Wartime toxin exposure: recognising the silent killer.

Wartime toxin exposures have been implicated in the genesis of malignancy in war veterans. Agent Orange, one toxin among many, has been linked to malignancy and the subcomponent phenoxyacetic acid has been associated with soft tissue sarcomas (STSs). This case demonstrates the association between a wartime toxin exposure (Agent Orange) and subsequent cancer development. Ultimately, we aim to highlight the importance of simple, specific questions in the patient history to account for previous wartime toxin exposures.

Toxic Epidemics: Agent Orange Sickness in Vietnam and the United States.

Social scientists studying toxic epidemics have often endeavored to shed light on the differences between scientists' and nonscientists' epistemic perspectives. Yet, little attention has been paid to the processes through which a toxic epidemic emerges as a phenomenon. A Luoi Valley of Central Vietnam was extensively sprayed with chemical defoliants (including Agent Orange) during the Vietnam War. The latent toxic effects of these chemicals, however, went largely unnoticed until the late 1990s. By juxtaposing the history through which the notion of "Agent Orange Sickness" emerged in the United States with an ethnographic study of A Luoi, I explore the notion of poison under which Agent Orange became recognizable as a poison.

Agent Orange exposure and disease prevalence in Korean Vietnam veterans: the Korean veterans health study.

Between 1961 and 1971, military herbicides were used by the United States and allied forces for military purposes. Agent Orange, the most-used herbicide, was a mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid, and contained an impurity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Many Korean Vietnam veterans were exposed to Agent Orange during the Vietnam War. The aim of this study was to evaluate the association between Agent Orange exposure and the prevalence of diseases of the endocrine, nervous, circulatory, respiratory, and digestive systems. The Agent Orange exposure was assessed by a geographic information system-based model. A total of 111,726 Korean Vietnam veterans were analyzed for prevalence using the Korea National Health Insurance claims data from January 2000 to September 2005. After adjusting for covariates, the high exposure group had modestly elevated odds ratios (ORs) for endocrine diseases combined and neurologic diseases combined. The adjusted ORs were significantly higher in the high exposure group than in the low exposure group for hypothyroidism (OR=1.13), autoimmune thyroiditis (OR=1.93), diabetes mellitus (OR=1.04), other endocrine gland disorders including pituitary gland disorders (OR=1.43), amyloidosis (OR=3.02), systemic atrophies affecting the nervous system including spinal muscular atrophy (OR=1.27), Alzheimer disease (OR=1.64), peripheral polyneuropathies (OR=1.09), angina pectoris (OR=1.04), stroke (OR=1.09), chronic obstructive pulmonary diseases (COPD) including chronic bronchitis (OR=1.05) and bronchiectasis (OR=1.16), asthma (OR=1.04), peptic ulcer (OR=1.03), and liver cirrhosis (OR=1.08). In conclusion, Agent Orange exposure increased the prevalence of endocrine disorders, especially in the thyroid and pituitary gland; various neurologic diseases; COPD; and liver cirrhosis. Overall, this study suggests that Agent Orange/2,4-D/TCDD exposure several decades earlier may increase morbidity from various diseases, some of which have rarely been explored in previous epidemiologic studies.

Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans.

OBJECTIVES: The aim of this study was to evaluate the association between Agent Orange exposure and self-reported diseases in Korean Vietnam veterans. METHODS: A postal survey of 114 562 Vietnam veterans was conducted. The perceived exposure to Agent Orange was assessed by a 6-item questionnaire. Two proximity-based Agent Orange exposure indices were constructed using division/brigade-level and battalion/company-level unit information. Adjusted odds ratios (ORs) for age and other confounders were calculated using a logistic regression model. RESULTS: The prevalence of all self-reported diseases showed monotonically increasing trends as the levels of perceived self-reported exposure increased. The ORs for colon cancer (OR, 1.13), leukemia (OR, 1.56), hypertension (OR, 1.03), peripheral vasculopathy (OR, 1.07), enterocolitis (OR, 1.07), peripheral neuropathy (OR, 1.07), multiple nerve palsy (OR, 1.14), multiple sclerosis (OR, 1.24), skin diseases (OR, 1.05), psychotic diseases (OR, 1.07) and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the division/brigade-level proximity-based exposure analysis, compared to the low exposure group. The ORs for cerebral infarction (OR, 1.08), chronic bronchitis (OR, 1.05), multiple nerve palsy (OR, 1.07), multiple sclerosis (OR, 1.16), skin diseases (OR, 1.05), and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the battalion/company-level analysis. CONCLUSIONS: Korean Vietnam veterans with high exposure to Agent Orange experienced a higher prevalence of several self-reported chronic diseases compared to those with low exposure by proximity-based exposure assessment. The strong positive associations between perceived self-reported exposure and all self-reported diseases should be evaluated with discretion because the likelihood of reporting diseases was directly related to the perceived intensity of Agent Orange exposure.

Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels and their association with age, body mass index, smoking, military record-based variables, and estimated exposure to Agent Orange in Korean Vietnam veterans.

OBJECTIVES: The aim of this study was to examine the levels of serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and evaluate their association with age, body mass index, smoking, military record-based variables, and estimated exposure to Agent Orange in Korean Vietnam veterans. METHODS: Serum levels of TCDD were analyzed in 102 Vietnam veterans. Information on age, body mass index, and smoking status were obtained from a self-reported questionnaire. The perceived exposure was assessed by a 6-item questionnaire. Two proximity-based exposures were constructed by division/brigade level and battalion/company level unit information using the Stellman exposure opportunity index model. RESULTS: The mean and median of serum TCDD levels was 1.2 parts per trillion (ppt) and 0.9 ppt, respectively. Only 2 Vietnam veterans had elevated levels of TCDD (>10 ppt). The levels of TCDD did not tend to increase with the likelihood of exposure to Agent Orange, as estimated from either proximity-based exposure or perceived self-reported exposure. The serum TCDD levels were not significantly different according to military unit, year of first deployment, duration of deployment, military rank, age, body mass index, and smoking status. CONCLUSIONS: The average serum TCDD levels in the Korean Vietnam veterans were lower than those reported for other occupationally or environmentally exposed groups and US Vietnam veterans, and their use as an objective marker of Agent Orange exposure may have some limitations. The unit of deployment, duration of deployment, year of first deployment, military rank, perceived self-reported exposure, and proximity-based exposure to Agent Orange were not associated with TCDD levels in Korean Vietnam veterans. Age, body mass index and smoking also were not associated with TCDD levels.

Agent Orange Exposure and Prevalence of Self-reported Diseases in Korean Vietnam Veterans / 예방의학회지

OBJECTIVES: The aim of this study was to evaluate the association between Agent Orange exposure and self-reported diseases in Korean Vietnam veterans. METHODS: A postal survey of 114 562 Vietnam veterans was conducted. The perceived exposure to Agent Orange was assessed by a 6-item questionnaire. Two proximity-based Agent Orange exposure indices were constructed using division/brigade-level and battalion/company-level unit information. Adjusted odds ratios (ORs) for age and other confounders were calculated using a logistic regression model. RESULTS: The prevalence of all self-reported diseases showed monotonically increasing trends as the levels of perceived self-reported exposure increased. The ORs for colon cancer (OR, 1.13), leukemia (OR, 1.56), hypertension (OR, 1.03), peripheral vasculopathy (OR, 1.07), enterocolitis (OR, 1.07), peripheral neuropathy (OR, 1.07), multiple nerve palsy (OR, 1.14), multiple sclerosis (OR, 1.24), skin diseases (OR, 1.05), psychotic diseases (OR, 1.07) and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the division/brigade-level proximity-based exposure analysis, compared to the low exposure group. The ORs for cerebral infarction (OR, 1.08), chronic bronchitis (OR, 1.05), multiple nerve palsy (OR, 1.07), multiple sclerosis (OR, 1.16), skin diseases (OR, 1.05), and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the battalion/company-level analysis. CONCLUSIONS: Korean Vietnam veterans with high exposure to Agent Orange experienced a higher prevalence of several self-reported chronic diseases compared to those with low exposure by proximity-based exposure assessment. The strong positive associations between perceived self-reported exposure and all self-reported diseases should be evaluated with discretion because the likelihood of reporting diseases was directly related to the perceived intensity of Agent Orange exposure.

Serum 2,3,7,8-Tetrachlorodibenzo-p-dioxin Levels and Their Association With Age, Body Mass Index, Smoking, Military Record-based Variables, and Estimated Exposure to Agent Orange in Korean Vietnam Veterans / 예방의학회지

OBJECTIVES: The aim of this study was to examine the levels of serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and evaluate their association with age, body mass index, smoking, military record-based variables, and estimated exposure to Agent Orange in Korean Vietnam veterans. METHODS: Serum levels of TCDD were analyzed in 102 Vietnam veterans. Information on age, body mass index, and smoking status were obtained from a self-reported questionnaire. The perceived exposure was assessed by a 6-item questionnaire. Two proximity-based exposures were constructed by division/brigade level and battalion/company level unit information using the Stellman exposure opportunity index model. RESULTS: The mean and median of serum TCDD levels was 1.2 parts per trillion (ppt) and 0.9 ppt, respectively. Only 2 Vietnam veterans had elevated levels of TCDD (>10 ppt). The levels of TCDD did not tend to increase with the likelihood of exposure to Agent Orange, as estimated from either proximity-based exposure or perceived self-reported exposure. The serum TCDD levels were not significantly different according to military unit, year of first deployment, duration of deployment, military rank, age, body mass index, and smoking status. CONCLUSIONS: The average serum TCDD levels in the Korean Vietnam veterans were lower than those reported for other occupationally or environmentally exposed groups and US Vietnam veterans, and their use as an objective marker of Agent Orange exposure may have some limitations. The unit of deployment, duration of deployment, year of first deployment, military rank, perceived self-reported exposure, and proximity-based exposure to Agent Orange were not associated with TCDD levels in Korean Vietnam veterans. Age, body mass index and smoking also were not associated with TCDD levels.

[Associations of exposure to dioxins and polychlorinated biphenyls with diabetes: based on epidemiological findings].

Persistent organic pollutants (POPs) are a group of chemical substances that have the common properties of resistance to biodegradation, wide-range transportation, high lipophilicity, bioaccumulation in fat, and biomagnification in the food chain. POPs are persistent in the environment worldwide and have potential adverse impacts on human health and the environment. Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are well known chemicals that are considered as POPs. The association between high-level exposure to dioxins and type 2 diabetes among U.S. Air Force veterans who had been exposed to Agent Orange contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during the Vietnam War was reported in the late 1990s. This association has been supported by similar epidemiologic studies, whose subjects were exposed to high doses of dioxins in their places of work involving phenoxyacid herbicide production and spraying, and in the industrial accident in Seveso, Italy. Recently, low-level exposure to dioxins and PCBs has been reported to be linked to type 2 diabetes. Cross-sectional studies in the U.S. general population and Japanese general population showed that body burden levels of some dioxins and PCBs were strongly associated with the prevalence of type 2 diabetes. Very recently, following these cross-sectional studies, several prospective studies have suggested that low-level exposure to some PCBs predicted the future risk of type 2 diabetes in the general population. Environmental exposure to some dioxins and PCBs, which mainly accumulate in adipose tissue, may play a role in the development of type 2 diabetes.

Assessing possible exposures of ground troops to Agent Orange during the Vietnam War: the use of contemporary military records.

BACKGROUND: Potential exposure of ground troops in Vietnam to Agent Orange and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) remains controversial despite the passage of 30 years since the Vietnam War. Because of uncertainty over the serum dioxin levels in ground troops at the end of their service in Vietnam, attempts have been made to develop a methodology for characterizing exposure of ground troops in Vietnam to Agent Orange and other herbicides based upon historical reconstruction from military records. Historical information is often useful in evaluating and modeling exposure, but such information should be reasonably accurate, complete, and reliable. METHODS: This paper reviews the procedures and supporting historical information related to the spraying of herbicides in Vietnam. The historical information is classified into two categories: procedural information and operational information. Procedural information covered the process and procedures followed in spraying herbicides from US Air Force fixed wing aircraft (Operation RANCH HAND) in Vietnam, and included approval procedures for spray missions, the criteria required to conduct a mission, the control exercised by the Forward Air Controller and the Tactical Air Control Center and the characteristics of the equipment used to apply the herbicides. Operational information includes data from the RANCH HAND Daily Air Activities Reports, which included geographic locations of specific spray missions, the amount of herbicide sprayed by a specific mission, reports of battle damage to spray aircraft, reports of fighter aircraft support for aerial spray missions, and any comments, such as reasons for canceling a mission. RESULTS: Historical information demonstrates that herbicide spray missions were carefully planned and that spraying only occurred when friendly forces were not located in the target area. RANCH HAND spray missions were either not approved or cancelled if approved when there were friendly forces in the area designated for spraying. Stringent criteria had to be met before spray missions could be approved. The operational information shows that spray missions for both defoliation and crop destruction were conducted in an extremely hostile environment. Heavy 'fighter suppression' with antipersonnel ordnance was used to minimize the impact of hostile ground fire on RANCH HAND aircraft. Procedures were in place that prohibited movement of troops into sprayed areas immediately after a mission due to the possible presence of unexploded ordnance delivered by fighter aircraft supporting RANCH HAND missions. The optimal nature of the spray equipment and application procedures minimized the possibility of significant spray drift. Conclusions. Few friendly troops were sprayed by fixed wing aircraft during Operation RANCH HAND, which delivered 95% of all defoliants used in Vietnam. Similarly, few troops were sprayed during helicopter or surface-based spray operations, which constituted the remaining 5% of defoliants. Detailed policies and procedures for approval and execution of spray missions ensured that friendly forces were not located in the areas targeted for spraying. Fighter aircraft assigned to accompany each spray mission frequently suppressed much of the hostile fire with bombs and other ordnance. Confirmed clearance of the target area was necessary to avoid friendly casualties. Historical records establish that these policies and procedures were strictly followed. Exposure of troops whether from direct spraying or movement through areas recently sprayed was very unlikely. The wartime military records of troop positions and herbicide operations are valuable for some purposes, but have specific limitations in exposure reconstruction. The completeness and accuracy of the geographic data (maps used by RANCH HAND and military ground units) were dependent upon the inherent precision of the map, the accuracy with which it depicted surface features, and the completeness and accuracy of the information on which it is based. Navigation by the crew using visual orientation and reference to the map was the only means that aircrew on spray missions had for establishing their locations. A Forward Air Controller independent of Operation RANCH HAND was present at the location of each spray target immediately before and during spraying operations to verify the target location and ensure that friendly forces were clear of the target area. Anecdotal reports of direct spraying of troops in Vietnam likely reflect the RANCH HAND missions spraying insecticide for mosquito control at regular intervals from March 1967 through February 1972. Outlook. The distribution and levels of serum dioxin in RANCH HAND veterans and the US Army Chemical Corps Vietnam veterans (the unit responsible for helicopter and ground-based spray operations) are distinguishable from typical levels in the population decades after the Vietnam conflict. An exposure model similar to that proposed in the 2003 report of the Institute of Medicine's Committee on 'Characterizing Exposure of Veterans to Agent Orange and Other Herbicides Used in Vietnam' was tested in 1988 by the Centers for Disease Control and Prevention and found to be a poor predictor of absorbed dose of TCDD. Military records during the Vietnam War lack the precision to determine that troops were directly sprayed with herbicides during Operation RANCH HAND, especially given the procedures in place to ensure clearance of friendly forces from the target area and the lack of elevated serum levels of TCDD in ground troops judged to have operated in heavily sprayed areas.

Poisoning due to chlorophenoxy herbicides.

Chlorophenoxy herbicides are used widely for the control of broad-leaved weeds. They exhibit a variety of mechanisms of toxicity including dose-dependent cell membrane damage, uncoupling of oxidative phosphorylation and disruption of acetylcoenzyme A metabolism. Following ingestion, vomiting, abdominal pain, diarrhoea and, occasionally, gastrointestinal haemorrhage are early effects. Hypotension, which is common, is due predominantly to intravascular volume loss, although vasodilation and direct myocardial toxicity may also contribute. Coma, hypertonia, hyperreflexia, ataxia, nystagmus, miosis, hallucinations, convulsions, fasciculation and paralysis may then ensue. Hypoventilation is commonly secondary to CNS depression, but respiratory muscle weakness is a factor in the development of respiratory failure in some patients. Myopathic symptoms including limb muscle weakness, loss of tendon reflexes, myotonia and increased creatine kinase activity have been observed. Metabolic acidosis, rhabdomyolysis, renal failure, increased aminotransferase activities, pyrexia and hyperventilation have been reported. Substantial dermal exposure to 2,4-dichlorophenoxy acetic acid (2,4-D) has led occasionally to systemic features including mild gastrointestinal irritation and progressive mixed sensorimotor peripheral neuropathy. Mild, transient gastrointestinal and peripheral neuromuscular symptoms have occurred after occupational inhalation exposure. In addition to supportive care, urine alkalinization with high-flow urine output will enhance herbicide elimination and should be considered in all seriously poisoned patients. Haemodialysis produces similar herbicide clearances to urine alkalinization without the need for urine pH manipulation and the administration of substantial amounts of intravenous fluid in an already compromised patient.

Specter orange.

Nearly 30 years after the Vietnam War, a chemical weapon used by U.S. troops is still exacting a hideous toll on each new generation in Vietnam. The dioxin (TCCD) that contaminated the herbicide Agent Orange is one of the most toxic molecules known to science. The contaminant persists in the soil. The United States has done nothing to combat the medical and environmental catastrophe that is overwhelming the country.