We performed a mixture risk assessment (MRA) case study of dietary exposure to the food contaminants lead, methylmercury, inorganic arsenic (iAs), fluoride, non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and polybrominated diphenyl ethers (PBDEs), all substances associated with declines in cognitive abilities measured as IQ loss. Most of these chemicals are frequently measured in human biomonitoring studies. A component-based, personalised modified reference point index (mRPI) approach, in which we expressed the exposures and potencies of our chosen substances as lead equivalent values, was applied to perform a MRA for dietary exposures. We conducted the assessment for four different age groups (toddlers, children, adolescents, and women aged 18-45 years) in nine European countries. Populations in all countries considered exceeded combined tolerable levels at median exposure levels. NDL-PCBs in fish, other seafood and dairy, lead in grains and fruits, methylmercury in fish and other seafoods, and fluoride in water contributed most to the combined exposure. We identified uncertainties for the likelihood of co-exposure, assessment group membership, endpoint-specific reference values (ESRVs) based on epidemiological (lead, methylmercury, iAs, fluoride and NDL-PCBs) and animal data (PBDE), and exposure data. Those uncertainties lead to a complex pattern of under- and overestimations, which would require probabilistic modelling based on expert knowledge elicitation for integration of the identified uncertainties into an overall uncertainty estimate. In addition, the identified uncertainties could be used to refine future MRA for cognitive decline.
- MeSH
- Arsenic * MeSH
- Dioxins * MeSH
- Fluorides MeSH
- Halogenated Diphenyl Ethers MeSH
- Humans MeSH
- Methylmercury Compounds * MeSH
- Adolescent MeSH
- Lead MeSH
- Polybrominated Biphenyls * MeSH
- Polychlorinated Biphenyls * MeSH
- Polychlorinated Dibenzodioxins * MeSH
- Mercury * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Dioxins adverse effects MeSH
- Endocrine Disruptors * pharmacology classification adverse effects MeSH
- Phenols adverse effects MeSH
- Child Nutritional Physiological Phenomena MeSH
- Nutritional Physiological Phenomena MeSH
- Glycine max adverse effects MeSH
- Phthalic Acids adverse effects MeSH
- Environmental Pollutants adverse effects MeSH
- Humans MeSH
- Obesity etiology MeSH
- Conservation of Natural Resources methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Popular Work MeSH
Sphingolipids (SLs) are important signaling molecules and functional components of cellular membranes. Although SLs are known as crucial regulators of neural cell physiology and differentiation, modulations of SLs by environmental neurotoxicants in neural cells and their neuronal progeny have not yet been explored. In this study, we used in vitro models of differentiated neuron-like cells, which were repeatedly exposed during differentiation to model environmental toxicants, and we analyzed changes in sphingolipidome, cellular morphology and gene expression related to SL metabolism or neuronal differentiation. We compared these data with the results obtained in undifferentiated neural cells with progenitor-like features. As model polychlorinated organic pollutants, we used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3'-dichlorobiphenyl (PCB11) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153). PCB153 revealed itself as the most prominent deregulator of SL metabolism and as potent toxicant during early phases of in vitro neurogenesis. TCDD exerted only minor changes in the levels of analysed lipid species, however, it significantly changed the rate of pro-neuronal differentiation and deregulated expression of neuronal markers during neurogenesis. PCB11 acted as a potent disruptor of in vitro neurogenesis, which induced significant alterations in SL metabolism and cellular morphology in both differentiated neuron-like models (differentiated NE4C and NG108-15 cells). We identified ceramide-1-phosphate, lactosylceramides and several glycosphingolipids to be the most sensitive SL species to exposure to polychlorinated pollutants. Additionally, we identified deregulation of several genes related to SL metabolism, which may be explored in future as potential markers of developmental neurotoxicity.
- MeSH
- Cell Differentiation drug effects MeSH
- Cell Line MeSH
- Environmental Pollutants toxicity MeSH
- Neurogenesis drug effects MeSH
- Neurons drug effects metabolism MeSH
- Neurotoxicity Syndromes etiology genetics MeSH
- Polychlorinated Biphenyls pharmacology toxicity MeSH
- Polychlorinated Dibenzodioxins toxicity MeSH
- Sphingolipids metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
This study presents four years ambient monitoring data of seventeen 2,3,7,8-chlorine substituted polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), twelve dioxin-like polychlorinated biphenyls (dl-PCBs) and sixteen polycyclic aromatic hydrocarbons (PAHs) designed by the US EPA at a background site in central Europe during 2011-2014. The concentrations expressed as toxic equivalents (TEQs) using the WHO2005-scheme for PCDD/Fs (0.2 fg m-3-61.1 fg m-3) were higher than for dl-PCBs (0.01 fg m-3-2.9 fg m-3), while the opposite was found in terms of mass concentrations. ΣPAHs ranged from 0.20 ng m-3 to 134 ng m-3. The mass concentration profile of PCDD/Fs, dl-PCBs and PAHs was similar throughout the four years. PCDD/Fs and PAHs concentrations were dominated by primary sources peaking in winter, while those of dl-PCBs were controlled by secondary sources characterized by a spring-summer peak. During 2011-2014, no significant decrease in the atmospheric levels of ΣPCDD/Fs was observed. On the other hand, the concentrations of Σdl-PCBs and ΣPAHs were decreasing, with halving times of 5.7 and 2.7 years, respectively. We estimated that 422 pg m-2 year-1-567 pg m-2 year-1 TEQ PCDD/Fs and 3.48 pg m-2 year-1-15.8 pg m-2 year-1 TEQ dl-PCBs were transferred from the air to the ground surfaces via dry particulate deposition during 2011-2014.
- MeSH
- Air Pollutants analysis MeSH
- Environmental Monitoring MeSH
- Polychlorinated Biphenyls analysis MeSH
- Polychlorinated Dibenzodioxins analysis MeSH
- Dibenzofurans, Polychlorinated analysis MeSH
- Polycyclic Aromatic Hydrocarbons analysis MeSH
- Seasons MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Brominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) are increasingly reported at significant levels in various matrices, including consumer goods that are manufactured from plastics containing certain brominated flame retardants. PBDD/Fs are known ligands for the aryl hydrocarbon receptor (AhR) but are not yet considered in the hazard assessment of dioxin mixtures. The aim of the present study was to determine if PBDD/Fs levels present in plastic constituents of toys could pose a threat to children's health. PBDD/Fs, unlike their chlorinated counterparts (PCDD/Fs), have not been officially assigned toxic equivalence factors (TEFs) by the WHO therefore, we determined their relative potency towards AhR activation in both human and rodent cell-based DR CALUX® bioassays. This allowed us to compare GC-HRMS PBDD/F congener levels, converted to total Toxic Equivalents (TEQ) by using the PCDD/F TEFs, to CALUX Bioanalytical Equivalents (BEQ) levels present in contaminated plastic constituents from children's toys. Finally, an estimate was made of the daily ingestion of TEQs from PBDD/Fs-contaminated plastic toys by child mouthing habits. It is observed that the daily ingestion of PBDD/Fs from contaminated plastic toys may significantly contribute to the total dioxin daily intake of young children.
- MeSH
- Biological Assay MeSH
- Cell Line MeSH
- Child MeSH
- Play and Playthings * MeSH
- Rats MeSH
- Environmental Pollutants analysis toxicity MeSH
- Humans MeSH
- Luciferases genetics MeSH
- Environmental Monitoring methods MeSH
- Plastics chemistry standards MeSH
- Gas Chromatography-Mass Spectrometry MeSH
- Polychlorinated Dibenzodioxins analysis toxicity MeSH
- Dibenzofurans, Polychlorinated analysis toxicity MeSH
- Child, Preschool MeSH
- Receptors, Aryl Hydrocarbon genetics MeSH
- Genes, Reporter MeSH
- Flame Retardants analysis toxicity MeSH
- Transfection MeSH
- Animals MeSH
- Check Tag
- Child MeSH
- Rats MeSH
- Humans MeSH
- Child, Preschool MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The aryl hydrocarbon receptor (AhR) activation has been shown to alter proliferation, apoptosis, or differentiation of adult rat liver progenitors. Here, we investigated the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated AhR activation on a human model of bipotent liver progenitors, undifferentiated HepaRG cells. We used both intact undifferentiated HepaRG cells, and the cells with silenced Hippo pathway effectors, yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), which play key role(s) in tissue-specific progenitor cell self-renewal and expansion, such as in liver, cardiac, or respiratory progenitors. TCDD induced cell proliferation in confluent undifferentiated HepaRG cells; however, following YAP, and, in particular, double YAP/TAZ knockdown, TCDD promoted induction of apoptosis. These results suggested that, unlike in mature hepatocytes, or hepatocyte-like cells, activation of the AhR may sensitize undifferentiated HepaRG cells to apoptotic stimuli. Induction of apoptosis in cells with silenced YAP/TAZ was associated with upregulation of death ligand TRAIL, and seemed to involve both extrinsic and mitochondrial apoptosis pathways. Global gene expression analysis further suggested that TCDD significantly altered expression of constituents and/or transcriptional targets of signaling pathways participating in control of expansion or differentiation of liver progenitors, including EGFR, Wnt/β-catenin, or tumor growth factor-β signaling pathways. TCDD significantly upregulated cytosolic proapoptotic protein BMF (Bcl-2 modifying factor) in HepaRG cells, which could be linked with an enhanced sensitivity of TCDD-treated cells to apoptosis. Our results suggest that, in addition to promotion of cell proliferation and alteration of signaling pathways controlling expansion of human adult liver progenitors, AhR ligands may also sensitize human liver progenitor cells to apoptosis.
- MeSH
- Adaptor Proteins, Signal Transducing genetics MeSH
- Apoptosis drug effects genetics MeSH
- Models, Biological * MeSH
- Cell Line MeSH
- Gene Expression drug effects MeSH
- Liver drug effects pathology MeSH
- Stem Cells drug effects pathology MeSH
- Humans MeSH
- RNA, Small Interfering genetics MeSH
- Polychlorinated Dibenzodioxins toxicity MeSH
- Cell Proliferation drug effects genetics MeSH
- Receptors, Aryl Hydrocarbon metabolism MeSH
- Signal Transduction MeSH
- Trans-Activators genetics MeSH
- Transfection MeSH
- Transcription Factors genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Bioactive compounds such as karrikinolide (KAR1 from smoke) and eckol (from the seaweed Ecklonia maxima) show promising effects on several important crop plants. These plant growth-stimulating organic biomolecules, along with crude extracts (smoke-water and Kelpak® product prepared from Ecklonia maxima), were tested on spinach plants. Eckol sprayed at 10-6 M significantly increased all the growth and biochemical parameters examined compared to control spinach plants. All tested plant growth biostimulants significantly increased total chlorophyll, carotenoids and protein content of spinach leaves. The cytokinin profile of spinach plants was also determined. Cis-zeatin, dihydrozeatin and isopentenyladenine types of cytokinins were promoted by both smoke- and seaweed-based biostimulants. In comparison to the control plants, the level of free sinapic acid was greater in all spinach plants treated with these biostimulants. The application of these biostimulants can help spinach crop by improving growth, yield and nutritional quality; moreover, they are organic and cost-effective.
- MeSH
- Cytokinins metabolism MeSH
- Dioxins isolation & purification pharmacology MeSH
- Furans isolation & purification pharmacology MeSH
- Hydroxybenzoates metabolism MeSH
- Smoke analysis MeSH
- Seaweed chemistry MeSH
- Phaeophyceae chemistry MeSH
- Pyrans isolation & purification pharmacology MeSH
- Plant Growth Regulators isolation & purification pharmacology MeSH
- Spinacia oleracea drug effects growth & development metabolism MeSH
- Crops, Agricultural drug effects growth & development metabolism MeSH
- Publication type
- Journal Article MeSH
Persistent organic pollutants (POPs) including PCDD/Fs, PCBs and organochlorine pesticides (OCPs) are among the most important and hazardous pollutants of soil. Food producing animals such as chicken, beef, sheep and goats can take up soil while grazing or living outdoors (free-range) and this can result in contamination. In recent decades, large quantities of brominated flame retardants such as polybrominated diphenyl ethers (PBDEs), short-chain chlorinated paraffins (SCCPs) and per- and polyfluorinated alkylated substances (PFAS) have been produced and released into the environment and this has resulted in widespread contamination of soils and other environmental matrices. These POPs also bioaccumulate and can contaminate food of animal origin resulting in indirect exposure of humans. Recent assessments of chicken and beef have shown that surprisingly low concentrations of PCBs and PCDD/Fs in soil can result in exceedances of regulatory limits in food. Soil contamination limits have been established in a number of countries for PCDD/Fs but it has been shown that the contamination levels which result in regulatory limits in food (the maximum levels in the European Union) being exceeded, are below all the existing soil regulatory limits. 'Safe' soil levels are exceeded in many areas around emission sources of PCDD/Fs and PCBs. On the other hand, PCDD/F and dioxin-like PCB levels in soil in rural areas, without a contamination source, are normally safe for food producing animals housed outdoors resulting in healthy food (e.g. meat, eggs, milk). For the majority of POPs (e.g. PBDEs, PFOS, PFOA, SCCP) no regulatory limits in soils exist. There is, therefore, an urgent need to develop appropriate and protective soil standards minimising human exposure from food producing animals housed outdoors. Furthermore, there is an urgent need to eliminate POPs pollution sources for soils and to control, secure and remediate contaminated sites and reservoirs, in order to reduce exposure and guarantee food safety.
- MeSH
- Food Safety * MeSH
- Soil Pollutants analysis MeSH
- Humans MeSH
- Meat analysis MeSH
- Environmental Monitoring legislation & jurisprudence methods MeSH
- Polychlorinated Biphenyls analysis MeSH
- Polychlorinated Dibenzodioxins analysis MeSH
- Dibenzofurans, Polychlorinated analysis MeSH
- Soil chemistry standards MeSH
- Eggs analysis MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Hearing loss is an injury that can develop over time, and people may not even be aware of it until it becomes a severe disability. Ototoxicants are substances that may damage the inner ear by either affecting the structures in the ear itself or by affecting the nervous system. We have examined the possibility that ototoxicants may present a health hazard in association with environmental exposures, adding to existing knowledge of their proven hazards under medical therapeutic conditions or occupational activities. In addition to the already described human environmental ototoxicants, mainly organochlorines such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), hexachlorocyclohexane (HCH) and hexachlorobenzene (HCB), we have examined the ubiquitous chemical stressors phthalates, bisphenol A/S/F/, PFCs, flame retardants (FRs) and cadmium for potential ototoxic properties, both as single substances or as chemical mixtures. Our literature review confirmed that these chemicals may disturb thyroid hormones homeostasis, activate aryl hydrocarbon receptor (AhR), and induce oxidative stress, which in turn may initiate a chain of events resulting in impairment of cochlea and hearing loss. With regard to auditory plasticity, diagnostics of a mixture of effects of ototoxicants, potential interactions of chemical and physical agents with effects on hearing, parallel deterioration of hearing due to chemical exposures and ageing, metabolic diseases or obesity, even using specific methods as brainstem auditory evoked potentials (BAEP) or otoacoustic emissions (OAEs) registration, may be difficult, and establishment of concentration-response relationships problematic. This paper suggests the establishment of a class of environmental oxotoxicants next to the established classes of occupational and drug ototoxicants. This will help to properly manage risks associated with human exposure to chemical stressors with ototoxic properties and adequate regulatory measures.
- MeSH
- Hydrocarbons, Chlorinated MeSH
- Dichlorodiphenyl Dichloroethylene MeSH
- Environmental Pollutants MeSH
- Humans MeSH
- Polychlorinated Biphenyls MeSH
- Polychlorinated Dibenzodioxins MeSH
- Dibenzofurans, Polychlorinated MeSH
- Ear, Inner drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The Gulf of Follonica (Italy) is impacted by the chemical pollution from ancient mining activity and present industrial processes. This study was aimed to determine the bioavailability of dioxin-like compounds (DLCs) in coastal marine environment and to assess the genotoxic potential of waste waters entering the sea from an industrial canal. Moderately high levels of DCLs compounds (∑ PCDDs + PCDFs 2.18–29.00 pg/g dry wt) were detected in Mytilus galloprovincialis transplanted near the waste waters canal and their corresponding Toxic Equivalents (TEQs) calculated. In situ exposed mussels did not show any genotoxic effect (by Comet and Micronucleus assay). Otherwise, laboratory exposure to canal waters exhibited a reduced genomic template stability (by RAPD-PCR assay) but not DNA or chromosomal damage. Our data reveal the need to focus on the levels and distribution of DLCs in edible species from the study area considering their potential transfer to humans through the consumption of sea food.
- MeSH
- Biological Availability MeSH
- Water Pollutants, Chemical analysis toxicity MeSH
- Dioxins analysis toxicity MeSH
- Humans MeSH
- Environmental Monitoring methods MeSH
- Mutagens analysis chemistry toxicity MeSH
- Mytilus drug effects genetics MeSH
- Random Amplified Polymorphic DNA Technique MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Italy MeSH
