ate the health effects of various chemicals used in the Gulf War. The first evaluated the health effects of depleted uranium, pyridostigmine bromide, sarin and cyclosarin, and vaccines (anthrax and botulinum toxoid) and produced Gulf War and Health, Volume 1, hereafter referred to as GW1 (IOM, 2000a). The second reviewed the health effects of solvents and pesticides and produced Gulf War and Health, Volume 2, hereafter referred to as GW2 (IOM, 2003a). The third is reviewing the health effects of the combustion products of oil-well fires, fuels, and synthetic compounds potentially used as propellants for Scud missiles.

Sarin (GB; o-isopropyl methylphosphonofluoridate) and cyclosarin (GF; cyclohexyl methylphosphonofluoridate) are highly toxic organophosphorus (OP) nerve agents produced for chemical-warfare. They were first synthesized in Germany before and during World War II (Somani, 1992), and the first military use of sarin occurred in the Iran–Iraq conflict in the 1980s (Brown and Brix, 1998). Sarin and cyclosarin exert many of their effects by irreversibly binding to and inactivating acetylcholinesterase (AChE), the enzyme responsible for metabolizing the neurotransmitter acetylcholine (ACh). The inactivation of AChE results in an increase in ACh at cholinergic synapses (Gunderson et al., 1992) and overstimulation of muscles and nerves. After sufficient exposure to sarin or other OP nerve agents, that overstimulation causes what has been termed the acute cholinergic syndrome (see Chapter 2).

Because of continued concerns of veterans, especially in light of recent toxicologic studies of low-dose exposure to sarin, the VA requested that IOM update its evaluation of the health effects of sarin. In response to that request, IOM convened the Committee on Gulf War and Health: Updated Literature Review of Sarin, which is responsible for the present report. The committee consists of several members of the committee responsible for GW2 (IOM, 2003a), which evaluated the health effects of pesticides and solvents used in the Gulf War.

POTENTIAL US TROOP EXPOSURE

During a cease-fire period in March 1991, troops from the US 37th and 307th engineering battalions destroyed enemy munitions throughout the occupied areas of southern Iraq (PAC, 1996). A large storage complex at Khamisiyah, Iraq, which contained more than 100 bunkers, was destroyed. Two sites in the complex—one of the bunkers and another site called the “pit”—contained stacks of 122-mm rockets loaded with sarin and cyclosarin (Committee on Veterans Affairs, 1998). According to the most recent estimates, 371 kg of sarin and cyclosarin combined was released (Winkenwerder, 2002). US troops performing demolitions were unaware of the presence of nerve agents because their detectors, being sensitive only to lethal or near-lethal concentrations of nerve agents (CDC, 1999), did not sound any alarms before demolition. It was not until October 1991 that inspectors from the United Nations Special Commission (UNSCOM) confirmed



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