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March 26, 2016
Table of Contents

1 Introduction
endocrine disruptor

Wikipedia

 

Endocrine disruptors are exogenous substances usually xenoestrogens that "interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body that are responsible for the maintenance of homeostasis (normal cell metabolism), reproduction, development, and/or behavior."

EDC studies have linked endocrine disruptors to adverse biological effects in animals, giving rise to concerns that low-level exposure might cause similar effects in human beings.




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 permanent.

Although the theory of 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, mostly in wildlife but also in humans. A concurrent statement expresses policy concerns.

Endocrine disrupting compounds encompass a variety of chemical classes, including hormones, plant constituents, pesticides, compounds used in the plastics industry and in consumer products, and other industrial by-products and pollutants. Some are pervasive and widely dispersed in the environment. 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. Others are rapidly degraded in the environment or human body or may be present for only short periods of time.

One example of the consequences of the exposure of developing animals, including humans, to hormonally active agents is the case of the drug diethylstilbestrol (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 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. 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.




Endocrine systems are found in most varieties of animals. The endocrine system consists of glands that secrete hormones, and receptors 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 hormones, are subject to feedback regulation, which tends to limit the sensitivity of these glands.

The theory of endocrine disruption posits that low-dose exposure to chemicals that interact with hormone receptors can interfere with reproduction, development, and other hormonally mediated processes. Furthermore, since endogenous hormones are already present in the body in biologically active concentrations, the theory holds that additional exposure to relatively small amounts of exogenous hormonally active substances can disrupt the proper functioning of the body's endocrine system. Thus, an endocrine disruptor might be able to elicit adverse effects at a much lower doses than a toxicant acting through a different mechanism.

The timing of exposure is also presumed to be critical, since different hormone pathways are active during different stages of development. Particularly with younger individuals that are growing rapidly, interfering with the hormonal communication processes these systems provide can have profound effects on the body. 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.

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.

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. Certain cancers and uterine abnormalities in women are associated with exposure to DES in the womb due to DES used 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 anal-genital distance and associated incomplete descent of testes and a smaller scrotum and penis.




One major objection to the theory of endocrine disruptors is the dosage effect. There is a large gap between high exposures seen in a some laboratory experiment versus the relatively low levels found in the environment.

The dosage objection could also be overcome if low concentrations of different endocrine disruptors were synergistic, which was asserted in a paper by Arnold.

The conventional relationship (more exposure equals higher risk) has been challenged by some studying endocrine disruptors. For example, it has been claimed that Tamoxifen and some phthalates have fundamentally different (and harmful) effects on the body at low doses than at high doses.




Food is a major mechanism by which people are exposed to pollutant. Diet is thought to account for up to 90% of a person's PCB and DDT body burden.

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.

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 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.




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, Polychlorinated biphenyls (PCB's), Bisphenol A, Polybrominated diphenyl ethers (PBDE's), and a variety of Phthalates.

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 beetles on crops beginning in 1936. An increase in the incidence of malaria, epidemic typhus, dysentery, and typhoid fever led to its use against the mosquitoes, lice, and houseflies that carried these diseases. Before World War II, pyrethrum, 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 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

.

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.

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. 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. 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.

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.

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,

Bisphenol A

Bisphenol A is found in some plastic water and baby bottles, plastic food containers, dental materials, and the linings of metal food and infant formula cans . 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 and prostate cancers, decreased sperm count, reproductive problems, early puberty, obesity, 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, Playtex, and Wal-Mart have agreed to remove this substance from their products by the end of 2008.

Polybrominated diphenyl ethers

Polybrominated diphenyl ethers (PBDEs) are a class of compounds found in flame retardants 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 began, the US military used these new plastic materials to improve weapons, protect equipment, and to replace heavy components in aircraft and vehicles.

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,

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. 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. 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,

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.

Other suspected endocrine disruptors

Some other examples of putative EDCs are polychlorinated dibenzo-dioxins (PCDDs) and -furan s (PCDFs), polycyclic aromatic hydrocarbons (PAHs), phenol derivatives and a number of pesticides (most prominent being organochlorine insecticides like endosulfan and DDT and its derivatives, the herbicide atrazine, and the fungicide vinclozolin), the contraceptive 17-alpha ethinylestradiol, as well as naturally occurring phytoestrogens such as genistein and mycoestrogens such as zearalenone.




Since being banned, the average human body burdens of DDT and PCB have been declining.




The multitude of possible endocrine disruptors are technically regulated in the United States by many laws, including: the Toxic Substances Control Act, the Federal Insecticide, Fungicide, and Rodenticide Act, the Food, Drug and Cosmetic Act, the Clean Water Act, the Safe Drinking Water Act, and the Clean Air Act.

The Congress of the United States has improved the evaluation and regulation process of drugs and other chemicals. The Food Quality Protection Act of 1996 and the Safe Drinking Water Act 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 or the androgen receptor) 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 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. however this study was conducted over a year before the EPA announced the final structure of the screening program.




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 our 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 bioaccumulate 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 cleanup 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 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. These case studies are encouraging due to the short amount of time needed to remediate the site and the high level of success achieved.




  • Endocrine system

  • Hormone

  • Obesogen

  • Precautionary principle

  • Theo Colborn

  • Xenoestrogen








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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "endocrine disruptor".


Last Modified:   2010-11-25


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