Evaluation of the risks for animal health related to the presence of hydroxymethylfurfural (HMF) in feed for honey bees

Abstract The European Commission has asked the EFSA to evaluate the risk for animal health related to the presence of hydroxymethylfurfural (HMF) in honey bee feed. HMF is a degradation product of particular sugars and can be present in bee feed. HMF is of low acute toxicity in bees but causes increased mortality upon chronic exposure. A benchmark dose lower limit 10% (BMDL10) of 1.16 μg HMF per bee per day has been calculated from mortalities observed in a 20‐day study and established as a Reference Point covering also mortality in larvae, drones and queens for which no or insufficient toxicity data were available. Winter bees have a much longer lifespan than summer bees and HMF shows clear time reinforced toxicity (TRT) characteristics. Therefore, additional Reference Point intervals of 0.21–3.1, 0.091–1.1 and 0.019–0.35 µg HMF/bee per day were calculated based on extrapolation to exposure durations of 50, 90 and 180 days, respectively. A total of 219 analytical data of HMF concentrations in bee feed from EU Member States and 88 from Industry were available. Exposure estimates of worker bees and larvae ranged between 0.1 and 0.48, and between 0.1 and 0.51 μg HMF/per day, respectively. They were well below the BMDL10 of 1.16 μg HMF/bee per day, and thus, no concern was identified. However, when accounting for TRT, the probability that exposures were below established reference point intervals was assessed to be extremely unlikely to almost certain depending on exposure duration. A concern for bee health was identified when bees are exposed to HMF contaminated bee feed for several months.

[1]  S. Gan,et al.  5-Hydroxymethylfurfural (HMF) levels in honey and other food products: effects on bees and human health , 2018, Chemistry Central Journal.

[2]  José Cortiñas Abrahantes,et al.  Update: use of the benchmark dose approach in risk assessment , 2017, EFSA journal. European Food Safety Authority.

[3]  R. Prior,et al.  Identification and urinary excretion of metabolites of 5-(hydroxymethyl)-2-furfural in human subjects following consumption of dried plums or dried plum juice. , 2006, Journal of agricultural and food chemistry.

[4]  L. Bailey.  The Effect of Acid-Hydrolysed Sucrose on Honeybees , 1966 .

[5]  K. Crailsheim,et al.  Effect of hydroxymethylfurfural (HMF) on mortality of artificially reared honey bee larvae (Apis mellifera carnica) , 2016, Ecotoxicology.

[6]  S. H. Bennekou,et al.  Scientific Opinion on the state of the art of Toxicokinetic/Toxicodynamic (TKTD) effect models for regulatory risk assessment of pesticides for aquatic organisms , 2018, EFSA journal. European Food Safety Authority.

[7]  R. J. Barker,et al.  Acceptance and sustenance value of naturally occurring sugars fed to newly emerged adult workers of honey bees (Apis mellifera L.) , 1974 .

[8]  G. Arnold,et al.  Modes of honeybees exposure to systemic insecticides: estimated amounts of contaminated pollen and nectar consumed by different categories of bees , 2005 .

[9]  A. I. Ruiz-Matute,et al.  Carbohydrate composition of high-fructose corn syrups (HFCS) used for bee feeding: effect on honey composition. , 2010, Journal of agricultural and food chemistry.

[10]  K. Hughes,et al.  Evolution and mechanisms of long life and high fertility in queen honey bees , 2008, AGE.

[11]  Geoffrey R. Williams,et al.  Long-term field-realistic exposure to a next-generation pesticide, flupyradifurone, impairs honey bee behaviour and survival , 2021, Communications Biology.

[12]  Vikas Nanda,et al.  Optimization of process parameters on hydroxymethylfurfural content, diastase and invertase activity of coriander honey , 2019, Journal of Food Science and Technology.

[13]  O. Winkler.  Beitrag zum nachweis und zur bestimmung von oxymethylfurfurol in honig und kunsthonig , 1955 .

[14]  C. Leclercq,et al.  Guidance of EFSA: Use of the EFSA Comprehensive European Food Consumption Database in exposure assessment , 2011 .

[15]  H. Lucero,et al.  Honey thermal treatment effects on hydroxymethylfurfural content , 2002 .

[16]  P. Semkiw,et al.  Suitability of Starch Syrups for Winter Feeding of Honeybee Colonies , 2016 .

[17]  K. Crailsheim,et al.  Nutrition and health in honey bees , 2010, Apidologie.

[18]  Gillian Eggleston,et al.  Formation of hydroxymethylfurfural in domestic high-fructose corn syrup and its toxicity to the honey bee (Apis mellifera). , 2009, Journal of agricultural and food chemistry.

[19]  P. Rosenkranz,et al.  From field to food—will pesticide-contaminated pollen diet lead to a contamination of royal jelly? , 2018, Apidologie.

[20]  J. Boesten,et al.  EFSA Guidance Document on the risk assessment of plant protection products on bees (Apis mellifera, Bombus spp. and solitary bees) , 2013 .

[21]  Reed M. Johnson,et al.  Effect of a Fungicide and Spray Adjuvant on Queen-Rearing Success in Honey Bees (Hymenoptera: Apidae) , 2013, Journal of economic entomology.

[22]  A. Gregorc,et al.  Hydroxymethylfurfural Affects Caged Honey Bees (Apis mellifera carnica) , 2019, Diversity.

[23]  Roman Ashauer,et al.  General unified threshold model of survival--a toxicokinetic-toxicodynamic framework for ecotoxicology. , 2011, Environmental science & technology.

[24]  C. Violeta.  THE QUALITY OF SYRUPS USED FOR BEE FEEDING BEFORE WINTER AND THEIR SUITABILITY FOR BEE WINTERING , 2006 .

[25]  Franck Carbonero,et al.  Impact of Maillard reaction products on nutrition and health: Current knowledge and need to understand their fate in the human digestive system , 2019, Critical reviews in food science and nutrition.

[26]  H. J. Jeuring,et al.  High performance liquid chromatography of furfural and hydroxymethylfurfural in spirits and honey. , 1980, Journal - Association of Official Analytical Chemists.

[27]  J. Taséi,et al.  Improvement of artificial feeding in a standard in vitro method for rearing Apis mellifera larvae , 2005 .

[28]  A. Gregorc,et al.  A preliminary laboratory study on the longevity of A. m. carnica honey bees after feeding with candies containing HMF , 2014 .

[29]  V. Fogliano,et al.  Acrylamide and 5-hydroxymethylfurfural (HMF): A review on metabolism, toxicity, occurrence in food and mitigation strategies , 2011 .

[30]  Z. Huang,et al.  Pathway of 5-hydroxymethyl-2-furaldehyde formation in honey , 2019, Journal of Food Science and Technology.

[31]  L. J. Chen,et al.  Distribution and metabolism of (5-hydroxymethyl)furfural in male F344 rats and B6C3F1 mice after oral administration. , 1999, Journal of toxicology and environmental health. Part A.

[32]  F. Nazzi,et al.  Possible side effects of sugar supplementary nutrition on honey bee health , 2020, Apidologie.

[33]  L. Maillard,et al.  Action des acides amines sur les sucres : formation des melanoidines par voie methodique , 1912 .

[34]  M. Berenbaum,et al.  Xenobiotic detoxification pathways in honey bees. , 2015, Current opinion in insect science.

[35]  E. Arena,et al.  Methods for the determination of HMF in honey: a comparison , 2005 .

[36]  Xiao-qing Miao,et al.  Salting-out-assisted liquid–liquid extraction of 5-hydroxymethylfurfural from honey and the determination of 5-hydroxymethylfurfural by high-performance liquid chromatography , 2019, Analytical Methods.

[37]  Anthony Hardy,et al.  Guidance on Uncertainty Analysis in Scientific Assessments , 2018, EFSA journal. European Food Safety Authority.

[38]  D. W. Ball.  The Chemical Composition of Honey. , 2007 .

[39]  A. Sabatini,et al.  Honey quality, methods of analysis and international regulatory standards: Review of the work of the International Honey Commission , 1999 .

[40]  G. Scarponi,et al.  Determination of very low levels of 5-(hydroxymethyl)-2-furaldehyde (HMF) in natural honey: comparison between the HPLC technique and the spectrophotometric white method. , 2012, Journal of food science.

[41]  J. Cresswell,et al.  Time-dependent effects on bumble bees of dietary exposures to farmland insecticides (imidacloprid, thiamethoxam and fipronil). , 2020, Pest management science.

[42]  Olivier Wilmart,et al.  Analyse du risque posé en santé animale par la présence de l'hydroxyméthylfurfural dans les sirops de nourrissement des abeilles domestiques , 2011 .

[43]  Claes Wohlin,et al.  Systematic literature studies: Database searches vs. backward snowballing , 2012, Proceedings of the 2012 ACM-IEEE International Symposium on Empirical Software Engineering and Measurement.

[44]  S. Karabournioti,et al.  THE EFFECT OF HEATING ON HONEY HMF AND INVERTASE , 2001 .

[45]  J. Simpson,et al.  Invertase in the Hypopharyngeal Glands of the Honeybee , 1968 .

[46]  M. Bin-Jumah,et al.  The Toxicological Aspects of the Heat-Borne Toxicant 5-Hydroxymethylfurfural in Animals: A Review , 2020, Molecules.

[47]  J. White,et al.  Spectrophotometric method for hydroxymethylfurfural in honey. , 1979, Journal - Association of Official Analytical Chemists.

[48]  A. Lampen,et al.  Toxicology and risk assessment of 5-Hydroxymethylfurfural in food. , 2011, Molecular nutrition & food research.

[49]  T. Jachimowicz,et al.  ZUR PROBLEMATIK DER VERWENDUNG VON INVERTZUCKER FÜR DIE BIENENFÜTTERUNG , 1975 .

[50]  Noa Simon Delso,et al.  Scientific Opinion on the science behind the development of a risk assessment of Plant Protection Products on bees (Apis mellifera, Bombus spp. and solitary bees) , 2012 .