, Volume 28, Issue 3, pp 354–366 | Cite as

The novel pesticide flupyradifurone (Sivanto) affects honeybee motor abilities

  • Hannah HesselbachEmail author
  • Ricarda Scheiner


Honeybees and other pollinators are threatened by changing landscapes and pesticides resulting from intensified agriculture. In 2018 the European Union prohibited the outdoor use of three neonicotinoid insecticides due to concerns about pollinators. A new pesticide by the name of “Sivanto” was recently released by Bayer AG. Its active ingredient flupyradifurone binds to the nicotinic acetylcholine receptor (AchR) in the honeybee brain, similar to neonicotinoids. Nevertheless, flupyradifurone is assumed to be harmless for honeybees and can even be applied on flowering crops. So far, only little has been known about sublethal effects of flupyradifurone on honeybees. Intact motor functions are decisive for numerous behaviors including foraging and dancing. We therefore selected a motor assay to investigate in how far sublethal doses of this pesticide affect behavior in young summer and long-lived winter honeybees. Our results demonstrate that flupyradifurone (830 µmol/l) can evoke motor disabilities and disturb normal motor behavior after a single oral administration (1.2 µg/bee). These effects are stronger in long-lived winter bees than in young summer bees. After offering an equal amount of pesticide (1.0–1.75 µg) continuously over 24 h with food the observed effects are slighter. For comparisons we repeated our experiments with the neonicotinoid imidacloprid. Intriguingly, the alterations in behavior induced by this pesticide (4 ng/bee) were different and longer-lasting compared to flupyradifurone, even though both substances bind to nicotinic acetylcholine receptors.


Honeybee Motor ability Acetylcholine receptor Insecticide Flupyradifurone Imidacloprid 



We thank our departmental beekeeper Dirk Ahrens for beekeeping. We thank Laura Degirmenci for help with the manuscript.


We thank the Heinrich Stockmeyer Stiftung, Bad Rothenfelde, for financial support to HH.

Author contributions

HH gained data. Both authors wrote the main manuscript text and HH prepared all of the figures. Both authors reviewed the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10646_2019_2028_MOESM1_ESM.pdf (317 kb)
Supplementary Information.
10646_2019_2028_MOESM2_ESM.mp4 (968 kb)
Supplementary Movie 1.
10646_2019_2028_MOESM3_ESM.mp4 (688 kb)
Supplementary Movie 2.


  1. Aizen MA, Harder LD (2009) The global stock of domesticated honey bees is growing slower than agricultural demand for pollination. Curr Biol 19:915–918. CrossRefGoogle Scholar
  2. Alkassab AT, Kirchner WH (2018) Assessment of acute sublethal effects of clothianidin on motor function of honeybee workers using video-tracking analysis. Ecotoxicol Environ Saf 147:200–205. CrossRefGoogle Scholar
  3. Beck ME, Gutbrod O, Matthiesen S (2015) Insight into the binding mode of agonists of the nicotinic acetylcholine receptor from calculated electron densities. Chemphyschem 16:2760–2767. CrossRefGoogle Scholar
  4. Beketov MA, Liess M (2008) Acute and delayed effects of the neonicotinoid insecticide thiacloprid on seven freshwater arthropods. Environ Toxicol Chem 27:461–470. CrossRefGoogle Scholar
  5. Bicker G (1999) Histochemistry of classical neurotransmitters in antennal lobes and mushroom bodies of the honeybee. Microsc Res Tech 45:174–183.<174:AID-JEMT5>3.3.CO;2-L CrossRefGoogle Scholar
  6. Breer H, Sattelle DB (1987) Molecular properties and functions of insect acetylcholine receptors. J Insect Physiol 33:771–790. CrossRefGoogle Scholar
  7. Butler CG (1945) The influence of various physical and biological factors of the environment on honeybee activity. An examination of the relationship between activity and nectar concentration and abundance. J Experiment Biol 21:5–12Google Scholar
  8. Campbell JW, Cabrera AR, Stanley-Stahr C, Ellis JD (2016) An Evaluation of the Honey Bee (Hymenoptera: Apidae) safety profile of a new systemic insecticide, flupyradifurone, under field conditions in Florida. J Econ Entomol 109:1967–1972. CrossRefGoogle Scholar
  9. Coulom H, Birman S (2004) Chronic exposure to rotenone models sporadic Parkinson’s disease in Drosophila melanogaster. J Neurosci 24:10993–10998. CrossRefGoogle Scholar
  10. Cresswell JE, Robert F-XL, Florance H, Smirnoff N (2014) Clearance of ingested neonicotinoid pesticide (imidacloprid) in honey bees (Apis mellifera) and bumblebees (Bombus terrestris). Pest Manag Sci 70:332–337. CrossRefGoogle Scholar
  11. Danner N, Keller A, Härtel S, Steffan-Dewenter I (2017) Honey bee foraging ecology: season but not landscape diversity shapes the amount and diversity of collected pollen. PLoS ONE 12:e0183716. CrossRefGoogle Scholar
  12. Delaplane KS, Mayer DF (2000) Crop pollination by bees. CABI, WallingfordCrossRefGoogle Scholar
  13. Desneux N, Decourtye A, Delpuech J-M (2007) The sublethal effects of pesticides on beneficial arthropods. Annu Rev Entomol 52:81–106. CrossRefGoogle Scholar
  14. EFSA (2015) Conclusion on the peer review of the pesticide risk assessment of the active substance flupyradifurone. EFS2 13:4020.
  15. Eiri DM, Nieh JC (2016) A nicotinic acetylcholine receptor agonist affects honey bee sucrose responsiveness and decreases waggle dancing. J Exp Biol 219:2081. CrossRefGoogle Scholar
  16. European Commission (2018a) Commission ImplementingRegulation (EU) 2018/783 of 29 May 2018 amending Implementing Regulation (EU) No 540/2011 as regards the conditions of approval of the active substance imidacloprid. Off J Eur Union 132:31–34. Accessed 21 Aug 2018Google Scholar
  17. European Commission (2018b) Commission ImplementingRegulation (EU) 2018/784 of 29 May 2018 amending Implementing Regulation (EU) No 540/2011 as regards the conditions of approval of the active substance clothianidin:L 132/35-39. Accessed 21 Aug 2018Google Scholar
  18. European Commission (2018c) Commission ImplementingRegulation (EU) 2018/785 of 29 May 2018 amending Implementing Regulation (EU) No 540/2011 as regards the conditions of approval of the active substance thiamethoxam. Off J Eur Union 132:40–44. Accessed 21 Aug 2018Google Scholar
  19. European Food Safety Authority (2012) Statement on the findings in recent studies investigating sub‐lethal effects in bees of some neonicotinoids in consideration of the uses currently authorised in Europe. EFS2 10:440. Google Scholar
  20. Friard O, Gamba M, Fitzjohn R (2016) BORIS: A free, versatile open-source event-logging software for video/audio coding and live observations. Methods Ecol Evol 7:1325–1330. CrossRefGoogle Scholar
  21. Gauglitz S, Pflüger H-J (2001) Cholinergic transmission via central synapses in the locust nervous system. J Comp Physiol A: Sens, Neural, Behav Physiol 187:825–836. CrossRefGoogle Scholar
  22. Glaberman S, White K (2014) Environmental fate and ecological risk assessment for foliar, soil drench, and seed treatment uses of the new insecticide flupyradifurone (BYI02960). U.S. Environmental Protection Agency Office of Pesticide Programs, Environmental Fate and Effects Division EFED, Environmental Risk Branch IV 187Google Scholar
  23. Goulson D, Nicholls E, Botías C, Rotheray EL (2015) Bee declines driven by combined stress from parasites, pesticides, and lack of flowers. Science 347:1255957. CrossRefGoogle Scholar
  24. Hallmann CA, Sorg M, Jongejans E, Siepel H, Hofland N, Schwan H, Stenmans W, Müller A, Sumser H, Hörren T, Goulson D, Kroon Hde (2017) More than 75 percent decline over 27 years in total flying insect biomass in protected areas. PLoS ONE 12:e0185809. CrossRefGoogle Scholar
  25. Henry M, Béguin M, Requier F, Rollin O, Odoux J-F, Aupinel P, Aptel J, Tchamitchian S, Decourtye A (2012) A common pesticide decreases foraging success and survival in honey bees. Science 336:348–350. CrossRefGoogle Scholar
  26. Hesselbach H, Scheiner R (2018) Effects of the novel pesticide flupyradifurone (Sivanto) on honeybee taste and cognition. Sci Rep 8:4954. CrossRefGoogle Scholar
  27. James RR, Xu J (2012) Mechanisms by which pesticides affect insect immunity. J Invertebr Pathol 109:175–182. CrossRefGoogle Scholar
  28. Jeschke P, Nauen R, Gutbrod O, Beck ME, Matthiesen S, Haas M, Velten R (2015) Flupyradifurone (Sivanto™) and its novel butenolide pharmacophore: Structural considerations. Pestic Biochem Physiol 121:31–38. CrossRefGoogle Scholar
  29. Klatt BK, Holzschuh A, Westphal C, Clough Y, Smit I, Pawelzik E, Tscharntke T (2014) Bee pollination improves crop quality, shelf life and commercial value. Proc Biol Sci 281:20132440. CrossRefGoogle Scholar
  30. Klein A-M, Vaissière BE, Cane JH, Steffan-Dewenter I, Cunningham SA, Kremen C, Tscharntke T (2007) Importance of pollinators in changing landscapes for world crops. Proc Biol Sci 274:303–313. CrossRefGoogle Scholar
  31. Knopper LD, Dan T, Reisig DD, Johnson JD, Bowers LM (2016) Sugar concentration in nectar: a quantitative metric of crop attractiveness for refined pollinator risk assessments. Pest Manag Sci 72:1807–1812. CrossRefGoogle Scholar
  32. Krupke CH, Hunt GJ, Eitzer BD, Andino G, Given K (2012) Multiple routes of pesticide exposure for honey bees living near agricultural fields. PLoS ONE 7:e29268. CrossRefGoogle Scholar
  33. Lambin M, Armengaud C, Raymond S, Gauthier M (2001) Imidacloprid‐induced facilitation of the proboscis extension reflex habituation in the honeybee. Arch Insect Biochem Physiol 48:129–134. CrossRefGoogle Scholar
  34. Lee D, O’Dowd DK (1999) Fast excitatory synaptic transmission mediated by nicotinic acetylcholine receptors in Drosophila neurons. J Neurosci 19:5311–5321. CrossRefGoogle Scholar
  35. Mitchell EAD, Mulhauser B, Mulot M, Mutabazi A, Glauser G, Aebi A (2017) A worldwide survey of neonicotinoids in honey. Science 358:109–111. CrossRefGoogle Scholar
  36. Mullin CA, Frazier M, Frazier JL, Ashcraft S, Simonds R, Vanengelsdorp D, Pettis JS (2010) High levels of miticides and agrochemicals in North American apiaries: implications for honey bee health. PLoS ONE 5:e9754. CrossRefGoogle Scholar
  37. Nation JL (2008) Insect physiology and biochemistry, 2nd edn. CRC Press, HobokenGoogle Scholar
  38. Nauen R, Ebbinghaus-Kintscher U, Schmuck R (2001) Toxicity and nicotinic acetylcholine receptor interaction of imidacloprid and its metabolites in Apis mellifera (Hymenoptera: Apidae). Pest Manag Sci 57:577–586. CrossRefGoogle Scholar
  39. Nauen R, Jeschke P, Velten R, Beck ME, Ebbinghaus-Kintscher U, Thielert W, Wolfel K, Haas M, Kunz K, Raupach G (2015) Flupyradifurone: a brief profile of a new butenolide insecticide. Pest Manag Sci 71:850–862. CrossRefGoogle Scholar
  40. Potts SG, Biesmeijer JC, Kremen C, Neumann P, Schweiger O, Kunin WE (2010) Global pollinator declines: trends, impacts and drivers. Trends Ecol Evol 25:345–353. CrossRefGoogle Scholar
  41. Pyakurel P, Shin M, Venton BJ (2018) Nicotinic acetylcholine receptor (nAChR) mediated dopamine release in larval Drosophila melanogaster. Neurochem Int 114:33–41. CrossRefGoogle Scholar
  42. Rinkevich FD, Margotta JW, Pittman JM, Danka RG, Tarver MR, Ottea JA, Healy KB (2015) Genetics, synergists, and age affect insecticide sensitivity of the honey bee, Apis mellifera. PLoS ONE 10:e0139841. CrossRefGoogle Scholar
  43. Rondeau G, Sánchez-Bayo F, Tennekes HA, Decourtye A, Ramírez-Romero R, Desneux N (2014) Delayed and time-cumulative toxicity of imidacloprid in bees, ants and termites. Sci Rep 4:5566. CrossRefGoogle Scholar
  44. Rortais A, Arnold G, Halm M-P, Touffet-Briens F (2005) Modes of honeybees exposure to systemic insecticides: Estimated amounts of contaminated pollen and nectar consumed by different categories of bees. Apidologie 36:71–83. CrossRefGoogle Scholar
  45. Sanchez-Bayo F, Goka K (2014) Pesticide residues and bees–a risk assessment. PLoS ONE 9:e94482. CrossRefGoogle Scholar
  46. Sánchez-Bayo F, Belzunces L, Bonmatin J-M (2017) Lethal and sublethal effects, and incomplete clearance of ingested imidacloprid in honey bees (Apis mellifera). Ecotoxicology 26:1199–1206. CrossRefGoogle Scholar
  47. Schneider CW, Tautz J, Grünewald B, Fuchs S (2012) RFID tracking of sublethal effects of two neonicotinoid insecticides on the foraging behavior of Apis mellifera. PLoS ONE 7:e30023. CrossRefGoogle Scholar
  48. Schröter U, Malun D, Menzel R (2007) Innervation pattern of suboesophageal ventral unpaired median neurones in the honeybee brain. Cell Tissue Res 327:647–667. CrossRefGoogle Scholar
  49. Smirle MJ (1993) The influence of colony population and brood rearing intensity on the activity of detoxifying enzymes in worker honey bees. Physiol Entomol 18:420–424. CrossRefGoogle Scholar
  50. Suchail S, Guez D, Belzunces LP (2001) Discrepancy between acute and chronic toxicity induces by imidacloprid and its metabolites in Apis mellifera. Environ Toxicol Chem 20:2482.<2482:DBAACT>2.0.CO;2 CrossRefGoogle Scholar
  51. Tan K, Wang C, Dong S, Li X, Nieh JC (2017) The pesticide flupyradifurone impairs olfactory learning in Asian honey bees (Apis cerana) exposed as larvae or as adults. Sci Rep 7:17772. CrossRefGoogle Scholar
  52. Tennekes HA (2010) The significance of the Druckrey-Küpfmüller equation for risk assessment–the toxicity of neonicotinoid insecticides to arthropods is reinforced by exposure time. Toxicology 276:1–4. CrossRefGoogle Scholar
  53. Tison L, Hahn M-L, Holtz S, Rößner A, Greggers U, Bischoff G, Menzel R (2016) Honey Bees’ behavior is impaired by chronic exposure to the neonicotinoid thiacloprid in the field. Environ Sci Technol 50:7218–7227. CrossRefGoogle Scholar
  54. Tosi S, Nieh JC (2017) A common neonicotinoid pesticide, thiamethoxam, alters honey bee activity, motor functions, and movement to light. Sci Rep 7:15132. CrossRefGoogle Scholar
  55. Tosi S, Costa C, Vesco U, Quaglia G, Guido G (2018) A 3-year survey of Italian honey bee-collected pollen reveals widespread contamination by agricultural pesticides. Sci Total Environ 615:208–218. CrossRefGoogle Scholar
  56. Whitworth AJ, Wes PD, Pallanck LJ (2006) Drosophila models pioneer a new approach to drug discovery for Parkinson’s disease. Drug Discov Today 11:119–126. CrossRefGoogle Scholar
  57. Williamson SM, Willis SJ, Wright GA (2014) Exposure to neonicotinoids influences the motor function of adult worker honeybees. Ecotoxicology 23:1409–1418. CrossRefGoogle Scholar
  58. Winston ML (1987) Biology of the honey bee, New edn. Harvard University Press, CambridgeGoogle Scholar

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Authors and Affiliations

  1. 1.Biocenter, Behavioral Physiology and Sociobiology, Am HublandUniversity of WürzburgWürzburgGermany
  2. 2.Faculty of Veterinary Medicine, Institute of Veterinary Anatomy, Histology and EmbryologyUniversity of LeipzigLeipzigGermany

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