the genotype—in order to characterize an individual’s PON1 status (Richter and Furlong, 1999). In Caucasian populations, the frequency of the R allele is about 0.3, but the frequency is 0.66 in the Japanese population (Yamasaki et al., 1997). This would make individuals in the Japanese population more sensitive to the toxicity of sarin, a fact that may have contributed to their morbidity and mortality after the terrorist attacks.

A recent study investigated PON1 genotype and serum enzyme activity in a group of 25 ill Gulf War veterans and 20 controls (Haley et al., 1999). Ill veterans were more likely than controls to possess the R allele (QR heterozygotes or R homozygotes) and to exhibit lower enzyme activity. This study raises the possibility that the R genotype (low sarin-hydrolyzing activity) may represent a risk factor for illness in Gulf War veterans. However, because of the very small size of the study, such findings necessitate further confirmation in a larger population (Furlong, 2000) (also see Chapter 6).

CONCLUSIONS

The committee reached the following conclusions after reviewing the literature on sarin. The committee was unable to formulate any conclusions about cyclosarin because of the paucity of toxicological and human studies.

The committee concludes that there is sufficient evidence of a causal relationship between exposure to sarin and a dose-dependent acute cholinergic syndrome that is evident seconds to hours subsequent to sarin exposure and resolves in days to months.

The acute cholinergic syndrome has been recognized for decades and has been documented in human studies summarized in this chapter. This syndrome, as well as cholinergic signs and symptoms, is evident seconds to hours after exposure (see Table 5.2) and usually resolves in days to months. The syndrome and the cholinergic signs and symptoms are produced by sarin’s irreversible inhibition of the enzyme acetylcholinesterase. Inactivation of the enzyme that 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.

Many health effects are reported in the literature to persist after sarin exposure: fatigue, headache, visual disturbances (asthenopia, blurred vision, and narrowing of the visual field), asthenia, shoulder stiffness, and symptoms of posttraumatic stress disorder; and abnormal test results, of unknown clinical



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