What is a ferazone molecule

Update on furan and its methyl analogues

Furan (derived from the Latin word furfur for bran) is a colorless, volatile liquid in its pure form and is also known under the names divinylene oxide, oxacyclopentadiene and oxol. The compound, which belongs to the group of oxygen-containing heteroaromatics, is insoluble in water, but readily soluble in organic solvents such as alcohols, ethers and acetone. Furan is used in the chemical industry to manufacture chemicals, resins and paints.

What are the methyl analogues of furan?

In general, compounds are referred to as “analogs” if they have structural or functional similarities. Methyl analogues of furan, such as 2-methyl-, 3-methyl- and 2,5-dimethylfuran, (see Figure 1) therefore have the basic structure of furan with one or more methyl (CH3) groups at different positions.
In addition to furan, these were found in thermally treated foods. They can arise during the preparation of the food or be added to the food as flavorings.

Figure 1: Structural formulas of furan (a), 2-methylfuran (b), 3-methylfuran (c) and 2,5-dimethylfuran (d)

Several pathways are described in the literature for generating furan in thermally treated foods. Furan can therefore be formed in the Maillard reaction through the breakdown of amino acids and reducing sugars. In addition, the formation through thermal oxidation of ascorbic acid, carotenoids and through lipid oxidation of polyunsaturated fatty acids is possible.

Where do furan and its methyl analogues occur?

In addition to the presence of furan in cigarette smoke, its occurrence in foods that have undergone thermal treatment has also been described for several years. Particularly high levels were found in roasted coffee and in foods that are heated in closed containers, such as canned meat, soup and vegetables. Furan has also been found in baby food, pastries, sauces, bread and beverages. It is estimated that adults ingest 85% of the amount of furan through coffee, while children are exposed to an increased extent through food in a jar and through their ingestion through fruit juices.

Can furan and its methyl analogues pose a health risk?

Furan itself was classified by the International Agency for Research on Cancer (IARC) as carcinogenic in animal experiments and as possibly carcinogenic for humans (Category 2b) as early as 1995. In the course of metabolism, epoxidation and the subsequent ring opening as well as the formation of a reactive 2-ene-1,4-dicarbonyl intermediate take place. In the context of a report by the CONTAM panel of the EFSA (European Food Safety Authority) it was also found that there is only a small difference between the furan exposure of humans and the dose that causes carcinogenic effects in animal experiments. Concerning the methyl analogues 2-methylfuran and 2,5-dimethylfuran, the toxicological EFSA assessment of a large number of aromatizing, furan-like substances also revealed concerns due to possible genotoxicity. In view of the structural similarity and the lack of options for other metabolic pathways such as hydrolysis or conjugation, a metabolic mechanism analogous to furan can take place. In addition, oxidation at the C1 atom of the alkyl-substituted compounds can result in the formation of a ketone. The EFSA also has data for one of these ketones which indicate a genotoxic potential. Due to the in part insufficient data on toxicology and exposure, the European Commission has commissioned EFSA to issue a scientific opinion on the risk to humans of the presence of furan and its methyl analogues in food. In the course of this, data on the occurrence of furan, 2-methylfuran, 3-methylfuran and 2,5-dimethylfuran in food were collected at the end of 2016.

How are furan and methylfurans analyzed?

Due to the slight volatility of the furan and the methylfurans, the analysis is carried out by means of headspace gas chromatography-mass spectrometry (headspace-GC-MS) or solid-phase-micro-extraction-GC-MS (SPME-GC-MS). Either an internal, fourfold deuterated furan standard or an external calibration can be used for quantification. Difficulties or sources of error in the analysis arise in particular due to the slight volatility of the furan molecule or due to the observation that, under certain conditions, furan generation is possible during the analysis.

Are there maximum levels for furan and methyl furans in food?

So far, maximum levels in food have not been set for either furan or methylfurans. However, due to the toxicological assessment of 2-methylfuran and 2,5-dimethylfuran, the flavoring industry has decided to no longer support the use of the two compounds as flavoring substances in Europe.