Xenoestrogens Articles 2

© 2012

Estrogenic effects in vitro and in vivo of the fungicide fenarimol

         (Andersen, Bonefeld-Jorgensen et al. 2006) Download

The fungicide fenarimol has the potential to induce endocrine disrupting effects via several mechanisms since it possesses both estrogenic and antiandrogenic activity and inhibits aromatase activity in cell culture studies. Hence, the integrated response of fenarimol in vivo is not easy to predict. In this study, we demonstrate that fenarimol is also estrogenic in vivo, causing significantly increased uterine weight in ovariectomized female rats. In addition, mRNA levels of the estrogen responsive gene lactoferrin (LF) were decreased in uteri, serum FSH levels were increased, and T3 levels decreased in fenarimol-treated animals. To our knowledge, only two other pesticides (o,p-DDT and methoxychlor) have previously been reported to induce an estrogenic response in the rodent uterotrophic bioassay. A pronounced xenoestrogenicity in serum samples from rats treated with fenarimol and estradiol benzoate (E2B) separately or in combination was observed, demonstrating the usefulness of this approach for estimating the integrated internal exposure to xenoestrogens. The MCF-7 cell proliferation assay was used to investigate further the dose-response curves for the estrogenic, antiestrogenic, and aromatase inhibiting properties of fenarimol in vitro. The results indicates that fenarimol exhibits a dual effect being aromatase inhibitor at low concentrations and estrogenic at higher concentrations.

Predictors of the total effective xenoestrogen burden (TEXB) in human adipose tissue. A pilot study

            (Arrebola, Fernandez et al. 2012) Download

The estrogenicity of biological extracts tested by appropriate bioassay is a standard method to evaluate the total effective xenoestrogen burden (TEXB). Information has been published on the combined effect of xenoestrogens after removing endogenous hormones. The main goal of the present study was to investigate the combined estrogenicity of endogenous and xenoestrogens in human adipose tissue samples with and without HPLC fractionation. The results suggest that both approaches may be useful to study interaction between xenoestrogens and endogenous hormones. TEXB of the whole extract provides information about the overall estrogenicity to which humans are exposed, useful to assess the potential contribution to health outcomes. Additionally, it is possible to identify the source and potency of the estrogenicity by using the method with fractionation, distinguishing the effect of organohalogenated chemicals (alpha-fraction) from that of endogenous hormones and more polar xenoestrogens (beta-fraction). Both methods are an integrative measure of internal estrogen load.

Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity

            (Axon, May et al. 2012) Download

Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERalpha and ERbeta, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERalpha-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings--sunset yellow and tartrazine--were identified as novel human ERalpha activators, activating the human ER with an EC(50%) concentration of 220 and 160 nM, respectively.

The role of environmental estrogens and autoimmunity

         (Chighizola and Meroni 2012) Download

The prevalence of autoimmune diseases has significantly increased over the recent years. It has been proposed that this epidemiological evidence could be in part attributable to environmental estrogens, compounds that display estrogen-like activity and are ubiquitously present in the environment. Environmental estrogens can be found in a wide variety of foods: phytoestrogens occur in plants such as clover and soy, while mycoestrogens are food contaminants produced by fungi. Meat, eggs and dairy products from animals given exogenous hormones contain relatively high concentration of estrogens. Among xenoestrogens, industrial estrogens are synthetic chemicals produced for specific purposes (pesticides, plastics, surfactants and detergents) while metalloestrogens are found in heavy metals. Estrogens can be also administered through medications (contraceptive pill, hormone replacement therapy, genistein, cimetidine, creams). There is a considerable burden of evidence in vitro and in animal models that these compounds may exert immunotoxic effects. However, to date there is no convincing data that exposure to environmental estrogens can be regarded as a risk for human health. In particular, there is no consensus whether prolonged exposure to relatively low concentrations of different estrogenic chemicals can affect the human immune system and induce clinically evident diseases in real-life scenario. Moreover, the effects on human health of the synergistic interactions between natural, medical, dietary and environmental estrogens have not been fully elucidated yet. Here we provide an extensive review of the in vivo and in vitro effects of environmental estrogens on the immune system, focusing on the evidences of association between exposure and autoimmune disorders.

Personal care products that contain estrogens or xenoestrogens may increase breast cancer risk

            (Donovan, Tiwary et al. 2007) Download

Established models of breast cancer risk, such as the Gail model, do not account for patterns of the disease in women under the age of 35, especially in African Americans. With the possible exceptions of ionizing radiation or inheriting a known genetic mutation, most of the known risk factors for breast cancer are related to cumulative lifetime exposure to estrogens. Increased risk of breast cancer has been associated with earlier onset of menses or later age at menopause, nulliparity or late first parity, use of hormonal contraceptives or hormone replacement therapy, shorter lactation history, exposure to light at night, obesity, and regular ingestion of alcohol, all of which increase circulating levels of unbound estradiol. Among African Americans at all ages, use of hormone-containing personal care products (PCPs) is more common than among whites, as is premature appearance of secondary sexual characteristics among infants and toddlers. We hypothesize that the use of estrogen and other hormone-containing PCPs in young African American women accounts, in part, for their increased risk of breast cancer prior to menopause, by subjecting breast buds to elevated estrogen exposure during critical windows of vulnerability in utero and in early life. These early life and continuing exposures to estrogenic and xenoestrogenic agents may also contribute to the increased lethality of breast cancer in young women in general and in African American women of all ages. Public disclosure by manufacturers of proprietary hormonally active ingredients is required for this research to move forward.

Endocrine disrupters: a review of some sources, effects, and mechanisms of actions on behaviour and neuroendocrine systems

            (Frye, Bo et al. 2012) Download

Some environmental contaminants interact with hormones and may exert adverse consequences as a result of their actions as endocrine disrupting chemicals (EDCs). Exposure in people is typically a result of contamination of the food chain, inhalation of contaminated house dust or occupational exposure. EDCs include pesticides and herbicides (such as dichlorodiphenyl trichloroethane or its metabolites), methoxychlor, biocides, heat stabilisers and chemical catalysts (such as tributyltin), plastic contaminants (e.g. bisphenol A), pharmaceuticals (i.e. diethylstilbestrol; 17alpha-ethinylestradiol) or dietary components (such as phytoestrogens). The goal of this review is to address the sources, effects and actions of EDCs, with an emphasis on topics discussed at the International Congress on Steroids and the Nervous System. EDCs may alter reproductively-relevant or nonreproductive, sexually-dimorphic behaviours. In addition, EDCs may have significant effects on neurodevelopmental processes, influencing the morphology of sexually-dimorphic cerebral circuits. Exposure to EDCs is more dangerous if it occurs during specific 'critical periods' of life, such as intrauterine, perinatal, juvenile or puberty periods, when organisms are more sensitive to hormonal disruption, compared to other periods. However, exposure to EDCs in adulthood can also alter physiology. Several EDCs are xenoestrogens, which can alter serum lipid concentrations or metabolism enzymes that are necessary for converting cholesterol to steroid hormones. This can ultimately alter the production of oestradiol and/or other steroids. Finally, many EDCs may have actions via (or independent of) classic actions at cognate steroid receptors. EDCs may have effects through numerous other substrates, such as the aryl hydrocarbon receptor, the peroxisome proliferator-activated receptor and the retinoid X receptor, signal transduction pathways, calcium influx and/or neurotransmitter receptors. Thus, EDCs, from varied sources, may have organisational effects during development and/or activational effects in adulthood that influence sexually-dimorphic, reproductively-relevant processes or other functions, by mimicking, antagonising or altering steroidal actions.

Environmental estrogens differentially engage the histone methyltransferase EZH2 to increase risk of uterine tumorigenesis

            (Greathouse, Bredfeldt et al. 2012) Download

Environmental exposures during sensitive windows of development can reprogram normal physiologic responses and alter disease susceptibility later in life in a process known as developmental reprogramming. For example, exposure to the xenoestrogen diethylstilbestrol during reproductive tract development can reprogram estrogen-responsive gene expression in the myometrium, resulting in hyperresponsiveness to hormone in the adult uterus and promotion of hormone-dependent uterine leiomyoma. We show here that the environmental estrogens genistein, a soy phytoestrogen, and the plasticizer bisphenol A, differ in their pattern of developmental reprogramming and promotion of tumorigenesis (leiomyomas) in the uterus. Whereas both genistein and bisphenol A induce genomic estrogen receptor (ER) signaling in the developing uterus, only genistein induced phosphoinositide 3-kinase (PI3K)/AKT nongenomic ER signaling to the histone methyltransferase enhancer of zeste homolog 2 (EZH2). As a result, this pregenomic signaling phosphorylates and represses EZH2 and reduces levels of H3K27me3 repressive mark in chromatin. Furthermore, only genistein caused estrogen-responsive genes in the adult myometrium to become hyperresponsive to hormone; estrogen-responsive genes were repressed in bisphenol A-exposed uteri. Importantly, this pattern of EZH2 engagement to decrease versus increase H3K27 methylation correlated with the effect of these xenoestrogens on tumorigenesis. Developmental reprogramming by genistein promoted development of uterine leiomyomas, increasing tumor incidence and multiplicity, whereas bisphenol A did not. These data show that environmental estrogens have distinct nongenomic effects in the developing uterus that determines their ability to engage the epigenetic regulator EZH2, decrease levels of the repressive epigenetic histone H3K27 methyl mark in chromatin during developmental reprogramming, and promote uterine tumorigenesis.

Endocrine disruptors in bottled mineral water: estrogenic activity in the E-Screen

            (Heinze 2011) Download

Susceptibility of estrogen receptor rapid responses to xenoestrogens: Physiological outcomes

            (Marino, Pellegrini et al. 2012) Download

17beta-Estradiol (E2) binding induces rapid modification in the conformation of its cognate receptors (i.e., ERalpha and ERbeta). These allosteric changes allow the association of ERs with cell specific transcriptional cofactors, thus determining cellular contexts specific variations in gene expression. In addition, E2-ER complexes could also interact with membrane and cytosolic signal molecules triggering extra-nuclear signalling pathways. The synergy between these mechanisms is necessary for E2-induced pleiotropic actions in target tissues. Besides E2, the ER ligand binding domains can accommodate many other natural and synthetic ligands. Several of these compounds act as agonist or antagonist of ER transcriptional activity due to their ability to modify the interactions between ERs and transcriptional co-regulators. However, the ability of natural or manmade ER ligands to affect the extra-nuclear interactions of the ERs has been rarely evaluated. Here, the ability of two diet-derived flavonoids (i.e., naringenin and quercetin) and of the synthetic food-contaminant bisphenol A to modulate specifically ER extra-nuclear signalling pathways will be reported. All the tested compounds bind to both ER subtypes even if lesser than E2 activating divergent signal transduction pathways. In fact, in the presence of ERalpha, both naringenin and quercetin decouple ERalpha activities by specifically interfering with ERalpha membrane initiating signals. On the other hand, bisphenol A, but not flavonoids, maintains ERbeta at the membrane thus impairing the activation of the downstream kinases. As a whole, extra-nuclear ER signals are highly susceptible to different ligands that, by unbalancing E2-induced cell functions drive cells to different functional endpoints.

The pancreatic beta-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes

            (Nadal, Alonso-Magdalena et al. 2009) Download

The estrogen receptor ERalpha is emerging as a key molecule involved in glucose and lipid metabolism. The main functions of pancreatic beta-cells are the biosynthesis and release of insulin, the only hormone that can directly decrease blood glucose levels. Estrogen receptors ERalpha and ERbeta exist in beta-cells. The role of ERbeta is still unknown, yet ERalpha plays an important role in the regulation of insulin biosynthesis, insulin secretion and beta-cell survival. Activation of ERalpha by 17beta-estradiol (E2) and the environmental estrogen bisphenol-A (BPA) promotes an increase of insulin biosynthesis through a non-classical estrogen-activated pathway that involves phosphorylation of ERK1/2. The activation of ERalpha by physiological concentrations of E2 may play an important role in the adaptation of the endocrine pancreas to pregnancy. However, if ERalpha is over stimulated by an excess of E2 or the action of an environmental estrogen such as BPA, it will produce an excessive insulin signaling. This may provoke insulin resistance in the liver and muscle, as well as beta-cell exhaustion and therefore, it may contribute to the development of type II diabetes.

Xenoestrogens down-regulate aryl-hydrocarbon receptor nuclear translocator 2 mRNA expression in human breast cancer cells via an estrogen receptor alpha-dependent mechanism

            (Qin, Zaha et al. 2011) Download

Environmental chemicals with estrogenic activity, known as xenoestrogens, may cause impaired reproductive development and endocrine-related cancers in humans by disrupting endocrine functions. Aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) is believed to play important roles in a variety of physiological processes, including estrogen signaling pathways, that may be involved in the pathogenesis and therapeutic responses of endocrine-related cancers. However, much of the underlying mechanism remains unknown. In this study, we investigated whether ARNT2 expression is regulated by a range of representative xenoestrogens in human cancer cell lines. Bisphenol A (BPA), benzyl butyl phthalate (BBP), and 1,1,1-trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p'-DDT) were found to be estrogenic toward BG1Luc4E2 cells by an E-CALUX bioassay. ARNT2 expression was downregulated by BPA, BBP, and o,p'-DDT in a dose-dependent manner in estrogen receptor 1 (ESR1)-positive MCF-7 and BG1Luc4E2 cells, but not in estrogen receptor-negative LNCaP cells. The reduction in ARNT2 expression in cells treated with the xenoestrogens was fully recovered by the addition of a specific ESR1 antagonist, MPP. In conclusion, we have shown for the first time that ARNT2 expression is modulated by xenoestrogens by an ESR1-dependent mechanism in MCF-7 breast cancer cells.

Endocrine disruptors in bottled mineral water: total estrogenic burden and migration from plastic bottles

            (Wagner and Oehlmann 2009) Download

BACKGROUND, AIM, AND SCOPE: Food consumption is an important route of human exposure to endocrine-disrupting chemicals. So far, this has been demonstrated by exposure modeling or analytical identification of single substances in foodstuff (e.g., phthalates) and human body fluids (e.g., urine and blood). Since the research in this field is focused on few chemicals (and thus missing mixture effects), the overall contamination of edibles with xenohormones is largely unknown. The aim of this study was to assess the integrated estrogenic burden of bottled mineral water as model foodstuff and to characterize the potential sources of the estrogenic contamination. MATERIALS, METHODS, AND RESULTS: In the present study, we analyzed commercially available mineral water in an in vitro system with the human estrogen receptor alpha and detected estrogenic contamination in 60% of all samples with a maximum activity equivalent to 75.2 ng/l of the natural sex hormone 17beta-estradiol. Furthermore, breeding of the molluskan model Potamopyrgus antipodarum in water bottles made of glass and plastic [polyethylene terephthalate (PET)] resulted in an increased reproductive output of snails cultured in PET bottles. This provides first evidence that substances leaching from plastic food packaging materials act as functional estrogens in vivo. DISCUSSION AND CONCLUSIONS: Our results demonstrate a widespread contamination of mineral water with xenoestrogens that partly originates from compounds leaching from the plastic packaging material. These substances possess potent estrogenic activity in vivo in a molluskan sentinel. Overall, the results indicate that a broader range of foodstuff may be contaminated with endocrine disruptors when packed in plastics.

Endocrine disruptors in bottled mineral water: estrogenic activity in the E-Screen

            (Wagner and Oehlmann 2011) Download

Human exposure to endocrine disruptors is well documented by biomonitoring data. However, this information is limited to few chemicals like bisphenol A or phthalate plasticizers. To account for so-far unidentified endocrine disruptors and potential mixture effects we employ bioassays to detect endocrine activity in foodstuff and consequently characterize the integrated exposure to endocrine active compounds. Recently, we reported a broad contamination of commercially available bottled water with estrogenic activity and presented evidence for the plastic packaging being a source of this contamination. In continuation of that work, we here compare different sample preparation methods to extract estrogen-like compounds from bottled water. These data demonstrate that inappropriate extraction methods and sample treatment may lead to false-negative results when testing water extracts in bioassays. Using an optimized sample preparation strategy, we furthermore present data on the estrogenic activity of bottled water from France, Germany, and Italy: eleven of the 18 analyzed water samples (61.1%) induced a significant estrogenic response in a bioassay employing a human carcinoma cell line (MCF7, E-Screen). The relative proliferative effects ranged from 19.8 to 50.2% corresponding to an estrogenic activity of 1.9-12.2 pg estradiol equivalents per liter bottled water. When comparing water of the same spring that is packed in glass or plastic bottles made of polyethylene terephthalate (PET), estrogenic activity is three times higher in water from plastic bottles. These data support the hypothesis that PET packaging materials are a source of estrogen-like compounds. Furthermore, the findings presented here conform to previous studies and indicate that the contamination of bottled water with endocrine disruptors is a transnational phenomenon.

Phytoestrogens and xenoestrogens: the contribution of diet and environment to endocrine disruption

            (Waring, Ayers et al. 2008) Download

Some endocrine disrupting compounds such as phthalates and phenols act non-genomically by inhibiting the sulfotransferase (SULT 1E1 and SULT 1A1) isoforms which inactivate estrogens by sulfonation. A range of environmental phenolic contaminants and dietary flavonoids was tested for inhibition of the human SULT 1A1, 1E1 and 2A1 isoforms. In particular, the plasticisers 4-n-octyl- and 4-n-nonyl-phenol inhibit SULT 1E1 with IC(50) values of 0.16 microM vs. 10nM estradiol while the 2-substituted chlorophenols show similar values. Flavonoids are also SULT inhibitors; tricin is a competitive inhibitor of SULT 1E1 with a K(i) of 1.5+/-0.8 nM. In a small pilot study to determine whether ingestion of soy flavonoids would affect SULT1A1 activity in vivo as well as in vitro, sulfonation of daidzein was reduced in a group of women 'at risk' of breast cancer, as compared with controls, although the SULT 1A1*1/SULT 1A1*2 allele ratio was not different. Endocrine disrupting effects in man may be multifactorial when components from both the diet and the environment act at the same point in steroid metabolism.

Estrogen- and xenoestrogen-induced ERK signaling in pituitary tumor cells involves estrogen receptor-alpha interactions with G protein-alphai and caveolin I

            (Watson, Jeng et al. 2012) Download

Multiple physiologic estrogens (estradiol, estriol, and estrone), as well as xenoestrogenic compounds (including alkylphenols and bisphenol A), can act via nongenomic signaling initiated by liganding of the plasma membrane estrogen receptor-alpha (mERalpha). We examined heterotrimeric G protein involvement leading to extracellular-regulated kinase (ERK) activation in GH3/B6/F10 rat anterior pituitary tumor cells that express abundant mERalpha, and smaller amounts of mERbeta and GPR30. A combination of microarrays, immunoblots, and quantitative immunoassays demonstrated the expression of members of all alpha, beta, and gamma G protein classes in these cells. Use of selective inhibitors showed that the G(alphai) subtype was the primary initiator of downstream ERK signaling. Using antibodies against the GTP-bound form of G(alpha) protein subtypes i and s, we showed that xenoestrogens (bisphenol A, nonylphenol) activated G(alphai) at 15-30s; all alkylphenols examined subsequently suppressed activation by 5min. GTP-activation of G(alphai) for all estrogens was enhanced by irreversible cumulative binding to GTPgammaS. In contrast, G(alphas) was neither activated nor deactivated by these treatments with estrogens. ERalpha and G(alphai) co-localized outside nuclei and could be immuno-captured together. Interactions of ERalpha with G(alphai) and caveolin I were demonstrated by epitope proximity ligation assays. An ERalpha/beta antagonist (ICI182780) and a selective disruptor of caveolar structures (nystatin) blocked estrogen-induced ERK activation. Conclusions: Xenoestrogens, like physiologic estrogens, can evoke downstream kinase signaling involving selective interactions of ERalpha with G(alphai) and caveolin I, but with some different characteristics, which could explain their disruptive actions.

Personal care products and endocrine disruption: A critical review of the literature

            (Witorsch and Thomas 2010) Download

This article reviews laboratory and epidemiological research into the endocrine disruptive effects of components of personal care products, namely, phthalate esters, parabens, ultraviolet (UV) filters, polycyclic musks, and antimicrobials. High doses of phthalates in utero can produce “phthalate syndrome,” demasculinizing effects in male rat offspring due to impaired testosterone production by fetal testes. However, evidence linking phthalate exposure to similar effects in humans appears inconclusive. Furthermore, phthalate exposure derived from personal care products is within safe limits and its principal bioavailable phthalate, diethyl phthalate (DEP), does not produce “phthalate syndrome.” Parabens exhibit very weak estrogen activity in vitro and in vivo, but evidence of paraben-induced developmental and reproductive toxicity in vivo lacks consistency and physiological coherence. Evidence attempting to link paraben exposure with human breast cancer is nonexistent. Select UV filters at high doses produce estrogenic, antithyroid, and other effects in rats in vivo. Again, no evidence links UV filter exposure to endocrine disruptive effects in humans. Some polycyclic musks weakly bind to estrogen, androgen, or progestin receptors and exhibit primarily antagonistic activity in vitro, which for the most part, has yet to be confirmed in vivo in mammals. The antimicrobials triclocarban and triclosan evoke weak responses mediated by aryl hydrocarbon, estrogen, and androgen receptors in vitro, which require confirmation in vivo. Preliminary observations suggest a novel interaction between triclocarban and testosterone. In conclusion, although select constituents exhibit interactions with the endocrine system in the laboratory, the evidence linking personal care products to endocrine disruptive effects in humans is for the most part lacking.


Andersen, H. R., E. C. Bonefeld-Jorgensen, et al. (2006). "Estrogenic effects in vitro and in vivo of the fungicide fenarimol." Toxicol Lett 163(2): 142-52.

Arrebola, J. P., M. F. Fernandez, et al. (2012). "Predictors of the total effective xenoestrogen burden (TEXB) in human adipose tissue. A pilot study." Reprod Toxicol 33(1): 45-52.

Axon, A., F. E. May, et al. (2012). "Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity." Toxicology 298(1-3): 40-51.

Chighizola, C. and P. L. Meroni (2012). "The role of environmental estrogens and autoimmunity." Autoimmun Rev 11(6-7): A493-501.

Donovan, M., C. M. Tiwary, et al. (2007). "Personal care products that contain estrogens or xenoestrogens may increase breast cancer risk." Med Hypotheses 68(4): 756-66.

Frye, C. A., E. Bo, et al. (2012). "Endocrine disrupters: a review of some sources, effects, and mechanisms of actions on behaviour and neuroendocrine systems." J Neuroendocrinol 24(1): 144-59.

Greathouse, K. L., T. Bredfeldt, et al. (2012). "Environmental estrogens differentially engage the histone methyltransferase EZH2 to increase risk of uterine tumorigenesis." Mol Cancer Res 10(4): 546-57.

Heinze, J. (2011). "Endocrine disruptors in bottled mineral water: estrogenic activity in the E-Screen." J Steroid Biochem Mol Biol 127(1-2): 136-8.

Marino, M., M. Pellegrini, et al. (2012). "Susceptibility of estrogen receptor rapid responses to xenoestrogens: Physiological outcomes." Steroids 77(10): 910-7.

Nadal, A., P. Alonso-Magdalena, et al. (2009). "The pancreatic beta-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes." Mol Cell Endocrinol 304(1-2): 63-8.

Qin, X. Y., H. Zaha, et al. (2011). "Xenoestrogens down-regulate aryl-hydrocarbon receptor nuclear translocator 2 mRNA expression in human breast cancer cells via an estrogen receptor alpha-dependent mechanism." Toxicol Lett 206(2): 152-7.

Wagner, M. and J. Oehlmann (2009). "Endocrine disruptors in bottled mineral water: total estrogenic burden and migration from plastic bottles." Environ Sci Pollut Res Int 16(3): 278-86.

Wagner, M. and J. Oehlmann (2011). "Endocrine disruptors in bottled mineral water: estrogenic activity in the E-Screen." J Steroid Biochem Mol Biol 127(1-2): 128-35.

Waring, R. H., S. Ayers, et al. (2008). "Phytoestrogens and xenoestrogens: the contribution of diet and environment to endocrine disruption." J Steroid Biochem Mol Biol 108(3-5): 213-20.

Watson, C. S., Y. J. Jeng, et al. (2012). "Estrogen- and xenoestrogen-induced ERK signaling in pituitary tumor cells involves estrogen receptor-alpha interactions with G protein-alphai and caveolin I." Steroids 77(5): 424-32.

Witorsch, R. J. and J. A. Thomas (2010). "Personal care products and endocrine disruption: A critical review of the literature." Crit Rev Toxicol 40 Suppl 3: 1-30.