Effects of dioxin exposure on reproductive and thyroid hormone levels and male sexual function in airbase military workers in Vietnam.

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.

Characterization of medaka (Oryzias latipes) AHRs and the comparison of two model fishes-Medaka vs. zebrafish: The subform-specific sensitivity to dioxin.

Dioxins and the emerging dioxin-like compounds (DLCs) have recruited increasing concerns about their environmental contamination, toxicity, health impacts, and mechanisms. Based on the structural similarity of dioxins and many DLCs, their toxicity was predominantly mediated by the dioxin receptor (aryl hydrocarbon receptor, AHR) in animals (including human), which can be different in expression and function among species and then possibly produce the species-specific risk or toxicity. To date, characterizing the AHR of additional species other than human and rodents can increase the accuracy of toxicity/risk evaluation and increase knowledge about AHR biology. As a key model, the medaka AHR has not been clearly characterized. Through genome survey and phylogenetic analysis, we identified four AHRs (olaAHR1a, olaAHR1b, olaAHR2a, and olaAHR2b) and two ARNTs (olaARNT1 and olaARNT2). The medaka AHR pathway was conserved in expression in nine tested tissues, of which olaAHR2a represented the predominant subform with greater abundance. Medaka AHRs and ARNTs were functional and could be efficiently transactivated by the classical dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), although olaAHR1a did not seem to cooperate with olaARNT2. In terms of function/sensitivity, the EC50 values of medaka olaAHR1a (9.01 ± 1.43 nM), olaAHR1b (4.00 ± 1.10 nM), olaAHR2a (8.75 ± 3.34 nM), and olaAHR2b (3.06 ± 0.81 nM) showed slight differences; however, they were all at the nM level. The sensitivity of four medaka AHRs to TCDD was similar to that of zebrafish dreAHR2 (the dominant form, EC50 = 3.14 ± 4.19 nM), but these medaka AHRs were more sensitive than zebrafish dreAHR1b (EC50 = 27.05 ± 18.51 nM). The additional comparison also indicated that the EC50 values in various species were usually within the nM range, but AHRs of certain subforms/species can vary by one or two orders of magnitude. In summary, the present study will enhance the understanding of AHR and help improve research on the ecotoxicity of dioxins/DLCs.

Quantum chemical pathways for the formation of 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) from 2,4,5-trichlorophenol: a mechanistic and thermo-kinetic study.

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).

Crosstalk of MAP3K1 and EGFR signaling mediates gene-environment interactions that block developmental tissue closure.

Aberrant regulation of signal transduction pathways can adversely derail biological processes for tissue development. One such process is the embryonic eyelid closure that is dependent on the mitogen-activated protein kinase kinase kinase 1 (MAP3K1). Map3k1 KO in mice results in defective eyelid closure and an autosomal recessive eye-open at birth phenotype. We have shown that in utero exposure to dioxin, a persistent environmental toxicant, induces the same eye defect in Map3k1+/- heterozygous but not WT pups. Here, we explore the mechanisms of the Map3k1 (gene) and dioxin (environment) interactions (GxE) underlying defective eyelid closure. We show that, acting through the aryl hydrocarbon receptor, dioxin activates epidermal growth factor receptor signaling, which in turn depresses MAP3K1-dependent Jun N-terminal kinase (JNK) activity. The dioxin-mediated JNK repression is moderate but is exacerbated by Map3k1 heterozygosity. Therefore, dioxin exposed Map3k1+/- embryonic eyelids have a marked reduction of JNK activity, accelerated differentiation and impeded polarization in the epithelial cells. Knocking out Ahr or Egfr in eyelid epithelium attenuates the open-eye defects in dioxin-treated Map3k1+/- pups, whereas knockout of Jnk1 and S1pr that encodes the sphigosin-1-phosphate (S1P) receptors upstream of the MAP3K1-JNK pathway potentiates the dioxin toxicity. Our novel findings show that the crosstalk of aryl hydrocarbon receptor, epidermal growth factor receptor, and S1P-MAP3K1-JNK pathways determines the outcome of dioxin exposure. Thus, gene mutations targeting these pathways are potential risk factors for the toxicity of environmental chemicals.

Human biomonitoring of PCDDs, PCDFs, and PCBs in women living in a Northern Italy industrial area.

In Brescia , a highly industrialized city in the Lombardy Region (Northern Italy) classified as a SIN (Contaminated Site of National Interest), a human biomonitoring study was carried out on breast milk of two groups of women residing in areas with presumably different levels of exposure to polychlorodibenzo-p-dioxins, polychlorodibenzofurans, and polychlorobiphenyls. This study was aimed at evaluating the possible difference between women living in Brescia and women living far from it but in the same Region. Between 2016 and 2018, 82 women were enrolled (41 "exposed" subjects and 41 "not exposed"), breast milk samples were collected, and a specific questionnaire was administered to the donors. Data obtained were processed by robust regression and Principal Component Factor Analysis. The differences in concentration between the two groups were significant for all the classes of analytes (except for PCDDs). The concentration increase rates from the not exposed to the exposed group resulted highly significant: some PCB congeners showed increase rates more than 1000 ng/g lb per one-unit change of the independent variable. Among the variables significantly associated with the observed concentrations, age showed the greatest influence, while BMI showed a counteracting effect. Consumption of vegetable oil and fruit resulted to possibly influence the chemicals body burden. For the not exposed group, the levels appear to be in line with the decreasing trend (2001-2018) observed for these contaminants in Italy.

Impact of dioxins on reproductive health in female mammals.

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.

Breast milk-mediated exposure to dioxins and antigen in infancy enhances antigen-specific antibody production capacity in adulthood in mice.

The immune system is sensitive to many chemicals. Among dioxin compounds, 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) is the most toxic environmental pollutant. The effects of perinatal maternal exposure to dioxins may persist into childhood. However, there have been no reports to date on the effects of exposure to dioxins during infancy, when the immune organs are developing. Therefore, we investigated the effects of TCDD and antigen exposure during lactation on immune function, especially antibody production capacity, in adult mice. Beginning the day after delivery, lactating mothers were orally administered TCDD or a mixture of TCDD and ovalbumin (OVA) daily for 4 weeks, until the pups were weaned. At 6 weeks of age, progeny mice were orally administered OVA daily for 10 weeks, while non-progeny mice were orally administered OVA or a mixture of TCDD and OVA daily for 10 weeks. Production of serum OVA-specific IgG was examined weekly. The amount of TCDD transferred from the mother to the progeny via breast milk was determined by measuring TCDD in the gastric contents of the progeny. A trend toward increasing IgA titer was observed in TCDD-treated mice, and production of IgE was observed only in progeny whose mothers were treated with TCDD and OVA. The results suggest that exposure to TCDD and OVA in breast milk can affect immune function in newborns.

Global trends of dioxin and dioxin-like PCBs in animal-origin foods: a systematic review and gap areas.

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.

Toxicity assessment of dioxins and their transformation by-products from inferred degradation pathways.

Due to the significant POPs characteristics, dioxins caused concern in public health and environmental protection. Evaluating the toxicity risk of dioxin degradation pathways is critical. OCDD, 1,2,3,4,6,7,8-HpCDD, and 1,2,3,4,6,7,8-HpCDF, which are highly abundant in the environment and have strong biodegradation capabilities, were selected as precursor molecules in this study. Firstly, their transformation pathways were deduced during the metabolism of biometabolism, microbial aerobic, microbial anaerobic, and photodegradation pathways, and density function theory (DFT) was used to calculate the Gibbs free energy to infer the possibility of the occurrence of the transformation pathway. Secondly, the carcinogenic potential of the precursors and their degradation products was evaluated using the TOPKAT modeling method. With the help of the positive indicator (0-1) normalization method and heat map analysis, a significant increase in the toxic effect of some of the transformation products was found, and it was inferred that it was related to the structure of the transformation products. Meanwhile, the strength of the endocrine disrupting effect of dioxin transformation products was quantitatively assessed using molecular docking and subjective assignment methods, and it was found that dioxin transformation products with a higher content of chlorine atoms and molecules similar to those of thyroid hormones exhibited a higher risk of endocrine disruption. Finally, the environmental health risks caused by each degradation pathway were comprehensively assessed with the help of the negative indicator (1-2) standardization method, which provides a theoretical basis for avoiding the toxicity risks caused by dioxin degradation transformation. In addition, the 3D-QSAR model was used to verify the necessity and rationality of this study. This paper provides theoretical support and reference significance for the toxicity assessment of dioxin degradation by-products from inferred degradation pathways.

Impacts of dioxin exposure on brain connectivity estimated by DTI analysis of MRI images in men residing in contaminated areas of Vietnam.

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.

Altered Sex Ratio at Birth with Maternal Exposure to Dioxins in Vietnamese Infants.

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.

A Comprehensive Evaluation of Dioxins and Furans Occurrence in River Sediments from a Secondary Steel Recycling Craft Village in Northern Vietnam.

This first study investigated the presence of dioxins and furans in river sediments around a craft village in Vietnam, focusing on Secondary Steel Recycling. Sediment samples were collected from various locations along the riverbed near the Da Hoi Secondary Steel Recycling village in Bac Ninh province. The analysis was conducted using a HRGC/HRMS-DFS device, detecting a total of 17 dioxin/furan isomers in all samples, with an average total concentration of 288.86 ng/kg d.w. The concentrations of dioxin/furan congeners showed minimal variation among sediment samples, ranging from 253.9 to 344.2 ng/kg d.w. The predominant compounds in the dioxin group were OCDD, while in the furan group, they were 1,2,3,4,6,7,8-HpCDF and OCDF. The chlorine content in the molecule appeared to be closely related to the concentration of dioxins and their percentage distribution. However, the levels of furan isomers did not vary significantly. The distribution of these compounds was not dependent on the flow direction, as they were mainly found in solid waste and are not water-soluble. Although the hepta and octa congeners had high concentrations, when converted to TEQ values, the tetra and penta groups (for dioxins) and the penta and hexa groups (for furans) contributed more to toxicity. Furthermore, the source of dioxins in sediments at Da Hoi does not only originate from steel recycling production activities but also from other combustion sites. The average total toxicity was 10.92 ng TEQ/kg d.w, ranging from 4.99 to 17.88 ng TEQ/kg d.w, which did not exceed the threshold specified in QCVN 43:2017/BTNMT, the National Technical Regulation on Sediment Quality. Nonetheless, these levels are still concerning. The presence of these toxic substances not only impacts aquatic organisms in the sampled water environment but also poses potential health risks to residents living nearby.

Germany's first Total Diet Study - Occurrence of non-dioxin-like polychlorinated biphenyls and polybrominated diphenyl ethers in foods.

The occurrence of persistent organic pollutants like polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in food represents a public health concern. The BfR MEAL Study was initiated to generate a comprehensive data base of occurrence data for chemicals in the most consumed foods in Germany. Non-dioxin-like PCBs (NDL-PCBs) and PBDEs were analysed in 300 foods, purchased and prepared representatively for the eating behaviour of the population in Germany. Highest levels of NDL-PCBs and PBDEs were detected in spiny dogfish, cod liver, herring, and eel. High NDL-PCB and PBDE levels were observed in other oily fish, wild boar meat, sheep liver, and high-fat dairy products. The comparison of food from conventional and organic production revealed higher NDL-PCB values in the food group 'meat and meat products' if produced organically. Occurrence data of this study will improve future dietary exposure and risk assessments in Germany.

Transcriptional and phenotypical alterations associated with a gradual benzo[a]pyrene-induced transition of human bronchial epithelial cells into mesenchymal-like cells.

The role of benzo[a]pyrene (BaP), a prominent genotoxic carcinogen and aryl hydrocarbon receptor (AhR) ligand, in tumor progression remains poorly characterized. We investigated the impact of BaP on the process of epithelial-mesenchymal transition (EMT) in normal human bronchial epithelial HBEC-12KT cells. Early morphological changes after 2-week exposure were accompanied with induction of SERPINB2, IL1, CDKN1A/p21 (linked with cell cycle delay) and chemokine CXCL5. After 8-week exposure, induction of cell migration and EMT-related pattern of markers/regulators led to induction of further pro-inflammatory cytokines or non-canonical Wnt pathway ligand WNT5A. This trend of up-regulation of pro-inflammatory genes and non-canonical Wnt pathway constituents was observed also in the BaP-transformed HBEC-12KT-B1 cells. In general, transcriptional effects of BaP differed from those of TGFß1, a prototypical EMT inducer, or a model non-genotoxic AhR ligand, TCDD. Carcinogenic polycyclic aromatic hydrocarbons could thus induce a unique set of molecular changes linked with EMT and cancer progression.

Gene Target Prediction of Environmental Chemicals Using Coupled Matrix-Matrix Completion.

Human exposure to toxic chemicals presents a huge health burden. Key to understanding chemical toxicity is knowledge of the molecular target(s) of the chemicals. Because a comprehensive safety assessment for all chemicals is infeasible due to limited resources, a robust computational method for discovering targets of environmental exposures is a promising direction for public health research. In this study, we implemented a novel matrix completion algorithm named coupled matrix-matrix completion (CMMC) for predicting direct and indirect exposome-target interactions, which exploits the vast amount of accumulated data regarding chemical exposures and their molecular targets. Our approach achieved an AUC of 0.89 on a benchmark data set generated using data from the Comparative Toxicogenomics Database. Our case studies with bisphenol A and its analogues, PFAS, dioxins, PCBs, and VOCs show that CMMC can be used to accurately predict molecular targets of novel chemicals without any prior bioactivity knowledge. Our results demonstrate the feasibility and promise of computationally predicting environmental chemical-target interactions to efficiently prioritize chemicals in hazard identification and risk assessment.

Proteomic insight towards key modulating proteins regulated by the aryl hydrocarbon receptor involved in ovarian carcinogenesis and chemoresistance.

Gynecological malignancies pose a severe threat to female lives. Ovarian cancer (OC), the most lethal gynecological malignancy, is clinically presented with chemoresistance and a higher relapse rate. Several studies have highly correlated the incidence of OC to exposure to environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a process mainly mediated through activating the aryl hydrocarbon receptor (AhR). We have previously reported that exposure of OC cells to TCDD, an AhR activator, significantly modulated the expression of several genes that play roles in stemness and chemoresistance. However, the effect of AhR activation on the whole OC cell proteome aiming at identifying novel druggable targets for both prevention and treatment intervention purposes remains unrevealed. For this purpose, we conducted a comparative proteomic analysis of OC cells A2780 untreated/treated with TCDD for 24 h using a mass spectrometry-based label-free shotgun proteomics approach. The most significantly dysregulated proteins were validated by Western blot analysis. Our results showed that upon AhR activation by TCDD, out of 2598 proteins identified, 795 proteins were upregulated, and 611 were downregulated. STRING interaction analysis and KEGG-Reactome pathway analysis approaches identified several significantly dysregulated proteins that were categorized to be involved in chemoresistance, cancer progression, invasion and metastasis, apoptosis, survival, and prognosis in OC. Importantly, selected dysregulated genes identified by the proteomic study were validated at the protein expression levels by Western blot analysis. In conclusion, this study provides a better understanding of the the cross-talk between AhR and several other molecular signaling pathways and the role and involvement of AhR in ovarian carcinogenesis and chemoresistance. Moreover, the study suggests that AhR is a potential therapeutic target for OC prevention and maintenance. SIGNIFICANCE: To our knowledge, this is the first study that investigates the role and involvement of AhR and its regulated genes in OC by performing a comparative proteomic analysis to identify the critical proteins with a modulated expression upon AhR activation. We found AhR activation to play a tumor-promoting and chemoresistance-inducing role in the pathogenesis of OC. The results of our study help to devise novel therapeutics for better management and prevention and open the doors to finding novel biomarkers for the early detection and prognosis of OC.

Environmentally relevant concentrations of 2,3,7,8-TCDD induced inhibition of multicellular alternative splicing and transcriptional dysregulation.

Alternative splicing (AS), found in approximately 95 % of human genes, significantly amplifies protein diversity and is implicated in disease pathogenesis when dysregulated. However, the precise involvement of AS in the toxic mechanisms induced by TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) remains incompletely elucidated. This study conducted a thorough global AS analysis in six human cell lines following TCDD exposure. Our findings revealed that environmentally relevant concentration (0.1 nM) of TCDD significantly suppressed AS events in all cell types, notably inhibiting diverse splicing events and reducing transcript diversity, potentially attributed to modifications in the splicing patterns of the inhibitory factor family, particularly hnRNP. And we identified 151 genes with substantial AS alterations shared among these cell types, particularly enriched in immune and metabolic pathways. Moreover, TCDD induced cell-specific changes in splicing patterns and transcript levels, with increased sensitivity notably in THP-1 monocyte, potentially linked to aberrant expression of pivotal genes within the spliceosome pathway (DDX5, EFTUD2, PUF60, RBM25, SRSF1, and CRNKL1). This study extends our understanding of disrupted alternative splicing and its relation to the multisystem toxicity of TCDD. It sheds light on how environmental toxins affect post-transcriptional regulatory processes, offering a fresh perspective for toxicology and disease etiology investigations.

Photodegradation of 2-chlorodibenzo-p-dioxin (2-CDD) on the surface of municipal solid waste incineration fly ash: Kinetics and product analysis.

Considering that waste incineration fly ash is the main carrier of dioxins and can migrate over long distances in the atmosphere, it is of great significance to study the photochemical transformation behavior of dioxins on the surface of fly ash. In this work, 2-chlorodibenzo-p-dioxin (2-CDD) was selected to conduct a systematic photochemical study. The influence of various factors on the photodegradation of 2-CDD were first explored, and the results showed that small particle size of fly ash, low concentration of 2-CDD and appropriate level of humidity were more conducive to photodegradation, with the highest degradation percentage reaching 76%-84%. The components of fly ash (Zn (Ⅱ), Al (Ⅲ), Cu (Ⅱ) and SiO2) also had a certain promoting effect on the degradation of 2-CDD, which increases the degradation efficiency by 10%-20%, because they could act as effective photocatalysts to produce free radicals for reaction. With a higher total light exposure intensity, natural light environments led to a more complete degradation of 2-CDD than laboratory Xe lamp irradiation (90% degradation Vs. 79% degradation). Based on chemical probe and radical quenching experiment, hydroxyl radical also contributed to 2-CDD photodegradation on fly ash. A total of 16 intermediate products were detected by mass spectrometry analysis, and four initial reaction pathways of 2-CDD were speculated in the process, including dechlorination, ether bond cleavage, hydroxyl substitution, and hydroxyl addition. According to the results of density functional theory calculation, the reaction channels of ether bond cleavage and •OH attack were determined. The toxicity assessment software tool (TEST) was used to assess the toxicity and bioconcentration coefficient of reaction products, and it was found that the overall toxicity of the photodegradation products was reduced. This study would provide new insights into the environmental fate of dioxins during long-range atmospheric migration process.

Results of an international interlaboratory study on dioxin-like activities in drinking-, river surface- and wastewater using DR CALUX bioassay.

Aquatic animals and consumers of aquatic animals are exposed to increasingly complex mixtures of known and as-yet-unknown chemicals with dioxin-like toxicities in the water cycle. Effect- and cell-based bioanalysis can cover known and yet unknown dioxin and dioxin-like compounds as well as complex mixtures thereof but need to be standardized and integrated into international guidelines for environmental testing. In an international laboratory testing (ILT) following ISO/CD 24295 as standard procedure for rat cell-based DR CALUX un-spiked and spiked extracts of drinking-, surface-, and wastewater were validated to generate precision data for the development of the full ISO-standard. We found acceptable repeatability and reproducibility ranges below 36 % by DR CALUX bioassay for the tested un-spiked and spiked water of different origins. The presence of 17 PCDD/Fs and 12 dioxin-like PCBs was also confirmed by congener-specific GC-HRMS analysis. We compared the sum of dioxin-like activity levels measured by DR CALUX bioassay (expressed in 2,3,7,8-TCDD Bioanalytical Equivalents, BEQ; ISO 23196, 2022) with the obtained GC-HRMS chemical analysis results converted to toxic equivalents (TEQ; van den Berg et al., 2013).

New mechanistic insight into catalytic decomposition of dioxins over MnOx-CeO2/TiO2 catalysts: A combined experimental and density functional theory study.

Elucidation of the catalytic decomposition mechanism of dioxins is pivotal in developing highly efficient dioxin degradation catalysts. In order to accurately simulate the whole molecular structure of dioxins, two model compounds, o-dichlorobenzene (o-DCB) and furan, were employed to represent the chlorinated benzene ring and oxygenated central ring within a dioxin molecule, respectively. Experiments and Density Functional Theory (DFT) calculations were combined to investigate the adsorption as well as oxidation of o-DCB and furan over MnOx-CeO2/TiO2 catalyst (denoted as MnCe/Ti). The results indicate that competitive adsorption exists between furan and o-DCB. The former exhibits superior adsorption capacity on MnCe/Ti catalyst at 100 °C - 150 °C, for it can adsorb on both surface metal atom and surface oxygen vacancies (Ov) via its O-terminal; while the latter adsorbs primarily by anchoring its Cl atom to surface Ov. Regarding oxidation, furan can be completely oxidized at 150 °C - 300 °C with a high CO2 selectivity (above 80 %). However, o-DCB cannot be totally oxidized and the resulting intermediates cause the deactivation of catalyst. Interestingly, the pre-adsorption of furan on catalyst surface can facilitate the catalytic oxidation of o-DCB below 200 °C, possibly because the dissociated adsorption of furan may form additional reactive oxygen species on catalyst surface. Therefore, this work provides new insights into the catalytic decomposition mechanism of dioxins as well as the optimization strategies for developing dioxin-degradation catalysts with high efficiency at low temperature.