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Research Article Open access CC BY 4.0

Risk Assessment of Furan Exposure in the Norwegian Population

Trine Husøy, Augustine Arukwe, Mona-Lise Bindrup, Anne Lise Brantsæter, Christiane Kruse Fæste, Ragna Bogen Hetland, Jan Alexander, Heidi Amlund, Knut Helkås Dahl, Gunnar Sundstøl Eriksen, Berit Granum, Kari Grave, Helle Katrine Knutsen, Jan Erik Paulsen, Anders Ruus, Tore Sanner, Inger-Lise Steffensen, Cathrine Thomsen, Vibeke Thrane, Janneche Utne Skåre

European Journal of Nutrition & Food Safety · pp. 44–46 · Published 19 Nov 2019

10.9734/ejnfs/2019/v11i130128

Abstract

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has on request of The Norwegian Food Safety Authority performed a risk assessment of furan intake in the Norwegian population based on the most recent national food consumption surveys. National occurrence data of furan concentrations in food were preferentially used in the risk assessment. When national data were lacking, VKM has used occurrence data of furan from other countries. The assessment has been performed by the VKM Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics and the VKM Panel on Contaminants.   Furan is a volatile and lipophilic compound formed in a variety of heat-treated commercial foods and contributes to the sensory properties of the product. The substance has been found in a number of foods such as coffee, canned and jarred foods including baby food containing meat and various vegetables. High concentrations of furan have been found in coffee and the presence of furan in jarred baby food and infant formulae has received much attention since such products may be the sole diet for many infants. The occurrence of furan in a variety of foods suggests that there are multiple routes of furan formation rather than a single mechanism.   The Norwegian Food Safety Authority has in 2008 and 2009 collected data on furan concentrations in different food products sold on the Norwegian market (Norwegian Food Safety Authority, 2008). In 2011, the Norwegian Food Safety Authority also decided to analyse commercial porridges for infants and children sold on the Norwegian market, to see if furan could be detected in such products.   The calculated furan exposures from food and beverages are based on data from the nationally representative food consumption surveys; Spedkost, Småbarnskost, Ungkost and Norkost. The consumption for each relevant food or food category in the dietary surveys were multiplied with the corresponding mean furan concentrations and totalled for each individual.   The liver is the main target organ for furan toxicity both in mice and rats, but the rat is the most sensitive species. A dose-dependent increase in hepatocellular adenomas and carcinomas was observed in mice and rats, and an increase in the incidence of cholangiocarcinomas was observed in rat liver. Cholangiocarcinomas in male and female rats were the most sensitive toxicological end point observed in rodents. On the basis of the available data, VKM considers that rat cholangiocarcinomas may be relevant for assessing human risk from furan.   Available in vivo data with furan indicate that a reactive metabolite, most likely cis-2-butene1,4-dial (BDA), is formed and that this metabolite can react with DNA and induce mutations. To VKM’s knowledge, no in vivo studies on genotoxicity of BDA have been performed, but BDA was found to be genotoxic in several in vitro tests. VKM therefore considers that a genotoxic mechanism in furan-induced carcinogenesis cannot be excluded and the substance was assessed as a genotoxic carcinogen.   VKM used the Margin of Exposure (MOE) approach in this risk assessment. The suitability of different studies on cholangiocarcinomas for dose-response modelling was considered. The 9-month interim evaluation of a 2-year study from NTP (1993) was chosen because it demonstrates a dose-response relationship. From this study, a point of departure of 0.02 mg/kg bw/day was chosen, based on a benchmark dose lower bound (BMDL10) of 0.14 mg furan/kg bw/day and a correction factor of 7 for shorter than full life-time (2 years) study duration.    For 6-, 12- and 24-month-old children, the main source of furan exposure is jarred baby food. For 4-, 9- and 13-year-old children, the major food source to the furan exposure is breakfast cereals. In adults, the major contribution to the furan exposure is coffee. The highest furan exposure was calculated for 12-month-old infants and ranged from 0.62-1.51 µg/kg bw/day. In adults the furan exposure ranged from 0.27-0.82 µg/kg bw/day.    For mean exposure among infants, children and adolescents, the MOE-values ranged from 29 in 12-month-infants to 2000 in the 13-year-old adolescents. Among high consumers in these groups, the MOE-values ranged from 13 to 400. In adults, the corresponding MOE-values ranged from 59 to 74 for mean furan exposure and from 24 to 26 for high exposure.   It should be noted that this risk assessment of furan contains notable uncertainties and limitations. The use of the 9-month interim study in rats including a correction factor of 7 to derive a point of departure, instead of a full life-time study (2-year) study, likely overestimates the hazard of furan. A possible over-diagnosis of the cholangiocarcinomas, due to the similarities in histopathology between cholangiofibrosis and cholangiocarcinomas in rats, may overestimate the hazard. There are also limitations in assessing food consumption and furan content in foods, leading to uncertainties in estimation of furan exposure.   VKM considers that the current exposure to furan in all age groups, particularly among infants and children, is of health concern.

Furan risk assessment intake BMD calculations cancer genotoxicity.

References (67)

  1. 1 Markers of the Validity of Reported Energy Intake [DOI]
  2. 2 Chromosome aberrations and sister chromatid exchanges in chinese hamster ovary cells: Evaluations of 108 chemicals [DOI]
  3. 3 Safety evaluation of certain contaminants in food
  4. 4 Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation
  5. 5 Application of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and carcinogenic [DOI]
  6. 6 Human Hepatic CYP2E1 Expression during Development [DOI]
  7. 7 Furan in food: Headspace method and product survey [DOI]
  8. 8 The physiological and pharmacological roles of cytochrome P450 isoenzymes [DOI]
  9. 9 Identification of cis-2-Butene-1,4-dial as a Microsomal Metabolite of Furan [DOI]
  10. 10 Toxicity and carcinogenicity of furan in human diet [DOI]
  11. 11 Kinetic Analysis of Furan Biotransformation by F-344 Rats in Vivo and in Vitro [DOI]
  12. 12 Characterization of Nucleoside Adducts of cis-2-Butene-1,4-dial, a Reactive Metabolite of Furan [DOI]
  13. 13 Characterization of Amino Acid and Glutathione Adducts ofcis-2-Butene-1,4-dial, a Reactive Metabolite of Furan [DOI]
  14. 14 Furan-induced dose–response relationships for liver cytotoxicity, cell proliferation, and tumorigenicity (furan-induced liver tumorigenicity) [DOI]
  15. 15 A Reactive Metabolite of Furan, cis-2-Butene-1,4-dial, Is Mutagenic in the Ames Assay [DOI]
  16. 16 Development of an analytical method and survey of foods for furan, 2-methylfuran and 3-methylfuran with estimated exposure [DOI]
  17. 17 Oxidation of furans with dimethyldioxirane [DOI]
  18. 18 Comparison of Women’s Diet Assessed by FFQs and 24-Hour Recalls with and without Underreporters: Associations with Biomarkers [DOI]
  19. 19 GLUTATHIONE TRAPPING TO MEASURE MICROSOMAL OXIDATION OF FURAN TO CIS-2-BUTENE-1,4-DIAL [DOI]
  20. 20 Subchronic Oral Toxicity Study of Furan in Fischer-344 Rats [DOI]
  21. 21 Validation of a semi-quantitative food-frequency questionnaire used among 12-month-old Norwegian infants [DOI]
  22. 22 Assessment of in vivo genotoxicity of the rodent carcinogen furan: evaluation of DNA damage and induction of micronuclei in mouse splenocytes [DOI]
  23. 23 In vivo genotoxicity of furan in F344 rats at cancer bioassay doses [DOI]
  24. 24 Genotoxicity of furan in Big Blue rats [DOI]
  25. 25 Furan carcinogenicity: DNA binding and genotoxicity of furan in rats in vivo [DOI]
  26. 26 Gene expression and epigenetic changes by furan in rat liver [DOI]
  27. 27 DNA damage in fetal liver cells of turkey and chicken eggs dosed with aflatoxin B1 [DOI]
  28. 28 DNA‐damaging activity of biotic and xenobiotic aldehydes in chinese hamster ovary cells [DOI]
  29. 29 Prediction of Furan Pharmacokinetics from Hepatocyte Studies: Comparison of Bioactivation and Hepatic Dosimetry in Rats, Mice, and Humans [DOI]
  30. 30 Energy intake in Swedish adolescents: validation of diet history with doubly labelled water [DOI]
  31. 31 Furan-Induced Cytolethality in Isolated Rat Hepatocytes: Correspondence with in Vivo Dosimetry [DOI]
  32. 32 Furan-induced liver cell proliferation and apoptosis in female B6C3F1 mice [DOI]
  33. 33 Degraded Protein Adducts of cis-2-Butene-1,4-dial Are Urinary and Hepatocyte Metabolites of Furan [DOI]
  34. 34 Tests for genotoxicity and mutagenicity of furan and its metabolite cis-2-butene-1,4-dial in L5178Y tk+/− mouse lymphoma cells [DOI]
  35. 35 Biomarkers of Furan Exposure by Metabolic Profiling of Rat Urine with Liquid Chromatography-Tandem Mass Spectrometry and Principal Component Analysis [DOI]
  36. 36 The Impact of Cytochrome P450 2E1‐Dependent Metabolic Variance on a Risk‐Relevant Pharmacokinetic Outcome in Humans [DOI]
  37. 37 Identification of a cis-2-Butene-1,4-dial-derived Glutathione Conjugate in the Urine of Furan-Treated Rats [DOI]
  38. 38 Studies on the interaction of furan with hepatic cytochrome P‐450 [DOI]
  39. 39 Toxic and genotoxic effects of oral administration of furan in mouse liver [DOI]
  40. 40 Furan is not genotoxic in the micronucleus assay in vivo or in vitro [DOI]
  41. 41 Validity and reproducibility.
  42. 42 Respiratory retention and acute toxicity of furan [DOI]
  43. 43 Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens [DOI]
  44. 44 Furan induction of DNA cross-linking and strand breaks in turkey fetal liver in comparison to 1,3-propanediol [DOI]
  45. 45 Production of liver preneoplasia and gallbladder agenesis in turkey fetuses administered diethylnitrosamine [DOI]
  46. 46 In ovo carcinogenicity assay (IOCA): evaluation of mannitol, caprolactam and nitrosoproline [DOI]
  47. 47 A Simple Method for Quantitative Risk Assessment of Non-Threshold Carcinogens Based on the Dose Descriptor T25 [DOI]
  48. 48 Foci of altered hepatocytes induced in embryonal turkey liver [DOI]
  49. 49 Detailed exposure assessment of dietary furan for infants consuming commercially jarred complementary food based on data from the DONALD study [DOI]
  50. 50 Dose dependence of diethylnitrosamine-induced nuclear enlargement in embryonal turkey liver [DOI]
  51. 51 IARC (International Agency for Research on Cancer)
  52. 52 Using Intake Biomarkers to Evaluate the Extent of Dietary Misreporting in a Large Sample of Adults: The OPEN Study [DOI]
  53. 53 Cytochrome P-4502E1: its physiological and pathological role [DOI]
  54. 54 Misreporting of energy and micronutrient intake estimated by food records and 24 hour recalls, control and adjustment methods in practice [DOI]
  55. 55 Evaluation of genotoxicity, pathological lesions, and cell proliferation in livers of rats and mice treated with furan [DOI]
  56. 56 Evidence of Oxidative Stress and Associated DNA Damage, Increased Proliferative Drive, and Altered Gene Expression in Rat Liver Produced by the Cholangiocarcinogenic Agent Furan [DOI]
  57. 57 Electrophilic Intermediates Produced by Bioactivation of Furan [DOI]
  58. 58 Application of the margin of exposure (MoE) approach to substances in food that are genotoxic and carcinogenic [DOI]
  59. 59 Data requirements for risk assessment of furan in food [DOI]
  60. 60 Nature of Variation in Diet [DOI]
  61. 61 Validation of a pre-coded food diary used among 13-year-olds: comparison of energy intake with energy expenditure [DOI]
  62. 62 Hepatobiliary Toxicity of Furan: Identification of Furan Metabolites in Bile of Male F344/N Rats [DOI]
  63. 63 Furan in heat processed food products including home cooked food products and ready‐to‐eat products [DOI]
  64. 64 1. Overview of the principles of nutritional epidemiology [DOI]
  65. 65 The em in ovo em carcinogenicity assay IOCA a review of an experimental approach for research on carcinogenesis and carcinogenicity testing [DOI]
  66. 66 Furan in Kaffee und anderen Lebensmitteln [DOI]
  67. 67 Validation of a semi-quantitative food-frequency questionnaire used among 2-year-old Norwegian children – Corrigendum [DOI]

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