A comprehensive review of furan in foods: From dietary exposures and in vivo metabolism to mitigation measures.

Furan is a thermal food processing contaminant that is ubiquitous in various food products such as coffee, canned and jarred foods, and cereals. A comprehensive summary of research progress on furan is presented in this review, including discussion of (i) formation pathways, (ii) occurrence and dietary exposures, (iii) analytical techniques, (iv) toxicities, (v) metabolism and metabolites, (vi) risk assessment, (vii) potential biomarkers, and (viii) mitigation measures. Dietary exposure to furan varies among different countries and age groups. Furan acts through various toxicological pathways mediated by its primary metabolite, cis-2-butene-1,4-dial (BDA). BDA can readily react with glutathione, amino acids, biogenic amines, or nucleotides to form corresponding metabolites, some of which have been proposed as potential biomarkers of exposure to furan. Present risk assessment of furan mainly employed the margin of exposure approach. Given the widespread occurrence of furan in foods and its harmful health effects, mitigating furan levels in foods or exploring potential dietary supplements to protect against furan toxicity is necessary for the benefit of food safety and public health.

Fast and Non-Destructive Profiling of Commercial Coffee Aroma under Three Conditions (Beans, Powder, and Brews) Using GC-IMS.

The flavor of coffee can be affected by the preparation parameters. In this investigation, the flavor profiles of three coffee brands under three conditions (bean, powder, and brew) were analyzed by gas chromatography-ion mobility spectrometry (GC-IMS) and the electronic nose (E-nose). The flavor results were further studied using multiple factor analysis (MFA). A total of 117 peaks were identified in all coffee samples by GC-IMS, and the principal component analysis (PCA) showed these coffee samples could be grouped and separated. A total of 37 volatile organic compounds (VOCs) were selected as biomarkers to distinguish coffee samples, including 5 aldehydes, 10 ketones, 8 alcohols, 2 acids, 4 esters, 5 furans, and 3 other compounds. The comparison between E-nose and GC-IMS data using partial least squares regression (PLSR) and MFA showed GC-IMS could present very close sample spaces. Compared with E-nose, GC-IMS could not only be used to classify coffee samples in a very short time but also provide VOC bio-markers to discriminate coffee samples.

Analysis of furan and its major furan derivatives in coffee products on the Chinese market using HS-GC-MS and the estimated exposure of the Chinese population.

The current study analysed concentrations of furan and its derivatives in coffee products commercially available in China based on an improved headspace gas chromatography-mass spectrometry (HS-GC-MS) method and estimated health risks. A total of 101 samples of coffee products on the Chinese market was analysed. Furan (98%, ND-6569 µg/kg) and 2-methylfuran (100%, 2-29639 µg/kg) were the compounds with the highest concentrations and detection rates in coffee products. The mean dietary exposure of Chinese consumers to furan and the sum of furan, 2-methylfuran and 3-methylfuran in coffee products was 0.09 and 0.46 µg/kg bw/day, respectively. For the neoplastic effects of furan, the margin of exposure (MOE) was 14,556 for the mean dietary exposure of consumers. For the non-neoplastic effects of furan, MOEs were 711 and 139 for furan and the sum of furan, 2-methylfuran and 3-methylfuran, respectively. Overall, a health concern is indicated for coffee consumers with MOEs below 10000.

Quantification of furan and 5 alkylfurans with complete separation of 2-ethylfuran and 2,5-dimethylfuran isomers in cereals, coffee and Infant products by GC-MS.

Alkylfurans have been found concurrently to furan in thermally processed food and might add to the overall exposure, thereby increase the health concern. The analytical methods developed for these compounds are based on gas chromatography separation coupled to mass spectrometry. Two of those alkylfurans, 2,5-dimethylfuran and 2-ethylfuran, are isomers, for which accurate quantification require either complete chromatographic separation or tandem mass spectrometry (MS/MS) selectivity. A new chromatographic method is reported using the Supelco Equity-1 column, demonstrating complete baseline separation of these two isomers, with a shorter runtime when using single mass spectrometry. Full validation was performed successfully for furan, 2- and 3-methylfuran, 2-ethylfuran, 2,5-dimethylfuran and 2-pentylfuran on different food matrices with recovery rates in the range of 80-110 %, repeatability below 14%, intermediate reproducibility below 22% as well as expanded uncertainty under 50%.

Scarlet Flax Linum grandiflorum (L.) In Vitro Cultures as a New Source of Antioxidant and Anti-Inflammatory Lignans.

In vitro cultures of scarlet flax (Linum grandiflorum L.), an important ornamental flax, have been established as a new possible valuable resource of lignans and neolignans for antioxidant and anti-inflammatory applications. The callogenic potential at different concentrations of α-naphthalene acetic acid (NAA) and thidiazuron (TDZ), alone or in combinations, was evaluated using both L. grandiflorum hypocotyl and cotyledon explants. A higher callus induction frequency was observed on NAA than TDZ, especially for hypocotyl explants, with a maximum frequency (i.e., 95.2%) on 1.0 mg/L of NAA. The presence of NAA (1.0 mg/L) in conjunction with TDZ tended to increase the frequency of callogenesis relative to TDZ alone, but never reached the values observed with NAA alone, thereby indicating the lack of synergy between these two plant growth regulators (PGRs). Similarly, in terms of biomass, NAA was more effective than TDZ, with a maximum accumulation of biomass registered for medium supplemented with 1.0 mg/L of NAA using hypocotyls as initial explants (DW: 13.1 g). However, for biomass, a synergy between the two PGRs was observed, particularly for cotyledon-derived explants and for the lowest concentrations of TDZ. The influence of these two PGRs on callogenesis and biomass is discussed. The HPLC analysis confirmed the presence of lignans (secoisolariciresinol (SECO) and lariciresinol (LARI) and neolignan (dehydrodiconiferyl alcohol [DCA]) naturally accumulated in their glycoside forms. Furthermore, the antioxidant activities performed for both hypocotyl- and cotyledon-derived cultures were also found maximal (DPPH: 89.5%, FRAP 866: µM TEAC, ABTS: 456 µM TEAC) in hypocotyl-derived callus cultures as compared with callus obtained from cotyledon explants. Moreover, the anti-inflammatory activities revealed high inhibition (COX-1: 47.4% and COX-2: 51.1%) for extract of hypocotyl-derived callus cultures at 2.5 mg/L TDZ. The anti-inflammatory action against COX-1 and COX-2 was supported by the IC50 values. This report provides a viable approach for enhanced biomass accumulation and efficient production of (neo)lignans in L. grandiflorum callus cultures.

Particle size and variety of coffee used as variables in mitigation of furan and 2-methylfuran content in espresso coffee.

In this study, the concentration of furan and 2-methylfuran in espresso coffee (EC) obtained from Arabica and Robusta coffee varieties was determined as a function of specific particle size. The particle size and coffee variety significantly influenced the level of furan and 2-methylfuran. In Arabica variety, furan and 2-methylfuran level increased with increasing particle size. Particularly, from C<200µm to C>425µm fractions, furan increased from 68.27 to 91.48 ng mL-1 while 2-methylfuran from 404.31 to 634.64 ng mL-1. In Robusta variety, the highest concentration of furan and 2-methylfuran occurred in ECs prepared using C300-425µm fraction showing values of 116.39 ng mL-1 and 845.14 ng mL-1, respectively, for furan and 2-methylfuran. On the basis of this experiment, it is possible to establish a mitigation strategy by manipulating the particle size and coffee variety in order to reduce the level of furan and 2-methylfuran in EC up to 11.4% and 18.8%, respectively.

Effect of various roasting, extraction and drinking conditions on furan and 5-hydroxymethylfurfural levels in coffee.

Furan and 5-hydroxymethylfurfural (5-HMF) were quantified in 108 coffee models prepared considering the species/origin of the coffee beans, roasting temperature/time, mesh size used to sieve the ground coffee beans, type of extraction water and extraction method. The effect of drinking conditions, such as adding sugar or cream, on furan and 5-HMF levels, was also studied. The range of furan and 5-HMF in coffee samples were 5-362 ppb and 51-1143 ppm, respectively. Furan levels were increased by 198-560% with increasing roasting temperature/time and by 106-399% in cold-brew extracts compared with espresso extracts. Among the mesh sizes used, 500 µm with espresso extraction, and 710 µm with cold-brew extraction led to maximal furan levels. 5-HMF concentration was highest in Robusta coffee and espresso extracts, and decreased by 17-76% with increasing roasting temperature/time. In a drinking condition study, furan level was remained unchanged, even when sugar or cream were added.

A novel UHPLC method for determining the degree of coffee roasting by analysis of furans.

The aim of this study was to develop a multi-analyte UHPLC method for furans and to apply it to commercial coffee samples as well as commercial roasting trials. Furans, as rising time-temperature indicators (TTIs), promised to be an alternative to unsatisfactory roasting temperature measurements. Consequently, a UHPLC-UV method for the determination of 5-hydroxymethyl-2-furfural (HMF), 5-hydroxymethyl-2-furoic acid (HMFA), 2-furfural (F), 5-methylfurfural (MF), 2-furyl methyl ketone (FMC), 2-furoic acid (FA), and for 3-caffeoylquinic acid (3-CQA) was developed and validated. Commercial roasted coffee beans contained 77.7-322 mg/kg HMF, 73.3-158 mg/kg HMFA, 109-200 mg/kg 2-F, 157-209 mg/kg MF, 12.3-32.8 mg/kg FMC, and 137-205 mg/kg FA. Roasting trial samples showed strong rising HMF contents (max.: Arabica: 769 mg/kg, Robusta: 364 mg/kg) followed by a distinct decline. Only MF and FA appeared as steady rising TTIs in the roasting process in Arabica and Robusta beans. 3-CQA fitted well as a decreasing TTI as expected.

Investigation on the mitigation effects of furfuryl alcohol and 5-hydroxymethylfurfural and their carboxylic acid derivatives in coffee and coffee-related model systems.

The mitigation of furfuryl alcohol, 5-hydroxymethylfurfural, 2-furoic acid, and 5-hydroxymethyl 2-furoic acid was conducted in two dry model systems mimicking coffee and an actual coffee system by incorporating 14 chemicals, that are categorized to phenolic acids, flavonoids, non-phenolic antioxidants, and non-antioxidant agents. Mitigation effects were determined as the decrease in the levels of the studied furan derivatives after the systems went through a controlled roasting process. Strong mitigation effects in the dry model systems were observed after the application of phenolic acids, quinic acid or EDTA. The mitigation effects of phenolic acids and flavonoids depended on the number and availability of phenolic hydroxyl groups. Certain agents exhibited a furan derivative-specific reducing effect while most of them showed a generalized effect. The mitigation efficacy decreased with the increasing complexity of the tested systems. In the coffee system, mitigation effects were almost completely lost in comparison with dry model systems. Still, taurine and sodium sulfite exerted the strongest mitigation effect in the coffee system.

Quantitative Determination and Validation of Four Ketones in Salvia miltiorrhiza Bunge Using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy.

Salvia mltiorrhiza Bunge (SMB) is native to China, whose dried root has been used as medicine. A few chromatographic- or spectrometric-based methods have already been used to analyze the lipid-soluble components in SMB. However, the methodology of qNMR on the extracts of fresh SMB root has not been verified so far. The purpose of this study was to establish a fast and simple method to quantify the tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone in fresh Salvia Miltiorrhiza Bunge root without any pre-purification steps using 1H-NMR spectroscopy. The process is as follows: first, 70% methanol aqueous extracts of fresh Salvia Miltiorrhiza Bunge roots were quantitatively analyzed for tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone using 1H-NMR spectroscopy. Different internal standards were tested and the validated method was compared with HPLC. 3,4,5-trichloropyridine was chosen as the internal standard. Twelve samples of Salvia Miltiorrhiza Bunge were quantitatively analyzed by qNMR and HPLC respectively. Then, the results were analyzed by chemometric approaches. This NMR method offers a fast, stable, and accurate analysis of four ketones: tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone in fresh roots of Salvia Miltiorrhiza Bunge.

Detection of Furan and five Alkylfurans, including 2-Pentylfuran, in various Food Matrices.

Next to furan, other alkylfurans such as 2- and 3-methylfuran, 2-ethylfuran, 2,5-dimethylfuran, and 2-pentylfuran have been found concurrently in thermal processed food and fruit juices. To ensure an accurate quantification of these compounds, a method based on isotope dilution using all six respective internal standards and gas chromatography coupled to mass spectrometry was developed. Two injection techniques, static head space (HS) and solid phase micro extraction (SPME), were tested and compared for their performance. Validation was based on a single laboratory validation under repeatability condition. Good data for both techniques in baby food and cereals were obtained. Furthermore, validation was conducted successfully on fruit juices and infant formula using SPME injection and on coffee using HS injection. LOQ for all matrices was established at 5 µg/kg and 200 µg/kg in coffee samples, which corresponds to the lowest fortification level. Recovery was between 80 % and 110 % and repeatability obtained below 16 % at 50 µg/kg (7.4 % at 10 mg/kg for coffee samples), except few slight outliers.

Comparative absorption kinetics of seven active ingredients of Eucommia ulmoides extracts by intestinal in situ circulatory perfusion in normal and spontaneous hypertensive rats.

Eucommia ulmoides Oliv. (E. ulmoides) is a valuable and nourishing medicinal herb in China that has been used in the treatment of hypertension. Given the fact that most traditional Chinese medicine is mainly used to treat disease, investigating the pharmacokinetics of traditional Chinese medicines in the pathological state is more useful than that in the normal state. However, the differences in the absorption kinetics of active ingredients of E. ulmoides extract between pathological and physiological conditions have not been reported. Therefore, in this study, the rat intestinal in situ circulatory perfusion model was used to investigate the differences in absorption kinetics of seven active ingredients of E. ulmoides extract in normal and spontaneously hypertensive rats, namely, genipinic acid, protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, (+)-pinoresinol di-O-ß-D-glucopyranoside and (+)-pinoresinol 4'-O-ß-D-glucopyranoside. Our results indicate that the pathological state of spontaneous hypertension may change the absorption of active components of E. ulmoides extracts, and these findings may provide a reference for improving the rational use of E. ulmoides in the clinic.

Spectrum-effect relationship for anti-tumor activity of shikonins and shikonofurans in medicinal Zicao by UHPLC-MS/MS and chemometric approaches.

Shikonin, shikonofuran and their derivatives are the main bioactive components of Zicao, a traditional Chinese medicine prepared with the dried roots of Lithospermum erythrorhizon, Arnebia euchroma or Arnebia guttata. To establish an efficient and sensitive method for studying material basis of Zicao, different scan modes of ultra-high performance liquid chromatography quadrupole time of flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) and UHPLC triple quadrupole linear ion trap mass spectrometry (QTRAP-MS/MS) were incorporated to make full use of the sensitivity of multiple reaction monitoring (MRM) and overcome its disadvantages. A total of 73 shikonins and shikonofurans compounds were detected in Zicao utilizing various scanning modes. Thereafter the characteristic chemical profile for shikonins and shikonofurans was established based on UHPLC-QTRAP-MS/MS, which was subsequently used to study the spectrum-effect relationship by correlating the relative quantity of compounds and the anti-tumor activity. As a result, 27 compounds were screened as the main active components inhibiting HeLa cells by othogonal partial least square (OPLS). Among them, shikonin, acetylshikonin have been reported to inhibit HeLa cells previously, and ß, ß-dimethylacrylshikonin has been reported to be active component by other method. Those results showed that chemical characteristic profile combined with chemometric methods was efficient and reliable for discovery of material basis in TCM, especially trace active compounds.

Identification and quantification of phytoprostanes and phytofurans of coffee and cocoa by- and co-products.

Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are isoprostanoids that result from the peroxidation of α-linolenic acid and are biomarkers of oxidative stress in plants and humans. These compounds exhibit several interesting biological activities (e.g. neuroprotection and anti-inflammatory activities). The aim of this research was to add value to coffee pulp (CP), cocoa husk (CH) and cocoa pod husk (CPH) by identifying and quantifying PhytoPs and PhytoFs by liquid chromatography-tandem mass spectrometry. The contents of PhytoPs and PhytoFs in CP, CH, and CPH were, respectively, 654.6, 474.3 and 179.9, and 543.2, 278.0 and 393.8 ng per g dry weight (dw). The main PhytoP found in CP (171.37 ng per g dw) and CPH (37.12 ng per g dw) was 9-epi-9-F1t-PhytoP, while ent-9-L1t-PhytoP was the most abundant in CH (109.78 ng per g dw). The main PhytoF found in all sources was ent-16(RS)-13-epi-ST-Δ14-9-PhytoF, at 196.56, 126.22, and 207.57 ng per g dw in CP, CH, and CPH, respectively. We provide the first complete profile of PhytoPs and PhytoFs for these agro-residues, which could be used in the functional food industry for enriching food or as nutritional supplements.

Dietary exposure to furan of the Austrian population.

In the period from 2007 to 2017 furan levels of foods were analysed by the Austrian Agency for Health and Food Safety. Based on these analytical data and the Austrian consumption data the dietary exposure of children and adults to furan was estimated by using a deterministic approach. For the adult population the mean and 95th percentile dietary exposures to furan were estimated at 0.31 µg/kg bodyweight per day and at 0.72 µg/kg bodyweight per day, respectively. The mean dietary exposure of children was estimated at 0.18 µg/kg bodyweight per day and is thus only about half as high as for Austrian adults. At the 95th percentile the dietary exposure of children was estimated at 0.49 µg/kg bodyweight per day. The main contributor to the total dietary exposure for adults is coffee followed by convenience products and for children the main contributors are grain products as well as convenience products, bread and snacks. Based on the BMDL10 of 0.064 mg/kg bodyweight per day for the development of cholangiofibrosis, the MOE-calculation revealed that the current levels of dietary exposure to furan are of concern for Austrian adult high consumers. The MOE-calculation, based on the BMDL10 of 1.31 mg/kg bodyweight per day for the development of hepatocellular adenomas, indicated a health concern for Austrian children and adults.

Aroma binding and stability in brewed coffee: A case study of 2-furfurylthiol.

The aroma stability of fresh coffee brew was investigated during storage over 60 min, there was a substantial reduction in available 2-furfurylthiol (2-FFT) (84%), methanethiol (72%), 3-methyl-1H-pyrole (68%) and an increase of 2-pentylfuran (65%). It is proposed that 2-FFT was reduced through reversible chemical binding and irreversible losses. Bound 2-FFT was released after cysteine addition, thereby demonstrating that a reversible binding reaction was the dominant mechanism of 2-FFT loss in natural coffee brew. The reduction in available 2-FFT was investigated at different pH and temperatures. At high pH, the reversible binding of 2-FFT was shown to protect 2-FFT from irreversible losses, while irreversible losses led to the reduction of total 2-FFT at low pH. A model reaction system was developed and a potential conjugate, hydroxyhydroquinone, was reacted with 2-FFT. Hydroxyhydroquinone also showed 2-FFT was released after cysteine addition at high pH.

Influence of lipid content and stirring behaviour on furan and furan derivative exposure in filter coffee.

Coffee has been determined as the dominant source of furan within an adult's diet. This study investigates the influence of coffee condiment use and stirring on the retention of furan. Three condiment lipid compositions were investigated, 0%, 3.5% and 35%, and kept at either 4 °C, 20 °C or 70 °C before addition to a freshly brewed cup of filter coffee which was subsequently mechanically stirred at three intensities, not stirred and moderately or heavily stirred. While five furans were monitored, furan, 2-methylfuran, 3-methylfuran, 2,5-dimethylfuran and 2,3-dimethylfuran, only two were quantifiable: furan and 2-methylfuran. Increasing condiment lipid concentration significantly increased retention of furan and 2-methylfuran, whereas stirring the coffee significantly increased furan release. A condiment temperature of 70 °C was found to significantly increase furan release.

Spatial distributions of furan and 5-hydroxymethylfurfural in unroasted and roasted Coffea arabica beans.

For the first time, the spatial distributions of the highly volatile compounds furan and 5-hydroxymethylfurfural (HMF) have been determined in cross sections of green and roasted Coffea arabica beans. The image maps were revealed by laser ablation DART imaging mass spectrometry (LADI-MS). The presence of these compounds was independently confirmed by GC-MS as well as argon DART-MS. Quantification of furan by GC-MS was completed with the final concentrations in roasted and unroasted beans determined to be 96.5 and 4.1 ng/g, respectively. Furan was observed to be distributed throughout the tissue of both green and roasted beans, while HMF was localized to the silver skin in green beans. Following roasting, the appearance of HMF was more diffuse. The implications of the broad distribution of furan on the one hand, and localization of HMF on the other, are discussed.

Identification and Quantitative Determination of Resin Acids from Corsican Pinus pinaster Aiton Oleoresin Using 13 C-NMR Spectroscopy.

Twenty-three resin samples have been obtained by tapping from individual Pinus pinaster adult trees grown in Corsica and submitted to acido-basic partition. Identification and quantitative determination of resin acids has been carried out using 13 C-NMR spectroscopy following a method developed by our group. The main components were dehydroabietic acid (up to 37.6 %), levopimaric acid (up to 35.5 %) and abietic acid (up to 24.7 %). A lignan, pinoresinol, has been identified in some samples. Within the 23 compositions, submitted to k-means analysis and Principal Component Analysis, two clusters have been perfectly differentiated, whose compositions were dominated by dehydroabietic acid (Group I, M=23.5 %, SD=6.3) and levopimaric acid (Group II, M=21.2 %; SD=6.2), respectively. Both compositions have been observed in the three locations of harvest.

Impact of consumer behavior on furan and furan-derivative exposure during coffee consumption. A comparison between brewing methods and drinking preferences.

This study examined the influence of consumer behavior on furan, 2-methylfuran, 3-methylfuran, 2,5-dimethylfuran and 2,3-dimethylfuran exposure in coffee. Coffees brewed using a filter, fully automatic, capsule machine or reconstituted instant coffee were found to have a significant different cup concentrations of furan derivatives. Coffee brewed with the fully automatic machine contained the highest furan and furan derivative concentrations (99.05 µg/L furan, 263.91 µg/L 2-methylfuran, 13.15 µg/L 3-methylfuran and 8.44 µg/L 2,5-dimethylfuran) whereas soluble coffee did not contain detectable levels, thereby contributing least to a consumer's dietary exposure. Furan and furan derivative concentrations were found to decrease significantly upon cooling, reducing consumer exposure by 8.0-17.2 % on average once the coffee reached drinking temperature 55-60 °C, in ceramic cups. Serving coffee in a ceramic or disposable cup were found to influence the cooling dynamics of the coffee but did not statistically influence the consumers exposure at a given temperature.