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Introduction

On August 2, 1990, Iraqi forces invaded Kuwait. Five months later, the United States and its coalition allies launched an air offensive; and in February 1991, ground troops were deployed in a 4-day ground war. By April 1991, an official cease-fire was signed, and the last troops returned to the United States by June. In all, almost 700,000 troops had been deployed in the Persian Gulf War.

The war was considered a military success with few injuries or deaths, but a number of veterans began experiencing symptoms after their return, such as fatigue, cognitive difficulties, and sleep disturbances. In response to growing concern of possible exposure to a biologic, chemical, or physical agent as the cause of the symptoms, Congress passed two laws in 1998: PL 105-277, the Persian Gulf War Veterans Act, and PL 105-368, the Veterans Programs Enhancement Act. Those laws directed the Department of Veterans Affairs (VA) to task the Institute of Medicine (IOM) to evaluate the scientific literature regarding associations between illness and exposure to toxic agents, environmental or wartime hazards, or preventive medicines or vaccines associated with Gulf War service. They also provided a specific list of agents for IOM to review (see Box 1-1). Seven volumes have been published thus far: Gulf War and Health, Volume 1: Depleted Uranium, Pyridostigmine Bromide, Sarin, Vaccines (IOM, 2000); Gulf War and Health, Volume 2: Insecticides and Solvents (IOM, 2003); Gulf War and Health: Updated Literature Review of Sarin (IOM, 2004); Gulf War and Health, Volume 3: Fuels, Combustion Products, and Propellants (IOM, 2005); Gulf War and Health, Volume 4: Health Effects of Serving in the Gulf War (IOM, 2006); Gulf War and Health, Volume 5: Infectious Diseases (IOM, 2007a); and Gulf War



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1 Introduction O n August 2, 1990, Iraqi forces invaded Kuwait. Five months later, the United States and its coalition allies launched an air offensive; and in February 1991, ground troops were deployed in a 4-day ground war. By April 1991, an official cease-fire was signed, and the last troops returned to the United States by June. In all, almost 700,000 troops had been deployed in the Persian Gulf War. The war was considered a military success with few injuries or deaths, but a number of veterans began experiencing symptoms after their return, such as fatigue, cognitive difficulties, and sleep disturbances. In response to growing con- cern of possible exposure to a biologic, chemical, or physical agent as the cause of the symptoms, Congress passed two laws in 1998: PL 105-277, the Persian Gulf War Veterans Act, and PL 105-368, the Veterans Programs Enhancement Act. Those laws directed the Department of Veterans Affairs (VA) to task the Institute of Medicine (IOM) to evaluate the scientific literature regarding asso- ciations between illness and exposure to toxic agents, environmental or wartime hazards, or preventive medicines or vaccines associated with Gulf War service. They also provided a specific list of agents for IOM to review (see Box 1-1). Seven volumes have been published thus far: Gulf war and Health, volume 1: Depleted Uranium, Pyridostigmine Bromide, sarin, vaccines (IOM, 2000); Gulf war and Health, volume 2: insecticides and solvents (IOM, 2003); Gulf war and Health: Updated literature review of sarin (IOM, 2004); Gulf war and Health, volume : Fuels, Combustion Products, and Propellants (IOM, 2005); Gulf war and Health, volume : Health effects of serving in the Gulf war (IOM, 2006); Gulf war and Health, volume : infectious Diseases (IOM, 2007a); and Gulf war 

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8 UPDateD literatUre review oF DePleteD UraniUm BOX 1-1 Agents Specified in PL 105-277 and PL 105-368 • The following organophosphorus pesticides:  Chlorpyrifos  Diazinon  Dichlorvos  Malathion • The following carbamate pesticides:  Proxpur  Carbaryl  Methomyl • Pyridostigmine bromide (used for nerve-agent prophylaxis) • The following chlorinated hydrocarbons and other pesticides and repellents:  Lindane  Pyrethrins  Permethrins  Rodenticides (bait)  DEET (repellent) • he following low-level nerve agents and precursor compounds at exposures T below those which produce immediately apparent incapacitating symptoms:  Sarin  Tabun • The following synthetic chemical compounds:  ustard agents at exposures below those which cause immediate blistering M  Volatile organic compounds  Hydrazine  Red fuming nitric acid  Solvents • The following sources of radiation:  Depleted uranium  Microwave radiation  Radiofrequency radiation • The following environmental particles and pollutants:  Hydrogen sulfide  Oil-fire byproducts  Diesel-heater fumes  Sand microparticles • Diseases endemic to the region, including the following:  Leishmaniasis  Sand fly fever  Infections due to pathogenic Escherichia coli  Shigellosis • ime-compressed administration of multiple live “attenuated” and toxoid T vaccines

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 introDUCtion and Health, volume 6: Physiologic, Psychologic, and Psychosocial effects of Deployment-related stress (IOM, 2007b). The present report updates the review of depleted uranium that appeared in the first volume. Since the passage of the two laws, the United States and its allies have deployed troops to the Persian Gulf region again, to Iraq (Operation Iraqi Free- dom). Operation Iraqi Freedom began on March 29, 2003, with the arrival of US and British troops in Iraq, in an effort to remove Saddam Hussein from power. Although major combat operations ended on May 1, 2003, US and coalition troops continue to be deployed to Iraq to fight insurgency and assist with recon- struction and security. About 1.5 million US troops (active-duty military person- nel and reservists) have been deployed to Operation Iraqi Freedom and Operation Enduring Freedom in Afghanistan (Report of the President’s Commission on Care for America’s Returning Wounded Warriors, 2007). As discussed in the following chapter, depleted uranium is used by the US military for both offensive and defensive purposes. Exposure of US troops to depleted uranium can occur as a result of friendly-fire incidents, cleanup opera- tions, and accidents. Exposure to depleted uranium was a reported concern among Operation Iraqi Freedom veterans participating in a retrospective review of vet- erans’ health and exposure concerns (Helmer et al., 2007). SuMMARY OF FINDINGS IN THE SECTION ON DEPLETED uRANIuM IN Gulf War and HealtH, Volume 1 When volume 1 was published in 2000, few studies on health outcomes of exposure to depleted uranium had been conducted. Therefore, the committee studied the health outcomes of exposure to natural and processed uranium in workers at plants that processed uranium ore for use in weapons and nuclear reactors. After evaluating the literature, the committee concluded that there was inadequate or insufficient evidence to determine whether an association exists between uranium and 14 health outcomes: lymphatic cancer, bone cancer, ner- vous system disease, reproductive or developmental dysfunction, nonmalignant respiratory disease, gastrointestinal disease, immune-mediated disease, effects on hematologic measures, genotoxic effects, cardiovascular effects, hepatic disease, dermal effects, ocular effects, and musculoskeletal effects. It also concluded that there was limited or suggestive evidence of no association between uranium and lung cancer at cumulative internal doses lower than 200 mSv and between ura- nium and clinically significant renal dysfunction. THE DEPARTMENT OF vETERANS AFFAIRS REquEST FOR THIS STuDY Studies on health outcomes of exposure to uranium and depleted uranium published through 1999 were included in volume 1. Since volume 1 was pub-

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10 UPDateD literatUre review oF DePleteD UraniUm lished in 2000, a number of new studies have been published. In addition, weapons systems that contain depleted uranium are being used in the military operations that began in Iraq in 2003, so there is potential for troop exposure to depleted uranium due to incidents of friendly fire and accidental fire. For those reasons, VA has asked IOM to update the 2000 report and to take into consider- ation information on health outcomes of exposure to depleted uranium that has been published since volume 1. THE COMMITTEE’S TASK In response to VA’s request, IOM entered into a contract with VA to conduct the following study: An IOM committee will review, evaluate, and summarize the scientific literature regarding the association between exposure to depleted ura- nium and long-term human health outcomes. The study committee will incorpo- rate literature published since IOM’s 2000 report, Gulf war and Health, volume 1: Depleted Uranium, Pyridostigmine Bromide, sarin, and vaccines, was written. The committee will make determinations on the strength of the evidence of asso- ciations between exposure to depleted uranium and human health outcomes. The report might identify data gaps and subjects of scientific uncertainty and make recommendations for addressing them. ORGANIZATION OF THIS REPORT Chapter 2 gives information about the chemistry of uranium and its mode of action and about how depleted uranium is used by the US military. It also discusses radiologic and chemical mechanisms of uranium’s action. The toxicol- ogy of uranium, including toxicokinetics and toxicodynamics, is summarized in Chapter 3. The committee’s approach to its task is described in Chapter 4. Chapter 5 reviews available information on exposure to depleted uranium in military per- sonnel and how it is detected in humans. The committee’s rationale for selecting specific clinical end points is presented, with background information on each, in Chapter 6. Chapter 7 contains a comprehensive description of epidemiologic studies on health outcomes in populations exposed to depleted uranium or natural uranium. The final chapter, Chapter 8, presents the committee’s conclusions. REFERENCES Helmer, D. A., M. Rossignol, M. Blatt, R. Agarwal, R. Teichman, and G. Lange. 2007. Health and exposure concerns of veterans deployed to Iraq and Afghanistan. Journal of occupational and environmental medicine 49(5):475-480. IOM (Institute of Medicine). 2000. Gulf war and health, volume 1: Depleted uranium, sarin, pyr- idostigmine bromide, vaccines. Washington, DC: National Academy Press. ———. 2003. Gulf war and health, volume 2: insecticides and solvents. Washington, DC: The National Academies Press.

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11 introDUCtion ———. 2004. Gulf war and health: Updated literature review of sarin. Washington, DC: The Na- tional Academies Press. ———. 2005. Gulf war and health, volume : Fuels, combustion products, and propellants. Wash- ington, DC: The National Academies Press. ———. 2006. Gulf war and health, volume : Health effects of serving in the Gulf war. Washington, DC: The National Academies Press. ———. 2007a. Gulf war and health, volume : infectious diseases. Washington, DC: The National Academies Press. ———. 2007b. Gulf war and health, volume 6: Physiologic, psychologic, and psychosocial effects of deployment-related stress. Washington, DC: The National Academies Press. Report of the President’s Commission on Care for America’s Returning Wounded Warriors. 2007. report of the president’s commission on care for america’s returning wounded warriors report. http://www.pccww.gov/ (accessed October 13, 2007).

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