Pesticide Chlorpyrifos Affects Heart and Liver Cells
From: Robina Suwol
Date: 23 Nov 2003
Remote Name: 220.127.116.11
NOT JUST NEUROTOXIC: PESTICIDE CHLORPYRIFOS
AFFECTS HEART AND LIVER CELLS
By Ben Harder, Science News, Nov. 15, 2003
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
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,
The report will appear in an upcoming issue of Environmental Health
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
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References and Sources
Aldridge, J.E., F.J. Seidler, and T.A. Slotkin. In press.
Developmental exposure to chlorpyrifos elicits sex-selective alterations of
serotonergic synaptic function in adulthood: Critical
periods and regional selectivity for effects on the serotonin transporter,
receptor subtypes, and cell signaling. Environmental
Meyer, A., F.J. Seidler, and T.A. Slotkin. In press. Developmental effects of
chlorpyrifos extend beyond neurotoxicity: Critical periods for immediate and
delayed-onset effects on cardiac and hepatic cell signaling. Environmental
Health Perspectives Available at
Harder, B. 2003. Farm harm: Ag chemicals may cause prostate cancer.
Science News 163(May 10):291. Available to subscribers at
Janice E. Chambers
Center for Environmental Health Sciences
College of Veterinary Medicine
Mississippi State University
Mississippi State, MS 39762-6100
264 McElroy Hall
Oklahoma State University
Stillwater, OK 74074
Theodore A. Slotkin
Box 3813 DUMC
Department of Pharmacology and Cancer Biology
Duke University Medical Center
Durham, NC 27710
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