Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet.
BACKGROUND
N,N-Diethyl-3-methylbenzamide (deet) remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system.


RESULTS
By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase.


CONCLUSIONS
These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.
Corbel
Vincent
V
Laboratoire de Lutte contre les Insectes Nuisibles, Institut de Recherche pour Développement, F-34 394 Montpellier, France. vincent.corbel@ird.fr
Stankiewicz
Maria
M
Pennetier
Cédric
C
Fournier
Didier
D
Stojan
Jure
J
Girard
Emmanuelle
E
Dimitrov
Mitko
M
Molgó
Jordi
J
Hougard
Jean-Marc
JM
Lapied
Bruno
B
D000818:Animals; D001667:Binding, Competitive; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000633:toxicity*; D002802:Cholinesterases / Q000378:metabolism*; D009033:Culicidae; D003671:DEET / Q000378:metabolism / Q000633:toxicity*; D003627:Data Interpretation, Statistical; D004331:Drosophila melanogaster / Q000201:enzymology; D005260:Female; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism; D007302:Insect Repellents / Q000378:metabolism / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity; D007700:Kinetics; D008297:Male; D051379:Mice; D008956:Models, Chemical; D009420:Nervous System / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010526:Periplaneta / Q000502:physiology; D010574:Pesticide Synergists; D001074:Propoxur / Q000633:toxicity; D015222:Sodium Channels / Q000187:drug effects; D055366:Synaptic Potentials / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D019476:Insect Proteins; D007302:Insect Repellents; D007306:Insecticides; D010574:Pesticide Synergists; D015222:Sodium Channels; D003671:DEET; D001074:Propoxur; D002802:Cholinesterases