has become a significant source of pollutant exposure.

Residents living in homes with wood floors treated in the 1960s with PCB-based wood finish have a much higher body burden than the general population. A study of indoor house dust and dryer lint of 16 homes found high levels of all 22 different PBDE congeners tested for in all samples. Recent studies suggest that contaminated house dust, not food, may be the major source of PBDE in our bodies. One study estimated that ingestion of house dust accounts for up to 82% of our PBDE body burden.

Research conducted by the Environmental Working Group found that 19 out of 20 children tested had levels of PBDE in their blood 3.5 times higher than the amount in their mothers' blood. It has been shown that contaminated housedust is a primary source of lead in young children's bodies. It may be that babies and toddlers ingest more contaminated housedust than the adults they live with, and therefore have much higher levels of pollutants in their systems.

Types of endocrine disruptors


All people are exposed to chemicals with estrogenic effects in their everyday life, because endocrine disrupting chemicals are found in low doses in literally thousands of products. Chemicals commonly detected in people include DDT
DDT
DDT is one of the most well-known synthetic insecticides. It is a chemical with a long, unique, and controversial history....

, polychlorinated biphenyl
Polychlorinated biphenyl
Polychlorinated biphenyls are a class of organic compounds with 2 to 10 chlorine atoms attached to biphenyl, which is a molecule composed of two benzene rings. The chemical formula for PCBs is C12H10-xClx...

s (PCB's), bisphenol A
Bisphenol A
Bisphenol A is an organic compound with two phenol functional groups. It is used to make polycarbonate plastic and epoxy resins, along with other applications....

 (BPA), polybrominated diphenyl ethers (PBDE's), and a variety of phthalates. There is some dispute in the scientific community surrounding the claim that these chemicals actually disrupt the endocrine system. Many believe that there is little evidence that the degree of exposure in humans is enough to warrant concern, while many others believe there is evidence that these chemicals pose some risk to human health.

Some researchers are investigating the health risks to children of endocrine disrupting chemicals. Bisphenol A has come under a great deal of scrutiny as it is a common component of plastic baby bottles. In March 2007, a class action lawsuit was filed in California charging that manufacturers and retailers of plastic baby bottles failed to warn consumers that their products contained Bisphenol A, a chemical that they allege poses developmental and health risks to infants and children.

DDT



Dichloro-diphenyl-trichloroethane (DDT) was first used as a pesticide against Colorado potato beetle
Colorado potato beetle
The Colorado potato beetle , also known as the Colorado beetle, the ten-striped spearman, the ten-lined potato beetle or the potato bug, is an important pest of potato crops. It is approximately 10 mm long, with a bright yellow/orange body and five bold brown stripes along the length of each...

s on crops beginning in 1936. An increase in the incidence of malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

, epidemic typhus
Typhus
Epidemic typhus is a form of typhus so named because the disease often causes epidemics following wars and natural disasters...

, dysentery
Dysentery
Dysentery is an inflammatory disorder of the intestine, especially of the colon, that results in severe diarrhea containing mucus and/or blood in the faeces with fever and abdominal pain. If left untreated, dysentery can be fatal.There are differences between dysentery and normal bloody diarrhoea...

, and typhoid fever
Typhoid fever
Typhoid fever, also known as Typhoid, is a common worldwide bacterial disease, transmitted by the ingestion of food or water contaminated with the feces of an infected person, which contain the bacterium Salmonella enterica, serovar Typhi...

 led to its use against the mosquitoes, lice, and houseflies that carried these diseases. Before World War II, pyrethrum
Pyrethrum
Pyrethrum refers to several Old World plants of the genus Chrysanthemum which are cultivated as ornamentals for their showy flower heads. Pyrethrum is also the name of a natural insecticide made from the dried flower heads of C. cinerariifolium and C...

, an extract of a flower from Japan, had been used to control these insects and the diseases they can spread. During World War II, Japan stopped exporting pyrethrum, forcing the search for an alternative. Fearing an epidemic outbreak of typhus, every British and American soldier was issued DDT, who routinely dusted beds, tents, and barracks all over the world.

DDT was approved for general, non-military use after the war ended. It became used worldwide to increase monoculture
Monoculture
Monoculture is the agricultural practice of producing or growing one single crop over a wide area. It is also known as a way of farming practice of growing large stands of a single species. It is widely used in modern industrial agriculture and its implementation has allowed for large harvests from...

 crop yields that were threatened by pest infestation, and to reduce the spread of malaria which had a high mortality rate in many parts of the world. Its use for agricultural purposes has since been prohibited by national legislation of most countries, while its use as a control against malaria vectors is permitted, as specifically stated by the Stockholm Convention on Persistent Organic Pollutants
Stockholm Convention on Persistent Organic Pollutants
Stockholm Convention on Persistent Organic Pollutants is an international environmental treaty, signed in 2001 and effective from May 2004, that aims to eliminate or restrict the production and use of persistent organic pollutants .- History :...


.

As early as 1946, the harmful effects of DDT on bird, beneficial insects, fish, and marine invertebrates were seen in the environment. The most infamous example of these effects were seen in the eggshells of large predatory birds, which did not develop to be thick enough to support the adult bird sitting on them. Further studies found DDT in high concentrations in carnivores all over the world, the result of biomagnification
Biomagnification
Biomagnification, also known as bioamplification or biological magnification, is the increase in concentration of a substance that occurs in a food chain as a consequence of:* Persistence...

 through the food chain. Twenty years after its widespread use, DDT was found trapped in ice samples taken from Antarctic snow, suggesting wind and water are another means of environmental transport. Recent studies show the historical record of DDT deposition on remote glaciers in the Himalayas.

More than sixty years ago when biologists began to study the effects of DDT on laboratory animals, it was discovered that DDT interfered with reproductive development. Recent studies suggest DDT may inhibit the proper development of female reproductive organs that adversely affects reproduction into maturity. Additional studies suggest that a marked decrease in fertility in adult males may be due to DDT exposure. Most recently, it has been suggested that exposure to DDT in utero can increase a child's risk of childhood obesity. DDT is still used as anti-malarial insecticide in Africa and parts of Southeast Asia in limited quantities.

Polychlorinated biphenyls



Polychlorinated biphenyls (PCBs) are a class of chlorinated compounds used as industrial coolants and lubricants. PCBs are created by heating benzene, a byproduct of gasoline refining, with chlorine. They were first manufactured commercially by the Swann Chemical Company in 1927. In 1933, the health effects of direct PCB exposure was seen in those who worked with the chemicals at the manufacturing facility in Alabama. In 1935, Monsanto acquired the company, taking over US production and licensing PCB manufacturing technology internationally.

General Electric was one of the largest US companies to incorporate PCBs into manufactured equipment. Between 1952 and 1977, the New York GE plant had dumped more than 500,000 pounds of PCB waste into the Hudson River. PCBs were first discovered in the environment far from its industrial use by scientists in Sweden studying DDT.

The effects of acute exposure to PCBs were well known within the companies who used Monsanto's PCB formulation who saw the effects on their workers who came into contact with it regularly. Direct skin contact results in a severe acne-like condition called chloracne. Exposure increases the risk of skin cancer, liver cancer, and brain cancer. Monsanto tried for years to downplay the health problems related to PCB exposure in order to continue sales.

The detrimental health effects of PCB exposure to humans became undeniable when two separate incidents of contaminated cooking oil poisoned thousands of residents in Japan and Taiwan, leading to a worldwide ban on PCB use in 1977. Recent studies show the endocrine interference of certain PCB congeners is toxic to the liver and thyroid, increases childhood obesity in children exposed prenatally, and may increase the risk of developing diabetes.

Bisphenol A (BPA)




Bisphenol A is commonly found in plastic bottles (including many baby bottles), plastic food containers, dental materials, and the linings of metal food and infant formula cans
Tin can
A tin can, tin , steel can, or a can, is a sealed container for the distribution or storage of goods, composed of thin metal. Many cans require opening by cutting the "end" open; others have removable covers. Cans hold diverse contents: foods, beverages, oil, chemicals, etc."Tin" cans are made...

. Another exposure comes from receipt paper commonly used at grocery stores and restaurants, because today the paper is commonly coated with a BPA containing clay for printing purposes. It is a known endocrine disruptor, and "hundreds of studies published in the decade" have found that laboratory animals exposed to low levels of it have elevated rates diabetes, mammary
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

 and prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

s, decreased sperm count, reproductive problems, early puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...

, obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

, and neurological problems. Some scientists believe that humans, especially infants, are currently exposed to levels that are known to cause harm in laboratory animals. The US FDA and the chemical industry maintain that it is safe, but the US Congress has taken steps to restrict the use of bisphenol A and has asked the FDA to reexamine it. Canada recently announced it plans to phase out the use of bisphenol A in baby bottles and metal formula cans. Nalgene
Nalgene
Thermo Scientific Nalgene is a brand of polyethylene plastic developed and manufactured by Nalge Nunc International originally developed for laboratory storage containers. It is now used in the manufacture of water containers, vials, bottles, bags and carboys for packaging, shipping, and storage...

, Playtex
Playtex
Playtex and PlayTex are a brand and trademark. It used to be associated with bras and women's undergarments. Currently there are two separate companies with the Playtex name....

, and Wal-Mart
Wal-Mart
Wal-Mart Stores, Inc. , branded as Walmart since 2008 and Wal-Mart before then, is an American public multinational corporation that runs chains of large discount department stores and warehouse stores. The company is the world's 18th largest public corporation, according to the Forbes Global 2000...

 have agreed to remove this substance from their products by the end of 2008. In August of that year, the FDA issued a draft reassessment, reconfirming their initial opinion that, based on scientific evidence, it is safe. However in October 2008, FDA's advisory Science Board sent FDA back to the drawing board, concluding that the Agency's assessment was "flawed" and hadn't proven the chemical to be safe for formula-fed infants. In January 2010, the FDA issued a report indicating that, due to findings of recent studies that used novel approaches in testing for subtle effects, both the National Toxicology Program at the National Institutes of Health as well as the FDA have some level of concern regarding the possible effects of BPA on the brain and behavior of fetuses, infants and younger children.

Polybrominated diphenyl ethers



Polybrominated diphenyl ethers (PBDEs) are a class of compounds found in flame retardant
Flame retardant
Flame retardants are chemicals used in thermoplastics, thermosets, textiles and coatings that inhibit or resist the spread of fire. These can be separated into several different classes of chemicals:...

s used in plastic cases of televisions and computers, electronics, carpets, lighting, bedding, clothing, car components, foam cushions and other textiles. Potential health concern: PBDE's are structurally very similar to Polychlorinated biphenyls (PCBs), and have similar neurotoxic effects.

In the 1930s and 1940s, the plastics industry developed technologies to create a variety of plastics with broad applications. Once World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...

 began, the US military used these new plastic materials to improve weapons, protect equipment, and to replace heavy components in aircraft and vehicles. After WWII, manufacturers saw the potential plastics could have in many industries, and plastics were incorporated into new consumer product designs. Plastics began to replace wood and metal in existing products as well, and today plastics are the most widely used manufacturing materials.

By the 1960s, all homes were wired with electricity and had numerous electrical appliances. Cotton and wood had been the dominant textile used to produce home furnishings, but now their home furnishings were composed of mostly synthetic materials. More than 500 billion cigarettes were consumed each year in the 1960s, as compared to less than 3 billion per year at the turn of the century. When combined with high density living, the potential for home fires was higher in the 1960s than it had ever been in the US. By the late 1970s, approximately 6000 people in the US died each year in home fires.

In 1972, in response to this situation, the National Commission on Fire Prevention and Control was created to study the fire problem in the US. In 1973 they published their findings in America Burning, a 192-page report that made recommendations to increase fire prevention. Most of the recommendations dealt with fire prevention education and improved building engineering, such as the installation of fire sprinklers and smoke detectors. The Commission expected that with the recommendations, a 5% reduction in fire losses could be expected each year, halving the annual losses within 14 years.

Historically, treatments with alum and borax were used to reduce the flammability of fabric and wood, as far back as Roman times. Since it is a non-absorbent material once created, flame retardant chemicals are added to plastic during the polymerization reaction when it is formed. Organic compounds based on halogens like bromine and chlorine are used as the flame retardant additive in plastics, and in fabric based textiles as well. The widespread use of brominated flame retardants may be due to the push from Great Lakes Chemical Corporation (GLCC) to profit from its huge investment in bromine. In 1992, the world market consumed approximately 150,000 tonnes of bromine-based flame retardants, and GLCC produced 30% of the world supply.

PBDEs have the potential to disrupt thyroid hormone balance and contribute to a variety of neurological and developmental deficits, including low intelligence and learning disabilities. Many of the most common PBDE's were banned in the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...

 in 2006. Studies with rodents have suggested that even brief exposure to PBDEs can cause developmental and behavior problems in juveniles and exposure interferes with proper thyroid hormone regulation. Research has correlated halogenated hydrocarbons, such as PCBs, with neurotoxicity. PBDEs are similar in chemical structure to PCBs, and it has been suggested that PBDEs act by the same mechanism as PCBs.

Phthalates



Phthalates are found in some soft toys, flooring, medical equipment, cosmetics and air fresheners. They are of potential health concern because they are known to disrupt the endocrine system of animals, and some research has implicated them in the rise of birth defects of the male reproductive system.

Although an expert panel has concluded that there is "insufficient evidence" that they can harm the reproductive system of infants, California and Europe have banned them from toys. One phthalate, Bis(2-ethylhexyl) phthalate
Bis(2-ethylhexyl) phthalate
Bisphthalate, commonly abbreviated DEHP, is an organic compound with the formula C6H42. It is sometimes called dioctyl phthalate and abbreviated DOP. It is the most important "phthalate," being the diester of phthalic acid and the branched-chain 2-ethylhexanol. This colourless viscous liquid is...

 (DEHP), used in medical tubing, catheters and blood bags, may harm sexual development in male infants. In 2002, the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 released a public report which cautioned against exposing male babies to DEHP. Although there are no direct human studies the FDA report states: "Exposure to DEHP has produced a range of adverse effects in laboratory animals, but of greatest concern are effects on the development of the male reproductive system and production of normal sperm in young animals. In view of the available animal data, precautions should be taken to limit the exposure of the developing male to DEHP". Similarly, phthalates may play a causal role in disrupting masculine neurological development when exposed prenatally.

Alkylphenols


Certain alkylphenols are degradation products from nonionic detergents. Nonylphenol is considered to be a low-level endocrine disruptor owing to its tendency to mimic estrogen.

Perfluorooctanoic acid


PFOA exerts hormonal effects including alteration of thyroid hormone levels. Blood serum levels of PFOA were associated with an increased time to pregnancy — or "infertility" — in a 2009 study. PFOA exposure is associated with decreased semen quality. PFOA appeared to act as an endocrine disruptor by a potential mechanism on breast maturation in young girls. A C8 Science Panel status report noted an association between exposure in girls and a later onset of puberty.

Other suspected endocrine disruptors


Some other examples of putative EDCs are polychlorinated dibenzo-dioxins
Dioxins and dioxin-like compounds
Dioxins and dioxin-like compounds are by-products of various industrial processes, and are commonly regarded as highly toxic compounds that are environmental pollutants and persistent organic pollutants . They include:...

 (PCDDs) and -furan
Polychlorinated dibenzofurans
Polychlorinated dibenzofurans are a group of halogenated organic compounds which are toxic environmental pollutants. They are known teratogens, mutagens, and suspected human carcinogens. PCDFs tend to co-occur with polychlorinated dibenzodioxins...

s (PCDFs), polycyclic aromatic hydrocarbon
Polycyclic aromatic hydrocarbon
Polycyclic aromatic hydrocarbons , also known as poly-aromatic hydrocarbons or polynuclear aromatic hydrocarbons, are potent atmospheric pollutants that consist of fused aromatic rings and do not contain heteroatoms or carry substituents. Naphthalene is the simplest example of a PAH...

s (PAHs), phenol derivatives
Phenols
In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of a hydroxyl group bonded directly to an aromatic hydrocarbon group...

 and a number of pesticides (most prominent being organochlorine insecticides like endosulfan
Endosulfan
Endosulfan is an off-patent organochlorine insecticide and acaricide that is being phased out globally. Endosulfan became a highly controversial agrichemical due to its acute toxicity, potential for bioaccumulation, and role as an endocrine disruptor...

 and DDT
DDT
DDT is one of the most well-known synthetic insecticides. It is a chemical with a long, unique, and controversial history....

 and its derivatives, the herbicide atrazine
Atrazine
Atrazine, 2-chloro-4--6--s-triazine, an organic compound consisting of an s-triazine-ring is a widely used herbicide. Its use is controversial due to widespread contamination in drinking water and its associations with birth defects and menstrual problems when consumed by humans at concentrations...

, and the fungicide vinclozolin
Vinclozolin
- Introduction :Vinclozolin is a common dicarboximide fungicide used to control various diseases in vineyards, and on fruits and vegetables such as raspberries, lettuce, kiwi, beans and onions. It is also used on turf on golf courses...

), the contraceptive 17-alpha ethinylestradiol
Ethinylestradiol
Ethynylestradiol , also ethynyl estradiol , is a derivative of estradiol. Ethynyl estradiol is an orally bio-active estrogen used in almost all modern formulations of combined oral contraceptive pills...

, as well as naturally occurring phytoestrogens
Phytoestrogens
Phytoestrogens are plant-derived xenoestrogens functioning as the primary female sex hormone not generated within the endocrine system but consumed by eating phytoestrogonic plants...

 such as genistein
Genistein
Genistein is one of several known isoflavones. Isoflavones, such as genistein and daidzein, are found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source, also in the medicinal plant, Flemingia vestita and coffee Besides functioning as...

 and mycoestrogens
Mycoestrogens
Mycoestrogens are estrogens produced by fungi. The most important mycoestrogen is zearalenone, produced by Fusarium species of fungi. Zearalenone is the main phyto-oestrogen consumed in the USA. It may be one dietary factor that can reduce the prevalence of breast cancer.-In Food:Mycoestrogens...

 such as zearalenone
Zearalenone
Zearalenone , also known as RAL and F-2 mycotoxin, is a potent estrogenic metabolite produced by some Gibberella species.Several Fusarium species produce toxic substances of considerable concern to livestock and poultry producers: namely, deoxynivalenol, T-2 toxin, HT-2 toxin, diacetoxyscirpenol ...

.

Temporal trends of body burden


Since being banned, the average human body burdens of DDT and PCB have been declining. Since their ban in 1972, the PCB body burden is 1/100 of what it was in the early 1980s (Weschler 2009). Monitoring programs of European breast milk samples have shown that PBDE levels are increasing. An analysis of PBDE content in breast milk samples from Europe, Canada, and the US shows that levels are 40 times higher for North American women than for European women, and that levels in North America are doubling each year.

Legal approach


The multitude of possible endocrine disruptors are technically regulated in the United States by many laws, including: the Toxic Substances Control Act
Toxic Substances Control Act
The Toxic Substances Control Act is a United States law, passed by the United States Congress in 1976, that regulates the introduction of new or already existing chemicals. It grandfathered most existing chemicals, in contrast to the Registration, Evaluation and Authorization of Chemicals ...

, the Federal Insecticide, Fungicide, and Rodenticide Act
Federal Insecticide, Fungicide, and Rodenticide Act
The Federal Insecticide, Fungicide, and Rodenticide Act , et seq. is a United States federal law that set up the basic U.S. system of pesticide regulation to protect applicators, consumers, and the environment. It is administered by the Environmental Protection Agency and the appropriate...

, the Food, Drug and Cosmetic Act, the Clean Water Act
Clean Water Act
The Clean Water Act is the primary federal law in the United States governing water pollution. Commonly abbreviated as the CWA, the act established the goals of eliminating releases of high amounts of toxic substances into water, eliminating additional water pollution by 1985, and ensuring that...

, the Safe Drinking Water Act
Safe Drinking Water Act
The Safe Drinking Water Act is the principle federal law in the United States intended to ensure safe drinking water for the public. Pursuant to the act, the Environmental Protection Agency is required to set standards for drinking water quality and oversee all states, localities, and water...

, and the Clean Air Act
Clean Air Act
A Clean Air Act is one of a number of pieces of legislation relating to the reduction of airborne contaminants, smog and air pollution in general. The use by governments to enforce clean air standards has contributed to an improvement in human health and longer life spans...

.

The Congress of the United States has improved the evaluation and regulation process of drugs and other chemicals. The Food Quality Protection Act
Food Quality Protection Act
The Food Quality Protection Act , or H.R.1627, was passed unanimously by Congress in 1996 and was signed into law by former U.S. President Bill Clinton on August 3, 1996...

 of 1996 and the Safe Drinking Water Act
Safe Drinking Water Act
The Safe Drinking Water Act is the principle federal law in the United States intended to ensure safe drinking water for the public. Pursuant to the act, the Environmental Protection Agency is required to set standards for drinking water quality and oversee all states, localities, and water...

 of 1996 simultaneously provided the first legislative direction requiring the EPA to address endocrine disruption through establishment of a program for screening and testing of chemical substances.

In 1998 the EPA announced the Endocrine Disruptor Screening Program by establishment of a framework for priority setting, screening and testing more than 85,000 chemicals in commerce. The basic concept behind the program is that prioritization will be based on existing information about chemical uses, production volume, structure-activity and toxicity. Screening is done by use of in vitro test systems (by examining, for instance, if an agent interacts with the estrogen receptor
Estrogen receptor
Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...

 or the androgen receptor
Androgen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...

) and via the use of in animal models, such as development of tadpoles and uterine growth in prepubertal rodents. Full scale testing will examine effects not only in mammals (rats) but also in a number of other species (frogs, fish, birds and invertebrates). Since the theory involves the effects of these substances on a functioning system, animal testing is essential for scientific validity, but has been opposed by animal rights
Animal rights
Animal rights, also known as animal liberation, is the idea that the most basic interests of non-human animals should be afforded the same consideration as the similar interests of human beings...

 groups. Similarly, proof that these effects occur in humans would require human testing, and such testing also has opposition.

After failing to meet several deadlines to begin testing, the EPA finally announced that they were ready to begin the process of testing dozens of chemical entities that are suspected endocrine disruptors early in 2007, eleven years after the program was announced. When the final structure of the tests was announced there was objection to their design. Critics have charged that the entire process has been compromised by chemical company interference. In 2005, the EPA appointed a panel of experts to conduct an open peer-review of the program and its orientation. Their results found that "the long-term goals and science questions in the EDC program are appropriate", however this study was conducted over a year before the EPA announced the final structure of the screening program.

Environmental and human body cleanup


There is evidence that once a pollutant is no longer in use, or once its use is heavily restricted, the human body burden of that pollutant declines. Through the efforts of several large-scale monitoring programs, the most prevalent pollutants in the human population are fairly well known. The first step in reducing the body burden of these pollutants is enacting policies that eliminate or phase out their production.

The second step toward lowering human body burden is awareness of and potentially labeling foods that are likely to contain high amounts of pollutants. This strategy has worked in the past - pregnant and nursing women are cautioned against eating seafood that is known to accumulate high levels of mercury. Ideally, a certification process should be in place to routinely test animal products for POP concentrations. This would help the consumer identify which foods have the highest levels of pollutants.

The most challenging aspect of this problem is discovering how to eliminate these compounds from the environment and where to focus remediation efforts. Even pollutants no longer in production persist in the environment, and bio-accumulate in the food chain. An understanding of how these chemicals, once in the environment, move through ecosystems, is essential to designing ways to isolate and remove them. Working backwards through the food chain may help to identify areas to prioritize for remediation efforts. This may be extremely challenging for contaminated fish and marine mammals that have a large habitat and who consume fish from many different areas throughout their lives.

Many persistent organic compounds, PCB, DDT and PBDE included, accumulate in river and marine sediments. Several processes are currently being used by the EPA to clean up heavily polluted areas, as outlined in their Green Remediation program.

One of the most interesting ways is the utilization of naturally occurring microbes that degrade PCB congeners to remediate contaminated areas.

There are many success stories of cleanup efforts of large heavily contaminated Superfund sites. A 10 acres (40,468.6 m²) landfill in Austin, Texas contaminated with illegally dumped VOCs was restored in a year to a wetland and educational park.

A US uranium enrichment site that was contaminated with uranium and PCBs was cleaned up with high tech equipment used to find the pollutants within the soil. The soil and water at a polluted wetlands site were cleaned of VOCs, PCBs and lead, native plants were installed as biological filters, and a community program was implemented to ensure ongoing monitoring of pollutant concentrations in the area. These case studies are encouraging due to the short amount of time needed to remediate the site and the high level of success achieved.

See also

  • Endocrine system
    Endocrine system
    In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...

  • Hormone
    Hormone
    A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

  • Obesogen
    Obesogen
    Obesogens are foreign chemical compounds that disrupt normal development and balance of lipid metabolism, which in some cases, can lead to obesity...

  • Precautionary principle
    Precautionary principle
    The precautionary principle or precautionary approach states that if an action or policy has a suspected risk of causing harm to the public or to the environment, in the absence of scientific consensus that the action or policy is harmful, the burden of proof that it is not harmful falls on those...

  • Theo Colborn
  • Xenoestrogen
    Xenoestrogen
    Xenoestrogens are a type of xenohormone that imitates estrogen. They are widely used industrial compounds such as PCB, BPA and Phthalates, that have estrogenic effects on a living organism even though they differ chemically from the naturally occurring estrogenic substances internally produced by...


External links