Acaricide, fungicide and drug interactions in honey bees (Apis mellifera)

PLoS One. 2013;8(1):e54092. doi: 10.1371/journal.pone.0054092. Epub 2013 Jan 29.


Background: Chemical analysis shows that honey bees (Apis mellifera) and hive products contain many pesticides derived from various sources. The most abundant pesticides are acaricides applied by beekeepers to control Varroa destructor. Beekeepers also apply antimicrobial drugs to control bacterial and microsporidial diseases. Fungicides may enter the hive when applied to nearby flowering crops. Acaricides, antimicrobial drugs and fungicides are not highly toxic to bees alone, but in combination there is potential for heightened toxicity due to interactive effects.

Methodology/principal findings: Laboratory bioassays based on mortality rates in adult worker bees demonstrated interactive effects among acaricides, as well as between acaricides and antimicrobial drugs and between acaricides and fungicides. Toxicity of the acaricide tau-fluvalinate increased in combination with other acaricides and most other compounds tested (15 of 17) while amitraz toxicity was mostly unchanged (1 of 15). The sterol biosynthesis inhibiting (SBI) fungicide prochloraz elevated the toxicity of the acaricides tau-fluvalinate, coumaphos and fenpyroximate, likely through inhibition of detoxicative cytochrome P450 monooxygenase activity. Four other SBI fungicides increased the toxicity of tau-fluvalinate in a dose-dependent manner, although possible evidence of P450 induction was observed at the lowest fungicide doses. Non-transitive interactions between some acaricides were observed. Sublethal amitraz pre-treatment increased the toxicity of the three P450-detoxified acaricides, but amitraz toxicity was not changed by sublethal treatment with the same three acaricides. A two-fold change in the toxicity of tau-fluvalinate was observed between years, suggesting a possible change in the genetic composition of the bees tested.

Conclusions/significance: Interactions with acaricides in honey bees are similar to drug interactions in other animals in that P450-mediated detoxication appears to play an important role. Evidence of non-transivity, year-to-year variation and induction of detoxication enzymes indicates that pesticide interactions in bees may be as complex as drug interactions in mammals.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acaricides / pharmacology*
  • Animals
  • Anti-Infective Agents / pharmacology
  • Beekeeping
  • Bees / genetics
  • Bees / physiology
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug Interactions
  • Fungicides, Industrial / pharmacology
  • Honey*
  • Inactivation, Metabolic*
  • Nitriles / pharmacology
  • Pesticides / pharmacology
  • Pyrethrins / pharmacology
  • Toluidines / pharmacology
  • Varroidae / drug effects*
  • Varroidae / pathogenicity


  • Acaricides
  • Anti-Infective Agents
  • Fungicides, Industrial
  • Nitriles
  • Pesticides
  • Pyrethrins
  • Toluidines
  • amitraz
  • fluvalinate
  • Cytochrome P-450 Enzyme System

Grant support

Funding support was provided by the United States Department of Agriculture, National Institute of Food and Agriculture, Agriculture and Food Research Initiative, Managed Pollinator Coordinated Agricultural Project 2009-85118-05718 ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.