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Endocrine disruptor: Official definitions, different modes of action, Discovery, contamination

S. Rajalakshmi
Written by S. Rajalakshmi. Posted in General Reference on 02 September 2009.
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Endocrine disruptor



The concept of endocrine modulator (or endocrine disruptor, endocrine disrupter, lure or hormonal Xenooestrogene ...) is a term coined in the late twentieth century to refer to any molecule or chemical compound, xenobiotic properties with hormone agonists.

These molecules act on the hormonal balance of species live animal (or plant in the case of hormones). They are often likely to have adverse effects on health by impairing functions such as growth, the development, the behavior, production, use and storage of energy, the hemodynamic and blood flow, sexual function and reproduction.

These molecules act at very low dose of the same order of magnitude as the physiological concentrations of hormones. It is therefore not a toxic effect in the usual sense poisoning but rather a discrete disturbance which may be difficult to recognize. They may have an impact on an individual, but sometimes its descendants (eg Distilbène in women and its children) or on entire populations (eg, snails or marine fish populations living in areas of endocrine disruptors are present, including alligators from California or Grebler exposed to DDT can not happen again, they have been studied already old).


Official definitions

The EU has defined the endocrine disruptor (PE) as an agent who seems to influence (or "disrupt") the functioning of the endocrine system and more precisely as "a substance or mixture that alters function exogenous endocrine, and thus inducing effects harmful to the health of an intact organism, its progeny or subpopulations "
The endocrine disruptor as an altéragène biological, physical or chemical meets the standard definition of the word pollution adopted by the AFNOR in France 
Regulation REACH allows to identify endocrine disrupters as substances of very high concern, may be subject to specific management measures 


Three different modes of action

These molecules interfere with the functioning of the endocrine glands and target organs by:
imitating the action of a hormone naturally (as a false key in the "biological locks" that exist in the organs and cells);
Blocking the action of a natural hormone (in saturating the receptors for example);
disturbance (difficulty or blocking the production, transport, or metabolism of hormones or receptors, induced by abnormal hormone action in the body that interferes with metabolic processes or growth and cell division. These disturbances are especially more serious as they occur early (fetus, embryo, young children, because of irreversible effects may be induced, including genital malformations).


Discovery

Since the 1950s, studies have demonstrated in many industrialized countries reduced male fertility - morphological changes and decrease in sperm - an increased frequency of cancer of the testis, the prostate and breast, and a pubertal female ever earlier. Studies epidemiological, and laboratory experiments have shown that exposure to molecules hormone agonists was at least partly responsible for these phenomena.

The hydrosphere is the recipient of numerous chemicals, including natural hormones and metabolites of hormones, natural or synthetic contained in birth control pills, or used for medical or veterinary treatment. Prove these hormones present in large quantities in wastewater entering treatment plants, but also, although less for many of them in the outfalls of sewage treatment of water urban waste. Some aquatic organisms are estimated to be good indicators (fish affected by disorders of fertility and abnormal type intersex). Some species are also hubs (mussels, zebra mussels) from a pollution of aquatic environments by these effluents.

In 1960, the United States, the decline in fertility mink found by farmers in the region of the Great Lakes was attributed to pollutants bio-accumulated by fish. In 1962, in Silent Spring, Rachel Carson highlighted the reproductive toxicity of DDT. In 1988, the seals of the North Sea were decimated. In Britain, fish males living downstream from a sewage treatment plant showed characters female. The discovery of altered reproductive system of alligators wild Florida boosted research on this subject in the years 1990. In the early 1990s there is an awareness of the presence in the environment of substances capable of disrupting the endocrine system. In Europe, Denmark, Germany and the United Kingdom have been drivers in this area of research. Observations on some animal populations raised enough suspicion to encourage further research in the field.


Kinetics of endocrine disruptors in the environment

The persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT), dioxins (PCDDs) and polychlorinated biphenyls (PCBs), labile and accumulates along food chains, can persist in the environment several decades, travel in different environmental compartments - atmosphere, biosphere, hydrosphere, lithosphere - beyond borders: it has shown that polar bears could be contaminated with DDT issued to thousands of kilometers.

In humans, infection can also be food, natural phytoestrogens with germ wheat, soy, beer / hops ...), or artificial products migrants from packaging, residues of pesticides, of detergents or drugs , or through ingestion of contaminated filter feeders such as shells 

An endocrine disrupter known human is diethylstilbestrol (DES), estrogen synthetic prescribed in France between 1948 and 1977 for pregnant women to prevent the risk of abortion. The 17-beta-estradiol - estrogen natural treatment prescribed in women after menopause (HRT) - and 17-α-ethynylestradiol, which is used in birth control pills. The various substances that are ingested by humans as medicines can be found downstream of sewage treatment facilities as are relatively ineffective in destroying these types of compounds. The amount of chemical that is found there is a function of weather conditions (ultraviolet radiation, and temperature) and microbial activity 

The bisphenol A, polybrominated diphenyl ethers (PBDEs), and a variety of phthalates and other endocrine disruptors are commonly found in small doses in many products and the environment  Some authors suggest that health risks are not significant while others believe that there is sufficient evidence to say that these substances pose a risk to human health and human fertility. 

Bisphenol A has attracted particular attention as a component of many plastic bottles. In March 2007, a class action lawsuit (class action lawsuit) was filed in California against manufacturers and retailers of plastic baby bottles, but failed to warn consumers that their products contain bisphenol A, which some might impair the health and development of infants and children 


Origin of different sources of contamination

Among the endocrine disruptors, are two major classes that are of either natural or synthetic. Some molecules antiandrogens used for medical (including veterinary) or contraceptives are still present in the urine and are not filtered by wastewater treatment plants. They pose serious problems of feminization of male fish in English rivers downstream of sewage treatment plants, which concern the fishermen and ecologists, but also professionals in public health who fear similar effects in humans.

It was initially thought the steroid estrogens mainly from human urine were primarily responsible for testicular dysgenesis syndrome observed in fish. A recent study sought if this syndrome was due to one or several causes, and specifically whether these fish were not exposed to cocktails of chemicals the effects of both estrogenic and anti-androgenic, and with what effects. For this, the concentration and activity products (estrogen and anti-androgens) were modeled in 51 rivers in the UK and compared the rates of wild fish affected by feminization syndrome in these rivers. The tests were mounted in addition to estrogen, the rivers contain various anti-androgenic substances, found in almost all the effluent treatment plant. Moreover, the model results confirm that the feminizing effects affecting wild fish could be better modeled and predicted better by taking better account of exposure to both anti-androgens and estrogens or antiandrogens alone. The authors conclude the multi-causal nature of the feminization of wild fish in the United Kingdom, involving both goods and steroidal estrogens or xenoestrogens and other contaminants (still unknown) with anti-androgen. This study concluded that it is a cocktail of various chemicals in water and diluted sewage into rivers, which inhibits testosterone production of fish and their capacity for good reproduction.


Types of endocrine disrupters

Often distinguished:
Natural compounds:
myco-oestrogens: zearalenone;
Phyto-oestrogens: isoflavonoids (eg present in hops and beer).
Synthetic compounds:
Antioxidants: alkylphenols;
compounds organometallic: salts of tributyltin (TBT);
detergents: alkylphenols, nonylphenol, nonylphenol polyethoxylate;
Drug: synthetic steroids, such as those used in birth control pills;
Pesticides: organochlorines (DDT, HCH, PCDD) or organo-nitrogen compounds (triazine);
plasticizers: alkylphenols, nonylphenol, phthalates;
polychlorinated biphenyls (PCBs).


Some examples of xenoestrogens

The xenoestrogens are substances with potential estrogenic (that is to say capable of inducing a female character) and released into the environment mainly due to human activity. Here are some examples:


Steroidal Estrogens

A sharp decline in fish catch has been observed in several rivers in central Switzerland. This reduction could come from the presence of xenoestrogens in water. The determination of estrogen in the middle of a river water is a variable difficult to measure. To calculate activity estrogen Total (expressed in equivalent 17_ß-estradiol, EQA), there must be a defining factor equivalence 17_ß-estradiol (FFA):  where Ci is the concentration of species i. The group of molecules that contributes the most to increase this value in domestic waste is the group of estrogen drugs Generally, the calculation is based on estrone (FFA = 0.4), the 17β-estradiol (FFA = 1) and 17α-éthynylœstradiol (FFA = 1.2).




Bisphenol A

Bisphenol A known to have properties of estrogen, is found in water in some polymers (including plastic bottles), plastic food packaging, dental materials, cans (tin type), and metal linings of canned food.
Health risk: it is a factor of deletion of spermatogenesis and is suspected to play a role in some miscarriages, obesity and certain cancers 


brominated flame retardants

Some of these agents (polybrominated diphenyl ethers and polybrominated diphenyl called "PBDEs) are used for fireproof materials as diverse as plastic televisions, computers, electronic components, electrical equipment and lighting, rugs, bedding, clothing, automotive components, foam cushions and other textile flame retardant.
Health risk: PBDEs have a chemical structure very similar to polychlorinated biphenyls (PCBs), and have the same effect neurotoxic, which is why it could disrupt hormonal systems thyroid and contribute to a variety of neurological and developmental deficit (including with neurological result of reduced learning ability and cognition). Some people may be more vulnerable, including for example the firefighters and personnel performing the sort of electronic waste. A study in Sweden compared the rates of PBDEs in various types of workers showed that recyclers of electronic equipment were particularly affected 

The use of some PBDEs were banned in the EU in 2006.


Phthalates

These compounds are mainly used as plasticizers to make plastics softer and more flexible. Phthalates are found in many objects (toys flexible, flooring, medical equipment, cosmetics, air fresheners, paints, adhesives, inks and adhesives)
Health risks: they are suspected to cause problems because these products are known to disrupt endocrine systems of animals (laboratory), and some studies suggest they are responsible for certain congenital malformations of the male reproductive tract 

One phthalate, Bis (2-ethylhexyl) phthalate (DEHP) is present in certain plastics used in medicine (catheters and blood bags). In 2002, the Food and Drug Administration has warned against exposure to DEHP in male infants on the basis of these effects on laboratory animals. According to the FDA: "Exposure to DEHP has produced a series of adverse effects in laboratory animals, but more worrying are the effects on the development of the male reproductive system and production of normal sperm in young animals" . The FDA has no studies on humans, but no studies can rule out similar effects. As a precaution, exposure to this product by developing organisms should be avoided believes the FDA 


Other suspected endocrine disruptors

Among the suspected products include: vinclozolin, zearalenone, the dioxins, the polychlorinated biphenyls (PCBs), PAHs, the furans, the phenols, various pesticides (including organochlorine, such as the insecticide endosulfan, the DDT and its derivatives).

S. Rajalakshmi

Author: S. Rajalakshmi

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