ABSTRACT
Chemically induced steatosis is characterized by lipid accumulation associated with mitochondrial dysfunction, oxidative stress and nucleus distortion. New approach methods integrating in vitro and in silico models are needed to identify chemicals that may induce these cellular events as potential risk factors for steatosis and associated hepatotoxicity. In this study we used high-content imaging for the simultaneous quantification of four cellular markers as sentinels for hepatotoxicity and steatosis in chemically exposed human liver cells in vitro. Furthermore, we evaluated the results with a computational model for the extrapolation of human oral equivalent doses (OED). First, we tested 16 reference chemicals with known capacities to induce cellular alterations in nuclear morphology, lipid accumulation, mitochondrial membrane potential and oxidative stress. Then, using physiologically based pharmacokinetic modeling and reverse dosimetry, OEDs were extrapolated from data of any stimulated individual sentinel response. The extrapolated OEDs were confirmed to be within biologically relevant exposure ranges for the reference chemicals. Next, we tested 14 chemicals found in food, selected from thousands of putative chemicals on the basis of structure-based prediction for nuclear receptor activation. Amongst these, orotic acid had an extrapolated OED overlapping with realistic exposure ranges. Thus, we were able to characterize known steatosis-inducing chemicals as well as data-scarce food-related chemicals, amongst which we confirmed orotic acid to induce hepatotoxicity. This strategy addresses needs of next generation risk assessment and can be used as a first chemical prioritization hazard screening step in a tiered approach to identify chemical risk factors for steatosis and hepatotoxicity-associated events.
Subject(s)
Chemical and Drug Induced Liver Injury , Drug-Related Side Effects and Adverse Reactions , Fatty Liver , Humans , Orotic Acid , Fatty Liver/chemically induced , Chemical and Drug Induced Liver Injury/etiology , LipidsABSTRACT
Among pharmaceutical products (PPs) recalcitrant to water treatments, diclofenac shows a high toxicity and remains at high concentration in natural aquatic environments. The aim of this study concerns the understanding of the adsorption mechanism of this anionic PP onto two organoclays prepared with two long-alkyl chains cationic surfactants showing different chemical nature for various experimental pH and temperature conditions. The experimental data obtained by a set of complementary techniques (X-ray diffraction, elemental analyses, gas chromatography coupled with mass spectrometry, and Fourier transform infrared spectroscopy) and the use of Langmuir, Freundlich and Dubinin-Radushkevish equation models, reveal that organoclays show a good affinity to diclofenac which is enhanced as the temperature is under 35°C and for pH above 4.5 (i.e. >pKa of diclofenac) while the chemical nature of surfactant appears to play a minor role. The thermodynamic parameters derived from the fitting procedure point out the strong electrostatic interaction with organic cations adsorbed within the interlayer space in the organoclays for the adsorption of diclofenac. This study stress out the application of organoclays for the adsorption of a recalcitrant PPs in numerous aquatic compartments that can be used as a complement with activated carbon for waste water treatment.
Subject(s)
Aluminum Silicates/chemistry , Diclofenac/chemistry , Surface-Active Agents/chemistry , Adsorption , Algorithms , Bentonite , Clay , Diclofenac/isolation & purification , Hydrogen-Ion Concentration , Models, Statistical , Temperature , Thermodynamics , Water Pollutants, ChemicalABSTRACT
The effects of temperature, time, solvent and sonication conditions under air and Argon are described for the preparation of micron and sub-micron sized vermiculite particles in a double-jacketed Rosett-type or cylindrical reactor. The resulting materials were characterized via X-ray powder diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Fourier Transform Infrared (FTIR) Spectroscopy, BET surface area analysis, chemical analysis (elemental analysis), Thermogravimetry analysis (TGA) and Laser Granulometry. The sonicated vermiculites displayed modified particle morphologies and reduced sizes (observed by scanning electron microscopy and laser granulometry). Under the conditions used in this work, sub-micron sized particles were obtained after 5h of sonication, whereas longer times promoted aggregation again. Laser granulometry data revealed also that the smallest particles were obtained at high temperature while it is generally accepted that the mechanical effects of ultrasound are optimum at low temperatures according to physical/chemical properties of the used solvent. X-ray diffraction results indicated a reduction of the crystallite size along the basal direction [001]; but structural changes were not observed. Sonication at different conditions also led to surface modifications of the vermiculite particles brought out by BET surface measurements and Infrared Spectroscopy. The results indicated clearly that the efficiency of ultrasound irradiation was significantly affected by different parameters such as temperature, solvent, type of gas and reactor type.
ABSTRACT
Smectites are usually used as a clay barrier at the bottom of subsurface waste landfills due to their low permeability and their capacity to retain pollutants. The Na- and Ca-saturated SWy2 montmorillonites were interacted with initial Zn(NO(3))(2) or Pb(NO(3))(2) concentrations ranging from 10(-6) to 10(-2)M with a solid/liquid ratio of 10 g L(-1) and using acetic acid/acetate as buffer at pH 5 in order to reproduce a biodegradable leachate of a young landfill. These experiments revealed that Zn and Pb sorption onto Na-SWy2 is higher than that onto Ca-SWy2 in the whole range of concentrations. Metal retention into both montmorillonites increases with the decrease in acetic acid/acetate concentration. The two-site protolysis model with no electrostatic term (2SPNE model) was used to model these experiments. As the experimental data of Zn sorption were well fitted, this model was validated and has been improved by taking into account the metal-acetate complexation in solution. In order to validate the model for Pb sorption, new selectivity coefficients have been determined, namely logK(c)(PbNa)=0.5 for Na-montmorillonite and logK(c)(PbCa)=0.3 for Ca-montmorillonite.