Non-invasive detection of drug toxicity in rats by solid-phase extraction and MALDI-TOF analysis of urine samples.

An access to fast and non-invasive techniques to infer or predict the drug-induced injury caused by newly developed drugs and to monitor therapeutic efficacy of established drugs during treatment are of the outmost importance in pharmaceutical industry and clinical diagnosis. Peptidome and low molecular weight proteome profiling is an emerging technique that allows the recognition of distinctive patterns and differentiation among diverse physiopathological conditions. In this article, we evaluated the utility of peptide/small protein profiling using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) coupled with WCX magnetic bead-based solid-phase extraction as a screening tool for drug toxicity assessment in urine samples. Given that drug-induced injury is primarily reflected in liver, three different, well-described hepatotoxic drugs were chosen for this work. These were: carbon tetrachloride (CCl(4)) which induces liver fibrosis, D(+)-galactosamine as a model for acute liver injury, and Escherichia coli-derived lipopolysaccharide to study the damage caused by endotoxins. The profiles obtained with a correct clustering analysis show that this methodology can be used as a non-invasive and straightforward approach to test for potential drug toxicity. Pharmaceutical research and drug development studies could benefit from this methodology as liver injury inducer compounds could be easily detected in vivo by non-invasive means, accelerating the launch of safer drugs to the market.

Bimetallic iron-aluminum particles for dechlorination of carbon tetrachloride.

Bimetallic iron-aluminum (Fe/Al) particles were synthesized and tested for their reactivity toward carbon tetrachloride using batch reactors and a flow-through column at near neutral pH. Preparation of bimetallic Fe/Al particles was conducted under acidic conditions under which iron was readily deposited onto the aluminum surface. The SEM image showed clusters of iron on the aluminum surface at the measured Fe:Al molar ratio of about 2:3. Results showed that the presence of zero-valent aluminum successfully prevented the formation of a passive layer at the iron surface and maintained the reactivity of iron. The dechlorination of carbon tetrachloride by bimetallic Fe/Al particles produced chloroform (9%), dichloromethane (17%) and methane (38%). Kinetic analysis suggests that bimetallic Fe/Al particles increased the reactivity toward carbon tetrachloride degradation by a factor of 10 compared to zero-valent iron and possessed a comparable reactivity with nano-sized Fe. The effectiveness of bimetallic Fe/Al particles was further confirmed by the continuous flow column study from which an ageing of bimetallic particles was also observed.

Degradation of aqueous carbon tetrachloride by nanoscale zerovalent copper on a cation resin.

Nanoscale zerovalent copper supported on a cation resin was successfully synthesized to enhance the removal of carbon tetrachloride (CCl(4)) from contaminated water. The use of the cation resin as a support prevents the reduction of surface area due to agglomeration of nanoscale zerovalent copper particles. Moreover, the cation resin recycles the copper ions resulting from the reaction between CCl(4) and Cu(0) by simultaneous ion exchange. The decline in the amount of CCl(4) in aqueous solution results from the combined effects of degradation by nanoscale zerovalent copper and sorption by the cation resin; thus the amount of CCl(4) both in aqueous solution and sorbed onto the resin were measured. The pseudo-first-order rate constant normalized by the surface-area and the mass concentration of nanoscale zerovalent copper (k(SA)) was 2.1+/-0.1 x 10(-2)lh(-1)m(-2), approximately twenty times that of commercial powdered zerovalent copper (0.04 mm). Due to the exchange between Cu(2+) and the strongly acidic ions (H(+) or Na(+)), the pH was between 3 and 4 in unbuffered solution and Cu(2+) at the concentration of less than 0.1 mg l(-1) was measured after the dechlorination reaction. In the above-ground application, resin as a support would facilitate the development of a process that could be designed for convenient emplacement and regeneration of porous reductive medium.

Laboratory batch experiments of the combined effects of ultrasound and air stripping in removing CCl4 and 1,1,1-TCA from water.

Ultrasonic and air-stripping techniques for removal of carbon tetrachloride (CCl4) and 1,1,1-trichloroethane (1,1,1-TCA) from water were studied in batch experiments. Ultrasound (US) is effective for destroying organic compounds in aqueous solutions whereas air stripping (AS) efficiently transfers volatile compounds from the liquid to the gas phase. In simultaneous US and AS experiments, synergistic effects were observed and attributed to the effect of US on the mass transfer process. Using a photographic method, ultrasonic break up of gas bubbles and changes in gas holdup ratios were examined. In the two different gas-sparging systems studied, ultrasonic waves did not break up gas bubbles. In contrast, bubbles from the smaller porous size diffuser were coalesced due to sonication. In addition, both photographic and gas holdup experiments demonstrated that ultrasonic irradiation increased the gas holdup ratio. The enhancement observed in the removal of the compounds appeared to be due to this greater ultrasonic gas holdup ratio.

A reactor model for pulsed pumping groundwater remediation.

A hybrid in situ bioremediation/pulsed pumping strategy has been developed to cost effectively remediate a carbon tetrachloride plume in Schoolcraft, Michigan. The pulsed pumping system uses a line of alternating injection and extraction wells perpendicular to the direction of natural groundwater flow. The wells pump periodically to clean the recirculation zone between adjacent wells. During the pump-off phase, natural groundwater flow brings new contaminant into the recirculation zone. The wells are pumped again prior to breakthrough of contaminant from the recirculation zone. A computationally efficient reactor model has been developed, which conceptually divides the aquifer into injection, extraction, and recirculation zones, which are represented by a network of chemical reactors. Solute concentration histories from three-dimensional finite difference simulations and from field data confirm the reactor model predictions. The reactor model is used to investigate the optimal well configuration, pumping rate, and pumping schedule for achieving maximum pollutant degradation.

Physical and chemical properties study of the activated carbon made from sewage sludge.

Preparation of activated carbon from sewage sludge is a promising way to produce a useful adsorbent for pollutants removal as well as to dispose of sewage sludge. The objective of this study was to investigate the physical and chemical properties of the activated carbon made from sewage sludge so as to give a basic understanding of its structure. The activated carbon was prepared by activating anaerobically digested sewage sludge with 5 M ZnCl2 and thereafter pyrolyzing it at 500 degrees C for 2 h under nitrogen atmosphere. The properties investigated in the present study included its surface area and pore size distribution, its elemental composition and ash content, its surface chemistry structure and its surface physical morphology. Furthermore, its adsorption capacities for aqueous phenol and carbontetrachloride were examined. The results indicated that the activated carbon made from sewage sludge had remarkable micropore and mesopore surface areas and notable adsorption capacities for phenol and carbon-tetrachloride. In comparison with commercial activated carbons, it displayed distinctive physical and chemical properties.

Enhanced remediation of carbon tetrachloride by Fe(II)-Fe(III) systems in the presence of copper ions.

The effect of Cu(II) ion on the dechlorination of carbon tetrachloride (CT) by Fe(II) associated with various iron oxides was investigated. Iron oxides including goethite, hematite, ferrihydrite and magnetite were selected as the model compounds. CT was dechlorinated to chloroform (CF) by 3 mM Fe(II) in iron oxide suspensions at pH 7.2. The dechlorination followed pseudo first-order kinetics and the pseudo first-order rate constants (k(obs)) were 0.048 h(-1), 0.0836 h(-1), 0.0609 h(-1) and 0.0144 h(-1) in goethite-, hematite-, ferrihydrite- and magnetite-amended systems, respectively. Addition of Cu(II) into systems increased the k(obs) for CT dechlorination significantly. A 3- to 120-fold increase in k(obs) relative to the systems without Cu(II) was observed when 0.5 mM Cu(II) was added to the Fe(II)-Fe(III) suspensions. The pH of the system is an important factor controlling the dechlorination rate of CT. The increase in concentrations of Fe(II) and iron oxides also enhanced the dechlorination efficiency and rate of CT. Moreover, a linear relationship between the k(obs) and Cu(II) concentration ranging between 0 and 0.4 mM was observed. Results obtained demonstrate the feasibility of using surface-bound iron species with Cu(III) for the detoxification of chlorinated solvents in the contaminated aquifers.

[Catalytic reduction of CCl4 in water by Fe0 and amended Fe0].

Various bimetallic reductants of Cu/Fe, Ag/Fe, Pd/Fe and Ni/Fe were prepared by plating Cu, Ag, Pd and Ni on the surface of Fe0. Reductive dechlorination of toxic pollutants of CCl4 in water with Fe0 and amended Fe0 by batch experiments was investigated. Results show that CCl4 in water can be rapidly dechlorinated by above five catalytic reductants, and the presence of Cu, Ag, Pd can enhance the dechlorination rate dramatically. The reaction of CCl4 with various reductants was followed the pseudo first order kinetics, and the dechlorination rate constant of CCl4 in water by Fe0, Cu/Fe, Ag/Fe, Pd/Fe and Ni/Fe was 0.0393, 0.0925, 0.158, 0.0496 and 0.0533 min(-1) respectively. The byproducts and pathway of dechlorination of CCl4 by Fe0 and amended Fe0 was identified by GC/MS. Results indicate that the products and dechlorination rate of CCl4 by various bimetallic reductants are varied. The main products are chloroform and dichloromethane in Cu/Fe and Ag/Fe system, and that is methane in Pd/Fe system. Hydrogenolysis is the dominant reaction pathway of CCl4 by Fe0 and amended Fe0.

Enhanced phytoremediation of volatile environmental pollutants with transgenic trees.

Small, volatile hydrocarbons, including trichloroethylene, vinyl chloride, carbon tetrachloride, benzene, and chloroform, are common environmental pollutants that pose serious health effects. We have developed transgenic poplar (Populus tremula x Populus alba) plants with greatly increased rates of metabolism and removal of these pollutants through the overexpression of cytochrome P450 2E1, a key enzyme in the metabolism of a variety of halogenated compounds. The transgenic poplar plants exhibited increased removal rates of these pollutants from hydroponic solution. When the plants were exposed to gaseous trichloroethylene, chloroform, and benzene, they also demonstrated superior removal of the pollutants from the air. In view of their large size and extensive root systems, these transgenic poplars may provide the means to effectively remediate sites contaminated with a variety of pollutants at much faster rates and at lower costs than can be achieved with current conventional techniques.

Unexpected Fe local order in iron oxide coated nanocrystalline magnesium oxides with exceptional reactivities against environmental toxins.

Mg oxide nanoparticles are very reactive materials used to mitigate atmospheric pollution and to sequester polluting molecules. Using Fe K-edge XAFS, we have studied the structure of iron oxide-coated MgO nanoparticles before and after reaction with CCl4. Before reaction, the local structure around Fe is totally different from that in iron oxide coatings on SrO and CaO nanoparticles, although these coated materials were prepared in the same way. In SrO and CaO, the iron oxide coating has been shown to be well separated from the bulk of the nanoparticle, whereas in MgO, Fe was found to mix with MgO. After reaction with CCl4, Fe-Cl bonds can be detected when the coated nanoparticle is saturated. Such Fe-Cl EXAFS signals have not been observed in previously studied nanoparticles.

Mechanisms and products of surface-mediated reductive dehalogenation of carbon tetrachloride by Fe(II) on goethite.

Natural attenuation processes of chlorinated solvents in soils and groundwaters are increasingly considered as options to manage contaminated sites. Under anoxic conditions, reactions with ferrous iron sorbed at iron(hyro)xides may dominate the overall transformation of carbon tetrachloride (CCl4) and other chlorinated aliphatic hydrocarbons. We investigated mechanisms and product formation of CCl4 reduction by Fe(II) sorbed to goethite, which may lead to completely dehalogenated products or to chloroform (CHCl3), a toxic product which is fairly persistent under anoxic conditions. A simultaneous transfer of two electrons and cleavage of two C-Cl bonds of CCl4 would completely circumvent chloroform production. To distinguish between initial one- or two-bond cleavage, 13C-isotope fractionation of CCl4 was studied for reactions with Fe(II)/ goethite (isotopic enrichment factor epsilon = -26.5% percent per thousand) and with model systems for one C-Cl bond cleavage and either single-electron transfer (Fe(II) porphyrin, epsilon = -26.1 percent per thousand) or partial two-electron transfer (polysulfide, epsilon = -22.2 percent per thousand). These epsilon values differ significantlyfrom calculations for simultaneous cleavage of two C-Cl bonds (epsilon approximately equal to -50 percent per thousand), indicating that only one C-Cl bond is broken in the critical first step of the reaction. At pH 7, reduction of CCl4 by Fe(II)/ goethite produced approximately 33% CHCl3, 20% carbon monoxide (CO), and up to 40% formate (HCOO-). Addition of 2-propanol-d8 resulted in 33% CDCl3 and only 4% CO, indicating that both products were generated from trichloromethyl radicals (*CCl3), chloroform by reaction with hydrogen radical donors and CO by an alternative pathway likely to involve surface-bound intermediates. Hydrolysis of CO to HCOO-was surface-catalyzed by goethite butwastoo slow to account for the measured formate concentrations. Chloroform yields slightly increased with pH at constant Fe(II) sorption density, suggesting that pH-dependent surface processes direct product branching ratios. Surface-stabilized intermediates may thus facilitate abiotic mineralization of CCl4, whereas the presence of H radical donors, such as natural organic matter, enhances formation of toxic CHCl3.