International Journal of Environmental Research and Public Health

Research

1034 KiB

Open AccessArticle

Combination Effects of (Tri)Azole Fungicides on Hormone Production and Xenobiotic Metabolism in a Human Placental Cell Line

by Svenja Rieke, Sophie Koehn, Karen Hirsch-Ernst, Rudolf Pfeil, Carsten Kneuer and Philip Marx-Stoelting

Int. J. Environ. Res. Public Health 2014, 11(9), 9660-9679; https://doi.org/10.3390/ijerph110909660 - 17 Sep 2014

Cited by 40 | Viewed by 7810

Abstract

Consumers are exposed to multiple residues of different pesticides via the diet. Therefore, EU legislation for pesticides requires the evaluation of single active substances as well as the consideration of combination effects. Hence the analysis of combined effects of substances in a broad [...] Read more.

Consumers are exposed to multiple residues of different pesticides via the diet. Therefore, EU legislation for pesticides requires the evaluation of single active substances as well as the consideration of combination effects. Hence the analysis of combined effects of substances in a broad dose range represents a key challenge to current experimental and regulatory toxicology. Here we report evidence for additive effects for (tri)azole fungicides, a widely used group of antifungal agents, in the human placental cell line Jeg-3. In addition to the triazoles cyproconazole, epoxiconazole, flusilazole and tebuconazole and the azole fungicide prochloraz also pesticides from other chemical classes assumed to act via different modes of action (i.e., the organophosphate chlorpyrifos and the triazinylsulfonylurea herbicide triflusulfuron-methyl) were investigated. Endpoints analysed include synthesis of steroid hormone production (progesterone and estradiol) and gene expression of steroidogenic and non-steroidogenic cytochrome-P-450 (CYP) enzymes. For the triazoles and prochloraz, a dose dependent inhibition of progesterone production was observed and additive effects could be confirmed for several combinations of these substances in vitro. The non-triazoles chlorpyrifos and triflusulfuron-methyl did not affect this endpoint and, in line with this finding, no additivity was observed when these substances were applied in mixtures with prochloraz. While prochloraz slightly increased aromatase expression and estradiol production and triflusulfuron-methyl decreased estradiol production, none of the other substances had effects on the expression levels of steroidogenic CYP-enzymes in Jeg-3 cells. For some triazoles, prochloraz and chlorpyrifos a significant induction of CYP1A1 mRNA expression and potential combination effects for this endpoint were observed. Inhibition of CYP1A1 mRNA induction by the AhR inhibitor CH223191 indicated AhR receptor dependence this effect. Full article

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

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741 KiB

Open AccessArticle

Dietary Exposure of Nigerians to Mutagens and Estrogen-Like Chemicals

by Iyekhoetin Matthew Omoruyi, Derek Ahamioje and Raimo Pohjanvirta

Int. J. Environ. Res. Public Health 2014, 11(8), 8347-8367; https://doi.org/10.3390/ijerph110808347 - 15 Aug 2014

Cited by 9 | Viewed by 6601

Abstract

Food and drinking water are poorly delineated sources of human exposure to chemical food mutagens and endocrine-disrupting chemicals. In this study, we investigated the presence of mutagens and chemicals exhibiting estrogenic activity in the daily diet of Nigerians, using in vitro assays. Commercially [...] Read more.

Food and drinking water are poorly delineated sources of human exposure to chemical food mutagens and endocrine-disrupting chemicals. In this study, we investigated the presence of mutagens and chemicals exhibiting estrogenic activity in the daily diet of Nigerians, using in vitro assays. Commercially processed foods or snacks and various brands of pure water sachets were extracted by solid-phase extraction and liquid-liquid extraction, respectively. Mutagenicity was determined by the conventional Ames test and two complementary assays on two strains of Salmonella (TA 100 and TA 98), while the estrogenic activity was assessed by a yeast bioluminescent assay, using two recombinant yeast strains (Saccharomyces cerevisiae BMAEREluc/ERα and S. cerevisiae BMA64/luc). A third of the food varieties investigated (chin-chin, hamburger, suya and bean cake) were mutagenic in all three assays, either in the presence or absence of S9 mix. Of the packed water samples, five out of the sixteen investigated (31%), were found to be estrogenic, with estradiol and bisphenol A equivalents ranging from 0.79 to 44.0 ng/L and 124.2 to 1,000.8 ng/L, respectively. Hence, although the current situation in Nigeria does not appear to be substantially worse than, e.g., in Europe, regular monitoring is warranted in the future. Full article

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

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628 KiB

Open AccessArticle

In Vitro Interactions between 17β-Estradiol and DNA Result in Formation of the Hormone-DNA Complexes

by Zbynek Heger, Roman Guran, Ondrej Zitka, Miroslava Beklova, Vojtech Adam and Rene Kizek

Int. J. Environ. Res. Public Health 2014, 11(8), 7725-7739; https://doi.org/10.3390/ijerph110807725 - 31 Jul 2014

Cited by 7 | Viewed by 7520

Abstract

Beyond the role of 17β-estradiol (E₂) in reproduction and during the menstrual cycle, it has been shown to modulate numerous physiological processes such as cell proliferation, apoptosis, inflammation and ion transport in many tissues. The pathways in which estrogens affect an [...] Read more.

Beyond the role of 17β-estradiol (E₂) in reproduction and during the menstrual cycle, it has been shown to modulate numerous physiological processes such as cell proliferation, apoptosis, inflammation and ion transport in many tissues. The pathways in which estrogens affect an organism have been partially described, although many questions still exist regarding estrogens’ interaction with biomacromolecules. Hence, the present study showed the interaction of four oligonucleotides (17, 20, 24 and/or 38-mer) with E₂. The strength of these interactions was evaluated using optical methods, showing that the interaction is influenced by three major factors, namely: oligonucleotide length, E₂ concentration and interaction time. In addition, the denaturation phenomenon of DNA revealed that the binding of E₂ leads to destabilization of hydrogen bonds between the nitrogenous bases of DNA strands resulting in a decrease of their melting temperatures (T_m). To obtain a more detailed insight into these interactions, MALDI-TOF mass spectrometry was employed. This study revealed that E₂ with DNA forms non-covalent physical complexes, observed as the mass shifts for app. 270 Da (Mr of E₂) to higher molecular masses. Taken together, our results indicate that E₂ can affect biomacromolecules, as circulating oligonucleotides, which can trigger mutations, leading to various unwanted effects. Full article

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

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2018 KiB

Open AccessArticle

First Year Growth in Relation to Prenatal Exposure to Endocrine Disruptors — A Dutch Prospective Cohort Study

by Marijke De Cock, Michiel R. De Boer, Marja Lamoree, Juliette Legler and Margot Van de Bor

Int. J. Environ. Res. Public Health 2014, 11(7), 7001-7021; https://doi.org/10.3390/ijerph110707001 - 10 Jul 2014

Cited by 61 | Viewed by 8104

Abstract

Growth in the first year of life may already be predictive of obesity later in childhood. The objective was to assess the association between prenatal exposure to various endocrine disrupting chemicals (EDCs) and child growth during the first year. Dichloro-diphenyldichloroethylene (DDE), mono(2-ethyl-5-carboxypentyl)phthalate (MECPP), [...] Read more.

Growth in the first year of life may already be predictive of obesity later in childhood. The objective was to assess the association between prenatal exposure to various endocrine disrupting chemicals (EDCs) and child growth during the first year. Dichloro-diphenyldichloroethylene (DDE), mono(2-ethyl-5-carboxypentyl)phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP), mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), polychlorinated biphenyl-153, perfluorooctanesulfonic acid, and perfluoro-octanoic acid were measured in cord plasma or breast milk. Data on weight, length, and head circumference (HC) until 11 months after birth was obtained from 89 mother-child pairs. Mixed models were composed for each health outcome and exposure in quartiles. For MEOHP, boys in quartile 1 had a higher BMI than higher exposed boys (p = 0.029). High DDE exposure was associated with low BMI over time in boys (0.8 kg/m² difference at 11 m). Boys with high MECPP exposure had a greater HC (1.0 cm difference at 11 m) than other boys (p = 0.047), as did girls in the second quartile of MEHHP (p = 0.018) and DDE (p < 0.001) exposure. In conclusion, exposure to phthalates and DDE was associated with BMI as well as with HC during the first year after birth. These results should be interpreted with caution though, due to the limited sample size. Full article

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

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210 KiB

Open AccessArticle

Association between Urine Phthalate Levels and Poor Attentional Performance in Children with Attention-Deficit Hyperactivity Disorder with Evidence of Dopamine Gene-Phthalate Interaction

by Subin Park, Bung-Nyun Kim, Soo-Churl Cho, Yeni Kim, Jae-Won Kim, Ju-Young Lee, Soon-Beom Hong, Min-Sup Shin, Hee Jeong Yoo, Hosub Im, Jae Hoon Cheong and Doug Hyun Han

Int. J. Environ. Res. Public Health 2014, 11(7), 6743-6756; https://doi.org/10.3390/ijerph110706743 - 27 Jun 2014

Cited by 33 | Viewed by 7542

Abstract

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child’s urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) [...] Read more.

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child’s urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms. Full article

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

205 KiB

Open AccessArticle

Higher Urinary Heavy Metal, Phthalate, and Arsenic but Not Parabens Concentrations in People with High Blood Pressure, U.S. NHANES, 2011–2012

by Ivy Shiue

Int. J. Environ. Res. Public Health 2014, 11(6), 5989-5999; https://doi.org/10.3390/ijerph110605989 - 5 Jun 2014

Cited by 67 | Viewed by 8585

Abstract

Link between environmental chemicals and human health has emerged but not been completely examined in risk factors. Therefore, it was aimed to study the relationships of different sets of urinary environmental chemical concentrations and risk of high blood pressure (BP) in a national, [...] Read more.

Link between environmental chemicals and human health has emerged but not been completely examined in risk factors. Therefore, it was aimed to study the relationships of different sets of urinary environmental chemical concentrations and risk of high blood pressure (BP) in a national, population-based study. Data were retrieved from United States National Health and Nutrition Examination Surveys, 2011–2012 including demographics, BP readings, and urinary environmental chemical concentrations. Analyses included chi-square test, t-test and survey-weighted logistic regression modeling. After full adjustment (adjusting for urinary creatinine, age, sex, ethnicity, and body mass index), urinary cesium (OR 1.56, 95%CI 1.11–2.20, P = 0.014), molybden (OR 1.46, 95%CI 1.06–2.01, P = 0.023), manganese (OR 1.42, 95%CI 1.09–1.86, P = 0.012), lead (OR 1.58, 95%CI 1.28–1.96, P < 0.001), tin (OR 1.44, 95%CI 1.25–1.66, P < 0.001), antimony (OR 1.39, 95%CI 1.10–1.77, P = 0.010), and tungsten (OR 1.49, 95%CI 1.25–1.77, P < 0.001) concentrations were observed to be associated with high BP. People with higher urinary mono-2-ethyl-5-carboxypentyl phthalate (OR 1.33, 95%CI 1.00–1.62, P = 0.006), mono-n-butyl phthalate (OR 1.35, 95%CI 1.13–1.62, P = 0.002), mono-2-ethyl-5-hydroxyhexyl (OR 1.25, 95%CI 1.05–1.49, P = 0.014), mono-n-methyl phthalate (OR 1.26, 95%CI 1.07–1.48, P = 0.007), mono-2-ethyl-5-oxohexyl (OR 1.25, 95%CI 1.07–1.48, P = 0.009), and monobenzyl phthalate (OR 1.40, 95%CI 1.15–1.69, P = 0.002) tended to have high BP as well. However, there are no clear associations between environmental parabens and high BP, nor between pesticides and high BP. In addition, trimethylarsine oxide (OR 2.47, 95%CI 1.27–4.81, P = 0.011) and dimethylarsonic acid concentrations (OR 1.42, 95%CI 1.12–1.79, P = 0.006) were seen to be associated with high BP. In sum, urinary heavy metal, phthalate, and arsenic concentrations were associated with high BP, although the causal effect cannot be established from the current study design. Elimination of environmental chemicals in humans would still need to be continued. Full article

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

Review

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988 KiB

Open AccessReview

Versatility or Promiscuity: The Estrogen Receptors, Control of Ligand Selectivity and an Update on Subtype Selective Ligands

by Hui Wen Ng, Roger Perkins, Weida Tong and Huixiao Hong

Int. J. Environ. Res. Public Health 2014, 11(9), 8709-8742; https://doi.org/10.3390/ijerph110908709 - 26 Aug 2014

Cited by 61 | Viewed by 8846

Abstract

The estrogen receptors (ERs) are a group of versatile receptors. They regulate an enormity of processes starting in early life and continuing through sexual reproduction, development, and end of life. This review provides a background and structural perspective for the ERs as part [...] Read more.

The estrogen receptors (ERs) are a group of versatile receptors. They regulate an enormity of processes starting in early life and continuing through sexual reproduction, development, and end of life. This review provides a background and structural perspective for the ERs as part of the nuclear receptor superfamily and discusses the ER versatility and promiscuity. The wide repertoire of ER actions is mediated mostly through ligand-activated transcription factors and many DNA response elements in most tissues and organs. Their versatility, however, comes with the drawback of promiscuous interactions with structurally diverse exogenous chemicals with potential for a wide range of adverse health outcomes. Even when interacting with endogenous hormones, ER actions can have adverse effects in disease progression. Finally, how nature controls ER specificity and how the subtle differences in receptor subtypes are exploited in pharmaceutical design to achieve binding specificity and subtype selectivity for desired biological response are discussed. The intent of this review is to complement the large body of literature with emphasis on most recent developments in selective ER ligands. Full article

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

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385 KiB

Open AccessReview

Impact of Bisphenol A on the Cardiovascular System — Epidemiological and Experimental Evidence and Molecular Mechanisms

by Xiaoqian Gao and Hong-Sheng Wang

Int. J. Environ. Res. Public Health 2014, 11(8), 8399-8413; https://doi.org/10.3390/ijerph110808399 - 15 Aug 2014

Cited by 135 | Viewed by 14502

Abstract

Bisphenol A (BPA) is a ubiquitous plasticizing agent used in the manufacturing of polycarbonate plastics and epoxy resins. There is well-documented and broad human exposure to BPA. The potential risk that BPA poses to the human health has attracted much attention from regulatory [...] Read more.

Bisphenol A (BPA) is a ubiquitous plasticizing agent used in the manufacturing of polycarbonate plastics and epoxy resins. There is well-documented and broad human exposure to BPA. The potential risk that BPA poses to the human health has attracted much attention from regulatory agencies and the general public, and has been extensively studied. An emerging and rapidly growing area in the study of BPA’s toxicity is its impact on the cardiovascular (CV) system. Recent epidemiological studies have shown that higher urinary BPA concentration in humans is associated with various types of CV diseases, including angina, hypertension, heart attack and coronary and peripheral arterial disease. Experimental studies have demonstrated that acute BPA exposure promotes the development of arrhythmias in female rodent hearts. Chronic exposure to BPA has been shown to result in cardiac remodeling, atherosclerosis, and altered blood pressure in rodents. The underlying mechanisms may involve alteration of cardiac Ca²⁺ handling, ion channel inhibition/activation, oxidative stress, and genome/transcriptome modifications. In this review, we discuss these recent findings that point to the potential CV toxicity of BPA, and highlight the knowledge gaps in this growing research area. Full article

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

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229 KiB

Open AccessReview

Bisphenol-A: Epigenetic Reprogramming and Effects on Reproduction and Behavior

by Guergana Mileva, Stephanie L. Baker, Anne T.M. Konkle and Catherine Bielajew

Int. J. Environ. Res. Public Health 2014, 11(7), 7537-7561; https://doi.org/10.3390/ijerph110707537 - 22 Jul 2014

Cited by 129 | Viewed by 13258

Abstract

Bisphenol A (BPA) is a synthetic compound used in the production of many polycarbonate plastics and epoxy resins. It is one of the most widely produced chemicals in the world today and is found in most canned goods, plastics, and even household dust. [...] Read more.

Bisphenol A (BPA) is a synthetic compound used in the production of many polycarbonate plastics and epoxy resins. It is one of the most widely produced chemicals in the world today and is found in most canned goods, plastics, and even household dust. Exposure to BPA is almost universal: most people have measurable amounts of BPA in both urine and serum. BPA is similar in structure to estradiol and can bind to multiple targets both inside and outside the nucleus, in effect acting as an endocrine disruptor. Research on BPA exposure has accelerated in the past decade with findings suggesting that perinatal exposure to BPA can negatively impact both male and female reproduction, create alterations in behavior, and act as a carcinogen. BPA can have both short term and long term effects with the latter typically occurring through epigenetic mechanisms such as DNA methylation. This review will draw on both human and animal studies in an attempt to synthesize the literature and examine the effects of BPA exposure on reproduction, behavior, and carcinogenesis with a focus on the potential epigenetic mechanisms by which it acts. Full article

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

212 KiB

Open AccessReview

Non-Genomic Effects of Xenoestrogen Mixtures

by René Viñas, Yow-Jiun Jeng and Cheryl S. Watson

Int. J. Environ. Res. Public Health 2012, 9(8), 2694-2714; https://doi.org/10.3390/ijerph9082694 - 31 Jul 2012

Cited by 57 | Viewed by 9559

Abstract

Xenoestrogens (XEs) are chemicals derived from a variety of natural and anthropogenic sources that can interfere with endogenous estrogens by either mimicking or blocking their responses via non-genomic and/or genomic signaling mechanisms. Disruption of estrogens’ actions through the less-studied non-genomic pathway can alter [...] Read more.

Xenoestrogens (XEs) are chemicals derived from a variety of natural and anthropogenic sources that can interfere with endogenous estrogens by either mimicking or blocking their responses via non-genomic and/or genomic signaling mechanisms. Disruption of estrogens’ actions through the less-studied non-genomic pathway can alter such functional end points as cell proliferation, peptide hormone release, catecholamine transport, and apoptosis, among others. Studies of potentially adverse effects due to mixtures and to low doses of endocrine-disrupting chemicals have recently become more feasible, though few so far have included actions via the non-genomic pathway. Physiologic estrogens and XEs evoke non-monotonic dose responses, with different compounds having different patterns of actions dependent on concentration and time, making mixture assessments all the more challenging. In order to understand the spectrum of toxicities and their mechanisms, future work should focus on carefully studying individual and mixture components across a range of concentrations and cellular pathways in a variety of tissue types. Full article

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

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206 KiB

Open AccessReview

Biomarker Genes for Detecting Estrogenic Activity of Endocrine Disruptors via Estrogen Receptors

by Eui-Man Jung, Beum-Soo An, Hyun Yang, Kyung-Chul Choi and Eui-Bae Jeung

Int. J. Environ. Res. Public Health 2012, 9(3), 698-711; https://doi.org/10.3390/ijerph9030698 - 24 Feb 2012

Cited by 25 | Viewed by 8250

Abstract

Endocrine disruptors (EDs) are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since [...] Read more.

Endocrine disruptors (EDs) are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D_9k (CaBP-9k), that may be used to assess estrogenic activity of EDs. Full article

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

Other

Jump to: Research, Review

219 KiB

Open AccessCommentary

Recent Evidence Regarding Triclosan and Cancer Risk

by Michael T. Dinwiddie, Paul D. Terry and Jiangang Chen

Int. J. Environ. Res. Public Health 2014, 11(2), 2209-2217; https://doi.org/10.3390/ijerph110202209 - 21 Feb 2014

Cited by 69 | Viewed by 15368

Abstract

Triclosan is a broad-spectrum antibacterial commonly used in cosmetics, dentifrices, and other consumer products. The compound’s widespread use in consumer products and its detection in breast milk, urine, and serum have raised concerns regarding its potential association with various human health outcomes. Recent [...] Read more.

Triclosan is a broad-spectrum antibacterial commonly used in cosmetics, dentifrices, and other consumer products. The compound’s widespread use in consumer products and its detection in breast milk, urine, and serum have raised concerns regarding its potential association with various human health outcomes. Recent evidence suggests that triclosan may play a role in cancer development, perhaps through its estrogenicity or ability to inhibit fatty acid synthesis. Our aims here are to review studies of human exposure levels, to evaluate the results of studies examining the effects of triclosan on cancer development, and to suggest possible directions for future research. Full article

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

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