5-(Hydroxymethyl)furfural

Odor of chamomile flowers

Butter, caramel, musty

1.2062 g/cu cm at 25 °C

Crystalline solid (needles)

Needles (ethyl ether-petroleum ether)

Freely soluble in methanol, ethanol, acetone, ethyl acetate, dimethylformamide. Soluble in ether, benzene, chloroform. Less soluble in carbon tetrachloride. Sparingly soluble in petroleum ether.

Soluble in common organic solvents

BP: 115 °C at 1 mm Hg

114.00 to 116.00 °C. @ 1.00 mm Hg

When heated to decomposition it emits acrid smoke and irritating fumes.

31.5 °C

35 - 35.5 °C

0.00528 [mmHg]

Index of refraction: 1.5627 at 18 °C

665 kcal/mol

Solid with an odor of chamomile flowers; mp = 31.5 deg C; [Merck Index] Beige or yellow hygroscopic solid; mp = 32-35 deg C; [Alfa Aesar MSDS]

Solid

This chemical does not meet GHS hazard criteria for 1.2% (4 of 344) of reports.

Warning

H315 (60.2%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (65.1%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H335 (64.2%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]；H412 (70.9%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P261, P264, P264+P265, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 344 reports by companies from 19 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 4 of 344 reports by companies.；There are 18 notifications provided by 340 of 344 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Chemical: 2-Furancarboxaldehyde, 5-(hydroxymethyl)-

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Status: Active Update: 02-06-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/33331；Status: Cease Manufacture Update: 21-12-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/27303

2-Furancarboxaldehyde, 5-(hydroxymethyl)-: Does not have an individual approval but may be used under an appropriate group standard

No evidence of carcinogenicity in 2-year studies of mice and rats; [NTP] A skin and strong eye irritant; [Alfa Aesar MSDS] See Furfural.

Skin Irrit. 2 (60.2%)；Eye Irrit. 2 (65.1%)；STOT SE 3 (64.2%)；Aquatic Chronic 3 (70.9%)

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

Using a liquid chromatographic analysis method with UV detection, 300 urine samples were analyzed for 5-hydroxymethyl-2-furfuraldehyde (HMF). HMF was detected in urine as its metabolite 5-hydroxymethyl-2-furoic acid (HMFA) at concentrations ranging from 0-100 mg/L with most samples around 10 mg/L (1). HMFA was also detected in urine during a 24 hr Norwegian dietary recall study at a level of 28.6 mg/L which was slightly higher than the estimated HMF intake of 27.6 mg/L indicating alternative sources of exposure to HMF may be present(2). Unmetabolized HMF was detected in the urine of 7 volunteers following consumption of 20 grams of plum jam containing 24 mg of HMF. After 6 hours, 163 ug of HMF was excreted; this is equivalent to approximately 0.75% of the ingested HMF(3).

Our previous study reported that co-administration of honey significantly increased the serum levels of glycyrrhetic acid (GA) after oral administration of glycyrrhizin (GZ) in rabbits. The components of honey are sucrose, glucose, fructose and 5-hydroxymethyl-furaldehyde (HMF). To clarify the causative component(s) in honey that altered the metabolic pharmacokinetics of GZ, rabbits were given GZ (150 mg /per/ kg) with and without glucose (5 g /per/ rabbit), fructose (5 g /per/ rabbit) and HMF (1 mg /per/ kg), respectively, in crossover designs. An HPLC method was used to determine concentrations of GZ and GA in serum as well as GA and 3-dehydroglycyrrhetic acid (3-dehydroGA) in feces suspension. A noncompartment model was used to calculate the pharmacokinetic parameters and analysis of variance was used for statistical comparison. Our results indicated that the area under curve (AUC) of GA was significantly increased by 29% when HMF was coadministered, whereas the pharmacokinetics of GZ and GA were not significantly altered by coadministration of glucose or fructose. An in-vitro study, using feces to incubate GZ and GA individually, indicated that HMF significantly inhibited the oxidation of GA to 3-dehydroGA and this may explain the enhanced GA absorption in-vivo. It was concluded that HMF is the causative component in honey that affects the presystemic metabolism and pharmacokinetics of GZ in-vivo.

Chemical analysis of several brands of peritoneal dialysis fluids (PD fluids) has revealed the presence of 2-furaldehyde, 5-HMF (5-hydroxymethylfuraldehyde), acetaldehyde, formaldehyde, glyoxal, and methylglyoxal. The aim of this study was to investigate if the in vitro side effects caused by glucose degradation products, mainly formed during heat sterilization, are due to any of these recently identified aldehydes. Cell growth media or sterile filtered PD fluids were spiked with different concentrations of thealdehydes. In vitro side effects were determined as the inhibition of cell growth of cultured mouse fibroblasts or stimulated superoxide radical release from human peritoneal cells. Our results demonstrate that the occurrences of 2-furaldehyde, 5-HMF, acetaldehyde, formaldehyde, glyoxal, or methylglyoxal in heat-sterilized PD fluids are probably not the direct cause of in vitro side effects. In order to induce the same magnitude of cell growth inhibition as the heat-sterilized PD fluids, the concentrations of 2-furaldehyde, glyoxal, and 5-HMF had to be 50 to 350 times higher than those quantified in the PD fluids. The concentrations of acetaldehyde, formaldehyde, and methylglyoxal observed in the heat-sterilized PD fluids were closer to the cytotoxic concentrations although still 3 to 7 times lower. Since none of these aldehydes caused in vitro toxicity at the tested concentrations, the toxicity found in PD fluids is likely to be due to another glucose degradation product, not yet identified. However, it is possible that these aldehydes may still have adverse effects for patients on peritoneal dialysis.

The effect of water activity (aw 0.98, 0.84 and 0.60) and reaction temperature (100, 120, 140 and 160 degrees C) on the mutagenic activity of the Maillard reaction products in heated ribose-lysine and glucose-lysine model systems, was investigated. In the ribose-lysine system, heated at 100 °C, the mutagenic activity of the mixture increased as the water activity was lowered. On the contrary, no dependence between mutagenic activity and water activity was observed in the glucose-lysine system. At higher temperatures, in both systems, the presence in the browned mixtures of an antibacterial activity interfering with the bacterial mutagenicity assay was observed. Under all the conditions tested, the ribose-lysine system turned out to be the most reactive by producing higher levels of mutagens. Furthermore, in this system, the antimicrobial interference was more easily detectable. In the model systems used, the browning reaction mixtures were analysed for their absorption spectrum between 200-460 nm, and for the accumulation of furfurals. The results obtained showed that, at temperatures between 120 and 140 degrees C there is a correlation among reaction temperature, absorbance at 420 and around 280 nm, mutagenic activity of the mixture and the level of furfurals. Changes in the levels of furfurals can be related to changes in mutagenicity of the browned mixtures.

Dietary casein cooked at 180 °C promotes the growth of aberrant crypt foci and colon cancer in rats initiated with azozymethane. We speculated that promotion was due to a product that could be extracted by a solvent, such as 5-hydroxymethyl-2-furaldehyde (HMF), with tumor promoting activity or the carcinogenic heterocyclic aromatic amines (HAA). This hypothesis was tested by extracting cooked casein with solvents and water The extracts were then 1) assayed by high-performance liquid chromatography for HMF and HAA, 2) measured for mutagenicity on a frame-shift-sensitive strain of Salmonella typhimurium, 3) fed for 100 days to azoxymethane-initiated rats to test the promoting effect on aberrant crypt foci. Data show that 1) no HMF or HAA was detected in cooked casein, 2) no mutagenicity was detected on strain TA98, with or without metabolic activation, and 3) promotion was not associated with the extracts but with the cooked casein residue...

For more Interactions (Complete) data for 5-Hydroxymethyl-2-furfuraldehyde (6 total), please visit the HSDB record page.

LC50; Species: Daphnia magna (Water Flea) weight 4-5 mg; Conditions: freshwater, static; Concentration: 62000 ug/L for 24 hr (95% confidence interval: 53000-78000 ug/L) /formulation/

LC50; Species: Daphnia magna (Water Flea) weight 4-5 mg; Conditions: freshwater, static; Concentration: 34000 ug/L for 72 hr (95% confidence interval: 27000-43000 ug/L) /formulation/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2(SRC), determined from a structure estimation method(2), indicates that 5-hydroxymethyl-2-furfuraldehyde (HMF) is expected to have very high mobility in soil(SRC). Volatilization of HMF from moist soil surfaces is not expected to be an important fate process(SRC)given an estimated Henry's Law constant of 5.41X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). HMF is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.28X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2011).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2(SRC), determined from a structure estimation method(2), indicates that 5-hydroxymethyl-2-furfuraldehyde is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.41X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of -0.09(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2011).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 5-hydroxymethyl-2-furfuraldehyde (HMF), which has an estimated vapor pressure of 5.28X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase HMF is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 0.2 days(SRC), calculated from its rate constant of 5.3X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). HMF absorbs light at wavelengths of 283 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

Fifteen of sixteen commercial baby foods (3 milk-based and 13 cereal based) were reported to contain 5-hydroxymethyl-2-furfuraldehyde (HMF) at levels ranging from 0.17-57.18 ug/g. The results indicated that 8 of 13 baby foods contained HMF at concentrations <1.0 ug/g with all the milk-based products being in this group. The remaining cereal-based foods > 1 ug/g ranged from 1.04-5.00 ug/g with one much higher result reported as 57.18 ug/g (possibly due to precessing temperature)(1). In another survey of breakfast cereals, HMF was detected in a range of 3.67-193.34 ug/g among 23 samples of commercial cereals from 6 brands tested in Spain(2).

5-Hydroxymethyl-2-furfuraldehyde (HMF)was detected in apple juice stored for 1 year. The reported concentrations correlated positively with storage temperature - about 1 mg/L at 3 °C for apples of different ripeness, 1.6 mg/L at 20 °C for juice from unripe apples and 6.7 mg/L at 20 °C for juice from ripe apples. A higher concentration of HMF was reported for stored apple juice made from ripe apples than from juice of unripe apples stored for the same length of time(1). In another study 4 out of 5 prune products analyzed contained HMF at levels ranging from 0.8-93.4 mg/100 mL. Fresh prune juice did not contain HMF and frozen juice from fresh prunes had the lowest value for HMF (0.8 mg/100 mL). Prune products undergoing processing had higher values; 93.4 mg/100 mL (dried prunes with pulp), 85.8 mg/100 mL (dried prunes without pulp), and 92.0 mg/100 mL (prune juice from concentrate(2). In another study HMF was detected in carbonated soft drinks (0.19-3.3 mg/kg), juices (0.6-75.5 mg/kg), fructose sachets (4.2 mg/kg), and Sudanese dates (147-310 mg/kg)(3). HMF was measured in commercial ground coffee and soluble coffee marketed in Spain. Levels of 110, 625, 1734, 2480 mg HMF/kg were obtained for natural, blend, torrefacto, and soluble coffee, respectively. The greatest variability of HMF was apparent in soluble coffee(4).

Concentrated food products including 7 fruit concentrates, 17 boiled juices and 12 tomato and paprika pastes were analyzed for 5-hydroxymethyl-2-furfuraldehyde (HMF) and found to contain between 0.4 and 3500 ppm. Fruit concentrates contained 0.4-4.5 ppm, boiled juices 12.8-3500 ppm, and 0.4-18 ppm for tomato and paprika pastes(1). HMF was found in natural honey (2.3-798 mg/kg), commercial honey (11-614 mg/kg), and jams (26.1-807 mg/kg)(2). In another study the levels of HMF detected in samples of high fructose corn syrup supplied by beekeepers was 26.91-102.31 ppm and by manufacturers 11.09-33.8 ppm. The results were much more variable from the beekeepers(3). This compound has also been detected in caramel, which is a widely used coloring agent in food and pharmaceutical syrups. Although concentrations reported in pharmaceutical syrups is very low, there is some concern regarding the possibility of interaction between 5-Hydroxymethylfurfural and active drugs with amino functional groups(4).

5-Hydroxymethyl-2-furfuraldehyde (HMF) is present in sherries and grape concentrate. Medium sherries were found to have concentrations in the range 20-340 ppm; sweet sherries 130-680 ppm. Concentration increases with sugar content and baking time(1). Another study analyzed various vinegars for 5-hydroxymethyl-2-furfural and reported levels ranging from 0.2-3251 mg/L(2). Individual results in mg/L ranged from 1.6-7.3 (malt vinegar), 13.8-34.8 (sherry vinegar), 0.3-8.7 (white wine vinegar), 0.3-10.7 (red wine vinegar), 1.5-19.2 (apple vinegar), 0.2-9.0 (table vinegar with caramel), 316.4-3251.3 (balsamic vinegar)(2). In wine HMF was found at a level of 6.25 ug/L in the initial wine, at levels of 27.1-52.1 ug/L in wine aged 12 months in oak barrels, and 19.7-85.0 ug/L in wine aged 21 months in oak barrels(3).

5-Hydroxymethyl-2-furfuraldehyde (HMF) formation was reported during the roasting of cocoa beans, toasting of bread, and baking of cookies. A cocoa bean roasting model system consisting of oxidized and nonoxidized cocoa butter reported HMF concentrations of 43.5 and 51.0 mg/kg respectively(1). A model bread made of three kinds of flour rye, wheat and whole wheat were investigated at toasting temperatures of 140, 160, and 180 °C. HMF concentration of untoasted was below the quantification limit (0.5 mg/kg). After toasting the breads at the highest temperature, (180 °C) the HMF concentrations reported were 46.69, 47.02, 17.25 mg/kg for rye, wheat and whole-wheat breads(2). Model cookies were baked at temperatures of 150, 200, and 300 °C and reported respective HMF concentrations of 0.3, 5 and 229 mg/kg dry basis when analyzed by HPLC(3). In commercial cookies, HMF was found at levels ranging from 0.5 to 74.6 mg/kg(4). HMF was also detected in popcorn at 100 ug/kg, (5) boiled Chinese chestnuts(6), and roasted earth-almonds (Cyperus esculentus L.)(7).

Reducing sugars in milk, such as lactose, can form 5-hydroxymethyl-2-furfuraldehyde when it is treated at temperatures in excess of 120 °C(1).

A study of hydroxymethyl-2-furfuraldehyde (HMF) exposure to the Spanish population from heat-processed food suggests the mean HMF intake was estimated to be 10 mg/day(-1) with coffee and bread being the most important food items, contributing nearly 85 percent to the total HMF daily exposure. Biscuits, breakfast cereals, beer, UHT milk and tomato products are also important for HMF exposure(1). Using a deterministic approach the dietary exposure to HMF via coffee consumption in the total Spanish population was estimated to be 8.57 mg/day but when specific contribution of each type of ground and soluble coffee in the consumption habits was considered it was estimated to be 5.26 mg HMF/day. A level of 8.57 mg HMF/day was calculated for persons with high consumption habits (95th percentile)(2). The daily dietary intake of HMF was determined using the HMF content in Norwegian food items and estimated the dietary intake of HMF in 53 volunteers by means of 24 h dietary recall. Coffee, prunes, dark beer, canned peaches, and raisins had the highest levels of HMF. The 95th percentile of the estimated daily dietary intake of HMF were 27.6 mg/day(3).

/OTHER TERRESTRIAL SPECIES/ Dimethyl malate (1) and 5-hydroxymethyl furfural (2) were isolated as insecticidal compounds by bioassay-guided fractionation from MeOH extract of the fruits of Cornus officinalis Sieb. et Zucc. /dowood/ Insecticidal activity against larvae of D. melanogaster /fruit fly/ was demonstrated: 1 and 2 gave the LC50 value of 6.15 and 11.8 umol/mL of diet concentration, respectively. Acute toxicity against adults of D. melanogaster, 1 and 2 had the insecticidal activity, with the LD50 value of 21.5 and 34.0 ug /per/ adult.

In a study of the organic composition of fine particle emissions from wood combustion, 5-hydroxymethyl-2-furfuraldehyde (HMF) was found in 5 out of 6 woods burned. The concentrations reported in mg/g organic carbon were 16.131, 14.388, 7.665, 16.901 for HMF in Northern red oak, paper birch, Eastern white pine, and balsam fir emissions respectively. HMF was detected but not quantified in Eastern hemlock emissions and not detected in red maple emissions(1). Hydroxymethylfurfural, isomer not specified, was detected in the particulate phase of wood combustion emissions with different airflow setups, with detections of 343, 911, and 1014 mg/kg dry wood burned reported, in an open, half-closed, and closed airflow configuration, respectively(2).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 5-hydroxymethyl-2-furfuraldehyde can be estimated to be 2(SRC). According to a classification scheme(2), this estimated Koc value suggests that 5-hydroxymethyl-2-furfuraldehyde is expected to have very high mobility in soil.

5-Hydroxymethyl-2-furfuraldehyde (HMF) was detected in apple juice(1), fresh prune juice(2), Sudanese dates(3) and in natural honey(4).

/HUMAN EXPOSURE STUDIES/ 5-Hydroxymethylfurfural has become a substance of interest since recent results showed a possible carcinogenic potential in consequence of a metabolic activation by sulfotransferases. 5-Hydroxymethylfurfural is formed either by acid catalysed degradation of reducing sugars or via the Maillard reaction. This work provides an overview of foods potentially containing high amounts of 5-hydroxymethylfurfural. It comprises dried fruits with a high sugar content that were exposed to heat for a long time. The concentration ranges from very low in, e. g. figs (1 mg/kg) to plums that contained up to 2,200 mg/kg. Several types of roasted coffee were analysed that contained from 300 to 2,900 mg/kg of 5-hydroxymethylfurfural. In a small human study with seven healthy volunteers the urine excretion of unmetabolised 5-hydroxymethylfurfural was investigated. After uptake of 20 g of plum jam containing 24 mg of 5-hydroxymethylfurfural, 163 ug (mean) were excreted within 6 hr, an equivalent of 0.75% of the ingested 5-hydroxymethylfurfural.

/GENOTOXICITY/ 5-Hydroxymethylfurfural (5-HMF) is known as an indicator of quality deterioration in a wide range of foods. 5-HMF is formed as an intermediate in the Maillard reaction and has been identified in a wide variety of heat-processed foods. In recent years, the presence of 5-HMF in foods has raised toxicological concerns: data have shown cytotoxic, genotoxic and tumoral effects but further studies suggest that 5-HMF does not pose a serious health risk. However the subject is still a matter of debate. /This study/ investigated the genotoxicity of the food-borne contaminant 5-HMF using the Ames test, the micronucleus (MN) and the single-cell gel electrophoresis (SCGE) assays in the human metabolically active HepG2 cell line. Cytotoxic effect of 5-HMF was first assessed using Alamar Blue as a sensitive sub-lethal assay. 5-HMF did not induce any ...mutation in bacteria whatever the concentration in the Ames test. Furthermore, it does not induce clastogenic or aneugenic effects in the HepG2 cells. In contrast, 5-HMF induced HepG2 DNA damage at concentrations from 7.87 to 25 mM in the comet assay suggesting a weak genotoxic effect of 5-HMF in the HepG2 cells probably repaired.

/GENOTOXICITY/ 5-Hydroxymethylfurfural (HMF), a heat-induced food toxicant present in a vast number of food items, has been suggested to be genotoxic after being bioactivated by the sulfotransferase SULT1A1. The comet assay was used to evaluate the DNA damaging effect of HMF in cell lines with different activities of SULT1A1: two human cell lines (Caco-2, low activity; and HEK293, higher activity), one cell line from mouse (L5178Y, no activity) and two cell lines from Chinese hamster (V79, negligible activity; and V79-hP-PST, high activity of human SULT1A1). HMF induced significant DNA damage in all cell lines after 3 hr exposure to 100 mM. Most sensitive were V79 and V79-hP-PST where HMF induced significant DNA damage at 25 mM. Consequently...the present study ... have shown that HMF is a DNA damaging agent in vitro independent of the activity of SULT1A1 in the cells. The HMF-induced DNA damage was only observed at rather high concentrations which usually was associated with a concomitant decrease in cell viability.

/GENOTOXICITY/ 5-(hydroxymethyl)-2-furfural (HMF), a common product of the Maillard reaction, occurs in many foods in high concentrations, sometimes exceeding 1 g/kg (in certain dried fruits and caramel products). The toxicological relevance of this exposure has not yet been clarified. Induction of aberrant colonic crypt foci had been reported for HMF, in vitro studies on genotoxicity/mutagenicity have given controversial results. To elucidate the toxic potential of HMF, cytotoxicity (trypan blue exclusion), growth inhibition (SRB assay), mutagenicity (HPRT assay), DNA damage (single-cell gel electrophoresis) and depletion of cellular glutathione were investigated in mammalian cells. Genotoxicity (SOS repair) was monitored in Salmonella typhimurium (umu assay). HMF induced moderate cytotoxicity in V79 cells (LC(50): 115 mM, 1 hr incubation) and in Caco-2 cells (LC(50): 118 mM, 1 hr incubation). Growth inhibition was monitored following 24 hr of incubation (V79, IC(50): 6.4 mM). DNA damage was detectable neither in these cell lines nor in primary rat hepatocytes up to the cytotoxic threshold concentration (75% absolute viability). Likewise, in primary human colon cells, obtained from biopsy material, DNA damage was not measurable. At 120 mM, already exhibiting some reduction in cell viability, HMF was weakly mutagenic at the hprt-locus in V79 cells (mutants/million cells: HMF 120 mM: 16 vs control: 3). Intracelluar glutathione was depleted by HMF (>or=50 mM) in V79 cells, in the human colon adenocarcinoma cell line Caco-2 and in primary rat hepatocytes down to approximately 30% of control (120 mM). Genotoxicity was observed with HMF in the umu assay without external activation (16 mM: 185 rel. umu units, %, P<0.001). The genotoxic potential was not altered by addition of rat liver microsomes. By comparison, the natural flavour constituent (E)-2-hexenal (HEX) was already cytotoxic, mutagenic and depleted glutathione at about 1000-fold lower concentrations. It induced

For more Human Toxicity Excerpts (Complete) data for 5-Hydroxymethyl-2-furfuraldehyde (10 total), please visit the HSDB record page.

Chemical: 2-Furancarboxaldehyde, 5-(hydroxymethyl)-

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Status: Active Update: 02-06-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/33331；Status: Cease Manufacture Update: 21-12-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/27303

2-Furancarboxaldehyde, 5-(hydroxymethyl)-: Does not have an individual approval but may be used under an appropriate group standard

The yeast Saccharomyces cerevisiae is able to adapt and in situ detoxify lignocellulose derived inhibitors such as furfural and /5-hydroxymethyl-2-furfural/ HMF. The length of lag phase for cell growth in response to the inhibitor challenge has been used to measure tolerance of strain performance. Mechanisms of yeast tolerance at the genome level remain unknown. Using systems biology approach, this study investigated comparative transcriptome profiling, metabolic profiling, cell growth response, and gene regulatory interactions of yeast strains and selective gene deletion mutations in response to HMF challenges during the lag phase of growth. /The study/ identified 365 candidate genes and found at least 3 significant components involving some of these genes that enable yeast adaptation and tolerance to HMF in yeast. First, functional enzyme coding genes such as ARI1, ADH6, ADH7, and OYE3, as well as gene interactions involved in the biotransformation and inhibitor detoxification were the direct driving force to reduce HMF damages in cells. Expressions of these genes were regulated by YAP1 and its closely related regulons. Second, a large number of PDR genes, mainly regulated by PDR1 and PDR3, were induced during the lag phase and the PDR gene family-centered functions, including specific and multiple functions involving cellular transport such as TPO1, TPO4, RSB1, PDR5, PDR15, YOR1, and SNQ2, promoted cellular adaptation and survival in order to cope with the inhibitor stress. Third, expressed genes involving degradation of damaged proteins and protein modifications such as SHP1 and SSA4, regulated by RPN4, HSF1, and other co-regulators, were necessary for yeast cells to survive and adapt the HMF stress. A deletion mutation strain rpn4 was unable to recover the growth in the presence of HMF...

To determine the mode of action of 5-hydroxymethylfurfural (5-HMF) extracted from wine-processed Fructus corni on hepatoprotective activities, the effects of 5-HMF on H(2)O(2)-induced human L02 hepatocytes injury was examined. Hepatocytes L02 injured by H(2)O(2) /were/ treated by 5-HMF. The morphological changes of the cells were observed under inverted phase-contrast, fluorescence, and transmission electron microscopy and the activities of caspase-9 and caspase-3 were tested by enzyme-linked immunosorbent detector. ...5-HMF improved the morphology of H(2)O(2)-treated human L02 hepatocytes, and also inhibited the level of caspase-9 and caspase-3...

The aim of the ... study was to evaluate the putative protective effect of 5-hydroxymethylfurfural (5-HMF) derived from processed Fructus Corni on human hepatocyte cell line (LO2) injured by hydrogen peroxide in vitro and the mechanism of its protection. The percentage of cell viability was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The hepatocyte cell apoptosis and cell cycle were detected by flow cytometric analysis. The content of nitric oxide and caspase-3 activity were quantified spectrophotometrically by enzyme-linked immunoassay. The study showed that incubation with 5-HMF caused significant increase in the viability of LO2 cell, decrease of cell apoptosis and recovery of cell cycle in LO2 cell injured by hydrogen peroxide, which was accompanied with the decreased nitric oxide level and caspase-3 activity...

5-Hydroxymethylfurfural (HMF), a heat-induced food toxicant present in a vast number of food items, has been suggested to be genotoxic after being bioactivated by the sulfotransferase SULT1A1. The comet assay was used to evaluate the DNA damaging effect of HMF in cell lines with different activities of SULT1A1: two human cell lines (Caco-2, low activity; and HEK293, higher activity), one cell line from mouse (L5178Y, no activity) and two cell lines from Chinese hamster (V79, negligible activity; and V79-hP-PST, high activity of human SULT1A1). HMF induced significant DNA damage in all cell lines after 3 hr exposure to 100 mM. Most sensitive were V79 and V79-hP-PST where HMF induced significant DNA damage at 25 mM. Consequently ...the present study ... have shown that HMF is a DNA damaging agent in vitro independent of the activity of SULT1A1 in the cells. The HMF-induced DNA damage was only observed at rather high concentrations which usually was associated with a concomitant decrease in cell viability.

For more Mechanism of Action (Complete) data for 5-Hydroxymethyl-2-furfuraldehyde (6 total), please visit the HSDB record page.

5-Hydroxymethylfurfural (HMF) is formed in carbohydrate-rich food during acid-catalysed dehydration and in the Maillard reaction from reducing sugars. HMF is found in mg quantities per kg in various foods. HMF is mainly metabolised to 5-hydroxymethyl-2-furoic acid (HMFA), but unknown quantities of the mutagenic 5-sulphoxymethylfurfural (SMF) may also be formed, making HMF potentially hazardous to humans...

5-Hydroxymethylfurfural (HMF) is formed when sugars are acidified or heated. It is present at high levels in numerous foods. HMF is inactive in standard genotoxicity tests, but can be metabolized to a chemically reactive intermediate, 5-sulfooxymethylfurfural (SMF), which is mutagenic and carcinogenic. ...direct parental administration of SMF to mice leads to abundant acute necrosis and proteinaceous casts in the proximal tubules as the dominating toxicological effect. Since proximal tubule cells actively mediate the excretion of many organic anions, we hypothesized that transporter-mediated uptake of SMF into the cells could be the reason for this selective organotoxicity. To test this hypothesis...human embryonic kidney (HEK293) cells stably expressing human (h) OAT1 or OAT3 /were used/. SMF was a competitive inhibitor of p-aminohippurate uptake by hOAT1 and estrone sulfate uptake by hOAT3 with K(i) values of 225 uM and 1.5mM, respectively. Moreover, the initial rates of SMF uptake were 5.2- and 3.1-fold higher in cells expressing hOAT1 and hOAT3, respectively, than in control HEK293 cells. Likewise, the sensitivity of hOAT1- and hOAT3-expressing cells to SMF cytotoxicity was significantly higher than that of control cells, and was reduced by addition of probenecid, an inhibitor of OATs. Taken together, these results indicate that OAT1 and OAT3 mediate the uptake of SMF into proximal tubule cells and thereby may be involved in SMF-induced nephrotoxicity.

5-Hydroxymethylfurfural (HMF), formed by acid-catalyzed dehydration and in the Maillard reaction from reducing sugars, is found at high levels in numerous foods. It was shown to initiate colon aberrant crypt foci in rats and skin papillomas and hepatocellular adenomas in mice. HMF is inactive in in vitro genotoxicity tests using standard activating systems but is activated to a mutagen by sulfotransferases. The product, 5-sulfoxymethylfurfural (SMF), is a stronger carcinogen than HMF. SMF has not been detected in the biotransfomation experiments conducted on HMF in humans and animals in vivo up to date. /This study/ report pharmacokinetic properties of HMF and SMF in FVB/N mice. Sensitive assays for the quantification of HMF and SMF by LC-MS/MS multiple reaction monitoring were devised. SMF, intravenously injected (4.4 umol/kg body mass), showed first-order elimination kinetics in blood plasma (t(1/2) = 7.9 min). HMF, injected intravenously (793 umol/kg body mass), demonstrated biphasic kinetics in plasma (t(1/2) = 1.7 and 28 min for the initial and terminal elimination phases, respectively); the volume of distribution of the central compartment corresponded approximately to the total body water. The maximum SMF plasma level was observed at the first sampling time, 2.5 min after HMF administration. On the basis of these kinetic data, it was estimated that between 452 and 551 ppm of the initial HMF dose was converted to SMF and reached the circulation. It is likely that additional SMF reacted with cellular structures at the site of generation and thus is ignored in this balance...

5-Hydroxymethyl-2-furaldehyde (HMF), is a major product of sugar degradation found in food and solutions used in parenteral nutrition. Labeled [(14)C]HMF was synthesized by dehydration of [(14C)]fructose on ion-exchange resin and administered per os (po) and intravenously (iv) to rats. Metabolic balance of radioactivity demonstrated that HMF or its metabolites are rapidly eliminated in the urine with a recovery of 95-100% after 24 hr. Literature reported, in some cases, 50% retention in the body. HMF was completely converted to two metabolites, which have been identified by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) as 5-hydroxymethyl-2-furoic acid and N-(5-hydroxymethyl-2-furoyl)glycine. Administration of high doses of HMF showed a similar rapid elimination, but a proportional reduction of the amount of the glycine conjugate produced. Whole-animal-body autoradiography confirm that shortly after administration radioactive material was present in the liver but was mostly in the kidney and the bladder. The only significant difference between po and iv administration was the presence of a higher level of radioactive material in the brain of iv-treated rats.

For more Metabolism/Metabolites (Complete) data for 5-Hydroxymethyl-2-furfuraldehyde (8 total), please visit the HSDB record page.

5-hydroxymethylfurfural has known human metabolites that include 5-Sulfooxymethylfurfural.

.../This study/ determined the /5-Hydroxymethylfurfural/ (HMF) content in Norwegian food items and estimated the dietary intake of HMF in 53 volunteers by means of 24 hr dietary recall. The estimated intakes of HMF were correlated with urinary excretion of /5-hydroxymethyl-2-furoic acid/ (HMFA). Coffee, prunes, dark beer, canned peaches and raisins had the highest levels of HMF. The 95th percentile of the estimated daily dietary intake of HMF and the 24hr urinary excretion of HMFA were 27.6 and 28.6 mg, respectively. Coffee, dried fruit, honey and alcohol were identified as independent determinants of urinary HMFA excretion. Most participants had lower estimated HMF intake than the amount of HMFA excreted in urine. In spite of this there was a significant correlation (r=0.57, P<0.001) between the estimated HMF intake and urinary HMFA...

....In a small human study with seven healthy volunteers the urine excretion of unmetabolised 5-hydroxymethylfurfural was investigated. After uptake of 20 g of plum jam containing 24 mg of 5-hydroxymethylfurfural, 163 ug (mean) were excreted within 6 hr, an equivalent of 0.75% of the ingested 5-hydroxymethylfurfural.

Cytoplasm；Extracellular

Used to make dialdehydes, glycols, ethers, aminoalcohols, and acetals; [Merck Index] A flavoring agent that naturally occurs in some foods and alcoholic beverages; [ExPub: EFSA] Renewable building block for organic syntheses. [HSDB] Formed when sugars such as fructose or glucose are heated in the presence of amino acids, and is ubiquitous in the diet; Also used to make phenol/furfural resins; [NTP]

In the synthesis of dialdehydes, glycols, ethers, amino alcohols, acetals. Aqueous acid catalyzes ring opening.

Formation of 5-hydroxymethyl-2-furfuraldehyde can be used as an index of excessive heat treatment and of deteriorative changes in food

Formation of 5-hydroxymethyl-2-furfuraldehyde can be used as an index of excessive heat treatment and of deteriorative changes in honey.

Renewable building block for organic syntheses

The acid-catalyzed dehydration of hexoses results in the formation of 5-hydroxymethylfurfural (HMF). Fructose and insulin are especially good starting materials.

... From fructose or inulin hydrolysates by acid-induced elimination of three molecular equivalents of water.

Prepared from the fructose portion of the sugar molecule in 57% yield

From glucose, cornstarch, sucrose, molasses

For more Methods of Manufacturing (Complete) data for 5-Hydroxymethyl-2-furfuraldehyde (6 total), please visit the HSDB record page.

2-Furancarboxaldehyde, 5-(hydroxymethyl)-: ACTIVE

In acid solution, either after standing for a prolonged time or after heating, dextrose undergoes polycondensation, ie, dehydration, yielding a mixture of di- and oligosaccharides, most of which are the disaccharides gentiobiose and isomaltose. In acid solution and at high temperature, dehydration leads to formation of 5-hydroxymethyl-2-furfuraldehyde.