Furan; a new processing toxin, that is recognized as possible human carcinogen (Group 2B) by the International Agency for Research on Cancer after research results that shown clearly, it cause cancer in rats and mice during animal experimental study. Furan is produced in different variety of foods and also from different precursors during processing and heat treatment. Furan is produced during processing from thermal degradation/Mailard reaction of reducing sugars, acids, thermal oxidation of ascorbic acid, oxidation of poly-unsaturated fatty acid and carotenoids. Furan is of great concern as safety point of view, as presence in variety of food like acrylamide. European Food Safety Authority (EFSA) initiated data collection on the presence of furan in foods from all the states members after FDA report on 2004 about furan. Recenlty EFSA published his report on furan in foods, its exposure and risk analysis in July 2010. However, for reliable risk assessment would need more data.
Furan in Food and Furan Toxicity
Introduction
Food safety is of great concern now a day, because compounds that are produces during food processing like acrylamide, polycyclic aromatic hydrocarbons, benzene and furan as regarding human health concern point of view (Jestoi et al., 2009).
Furan (C4H4O) is a volatile, colorless and low molecular weight of 68 with the boiling point of 31°C (NTP, 1993) has been classified by International Agency for Research on Cancer (IARC, 1995) as a possible human carcinogen (Group 2B). This category (Group 2B) is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. Furan and its derivatives have been linked with the flavor of foods that are found naturally in many foods and drinks at very low level not only in commercially prepared foods but also in homemade foods. Maga (1979) who renowned earlier that furan is formed during Mailard reactions and present in a number of foods with highest level found in coffee.
Since 2004, most of the research facilities around the world, also including US-FDA examined the furan not only as flavor but also novel harmful substance in jarred and canned foods. The European Food Safety Authority (EFSA) has articulated that furan is obviously carcinogenic in rats and mice. Furan induced carcinogenicity is probably due to a genotoxic mechanism (EFSA, 2004a; Durling et al., 2007) and hepato-toxicity (Jun et al., 2008).
Recently, FDA (Food and Drug Administration) reported that furan is present in a number of foods that undergo thermal treatment, particularly canned and jarred foods (FDA 2004a). The researchers from the Swiss Federal Office of Public Health also published similar results (Reinhard et al., 2004). Toxicological properties of furan on human health have been studied both genotoxic (Stich et al., 1981) and non-genotoxic mecahnisms (Fransson-Steen et al., 1997; Wilson et al., 1992). Lee and his colleagues (2009) analyzed the human blood for residual furan and reported that furan was detected in 21 individuals in which 13 were males and 8 females with ranging up to 17.86 ppb (ng furan/g food). In other research carried out in Germany reported that average exposure of 6 month old infants to furan give the evidence of possibly public health risk (Lachenmeier et al., 2009). In Taiwan, the daily intake for 6 month old baby 0.05-0.56 µg/kg body weight/day from the infant formula (Liu and Tsai, 2010).
Compound structure and physico-chemical characteristics
Furan (C4H4O) is a basic heterocyclic compound, consisting of aromatic ring of 5 atoms with one atom of oxygen. It consist colorless liquid at normal pressure and temperature and highly volatile. In 1870, furan was synthesized by Heinrich Limpricht and at that time it was called tetraphenols. Furan structure is shown in figure 1 while physic-chemical properties in table 1.
Table 1: Physico-chemical properties of furan*
Physical properties | Chemical properties | Toxicology | |||
Melting temperature | -85.6 °C | Empirical formula | C4H4O | DL50 | 7mg/kg (mouse, intraperitoneal) 5.2mg/kg (rat, intraperitoneal) |
Boiling temperature | 31.5 °C | Molecular weight | 68.07 g/mol | CL50 | Rat: 20ppm for 4 hrs. |
Solubility | 10 g (water, 20 °C) | Dipole moment | 0.66 D | – | – |
Density | 0.9644 g/cm3 (0 °C) | Molecular diameter | 0.502 nm | – | – |
Auto-ignition temperature | 390 °C | – | – | – | – |
*Wikipedia, 2011.
Furan in food
Earlier research on furan, its presence in variety of food and showed carcinogenic on high dose animals tests, hence considered possibly carcinogenic to human. So, it is dire need to monitor furan in processing food. In 2004, FDA performed comprehensive study using large number of food samples and found furan level up to 120 ppb. After this, European Food Safety Authority (EFSA) followed the FDA initiative and began to collect information on the methods of analysis, occurrence and formation in food, exposure through consumption, and the toxicity of furan. Furan level more than 100 µg/ kg were found in coffee, baby food, and sauces and soups (EFSA, 2004a). Afterwards EFSA regularly call for more information on the occurrence of furan in foods (EFSA, 2006).
Table 2: Furan values in different food products (FDA, 2004)
Food Type | Product | Furan (ppb) | Food Type | Product | Furan (ppb) |
Baby Foods | Gerber 100% Apple Juice, Lot 1 | 3.2 | Coffee | Maxwell House Coffee (brewed) | 37.4 |
Gerber 100% Apple Juice, Lot 2 | 3.4 | Maxwell House Coffee (brewed) | 40.4 | ||
Beechnut Naturals Apple Juice | 2.5 | Folgers Classic Roast Coffee Crystals | < 2.0 | ||
Beechnut Naturals Apple Juice | 2.6 | Folgers French Roast Coffee (brewed) | 44.7 | ||
Earth’s Best Apple Juice | 8.2 | Nescafé Classic Instant Coffee | < 2.0 | ||
Gerber 1st Foods Applesauce, Lot 1 | 4.4 | Nescafé Classic Instant Coffee | < 2.0 | ||
Gerber 1st Foods Applesauce, Lot 1 | 5.2 | Starbucks Yukon Blend whole bean (brewed) | 84.2 | ||
Gerber Tender Harvest Organic Apples | 4.7 | Maxwell House Sanka Decaffeinated Coffee (brewed) | 33.6 | ||
Gerber 1st Foods Applesauce, Lot 2 | 3.2 | Maxwell House Sanka Decaffeinated Instant Coffee | < 2.0 | ||
Gerber 1st Foods Applesauce, Lot 2 | 3.6 | Folgers Classic Decaf (brewed) | 42.5 | ||
Beechnut Naturals Stage 1 Applesauce, Lot 1 | 4.7 | Folgers Classic Decaf (brewed) | 38.3 | ||
Beechnut Naturals Stage 1 Applesauce, Lot 1 | 3.7 | Folgers Classic Decaf (brewed) | 52.6 | ||
Beechnut Naturals Stage 1 Applesauce, Lot 2 | 4 | Nescafé Taster’s Choice Decaffeinated Instant Coffee | 4.8 | ||
Earth’s Best First Apples | 5.3 | Nescafé Taster’s Choice Decaffeinated Instant Coffee | 7.2 | ||
Gerber 1st Foods Sweet Potatoes | 74.9 | Mixtures (e.g. soups, sauces, broths, chili) | Ragu Old World Style Traditional Pasta Sauce | 11 | |
Gerber 1st Foods Sweet Potatoes | 90.2 | Ragu Old World Style Traditional Pasta Sauce | 26.1 | ||
Gerber 1st Foods Sweet Potatoes | 93.1 | Francesco Rinaldi Traditional Spaghetti Sauce | < 5.0 | ||
Gerber 1st Foods Sweet Potatoes | 91 | Francesco Rinaldi Traditional Spaghetti Sauce | < 5.0 | ||
Gerber 1st Foods Sweet Potatoes | 64.7 | Prego Traditional Spaghetti Sauce, Lot 1 | 5.9 | ||
Gerber 1st Foods Sweet Potatoes | 58 | Prego Traditional Spaghetti Sauce, Lot 1 | 6.1 | ||
Beechnut Naturals Stage 1 Tender Golden Sweet Potatoes, Lot 1 | 74.4 | Prego Traditional Spaghetti Sauce, Lot 2 | < 5.0 | ||
Beechnut Naturals Stage 1 Tender Golden Sweet Potatoes, Lot 2 | 75.7 | College Inn Chicken Broth, Lot 1 | 8.2 | ||
Beechnut Naturals Stage 1 Tender Golden Sweet Potatoes, Lot 2 | 81.1 | College Inn Chicken Broth, Lot 2 | 6.7 | ||
Beechnut Naturals Stage 1 Tender Golden Sweet Potatoes, Lot 2 | 84.2 | Swanson Chicken Broth, Lot 1 | 12.7 | ||
Beechnut Naturals Stage 1 Tender Golden Sweet Potatoes, Lot 2 | 79.7 | Swanson Chicken Broth, Lot 2 | 9.7 | ||
Beechnut Naturals Stage 1 Tender Golden Sweet Potatoes, Lot 2 | 87.1 | Campbell’s Chicken Broth, Lot 1 | 15.2 | ||
Beechnut Naturals Stage 1 Tender Golden Sweet Potatoes, Lot 2 | 87.5 | Campbell’s Chicken Broth, Lot 1 | 18.2 | ||
Earth’s Best First Sweet Potatoes | 88.1 | Campbell’s Chicken Broth, Lot 2 | 13.3 | ||
Earth’s Best First Sweet Potatoes | 82.9 | Campbell’s Chunky Old Fashioned Vegetable Beef Soup | 52 | ||
Earth’s Best First Sweet Potatoes | 73.8 | Campbell’s Chunky Beef with Country Vegetables | 49.7 | ||
Organic Baby Sweet Potatoes | 108 | Progresso Rich & Hearty Slow Cooked Vegetable Beef Soup | 81.4 | ||
Organic Baby Sweet Potatoes | 72.7 | Progresso Traditional Beef & Vegetables Soup | 110 | ||
Gerber 1st Foods Carrots | 38.2 | Safeway Hearty Beef and Country Vegetables Soup, Lot 1 | 125 | ||
Gerber 1st Foods Carrots | 39.6 | Safeway Hearty Beef and Country Vegetables Soup, Lot 2 | 110 | ||
Beechnut Naturals Stage 1 Tender Sweet Carrots | 50.6 | Hormel Chili with Beans | 77 | ||
Earth’s Best First Carrots, Lot 1 | 20.2 | Giant Chili with Beans, Lot 1 | 66.3 | ||
Earth’s Best First Carrots, Lot 2 | 26 | Giant Chili with Beans, Lot 2 | 94.4 | ||
Organic Baby Carrots | 47.6 | Castleberry’s Hot Dog Chili Sauce, Lot 1 | 46 | ||
Organic Baby Carrots | 40.8 | Castleberry’s Hot Dog Chili Sauce, Lot 2 | 35 | ||
Gerber 1st Foods Green Beans | 39.6 | Franco-American Spaghetti, Lot 1 | 39.2 | ||
Gerber 1st Foods Green Beans | 42.6 | Franco-American Spaghetti, Lot 1 | 42.9 | ||
Beechnut Naturals Stage 2 Tender Young Green Beans | 34 | Franco-American Spaghetti, Lot 2 | 36.7 | ||
Beechnut Naturals Stage 2 Tender Young Green Beans | 34.2 | Food Lion Mini Beef Ravioli, Lot 1 | 42.2 | ||
Organic Baby Green Beans & Rice | 72 | Food Lion Mini Beef Ravioli, Lot 2 | 42.7 | ||
Organic Baby Green Beans & Rice | 66.5 | Chef Boyardee Beefaroni, Lot 1 | 29.8 | ||
Gerber 1st Foods Squash | 38 | Chef Boyardee Beefaroni, Lot 2 | 42.3 | ||
Gerber 1st Foods Squash | 39.4 | Fish | StarKist Solid White Albacore Tuna in water | < 5.0 | |
Gerber 1st Foods Squash | 51.3 | Chicken of the Sea Chunk White Tuna in water | 6.4 | ||
Beechnut Naturals Stage 1 Butternut Squash, Lot 1 | 57 | Bumble Bee Solid White Albacore in water, Lot 1 | < 5.0 | ||
Beechnut Naturals Stage 1 Butternut Squash, Lot 1 | 52.2 | Bumble Bee Solid White Albacore in water, Lot 2 | < 5.0 | ||
Beechnut Naturals Stage 1 Butternut Squash, Lot 2 | 41.9 | Chicken of the Sea Solid White Albacore Tuna in water, Lot 1 | 6.3 | ||
Earth’s Best Winter Squash | 55.1 | Chicken of the Sea Solid White Albacore Tuna in water, Lot 2 | 7.1 | ||
Beechnut Naturals Stage 2 Chicken Dinner | 29.4 | Canned Fruit, Fruit Juices and Vegetables | Bush’s Original Baked Beans, Lot 1 | 56.3 | |
Earth’s Best Chicken and Stars | 15.9 | Bush’s Original Baked Beans, Lot 2 | 61 | ||
Gerber 3rd Foods Pears | 5.2 | Hanover Baked Beans Brown Sugar & Bacon, Lot 1 | 89.7 | ||
Beechnut Naturals Stage 1 Bartlett Pears, Lot 1 | 5.8 | Hanover Baked Beans Brown Sugar & Bacon, Lot 2 | 117 | ||
Beechnut Naturals Stage 1 Bartlett Pears, Lot 2 | < 5.0 | Hanover Baked Beans Brown Sugar & Bacon, Lot 2 | 122 | ||
Earth’s Best First Pears | 5.8 | Campbell’s Pork & Beans, Lot 1 | 78.6 | ||
Gerber 1st Foods Bananas (in plastic containers) | 13 | Campbell’s Pork & Beans, Lot 2 | 78.7 | ||
Gerber Tender Harvest Organic Bananas | 17.6 | Campbell’s Pork & Beans, Lot 2 | 85.6 | ||
Beechnut Naturals Stage 1 Chiquita Bananas, Lot 1 | 31.7 | Del Monte Sweet Corn Cream Style | 39.1 | ||
Beechnut Naturals Stage 1 Chiquita Bananas, Lot 2 | 26.1 | Giant Home Sliced Green Beans | 6.3 | ||
Earth’s Best First Bananas | 17.7 | Green Giant Cut Green Beans | 5.9 | ||
Gerber 2nd Foods Garden Vegetables, Lot 1 | 76 | Musselman’s Premium Natural Apple Juice, Lot 1 | 2.5 | ||
Gerber 2nd Foods Garden Vegetables, Lot 1 | 73.4 | Musselman’s Premium Natural Apple Juice, Lot 2 | 3.4 | ||
Gerber 2nd Foods Garden Vegetables, Lot 2 | 112 | Giant Orchard Harvest Apple Juice, Lot 1 | < 2.0 | ||
Gerber 2nd Foods Garden Vegetables, Lot 3 | 79.4 | Giant Orchard Harvest Apple Juice, Lot 2 | < 2.0 | ||
Beechnut Naturals Stage 2 Mixed Vegetables, Lot 1 | 61.5 | Motts 100% Apple Juice | < 2.0 | ||
Beechnut Naturals Stage 2 Mixed Vegetables, Lot 2 | 68.1 | White House 100% Apple Juice | < 2.0 | ||
Earth’s Best Garden Vegetables | 51 | Minute Maid 100% Apple Juice (juice box) | < 2.0 | ||
Infant Formulas | Enfamil with Iron Concentrate | 16.8 | Giant Concord Grape Juice | 3.2 | |
Enfamil with Iron Concentrate | 18.8 | Giant White Grape Juice | < 2.0 | ||
Enfamil with Iron Concentrate | 12.7 | Welch’s White Grape Juice | ND | ||
Enfamil ProSobee Concentrate | 8.5 | Welch’s Concord Grape Juice | < 2.0 | ||
Good Start Supreme Concentrate | ND* | Libby’s Juicy Juice white grape flavored | 2.3 | ||
Good Start Supreme Ready to Feed | ND | Libby’s Juicy Juice grape flavored | 2.8 | ||
Good Start Supreme DHA & ARA Concentrate | ND | Northland Cranberry Juice | 3.4 | ||
Similac with Iron Concentrate, Lot 1 | 8.5 | Ocean Spray Light Cranberry Juice Cocktail | ND | ||
Similac with Iron Concentrate, Lot 2 | 11.6 | Ocean Spray Cranberry Juice Cocktail | < 2.0 |
ND*: Not detectable
Mechanism and Pathway of Furan Formation during Processing of Food
Furan is formed during processing of foods by various ways. Maga (1979) proposed that primary source of furan by the thermal degradation of carbohydrates especially glucose, lactose and fructose. Later on, FDA reported that carbohydrate/amino acid mixtures and vitamins have been used to generate furan in food. Furthermore, furan is produced from ascorbic acid, oxidation of polyunsaturated fatty acids (PUFA) and carotenoids (Becalski and Seaman, 2005) but specific mechanism proposed by Perez and Yaylayan (2004) shown in Figure 4.
Literature indicated that these are the following mechanisms by which furan is produced. (1) Thermal degradation/Maillard reaction reducing sugars, alone or in the presence of amino acids (Maga, 1979; Perez and Yaylayan, 2004), (2) thermal degradation of certain amino acids (Perez and Yaylayan, 2004; Mark et al., 2006; Limacher et al., 2008), (3) thermal oxidation of ascorbic acid (Becalski and Seaman, 2005; Fan, 2005), (4) poly-unsaturated fatty acids and (5) carotenoids (Yaylayan. 2006).
Furan formation from amino acid degradation
Serine or cysteine is the amino acids that have no need of any other resource to produce furan by thermal degradation. Both amino acids metabolized to acetaldehyde and glycolaldehyde that are react by aldol condensation to produce aldotetrose derivatives and finally convert into furan (Figure 2). But some of the amino acids such as alanine, threonine, and aspartic acid are not able to produce furan by thermal degradation alone (Figure 3). They just create acetaldehyde which furthers needs other components that furnished glycolaldehyde such as reducing sugars, serine, or cysteine (Perez and Yaylayan, 2004).
Different pathways are proposed by different researchers for the generation of acetaldehyde and glycolaldehyde from serine such as decarboxylation and ethanolamine which leads to release ammonia and form acetaldehyde, depends on C-label patterns. While glycolaldehyde with or without reducing sugars is produced by Strecker type reactions (Yaylayan, 2003).
Furan formation from carbohydrate degradation
Furan was chiefly produced from the integral sugar at high temperature conditions in the absence of amino acids. Formic and acetic acids are the byproducts that were identified during sugar degradation give the evidence of splitting C1 or C2 units from hexoses. Half of the furan is generated by the recombination of sugar structure in the aqueous solutions (Limacher et al., 2008).
Perez & Yaylayan (2004) reported that there are four pathways A, B, C and D for the carbohydrate degradation to form aldotetrose derivatives that undergoes cyclisation to form furan (Figure 5). They also compared the relative efficiency of different sugars to form furan by the following order D-erythrose > D-ribose > D-sucrose > D-glucose = D-fructose. During pathways A and D, in the presence of amino acids, reducing sugars generate reactive intermediates such as 1-deoxy and 3-deoxyosones via Maillard reactions. While in pathway B, aldotetrose is generated by retro-aldol cleavage without amino acids involvement but to a lesser extent and formation of 2-deoxy-3-keto-aldotetrose (pathway C). All the aldotetroses derivatives resulting from different pathways are easily converted into furan (Figure 4). Pentose sugars produce more furan in the presence of amino acids.
Furan formation from ascorbic acid degradation
Ascorbic acid produce acetaldehyde and glycolaldehyde when heated at 180 °C and later on aldol condensation converted into furan (Vernin et al., 1998), however formation of 2,3-diketogulonic acid (DKG) by quickly oxidizing of ascorbic acid (Liao and Seib, 1987). DKG converted into aldotetrose and then into furan as mention by Perez and Yaylayan (2004) shown in Figure 6. In non-oxidizing conditions ascorbic acid produce 3-deoxypentosulose (DP) by beta-elimination and decarboxylation (Niemela, 1987), then follow ribose pathway to form furan.
Furan formation from polyunsaturated fatty acids (PUFAs)
Model systems study shown that only polyunsaturated fatty acids such as linoleic and linolenic acid can produce furan by heating at 118°C for 30 minutes (Becalski and Seaman, 2005). Linolenic acid have four time fold more capability to produce furan than linoleic acid and ferric chloride also play a role to boost up the furan formation. Currently, a furan derivative; 5-pentylfuran is being used as a chemical marker to detect rancidity in fats and oils, so these finding not surprising. Recently, Vichi et al. (2003) found the correlation between 5-pentylfuran formations with the passage of oxidation time of olive oil.
Formation of lipid hydro peroxides from PUFA either by non-enzymatically or enzymatically and by homolytic cleavages of PUFA hydro peroxides resulting from transitional metal ions to form 2-alkenals, 4-oxo-2-alkenals and 4-hydroxy-2-alkenals as shown in Figure 7. Furan is formed by cyclization and subsequent dehydration from corresponding 4-hydroxy-2-butena (Perez and Yaylayan, 2004). This process converts the more toxic 4-hydroxy-2-alkenals such as 4-hydroxy-2-nonenal that have capability to modify the protein, DNA and LDL, into less toxic and more volatile furan derivatives.
Metabolism and Toxicology of Furan
Furan is promptly and extensively absorbed by the intestine and lungs (Egle & Gochberg 1979; Burka et al., 1991) due to its low polarity that make it easy to pass through biological membranes and enter into various organs as reported by many researchers. Burka and his colleagues (1991) reported that the recovery of radioactivity expressed as furan equivalent in liver, kidney, large intestine, small intestine, stomach, blood and lungs was 307, 60, 25, 13, 6, 6, and 4 nmol/g of tissue respectively, after 24 hours oral gavage of [14C]-labeled furan at dose of 8 mg/kg of body weight. However, after seven days treatment, the radioactivity below detection level but repeating dosing shown that accumulation of radioactivity found predominantly in liver and kidney.
Absorbed furan is metabolized quickly by cytochrome P-450 enzymes (principally CYP2E1) to form carbon dioxide and cis-2-butene-1,4-dial (Chen et al., 1995). Metabolites of furan such as Cis-2-butene-1, 4-dial (BDA) known as reactive and cytotoxic that bind to proteins and nucleosides (Burka et al., 1991; Byrns et al., 2002). This metabolite is resulting of the oxidation of one of the double bonds of furan with the possibility first formed epoxide intermediate that undergoes rearrangement and ring opening (Figure 8) and as a mono-glutathione conjugate in the urine of rats (Peterson et al., 2004).
Metabolic activation by Cytochrome P450 (CPY) enzyme that is involved in furan induced toxicity shown by both in vitro and in vivo studies. Inhibition and induction experiments by Kedderis and his colleagues (1993) publicized that CYP2E1 is foremost enzyme involved in furan biotransformation demonstrating enhanced furan metabolism by pre-treatment of rats with acetone (induction of CYP2E1) but not with phenobarbital (induction of CYP2B2 isozymes). However later on, Kedderis and Held (1996) reported that human hepatocytes in primary culture experiments shown that metabolism by the CYPE1 is so rapid that the rate limiting step in elimination of ingested furan is the speed of its delivery to liver.
Furan is potent carcinogen to many organs shown by different toxicity studies. US National Toxicology Program (NTP) carried out experiment on furan toxicity and reported that mortality was increased in both species rats and mice over 16 days when furan gavage at doses of between 20 and 160 mg/kg. While low maximum dose administration for 13 weeks result in weight loss, increase in liver and kidney weights, decrease thymus weight and toxic lesions of the liver and kidney in rats and mice and severity increase with dose (NTP, 1993). Increase in hepatocellular adenomas and carcinomas was observed when furan is administered to 50 mice at dose rate 8 or 15 mg/kg body weight for 5 days/week for 2 years. In other study shown that cholangio-carcinoma of the liver in all 50 rats was observed after higher maximum dose of furan administered.
NTP (1993) reported that furan is not mutagenic with or without S9 metabolic activation to some of Salmonella typhimurium while Lee et al. (1994) illustrated the furan mutagenicity on strain of TA100. Furan is also involved in loss of ATP after bio-activation of metabolites (Kedderis and Ploch, 1999; Mugford et al., 1997).
Recently, effect of furan on reproductive system of male rats was studied. In this study furan was gavage at dose 2, 4 and 8 mg/kg/day for 90 days to 3 or 4 weeks old rats. Result indicated that significantly reduction in weight of seminal vesicle, decrease in testosterone level, histological examination revealed that impairment in testis, epididymis and prostate gland, no effect on sperm counts and its morphology while apoptotic cells in testis increase significantly (Karacaoglu and Selmanoglu, 2010). These results give the evidence that furan induces toxicity in male reproductive system.
Table 3: Toxicity study of furan in different animals*
Organism | Test Type | Route | Reported Dose | Effect | Source of Information |
Dog | LDLo | intravenous | 140mg/kg | BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD, BLOOD: HEMORRHAGE | Journal of Pharmacology and Experimental Therapeutics. Vol. 26, p. 281, 1926. |
Dog | LDLo | oral | 234mg/kg | GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS, GASTROINTESTINAL: NAUSEA OR VOMITING, BLOOD: HEMORRHAGE | Journal of Pharmacology and Experimental Therapeutics. Vol. 26, p. 281, 1926. |
Mouse | LC50 | inhalation | 120mg/m3/1H | LUNGS, THORAX, OR RESPIRATION: ACUTE PULMONARY EDEMA, LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES | Egle and Gochberg, 1979 |
Rabbit | LDLo | oral | 234mg/kg | GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS, GASTROINTESTINAL: NAUSEA OR VOMITING, BLOOD: HEMORRHAGE | Journal of Pharmacology and Experimental Therapeutics. Vol. 26, p. 281, 1926. |
Rat | LC50 | inhalation | 3398ppm/1H | SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE | Hazelton Laboratories, Reports. Vol. HLA468-102, p. 1987. |
*NLM, 2011
Furan and Mitigation Measures
Furan as a possible carcinogen to human having chance to become a genotoxic so their level in food should kept ALARA-as low as reasonably achievable (EFSA, 2004). Reduction of heat induced toxins in the food is difficult but can be reduced by changing heating method or reduction in furan precursors by using different method.
By two reasons, reduction of furan in food is more challenging among process toxins. First, concerning microbiology safety of foods during pasteurization and sterilization, there is a little chance to lower heating time with respect to temperature. Second, is due to wide range of furan precursors. As we know, ascorbic acid and polyunsaturated fatty acids are desirable components because of health claims, but on the other hand ascorbic acid showing a highest potential to form furan followed by PUFA and sugars (Stadler, 2006).
As mitigation measure, if we consider volatility of furan, then again limited application due to microbiological reason in canned and jarred foods being packed hermetically and concerning coffee it is difficult to retain all flavors and aroma substances while removing furan. Roberts et al. (2008) suggested that the level of furan is decreased in canned and jarred foods due to evaporation after heating but in contrast, furan is persistent in food and not lost to a significant level after simple heating (Crews and Castle, 2007a; Hasnip et al., 2006).
Recently, intervention in the reaction mechanisms is appeared to best approach for the reduction of furan in food as reported by Shinoda et al. (2005) that furfural formation from the ascorbic acid in model juice was suppressed in the presence of ethanol and mannitol that act as free radical scavengers. To minimize autoxidation of unsaturated fatty acid ultimately reduction in furan formation in food. Therefore, reduction of furan is might be possible due to modification within heating system.
Fan and Mastov (2006) reported that furan in water system was sensitive to irradiation and with increase dose of irradiation, furan decrease swiftly. Furan reduction takes place in two phases; first, rapid reduction at dose 0 to 0.4 kGy, second, with slow rate reduction between 0.4 to 1.0 kGy. Approximately 78% of furan was devastated at 0.4 kGy. Fresh cut fruits and vegetables (19 Samples) were subjected to 5 kGy gamma rays at 4 °C and result shown that all samples have furan level less that 1 ng/g to non-detectable level. Only in those fruits that had high simple sugar and low pH, furan is produced at low level by irradiation (Fan and Sokorai, 2008).
In other studies on effect of consumer cooking on furan illustrated that microwave heating of food has no remarkable reduction in furan however, decrease furan level in jarred and canned food after heating the food in saucepan. Furan level also decreases slightly when foods on standing before consumption for some time (Roberts et al., 2008). These observations attributed to the volatility of furan.
To date, only limited data is available on occurrence as well as consumption of furan. Due to this reason the Scientific Panel on Contaminants in the Food Chain EFSA has decided to report estimated exposure range rather than average exposure (EFSA, 2004). A high proportion of baby food samples that are sold in jars and cans are of great importance due to sole diet of many babies. The dietary intake of baby foods from glass jars was less than 0.2 to 26 mg furan/day or less than 0.03 to 3.5 mg/kg of body weight for 6 month old baby of weight 7.5 kg (EFSA, 2004) while the dietary exposure for adult form canned or jarred vegetable (35 sample), from beer (12 samples) and coffee (45 samples) were estimated 1.1 to 23, 1.3 to 50 and 2.4 to 116 mg/person, respectively.
Legislation and Control
In May 2004 the US Food and Drug Administration (FDA) circulated the results of a survey concerning the presence of furan, after this EFSA assembled a scientific report on furan in food on 7 December 2004. In this report EFSA decided that available data showed relatively small difference between possible human exposer and doses in experimental animal carcinogenicity, so that, for reliable risk assessment would need further data.
The European Commission (2007/196/EC) also focused on data collection in 2007 during commission recommendation on the monitoring of the presence of furan in foodstuffs. Recently, July 2010, The European Food Safety Authority (EFSA) has issued a report updating results of monitoring on the levels of furan found in food. Up to date, seventeen Member States and Norway submitted to EFSA’s Data Collection and Exposure unit (DATEX) the analytical results for a total of 4,186 food samples collected between 2004 and 2009.
Summary
Food safety is of great concern regarding public health point of view. Every day consumer’s perception for food is continuously changing due to different factors such as health conscious awareness, busy life and ready of cook foods etc. Food business man changes the processing conditions to produce safe and good quality product that meets the consumer’s requirements. Furan; a process toxin, which is produced during heat processing of food. International Agency for Research on Cancer (IARC) in 1995 was categories this compound as possible human carcinogen (Group 2B) after research study on animals. Earlier research on furan, its presence in a variety of foods and evidence of carcinogen to animals at high dose was creating a dire need to monitor furan in processing foods. In 2004, Food and Drug Administration (FDA) reported that furan is present in a number of foods that undergoes thermal treatment particularly canned and jarred foods. After this, the European food safety authority (EFSA) initiated the collection of data from all member states concerning furan presence in food to carry out risk analysis.
Furan is promptly and extensively absorbed by the intestine and lungs due to its low polarity that make it easy to pass through biological membranes and enter into various organs such as liver, kidney, large intestine, small intestine, stomach, blood and lungs. Absorbed furan is metabolized quickly by cytochrome P-450 enzymes to form carbon dioxide and cis-2-butene-1,4-dial; known as reactive and cytotoxic that bind to protein and nucleosides. Furan is potent carcinogen to many organs shown by different toxicity studies. Reduction of heat induced toxins in the food is difficult but can be reduced by changing heating method or reduction in furan precursors by using different methods.
To date, only limited data is available on occurrence as well as consumption of furan. Due to this reason the Scientific Panel on Contaminants in the Food Chain, EFSA has decided to report estimated exposure range rather than average exposure. Recently, in July 2010 EFSA issued a report updating results of monitoring on the levels of furan found in food.
