Amitraz, the active chemical in popular varroa treatments Apivar and Apitraz, has become a staple in New Zealand beekeeper’s pest management plans. How does it work and is there any downside to use of this highly successful varroa control agent? Science writer Dave Black explores the science of amitraz and uncovers that while the good news outweighs the bad, there is still no free lunch when it comes to introducing chemicals to your beehives.
While New Zealand beekeepers have managed to reduce their dependence on chemistry for the detection and control of Varroa destructor most of us haven’t been able to forget about it altogether. The pyrethroid miticides tau-fluvalinate (Apistan) and flumethrin (Bayvarol) were always going to need a ‘support act’ and for us, with the benefit of seeing things unfold elsewhere, the most obvious candidate was amitraz. This could be supplied in the same safe form beekeepers were used to handling, as Apivar or Apitraz, both of which declared 500mg of the active ingredient in each plastic strip. No one regards amitraz as a universally ‘safe’ chemical (nothing is) but it had some important things in its favour.
Using miticides of any kind in a beehive comes with a cost and it’s important we understand this as completely as possible to ensure the treatment we apply isn’t worse than the problem we are trying to cure. One of the things that makes amitraz valuable is that its effect is quite different from the effect of a pyrethroid. That way, before varroa fully adapt to resist pyrethroids we have something else to use. By sheer luck, it also turns out that varroa mites are much more sensitive to amitraz than bees are, and it’s not just a matter of scale. That means, our bees are less likely to suffer from ‘off-target’ doses or residues and the quantity we use can be minimised. Our ‘safety margin’ (that is the difference in dose size between ‘effective at killing varroa’ and ‘effective at killing bees’) with amitraz, while about a third of that for Apistan, is more than double that for oxalic acid or thymol (Johnson,2013).
How Does Amitraz Work?
In the last couple of years it has become much clearer how amitraz works to kill varroa mites, and correspondingly, how mites can change to survive exposure to amitraz, and actually, why bees are not as susceptible (Ye, 2020, Guo, 2021, Hernandez‑Rodriguez, 2021). There were two alternative possibilities, the pest either working out how to ‘de-toxify’ the thing that’s doing the damage, or modifying the ‘target’ of the treatment so it can’t be damaged. While we thought we knew what the target was in the case of mites – octopamine receptors – we were wrong about the detail. That’s probably why studies of the effects of amitraz are sometimes quite inconclusive, even contradictory.
Octopamine is the invertebrate equivalent of adrenalin for humans, first identified in an octopus. It’s a neuromodulator and can have a wide-ranging effect on the whole nervous system. Amitraz attaches to the octopamine receptors, mimicking the action of octopamine in some respects but with a catastrophic and slowly lethal cascade of uncoordinated signals. We now know which of the several possible receptors in mites amitraz affects (it has the catchy name Octβ2R) and that in V.destructor two different amino acid modifications (one present in the US, one in France) confer resistance. We also know that the reason honeybees tolerate amitraz is because their version of Octβ2R is different again, with three different amino acid substitutions.
Amitraz’s Effect on Bees – Good and Bad News.
Even if amitraz is relatively non-toxic for honeybees, some level of sub-lethal effects are quite credible given that amitraz works by being similar to octopamine. It’s almost obvious that, like adrenalin, it might have an effect on heart rate isn’t it? Researchers have investigated many aspects of their physiology, reproduction, and behaviour in the last 20 years and so far produced inconclusive results about ill-effects. There are plausible molecular mechanisms and changes in gene expression caused by amitraz, so we can’t discount it.
The other ‘good news’ is that amitraz degrades very rapidly, and is quite insoluble in watery solutions like honey. If you try hard enough you can only dissolve 1 thousandths of a gram of amitraz in a litre water (1mg), compared to 300,000mg in the organic solvent acetone, so we aren’t worried by amitraz being consumed by people eating honey. Many insecticides are transformed into active forms inside insects and amitraz is one example. Amitraz is quickly processed to produce the active metabolite DPMF, (2,4-dimethylformanilide). Although both amitraz and DPMF are potent Octβ2R stimulants, DPMF is 11 times more potent than amitraz on the Octβ2R from Varroa mites.
The ‘bad news’ is that these chemicals will bind to lipids, like beeswax (they, like most current miticides, are ‘lipophilic’). In wax amitraz itself also quickly disappears, breaking down during the course of a day into DPMF and two other compounds. DPMF was detectable for about a week and only one residue (‘DMF’) is detectable even after the wax has been reprocessed (Korta, 2021). DMF is not currently known to be harmful as far as bees, mites or people are concerned.
A recent report (Marti, 2022) from an extensive Swiss study of foundation wax produced by all their major commercial manufacturers (covering 321 samples) in 2019 found DMF in half the samples (in parts per billion, a maximum value of 32.1µg/kg). As Switzerland has never authorised the use of any amitraz products, the residue came from illegal use and/or imported wax. Switzerland has monitored its recycled wax for thirty years, and regularly detects residues from products that have been discontinued for years or never been authorised.
So What?
Now we know amitraz residues persist in wax, the obvious question is, does it matter? Can chemicals retained in wax affect the health of the bees and their offspring that live on it? Because, even if (a big if) amitraz has little to no effect as a mite treatment, what happens when we add it to the ever increasing store of contaminates bound up in wax comb? An often quoted US survey found 87 different residues in hive wax (Mullin, 2010). Switzerland is probably the only country in which the number of lipophilic pesticides and fungicides found in beeswax is decreasing. The effect of the simultaneous exposure to several residual medicines and pollutants in the form of widespread agricultural chemicals of all kinds may be just emerging.
For example, one of the few bioassays looking at the interactions between possible chemical combinations observed bees that had been ‘pre-treated’ with a small sub-lethal dose of amitraz found an Apistan application five times as toxic, even though a pre-treatment with Apistan did not make amitraz treatment more toxic (Johnson, 2013). Other studies have suggested combinations of miticides that lower sperm viability, egg-laying rate, and larval mortality, and so on, but the combined effect of these residual chemicals and their dose becomes extremely difficult to untangle. And remember, it’s DMF persisting in wax, not amitraz, so that may not be a valid assay in any case.
When it comes to honeybees these days it seems we are all doctors, or at least pharmacists, so here is a little counsel from the experts. The modern, popular version of Medicine’s Hippocratic Oath erroneously advises in Latin, “First, do no harm”. The nearest actual source in the Greek medical texts instead suggests that you are either “to do good, or to do no harm”. It may be a Hobson’s choice, but do your best.
Dave Black is a commercial-beekeeper-turned-hobbyist, now working in the kiwifruit industry. He is a regular science writer providing commentary on “what the books don't tell you”, via his Substack Beyond Bee Books, to which you can subscribe here.
References:
Ye L, Liu P, Shi T, Wang A, Zhu Y, Li L, et al. (2020) Transcriptomic analysis to elucidate the response of honeybees (Hymenoptera: Apidae) to amitraz treatment. PLoS ONE 15(3): e0228933. https://doi.org/10.1371/journal.pone.0228933
Guo et al.,(2021) An octopamine receptor confers selective toxicity of amitraz on honeybees and Varroa mites https://doi.org/10.7554/eLife.68268
Hernandez‑Rodriguez, Carmen Sara et al (2021) Resistance to amitraz in the parasitic honey bee mite Varroa destructor is associated with mutations in the β‑adrenergic‑like octopamine receptorJournal of Pest Science (2022) 95:1179–1195 https://doi.org/10.1007/s10340-021-01471-3
E. Korta et al, (2001) Study of Acaricide Stability in Honey. Characterization of Amitraz Degradation Products in Honey and Beeswax, J. Agric. Food Chem., 49, 5835-5842 https://pubs.acs.org/doi/pdf/10.1021/jf010787s
Joshua N. G. Marti, Verena Kilchenmann, Christina Kast, (2022) Evaluation of pesticide residues in commercial Swiss beeswax collected in 2019 using ultra‑high performance liquid chromatographic analysis Environmental Science and Pollution Research (2022) 29:32054–32064 https://doi.org/10.1007/s11356-021-18363-9
Mullin CA, Frazier M, Frazier JL, Ashcraft S, Simonds R, et al. (2010) High Levels of Miticides and Agrochemicals in North American Apiaries: Implications for Honey Bee Health. PLoS ONE 5(3): e9754. https://doi:10.1371/journal.pone.0009754
Johnson RM, Dahlgren L, Siegfried BD, Ellis MD (2013) Acaricide, Fungicide and Drug Interactions in Honey Bees (Apis mellifera). PLoS ONE 8(1): e54092. https://doi:10.1371/journal.pone.0054092
