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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."