Steroidal and phenolic endocrine disrupting chemicals (EDCs) in surface water of Bahe River, China: Distribution, bioaccumulation, risk assessment and estrogenic effect on Hemiculter leucisculus.

This study investigated selected steroidal and phenolic endocrine disrupting compounds (EDCs) in the surface water of the Bahe River (China) using gas chromatography mass spectrometry (GC-MS). Their effect on the wild sharpbelly Hemiculter leucisculus was investigated. The concentrations of 4-t-octylphenol, nonylphenol, bisphenol-A, estrone, 17 ß-estradiol, 17 α-Ethinylestradiol, and estriol were up to 126.0, 634.8, 1573.1, 55.9, 23.9, 31.5, and 5.2 ng L-1 in the surface water, and up to 26.4, 103.5, 146.9, 14.2, 9.3, 13.8, and 1.3 ng g-1 in the fish muscle tissue, respectively. High estrogen equivalent levels and hazard quotients were found in the middle and lower reaches of the river, and the pollution in these regions caused enhanced growth conditions, inhibition of gonad growth, and suppression of spermatogenesis in H. leucisculus. The up-regulation of Vitellogenin mRNA expression in male fish, collected from relatively heavily EDCs contaminated areas, indicates a potential estrogenic effect. The differential expression profiles of genes related to steroidogenesis at all sampling sites suggests that these endpoints may play an important role for the pollution monitoring of estrogenic EDCs in the Bahe River.

Hormone dust exposure a reversible cause of precocious pseudopuberty in siblings.

A seven year old female child presented with two episodes of vaginal bleeding and bilateral breast development. Examination showed normal anthropometric measurements and external genitalia of prepubertal type. Her 5-year old younger brother and her father had gynaecomastia. Search for a structural cause for precocious puberty was negative. Occupational exposure of her father to hormonal dust was identified as the cause. All pubertal changes reverted to normal after observing suitable precautions.

Role of xenoestrogens and endogenous sources of estrogens on the occurrence of premenopausal breast cancer in Iran.

Breast cancer affects Iranian women one decade younger than their counterparts in other countries and the underlying risk factors have remained controversial. The aryl hydrocarbon receptor (AhR) mediates endocrine disruptive activities of polyaromatic hydrocarbons (PAHs) and dioxins, which may compromise ovarian functions of women in polluted environments. This study focused on tissue expression levels of AhR and associations with exposure to chemicals with estrogen-like activities (xenoestrogens) and other reproductive factors in premenopausal breast cancer patients. Fifty cases who underwent surgery from June 2009 to June 2010 were matched with 100 controls by age and hospital records. AhR overexpression was detected in 87% of epithelial cells of young breast cancer patients. Living near factories generating PAHs and dioxins was considered as a major risk factor in premenopausal breast cancer (p=0.001, OR=4.8). History of idiopathic infertility was identified as a second significant risk factor (p=0.002, OR=3.50), which could be affected by endogenous estrogen levels. Long term (>5 yrs) consumption of oral contraceptive pills was identified as the third most important risk factor (p=0.006, OR=2.27). Adiposity and abnormal weight gain after 18 years were considered as two major background factors, which may contribute to the levels of endogenous estrogens. Direct and indirect exposure to cigarette smoke (p=0.005, OR=1.43) was considered as a weak risk factor without association with AhR levels. It seems that AhR overexpression is affected by exposure to xenoestrogens and by adiposity. Early occurrence of breast cancer in Iran may be a result of interactions between hormonal and environmental factors.

Environmental oestrogens and breast cancer: evidence for combined involvement of dietary, household and cosmetic xenoestrogens.

UNLABELLED: Many environmental compounds with oestrogenic activity are measurable in the human breast and oestrogen is a known factor in breast cancer development. Exposure to environmental oestrogens occurs through diet, household products and cosmetics, but concentrations of single compounds in breast tissue are generally lower than needed for assayable oestrogenic responses. Results presented here and elsewhere demonstrate that in combination, chemicals can give oestrogenic responses at lower concentrations, which suggests that in the breast, low doses of many compounds could sum to give a significant oestrogenic stimulus. Updated incidence figures show a continued disproportionate incidence of breast cancer in Britain in the upper outer quadrant of the breast which is also the region to which multiple cosmetic chemicals are applied. CONCLUSION: If exposure to complex mixtures of oestrogenic chemicals in consumer products is a factor in breast cancer development, then a strategy for breast cancer prevention could become possible.

Developmental estrogen exposures predispose to prostate carcinogenesis with aging.

Prostate morphogenesis occurs in utero in humans and during the perinatal period in rodents. While largely driven by androgens, there is compelling evidence for a permanent influence of estrogens on prostatic development. If estrogenic exposures are abnormally high during the critical developmental period, permanent alterations in prostate morphology and function are observed, a process referred to as developmental estrogenization. Using the neonatal rodent as an animal model, it has been shown that early exposure to high doses of estradiol results in an increased incidence of prostatic lesions with aging which include hyperplasia, inflammatory cell infiltration and prostatic intraepithelial neoplasia or PIN, believed to be the precursor lesion for prostatic adenocarcinoma. The present review summarizes research performed in our laboratory to characterize developmental estrogenization and identify the molecular pathways involved in mediating this response. Furthermore, recent studies performed with low-dose estradiol exposures during development as well as exposures to environmentally relevant doses of the endocrine disruptor bisphenol A show increased susceptibility to PIN lesions with aging following additional adult exposure to estradiol. Gene methylation analysis revealed a potential epigenetic basis for the estrogen imprinting of the prostate gland. Taken together, our results suggest that a full range of estrogenic exposures during the postnatal critical period - from environmentally relevant bisphenol A exposure to low-dose and pharmacologic estradiol exposures - results in an increased incidence and susceptibility to neoplastic transformation of the prostate gland in the aging male which may provide a fetal basis for this adult disease.

Endocrine (sexual) disruption is not a prominent feature in the pike (Esox lucius), a top predator, living in English waters.

The high incidence of intersex roach (Rutilus rutilus) in some United Kingdom rivers that has been associated with exposure to sewage treatment works (STWs) effluent led us to hypothesize that top predator fish also may be affected by estrogenic chemicals, because they are likely to bioaccumulate lipophilic compounds through a predator-prey relationship. To investigate this possibility, pike (Esox lucius) were sampled both upstream and downstream of STWs and then examined for total estrogenic activity of their bile, as measured using a yeast-based estrogen assay to determine the degree of recent exposure of the pike to estrogens and vitellogenin induction, and for possible disruption of sexual development, as measured using histological analysis of the gonads. No evidence of severe disruption was found in the sampled fish, which came from 16 sampling sites that were representative of English rivers. However, 14% of pike were intersex, of which 15 of 16 showed patches of male germ cells among predominantly female gonadal tissue. The incidence of masculinization was independent of whether the pike had been sampled upstream or downstream of STWs. Although pike are gonochoristic, it is not known if this masculinization of presumptive female pike is normal or, instead, indicative of endocrine disruption. Vitellogenin concentrations were not elevated in male pike at sites either upstream or downstream of STWs. The results suggest that sexual disruption is not common in pike, a fish at the top of the food chain in the freshwaters of England.

Life-cycle exposure of fathead minnows (Pimephales promelas) to an ethinylestradiol concentration below 1 ng/L reduces egg fertilization success and demasculinizes males.

Forty-eight hours after fertilization, fathead minnow (Pimephales promelas) eggs were exposed to the synthetic estrogen 17alpha-ethinylestradiol (EE2) at nominal concentrations of 0.32 and 0.96 ng/L and measured concentrations of 3.5, 9.6, and 23 ng/L. The fish were observed through the larval, juvenile, and adult stages. Growth, secondary sex characteristics, the liver somatic index, the gonadosomatic index, and fecundity were examined after several lengths of exposure. No significant changes were seen in fry or juvenile growth from 8 to 30 days posthatch (dph). An increase in the ovipositor index (a female secondary sex characteristic) was the most sensitive early response at 60 dph and was seen in fish exposed to EE2 concentrations > or = 3.5 ng/L. Continuation of the EE2 exposure until 150 dph, through maturation and reproduction, allowed measurement of two sensitive end points: decreased egg fertilization and sex ratio (skewed toward females), both of which were significantly affected at the lowest EE2 concentration tested, 0.32 ng/L. The next most sensitive end point was demasculinization (decreased male secondary sex characteristic index) of males exposed to an EE2 concentration of 0.96 ng/L. The effects of low concentrations of EE2 (0.32 and 0.96 ng/L) were manifested in male fish (decreased male sex characteristics and reduced egg fertilization success), whereas female fish showed no changes in the gonadosomatic index. Exposure to higher EE2 concentrations negatively affected females, as shown by a reduced gonadosomatic index at 150 dph in fish exposed to > or =3.5 ng/L EE2. Although there were some end points that showed changes at 60 dph, the reproductive end points and external sex characteristics measured in mature fish at 150 dph were more sensitive, with response thresholds of EE2 ranging from 0.32 to 0.96 ng/L. The concentrations of EE2 that negatively affected fathead minnows were similar to or lower than those detected in many municipal wastewater effluents. In conclusion, life-cycle exposure of fathead minnows proved to be a very sensitive bioassay, and responses were seen at concentrations of less than 1 ng/L, which are environmentally relevant concentrations of EE2.

Histological evidence of intersex in feral sharptooth catfish (Clarias gariepinus) from an estrogen-polluted water source in Gauteng, South Africa.

This is the first histological evidence of intersex in a fish species inhabiting a South African water source. One hundred catfish (Clarias gariepinus) were collected randomly from the Marais Dam (MD) and the Rietvlei Dam (RVD) in the Rietvlei Nature Reserve (RNR), South Africa. These dams drain water from a stream that receives effluent from industrial sites, agricultural activities, informal settlements, and municipal treatment plants. Each fish was evaluated macroscopically and had blood drawn, and its gonads were macroscopically and histologically examined to verify intersex potentially related to endocrine disruption. Gonadal histology of several fish showed primary oocytes scattered in testicular tissue, indicative of intersex. The results showed intersexuality in 20% of fish from both the dams. The GSI value for intersex fish was closer to male GSI values, suggesting that the sampled intersex fish were more likely to have occurred from the feminization of male catfish. Target chemical analyses showed that the water, sediment, and serum samples tested positive for p-nonylphenol (p-NP). The p-NP level in water and sediment at MD was 6360 and 4.0 microg/kg, respectively, whereas in sediment at RVD it was 113 microg/kg. Commonly found in the effluent from sewage treatment plants, p-NP in water and sediment indicates estrogenic water pollution, which might affect wildlife and humans dependent on these sources.

Breast cancer risk and the combined effect of environmental estrogens.

OBJECTIVE: The present study aimed to determine whether the combined effects of environmental estrogens measured as the total effective xenoestrogen burden (TEXB-alpha) are a risk factor for breast cancer over and above the risk potentially linked to specific pesticides. METHODS: We measured the levels of 16 organochlorine pesticides as well as TEXB in adipose tissue of 198 women at the time of breast cancer diagnosis. These were compared with findings in 260 age and hospital matched control women without breast cancer. RESULTS: The median levels of p,p'-DDE (1,1-dichloro-2,2-bis( p -chlorophenyl)ethylene), aldrin, endosulfan ether and lindane (the pesticides detected in > 40% of the study population) were higher in cases than controls, although the differences did not reach statistical significance. After adjusting for potential confounders, the odds ratio (OR) for breast cancer in women with detectable levels of aldrin was 1.55 (95% confidence interval (CI) 1.00-2.40). Among the postmenopausal women, the OR for aldrin and lindane was 1.84 (95% CI 1.06-3.18) and 1.76 (95% CI 1.04-2.98), respectively. Among cases with body mass index (BMI) below the median (28.6 kg/m2), the OR was 3.42 (95% CI 1.22-9.58) for women in the highest quartile of TEXB-alpha versus those in the lowest. The subgroup of leaner postmenopausal women showed an increased risk (OR: 5.67; 95% CI 1.59-20.21) for those in the highest tertile versus those in the lowest. CONCLUSIONS: We found an increased risk for breast cancer in the leaner women, especially in the leaner postmenopausal subgroup, related to the TEXB-alpha. The pesticides aldrin and lindane are also individually associated with risk.

Sediments are major sinks of steroidal estrogens in two United Kingdom rivers.

The occurrence of intersex fish in a number of European rivers has been attributed to exposure to estrogenic chemicals present in sewage treatment work (STW) effluents. To further understand the environmental fate of these contaminants, the estrogenic activity of effluents, water, and sediments were investigated both upstream and downstream of the major STW discharge in two United Kingdom rivers. Estrogenic activity, determined using the yeast estrogen-receptor transcription screen, of the major STW effluents on both rivers was similar, ranging from 1.4 to 2.9 ng 17beta-estradiol equivalents (EEQ)/L. Estrogenic activities of surface waters 1 km upstream and downstream of both STW inputs were less than the limits of detection (0.04 ng/L); however, levels of estrogenic activity in sediments were between 21.3 and 29.9 ng EEQ/kg and were similar at both upstream and downstream sites. Effluent and sediment extracts were fractionated by reverse phase-high-performance liquid chromatography, and estrogenic active fractions were further analyzed by gas chromatography-mass spectrometry. The major active chemicals in the two effluents and in the sediments were estrone with lesser amounts of 17beta-estradiol; however, at one site, a number of other unidentified estrogenic fractions were detected in the sediments. These results suggest that riverine sediments are a major sink and a potential source of persistent estrogenic contaminants.

Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent.

It is now well established that there is a diverse array of chemicals discharged into the environment that can mimic or antagonise the action of hormones. These endocrine-disrupting chemicals (EDCs) can thus interact with physiological systems and cause alterations in development, growth and reproduction in wildlife that are exposed to them. As yet, however, there is little information on the relative sensitivities of different wildlife groups to these chemicals and/or mixtures of them (e.g. estrogenic effluents) and hence, there are fundamental shortfalls in our knowledge of the ecological importance of endocrine disruption in wildlife. In this study, the effects of exposure to individual estrogenic chemicals (17alpha-ethinylestradiol; EE2, bisphenol-A, and 4-tert octylphenol) and a mixture containing these chemicals (treated sewage effluent) on embryo production in the prosobranch mollusc, Potamopyrgus antipodarum, were studied and compared with the effects of EE2 and the same estrogenic effluent on vitellogenin induction and/or egg production in various species of freshwater fish (fathead minnow; Pimaphales promelas, rainbow trout (Oncorhynchus mykiss); Cyprinus carpio, carp; Cyprinus carpio). The lab-based studies demonstrated that all of the tested chemicals (known to be estrogenic and to cause reproductive effects in fish) also affected embryo production in P. antipodarum. Furthermore, exposure to EE2 induced similar reproductive responses in the snails as in the fathead minnow (Pimephales promelas), stimulating egg/embryo production at low doses (up to 1 ng/l in the minnow and 25 ng/l in the snail) and causing inhibitory effects at higher doses. A similar pattern of embryo production occurred in P. antipodarum when it was exposed to a graded concentration of treated sewage effluent containing mixtures of estrogenic EDCs and hence, the total number of new embryos produced by the snails increased steadily over the 9 weeks exposure period in treated snails. Plasma vitellogenin concentrations in two species of male fish (the rainbow trout and the carp) also increased over the same time period. These data indicate that both the nature of the response and the relative sensitivities to environmental estrogens in P. antipodarum and three different fish species fish are comparable. P. antipodarum is thus, potentially a sensitive test organism for assessing estrogenicity of chemicals with a relevance to their activity in vertebrates.

Environmental endocrine disrupters dysregulate estrogen metabolism and Ca2+ homeostasis in fish and mammals via receptor-independent mechanisms.

Xenoestrogen endocrine disrupters (EDs) in the environment are thought to be responsible for a number of examples of sexual dysfunction that have recently been reported in several species. There is growing concern that these compounds may also cause abnormalities of the male reproductive tract and reduced spermatogenesis in man. Whilst some effects of EDs may be receptor-mediated, there is growing evidence that these compounds can exert potent effects in vivo by directly interacting with cellular enzyme targets. Here we report on, and review, the effects of alkylphenols and other EDs on two such enzymes: (1) sulfotransferases, which convert active estrogenic steroids to inactive steroid sulfates; and (2) Ca(2+)-ATPases, which are responsible for maintaining low, physiological, intracellular Ca(2+) concentrations. These enzymes are potently inhibited by EDs in both fish and mammalian species. The increased concentrations of active estrogens and the likely cytotoxic effects of elevated concentrations of intracellular Ca(2+) arising from these effects may underlie some of the endocrine disrupting potential of these widespread industrial pollutants.

Manure-borne estrogens as potential environmental contaminants: a review.

Livestock wastes are potential sources of endocrine disrupting compounds to the environment. Steroidal estrogen hormones such as estradiol, estrone, and estriol are a particular concern because there is evidence that low nanogram per liter concentrations of estrogens in water can adversely affect the reproductive biology of fish and other aquatic vertebrate species. We performed a literature review to assess the current state of science regarding estrogen physicochemical properties, livestock excretion, and the fate of manure-borne estrogens in the environment. Unconjugated steroidal estrogens have low solubility in water (0.8-13.3 mg L(-1)) and are moderately hydrophobic (log Kow 2.6-4.0). Cattle excrete mostly 17alpha-estradiol, 17beta-estradiol, estrone, and respective sulfated and glucuronidated counterparts, whereas swine and poultry excrete mostly 17beta-estradiol, estrone, estriol, and respective sulfated and glucuronidated counterparts. The environmental fate of estrogens is not clearly known. Laboratory-based studies have found that the biological activity of these compounds is greatly reduced or eliminated within several hours to days due to degradation and sorption. On the other hand, field studies have demonstrated that estrogens are sufficiently mobile and persistent to impact surface and groundwater quality. Future research should use standardized methods for the analysis of manure, soil, and water. More information is needed about the types and amounts of estrogens that exist in livestock wastes and the fate of manure-borne estrogens applied to agricultural lands. Field and laboratory studies should work toward revealing the mechanisms of estrogen degradation, sorption, and transport so that the risk of estrogen contamination of waterways can be minimized.

Testicular cancer and occupational exposures with a focus on xenoestrogens in polyvinyl chloride plastics.

In a case-control study of 148 cases of testicular cancer and 314 healthy controls information was collected on lifetime working histories and specific exposures. The main finding was a six-fold increase in the risk for seminoma, one type of testicular cancer, among plastic workers exposed to polyvinyl chloride (PVC). No overrisks were observed for other plastics than PVC. There may be an aetiological link to xenoestrogens, i.e. chemicals in the environment with oestrogenic properties. Phthalates are used in PVC as plasticizer and have oestrogenic properties that could promote the growth of endocrine sensitive tumour cells. However, this "endocrine disruptors" hypothesis must be further evaluated in experimental models with regard to the causative mechanisms of the oestrogenic tumour promotion.

[Occlusion of the right common carotid artery due to oral estrogen overdose]. / Oclusión de la arteria carótida primitiva derecha por sobredosificación de estrógenos orales.

INTRODUCTION: Continuous use of oral anticontraceptive agents has been related to adverse vascular changes in the form of venous or arterial thromboses and cerebrovascular accidents (CVA). In our case, we describe a CVA due to occlusion of the common carotid artery after an acute massive overdose of estrogens due to error of dosage when using Yuzpe's system or emergency post-coital therapy. CLINICAL CASE: We describe a 26 year old woman with no previous clinical history, who smoked 20 cigarettes per day, did not take oral contraceptive pills and suffered an acute left facial-brachial-crural hemiplegia together with reduced level of consciousness. Imaging tests showed acute occlusion of the right common carotid artery. Etiological study of the patient's cerebral vascular accident was negative. The only etiopathogenic factor to be related was having taken oral contraceptive agents for three days after coitus as emergency post-coital treatment. This treatment was incorrect, since the dose of estrogens was four times that recommended. CONCLUSIONS: The continued use of estrogens, especially at doses over 30 micrograms per day, was considered responsible for approximately 10% of CVAs in young people. The risk of cerebral vascular accident is greater when there is associated migraine and/or smoking. We describe a patient who showed that the acute use of high doses of estrogens may also cause arterial occlusion, in this case in the common carotid artery.

Effects of oestradiol on plasma concentrations of luteinizing hormone in ovariectomized ewes with clover disease.

The effects of oestradiol on plasma luteinizing hormone (LH) concentrations were examined in 15 ovariectomized control ewes and 15 similar ewes with permanent infertility after prolonged grazing on oestrogenic clover pasture ('clover disease'). Before treatment, the plasma concentrations of LH were similar in the control and affected ewes. After intravenous injection with 40 micrograms oestradiol-17 beta during the anoestrous season, the decline in LH concentration was greater in the clover-affected ewes and the subsequent elevation above original baseline levels was smaller. After intramuscular injection with 15 or 30 micrograms oestradiol benzoate during the normal breeding season, fewer clover-affected ewes showed a surge of LH, and the response was both reduced and retarded. This difference between the two groups has not been observed in studies on intact ewes, and it is suggested that in intact ewes the difference is masked by a greater tonic LH activity in affected ewes. The results of the present study are consistent with the hypothesis that prolonged exposure to oestrogenic pasture has a differentiating, or 'androgenizing' effect on the adult ewe.