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Reprinted from ScienceDaily Magazine ...

Source: Duke University Medical Center

Date Posted: Thursday, May 02, 2002

Web Address: http://www.sciencedaily.com/releases/2002/05/020502071936.htm

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DEET Brain Effects In Animals Warrant Caution

DURHAM, N.C. -- A Duke University Medical Center pharmacologist is

recommending caution when using the insecticide DEET, after his animal

studies last year found the chemical causes diffuse brain cell death and

behavioral changes in rats after frequent and prolonged use.

Mohamed Abou-Donia, Ph.D. has also called for further government testing of

the chemical's safety in short-term and occasional use, especially in view

of Health Canada's recent decision to ban products with more than 30 percent

of the chemical. Every year, approximately one-third of the U.S. population

uses insect repellents containing DEET, available in more than 230 products

with concentrations up to 100 percent.

While the chemical's risks to humans are still being intensely debated,

Abou-Donia says his 30 years of research on pesticides' brain effects

clearly indicate the need for caution among the general public.

His numerous studies in rats, two of them published last year, clearly

demonstrate that frequent and prolonged applications of DEET cause neurons

to die in regions of the brain that control muscle movement, learning,

memory and concentration. Moreover, rats treated with an average human dose

of DEET (40 mg/kg body weight) performed far worse than control rats when

challenged with physical tasks requiring muscle control, strength and

coordination. Such effects are consistent with physical symptoms in humans

reported in the medical literature, especially by Persian Gulf War veterans,

said Abou-Donia.

" If used sparingly, infrequently and by itself, DEET may not have negative

effects – the literature here isn't clear, " he said. " But frequent and heavy

use of DEET, especially in combination with other chemicals or medications,

could cause brain deficits in vulnerable populations. "

Children in particular are at risk for subtle brain changes caused by

chemicals in the environment, because their skin more readily absorbs them,

and chemicals more potently affect their developing nervous systems, said

Abou-Donia. Commonly used preparations like insecticide-based lice-killing

shampoos and insect repellents are assumed to be safe because severe

consequences are rare in the medical literature. Yet subtle symptoms -- such

as muscle weakness, fatigue or memory lapses --might be attributed

erroneously to other causes, he said.

With heavy exposure to DEET and other insecticides, humans may experience

memory loss, headache, weakness, fatigue, muscle and joint pain, tremors and

shortness of breath, said Abou-Donia. His earlier research, examining the

brain effects of three chemicals used during the Persian Gulf War, clearly

demonstrated that chickens exhibited similar signs that the Gulf War

veterans complained of upon returning from service. (Journal of Toxicology

and Experimental Health, May, 1996, Volume 48, p. 35 - 56).

Such overt symptoms are not seen immediately after use but may manifest

themselves months or years after exposure, making a cause-and-effect

relationship difficult to establish , said Abou-Donia. By studying animals

such as chickens and rats, however, researchers are able to compress the

time between exposure and the onset of symptoms: 10 months of a rat's life

is several years in a human's life. Moreover, researchers can study layers

of the rats' brains at various stages after exposure to measure the

chemical's effects on the brain.

Indeed, Abou-Donia's two most recent studies demonstrate the severe brain

and behavioral deficits that rats experience after two months of daily skin

applications with DEET and permethrin, another common insecticide,

(Experimental Neurology, 2001, volume 172 , p.153- 171); and following 60

days of exposure to DEET and permethrin, and 15 days of pyridostigmine

bromide, an anti-nerve gas agent (Journal of Toxicology and Environmental

Health, 2001, volume 64, p. 373-384). Both studies examined the effects of

each drug alone and in combination.

In each study, the treated animals initially appeared to be normal, just

like the control group, said Abou-Donia. But when challenged with

neurobehavioral tasks that required muscle control, strength and

coordination, the rats demonstrated serious impairments.

Moreover, a detailed analysis of their brains clearly showed that large

numbers of brain cells were dying within three critical brain structures:

the cerebral cortex, which controls muscles and movement; the hippocampal

formation, which controls memory, learning and concentration; and the

cerebellum, which synchronizes body movements.

In addition, many of the surviving brain cells showed signs of degeneration

and damage consistent with the presence of harmful byproducts called oxygen

free radicals (also known as reactive oxygen species), which can damage DNA

and cell membranes in the brain and the nervous system.

The most severe brain cell changes and sensorimotor deficits were seen among

rats exposed to combinations of DEET, permethrin and the anti-nerve gas

agent pyridostigmine bromide, which reduces the body's normal ability to

inactivate pesticides. Such findings confirmed Abou-Donia's 1996 and 2001

animal studies demonstrating that harmless doses of these three chemicals

proved highly toxic to the brain and nervous system when used in

combination.

" The take home message is to be safe and cautious when using insecticides, "

said Abou-Donia. " Never use insect repellents on infants, and be wary of

using them on children in general. Never combine insecticides with each

other or use them with other medications. Even so simple a drug as an

antihistamine could interact with DEET to cause toxic side effects. Don't

spray your yard for bugs and then take medications. Until we have more data

on potential interactions in humans, safe is better than sorry. "

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