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Densities, r, of 2-Ethoxyethanol (EGMEE) + 1,4-Dioxane (DXN) and 2-Butoxyethanol (EGMBE) + 1,4-Dioxane (DXN) systems have been measured in the whole range of composition at an interval of 5 K ranging from 303.15 to 323.15 K. Excess molar volumes, , partial molar volumes, , thermal expansivities,a, and excess thermal expansivities, aE, have been estimated from the experimental values of ρ. All of the derived properties have been fitted to appropriate polynomials. Values of and aE were fitted to the Redlich-Kister polynomial equation and their variations with composition and temperature have been discussed in terms of molecular interaction in the mixtures. Values of and aE were all positive and were attributed due to specific interactions.

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Conductance data of some higher homologues of quaternary ammonium salts, namely, tetrapentylammonium bromide (Pen4NBr), tetrahexylammonium bromide (Hex4NBr), and tetraheptylammonium bromide (Hep4NBr) in 2-butoxyethanol (1) + water (2) mixture with 0.20, 0.40 and 0.60 mass fraction of 2-butoxyethanol were reported at 298.15, 303.15, 308.15, and 313.15 K. The 1978 Fuoss conductance-concentration equation was used to analyze the measured experimental conductance data. The values of limiting molar conductance ( Λ 0 ), ionic association constant (KA) and the association diameter (R) were obtained from the analysis. The ionic contributions to the limiting molar conductances were estimated using tetrabutylammonium tetraphenylborate (Bu4NBPh4) as the "reference electrolyte". A weak electrostatic ion solvent interaction was observed for these three salts from their calculated KA and R values. The study also revealed that in all solvent compositions and experimental temperatures, these salts exist as free ions. The association constants of the electrolytes do not vary significantly as a function of temperature. However, as the temperature was increased or solvent compositions were changed, a noticeable variation in the single-ion conductivity values as well as Walden product for the ions were seen. [ABSTRACT FROM AUTHOR]

A total of 11 bacterial strains capable of completely degrading 2-butoxyethanol (2-BE) were isolated from forest soil, a biotrickling filter, a bioscrubber, and activated sludge, and identified by 16S rRNA gene sequence analysis. Eight of these strains belong to the genus Pseudomonas; the remaining three strains are Hydrogenophaga pseudoflava BOE3, Gordonia terrae BOE5, and Cupriavidus oxalaticus BOE300. In addition to 2-BE, all isolated strains were able to grow on 2-ethoxyethanol and 2-propoxyethanol, ethanol, n-hexanol, ethyl acetate, 2-butoxyacetic acid (2-BAA), glyoxylic acid, and n-butanol. Apart from the only gram-positive strain isolated, BOE5, none of the strains were able to grow on the nonpolar ethers diethyl ether, di-n-butyl ether, n-butyl vinyl ether, and dibenzyl ether, as well as on 1-butoxy-2-propanol. Strains H. pseudoflava BOE3 and two of the isolated pseudomonads, Pseudomonas putida BOE100 and P. vancouverensis BOE200, were studied in more detail. The maximum growth rates of strains BOE3, BOE100, and BOE200 at 30 °C were 0.204 h−1 at 4 mM, 0.645 h−1 at 5 mM, and 0.395 h−1 at 6 mM 2-BE, respectively. 2-BAA, n-butanol, and butanoic acid were detected as potential metabolites during the degradation of 2-BE. These findings indicate that the degradation of 2-BE by the isolated gram-negative strains proceeds via oxidation to 2-BAA with subsequent cleavage of the ether bond yielding glyoxylate and n-butanol. Since Gordonia terrae BOE5 was the only strain able to degrade nonpolar ethers like diethyl ether, the degradation pathway of 2-BE may be different for this strain. [ABSTRACT FROM AUTHOR]

Abstract Background Studies on the hematologic toxicity of ethylene glycol ethers in humans are limited. Therefore, the aim of this study was to examine the association between exposure to solvents (containing 2-butoxyethanol and 2-ethoxyethanol) and hematological effects. Methods Thirty-four screen-printing workers who were exposed to 2-butoxyethanol and 2-ethoxyethanol and 37 non-exposed clerical workers were selected using data from the health care facilities that provided regular health screening services. Student’s t-tests and Pearson’s chi-square tests were used to compare differences in hematological parameters between the exposed and the control groups. A multivariate analysis was performed using the multiple logistic regression models to adjust for other variables. Results The chi-square test showed the reticulocyte percentages and corrected reticulocyte counts to be significantly higher in the exposed group. The t-tests showed a significant increase in white blood cell counts, reticulocyte percentages, and corrected reticulocyte count (i.e., reticulocyte index) in the exposed group, with p-values of 0.002, 0.004, and 0.002, respectively. Multivariate analysis showed the odds ratio for the corrected reticulocyte counts to be 16.30 for the exposed group, when compared with that of the control group. Conclusions Exposure to 2-butoxyethanol and 2-ethoxyethanol was significantly associated with reticulocytosis, necessitating the implementation of preventive measures for workers prone to occupational exposure to ethylene glycol ethers.

An experimental investigation was conducted to discover the effects of oxygenate mixture as additives in Jatropha biodiesel on the performance and emission characteristics of a direct injection compression ignition engine. The experiments were conducted in an instrumented single cylinder air cooled four stroke direct injection diesel engine (running at constant speed of 1500 rpm and injection timing of 26° bTDC), AC alternator and an electric loading device. Four oxygenate additives, namely, Dimethyl carbonate (C3H6O3), Ethylene glycol (C2H6O2), Propylene glycol (C3H8O2) and 2-Butoxyethanol (C6H14O2) were selected, and nine different combinational oxygenate test fuels were prepared attaining ratios of 1, 2 and 4% volume of oxygenates with biodiesel. Reduction in CO by 60%, Unburned HC by 11% and smoke emissions by 27% were observed for the test fuels without conciliating the brake thermal efficiency improvement by 6%, while NO emission increased marginally by 4%. [ABSTRACT FROM AUTHOR]

This publication reports the outcome of an acute inhalation toxicity study with guinea pigs by nose-only exposure to the substance 2-butoxyethanol at exposures close to the maximum attainable saturation vapour concentration. We describe the methods used to ensure exposure only to saturation vapour at a level as high as could be practically achieved whilst avoiding aerosol formation. We consider the practical difficulties and implications of testing substances at or close to their saturation vapour concentration and the criteria that should be used to critically assess such studies, especially with reference to the GHS (Globally Harmonised System) for classification and labelling, where a clear differentiation between gases, vapours and dust and mists applies. Guinea pigs showed no adverse effects when exposed for 4 h to the maximum attainable concentration of pure 2-butoxyethanol vapour. If guinea pigs are regarded as the most appropriate species to assess short term toxicity to humans from exposure to 2-butoxyethanol, because they are like humans not sensitive to haemolysis of red blood cells caused by exposure to the substance, then the data from this study shows that 2-butoxyethanol presents a low acute inhalation toxicity hazard. • Guinea pigs show no adverse effects when exposed by inhalation to saturated vapour of 2-butoxyethanol at 3 mg/L for 4 h. • Saturated vapour concentrations calculated according to thermodynamic laws cannot be reached in real testing setups. • 2-butoxyethanol vapour is expected to have a low acute inhalation toxicity to humans. [ABSTRACT FROM AUTHOR]

Biotrickling filter (BTF) tend to accumulate biomass leading to clogging and a subsequent increase in pressure losses and energy demands at high volatile organic compound (VOC) loadings under long-term conditions. Besides higher pressure losses and energy demands, the treatment performance gradually declines due to inhomogeneous gas distribution within the biofilm. Clogging prevention techniques are highly interesting regarding the design of BTFs, high performance levels, energy efficiency and corresponding costs. Squeezing out and backflushing as clogging prevention techniques with optional addition of auxiliary gas injections and chemicals were tested under various conditions. Five BTFs equipped with 17.6 L of different Poret ® PPI10 PU foam structures were used to analyze removal efficiencies of both biomass and 2-butoxyethanol as VOC, testing different clogging prevention techniques in comparison to two reference systems without prevention steps. Up to 109.5 g organic dry matter were removed (270 s of gas injection, 0.2 w% sodium hydroxide). With removal efficiencies of 91.7% and 72.8% and corresponding elimination capacities of 36.6 and 56.2 g C·m −3 ·h −1 the highest performance levels were achieved at specific loadings of 39.9 and 77.1 g C·m −3 ·h −1 at 12.6 s of empty bed residence time (EBRT), using a PU foam cylinder as package material. Removal efficiencies were evaluated in a pilot system with 2.1 m³ of package volume and 8.9 s of EBRT for treatment of air containing 95% 2-butoxyethanol and 5% styrene according to a waste gas problem in aviation industries. Even though additional installations like a compressor and different valves were necessary, total construction costs, total operational costs and energy costs for the BTF with clogging prevention techniques were reduced by nearly 10%, 20%, and 40% compared to conventional BTFs. Variations in microbial community over time were also tested. [ABSTRACT FROM AUTHOR]

Changes in fluid composition during hydraulic fracturing (HF) for natural gas production can impact well productivity and the water quality of the fluids returning to the surface during productivity. Shale formation conditions can influence the extent of fluid transformation. Oxidizers, such as sodium persulfate, likely play a strong role in fluid transformation. This study investigates the oxidation of 2-butoxyethanol (2-BE), a surfactant used in HF, by sodium persulfate in the presence of heat, pH changes, Fe(II), and shale rock. Increasing temperature and Fe(II) concentrations sped up 2-BE oxidation, while pH played little to no role in 2-BE degradation. The presence of shale rock impeded 2-BE oxidation with increasing shale concentrations causing decreasing pseudo-first-order reaction rate constant to be observed. Over the course of reactions containing shales, dissolved solids were tracked to better understand how reactions with minerals in the shale impact water quality. [ABSTRACT FROM AUTHOR]

Poly(acrylic acid) (PAA) is a well known weak polyelectrolyte in water but little is known about the solvation behavior of PAA in the mixtures of alcohol + water. In this study, the solvation behavior of PAA in the mixed solvents composed of 2-butoxyethanol (2BE) + water were investigated by measurements of volumetric properties, electrical conductivity, resonance light scattering and dynamic light scattering. All the measured experimental properties showed extrema or abrupt changes at a 2BE mole fraction of about 0.017 in 2BE + water. This may be explained by the formation of aggregates of 2BE and water, which is a poor solvent for PAA and results in cononsolvency of PAA in the mixture of the two good solvents, 2BE and water. We found that the volumetric property is sensitive to the occurrence of the specific aggregate of 2BE and water and the interactions in the complex fluid mixtures. [ABSTRACT FROM AUTHOR]

The effect of 2-butoxyethanol as an additive on simple gas hydrate formation in the presence of kinetic hydrate inhibitors such as modified starch, polyvinylcaprolactam, and Gaffix VC-713 under various conditions in a flow mini-loop apparatus has been studied. A laboratory flow mini-loop apparatus has been designed and manufactured to measure the induction time of simple gas hydrate formation. Hydrate formers (such as C1, C2, C3, i-C4, and CO2) are contacted with water containing dissolved inhibitor in the presence of 2-butoxyethanol as an additive at desired temperature and pressure. The effect of 2-butoxyethanol on the induction time during gas hydrate formation was investigated in the presence and absence of modified starch, polyvinylcaprolactam, and Gaffix VC-713 as kinetic inhibitors. Results show that the induction time is prolonged in the presence of Gaffix VC-713 compared to polyvinylcaprolactam and modified starch as inhibitors. Moreover, the induction time in the presence of 2-butoxyethanol is greater than in the absence of this additive for simple gas hydrate formation. As a result, the performance of kinetic hydrate inhibitors was enhanced in the presence of 2-butoxyethanol for natural gas components during gas hydrate formation. [ABSTRACT FROM AUTHOR]

2-Butoxyethanol (2-BE) is a clear colorless liquid that smells like ether. It is used as a solvent in spray lacquers, varnishes, varnish removers, herbicides, liquid soaps, cosmetics, industrial and household cleaners, and dry-cleaning compounds. 2-BE causes cellular damage via formation of reactive oxygen species. Acacia nilotica (A.nilotica) leaf extract exhibited significant antimutagenic and DNA-protective effects against oxidative damage due to the presence of alkaloids, volatile essential oils, phenols and phenolic glycosides; it is considered an excellent free radical scavenging antioxidant owing to the high number of hydroxyl groups. Silymarin (SIL) is a standardized mixture of antioxidant flavonolignans (silybin and silibinin). Silybum marianum (Milk thistle) family Asteraceae is an ancient medicinal plant from which SIL is extracted. It is a free radical scavenger and a membrane stabilizer that prevents lipid peroxidation. In the present study, we investigated the effects of extracts of A.nilotica leaves and SIL on the toxicity of 2-BE. Materials and Methods: 2-BE was given orally to male albino mice for 28 days at dose (450μl/kg b.wt). A. nilotica leaf extract (25 mg/kg b.wt) was dissolved in water and was administered orally for 14 days prior to 28 days treatment of 2-BE and during the 28 days. Also SIL (20 mg/kg b.wt) was administered orally for 14 days prior to 28 days treatment of 2BE and during the 28 days. Result: In the present work, genotoxic effects were induced by 2-BE through oral administration, and the protective effect of A. nilotica and SIL are studied. 2-BE induced a significant increase in the structural as well as numerical chromosomal aberrations. The frequency of chromosomal aberrations showed significant decrease when mice treated with A. nilotica extract and SIL. Also, there were significant increases in micronuclei. A. nilotica extract and SIL administration significant decreases micronuclei induced by 2-BE. However 2-BE induced a significant decrease in mitotic index. Administration of both A. nilotica extract and SIL significant increase mitotic index in mice treated with 2-BE. Exposure of mice to 2-BE caused significant changes in the hematological paramters as well as significant increases in the activities of serum enzymes alanine aminotransferases (ALAT), aspartate aminotransferases (ASAT) and alkaline phosphatase (ALP). Also, 2-BE induced a significant decrease in the content of liver reduced glutathione (GSH), however, induced a significant increase in the level of hepatic lipid peroxidation end product (MDA) of male mice. Coadministration of both A. nilotica extract and SIL to 2-BE-intoxicated mice ameliorated the above-mentioned parameters. Conclusion: 2-BE induced mutagenic and liver injury in male mice. A.nilotica and SIL are found to reduce the percentage of chromosomal aberration and micronuclei cells as they are a powerful antioxidant, they are able to scavenger reactive oxygen species (free radicals) formed by 2-BE in the cells, these free radicals damage DNA and hence cause defects in the chromosomes. A. nilotica extract and SIL could be used as a protective agent against mutagenic and hepatic injuries resulting from 2-BE. The protective action of SIL is more effective than A. nilotica. [ABSTRACT FROM AUTHOR]

• Diffusion and natural convection driven phase separation behaviors are explored. • Liquid-liquid phase separation rate driven by natural convection is 0.39%·s−1 on average. • Solutions with a mass fraction of 27.4∼35% present the best cooling performance. Partially miscible solutions with lower critical solution temperature (LCST) have significant potential in improving the cooling performance of microchannel heat sinks, reducing pressure drop, and ensuring stable operation of the cooling system. Thereby, it is essential and meaningful to clearly understand the liquid-liquid phase separation process driven by natural convection and diffusion to enhance the cooling performance in microchannels further. In this paper, the liquid-liquid phase separation behaviors of 2-Butoxyethanol/water solutions in a slit cavity were visually investigated. Moreover, the effect of driven force was discussed on the temperature distribution, motion of boundaries and phase separation rate. Furthermore, the effect of the mass fraction was discussed on the phase separation temperature range and phase separation rate. The results proved that the phase separation rate was kept at 0.39%·s−1 on average in the whole slit cavity by the natural convection, whereas the driving force of diffusion was so weak that the phase separation rate rapidly decreased along the vertical direction. That means reasonable enhancements of the disturbance in the microchannel could significantly increase the phase separation rate. Moreover, the phase separation rate increased with an increase in the mass fraction, and the solution with the best cooling performance could be found at 27.4%≤ ω 2- BE ≤35%. The results are expected to provide theoretical guidance to prepare solutions with suitable phase separation temperature range and excellent cooling performance. [ABSTRACT FROM AUTHOR]

EGBE is also known as 2-butoxyethanol (2BE). EGBE is widely used as a solvent in various applications, such as in surface coatings, spray lacquer, quick-dry lacquers, enamels, varnishes, varnish removers, latex paint, metal cleaners, and in commercially available cleaning products. 2-Butoxyethanol causes cellular damage via formation of reactive oxygen species. Quercetin, a flavonol group of plant flavonoid, has generated interest because of its potential antioxidant, anti-proliferative, chemoprotective and anti-inflammatory properties. Quercetin exhibited significant antimutagenic and DNA-protective effects against oxidative damage due to the presence of hydroxyl groups in the molecule; it is considered an excellent free radical scavenging antioxidant owing to the high number of hydroxyl groups. Materials and Methods: 2BE was given orally to male mice for seven days at two doses (450µl &900µl/kg b.w.). Quercetin was dissolved in corn oil. The animals in positive control group were treated with only corn oil. Quercetin (20 mg/kg b.w.) was administered orally for 7 days prior to 7 days treatment of 2BE for the two doses. Quercetin (20 mg/kg b.w.) was also administered for 14 days (7 days before and 7 days during the period of treatment with two doses of 2BE). Result: the two doses of 2BE induced both micronuclei (2.88% and 12.77%) and chromosomal aberration in (50% & 72.8%, respectively) of cells. Quercetin administration lowered the frequency of micronuclei and chromosome aberration. Conclusion: These effects of quercetin are to be taken into consideration while evaluating the possible use of quercetin as a protective agent. [ABSTRACT FROM AUTHOR]

Abstract: Coral-reef communities worldwide are in decline and one category of threats is chemical pollution. Although the Loop Current ultimately isolated the Florida reef tract from oil and oil dispersants in the aftermath of the Deepwater Horizon oil spill in 2010, the initial threat of exposure highlighted the need for reliable bioassay protocols for predicting the effects of chemical pollutants on coral-reef communities, as well as in monitoring possible exposure. Amphistegina spp. are relatively large, benthic, shelled protists (Class Foraminifera) that are common on coral reefs at euphotic depths worldwide. These foraminifers harbor algal symbionts in a relationship analogous to that of corals that host zooxanthellae, making such foraminifers useful proxies for responses of zooxanthellate corals to environmental insults. Amphistegina and other large foraminifers are easy to collect and work with in statistically rigorous sample sizes, features that have led to their use as general bioindicators of reef water quality. The goal of this study was to develop bioassay protocols for chemical pollutants utilizing Amphistegina gibbosa d'Orbigny, the species found ubiquitously on Caribbean and western Atlantic reefs. A protocol was developed to identify the 48-h Lethal Concentration (LC) 50, the concentration of a test chemical in seawater that killed 50% of the specimens during 48-h exposure. Two chemicals found in oil dispersants employed in the clean-up efforts in the Gulf of Mexico, propylene glycol and 2-butoxyethanol, were used as test chemicals. Some individuals, which had appeared to be dead at the end of the 48-h exposure period, recovered following rinsing and removal to clean seawater. This observation required further definition of an Acute Concentration (AC) 50, the concentration of chemical in seawater that killed or rendered inactive 50% of the specimens during a 48-hour exposure. We also evaluated several indicators of chronic effects of the short-term exposure. All concentrations of propylene glycol tested resulted in significantly higher incidences of bleaching (color loss in the foraminifers due to loss of, or damage to, algal symbionts). As bleaching is a common stress response in zooxanthellate corals, even short-term exposure to dispersant chemicals may increase susceptibility to bleaching. [Copyright &y& Elsevier]

Highlights: [•] Acute toxicity data for EGBE from rats or rabbits is not representative of effects in humans. [•] Hemolysis is the response elicited in rats and rabbits; humans and guinea pigs are insensitive. [•] 2-Butoxyacetic acid, a metabolite of EGBE, is responsible for the sensitivity of rats and rabbits. [•] Rat and rabbit erythrocytes are sensitive to hemolysis; those from humans and guinea pigs are not. [•] Toxicity data from guinea pigs along with supporting human data was used to classify EGBE under GHS. [Copyright &y& Elsevier]

Highlights: [•] WHO IPCS has released a guidance document on PBPK modeling in risk assessment. [•] Communication between modelers and risk assessors is key to regulatory use of models. [•] A template for model documentation is described here and in the guidance. [•] A case study is provided for 2-butoxyethanol to illustrate use of the template. [ABSTRACT FROM AUTHOR]

After the incident on the Deepwater Horizon platform, around 1.8 million gallons of dispersants were used in the field as part of the response cleanup efforts. This study describes an online solid phase extraction-liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method and a direct-injection LC-MS/MS method for the analysis of dioctyl sulfosuccinate (DOSS; a component in Corexit® EC9500A) in seawater at trace levels, with method detection limits (MDLs) of 7.0 and 440 ng/L and run times of 7 and 17 min, respectively. Stability and preservation studies demonstrated that samples at 4.7 μg/L could be preserved for up to 150 days without loss of analyte when stored with 33 % acetonitrile in glass containers. Data acquisition was performed by heated electrospray ionization (ESI) MS/MS operating in negative mode. Methods were validated in terms of percent recovery in fortified blank and matrix samples and to evaluate carryover. A simple modification of the direct-injection method allowed quantitation of 2-butoxyethanol, a dispersant component specific to the Corexit® EC9527A formulation. This method was used to simultaneously quantify DOSS and 2-butoxyethanol in two Corexit® formulations and extracts from an MC-252 source oil standard. MDLs in crude oil were 0.723 and 4.46 mg/kg, respectively, with recoveries of (92 ± 9)% for DOSS and (104 ± 8)% for 2-butoxyethanol. Detection of both indicators was achieved in a single chromatographic run by ESI-MS/MS operating sequentially in positive and negative mode. Corexit® EC9500A and Corexit® EC9527A were found to contain (21 ± 2)% and (22 ± 5)% w/w DOSS and 0 and (37 ± 2)% w/w 2-butoxyethanol, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Aggregation and microheterogeneity in dilute aqueous solutions of 2-butoxyethanol (BE) are investigated employing molecular dynamic simulations. Solutions ranging in concentration from infinite dilution to the BE mole fraction, XBE =0.06, are considered, over the temperature range 300–338.13K. This range includes temperatures both below and above the lower critical solution temperature (LCST) of BE-water solutions. At all temperatures considered, BE association begins at a very low concentration and proceeds very rapidly up to XBE ≈0.02, then continues more slowly with the BE aggregates increasing in size with increasing concentration. Physically, the aggregates are loosely formed structures with significant amounts of water remaining in the BE-rich regions. The aggregation appears mainly driven by association of the hydrophobic tails of BE. As is characteristic of entropy driven hydrophobic association, BE aggregation occurs more rapidly and the aggregates increase in size with increasing temperature. Both the aggregate size and their growth with increasing temperature are in qualitative with size estimates from small angle neutron scattering (SANS) experiments. At temperatures above the experimental LCST, we observe demixing at a value of XBE that lies within the two phase region. At higher temperatures and concentrations, the aggregate size approaches the length of the simulation cell, even when 64,000 molecules (water plus BE) are included in the sample. Finite-size effects come into play when the length scales associated with aggregation and microheterogeneity become comparable with the length of the simulation cell, and this important simulation issue is discussed. [Copyright &y& Elsevier]

Abstract: Absorption of 2-butoxyethanol (BE) from neat and aqueous solutions of BE was measured through rat skin in vitro and in vivo and through silicone membranes. Like previous studies in human and guinea pig skin, BE flux increased proportional to BE concentration only when the weight fraction of BE (w BE )0.8. Experimental values of thermodynamic activity for BE and water in aqueous solutions of BE are presented. Except when the water content in the vehicle is small, skin is fully hydrated and the flux of a BE through it is proportional to the thermodynamic activity of BE. When w BE >0.8, there is a sharp drop in the activity-normalized BE flux through skin, which coincides with a decrease in water activity from 0.9 at w BE =0.8 to zero for neat BE. These observations are consistent with reduced BE flux arising from skin dehydration. From an analysis of previously published data, the activity-normalized flux of BE through hydrated human skin was determined to be 2–4mgcm−2 h−1, which is in reasonable agreement with predictions of its maximum flux. [Copyright &y& Elsevier]

Densities, viscosities and speeds of sound, at T = 298.15 K, in the binary mixtures of nitrobenzene with 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol and 2-butoxyethanol have been measured as a function of composition. From the experimental data excess molar volumes V E, excess energies of activation for viscous flow (G* E), excess isentropic compressibility ( ) and the deviations in the viscosity (Δln η) from a mole fraction average have been calculated. The viscosity data were correlated with equations of Hind et al., Grunberg and Nissan, Frenkel, and McAllister. The results are discussed in terms of intermolecular interactions and structure of studied binary mixtures. [ABSTRACT FROM PUBLISHER]

Abstract: Relative permittivities, at T =(293.15, 298.15, 303.15, 308.15, and 313.15)K, in the binary mixtures of nitrobenzene with 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol have been measured as a function of composition. From the experimental results, the deviations in the relative permittivity at T =(293.15, 298.15, 303.15, 308.15, and 313.15)K and the excesses of temperature coefficient of relative permittivity at T =298.15K from a mole fraction average have been calculated. The results are discussed in terms of intermolecular interactions and structure of studied binary mixtures. [Copyright &y& Elsevier]

2-propoxyethanol (CE) and 2-butoxyethanol (CE) are nonionic surfactants which are a particularly interesting class of substances due to both inter-molecular and intra-molecular association, related to the presence of O and OH in the same molecule. Binary (vapor+liquid) equilibrium data were measured for cyclohexane+2-propoxyethanol and cyclohexane+2-butoxy ethanol systems at temperatures ranging from 303.15 K to 323.15 K at 10 K intervals. A static apparatus was used in this study. Two systems show positive deviation from Raoult's law and no azeotrope. The experimental data were correlated well with Peng-Robinson-Stryjek-Vera equation of state using Wong-Sandler mixing rule incorporating the non-random-two-liquid model. [ABSTRACT FROM AUTHOR]

Abstract: The density, relative permittivity, viscosity and speed of sound at T =(293.15, 298.15, 303.15, 308.15, and 313.15)K in the binary mixtures of nitromethane with 2-methoxyethanol and 2-butoxyethanol have been measured as a function of composition. From the experimental results, the excess molar volumes VE , excess Gibbs free energy of activation for viscous flow , excess isentropic compressibility and the deviations in the relative permittivity, viscosity, and speed of sound from a mole fraction average have been calculated. The viscosity data, at T =298.15K, were correlated with equations of Hind et al., Grunberg and Nissan, Frenkel, and McAllister. The results are discussed in terms of intermolecular interactions and structure of studied binary mixtures. [ABSTRACT FROM AUTHOR]

Viscosities, at T = 293.15, 298.15 and 303.15 K, in the binary mixtures of 2-butoxyethanol with ethylene glycol, diethylene glycol, triethylene glycol and tetraethylene glycol have been measured as a function of composition. The deviations in the viscosity have been calculated from the experimental data. The viscosity data, at T = 298.15 K, were correlated with equations of Hind et al. (J. Chem. Soc. Faraday Trans. 56, 328 (1960)) and Grunberg and Nissan (Nature, 164, 799 (1949)). The results are discussed in terms of intermolecular interactions and structural properties of studied binary mixtures. [ABSTRACT FROM AUTHOR]

Abstract: Female rats develop haemolytic anaemia and disseminated thrombosis and infarction in multiple organs, including bone, when exposed to 2-butoxyethanol (BE). There is growing evidence that vascular occlusion of the subchondral bone may play a part in some cases of osteoarthritis. The subchondral bone is the main weight bearer as well as the source of the blood supply to the mandibular articular cartilage. Vascular occlusion is thought to be linked to sclerosis of the subchondral bone associated with disintegration of the articular cartilage. The aim of this study was to find out whether this model of haemolysis and disseminated thrombosis supports the vascular hypothesis of osteoarthritis. Six female rats were given BE orally for 4 consecutive days and the two control rats were given tap water alone. The rats were killed 26 days after the final dose. The mandibular condyles showed histological and radiological features consistent with osteoarthritis in three of the four experimental rats and in neither of the control rats. These results may support the need to explore the vascular mechanism of osteoarthritis further. [ABSTRACT FROM AUTHOR]

Abstract: 2-Butoxyethanol increases hemangiosarcomas selectively in male mouse liver after chronic inhalation through mechanisms that have not fully been elucidated. Hemolysis, a primary toxic effect associated with 2-butoxyethanol exposure in rodents, increased hemosiderin (iron) deposition in Kupffer cells in the liver. These findings, along with the induction of hepatic neoplastic lesions, led to our hypothesis that the induction hemangiosarcomas by 2-butoxyethanol is due to the activation of Kupffer cells, subsequent to hemolysis, that results in the induction of DNA synthesis in target cells (endothelial cells); allowing for the selective proliferation of preneoplastic target cells and/or the promotion of new initiated cells. The present studies were conducted to determine whether Kupffer cells contributed to 2-butoxyethanol-induced endothelial DNA synthesis in the liver, thereby determining whether a linkage exists between these events. Male B6C3F1 mice were treated with 450 and 900mg/kg 2-butoxyethanol (via daily gavage; 5×/week) for 7 days in the presence or absence of Kupffer cell depletion (via clodronate-encapsulated liposomes). 2-Butoxyethanol (450 and 900mg/kg/day) increased the number of F4/80 stained cells (Kupffer cells) compared to controls (∼1.3- and ∼1.6-fold over control, respectively). Clodronate liposome treatment reduced the number of Kupffer cells by >90%, as assessed by F4/80 immunohistochemistry. Increased hemolysis, measured by increases in relative spleen weights and decreased hematocrit was confirmed in 2-butoxyethanol treated mice. The percentage of iron-stained endothelial cells increased by ∼11-fold over control, and endothelial cell DNA synthesis increased ∼1.7-fold over control in 2-butoxyethanol exposed mice. Importantly, Kupffer cell depletion reduced 2-butoxyethanol-induced iron staining and hepatic endothelial cell DNA synthesis. These studies provide evidence supporting the hypothesis that the Kupffer cell modulates 2-butoxyethanol-induced endothelial cell DNA synthesis, and therefore may contribute to hemangiosarcoma induction by 2-butoxyethanol. [Copyright &y& Elsevier]

To understand the molecular mechanisms underlying compound-induced hemangiosarcomas in mice, and therefore, their human relevance, a systems biology approach was undertaken using transcriptomics and Causal Network Modeling from mice treated with 2-butoxyethanol (2-BE). 2-BE is a hemolytic agent that induces hemangiosarcomas in mice. We hypothesized that the hemolysis induced by 2-BE would result in local tissue hypoxia, a well-documented trigger for endothelial cell proliferation leading to hemangiosarcoma. Gene expression data from bone marrow (BM), liver, and spleen of mice exposed to a single dose (4 h) or seven daily doses of 2-BE were used to develop a mechanistic model of hemangiosarcoma. The resulting mechanistic model confirms previous work proposing that 2-BE induces macrophage activation and inflammation in the liver. In addition, the model supports local tissue hypoxia in the liver and spleen, coupled with increased erythropoeitin signaling and erythropoiesis in the spleen and BM, and suppression of mechanisms that contribute to genomic stability, events that could be contributing factors to hemangiosarcoma formation. Finally, an immunohistochemistry method (Hypoxyprobe) demonstrated that tissue hypoxia was present in the spleen and BM. Together, the results of this study identify molecular mechanisms that initiate hemangiosarcoma, a key step in understanding safety concerns that can impact drug decision processes, and identified hypoxia as a possible contributing factor for 2-BE–induced hemangiosarcoma in mice. [ABSTRACT FROM PUBLISHER]

2-Butoxyethanol and sorbitan monolaurate are major components of oil dispersants that are applied in large quantities to control oil spill in the aquatic environment. An important question is whether aquatic animals are equipped with mechanisms for the detoxification of these oil dispersant compounds. The current study aimed to examine whether zebrafish cytosolic sulfotransferases (SULTs) are capable of sulfating 2-butoxyethanol and sorbitan monolaurate. A systematic analysis of 18 zebrafish SULTs revealed that SULT3 ST1 showed the strongest sulfating activity toward 2-butoxyethanol, while SULT1 ST3 displayed the strongest sulfating activity toward sorbitan monolaurate. The pH-dependence of these two SULTs in mediating the sulfation of 2-butoxyethanol or sorbitan monolaurate was examined. Taken together, these results implied that SULT-mediated sulfation may function in the detoxification of these two oil dispersant compounds. [ABSTRACT FROM AUTHOR]

Abstract: Densities and relative permittivities at T =(293.15, 298.15, and 303.15) K in the binary mixtures of 2-butoxyethanol with ethylene glycol, diethylene glycol, triethylene glycol and tetraethylene glycol have been measured as a function of composition. From the experimental data excess molar volumes and deviations in relative permittivity have been calculated over the entire composition range. Both excess molar volumes and relative permittivity deviations have been correlated using Redlich–Kister type polynomial equation by the method of least-squares for the estimation of the binary coefficients and the standard errors. The experimental and calculated quantities were used to analyze the mixing behaviour of the components. [Copyright &y& Elsevier]

Abstract: Administration of a low priming dose of 2-butoxyethanol (BE, 500 mg/kg, p.o.) 7 days prior to a larger LD90 dose (1500 mg BE/kg, p.o.) offers protection against the lethal dose-induced hemolysis and death in female Sprague Dawley rats because of prompt and efficient replacement of red blood cells (RBCs) with new resilient RBCs. The objective of the present work was to analyze the altered proteome of RBCs upon priming with BE in order to identify the potential anti-hemolytic survival proteins induced in the primed rat RBCs (P-RBCs) as opposed to vehicle-treated RBCs (V-RBCs). The RBCs from the two groups were fractionated into membrane and cytosolic fractions. The cytosolic fractions were further fractionated for proteomic analysis into 3 fractions. The fractions were labeled with Cy3 and Cy5 fluorescent dyes and subjected to 2-dimensional differential gel electrophoresis (DIGE) to analyze the protein profiles. Seven membrane and 8 cytosolic proteins were found to be significantly increased (≥2.5 fold) in P-RBCs as compared to V-RBCs. The identified proteins can be classified into antioxidant, membrane skeleton, protein turnover, lipid raft, and energy metabolism components. Increased levels of the proteins from antioxidant and membrane skeleton groups were confirmed by Western blot analysis. The study provides the first report on protein profiling of rat RBCs as well as on alteration of the proteome upon exposure to a priming dose of hemotoxicant. Further studies are needed to prove the protective role of the identified proteins and will initiate the field of survival/protective/anti-hemolytic proteins in RBCs. [Copyright &y& Elsevier]

Abstract: Surfactants are important materials with numerous applications in the cosmetic, pharmaceutical, and food industries due to inter-associating and intra-associating bond. We present a lattice fluid equation-of-state that combines the quasi-chemical nonrandom lattice fluid model with Veytsman statistics for (intra+inter) molecular association to calculate phase behavior for mixtures containing nonionic surfactants. We also measured binary (vapor+liquid) equilibrium data for {2-butoxyethanol (C4E1)+ n-hexane} and {2-butoxyethanol (C4E1)+ n-heptane} systems at temperatures ranging from (303.15 to 323.15)K. A static apparatus was used in this study. The presented equation-of-state correlated well with the measured and published data for mixtures containing nonionic surfactant systems. [Copyright &y& Elsevier]

Densities (ρ) at 293.15, 298.15, 303.15, 308.15, and 313.15 K, viscosities (η) at 293.15, 298.15, and 303.15 K and refractive indexes (n) at 298.15 K of binary mixtures of ethyl tert-butyl ether (1) + 2-butoxyethanol (2), are reported. The excess molar volumes (VE) and the viscosities, and refractive index deviations (Δln η and Δn) were calculated from these experimental data. The results are discussed in terms of intermolecular interactions. [ABSTRACT FROM AUTHOR]

By regulatory authorities the rat is considered to be a suitable animal model to predict the percutaneous absorption of hazardous substances in humans. In our study, the percutaneous penetration of 2-butoxyethanol (BE) and toluene was compared in different rat models. Intradermal microdialysis and static diffusion cells were used in in vivo and in vitro experiments with haired Wistar and hairless Lewis rats. Microdialysis experiments showed a steady-state penetration for BE and a penetration maximum for toluene in both rat strains at ∼60 min after beginning of exposure. However, in diffusion cell experiments the penetration of the test compounds in both rat strains increased until the end of exposure (4 h). Additionally, in microdialysis experiments BE penetrated in hairless rats in a higher amount than in haired rats (factor: 1.4; P < 0.01), for toluene it was just the opposite (factor: 1.9; P < 0.001). In diffusion cell experiments, the penetrated amounts of both compounds were higher in hairless rats compared to haired rats. The fluxes for BE were in diffusion cell experiments at a factor of 14.5 (haired rat) and 18.1 (hairless rat) higher than in microdialysis experiments, the difference factor for toluene was 2.6 (haired rat) and 12.9 (hairless rat). The lag times indicate a significantly faster penetration in microdialysis experiments compared with diffusion cell experiments ( P < 0.001). There are great differences in percutaneous penetration behaviour between the techniques and the rat strains. The diffusion cell method has difficulties to describe the percutaneous penetration kinetics, whereas microdialysis describes it more reliable. Due to these differences the reliability of a conversion factor for the transfer of percutaneous absorption data from rat to human skin, as proposed in the literature, is questionable. [ABSTRACT FROM AUTHOR]

Abstract: We determined percutaneous absorption kinetics of 2-butoxyethanol (BE) in volunteers using microdialysis. Four male volunteers were dermally exposed twice to 90% and 50% aqueous solutions (v/v) of BE for 4.5h. To determine percutaneous absorption kinetics the concentration of BE was measured in the dialysate samples collected at 30min-intervals throughout exposure. The systemic absorption, which is needed to determine recovery of the BE in the dialysate, was estimated from the concentration of the main metabolite of BE, free butoxyacetic acid (BAA) in urine. A pseudo steady-state percutaneous absorption was reached approximately at 2h of exposure for both BE concentrations. The maximum dermal flux of 50% BE was higher than that of 90% BE (2.8±0.4, 1.9±0.6mgcm−2 h−1, respectively). The more diluted BE solution showed shorter lag time: 25min versus 39min. The amount of BAA was determined in the pooled dialysate samples collected at 4 and 4.5h. The dermal metabolism seems to be low, the BAA amount ranged from 0.03% to 1.9% of the BE in the same dialysate. Our study demonstrates applicability of microdialysis technique for assessment of percutaneous absorption kinetics and dermal metabolism without interference from the systemic compartment. [Copyright &y& Elsevier]

Abstract: In hemolytic disorders, such as sickle cell disease and β-thalassemia, the mechanisms of thrombosis are poorly understood. Appropriate animal models would increase the understanding of the pathophysiology of thrombosis. We previously reported that rats exposed to 2-butoxyethanol (2-BE) developed hemolytic anemia and disseminated thrombosis resembling sickle cell disease and β-thalassemia. To characterize our model further, we investigated age- and dose-related differences in sensitivity to 2-BE. We exposed groups of 6- and 12-week-old F344 rats (5 animals/group) to 62.5, 125, and 250mg/kg/day of 2-BE for up to 4 days. Blood was collected on days 2–4 for complete blood count and measurement of intracellular adhesion molecule-1 (ICAM-1). Histopathological evaluation was performed to find evidence of disseminated thrombosis. The maximum hemolytic response, resulting in decreased erythrocyte count and higher mean cell volume (MCV) occurred in the 12-week-old rats treated with the highest dose of 2-BE (250mg/kg, p<0.0001). The highest increase in ICAM-1 levels occurred in the 12-week-old rats treated with 125 and 250mg/kg 2-BE (p<0.0001). No intravascular thrombi were noted in the 6-week-old 2-BE-treated animals. The majority of intravascular thrombi occurred in the 12-week-old rats treated with 250mg/kg 2-BE. Because our findings show age- and dose-related sensitivities, we suggest that 12-week-old rats and doses of 250mg/kg be used in the 2-BE model. [Copyright &y& Elsevier]

Abstract: Introduction: In hemolytic diseases such as sickle cell disease and β-thalassemia, the mechanisms of thrombosis are poorly understood, however erythrocyte/endothelium interactions are thought to play an important role. Appropriate animal models would increase our understanding of the pathophysiology of thrombosis and aid in the development of new therapeutic strategies. We previously reported that rats exposed to 2-butoxyethanol (2-BE) develop hemolysis and enhanced adherence of erythrocytes to the extracellular matrix, possibly secondary to the recruitment of cellular adhesion molecules at the erythrocyte/endothelium interface. Methods: We exposed rats to 250 mg/kg/day of 2-BE for 4 days, and collected blood for coagulation markers on each day. Results: As previously observed, erythrocytes dropped precipitously (8.0 to 1.8×106/μl in 48 h), and diffuse microvascular thrombosis developed in the heart, lungs, liver, bones and eyes. Prothrombin times, activated partial thromboplastin times, fibrinogen, and antithrombin-III were unchanged between treated and control rats, indicating that hemostasis is largely unperturbed. However the thrombin–antithrombin III levels in the 2-BE treated rats for all days were 3–7 times greater than the control rats. The plasma intercellular adhesion molecule-1 (ICAM-1) levels of 2-BE treated animals were approximately twice that of the controls on days 2 and 3 and 1.5 times the controls on day 4 (P <0.05). Conclusion: Our findings are consistent with the observations of increased erythrocyte aggregation, increased erythrocyte/endothelium interaction, and increased plasma ICAM-1 levels observed in sickle cell disease and β-thalassemia patients. This model may be useful for studying therapeutic agents that disrupt erythrocyte/endothelium interactions. [Copyright &y& Elsevier]

Abstract: A physiologically based pharmacokinetic (PBPK) model describing the disposition of 2-butoxyethanol (2-BE) was developed in order to predict the urinary concentration of its major metabolite, butoxyacetic acid (BAA) under a range of exposure scenarios. Based on Corley et al. [Corley, R.A., Bormett, G.A., Ghanayem, B.I., 1994. Physiologically based pharmacokinetics of 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in rats and humans. Toxicol. Appl. Pharmacol. 129, 61–79], the model included such features as multiple entry routes into the body, varying workload conditions, metabolism in the liver and elimination of free BAA in urine by glomerular filtration and acid transport. A bladder compartment simulating the fluctuations in metabolite concentration in urine caused by micturition formed a novel aspect of the model. Good agreement between model predictions and existing experimental data of total BAA levels in the blood and urine over various exposure conditions were observed. The mechanistically based PBPK model allowed comparison of disparate studies and also enabled the prediction of urinary concentrations of BAA post-shift. By calculating the total amount of BAA, any inter-individual variability in conjugation is taken into account. This led us to conclude that a biological monitoring guidance value should be proposed for total rather than free BAA with a value of 250mmol/mol of creatinine (post-shift), based on an 8h exposure to 25ppm 2-BE at resting working conditions. [Copyright &y& Elsevier]

An international, interdisciplinary working group of expert scientists met in June 2004 to develop IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans (IARC Monographs) on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. Each IARC Monograph includes a critical review of the pertinent scientific literature and an evaluation of an agent's potential to cause cancer in humans. After a thorough discussion of the epidemiologic, experimental, and other relevant data, the working group concluded that formaldehyde is carcinogenic to humans, based on sufficient evidence in humans and in experimental animals. In the epidemiologic studies, there was sufficient evidence that formaldehyde causes nasopharyngeal cancer, "strong but not sufficient" evidence of leukemia, and limited evidence of sinonasal cancer. The working group also concluded that 2-butoxyethanol and 1-tert-butoxy-2-propanol are not classifiable as to their carcinogenicity to humans, each having limited evidence in experimental animals and inadequate evidence in humans. These three evaluations and the supporting data will bepublished as Volume 88 of the IARC Monographs. [ABSTRACT FROM AUTHOR]

Abstract: Hemolysis is the principal toxicity of acute exposure to ethylene glycol monobutyl ether (EGBE) in rats. EGBE itself is not an active hemolytic agent, but its metabolite, butoxyacetic acid (BAA) formed as a result of dehydrogenase activity is a potent hemolysin. Here we address the role of osmolarity and cation composition of the suspending buffers in the mechanism of BAA-induced hemolysis of rat red blood cells in vitro. Rat erythrocytes were protected from BAA-induced cell swelling and hemolysis by the addition of sucrose to the suspending media. Hemolysis and cell swelling were also reduced by replacing external sodium with potassium. When calcium was not present in the suspending medium or when chelated by EGTA, hemolysis was increased after 2h incubation with 1mM or 2mM BAA. Addition of as little as 0.05mM CaCl2 reduced hemolysis significantly while the addition of MgCl2 had no effect. The dose-response relationship between BAA concentration and hemolysis determined in the presence or absence of calcium showed an increased effect of BAA in the absence of calcium. BAA-induced spherocytosis and cell fragmentation were more pronounced in the absence of calcium. The time course of BAA-induced hemolysis in the presence and absence of calcium demonstrated that the effect of calcium is to delay the onset of hemolysis. Increased intracellular calcium as a result of exposure to BAA was verified by atomic absorption spectroscopy. Charybdotoxin, an inhibitor of the calcium activated potassium channel, blocked the protective effect of calcium suggesting that the delay of onset of hemolysis in the presence of calcium is due to potassium loss caused by this channel. We conclude that the mode of action of BAA is to cause a colloid osmotic lysis of the rat red blood cell. Hemolysis requires external sodium and is associated with calcium uptake. Calcium appears to delay the onset of hemolysis. We speculate that: (1) BAA causes sodium and calcium to enter the cell; (2) calcium initially has a protective effect via the calcium activated potassium channel which facilitates the loss of potassium thereby, compensating for the osmotic effect of increased cell sodium; (3) calcium subsequently may have other deleterious effects through activation of proteases and externalization of phosphatidylserine in the exterior leaflet of the membrane. [Copyright &y& Elsevier]