cholinergic signs or symptoms or detectable change in blood cholinesterase activity (Brown and Brix, 1998).

Although there were no medical reports at the time of the release at Khamisiyah that were consistent with the signs and symptoms of acute exposure to sarin (PAC, 1996), there is concern that exposure of US troops during the Gulf War might have occurred. The level of exposure would have been insufficient to produce the acute cholinergic syndrome. Therefore, this chapter reviews available human studies, focusing mainly on epidemiologic studies of the long-term health effects of sarin, and is organized by study population.

Relatively few studies have looked at the long-term health effects of low-dose exposure to sarin or cyclosarin, but a number of epidemiologic studies have been conducted on organophosphorus (OP) insecticides, which have some common mechanisms of action. The health effects of those insecticides are reviewed in Gulf War and Health: Volume 2 (IOM, 2003), and the conclusions of that report and epidemiologic studies that have been published since that report was prepared are discussed in Appendix A.

INTENTIONALLY EXPOSED MILITARY VOLUNTEERS

In the past, military authorities (including those of the US and the UK) have conducted dosing studies of chemicals in healthy servicemen who volunteer after being informed of the protocol and risks involved. Although questions remain regarding the ethics of such studies and their ethical acceptability by current standards, such studies have been conducted in the past with servicemen voluntarily exposed to sarin and other chemical-warfare agents. The studies are reviewed in this section, and those published since the preparation of GW1 are summarized in Table 3-1.

US Military Studies

From 1958 to 1975, the US Army studied nearly 7,000 servicemen who had voluntarily agreed to be exposed to an array of chemical-warfare agents at Edgewood Arsenal, Maryland. At the request of the Army, the Medical Follow-up Agency (MFUA; now part of the Institute of Medicine) of the National Research Council designed and conducted two studies of the long-term health effects of those exposures. The first, a followup at least 10 years after exposure (NRC, 1985), was described in GW1 (IOM, 2000). The study examined current health status and hospital admissions to military or Veterans’ Administration hospitals. In that survey, the subgroup exposed to a variety of anticholinesterases as a class had no long-term health consequences of exposure, but the study had low statistical power and other methodologic problems acknowledged by the authors.

Since the preparation of GW1 (IOM, 2000), MFUA conducted a second



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