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.

[Oxidative stress and antioxidant therapy with alpha-lipoic acid inclusion in acute poisoning by herbicide based on 2,4-dichlorphenoxyacetic acid].

In patients with acute poisoning amine salt herbicide 2,4-D develops oxidative stress with simultaneous inhibition of intracellular and extracellular antioxidant factors. These changes are more pronounced with neurological disorders that occur in conjunction with a toxic damage of liver or heart. The inclusion of a comprehensive detoxification therapy alpha-lipoic acid not only promotes a more pronounced therapeutic effect but also an earlier recourse cytolytic syndrome, a marked recovery of levels of malondialdehyde and indices of antioxidant system (superoxide dismutase and ceruloplasmin) than for patients in the comparison group.

[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.

Clinical study and observation on the effect of hemoperfusion therapy treatment on central nervous system injury in patients with 2,4-dichlorophenoxyacetic acid poisoning.

OBJECTIVE: To evaluate the curative effect of hemoperfusion therapy on central nervous system injury in patients with 2,4-dichlorophenoxyacetic acid poisoning. PATIENTS AND METHODS: A total of 60 patients with 2,4-dichlorophenoxyacetic acid poisoning were enrolled in this study. They were admitted to the Emergency Department of Qinghai Provincial People's Hospital from 2015 to 2018 and were randomly divided into two groups by random number table method. One group was control group (routine treatment group), and the other group was the treatment group (hemoperfusion therapy was added on the basis of routine treatment). Glasgow coma score (GCS), APACHE II score, and MMSE score were used to evaluate the effects before treatment and 7 days after treatment. The results were statistically analyzed. RESULTS: After treatment, GCS in the treatment group was higher than that in the control group, while APACHE II score was lower than that in the control group, and MMSE score was significantly higher than that in the control group, with statistically significant difference (p<0.05). The effective rate in the control group was only 26.67%, and that in the treatment group was 86.67%, with statistically significant difference (c2=19.62, p<0.001). CONCLUSIONS: Hemoperfusion therapy can promote the recovery of central nervous system in patients with 2,4-dichlorophenoxyacetic acid poisoning, reduce the injury of other organs, and significantly reduce the mortality of patients.

Confirmed 2,4-dichlorophenoxyacetic acid toxicosis in a dog.

A 2-year-old, intact male Weimaraner was evaluated for episodic extensor rigidity and a stiff gait of 24 hours' duration. Percussion of the proximal appendicular muscles with a reflex hammer resulted in formation of dimples consistent with myotonia. Electromyography identified myotonic potentials. Residues of 2,4-dichlorophenoxyacetic acid (2,4-D) were detected in both serum and urine. The dog was treated with intravenous fluid therapy for 36 hours, and clinical signs improved dramatically. Toxicosis with 2,4-D should be considered a differential for acquired myotonia in dogs with or without systemic signs. Exposed dogs with only clinical signs of myotonia can have good clinical outcomes. A confirmed clinical case of 2,4-D toxicosis in the dog has not previously been reported.

Case series of 2,4-D poisoning in Tikur Anbessa Teaching Hospital.

2,4-D (2, 4 dichlophenoxy acetic acid) poisoning is a rare phenomenon, but it is appearing more frequently as agrochemical usage of these agents is increasing in Ethiopia. Here the clinical features and outcomes of three cases due to 2, 4-D poisoning are described and discussion is made with literature review.

Determination of the phenoxyacid herbicides MCPA, mecoprop and 2,4-D in kidney tissue using liquid chromatography with electrospray tandem mass spectrometry.

An analytical method was developed to determine the phenoxyacid herbicides 2,4-D, MCPA and mecoprop in kidney tissue from animals where poisoning is suspected. Samples were Soxhlet extracted using diethyl ether and the extracts cleaned-up using anion exchange solid phase extraction cartridges. Analysis was performed using liquid chromatography with negative-ion electrospray tandem mass spectrometry (LC-MS/MS). The method was evaluated by analysing control kidney samples fortified at 1 and 5 mg/kg. Mean recoveries ranged from 82 to 93% with relative standard deviations from 3.2 to 19%. The limit of detection was estimated to be 0.02 mg/kg.

2,4-D (ethyl ester) poisoning: experience at a tertiary care centre in northern India.

2,4-Dichlorphenoxyacetic acid (2,4-D) is a selective herbicide widely used to kill broad-leaved plants in wheat cultivation. Only a few cases of documented poisoning cases with this compound have been reported from India. Since the initial manifestations are not very different from anticholinesterase poisoning, the chances of misdiagnosis are high. Anticholinesterase compounds are the most commonly used insecticides and are implicated as the commonest cause of agrochemical poisoning in India. This report aims to make physicians aware that not all cases of agrochemical poisoning are caused by anticholinesterase insecticides. Efforts must be made to correctly identify the offending compound for appropriate management.

2,4-D poisoning: a review with illustration of two cases.

2,4-D (2,4-dichlorphenoxyacetic acid) is a chlorphenoxy group pesticide. Its relative safety and broad leaf selectivity makes it a favourite herbicide of many home gardeners and agricultural workers. Severe systemic toxicity requiring hospital admission and intensive care usually occurs following intentional oral ingestion. 2,4-D poisoning is an under-recognised cause of a potentially lethal toxic syndrome, especially in low- and middle-income countries, where such compounds are widely used in farming and readily available in households. It warrants close monitoring and high-quality supportive care along with plasma alkalinisation or extracorporeal removal of the toxin. We present a short review on 2,4-D poisoning and describe two illustrative cases with significant oral ingestion resulted in early and rapidly developing systemic toxicity. Both patients were admitted to the intensive care unit; one patient was managed with alkaline diuresis and other case required three sessions of haemodialysis.

Urinary alkalinisation for acute chlorophenoxy herbicide poisoning.

BACKGROUND: Acute poisoning with chlorophenoxy herbicides (such as 2,4-D, MCPA, 2,4,5-T and mecoprop) is reported worldwide, potentially causing severe toxicity and death in exposed patients. Animal studies support the application of urinary alkalinisation (particularly using sodium bicarbonate) in the management of acute chlorophenoxy herbicide poisoning to facilitate excretion of these herbicides. Some case reports of human exposure have suggested benefit from urinary alkalinisation also. OBJECTIVES: To assess the efficacy of urinary alkalinisation, in particular sodium bicarbonate, for the treatment of acute chlorophenoxy herbicide poisoning. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CENTRAL, Current Awareness in Clinical Toxicology, Info Trac, http://www.google.com.au, and Science Citation Index of studies identified by the previous searches. The bibliographies of identified articles were reviewed and experts in the field were contacted. SELECTION CRITERIA: Randomised controlled trials of urinary alkalinisation in patients ingesting a chlorophenoxy herbicide and presenting within 24 to 48 hours of poisoning were sought. The quality of studies and eligibility for inclusion was assessed using criteria by Jadad and Schulz. DATA COLLECTION AND ANALYSIS: Authors independently extracted data from the identified studies using a pre-designed form. Study design, including the method of randomisation, participant characteristics, type of intervention and outcomes were all recorded. MAIN RESULTS: No studies were identified which satisfied inclusion criteria. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of urinary alkalinisation for acute chlorophenoxy herbicide poisoning. A well conducted randomised controlled trial is urgently required to determine whether the efficacy and indications of this treatment.

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.

Clinical presentation and management of acute 2,4-D oral ingestion.

2,4-D, an extensively used herbicide, was intentionally ingested by a 61-year-old woman. An initial serum 2,4-D concentration of 392 mg/L was measured. The prominent clinical feature was marked central nervous system depression; primary laboratory abnormalities were extreme elevation of creatine kinase activity, and transitory elevation of AST and lactate dehydrogenase enzyme activities. Alkaline diuresis was initiated early and decreased the half-life of the drug from an initial 39.5 to 2.7h. It is concluded that alkaline diuresis to produce urine pH in the range of 7.5 to 8.5 should be considered in the management of an overdose patient with central nervous system depression and a history of 2,4-D ingestion.

Effects of 2,4-dichlorophenoxyacetic acid on central nervous system of developmental rats. Associated changes in ganglioside pattern.

Neonate rats were treated with 2,4-dichlorophenoxyacetic acid (2,4-D) from the 7th or 12th until the 17th or 25th postnatal day. Two drug dosages were used: 70 and 100 mg/kg body weight of 2,4-D. At the 17th day of age, no changes were observed in body weight, protein and DNA content. However, 25-day-old treated pups showed diminutions in body and brain weight, protein and DNA levels, depending on doses and period of treatment. With respect to ganglioside levels, few changes were observed in treated animals until the 17th day of age. However, at the 25th day, with higher dose and longer treatment a diminution in all parameters analyzed was observed. These results suggest a delay in CNS development when pups were exposed to a very severe chemical injury with 2,4-D. On the other hand, when the chemical injury was not too severe, the brain would be capable to trigger biochemical mechanisms producing a plasticity response which is expressed as changes in ganglioside content and composition.