Abstract
1. Long term effects of low doses of highly toxic organophosphorus agent sarin on behavioral and neurophysiological functions were studied in rats exposed to sarin by inhalation. The toxic effects of sarin were monitored using a functional observational battery (FOB), an automatic measurement of motor activity and a test of excitability of central nervous system at 3, 6 and 12 months following sarin exposure. 2. The results indicate that sarin at symptomatic as well as asymptomatic doses (level 2 and 3) is able to induce some neurotoxic effects (a decrease in activity and mobility, an alteration of gait, an increase in stereotyped behavior) including an increase in the excitability of central nervous system (an increase in convulsive activity following the administration of pentamethylenetetrazole) in rats at 3 months following inhalation exposure. Some sings of increased excitability were also observed in sarin-exposed rats following 6 or 12 months (an increase in exploratory activity, body temperature and a hindlimb grip strength at 6 months following exposure to sarin at asymptomatic doses, an increase in tail-pinch response at 12 months following exposure to sarin at symptomatic doses). 3. Therefore, nerve agents such as sarin seem to be harmful not only at high, clinically symptomatic doses but also at low, clinically asymptomatic doses because of long term manifestation of alteration of neurophysiological functions in sarin-exposed rats without disruption of cholinergic nervous system.
Highlights
Many Persian Gulf War veterans have returned with an array of unexplained complaints including chronic fatigue, muscle and joint pain, gastrointestinal complaints, loss of concentration, forgetfulness, emotional changes, impotence, headaches and insomnia that defy diagnostic classification (17)
The results indicate that sarin at symptomatic as well as asymptomatic doses is able to induce some neurotoxic effects including an increase in the excitability of central nervous system in rats at 3 months following inhalation exposure
Some sings of increased excitability were observed in sarin-exposed rats following 6 or 12 months
Summary
Many Persian Gulf War veterans have returned with an array of unexplained complaints including chronic fatigue, muscle and joint pain, gastrointestinal complaints, loss of concentration, forgetfulness, emotional changes, impotence, headaches and insomnia that defy diagnostic classification (17). Some researchers have concluded on the basis of structured interviews regarding exposures sustained in the Gulf that some cases of neuropsychologic impairment might have been due to exposures to chemical warfare agents and that some may be linked to pyridostigmine bromide, organophosphorus insecticides, the insect repellent DEET (N,N-diethyl-m-toluamide) and other pesticides (5,6,7). Haley and his co-workers suggest that some cases of illness in Gulf War veterans may represent chronic neurotoxicity caused by low-dose exposure to chemical warfare agents because neurotoxic chemical warfare agents (nerve agents), notably sarin, had been released in certain areas of the Gulf during the war destruction of Iraqi ammunition bunkers (11). Exposure to high doses of nerve agents can result in severe brain pathology (10)
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