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Metabolism and excretion of [14C]furfural in the rat and mouse.

The fate of furfural (2-furancarboxaldehyde) was investigated in male and female Fischer 344 (F344) rats given single oral doses of 1, 10 and 60 mg/kg and male and female CD1 mice given 1, 20 and 200 mg/kg [carbonyl-14C]furfural. There was a very high recovery (more than 90% of dose) of radioactivity in all dose groups in 72 hr. The major route of elimination was by the urine, with much smaller amounts present in the faeces and exhaled as 14CO2. The residue in the carcass after 72 hr was less than 1% of the administered dose. Furoylglycine and furanacryloylglycine were identified as the major urinary metabolites by high-performance thin-layer chromatography, radio-HPLC, gas chromatography-mass spectrometry and 1H-nuclear magnetic resonance spectroscopy, by comparison with synthetic reference compounds. There were only subtle differences in the metabolic profile as a function of dose size, sex and species. An additional minor polar metabolite was excreted by male rats and mice, and the parent acids of the glycine conjugates were excreted at the higher doses. The results are discussed in terms of the participation of xenobiotics in the chain elongation reactions of fatty acid biosynthesis.

Acrylates↗

Cytotoxicity and induction of repairable DNA damage by photoactivated 5-nitrofurfural.

5-Nitrofurfural (NFA) an important photodecomposition product and metabolite of medicinal nitrofurans is phototoxic in bacterial test systems. Its major photodecomposition product 5-hydroxymethylene-2(5H)-furanone (HMF) appears to be responsible for this. Furthermore HMF and photoactivated nitrofurfural can induce repairable DNA damage in Escherichia coli bacteria. These effects may be important with respect to skin and allergic reactions and carcinogenicity appearing in nitrofuran therapy.

DNA Repair↗

Formation of methemoglobin by photoactivation of nitrofurantoin or of 5-nitrofurfural in rats exposed to UV-A light.

The antibacterial drug nitrofurantoin (NFT) is notorious for causing hemolytic anemia, which may be related to the methemoglobinemia, another side-effect of NFT. As NFT is photolabile, and nitrite, well known as a MetHb generator, is an important photoproduct of NFT, it seems not unlikely that light is a cause of NFT-induced MetHb formation. When rats were irradiated with UV-A immediately after oral NFT administration, the amount of MetHb significantly increased: 0.97 +/- 0.37% n = 36 (P less than 0.001 Student's t-test, control value: 0.5%). An increase in MetHb was also observed with rats simultaneously exposed to UV-A and the major photodecomposition product of NFT, viz. 5-nitrofurfural. In addition in vitro experiments proved the formation of MetHb as a result of photoactivation of NFT. Nitrite, photochemically formed from nitrofurfural and from the metabolite nitrofuroic acid, plays an important role. A dark reaction of the other photoproduct, nitrofurfural, with hemoglobin also appeared to cause a considerable amount of MetHb in vitro. However, because of rapid deactivation of nitrofurfural by either photodecomposition or metabolism, this dark reaction is not expected to contribute to the in vivo MetHb formation.

Animals↗

Mutagenicity of furfural in plasmid DNA.

Furfural is recognized as a dietary mutagen and is present in various foods and beverages. We have examined the mutagenic effect of furfural induced lesions in plasmid pBluescript SK(+/-). There was a progressive decrease in the transformation capacity of the plasmid as a function of furfural concentration with a concomitant increase in the number of mutant plasmids. Several mutant plasmids with reduced transformation capacity and a molecular size similar to the parental plasmid were isolated. A stretch of DNA of 108 basepairs within the multiple cloning region was sequenced. It was observed that the number of mutagenic events in the case of furfural damaged plasmid was not significantly greater than in spontaneously arisen mutants. These results were interpreted to indicate that furfural mediated DNA damage is efficiently repaired.

Base Sequence↗

An unusually heavy contamination of honey products by Clostridium botulinum type F and Bacillus alvei.

Many spores (1-60/g) of Clostridium botulinum type F were detected in different containers of honey products of the same brand. Microbiological and physicochemical properties of the contaminated honey were compared with those of the negative one. No difference in pH, hydroxymethyl furfural contents or diastase activity was found between them. The total counts of anaerobes other than C. botulinum and of yeast were also similar, whereas the aerobe counts, which were proportionally related with the C. botulinum counts, were higher in the positive honey than in the negative one. Motile colony-forming Bacillus alvei was predominant among the aerobes. B. alvei stimulated the toxin production by C. botulinum type F in culture medium incubated under aerobic conditions. The high count of C. botulinum in the honey might have been due to the possible stimulation of growth by B. alvei or some other microorganisms at some stage of honey ripening.

Aerobiosis↗

Quantitation of 5-hydroxymethylfurfural (5-HMF) and related substances in dextrose injections containing drugs and bisulfite.

The spectrophotometric test for 5-hydroxymethylfurfural and related substances, which is included in multiple compendial monographs for dextrose-containing injections, was modified to eliminate interference of bisulfite anion. Experimental formulations containing heparin or dopamine hydrochloride were used in this study. The modified assay was shown to be accurate, precise and rugged. With an appropriate standard, the method can be used to measure 5-HMF in solutions with an approximate quantitation limit of 0.06 ppm.

Dopamine↗

Irreversible photobinding of nitrofurantoin and of nitrofurfural to plasma proteins in vitro.

Allergic reactions form a serious problem in therapy with the urinary antiseptic nitrofurantoin (NFT). The formation of conjugates between NFT and plasma proteins is considered to be a first step in the development of such reactions. We investigated the possibility that UV-A irradiation of NFT in the presence of plasma proteins results in covalent binding. Binding to blood cell proteins was +/- 100X less. Efficient photobinding to albumin was demonstrated for NFT (up to 50 nmol mg-1 protein) and its photoproduct 5-nitrofurfural. Incubation of photodecomposition products from these two nitrofurans with plasma proteins also resulted in irreversible binding. Protein amino and, to a lesser extent, thiol groups proved to be targets for binding. Furthermore, upon photolysis both compounds induced a significant decrease in the iso-electric point of albumin. Photobinding, along with such alterations in the structure of plasma proteins, may well be able to trigger immunological responses when taking place in vivo. In this manner activation of nitrofurantoin by light may be a cause of allergic reactions by nitrofurantoin.

Animals↗

Separation of phenols and furfural by pervaporation and reverse osmosis membranes from biomass--superheated steam pyrolysis-derived aqueous solution.

The separation of valuable chemicals from raw products, where a great number of chemicals coexist, is the key technology in biomass refinery. In this study, the applicability of membrane separation of valuable chemicals from our currently developed portable superheated steam (SHS) biomass pyrolysis process was demonstrated. Phenols (phenol, p-cresol, guaiacol, methyl guaiacol, and ethyl guaiacol), furfural, and acetone were successfully separated by pervaporation using the silicone rubber membrane from model solutions and an actual SHS derived aqueous solution. The solution was also concentrated effectively by reverse osmosis separation using a polyamide membrane. When a high concentration of SHS solution was fed to the pervaporation process, a phase-separated permeate was obtained, which indicated that the reverse osmosis concentration combined with pervaporation separation is useful for the superheated steam process.

Acetone↗

Hydrolysis of sorghum straw using phosphoric acid: evaluation of furfural production.

Sorghum straw is a waste that has been studied scarcely. The main application is its use as raw material for xylose production. Xylose is a hemicellulosic sugar mainly used for its bioconversion toward xylitol. An alternative use could be its conversion toward furfural. The objective of this work was to study the furfural production by hydrolysis of sorghum straw with phosphoric acid at 134 degrees C. Several concentrations of H(3)PO(4) in the range 2-6% and reaction time (range 0-300 min) were evaluated. Kinetic parameters of mathematical models for predicting the concentration of xylose, glucose, arabinose, acetic acid and furfural in the hydrolysates were found. Optimal conditions for furfural production by acid hydrolysis were 6% H(3)PO(4) at 134 degrees C for 300 min, which yielded a solution with 13.7 g furfural/L, 4.0 g xylose/L, 2.9 g glucose/L, 1.1g arabinose/L and 1.2g acetic acid/L. The furfural yield of the process was 0.1336 g furfural/g initial dry matter was obtained. The results confirmed that sorghum straw can be used for furfural production when it is hydrolyzed using phosphoric acid.

Acetic Acid↗

Glucose reactions with acid and base catalysts in hot compressed water at 473 K.

The effects of the homogeneous catalysts (H(2)SO(4) and NaOH) and heterogeneous catalysts (TiO(2) and ZrO(2)) on glucose reactions were examined in hot compressed water (473 K) by a batch-type reactor. From the homogeneous catalyst studies, we confirmed that the acid catalyst promoted dehydration, while isomerization of glucose to fructose was catalyzed by alkali. Anatase TiO(2) was found to act as an acid catalyst to promote formation of 5-hydroxymethylfuraldehyde (HMF). Zirconia (ZrO(2)) was a base catalyst to promote the isomerization of glucose. The effects of the additives were also confirmed through fructose reactions.

Catalysis↗

Acidic cesium salts of 12-tungstophosphoric acid as catalysts for the dehydration of xylose into furfural.

Cesium salts of 12-tungstophosphoric acid, Cs(x)H(3-x)PW(12)O(40) (Cs(x)PW), in the bulk form or supported on medium-pore MCM-41 (3.7 nm) or large-pore (9.6 nm) micelle-templated silicas are active solid acid catalysts for the cyclodehydration of xylose into furfural, in a toluene/water solvent system (T/W) or in dimethyl sulfoxide (DMSO). The catalytic results are comparable to those obtained using sulfuric acid, under similar reaction conditions. The initial activities increase in the order H(3)PW(12)O(40)<Cs(2.0)PW<Cs(2.5)PW<silica-supported CsPW catalysts (15, 34wt% PW). Higher HPA loadings, larger pore diameter of the parent silica support, and higher reaction temperatures lead to higher furfural yields. The stability and reusability of the MCM-41-supported CsPW is higher in DMSO than in T/W.

Catalysis↗

Quantitative analysis of 2-furfural and 5-methylfurfural in different Italian vinegars by headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry using isotope dilution.

A new method was developed for the determination of 2-furfural (2-F) and 5-methylfurfural (5-MF), two products of Maillard reaction in vinegar, with head-space solid-phase microextraction (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS). A divinylbenzene (DVB)/carboxen (CAR)/polydimethylsiloxane (PDMS) fibre was used and SPME conditions were optimised, studying ionic strength effect, temperature effect and adsorption time. Both analytes were determined by calibration established on 2-furfural-d4 (2-F-d4). The method showed good linearity in the range studied (from 16 to 0.12 mg/l), with a regression coefficient r2 of 0.9999. Inter-batch precision and accuracy were found between 14.9 and 6.0% and between -11.7 and 0.2%, respectively. Detection limit was 15 microg/l. The method is simple and accurate and it has been applied to a series of balsamic and non-balsamic vinegars.

Acetic Acid↗

Diffusive sampling of airborne furfural by solid-phase microextraction device with on-fiber derivatization.

The solid-phase microextraction (SPME) device was used as a diffusive sampler for airborne furfural. The polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber was used, and O-2,3,4,5,6-(pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA) was first loaded onto the fiber. The SPME fiber assembly was then inserted into a PTFE tubing as a diffusive sampler. Known concentrations of furfural around the threshold limit values (TLVs)/time-weighted average and specific relative humidities (RHs) were generated by syringe pumps in a dynamic generation system. Validations of the SPME diffusive sampling with the US Occupational Safety and Health Administration (OSHA) organic method 72 were performed side-by-side in an exposure chamber at 25 degrees C. Gas chromatography/mass spectrometry (GC/MS) was used for sample analysis. The experimental sampling constant of the sampler was found to be (1.75 +/- 0.03) x 10(-2) (cm3 min(-1)) at 25 degrees C, whereas face velocity (0-0.25 ms(-1)) as well as RHs (10-80%) were proven to have no effects on the sampler. The correlations between the results from both SPME device and OSHA organic method 72 were found to be linear (r = 0.9849) and consistent (slope = 0.99 +/- 0.03). However, the variations of diffusion coefficients at different temperatures needs to be considered, and the adjustment of sampling constant was a must when sampling at temperatures different from 25 degrees C.

Chromatography, Gas↗

Analysis of 5-hydroxymethylfurfural in foods by gas chromatography-mass spectrometry.

A new, simple and selective method for the analysis of 5-hydroxymethylfurfural (HMF) in foods by gas chromatography coupled to mass spectrometry (GC-MS) is proposed. Several derivatising procedures based on the formation of an HMF silylated derivative using different reagents were studied. Among the derivatising reagents examined, N,O-bis-trimethylsilyltrifluoroacetamide (BSTFA) provided the best derivatisation yield. Sample clean-up was also optimised, using either liquid-liquid extraction with dichloromethane or solid-phase extraction (SPE) with several commercially available cartridges, and the best results were obtained using ENV+ cartridges. Quality parameters such as day-to-day and run-to-run precision (RSD<10%), linearity (between 25 and 700 ng g(-1)) and detection limit (6 ng g(-1)) were established. This method was successfully applied to the analysis of HMF content in several Spanish food samples from a local market, such as jam, honey, orange juice and bakery products.

Acetamides↗

Subacute (28-day) toxicity of furfural in Fischer 344 rats: a comparison of the oral and inhalation route.

The subacute oral and inhalation toxicity of furfural vapour was studied in Fischer 344 rats to investigate whether route-to-route extrapolation could be employed to derive the limit value for inhalation exposure from oral toxicity data. Groups of 5 rats per sex were treated by gavage daily for 28 days at dose levels of 6-192 mg/kg bw/day, or exposed by inhalation to concentrations of 20-1280 mg/m3 (6 h/day, 5 days/week) or 160-1280 mg/m3 (3 h/day, 5 days/week) for 28 days. Controls received vehicle (corn oil) or were exposed to clean air. Daily oral treatment with the highest dose of furfural (initially 192 mg/kg bw/day, later reduced to 144 mg/kg bw/day and finally to 120 mg/kg bw/day) resulted in mortality, and in increases in absolute and relative kidney and liver weight in surviving females of this group. Exposure of rats by inhalation for 6 h/day, 5 days/week for 28 days induced mortality at concentrations of 640 mg/m3 and above within 1-8 days. At 640 mg/m3 (3 h/day) and at 320 mg/m3 (3 and 6 h/day) and below, however, exposure was tolerated without serious clinical effects. In contrast, histopathological nasal changes were seen even at the lowest concentration of 20 mg/m3. With increasing exposure concentration, the nasal effects increased in incidence and severity and also expanded from the anterior part to the posterior part, including the olfactory epithelium. It was concluded that the no-observed-adverse-effect level (NOAEL) for oral toxicity was 96 mg/kg bw/day. The NOAEL for systemic inhalation toxicity was comparable, i.e. 92 mg/kg bw/day (corresponding to 320 mg/m3 (6 h/day) or 640 mg/m3 (3 h/day)) assuming 100% absorption. The presence of the histopathological nasal changes at the lowest tested concentration of 20 mg/m3 (corresponding to 6 mg/kg bw/day) proves that for locally acting substances like furfural extrapolation from the oral to the inhalation route is not valid.

Administration, Inhalation↗

Effect of storage period under variable conditions on the chemical and physical composition and colour of Spanish refrigerated orange juices.

The effects of the physicochemical and quality characteristics of various minimally pasteurized refrigerated orange Spanish juices and their changes with storage time and temperature were investigated. Essential oils, acidity, conductivity, diacetyl index, hydroxymethylfurfural, formol index, viscosity and ascorbic acid varied with storage time more significantly at 10 degrees C than at 4 degrees C. Density, colour and pectinmethylesterase did not vary at 4 degrees C. Some of the parameters could be used as indicators of quality loss or spoilage of the juices. The degradation kinetics of the concentration of remaining ascorbic acid against time follows a straight line whose slope indicates the degradation rate. A period of at least 42 days at 4 degrees C and 35 days at 10 degrees C was established as the shelf life of the juices.

Amino Acids↗

Furanic compounds in different coffee extraction systems: Analysis of the main influencing factors and correlation with acrylamide.

This study investigates how different coffee types representative of distinct roast profiles and brewing methods jointly affect the occurrence of furanic compounds and acrylamide in brewed coffee. Coffees were prepared using eight extraction methods (AeroPress, Clever, Chemex, French Press, Moka, Pure Brew, Turkish and V60). Five furanic compounds (furfural, furfuryl acetate, 5-methylfurfural, furfuryl alcohol and 5-hydroxymethylfurfural) were quantified in coffee powders and brews by HS-SPME-GC-MS, while acrylamide was determined by UHPLC-MS/MS. Moka and Turkish brews consistently exhibited the highest concentrations of furanic compounds, whereas paper-filtered pour-over methods (V60 and Chemex) showed the lowest levels. Pearson correlation analysis revealed coffee-dependent relationships between furanic compounds, acrylamide and extraction parameters with the strongest associations observed in dark-roasted coffee, reflecting advanced Maillard reaction chemistry. Overall, these results demonstrate that contaminant levels arise from the combined effects of intrinsic coffee chemistry and brewing mechanics and support targeted mitigation strategies: such as roast selection and brewing method optimization.

Acrylamide↗

Purification and characterization of a furfural reductase (FFR) from Escherichia coli strain LYO1--an enzyme important in the detoxification of furfural during ethanol production.

Furfural, an inhibitor of ethanol production from hemicellulose acid hydrolysates, is reductively detoxified to furfuryl alcohol by the ethanologenic bacterium Escherichia coli strain LYO1. Furfural reductase was purified 106-fold from this bacterium to approximately 50% homogeneity. It has a native molecular mass of 135 kDa, determined by gel filtration, and subunit molecular mass of approximately 68 kDa, determined by denaturing gel electrophoresis, indicating the holoenzyme is a dimer of two similar if not identical subunits. The enzyme shows strong activity from pH 4 to 8 (optimum pH 7.0), relatively high temperature tolerance (50-55 degrees C), and an apparent Km and Vmax for furfural of 1.5x10(-4)M and 28.5 micromol/min/mg of protein, respectively. It catalyzes the essentially irreversible reduction of furfural with NADPH, is specific for NADPH as cofactor, and is relatively specific for the reduction of furfural and benzaldehyde; 2-acetylfuran, xylose, and glucose were not reduced, while acetaldehyde was reduced at a rate 25-fold lower than furfural. This is the first description of a furfural reductase which, based upon size and substrate specificity, appears to represent a new type of alcohol-aldehyde oxido-reductase. The conversion of relatively toxic furfural to less toxic furfuryl alcohol suggests a beneficial role for this enzyme in mitigating furfural toxicity encountered during ethanol production from lignocellulosic biomass.

Aldehyde Reductase↗