Several factors have been proposed to explain the honeybee decline including nutrition, queen quality, intoxication by pesticides and parasitic diseases. The honeybee, Apis mellifera, may be exposed to a wide range of pesticides when foraging or consuming contaminated food stocked into the hive. Two classes of systemic pesticides, neonicotinoids and phenylpyrazoles, are mainly suspected for negative effects on honeybee health. There are intense debates about the use and the eventual restriction of these pesticides. In many studies, the lack of knowledge about their toxicological profile has prevented drawing conclusions about a AZD6244 causal link between exposure to insecticides and the honeybee decline. This is partly due to the fact that the assessment of the risk posed by pesticides is mainly based on the determination of acute toxicity using LD50 as the critical toxicological value. This approach is contested because it cannot account for chronic toxicity and sublethal effects that are highly important elements of neonicotinoid and phenylpyrazole toxicity in honeybees. Masitinib side effects Indeed, low doses of neonicotinoids and phenylpyrazoles induce a broad range of sublethal effects such as behavioral or physiological alterations in honeybees and other beneficial arthropods. The adverse effects usually induced by pesticides are limited by the action of a large set of metabolic enzymes. Although honeybees have fewer genes involved in detoxification than other insects, they are not necessarily more sensitive to pesticides. In honeybees, detoxification processes occur mainly in both midgut and fat body, very similar to those of mammals. Induction of microsomal monooxygenases and glutathione-Stransferase is one of the key mechanisms of insect sensitivity to pesticides. The role of detoxification enzymes, however, is not limited to the protection of insect against the deleterious effects of pesticides. These enzymes are also involved in the metabolism of endogenous compounds such as hormones and pheromones. Therefore, changes in the activity of the detoxification system can lead to variations in honeybee sensitivity to pesticides and more generally to alteration of their physiological homeostasis. Parasites may also impact insect homeostasis to promote their development.