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Environment and Exposures OVERVIEW There have been special concerns about a range of both naturally occurring and either purposeful or accidental environmental exposures of troops during Me Persian Gulf War (POW) that are discussed in this chapter. Objective indicators of harmful environmental exposures in the Persian Gulf (PG) were limited in scope during the POW and are not readily usable for research purposes. Monitors of air and soil contaminants were not operating for the full period of Operation Desert Shield/Storm (ODS/S), and other kinds of exposures were not measured. Exposure indicators of other than air or soil were not available. Autopsies of animals and humans and follow-up examinations of military working dogs (MWDs) have not indicated the presence of excessive toxic or heavy metals, particularly when data before and after the oil well fires are compared. Official reports of acute health consequences from exposure to air pollutants were rare. It is clear from written descriptions and reports by veterans that the PG was a hostile environment. Desert conditions, the absence of amenities, uncomfortable temperatures and humidities, extremes in rainfall, blowing sand, insects, animals, fumes, and smoke all contributed to adverse living conditions. In addition, wartime conditions, including measures uniquely designed to protect the troops, necessitated other exposures such as vaccines against possible biological warfare (BOO) agents, pyridostigmine bromide (PB) to protect against possible chemical warfare (COO) agents, and pesticides to 36

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ENVIRONMENT AND EXPOSURES 37 protect against bites from insects carrying diseases such as sandfly fever and leishmaniasis. Depleted uranium (DU), used in munitions and tank armor, was a limited but real wartime exposure. Unfortunately, there was no systematic accumulation of data on these exposures, making research into their possible health effects exceptionally difficult, if not impossible. In the midst of these adverse environmental and wartime-related exposures, soldiers were vulnerable to all of the exposures connected with their particular occupations in the Gulf, such as chemical-agent-resistant coatings (CARCs), solvents, and vehicle exhaust fumes. Information about "unofficial" exposures, such as the combustion products of leaded fuels in heaters that were sometimes unventilated or nonregulation, wearing flea collars to protect against insect bites, and ingesting alcohol substitutes in the absence of approved alcohol consumption is available only from self-reports. Not surprisingly, the above scenario creates a picture of an extremely stressful environment, filled with the dangers and trauma of war, combined with a hostile living and work environment. Contributing to this stress were the lack of sanitary conditions and privacy (particularly when men and women were serving together); the speed of being "called-up" to duty and thrown into this environment; "watchful waiting" for the shooting war to begin or SCUD missiles to explode; apprehension heightened by drills and training exercises relating to the threat of chemical and biological warfare (CBW); intense workloads; and sleep deprivation. Additionally, issues related to unit cohesion, leadership, morale, and knowledge of family stresses back home varied among individuals but are important for full understanding of the experience of the entire deployed cohort. Although a wide range of possible exposures might be associated with adverse health outcomes in PG veterans, data on these exposures are often not available; when they are available, they are poorly documented. This lack of exposure information is at the core of the frustration in obtaining answers from epidemiologic studies. Self-reports of exposure and estimates of individual exposure from unit-level measurements will be subject to so much error that they are likely to yield inconclusive results and additional questions. This situation leads us to recommend improvements in collecting data on exposure assessment in future military deployments. We divide our more detailed discussion of exposures into two broad categories: the physical environment, which includes both the natural and the man-made environments, and psychosocial exposures. Generally, it is relatively straightforward to list potential causative agents, but exposure estimates related to POW operations are crude and unreliable. Efforts are under way to obtain additional estimates and improve current estimates, but there is little potential for substantial improvement. The working conditions and exposures that veterans encountered in the PG include the natural environment of the POW theater of operations, as well as

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38 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR occupational and combat-related exposures and situational stresses that combine all of the aforementioned. The environment and exposures of interest included those enumerated earlier, as well as dirt, sanitary conditions, endemic infectious diseases, flora and fauna, oil well spills and fires, pesticides, oil and petroleum products (especially jet fuel and diesel fuel containing lead additives), mycotoxins, and decontamination solutions. Occupational exposures were related mainly to general maintenance operations and include battery repair, cleaning and degreasing, electronic and radio repair, generator repair, grinding and sanding, sandblasting, lathing and milling, painting (especially with isocyanate-based paints), refrigeration servicing, vehicle repair, weapons repair, and welding and cutting. Work shifts were often longer than peacetime work schedules (e.g., 12- 16 hours), with fewer "time-off' periods (e.g., weekends and holidays), so that permissible exposure levels based on 8-hour shifts may not afford protection similar to that in civilian settings. The environment also was made more complex by the exposure of a large number of troops to potentially life-saving vaccinations, to medications administered in an effort to protect troops from chemical warfare (e.g., pyridostigmine), to clothing treated with permethrin, and to insect repellents (especially N. N-diethyl-m-toluamide Deem. All of this took place in a background of the barrage of news reports that reinforced the unknown nature of the threat the soldiers faced. The possibility of CBW was considered very real; most combatants expected the Iraqis to launch attacks by missiles containing both explosives and chemical or biological weapons. In addition, some accustomed ways of-relieving stress were simply absent. For example, interchange with the indigenous population was almost entirely forbidden, and there were severe restrictions on the availability of alcoholic beverages. The ease of communication with home, while in certain respects providing emotional support, also served to keep some people focused on what they had left, as well as on their current task. Finally, the level of casualties was very low; the lack of battle casualties in the PG may have diminished the possibility of rationalizing an acceptable trauma as a way to explain puzzling tensions and anxieties. The absence of this traditional military avenue for both experience and release of stress, and for explanation of the psychological symptoms being experienced, may have unmasked emotional conflicts that were perhaps harder to understand than when or if they had been experienced in previous conflicts. Thus, service personnel stationed in the Gulf were exposed to an extraordinary array of environmental conditions. Their complex experiences combined to yield what is truly a varied and sometimes confusing picture of exposure that has proven difficult to understand, much less reconstruct. Herein, we delineate the relevant exposures by reviewing available data, recognizing that these exposures combined to produce an environment that is more complex than can be easily described or evaluated.

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ENVIRONMENTAND EXPOSURES NATURAL ENVIRONMENT 39 Characteristics of the natural environment in the PG were discussed in the committee's first report and are summarized as follows. Mean daily low and high temperatures, respectively, were 80F and 108F in July (temperatures could reach 130F on a summer day [Young et al., 1992~) and 45F and 65F in the winter in the coastal region. Temperatures in the northwest desert were reported to be lower. Except in coastal regions, the relative humidity was less than 40% during the summer (less than 6% inland [Young et al., 19923), but more than 60% during the rainy season (December through March). Solar heat was intense in the summer. Rain was minimal but sometimes caused tents to flood. Many troops were located in desert settings. Sand was ubiquitous and often powdery, and persons with respiratory conditions sometimes reported pulmonary symptoms. Whether these symptoms were properly attributed to sand rather than to the type of living structure (tent versus air-conditioned building) or other problems has not been determined (Richards et al., 1993b). Review of sanitation in the PG theater is not currently possible from available records. The following has been reported as a summary of the sanitary conditions (O'Donnell, 1994~: Staging areas near ports of entry were characterized by crowded tent living with strains on latrine facilities, showers, and feeding. The prototype four-seat latrines were mass produced by contract in country. Latrines were designed for suction removal of waste by contractors or but out. Early designs permitted ingress of flies. In the desert environment, daily burning out of waste cans employed mainly diesel filer. Smoke from such fires was common, though rapidly dispersed by prevailing winds. Solid waste disposal was handled by contract in the staging areas and by burning in pits in the desert. Locations for bum pits and latrines were usually chosen carefully to minimize nuisance from smoke, smells, and flies. When shower/bath units were not available, many field expedients were improvised. Likewise for laundry. As shower setups became available or were improvised, an unforeseen problem was heating the water once the cooler weather set in. Time intervals between showers and unicorn laundering were sometimes lengthy. Anecdotal reports suggest that living and working areas were subject to smoke from waste fires for the duration of the fire. Efforts to minimize the nuisance of latrines and burn pits were not always successful because of wind shifts. The possibility that troops were exposed to contaminated water or food was low, because local drinking water was processed and treated before use. Troops were usually provided with sealed containers of drinking water; food was provided at mess halls or as a meal ready-to-eat (MRE) sealed in plastic; personnel generally did not eat food produced in local areas.

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40 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR An exposure of concern to troops in the PGW was the bite of the sand fly, which may carry the parasite that causes leishmaniasis and sandfly fever. Many cases of cutaneous leishmaniasis were expected, and a small number were in fact observed. What had not been expected was the appearance of a new manifestation of leishmaniasis caused by Leishmania tropica (Magill et al., 1993; MMWR, 1992~; L. tropica usually causes cutaneous disease but was described with visceral symptoms as viscerotropic leishmaniasis. Visceral leishmaniasis usually is caused by L. donovani, but exposures during ODS/S included L. tropica, which is hard to detect and makes the diagnosis or exclusion of leishmaniasis more difficult. At least 12 cases of visceral disease have been reported, but diagnosis is difficult and requires isolation of the parasite from bone marrow and no sufficiently selective and specific serology and skin tests have yet been developed. It has been postulated by some that this new form of the disease may be an explanation for some of the undiagnosed illnesses in PGW veterans. The committee's first report recommended support of continued research on leishmaniasis, especially to develop improved techniques for diagnosis, and further study of the ecology of the disease. Both the Department of Veterans Affairs (DVA) and the Department of Defense (DoD) have continued to support basic scientific research in response to these recommendations (see Appendix F), particularly the development of a skin test to diagnose leishmaniasis. Other exposures to fauna also have been described (O'Donnell, 1994~: Filth flies were a universal problem in the warm months. Latrines and food sources were attractants. The use of screening, self-closing doors, fly traps, fly bait, and pesticides were moderately successful suppressants. Various types of scorpions and snakes such as the horned viper were common in the desert, and envenomation of personnel occurred occasionally. Although biting spiders were present, they were not a problem. Mosquitoes were a factor only in the Euphrates Valley. Bared flies were present, as evidenced by the cases of leishmaniasis, but were difficult to find even when searched for. Sheep and camels were commonly observed in the desert. Dead sheep were open reported, but veterinary inquiries disclosed no signs of unexpected causes of death. Unit pets or mascots were officially banned but some small units adopted stray dogs and obtained veterinary care through Saudi sources. There have been numerous and persistent reports in presentations by individuals who were present during the PGW of finding large numbers of dead sheep, goats, camels, and other animals in the region. One published report assessed the histopathologic and chemical analysis of 26 feral cats exposed to the Kuwait oil fires (Moeller et al., 1994~; the analysis concluded that there was little evidence of harm from the environment. This has engendered some concern that the cause of death of these animals was chemical and/or biological

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EN, FIR ONMENT AND E)fP OS URES 41 weapons used in the Gulf at the time of the war. Additionally, veterinarians in Kuwait found no animal deaths due to chemical or biological weapon use, although many animals were killed by Iraqi soldiers and many died from water deprivation. In an effort to evaluate this matter further, the committee has attempted to locate and review as much relevant material as possible, including internal documents of the U.S. armed services that were generated both at the time of the PGW and later. The Army was well aware at the outset of the PGW that zoonotic diseases could be a major issue. Defense against chemical and biological weapons was a high priority. As a result, Army veterinarians, Air Force Special Operations Medical Officers, Army Chemical Warfare Specialists, and physicians specializing in infectious diseases were in the theater to evaluate any unusual animal deaths. An investigation of thousands of dead sheep was conducted early in Operation Desert Storm (ODS) after dead animals had been observed in various locations and at different times by Army medical personnel. The team estimated that the animals had been dead for various periods, ranging from days to months. Several investigative teams concluded that the areas in which the animals were found seemed to be dumping grounds for those that had succumbed to indigenous bacterial illness. Biological samples from this site were analyzed by the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and found to be negative for anthrax. Other reports of dead sheep were received but were not investigated due to poor weather conditions and inadequate description of the location of the dead animals. However, the U.S. agriculture attache advised military authorities that a 5-10 percent death rate from endemic infectious agents in sheep was common and that dead sheep were routinely stacked along common roadways to allow government inspectors to check ear tags and arrange for indemnity payments. This information was disseminated to U.S. Army veterinarians, and based on a lack of clinical signs in animals grazing nearby, no further clinical investigations were conducted during ODS. During the ground war, one on-site investigation of dead sheep was conducted and was negative for chemical or biological weapon use. After the war, discussions with local veterinarians confirmed that the practice of placing dead sheep by roadsides is common. Local practitioners have been consistently unaware of any unusual occurrences of death of sheep during or after ODS. Veterinarians and other medical personnel reported nearly unanimously that animal deaths from enzootic disease and trauma were common on the open range, even in the absence of military forces. These enzootic diseases are not known to be transmitted to people under the circumstances that existed during ODS/S (Stevens, 1995~. Approximately 140 MWDs were deployed to various locations in the PG (Dutton, 1995~. Since the PGW, 3 1 of these dogs have been euthanized because of arthritis, senility, cancer, temperament, multiple organ failure, and visual or

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42 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR inner ear problems; 5 died of natural causes (1 of heart failure and 4 of twisted stomach). No evidence of unusual morbidity or mortality was reported. The committee reviewed a protocol for a study of 129 MWDs identified as deployed to the Gulf between August 1, 1990, and February 28, 1991. From this cohort of deployed dogs, pathological specimens will be examined for approximately 20 MWDs that had died or been humanely euthanized and approximately 20 matched MWDs that had not been deployed to the Gulf. Additionally, MWDs deployed to the Gulf will be compared to a similar number not deployed to the Gulf (including follow-up until death or humane euthanasia) for pathologic, clinical, and demographic differences. MAN-MADE ENVIRONMENT Pesticides Reports to this and other panels (such as the DVA's PG Expert Scientific Panel) have been made on the use and safety of pesticides in the PG and in general (Berte, 1994~. The pesticides available in the PG during ODS/S included (in pounds) malathion (45,770), chlorpyrifos (8,410), D-phenothrin (1,858), methomyl (903), and lindane (539~. Pyrethrin, dichlorvos (DDVP), carbaryl, propoxur, and diazinon were also available but in amounts less than 330 pounds. It is not known how much of this inventory of pesticides was actually used or what troop exposures may have resulted (Bolton, 1995~. The use of pesticides in the Gulf was reported to have followed strict guidelines (Bolton, 1995~. They were used only after arthropod surveys that identified individual pests and estimated arthropod prevalence. Distribution of pesticides was prohibited unless approved by the local commander. Distribution or use for other than personal purposes was restricted to trained or certified personnel or contractors. There were some reports by troops of rash from misuse of dog flea collars. The insect repellent permethrin was used to treat uniforms in the PG; the material used to make the uniforms used during ODS/S was not pretreated in the factor with permethrin. Some troops were reported to have both used Deet on their skin and treated their clothing with permethrin between August and October 1990 (the peak occurrence of arthropods). From October 1990 to February 1991, the need for Deet and permethrin decreased as the population of arthropods declined (Bolton, 19959. Personal application of the insect repellent (33 percent Deet) provided to soldiers for use on the skin has been calculated based on the amount of repellent ordered for the Gulf operation and the amount returned (Bolton, 1995~. An average of approximately 2.7 tubes of repellent was available for use per soldier. The recommended deployment issue was two tubes per person, with each 60-ml tube containing an estimated 24 applications, or enough for

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ENVIRONMENT AND EXPOSURES 43 approximately 12 days. Similar calculations indicate an average of 0.1 bottle (2 ounces) of 75 percent Deet per soldier to be used for personal application to clothing; this material could also have been applied to skin. The virtual absence of reports of sandily fever (Richards et al., 1991) and negative findings for sandily fever in tests of pre- and postdeployment sera (Richards et al., 1993a) suggest that vector control was generally good. This inference has been reinforced in reports that the deployed troops had no known outbreaks of sandily fever, no evidence of typhus or spotted fever-group rickettsia infection, 1 case of West Nile fever, 20 cases of cutaneous leishmaniasis, 12 cases of visceral leishmaniasis, and 7 cases of malaria (Bolton, 1995; Hyams et al., 1995). There has been some concern about the delayed effects of pesticide exposure. This concern is particularly prominent for organophosphorus pesticides, which have been reported to be associated with a delayed neurotoxicity (Abou-Donia and Lapadula, 1990~. The early biochemical events associated with organophosphate- induced delayed neurotoxicity (OPIDN) remain unidentified. There are striking species differences in susceptibility to OPIDN, as well as differences in the potency of organophosphate compounds (Abou-Donia and Lapadula, 1990~. Where comparative assays have been developed, the chicken is a commonly used model system to assess the potency of compounds to induce OPIDN (Abou-Donia and Lapadula, 1990~. In humans, symptoms of necrologic dysfunction typically begin within 2 weeks of cessation of overexposure. Patients generally complain initially of symmetric lower extremity weakness, with subsequent progression lasting 3 - months after onset of symptoms. The patient may then enter a "stationary" phase of the illness, often lasting 3-12 months. Improvement may be observed ~18 months after onset of initial symptoms. Even in the most severe cases, there is usually improvement in the upper extremity impairment. Spinal cord damage can be permanent in the most severely affected patients. Specific agents have been studied to determine their ability to induce this condition. Chlorpyrifos, one of the pesticides used in the POW, was reviewed recently by Richardson (1995), who concluded that exposure as a result of "normal use" is unlikely to result in OPIDN. However, a report of eight cases of reversible necrologic disease in individuals with an exposure to an unknown amount of chlorpyrifos has raised some concern that a mild reversible sensory neuropathology may be associated with subchronic administration. In general, it appears that the average personal usage of the pesticides available in the POW theater of operations was low and unlikely to be associated with the induction of chronic disease. Fuels and Decontamination Solution Many different fuels were used in the PG both for vehicles and for heaters, cooking stoves, and portable generators. The exhaust produced by these fuels

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44 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR (particularly the reported use of unventilated heaters in living quarters that might have contained mixtures of diesel and jet fuel) could have caused a variety of exposures to combustion products, including lead. Information received in response to a request to DoD on whether leaded fuel was used in tent heaters stated that U.S. Central Command records indicated that approximately 145,000 gallons of gasoline (leaded and from local sources) were consumed per day in the theater between August 1, 1990, and March 30, 1991. These records did not indicate whether the fuel was used for heating tents; it was intended for use in vehicles, cooking, and power generation. The individual services provided information on the use of leaded gasoline in tent heaters as follows: Air Force, electric heat exclusively; Navy, kerosene and diesel fuel only; Marine Corps, diesel only; Army, "has no record of leaded fuel use in tent heaters" (Cusick, 1996~. To investigate further possible effects from this exposure, in combination with other exposures that were prevalent at various times in the Gulf, DoD has funded a laboratory study in rats to evaluate the toxicity of simulated PGW exposures. This research initiative has as its chief aim the investigation of rodent responses to exposure conditions similar to those experienced by PGW veterans. In an effort to construct a rodent model of unexplained illness in PGW veterans, Sprague- Dawley rats will be subjected to controlled experimental exposure to Deet, pyridostigmine, and a mixture of diesel and jet fuel followed by an electrical shock; controls will help to delineate possible effects of chamber exposures alone, compared with exposures with stress-producing electrical shock. Postexposure testing will include examination of central nervous system (CNS) integrity (auditory startle and adaptation to auditory stimulus and photosensitivity), testing of motor skills (grip and total activity), neurotransmitter analysis at sacrifice, two-dimensional gel electrophoresis to investigate whether novel stress-related proteins are produced in stressed animals, clinical chemistry, and measures of immune function. This ambitious protocol, as reviewed, may produce hypothesis-generating data. However, generalization of any results to veterans will necessarily be problematic. No variation in dosing will be done, and no dose-rate considerations are included. Although these animals are useful models for some known human conditions, the applicability of any adverse (or the opposite) outcomes noted in these studies will inevitably be questioned. Oil Well Fires and Spills Many agencies were involved in monitoring and measuring various aspects of the oil well fires and smoke (EPA, 1991; U.S. Gulf Environmental Technical Assistance, 1992; WMO, 1991, 1992~. Several efforts have been made to determine whether the oil well fires and spills created by retreating Iraqi forces affected the health of U.S. troops (DoD, 1993; USAEHA, 1992, 19949. One major effort at environmental assessment and health impact was undertaken by the

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ENVIRONMENT AND EXPOSURES 45 former U.S. Army Environmental Hygiene Agency (USAEHA), currently known as the U.S. Army Center for Health Promotion and Preventive Medicine (USACHPPM). Although exposures began when the first oil well fires were ignited by the Iraqi armed forces during their retreat in February 1991, and some lasted until November 1, 1991, USAEHA could not launch a successful air- sampling effort until the beginning of May, after the more stagnant air conditions of the winter months had passed. Those who undertook the sampling efforts did so with this knowledge. They intended to address the problem as thoroughly as possible by the use of meteorological modeling. A geographical information system (GIS) is being developed to integrate information over space and time on airborne and soil-based exposures, on meteorological conditions throughout the study interval, and on unit troop movements during ODS. Once this model is available, exposure of individual troops can be estimated throughout the region, although further work will still be needed to validate the model and estimate its . . precision. There were as many as 10 fixed air-sampling stations in the theater, but 2 of them operated for less than 2 weeks and 2 more operated for only 2 months. Three were in operation through the end of December 1991. These fixed sites were located where troops were concentrated, and soil was sampled from the same areas. The results are to be combined with National Oceanic and Atmospheric Administration (NOAA)-assisted modeling and records of troop movements using the GIS to estimate reasonable maximum individual exposures (RMEs) to the chemical substances sampled. Data available include air and soil pathway analysis and industrial hygiene sampling. Air and soil quality was estimated not to have deteriorated during the sampling interval, and a reference to earlier sampling suggests that air quality at some sites was even higher than before the war. Increases in toxic metals in soil were not found during sampling except for metals unrelated to Kuwaiti crude oil. Air pollutants expected from the oil fires were classified into four categories: reactants (uncombusted crude oil components), combustion products (e.g., carbon dioxide and water), incomplete combustion products (e.g., carbon monoxide), and products of secondary reactions (photolysis). The substances included short-chain and low to medium molecular weight aliphatics such as butane and heptane (both straight and branched chain) in the range of C2 to C40, simple and polycyclic aromatic hydrocarbons (PAHs), benzene, heterocyclic compounds including naphthalene and xylene, and substituted compounds such as methylated and halogenated compounds. Air samples were assayed for suspended particulates, both total and less than 10 Em in diameter, and for a series of volatile organics, PAHs, and metals. A subsample was examined for sulfur dioxide, nitrogen dioxide, coal-tar pitch volatiles, and acid aerosols. These agents were chosen as likely to provide a reasonable estimate of the most important particulates of the oil well fires and spills. The sampling was designed so that results could be used to estimate risks of cancer and subchronic noncancer diseases.

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46 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR So far, based on our present knowledge, none of the individual agents sampled or detected seems likely to cause symptoms that would persist for months or years after return from the PG. However, the modeling now in progress may offer some improved understanding of the general environment of troops located in different parts of the war zone or may raise questions about interactive effects or combined exposures. The USAEHA sampling (after May 1991) documented little deterioration of general air quality during that period of air monitoring. Although substantial increases were noted in particulates, concentrations were still considered "normal" for this area of the Middle East. Exposures to organic compounds were similar to levels observed in Houston and Philadelphia, cities with major petrochemical industries. There were relatively high concentrations of naturally occurring metals, apparently from wind-blown surface soils. There was some concern about ingestion and dermal absorption of air pollutants that had settled out, and these routes of exposure have been considered (USAEHA, 19949. However, no measurements were taken, so possible exposures through these additional routes can be estimated only by mathematical models. Further work by USAEHA is expected to provide a model of exposure distributions and to incorporate information from earlier, more limited sampling that might improve estimates of exposures at troop encampments. This work also will examine the frequency and duration of exposures. The model will have to be validated and its precision estimated before evaluating the relevance of the data. The Armed Forces Institute of Pathology (AFIP) has completed a study of 351 autopsies of U.S. personnel who died between August 1990 and November 1991 in Southwest Asia (SWA) during ODS/S and shortly thereafter. Reviewed were written autopsy records, histopathologic specimens, and toxicologic findings. A group of 149 individuals who died before the oil fires were lit was compared with a group of 202 who died after the fires were lit. No evidence was found to support an association between autopsy, histopathologic, and toxicologic findings and any environmental exposures, including smoke from oil well fires. Analysis for heavy metals from blood and tissue obtained at autopsy did not indicate elevated levels attributable to exposure in the Gulf environment (Peterson and Kalasinsky, 1996~. The initial findings (AFIP, 1994) reviewed by this committee indicated that lead levels were elevated in some of the specimens (IOM, 1995a). Since that time, investigators from AFIP have stated that with respect to lead, no valid toxicological conclusions can be drawn because some specimens were reportedly drawn and stored in collection vessels containing lead. The methods and findings of this study are being prepared for submission to a peer-reviewed journal.

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56 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR use of DU-containing systems. Studies have shown that with the exception of warehouses in which large quantities of DU munitions were stored, the estimated annual exposure did not exceed the current standard of 100 mrem/year for the general population (GAO, 1993a). Where this limit might be exceeded, standard radiation protection programs were in place (Daxon, 1994~. The radiological and toxicological hazards associated with long-term exposure to imbedded fragments are uncertain. There are no known studies of the long-term effects of DU metal implanted in tissues. Few ODS/S personnel were exposed to DU. Activities of the 144th Service and Supply Company in fighting fires, recovering vehicles, and cleaning the 29 tanks damaged by DU munitions led to the potential exposure of 27 soldiers. Results from testing 12 of these soldiers were reported as negative (GAO, 1993a), and the remaining 15 soldiers chose not to be tested (DSB, 1994~. It is possible that there was wider exposure to DU of troops who entered destroyed enemy vehicles either on duty or as sightseers or of combat-support troops who were exposed to battle dust after tank battles or to contaminated smoke from explosion and fire in the destruction of ammunition storage. ~ friendly fire incident wounded approximately 35 U.S. soldiers, of whom approximately 22 were suspected to have retained DU fragments (Daxon, 1993~. These wounded soldiers were offered close follow-up after the war as part of a DVA-funded medical surveillance program. Thirty-three of these 35 soldiers continue to be followed and studied. After 3 years, 15 of the 33 soldiers had detectable shrapnel. The initial work has demonstrated no evidence of toxicologic effects, but it has been noted that uranium excretion is significantly higher in soldiers with known retained shrapnel, supporting the contention that the shrapnel is not inert (Keogh, 1995~. Currently, two animal studies funded by DoD are under way to evaluate the long-term effects of DU. The first study is designed to investigate a rodent model of DU tumorigenesis and is being conducted by investigators at the Armed Forces Radiation Research Institute. Since little is known of the precise tumorigenic potential of this material, these researchers propose to conduct a long-term study in male F344 rats. The protocol includes a low- and high-dose 2- to 3-year exposure to implanted natural uranium wires. At the same time a companion study of the renal toxicity of DU is also proposed. This study will investigate the kinetics of renal excretion of uranium and possible toxicity from long-term exposure. These studies are useful in that they provide additional information about the chronic toxicity of uranium compounds. However, since the investigators must use nondepleted uranium and since available data indicate that the carcinogenicity of this compound is likely to be low, it is not known whether these experiments will add important new information. The second study, conducted at the Inhalation Toxicology Research Institute, is a 3-year rodent study utilizing three doses of DU with implanted

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ENrVIRONMENT AND EXPOSURES 57 tantalum and nonimplanted sham controls to study the behavioral effects of DU and the histologic and biochemical effects of implanted exposure and to evaluate uranium distribution throughout the body. CNS effects of exposure will be studied by evaluation of autonomic, sensorimotor, and neuromuscular alterations. Excitability and arousal also will be measured. Peripheral nerve conduction will be measured and hippocampal electrophysiology will be studied. Blood and urine samples will be collected and chemistries done. The bones (femur), hippocampus, sciatic nerve, kidney, liver, spleen, and muscles will be studied histologically. Renal function will be examined in detail. Finally, the tissue distribution of uranium will be quantified. This protocol will provide detailed information on the toxicity of DU in rodents, which is useful information. However, studies already completed suggest that there is little evidence that DU will produce any novel toxic picture. PSYCHOSOCIAL EXPOSURES A wide array of potentially toxic environmental agents has been considered in relation to health and ODS/S service. These include not only physical and chemical hazards but also the personal, social, and organizational context of service in the Gulf, the stressors present or generated in each domain, and the effects of these stressors on service personnel. Both physiological and psychological stress responses occur when humans are confronted with demands to adapt, change, or reorganize their lives or ways of thinking about themselves and those about them (Stretch et al., 1996~. Stressors are those events or circumstances that produce challenge or threat. It is not easy to compare the levels of stress, or the responses to stress, in the POW with those in previous military engagements. One difference is that PG military personnel did not have the level of detachment possible in prior conflicts. Easy telephone communication to family and friends, up-to-date news services, even the very rapid mobilization itself tended to keep people's "heads" back home while their bodies were in the Gulf theater. Another difference was that some of the accustomed ways of relieving stress were simply absent, among them interchange with the indigenous population (almost entirely forbidden) and access to alcoholic beverages (also forbidden). Further, the stress was acute, and it was everywhere, even far from the front lines. Entry into that situation was rapid, with little opportunity to prepare or be prepared. Similarly, reentry into U.S. society was rapid, with very little time or opportunity to accommodate. A further difference of the POW from most earlier conflicts is that U.S. combat troops in the PG experienced very low levels of casualties and benefited from vastly improved means of dealing with infectious diseases. Puzzling reactions and symptoms seen during and after prior conflicts may have been incorrectly attributed to battle casualties and infectious diseases that were

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58 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR considered unavoidable and even relatively acceptable outcomes of war. Thus, the lower prevalence of battle injuries and infections in the Gulf theater may have unmasked psychophysiological symptoms that were present in earlier conflicts but attributed to injury and casualty. The individual's perception and appraisal of events play a strong role in shaping the impact of stress. Most personnel who served in the PG would probably concur that the constant threat of CBW was stressful, that SCUD attacks and uncertain risk of other attacks or counterattacks by the Iraqi army were stressful, and that field conditions were often stressful. At the same time, each individual perceived the specific events associated with his or her experience in the POW as more or less stressful. Moreover, events in the theater were experienced in the context of life situations predating the POW, and the novel stressors of deployment were superimposed on the unique physical, physiologic, and mental state of each person. In anticipation of the psychological stress that would be created by a high- threat deployment to a harsh environment for ODS/S, DoD initiated a series of studies of the stress of deployment by sending a research team to SWA during September 1990 as the theater was being established. Beginning with that initial study, a 2-year program of studies after ODS/S has been conducted under the leadership of Dr. David Marlowe, Chief, Department of Military Psychiatry, Walter Reed Army Institute of Research (WRAIR). This program has focused on the stresses and psychological consequences of ODS/S and, more recently, has addressed symptoms experienced by the troops. This program has gathered data describing the stressors associated with ODS/S deployment from a variety of sources, as follows: 1. data collected before combat from active army in SWA (approximately 1,200 persons in individual and group interviews, plus 2,850 by questionnaire); 2. data collected after combat, time 1 (approximately 800 persons in individual and group interviews, plus 9,800 deployers and 830 controls by questionnaire); 3. data collected after combat, time 2 (4,585 deployers and 2,249 controls by questionnaire); 4. data collected from Pennsylvania and Hawaii, 2 years after combat (1,739 deployed and 2,512 not deployed by questionnaire); and 5. additional data collected 2 years after combat from U.S. Army National Guard and U.S. Army reserve troops (1,420 deployed to SWA and 1,995 not deployed) and U.S. Army Individual Ready Reserves (IRR) (500 deployed to SWA and 695 not deployed to SWA by questionnaire). These studies are discussed in sequence below. Studies of active duty units included men only; studies with reserve units included men and 8-9% women (Marlowe, 1996~.

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ENVlRONMENTAND EXPOSURES 59 Stressors Associated with Deployment Studies of stress experienced by POW veterans deployed prior to the beginning of the ground war were conducted during September and October 1990 (Marlowe et al., 1990a) and during November and December 1990 (Marlowe et al., 1990b); major findings are presented. Active Army members participated in individual or small-group interviews with others of the same rank. The purposes of these studies were to determine how stressful the deployment was and the sustainability over time of the force in the theater. The most consistently reported source of stress during this period was lack of knowledge of probable tour length and return date, as well as lack of knowledge of whether the troops would be called on for a protracted siege or combat in other words, uncertainty about the parameters of deployment. Examples of other stressors for some persons or groups in the theater include separation from family and concerns about home; difficulties with mail or telephone communications with home; heavy workload and sleep deprivation, especially for combat support and service units; unsatisfactory living conditions, including extreme crowding with resultant interpersonal pressure and hostility; apprehensions about being in imminent danger; social and psychological isolation of members of combat arms units; leadership issues including poor morale; the lack of recreation facilities; heat, sand, and the desert environment; and the severity of climatic conditions. Once telecommunications were in place, soldiers could benefit from communicating with their families at home, which remained a primary source of support (Wright et al., 1991~. Major contributors to the stresses of ODS deployment included the high estimation of Iraqi military capabilities and media anticipation of very high casualties, the threat of CBW with related fears about the adequacy of MOPP (mission objective protective posture) gear, and concerns about terrorism and infiltration. For support troops, particularly those arriving later in the theater, there was increasing apprehension about Iraqi capacities and the effectiveness of U.S. gear. Confusion about and multiple changes in deployment departure dates were also contributing factors (Marlowe, 1995~. Anticipation of Combat As conditions in the theater matured, access to amenities improved, deprivation decreased, and events became more focused. Soldiers began to experience more stress related to the anticipation of combat. The most salient of these anticipated stressors were having a buddy killed, attack by enemy aircraft, attack by enemy tanks, being wounded or killed, attack by enemy artillery, COW attack, and inadequate medical care. The most prevalent of these were chemical or biological attack (65%) and having a buddy killed (55%) (Marlowe, 1995~. Confusion about media estimates of potential casualty rates was a major

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60 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR concern for those in combat units, whereas concern about failure of weapons systems at critical points in the event of combat was more evident among support units (Wright et al., 1991~. It was evident to researchers at this early time that deployment was more disruptive for reservists and their families than for active duty service members. Unexpected, relatively sudden changes in circumstances created significant financial and job-related concerns for many reasons. The ODS experience of support units, many of whom were reservists, also differed from that of combat units, most of whom were on active duty. Many support units had heavier workloads, crowded and primitive living arrangements, and less clearly defined roles and missions (Wright et al., 1991~. Time spent in SWA prior to the initiation of war increased stress, probably because of the stringent conditions of deployment for combat alms troops. Anticipation of combat was stressful, but commencement of the ground war actually relieved the stress that had built up over months of anticipation (WRAIR, 1992~. Combat Exposure Major fears during the initial assault were of CBW, augmented by conflicting information about the effective life of MOPP gear and conflicting beliefs about the effects of antichemical and antibiological medications. As many as 40% of soldiers in all units studied experienced incoming indirect fire; 40% of one unit and 70% of another reported experiencing mines and booby traps; 40% in two units claimed to have fired rounds at the enemy and 30% to have engaged in a firelight; about 18% in two units claimed a confirmed "kill"; about 80% in one unit and 60% in another saw enemy killed or wounded in action; and about 44% in one unit and 36% in another saw civilians killed or wounded in action (WRAIR, 1992~. Less than 2% of the soldiers in all three brigades were injured or wounded themselves. About 14% in two units reported seeing an American soldier wounded; fewer reported seeing an American soldier killed. More than 10% reported a buddy wounded or injured. About 25% in one brigade, and 8 and 10% in two others, reported seeing an American wounded by friendly fire; 1-3% of persons in these units indicated they had seen an American killed. More than 20% in two units felt at some point that they were in imminent danger of being killed (WRAIR, 1992~. Although actual casualty rates were low, perceptions of danger were widespread due to fears of CBW. The most stressful events were those involving lethality or injury. The greatest combat trauma was in circumstances of "intimate violence" (e.g., vehicles in which a crew member was killed or wounded). Friendly fire had the greatest emotional impact when it involved parties from the same company or battalion. There were few combat stress casualties requiring intervention in the field (WRAIR, 1992~.

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ENVIRONMENT AND EXPOSURES 61 Additional factors that some troops identified as stressful during postcombat debriefings included having to take "untried experimental" drugs and vaccines (PB, anthrax vaccine) with rumored "terrible" side effects, continued attacks on civilians by Iraqis, oil fires and smoke, concern about time of return home, accidental losses of unit members, concern about family and family adjustment on return, and memories of traumatic events (Marlowe, 1995). Aftermath and Long-Term Adjustment Stress related to combat was only one of several categories of stressors affecting soldiers after their return home from ODS. Stressors that were part of the aftermath of combat experienced by the VIIth Corps 6-12 months after ODS included the following in descending order of significance: unitlworkplace climate, ODS-related stressors, reassignment and movement, downsizing of military, and family issues (Marlowe, 19954. ODS-related stressors include concerns with ODS experiences in the field and problems after return from the theater. Two years after return from ODS, four intercurrent stress factors, in descending order of significance, were reported by members of the XVIIIth Corps as follows: ODS-related issues, health and finances, unit climate, and downsizing or job future issues (Marlowe, 1995~. Although major sources of stress 1 and 2 years after ODS were related to current life issues for most soldiers, a significant subgroup still saw their life problems as arising out of ODS/S experiences (Marlowe, 1995~. During 1993, at the request of Congress, DoD conducted additional studies of veterans in Pennsylvania and Hawaii. A total sample of 4,334 veterans responding to a survey was studied (31% response rate): 1,739 were deployed during ODS/S (1,524 to the PG and 215 to other locations), 2,512 were not deployed, and 83 had an unknown deployment status. There were 715 active duty soldiers and 766 reservists among the deployed and 1,576 active duty troops and 948 reservists among the nondeployed (Stretch et al., 1995, 1996~. Although the response rate is low, opening the possibility of bias in the findings, the general orders of magnitude of the stressors may be reliable. Stressor clusters of deployment identified retrospectively in the Pennsylvania and Hawaii study by reservists included possible exposure to traumatic events, actual exposure to traumatic events, stresses of waiting for deployment, stresses in the theater, and stresses at home. The pattern of stressors was similar for the active duty component, with the exception of their exposure to explicit stressors of combat such as being fired on by the enemy and engaging the enemy in firefights. Exposure to oil fires and concern about that exposure also have been stressors. Two years after the end of ODS/S, 50% of

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62 HEAL TH CONSEQ UENCES OF THE PERSIAN G ULF WAR those who claimed exposure to oil well fires had at least moderate concern over that exposure (USAMRMC, 1994~. When asked to rate their current stress levels (two years after ODS), 66 and 67% of the active duty and reserve study participants who were deployed said they were experiencing moderate to extreme stress compared with 59 and 55% of the nondeployed active duty and reserve troops. When asked about the effects of stress on their lives, 46 and 41% of the active duty and reserve troops who were deployed responded that the effects were moderate or greater, compared with 35 and 30%, respectively, of the nondeployed (USAMRMC, 19943. In sum, "deployment of American forces to SWA created an interacting nexus of acute, subacute, and enduring chronic stressors and stress responses" (USAMRMC, 19949. Troops had been prepared for prolonged imminent danger from combat and simultaneously had to deal with a variety of other war-related changes, including a demanding workload. Stressors identified in DoD studies were also indicated in DVA studies. Reserve troops studied after they returned from ODS/S (N= 215) by Sutker et al. (1993) identified (as stressful) separation from home, family, and friends (18%~; SCUD missile attacks (15%~; austere physical environment (13%~; loss of control, uncertainty, and fear of the unknown (8%~; lack of leadership (7%~; protracted delays in return home after hostilities (5%~; inadequate supplies and equipment (5%~; prolonged truck transport in the desert (4%~; lack of information (4%~; and financial difficulties (3%~. These findings were borne out by Wolfe et al. (1992c, 1993) in studies ofthe Fort Devens Reunion Survey. Concems that existing scales to assess war stress are not sensitive to experiences of women, ethnically diverse groups, or married and older military personnel (a rapidly growing segment of the volunteer-based U.S. forces) prompted Wolfe et al. (1993) to assess 2,344 POW veterans (including 208 women) to investigate the following three major stressor categories: traditional wartime activities, nontraditional wartime events, and non-war zone deployment-related experiences (domestic, vocational, and psychosocial stressors). Veterans returning through Fort Devens, Massachusetts (including active duty personnel, reservists, and National Guard men and women), were evaluated within 5 days of their return from ODS/S and before they rejoined their families. Stressors predictive of posttraumatic stress disorder (PTSD) were measured by the Lauffer combat exposure scale score, a checklist expanded to reflect ODS war zone experiences, and an open-ended format where respondents described the most distressing incident of their deployment (Wolfe et al., 1993~. These same stressors were associated with Mississippi Scale scores (PTSD) and Brief Symptom Inventory (BSI)/General Severity Index (GSI) scores indicating general psychological distress (Wolfe et al., 1993~. Sutker et al. (1993) found that high levels of war zone stress, estimated by the ODS war zone stress exposure scale (developed by J. Wolfe and described

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ENVIRONMENT AND EXPOSURES 63 earlier) were associated with greater numbers of psychological symptoms, negative moods, PTSD symptoms, and physical or somatic symptoms among 215 veterans evaluated in New Orleans. Sutker et al. (1994a,b) also evaluated the influence of particularly gruesome war zone trauma in studies of troops mobilized to the PG for graves registration duty. This duty involved handling the dead, as well as mutilated body parts (e.g., matching body parts to the remainder of a corpse). Among 24 personnel studied, 46% met criteria for PTSD. This study was replicated with a larger sample (N= 60) of reservists who had been activated for service. Among those who were deployed to the PG, 48% had a current diagnosis of PTSD and 65% had PTSD in their lifetime. Among those who were not deployed there were no reports of current or lifetime PTSD (Sutker et al., 1994b). These DVA- sponsored studies have contributed uniquely to understanding the stressors related to the transition home from the theater, and the data may be useful in planning support for troops (especially reservists) in the future. Gender Differences in Exposure to Stress Women's health problems may be linked not only to their experiences with the declared enemy in the POW but also to actions by U.S. troops (e.g., sexual harassment or assault). Sexual harassment and assault during deployment created social and physical stressors that may cause symptoms in the years after the POW (Wolfe et al., 1992b). Sexual assault and harassment were studied among 142 women reservists who served in the Gulf and responded to a questionnaire 1 year after return. These women were a self-selected sample of a larger group of 241 women originally studied by Wolfe. Of the participants, 8% reported attempted or completed sexual assault, 31% reported physical harassment, and 63% reported verbal harassment during their Gulf War deployment (Wolfe et al., 1992b). Issues raised regarding some additional stressors for women included gender discrimination and low supplies of feminine sanitary products. Concerns for privacy, important to both men and women, become particularly crucial when men and women serve together in close proximity, as they did in the Gulf. Studies currently under way are examining further the effects of stress from harassment among women. In addition to studies of sexual harassment, this committee supports the recommendations of another IOM committee that recently reported in detail on research needs resulting from military women and men living and working together in close quarters, in addition to those related to sexual harassment, including the following (IOM, 1995b): the extent and impact of sex-role stereotyping of military women by military officers, noncommissioned officers, and enlisted personnel;

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64 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR the prevalence, contributing factors, and effect of physical arid sexual assaults and sexual harassment of women in the Armed Forces; effects of promilitary sexual abuse or violence history and military traumatic experiences on psychological health arid job performance; outcomes of treatment for traumatized servicewomen; and . strategies for harming sanitary needs. DVA ENVIRONMENTAL HAZARDS RESEARCH CENTERS In January 1994, DVA announced a program to establish centers for basic and clinical science studies of environmental hazards. Up to $500,000 per year for 5 years would be provided for support of the centers to engage in basic research on environmental health effects, with special emphasis on the diagnosis and treatment of medical problems currently being reported by POW veterans. The DVA was especially interested in new initiatives that complemented current activities and suggested that interorganizational agreements and scientific affiliations be encouraged, if they were justified and properly set up; this would include collaboration with non-DVA researchers. The environmental hazards research centers (EHRCs) were established in July 1994 in the DVA Medical Centers (VAMCs) in Boston, Massachusetts; East Orange, New Jersey; and Portland, Oregon. The environmental centers were fully funded by the end of 1994. The committee received written materials and heard oral presentations by representatives from each of the DVA EHRCs. Overall, the research activities, selected for funding by the DVA Central Office, are investigator-initiated, reflect local interests and expertise, and will have some serious limitations in broader use for either understanding causes of illness in returning PG veterans or assisting in determining whether returning veterans had illnesses different from or more frequent than might have occurred had these persons not been deployed. It is unclear whether or how these funded research activities are being managed by any research coordinating body of either DoD or DVA. The committee learned, as this report was being finalized, that the centers were reviewed on-site in March 1996 by external reviewers and that comments and responses by the EHRCs will be reviewed by the Research Working Group (RWG) of the PG Veterans Coordinating Board. Research at the Portland EHRC is focused on unexpected illnesses as reported by returning PG veterans, with a particular focus on threats to the necrologic and musculoskeletal systems (reflecting complaints reported by veterans with symptoms but without diagnoses). As is true elsewhere, few data documenting actual exposures are available. Temporal segments of activity (Operation Desert Shield only, Operation Desert Storm only, desert cleanup only, etc.) are highly inaccurate surrogates for exposures and create the potential

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ENVIRONMENT AND EXPOSURES 65 for unknown heterogeneity and misclassification. A majority of Portland's respondents to date have not elected to join the DVA PG Health Registry (PGHR), further emphasizing that the PGHR is not an appropriate tool for research. Use of sophisticated neuroendocrine tests performed many years after the conflict can have only limited usefulness in characterizing risks of deployment or reentry after the conflict. Researchers at the East Orange, New Jersey, EHRC hypothesize that chronic fatigue and chemical sensitivity are associated with many of the unexplained symptoms and illnesses among returning PG veterans. Criteria for chronic fatigue syndrome (CFS) changed from those proposed in 1988 to less restrictive criteria in 1994. The syndrome is poorly characterized and not universally accepted as valid. If chronic fatigue and chemical sensitivity become accepted medical entities, the lack of population-based estimates of frequency and severity will still complicate assessment of whether these syndromes among returning veterans are associated with or caused by military service. The use of extensive (and expensive) laboratory tests of immune function, interferons, and cytokines and the numerous magnetic resonance imagings (MRIs) of these people raise questions about resource allocation. Developing objective measures of the effects of chemical exposures on possibly chemically sensitive individuals has been proposed as one of the center projects and may be of some utility in civilian settings, but it will have little practical application in the mobilization and deployment of large numbers of healthy troops unless future epidemiologic work, utilizing accepted diagnostic criteria, demonstrates an increased prevalence among deployed veterans. Such measures might then be used as Remobilization screening to assist in later diagnostic evaluation of symptomatic individuals. The project that hypothesizes individual differences in susceptibility to stress and vulnerability is intriguing, although the challenges of interspecies extrapolation from rodent models will require careful interpretation. Studies at the Boston EHRC will, in part, continue to utilize the longitudinal follow-up of a group of PG veterans who returned through Fort Devens, Massachusetts. Although this appears to be a strength, the small number of participants is likely to limit investigators' abilities to address their research questions. Clinical studies of the hypotheses that higher exposures to combustion products of oil well fires impair pulmonary function 5 years or more after exposure are unlikely to be fruitful, in part because of the small sample size. A state-specific study (Massachusetts) of differential cancer incidence among returnees may have too few events to justify support, particularly given the young age of most of the deployed force. If this were to be judged as an important undertaking, a larger group-perhaps even the entire cohort of approximately 697,000 returning veterans-could better address such questions of cancer incidence and mortality.

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66 HEALTH CONSEQUENCES OF THE PERSIAN GULF WAR In summary, the DVA-funded EHRCs facilitate the application of research skills available at selected VAMCs across the United States, but these research efforts will have limited ability, individually or collectively, to contribute to understanding the health effects of military service in the POW. The committee has not evaluated other uses of these research programs.