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Honey bees (Apis mellifera) are generalist pollinators that forage for nectar and pollen of a very large variety of plant species, exposing them to a diverse range of secondary metabolites produced as chemical defences against herbivory. Honey bees can tolerate high levels of many of these toxic compounds, including the alkaloid nicotine, in their diet without incurring apparent fitness costs. Very little is known about the underlying detoxification processes mediating this tolerance. We examined the metabolic fate of nicotine in newly emerged worker bees using radiolabeled nicotine and LC-MS/MS analysis to determine the kinetic distribution profile of nicotine as well as the absence or presence and identity of any nicotine-derived metabolites. Nicotine metabolism was extensive; virtually no unmetabolised nicotine were recovered from the rectum. The major metabolite found was 4-hydroxy-4-(3-pyridyl) butanoic acid, the end product of 2'C-oxidation of nicotine. It is the first time that 4-hydroxy-4-(3-pyridyl) butanoic acid has been identified in an insect as a catabolite of nicotine. Lower levels of cotinine, cotinine N-oxide, 3'hydroxy-cotinine, nicotine N-oxide and norcotinine were also detected. Our results demonstrated that formation of 4-hydroxy-4-(3-pyridyl) butanoic acid is quantitatively the most significant pathway of nicotine metabolism in honey bees and that the rapid excretion of unmetabolised nicotine does not contribute significantly to nicotine tolerance in honey bees. In nicotine-tolerant insects that do not rely on the rapid excretion of nicotine like the Lepidoptera, it is possible that the 2'C-oxidation of nicotine is the conserved metabolic pathway instead of the generally assumed 5'C-oxidation pathway., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The effects of pesticides on honeybee larvae are less understood than for adult bees, even though larvae are chronically exposed to pesticide residues that accumulate in comb and food stores in the hive. We investigated how exposure to a plant alkaloid, nicotine, affects survival, growth and body composition of honeybee larvae. Larvae of Apis mellifera scutellata were reared in vitro and fed throughout development on standard diets with nicotine included at concentrations from 0 to 1000μg/100g diet. Overall mortality across all nicotine treatments was low, averaging 9.8% at the prepupal stage and 18.1% at the white-eyed pupal stage, but survival was significantly reduced by nicotine. The mass of prepupae and white-eyed pupae was not affected by nicotine. In terms of body composition, nicotine affected water content but did not influence either protein or lipid stores of white-eyed pupae. We attribute the absence of consistent negative effects of dietary nicotine to detoxification mechanisms in developing honeybees, which enable them to resist both natural and synthetic xenobiotics., (Copyright © 2014 Elsevier Ltd. All rights reserved.)