Introduction to Endogenous Estrogens

Estrogens, a class of sex steroid hormones responsible for the development of gender-specific characteristics in females, also play what is considered to be one of the most crucial roles in longitudinal skeletal growth - regulating fusion of the growth plates. The three major naturally occuring estrogens found in the human body are Estradiol, Estriol, and Estrone. (Fig. 1). These estrogens are produced in the body via a series of enzymatic chemical reactions starting from cholesterol and including androgens as precursors in the reaction scheme.

Over the past decade estrogens have been discovered by researchers to be the sole hormone unequivocally responsible for the regulation of growth plate fusion in both males and females [1, 2]. The female body contains much higher levels of estrogens than males, and this is the direct reason why females are shorter on average than males and stop growing taller several years sooner. However, the male body also produces estrogens and these hormones play an equally important role in the regulation of growth plate fusion within the male body.

Classifications of Exogenous Estrogens

Exogenous estrogens include bioidentical hormones as well as natural and synthetic estrogenic compounds that are introduced into the body from an external source where they proceed to exert estrogenic effects that can mimic the bodies own estrogens.

There are 5 major classes of exogenous estrogens that can be introduced into the body;

-- Bioidentical Estrogens

Synthetically produced estrogens identical to the bodies naturally occuring Estradiol, Estriol, or Estrone. Commonly used in hormone replacement therapies.

-- Pharmacological Estrogens

Synthetic compounds often structurally similar derivatives of the bodies own estrogens, developed for clinical use in the treatment of various diseases and disorders primarily afflicting women.

-- Xenoestrogens

Synthetic compounds that may or may not be structurally related to the bodies own estrogens, but elicit undesired and unintended estrogenic effects in bodily tissues.

-- Phytoestrogens

Naturally occuring phytonutrient compounds found throughout plants in nature that elicit estrogenic effects.

-- Mycoestrogens

Naturally occuring myconutrient compounds found throughout fungi in nature that elicit estrogenic effects.

This article will focus on the unintentional exposure to xenoestrogens encountered in the day to day life of the average person. It will also touch base on how to identify some of the major sources of exposure and what realistic measures you can take to limit that exposure.

What is a Xenoestrogen?

Xenoestrogens are hormonally active compounds that can exert a weak to strong estrogenic effect throughout the tissues of the human body by binding to the estrogen receptors thereby mimicking the bodies own estrogens. Xenoestrogens are often a chemical or by-product of synthetic man-made materials. Their pharmacologic effects are an unintended and undesired chemical property. Human exposure to xenoestrogens is also an unintended but common occurrence.

Negative Effects of Xenoestrogens

In breast cancer, a women's lifetime exposure to estrogens, known as her "estrogen window", is one of the major risk factors dictating her risk for developing the disease. The estrogen window also plays an important, yet overlooked, role in the physiological process of height growth in both males and females. The amount of estrogens, wether synthetic, natural, endogenous, or exogenous, that an adolescent is exposed to during their childhood and throughout their pubertal growth phase, can be a major factor dictating both their growth velocity and duration of their growth phase, which ultimately impacts their final adult height.

Xenoestrogens can exert estrogenic effects within the bodies growth plates in a manner identical to those your bodies own endogenous estrogens exert. Because xenoestrogens can bind to estrogen receptors throughout the body and promote an estrogenic effect, it is therefore possible for xenoestrogens to accelerate growth plate maturation eventually leading to premature fusion in males and females. Premature fusion of the long-bone and vertebrae growth plates can result in a significant loss of final adult height. Extreme exposure to xenoestrogens could even result in the development or worsening of health disorders such as breast cancer in females, gynecomastia (male breast growth), and a host of pubertal development and reproductive issues in both males and females.

Many of these synthetic man-made estrogenic compounds are also considered an environmental pollutant and have been linked to disturbances in wildlife found living in habitats polluted with high levels of xenoestrogens.

Sources of Xenoestrogen Exposure

As the technologies of modern society advance, we are exposed to a greater number of synthetic man-made materials, chemicals, and environmental pollutants. These synthetic materials are the leading source for exposure to xenoestrogens and may threaten the health and wellness of most living organisms.

Researchers have identified several major classes of materials and products that have been shown or suggested to contain xenoestrogens and have a high risk for frequent contact with humans;

-- Cosmetic Preservatives

A large number of hygiene and cosmetic products contain a class of preservatives called Parabens. Parabens is the name given to a group of p-hydroxybenzoic acid (PHBA) esters including; Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben. While acute toxicity studies in animals have indicated that parabens are not significantly toxic when given through various routes of administration, more recent studies have shown that parabens exert unintended estrogenic effects and are therefore classifiable as xenoestrogens [3]. Propylparaben has been shown to affect sperm levels, while Butylparaben was shown to decrease epididymis and seminal vesicle weight, effects that some scientists have suggested may correlate with excess estrogenic actions in the male body. However, estrogen receptor kinetic studies of parabens have suggested they only possess a weak estrogenic response at least 1000x less potent than the bodies endogenous estrogen, estradiol [4]. Based on the existing research, it would seem unlikely that exposure to this class of xenoestrogens alone could exert a potent enough estrogenic response to yield a significant impact on the final adult height of a growing adolescent [5].

-- Food Preservatives

Food preservatives are added to many food items to increase their shelf-life by retarding rancidity. Butylated hydroxyanisole, commonly abbreviated as BHA, is a frequently used food preservative that has been shown to possess estrogenic activity and is therefore a xenoestrogen [6]. In this study, BHA was identified as a weak xenoestrogen, exerting a mild effect in the parameters tested with just a fraction the estrogenic potency of estradiol. However, when using cell cultures, BHA stimulated the growth of estrogen-positive breast cancer cells, an outcome that demonstrates the potential for sufficient estrogenicity to impact cellular activity. A Japanese study further showed that when present in high quantities, BHA had the capacity to compete with estradiol for competitive binding to alpha and beta estrogen receptors [7]. Despite this, the low concentrations of BHA commonly used in the preservation of food combined with its weak estrogenic potency render BHA a minimally disruptive xenoestrogen on its own. In low doses however, BHA could have a cumulative effect with the bodies own estrogens and the exposure to other xenoestrogens.

-- Plastics and Plastic Additives

One of the most common types of synthetic materials that we come into daily contact with are plastics and the additives used in their production. Researchers have long known the existence of xenoestrogens in certain plastics. Of particular risk for rampant exposure is the use of plastics in food and beverage products. The consumption of food and beverage products packaged in plastics is an optimal source and pathway for exposure to xenoestrogens contained within these plastics via oral consumption. Several plastic additives still used in the production of household plastic products have been shown to possess estrogenic activity and can therefore be considered xenoestrogens. These xenoestrogens could pose a serious risk to the final adult height achieved in growing adolescents, in part due to their frequent and heavy use in consumable products.

BISPHENOL A

An important monomer in the production of polycarbonate plastics, bisphenol A, commonly abbreviated as BPA, was first identified as possessing estrogenic effects as early as the 1930s [8]. Polycarbonate plastics are a group of thermoplastic polymers. Their ability to be easily moulded and thermoformed has led to their enormous use by the modern chemical industry as commodity plastics for products like shampoo and water bottles. Of particular concern here is the widespread use of polycarbonate plastics in the packaging of food and beverage products, leading to high probability for human exposure to the polycarbonate additive BPA. BPA is a direct disruptor of the endocrine system through its estrogenic effects [9, 10], and is therefore a xenoestrogen. Recent studies have observed adverse estrogenic effects on the human body associated with the exposure to BPA [11, 12, 13], further cementing its status as a potent xenoestrogen. Another novel study through the University of Cincinnati has suggested that the presence of hot liquids in polycarbonate packaging can significantly increase the release of, and thereby the exposure to, the potent xenoestrogen BPA [14]. In this study, the rate of BPA released into the beverage increased by up to 55x faster when the polycarbonate plastic water bottle was briefly exposed to boiling water. Other studies have also shown that the repeated scrubbing and dish-washing of polycarbonate plastics increases their release of BPA. In recent years a significant body of research has been developed on the estrogenic properties of BPA, leaving no doubt that BPA is a potent xenoestrogen widely used in common household products thereby having significant potential for the frequent exposure to. BPA is sometimes also used as an antioxidant in plasticizers during the production of another widely used household plastic, polyvinyl chloride (PVC).

PHTHALATES

Plasticizers are synthetic chemicals added to various types of plastics to increase their flexibility. Phthalates are common plasticizers mainly used as softening agents in the production of the household plastics polyvinyl chloride, better known as PVC, and polyethylene terephthalate, better known as PET. The most widely-used phthalates are di-2-ethylhexyl phthalate (DEHP), diisodecyl phthalate (DIDP), and diisononyl phthalate (DINP), with DEHP being the dominant plasticizer used in PVC and PET. PVC and PET are cheap, durable, and easy to form into almost any shape and size. These desireable characteristics have led to their widespread use in the manufacture of a vast array of products including flexible hoses and tubing, plumbing pipes, inflatable products, childrens toys, upholstery, and even clothing. Since the massive rise in the use of PVC and PET, people are increasingly exposed to the phthalates employed in their production, a fact solidified in an analysis performed by the Centers for Disease Control and Prevention in which the majority of americans tested were found to have the metabolites of multiple phthalates in their urine. The most common route for the intake of phthalates is through the diet, however, inhalation exposure is also a significant source [15]. In studies of rodents exposed to certain phthalates, high doses were shown to change hormone levels and cause birth defects [15]. A recent study conducted by British researchers showed that the phthalate DBP and its metabolite monobutyl phthalate (MBP) suppressed steroidogenesis, the production of androgens, by fetal leydig cells in primates and rodents [16]. A consumable item contamination study performed by Iranian scientists found that during storage of a yogurt food product in PET containers there was shown an elevation in levels of the phthalate DEHP that leached into the yogurt from the plastic containers [17]. The study concluded that storage temperature was a major factor in the rate of contaminant migration from the containers into the food product, thereby discerning the role ambient temperature plays in the leaching of phthalates and other possible plastic-based xenoestrogens into food and beverage products. It is therefore plausible that even the atmospheric temperature in various parts of the world could contribute to varying levels of xenoestrogen leaching from certain kinds of plastic packagings, with those living in warmer climates having a greater risk for exposure to plastic-based xenoestrogens. There still remains a cloud of controversy surrounding wether phthalates are truly estrogenic or not, and conflicting studies have been the basis for both sides of the argument. In support of the argument that phthalates are indeed estrogenic is a study out of Puerto Rico in which girls who developed premature breast growth at an early age were also shown to have much higher concentrations of phthalates present in their bodies verse girls who did not prematurely develop breasts [18]. At the very least, studies have repeatedly shown phthalates to be anti-androgenic, and this effect alone could decrease longitudinal growth velocity in adolescents as well as spawn a host of other developmental problems, especially in pubertal males.

-- Herbicides and Insecticides

Herbicides and insecticides are chemical toxins, commonly available on store shelves, that are used to kill undesired plants and insects. Insecticides, also known as pesticides, are particularly common in the agriculture industry, and are often sprayed onto fruit and vegetable produce you eat on a daily basis. Atrazine, one of the most commonly used herbicides in the US as a weed killer, has been suggested as being a xenoestrogen, although this classification still remains in dispute with numerous conflicting studies and conflicting ideas of what criteria defines a true xenoestrogen. Relatively all the known estrogenic herbicides and insecticides have been banned for use in most of the developed nations of the world, however large amounts still persist in the environment. For those living in countries where such chemicals are still in use extra precautions should be taken when consuming fruit and vegetable produce. One of the simplest ways to reduce exposure is by sufficiently washing and scrubbing all produce prior to consumption to remove surface contaminants.

-- Ultraviolet Radiation Protectorants

4-Methylbenzylidene camphor, abbreviated as 4-MBC, is an organic camphor derivative used in sunscreen lotions and sprays by the cosmetic industry for its ability to protect the skin against sun damage from UV radiation. Over the past decade, several studies have raised the issue that 4-MBC is a xenoestrogen and as such can disrupt the endocrine system and human development in a negative manner. A study in Switzerland showed significant uterine growth within juvenile rodents following exposure to 4-MBC [19], a sign of high estrogenicity, whereas another study showed only a relatively minor effect in response to 4-MBC [20]. 4-MBC is not approved for use in the USA and is prohibited for use in Japan. However, 4-MBC is still approved for cosmetic use in sunscreen products throughout Europe and Canada.

-- Other Sources of Xenoestrogens

Their remains many other xenoestrogens not covered in this article and as researchers continue to delve into the physiological effects of the thousands of unregulated industrial materials we are exposed to on a daily basis this number will certainly rise. It would be impossible to cover them all in this article, so instead some of the most commonly encountered xenoestrogens were chosen.

Primary Routes of Xenoestrogen Intake

The everyday intake of xenoestrogens into the body occurs through a range of pathways and while diet is likely the most common route of xenoestrogen intake following exposure, it may not be the most harmful.

-- Oral Consumption

Certainly the most common route of xenoestrogen intake, oral consumption may be one of the least harmful. When foreign substances are digested by the stomach they must first pass through the liver before entering bloodstream circulation. This process is referred to as first-pass liver metabolism. The liver functions to remove or reduce the level of toxins orally ingested through filtration and metabolic degradation. It is therefore likely that a large portion of orally ingested xenoestrogens are removed or destroyed during first pass liver metabolism thereby reducing their harmful impact upon entering circulation. In other instances however, the metabolites of certain toxins are infact themselves as toxic or even more toxic than the initial substance ingested. In this case, liver metabolism may actually increase the harmfulness of the compounds.

-- Transdermal Absorption

This article has covered multiple sources of xenoestrogens that involve transdermal exposure. Transdermal absorption is the route of intake of a compound through the surface of the skin. Transdermally absorbed compounds directly enter the bloodstream thus bypassing first-pass liver metabolism. It is therefore possible for transdermally absorbed xenoestrogens to be significantly more harmful as a result of their avoidance of the bodies liver metabolism upon their initial entry into circulation. Examples of transdermal xenoestrogen exposure include cosmetics applied to the skins surface and shampoos packaged in plastic bottles containing known xenoestrogens.

-- Lung Inhalation

The inhalation of xenoestrogens into the lungs is another significant route for their intake into the body. During the manufacture of plastics and other materials that contain xenoestrogens, some of these compounds may be expelled from the factory as airborne environmental pollutants scattering them over a large area in and around industrial zones. Because inhaled compounds avoid first-pass liver metabolism, the inhalation of xenoestrogens may prove more harmful than their oral intake.

- Nasal Insufflation

When inhaling through the nose, some of the inhaled molecules end up caught in the nasal cavity where they are plastered against the nasal wall. Nasal mucus then proceeds to dissolve the molecules and they are absorbed through the mucus membranes on the wall of the nasal cavity directly into the bloodstream thereby avoiding first-pass liver metabolism.

Cumulative and Synergistic Xenoestrogen Exposure

Many of the xenoestrogens covered in this article are relatively weak on their own when compared to the bodies natural estrogens, however, something worth serious consideration is the cumulative and synergistic effects these xenoestrogens could have following repeated daily exposure and when mixed with one another in the body. In one novel study using mild xenoestrogens, researchers found that the administration of multiple polychlorinated biphenyls (PCBs) in combination together exerted up to 20x the ability to switch the sex of incubating turtles as either of these weak xenoestrogens had when administered alone [21]. During the incubation period of turtle eggs, estrogenic activity plays an important role in determining the sex of the developing embryos and under conditions known to promote male gender differentiations, an increase in the number of female hatchlings in response to one or more foreign chemicals shows estrogenic activity of these compounds. The significant synergy in estrogenicity this study discovered when two weak xenoestrogens were administered in combination with one another highlights the all to real potential for even mild xenoestrogens to exert powerful estrogenic effects when intermixed within the body. In an even more stunning study conducted by the same researchers, the estrogenic synergies among several pesticide xenoestrogens were nothing short of a shock. During the study they had to use 160x as much of the pesticide endosulfan and 1600x as much dieldrin alone to match the estrogenicity of the two combined. An even more concerning discovery during the study was that the non-estrogenic pesticide chlordane proved almost as potent as dieldrin in boosting the estrogenicity of endosulfan when the two compounds were administered in combination [22]. The data ascertained from these studies suggests that two binding sites may exist on estrogen receptors and that when both sites are simultaneously occupied by two different compounds a significant estrogenic synergy can occur, even when the receptor sites are occupied by weak xenoestrogens. However, it cannot be concluded that all weak xenoestrogens will exhibit similar synergy or prove toxic in animals. Nonetheless, the studies do suggest the potential for dramatic potentiation of estrogenic activity when multiple xenoestrogens are present and therefore even those weak xenoestrogens covered in this article could inflict a significantly more pronounced impact on the rate of growth plate maturation when present in the body at the same time. There is also a cumulative effect of xenoestrogens following repeated daily exposure and intake that could result in a more potent estrogenic effect overtime. The body has a tendency to store chemicals within its fat deposits where a significant and sudden loss in fat can release large quantities of toxins and chemicals into the bloodstream that have built up in the bodies fatty tissue.

Reducing Exposure to Xenoestrogens

An adolescent male wakes up in the morning and is greeted by a warm, beautiful summer day. He starts his day with a hot shower where he lathers on his preferred shampoo. After exiting the shower he applies a facial moisturizing lotion that he swears will keep wrinkles at bay for the next 30 years. He then makes his way downstairs where he grabs his favorite plastic shaker bottle hot out of the dishwasher and whips himself up a protein shake while munching on some fresh fruit and berries. Before leaving the house to hit the beach, his mother slathers some SPF 30 sunscreen lotion onto his body and lectures him on the importance of wearing his hat in the sun. A far fetched scenario? Not by a long shot. It is an overview of everyday living like this that can open your eyes to the sheer volume and array of xenoestrogen exposure we all encounter in our day to day lives. Before this youth has even gotten out the front door of his house he has unknowingly been exposed to a half dozen different sources of potential xenoestrogens through multiple routes of intake into the body over a period of time that could amount to little more than an hour of his day.

The plastic bottle of his shampoo has leached bisphenol A and phthalates into the bubbling ooze at an alarming rate over the weeks of repeated exposure to hot water and steam while sitting on the showers shelf. His miracle facial moisturizer is kept fresh by the addition of paraben preservatives. His favorite shaker bottle riddled with the accumulation of scratches over the months of use and washing is made of polycarbonate plastic still warm to the touch after being removed from the dishwasher. Water he drew from the tap for his protein shake surged through the plastic PVC pipes of his homes plumbing system. The fresh fruit and berries he snacks on are caked with layer after layer of insecticide residue that remains present after just a quick rinse under the tap. All the while the sunscreen lotion his mother insistently applies in copious amounts to prevent harm to her son contains 4-methylbenzylidene as a UV protectorant, a chemical name he couldnt pronounce even if he knew what it was.

In the modern world sources for xenoestrogen exposure have seeped into practically every facet of our lives and the goal of reducing your exposure is surely a daunting task, but with a little motivation and a lot of attention it can be done, even in this day and age. Organic produce has been making a comeback in recent years and is as easy as its been in decades to find, even at major grocery store chains. Eating organic produce will significantly reduce your exposure to potentially harmful insecticides and herbicides commonly used in modern agricultural practices. Avoiding certain types of plastics may be a much more challenging goal to achieve, but perhaps the most beneficial. Plastic-based products can be found anywhere and everywhere and trying to phase out their use is going to leave you with limited and often inconvenient options. One major way to reduce your exposure to plastics and their additives is by cooking your own food from scratch rather than buying processed foods that are often packaged in many of the plastics covered in this article, not to mention being loaded with food preservatives like BHA. Avoid beverage, hygiene, and cosmetic products bottled in polycarbonate (PC), polyvinyl chloride (PVC), and polyethylene terephthalate (PET) plastics. If you use a shampoo contained in a plastic bottle then try to keep it out of the shower as much as possible to avoid the excess heat. When washing plastic containers in the dishwasher, try using the cold water option, not only is it more energy efficient but it will also reduce leaching of xenoestrogens. Not sure what type of plastics you've got? Plastic containers are usually required to have special markings indicating what type of plastic they are made out of and wether or not they are recyclable (Fig. 2). These markings are commonly found on the bottom of the container, but they may also be present on the packages labeling. Steering clear of the plastic materials covered in this article is a smart choice, but perhaps your best bet is ditching the use of plastics altogether, or at least, in your consumable items. Of course this is much easier said than done. Another option is to skim over the ingredients of your favorite cosmetics and toss out those listing any of the aforementioned parabens as the preservatives of choice. If you live in Europe or Canada and love to soak up every last ray of sunshine on the rare occasions it does shine then try to swap any sunscreens containing 4-methylbenzylidene for more healthier UV blockers like titanium dioxide and zinc oxide. Incorporating these changes could make a significant difference in extending the longevity of an adolescents longitudinal growth phase.

Sounds challenging? In a way it most certainly is. We've become so dependent upon these potentially harmful and environmentally damaging synthetic materials for the sake of our convenience that alternative options have almost vanished from the boundaries of our developed nations. The idea of willingly choosing to pursue a more inconvenient and less efficient lifestyle has become this generations definition of intolerable. Regardless, if your goal is to squeeze out every last micron of height growth then pursuing the task of reducing your exposure to xenoestrogens is a great place to start.

Conclusions and Discussions

While the subject of xenoestrogens and their relevance in modern day diseases and disorders still remains a highly debated and rapidly developing subject, there is clear evidence supporting not only the existence of these synthetic estrogenic compounds, but also their implications in our health and environment. The research and understanding of xenoestrogens found throughout what are sometimes considered 'non-toxic' synthetic materials and chemicals continues to expand. However, even as this research advances, so too does the continued and increasing use of poorly regulated man-made materials in everyday products we are constantly exposed to.

With the continued rise in our daily exposure to synthetic materials and chemicals, combined with ever increasing levels of environmental pollutants, the incidences of modern day diseases like cancer will likely continue their upward trends. It is ultimately up to governments to ban the use of these materials and responsible companies to voluntarily phase out their use of compounds shown to have negative interactions with people and the environment. Until such dramatic yet sensible actions are taken, modern day diseases and disorders will continue to inflict millions of people every year with no foreseeable end in sight.

However, you, the individual person, can take precautious measures to reduce or even eliminate your daily exposure to these xenoestrogens not only to perhaps improve your final adult height, but also protect your overall health. By identifying these materials and products that contain xenoestrogens and determining what actions, if any, you can take to lower your exposure, you may be able to prevent a loss in final adult height by preserving the duration of your bodies natural growth period.

Ultimately the choice is yours, and wether you make the proactive decision or not will likely depend upon how truly serious and committed you are to ensuring you achieve or exceed the height your genetics have determined for you to have.

Research References

[1] van der Eerden BCJ, Karperien M, Wit JM. (2003) Systemic and local regulation of the growth plate

[2] Martina Weise, Stacy De-Levi, Kevin M. Barnes, Rachel I. Gafni, Veronica Abad, Jeffrey Baron. (2001) Effects of estrogen on growth plate senescence and epiphyseal fusion

[3] No Authors Listed (2008) Final amended report on the safety assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in cosmetic products

[4] Routledge EJ, Parker J, Odum J, Ashby J, Sumpter JP. (1998) Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic

[5] Golden R, Gandy J, Vollmer G. (2005) A review of the endocrine activity of parabens and implications for potential risks to human health

[6] Susan Jobling, Tracey Reynolds, Roger White, Malcolm G. Parker, John P. Sumpter. (1995) A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic

[7] Okubo T, Kano I. (2003) Studies on estrogenic activities of food additives with human breast cancer MCF-7 cells and mechanism of estrogenicity by BHA and OPP

[8] Dodds EC, Lawson W. (1936) Synthetic Œstrogenic agents without the phenanthrene nucleus

[9] Okada H, Tokunaga T, Liu X, Takayanagi S, Matsushima A, Shimohigashi Y. (2008) Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor-gamma

[10] vom Saal FS, Myers JP. (2008) Bisphenol A and risk of metabolic disorders

[11] O'Connor, Chapin. (2003) Critical evaluation of observed adverse effects of endocrine active substances on reproduction and development, the immune system, and the nervous system

[12] Le HH, Carlson EM, Chua JP, Belcher SM. (2008) Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons

[13] Zsarnovszky A, Le HH, Wang HS, Belcher SM. (2005) Ontogeny of rapid estrogen-mediated extracellular signal-regulated kinase signaling in the rat cerebellar cortex: potent nongenomic agonist and endocrine disrupting activity of the xenoestrogen bisphenol A

[14] Belcher S, University of Cincinnati. (2008) Hot liquids release potentially harmful chemicals in polycarbonate plastic bottles

[15] U.S. CDC (2005) Third national report on human exposure to environmental chemicals

[16] Hallmark N, Walker M, McKinnell C, Mahood IK, Scott H, Bayne R, Coutts S, Anderson RA, Greig I, Morris K, Sharp RM. (2007) Effects of monobutyl and di(n-butyl) phthalate in vitro on steroidogenesis and leydig cell aggregation in fetal testis explants from the rat: comparison with effects in vivo in the fetal rat and neonatal marmoset and in vitro in the human

[17] Mehdi Farhoodi, Zahra Emam-Djomeh, Abdolrasul Oromiehie, M. Reza Ehsani. (2007) Migration of selected contaminants (DEHA, DEHP and ethylene glycol) from PET bottles into Iranian yogurt drink during storage time

[18] Ivelisse Colón, Doris Caro, Carlos J. Bourdony, Osvaldo Rosario. (2000) [i]Identification of phthalate esters in the serum of young puerto rican girls with premature breast development

[19] No Authors Listed (2001) Sun block has endocrine disruptor chemicals

[20] Mueller SO, Kling M, Arifin Firzani P. (2003) Activation of estrogen receptor alpha and ERbeta by 4-methylbenzylidene-camphor in human and rat cells: comparison with phyto- and xenoestrogens

[21] Crews D, Bergeron JM, McLachlan JA. (1995) The role of estrogen in turtle sex determination and the effect of PCBs

[22] Arnold SF, Klotz DM, Vonier PM, Collins BM, McLachlan JA. (1996) Synergism in estrogen-regulated gene expression

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