Mechanistic insights into the synergistic activation of the RXR-PXR heterodimer by endocrine disruptor mixtures.

Humans are chronically exposed to mixtures of xenobiotics referred to as endocrine-disrupting chemicals (EDCs). A vast body of literature links exposure to these chemicals with increased incidences of reproductive, metabolic, or neurological disorders. Moreover, recent data demonstrate that, when used in combination, chemicals have outcomes that cannot be predicted from their individual behavior. In its heterodimeric form with the retinoid X receptor (RXR), the pregnane X receptor (PXR) plays an essential role in controlling the mammalian xenobiotic response and mediates both beneficial and detrimental effects. Our previous work shed light on a mechanism by which a binary mixture of xenobiotics activates PXR in a synergistic fashion. Structural analysis revealed that mutual stabilization of the compounds within the ligand-binding pocket of PXR accounts for the enhancement of their binding affinity. In order to identify and characterize additional active mixtures, we combined a set of cell-based, biophysical, structural, and in vivo approaches. Our study reveals features that confirm the binding promiscuity of this receptor and its ability to accommodate bipartite ligands. We reveal previously unidentified binding mechanisms involving dynamic structural transitions and covalent coupling and report four binary mixtures eliciting graded synergistic activities. Last, we demonstrate that the robust activity obtained with two synergizing PXR ligands can be enhanced further in the presence of RXR environmental ligands. Our study reveals insights as to how low-dose EDC mixtures may alter physiology through interaction with RXR-PXR and potentially several other nuclear receptor heterodimers.

Metabolism of benzo[a]pyrene after low-dose subchronic exposure to an industrial mixture of carcinogenic polycyclic aromatic hydrocarbons in rats: a cocktail effect study.

Polycyclic aromatic hydrocarbons (PAHs) are interesting environmental pollutants for understanding cocktail effects. High-molecular-weight-PAHs (HMW-PAHs) are classified as probable or possible carcinogens; only benzo[a]pyrene (B[a]P) is a certain carcinogen in humans. Their toxicity depends on their metabolic activation. While 3-hydroxybenzo[a]pyrene (3-OHB[a]P) represents its detoxification pathway, trans-anti-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (tetrol-B[a]P) represents the carcinogenicity pathway. The objective was to study the metabolism of B[a]P and HMW-PAHs during chronic low-dose exposure to B[a]P or a PAH mixture. Rats were exposed orally 5 times/week for 10 weeks to low-levels of B[a]P (0.02 and 0.2 mg.kg-1.d-1) or to an industrial mixture extracted from coal tar pitch (CTP) adjusted to 0.2 mg.kg-1.d-1 B[a]P. Urinary levels of monohydroxy-, diol-, and tetrol-PAH were measured during weeks 1 and 10 by HPLC-fluorescence and GC‒MS/MS. After 1 week, the percentages of B[a]P eliminated as 3-OHB[a]P and tetrol-B[a]P were not different depending on the dose of B[a]P, whereas they were reduced by half in the CTP group. Repeated exposure led to an increase in the percentages of the 2 metabolites for the 0.02-B[a]P group. Moreover, the percentage of B[a]P eliminated as 3-OHB[a]P was equal in the 0.2-B[a]P and CTP groups, whereas it remained halved for tetrol-B[a]P in the CTP group. The percent elimination of HMW-PAH metabolites did not vary between weeks 1 and 10. Thus, dose, duration of exposure and chemical composition of the mixture have a major influence on PAH metabolism that goes beyond a simple additive effect. This work contributes to the reflection on determination of limit values and risk assessments in a context of poly-exposures.

Pesticide impacts on avian species with special reference to farmland birds: a review.

For decades, we have observed a major biodiversity crisis impacting all taxa. Avian species have been particularly well monitored over the long term, documenting their declines. In particular, farmland birds are decreasing worldwide, but the contribution of pesticides to their decline remains controversial. Most studies addressing the effects of agrochemicals are limited to their assessment under controlled laboratory conditions, the determination of lethal dose 50 (LD50) values and testing in a few species, most belonging to Galliformes. They often ignore the high interspecies variability in sensitivity, delayed sublethal effects on the physiology, behaviour and life-history traits of individuals and their consequences at the population and community levels. Most importantly, they have entirely neglected to test for the multiple exposure pathways to which individuals are subjected in the field (cocktail effects). The present review aims to provide a comprehensive overview for ecologists, evolutionary ecologists and conservationists. We aimed to compile the literature on the effects of pesticides on bird physiology, behaviour and life-history traits, collecting evidence from model and wild species and from field and lab experiments to highlight the gaps that remain to be filled. We show how subtle nonlethal exposure might be pernicious, with major consequences for bird populations and communities. We finally propose several prospective guidelines for future studies that may be considered to meet urgent needs.

Development of a new approach using mathematical modeling to predict cocktail effects of micropollutants of diverse origins.

A wide variety of micropollutants (MP) of diverse origins is present in waste and surface waters without knowing the effect of their combination on ecosystems and human. The impact of chemical mixtures is poorly documented and often limited to binary mixtures using MP of the same category. Knowing that it is not realistic to test every possible combination found in mixtures, we aimed to develop a new method helping to predict cocktail effects. Six chemicals of agriculture, industry or pharmaceutical origin were selected: cyproconazole, diuron, terbutryn, bisphenol A, diclofenac and tramadol. Individual MP were first used in vitro to determine the concentration at which 10% (Effective Concentration EC10) or 25% (EC25) of their maximal effect on human cytotoxicity was observed. Using an Orthogonal Array Composite Design (OACD), relevant complex mixtures were then tested. Multiple linear regression was applied for response surface modeling in order to evaluate and visualize the influence of the different MP in mixtures and their potential interactions. The comparison of the predicted values obtained using the response surface model with those obtained with the model of independent effects, evidenced that the hypothesis of independence was unjustified. The cocktail effect was further investigated by considering micropollutant response surfaces pairwise. It was deduced that there was a neutralizing effect between bisphenol A and tramadol. In conclusion, we propose a new method to predict within a complex mixture of MP the combinations likely involved in cocktail effects. The proposed methodology coupling experimental data acquisition and mathematical modeling can be applied to all kind of relevant bioassays using lower concentrations of MP. Situations at high ecological risk and potentially hazardous for humans will then be identified, which will allow to improve legislation and policies.

In Vitro Cocktail Effects of PCB-DL (PCB118) and Bulky PCB (PCB153) with BaP on Adipogenesis and on Expression of Genes Involved in the Establishment of a Pro-Inflammatory State.

(1) Objective: Highlight the in vitro effects of 3T3-L1 cell exposure to polychlorinated biphenyls (PCB118 and 153) or benzo(a)pyrene (BaP) alone or as a cocktail on adipogenesis (ADG) by focusing on changes in lipid metabolism and inflammatory-related genes expression (INFG) and ADG-related genes expression (ADGG); (2) Results: Treatment from the early stage of cell differentiation by BaP alone or in combination with PCBs decreased the expression of some of the ADGG (PPARγGlut-4, FAS, Lipin-1a, Leptin, and Adiponectin). BaP enhanced the INFG, especially MCP-1 and TNFα. Co-exposure to BaP and PCB153 showed a synergistic effect on TNFα and IL6 expression. Treatment with BaP and PCBs during only the maturation period up-regulated the INFG (IL6, TNFα, CXCL-10 & MCP-1). PCB118 alone also enhanced TNFα, CXCL-10, and PAI-1 expression. The change in MCP-1 protein expression was in agreement with that of the gene. Finally, the BaP-induced up-regulation of the xenobiotic responsive element (XRE)-controlled luciferase activity was impaired by PCB153 but not by PCB118; (3) Conclusion: BaP and PCBs down-regulate a part of ADGG and enhance INFG. The direct regulatory effect of PCBs on both ADGG and INFG is usually rather lower than that of BaP and synergistic or antagonistic cocktail effects are clearly observed.

Nickel acts as an adjuvant during cobalt sensitization.

Metal allergy is the most frequent form of contact allergy with nickel and cobalt being the main culprits. Typically, exposure comes from metal-alloys where nickel and cobalt co-exist. Importantly, very little is known about how co-exposure to nickel and cobalt affects the immune system. We investigated these effects by using a recently developed mouse model. Mice were epicutaneously sensitized with i) nickel alone, ii) nickel in the presence of cobalt, iii) cobalt alone, or iv) cobalt in the presence of nickel, and then followed by challenge with either nickel or cobalt alone. We found that sensitization with nickel alone induced more local inflammation than cobalt alone as measured by increased ear-swelling. Furthermore, the presence of nickel during sensitization to cobalt led to a stronger challenge response to cobalt as seen by increased ear-swelling and increased B and T cell responses in the draining lymph nodes compared to mice sensitized with cobalt alone. In contrast, the presence of cobalt during nickel sensitization only induced an increased CD8(+) T cell proliferation during challenge to nickel. Thus, the presence of nickel during cobalt sensitization potentiated the challenge response against cobalt more than the presence of cobalt during sensitization to nickel affected the challenge response against nickel. Taken together, our study demonstrates that sensitization with a mixture of nickel and cobalt leads to an increased immune response to both nickel and cobalt, especially to cobalt, and furthermore that the adjuvant effect appears to correlate with the inflammatory properties of the allergen.

Determination of the maximum bioaccumulation capacity of various metals in leaves of two Tillandsia species.

Tillandsia species are plants from the Bromeliaceae family which display biomonitoring capacities in both active and passive modes. The bioaccumulation potential of Tillandsia aeranthos (Loisiel.) Desf. and Tillandsia bergeri Mez acclimated to Southern/Mediterranean Europe has never been studied. More generally, few studies have detailed the maximum accumulation potential of Tillandsia leaves through controlled experiments. The aim of this study is to evaluate the maximum accumulation values of seven metals (Co, Cu, Mn, Ni, Pb, Pt, and Zn) in T. aeranthos and T. bergeri leaves. Plants were immersed in different mono elemental metallic solutions of Co (II), Cu (II), Mn (II), Ni (II), Pb (II), Pt (IV), and Zn (II) ions at different concentrations. In addition, cocktail solutions of these seven metals at different concentrations were prepared to study the main differences and the potential selectivity between metals. After exposure, the content of these metals in the leaves were measured by inductively coupled plasma-optical emission spectrometry. Data sets were evaluated by a fitted regression hyperbola model and principal component analysis, maximum metal loading capacity, and thermodynamic affinity constant were determined. The results showed important differences between the two species, with T. bergeri demonstrating higher capacity and affinity for metals than T. aeranthos. Furthermore, between the seven metals, Pb and Ni showed higher enrichment factors (EF). T. bergeri might be a better bioaccumulator than T. aeranthos with marked selectivity for Pb and Ni, metals of concern in air quality biomonitoring.

Combined effects of micropollutants and their degradation on prokaryotic communities at the sediment-water interface.

Pesticides and pharmaceuticals enter aquatic ecosystems as complex mixtures. Various processes govern their dissipation and effect on the sediment and surface waters. These micropollutants often show persistence and can adversely affect microorganisms even at low concentrations. We investigated the dissipation and effects on procaryotic communities of metformin (antidiabetic drug), metolachlor (agricultural herbicide), and terbutryn (herbicide in building materials). These contaminants were introduced individually or as a mixture (17.6 µM per micropollutant) into laboratory microcosms mimicking the sediment-water interface. Metformin and metolachlor completely dissipated within 70 days, whereas terbutryn persisted. Dissipation did not differ whether the micropollutants were introduced individually or as part of a mixture. Sequence analysis of 16S rRNA gene amplicons evidenced distinct responses of prokaryotic communities in both sediment and water. Prokaryotic community variations were mainly driven by matrix composition and incubation time. Micropollutant exposure played a secondary but influential role, with pronounced effects of recalcitrant metolachlor and terbutryn within the micropollutant mixture. Antagonistic and synergistic non-additive effects were identified for specific taxa across taxonomic levels in response to the micropollutant mixture. This study underscores the importance of considering the diversity of interactions between micropollutants, prokaryotic communities, and their respective environments when examining sediment-water interfaces affected by multiple contaminants.

High-Entropy Materials for Prospective Biomedical Applications: Challenges and Opportunities.

With their unique structural characteristics, customizable chemical composition, and adjustable functional characteristics, high-entropy materials (HEMs) have triggered a wide range of interdisciplinary research, especially in the biomedical field. In this paper, the basic concept, core properties, and preparation methods of HEMs are first summarized, and then the application and development of HEMs in the field of biomedical are briefly described. Subsequently, based on the diverse and comprehensive properties of HEMs and a few reported cases, the possible application scenarios of HEMs in biological fields such as biosensors, antibacterial materials, therapeutics, bioimaging, and tissue engineering are prospectively predicted and discussed. Finally, their potential advantages and major challenges is summarized, which may provide useful guidance and principles for researchers to develop and optimize novel HEMs.

Dendritic quinary PtRhMoCoFe high-entropy alloy as a robust immunosensing nanoplatform for ultrasensitive detection of biomarker.

Recently, high-entropy alloys have superior physicochemical properties as compared to conventional alloys for their glamorous "cocktail effect". Nevertheless, they are scarcely applied to electrochemical immunoassays until now. Herein, uniform PtRhMoCoFe high-entropy alloyed nanodendrites (HEANDs) were synthesized by a wet-chemical co-reduction method, where glucose and oleylamine behaved as the co-reducing agents. Then, a series of characterizations were conducted to illustrate the synergistic effect among multiple metals and fascinating structural characteristics of PtRhMoCoFe HEANDs. The obtained high-entropy alloy was adopted to build a electrochemical label-free biosensor for ultrasensitive bioassay of biomarker cTnI. In the optimized analytical system, the resultant sensor exhibited a dynamic linear range of 0.0001-200 ng mL-1 and a low detection limit of 0.0095 pg mL-1 (S/N = 3). Eventually, this sensing platform was further explored in serum samples with satisfied recovery (102.0 %). This research renders some constructive insights for synthesis of high-entropy alloys and their expanded applications in bioassays and bio-devices.

High-Entropy MXene as Bifunctional Mediator toward Advanced Li-S Full Batteries.

The development of high-energy-density Li-S batteries (LSBs) is still hindered by the disturbing polysulfide shuttle effect. Herein, with clever combination between "high entropy" and MXene, an HE-MXene doped graphene composite containing multiple element quasi-atoms as bifunctional mediator for separator modification (HE-MXene/G@PP) in LSBs is proposed. The HE-MXene/G@PP offers high electrical conductivity for fast lithium polysulfide (LiPS) redox conversion kinetics, abundant metal active sites for efficient chemisorption with LiPSs, and strong lipophilic characteristics for uniform Li+ deposition on lithium metal surface. As demonstrated by DFT theoretical calculations, in situ Raman, and DRT results successively, HE-MXene/G@PP efficiently captures LiPSs through synergistic modulation of the cocktail effect and accelerates the LiPSs redox reaction, and the lattice distortion effect effectively induces the homogeneous deposition of dendritic-free lithium. Therefore, this work achieves excellent long-term cycling performance with a decay rate of 0.026%/0.031% per cycle after 1200 cycles at 1 C/2 C. The Li||Li symmetric cell still maintains a stable overpotential after 6000 h under 40 mA cm-2/40 mAh cm-2. Furthermore, it delivers favorable cycling stability under 7.8 mg cm-2 and a low E/S ratio of 5.6 µL mg-1. This strategy provides a rational approach to resolve the sulfur cathode and lithium anode problems simultaneously.

Comparative effects of trace metal elements released from dissolution of aluminum-based galvanic anodes, aluminum chloride, zinc chloride, and their mixture on the development of the Pacific oyster D-larvae, Crassostrea gigas.

As the most abundant metal in the earth's crust, aluminum (Al) is used in many sectors, and nowadays, there is an increase in anthropogenic releases to aquatic ecosystems. This is particularly true in the context of corrosion protection systems involving galvanic anodes, which are mostly made of Al. Corroded instead of the steel structures they protect, galvanic anodes are described as sacrificial anodes. In contact with seawater, they undergo oxidation and release various metals in the form of ions or oxy-hydroxides into the marine environment, mainly Al and zinc (Zn). Several studies agree that Al increases the incidence of abnormal development in bivalve larvae from 150 µg L-1 which is close to the highest Al concentrations recorded in coastal waters. Therefore, we studied the impact of the cocktail of metals released by aluminum-based galvanic anodes on the development of Crassostrea gigas larvae, which we compared to the effects of aluminum chloride hexahydrate and zinc chloride alone and their mixture. The anode solution was realized thanks to an experimental device simulating the dissolution of a galvanic anode in the marine environment in order to reproduce the cocktail of metal species. We calculated an EC50 of 193.55 µg L-1 and 100.05 µg L-1 for Al and Zn chloride alone, respectively, and we highlighted an EC50 of 190.22 µg L-1 for the galvanic anode based on Al concentration. The mixture of the two metals in their chloride form resulted in the observation of additive and synergistic effects, which underlines the importance of considering the cocktail effect in ecotoxicological studies.

Non-target biotransformation enzymes as a target for triazole-zinc mixtures.

Triazoles inhibit lanosterol 14α-demethylase and block ergosterol biosynthesis in fungal pathogens. However, they also interact with other cytochrome P450 enzymes and influence non-target metabolic pathways. Disturbingly, triazoles may interact with essential elements. The interaction of penconazole (Pen), cyproconazole (Cyp) and tebuconazole (Teb) with Zn2+ results in the formation of deprotonated ligands in their complexes or in the creation of complexes with Cl- as a counterion or doubly charged complexes. Triazoles, as well as their equimolar cocktails with Zn2+ (10-6 mol/L), decreased the activities of the non-target enzymes CYP19A1 and CYP3A4. Pen most decreased CYP19A1 activity and was best bound to its active centre to block the catalytic cycle in computational analysis. For CYP3A4, Teb was found to be the most effective inhibitor by both, activity assay and interaction with the active centre. Teb/Cyp/Zn2+ and Teb/Pen/Cyp/Zn2+ cocktails also decreased the CYP19A1 activity, which was in correlation with the formation of numerous triazole-Zn2+ complexes.

High Entropy Sulfide Nanoparticles as Lithium Polysulfide Redox Catalysts.

The polysulfide shuttle contributes to capacity loss in lithium-sulfur batteries, which limits their practical utilization. Materials that catalyze the complex redox reactions responsible for the polysulfide shuttle are emerging, but foundational knowledge that enables catalyst development remains limited with only a small number of catalysts identified. Here, we employ a rigorous electrochemical approach to show quantitatively that the lithium polysulfide redox reaction is catalyzed by nanoparticles of a high entropy sulfide material, Zn0.30Co0.31Cu0.19In0.13Ga0.06S. When 2% by weight of the high entropy sulfide is added to the lithium sulfur cathode composite, the capacity and Coulombic efficiency of the resulting battery are improved at both moderate (0.2 C) and high (1 C) charge/discharge rates. Surface analysis of the high entropy sulfide nanoparticles using X-ray photoelectron spectroscopy provides important insights into how the material evolves during the cycling process. The Zn0.30Co0.31Cu0.19In0.13Ga0.06S nanoparticle catalyst outperformed the constituent metal sulfides, pointing to the role that the high-entropy "cocktail effect" can play in the development of advanced electrocatalytic materials for improved lithium sulfur battery performance.

Atomic Diffusion Rate Dominated Fabrication of High Entropy Phosphide with Heterogeneous Aggregation for Oxygen Evolution Reaction.

The synthesis of high-entropy phosphide (HEP) remains a great challenge owing to the different migration rates of different metallic atoms. Herein, a new metal organic gel (MOG) precursor strategy is proposed for HEP synthesis by controlling the migration rate of different atoms in an organic gel. The MOG precursor with five kinds of metal and phosphor species homogeneously dispersing is formed through a facile solvothermal method, which is calcined at 900 °C to obtain carbon-supported HEP FeCoNiMnCdP (MPC-5). The difference in the atom radius and the influence of MOG on the migration rate result in heterogeneous aggregation of different atoms in the product, which increases the defects in the product to a certain extent. In addition, the presence of carbon and nitrogen in the gel simultaneously realizes carbon coating and nitrogen doping. Combining the above advantages, the MPC-5 shows excellent oxygen evolution reaction (OER) catalytic performance with an overpotential of 250 mV at 10 mA·cm-2, superior to many recently reported OER electrocatalysts. This work provides a new strategy to solve the differences in the migration rates of different metals to obtain pure phase high-entropy phosphides, which is conducive to the further development of high-entropy materials and their applications in the energy and catalysis fields.

High-content analysis shows synergistic effects of low perfluorooctanoic acid (PFOS) and perfluorooctane sulfonic acid (PFOA) mixture concentrations on human breast epithelial cell carcinogenesis.

Perfluoroalkyl substances (PFAS) have been associated with cancer, but the potential underlying mechanisms need to be further elucidated and include studies of PFAS mixtures. This mechanistic study revealed that very low concentrations (500 pM) of the binary PFOS and PFOA mixture induced synergistic effects on human epithelial breast cell (MCF-10A) proliferation. The cell proliferation was mediated by pregnane X receptor (PXR) activation, an increase in cyclin D1 and CDK6/4 levels, decrease in p21 and p53 levels, and by regulation of phosphor-Akt and ß-catenin. The PFAS mixture also altered histone modifications, epigenetic mechanisms implicated in tumorigenesis, and promoted cell migration and invasion by reducing the levels of occludin. High-content screening using the cell painting assay, revealed that hundreds of cell features were affected by the PFAS mixture even at the lowest concentration tested (100 pM). The detailed phenotype profiling further demonstrated that the PFAS mixture altered cell morphology, mostly in parameters related to intensity and texture associated with mitochondria, endoplasmic reticulum, and nucleoli. Exposure to higher concentrations (≥50 µM) of the PFOS and PFOA mixture caused cell death through synergistic interactions that induced oxidative stress, DNA/RNA damage, and lipid peroxidation, illustrating the complexity of mixture toxicology. Increased knowledge about mixture-induced effects is important for better understanding of PFAS' possible role in cancer etiology, and may impact the risk assessment of these and other compounds. This study shows the potential of image-based multiplexed fluorescence assays and high-content screening for development of new approach methodologies in toxicology.

High-Entropy Co-Free O3-Type Layered Oxyfluoride: A Promising Air-Stable Cathode for Sodium-Ion Batteries.

Sodium-ion batteries have recently emerged as a promising alternative to lithium-based batteries, driven by an ever-growing demand for electricity storage systems. The present workproposes a cobalt-free high-capacity cathode for sodium-ion batteries, synthesized using a high-entropy approach. The high-entropy approach entails mixing more than five elements in a single phase; hence, obtaining the desired properties is a challenge since this involves the interplay between different elements. Here, instead of oxide, oxyfluoride is chosen to suppress oxygen loss during long-term cycling. Supplement to this, lithium is introduced in the composition to obtain high configurational entropy and sodium vacant sites, thus stabilizing the crystal structure, accelerating the kinetics of intercalation/deintercalation, and improving the air stability of the material. With the optimization of the cathode composition, a reversible capacity of 109 mAh g-1 (2-4 V) and 144 mAh g-1 (2-4.3 V) is observed in the first few cycles, along with a significant improvement in stability during prolonged cycling. Furthermore, in situ and ex situ diffraction studies during charging/discharging reveal that the high-entropy strategy successfully suppresses the complex phase transition. The impressive outcomes of the present work strongly motivate the pursuit of the high-entropy approach to develop efficient cathodes for sodium-ion batteries.

Feeding on grains containing pesticide residues is detrimental to offspring development through parental effects in grey partridge.

Numerous toxicological studies have shown that ingestion of pesticides can induce physiological stress in breeding birds, with adverse consequences on egg laying parameters and offspring quality through parental effects. However, previous studies do not mimic current levels of pesticide residues in typical landscapes, and they do not consider potential cocktail effects of pesticides as they occur in the wild. Herein, we explored whether realistic pesticide exposure affected reproduction parameters and offspring condition through parental effects in Grey partridge. We fed 24 breeding pairs with either seeds from conventional agriculture crops treated with various pesticides during cropping, or organic grains without pesticide residues as controls. The conventional and organic grain diets mimicked food options potentially encountered by wild birds in the field. The results showed that ingesting low pesticide doses over a long period had consequences on reproduction and offspring quality without altering mortality in parents or chicks. Compared with organic pairs, conventional pairs yielded smaller chicks at hatching that had a lower body mass index at 24 days old. Additionally, these chicks displayed lower haematocrit when body mass index was higher. Therefore, ingestion of conventional grains by parents resulted in chronic exposure to pesticide residues, even at low doses, and this had detrimental consequences on offspring. These results demonstrate a sublethal effect of pesticide residues through parental effects. The consequences of parental exposure on chicks might partly explain the decline in wild Grey partridge populations, which raises questions for avian conservation and demography if current agrosystem approaches are continued.

Commercial Fungicide Toxic Effects on Terrestrial Non-Target Species Might Be Underestimated When Based Solely on Active Ingredient Toxicity and Standard Earthworm Tests.

The ecosystem services provided by earthworms are lost when land management reduces their populations, hence, the importance of thorough assessments of management effects on this group. The present study aimed to: (1) review the possible influence of other ingredients within the formulations of two commercial fungicides; (2) assess the sublethal effects of these commercial fungicides on Eisenia fetida; and (3) assess the acute lethal effects of one commercial fungicide on both Glossoscolex rione and E. fetida. Examining all components of the studied commercial formulations revealed that alongside the toxic active ingredients are other ingredients that are equally as or more toxic than the former and may even be in higher concentrations. The inhibition concentration of 10% of E. fetida's progeny (IC10) was estimated at 133 mg kg−1 for PROSARO® and 1544 mg kg−1 for SWING PLUS®. Both fungicides showed an effect of hormesis on the progeny. In this first toxicity study with G. rione, it was found that this species is more sensitive to PROSARO® than E. fetida, with preliminary 14 day-lethal concentrations of 285 mg kg−1 for the former and >1000 mg kg−1 for the latter.

Ecotoxicological risk assessment of contaminants of emerging concern identified by "suspect screening" from urban wastewater treatment plant effluents at a territorial scale.

Urban wastewater treatment plants (WWTP) are a major vector of highly ecotoxic contaminants of emerging concern (CECs) for urban and sub-urban streams. Ecotoxicological risk assessments (ERAs) provide essential information to public environmental authorities. Nevertheless, ERAs are mainly performed at very local scale (one or few WWTPs) and on pre-selected list of CECs. To cope with these limits, the present study aims to develop a territorial-scale ERA on CECs previously identified by a "suspect screening" analytical approach (LC-QToF-MS) and quantified in the effluents of 10 WWTPs of a highly urbanized territory during three periods of the year. Among CECs, this work focused on pharmaceutical residue and pesticides. ERA was conducted following two complementary methods: (1) a single substance approach, based on the calculation for each CEC of risk quotients (RQs) by the ratio of Predicted Environmental Concentration (PEC) and Predicted No Effect Concentration (PNEC), and (2) mixture risk assessment ("cocktail effect") based on a concentration addition model (CA), summing individual RQs. Chemical results led to an ERA for 41 CEC (37 pharmaceuticals and 4 pesticides) detected in treated effluents. Single substance ERA identified 19 CECs implicated in at least one significant risk for streams, with significant risks for DEET, diclofenac, lidocaine, atenolol, terbutryn, atorvastatin, methocarbamol, and venlafaxine (RQs reaching 39.84, 62.10, 125.58, 179.11, 348.24, 509.27, 1509.71 and 3097.37, respectively). Mixture ERA allowed the identification of a risk (RQmix > 1) for 9 of the 10 WWTPs studied. It was also remarked that CECs leading individually to a negligible risk could imply a significant risk in a mixture. Finally, the territorial ERA showed a diversity of risk situations, with the highest concerns for 3 WWTPs: the 2 biggest of the territory discharging into a large French river, the Rhône, and for the smallest WWTP that releases into a small intermittent stream.