Dioxin
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BACKGROUND: Children and consumers are exposed to increasingly complex mixtures of known and as-yet-unknown toxic chemicals from toys and products. However traditional chemical analysis methods only evaluate a small number of chemicals at a time thereby restricting consumer awareness of the full range of potentially harmful chemicals in products. METHODS: We used high-throughput effect-based non-animal methods to investigate exposures to complex chemical mixtures of several kinds of brominated flame retardants (BFRs) for their dioxin- and thyroid hormone-like activities in various kinds of consumer products and toys from 26 different countries, on four continents (Africa, America, Asia and Europe) in combination with chemical analysis of various polybrominated flame retardants (BFRs) and their impurities (such as polyhalogenated PCDD/Fs and PBDD/Fs). RESULTS: We found high levels of polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) in toys and now, for the first time, also in consumer products that are manufactured from black plastics containing certain brominated flame retardants (BFRs). The presence of PBDD/PBDFs as well as other BFRs in various black plastic materials from additional countries as well as additional kinds of consumer products as confirmed by effect-based in vitro reporter gene DR CALUX and TTR-TRβ CALUX assays as well as congener-specific chemical analysis. We compared total Toxicity Equivalent (TEQ) levels of PBDD/F-TEQs analysed by chemical analysis to by CALUX bioassay measured Biological equivalence (BEQ) concentrations (for further info see at ISO 23196, ISO, 2022). In the case of TBBPA, both chemical and TTR-TRβ CALUX analysis measure direct the amount of TBBPA. Finally, the daily ingestion of 2,3,7,8-TCDD equivalents from PBDD/Fs-contaminated plastic toys by child mouthing habits have been related to our earlier study (Budin et al., 2020). CONCLUSIONS: Interaction of children with such contaminated plastics may significantly contribute to the daily uptake of dioxin- and thyroid hormone transport disrupting-like compounds. Effect-based bioassays for dioxin- and thyroid hormone-like activities are relevant to pick-out such complex mixtures of known and yet unknown (and therefore not regulated) substances for safer and more sustainable plastics. Low POPs Content Levels and other mechanisms set under the Basel and Stockholm Conventions are set far too high to prevent a significant flow of BFRs and PBDD/Fs into consumer products.
- Klíčová slova
- Consumer products, DR CALUX, Dioxins, Polybrominated dibenzo-p-dioxin and dibenzofurans (PBDD/PBDFs), TTR -TRβ CALUX, Tetrabromo-bisphenol A (TBBPA),
- MeSH
- dibenzofurany analýza MeSH
- dioxiny * analýza MeSH
- dítě MeSH
- hormony štítné žlázy MeSH
- komplexní směsi MeSH
- lidé MeSH
- plastické hmoty chemie MeSH
- polychlorované dibenzodioxiny * analýza MeSH
- retardanty hoření * analýza MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dibenzofurany MeSH
- dioxiny * MeSH
- hormony štítné žlázy MeSH
- komplexní směsi MeSH
- plastické hmoty MeSH
- polychlorované dibenzodioxiny * MeSH
- retardanty hoření * MeSH
Untargeted metabolomic approaches offer new opportunities for a deeper understanding of the molecular events related to toxic exposure. This study proposes a metabolomic investigation of biochemical alterations occurring in urine as a result of dioxin toxicity. Urine samples were collected from Czech chemical workers submitted to severe dioxin occupational exposure in a herbicide production plant in the late 1960s. Experiments were carried out with ultra-high pressure liquid chromatography (UHPLC) coupled to high-resolution quadrupole time-of-flight (QTOF) mass spectrometry. A chemistry-driven feature selection was applied to focus on steroid-related metabolites. Supervised multivariate data analysis allowed biomarkers, mainly related to bile acids, to be highlighted. These results supported the hypothesis of liver damage and oxidative stress for long-term dioxin toxicity. As a second step of data analysis, the information gained from the urine analysis of Victor Yushchenko after his poisoning was examined. A subset of relevant urinary markers of acute dioxin toxicity from this extreme phenotype, including glucuro- and sulfo-conjugated endogenous steroid metabolites and bile acids, was assessed for its ability to detect long-term effects of exposure. The metabolomic strategy presented in this work allowed the determination of metabolic patterns related to dioxin effects in human and the discovery of highly predictive subsets of biologically meaningful and clinically relevant compounds. These results are expected to provide valuable information for a deeper understanding of the molecular events related to dioxin toxicity. Furthermore, it presents an original methodology of data dimensionality reduction by using extreme phenotype as a guide to select relevant features prior to data modeling (biologically driven data reduction).
- Klíčová slova
- Biomarkers, Dimensionality reduction, Dioxin, Extreme phenotype, Steroidomics, Toxicity,
- MeSH
- biologické markery moč MeSH
- data mining MeSH
- játra účinky léků metabolismus MeSH
- lidé MeSH
- metabolomika metody MeSH
- monitorování životního prostředí metody MeSH
- oxidační stres účinky léků MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- pracovní expozice analýza MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- polychlorované dibenzodioxiny MeSH
This study aimed at evaluating and comparing five integrative samplers for the monitoring of indicator and dioxin-like polychlorinated biphenyls (PCBs) in water: semi-permeable membrane device (SPMD), silicone rubber, low-density polyethylene (LDPE) strip, Chemcatcher and a continuous-flow integrative sampler (CFIS). These samplers were spiked with performance reference compounds (PRCs) and then simultaneously exposed under constant agitation and temperature in a 200 L stainless steel tank for periods ranging from one day to three months. A constant PCB concentration of about 1 ng·L(-1) was achieved by immersing a large amount of silicone rubber sheets ("dosing sheets") spiked with the target PCBs. The uptake of PCBs in the five samplers showed overall good repeatability and their accumulation was linear with time. The samplers SPMD, silicone rubber and LDPE strip were the most promising in terms of achieving low limits of quantification. Time-weighted average (TWA) concentrations of PCBs in water were estimated from uptake of PCBs using the sampling rates calculated from the release of PRCs. Except for Chemcatcher, a good agreement was found between the different samplers and TWA concentrations ranged between 0.4 and 2.8 times the nominal water concentration. Finally, the influence of calculation methods (sampler-water partition coefficients, selected PRCs, models) on final TWA concentrations was studied.
- Klíčová slova
- Integrative samplers, Modeling, Polychlorinated biphenyls, Time weighted average concentration, Water monitoring,
- MeSH
- chemické látky znečišťující vodu analýza MeSH
- dioxiny analýza MeSH
- monitorování životního prostředí přístrojové vybavení metody MeSH
- polychlorované bifenyly analýza MeSH
- polychlorované dibenzodioxiny MeSH
- teplota MeSH
- voda chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- chemické látky znečišťující vodu MeSH
- dioxiny MeSH
- polychlorované bifenyly MeSH
- polychlorované dibenzodioxiny MeSH
- voda MeSH
Changes in pollutant loads in relatively dynamic river sediments, which contain very complex mixtures of compounds, can play a crucial role in the fate and effects of pollutants in fluvial ecosystems. The contamination of sediments by bioactive substances can be sensitively assessed by in vitro bioassays. This is the first study that characterizes detailed short- and long-term changes in concentrations of contaminants with several modes of action in river sediments. One-year long monthly study described seasonal and spatial variability of contamination of sediments in a representative industrialized area by dioxin-like and endocrine disruptive chemicals. There were significant seasonal changes in both antiandrogenic and androgenic as well as dioxin-like potential of river sediments, while there were no general seasonal trends in estrogenicity. Aryl hydrocarbon receptor-dependent potency (dioxin-like potency) expressed as biological TCDD-equivalents (BIOTEQ) was in the range of 0.5-17.7 ng/g, dry mass (dm). The greatest BIOTEQ levels in sediments were observed during winter, particularly at locations downstream of the industrial area. Estrogenicity expressed as estradiol equivalents (EEQ) was in the range of 0.02-3.8 ng/g, dm. Antiandrogenicity was detected in all samples, while androgenic potency in the range of 0.7-16.8 ng/g, dm dihydrotestosterone equivalents (DHT-EQ) was found in only 30 % of samples, most often during autumn, when antiandrogenicity was the least. PAHs were predominant contaminants among analyzed pollutants, responsible, on average, for 13-21 % of BIOTEQ. Longer-term changes in concentrations of BIOTEQ corresponded to seasonal fluctuations, whereas for EEQ, the inter-annual changes at some locations were greater than seasonal variability during 1 year. The inter- as well as intra-annual variability in concentrations of both BIOTEQ and EEQ at individual sites was greater in spring than in autumn which was related to hydrological conditions in the river. This study stresses the importance of river hydrology and its seasonal variations in the design of effective sampling campaigns, as well as in the interpretation of any monitoring results.
- MeSH
- biotest MeSH
- chemické látky znečišťující vodu analýza MeSH
- chemické znečištění vody statistika a číselné údaje MeSH
- dioxiny analýza MeSH
- endokrinní disruptory analýza MeSH
- geologické sedimenty chemie MeSH
- monitorování životního prostředí * MeSH
- polychlorované dibenzodioxiny analýza MeSH
- polycyklické aromatické uhlovodíky analýza MeSH
- receptory aromatických uhlovodíků MeSH
- řeky chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chemické látky znečišťující vodu MeSH
- dioxiny MeSH
- endokrinní disruptory MeSH
- polychlorované dibenzodioxiny MeSH
- polycyklické aromatické uhlovodíky MeSH
- receptory aromatických uhlovodíků MeSH
The aryl hydrocarbon receptor (AHR) is a member of the basic helix-loop-helix/Per-ARNT-Sim (bHLH-PAS) family of transcription factors and has broad biological functions. Early after the identification of the AHR, most studies focused on its roles in regulating the expression of drug-metabolizing enzymes and mediating the toxicity of dioxins and dioxin-like compounds (DLCs). Currently, more diverse functions of AHR have been identified, indicating that AHR is not just a dioxin receptor. Dioxins and DLCs occur ubiquitously and have diverse health/ecological risks. Additional research is required to identify both shared and compound-specific mechanisms, especially for emerging DLCs such as polyhalogenated carbazoles (PHCZs), polychlorinated diphenyl sulfides (PCDPSs), and others, of which only a few investigations have been performed at present. Many of the toxic effects of emerging DLCs were observed to be predominantly mediated by the AHR because of their structural similarity as dioxins, and the in vitro TCDD-relative potencies of certain emerging DLC congeners are comparable to or even greater than the WHO-TEFs of OctaCDD, OctaCDF, and most coplanar PCBs. Due to the close relationship between AHR biology and environmental science, this review begins by providing novel insights into AHR signaling (canonical and non-canonical), AHR's biochemical properties (AHR structure, AHR-ligand interaction, AHR-DNA binding), and the variations during AHR transactivation. Then, AHR ligand classification and the corresponding mechanisms are discussed, especially the shared and compound-specific, AHR-mediated effects and mechanisms of emerging DLCs. Accordingly, a series of in vivo and in vitro toxicity evaluation methods based on the AHR signaling pathway are reviewed. In light of current advances, future research on traditional and emerging DLCs will enhance our understanding of their mechanisms, toxicity, potency, and ecological impacts.
- Klíčová slova
- AHR ligands, Aryl hydrocarbon receptor, Dioxin-like compounds, Molecular mechanisms, Toxicity evaluation,
- MeSH
- dioxiny * toxicita MeSH
- karbazoly MeSH
- krysa rodu Rattus MeSH
- polychlorované bifenyly * MeSH
- potkani Sprague-Dawley MeSH
- receptory aromatických uhlovodíků genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- dioxiny * MeSH
- karbazoly MeSH
- polychlorované bifenyly * MeSH
- receptory aromatických uhlovodíků MeSH
Polychlorinated biphenyls (PCBs) are persistent, bioaccumulative and toxic contaminants in the environment. Individual PCB congeners exhibit different physico-chemical properties and biological activities which result in different environmental distributions and toxicity profiles. The variable composition of PCB residues in environmental matrices and their different mechanisms of toxicity, complicate the development of scientifically based regulations for the risk assessment. Various approaches for the assessment of risks of PCBs have been critically examined. Recent developments in the toxic equivalency factor (TEF) approach for the assessment of toxic effects due to dioxin-like PCBs have been examined. PCB exposure studies which describe non-dioxin-like toxic effects, particularly neuro-behavioral effects and their effective doses in animals were also considered. A comparative assessment of effective doses for dioxin-like and non-dioxin-like effects by PCBs was made to evaluate the relative significance of non-ortho and ortho-substituted PCBs in risk assessment. Using mink as an example, relative merits and implications of using TEF and total PCB approaches for assessing the potential for toxic effects in wildlife was examined.
- MeSH
- dioxiny toxicita MeSH
- divoká zvířata MeSH
- hodnocení rizik * MeSH
- polychlorované bifenyly toxicita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Geografické názvy
- Spojené státy americké MeSH
- Názvy látek
- dioxiny MeSH
- polychlorované bifenyly MeSH
The environmental contaminant 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) belongs to the category of highly toxic, persistent organic pollutants that accumulate in animal fat and plant tissues. Today, background TCDD levels in human fat are showing a decreasing trend. The food chain is the main source of exposure in the human population. TCDD regulates the expression of a wide range of drug-metabolizing enzymes and has an impact on a large number of biological systems. The most pronounced effects have occurred in occupational settings following the uncontrolled formation of TCDD after industrial accidents, as well as in rare intentional intoxications. Although the acute effects of TCDD exposure are well described in the literature, the long-term consequences have been underevaluated. The most well-known symptoms of severe acute intoxication are chloracne, porphyria, transient hepatotoxicity, and peripheral and central neurotoxicity. Because of the long-term persistence of TCDD in the human body, atherosclerosis, hypertension, diabetes, vascular ocular changes, and signs of neural system damage, including neuropsychological impairment, can be present several decades after massive exposure. Such chronic effects are nonspecific, multifactorial, and may be causally linked to TCDD only in heavily intoxicated subjects. This opinion is supported by the dose-dependent effect of TCDD found in exposed workers and by experimental animal studies.
- MeSH
- ateroskleróza chemicky indukované MeSH
- diabetes mellitus chemicky indukované MeSH
- hypertenze chemicky indukované MeSH
- látky znečišťující životní prostředí toxicita MeSH
- lidé MeSH
- nemoci nervového systému chemicky indukované MeSH
- oční nemoci chemicky indukované MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- látky znečišťující životní prostředí MeSH
- polychlorované dibenzodioxiny MeSH
Aerobic composting and anaerobic digestion plays an important role in reduction of organic waste by transforming the waste into humus, which is an excellent soil conditioner. However, applications of chemical-contaminated composts on soils may have unwanted consequences such as accumulation of persistent compounds and their transfer into food chains. The present study investigated burden of composts and digestates collected in 16 European countries (88 samples) by the compounds causing dioxin-like effects as determined by use of an in vitro transactivation assay to quantify total concentrations of aryl hydrocarbon receptor-(AhR) mediated potency. Measured concentrations of 2,3,7,8-Tetrachlorodibeno-p-dioxin (2,3,7,8-TCDD) equivalents (TEQbio) were compared to concentrations of polycyclic aromatic hydrocarbons (PAHs) and selected chlorinated compounds, including polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), co-planar polychlorinated biphenyls (PCBs), indicator PCB congeners and organochlorine pesticides (OCPs). Median concentrations of TEQbio (dioxin-like compounds) determined by the in vitro assay in crude extracts of various types of composts ranged from 0.05 to 1.2 with a maximum 8.22μg (TEQbio)kg(-1) dry mass. Potencies were mostly associated with less persistent compounds such as PAHs because treatment with sulfuric acid removed bioactivity from most samples. The pan-European investigation of contamination by organic contaminants showed generally good quality of the composts, the majority of which were in compliance with conservative limits applied in some countries. Results demonstrate performance and added value of rapid, inexpensive, effect-based monitoring, and points out the need to derive corresponding effect-based trigger values for the risk assessment of complex contaminated matrices such as composts.
- Klíčová slova
- Biodetection tools, Compost, Digestate, Dioxin, Effect-based monitoring, PAHs,
- MeSH
- biotest MeSH
- chlorované uhlovodíky analýza farmakologie MeSH
- dioxiny analýza farmakologie MeSH
- hodnocení rizik MeSH
- krysa rodu Rattus MeSH
- látky znečišťující půdu analýza farmakologie MeSH
- nádorové buněčné linie MeSH
- polycyklické aromatické uhlovodíky analýza farmakologie MeSH
- půda chemie MeSH
- receptory aromatických uhlovodíků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- chlorované uhlovodíky MeSH
- dioxiny MeSH
- látky znečišťující půdu MeSH
- polycyklické aromatické uhlovodíky MeSH
- půda MeSH
- receptory aromatických uhlovodíků MeSH
OBJECTIVES: The aim of this study, performed in 2008, was to evaluate the consequences of severe occupational intoxication with 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) that occurred during production of the herbicide trichlorophenoxyacetic acid in the period 1965-1968. DESIGN: Examination of 11 men, mean age 64.4+/-1.5 years, included: internal and neurological examination, eye fundus examination, TCDD in plasma, thyroid-stimulating hormone (TSH), testosterone and serum lipids, ultrasonography of the carotid artery, nerve conduction study (NCS), electroencephalography (EEG), visual evoked potential (VEP), Lanthony test of acquired visual impairment, single photon emission computer tomography (SPECT) of the brain, neuropsychological examination and carbohydrate-deficient transferrin (CDT), a marker of chronic ethanol intake. RESULTS: Mean TCDD level in 2008 was still 274.0+/-181.2 pg/g blood lipids (reference level is 2-3 pg/g). All (100%) patients had residues of chloracne/chloracne consequences, atherosclerotic changes on the eye fundus and plaques in the carotid arteries. Progression of intima-media thickness (IMT) from a mean of 0.84+/-0.14 mm in 2003 to 1.09+/-0.18 mm in 2008 was observed. Ninety-one per cents of patients had impairment in SPECT of the brain; and 55% of patients had hyperfixation of the perfusion indicator as a measure of increased neuronal activity. Additionally, 91 % of patients were treated for hyperlipidaemia, 73 % for hypertension, 55 % for diabetes type 2, 45 % for ischemic heart disease, and 36 % for psychological disorders. The Lanthony test demonstrated acquired dyschromatopsia in 80 % of patients. Mean colour confusion index (CCI) was 1.438, which indicates impairment since 2003, when the index was 1.302. CDT was in the normal range and did not correlate with CCI. Neuropsychological status appeared stabilized in all 8 patients examined, with impairment in one or more parameter (memory, attention, verbal fluency, psychomotor speed, motorics) in comparison to the norm. CONCLUSION: Forty years after intoxication, the blood level of TCDD is still 100 times higher than in the general population. Other PCDD/Fs were not elevated. A high percentage of subjects suffer from neurological and vascular disorders. No association of alcohol consumption with neurological impairment was seen, and the highly significant correlation between CCI and TCDD blood concentration suggests that acquired colour impairment was associated with TCDD but not with alcohol consumption. IMT significantly increased during past 5 years. The patients obviously need complex treatment, including intense hypolipidaemic and antidepressant therapy.
- MeSH
- cholesterol krev MeSH
- chronická nemoc epidemiologie MeSH
- látky znečišťující životní prostředí krev toxicita MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- polychlorované dibenzodioxiny krev toxicita MeSH
- pracovní expozice * MeSH
- prevalence MeSH
- triglyceridy krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cholesterol MeSH
- látky znečišťující životní prostředí MeSH
- polychlorované dibenzodioxiny MeSH
- triglyceridy MeSH
Aryl hydrocarbon receptor (AhR) is a transcription factor, the activity of which is modulated by hormones including glucocorticoids and estrogens. In this study, we examined the effects of triiodothyronine (T3), a ligand and activator of thyroid hormone receptor (TR), on transcriptional activity of AhR and the expression of its target gene CYP1A1. Study was carried out in human hepatocellular carcinoma cells HepG2 and primary cultures of human hepatocytes (HH). Gene reporter assay in stably transfected AZ-AhR cells revealed that T3 dose-dependently augmented 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible AhR-dependent luciferase activity. In contrast, T3 had no effect on TCDD-inducible expression of CYP1A1 mRNA, protein and catalytic activity. Incubation of human hepatocytes with T3 had modulatory and inter-individual (7 cell cultures from 7 different liver donors) effects on both basal and dioxin-inducible CYP1A1/2. Since there was no correlation between T3 effects on CYP1A expression and T3-dependent expression of Spot14 mRNA, the involvement of additional factors besides TR is supposed. Overall, the co-incubation of normal and cancer human hepatic cells with TCDD and T3 suggested transcriptional cross-talk between AhR and TR, which may have physiological and toxicological implications.
- Klíčová slova
- CYP1A2, Dioxin receptor, Receptors cross-talk, S14, Triiodothyronine,
- MeSH
- buňky Hep G2 MeSH
- cytochrom P-450 CYP1A1 biosyntéza genetika MeSH
- dospělí MeSH
- hepatocyty účinky léků metabolismus MeSH
- induktory cytochromu P450 CYP1A2 toxicita MeSH
- interakce mezi receptory a ligandy MeSH
- kokultivační techniky MeSH
- lidé středního věku MeSH
- lidé MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- receptory aromatických uhlovodíků genetika metabolismus MeSH
- receptory thyreoidních hormonů metabolismus MeSH
- senioři MeSH
- trijodthyronin farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- CYP1A1 protein, human MeSH Prohlížeč
- cytochrom P-450 CYP1A1 MeSH
- induktory cytochromu P450 CYP1A2 MeSH
- polychlorované dibenzodioxiny MeSH
- receptory aromatických uhlovodíků MeSH
- receptory thyreoidních hormonů MeSH
- trijodthyronin MeSH