During foraging activities honeybees are frequently exposed to different xenobiotics, most of them are agrochemical pesticides and beehive chemicals. Many pesticides are applied together and synergism is likely to occur in different organisms. The risk of synergisms is neglected and relatively few studies were performed concerning the effects and synergy mechanism of different xenobiotic combinations in honeybees. The understanding of synergy mechanisms between xenobiotics is very important for the control of defined mixtures use and also for the prediction of potential toxicity of newly developed substances in agriculture and apiculture. This review is focused on the effects, mechanisms and molecular targets of xenobiotics in honeybees and possible complex mechanisms of their synergisms. The main threat for honeybees are insecticides which primary molecular targets are few neuronal molecules therefore causing the impairment of neuronal system that have a profound effect on honeybee behavior, cognitive functions and physiology. However, the majority of synergistic effects observed in honeybees were ascribed to the inhibition of etoxifying midgut enzymes P450 involved in xenobiotic metabolism since most of studies were done with the mixtures xenobiotic/P450 inhibitor. The main inhibitors of P450 enzymes are specific compounds used to prolong the effects of pesticides aswell as some fungicides. Some insecticides can also interact with these enzymes and influence the xenobiotis. Although the primary mechanisms of action of individual xenobiotics especially insecticides are well known and there are possible interactions in honeybees at their primary target sites, this issue is underestimated and it warrants further investigation.

Aegerolysin proteins ostreolysin A6 (OlyA6), pleurotolysin A2 (PlyA2) and erylysin A (EryA) produced by the mushroom genus Pleurotus bind strongly to an invertebrate-specific membrane sphingolipid, and together with a protein partner pleurotolysin B (PlyB), form transmembrane pore complexes. This pore formation is the basis for the selective insecticidal activity of aegerolysin/PlyB complexes against two economically important coleopteran pests: the Colorado potato beetle and the western corn rootworm. In this study, we evaluated the toxicities of these aegerolysin/PlyB complexes using feeding tests with two ecologically important non-target arthropod species: the woodlouse and the honey bee. The mammalian toxicity of the EryA/PlyB complex was also evaluated after intravenous administration to mice. None of the aegerolysin/PlyB complexes were toxic against woodlice, but OlyA6/PlyB and PlyA2/PlyB were toxic to honeybees, with 48 h mean lethal concentrations (LC₅₀) of 0.22 and 0.39 mg/mL, respectively, in their food. EryA/PlyB was also tested intravenously in mice up to 3 mg/kg body mass, without showing toxicity. With no toxicity seen for EryA/PlyB for environmentally beneficial arthropods and mammals at the tested concentrations, these EryA/PlyB complexes are of particular interest for development of new bioinsecticides for control of selected coleopteran pests.

Honey bees are important plant pollinators and honey producers. Contamination of the environment with metals can lead to a decline in honey bee populations. Copper (Cu) and zinc (Zn) salts are commonly used as fungicides and foliar fertilizers. In this study, we investigated the effects of 10-day chronic oral exposure to different concentrations of Cu (CuSO₄) and Zn (ZnCl₂) on survival and feeding rates of Carniolan honey bees in laboratory conditions. We found that mortality in honey bee workers increased in a concentration-dependent manner and that Cu (lethal concentration [LC₅₀] = 66 mg/l) was more toxic than Zn (LC₅₀ = 144 mg/l). There was no difference in the feeding rate of Cu-treated bees for the different concentrations tested, but the feeding rate decreased with the increase in Zn concentration. To determine feeding preference or avoidance for Cu and Zn, we conducted 2-choice 24-h feeding experiments. We demonstrated that honey bees preferred Zn-containing solutions compared to the control diet. A two-choice experiment with Cu showed a tendency for honey bees to be deterred by Cu at high concentrations; however, it was not statistically significant. In summary, our results suggest that honey bee workers may suffer adverse effects when exposed to ecologically relevant concentrations of Cu and Zn.