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This study aims to identify the occurrence and characteristics of PCDD/Fs in soil and sediment samples from secondary copper and aluminum villages in northern Vietnam using the HRGC/MS system. Additionally, it assesses the impact of PCDD/Fs on human health and the potential ecological risks they pose. The residual concentrations of PCDD/Fs in soil and sediment samples collected from the secondary copper Dai Bai village and secondary aluminum Man Xa village were as follows: 0.37 ± 0.29 ng TEQ/kg d.w. (ranging from 0.06 to 0.63 ng TEQ/kg d.w.); 4.88 ± 0.51 ng TEQ/kg d.w. (ranging from 0.512 to 12.17 ng TEQ/kg d.w.); 11.2 ± 5.31 ng TEQ/kg d.w. (ranging from 5.12 to 15.2 ng TEQ/kg d.w.); and 21 ± 12.7 ng TEQ/kg d.w. (ranging from 0.37 to 31.6 ng TEQ/kg d.w.), respectively. The distribution of PCDD/Fs indicated Octa- and Hepta-CDD/Fs as the dominant congeners with high chlorine content. The TEQ levels of PCDD/Fs in all soil and sediment samples were found to be below the allowable limit according to Vietnamese regulations, with the top contributor being 2,3,4,7,8-PeCDF. Samples collected near the production areas exhibited higher levels of PCDD/Fs compared to those collected farther away. The UNEP toolkit was utilized to determine the permissible dioxin TEQ concentrations suitable for livestock farming. The lifetime average daily doses (LADD) of PCDD/Fs via soil ingestion in Man Xa and Dai Bai were calculated as 0.04 × 10−3 and 1.54 × 10−3 pg TEQ/kg d.w. respectively. The relative cancer risks for humans were estimated at 0.05 × 10−12 and 2.05 × 10−12. Furthermore, the ecological risk assessment method indicates that dioxin in all soil and sediment samples near the aluminum recycling craft village had a negative impact on the ecosystem. In contrast, sediment samples taken away from the aluminum recycling craft village and all sediment soil samples in the bronze casting village did not show negative impacts on the ecosystem. [ABSTRACT FROM AUTHOR]

The open burning of sugarcane residue is commonly used as a low-cost and fast method during pre-harvest and post-harvest periods. However, this practice releases various pollutants, including dioxins. This study aims to predict polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs or dioxins) emissions using the grey model (GM (1,1)) and to map the annual flux spatial distribution at the provincial level from 2023 to 2028. An annual emission inventory at the provincial level was developed using the activity rate of dry crop residue from national agencies and literature, following the guidelines set by the United Nations Environment Programme (UNEP). Emission distributions from 2016 to 2022 were then mapped. The average PCDD/F emission values show significant variation among the provinces, averaging 309 pg TEQ/year. Spatially, regions with intensive sugarcane production, such as Lampung and East Java consistently show high emissions, often exceeding 400 pg/m2. Emissions calculated using the UNEP emission factor tend to be higher compared to other factors, due to its generic nature and lack of regional specificity. Emission predictions using GM (1,1) indicate that North Sumatra is expected to experience a steady increase in PCDD/Fs emissions, whereas South Sumatra and Lampung are projected are projected to see a slight decline. This forecast assumes no changes in regional intervention strategies. Most regions in Java Island show a gradual increase in emissions, except for East Java, which is predicted to have a slight decline from 416 pg/year in 2023 to 397 pg/year in 2028. Additionally, regions such as Gorontalo and parts of East Java are projected to remain 'hotspots' with consistently high emissions, highlighting the need for targeted interventions. To address emission hotspots, this study emphasizes the need for cleaner agricultural practices, enhanced enforcement of environmental regulations, and the integration of advanced monitoring technologies to mitigate the environmental and health impacts of PCDD/F emissions in Indonesia. Future studies should consider developing monthly emissions profiles to better account for local agricultural practices and seasonal conditions. The emission data generated in this study, which include both spatial and temporal distributions, are valuable for air quality modeling studies and can help assess the impact of current and future emissions on ambient air quality. [ABSTRACT FROM AUTHOR]

In this study, data from 23 domestic cremation facilities measured for 5 years (from 2016 to 2020) of 13 domestic cremation facilities was used to calculate the emission factors of dioxins (PCDD/DFs) of cremation facilities that use Liquified Natural Gas (LNG) as combustion fuel. We performed a statistical analysis for the first time to estimate the emission factor using limited measurement results from cremation facilities that are not easily accessible. We attempted to identify the emission concentration of dioxin as a representative persistent organic pollutants substance and developed a statistically based dioxin emission factor. The concentration of dioxins (PCDD/DFs) in the cremation facility ranged 0.001–4.440 ng I-TEQ/Sm3 with an average concentration of 0.719 ng I-TEQ/Sm3. The emission factor calculated using the 23 measured data showed 0.010–21.485 μg I-TEQ/Cremation. A Monte Carlo Simulation was conducted using probability density distribution and parameter estimation. Consequently, 10,000 emission factors were selected, and the Pareto distribution was predicted to be the most appropriate probability density distribution. The emission factor values through Monte Carlo simulation showed a minimum value of 1.490 × 10–08 μg I-TEQ/Cremation and a maximum value of 7816 μg I-TEQ/Cremation. The average value was calculated as 39.920 μg I-TEQ/Cremation. Each parameter of the Pareto distribution is shape parameter (α) 1.026, location parameter (μ) – 1.021, and scale parameter (λ) 1.021. As a result of this study, the median value of the cumulative density function was selected as a representative value for the dioxin emission factor of cremation facilities and the emission factor was 0.986 μg I-TEQ/ Cremation. The 95% confidence interval in the Pareto distribution was presented as 0.026 μg I-TEQ/Cremation to 36.216 μg I-TEQ/ Cremation. [ABSTRACT FROM AUTHOR]

Abstract Polychlorinated biphenyls (PCBs) and dioxin are persistent endocrine disrupting chemicals (EDCs) and have been associated with an increased risk of metabolic syndrome (MetS). The aim of this systematic review and meta-analysis was to assess the associations of PCBs and dioxin with MetS and its risk factors, including obesity, hypertriglyceridaemia (HTG), hypertension (HTN) and diabetes mellitus (DM). We searched three electronic databases for epidemiological studies concerning PCBs and dioxin with MetS published up to the end of 2023. Meta-analysis was performed for MetS itself and each of the MetS risks based on a random-effects meta-analysis model, and odds ratios (ORs) with 95% confidence intervals (CIs) were obtained. Publication bias was assessed based on Egger’s test. Eleven studies were included from three databases up to 2023. There were 40,528 participants aged 18–89, where 18–100% of them were males, included in our meta-analysis. The meta-analysis results showed a strong association between PCB exposure and DM (OR = 3.593, 95% CI 2.566, 5.031), while most of the risk factors for MetS, including obesity (OR = 1.875, 95% CI 0.883, 3.979), HTN (OR = 1.335, 95% CI 0.902, 1.976) and HTG (OR = 1.611, 95% CI 0.981, 2.643), were weakly associated with PCB. Furthermore, both PCBs (OR = 1.162, 95% CI 0.994, 1.357) and dioxin (OR = 2.742, 95% CI 1.936, 3.883) were found to be weakly and strongly associated with MetS, respectively. Meta-regression analysis showed that DM in the Asian population is associated with PCB exposure, while HTG in the Northern American population is associated with PCB exposure. Our meta-analysis has demonstrated a strong relationship between DM and PCBs, while the relationship between PCBs with MetS and other risk factors is less pronounced. Additionally, MetS is weakly associated with dioxin exposure. To improve primary care outcomes, healthcare providers should consider incorporating the assessment of patients' risk of exposure to PCBs and dioxins into their evaluation procedures for more targeted medical interventions.

Dioxins are endocrine disruptors that may disturb male sexual and reproductive function. Studies on human populations are limited, and their results are controversial. This study evaluated the impact of dioxin exposure on reproductive and thyroid hormone levels and sexual function in men. A total of 140 men working in four military airbases (three bases were formerly contaminated with dioxin by the herbicide spraying campaign in the Vietnam War) were recruited to measure the serum dioxin levels. Four reproductive hormones (testosterone, follicle-stimulating hormone, luteinizing hormone (LH), and prolactin) and three thyroid hormones (free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone) were measured. Male sexual function endpoints including sexual drive, erection, ejaculation, problems, and overall satisfaction were assessed by the Brief Male Sexual Function Inventory. The percentage of subjects with low testosterone and LH levels was 19.6% and 16.7%, respectively. Dioxins, especially 2,3,7,8-tetrachlorodibenzo-P-dioxin and toxic equivalent concentrations of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans, were inversely associated with testosterone and prolactin levels, but positively associated with FT3 and FT4, and showed adverse relationships with sexual function, such as sexual drive, problems, and overall satisfaction. Our results suggested that exposure to dioxin disrupts the homeostasis of reproductive and thyroid hormones leading to adverse effects on male sexual function. [ABSTRACT FROM AUTHOR]

Context: Dioxins, specifically 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD), are highly toxic dioxins known for their severe health impacts and persistent environmental pollutants. This study focuses on understanding the formation pathways of TCDD from its precursor molecule 2,4,5-trichlorophenol (2,4,5-TCP). In our exploration of reaction pathways from 2,4,5-trichlorophenol (TCP), we delve into three reaction mechanisms: free-radical, direct condensation, and anionic. Our findings highlight the significance of the radical mechanism, particularly propagated by H radicals, with a notable increase in dioxin formation around 900 K. These results are consistent with experimental observations indicating an increase in the conversion of trichlorophenol from 600 to 900 K in the non-catalytic gas phase reaction. Thermodynamic parameters (∆H, ∆S, and ∆G), reaction barriers, and rate constants (k) were calculated across a temperature range of 300–1200 K to support the findings and provide insights into the optimal temperature range for controlling dioxins during the incineration process. Method: In this study, quantum chemical calculations were conducted using density functional theory (DFT) with the B3LYP functional and the 6–311 + + G(d,p) basis set in Gaussian 16 software. Stationary points, including transition states (TS), were confirmed with frequency calculations. Intrinsic reaction coordinate (IRC) calculations ensured minimum energy paths between TS and products, visualized in GaussView 6.0 Program. Single-point energy calculations utilized a more precise basis set, 6–311 + + G(3df,2p), for enhanced energy accuracy, incorporating zero-point vibrational energy (ZPE) and other energy corrections. These calculations were repeated over a temperature range of 298.15–1200 K at 1 atm pressure. Finally, rate constant (k) expressions associated with TCDD formation were determined using transition state theory (TST). [ABSTRACT FROM AUTHOR]

Dioxins and dioxin-like polychlorinated biphenyls are a group of lipophilic compounds classified under persistent environmental pollutants (POPs). Significant sources of dioxin emissions include industrial effluents, open burning practices, and biomedical and municipal waste incinerators. These emissions will enter the food chain and accumulate in animal-origin foods (AOFs). A systematic review was conducted to analyze the global levels of dioxins and dioxin-like PCBs in AOFs using PRISMA guidelines 2020. The data on the dioxin contamination in AOFs were extracted from 53 publications based on their presence in eggs, meat and meat products, milk and dairy products, marine fish and fish products, and freshwater fish and crabs. A gap analysis was conducted based on the systematic review to understand the grey areas to be focused on the future. No trend of dioxin contamination in AOFs was observed. A significant gap area was found in the need for nationwide data generation in countries without periodic monitoring of AOFs for dioxin contamination. Source apportionment studies need to be explored for the dioxin contamination of AOFs. Large-scale screening tests of AOFs using DR-CALUX based on market surveys are required for data generation. The outcomes of the study will be helpful for stakeholders and policyholders in framing new policies and guidelines for food safety in AOFs. [ABSTRACT FROM AUTHOR]

Abstract Background Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact to the cardiorespiratory systems. The mechanisms underlying tobacco smoke toxicity in skeletal muscle are not fully resolved. In this study, the role of the aryl hydrocarbon receptor (AHR), a transcription factor known to be activated with tobacco smoke, was investigated. Methods AHR related gene (mRNA) expression was quantified in skeletal muscle from adult controls and patients with chronic obstructive pulmonary disease (COPD), as well as mice with and without cigarette smoke exposure. Utilizing both skeletal muscle‐specific AHR knockout mice exposed to chronic repeated (5 days per week for 16 weeks) cigarette smoke and skeletal muscle‐specific expression of a constitutively active mutant AHR in healthy mice, a battery of assessments interrogating muscle size, contractile function, mitochondrial energetics, and RNA sequencing were employed. Results Skeletal muscle from COPD patients (N = 79, age = 67.0 ± 8.4 years) had higher levels of AHR (P = 0.0451) and CYP1B1 (P

Extensive research has been conducted to investigate the toxicological impact of dioxins on mammals, revealing profound effects on the female reproductive system in both humans and animals. Dioxin exposure significantly disrupts the intricate functions of the ovary, a pivotal organ responsible for reproductive and endocrine processes. This disruption manifests as infertility, premature ovarian failure, and disturbances in sex steroid hormone levels. Comprehensive studies, encompassing accidental human exposure and experimental animal data, have raised a wealth of information with consistent yet varied conclusion influenced by experimental factors. This review begins by providing an overarching background on the ovary, emphasizing its fundamental role in reproductive health, particularly in ovarian steroidogenesis and hormone receptor regulation. Subsequently, a detailed examination of the Aryl hydrocarbon Receptor (AhR) and its role in governing ovarian function is presented. The review then outlines the sources and toxicity of dioxins, with a specific focus on AhR involvement in mediating reproductive toxicity in mammals. Within this context, the impact of dioxins, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on Folliculogenesis and Preimplantation embryos is discussed. Furthermore, the review delves into the disruptions of the female hormonal system caused by TCDD and their ramifications in endometriosis. Notably, variations in the effects of TCDD on the female reproductive and hormonal system are highlighted in relation to TCDD dose, animal species, and age. As a forward-looking perspective, questions arise regarding the potential involvement of molecular mechanisms beyond AhR in mediating the female reproductive toxicity of dioxins. [ABSTRACT FROM AUTHOR]

Introduction: Effects of dioxin exposure on gray matter volume have been reported in previous studies, but a few studies reported effects of dioxin exposure on white matter structure. Therefore, this study was undertaken to investigate the impact of dioxin exposure on white matter microstructure in men living in the most severely dioxin-contaminated areas in Vietnam. Methods: In 2019 brain MRI scans from 28 men living near Bien Hoa airbase were obtained at Dong Nai General Hospital, Vietnam, on a 3 T scanner using a conventional diffusion tensor imaging sequence. Two exposure markers were indicated by perinatal exposure estimated by assessment of maternal residency in a dioxin-contaminated area during pregnancy and by measurement of blood dioxin levels. A general linear model was used to compare fractional anisotropy (FA) values in 11 white matter tracts in both hemispheres between groups with and without perinatal dioxin exposure and groups with high and low blood dioxin levels after adjusting for covariates. Results: The adjusted mean FA value in the left cingulum hippocampal part (CGH) was significantly lower in the perinatal dioxin exposure group compared with the group without perinatal dioxin exposure. The high blood TCDD group showed significantly reduced FA values in the left and right CGH and right uncinate fasciculus (UNC). Moreover, the high blood TEQ-PCDDs group showed significantly lower FA values in the left and right CGH and the left UNC. There were no significant differences in FA values between the groups with high and low TEQ-PCDFs levels or between the groups with high and low TEQ-PCDD/Fs levels. Discussion: It was concluded that dioxin exposure during the perinatal period and adulthood may alter the microstructure of white matter tracts in individuals with neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Excess female births (lower sex ratio at birth) associated with paternal exposure to 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) have been reported in Italy. However, no significant effects of maternal TCDD exposure on the sex ratio were reported. We investigated the effects of maternal TCDD exposure and the toxic equivalent quantity of polychlorinated dibenzo-p-dioxins/dibenzofurans (TEQ-PCDD/Fs) on the sex ratio at birth in 576 Vietnamese infants from three birth cohorts. TCDD and TEQ-PCDD/Fs in breast milk were stratified (low, mild, moderate, and high) as maternal exposure markers. Logistic regression analysis was used to investigate associations between female birth and dioxin exposure groups after adjusting for confounders. In sprayed and unsprayed areas, adjusted odds ratios (ORs) of female birth (reference: low-TCDD group) were 2.11 in the moderate-TCDD group and 2.77 in the high-TCDD group, which were significantly associated with increased TCDD exposure. In sprayed areas, a significantly increased OR in the high-TCDD group was observed. No significant associations, however, were found between having a girl and TEQ-PCDD/F levels. These results suggest that maternal TCDD exposure may alter the sex ratio at birth among Vietnamese residents of areas with high dioxin contamination. [ABSTRACT FROM AUTHOR]

Herbicide-/dioxin-contaminated contamination in Vietnam is an environmental issue nowadays, despite Agent Orange being sprayed a long time ago. High levels of dioxin in military airbases cause hot spots of dioxin contamination sites in which potential biological source of microorganisms has developed. Understanding microorganism structure in contaminated soil is crucial for the bioremediation of the sites. Illumina Miseq platform was applied to sequence V3-V4 amplicons of long-term contaminated communities to evaluate the bacterial distribution. Contaminated soil from different regions Bien Hoa and Phu Cat showed a low level of connectedness; the species richness of Bien Hoa was much higher than that of Phu Cat. However, they shared similarities in the most abundant bacterial phyla: Actinobacteriota, Chloroflexi, Proteobacteria, Acidobacteriota, and Planctomycetota. Several xenobiotic-degrading genera were found, such as Terrabacter, Nocardioides, and Streptomyces of Actinobacteriota; Bacillus, Paenibacillus, and Clostridium of Firmicutes; Burkholderia, Sphingomonas, Pseudomonas and Klebsiella of Proteobacteria. Seven bacterial isolates grew on dioxin-containing medium belonging to Firmicutes, they were classified in order Bacillales, in which two strains belong to Paenibacillaceae, and the rests are in Bacillaceae. Two isolates removed more than 80% of total toxicity (mainly 2,3,7,8-Tetrachlorodibenzo-p-dioxin); strain PC5 is the first dioxin-degrading bacterium recognized in the genus Neobacillus. [ABSTRACT FROM AUTHOR]

The open burning of sugarcane residue is commonly used as a low-cost and fast method during pre-harvest and post-harvest periods. However, this practice releases various pollutants, including dioxins. This study aims to predict polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs or dioxins) emissions using the grey model (GM (1,1)) and to map the annual flux spatial distribution at the provincial level from 2023 to 2028. An annual emission inventory at the provincial level was developed using the activity rate of dry crop residue from national agencies and literature, following the guidelines set by the United Nations Environment Programme (UNEP). Emission distributions from 2016 to 2022 were then mapped. The average PCDD/F emission values show significant variation among the provinces, averaging 309 pg TEQ/year. Spatially, regions with intensive sugarcane production, such as Lampung and East Java consistently show high emissions, often exceeding 400 pg/m2. Emissions calculated using the UNEP emission factor tend to be higher compared to other factors, due to its generic nature and lack of regional specificity. Emission predictions using GM (1,1) indicate that North Sumatra is expected to experience a steady increase in PCDD/Fs emissions, whereas South Sumatra and Lampung are projected are projected to see a slight decline. This forecast assumes no changes in regional intervention strategies. Most regions in Java Island show a gradual increase in emissions, except for East Java, which is predicted to have a slight decline from 416 pg/year in 2023 to 397 pg/year in 2028. Additionally, regions such as Gorontalo and parts of East Java are projected to remain ‘hotspots’ with consistently high emissions, highlighting the need for targeted interventions. To address emission hotspots, this study emphasizes the need for cleaner agricultural practices, enhanced enforcement of environmental regulations, and the integration of advanced monitoring technologies to mitigate the environmental and health impacts of PCDD/F emissions in Indonesia. Future studies should consider developing monthly emissions profiles to better account for local agricultural practices and seasonal conditions. The emission data generated in this study, which include both spatial and temporal distributions, are valuable for air quality modeling studies and can help assess the impact of current and future emissions on ambient air quality.

This research investigated the hydrogen production and energy conversion from automobile shredder residues (ASRs) and paper mill sludge (PMS) co-gasified in a full-scale fluidized bed gasification plant. The results obtained from full-scale tests provided important information on the feasible assessment of ASRs-to-energy and the selection of alternative technologies for ASRs. Based on the analysis results of produced gas composition, H 2 , CO, and CH 4 composition produced from paper-mill sludge gasified were 4.17%–6.01%, 3.08%–4.32%, 1.71%–2.4%, respectively. Another C 2 gas composition ranged from 2.9% to 3.59%. The heating value of produced gas ranged between 1.64 MJ/Nm3 and 2.18 MJ/Nm3. In the case of 10% ASR addition, the heating value of produced gas was slightly increased to 1.84 MJ/Nm3-2.34 MJ/Nm3. The dioxin emission concentration of flue gas was approximately 0.064 ng I-TEQ/Nm3. It can comply with Taiwan regulation thresholds. The dioxin leaching concentrations of residues derived from gasification were also in compliance with regulation limits by the TCLP test. Meanwhile, in the case of 10% ASRs addition, the dioxin equivalence concentration of gasified residue was nearly 0.002 ng I-TEQ/Nm3. It was far below the current regulation standard limit. In summary, the results of this research have proved the performance of ASRs-to-energy by co-gasified with paper mill sludge using a full-scale gasification plant. The results obtained from this research also provided the information for selecting ASRs alternative technologies and operating full-scale gasifiers in the future. [Display omitted] • This study has confirmed the feasibility of co-gasification of calcium-rich PMS and chlorine-rich ASRs. • Adding 5%–15% of ASRs can maintain the regular operation of the full-scale commercial gasifier. • The synthesis gas has a composition of 4.91 vol% H 2 and 2.06 vol% CO, with a LHV of 1.93 MJ/Nm3. • The HCl emission could comply with regulation thresholds in co-gasification. • Dioxin reformation reduced significantly in co-gasification of PMS and ASRs. [ABSTRACT FROM AUTHOR]

One gene, the immunoglobulin heavy chain (IgH) gene, is responsible for the expression of all the different antibody isotypes. Transcriptional regulation of the IgH gene is complex and involves several regulatory elements including a large element at the 3' end of the IgH gene locus (3'RR). Animal models have demonstrated an essential role of the 3'RR in the ability of B cells to express high affinity antibodies and to express different antibody classes. Additionally, environmental chemicals such as aryl hydrocarbon receptor (AhR) ligands modulate mouse 3'RR activity that mirrors the effects of these chemicals on antibody production and immunocompetence in mouse models. Although first discovered as a mediator of the toxicity induced by the high affinity ligand 2,3,7,8-tetracholordibenzo-p-dioxin (dioxin), understanding of the AhR has expanded to a physiological role in preserving homeostasis and maintaining immunocompetence. We posit that the AhR also plays a role in human antibody production and that the 3'RR is not only an IgH regulatory node but also an environmental sensor receiving signals through intrinsic and extrinsic pathways, including the AhR. This review will 1) highlight the emerging role of the AhR as a key transducer between environmental signals and altered immune function; 2) examine the current state of knowledge regarding IgH gene regulation and the role of the AhR in modulation of Ig production; 3) describe the evolution of the IgH gene that resulted in species and population differences; and 4) explore the evidence supporting the environmental sensing capacity of the 3'RR and the AhR as a transducer of these cues. This review will also underscore the need for studies focused on human models due to the premise that understanding genetic differences in the human population and the signaling pathways that converge at the 3'RR will provide valuable insight into individual sensitivities to environmental factors and antibody-mediated disease conditions, including emerging infections such as SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) might contribute to the increase in female-specific cancers in Western countries. 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) is considered the "prototypical toxicant" to study EDCs' effects on reproductive health. Epigenetic regulation by small noncoding RNAs (sncRNAs), such as microRNAs (miRNA), is crucial for controlling cancer development. The aim of this study was to analyze transcriptional activity and sncRNA expression changes in the KGN cell line after acute (3 h) and chronic (72 h) exposure to 10 nM TCDD in order to determine whether sncRNAs' deregulation may contribute to transmitting TCDD effects to the subsequent cell generations (day 9 and day 14 after chronic exposure). Using Affymetrix GeneChip miRNA 4.0 arrays, 109 sncRNAs were found to be differentially expressed (fold change < −2 or >2; p-value < 0.05) between cells exposed or not (control) to TCDD for 3 h and 72 h and on day 9 and day 14 after chronic exposure. Ingenuity Pathway Analysis predicted that following the acute and chronic exposure of KGN cells, sncRNAs linked to cellular development, growth and proliferation were downregulated, and those linked to cancer promotion were upregulated on day 9 and day 14. These results indicated that TCDD-induced sncRNA dysregulation may have transgenerational cancer-promoting effects. [ABSTRACT FROM AUTHOR]

Dioxins and dioxin-like compounds (DLCs) are common pollutants hazardous to human health. We applied 12 dioxins and DLCs data of 1851 participants (including 484 arthritis patients) from National Health Examination Survey (NHANES) 2001–2004 and quadrupled them into rank variables. Multivariate logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were used to explore the relationship between individual or mixed exposure to the pollutants and arthritis after adjusting for multiple covariates. In multivariable logistic regression with an individual dioxin or DLC, almost every chemical was significantly positively associated with arthritis, except PCB66 (polychlorinated biphenyl 66) and 1,2,3,4,6,7,8-heptachlorodibenzofuran (hpcdf). The WQS model indicated that the combined exposure to the 12 dioxins and DLCs was positively linked to arthritis (OR: 1.884, 95% CI: 1.514–2.346), with PCB156 (weighted 0.281) making the greatest contribution. A positive trend between combined exposure and arthritis was observed in the BKMR model, with a posterior inclusion probability (PIP) of 0.987 for PCB156, which was also higher than the other contaminants. [ABSTRACT FROM AUTHOR]

Extensive research has been conducted to investigate the toxicological impact of dioxins on mammals, revealing profound effects on the female reproductive system in both humans and animals. Dioxin exposure significantly disrupts the intricate functions of the ovary, a pivotal organ responsible for reproductive and endocrine processes. This disruption manifests as infertility, premature ovarian failure, and disturbances in sex steroid hormone levels. Comprehensive studies, encompassing accidental human exposure and experimental animal data, have raised a wealth of information with consistent yet varied conclusion influenced by experimental factors. This review begins by providing an overarching background on the ovary, emphasizing its fundamental role in reproductive health, particularly in ovarian steroidogenesis and hormone receptor regulation. Subsequently, a detailed examination of the Aryl hydrocarbon Receptor (AhR) and its role in governing ovarian function is presented. The review then outlines the sources and toxicity of dioxins, with a specific focus on AhR involvement in mediating reproductive toxicity in mammals. Within this context, the impact of dioxins, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on Folliculogenesis and Preimplantation embryos is discussed. Furthermore, the review delves into the disruptions of the female hormonal system caused by TCDD and their ramifications in endometriosis. Notably, variations in the effects of TCDD on the female reproductive and hormonal system are highlighted in relation to TCDD dose, animal species, and age. As a forward-looking perspective, questions arise regarding the potential involvement of molecular mechanisms beyond AhR in mediating the female reproductive toxicity of dioxins.

The amount of medical waste generated has increased enormously since the COVID-19 outbreak. An incineration process is the main method that is usually used to treat this waste, causing an increase in both medical waste bottom ash (MWBA) and medical waste fly ash (MWFA). In this work, the physical and chemical characteristics of MWFA and MWBA were reviewed. This ash contains high levels of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofurans (PCDFs), and heavy metals. Furthermore, medical waste ash appears to have high leachability in the toxicity characteristics leaching procedure (TCLP) test and the European standard test (EN 12457). Owing to its toxicity, medical ash can be treated using various methods prior to disposal based on the covered review. These techniques include chemical, supercritical fluid, cement-based, melting, microwave, and mechanochemical techniques. The shortcomings of some of these treatment methods have been identified, such as the emission of high levels of chlorine from the melting technique, limited applications of the flotation method on the industrial scale, long-term stability of leachate treated by cement-based methods that have not been confirmed yet, and high energy consumption in the supercritical technique. This review also covers possible applications of medical waste ash in cement production, agriculture, and road construction. HIGHLIGHTS Medical waste ash contains high concentrations of dioxins.; Heavy metals in medical waste ash have a high leachability in the soil and groundwater.; Further investigations to solve multiple problems in treatment techniques of medical waste ash are required.; Medical waste ashes have been found to be beneficial in concrete production.;

Abstract Background Health outcomes among Agent Orange/dioxin (dioxin) victims are significant due to many individuals requiring daily assistance, informal care, and rehabilitation support. This study aimed to identify the information needs of informal caregivers of dioxin victims in Vietnam. Methods A cross-sectional study was conducted in Quynh Phu district, Thai Binh province – an area with a large number of dioxin victims, from June 2019 to June 2020. Quantitative data were collected from 124 caregivers of victims via structured interviews. Qualitative data were collected using semi-structured interview guides with in-depth interviews (IDI) (n = 36) and two focus group discussions (FGD) (n = 12). Results The results demonstrated that all caregivers of dioxin victims were family members, predominantly older (71.8%), 61.5 years old on average, living on low incomes (87.9%), and were farmers (80.7%). Almost all participants (96.8%) reported having information needs, particularly concerning dioxin’s harms, nutrition, dioxin-related policies and rehabilitation, and psychological support for patients. Caregivers reported that they would like to receive information via health staff counselling (85.0%), television (75.0%), and community loudspeaker (65.8%). Notably, the majority of caregivers reported the need for information regarding psychological support (70.0%). These findings are consistent with qualitative data, which identify an urgent need to provide information, especially through health staff and digital resources. Conclusion Many families with dioxin victims lived with little support and information, highlighting their high demand for information about care and rehabilitation. Thus, the healthcare system should promote information support, policy, and psychological support for caregivers and victims. An online support system for caregivers and victims is also recommended.

The amount of medical waste generated has increased enormously since the COVID-19 outbreak. An incineration process is the main method that is usually used to treat this waste, causing an increase in both medical waste bottom ash (MWBA) and medical waste fly ash (MWFA). In this work, the physical and chemical characteristics of MWFA and MWBA were reviewed. This ash contains high levels of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofurans (PCDFs), and heavy metals. Furthermore, medical waste ash appears to have high leachability in the toxicity characteristics leaching procedure (TCLP) test and the European standard test (EN 12457). Owing to its toxicity, medical ash can be treated using various methods prior to disposal based on the covered review. These techniques include chemical, supercritical fluid, cement-based, melting, microwave, and mechanochemical techniques. The shortcomings of some of these treatment methods have been identified, such as the emission of high levels of chlorine from the melting technique, limited applications of the flotation method on the industrial scale, long-term stability of leachate treated by cement-based methods that have not been confirmed yet, and high energy consumption in the supercritical technique. This review also covers possible applications of medical waste ash in cement production, agriculture, and road construction. [ABSTRACT FROM AUTHOR]

Previously, we showed that 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR) ligand and a potent and persistent toxicant and carcinogenic agent, induces high levels of murine myeloid-derived suppressor cell (MDSC) when injected into mice. In the current study, we demonstrate that Resveratrol (3,4,5-trihydroxy-trans-stilbene; RSV), an AhR antagonist, reduces TCDD-mediated MDSC induction. RSV decreased the number of MDSCs induced by TCDD in mice but also mitigated the immunosuppressive function of TCDD-induced MDSCs. TCDD caused a decrease in F4/80+ macrophages and an increase in CD11C+ dendritic cells, while RSV reversed these effects. TCDD caused upregulation in CXCR2, a critical molecule involved in TCDD-mediated induction of MDSCs, and Arginase-1 (ARG-1), involved in the immunosuppressive functions of MDSCs, while RSV reversed this effect. Transcriptome analysis of Gr1+ MDSCs showed an increased gene expression profile involved in the metabolic pathways in mice exposed to TCDD while RSV-treated mice showed a decrease in such pathways. The bio-energetic profile of these cells showed that RSV treatment decreased the energetic demands induced by TCDD. Overall, the data demonstrated that RSV decreased TCDD-induced MDSC induction and function by altering the dynamics of various myeloid cell populations involving their numbers, phenotype, and immunosuppressive potency. Because MDSCs play a critical role in tumor growth and metastasis, our studies also support the potential use of RSV to attenuate the immunosuppressive properties of MDSC. [ABSTRACT FROM AUTHOR]

Previously, we reported that the global brain volume was significantly higher in men with estimated perinatal dioxin exposure in Vietnam. In this study, we aimed to clarify which brain lobes, consisting of several gyri, contributed to the increased global brain volume. We then analyzed associations between changes in brain volume and social anxiety symptoms to investigate the role of structural changes of the brain on social anxiety following perinatal dioxin exposure. Thirty-three men living near the dioxin-contaminated Bien Hoa airbase, underwent MRI examination. The regional gray matter volumes were extracted using the SPM12 in a MATLAB environment, and compared between subgroups with and without perinatal dioxin exposure estimated from their maternal residency in Bien Hoa during pregnancy. The social anxiety questionnaire for adults (SAQ-A30) was used to assess social anxiety. In both hemispheres, higher gray matter volume in the frontal and temporal lobes, particularly in the superior frontal gyrus, superior temporal gyrus, and temporal pole were found in men with perinatal dioxin exposure. Superior temporal gyrus volume was significantly higher in men with perinatal exposure also after adjusting for reduction of its volume associated with increasing 1,2,3,7,8-PentaCDD levels in blood. Increased volume of these gyri, which showed higher volume in men with perinatal exposure, was associated with increased SAQ-A30 scores. Perinatal dioxin exposure may increase the brain volume of gyri involved in social behavior, which was associated with increased social anxiety symptoms, suggesting functional effects accompanied the morphological effects of dioxin exposure. [ABSTRACT FROM AUTHOR]

Non‐coding microRNAs (miRNAs) have important roles in regulating the expression of liver mRNAs in response to xenobiotic‐exposure, but their roles concerning dioxins such as TCDD (2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin) are less clear. This report concerns the potential implication of liver (class I) and circulating (class II) miRNAs in hepatotoxicity of female and male mice after acute exposure to TCDD. The data show that, of a total of 38 types of miRNAs, the expression of eight miRNAs were upregulated in both female and male mice exposed to TCDD. Inversely, the expression of nine miRNAs were significantly downregulated in both animal genders. Moreover, certain miRNAs were preferentially induced in either females or males. The potential downstream regulatory effects of miRNAs on their target genes was evaluated by determining the expression of three group of genes that are potentially involved in cancer biogenesis, other diseases and in hepatotoxicity. It was found that certain cancer‐related genes were more highly expressed females rather than males after exposure to TCDD. Furthermore, a paradoxical female‐to‐male transcriptional pattern was found for several disease‐related and hepatotoxicity‐related genes. These results suggest the possibility of developing of new miRNA‐specific interfering molecules to address their dysfunctions as caused by TCDD. [ABSTRACT FROM AUTHOR]

This paper exposes the New Zealand (NZ) government's longstanding campaign to silence evidence of health impacts from dioxin-containing emissions during the production of the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in New Plymouth in the 1960s. Our analysis of official documentation and related literature between 1960–2005 reveals a series of investigations engaging various silencing mechanisms that have culminated in a case of historical pollution. By doing so, they have intensified the acute injuries, chronic disease and multigenerational impacts stemming from the emissions, while discounting the lived experiences of suffering. We argue that silencing be seen as an epistemic violence that is intertwined with, but stands in evidence of, actions to ignore and deny harms that could be utilized in securing the long overdue acknowledgement and appropriate assistance for the Paritutu community. [ABSTRACT FROM AUTHOR]

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Study questionIs there an association between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and fecundability and infertility among Seveso women and their daughters?Summary answerTCDD exposure is associated with a decrease in fecundability and increased risk of infertility in women, as well as their daughters.What is known alreadyIn animal studies, maternal exposure to TCDD is associated with decreased fertility in offspring. Effects of TCDD are mediated by activation of the aryl hydrocarbon receptor (AHR) pathway.Study design, size, durationThe Seveso Women's Health Study (SWHS) has followed 981 women exposed to TCDD in a 1976 accident since 1996. In 2014, we initiated the Seveso Second Generation Study to follow-up their children.Participants/materials, setting, methodsWe obtained information on pregnancy history including time of trying to conceive from SWHS women and their daughters who were 18 years or older. We considered TCDD exposure as initial 1976 serum TCDD concentration and estimated TCDD at pregnancy. We examined relationships of TCDD exposure with time to pregnancy (TTP, the monthly probability of conception within the first 12 months of trying) and infertility (≥12 months of trying to conceive). We also assessed contributions of polymorphisms in the AHR pathway via genetic risk score.Main results and the role of chanceAmong SWHS women (n = 446), median TTP was 3 months and 18% reported taking ≥12 months to conceive. Initial 1976 TCDD (log10) was associated with longer TTP (adjusted fecundability odds ratio = 0.82; 95% CI 0.68-0.98) and increased risk of infertility (adjusted relative risk = 1.35; 95% CI 1.01-1.79). TCDD at pregnancy yielded similar associations. Among SWHS daughters (n = 66), median TTP was 2 months and 11% reported taking ≥12 months to conceive. Daughters showed similar, but non-significant, associations with maternal TCDD exposure.Limitations, reasons for cautionA limitation of this study is time to pregnancy was reported retrospectively, although previous studies have found women are able to recall time to conception with a high degree of accuracy many years after the fact. The number of SWHS daughters who had a live birth was small and we were unable to examine fecundability of SWHS sons.Wider implications of the findingsConsistent with previous findings in animal studies, our study found that TCDD exposure may be associated with decreased fertility in Seveso mothers and potentially in their daughters exposed in utero. There may be susceptible genetic subgroups. The literature has largely considered the genetics of the AHR pathway in the context of male fertility but not female fertility, despite strong biological plausibility. These findings should be replicated in larger populations and of different ancestry. Future studies in Seveso should examine the sons and the grandchildren of exposed mothers given the animal literature suggesting potential heritable epigenetic effects.Study funding/competing interest(s)This study was supported by grant numbers F06 TW02075-01 from the National Institutes of Health, R01 ES07171 and 2P30-ESO01896-17 from the National Institute of Environmental Health Sciences, R82471 from the U.S. Environmental Protection Agency and #2896 from Regione Lombardia and Fondazione Lombardia Ambiente, Milan, Italy. J.A. was supported by F31ES026488 from the National Institutes of Health. The authors declare they have no actual or potential competing financial interests.Trial registration numberN/A.

Excess female births (lower sex ratio at birth) associated with paternal exposure to 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) have been reported in Italy. However, no significant effects of maternal TCDD exposure on the sex ratio were reported. We investigated the effects of maternal TCDD exposure and the toxic equivalent quantity of polychlorinated dibenzo-p-dioxins/dibenzofurans (TEQ-PCDD/Fs) on the sex ratio at birth in 576 Vietnamese infants from three birth cohorts. TCDD and TEQ-PCDD/Fs in breast milk were stratified (low, mild, moderate, and high) as maternal exposure markers. Logistic regression analysis was used to investigate associations between female birth and dioxin exposure groups after adjusting for confounders. In sprayed and unsprayed areas, adjusted odds ratios (ORs) of female birth (reference: low-TCDD group) were 2.11 in the moderate-TCDD group and 2.77 in the high-TCDD group, which were significantly associated with increased TCDD exposure. In sprayed areas, a significantly increased OR in the high-TCDD group was observed. No significant associations, however, were found between having a girl and TEQ-PCDD/F levels. These results suggest that maternal TCDD exposure may alter the sex ratio at birth among Vietnamese residents of areas with high dioxin contamination.

Dioxins are highly toxic compounds that pose significant risks to human health and the environment. Burning plastics is a major source of dioxin emissions, contributing to their presence in the environment. This review paper presents a scientometric analysis of publications spanning four decades (1987-2023) aiming to investigate the relationship between plastics and dioxin emissions. Relevant scientific articles were retrieved from the Scopus database, and quantitative analyses were carried out using the VOSviewer tool. Data on literature coupling, keyword co-occurrence, authorship, and countries/regions activities were extracted, mapped, interpreted, and validated. Additionally, a systematic literature review was conducted to provide comprehensive insights into the existing research on smart sensing technologies and strategies employed to mitigate dioxin emissions from plastic waste incineration. The findings showed that the number of articles and publications on dioxin emissions from plastic waste has rapidly increased since 2005, indicating growing research interest. The main keywords used for the analysis included “air pollutants”, “waste management”, “mass spectrometry”, and “toxicity”. The results of this paper contribute to a broader understanding of the complex relationship between plastics and environmental degradation, facilitating informed decision-making and smart technology integration for a more sustainable future.

[Display omitted] • Low-temperature thermal treatment is highly efficient and low energy consumption. • The degradation and ash discharge phases of dioxins are comprehensively considered. • Temperature is the main factor for the degradation and ash discharge stages. • The increase in oxygen content promotes the desorption of dioxins to the gas phase. • Below 200℃, the oxygen content has little effect on the ash discharge stage. Dioxins in municipal solid waste incineration fly ash (MSWIFA) can cause significant risks to the environment and human health. In this study, the low-temperature thermal treatment of MSWIFA under industrial conditions was simulated in the laboratory to investigate the process parameters for dioxin degradation and ash discharge stages. Correlation analysis and dioxin fingerprint characterization were used to analyze the degradation and ash discharge processes. The degradation efficiency of low-temperature thermal treatment was influenced by multiple factors. At 400℃ for 90 min and 1% O 2 , the dioxin removal rate was 95.80%, the detoxification rate was 91.73%, and the residual dioxin toxicity in MSWIFA was 22.7 ± 17.8 ng I-TEQ/kg, which was in line with the limit value of 50 ng I-TEQ/kg in the "Technical specification for pollution control of fly-ash from municipal solid waste incineration" (HJ1134-2020). The increase in dioxins during ash discharge did not follow a linear relationship with the process parameters. This was assumed to be related to the MSWIFA composition, as some components containing P, Si, and Al at 150 °C may inhibit dioxin formation. The dioxin increased only by 0.79 ± 2.65 ng/kg, an increase in toxicity of 0.42 ± 0.10 ng I-TEQ/kg, when treated at 150 °C for 30 min and 10% O 2. [ABSTRACT FROM AUTHOR]

Background: Health outcomes among Agent Orange/dioxin (dioxin) victims are significant due to many individuals requiring daily assistance, informal care, and rehabilitation support. This study aimed to identify the information needs of informal caregivers of dioxin victims in Vietnam. Methods: A cross-sectional study was conducted in Quynh Phu district, Thai Binh province – an area with a large number of dioxin victims, from June 2019 to June 2020. Quantitative data were collected from 124 caregivers of victims via structured interviews. Qualitative data were collected using semi-structured interview guides with in-depth interviews (IDI) (n = 36) and two focus group discussions (FGD) (n = 12). Results: The results demonstrated that all caregivers of dioxin victims were family members, predominantly older (71.8%), 61.5 years old on average, living on low incomes (87.9%), and were farmers (80.7%). Almost all participants (96.8%) reported having information needs, particularly concerning dioxin's harms, nutrition, dioxin-related policies and rehabilitation, and psychological support for patients. Caregivers reported that they would like to receive information via health staff counselling (85.0%), television (75.0%), and community loudspeaker (65.8%). Notably, the majority of caregivers reported the need for information regarding psychological support (70.0%). These findings are consistent with qualitative data, which identify an urgent need to provide information, especially through health staff and digital resources. Conclusion: Many families with dioxin victims lived with little support and information, highlighting their high demand for information about care and rehabilitation. Thus, the healthcare system should promote information support, policy, and psychological support for caregivers and victims. An online support system for caregivers and victims is also recommended. [ABSTRACT FROM AUTHOR]

Epidemiological studies report associations between early-life exposure to persistent organic pollutants (POPs) and impaired metabolic homeostasis in adulthood. We investigated the impact of early-life exposure to low-dose 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD or 'dioxin') on the establishment of β-cell area during the perinatal period, as well as β-cell health and glucose homeostasis later in life. Adult female mice were injected with either corn oil (CO; vehicle control) or TCDD (20 ng/kg/day) 2×/week throughout mating, pregnancy, and lactation; offspring were thus indirectly exposed to maternal TCDD in utero and during lactation, with pollutant exposure ending at weaning. All offspring were maintained on chow diet from weaning until 12–17 weeks of age, after which a subset of CO- and TCDD-exposed offspring were transferred to a 45% high fat diet (HFD) as a metabolic stressor for an additional 10 weeks. TCDD significantly upregulated cytochrome P450 1a1 (Cyp1a1) gene expression in offspring pancreas at birth and weaning, indicating that maternal TCDD directly reaches the developing pancreas. TCDD-exposed pups were transiently hypoglycemic at birth and females were born with reduced % β-cell area, which persisted into adulthood. Early-life TCDD exposure had no persistent long-term effects on glucose homeostasis in chow-fed offspring, but when transferred to HFD, TCDD-exposed female offspring had a delayed onset of HFD-induced hyperglycemia, more pronounced HFD-induced hyperinsulinemia, and increase % PCNA+ β-cells compared with CO-exposed female offspring. This study demonstrates that early-life exposure of mice to TCDD has modest effects on metabolic health in chow-fed offspring but alters metabolic adaptability to HFD feeding in females. [ABSTRACT FROM AUTHOR]

Aryl hydrocarbon receptor (AhR) is a basic helix-loop-helix transcription factor activated by polycyclic aromatic hydrocarbons of synthetic and natural origin. While a number of novel AhR ligands have been recently identified, little is known about their possible influence on AhR levels and stability. We used western blot, qRT-PCR and immunocytochemistry to determine the effects of AhR ligands on AhR expression in N-TERT (N-TERT1) immortalized human keratinocytes, and immunohistochemistry to assess patterns of AhR expression in human and mouse skin and skin appendages. While AhR was highly expressed in cultured keratinocytes and in the skin, it was found primarily in the cytoplasm, but not in the nucleus, suggesting its inactivity. At the same time, treatment of N-TERT cells with proteasomal inhibitor MG132 and eventual inhibition of AhR degradation resulted in nuclear AhR accumulation. Treatment of keratinocytes with AhR ligands such as TCDD, FICZ, caused near-complete disappearance of AhR, and treatment with I3C resulted in substantially diminished level of AhR possibly due to ligand-induced AhR degradation. The AhR decay was blocked by proteasome inhibition, indicating degradation-based mechanism of regulation. Additionally, AhR decay was blocked by ligand-selective AhR antagonist CH223191, implying substrate-induced mechanism of degradation. Furthermore, degradation of AhR was blocked in N-TERT cells with knockdown of AhR dimerization partner ARNT (HIF1β), suggesting that ARNT is required for AhR proteolysis. However, addition of hypoxia mimetics (HIF1 pathway activators) CoCl 2 and DMOG had only minor effects on degradation of AhR. Additionally, inhibition of HDACs with Trichostatin A resulted in enhanced expression of AhR in both untreated and ligand-treated cells. These results demonstrate that in immortalized epidermal keratinocytes AhR is primarily regulated post-translationally via proteasome-mediated degradation, and suggest potential means to manipulate AhR levels and signaling in the skin. Overall, the AhR is regulated via multiple mechanisms, including proteasomal ligand- and ARNT-dependent degradation, and transcriptional regulation by HDACs, implying complex system of balancing its expression and protein stability. • AhR is widely expressed in skin compartments, but found mostly in cytoplasm. • AhR is primarily regulated post-translationally by proteasome-mediated degradation. • AhR degradation is specifically driven by its ligands. • Ligand-induced AhR degradation is nearly abolished by ARNT knockdown. [ABSTRACT FROM AUTHOR]

BackgroundDioxins are persistent organic pollutants generated from industrial combustion processes such as waste incineration. To date, results from epidemiologic studies of dioxin exposure and breast cancer risk have been mixed.ObjectivesTo prospectively examine the association between ambient dioxin exposure using a nationwide spatial database of industrial dioxin-emitting facilities and invasive breast cancer risk in the Nurses' Health Study II (NHSII).MethodsNHSII includes female registered nurses in the US who have completed self-administered biennial questionnaires since 1989. Incident invasive breast cancer diagnoses were self-reported and confirmed by medical record review. Dioxin exposure was estimated based on residential proximity, duration of residence, and emissions from facilities located within 3, 5, and 10 km around geocoded residential addresses updated throughout follow-up. Cox regression models adjusted for breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsFrom 1989 to 2013, 3840 invasive breast cancer cases occurred among 112,397 participants. There was no association between residential proximity to any dioxin facilities (all facilities combined) and breast cancer risk overall. However, women who resided within 10 km of any municipal solid waste incinerator (MSWI) compared to none had increased breast cancer risk (adjusted HR = 1.15, 95% CI: 1.03, 1.28), with stronger associations noted for women who lived within 5 km (adjusted HR = 1.25, 95% CI: 1.04, 1.52). Positive associations were also observed for longer duration of residence and higher dioxin emissions from MSWIs within 3, 5, and 10 km. There were no clear differences in patterns of association for ER + vs. ER-breast cancer or by menopausal status.DiscussionResults from this study support positive associations between dioxin exposure from MSWIs and invasive breast cancer risk.

In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with delayed pubertal development in animal studies. No epidemiologic study has investigated this association. We examined the relationship of in utero exposure to TCDD with reported age at onset of menarche in female children born to a unique cohort of TCDD-exposed women resulting from an explosion in Seveso, Italy, on 10 July 1976.MethodsIn 2014, nearly 40 years after the explosion, we enrolled postexplosion offspring, 2 to 39 years of age, in the Seveso Second Generation Study. Age at onset of menarche (years) was collected for 316 daughters by maternal report or self-report at interview. In utero TCDD exposure was defined by maternal TCDD serum concentrations extrapolated to the pregnancy.ResultsAt interview, 287 daughters were postmenarche and reported age at menarche averaged 12.1 years (±1.3 years). Overall, we found no change in risk of menarche onset with a 10-fold increase in in utero TCDD exposure (hazard ratio [HR] = 0.86; 95% confidence interval [CI] = 0.71, 1.04). When we considered maternal menarche status in 1976 as a potentially sensitive developmental exposure window, in utero TCDD (log10) was associated with later age at menarche among daughters whose mothers were premenarche (HR = 0.71; 95% CI = 0.52, 0.97) but not postmenarche (HR = 0.89; 95% CI = 0.71, 1.12) at the time of the explosion (P int = 0.24).ConclusionsThese results suggest that in utero TCDD exposure may alter pubertal timing among daughters of women who were prepubescent at the time of the Seveso accident.

BackgroundExposure to endocrine disrupting compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during susceptible developmental windows may alter risk of metabolic disease later in life. Animal studies of in utero and lactational TCDD exposure report associations with alterations in insulin sensitivity and energy homeostasis, but epidemiologic evidence is limited. We examined the relationship of prenatal TCDD exposure with markers of glucose homeostasis in the Seveso Second Generation study, a unique cohort of children born to TCDD-exposed women resulting from a 1976 explosion in Seveso, Italy.MethodsWe included 426 children who were 18 years or older with complete follow-up data including a fasting blood draw. Insulin and glucose were measured and the updated homoeostatic model assessment was used to estimate insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B). Prenatal TCDD exposure was defined in two ways, as initial maternal serum TCDD concentration and TCDD estimated at pregnancy.ResultsThe children (222 female, 204 male) averaged 28.6 (±6.0) years. We found a 10-fold increase in TCDD estimated at pregnancy was inversely associated with insulin (adj-β = -1.24 μIU/mL, 95% confidence interval (CI): -2.38, -0.09) and HOMA2-B (adj-β = -10.2% decrease, 95% CI: -17.8, -1.9) among daughters, but not sons (insulin: adj-β = 0.57 μIU/mL, 95% CI: -0.84, 1.98, P for interaction = 0.04; and HOMA2-B: adj-β = 0.8% increase, 95% CI -10.7, 13.9, P for interaction = 0.11). Similar effect modification was observed for TCDD estimated at pregnancy and HOMA2-IR (P for interaction = 0.13). The models for initial maternal serum TCDD showed similar effect modification by child sex. The observed associations in daughters showed evidence of mediation by body mass index, which we have previously found to be associated with prenatal TCDD exposure in female offspring.ConclusionThese results suggest prenatal exposure to TCDD is associated with lower insulin resistance and beta compensation in female offspring, and show evidence of mediation by body mass index.

New bronchopulmonary dysplasia (BPD) is a neonatal disease that is theorized to begin in utero and manifests as reduced alveolarization due to inflammation of the lung. Risk factors for new BPD in human infants include intrauterine growth restriction (IUGR), premature birth (PTB) and formula feeding. Using a mouse model, our group recently reported that a paternal history of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure increased his offspring's risk of IUGR, PTB, and new BPD. Additionally, formula supplementation of these neonates worsened the severity of pulmonary disease. In a separate study, we reported that a paternal preconception fish oil diet prevented TCDD-driven IUGR and PTB. Not surprisingly, eliminating these two major risk factors for new BPD also significantly reduced development of neonatal lung disease. However, this prior study did not examine the potential mechanism for fish oil's protective effect. Herein, we sought to determine whether a paternal preconception fish oil diet attenuated toxicant-associated lung inflammation, which is an important contributor to the pathogenesis of new BPD. Compared to offspring of standard diet TCDD-exposed males, offspring of TCDD-exposed males provided a fish oil diet prior to conception exhibited a significant reduction in pulmonary expression of multiple pro-inflammatory mediators (Tlr4, Cxcr2, Il-1 alpha). Additionally, neonatal lungs of pups born to fish oil treated fathers exhibited minimal hemorrhaging or edema. Currently, prevention of BPD is largely focused on maternal strategies to improve health (e.g., smoking cessation) or reduce risk of PTB (e.g., progesterone supplementation). Our studies in mice support a role for also targeting paternal factors to improve pregnancy outcomes and child health. [ABSTRACT FROM AUTHOR]

Most skin manifestations of exposure to toxic compounds are a consequence of a direct contact with the toxicants. However, some toxicants may reach the skin following systemic exposure, and promote skin diseases. Good examples of such chemicals are dioxin-like compounds. This family of lipophilic molecules comprises polychlorinated (dibenzodioxins, dibenzofurans and biphenyls). The most potent member of this family is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Following oral ingestion of as little as a few mg TCDD, skin lesions appear in a couple of weeks, starting from the face and diffuse then on the trunk and limbs. This syndrome was historically called “chloracne” and the skin lesions have now been shown to be skin hamartoma induced by TCDD. Sebaceous glands release their lipid content on the surface of the skin by a holocrine secretion, and so any lost sebocyte should be transmitted to progenitor cells to differentiate and migrate to the sebaceous gland to replace the lost sebocyte. TCDD acts by inducing a switch in this signal and skin hamartoma develop in place of new sebocytes.

Endocrine-disrupting chemicals (EDCs) might contribute to the increase in female-specific cancers in Western countries. 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) is considered the “prototypical toxicant” to study EDCs’ effects on reproductive health. Epigenetic regulation by small noncoding RNAs (sncRNAs), such as microRNAs (miRNA), is crucial for controlling cancer development. The aim of this study was to analyze transcriptional activity and sncRNA expression changes in the KGN cell line after acute (3 h) and chronic (72 h) exposure to 10 nM TCDD in order to determine whether sncRNAs’ deregulation may contribute to transmitting TCDD effects to the subsequent cell generations (day 9 and day 14 after chronic exposure). Using Affymetrix GeneChip miRNA 4.0 arrays, 109 sncRNAs were found to be differentially expressed (fold change < −2 or >2; p-value < 0.05) between cells exposed or not (control) to TCDD for 3 h and 72 h and on day 9 and day 14 after chronic exposure. Ingenuity Pathway Analysis predicted that following the acute and chronic exposure of KGN cells, sncRNAs linked to cellular development, growth and proliferation were downregulated, and those linked to cancer promotion were upregulated on day 9 and day 14. These results indicated that TCDD-induced sncRNA dysregulation may have transgenerational cancer-promoting effects.

BackgroundExposure to endocrine-disrupting chemicals (EDCs) during sensitive developmental windows, such as in utero, may influence disease later in life but direct measurement of fetal hormones is not feasible. The ratio of the length of the second finger digit to the fourth digit (2D:4D), a sexually dimorphic trait, is a biomarker of androgen levels and the androgen/estrogen balance in utero. However, it is unclear whether in utero EDC exposure might alter 2D:4D ratio.AimsWe examined 2D:4D ratio in Seveso children in relation to in utero exposure to a potent EDC, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) using linear regression.Study designThe Seveso Women's Health Study (SWHS) is a historical cohort study, following the health of women exposed to TCDD during a 1976 explosion in Seveso, Italy. Individual-level TCDD was measured for SWHS in serum collected soon after the accident. In 2014, the SWHS children born after the explosion were enrolled in the Seveso Second Generation Study.Subjects594 SWHS children born post-explosion to 397 mothers.Outcome measuresRight hand 2D:4D ratio.ResultsOn average, 2D:4D ratio for males was significantly lower than for females (p