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.

[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.

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.

Posttraumatic stress disorder among Vietnam veterans on the Agent Orange Registry. A case-control analysis.

Some of the readjustment problems of Vietnam veterans have been attributed to posttraumatic stress disorder (PTSD). This case-control study compared demographic and military characteristics of 374 Vietnam veterans who had PTSD with 373 healthy Vietnam veterans. Veterans were chosen from the Agent Orange Registry, a Department of Veterans Affairs computerized database of approximately 200,000 Vietnam veterans who volunteered for a physical examination. Case patients and control subjects were frequently-matched by age, year of Registry examination, and race. Crude odds ratios (OR) were used to evaluate the risk of PTSD associated with certain characteristics of Vietnam service, as there was no apparent confounding by other military factors. Being wounded in Vietnam (OR, 2.33; 95% confidence interval (CI), 1.49-3.65) and having a combat job in Vietnam (OR, 1.54; 95% CI, 1.15-2.06) were the only risk factors for PTSD. Those who had noncombat jobs but were wounded had the highest risk of PTSD (OR, 3.56; 95% CI, 1.26-10.06).

Mortality of power workers exposed to phenoxy herbicides and polychlorinated biphenyls in waste transformer oil.

Herbicide spray crews employed by a Canadian power company between 1950 and 1967 had a higher than expected death rate, with a standardized mortality ratio of 157% (CI 130%-194%). In 1991, the cohort consisted of 225 former sprayers of whom 127 were still alive and 98 had died. Eligibility for inclusion in the cohort was based on employer records; and a history of spraying for 30 days or more in at least one spray season. Deaths expected were based on age-specific population mortality rates for New Brunswick. The all-age SMR for the total cohort was 159%. After 1958, however, waste transformer oil was added to the phenoxy-herbicide spray mixture, the oil representing 10% of the final mixture. Spray crews wore no protective clothing. Subdividing the cohort into spray years 1950-1958 and 1959-1967 yielded SMRs of 146% (CI 115%-184%); and 215% (CI 139%-318%), respectively. The transformer oil was used during the period 1959-1967. Most excess deaths were due to cardiovascular disease.

Collective judicial management of mass toxic tort controversies: lessons and issues from the Agent Orange litigation.

Viewing the Agent Orange litigation as a case study, this article explores the feasibility and desirability of strengthening the powers of the courts to manage toxic tort controversies en masse. The Agent Orange lawsuit, brought on behalf of potentially millions of Vietnam War veterans and family members, charged that herbicides used for military purposes during the war caused a wide range of health problems. This article first reviews the current national debate over how mass toxic tort controversies should be handled, including key legislative reform options, and describes how attention is increasingly focused on ways that the court system might better cope with mass toxic torts. The principal events of the Agent Orange litigation are then summarized, by which the litigation was consolidated into a massive class action, the class action was settled, and a streamlined plan for distributing the settlement fund was adopted. The article evaluates the outcome of the litigation, and discusses whether the solution there can and should be broadly applied to other mass toxic tort cases. This question depends, in part, on a series of complex legal and practical issues, but the author suggests that the question will also depend on what institutional role we expect the judiciary to play within society.

Science and persuasion: environmental disease in U.S. courts.

The U.S. system for determining liability for environmental disease requires plaintiffs to demonstrate that the defendant was the legal cause of their illnesses. The determination of cause takes place in an adversary setting. Both sides in the dispute present evidence about causation to a lay judge or jury, who is responsible for deciding whether the defendant is legally responsible. In injury cases this generally means providing evidence of a specific, concrete event or condition that gave rise to the plaintiff's harm. Environmental disease usually presents a very different picture, one in which there is considerable uncertainty about the relationship between exposure to toxic substances and the plaintiff's disease. Scientific evidence about this uncertain link is often an essential part of the case. The reliance on scientific evidence appears to present almost insurmountable problems of proof of causation to the plaintiff. The law requires the plaintiff to demonstrate that, without the defendant's action, the harm would not have occurred. This strict requirement appears incompatible with the substantial scientific uncertainty about the cause of many environmental diseases. A second attribute of legal causation is that it is based on common experience, and is easily understood by lay citizens who are likely to be the final arbiters of causation. Scientific explanations of environmental disease causation, on the other hand, may not draw on common experience and may not have the intuitive appeal necessary to convince a lay decision-maker. Because scientific evidence of causation is difficult for a lay judge or jury to understand, and because of the adversary use of experts with very different opinions about causation, it might be expected that plaintiffs would have a great deal of difficulty demonstrating causation in environmental liability cases. However, the U.S. legal system appears to have accommodated to the plaintiff's difficulty in meeting the formal burden of persuasion. The courts allow juries considerable leeway in using their own experience and beliefs to determine causation, as long as there is some scientific evidence to support the plaintiff's contention. The U.S. environmental disease liability system has been criticized by some for plaintiffs' difficulty in proving causation and by others because plaintiffs can win cases without evidence that would be convincing to a scientist.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Porphyria and chemicals.

Porphyria is a genetic family of diseases that is most frequently described as neuropsychiatric or toxogenetic. It is well known to be initiated by drugs, infections, heavy metals, hormones, chemicals and fasting. There are extensive lists of drugs that have been known to cause attacks. Others are thought to be likely to cause attacks on the basis of animal studies or in vitro studies. It has become obvious that lists of chemicals capable of causing illness in porphyrics are sorely lacking. Chemicals that have the same base as drugs that are labeled in the PDR (Physicians Desk Reference) as porphyrogenic have no such labeling in their MSDS (Material Safety Data Sheet). This article is intended to point out why porphyria needs to be considered when illness occurs after chemical exposure. The capability of testing enzymes in the porphyrin pathway allows us to evaluate these patients more thoroughly, for we are now aware that the standard measures for recognizing these diseases are often inadequate. Three examples where illness has occurred after environmental exposure to chemicals will serve as illustrations. One, a documented porphyria, is the Turkish porphyria. The other two are not yet documented as porphyria, but may be some day. One is Agent Orange which caused illness in Vietnam, and the other is exposure to unknown sources of what has been named the Gulf War syndrome.

Immunotoxicological effects of Agent Orange exposure to the Vietnam War Korean veterans.

Immunomodulatory effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) demonstrated using animals are thymic atrophy, downregulation of cytotoxic T or B lymphocyte differentiation or activation, whereas human immunotoxicities have not been investigated well. This study was undertaken to evaluate overall immunologic spectrum of the Vietnam War Korean veterans exposed to Agent Orange contaminated with TCDD. Quantity of red blood cells, hemoglobin and hematocrit in the veterans suffered from chronic diseases associated with Agent Orange exposure (Veterans-patient group) were decreased in comparison with those of the veterans without the diseases and the age-matched healthy controls, but no differences in leukocyte populations. Plasma IgG levels were lowered in the veterans than the controls, owing to significant decrease in the IgG1 levels. Increase in the IgE levels was observed in the plasma from the veterans. Alteration of T cell-mediated immunity was also resulted from activation of peripheral blood mononuclear cells with polyclonal T cell activators. Production of IFNgamma, a major cytokine mediating host resistance against infection or tumoregenesis, was lowered in the veterans-patient group. However, production of IL-4 and IL-10, representative cytokines involved with hypersensitivity induction, was enhanced in the patient group. Overall, this study suggests that military service in Vietnam and/or Agent Orange exposure disturbs immune-homeostasis resulting in dysregulation of B and T cell activities.

'Proximal-type' epithelioid sarcoma: is Agent Orange still at large?

BACKGROUND AND AIMS: Proximal-type epithelioid sarcomas of the perineum are extremely rare. The authors provide an overview of this condition in relation to the history of exposure to Agent Orange. PATIENT AND METHODS: A 54-year-old man presented with a rapidly growing perineal subcutaneous mass that was shown to be a proximal-type epithelioid sarcoma. The case is discussed. An Internet Medline search was performed and the current literature reviewed. RESULTS: Only 4 primary perineal sarcomas have been described in the literature. Epithelioid sarcomas are uncommon, aggressive tumours with a propensity for locoregional recurrence. They are recognised by the US Veterans Affairs department as linked to exposure to Agent Orange, an organochlorine defoliant containing the contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, the role of Agent Orange in sarcomagenesis is still controversial. CONCLUSION: Unusual soft tissue swellings in a background of chemical exposure should be investigated thoroughly with a view to early, appropriate treatment.

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.

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.

Incidence of CTCL in Vietnam veterans.

The causative factors of cutaneous T-cell lymphoma (CTCL) are unclear. Exposure to herbicides has been linked to the development of other lymphomas. Three Vietnam Veterans with CTCL treated at a photopheresis unit in New Jersey report positive histories of exposure to Agent Orange, a herbicide used during the war.