Xenoestrogen
Encyclopedia
Xenoestrogens are a type of 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...

 that imitates estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

. They are widely used industrial compounds such as PCB, BPA
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....

 and 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...

, that have estrogenic effects on a living organism even though they differ chemically from the naturally occurring estrogenic substances internally produced by the 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"...

 of the organism. Their potential ecological and human health impact is currently under extensive study by many scientific institutions and independent researchers. The word xenoestrogen is derived from the Greek words ξένο (xeno, meaning foreign), οἶστρος (estrus, meaning sexual desire) and γόνο (gene, meaning "to generate") and literally means "foreign estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

". Xenoestrogens are also called "environmental hormones" or "EDC" (Endocrine Disrupting Compounds). Most scientists that study xenoestrogens, including 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...

, regard them as serious environmental hazards that have hormone disruptive effects
Endocrine disruptor
Endocrine disruptors are chemicals that interfere with endocrine in animals, including humans. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders...

 on both wildlife and humans.

As a heterogeneous group of chemicals that are hormonally active agents, xenoestrogens are similar to other estrogens, such as 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...

 (estrogenic substances from plants) 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...

 (estrogenic substances from fungi
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

, which can be considered as one type of mycotoxin). Xenoestrogens include pharmacological estrogens (estrogenic action is an intended effect, as in the drug ethinyl estradiol used in contraceptive pill), but other chemicals may also have estrogenic effects. Xenoestrogens have been introduced into the environment by industrial, agricultural and chemical companies and consumers only in the last 70 years or so, but archiestrogens have been a ubiquitous part of the environment even before the existence of the human race given that some plants (like the cereals and the legumes) are using estrogenic substances possibly as part of their natural defence against herbivore
Herbivore
Herbivores are organisms that are anatomically and physiologically adapted to eat plant-based foods. Herbivory is a form of consumption in which an organism principally eats autotrophs such as plants, algae and photosynthesizing bacteria. More generally, organisms that feed on autotrophs in...

 animals by controlling their male fertility http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1474615/ .

Effects

Xenoestrogens have been implicated in a variety of medical problems and during the last 10 years many scientific studies gave much hard evidence of adverse effects in the human health as well as the wildlife (some on line scientific papers http://toxsci.oxfordjournals.org/content/78/1/156.abstracthttp://tih.sagepub.com/content/14/1-2/239.abstracthttp://toxsci.oxfordjournals.org/content/81/1/179.abstracthttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3G-436W01M-8&_user=10&_coverDate=06%2F10%2F2001&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1543386781&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=c06f841c4a6575501636d77a546f2186&searchtype=ahttp://www.fertstert.org/article/S0015-0282(02)04389-3/abstracthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519239/http://humrep.oxfordjournals.org/content/17/8/1973.fullhttp://informahealthcare.com/doi/abs/10.3109/01674829609025667http://tih.sagepub.com/content/15/1-2/152.abstracthttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6K-51BP6NK-1&_user=10&_coverDate=10%2F29%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1543405987&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=16eea72a530fcff8d58e0b15199f4852&searchtype=a).

There is a concern that xenoestrogens may act as false messengers and disrupt the process of reproduction. Xenoestrogens, like all estrogens, can increase growth of the endometrium
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...

, so treatments for endometriosis
Endometriosis
Endometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...

 include avoidance of products which contain them. Likewise, they are avoided in order to prevent the onset or aggravation of adenomyosis
Adenomyosis
Adenomyosis is a medical condition characterized by the presence of ectopic glandular tissue found in muscle. The term adenomyosis is derived from the terms adeno- , myo- , and -osis...

. Studies have implicated observations of disturbances in wildlife with estrogenic exposure. For example, discharge from human settlement including runoff and water flowing out of wastewater treatment plants release a large amount of xenoestrogens into streams, which lead to immense alterations in aquatic life. With a bioaccumulation factor of 10^5 –10^6, fish are extremely susceptible to pollutants . Streams in more arid conditions are thought to have more effects due to higher concentrations of the chemicals arising from lack of dilution

When comparing fish from above a wastewater treatment plant and below a wastewater treatment plant, studies found disrupted ovarian and testicular histopathology, gonadal intersex, reduced gonad size, vitellogenin induction, and altered sex ratios .

The sex ratios are female biased because xenoestrogens interrupt gonadal configuration causing complete or partial sex reversal. When comparing adjacent populations of white sucker fish, the exposed female fish can have up to five oocyte stages and asynchronously developing ovaries versus the unexposed female fish who usually have two oocyte stages and group-synchronously developing ovaries. Previously, this type of difference has only been found between tropical and temperate species

Sperm concentrations and motility perimeters are reduced in male fish exposed to xenoestrogens in addition to disrupt stages of spermatogenesis . Moreover, xenoestrogens have been leading to vast amounts of intersex in fish. For example, one study indicates the numbers of intersex in white sucker fish to be equal to the number of males in the population downstream of a waste water treatment plant. No intersex members were found upstream from the plant. Also, they found differences in the proportion of testicular and ovarian tissue and it’s degree of organization between the intersex fish . Furthermore, xenoestrogens expose fish to CYP1A inducers through inhibiting a putative labile protein and enhancing the Ah receptor, which has been linked to epizootics of cancer and the initiation of tumors .

The induction of CYP1A has been established to be a good bioindicator for xenoestrogen exposure. In addition, xenoestrogens stimulate vitellogenin (Vtg), which acts as a nutrient reserve, and Zona readiata proteins (Zrp), which forms eggshells. Therefore, Vtg and Zrp are biomarkers to exposure for fish .

Another potential effect of xenoestrogens is on oncogene
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...

s, specifically in relation to breast cancer
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...

. Some scientists doubt that xenoestrogens have any significant biological effect, in the concentrations found in the environment. However, there is substantial evidence in a variety of recent studies to indicate that xenoestrogens can increase breast cancer growth in tissue culture
Tissue culture
Tissue culture is the growth of tissues or cells separate from the organism. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, such as broth or agar...

.

It has been suggested that very low levels of a xenoestrogen, 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....

, could affect fetal neural signalling more than higher levels, indicating that classical models where dose equals response may not be applicable in susceptible tissue. As this study involved intra-cerebellar injections, its relevance to environmental exposures is unclear, as is the role of an estrogenic effect compared to some other toxic effect of bisphenol A.

Other scientists argue that the observed effects are spurious and inconsistent, or that the quantities of the agents are too low to have any effect. A 1997 survey of scientists in fields pertinent to evaluating estrogens found that 13 percent regarded the health threats from xenoestrogens as "major," 62 percent as "minor" or "none," and 25 percent were unsure.

There has been speculation that falling sperm counts in males may be due to increased oestrogen exposure in utero. Sharpe in a 2005 review indicated that external estrogenic substances are too weak in their cumulative effects to alter male reproductive functioning, but indicates that the situation appears to be more complex as external chemicals may affect the internal testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

-estrogen balance.

Presence

The ubiquitous presence of such estrogenic substances is a significant health concern, both individually and for a population. Life relies on the transmission of biochemical information to the next generation, and the presence of xenoestrogens may interfere with this transgenerational information process through "chemical confusion" (Vidaeff and Sever), who state: "The results do not support with certainty the view that environmental estrogens contribute to an increase in male reproductive disorders, neither do they provide sufficient grounds to reject such a hypothesis."

A 2008 report demonstrates further evidence of widespread effects of feminizing chemicals on male development in each class of vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

 species as a worldwide phenomenon. 99% percent of over 100,000 recently introduced chemicals are underregulated, according to the European Commission.

Agencies such as the United States Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...

 and the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 International Programme on Chemical Safety
International Programme on Chemical Safety
The International Programme on Chemical Safety was formed in 1980 and is a collaboration between three United Nations bodies—the World Health Organization, the International Labour Organization and the United Nations Environment Programme to establish the scientific basis for safe use of...

 are charged to address these issues.

Chemicals shown to have estrogenic effects

  • alkylphenol
    Alkylphenol
    Alkylphenols are a family of organic compounds obtained by the alkylation of phenols. The term is usually reserved for commercially important propylphenol, butylphenol, amylphenol, heptylphenol, octylphenol, nonylphenol, dodecylphenol and related "long chain alkylphenols"...

    s (intermediate chemicals used in the manufacture of other chemicals)
  • 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...

     (weedkiller)
  • 4-Methylbenzylidene camphor
    4-Methylbenzylidene camphor
    4-Methylbenzylidene camphor is an organic camphor derivative that is used in the cosmetic industry for its ability to protect the skin against UV, specifically UV B radiation. As such it is used in sunscreen lotions and other skincare products claiming a SPF value...

     (4-MBC) (sunscreen lotions)
  • butylated hydroxyanisole
    Butylated hydroxyanisole
    Butylated hydroxyanisole is an antioxidant consisting of a mixture of two isomeric organic compounds, 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole. It is prepared from 4-methoxyphenol and isobutylene. It is a waxy solid used as a food additive with the E number E320...

    , BHA (food preservative)
  • 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....

     (monomer for polycarbonate plastic and epoxy resin; antioxidant in plasticizers)
  • dichlorodiphenyldichloroethylene
    Dichlorodiphenyldichloroethylene
    Dichlorodiphenyldichloroethylene is a chemical compound formed by the loss of hydrogen chloride from DDT, of which it is one of the more common breakdown products. DDE is fat soluble which tends to build up in the fat of animals. Due to its stability in fat, DDE is rarely excreted from the body,...

     (one of the breakdown products of DDT)
  • dieldrin
    Dieldrin
    Dieldrin is a chlorinated hydrocarbon originally produced in 1948 by J. Hyman & Co, Denver, as an insecticide. Dieldrin is closely related to aldrin, which reacts further to form dieldrin. Aldrin is not toxic to insects; it is oxidized in the insect to form dieldrin which is the active compound...

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

     (banned insecticide)
  • 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...

     (widely banned insecticide)
  • erythrosine
    Erythrosine
    Erythrosine, also known as Red No. 3, is an organoiodine compound, specifically a derivative of fluorone. It is cherry-pink synthetic, primarily used for food coloring. It is the disodium salt of 2,4,5,7-tetraiodofluorescein...

    , FD&C Red No. 3
  • 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...

     (combined oral contraceptive pill) (released into the environment as a xenoestrogen)
  • heptachlor
    Heptachlor
    Heptachlor is an organochlorine compound that was used as an insecticide. Usually sold as a white or tan powder, heptachlor is one of the cyclodiene insecticides. In 1962, Rachel Carson's Silent Spring questioned the safety of heptachlor and other chlorinated insecticides. Due to its highly...

     (restricted insecticide)
  • lindane
    Lindane
    Lindane, also known as gamma-hexachlorocyclohexane, , gammaxene, Gammallin and erroneously known as benzene hexachloride , is an organochlorine chemical variant of hexachlorocyclohexane that has been used both as an agricultural insecticide and as a pharmaceutical treatment for lice and...

    , hexachlorocyclohexane (restricted insecticide)
  • metalloestrogen
    Metalloestrogen
    Metalloestrogens are a class of inorganic xenoestrogens which can affect the gene expression of human cells responding to estrogen. Effects are related to the physiologic function of estrogen because metalloestrogens have shown affinity for estrogen receptors...

    s (a class of inorganic xenoestrogens)
  • methoxychlor
    Methoxychlor
    Methoxychlor is a synthetic organochlorine used as an insecticide.-Usage:Methoxychlor is used to protect crops, ornamentals, livestock, and pets against fleas, mosquitoes, cockroaches, and other insects...

     (banned insecticide)
  • nonylphenol
    Nonylphenol
    Nonylphenol is a family of closely related organic compounds, a subset of the alkylphenols. This collection of compounds is a precursor to commercially important detergents...

     and derivatives (industrial surfactants; emulsifiers for emulsion polymerization; laboratory detergents; pesticides)
  • pentachlorophenol
    Pentachlorophenol
    Pentachlorophenol is an organochlorine compound used as a pesticide and a disinfectant. First produced in the 1930s, it is marketed under many trade names...

     (restricted general biocide and wood preservative)
  • 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, PCBs (banned; formerly used in electrical oils, lubricants, adhesives, paints)
  • parabens (lotions)
  • phenosulfothiazine (a red dye)
  • 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...

     (plasticizer
    Plasticizer
    Plasticizers or dispersants are additives that increase the plasticity or fluidity of the material to which they are added; these include plastics, cement, concrete, wallboard, and clay. Although the same compounds are often used for both plastics and concretes the desired effects and results are...

    s)
    • DEHP (plasticizer for PVC)
  • Propyl gallate
    Propyl gallate
    Propyl gallate, or propyl 3,4,5-trihydroxybenzoate is an ester formed by the condensation of gallic acid and propanol. Since 1948, this antioxidant has been added to foods containing oils and fats to prevent oxidation. As a food additive, it is used under the E number E310.-Description:Propyl...

     (used to protect oils and fats in products from oxidation)

See also

  • 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...

     (obsolete pharmacological estrogen)
  • Endocrine disruptor
    Endocrine disruptor
    Endocrine disruptors are chemicals that interfere with endocrine in animals, including humans. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders...

  • Environmental exogenous hormones
    Environmental exogenous hormones
    Environmental exogenous estrogens, otherwise referred to as xenoestrogens, are endocrine disruptors, structurally similar to estrogens. Xenoestrogens are clinically significant because they can mimic the effects of endogenous estrogen and thus have been implicated in precocious puberty and other...

  • Environmental xenobiotic
  • Epidemiology and etiology of breast cancer
    Epidemiology and etiology of breast cancer
    Risk factors of breast cancer may be divided into preventable and non preventable. Their study belongs in the field of epidemiology. Breast cancer, like other forms of cancer, is considered to result from multiple environmental and hereditary risk factors....

  • List of breast carcinogenic substances
  • 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...

  • SULT2B1
    SULT2B1
    Sulfotransferase family cytosolic 2B member 1 is an enzyme that in humans is encoded by the SULT2B1 gene.-Further reading:...

  • Xenobiotic
    Xenobiotic
    A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual...


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