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."