Epigenetic link between Agent Orange exposure and type 2 diabetes in Korean veterans.

Conflicting findings have been reported regarding the association between Agent Orange (AO) exposure and type 2 diabetes. This study aimed to examine whether AO exposure is associated with the development of type 2 diabetes and to verify the causal relationship between AO exposure and type 2 diabetes by combining DNA methylation with DNA genotype analyses. An epigenome-wide association study and DNA genotype analyses of the blood of AO-exposed and AO-unexposed individuals with type 2 diabetes and that of healthy controls were performed. Methylation quantitative trait locus and Mendelian randomisation analyses were performed to evaluate the causal effect of AO-exposure-identified CpGs on type 2 diabetes. AO-exposed individuals with type 2 diabetes were associated with six hypermethylated CpG sites (cg20075319, cg21757266, cg05203217, cg20102280, cg26081717, and cg21878650) and one hypo-methylated CpG site (cg07553761). Methylation quantitative trait locus analysis showed the methylation levels of some CpG sites (cg20075319, cg20102280, and cg26081717) to be significantly different. Mendelian randomisation analysis showed that CpG sites that were differentially methylated in AO-exposed individuals were causally associated with type 2 diabetes; the reverse causal effect was not significant. These findings reflect the need for further epigenetic studies on the causal relationship between AO exposure and type 2 diabetes.

A Review about the Mycoremediation of Soil Impacted by War-like Activities: Challenges and Gaps.

(1) Background: The frequency and intensity of war-like activities (war, military training, and shooting ranges) worldwide cause soil pollution by metals, metalloids, explosives, radionuclides, and herbicides. Despite this environmentally worrying scenario, soil decontamination in former war zones almost always involves incineration. Nevertheless, this practice is expensive, and its efficiency is suitable only for organic pollutants. Therefore, treating soils polluted by wars requires efficient and economically viable alternatives. In this sense, this manuscript reviews the status and knowledge gaps of mycoremediation. (2) Methods: The literature review consisted of searches on ScienceDirect and Web of Science for articles (1980 to 2023) on the mycoremediation of soils containing pollutants derived from war-like activities. (3) Results: This review highlighted that mycoremediation has many successful applications for removing all pollutants of war-like activities. However, the mycoremediation of soils in former war zones and those impacted by military training and shooting ranges is still very incipient, with most applications emphasizing explosives. (4) Conclusion: The mycoremediation of soils from conflict zones is an entirely open field of research, and the main challenge is to optimize experimental conditions on a field scale.

Agent Orange Herbicidal Toxin-Initiation of Alzheimer-Type Neurodegeneration.

Background: Agent Orange (AO) is a Vietnam War-era herbicide that contains a 1 : 1 ratio of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Emerging evidence suggests that AO exposures cause toxic and degenerative pathologies that may increase the risk for Alzheimer's disease (AD). Objective: This study investigates the effects of the two main AO constituents on key molecular and biochemical indices of AD-type neurodegeneration. Methods: Long Evans rat frontal lobe slice cultures treated with 250µg/ml of 2,4-D, 2,4,5-T, or both (D + T) were evaluated for cytotoxicity, oxidative injury, mitochondrial function, and AD biomarker expression. Results: Treatment with the AO constituents caused histopathological changes corresponding to neuronal, white matter, and endothelial cell degeneration, and molecular/biochemical abnormalities indicative of cytotoxic injury, lipid peroxidation, DNA damage, and increased immunoreactivity to activated Caspase 3, glial fibrillary acidic protein, ubiquitin, tau, paired-helical filament phosphorylated tau, AßPP, Aß, and choline acetyltransferase. Nearly all indices of cellular injury and degeneration were more pronounced in the D + T compared with 2,4-D or 2,4,5-T treated cultures. Conclusions: Exposures to AO herbicidal chemicals damage frontal lobe brain tissue with molecular and biochemical abnormalities that mimic pathologies associated with early-stage AD-type neurodegeneration. Additional research is needed to evaluate the long-term effects of AO exposures in relation to aging and progressive neurodegeneration in Vietnam War Veterans.

Association of UGT1A1 gene variants, expression levels, and enzyme concentrations with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin.

Among the congener of dioxin, 2,3,7,8-TCDD is the most toxic, having a serious long-term impact on the environment and human health. UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in the detoxification and excretion of endogenous and exogenous lipophilic compounds, primarily in the liver and gastrointestinal tract. This study aimed to investigate the association of UGT1A1 gene polymorphisms, expression levels, and enzyme concentration with Agent Orange/Dioxin exposure. The study included 100 individuals exposed to Agent Orange/Dioxin nearby Da Nang and Bien Hoa airports in Vietnam and 100 healthy controls. UGT1A1 SNP rs10929303, rs1042640 and rs8330 were determined by Sanger sequencing, mRNA expression was quantified by RT-qPCR and plasma UGT1A1 concentrations were measured by ELISA. The results showed that UGT1A1 polymorphisms at SNPs rs10929303, rs1042640 and rs8330 were associated with Agent Orange/Dioxin exposure (OR = 0.55, P = 0.018; OR = 0.55, P = 0.018 and OR = 0.57, P = 0.026, respectively). UGT1A1 mRNA expression levels and enzyme concentration were significantly elevated in individuals exposed to Agent Orange/Dioxin compared to controls (P < 0.0001). Benchmark dose (BMD) analyses showed that chronic exposure to 2,3,7,8-TCDD contamination affects the UGT1A1 mRNA and protein levels. Furthermore, UGT1A1 polymorphisms affected gene expression and enzyme concentrations in individuals exposed to Agent Orange/Dioxin. In conclusion, UGT1A1 gene polymorphisms, UGT1A gene expression levels and UGT1A1 enzyme concentrations were associated with Agent Orange/Dioxin exposure. The metabolism of 2,3,7,8-TCDD may influence UGT1A gene expression and enzyme concentrations.

Exposure to Agent Orange is associated with increased recurrence after surgical treatment of stage I non-small cell lung cancer.

OBJECTIVE: Approximately 3 million Americans served in the armed forces during the Vietnam War. Veterans have a higher incidence rate of lung cancer compared with the general population, which may be related to exposures sustained during service. Agent Orange, one of the tactical herbicides used by the armed forces as a means of destroying crops and clearing vegetation, has been linked to the development of several cancers including non-small cell lung cancer. However, traditional risk models of lung cancer survival and recurrence often do not include such exposures. We aimed to examine the relationship between Agent Orange exposure and overall survival and disease recurrence for surgically treated stage I non-small cell lung cancer. METHODS: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with pathologic I non-small cell lung cancer. We included adult patients who served in the Vietnam War and underwent surgical resection between 2010 and 2016. Our 2 comparison groups included those with identified Agent Orange exposure and those who were unexposed. We used multivariable Cox proportional hazards and Fine and Gray competing risk analyses to examine overall survival and disease recurrence for patients with pathologic stage I disease, respectively. RESULTS: A total of 3958 Vietnam Veterans with pathologic stage I disease were identified (994 who had Agent Orange exposure and 2964 who were unexposed). Those who had Agent Orange exposure were more likely to be male, to be White, and to live a further distance from their treatment facility (P < .05). Tumor size distribution, grade, and histology were similar between cohorts. Multivariable Cox proportional hazards modeling identified similar overall survival between cohorts (Agent Orange exposure hazard ratio, 0.97; 95% CI, 0.86-1.09). Patients who had Agent Orange exposure had a 19% increased risk of disease recurrence (hazard ratio, 1.19; 95% CI, 1.02-1.40). CONCLUSIONS: Veterans with known Agent Orange exposure who undergo surgical treatment for stage I non-small cell lung cancer have an approximately 20% increased risk of disease recurrence compared with their nonexposed counterparts. Agent Orange exposure should be taken into consideration when determining treatment and surveillance regimens for Veteran patients.

Effects of defoliant exposure and medication use on the development of Parkinson's disease in veterans.

BACKGROUND: Vietnam-era veterans were exposed to Agent Orange (AO), which is associated with a high prevalence of Parkinson's disease (PD). However, little is known about the development of PD-like symptoms caused by drug-induced parkinsonism (DIP) in such populations. This study aimed to investigate PD incidence and PD risk following exposure to AO or DIP-risk drugs in veterans. METHODS: A retrospective cohort study was conducted using 12 years (2009-2020) of electronic medical records of the Veterans Health Service Medical Center, the largest Veterans Affairs hospital in South Korea (n = 37,246; 100% male; age, 65.57 ± 8.12 years). Exposure to AO or DIP-risk drugs, including antipsychotic, prokinetic, anti-epileptic, dopamine-depleting and anti-anginal agents, was assessed in veterans with PD, operationally defined as having a PD diagnosis and one or more prescriptions for PD treatment. The PD risk was calculated using multiple logistic regression analysis adjusted for age and comorbidities. RESULTS: The rates of DIP-risk drug use and AO exposure were 37.92% and 62.62%, respectively. The PD incidence from 2010 to 2020 was 3.08%; 1.30% with neither exposure, 1.63% with AO exposure, 4.38% with DIP-risk drug use, and 6.33% with both. Combined exposure to AO and DIP-risk drugs increased the PD risk (adjusted odds ratio = 1.68, 95% confidence interval, 1.36-2.08, P < 0.001). CONCLUSIONS: The PD incidence was 1.31 times higher with AO exposure alone and 1.68 times higher with AO exposure and DIP-risk drug use. The results suggest the necessity for careful monitoring and DIP-risk drug prescription in patients with AO exposure.

Agent Orange Causes Metabolic Dysfunction and Molecular Pathology Reminiscent of Alzheimer's Disease.

Background: Agent Orange, an herbicide used during the Vietnam War, contains 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Agent Orange has teratogenic and carcinogenic effects, and population-based studies suggest Agent Orange exposures lead to higher rates of toxic and degenerative pathologies in the peripheral and central nervous system (CNS). Objective: This study examines the potential contribution of Agent Orange exposures to neurodegeneration. Methods: Human CNS-derived neuroepithelial cells (PNET2) treated with 2,4-D and 2,4,5-T were evaluated for viability, mitochondrial function, and Alzheimer's disease (AD)-related proteins. Results: Treatment with 250µg/ml 2,4-D or 2,4,5-T significantly impaired mitochondrial function, caused degenerative morphological changes, and reduced viability in PNET2 cells. Correspondingly, glyceraldehyde-3-phosphate dehydrogenase expression which is insulin-regulated and marks the integrity of carbohydrate metabolism, was significantly inhibited while 4-hydroxy-2-nonenal, a marker of lipid peroxidation, was increased. Tau neuronal cytoskeletal protein was significantly reduced by 2,4,5-T, and relative tau phosphorylation was progressively elevated by 2,4,5-T followed by 2,4-D treatment relative to control. Amyloid-ß protein precursor (AßPP) was increased by 2,4,5-T and 2,4-D, and 2,4,5-T caused a statistical trend (0.05 < p<0.10) increase in Aß. Finally, altered cholinergic function due to 2,4,5-T and 2,4-D exposures was marked by significantly increased choline acetyltransferase and decreased acetylcholinesterase expression, corresponding with responses in early-stage AD. Conclusion: Exposures to Agent Orange herbicidal chemicals rapidly damage CNS neurons, initiating a path toward AD-type neurodegeneration. Additional research is needed to understand the permanency of these neuropathologic processes and the added risks of developing AD in Agent Orange-exposed aging Vietnam Veterans.

Information needs of informal caregivers in caring and rehabilitation for dioxin victims in Vietnam.

BACKGROUND: Health outcomes among Agent Orange/dioxin (dioxin) victims are significant due to many individuals requiring daily assistance, informal care, and rehabilitation support. This study aimed to identify the information needs of informal caregivers of dioxin victims in Vietnam. METHODS: A cross-sectional study was conducted in Quynh Phu district, Thai Binh province - an area with a large number of dioxin victims, from June 2019 to June 2020. Quantitative data were collected from 124 caregivers of victims via structured interviews. Qualitative data were collected using semi-structured interview guides with in-depth interviews (IDI) (n = 36) and two focus group discussions (FGD) (n = 12). RESULTS: The results demonstrated that all caregivers of dioxin victims were family members, predominantly older (71.8%), 61.5 years old on average, living on low incomes (87.9%), and were farmers (80.7%). Almost all participants (96.8%) reported having information needs, particularly concerning dioxin's harms, nutrition, dioxin-related policies and rehabilitation, and psychological support for patients. Caregivers reported that they would like to receive information via health staff counselling (85.0%), television (75.0%), and community loudspeaker (65.8%). Notably, the majority of caregivers reported the need for information regarding psychological support (70.0%). These findings are consistent with qualitative data, which identify an urgent need to provide information, especially through health staff and digital resources. CONCLUSION: Many families with dioxin victims lived with little support and information, highlighting their high demand for information about care and rehabilitation. Thus, the healthcare system should promote information support, policy, and psychological support for caregivers and victims. An online support system for caregivers and victims is also recommended.

Groundwater constituents and the incidence of kidney cancer.

BACKGROUND: Kidney cancer incidence demonstrates significant geographic variation suggesting a role for environmental risk factors. This study sought to evaluate associations between groundwater exposures and kidney cancer incidence. METHODS: The authors identified constituents from 18,506 public groundwater wells in all 58 California counties measured in 1996-2010, and obtained county-level kidney cancer incidence data from the California Cancer Registry for 2003-2017. The authors developed a water-wide association study (WWAS) platform using XWAS methodology. Three cohorts were created with 5 years of groundwater measurements and 5-year kidney cancer incidence data. The authors fit Poisson regression models in each cohort to estimate the association between county-level average constituent concentrations and kidney cancer, adjusting for known risk factors: sex, obesity, smoking prevalence, and socioeconomic status at the county level. RESULTS: Thirteen groundwater constituents met stringent WWAS criteria (a false discovery rate <0.10 in the first cohort, followed by p values <.05 in subsequent cohorts) and were associated with kidney cancer incidence. The seven constituents directly related to kidney cancer incidence (and corresponding standardized incidence ratios) were chlordane (1.06; 95% confidence interval [CI], 1.02-1.10), dieldrin (1.04; 95% CI, 1.01-1.07), 1,2-dichloropropane (1.04; 95% CI, 1.02-1.05), 2,4,5-TP (1.03; 95% CI, 1.01-1.05), glyphosate (1.02; 95% CI, 1.01-1.04), endothall (1.02; 95% CI, 1.01-1.03), and carbaryl (1.02; 95% CI, 1.01-1.03). Among the six constituents inversely related to kidney cancer incidence, the standardized incidence ratio furthest from the null was for bromide (0.97; 95% CI, 0.94-0.99). CONCLUSIONS: This study identified several groundwater constituents associated with kidney cancer. Public health efforts to reduce the burden of kidney cancer should consider groundwater constituents as environmental exposures that may be associated with the incidence of kidney cancer.

Association of PKLR gene copy number, expression levels and enzyme activity with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin in Vietnam.

2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is the most toxic congener of dioxin and has serious long-term effects on the environment and human health. Pyruvate Kinase L/R (PKLR) gene expression levels and gene variants are associated with pyruvate kinase enzyme deficiency, which has been identified as the cause of several diseases linked to dioxin exposure. In this study, we estimated PKLR gene copy number and gene expression levels using real-time quantitative PCR (RT-qPCR) assays, genotyped PKLR SNP rs3020781 by Sanger sequencing, and quantified plasma pyruvate kinase enzyme activity in 100 individuals exposed to Agent Orange/Dioxin near Bien Hoa and Da Nang airfields in Vietnam and 100 healthy controls. The means of PKLR copy numbers and PKLR gene expression levels were significantly higher, while pyruvate kinase enzyme activity was significantly decreased in Agent Orange/Dioxin-exposed individuals compared to healthy controls (P < 0.0001). Positive correlations of PKLR gene copy number and gene expression with 2,3,7,8-TCDD concentrations were observed (r = 0.2, P = 0.045 and r = 0.54, P < 0.0001, respectively). In contrast, pyruvate kinase enzyme activity was inversely correlated with 2,3,7,8-TCDD concentrations (r = -0.52, P < 0.0001). PKLR gene copy number and gene expression levels were also inversely correlated with pyruvate kinase enzyme activity. Additionally, PKLR SNP rs3020781 was found to be associated with 2,3,7,8-TCDD concentrations and PKLR gene expression. In conclusion, PKLR copy number, gene expression levels, and pyruvate kinase enzyme activity are associated with 2,3,7,8-TCDD exposure in individuals living in Agent Orange/Dioxin-contaminated areas.

Human 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure and thyroid cancer risk.

Thyroid cancer incidence has been steadily rising since the 1970s and exposure to environmental pollutants, including persistent organic pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxins, has emerged as a potential explanation for this increase. This study aimed to summarize available human studies on the association between TCDD exposure and thyroid cancer. A systematic review of the literature was performed searching the National Library of Medicine and National Institutes of Health PubMed, Embase, and Scopus databases, through January 2022, using the following keywords: "thyroid", "2,3,7,8-tetrachlorodibenzo-p-dioxin", "TCDD", "dioxin", and "Agent Orange". Six studies were included in this review. Three studies evaluated the acute exposure to the chemical factory accident in Seveso, Italy, and found a non-significant increase in the risk of thyroid cancer. Two studies investigating Agent Orange exposure among United States Vietnam War veterans found a significant risk of thyroid cancer following exposure. No association was found in one study evaluating TCDD exposure through herbicides. The current study highlights the limited information on the potential association between TCDD exposure and thyroid cancer and thus the need for future human studies, especially considering the persistent human exposure to dioxins in the environment.

An analysis of birth defects and developmental disabilities for children of participants of the Air Force Health Study.

Analyses were conducted of the occurrence of eight general categories of birth defects and developmental disabilities for children fathered by participants of the Air Force Heath Study (AFHS). Participants were male Air Force veterans of the Vietnam War. Children were categorized into conceived before and after the start of the participant's Vietnam War service. Analyses accounted for correlation between outcomes for multiple children fathered by each of the participants. For each of the eight general categories of birth defects and developmental disabilities, the probability of its occurrence increased substantially for children conceived after compared to before the start of Vietnam War service. These results support the conclusion of an adverse effect on reproductive outcomes due to Vietnam War service. Data for children conceived after the start of Vietnam War service for participants with measured dioxin values were used to estimate dose-response curves for the effect of dioxin exposure on the occurrence of each of the eight general categories of birth defects and developmental disabilities. These curves were assumed to be constant up to a threshold and then monotonic after that threshold. For seven of the eight general categories of birth defects and developmental disabilities, the estimated dose-response curves increased nonlinearly after associated thresholds. These results support the conclusion that the adverse effect to conception after the start of Vietnam War service may be attributable to high enough exposures to dioxin, a toxic contaminant of Agent Orange used for herbicide spraying in the Vietnam War.

Cancer risk in Vietnam war veterans from the Korean Vietnam war veterans' health study cohort.

Introduction: During the Vietnam War, several unknown chemicals, such as Agent Orange, were used in Vietnam by the military. Therefore, there have been continuous health concerns among the Vietnamese population and veterans exposed to these hazardous chemicals. This study aimed to investigate the risk of all cancers and also organ-specific cancers among Korean veterans of the Vietnam War. Methods: This study used a national representative cohort that included all Korean Vietnam War veterans as the interest group, with 1:4 age-sex-region-matched general Korean citizens as the reference group, from 2002 to 2018. Age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for all cancers and for 31 organ-specific cancer categories based on the medical facility visit data. Results: An increased SIR of 1.07 (95% CI, 1.06-1.08) was observed for all cancers among the veterans. There was a significantly increased risk of cancer among 22/31 organspecific cancers, with 18 cancer categories showing a significantly higher risk than all cancers. The highest risk was observed for "malignant neoplasms of other parts of the central nervous system" (SIR, 1.71; 95% CI, 1.51-1.92). Discussion: This study evaluated the risk of cancer among Korean Vietnam War veterans. Further studies are warranted to investigate various health determinants in the veterans as well as the Vietnamese population.

Microbial Communities Along 2,3,7,8-tetrachlorodibenzodioxin Concentration Gradient in Soils Polluted with Agent Orange Based on Metagenomic Analyses.

The 2,3,7,8-tetrachlorodibenzodioxin (TCDD), a contaminant in Agent Orange released during the US-Vietnam War, led to a severe environmental crisis. Approximately, 50 years have passed since the end of this war, and vegetation has gradually recovered from the pollution. Soil bacterial communities were investigated by 16S metagenomics in habitats with different vegetation physiognomies in Central Vietnam, namely, forests (S0), barren land (S1), grassland (S2), and developing woods (S3). Vegetation complexity was negatively associated with TCDD concentrations, revealing the reasoning behind the utilization of vegetation physiognomy as an indicator for ecological succession along the gradient of pollutants. Stark changes in bacterial composition were detected between S0 and S1, with an increase in Firmicutes and a decrease in Acidobacteria and Bacteroidetes. Notably, dioxin digesters Arthrobacter, Rhodococcus, Comamonadaceae, and Bacialles were detected in highly contaminated soil (S1). Along the TCDD gradients, following the dioxin decay from S1 to S2, the abundance of Firmicutes and Actinobacteria decreased, while that of Acidobacteria increased; slight changes occurred at the phylum level from S2 to S3. Although metagenomics analyses disclosed a trend toward bacterial communities before contamination with vegetation recovery, non-metric multidimensional scaling analysis unveiled a new trajectory deviating from the native state. Recovery of the bacterial community may have been hindered, as indicated by lower bacterial diversity in S3 compared to S0 due to a significant loss of bacterial taxa and recruitment of fewer colonizers. The results indicate that dioxins significantly altered the soil microbiomes into a state of disorder with a deviating trajectory in restoration.

Long-term effects of defoliant exposure on brain atrophy progression in humans.

As the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin is classified as a group 1 human carcinogen. We investigated the long-term effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on the progression of brain atrophy in humans. We retrospectively selected 546 patients exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (exposed group) and 1353 patients not exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (control group). The patients in both groups underwent brain T1-weighted magnetic resonance imaging (MRI) twice. We divided the patients into two propensity score-matched groups, analyzed voxel-wise whole brain atrophy in the MRI images of each patient, and compared the progression of brain atrophy between the two groups. The exposed group showed significant brain atrophy progression in the bilateral frontal and temporal lobes, compared with the control group. The ventrolateral prefrontal area in the frontal lobe and whole temporal lobe were the main atrophic regions in the exposed group, compared with the control group. The neurotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin can damage the brain, even in patients exposed to it over 40 years ago. Humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin should thus be evaluated for progression of brain atrophy.

The Relationship of Dioxin Levels in Serum of 9-Year-Old Vietnamese Children and Their Mothers' Breast Milk.

In this study, we measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in the blood of 9-year-old children living in a dioxin hotspot area and a nonexposed area in Vietnam. Forty-five blood samples were collected in the hotspot area while twelve pooled blood samples were collected in the nonexposed area. We found that the dioxin level of children in the hotspot was significantly higher than that of children in the nonexposed area. The total TEQ of PCDD/Fs in the hotspot and the nonexposed was 10.7 and 3.3 pg TEQ/g fat, respectively. However, TCDD, the maker of Agent Orange, was not detected in the blood of children in the hotspot area. In the hotspot area, four congeners 1,2,3,4,6,7,8-HpCDD, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 1,2,3,4,6,7,8-HpCDF in mothers' breast milk showed a significantly positive correlation with those in children's serum although the correlations of 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF were not significant. In addition, the duration of breastfeeding also correlates with dioxins in children. These results suggested that children in the hotspot area were exposed to dioxin through mothers' milk and other foods or environmental factors. The present study is the first study that shows dioxin levels in Vietnamese children.

Cohort Profile: The Korean Vietnam War Veterans' Health Study Cohort (KOVECO).

During the Vietnam War, many troops and citizen were exposed to large amounts of Agent Orange (AO), and the hazardous effects of AO are continuously being researched and reported. The Korean Vietnam War Veterans' Health Study Cohort (KOVECO) is a retrospective cohort to demonstrate the health status of the Korean Vietnam War veterans and their second-generation offsprings. The KOVECO is a collaboration of data from the Ministry of Patriots and Veterans Affairs and the National Health Insurance Sharing Service from 2002 to 2018. The study participants were all Korean Vietnam War veterans and their second-generation offsprings, and the references were the general population in which gender and region were matched with the participants. As of 2002, 191,272 Vietnam War veterans (1,000,320 comparisons) and 1,963,402 s-generations (1,173,061 references) were included in the cohort. The KOVECO consists of personal information, medical facility visit information, and general health examination information. The KOVECO could act as a health surveillance system, which would be able to detect long-term health effects caused by exposure to AO and provide a direction for policy making through academic research.

Adverse effects of dioxins on cognitive ability and motor performance of 5-year-old children residing in a hotspot of dioxin contamination originating from Agent Orange in Vietnam: A prospective cohort study.

Bien Hoa airbase is the most dioxin-polluted hotspot in Vietnam. In 2012, a birth cohort living around Bien Hoa airbase was recruited for assessment of physical and neurological development. In the present study, neurodevelopment scores at 5 years of age were assessed by the Kaufman Assessment Battery for Children, Second Edition and the Movement Assessment Battery for Children, Second Edition for 185 children in Bien Hoa and 104 children in Ha Dong (unexposed control group) to clarify the effects of dioxin. 2,3,7,8-tetrachlorodibenzo-p-dioxin concentrations in breast milk of women in Bien Hoa were approximately three times higher than those of women in Ha Dong (2.33 vs. 0.69 pg/g fat, p < 0.001). In general, neurodevelopment scores were lower in Bien Hoa children than in Ha Dong children. In boys, scores differed for number recall (12.6 vs. 14.0, p = 0.036), triangles (10.7 vs. 12.4, p = 0.005), manual dexterity (8.3 vs. 9.7, p = 0.037), balance (7.4 vs. 10.3, p < 0.001), and total movement scores (8.0 vs. 10.1, p = 0.003). After adjusting for covariates, linear regression analysis indicated that the scores of the triangles, balance, and total movement tests were inversely associated with levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin and of toxic equivalency of polychlorinated dibenzodioxins and polychlorinated dibenzofurans. In girls, scores differed for the triangles test (11.0 vs. 12.6, p = 0.005), hand movement test (9.6 vs. 11.3, p = 0.003), and balance test (9.1 vs. 10.7, p = 0.050); toxic equivalency of polychlorinated dibenzofurans was inversely associated with hand movement and balance scores. Overall, perinatal dioxin exposure appears to have a long-term impact on neurodevelopment.

Agent Orange and dioxin-induced myeloid leukemia: a weaponized vehicle of leukemogenesis.

Agent Orange (AO) was the dominant weaponized herbicide employed by the United States (US) military during the Vietnam war. AO, however, was found to be regularly contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin known; furthermore, AO was commonly diluted in the field with other aromatic hydrocarbons to assist with delivery mechanisms. Unbeknownst to the US military and the millions exposed, these events have likely contributed to the development of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) that has affected many veterans. Null studies regarding an association between AO exposure and AML/MDS are limited in their methodology and application. The acknowledgement that the known carcinogen TCDD was a contaminant in AO when paired with a strong biological plausibility for its leukemogenicity and an observed increased risk of AML/MDS in TCDD-exposed individuals should suffice to establish causal association and that veterans to whom this might apply should be awarded appropriate indemnity.

Fingerprinting and source apportionment of dioxin contamination of soils and chicken eggs in Southeast and Central Vietnam.

Free-range chicken eggs and topsoil samples from private households in Southeast and South Central Coast of Vietnam were investigated to identify potential PCDD/F sources using Positive Matrix Factorization (PMF) approach. The PMF-extracted egg congener patterns were transformed to soil patterns using bioaccumulation factors and then compared to extracted soil and known dioxin sources patterns described in the literature. Free-range chicken egg PCDD/F profiles allowed to more precisely identify and distinguish potential PCDD/F sources. Five main PCDD/F sources were identified: open burning, vehicle emissions, background atmospheric deposition, Agent Orange, and so-called OCDD dechlorination pattern. The latter is characteristic for natural formation or ultimate weathering under tropical conditions of any primary source with predominant OCDD. Agent Orange source contribution ranged from 48 to 96% in soils, from 9 to 94% in eggs in hotspots, and from 10 to 31% in soil and from 4 to 45% in eggs in sprayed areas, respectively. Contributions of other sources varied significantly between sites.