International audience | Current European Union regulation regarding polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in food and feed is based on Toxic Equivalent Quotient (TEQ) concept. For confirmatory purpose, the isotope-dilution method associated to a measurement by gas chromatography coupled with high resolution mass spectrometry is usually the method of choice for precisely measuring the 29 target congeners in three separated fractions. Time and cost related to these analyses are very significant. Various kinds of screening concepts can be considered. In the present study, we elaborated and validated a prediction model for the 2005 World Health Organization TEQ in fish, based on the measurement of 4 PCDD/F and 2 non-ortho dl-PCB congeners, potentially analyzable in a single extracted fraction by gas chromatography coupled with mass spectrometry. Large independent datasets have been used for model elaboration (n = 108) and validation (n = 363, n = 357 and n = 6).

After the exploitation of coal mines in the 19th and 20th centuries in northern France, many mining slag heaps (SH) were left without any particular management or monitoring. Currently, the influence of these SHs on the quality of surrounding wetlands is hardly known.The purpose of this work is to determine the water quality in the neighbourhood of two SHs located near the city of Douai and its influence on the distribution of aquatic invertebrates in local wetlands. Our approach involves (1) the spatial and temporal characterization of the water composition (anions, major elements, sulphide, DOC and alkalinity) and of the biological diversity (aquatic invertebrates) and (2), based on this chemical and biological screening, the establishment of relationships between water quality and biodiversity distribution through multivariate data analysis. The results clearly indicate that substantial leaching from the slag heaps occurs, given the very high concentrations of dissolved sulphates (in the range of 2 g L⁻¹). While the pH remains weakly basic, indicating that the leaching water has been neutralized by the highly carbonated regional substratum, high levels of biodegradable organic matter and sulphate contents have been noticed. They sporadically cause significant drops in dissolved oxygen and the occurrence of dissolved sulphides that massively reduce biodiversity, qualitatively and quantitatively. In Summer, oxygen saturation is generally lower due to the higher rate of organic matter degradation, and the risk of anoxic episodes therefore increases. Finally, as wetlands are vulnerable environments, these preliminary results suggest that monitoring and management of these sites must be attempted quickly to avoid the degradation of those valuable habitats.

Ny-Ålesund, one of four permanent settlements on Spitsbergen in Svalbard, is a research town that includes scientific institutes from many countries. Because of daily-used chemicals (e.g., pharmaceutical and personal care products (PPCPs)) used by residents in the area, generated sewage is considered as a point source in the Kongsfjorden. The aim of the present study was to identify and quantify organic pollutants in the effluent and along the shoreline and offshore via target, suspect, and non-target screening using liquid chromatography–high-resolution mass spectrometry. We tentatively identified 30 compounds using the suspect and non-target screening methods in effluent samples from our first visit to the settlement in 2016. Among these, 3 were false positive, 24 were confirmed, and the 3 remaining compounds were not confirmed because of a lack of reference standards. Of the confirmed, 21 were quantifiable and considered target compounds for the 2nd year study. The quantified compounds in the effluent samples in 2017 totaled 17, including PPCPs, pesticides, perfluorinated compounds, and their metabolites. Some of the compounds, such as caffeine, paraxanthine/theophylline, acetaminophen, cetirizine, diethyl toluamide (DEET), and icaridin, were also detected in the receiving seawater. The concentration range was from 4 to 280,000 ng/L in the effluent and 2–98 ng/L in the seawater. Other 24 compounds were tentatively identified in the second-year effluent samples. Five were further confirmed using reference standards. Prioritization was performed on the 47 substances screened in Ny-Ålesund using the exposure and toxicity index. As the result, the top seven substances of concern present were perfluorooctanesulfonic acid (PFOS), triphenyl phosphate (TPHP), irbesartan, DEET, acetaminophen, caffeine, and paraxanthine/theophylline. As the effluent was identified as a source of the concerned organic pollutants, an emission reduction strategy should take place for protection of Arctic Fjorden environment.

Aryl phosphorus-containing flame retardants (aryl-PFRs) have been frequently detected with increasingly used worldwide as one of alternatives for brominated flame retardants. However, information on their adverse effects on human health and ecosystem is insufficient, with limited study on their molecular mode of action in vitro. In this study, the cytotoxicity, DNA damage, mitochondrial impairment and the involved molecular mechanisms of certain frequently detectable aryl-PFRs, including 2-ethylhexyldiphenyl phosphate (EHDPP), methyl diphenyl phosphate (MDPP), bisphenol-A bis (diphenyl phosphate) (BDP), isodecyl diphenyl phosphate (IDPP), cresyl diphenyl phosphate (CDP) and the structurally similar and widely used organophosphorus pesticide chlorpyrifos (CPF), were evaluated in A549 cells using high-content screening (HCS) system. Aryl-PFRs showed different lethal concentration 50 (LC50) values ranging from 97.94 to 546.85 μM in A549 cells using CCK-8 assay. EHDPP, IDPP, CDP, MDPP and CPF demonstrated an ability to induce DNA damage, evidenced by increased DNA content and S phase-reducing cell cycle arrest effect using fluorophore dye cocktail assay. Additionally, the selected aryl-PFRs induced mitochondrial impairment by the increasing mitochondrial mass and decreasing mitochondrial membrane potential. Moreover, BDP, MDPP, and CDP, which contain short alkyl chains showed their potential oxidative stress with intracellular ROS and mitochondrial superoxide overproduction from an initially relatively low concentration. Additionally, based on the promotion of firefly luminescence in p53-transfected A549 cells, p53 activation was found to be involved in aryl-PFRs-induced DNA damage. Further real-time PCR results showed that all selected aryl-PFRs triggered p53/p21/gadd45β-, and p53/p21/mdm2-mediated cell cycle pathways, and the p53/bax mediated apoptosis pathway to induce DNA damage and cytotoxic effects. These results suggest that aryl-PFRs (e.g., BDP, MDPP, CDP) cause oxidative stress-mediated DNA damage and mitochondrial impairment, and p53-dependent pathway was involved in the aryl-PFRs-induced DNA damage and cell cycle arrest. In conclusion, this study improves the understanding of PFRs-induced adverse outcomes and the involved molecular mechanism.

Phthalate esters (PAEs), as widely used plasticizers, have been concerned for their possible disruption of estrogen functions via binding to and activating the transcription of estrogen receptors (ERs). Nevertheless, the computational interpretation of the mechanism of ERs activities modulated by PAEs at the molecular level is still insufficient, which hinders the reliable screening of the ERs-active PAEs with high speed and high throughput. To bridge the gap, the in silico simulations considering the effects of coactivators were accomplished to explore the molecular mechanism of action for the purpose of predicting the estrogenic potencies of PAEs. The transcriptional activation functions of human ERα (hERα) modulated by PAEs is predicted via the simulations including binding interaction of PAEs and hERα, conformational changes of PAEs-hERα complexes and recruitment of coactivators. Molecular insight into the diverse estrogen mechanism of action among PAEs with regard to hERα agonists and selective estrogen receptor modulators (SERMs) is provided. Agonist-modulated conformational change of hERα leads to the optimal exposure of its Activation Function 2 (AF-2) surface which, in turn, facilitates the recruitment of coactivators, therefore promoting the transcriptional activation functions of hERα. Conversely, binding interaction of hERα with SERMs among PAEs leads to the conformational change with blocked AF-2 surface, thus preventing the recruitment of coactivators and consequently inhibiting the AF-2 activity. The two-hybrid recombinant yeast is experimentally used for verification. The established in silico evaluation methodology exhibits great promise to speed up the prediction of chemicals which work as hERα agonist or SERMs.

The information acquired by high resolution quadrupole-time of flight mass spectrometry (QTOF-MS) allows target analysis as well as retrospective screening for the presence of suspect or unknown emerging pollutants which were not included in the target analysis. Targeted quantification of eight azole antifungal drugs in wastewater effluent as well as new and relatively simple retrospective suspect and non-target screening strategy for emerging pollutants using UHPLC-QTOF-MS is described in this work. More than 300 (parent compounds and transformation products) and 150 accurate masses were included in the retrospective suspect and non-target screening, respectively. Tentative identification of suspects and unknowns was based on accurate masses, peak intensity, blank subtraction, isotopic pattern (mSigma value), compound annotation using data bases such as KEGG and CHEBI, and fragmentation pattern interpretation. In the targeted analysis, clotrimazole, fluconazole, itraconazole, ketoconazole and posaconazole were detected in the effluent wastewater sample, fluconazole being with highest average concentration (302.38 ng L⁻¹). The retrospective screening resulted in the detection of 27 compounds that had not been included in the target analysis. The suspect compounds tentatively identified included atazanavir, citalopram, climbazole, bezafibrate estradiol, desmethylvenlafaxine, losartan carboxylic acid and cetirizine, of which citalopram, estradiol and cetirizine were confirmed using a standard. Carbamazepine, atrazine, efavirenz, lopinavir, fexofenadine and 5-methylbenzotriazole were among the compounds detected following the non-targeted screening approach, of which carbamazepine was confirmed using a standard. Given the detection of the target antifungals in the effluent, the findings are a call for a wide assessment of their occurrence in aquatic environments and their role in ecotoxicology as well as in selection of drug resistant fungi. The findings of this work further highlights the practical benefits obtained for the identification of a broader range of emerging pollutants in the environment when retrospective screening is applied to high resolution and high accuracy mass spectrometric data.

Environmental chemicals such as phthalate esters may have adverse effects on anogenital distance (AGD), but the evidence in both genders has not been reviewed systematically. The objective of the present study is to conduct a systematic review and meta-analysis of studies that analyzed the relationship between exposure to phthalates and AGD. English papers published up to March 2018 were searched in PubMed, Scopus, Clarivate-Web of Science, and Google scholar. We applied fixed-effects models to calculate pooled beta coefficient [β]. In the case of heterogeneity, random-effects models were used. Using the comprehensive search strategies, 313 papers were identified and after screening, 10 of them were included in this study. In primary analyses, we found that exposure to phthalates was not associated with short AGD (β = −0.11; 95% CI, −0.27, 0.06; I² = 0%). However, results of subgroup analyses indicated that in boys, the sum of di-2-ethylhexyl phthalate (∑DEHP) metabolites had significant association with the risk of shortened anopenile distance (AGDAP) (β = −0.915, 95% CI: 1.629, −0.2) and anoscrotal distance (AGDAS) (β = −0.857, 95% CI: 1.455, −0.26). In addition, urinary monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monoisobutyl phthalate (MiBP) were associated with short AGDAP. We also observed significant association between monobenzylphthalate (MBzP) and anofourchette distance (AGDAF) in girls. Our study provided findings on significant association of exposure to ∑DEHP metabolites, MBP, MEP, and MiBP with shortened AGDAP in boys. The mechanisms of phthalates effect on AGD may involve receptors and enzymes involved in steroidgenesis, negative influence on Leydig cells, cell proliferation, gonocyte cell numbers, and testosterone production.

The Hooghly River (HR) estuary is the first deltaic off-shoot of the perennial and transboundary river, Ganga, India. HR receives industrial and domestic waste along with storm-water run-off from Kolkata city and the adjoining districts. Organic micropollutants (OMPs) have been collectively termed for plasticizers, pharmaceuticals and personal care products, which are extensively consumed and disposed in the waste streams. Hence emerging OMPs were investigated to obtain the first baseline data from the Hooghly riverine sediment (HRS) along urban and suburban transects using gas chromatography mass spectrometry (GC-MS). The concentration range of OMPs in the HRS varied between 3 and 519 ng/g for carbamazepine, 5–407 ng/g for non-steroidal anti-inflammatory drugs (NSAIDs), 2–26 ng/g for musk ketone, 2–84 ng/g for triclosan, 2–199 ng/g for bisphenol A (BPA), 2–422 ng/g for plasticizers (phthalic acid esters (PAEs) and bis (2-ethylhexyl) adipate (DEHA)) and 87–593 ng/g for parabens. Carbamazepine concentration in sediment was an useful marker for untreated wastewater in urban waterways. High concentrations of BPA and PAEs in the suburban industrial corridor together with significant correlation between these two type of OMPs (r2 = 0.5; p < 0.01) likely reflect a common source, possibly associated with the plastic and electronic scrap recycling industries. Among all the categories of OMPs, plasticizers seems to exhibit maximum screening level ecological risk through out the study area.

Several organic contaminants (OCs) have been detected in bald eagle (Haliaeetus leucocephalus) nestling (eaglet) plasma in the upper Midwestern United States. Despite frequent and relatively high concentrations of OCs in eaglets, little is understood about potential biological effects associated with exposure. We screened an existing database of OC concentrations in eaglet plasma collected from the Midwestern United States against bioactivity information from the ToxCast database. ToxCast bioactivity information consists of concentrations expected to elicit responses across a range of biological space (e.g. cellular, developmental, etc.) obtained from a series of high throughput assays. We calculated exposure—activity ratios (EAR) by calculating the ratio of plasma concentrations to concentrations available in ToxCast. Bioactivity data were not available for all detected OCs. Therefore, our analysis provides estimates of potential bioactivity for 19 of the detected OCs in eaglet plasma. Perfluorooctanesulfonic acid (PFOS) EAR values were consistently the highest among all study areas. Maximum EAR values were ≥1 for PFOS, perfluorononanoic acid, and bisphenol A in 99.7, 0.53 and 0.26% of samples, indicating that some plasma concentrations were greater than what may be expected to elicit biological responses. About 125 gene targets, indicative of specific biological pathways, were identified as potentially being affected. Inhibition of several CYP genes, involved in xenobiotic metabolism, were most consistently identified. Other identified biological responses have potential implications for motor coordination, cardiac functions, behavior, and blood circulation. However, it is unclear what these results mean for bald eagles, given that ToxCast data are generated using mammalian-based endpoints. Despite uncertainties and limitations, this method of screening environmental data can be useful for informing future monitoring or research focused on understanding the occurrence and effects of OCs in bald eagles and other similarly-positioned trophic species.