bition of AChE. Inactivation of this enzyme, which normally breaks down the neurotransmitter acetylcholine, leads to the accumulation of acetylcholine at cholinergic synapses. Excess quantities of acetylcholine result in widespread overstimulation of muscles and nerves. At high doses, convulsions and death can occur.

The committee concludes that there is limited/suggestive evidence of an association between exposure to sarin at doses sufficient to cause acute cholinergic signs and symptoms and subsequent long-term health effects.

After sarin exposure, many health effects are reported to persist (e.g., fatigue; headache; visual disturbances such as asthenopia, blurred vision, and narrowing of the visual field; asthenia; shoulder stiffness; symptoms of posttraumatic stress disorder; and abnormal test results, of unknown clinical significance, on the digit symbol test of psychomotor performance, electroencephalogram records of sleep, event-related potential, visual evoked potential, and computerized posturography).

These conclusions are based on retrospective controlled studies of three different exposed populations who experienced acute cholinergic signs and symptoms after exposure to sarin. One population consisted of industrial workers accidentally exposed to sarin in the United States; the other two populations were civilians exposed during terrorism episodes in Japan. The health effects listed above were documented at least 6 months after sarin exposure, and some persisted up to a maximum of 3 years, depending on the study. Whether the health effects noted above persist beyond the 3 years has not been studied.

The committee concludes that there is inadequate/insufficient evidence to determine whether an association does or does not exist between exposure to sarin at low doses insufficient to cause acute cholinergic signs and symptoms and subsequent long-term adverse health effects.

On the basis of positive findings in a study of nonhuman primates and studies of humans exposed to organophosphate insecticides, it is reasonable to hypothesize that long-term adverse health effects can occur after exposure to low levels of sarin. Studies of industrial workers exposed to low levels of organophosphate insecticides consistently show a higher prevalence of neurological and/or psychiatric symptom reporting. However, there are no well-controlled studies of long-term health effects in humans exposed to sarin at doses that do not produce acute signs and symptoms.



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