DEET, Already linked to Gulf War illness, Now linked to Neural Damage in Mice

More research needed to see if compound has same effect in humans, experts say

By Amanda Gardner, HealthDay Reporter

WEDNESDAY, Aug. 5 (HealthDay News) -- New French research suggests the main ingredient used in many insect repellants may affect the central nervous system, at least in mice.

And combining this ingredient -- DEET (N,N-Diethyl-3-methylbenzamide) -- with carbamates, a type of pesticide that is often used with DEET, compounded the effects.

Although the authors, publishing online Aug. 5 in BMC Biology, warn of potential dangers to humans, they also acknowledge the need for more studies on the subject.

Meanwhile, people should probably worry more about the health risks from mosquitoes and other insects than about the potential harms of DEET, experts said.

"This work was done primarily in test tubes in order to try to understand some of the mechanisms," said Dr. Ted Schettler, science director of the Science & Environmental Health Network. "The mechanistic information is very useful but the jury is still out on what implications this has for humans."

"DEET has been used for a very long time with very few bad outcomes," added Susan Paskewitz, a professor of entomology at the University of Wisconsin, Madison. "People have killed themselves by drinking it, but you can do that with alcohol or salt. And a few have had neurological symptoms after application for long periods and high doses."

As for the combination of DEET and carbamates, Paskewitz added, "if there are the kinds of synergies suggested by the study, they aren't happening very often. I also would guess that the actual concentration in the body is much lower than they had to use in the study to see an effect in the mouse tissues."

But by better understanding the mechanisms by which DEET works, scientists may be able to come up with better repellant products, said Paul Sanberg, distinguished professor of neurosurgery and director of the University of South Florida Center for Aging and Brain Repair in Tampa.

DEET is the most common active ingredient in insect repellents and is used worldwide by about 200 million people annually. However, relatively little is known about how the compound actually works.

From this study, it now appears that not only does DEET change the behavior of insects, it also inhibits the acetylcholinesterase enzyme, which is involved in the central nervous system, in both insects and mice.

Organophosphates and carbamate insecticides employ the same mechanism of action and, when combined with DEET in these experiments, increased the toxicity of the chemicals.

"This study demonstrates the vital importance of looking at chemicals in combination," Schettler said. "This shows that when you combine chemicals, you can get unpredictable results."

The authors, from different research institutions in France, say this is the first time a molecular target for DEET has been identified.

Interestingly, the class of drugs known as cholinesterase inhibitors are used to treat Alzheimer's and can delay the decline of symptoms for up to a year.

Sanberg said the effects of DEET, like many chemicals and drugs, can simply depend on the individual using it.

An earlier study found a strong association between exposure to acetylcholinesterase inhibitors and the Gulf War illness suffered by many veterans. Organophosphates have also been linked with acute lymphoblastic leukemia, the most common form of leukemia in children.

More information

The U.S. Environmental Protection Agency has more on DEET.

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Popular Insect Repellent Deet Is Neurotoxic

(ScienceDaily - Aug. 6, 2009) — The active ingredient in many insect repellents, deet, has been found to be toxic to the central nervous system.

Researchers say that more investigations are urgently needed to confirm or dismiss any potential neurotoxicity to humans, especially when deet-based repellents are used in combination with other neurotoxic insecticides.

Vincent Corbel from the Institut de Recherche pour le Développement in Montpellier, and Bruno Lapied from the University of Angers, France, led a team of researchers who investigated the mode of action and toxicity of deet (N,N-Diethyl-3-methylbenzamide). Corbel said, "We've found that deet is not simply a behavior-modifying chemical but also inhibits the activity of a key central nervous system enzyme, acetycholinesterase, in both insects and mammals".

Discovered in 1953, deet is still the most common ingredient in insect repellent preparations. It is effective against a broad spectrum of medically important pests, including mosquitoes. Despite its widespread use, controversies remain concerning both the identification of its target sites at the molecular level and its mechanism of action in insects. In a series of experiments, Corbel and his colleagues found that deet inhibits the acetylcholinesterase enzyme – the same mode of action used by organophosphate and carbamate insecticides.

These insecticides are often used in combination with deet, and the researchers also found that deet interacts with carbamate insecticides to increase their toxicity. Corbel concludes, "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".

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Journal reference:

1. Vincent Corbel, Maria Stankiewicz, Cedric Pennetier, Didier Fournier, Jure Stojan, Emmanuelle Girard, Mitko Dimitrov, Jordi Molgo, Jean Marc Hougard and Bruno Lapied. Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet. BMC Biology, (in press) [link]

Adapted from materials provided by BioMed Central, via EurekAlert!, a service of AAAS.