Xenoestrogen

Xenoestrogens are "foreign" estrogens often 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 the endocrine system 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". Xenoestrogens are also called "environmental hormones" or "EDC" (Endocrine Disrupting Compounds). Most scientists that study xenoestrogens, including The Endocrine Society, regard them as serious environmental hazards that have hormone disruptive effects 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 (estrogenic substances from plants) and mycoestrogens (estrogenic substances from fungi, 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 animals by controlling their male fertility.

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 ).

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, so treatments for endometriosis include avoidance of products which contain them. Likewise, they are avoided in order to prevent the onset or aggravation of adenomyosis. 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 oncogenes, specifically in relation to breast cancer. 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.

It has been suggested that very low levels of a xenoestrogen, Bisphenol A, 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-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 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 and the World Health Organization International Programme on Chemical Safety are charged to address these issues.

Chemicals shown to have estrogenic effects

 * alkylphenols (intermediate chemicals used in the manufacture of other chemicals)
 * atrazine (weedkiller)
 * 4-Methylbenzylidene camphor (4-MBC) (sunscreen lotions)
 * butylated hydroxyanisole, BHA (food preservative)
 * bisphenol A (monomer for polycarbonate plastic and epoxy resin; antioxidant in plasticizers)
 * dichlorodiphenyldichloroethylene (one of the breakdown products of DDT)
 * dieldrin (banned insecticide)
 * DDT (banned insecticide)
 * endosulfan (widely banned insecticide)
 * erythrosine, FD&C Red No. 3
 * ethinylestradiol (combined oral contraceptive pill) (released into the environment as a xenoestrogen)
 * heptachlor (restricted insecticide)
 * lindane, hexachlorocyclohexane (restricted insecticide)
 * metalloestrogens (a class of inorganic xenoestrogens)
 * methoxychlor (banned insecticide)
 * nonylphenol and derivatives (industrial surfactants; emulsifiers for emulsion polymerization; laboratory detergents; pesticides)
 * pentachlorophenol (restricted general biocide and wood preservative)
 * polychlorinated biphenyls, PCBs (banned; formerly used in electrical oils, lubricants, adhesives, paints)
 * parabens (lotions)
 * phenosulfothiazine (a red dye)
 * phthalates (plasticizers)
 * DEHP (plasticizer for PVC)
 * Propyl gallate (used to protect oils and fats in products from oxidation)