Chlorinated and brominated polycyclic aromatic hydrocarbons (Cl/Br-PAHs) are persistent organic pollutants with potential carcinogenic toxicities that are even higher than those of their parent PAH congeners. Current knowledge of Cl/Br-PAH sources and emission characteristics is lacking. Electric arc furnace (EAF) steelmaking is a potential source for Cl/Br-PAHs, considering that preheating of raw materials before they enter the EAF could produce suitable conditions for Cl/Br-PAHs formation. In this field study, we identified EAFs as an important source of Cl/Br-PAHs and clarified their emission concentrations, fingerprints by gas chromatography coupled with high-resolution magnetic mass spectrometry. Potential formation mechanisms of Cl/Br-PAHs were also proposed. The mass concentration ranges for Σ₁₈Cl-PAHs and Σ₁₈Br-PAHs in stack gas were 25.85–4191 ng Nm⁻³ and 1.02–341 ng Nm⁻³, respectively. The variation of concentration indicated that the steel scrap composition greatly affected the production of Cl/Br-PAHs. The congener ratios including 6-chlorobenzo [a]pyrene/3-chlorofluoranthene and 1-chloroanthracene/1-chloropyrene could be used to estimate the influence of industrial sources on Cl-PAH occurrences in the air. Ring structure growth was the dominant formation pathway for Cl/Br-PAHs, distinctly different from dioxin formation mechanisms dominated by precursor dimerization and chlorination.

Breast milk samples were collected from 51 mothers in a seaside city Dalian, where the residents usually have higher dietary exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) due to the larger consumption of seafood. The lipid-basis concentrations of ∑Cl₂–₈DD/Fs, ∑Cl₂–₁₀Bs, and total toxicity equivalent (WHO-TEQ) were measured to be in the ranges of 35.7–2727.8 pg/g, 4.91–52.64 ng/g, and 2.27–36.30 pg/g, respectively. The average proportion of ∑Cl₂–₃DD/Fs was higher than that of ∑Cl₄–₇DD/Fs in the collected human breast milk samples, suggesting that the health risk of Cl₂–₃DD/Fs should be especially concerned. The concentration data of PCDD/Fs and PCBs in human breast milk essentially followed a positive skew probability distribution. Women in high-level exposure scenarios exhibited a higher potential to accumulate homologues Cl₄DFs, Cl₇DFs, Cl₈DF, and Cl₆Bs in breast milk. Three PCDD/F congeners (1,2,3,6,7,8-Cl₆DF, 1,2,3,4,7,8-Cl₆DF, and 1,2,3,4,6,7,8-Cl₇DD) and three PCB congeners (PCB 126, PCB 138, and PCB 169) were identified as good indicators for the accumulation of PCDD/Fs and PCBs in human breast milk, respectively. The food-to-milk accumulation factors (FMAF) were calculated to evaluate the accumulation potentials of different PCDD/F and PCB congeners in human breast milk via dietary exposure. The calculated FMAF value presented a non-monotonic variation with the logarithm of n-octanol–water partition coefficient (log KOW) with a peak at a log KOW value of about 7.3 and a valley at a log KOW value of about 8. The mean value of the estimated daily intake (EDI) of total WHO-TEQ for breast-fed infants in Dalian, predicted by Monte Carlo simulation, was 10 folds higher than the upper range of the tolerable daily intake (TDI) value (4 pg WHO-TEQ/kg bw/d), suggesting continued and enhanced efforts should be made to reduce the exposure risk of infants to PCDD/Fs and PCBs.

Although huge interspecies differences in the response to dioxins have been acknowledged, toxic equivalency factors derived from rodent studies are often used to assess human health risk. To determine interspecies differences, we first developed a toxicokinetic model in humans by measuring dioxin concentrations in environmental and biomonitoring samples from Southern China. Significant positive correlations between dioxin concentrations in blood and age were observed for seven dioxin congeners, indicating an age-dependent elimination rate. Based on toxicokinetic models in humans, the half-lives of 15 dioxin congeners were estimated to be 1.60–28.55 years. In consideration that the highest contribution to total toxic equivalency in blood samples was by 12378-polychlorinated dibenzo-p-dioxin (P₅CDD), this study developed a physiologically based pharmacokinetic (PBPK) model of 12378-P₅CDD levels in the liver, kidney, and fat of C57/6J mice exposed to a single oral dose, and the half-life was estimated to be 26.1 days. Based on estimated half-lives in humans and mice, we determined that the interspecies difference of 12378-P₅CDD was 71, much higher than the default usually used in risk assessment. These results could reduce the uncertainty human risk assessment of 12378-P₅CDD, and our approach could be used to estimate the interspecies differences of other dioxin congeners.

Gut microbiota is of critical importance to host health. Aryl hydrocarbon receptor (AhR) is found to be closely involved in the regulation of gut microbial dynamics. However, it is still not clear how AhR signaling shapes the gut microbiota. In the present study, adult zebrafish were acutely exposed to an AhR antagonist (CH223191), an AhR agonist (polychlorinated biphenyl 126; PCB126) or their combination for 7 d. Overall intestinal health and gut microbial community were temporally monitored (1 d, 3 d and 7 d) and inter-compared among different groups. The results showed that single exposure to PCB126 significantly disrupted the overall health of intestines (i.e., neural signaling, inflammation, epithelial barrier integrity, oxidative stress). However, CH223191 failed to inhibit but enhanced the physiological toxicities of PCB126, implying the involvement of extra mechanisms rather than AhR in the regulation of intestinal physiological activities. Dysbiosis of gut microbiota was also caused by PCB126 over time as a function of sex. It is intriguing that CH223191 successfully abolished the holistic effects of dioxin on gut microbiota, which inferred that growth of gut microbes was directly controlled by AhR activation without the involvement of host feedback modulation. When coming to detailed alterations at certain taxon, both antagonistic and synergistic interactions existed between CH223191 and dioxin, depending on fish sex, exposure duration and bacterial species. Correlation analysis found that gut inflammation was positively associated with pathogenic Legionella bacteria, but was negatively associated with epithelial barrier integrity, suggesting that integral intestinal epithelial barrier can prevent the influx of pathogenic bacteria to induce inflammatory response. Overall, this study has deciphered, for the first time, the direct regulative effects of AhR activity on gut microbiota. Future research is warranted to elucidate the specific mechanisms of AhR action on certain bacterial population.

The aryl hydrocarbon receptor (AhR) plays an important role in mediating dioxins toxicity. Currently, genes of P450 families are major research interests in studies on AhR-mediated gene alterations caused by dioxins. Genes related to other metabolic pathways or processes may be also responsive to dioxin exposures. Amino acid transporter B0AT1 (encoded by SLC6A19) plays a decisive role in neutral amino acid transport which is present in kidney, intestine and liver. However, effects of dioxins on its expression are still unknown. In the present study, we focused on the effects of dioxin and dioxin-like compounds on SLC6A19 expression in HepG2 cells. We identified SLC6A19 as a novel putative target gene of AhR activation in HepG2 cells. 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) increased the expression of SLC6A19 in time- and concentration-dependent manners. Using AhR antagonist CH223191 and/or siRNA assays, we demonstrated that certain AhR agonists upregulated SLC6A19 expression via AhR, including TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PeCDD), 2,3,4,7,8- pentachlorodibenzofuran (2,3,4,7,8-PeCDF) and PCB126. In addition, the expression of B0AT1 was also significantly induced by TCDD in HepG2 cells. Our study suggested that dioxins might affect the transcription and translation of SLC6A19 in HepG2 cells, which might be a novel putative gene to assess dioxins' toxicity in amino acid transport and metabolism in liver.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that initiates a transcriptional pathway responsible for the expression of CYP1A subfamily members, key to the metabolism of xenobiotic compounds. Toxic planar halogenated aromatic hydrocarbons, including dioxin and PCBs, are capable of activating the AHR, and while dioxin and PCB inputs into the environment have been dramatically curbed following strict regulatory efforts in the United States, they persist in the environment and exposures remain relevant today. Little is known regarding the effects that long-term chronic exposures to dioxin or dioxin-like compounds might have on the development and subsequent health of offspring from exposed individuals, nor is much known regarding AHR expression in reptilians. Here, we characterize AHR and CYP1A gene expression in embryonic and juvenile specimen of a long-lived, apex predator, the American alligator (Alligator mississippiensis), and investigate variation in gene expression profiles in offspring collected from sites conveying differential exposures to environmental contaminants. Both age- and tissue-dependent patterning of AHR isoform expression are detected. We characterize two downstream transcriptional targets of the AHR, CYP1A1 and CYP1A2, and describe conserved elements of their genomic architecture. When comparisons across different sites are made, hepatic expression of CYP1A2, a direct target of the AHR, appears elevated in embryos from a site associated with a dioxin point source and previously characterized PCB contamination. Elevated CYP1A2 expression is not persistent, as site-specific variation was absent in juveniles originating from field-collected eggs but reared under lab conditions. Our results illustrate the patterning of AHR gene expression in a long-lived environmental model species, and indicate a potential contemporary influence of historical contamination. This research presents a novel opportunity to link contamination events to critical genetic pathways during embryonic development, and carries significant potential to inform our understanding of potential health effects in wildlife and humans.

Polybrominated dibenzo-p-dioxins (PBDDs) and hydroxylated polybrominated diphenyl ethers (OH-PBDEs) can be formed from bromophenols (BPs) by thermal degradation, biosynthesis or phototransformation. However, it is unknown whether PBDDs and OH-PBDEs can be formed during the chemical production processes that utilize BPs as raw materials. 2,4,6-tribromophenol (2,4,6-TBP) is an important raw material for the synthesis of 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), a novel brominated flame retardant. In this study, PBDDs, polybrominated dibenzofurans (PBDFs) and OH-PBDEs have been identified and quantified in commercially available BTBPE and 2,4,6-TBP. Furthermore, their formation as unintentional by-products during the laboratory synthesis of BTBPE from 2,4,6-TBP and 1,2-dibromoethane in the presence of sodium carbonate has also been investigated. 2,3,7,8-substituted PBDDs and PBDFs (2,3,7,8-PBDD/Fs) were undetectable in commercial samples of BTBPE and present in low levels (nanogram per gram) in 2,4,6-TBP. Two tetrabrominated dibenzo-p-dioxins (TeBDDs), namely 1,3,6,8- and 1,3,7,9-TeBDD, and three hydroxylated pentabrominated diphenyl ethers (OH-pentaBDEs), namely 4′-OH-BDE121, 2′-OH-BDE121, and 6′-OH-BDE100, were identified or tentatively identified, and quantitatively estimated to be at concentrations in the range of undetectable to several thousands of nanograms per gram in commercial BTBPE and 2,4,6-TBP. TeBDDs and OH-pentaBDEs were formed as by-products from 2,4,6-TBP during BTBPE synthesis. Further studies need to be conducted in order to determine whether PBDD/Fs and OH-PBDEs are also formed during the industrial synthesis of other chemical compounds that utilize BPs as raw materials or intermediates.

This study investigates reaction pathways for the formation of pre-PXDD/F intermediates via a radical/molecule mechanism. Thermodynamic and kinetic parameters for the combination reactions of 2-bromophenol (2-BP) and 2-chlorophenol (2-CP) precursors with key radical species including the phenoxy radicals, the phenyl radicals and the phenoxyl diradicals were calculated in detail. The couplings of phenoxy radicals with 2-B(C)P tend to produce pre-PXDD intermediates of halogenated o-phenoxyphenol. The combinations of phenyl and phenoxyl diradicals with 2-B(C)P produce two types of structures, i.e., dihydroxybiphenyl and o-phenoxyphenyl, which exclusively act as prestructures of PXDFs. These condensation reactions, especially those involving the phenyl C atom sites in phenyl and phenoxyl diradicals, are proven to be both thermodynamically and kinetically favorable and are nearly comparable with the corresponding steps involved in the radical/radical reactions. Most importantly, reactions of phenyl and phenoxyl diradicals with halogenated phenols solely lead to the formation of PXDFs, which to some extent provides a plausible explanation for the high PXDF-to-PXDD ratios in the real environment. Therefore, our study reveals the pivotal role of the radical/molecule mechanism in homogeneous gas-phase PXDD/F formation, especially in PXDF formation. The present results fill in a knowledge gap that has hitherto existed regarding dioxin formation and improve our understanding of PXDD/F formation characteristics in the environment.

The rapid growth of the production of electrical and electronic products has meant an equally rapid growth in the amount of electronic waste (e-waste), much of which is illegally imported to India, for disposal presenting a serious environmental challenge. The environmental impact during e-waste recycling was investigated and metal as well as other pollutants [e.g. polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs)] were found in excessive levels in soil, water and other habitats. The most e-waste is dealt with as general or crudely often by open burning, acid baths, with recovery of only a few materials of value. As resulted of these process; dioxins, furans, and heavy metals are released and harmful to the surrounding environment, engaged workers, and also residents inhabiting near the sites. The informal e-waste sectors are growing rapidly in the developing countries over than in the developed countries because of cheapest labor cost and week legislations systems. It has been confirmed that contaminates are moving through the food chain via root plant translocation system, to the human body thereby threatening human health. We have suggested some possible solution toward in which plants and microbes combine to remediate highly contaminated sites.

High levels of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were detected in free-range eggs, and these levels reached a concentration of 29.84 ± 7.45 pg of WHO-TEQ/g of fat. This value exceeded the EU maximum permitted level of 2.5 pg of WHO-TEQ/g of fat for PCDD/F congeners by twelve-fold. A chemical analysis (HRGC-HRMS) revealed elevated amounts of OCDD, OCDF, HxCDD, HpCDD and HpCDF. During the investigation, samples of feed, soil, wall scrapings, wooden ceiling of the henhouse and tissues from laying hens were examined for dioxin contents (30 samples altogether). The long and complicated investigation found that the source of dioxins in the poultry farm was pentachlorophenol-treated wood, which was used as structural components in the 40-year-old farm building adapted to a henhouse. The wooden building material contained PCDD/Fs at a concentration of 3922.60 ± 560.93 pg of WHO-TEQ/g and 11.0 ± 2.8 μg/kg of PCP. The potential risk associated with dioxin intake was characterized by comparing the theoretically calculated weekly and monthly intakes with the toxicological reference values (TRVs), namely the Tolerable Weekly Intake (TWI) and Provisional Tolerable Monthly Intake (PTMI) values of 14 pg of WHO-TEQ/kg of bw and 70 pg of WHO-TEQ/kg of bw, respectively. The intake of dioxins estimated for high egg consumers (approximately 5–6 eggs/week) exceeded the TWI and PTMI values, which may pose a risk of delayed adverse health effects. The estimated dose of PCDD/Fs and DL-PCBs for children consuming 5 eggs per week exceeded the TWI by as much as 450% because of their nearly 5-fold-lower body weight. Although the dioxin intake estimated for the average consumption of eggs in the general population did not exceed any of the TRVs applied (58.7% TWI and 51.1% PTMI), such a situation should be considered unacceptable from a public health perspective because eggs are not the only source of these contaminants.