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2131 KiB

Open AccessArticle

Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly Used in Sunscreen Products

by Huixiao Hong, Diego Rua, Sugunadevi Sakkiah, Chandrabose Selvaraj, Weigong Ge and Weida Tong

Int. J. Environ. Res. Public Health 2016, 13(10), 958; https://doi.org/10.3390/ijerph13100958 - 29 Sep 2016

Cited by 18 | Viewed by 6311

Abstract

Sunscreen products are predominantly regulated as over-the-counter (OTC) drugs by the US FDA. The “active” ingredients function as ultraviolet filters. Once a sunscreen product is generally recognized as safe and effective (GRASE) via an OTC drug review process, new formulations using these ingredients [...] Read more.

Sunscreen products are predominantly regulated as over-the-counter (OTC) drugs by the US FDA. The “active” ingredients function as ultraviolet filters. Once a sunscreen product is generally recognized as safe and effective (GRASE) via an OTC drug review process, new formulations using these ingredients do not require FDA review and approval, however, the majority of ingredients have never been tested to uncover any potential endocrine activity and their ability to interact with the estrogen receptor (ER) is unknown, despite the fact that this is a very extensively studied target related to endocrine activity. Consequently, we have developed an in silico model to prioritize single ingredient estrogen receptor activity for use when actual animal data are inadequate, equivocal, or absent. It relies on consensus modeling to qualitatively and quantitatively predict ER binding activity. As proof of concept, the model was applied to ingredients commonly used in sunscreen products worldwide and a few reference chemicals. Of the 32 chemicals with unknown ER binding activity that were evaluated, seven were predicted to be active estrogenic compounds. Five of the seven were confirmed by the published data. Further experimental data is needed to confirm the other two predictions. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α

by Xueyan Chen, Ugur Uzuner, Man Li, Weibing Shi, Joshua S. Yuan and Susie Y. Dai

Int. J. Environ. Res. Public Health 2016, 13(9), 869; https://doi.org/10.3390/ijerph13090869 - 31 Aug 2016

Cited by 13 | Viewed by 6397

Abstract

Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed [...] Read more.

Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER) and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD) when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX) assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Association between Exposure to Endocrine Disruptors in Drinking Water and Preterm Birth, Taking Neighborhood Deprivation into Account: A Historic Cohort Study

by Marion Albouy-Llaty, Frédérike Limousi, Camille Carles, Antoine Dupuis, Sylvie Rabouan and Virginie Migeot

Int. J. Environ. Res. Public Health 2016, 13(8), 796; https://doi.org/10.3390/ijerph13080796 - 9 Aug 2016

Cited by 22 | Viewed by 5793

Abstract

Background: The relationship between preterm birth (PTB) and endocrine disruptor exposure in drinking-water has only occasionally been studied. The objective of this work was to investigate the relation between exposure to atrazine metabolites, or atrazine/nitrate mixtures, in drinking-water during pregnancy and prevalence [...] Read more.

Background: The relationship between preterm birth (PTB) and endocrine disruptor exposure in drinking-water has only occasionally been studied. The objective of this work was to investigate the relation between exposure to atrazine metabolites, or atrazine/nitrate mixtures, in drinking-water during pregnancy and prevalence of PTB neonates, while taking neighborhood deprivation into account. Method: A historic cohort study in Deux-Sèvres, France, between 2005 and 2010 with a multiple imputation model for data of exposure to atrazine metabolites and a logistic regression were carried out. Results: We included 13,654 mother/neonate pairs living in 279 different census districts. The prevalence of PTB was 4%. Average atrazine metabolite concentration was 0.019 ± 0.009 (0.014–0.080) µg/L and 39% of mothers lived in less deprived areas. The individual data were associated with risk of PTB. The risk of PTB when exposed to highest concentration of atrazine metabolite adjusted for confounders, was ORa 1.625 95% CI [0.975; 2.710]. Taking, or not, neighborhood deprivation into account did not change the result. Exposure to atrazine/nitrate mixtures remained non-significant. Conclusions: Even if we took neighborhood deprivation into account, we could not show a significant relationship between exposure to atrazine metabolites, or mixtures, in drinking-water during the second trimester of pregnancy and PTB. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Experimental Data Extraction and in Silico Prediction of the Estrogenic Activity of Renewable Replacements for Bisphenol A

by Huixiao Hong, Benjamin G. Harvey, Giuseppe R. Palmese, Joseph F. Stanzione, Hui Wen Ng, Sugunadevi Sakkiah, Weida Tong and Joshua M. Sadler

Int. J. Environ. Res. Public Health 2016, 13(7), 705; https://doi.org/10.3390/ijerph13070705 - 12 Jul 2016

Cited by 49 | Viewed by 6082

Abstract

Bisphenol A (BPA) is a ubiquitous compound used in polymer manufacturing for a wide array of applications; however, increasing evidence has shown that BPA causes significant endocrine disruption and this has raised public concerns over safety and exposure limits. The use of renewable [...] Read more.

Bisphenol A (BPA) is a ubiquitous compound used in polymer manufacturing for a wide array of applications; however, increasing evidence has shown that BPA causes significant endocrine disruption and this has raised public concerns over safety and exposure limits. The use of renewable materials as polymer feedstocks provides an opportunity to develop replacement compounds for BPA that are sustainable and exhibit unique properties due to their diverse structures. As new bio-based materials are developed and tested, it is important to consider the impacts of both monomers and polymers on human health. Molecular docking simulations using the Estrogenic Activity Database in conjunction with the decision forest were performed as part of a two-tier in silico model to predict the activity of 29 bio-based platform chemicals in the estrogen receptor-α (ERα). Fifteen of the candidates were predicted as ER binders and fifteen as non-binders. Gaining insight into the estrogenic activity of the bio-based BPA replacements aids in the sustainable development of new polymeric materials. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

2,4,6-Tribromophenol Interferes with the Thyroid Hormone System by Regulating Thyroid Hormones and the Responsible Genes in Mice

by Dongoh Lee, Changhwan Ahn, Eui-Ju Hong, Beum-Soo An, Sang-Hwan Hyun, Kyung-Chul Choi and Eui-Bae Jeung

Int. J. Environ. Res. Public Health 2016, 13(7), 697; https://doi.org/10.3390/ijerph13070697 - 12 Jul 2016

Cited by 26 | Viewed by 5533

Abstract

2,4,6-Tribromophenol (TBP) is a brominated flame retardant (BFR). Based on its affinity for transthyretin, TBP could compete with endogenous thyroid hormone. In this study, the effects of TBP on the thyroid hormone system were assessed in mice. Briefly, animals were exposed to 40 [...] Read more.

2,4,6-Tribromophenol (TBP) is a brominated flame retardant (BFR). Based on its affinity for transthyretin, TBP could compete with endogenous thyroid hormone. In this study, the effects of TBP on the thyroid hormone system were assessed in mice. Briefly, animals were exposed to 40 and 250 mg/kg TBP. Thyroid hormones were also administered with or without TBP. When mice were treated with TBP, deiodinase 1 (Dio1) and thyroid hormone receptor β isoform 2 (Thrβ2) decreased in the pituitary gland. The levels of deiodinase 2 (Dio2) and growth hormone (Gh) mRNA increased in response to 250 mg/kg of TBP, and the relative mRNA level of thyroid stimulating hormone β (Tshβ) increased in the pituitary gland. Dio1 and Thrβ1 expression in the liver were not altered, while Dio1 decreased in response to co-treatment with thyroid hormones. The thyroid gland activity decreased in response to TBP, as did the levels of free triiodothyronine and free thyroxine in serum. Taken together, these findings indicate that TBP can disrupt thyroid hormone homeostasis and the presence of TBP influenced thyroid actions as regulators of gene expression. These data suggest that TBP interferes with thyroid hormone systems Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Comparison of Individual and Combined Effects of Four Endocrine Disruptors on Estrogen Receptor Beta Transcription in Cerebellar Cell Culture: The Modulatory Role of Estradiol and Triiodo-Thyronine

by Gergely Jocsak, David Sandor Kiss, Istvan Toth, Greta Goszleth, Tibor Bartha, Laszlo V. Frenyo, Tamas L. Horvath and Attila Zsarnovszky

Int. J. Environ. Res. Public Health 2016, 13(6), 619; https://doi.org/10.3390/ijerph13060619 - 22 Jun 2016

Cited by 11 | Viewed by 6118

Abstract

Background: Humans and animals are continuously exposed to a number of environmental substances that act as endocrine disruptors (EDs). While a growing body of evidence is available to prove their adverse health effects, very little is known about the consequences of simultaneous [...] Read more.

Background: Humans and animals are continuously exposed to a number of environmental substances that act as endocrine disruptors (EDs). While a growing body of evidence is available to prove their adverse health effects, very little is known about the consequences of simultaneous exposure to a combination of such chemicals; Methods: Here, we used an in vitro model to demonstrate how exposure to bisphenol A, zearalenone, arsenic, and 4-methylbenzylidene camphor, alone or in combination, affect estrogen receptor β (ERβ) mRNA expression in primary cerebellar cell cultures. Additionally, we also show the modulatory role of intrinsic biological factors, such as estradiol (E2), triiodo-thyronine (T3), and glial cells, as potential effect modulators; Results: Results show a wide diversity in ED effects on ERβ mRNA expression, and that the magnitude of these ED effects highly depends on the presence or absence of E2, T3, and glial cells; Conclusion: The observed potency of the EDs to influence ERβ mRNA expression, and the modulatory role of E2, T3, and the glia suggests that environmental ED effects may be masked as long as the hormonal milieu is physiological, but may tend to turn additive or superadditive in case of hormone deficiency. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

The Risk of Breast Cancer in Women Using Menopausal Hormone Replacement Therapy in Taiwan

by Jui-Yao Liu, Tzeng-Ji Chen and Shinn-Jang Hwang

Int. J. Environ. Res. Public Health 2016, 13(5), 482; https://doi.org/10.3390/ijerph13050482 - 11 May 2016

Cited by 12 | Viewed by 5881

Abstract

Menopausal hormone replacement therapy (HRT) increases the risk of breast cancer in Western countries; however, there are fewer reports from the Asian population, which has a lower incidence of breast cancer. A population-based retrospective cohort study was conducted by analyzing longitudinal National Health [...] Read more.

Menopausal hormone replacement therapy (HRT) increases the risk of breast cancer in Western countries; however, there are fewer reports from the Asian population, which has a lower incidence of breast cancer. A population-based retrospective cohort study was conducted by analyzing longitudinal National Health Insurance claim data of a 200,000-person national representative cohort. A total of 22,929 women aged ≥45 years in 1997 without previous diagnosis of breast cancer were enrolled and stratified into two birth cohorts born before or after 1933. HRT prescriptions were traced in outpatient data files and incident breast cancer cases were identified from 1997 to 2004. The Cox proportional hazards model was used to analyze breast cancer hazard ratio (HR). HRT users were censored after they discontinued HRT. The results showed that women born during 1933–1952 had a twofold increased risk of breast cancer (HR = 2.10, 95% CI = 1.47–3.00) compared with women born before 1933, when adjusted for HRT use. When adjusted for the birth-cohort difference, HRT users had significantly increased breast cancer HR versus non-users after four years of use (adjusted HR = 1.48, 95% CI = 1.03–2.13); the HR further increased to 1.95 (95% CI = 1.34–2.84) after eight years of use. In conclusion, a longer duration of current HRT use was associated with a higher risk of breast cancer independent of the birth-cohort difference. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

A Preliminary Link between Hydroxylated Metabolites of Polychlorinated Biphenyls and Free Thyroxin in Humans

by Eveline Dirinck, Alin C. Dirtu, Govindan Malarvannan, Adrian Covaci, Philippe G. Jorens and Luc F. Van Gaal

Int. J. Environ. Res. Public Health 2016, 13(4), 421; https://doi.org/10.3390/ijerph13040421 - 13 Apr 2016

Cited by 11 | Viewed by 5085

Abstract

Background: Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (HO-PCBs) interfere with thyroid hormone action both in vitro and in vivo. However, epidemiologic studies on the link between PCB exposure and thyroid function have yielded discordant results, while very few data are [...] Read more.

Background: Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (HO-PCBs) interfere with thyroid hormone action both in vitro and in vivo. However, epidemiologic studies on the link between PCB exposure and thyroid function have yielded discordant results, while very few data are available for HO-PCBs. Objectives: Our study aimed at investigating the relationship between clinically available markers of thyroid metabolism and serum levels of both PCBs and HO-PCBs. Subjects and Methods: In a group of 180 subjects, thyroid-stimulating hormone (TSH) and free thyroxin (fT4), 29 PCBs (expressed both in lipid weight and in wet weight) and 18 HO-PCBs were measured in serum. Results: In regression models, adjusted for gender, age, current smoking behavior, BMI and total lipid levels, serum levels of 3HO-PCB118 and 3HO-PCB180, and PCB95_lw, PCB99_lw and PCB149_lw were independent, significant predictors of fT4. A stepwise, multiple regression with gender, age, current smoking behavior, BMI and total lipid levels and all five previously identified significant compounds retained age, BMI, PCB95_lw, PCB99_lw and 3HO-PCB180 as significant predictors of fT4. TSH levels were not predicted by serum levels of any of the PCBs or HO-PCBs. Conclusions: Our study indicates that in vivo, circulating fT4 levels can be linked to serum levels of several PCBs and hydroxylated PCB metabolites. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Pathway Analysis Revealed Potential Diverse Health Impacts of Flavonoids that Bind Estrogen Receptors

by Hao Ye, Hui Wen Ng, Sugunadevi Sakkiah, Weigong Ge, Roger Perkins, Weida Tong and Huixiao Hong

Int. J. Environ. Res. Public Health 2016, 13(4), 373; https://doi.org/10.3390/ijerph13040373 - 26 Mar 2016

Cited by 10 | Viewed by 6218

Abstract

Flavonoids are frequently used as dietary supplements in the absence of research evidence regarding health benefits or toxicity. Furthermore, ingested doses could far exceed those received from diet in the course of normal living. Some flavonoids exhibit binding to estrogen receptors (ERs) with [...] Read more.

Flavonoids are frequently used as dietary supplements in the absence of research evidence regarding health benefits or toxicity. Furthermore, ingested doses could far exceed those received from diet in the course of normal living. Some flavonoids exhibit binding to estrogen receptors (ERs) with consequential vigilance by regulatory authorities at the U.S. EPA and FDA. Regulatory authorities must consider both beneficial claims and potential adverse effects, warranting the increases in research that has spanned almost two decades. Here, we report pathway enrichment of 14 targets from the Comparative Toxicogenomics Database (CTD) and the Herbal Ingredients’ Targets (HIT) database for 22 flavonoids that bind ERs. The selected flavonoids are confirmed ER binders from our earlier studies, and were here found in mainly involved in three types of biological processes, ER regulation, estrogen metabolism and synthesis, and apoptosis. Besides cancers, we conjecture that the flavonoids may affect several diseases via apoptosis pathways. Diseases such as amyotrophic lateral sclerosis, viral myocarditis and non-alcoholic fatty liver disease could be implicated. More generally, apoptosis processes may be importantly evolved biological functions of flavonoids that bind ERs and high dose ingestion of those flavonoids could adversely disrupt the cellular apoptosis process. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals

by Huixiao Hong, Jie Shen, Hui Wen Ng, Sugunadevi Sakkiah, Hao Ye, Weigong Ge, Ping Gong, Wenming Xiao and Weida Tong

Int. J. Environ. Res. Public Health 2016, 13(4), 372; https://doi.org/10.3390/ijerph13040372 - 25 Mar 2016

Cited by 15 | Viewed by 6178

Abstract

Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through [...] Read more.

Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold² software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Influence of Occupational and Environmental Exposure to Low Concentrations of Polychlorobiphenyls and a Smoking Habit on the Urinary Excretion of Corticosteroid Hormones

by Maria Nicolà D’Errico, Piero Lovreglio, Ignazio Drago, Pietro Apostoli and Leonardo Soleo

Int. J. Environ. Res. Public Health 2016, 13(4), 360; https://doi.org/10.3390/ijerph13040360 - 25 Mar 2016

Cited by 2 | Viewed by 4476

Abstract

The effects of occupational exposure to low concentrations of polychlorobiphenyls (PCBs) on the urinary excretion of corticosteroid hormones were evaluated, taking into account the influence of cigarette smoking. The study included 26 males working as electrical maintenance staff in a steel factory, previously [...] Read more.

The effects of occupational exposure to low concentrations of polychlorobiphenyls (PCBs) on the urinary excretion of corticosteroid hormones were evaluated, taking into account the influence of cigarette smoking. The study included 26 males working as electrical maintenance staff in a steel factory, previously exposed to a mixture of PCBs (exposed workers), and 30 male workers with no occupational exposure to PCBs (controls). Serum PCBs (33 congeners), urinary 17-hydroxycorticosteroids, 17-ketosteroids (KS) and pregnanes, and their respective glucuronidated and sulfonated compounds, were determined for each subject. PCBs were significantly higher in the exposed workers than controls, and were correlated with age. Both the urinary concentrations of the total 17-KS and pregnanes, and those of some single steroids and their glucuronidated compounds, were significantly lower in the exposed workers than controls, but higher in smokers than the non-smokers + ex-smokers. Two-way analysis of variance showed a negative association between serum PCBs and both total glucuronidated 17-KS and total and glucuronidated pregnanes, and a positive association between cigarette smoking and both total and glucuronidated 17-KS. PCBs seem to act as endocrine disruptors by reducing the urinary excretion of corticosteroid hormones, particularly of the glucuronidated fraction. Cigarette smoking could boost these effects of PCBs in smokers. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

The Effect of Exposure to Persistent Organic Pollutants on Metabolic Health among KOREAN Children during a 1-Year Follow-Up

by Hye Ah Lee, Su Hyun Park, Young Sun Hong, Eun Hee Ha and Hyesook Park

Int. J. Environ. Res. Public Health 2016, 13(3), 270; https://doi.org/10.3390/ijerph13030270 - 29 Feb 2016

Cited by 34 | Viewed by 5482

Abstract

Previous evidence suggests the potential for adverse effects of persistent organic pollutants (POPs) on metabolic health even at low-dose exposure levels common among the general population, but there is less evidence of these associations among children. Therefore, as part of a prospective cohort [...] Read more.

Previous evidence suggests the potential for adverse effects of persistent organic pollutants (POPs) on metabolic health even at low-dose exposure levels common among the general population, but there is less evidence of these associations among children. Therefore, as part of a prospective cohort study, 214 children were measured for POPs exposure. After the 1-year follow-up, we assessed the effect of circulating POPs exposure among 158 children aged 7–9 years (at baseline) on the change of metabolic components of metabolic syndrome using multiple regression analysis. In addition, we calculated the continuous metabolic syndrome (cMetS) score and assessed the variation among individuals by POPs exposure. The concentrations of marker polychlorinated biphenyls (PCBs) were significantly associated with increased change in diastolic blood pressure (BP) and triglyceride levels during a 1-year follow-up, after controlling for sex, age, household income, and change in body mass index. Total PCBs also showed a marginal association with increasing cMetS score from the baseline. Of the metabolic components, change in diastolic BP over time showed a notable association with specific PCBs, but no association with organochlorine pesticides. Here, we found that low-dose exposures to PCBs among children in the general population could negatively influence metabolic health, particularly diastolic BP. Increased disease sensitivity during childhood can continue to adulthood, thus, these results support the need for continuous assessment of the health impact of POPs. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels

by Nicolas Defarge, Eszter Takács, Verónica Laura Lozano, Robin Mesnage, Joël Spiroux de Vendômois, Gilles-Eric Séralini and András Székács

Int. J. Environ. Res. Public Health 2016, 13(3), 264; https://doi.org/10.3390/ijerph13030264 - 26 Feb 2016

Cited by 156 | Viewed by 31277

Abstract

Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution [...] Read more.

Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18–2000 times for co-formulants, 8–141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Environmental Exposure to Triclosan and Semen Quality

by Wenting Zhu, Hao Zhang, Chuanliang Tong, Chong Xie, Guohua Fan, Shasha Zhao, Xiaogang Yu, Ying Tian and Jun Zhang

Int. J. Environ. Res. Public Health 2016, 13(2), 224; https://doi.org/10.3390/ijerph13020224 - 17 Feb 2016

Cited by 56 | Viewed by 7632

Abstract

Triclosan (2,4,4′-trichloro-2′-hydroxy-diphenyl ether, TCS) is widely used in personal care, household, veterinary and industrial products. It was considered as a potential male reproductive toxicant in previous in vitro and in vivo studies. However, evidence from human studies is scarce. Our study aims to [...] Read more.

Triclosan (2,4,4′-trichloro-2′-hydroxy-diphenyl ether, TCS) is widely used in personal care, household, veterinary and industrial products. It was considered as a potential male reproductive toxicant in previous in vitro and in vivo studies. However, evidence from human studies is scarce. Our study aims to investigate the relationship between TCS exposure and semen quality. We measured urinary TCS concentrations in 471 men recruited from a male reproductive health clinic. TCS was detected in 96.7% of urine samples, with a median concentration of 0.97 ng (mg·creatinine)⁻¹ (interquartile range, 0.41–2.95 ng (mg·creatinine)⁻¹). A multiple linear regression analysis showed a negative association between natural logarithm (Ln) transformed TCS concentration (Ln-TCS) and Ln transformed number of forward moving sperms (adjusted coefficient β = −0.17; 95% confidence interval (CI) (−0.32, −0.02). Furthermore, among those with the lowest tertile of TCS level, Ln-TCS was negatively associated with the number of forward moving sperms (β = −0.35; 95% CI (−0.68, −0.03)), percentage of sperms with normal morphology (β = −1.64; 95% CI (−3.05, −0.23)), as well as number of normal morphological sperms, sperm concentration and count. Our findings suggest that the adverse effect of TCS on semen quality is modest at the environment-relevant dose in humans. Further studies are needed to confirm our findings. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Association of PAEs with Precocious Puberty in Children: A Systematic Review and Meta-Analysis

by Yi Wen, Shu-Dan Liu, Xun Lei, Yu-Shuang Ling, Yan Luo and Qin Liu

Int. J. Environ. Res. Public Health 2015, 12(12), 15254-15268; https://doi.org/10.3390/ijerph121214974 - 1 Dec 2015

Cited by 42 | Viewed by 6702

Abstract

Background: Precocious puberty (PP) currently affects 1 in 5000 children and is 10 times more common in girls. Existing studies have tried to detect an association between phathalic acid esters (PAEs) and PP, but the results did not reach a consensus. Objective [...] Read more.

Background: Precocious puberty (PP) currently affects 1 in 5000 children and is 10 times more common in girls. Existing studies have tried to detect an association between phathalic acid esters (PAEs) and PP, but the results did not reach a consensus. Objective: To estimate the association between PAEs and children with PP based on current evidence. Methods: Databases including PubMed (1978 to March 2015), OVID (1946 to March 2015), Web of Science (1970 to March 2015), EBSCO (1976 to March 2015), CNKI (1979 to March 2015), WANFANG DATA (1987 to March 2015), CBM (1978 to March 2015) and CQVIP (1989 to March 2015) were searched to identify all case-control studies that determined the exposure and concentration of PAEs and their metabolites in children with PP. Meta-analysis of the pooled standard mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI) were calculated. Results: A total of 14 studies involving 2223 subjects were finally included. The pooled estimates showed that PP was associated with di-(2-ethylhexyl)-phthalate (DEHP) exposure (OR: 3.90, 95% CI: 2.77 to 5.49). Besides, the concentration of DEHP (SMD: 1.73, 95% CI: 0.54 to 2.91) and di-n-butyl phthalate (DBP) (SMD: 4.31, 95% CI: 2.67 to 5.95) in the PP group were significantly higher than those in the control group, respectively, while no difference was detected between case and control groups in either serum or urinary concentration of mono-(2-ethylhexyl)-phthalate (MEHP), monobutyl phthalate (MBP), mono(2-ethyl-5-oxohexyl) phthalate(MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), monomethyl phthalate (MMP), monobenzyl phthalate (MBzP) or monoethyl phthalate (MEP). Conclusions: Exposure of DEHP and DBP might be associated with PP risk for girls, however, there is no evidence to show an association between the exposure to most PAE metabolites and PP. Given the moderate strength of the results, well-designed cohort studies with large sample size should be performed in future. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China

by Mingyue Zhang, Zhenghua Duan, Yinghong Wu, Zhen Liu, Ke Li and Lei Wang

Int. J. Environ. Res. Public Health 2015, 12(12), 15110-15117; https://doi.org/10.3390/ijerph121214964 - 30 Nov 2015

Cited by 11 | Viewed by 5320

Abstract

Background: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA) and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of [...] Read more.

Background: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA) and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. Methods: In this study, BPA and phytoestrogens in urine specimens (n = 256) collected from children in China were measured by liquid chromatography (LC)-tandem mass spectrometry (MS/MS). Results: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. Conclusions: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Induction of the Estrogenic Marker Calbindn-D_9k by Octamethylcyclotetrasiloxane

by Dongoh Lee, Changhwan Ahn, Beum-Soo An and Eui-Bae Jeung

Int. J. Environ. Res. Public Health 2015, 12(11), 14610-14625; https://doi.org/10.3390/ijerph121114610 - 17 Nov 2015

Cited by 14 | Viewed by 5294

Abstract

Interrupting the hormonal balance of an organism by interfering with hormones and their target receptors gives rise to various problems such as developmental disorders. Collectively, these reagents are known as endocrine disruptors (EDs). Cyclic volatile methyl siloxanes (cVMSs) are a group of silicone [...] Read more.

Interrupting the hormonal balance of an organism by interfering with hormones and their target receptors gives rise to various problems such as developmental disorders. Collectively, these reagents are known as endocrine disruptors (EDs). Cyclic volatile methyl siloxanes (cVMSs) are a group of silicone polymers that including octamethylcyclotetrasiloxane (D4). In the present study, we examined the estrogenicity of D4 through in vitro and in vivo assays that employed calcium-binding protein 9K (calbindin-D_9k; CaBP-9K) as a biomarker. For in vitro investigation, GH3 rat pituitary cells were exposed to vehicle, 17β-estradiol (E2), or D4 with/without ICI 182 780 (ICI). CaBP-9K and progesterone receptor (PR) both were up-regulated by E2 and D4 which were completely blocked by ICI. Transcription of estrogen receptor α (ER α) was decreased by E2 and D4 but increased by ICI. D4 was also administered to immature female rats for an uterotrophic (UT) assay and detection of CaBP-9K. Ethinyl estradiol (EE) or D4 was administered subcutaneously with or without ICI. Although uterine weight was not significant altered by D4, an effect thought to be due to cytochrome P450 (CYP), it induced CaBP-9K and PR gene expression. Based on these results we reveal that D4 has estrogenic potential proven under in vitro and in vivo experimental conditions. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Associations between Bisphenol A Exposure and Reproductive Hormones among Female Workers

by Maohua Miao, Wei Yuan, Fen Yang, Hong Liang, Zhijun Zhou, Runsheng Li, Ersheng Gao and De-Kun Li

Int. J. Environ. Res. Public Health 2015, 12(10), 13240-13250; https://doi.org/10.3390/ijerph121013240 - 22 Oct 2015

Cited by 54 | Viewed by 7353

Abstract

The associations between Bisphenol-A (BPA) exposure and reproductive hormone levels among women are unclear. A cross-sectional study was conducted among female workers from BPA-exposed and unexposed factories in China. Women’s blood samples were collected for assay of follicle-stimulating hormone (FSH), luteinizing hormone (LH), [...] Read more.

The associations between Bisphenol-A (BPA) exposure and reproductive hormone levels among women are unclear. A cross-sectional study was conducted among female workers from BPA-exposed and unexposed factories in China. Women’s blood samples were collected for assay of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-Estradiol (E2), prolactin (PRL), and progesterone (PROG). Their urine samples were collected for BPA measurement. In the exposed group, time weighted average exposure to BPA for an 8-h shift (TWA8), a measure incorporating historic exposure level, was generated based on personal air sampling. Multiple linear regression analyses were used to examine linear associations between urine BPA concentration and reproductive hormones after controlling for potential confounders. A total of 106 exposed and 250 unexposed female workers were included in this study. A significant positive association between increased urine BPA concentration and higher PRL and PROG levels were observed. Similar associations were observed after the analysis was carried out separately among the exposed and unexposed workers. In addition, a positive association between urine BPA and E2 was observed among exposed workers with borderline significance, while a statistically significant inverse association between urine BPA and FSH was observed among unexposed group. The results suggest that BPA exposure may lead to alterations in female reproductive hormone levels. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Open AccessArticle

Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF

by Tianle Tang, Yang Yang, Yawen Chen, Wenhao Tang, Fuqiang Wang and Xiaoping Diao

Int. J. Environ. Res. Public Health 2015, 12(10), 13069-13084; https://doi.org/10.3390/ijerph121013069 - 16 Oct 2015

Cited by 57 | Viewed by 6906

Abstract

Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function [...] Read more.

Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3′,5-triiodothyronine (TT3), total 3,5,3′,5′-tetraiodothyronine (TT4), free 3,3′,5-triiodothyronine (FT3) and free 3,5,3′,5′-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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Recent Advances on Endocrine Disrupting Effects of UV Filters

by Jiaying Wang, Liumeng Pan, Shenggan Wu, Liping Lu, Yiwen Xu, Yanye Zhu, Ming Guo and Shulin Zhuang

Int. J. Environ. Res. Public Health 2016, 13(8), 782; https://doi.org/10.3390/ijerph13080782 - 3 Aug 2016

Cited by 148 | Viewed by 14649

Abstract

Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants [...] Read more.

Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives. Full article

(This article belongs to the Special Issue Endocrine Disruptors and Public Health)

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