2
Background

This chapter provides background information on a number of topics related to the committee’s charge. It begins with accounts of the development of a military aerial herbicide delivery system and the Operation Ranch Hand spray program during the Vietnam War. The early history of the Agent Orange controversy is then reviewed along with the first studies of Vietnam veterans’ health. A detailed description of the Air Force Health Study (AFHS) follows—its origins, the development of the protocol, identification of the exposed and comparison cohorts, means by which exposure was characterized, collection and analysis of data, results of the research,1 and cost of conducting the study. The Department of Veterans Affairs (VA) compensation policy for health problems deemed to be associated with wartime exposure to herbicides is also outlined. The chapter concludes with a discussion of the Institute of Medicine’s (IOM) comprehensive reviews of the literature regarding adverse health outcomes and herbicide and dioxin exposure, as well as the role of AFHS reports and papers in that work.

This information forms the foundation for many of the committee’s findings, conclusions, and recommendations in succeeding chapters.

DEVELOPMENT OF A MILITARY AERIAL HERBICIDE DELIVERY SYSTEM

It has been said that the seeds of the Agent Orange controversy were planted during World War II (WWII) when the conquest of islands in the Pacific theater

1  

This chapter is not intended to provide a critical review of the research results—a task outside of the committee’s charge—but rather to recap the content of the reports and papers prepared by the investigators over the years.



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Disposition of the Air Force Health Study 2 Background This chapter provides background information on a number of topics related to the committee’s charge. It begins with accounts of the development of a military aerial herbicide delivery system and the Operation Ranch Hand spray program during the Vietnam War. The early history of the Agent Orange controversy is then reviewed along with the first studies of Vietnam veterans’ health. A detailed description of the Air Force Health Study (AFHS) follows—its origins, the development of the protocol, identification of the exposed and comparison cohorts, means by which exposure was characterized, collection and analysis of data, results of the research,1 and cost of conducting the study. The Department of Veterans Affairs (VA) compensation policy for health problems deemed to be associated with wartime exposure to herbicides is also outlined. The chapter concludes with a discussion of the Institute of Medicine’s (IOM) comprehensive reviews of the literature regarding adverse health outcomes and herbicide and dioxin exposure, as well as the role of AFHS reports and papers in that work. This information forms the foundation for many of the committee’s findings, conclusions, and recommendations in succeeding chapters. DEVELOPMENT OF A MILITARY AERIAL HERBICIDE DELIVERY SYSTEM It has been said that the seeds of the Agent Orange controversy were planted during World War II (WWII) when the conquest of islands in the Pacific theater 1   This chapter is not intended to provide a critical review of the research results—a task outside of the committee’s charge—but rather to recap the content of the reports and papers prepared by the investigators over the years.

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Disposition of the Air Force Health Study of operations exacted enormous human tolls on the U.S. Army and Marine Corps units mounting first-wave beach assaults (Galston, 2001). At the time, high explosives designed expressly for tree destruction had been used by the military as one tactical option to eliminate the enemy advantage afforded by the dense indigenous vegetation. This tactic was eventually abandoned, as fallen trees could still provide effective cover and concealment for defensive enemy positions along targeted beachheads (Minarik, 1964). Prior to WWII, the U.S. Army Air Corps had assembled the basic physical apparatus of aerial chemical delivery systems as part of its chemical warfare research and development effort (Buckingham, 1982). Methods for low-altitude application were well beyond preliminary developmental stages, and the atmospheric conditions necessary for the delivery of effective chemical concentrations to targets had also been characterized (Buckingham, 1982). Despite their availability during WWII, aerial chemical delivery systems for herbicide application were not widely implemented in the Pacific theater.2 The technology was, however, employed at many locations including Morotai, Palau, Iwo Jima, and Okinawa in an effort to rid regions of strategic importance of disease-carrying vectors (Cecil, 1986).3 In the 1950s, the British military effectively used aerially disseminated herbicides,4 a fact that did not go unnoticed by U.S. military planners and the State Department as the situation grew more volatile in Southeast Asia (SEA) during the late 1950s and early 1960s (Buckingham, 1997). By the time President Kennedy took office in 1961, the U.S. military possessed a fairly well-developed arsenal of herbicidal agents. Three years prior to Kennedy’s inauguration, an efficient large-capacity system for the delivery of liquid agents had become standard U.S. Air Force (USAF) inventory (Buckingham, 1982). This system, referred to as the MC-1 Hourglass, comprised a 1,000-gallon tank, pump, and pipe assembly with six nozzles and emergency dumping capabilities (IOM, 1994). The MC-1 was the forerunner of the spray system that was ultimately fitted to the Fairchild C-123s flown in Vietnam. Meanwhile, in 1959, an H-21 helicopter was successfully used for aerial delivery of herbicides to clear a grove of nuisance sugar maples from an artillery firing range at Camp Drum, New York.5 The herbicide used at Camp Drum was a 50:50 mixture of two phenoxyacetic acids: 2,4-dichlorophenoxyacetic acid 2   Limited aerial spray tests did occur on some Japanese-controlled islands to demarcate navigation points and to remove dense tropical foliage (Buckingham, 1997). 3   Vector-borne disease (malaria, dengue, filariasis, and fly-borne dysentery) was the major cause of lost man-hours for the Army Air Corps in the Pacific during WWII. Copper acetate arsenite (Paris Green dust) and dichlorodiphenyltrichloroethane (DDT) were among the insecticides used in the Pacific to destroy adult and larval vector populations (Cecil, 1986). 4   During the Malayan Emergency (1953–1954) the British used helicopters and some fixed-wing aircraft for successful aerial delivery of sodium arsenate, and later, a mixture of trioxene and diesolene to agricultural targets (Buckingham, 1982). 5   Known today as Fort Drum.

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Disposition of the Air Force Health Study (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T).6 The herbicide application achieved the desired effect: within one month, treated trees were undergoing abscission (falling) of leaves and significant regrowth was not observed the following year (Warren, 1968). The organic acid mixture used at Camp Drum was only one herbicidal candidate of more than 1,000 compounds tested during and after WWII at the Army Chemical Corps laboratories at Fort Detrick, Maryland (Midwest Research Institute, 1967). Early synthetic pesticides were mainly inorganic compounds. The emergence of organic compounds as effective herbicidal agents can be attributed to the isolation and ultimate synthesis of compounds during the 1930s that were found to act as chemical messengers (hormones) in plants (Butler, 2005).7 Defoliants are a subclass of herbicides that induce abscission.8 Their application can, but does not necessarily, destroy the entire plant (Buckingham, 1982). Both 2,4-D and 2,4,5-T act as plant hormones, and application of species-appropriate concentrations ultimately induces abscission. By the end of WWII, 2,4-D had found widespread use in the agricultural and forestry industries. More than 5 million pounds of 2,4-D were produced in 1945 and Weedone, which was released that same year, was the first 2,4-D-containing weed killer marketed in the United States for general use (Cecil, 1986). Both civilian and military WWII-era research efforts led to the same conclusion with respect to chlorophenoxy herbicides: formulations containing a combination of 2,4-D and 2,4,5-T were found to exhibit the most effective level of selective herbicidal activity for both broad-leafed and woody plants.9 Thus, the herbicides used in Vietnam were not novel compounds. Just one year prior to the launch of herbicidal missions in Vietnam, hundreds of thousands of miles of U.S. roads, railways, and utility easements as well as tens of millions of acres of agricultural land had been treated with chlorophenoxy herbicides, an appreciable percentage of which had been disseminated aerially (Buckingham, 1982). 6   The mixture tested at Camp Drum in 1959 was actually Agent Purple, which was a 50:30:20 mixture of n-butyl 2,4-D, n-butyl 2,4,5-T, and isobutyl 2,4,5-T (Stellman et al., 2003). 7   Butler (2005) summarizes the history of the development of 2,4-D and 2,4,5-T and the subsequent discovery of 2,3,7,8-tetrachlorodibenzo-p-dioxin as a 2,4,5-T contaminant. 8   Abscission is typically governed by changes in diurnal cycle duration and occurs when auxin (3-indoleacetic acid) levels increase, ultimately leading to the production of enzymes that digest the structural plant material that secures the leaf to the plant stem. Both 2,4-D and 2,4,5-T trigger this same chain of chemical events (Galston, 2001). 9   The selectivity of these compounds is based, in part, on leaf surface area in the horizontal plane, meaning horizontally planar leaves make better herbicide collection areas than leaves that grow predominately in the vertical plane (Buckingham, 1982). Selectivity holds true up to a certain threshold concentration (Cecil, 1986) and is also governed by variation in plant growth, absorption, and metabolism rates (Lavy, 1987).

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Disposition of the Air Force Health Study OPERATION RANCH HAND The defoliation initiative that eventually became known as Operation Ranch Hand officially began in January 1962 (Buckingham, 1982). Aerial defoliants were used in Vietnam to efficiently clear vegetation providing concealment for enemy movements, bunkers, and other structures (McConnell, 1970). Major supply and communication routes vital to the U.S. mission, and therefore to the safety of U.S. military personnel, were under constant threat of guerrilla ambush as the Viet Cong had in many areas established complex networks of tunnels, caves, and trenches that under the cover of the dense jungle canopy were difficult, if not impossible, to detect from the air. These conditions put U.S. ground forces at a great disadvantage (Cecil, 1986). Defoliant operations in a much-reduced capacity also targeted agricultural concerns considered to be potential food sources for enemy troops.10 Although the Army Corps of Chemical Engineers and the Navy were also involved in defoliant missions,11 the bulk of defoliation efforts in Operation Trail Dust12 were undertaken by a largely volunteer group of Air Force personnel who eventually became known as the Ranch Hands. In July of 1961, before the Ranch Hands arrived in South Vietnam, the Combat Development and Test Center at Saigon received its first shipments of defoliant chemicals from the United States (Buckingham, 1982) and, beginning in August of that same year, spray tests were conducted by the (South) Viet Nam Air Force using H-34 helicopter dissemination of Dinoxol, Trinoxol, and Concentrate 4813 (Cecil, 1986). Two months earlier, the Office of the Secretary of Defense tasked researchers at Ft. Detrick with a feasibility study of Vietnamese jungle defoliation (Young and Reggiani, 1988). Eighteen spray tests formed the basis of their analyses and in weighing the costs and strategic benefits, researchers determined that the most effective defoliant regimen for the region would involve the application of two distinct classes of herbicides—chlorophenoxy acids and cacodylic acids (Young and Reggiani, 1988). The original unit, officially named Tactical Air Force Transport Squadron Provisional 1 (Buckingham, 1982) began trial operations in Vietnam in 1962 with three modified C-123 aircraft (McConnell, 1970). The unit initially com- 10   Farmgate was the operational code name for the food deprivation project (Stellman et al., 2003). 11   Ground delivery of herbicides also took place to a much lesser degree. Truck- and trailer-mounted sprayer units called “Buffalo” turbines as well as hand-held and backpack sprayers were used for treatment of roadsides and base perimeters (Stellman et al., 2003; Young and Reggiani, 1988). The “brown water Navy” treated the banks of inland rivers (Bullman et al., 1994). 12   Operation Trail Dust was the code name of the U.S.–Vietnam allied herbicide program and Operation Ranch Hand referred specifically to the C-123 mission (Stellman et al., 2003). 13   Dinoxol was a 50:50 formulation of butoxyethanol esters of 2,4-D and 2,4,5-T. The active ingredient in Trinoxol was 2,4,5-T. Concentrate 48 (Weedone) contained the ethyl ester of 2,4-D (Cecil, 1986).

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Disposition of the Air Force Health Study prised six pilots and 12 enlisted personnel (Buckingham, 1982) and was later supplemented with volunteers from Pope Air Force Base (AFB), North Carolina. At Pope AFB, Capt. Carl W. Marshall recruited from a pool of Air Force personnel who had volunteered for an earlier USAF counterinsurgency mission code-named Jungle Jim (Buckingham, 1982). USAF personnel from this pool readily volunteered for the new mission, which had been packaged as a 120-day temporary duty assignment to SEA during which unit members would don civilian attire and fly unmarked aircraft. Potential volunteers were also informed that if captured, the U.S. military would renounce any affiliation with them. Ultimately, six spray aircraft and 69 USAF personnel left for SEA in November 1961 as the first defoliation unit deployment (Buckingham, 1982) and arrived at Clark AFB in the Philippines on December 6. The first three spray-ready planes were ordered to Saigon on January 7, 1962 (Buckingham, 1982) and a shipment of Agents Blue and Purple arrived at Tan Son Nhut Air Base on January 9 (Young and Reggiani, 1988). The initial choice of Agents Blue—a water-soluble liquid containing the active ingredient hydroxydimethylarsine oxide (cacodylic acid)—and Purple—a 50:30:20 mixture of n-butyl 2,4-D, n-butyl 2,4,5-T, and isobutyl 2,4,5-T—was consistent with the recommendation that had been made by Ft. Detrick researchers a year earlier. On January 10, 1962, Ranch Hands flew their first spray mission using Agent Purple. While the application was ineffective—which was later thought to be attributable to the delivery of a suboptimal concentration of herbicide—Ranch Hand crews discovered that the herbicide destroyed the rubber seals of the Hourglass spray system (Buckingham, 1982). Thus, the Ranch Hands, operating under the call signs Cowboy and later Hades,14 were required to develop their own operational tactics tailored to indigenous conditions during their first year in Vietnam. By June 1962, the Ranch Hands were ready to fly their first tactical missions. In 1968 the Special Aerial Spray Flight received the new unit designation of 12th Special Operations Squadron (McConnell, 1970). Generally, excepting missions associated with Operation Mule Train, Operation Flyswatter, and the Tet Offensive,15 the 12th Special Operations Squadron was engaged exclusively in the execution of defoliant operations. Over time, the unit developed a group persona that, like their mission, made them somewhat unique among their fellow service members. Contrary to initial plans of anonymity, the Ranch Hands wore 14   In 1966 the 12th Air Commando Squadron moved from Tan Son Nhut to Ben Hoa. The change in call sign accompanied the move (Cecil, 1986). 15   Operation Mule Train comprised logistical missions in 1962 and 1963, which the Special Aerial Spray Flight supported. Operation Flyswatter missions were carried out to kill malaria-carrying mosquitoes and other insects. The Ranch Hands flew airlift support missions during the 1968 Tet Offensive (Cecil, 1986).

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Disposition of the Air Force Health Study special insignia as well as purple scarves16 that were a source of controversy17 among USAF commanders and which would eventually come to be recognized as a unit symbol (Cecil, 1986). Like the purple scarf, the Chinese character for purple at the center of the Ranch Hand unit insignia echoed the namesake of one of the earliest herbicide agents used in Vietnam (Cecil, 1986). Prior to each Ranch Hand mission, a flight mechanic or a crew chief facilitated herbicide loading. Herbicides were not loaded directly from the 18-gauge, 205-liter steel drums that were used for transport by all of the 11 companies18 that manufactured herbicides for the military (Young and Reggiani, 1988). Drums were offloaded from cargo vessels, transported to Ranch Hand unit locations, and then herbicide was transferred from drums to F-6 trailer tanks.19 An assembly of pumps, pipes, and hoses allowed the F-6 to remain stationary during aircraft tank filling. Residuals (2–5 liters per drum) were collected from inverted drums in a drip pan and used to treat base perimeters. It was common for military personnel to utilize discarded drums to fortify defensive positions and to construct barriers (Young and Reggiani, 1988). Three to six C-123s typically made up a tactical formation (Meek, 1981). When mission20 requirements were at their highest levels between 1967 and 1969, more than 10 C-123s would fly in a single formation (Boyne, 2000; Cecil, 1986). C-123s normally at or above their weight limit were required to fly “low and slow,” typically at 150 feet and 130 knots for targets to be effectively treated. This meant that Ranch Hand aircraft were extremely vulnerable to enemy fire. Early formations flew at an altitude of 3,000 feet on target approach and then went into a 2,500 feet per second dive to the optimum spray delivery altitude of 150 feet. It was soon discovered that the high altitude approach was costing the aviators the element of surprise. A reverse approach was later used and formations would fly as low as 20 feet and then abruptly climb to the optimum spray altitude (Boyne, 2000). Shortly after a ground fire incident that disabled the hy- 16   The purple scarf became part of the Ranch Hand uniform after a violet scarf had been presented to one of the flight commanders by South Vietnam Prime Minister Nguyen Cao Ky, who had accompanied the Ranch Hands on some of their early missions (Cecil, 1986). 17   Policy coming from (commander of U.S. forces) General William Westmoreland’s office forbade the wearing of the purple scarves. However, threats made by Prime Minister Ky to close Tan Son Nhut over the wearing of the purple scarves resulted in an exception to the USAF uniform policy for Ranch Hands (Cecil, 1986). 18   In a class action lawsuit initiated in 2004, more than 30 Agent Orange manufacturers are named (de Sola, 2004). 19   Each F-6 tank could accommodate approximately 78 drums of herbicide (Young and Reggiani, 1988). 20   Each single aircraft take-off/landing cycle was termed a sortie; a mission was the collective reference to sorties flown with a common target. A project was all missions related to a specific target (Lavy, 1987; Young and Reggiani, 1988).

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Disposition of the Air Force Health Study draulic system of one C-123, which controlled the spray pump and herbicide shut-off valve, the decision was made to fly future missions with the rear cargo door open so that if an onboard flare was ignited by incoming fire it could be shuttled out the back door (Buckingham, 1982). Although the open rear door reduced the risk of injury to crew members and of damage to the spray system from internal fire and potential onboard herbicide combustion or leakage, in cases where the hydraulic lines suffered direct hits from enemy fire, the cargo area and flight mechanic could be sprayed with herbicide. Bottles of distilled water were installed in the cargo bay to flush eyes after such events (Buckingham, 1982). The open aft door of the fuselage also allowed the flight mechanic who operated the spray console to drop smoke grenades marking enemy positions for fire-support aircraft (Meek, 1981). Additionally, both cockpit side windows remained open for ventilation during missions (Meek, 1981) and to prevent crew injury resulting from flying Plexiglas shards should a window sustain a direct hit (RHAC, 2000). These operational conditions resulted in a situation where the crews of lead aircraft of the formation were exposed to spray mist carried forward by the internal aft-forward airflow created by the open door and windows. Aircraft in positions other than the lead were not only flying directly into the spray paths of aircraft before them in the formation (Cecil, 1986), but they were also drawing into the fuselage some of their own spray mist (Meek, 1981; Wilcox, 1989). Other conditions under which Ranch Hands were subject to herbicide exposure included the use of herbicides as hand cleaners (efficient for grease and oil removal), during the removal of debris from nozzles (rubber bits from dissolved seals), and through the maintenance of the herbicide tank valve (the maintenance person was required to actually enter the tank to lubricate the dump valve) (RHAC, 2000). Flight conditions for the Ranch Hands improved with the introduction of a new spray system and jet-powered aircraft. In July of 1966 the MC-1 Hourglass system was replaced by the A/A45Y-1 spray system (Cecil, 1986). The A/A45Y-1 provided a flow rate of 250 gallons per minute, improved spray pattern evenness, and allowed the entire herbicide payload to be dumped in just 30 seconds in emergency situations (Cecil, 1986). The introduction of the C-123K—the K in the nomenclature referred to the jet version of the C-123—in 1968 reduced hits from enemy fire by 28 percent (Cecil, 1986). This reduction was attributed in part to the greater number of targets that the enemy had to fire at—formation numbers increased to as high as 12 aircraft on some missions (Cecil, 1986). The new jet-equipped C-123Ks had also undergone some structural improvements to better protect the engines from enemy fire and to reduce windshield shattering. They were fitted with larger spray pumps that were able to maintain a constant spray flow rate (3 gallons per acre) during airspeed fluctuations (Cecil, 1986). By the time that the jet-equipped C-123Ks arrived in 1968, the Ranch Hand mission, technically, had already peaked; mission requirements had steadily in-

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Disposition of the Air Force Health Study TABLE 2-1 Herbicides Used in Vietnam Between 1961 and 1971 Herbicide Designation Years Used Millions of Gallons Potentially Used in Vietnama Active Ingredient(s)b,c Agent Pink 1961; 1965 0.013 n-butyl, isobutyl esters of 2,4,5-T Agent Green 1961–1965d 0.008 n-butyl ester of 2,4,5-T Agent Purple 1962–1965 0.499 n-butyl ester of 2,4-D; n-butyl and isobutyl esters of 2,4,5-T Agent Orange Ie 1965–1970 12.054 n-butyl esters of 2,4-D and 2,4,5-T Agent Orange II 1968–? 0.948 n-butyl ester of 2,4-D and isooctyl ester of 2,4,5-T Agent White 1966–1971 5.425 Picloram Agent Bluef 1962–1971 1.251 Cacodylic acid aIn some instances procurement records are represented versus spray volumes (Stellman et al., 2003). bYoung and Reggiani, 1988. cStellman et al., 2003. dEstimated to be within the Agent Pink usage time frame. eThere were two Agent Orange formulas used in Vietnam. The original formula was a 50:50 mixture of 2,4-D and the n-butyl ester of 2,4,5-T. In the formula known as Agent Orange II the isooctyl ester of 2,4,5-T was used. Improved production methods allowed synthesis to occur at lower temperatures, ultimately reducing levels of TCDD contamination in the 2,4,5-T component of Agent Orange II (Stellman et al., 2003). fTwo herbicides were referred to as Agent Blue. One was a powder (cacodylic acid/sodium chloride mix) and the other was a water-based solution (cacodylic acid/sodium cacodylate) (Stellman et al., 2003). SOURCE: Adapted from Stellman et al., 2003. creased through 1967 and then gradually began to decline (Buckingham, 1997). By the end of 1970 President Nixon had issued an order to phase out the herbicide mission (Cecil, 1986). Between 1962 and 1971 Ranch Hands flew 19,977 sorties (IOM, 2003b), and herbicides had been sprayed on nearly 10 percent of the South Vietnamese landmass (Table 2-1) (Alcott, 1995). The last fixed-wing application of herbicides took place on January 7, 197121 (Buckingham, 1982). It has been claimed (Gough, 1986) that the Ranch Hand mission resembled civilian crop-dusting to some degree—both required excellent piloting skills for extremely 21   The last helicopter application took place on October 31, 1971 (Buckingham, 1982).

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Disposition of the Air Force Health Study low-altitude flight, but Ranch Hand C-123s were generally dangerously overweight during takeoff, were far less maneuverable than civilian crop dusting aircraft (110-foot wingspan), and when pilots were required to execute the most difficult of maneuvers (60° banks at treetop level), they normally did so under enemy fire (Boyne, 2000). Largely due to the receipt of the Purple Heart, the Ranch Hand unit ended up being the most highly decorated USAF unit in Vietnam (Gough, 1986). THE AGENT ORANGE CONTROVERSY Initial Concerns over the Use of Herbicides in Vietnam As early as 1963 the American public was made aware through media reports of the use of herbicides in Vietnam (Buckingham, 1997). As media coverage continued to draw attention to the potential legal, political, and ethical consequences of the defoliant operations, concerns about ecological and human health impacts were also mounting. The year before the first missions disseminating Agent Orange were flown in Vietnam (March 1965) (Cecil, 1986), the Federation of American Scientists publicly condemned the use of herbicide in Vietnam, marking the beginning of a concerted campaign against U.S. military use of defoliants (Young and Reggiani, 1988). Several scientific organizations petitioned for the cessation of spraying and for the investigation of the short- and long-term consequences of the military’s herbicide use. Under increasing pressure from the scientific community and in response to increasing media coverage of what was rapidly becoming a major domestic controversy, the Department of Defense (DOD) commissioned a series of studies related to herbicide exposure. Two studies were instrumental in the eventual modification of U.S. military policy governing the use of herbicides. The first was a literature survey carried out by the Midwest Research Institute (MRI) that resulted in a recommendation of further Agent Blue (an arsenical) research, but did not specifically address the major herbicidal mixtures (Agents Purple and Orange) used in Vietnam (Butler, 2005). Additionally, the MRI study was not able to draw definitive conclusions regarding the long-term effects of herbicide exposure (Young and Reggiani, 1988).The second study, conducted by Bionetics Research Laboratories under contract from the National Cancer Institute, evaluated the potential teratogenic effects of 2,4,5-T exposure (Galston, 2001). Results from the Bionetics study, reported in 1968, indicated that 2,4,5-T exposure could elicit teratogenic outcomes in some species. In response to these results, as well as increasing media reports implicating Agent Orange as a causative agent for myriad health problems, the use of 2,4,5-T was domestically restricted on April 15, 1970, and the DOD concomitantly suspended 2,4,5-T’s military use (Butler, 2005). Later that year, Congress requested (Pub. L. 91-441) the National Academy of Sciences (NAS) to form a committee whose task would be to conduct a com-

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Disposition of the Air Force Health Study prehensive evaluation of the physiological and ecological impacts of herbicidal operations in Vietnam (NAS, 1974). In their report published in 1974, the committee stated that they could not determine whether exposure to herbicides in Vietnam was responsible for any deleterious health outcomes among war veterans or civilian populations. The committee also noted that when defoliant operations were initiated in Vietnam, it was not widely known22 that the 2,4,5-T stores were contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Records were reviewed from three Saigon hospitals, but no convincing association between birth defects and herbicidal exposure was found.23 The committee, in conclusion, suggested that Congress fund further evaluation of potential adverse ecological and physiological outcomes associated with defoliant operations in Vietnam. Early Studies of Vietnam Veterans’ Health In 1979, Pub. L. 96-151 was endorsed by President Carter and required the Veterans Administration—known today as the Department of Veterans Affairs—to conduct studies of adverse health outcomes among Vietnam veterans exposed to TCDD-containing herbicides (Young and Reggiani, 1988). In the same year, the Agent Orange Working Group (AOWG) was established. The AOWG comprised several governmental entities under the executive branch with a vested interest in the health effects associated with exposure to Agent Orange. In 1980, the congressional Office of Technology Assessment (OTA) became an active member of the AOWG, and in 1981 President Reagan incorporated the AOWG into the Cabinet Council on Human Resources, greatly increasing the influence of the AOWG (Young and Reggiani, 1988). By congressional mandate, the VA was required to produce a study protocol within 180 days of the passage of Pub. L. 96-151. The VA failed to meet this deadline, and the protocol that finally made its way to the OTA was declared inadequate. It was not until 1982 that the VA submitted a protocol for review that was approved by the OTA. However, by that time, the AOWG’s priorities had shifted to the study of the Vietnam experience; i.e., in the health status of Vietnam veterans vs. non-Vietnam veterans. This resulted in pressure on the VA to shift from a study of the health effects of Agent Orange to a study of the Vietnam experience. Ultimately, Congress decided to transfer the responsibility for the execution of such studies from the VA to the 22   German researchers Georg Sorge and Karl Schulz had, in the 1950s, isolated TCDD from 2,4,5-T samples and in 1957 published three papers in scientific journals (in German) relating the occurrence of chloracne with TCDD exposure in occupational settings (Butler, 2005). 23   The committee did cite in their report the existence of a series of unconfirmed reports of respiratory illness among Montagnard (inhabitants of the highland regions of southern Vietnam) children that warranted further investigation (NAS, 1974).

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Disposition of the Air Force Health Study Centers for Disease Control (CDC)—known today as the Centers for Disease Control and Prevention. The CDC, instead of choosing between a study of Agent Orange or the Vietnam experience, decided to conduct both studies (Young and Reggiani, 1988). The Vietnam Experience Study was eventually conducted, but researchers ran into difficulties trying to carry out the Agent Orange Study. In short, the CDC had formulated an exposure index based on the assumptions that all members of a battalion were located at the centroid of the reported locations of their component units and that the entire battalion was considered to be exposed if that “average” location was within 2 kilometers of an active spray tract (OTA, 1983). The OTA rejected the CDC’s proposed exposure model, noting that as the model was designed, it was an inadequate representation of actual troop locations, and as such, could not establish the magnitude of exposure at even the battalion level.24 A year later the CDC developed an assay (Patterson et al., 1987) for measuring serum 2,3,7,8-TCDD levels—hereafter referred to as simply serum TCDD—which presumably could serve as a biomarker of Agent Orange exposure. With the advent of the serum TCDD assay, the CDC conducted the Agent Orange Validation Study to determine the feasibility of an Agent Orange study using both military records and serum TCDD levels as surrogates of in-theater herbicide exposure (VA, 2003). Serum TCDD levels were measured for 696 ground troops who had served in Vietnam and 97 Vietnam veterans who had not served in the theater of conflict. Mean serum TCDD levels were “nearly identical”25 for both groups. Additionally, serum TCDD measures could not be correlated with exposure indices based on existing military records or self-reports of Agent Orange exposure. The CDC, with the assent of the AOWG and the OTA as well as the Science Panel of the Domestic Policy Council, cancelled the planned Agent Orange Study (VA, 2003).26 By the time the CDC Agent Orange study was cancelled, CDC and AFHS investigators had already begun collaboration on a serum TCDD assay pilot study of Ranch Hand sera (RHAC, 2000). A detailed overview of Vietnam veterans’ studies is provided in Appendix E. 24   The CDC presented as an example a calculated centroid battalion location with an associated range of ~40 kilometers. OTA concluded that it was impossible to know how battalion members were distributed within the circumscribed area and that individuals could have been as far as ~20 kilometers from the centroid (OTA, 1983). 25   Mean serum TCDD levels were approximately 4 ppt for both groups (CDC, 1988). 26   A proposed UCLA Agent Orange study was also cancelled as its protocol was deemed inadequate by President Reagan’s AOWG (Cecil, 1986).

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Disposition of the Air Force Health Study the Cycle 6 physical examinations, questionnaires, and participants’ database, of which ~$16.0 million was in the two years where examinations were being conducted (DTIC, 2003, 2004, 2005). Processing and documentation of the database has averaged ~$2.8 million per year over the past five years’ budgets. The AFHS FY 2006 budget (DTIC, 2005) includes allocations to perform documentation and organization of the data assets in anticipation of their future disposition: Continue to process and document examination data. Continue archiving previous cycles’ examination data and digitize and archive the Cycle 6 data as received. Conduct medical records coding and verification of examination database and Cycles 1 through 6 coding…. Prepare for and complete transition or turnover of archives and specimens to designated agencies. A total of $1,612,000 is assigned to these and other data analysis and support tasks.74 The documentation and organization activities were apparently planned as a routine part of the study’s shutdown and were not related to the Veterans and Agent Orange–series report recommendations concerning the AFHS discussed in the Chapter 1. In Chapters 3 and 4, the committee offers several recommendations regarding how the data assets should be documented and organized. It believes that these activities may well fall under the existing budget items listed above. Study staffing levels have varied over time; personnel comprised two USAF active duty personnel, 10 federal civil service, and 26 contract employees at the beginning of 2005 (Michalek, 2005). There have also been additional outside personnel associated with analysis and data gathering contracts. COMPENSATION AND BENEFITS FOR VIETNAM VETERANS The Department of Veterans Affairs and Public Law 102-4 When illness or injury is related to military service, the VA provides medical care, vocational rehabilitation, and a range of other federal benefits as appropriate to those veterans (or their dependents) whose cases have been declared service connected (Brown, 2005). For injuries and acute diseases with clearly defined causes or exposures, proof of service connection is relatively straight forward, and if a veteran can provide the VA disability rating specialist with the necessary supporting documentation, then benefits are awarded according to the degree of the severity of the disease or injury. The disability rating scheme is based on a graduated scale ranging from 10 to 100 percent. Compensation grants related to 74   The other tasks specified in the line item were: support of the annual mortality analysis, conduct of data analysis for journals and reports to Congress, and continued maintenance of study’s local area network. An additional $1,677,000 was allocated for data analysis under a separate line item.

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Disposition of the Air Force Health Study environmental or occupational exposures such as Agent Orange represent some of the most difficult disability cases to adjudicate (Brown, 2005). Proof of service connection is far more difficult to establish for longer-latency chronic diseases for which a substantial lapse of time since exposure has occurred. To establish direct service connection the onus is on the veteran to meet minimum VA evidentiary criteria: “evidence of a scientific association,” “evidence of military exposure,” “evidence of exposure magnitude,” and “evidence of temporal plausibility” (Brown, 2005). Claims are decided on an individual basis, and if the evidence indicates that “a veteran’s illness or injury is at least as likely as not to have been caused by the environmental or occupational exposure” (Brown, 2005), then the claim is settled in favor of the veteran or his or her dependents. Excepting the evidentiary requirements listed above, the VA can grant benefits based on what is known as a presumptive service connection (Brown, 2005). A condition presumed to be connected to military service generally needs to manifest within a prescribed postservice time frame and must result in at least 10 percent disability. Presumptive connection relieves the veteran of the task of meeting the burden of proof75 of service connection. Agent Orange claims proved to be problematic for the VA and veterans seeking compensation, as the nature of exposure at the individual level was largely unknown and the toxicokinetics (relationship between dose and transport to site of toxic activity) and toxicodynamics (mechanisms of toxicants at the site of toxic activity and the downstream functional consequences) of 2,4-D and 2,4,5-T as well as that of TCDD have yet to be fully elucidated (Bier, 2003; Brown, 2005). To expedite the compensation awards process in the case of Agent Orange-related claims, in 1991 Congress placed provisions into Pub. L. 102-4, The Agent Orange Act of 1991. Pub. L. 102-4 required the VA to contract with the NAS to independently review all available scientific data pertaining to the health effects of herbicides used during the Vietnam War (not limited to Agent Orange) and dioxin exposure.76 Although respective NAS committees evaluate the strength of the evidence between specific outcomes and herbicide/dioxin exposure, it is the VA that has the ultimate authority regarding compensation policy and dispensation of awards. The VA is not limited to the input of the NAS, and has its own panel of experts that recommends actions to the Secretary of Veterans Affairs regarding the establishment of presumptive service connection for a particular health outcome. NAS reports consti- 75   When many veterans separate from service they often retain only the minimum documentation of their service experience—their ETS (end of term of service) orders and their DD214/DD13. They may not possess a complete copy of their medical record. Recovering these documents and reconstructing service experience years and even decades after separation from service can be an onerous task, and veterans may not have access to germane documentation. 76   Pub. L. 102-4 also called for the IOM to conduct biennial reviews of related material for a follow-up period of 10 years (IOM, 1999). In 2001, Pub. L. 107-103 extended IOM biennial reviews through 2014 (IOM, 2005).

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Disposition of the Air Force Health Study tute an important input to this process, but the VA can and has made decisions on other bases. AFHS Research and the Institute of Medicine’s “Veterans and Agent Orange” Reports In accordance with Pub. L. 102-4, the VA asked the NAS to form a series of committees to “determine (to the extent that available scientific data permit meaningful determinations)” the following regarding associations between specific health outcomes and exposure to TCDD and other chemical compounds in herbicides: whether a statistical association with herbicide exposure exists, taking into account the strength of the scientific evidence and the appropriateness of the statistical and epidemiologic methods used to detect the association; the increased risk of the disease among those exposed to herbicides during service in the Republic of Vietnam during the Vietnam era; and whether there exists a plausible biological mechanism or other evidence of a causal relationship between herbicide exposure and the disease. In fulfillment of its charge, the first committee given this task assembled a list of health outcomes to evaluate based on an exhaustive literature survey that included more than 6,000 abstracts and articles, 230 of which were epidemiologic investigations. Fourteen of the 230 studies were related to the Air Force Health Study. Thirty-two outcomes or categories of outcomes were identified. Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (VAO) (IOM, 1994), was the first comprehensive evaluation published under the congressional mandate. Determinations of health risks related to veterans were based on the appropriateness and strength of statistical association reported in the scientific literature as well as biologic plausibility and mechanistic evidence of or inference to causality77 (IOM, 1994). The strength of the scientific evidence is characterized by a qualitative scale based on criteria first established by the International Agency for Research on Cancer (IARC, 1977): sufficient evidence of an association, limited or suggestive evidence of an association, 77   While evidence of causality is considered, diseases are classified on the basis of “statistical association, not on causality” (IOM, 1994).

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Disposition of the Air Force Health Study inadequate or insufficient evidence to determine whether an association exists, and limited or suggestive evidence of no association.78 AFHS mortality and morbidity results were reviewed in great detail with respect to all major disease categories and contributed with varying degrees of influence to the overall knowledge foundation on which the original report of the Veterans and Agent Orange (VAO) series was based. A total of 13 reports and papers were cited (IOM, 1994). Application and interpretation of AFHS results by the committee was limited by the statistical methods and results presentation employed by investigators. The committee noted specifically that inclusion of more Cycle 1 data,79 statement of a priori hypotheses, and greater “exploration of an overall effect” would have improved the clarity and generalizability of AFHS outcomes (IOM, 1994). Two then-new AFHS publications (AFHS, 1995; Wolfe et al., 1995a) were reviewed in VAO Update 1996 (IOM, 1996). The AFHS 1995 mortality update was one of three studies of “high quality” that led to the addition of spina bifida to the disease category of limited or suggestive evidence of an association. The previously reviewed (IOM, 1994) AFHS 1990 report of increased risk of nonmelanomic skin cancer among Ranch Hand subjects contributed to the category change of skin cancer from limited or suggestive evidence of no association to inadequate or insufficient evidence to determine whether an association exists. In VAO Update 1998 (IOM, 1999), urinary bladder cancer was upgraded from a condition for which there was limited or suggestive evidence of no association to an outcome for which there was inadequate or insufficient evidence to determine whether an association exists. AFHS findings did not contribute to this change. 78   Sufficient evidence of an association is declared when “a positive association has been observed between herbicides and the outcome in studies in which chance, bias, and confounding could be ruled out with reasonable confidence.” Limited or suggestive evidence of an association refers to conditions for which “evidence is suggestive of an association between herbicides and the outcome but is limited because chance, bias, and confounding could not be ruled out with confidence.” Inadequate or insufficient evidence to determine whether an association exists is the determination made when “the available studies are of insufficient quality, consistency, or statistical power to permit a conclusion regarding the presence or absence of an association.” Limited or suggestive evidence of no association describes outcomes for which “several adequate studies, covering the full range of levels of exposure that human beings are known to encounter, are mutually consistent in not showing a positive association between exposure to herbicides and the outcome at any level of exposure” (IOM, 1994). 79   The committee concluded that—using Models 1 and 2—the “most relevant baseline data” had been excluded from most analyses of the reproductive data and that the committee’s critique of methods used in reproductive analyses could be generally applied to the AFHS (IOM, 1994).

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Disposition of the Air Force Health Study In 1999, the VA commissioned an evaluation of type 2 diabetes risk by the IOM independent of the biennial VAO updates. The IOM released Veterans and Agent Orange: Herbicide/Dioxin Exposure and Type 2 Diabetes in 2000. The results of the AFHS Cycle 5 morbidity analyses (AFHS, 2000) related to diabetes and the contents of a paper on the cohort (Longnecker and Michalek, 2000) were reviewed in great detail. Endpoints measured included type 2 diabetes incidence, time to disease onset, severity of disease, and a battery of related laboratory tests. These metrics were analyzed using four different exposure models that were run adjusted and unadjusted for the age, race, military occupation, personality type, body fat, and family history (IOM, 2000). Further analyses carried out at the request of the IOM committee served to strengthen the importance of AFHS results (Personal communication, J.E. Michalek, Air Force Health Study, July 28, 2000). These indicated an increased prevalence of and a decreased time to onset of type 2 diabetes was associated with dioxin exposure among Ranch Hand subjects. Previously VAO-reviewed AFHS material (Henriksen et al., 1997) was also considered in the committee’s conclusion that there was limited or suggestive evidence of an association between herbicide or dioxin exposure and type 2 diabetes (IOM, 2000). Two AFHS papers were cited in the report’s discussion of the biologic plausibility of an association between diabetes and dioxin exposure: Michalek and Tripathi (1999), reporting a compensatory metabolic relation between dioxin and insulin regulation in study participants; and Longnecker and Michalek (2000), finding an apparent association between serum dioxin levels and fasting glucose levels among nondiabetic AFHS comparison group members with less than 10 ppt serum dioxin. Nine then-new AFHS reports and papers (including those addressed in the type 2 diabetes report) were reviewed in Veterans and Agent Orange: Update 2000 (IOM, 2001). Other than the type 2 diabetes decision, there were no changes to the categorizations of health outcomes from the previous update as the new literature supported existing conclusions. No new major AFHS reports had been released at the time the next two update reports were published.80 However, a number of journal articles related to AFHS (Barrett et al., 2001; Michalek et al., 2001a,b,c; Steenland et al., 2001) were reviewed in both VAO Update 2002 (IOM, 2003a) and VAO Update 2004 (IOM, 2005; Akhtar et al., 2004; Barrett et al., 2003; Michalek et al., 2003; Pavuk et al., 2003). No changes were made in the strength of evidence categories by either of the IOM committees because, again, new evidence supported existing conclusions.81 A table adapted from VAO Update 2004 (IOM, 2005) is included as Appendix C. It provides, as part of a comprehensive list of the Vietnam veterans’ 80   The Cycle 6 follow-up examination results were not released until July of 2005. 81   A new health outcome—chronic lymphocytic leukemia—was added in 2002 (IOM, 2003a).

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Disposition of the Air Force Health Study health outcomes literature, summary information on AFHS publications and indicates in which volume of the VAO report series a review may be found. The table includes information on the type of study, a summary description of the topics addressed, and the size of the study population. Additional information on, and reviews of, the AFHS reports and papers may be found in the text of the Veterans and Agent Orange reports referenced in the Appendix. In the period since the Agent Orange Act of 1991 was passed, the AFHS has contributed to the establishment of a presumptive service connection82 for type 2 diabetes in Vietnam veterans and for spina bifida in their offspring. As of September 2004, 191,649 Vietnam-era veterans were receiving compensation for diabetes mellitus (VA, 2005), and 1,187 children of Vietnam veterans were receiving compensation for spina bifida as of September 2005, the majority of which are presumptively connected to Vietnam service (G. Peters, Veterans Benefits Administration, personal communication, September 2, 2005). The Veterans Benefits Administration of the VA does not have complete documentation on the number of Vietnam veterans who have received compensation for conditions recognized as service connected due to their association with herbicide or dioxin exposure. REFERENCES AFHS (Air Force Health Study). 1982. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Study Protocol, Initial Report. Brooks AFB, TX: USAF School of Aerospace Medicine. SAM-TR-82-44. AFHS. 1983. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Baseline Mortality Study Results. Brooks AFB, TX: USAF School of Aerospace Medicine. NTIS AD-A130 793. AFHS. 1984a. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Baseline Morbidity Study Results. Brooks AFB, TX: USAF School of Aerospace Medicine. NTIS AD-A-138-340. AFHS. 1984b. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Mortality Update: 1984. Brooks AFB, TX: USAF School of Aerospace Medicine. NTIS-AD-A-162-687. AFHS. 1985. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Mortality Update: 1985. Brooks AFB, TX: USAF School of Aerospace Medicine. NTIS-AD-A-163-237. 82   As of March 3, 2005, the VA recognized the following diseases as presumptively connected to Vietnam service: chloracne, Hodgkin’s disease, multiple myeloma, non-Hodgkin’s lymphoma, porphyria cutanea tarda, respiratory cancers (lung, bronchus, larynx, and trachea), soft-tissue sarcoma, acute and subacute peripheral neuropathy, prostate cancer, and spina bifida in offspring of veterans (VA, 2003).

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Disposition of the Air Force Health Study AFHS. 1986. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Mortality Update: 1986. Brooks AFB, TX: USAF School of Aerospace Medicine. USAFSAM-TR-86-43. AFHS. 1987. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. First Follow-up Examination Results. 2 vols. Brooks AFB, TX: USAF School of Aerospace Medicine. USAFSAM-TR-87-27. AFHS. 1989. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Mortality Update: 1989. Brooks AFB, TX: USAF School of Aerospace Medicine. USAFSAM-TR-89-9. AFHS. 1990. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. 2 vols. Brooks AFB, TX: USAF School of Aerospace Medicine. USAFSAM-TR-90-2. AFHS. 1991a. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Mortality Update: 1992. Brooks AFB, TX: Armstrong Laboratory. AL-TR-1991-0132. AFHS. 1991b. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Serum Dioxin Analysis of 1987 Examination Results. 9 vols. Brooks, AFB, TX: USAF School of Aerospace Medicine. AL-TR-91-0009. AFHS. 1992. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Reproductive Outcomes. Brooks AFB, TX: Armstrong Laboratory. AL-TR-1992-0090. AFHS. 1993. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Mortality Update: 1993. Brooks AFB, TX: Armstrong Laboratory. AL/ AO-TR-1993-0161. AFHS. 1994. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Mortality Update: 1994. Brooks AFB, TX: Armstrong Laboratory. AL/ AO-TR-1994-0128. AFHS. 1995. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. 1992 Followup Examination Results. Brooks AFB, TX: Epidemiologic Research Division. Armstrong Laboratory. AL-TR-920107. AFHS. 1996. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Mortality Update 1996. Brooks AFB, TX: Epidemiologic Research Division. Armstrong Laboratory. AL/AO-TR-1996-0068. AFHS. 1998. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Reproductive Outcome Update. Brooks AFB, TX: Epidemiologic Research Division. Armstrong Laboratory. AFRL-HE-BR-TR-1998-0073. AFHS. 2000. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. 1997 Follow-up Examination Results. Brooks AFB, TX: Human Systems Program Office. Armstrong Laboratory. AFRL-HE-BR-TR-2000-02. AFHS. 2005. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. 2002 Followup Examination Results. Brooks AFB, TX: Epidemiologic Research Division. Armstrong Laboratory. AFRL-HE-BR-SR-2005-0003. Akhtar FZ, Garabrant DH, Ketchum NS, Michalek JE. 2004. Cancer in US Air Force veterans of the Vietnam War. Journal of Occupational and Environmental Medicine 46(2):123–136. Alcott EB. 1995. A History of the Ranch Hand Epidemiologic Investigation. Brooks AFB, TX: Office of History, Human Systems Center. Barrett DH, Morris RD, Akhtar FZ, Michalek JE. 2001. Serum dioxin and cognitive functioning among veterans of Operation Ranch Hand. Neurotoxicology 22:491–502. Barrett DH, Morris RD, Jackson WG Jr, Michalek JE. 2003. Serum dioxin and psychological functioning in US Air Force veterans of the Vietnam War. Military Medicine 168(2):153–159.

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Disposition of the Air Force Health Study Bier D. 2003. Amino acid pharmacokinetics and safety assessment. Journal of Nutrition 133(6 Suppl. 1):2034S–2039S. Boyne WJ. 2000. Ranch Hand: Even then, the defoliation missions over Vietnam were controversial. Air Force Magazine 83(8):84–89. [Online]. Available: http://www.afa.org/magazine/Aug2000/ 0800ranch.asp [accessed April 7, 2005]. Brown M. 2005. The role of science in the Department of Veterans Affairs disability compensation policies for environmental and occupational illnesses and injuries. Journal of Law and Policy 13(2):593–612. Buckingham WA. 1982. Operation Ranch Hand: The Air Force and Herbicides in Southeast Asia, 1961–1971. Washington, DC: Office of Air Force History. Buckingham WA. 1997. Operation Ranch Hand: Herbicides in Southeast Asia, 1961–1971. [Online]. Available: http://www.cpcug.org/user/billb/ranchhand/ranchhand.html [accessed May 12, 2005]. Bullman TA, Watanabe KK, Kang HK. 1994. Risk of testicular cancer associated with surrogate measures of Agent Orange exposure among Vietnam veterans on the Agent Orange Registry. Annals of Epidemiology 4:11–16. Butler DA. 2005. Connections: the early history of scientific and medical research on “Agent Orange.” Journal of Law and Policy 13(2):527–552. CDC (The Centers for Disease Control Veterans Health Studies). 1988. Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels in US Army Vietnam-era veterans. Journal of the American Medical Association 260:1249–1254. Cecil PF. 1986. Herbicidal Warfare: The Ranch Hand Project in Vietnam. New York: Praeger. Cook RR, Townsend JC, Ott MG, Silverstein LG. 1980. Mortality experience of employees exposed to 2,3,7,8-teterachlorodibenzo-p-dioxin (TCDD). Journal of Occupational Medicine 22:530–532. de Sola D. 2004. Vietnamese sue over Agent Orange (CNN Law Center). [Online]. Available: http://www.cnn.com/2004/LAW/08/15/agent.orange.suit/index.html [accessed October 10, 2005]. DTIC (Defense Technical Information Center). February 1999. RDT&E Budget Item Justification Sheet, Ranch Hand II Epidemiology Study, PE number: 0605306F. [Online]. Available: http://www.dtic.mil/descriptivesum/Y2000/AirForce/0605306f.pdf [accessed August 31, 2005]. DTIC. February 2000. RDT&E Budget Item Justification Sheet, Ranch Hand II Epidemiology Study, PE number: 0605306F. [Online]. Available: http://www.dtic.mil/descriptivesum/Y2001/AirForce/0605306f.pdf [accessed August 31, 2005]. DTIC. June 2001. RDT&E Budget Item Justification Sheet, Ranch Hand II Epidemiology Study, PE number: 0605306F. [Online]. Available: http://www.dtic.mil/descriptivesum/Y2002/AirForce/0605306f.pdf [accessed August 31, 2005]. DTIC. February 2002. RDT&E Budget Item Justification Sheet, Ranch Hand II Epidemiology Study, PE number: 0605306F. [Online]. Available: http://www.dtic.mil/descriptivesum/Y2003/AirForce/0605306f.pdf [accessed August 31, 2005]. DTIC. February 2003. RDT&E Budget Item Justification Sheet, Ranch Hand II Epidemiology Study, PE number: 0605306F. [Online]. Available: http://www.dtic.mil/descriptivesum/Y2004/AirForce/0605306f.pdf [accessed August 31, 2005]. DTIC. February 2004. RDT&E Budget Item Justification Sheet, Ranch Hand II Epidemiology Study, PE number: 0605306F. [Online]. Available: http://www.dtic.mil/descriptivesum/Y2005/AirForce/0605306f.pdf [accessed August 31, 2005]. DTIC. February 2005. RDT&E Budget Item Justification Sheet, Ranch Hand II Epidemiology Study, PE number: 0605306F. [Online]. Available: //www.dtic.mil/descriptivesum/Y2006/AirForce/0605306f.pdf [accessed August 31, 2005]. 500 vets claim herbicide effects. 1978, October 12. The Washington Post. [Online]. Available: http://pqasb.pqarchiver.com/washingtonpost_historical/results.html?st=basic&uid=&MAC=50a23aa1f3f5c6104e90e36051420d61&QryTxt=500+vets+claim+herbicide+effects&sortby=REVERSE_CHRON&restrict=articles [accessed February 7, 2005].

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