Dioxin-like Compounds Research Articles

The 2022 world health organization reevaluation of human and mammalian toxic equivalency factors for polychlorinated dioxins, dibenzofurans and biphenyls

In October 2022, the World Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated. In contrast to earlier panels that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the 2006 REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive “Best-Estimate” TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The “Best-Estimate” TEF derived from the model was used to assign 2022 WHO-TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs.

Feasibility Analysis of Municipal Solid Waste Incineration for Harmless Treatment of Potentially Virulent Waste

The outbreak of major health emergencies, such as the COVID-19 pandemic, has posed numerous challenges to waste management. Environmentally sound treatment of such epidemic-related municipal solid waste (MSW) plays a vital role in interrupting virus transmission. In this study, the furnace type, incineration process and control parameters of an MSW incinerator were comparatively analyzed with those of a medical waste incinerator and hazardous waste incinerator according to China’s MSW incineration pollution control standards. In addition, changes in flue gas emissions data before, during and after the outbreak of the pandemic were empirically analyzed. The study revealed the following: (1) the feasibility of MSW incinerators to meet the harmless disposal of potentially viral municipal solid waste (PVMSW); (2) the priority order of incinerator types for MSW incinerators in the disposal of potentially virulent waste was grate furnace incinerator > fluidized bed incinerator > cement kiln; and (3) when MSW incinerators treated PVMSW, the emissions of dioxin compounds in the flue gas fluctuated between 0.00052 and 0.031 ng TEQ/m3, HCl emissions fluctuated between 1.6 and 23.742 mg/m3, CO emissions fluctuated between 0.18 and 59.15 mg/m3, heavy metal emissions fluctuated between 0.000008 and 0.855 mg/m3, and particulate matter emissions fluctuated between 0.64 and 12.13 mg/m3. All emissions met the flue gas emission standards. This study verified the feasibility of using MSW incinerators to treat PVMSW during a sudden major pandemic and provided a theoretical basis for the environmentally sound collaborative treatment of PVMSW and a reference for the emergency management and sustainable development of MSW.

Development and application of a systematic and quantitative weighting framework to evaluate the quality and relevance of relative potency estimates for dioxin-like compounds (DLCs) for human health risk assessment

The toxic equivalency factors (TEFs) approach for dioxin-like chemicals (DLCs) is currently based on a qualitative assessment of a heterogeneous data set of relative estimates of potency (REPs) spanning several orders of magnitude with highly variable study quality and relevance. An effort was undertaken to develop a weighting framework to systematically evaluate and quantitatively integrate the quality and relevance for development of more robust TEFs. Six main-study characteristics were identified as most important in characterizing the quality and relevance of an individual REP for human health risk assessment: study type, study model, pharmacokinetics, REP derivation method, REP derivation quality, and endpoint. Subsequently, a computational approach for quantitatively integrating the weighting framework parameters was developed and applied to the REP2004 database. This was accomplished using a machine learning approach which infers a weighted TEF distribution for each congener. The resulting database, weighted for quality and relevance, provides REP distributions from >600 data sets (including in vivo and in vitro studies, a range of endpoints, etc.). This weighted database provides a flexible platform for systematically and objectively characterizing TEFs for use in risk assessment, as well as providing information to characterize uncertainty and variability. Collectively, this information provides risk managers with information for decision making.

Exposure to the aryl hydrocarbon receptor agonist dioxin disrupts formation of the muscle, nerves, and vasculature in the developing jaw

Human exposure to environmental pollutants can disrupt embryonic development and impact juvenile and adult health outcomes by adversely affecting cell and organ function. Notwithstanding, environmental contamination continues to increase due to industrial development, insufficient regulations, and the mobilization of pollutants as a result of extreme weather events. Dioxins are a class of structurally related persistent organic pollutants that are highly toxic, carcinogenic, and teratogenic. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent dioxin compound and has been shown to induce toxic effects in developing organisms by activating the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor targeted by multiple persistent organic pollutants. Contaminant-induced AHR activation results in malformations of the craniofacial cartilages and neurocranium; however, the mechanisms mediating these phenotypes are not well understood. In this study, we utilized the optically transparent zebrafish model to elucidate novel cellular targets and potential transcriptional targets underlying TCDD-induced craniofacial malformations. To this end, we exposed zebrafish embryos at 4 h post fertilization to TCDD and employed a mixed-methods approach utilizing immunohistochemistry staining, transgenic reporter lines, fixed and in vivo confocal imaging, and timelapse microscopy to determine the targets mediating TCDD-induced craniofacial phenotypes. Our data indicate that embryonic TCDD exposure reduced jaw and pharyngeal arch Sox10+ chondrocytes and Tcf21+ pharyngeal mesoderm progenitors. Exposure to TCDD correspondingly led to a reduction in collagen type II deposition in Sox10+ domains. Embryonic TCDD exposure impaired development of tissues derived from or guided by Tcf21+ progenitors, namely: nerves, muscle, and vasculature. Specifically, TCDD exposure disrupted development of the hyoid and mandibular arch muscles, decreased neural innervation of the jaw, resulted in compression of cranial nerves V and VII, and led to jaw vasculature malformations. Collectively, these findings reveal novel structural targets and potential transcriptional targets of TCDD-induced toxicity, showcasing how contaminant exposures lead to congenital craniofacial malformations.

Non-target and target analysis to identify and characterize thiophenes in soil from an abandoned coking plant

There is concern about the large amounts of aromatic compounds emitted during coking. Previous studies of coking emissions have been focused on polycyclic aromatic hydrocarbons, dioxin-like compounds, phenols, and volatile organic compounds, but previously unidentified compounds produced during coking may also harm human health. Here, the main pollutants in 69 soil samples from an abandoned coking plant were identified by non-target screening using two-dimensional gas chromatography time-of-flight mass spectrometry. Polycyclic aromatic hydrocarbons, long-chain alkanes, and thiophenes were dominant. High concentrations of thiophenes (benzothiophenes, dibenzothiophenes, and benzonaphtholthiophenes) were found. Quantitative analysis of 12 thiophenes (selected because of their concentrations and detection frequencies) was performed, and the concentrations were 0.03–647 μg/g dry weight, which were extremely high compared with concentrations in soil from uncontaminated sites and other industrial sites. Dibenzothiophene and benzo[b]naphtho[2,1-d]thiophene were dominant, accounting for 69% of the total thiophene concentration. Thiophene profiles in very contaminated areas were different from the profile in coal but similar to the profile in tar. Thiophenes in soil at the coking plant may have been supplied in tar leaks, wastewater, coke oven gases, and exhaust gases. A toxicity assessment indicated a strong likelihood of oxidative stress being induced by exposure to multiple thiophenes at the coking plant. The results suggest that thiophene emissions from coking plants should attract more attention than currently.

Development of skin diseases following systemic exposure: example of dioxins.

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. Sweat 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.

Unravelling the impacts of sulfur dioxide on dioxin catalytic decomposition on V2O5/AC catalysts

Dioxins are high chlorine, toxic, and persistent organic pollutants that exert significant pressure on both human and the environment. From the analysis of current pollutant removal of the whole life cycle, such as integrated removal of NOx, SO2 and dioxins in a system, the dioxins oxidation activity as well as the distribution of oxidation products in the presence of SO2 are still a challenge. In this study, dibenzofuran (DBF) was regarded as a model dioxin compound, and V2O5/AC was used as a catalyst to investigate the impact of SO2 on degradation activity and the degradation path of DBF. Various characterization results showed that SO2 could promote the transformation of DBF to intermediates through a reaction with lattice oxygen and lower the apparent activated energy of DBF catalytic oxidation on V2O5/AC catalysts. The density functional theory (DFT) calculations confirmed that SO2 improved the oxidation ability of lattice oxygen on V2O5/AC. The ethyl hydrogen fumarate intermediate decreased and the small-molecule byproducts increased, providing further evidence that SO2 accelerates the degradation of DBF and its intermediates. However, the formation of VOSO4 would inevitably deteriorate the adsorption and oxidation abilities of V2O5/AC. A model is pioneered to describe the relationship between SO2 promotion and VOSO4 inhibition on DBF catalytic oxidation on a V2O5/AC catalyst. This study is expected to provide theoretical guidance for the collaborative abatement of multi-pollutants in flue gas.

A multi-tiered hierarchical Bayesian approach to derive toxic equivalency factors for dioxin-like compounds

In 2005, the World Health Organization (WHO) re-evaluated Toxic Equivalency factors (TEFs) developed for dioxin-like compounds believed to act through the Ah receptor based on an updated database of relative estimated potency (REP)(REP2004 database). This re-evalution identified the need to develop a consistent approach for dose-response modeling. Further, the WHO Panel discussed the significant heterogeneity of experimental datasets and dataset quality underlying the REPs in the database. There is a critical need to develop a quantitative, and quality weighted approach to characterize the TEF for each congener. To address this, a multi-tiered approach that combines Bayesian dose-response fitting and meta-regression with a machine learning model to predict REPS' quality categorizations was developed to predict the most likely relationship between each congener and its reference and derive model-predicted TEF uncertainty distributions. As a proof of concept, this ‘Best-Estimate TEF workflow’ was applied to the REP2004 database to derive TEF point-estimates and characterizations of uncertainty for all congeners. Model-TEFs were similar to the 2005 WHO TEFs, with the data-poor congeners having larger levels of uncertainty. This transparent and reproducible computational workflow incorporates WHO expert panel recommendations and represents a substantial improvement in the TEF methodology.

Connecting Suborganismal Data to Bioenergetic Processes: Killifish Embryos Exposed to a Dioxin-Like Compound.

A core challenge for ecological risk assessment is to integrate molecular responses into a chain of causality to organismal or population-level outcomes. Bioenergetic theory may be a useful approach for integrating suborganismal responses to predict organismal responses that influence population dynamics. We describe a novel application of dynamic energy budget (DEB) theory in the context of a toxicity framework (adverse outcome pathways [AOPs]) to make quantitative predictions of chemical exposures to individuals, starting from suborganismal data. We use early-life stage exposure of Fundulus heteroclitus to dioxin-like chemicals (DLCs) and connect AOP key events to DEB processes through "damage" that is produced at a rate proportional to the internal toxicant concentration. We use transcriptomic data of fish embryos exposed to DLCs to translate molecular indicators of damage into changes in DEB parameters (damage increases somatic maintenance costs) and DEB models to predict sublethal and lethal effects on young fish. By changing a small subset of model parameters, we predict the evolved tolerance to DLCs in some wild F. heteroclitus populations, a data set not used in model parameterization. The differences in model parameters point to reduced sensitivity and altered damage repair dynamics as contributing to this evolved resistance. Our methodology has potential extrapolation to untested chemicals of ecological concern. Environ Toxicol Chem 2023;00:1-14. © 2023 Oak Ridge National Laboratory and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

INFLUENCE OF THE FACTORS OF ENVIRONMENT ON THE QUALITY OF THE FEED IN THE KARAGANDA OBLAST

In the article, the authors present the results of assessing the quality and safety of feed in various districts of the Karaganda region. The following feed studies were carried out: organoleptic and physico-chemical indicators; the total toxicity and residual amount of heavy metal compounds were determined; the quality and safety of feed from various areas of the study area were assessed; organoleptic and physico–chemical indicators of animal feed were carried out; the dynamics of seasonal accumulation of residual amounts of heavy metal compounds in feed was also established.
 The following contaminants are most dangerous in feed: toxins of microorganisms (including fungi), toxic elements (heavy elements), antibiotics, pesticides, nitrates, nitrites, dioxins and dioxin-like compounds, radionucleides.
 According to the ecological situation, the Karaganda region is one of the ecologically unfavorable territories of our country. This is due to the large concentration of ferrous and non-ferrous metallurgy, energy complexes and other industrial objects, such as Arcelor Mittal Temirtau and Kazakhmys.
 From the atmosphere, toxic substances enter the soil and penetrate it directly or with precipitation.
 Therefore, the study of the influence of environmental factors on feed in the conditions of the Karaganda region is of great practical and theoretical importance.

Preliminary results from the Tunisian monitoring program on POPs in air under the Stockholm Convention

Persistent organic pollutants (POPs) have been measured using passive air samplers (PASs) over two years (2017–2018) in the city of Tunis within the framework of the UNEP/GEF GMP2 projects to support Stockholm Convention implementation. Several POPs, although banned for a long time from Tunisia, were registered in relatively high amounts in the atmospheric compartment. The most unexpected compound is hexachlorobenzene (HCB), with concentrations ranging from 5.2 ng/PUF to 16 ng/PUF. Furthermore, the current results seem to confirm the presence of dichlorodiphenyltrichloroethane (DDT) and its transformation products and hexachlorocyclohexanes (HCHs) at relatively high concentrations (4.6 ng/PUF to 9.4 ng/PUF and 2.7 ng/PUF to 5.1 ng/PUF, respectively), followed by hexabromocyclododecane (HCBD), which varies from 1.5 ng/PUF to 7.7 ng/PUF. Nondioxin-like PCB (ndl-PCB) concentrations in Tunis were very high (62.0 ng/PUF to 419.3 ng/PUF), higher than those in other African countries participating in this project. Uncontrolled combustion seems to be one of the most important sources of the emanation of dioxin compounds dl-PCBs and Polychlorinated dibenzodioxins PCDD/polychlorinated dibenzofurans PCDF. Toxic equivalents (TEQs) ranged from 4.1 pg WHO-TEQ/PUF to 6.4 pg WHO-TEQ/PUF. The perfluorinated compounds (PFAS) and congeners of polybrominated diphenyl ethers (PBDEs) show relatively low amounts that remain below the African continent average. The PFAS pattern suggests a local source rather than long-range transport. These results constitute the first exhaustive work capable of providing an overview of the levels of POPs in the air in Tunis. As a result, it will be possible to set up an adequate monitoring program with specific investigations and experimental studies.

Partitioning behavior and mechanism of polyhalogenated carbazoles in water and suspended particulate matter

Polyhalogenated carbazoles (PHCZs), known as new dioxin-like compounds, are a new class of emerging environmental contaminants that have received increasing attention in recent years due to their wide distribution and dioxin-like toxicity. This study investigated the partition characteristics and adsorption mechanisms of eight PHCZs in the aqueous phase and suspended particulate matter (SPM). The competitive impact of humic acid (HA) on the adsorption of PHCZs was revealed when the effects of various environmental conditions (HA, temperature, perturbation disturbance, and pH) behavior were explored. The key finding of this study is that SPM, which is its effective vector, could adsorb 70.7 % of ΣPHCZs. The equilibrium adsorption amount is ranked as 3,6-ICZ > 3,6-BCZ > 2,7-BCZ > 3,6-CCZ > 1,3,6,8-BCZ > 3-BCZ > 2-BCZ > CZ. The halogen species, the degree of halogenation, and the substitution position of the PHCZs influence the amount of adsorption, where the log Kow values, the steric effect (Es), and the density contribute the most to the amount of adsorption, and the specific adsorption mechanisms are van der Waals force, π-π, hydrogen bonding, and nonspecific hydrophobic interactions. The adsorption reaction of PHCZs by SPM is endothermic, and the amount of adsorption increases with increasing temperature, oscillation velocity, and decrease in pH. HA may reduce the adsorption sites of hydroxyl, carbonyl, amide groups, and π-π bonds on SPM for PHCZs, while the SPM@HA conjugates can provide new sites for the adsorption of PHCZs. According to the experimental findings of this study, SPM plays a significant role in contaminant transport. As a result, when conducting environmental investigations of PHCZs and even other hydrophobic contaminants, we must fully consider the level of contaminants present in SPM to reveal the ecological risks accurately.

In vitro bioassays to monitor complex chemical mixtures at a carbon-based indirect potable reuse plant

Potable water reuse technologies are used to treat wastewater to drinking water quality to help sustain a community's water resources. California has long led the adoption of potable water reuse technologies in the United States and more states are exploring these technologies as water resources decline. Reuse technologies also need to achieve adequate reductions in microbial and chemical contaminant risks to meet public health goals and secure public acceptance. In vitro bioassays are a useful tool for screening if reuse treatment processes adequately reduce toxicity associated with a range of chemical classes that are contaminants of concern. In this study, we used an aryl hydrocarbon receptor (AhR) and an estrogen receptor luciferase bioassay to detect the presence of dioxin-like and estrogenic compounds across a 3800 m3/d carbon-based indirect potable reuse plant that uses carbon-based treatment (SWIFT-RC). Our results demonstrate significant removal of dioxin-like compounds across the SWIFT-RC treatment train. Estrogenicity declined across the treatment train for some months but was extremely variable and low with many samples falling below the method quantification level; consequently, we were not able to reliably determine estrogenicity trends for SWIFT-RC. Comparing the bioanalytical equivalent concentrations detected in the SWIFT-RC water with established monitoring trigger levels from the state of California suggests that SWIFT-RC produced water that met the bioassay guidelines. The log total organic carbon concentration and AhR assay equivalent concentrations are weakly correlated when data across all SWIFT-RC processes are included. Overall, this research demonstrates the performance of in vitro bioassays at a demonstration-scale carbon-based IPR system and highlights both the potential utility and challenges associated with these methods for assessing system performance.

69 Activation of the Aryl Hydrocarbon Receptor - a Major mode of Combustion Particle Toxicity?

Abstract Combustion-derived particles constitute an important part of the fine fraction of particulate matter with aerodynamic diameter less than 2.5 microns (PM2.5) and are considered central for the adverse effects of air pollution. Understanding the mechanisms of combustion particle toxicity may shed light on the components and characteristics of outdoor air PM driving adverse health effects. This may also enable more targeted and efficient policies to improve air quality and promote health and wellbeing. The aryl hydrocarbon receptor (AhR) is a ligand dependent transcription factor, originally discovered for its ability to bind polycyclic aromatic hydrocarbons (PAHs) and dioxin-like compounds and regulate PAH metabolism. It is now clear that AhR regulates a variety of biological and toxicological responses, overlapping to a considerable degree with the effects of combustion PM and ambient PM2.5. Studies from our lab and others also suggest that AhR activation is among the most sensitive responses to combustion PM exposure, induced at orders of magnitude lower concentrations than many other endpoints. This talk will discuss the potential role of the AhR and PAHs in combustion PM toxicity based on previous and ongoing work, with a main focus on intracellular signalling and regulation of inflammatory reactions in lung epithelial cells and vascular endothelial cells.

Functional characterization of common carp (Cyprinus carpio) AHRs: Subform-specific sensitivity to dioxin and interspecies differences

Dioxins are widely known to bioaccumulate in the body and produce a wide spectrum of toxic effects on both humans and wildlife. In addition, some novel sorts of compounds that were similar in structure and effect were gradually identified and termed dioxin-like compounds (DLCs). The toxicity of dioxins as well as DLCs is predominantly mediated by the dioxin receptor (aryl hydrocarbon receptor, AHR) in animals, which is usually differentially expressed and functionally distinct (especially the sensitivity to dioxins) among species, possibly resulting in species-specific variations in the toxicity of dioxins. Therefore, detailed functional exploration of the AHRs of a given species, such as the common carp (which is a vital wild and commercial species with a broad geological distribution) in the current study, will enable a comprehensive ecotoxicity evaluation. Through genome survey and phylogenetic analysis, we identified three AHRs (AHR1a, AHR1b, and AHR2) and two ARNTs (ARNT1 and ARNT2). AHR2 was observed to have greater expression abundance in the gill and brain, and may serve as the predominant subform. Those AHRs and ARNTs are functional, and the AHRs can be efficiently transactivated by the classical dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We individually determined the EC50 values of AHR1a (0.41 ± 0.24 nM), AHR1b (12.80 ± 3.28 nM), and AHR2 (0.64 ± 0.49 nM), and found that: 1) The AHR sensitivities of common carp and zebrafish (phylogenetically close species) are relatively similar. AHR1a and the predominant form AHR2 have greater sensitivity to TCDD. 2) ARNT1 and ARNT2 do not produce different sensitivities, but with distinct induction fold, of a given AHR transactivation when cooperating as the partner; 3) Distinct AHR subforms of the same or distinct species can have even one or two orders of magnitude differences in sensitivity. In summary, the current study will add to the knowledge of AHR biology and help improve ecotoxicology research on dioxins and DLCs.

Polychlorinated naphthalenes in milk-based infant and toddler formula sold on the Chinese market

Polychlorinated naphthalenes (PCNs) are dioxin-like compounds that have been reported to be present in a wide variety of foodstuffs. Milk-based infant and toddler formula sometimes plays an important role in the diet of young children and could potentially cause adverse effects if contaminated with PCNs. This study investigated the concentrations of PCNs in commercial milk-based formula produced in different countries and sold on the Chinese market for three age groups: 0–6, 6–12 and 12–36 months. The total concentrations of PCNs in 72 samples from different countries of formula based on cow milk ranged from 7.8 to 30.3 pg/g whole weight (ww). Although the PCN concentrations in formula produced in Asia, Europe and South Pacific varied, all had comparable toxic equivalent (TEQ) values. Tri-CNs were the predominant PCN homologue in all samples. No significant differences in the concentrations of PCNs were found between samples of formula for each of the three age groups. The mean TEQ for PCNs in goat milk formula samples (0.0031 pg TEQ/g ww) was higher than the value for cow milk formula (0.0009 pg TEQ/g ww) produced in China, and the proportion of higher chlorinated PCNs in goat milk formula was also higher. Based on dry weight, the mean concentration of PCNs in the raw cow milk (119 pg/g dry weight (dw)) used to produce infant and toddler formula was higher than that in the actual formula (24.2 pg/g dw), and the PCN profiles also varied between the raw milk and formula. A risk assessment indicated that, in China, consuming formula poses a lower risk to infants and toddlers from based on exposure to PCNs compared with consuming breast milk.

Characterization of PCDD/F and dl-PCB levels in air in Gipuzkoa (Basque Country, Spain)

This research examines the levels and trends of pollutants, specifically 17 congeners of PCDD/Fs and 12 dl-PCBs, in the air measured in the province of Gipuzkoa (Basque Country, Spain). The study used PCDD/Fs, dl-PCB, and the sum of dioxin-like compounds as separate response variables. A total of 113 air samples were collected and analyzed using the method described in the European Standard (EN-1948:2006) from two industrial areas. The results were analyzed using non-parametric test to assess the variability of these pollutants based on different factors (year, season and day of the week) and General Linear Models to assess the weight of each factor. The study found that the toxic equivalents (TEQs) for PCDD/Fs were 12.29 fg TEQm−3 and for dl-PCBs were 1.63 fg TEQm−3, which were in a similar range or lower than those observed in other national and international studies in industrial areas. The results showed temporal variations, with higher levels of PCDD/Fs in autumn-winter than in spring-summer and higher levels of PCDD/Fs and dl-PCBs during weekdays than on weekends. The industrial area where the energy recovery plant (ERP) will be located had higher levels of air pollutants due to the presence of two PCDD/Fs emitting industries nearby, as indicated by the Spanish Registry of Polluting Emission Sources. Both industrial areas showed similar profiles of PCDD/Fs and dl-PCBs, with the PCDD/F profiles dominated by OCDD, 1,2,3,4,6,7,8-HpCDD, and 1,2,3,4,6,7,8-HpCDF in terms of concentrations and 1,2,3,7,8-PeCDD, 2,3,4,7,8-PeCDF, and 2,3,7,8-TCDD in terms of TEQs. The dl-PCB profiles were dominated by PCB 118, PCB 105, and PCB 77 in terms of concentrations and PCB 126 in terms of TEQs. The findings of this study can serve as an indicator of the potential impact of ERP on the health of the resident population and the environment.

Comparative analysis of two new zebrafish models: The cyp1a low-expression line and cyp1a knockout line under PAHs exposure

Cytochrome P450 1 (CYP1) is an important enzyme family involved in the metabolism of pollutants, and used as a biomarker to monitor environmental pollution. In this study, a fluorescence-labeled cyp1a zebrafish line, named as KI (cyp1a+/+-T2A-mCherry) (KICM), was originally constructed to monitor dioxin-like compounds in the environment. However, the cyp1a gene expression in the KICM line was inhibited by the fluorescence labeling, thus leading to a significantly increased sensitivity of KICM zebrafish line to PAHs. Then, a cyp1a knockout zebrafish line, named KOC, were constructed for comparative analysis with the cyp1a low-expression line. Interestingly, knockout of the cyp1a gene did not increase the sensitivity of zebrafish to PAHs as significantly as the cyp1a low-expression line. So, the expression levels of related genes in the aryl hydrocarbon receptor pathway were analyzed and the results showed that the expression level of cyp1b in KOC group was significantly higher than that of wild type and KICM under the same PAH exposure. This indicated that the effect of losing cyp1a was compensated by inducing expression of cyp1b. In conclusion, two new zebrafish models including cyp1a low-expression line and cyp1a knockout line were constructed in this study, which may provide a convenient model for subsequent studies on the toxicity mechanism of PAHs and the role of cyp1a in detoxification.

Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, pesticides, and diabetes in the Anniston Community Health Survey follow-up (ACHS II): single exposure and mixture analysis approaches

Dioxins and dioxin-like compounds measurements were added to polychlorinated biphenyls (PCBs) and organochlorine pesticides to expand the exposure profile in a follow-up to the Anniston Community Health Survey (ACHS II, 2014) and to study diabetes associations. Participants of ACHS I (2005–2007) still living within the study area were eligible to participate in ACHS II. Diabetes status (type-2) was determined by a doctor's diagnosis, fasting glucose ≥125 mg/dL, or being on any glycemic control medication. Incident diabetes cases were identified in ACHS II among those who did not have diabetes in ACHS I, using the same criteria. Thirty-five ortho-substituted PCBs, 6 pesticides, 7 polychlorinated dibenzo-p-dioxins (PCDD), 10 furans (PCDF), and 3 non-ortho PCBs were measured in 338 ACHS II participants. Dioxin toxic equivalents (TEQs) were calculated for all dioxin-like compounds. Main analyses used logistic regression models to calculate odds ratios (OR) and 95 % confidence intervals (CI). In models adjusted for age, race, sex, BMI, total lipids, family history of diabetes, and taking lipid lowering medication, the highest ORs for diabetes were observed for PCDD TEQ: 3.61 (95 % CI: 1.04, 12.46), dichloro-diphenyl dichloroethylene (p,p’-DDE): 2.07 (95 % CI 1.08, 3.97), and trans-Nonachlor: 2.55 (95 % CI 0.93, 7.02). The OR for sum 35 PCBs was 1.22 (95 % CI: 0.58–2.57). To complement the main analyses, we used BKMR and g-computation models to evaluate 12 mixture components including 4 TEQs, 2 PCB subsets and 6 pesticides; suggestive positive associations for the joint effect of the mixture analyses resulted in ORs of 1.40 (95% CI: -1.13, 3.93) for BKMR and 1.32 (95% CI: -1.12, 3.76) for g-computation. The mixture analyses provide further support to previously observed associations of trans-Nonachlor, p,p’- DDE, PCDD TEQ and some PCB groups with diabetes.

Excretion of polybrominated diphenyl ethers and AhR activation in breastmilk among firefighters.

Excretion of toxicants accumulated from firefighter exposures through breastmilk represents a potential hazard. We investigated if firefighting exposures could increase the concentration of polybrominated diphenyl ethers (PBDEs) and aryl hydrocarbon receptor (AhR) activation in excreted breastmilk. Firefighters and non-firefighters collected breastmilk samples prior to any firefighting responses (baseline) and at 2, 8, 24, 48, and 72 hours after a structural fire (firefighters only). Five PBDE analytes (BDEs 15, 28, 47, 99, and 153) detected in at least 90% of samples were summed for analyses. The AhR in vitro DR CALUX® bioassay assessed the mixture of dioxin-like compounds and toxicity from breastmilk extracts. Baseline PBDEs and AhR response were compared between firefighters and non-firefighters. Separate linear mixed models assessed changes in sum of PBDEs and AhR response among firefighters over time and effect modification by interior or exterior response was assessed. Baseline PBDE concentrations and AhR responses did not differ between the 21 firefighters and 10 non-firefighters. There were no significant changes in sum of PBDEs or AhR response among firefighters over time post-fire, and no variation by interior or exterior response. Plots of sum of PBDEs and AhR response over time demonstrated individual variation but no consistent pattern. Currently, our novel study results do not support forgoing breastfeeding after a fire exposure. However, given study limitations and the potential hazard of accumulated toxicants from firefighter exposures excreted via breastfeeding, future studies should consider additional contaminants and measures of toxicity by which firefighting may impact maternal and child health.