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Not Just Neurotoxic: Pesticide chlorpyrifos affects heart and liver cells

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12:41pm, November 12, 2003
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A pesticide known to be toxic to the brain at high doses may have subtle effects throughout the body, researchers suggest. They have found abnormalities in heart and liver tissues of animals exposed during early development to chlorpyrifos.

At high doses, this chemical, which belongs to a group of pesticides called organophosphates, can cause headache, nausea, and other symptoms. Lower doses during fetal growth and early life have been shown to alter brain development and adult behavior in laboratory animals.

To reduce exposures in children and cut the chemical's prevalence in urban waterways, where it is commonly detectable, the Environmental Protection Agency in 2000 restricted certain uses of chlorpyrifos. It's nevertheless widely used legally in the United States to protect fruit and vegetable crops and to fight insects in buildings and lawns.

To test for effects of the chemical outside the nervous system, researchers at Duke University in Durham, N.C., injected rats daily with 1, 2, or 5 milligrams of chlorpyrifos per kilogram of body weight for 4 consecutive days. Some animals received the injections while they were pregnant, and their offspring were then studied for possible effects. Other animals were exposed during the first or second week of life. The researchers looked for effects shortly after exposure and when the animals were juveniles and adults.

The doses of chlorpyrifos were too low to cause immediate symptoms, but rats exposed in utero or during the first week after birth later showed subtle biochemical abnormalities. Chlorpyrifos exposure in older animals seldom had an effect, suggesting that a "window of vulnerability" closes soon after birth, say Theodore A. Slotkin and his colleagues at Duke.

The abnormalities affect adenylyl cyclase signaling, a process by which cells communicate, and in some experiments, effects were evident only in male rats. Because adenylyl cyclase signaling modifies insulin production, glucose metabolism, and heart rate, the findings imply that early exposure to chlorpyrifos and other organophosphates could increase risks for cardiovascular and metabolic disorders that typically arise later in life, Slotkin argues.

The report will appear in an upcoming issue of Environmental Health Perspectives.

In another paper to appear in that journal, Slotkin and his colleagues report that chlorpyrifos exposure also influences the programming of immature brain cells that controls their response to serotonin. That neurotransmitter acts through a different mechanism than the one previously shown to be responsible for chlorpyrifos' neurotoxic effects.

The doses used in the new experiments are much higher and shorter-term than those that people typically experience, says organophosphate toxicologist Subramanya Karanth of Oklahoma State University in Stillwell. A more relevant dose for revealing long-term effects of exposure during development would be in the range of 0.1 mg/kg per day for a month. Furthermore, he says, feeding chlorpyrifos to rats rather than injecting the chemical would better reflect the dietary exposure that most people experience. "Further research should be done to determine whether changes occur at levels of exposure encountered in the environment," says Janice E. Chambers of Mississippi State University in Mississippi State.

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