Hexachlorobenzene Exposure Research Articles

Hexachlorobenzene and omega-3 fatty acid intake from traditional foods in the northern Yukon: A risk and benefit analysis

A human biomonitoring study was conducted in the community of Old Crow, Yukon, in 2019, finding that levels of hexachlorobenzene (HCB) in plasma were elevated in the community relative to the general Canadian population. The aim of this study was to estimate dietary intake of both hexachlorobenzene, and the nutrient omega-3 fatty acids from locally harvested traditional foods in Old Crow, with the aim of identifying possible regional sources of exposure. A stochastic model was constructed to estimate intake of both hexachlorobenzene and the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Average predicted hexachlorobenzene exposure levels from traditional food consumption in Old Crow were below the tolerable daily intake of 1600–1700 ng/kg body weight/day in both average (18 ng/kg body weight/day) and short-term maximum (27 ng/kg body weight/day) exposure models. The primary contributors to average hexachlorobenzene intake were caribou fat, bone marrow, ribs, and kidneys, and Chinook salmon muscle. Average estimated dietary EPA + DHA intake levels from traditional foods were below the recommendation of 2.1 to 3.2 g of EPA + DHA per week in the average (1.6 g/week) exposure model, but above this recommendation in the short-term maximum model (3.3 g/week). The primary contributors to average EPA + DHA intake were the meat of Chinook, coho, and, chum salmon muscle, and whitefish muscle and eggs. The results of this study support the message that traditional foods continue to be an important source of nutrients and other health benefits and that the health benefits of traditional foods generally outweigh contaminant risks.

Prenatal Exposure to Multiple Endocrine-Disrupting Chemicals and Childhood BMI Trajectories in the INMA Cohort Study.

Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children's body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4'-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%-32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE (95% CI: 1.05, 1.35); RRR for (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the ; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. https://doi.org/10.1289/EHP11103.

Breast cancer progression and kynurenine pathway enzymes are induced by hexachlorobenzene exposure in a Her2-positive model.

Breast cancer is one of the leading cancers among women worldwide. Given the evidence that pesticides play an important role in breast cancer, interest has grown in pesticide impact on disease progression. Hexachlorobenzene (HCB), an aryl hydrocarbon receptor (AhR) ligand, promotes triple-negative breast cancer cell migration and invasion. Estrogen receptor β (ERβ) inhibits cancer motility, while G protein-coupled ER (GPER) modulates the neoplastic transformation. Tryptophan is metabolized through the kynurenine pathway by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO), with kynurenine signaling activation often predicting worse prognosis in cancer. In this context, we examined the HCB (0.005; 0.05; 0.5 and 5μM) effect on LM3 cells, a human epidermal growth factor receptor 2 (HER2)-positive breast cancer model. Results show that HCB increases IDO and TDO mRNA levels and promotes cell viability, proliferation and migration through the AhR pathway. Moreover, HCB boosts mammosphere formation, vascular endothelial growth factor and cyclooxygenase-2 expression and reduces IL-10 levels. For some parameters, U-shaped or inverted U-shaped dose-response curves are shown. HCB alters ER levels, reducing ERβ while increasing GPER. These results demonstrate that exposure to environmentally relevant concentrations of HCB up-regulates the kynurenine pathway and dysregulates ERβ and GPER levels, collaborating in HER2-positive breast cancer progression.

Organochlorine pesticides and polycyclic aromatic hydrocarbons in serum of Beijing population: Exposure and health risk assessment

Organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, but large-scale human biomonitoring and health risk assessment data on these contaminants remain limited. In this study, concentrations of 6 OCPs and 5 PAHs were determined by GC–MS/MS in 1268 human serum samples which were collected from the participants in 2017 Beijing Chronic Disease and Risk Factor Surveillance. The detection frequencies of OCPs and PAHs ranged from 64.7 % to 96.5 % and 89.4 % to 99.6 %, respectively. The most abundant contaminants in OCPs and PAHs were pentachlorophenol (PCP) and pyrene (Pyr) with median concentrations reaching up to 3.13 and 8.48 μg/L, respectively. Nonparametric tests were employed to assess the correlations among contaminants levels, demographic characteristics (age, gender, body mass index, residence) and serum biochemical indexes. Significantly higher serum levels of all PAHs were observed in suburb residents than that in urban residents (P < 0.001). Binary logistic regression analysis demonstrated that exposure to benzo(a)pyrene (OR 2.17 [1.29, 3.63]), phenanthrene (OR 1.06 [1.02, 1.11]), fluoranthene (OR 1.04 [1.02, 1.07]) and Pyr (OR 1.02 [1.01, 1.03]) might increase the occurrence of hyperglycemia, and exposure to hexachlorobenzene (HCB) (OR 1.53 [1.05, 2.22]) and pentachlorobenzene (OR 1.14 [1.02, 1.27]) were positively associated with hyperlipidemia. Furthermore, the hazard quotients (HQs) for serum HCB, PCP and p,p’-dichlorodiphenyldichloroethylene were calculated based on health-based guidance values to predict health risks. 0.2 % and 4.3 % of serum samples showed HQ values exceeding 1 for HCB and PCP, respectively, in case of the non-carcinogenic risk, while 23.1 % of HQs for HCB were above 1 in case of the carcinogenic risk for a risk level 10−5. Our study reveals that the body burden of the Beijing general population relative to OCPs and PAHs was nonnegligible. The past exposure of HCB and PCP might adversely affect the health status of the Beijing population.

Endocrine disruptor hexachlorobenzene induces cell migration and invasion, and enhances aromatase expression levels in human endometrial stromal cells

Endometriosis is the presence and growth of endometrial tissue outside of the uterus. Previous studies have suggested that endocrine disrupting chemicals such as organochlorine pesticides could be a risk factor for endometriosis. Hexachlorobenzene (HCB) is a weak ligand of the aryl hydrocarbon receptor (AhR) and promotes metalloproteinase and cyclooxygenase-2 (COX-2) expression, as well as, c-Src activation in human endometrial stromal cells (T-HESC) and in rat endometriosis model. Our aim was to evaluate the effect of HCB exposure on oestrogen receptor (ER) ɑ and β, progesterone receptor (PR) and aromatase expression, as well as, on cell migration and invasion in T-HESC and primary cultures of endometrial stromal cells from eutopic endometria of control subjects (ESC). Results show that HCB increases ERɑ and aromatase protein levels and reduces PR content in both T-HESC and ESC. However, the pesticide only increases ERβ expression in ESC, without changes in T-HESC. Moreover, cell migration and invasion are promoted by pesticide exposure involving the AhR, c-Src, COX-2 and ER pathways in T-HESC. HCB also triggers ERɑ activation via phosphorylation in Y537 through AhR/c-Src pathway. Our results provide experimental evidence that HCB induces alterations associated with endometriosis, suggesting that these mechanisms could contribute to pesticide exposure-induced endometriosis development.

The endocrine disruptor hexachlorobenzene can cause oxidative damage in the testis of mice.

Hexachlorobenzene is a widespread endocrine disruptor. However, the effect of hexachlorobenzene on the reproductive toxicity of male animals is not described in detail. To investigate the toxic effects of hexachlorobenzene in mouse testes, hexachlorobenzene (100, 400 and 1,600mg/kg) is fed to mice. The morphology of the testes was analysed by haematoxylin and eosin staining. We also investigated the expression of biomarkers for oxidative stress. Database screening identified proteins that interact with hexachlorobenzene and the aryl hydrocarbon receptor, a weak ligand of hexachlorobenzene. Gene enrichment analysis and protein-protein interaction analyses were also performed. Real-time PCR detected the expression levels of the aryl hydrocarbon receptor in four different stages of testicular cells. We identified significantly increased activity levels of superoxide dismutase (p<0.05) and catalase (p<0.05) in mouse testes that had been subjected to oxidative damage. The cell thickness and the number of cell layers in the seminiferous tubules had decreased by varying degrees after the hexachlorobenzene treatment. Particularly, cytokines and proteins involved in transcriptional regulation showed enrichment. The highest levels of aryl hydrocarbon receptor expression were detected in the spermatocytic cell line. Hexachlorobenzene exposure caused testicular damage in mice. The toxicity characteristics of hexachlorobenzene were not dose-dependent.

Hexachlorobenzene, a pollutant in hypothyroidism and reproductive aberrations: a perceptive transgenerational study.

Hexachlorobenzene (HCB), a widespread environmental pollutant, contributes to endocrine disruption resulting in hypothyroidism. We investigated the effect of chronic exposure of HCB to explore the functional interconnection between hypothyroidism and infertility. All observations were made through the F1 and F2 generations. Thyroidectomy was also performed to evaluate the contribution of the thyroid gland in affecting ovarian dysfunction and reproductive aberrations. We confirmed that the preconception exposure of HCB leads to hypothyroidism which was reflected by an increase in the body weight, alteration in the thyroid hormones, and alteration of the lipid profile. Hypothyroid female rats exhibited a poor reproductive profile with altered steroidogenic pathways, altered estrus cyclicity, reduced litter size, and stunted growth. The external supplementation of thyroxine in thyroidectomized animals rescues the reproductive aberrations confirming the protective role of the thyroid gland in reproductive biology. All results highlight the jeopardizing functional connection of the thyroid and ovary due to HCB, leading to serious consequences on upcoming generations.

Exposure to environmental contaminants and risk of pregnancy induced hypertension and gestational diabetes mellitus

Introduction: Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB), are ubiquitously found in the environment and resistant to degradation. POPs, along with persistent organochlorine pesticides including p,p'-dichlorodiphenyl dichloroethylene (DDE) and heavy metals have been associated with various pregnancy outcomes but results are inconsistent.Objective: We assessed the associations between prenatal exposures to organochlorines and heavy metals and the development of gestational diabetes mellitus (GDM) and pregnancy induced hypertension (PIH). Methods: We used existing exposure models to predict prenatal levels of PCBs (using the sum of 4 prevalent congeners), DDE, HCB, lead (Pb) and mercury (Hg) for all pregnant women living in southeast Massachusetts between 1993-1998 (n=10,270). Outcome and covariate data were obtained from Massachusetts birth records. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for GDM and PIH were estimated using multivariable logistic regression models. Results: Approximately 1.8% of women in this study population developed GDM and 1.9% of women developed PIH. PCBs, DDE and HCB were strongly associated with the development of GDM, while no associations were observed for Pb and Hg exposure. After adjusting for weight gain during pregnancy, smoking during pregnancy, parity, race, and socioeconomic factors, the effects of PCBs (OR: 1.56; 95% CI: 1.10-2.22) and DDE (OR: 2.84; 95% CI: 1.90-4.25) on GDM remained. However, the risk associated with HCB exposure was no longer significant after adjusting for confounders. Associations with PIH were null.Conclusions: These results suggest that women with high prenatal levels of PCBs and DDE may have a higher risk of developing GDM. We found no associations between PIH and exposures to organochlorines and heavy metals.

Prenatal environmental exposures and associations with teen births.

Background:Children’s prenatal exposure to multiple environmental chemicals may contribute to subsequent deficits in impulse control, predisposing them to risk-taking.Objective:Our goal was to investigate associations between prenatal exposure mixtures and risk of teen birth, a manifestation of high-risk sexual activity, among 5,865 girls (1st generation) born in southeast Massachusetts from 1992-1998.Methods:Exposures included prenatal modeled polychlorinated biphenyls (PCBs), ρ,ρ′-dichlorodiphenyl dichloroethylene (DDE), hexachlorobenzene (HCB), lead (Pb), and mercury (Hg). We fit adjusted generalized additive models with multivariable smooths of exposure mixtures, 1st generation infant’s birth year, and maternal age at 1st generation birth. Predicted odds ratios (ORs) for teen birth were mapped as a function of joint exposures. We also conducted sensitivity analyses among 1st generation girls with measured exposure biomarkers (n=371).Results:The highest teen birth risk was associated with a mixture of high prenatal HCB, Hg, Pb, and PCB, but low DDE exposure, with similar associations in sensitivity analyses. The highest OR predicted for girls born in 1995 to mothers of median age (26 years) was at the 95th percentile of the HCB and PCB exposure distributions (OR=3.09; 95% confidence interval: 0.29, 32.4). Additionally, girls born earlier in the study period or to teen mothers were at increased risk of teen birth.Significance:Prenatal environmental chemical exposures and sociodemographic characteristics may interact to substantially increase risk of teen births.

AhR ligands reactivate LINE-1 retrotransposon in triple-negative breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG

Breast cancer is the most common cancer type in females worldwide. Environmental exposure to pesticides affecting hormonal homeostasis does not necessarily induce DNA mutations but may influence gene expression by disturbances in epigenetic regulation. Expression of long interspersed nuclear element-1 (LINE-1) has been associated with tumorigenesis in several cancers. In nearly all somatic cells, LINE-1 is silenced by DNA methylation in the 5́′UTR and reactivated during disease initiation and/or progression. Strong ligands of aryl hydrocarbon receptor (AhR) activate LINE-1 through the transforming growth factor-β1 (TGF-β1)/Smad pathway. Hexachlorobenzene (HCB) and chlorpyrifos (CPF), both weak AhR ligands, promote cell proliferation and migration in breast cancer cells, as well as tumor growth in rat models. In this context, our aim was to examine the effect of these pesticides on LINE-1 expression and ORF1p localization in the triple-negative breast cancer cell line MDA-MB-231 and the non-tumorigenic epithelial breast cell line NMuMG, and to evaluate the role of TGF-β1 and AhR pathways. Results show that 0.5 μM CPF and 0.005 μM HCB increased LINE-1 mRNA expression through Smad and AhR signaling in MDA-MB-231. In addition, the methylation of the first sites in 5́′UTR of LINE-1 was reduced by pesticide exposure, although the farther sites remained unaffected. Pesticides modulated ORF1p localization in MDA-MB-231: 0.005 μM HCB and 50 μM CPF increased nuclear translocation, while both induced cytoplasmic retention at 0.5 and 5 μM. Moreover, both stimulated double-strand breaks, enhancing H2AX phosphorylation, coincidentally with ORF1p nuclear localization. In NMuMG similar results were observed, since they heighten LINE-1 mRNA levels. CPF effect was through AhR and TGF-β1 signaling, whereas HCB action depends only of AhR. In addition, both pesticides increase ORF1p expression and nuclear localization. Our results provide experimental evidence that HCB and CPF exposure modify LINE-1 methylation levels and induce LINE-1 reactivation, suggesting that epigenetic mechanisms could contribute to pesticide-induced breast cancer progression.

Cancer incidence in an Austrian alpine valley 1983-2012 : Adescriptive study.

SummaryAfter one of Austria’s largest environmental scandals in 2014, which involved the release of hexachlorobenzene (HCB) in the Carinthian valley Görtschitztal, concerns about increased cancer rates have arísen in the affected local population. A descriptive study was conducted to examine the cancer incidence rates between 1983 and 2012. Data from the affected area (Görtschitztal, district St. Veit) were compared to data from the neighboring area within the same district and Carinthia excluding St. Veit, considering incidence rates of liver, lung, kidney, thyroid cancer and mesothelioma. Prostate cancer and carcinoma in situ were both included and excluded from overall cancer incidents in order to prevent potential bias due to screening programs. Considering the observed variability at an overall level, no conspicuous differences in cancer incidences could be found (Carinthia: 495, St. Veit West: 408, St. Veit East: 572 cases per 100,000 person-years in 2012). For some cancer types, e. g. liver, thyroid cancer and mesothelioma, the affected region showed a higher increase in rates than the neighboring area or Carinthia overall; however, these increased rates date back to a time prior to the HCB exposure, suggesting other carcinogenic influences, such as asbestos exposure from antecedent years.

Using Birth Cohort Data to Estimate Prenatal Exposures for All Births around the New Bedford Harbor Superfund Site in Massachusetts

Introduction: Children born near New Bedford, Massachusetts, USA have been prenatally exposed to environmental chemicals, in part due to an older housing stock, high fish consumption rates, and proximity to the New Bedford Harbor (NBH) Superfund site. Chemical exposure measures are not available for the general population, limiting epidemiologic investigations and potential interventions. Our objective was to leverage available sociodemographic and biomonitoring data from the New Bedford Cohort (NBC) to retrospectively estimate prenatal exposures for all 10,273 births between 1993-1998 in the 4 towns neighboring the NBH Superfund site.Methods: The NBC, a population-based cohort of 788 mother-infant pairs born between 1993-1998 near the NBH, collected questionnaire data and prenatal exposure biomarkers including cord serum polychlorinated biphenyls (PCB), &amp;#961;,&amp;#961;&amp;#8242;-dichlorodiphenyl dichloroethylene (DDE), hexachlorobenzene (HCB), cord blood lead (Pb), and maternal hair mercury (Hg). We used bootstrapped samples of the NBC data to build prenatal exposure models, with multivariable smooths of birth location, birth year, maternal age at birth, and other NBC maternal sociodemographic characteristics as predictors.Results: Maternal country of birth was the strongest exposure predictor across all exposures with women from the Azores and Cape Verde having the highest levels. Maternal age, education, and marital status also were important predictors. The PCB, DDE, HCB, Pb, and Hg exposure models explained 55%, 53%, 41%, 43% and 38% of the variance, respectively.Conclusions: Our analyses suggest that multiple prenatal exposures can be estimated at the population level by modeling available data for a subset of the population. Predictive models using multivariable smoothing explained reasonable amounts of variance. Other exposure models with comparable performance have been used successfully in epidemiologic investigations to characterize exposure-outcome associations.

Hexachlorobenzene exposure induces cell migration and invasion through AhR, COX-2, ER and c-Src in human endometrial stromal cells

Hexachlorobenzene exposure induces cell migration and invasion through AhR, COX-2, ER and c-Src in human endometrial stromal cells

Environmental pollutant hexachlorobenzene induces hypertension in a rat model

Hexachlorobenzene (HCB) is a dioxin-like environmental pollutant, widely distributed in the environment. New research links exposure to high levels of persistent organic environmental toxicants to cardiovascular disease, however little is known about the effect of HCB on vascular function and on blood pressure. The purpose of the present study was to evaluate biochemical and cardiovascular changes resulting from subchronic HCB exposure. Adult female Sprague-Dawley rats were treated with vehicle or HCB (5 or 500 mg/kg b.w) for 45 days. Systolic blood pressure (BP), recorded by tail cuff plethysmography, was significantly increased at 35, 40 and 45 days of 500 mg/kg HCB-treatment. HCB (500 mg/kg) increased arterial thickness, while both 5 and 500 mg/kg HCB decreased proliferating cell nuclear antigen (PCNA) protein levels and cellular nuclei in abdominal aortas indicating a hypertrophic process. Also, aortas from both groups of HCB-treated rats presented higher sensitivity to noradrenalin (NA) and a significant decrease in maximum contractile response. Arteries from 500 mg/kg HCB-treated rats showed a significant increase in the levels of transforming growth factor-β1 (TGF-β1) mRNA and angiotensin II type1 receptor (AT1), and a significant decrease in estrogen receptor alpha (ERα), endothelial nitric oxidide synthase (eNOS) protein expression and deiodinase II (DII) mRNA levels. In conclusion, we have demonstrated for the first time that subchronic HCB administration significantly increases BP and alters associated cardiovascular parameters in rats. In addition, HCB alters the expression of key vascular tissue molecules involved in BP regulation, such as TGF-β1, AT1, ERα, eNOS and DII.

A dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling

Hexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound that binds weakly to the aryl hydrocarbon receptor (AhR). Because AhR and transforming growth factor β1 (TGF-β1) converge to regulate common signaling pathways, alterations in this crosstalk might contribute to developing preneoplastic lesions. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling in mouse mammary gland, through AhR+/+ and AhR−/− models. Results showed a differential effect in mouse mammary epithelial cells (NMuMG), depending on the dose: 0.05μM HCB induced cell migration and TGF-β1 signaling, whereas 5μM HCB reduced cell migration, promoted cell cycle arrest and stimulated the dioxin response element (DRE) -dependent pathway. HCB (5μM) enhanced α-smooth muscle actin expression and decreased TGF-β receptor II mRNA levels in immortalized mouse mammary fibroblasts AhR+/+, resembling the phenotype of transformed cells. Accordingly, their conditioned medium was able to enhance NMuMG cell migration. Assays in C57/Bl6 mice showed HCB (3mg/kg body weight) to enhance ductal hyperplasia, cell proliferation, estrogen receptor α nuclear localization, branch density, and the number of terminal end buds in mammary gland from AhR+/+ mice. Primary culture of mammary epithelial cells from AhR+/+ mice showed reduced AhR mRNA levels after HCB exposure (0.05 and 5μM). Interestingly, AhR−/− mice exhibited an increase in ductal hyperplasia and mammary growth in the absence of HCB treatment, thus revealing the importance of AhR in mammary development. Our findings show that environmental HCB concentrations modulate AhR and TGF-β1 signaling, which could contribute to altered mammary branching morphogenesis, likely leading to preneoplastic lesions and retaining terminal end buds.

Partitioning of hexachlorobenzene between human milk and blood lipid

In epidemiological studies on the toxic effects of prenatal exposure to hexachlorobenzene (HCB), researchers report HCB concentrations, either as wet-weight or per lipid weight basis, in matrices like breast milk, and maternal and cord blood. Conversion of exposures across matrices is needed for comparisons of concentrations and dose effect across cohorts. Using data from a birth cohort study in eastern Slovakia, we derived the maternal blood to cord blood HCB concentration ratio utilizing measured concentrations in 1027 paired maternal and cord blood samples, on a per-lipid basis. In addition to data from the Slovak study, the maternal milk to maternal serum ratio was summarized from 23 published studies on partitioning of HCB between human milk lipid and blood lipid. We identified two distinct groups of milk:blood ratios, those ≤0.45 and those ≥0.85. We assumed that using partition ratios ≤0.45 will underestimate HCB exposure estimates. Taking into account this precautionary measure, we suggest a conversion ratio of 1.21, which is the median of the 16 ratios identified in our literature review. We consider our estimate as conservative and providing appropriate safety in risk analysis.

Structure and function of the bacterial communities during rhizoremediation of hexachlorobenzene in constructed wetlands.

Vertical flow constructed wetlands (VF CWs) are considered to be effective for treating organic pollutants. The rhizosphere of macrophytes such as Phragmites sp., Typha sp. serves as an active and dynamic zone for the microbial degradation of organic pollutants. However, it is still not clear how soil bacterial communities respond to macrophytes and pollutants during the process. For this purpose, the seedlings of Phragmites australis and Typha angustifolia were planted respectively in the VF CWs added with HCB at a dose of 2mg/kg. During 96days of cultivation, we monitored hexachlorobenzene (HCB) removal efficiency by GC/MS and the structure of the rhizosphere bacterial communities in the different VF CWs by denaturing gradient gel electrophoresis (DGGE), and constructed bacterial clone library based on PCR-amplified 16S rRNA gene. As expected, the rhizosphere bacterial communities also remained insensitive to HCB exposure in the wetland soil. The diversity of these microbes presented two stages, from the varied up and down to equilibrium in the entire experimental period. Molecular analysis revealed that the phylum Firmicutes dominated over the bacterial communities. The genera that increased under HCB stress included the well-known HCB-degrading bacteria (Pseudomonas sp. and Alcaligenes sp.) and other common bacteria found in contaminated soil but with lesser known practical functions (Burkholderia sp., Lysinibacillus fusiformis, and Bacillus cereus). Furthermore, there was a certain variance in the relative abundances of the bacterial phyla and HCB removal efficiency among different VF CW treatments. The degradation of HCB in T. angustifolia microcosms was faster than that in P. australis and unvegetated wetlands, and the highest bacterial diversity and richness was found in the VF CWs comprising T. angustifolia.

Persistent organic pollutants in early pregnancy and risk of gestational diabetes mellitus

BackgroundPersistent organic pollutants (POPs) are a group of diverse substances, including polychlorinated biphenyls (PCBs) and organochlorine pesticides that are resistant to biodegradation and ubiquitously present in our environment. Exposure to endocrine disrupting chemicals such as POPs has been linked to type 2 diabetes and metabolic disturbances in epidemiological and animal studies, but little is known about POPs exposure during pregnancy and the development of gestational diabetes mellitus (GDM). The purpose of this study was to determine the extent to which exposure to current low levels of different POPs in the first trimester of pregnancy is associated with GDM risk in 939 women from the “Rhea” pregnancy cohort in Crete, Greece. MethodsConcentrations of several PCBs, dichlorodiphenyldichloroethene (DDE), and hexachlorobenzene (HCB) were determined in first trimester maternal serum by triple quadrupole mass spectrometry. We defined total PCBs as the sum of all congeners, nondioxin-like PCBs as the sum of PCB 153, 138, 170 and 180, and dioxin-like PCBs as the sum of PCB 118 and 156. Pregnant women were screened for gestational diabetes mellitus (GDM) between 24 and 28weeks of gestation, and GDM was defined by the criteria proposed by Carpenter and Coustan. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression models. ResultsOf the 939 women, 68 (7%) developed GDM. Serum concentrations of POPs were higher in women with GDM. Women in the medium and high tertiles of PCBs had 3.90 (95% CI: 1.37, 11.06) and 3.60 (95% CI: 1.14, 11.39) fold respectively higher odds of developing GDM compared to women in the lowest tertile of PCB exposure after adjusting for pre-pregnancy BMI and several other confounders. Odds of GDM for women in the medium and high tertiles of dioxin-like PCBs was 5.63 (95% CI: 1.81, 17.51) and 4.71 (95% CI: 1.38, 16.01) and for nondioxin-like PCBs 2.36 (95% CI: 0.89, 6.23) and 2.26 (95% CI: 0.77, 6.68) respectively. Prenatal DDE and HCB exposure were not significantly associated GDM risk. ConclusionsThese findings suggest that women with high PCBs levels in early pregnancy had higher risk for GDM. Further studies are needed to replicate these results and to evaluate potential biological mechanisms underlying the observed associations.

Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells

Hexachlorobenzene (HCB) is an organochlorine pesticide that induces toxic reproductive effects in laboratory animals. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is characterized by the presence of functional endometrial tissues outside the uterine cavity. Experimental studies indicate that exposure to organochlorines can interfere with both hormonal regulation and immune function to promote endometriosis. Altered expression of metalloproteinases (MMPs) in patients with endometriosis, suggests that MMPs may play a critical role. In the endometriotic lesions, prostaglandin E2 (PGE2) produced by cyclooxygenase-2 (COX-2), binds to its EP4 receptor (EP4), and via c-Src kinase induces MMPs activation, promoting endometriosis. We examined the HCB action on MMP-2 and MMP-9 activities and expression, COX-2 levels, PGE2 signaling, and the AhR involvement in HCB-induced effects. We have used different in vitro models: (1) human endometrial stromal cell line T-HESC, (2) primary cultures of Human Uterine Fibroblast (HUF), and (3) primary cultures of endometrial stromal cells from eutopic endometrium of control (CESC) and subjects with endometriosis (EESC). Our results show that HCB enhances MMP-2 and MMP-9 activities in T-HESC, HUF and ESC cells. The MMP-9 levels were elevated in all models, while the MMP-2 expression only increased in ESC cells. HCB enhanced COX-2 and EP4 expression, PGE2 secretion and the c-Src kinase activation in T-HESC. Besides, we observed that AhR is implicated in these HCB-induced effects. In conclusion, our results show that HCB exposure could contribute to endometriosis development, affecting inflammation and invasion parameters of human endometrial cells.

The metabolic fingerprint of p,p′-DDE and HCB exposure in humans

BackgroundDichlorodiphenyldichloroethylene (p,p′-DDE) and hexachlorobenzene (HCB) are organochlorine pesticides with well-known endocrine disrupting properties. Exposure to p,p′-DDE and HCB concerns human populations worldwide and has been linked to metabolic disorders such as obesity and type 2 diabetes, but details about these associations in humans from the general population are largely unknown. ObjectivesWe investigated the associations between p,p′-DDE and HCB exposure and global metabolomic profiles in serum samples from 1016 participants from the Swedish population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. MethodsHCB and p,p′-DDE levels were determined using gas chromatography coupled to high-resolution mass spectrometry (GC–HRMS). Metabolite levels were determined by using a non-targeted metabolomics approach with ultra-performance liquid chromatography coupled to time-of- flight mass spectrometry (UPLC–TOFMS). Association analyses were performed using multivariate linear regression. ResultsWe found circulating levels of p,p-DDE and HCB to be significantly associated with circulating levels of 16 metabolites following adjustment for age, sex, education level, exercise habits, smoking, energy intake, and alcohol intake. The majority of the 16 metabolites belong to lipid metabolism pathways and include fatty acids, glycerophospholipids, sphingolipids, and glycerolipids. Overall, p,p′-DDE and HCB levels were found to be correlated to different metabolites, which suggests that different metabolic fingerprints may be related to circulating levels of these two pesticides. ConclusionsOur findings establish a link between human exposure to organochlorine pesticides and metabolites of key metabolic processes mainly related to human lipid metabolism.