Editorial

4 pages, 172 KiB

Open AccessEditorial

Dioxin and Dioxin-like Compounds and Human Health

by Muneko Nishijo

Toxics 2023, 11(6), 512; https://doi.org/10.3390/toxics11060512 - 06 Jun 2023

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In epidemiological studies, associations of dioxin and dioxin-like (dl)-compound exposure with metabolic diseases, including diabetes and metabolic syndrome, in adults and with neurodevelopmental problems and earlier/later puberty in children have been suggested in the general population and in environmentally exposed populations [...] Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

Research

Jump to: Editorial, Review, Other

19 pages, 2854 KiB

Open AccessFeature PaperArticle

Coupling Environmental Whole Mixture Toxicity Screening with Unbiased RNA-Seq Reveals Site-Specific Biological Responses in Zebrafish

by Christian I. Rude, Lane G. Tidwell, Susan C. Tilton, Katrina M. Waters, Kim A. Anderson and Robyn L. Tanguay

Toxics 2023, 11(3), 201; https://doi.org/10.3390/toxics11030201 - 21 Feb 2023

Cited by 3 | Viewed by 1340

Abstract

Passive sampling device (PSD) extracts paired with developmental toxicity assays in Danio Rerio (zebrafish) are excellent sensors for whole mixture toxicity associated with the bioavailable non-polar organics at environmental sites. We expand this concept by incorporating RNA-Seq in 48-h post fertilization zebrafish statically [...] Read more.

Passive sampling device (PSD) extracts paired with developmental toxicity assays in Danio Rerio (zebrafish) are excellent sensors for whole mixture toxicity associated with the bioavailable non-polar organics at environmental sites. We expand this concept by incorporating RNA-Seq in 48-h post fertilization zebrafish statically exposed to PSD extracts from two Portland Harbor Superfund Site locations: river mile 6.5W (RM 6.5W) and river mile 7W (RM 7W). RM 6.5W contained higher concentrations of polycyclic aromatic hydrocarbons (PAHs), but the diagnostic ratios of both extracts indicated similar PAH sourcing and composition. Developmental screens determined RM 6.5W to be more toxic with the most sensitive endpoint being a “wavy” notochord malformation. Differential gene expression from exposure to both extracts was largely parallel, although more pronounced for RM 6.5W. When compared to the gene expression associated with individual chemical exposures, PSD extracts produced some gene signatures parallel to PAHs but were more closely matched by oxygenated-PAHs. Additionally, differential expression, reminiscent of the wavy notochord phenotype, was not accounted for by either class of chemical, indicating the potential of other contaminants driving mixture toxicity. These techniques offer a compelling method for non-targeted hazard characterization of whole mixtures in an in vivo vertebrate system without requiring complete chemical characterization. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

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Graphical abstract

18 pages, 2982 KiB

Open AccessFeature PaperArticle

Dioxin Congener Patterns in Breast Milk Samples from Areas Sprayed with Herbicide during the Vietnam War 40 Years after the War Ended

by Muneko Nishijo, Hoa Thi Vu, Tai Pham-The, Thao Ngoc Pham, Nghi Ngoc Tran, Hideaki Nakagawa and Hisao Nishijo

Toxics 2022, 10(6), 323; https://doi.org/10.3390/toxics10060323 - 13 Jun 2022

Cited by 2 | Viewed by 1894

Abstract

Large amounts of herbicides containing polychlorinated dibenzo-p-dioxins and dibenzo-furans (PCDD/Fs) were sprayed in South Vietnam during the Vietnam War. Levels of PCDD/Fs in the environment of South Vietnam remained high even 40 years later. A total of 861 breast milk samples (597 from [...] Read more.

Large amounts of herbicides containing polychlorinated dibenzo-p-dioxins and dibenzo-furans (PCDD/Fs) were sprayed in South Vietnam during the Vietnam War. Levels of PCDD/Fs in the environment of South Vietnam remained high even 40 years later. A total of 861 breast milk samples (597 from three areas sprayed with herbicides, Quang Tri, Da Nang, and Bien Hoa, and 264 from three unsprayed areas in North Vietnam) were collected between 2007 and 2015 and the PCDD/F concentrations in the samples were determined. Levels of TEQ-PCDD/Fs and 17 PCDD/F congeners were higher in the sprayed area samples than the unsprayed area samples. We found particular PCDD/F congener patterns for different areas. High tetrachlorodibenzo-p-dioxin (TCDD) concentrations were found in Bien Hoa, high TCDD and 1,2,3,6,7,8-hexadibenzo-p-dioxin concentrations were found in Da Nang, and high 1,2,3,4,6,7,8-heptadibenzo-p-dioxin concentrations were found in Quan Tri. High 1,2,3,4,7,8-hexadibenzofuran and 1,2,3,4,6,7,8-heptadibenzofuran concentrations were also found in Da Nang and Quang Tri. However, breast feeding may have caused associations between the TCDD and polychlorinated dibenzofuran congener concentrations. Advanced statistical analysis will need to be performed in future to assess the characteristic PCDD/F congener profiles in breast milk samples from areas of Vietnam previously sprayed with herbicides. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

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12 pages, 751 KiB

Open AccessArticle

Histopathological Alterations in the Livers of Chronic Hepatitis Patients Exposed to Agent Orange/Dioxin in Vietnam

by Phu Quang Pham, Vuong Ba Nguyen, Tai The Pham, Nhuong Xuan Duong, Ha Trong Nguyen, Quang Van Ha, Thuan Duc Nguyen, Tuan Minh Hoang, Dong Tien Dinh, Quynh Thi Nhu Tran, Linh Kim Bui, Thuy Thi Vu, Manh Van Phan, Tuan Minh Luong, Khanh Nguyen, Dung Anh Vu and Thao Ngoc Pham

Toxics 2022, 10(6), 315; https://doi.org/10.3390/toxics10060315 - 10 Jun 2022

Cited by 2 | Viewed by 2083

Abstract

We investigated changes in some laboratory indices and the liver histology of chronic hepatitis patients who were exposed to dioxin. In 2014, we collected liver biopsy samples for histopathological examination from 33 chronic hepatitis patients living around the Da Nang Airbase, which is [...] Read more.

We investigated changes in some laboratory indices and the liver histology of chronic hepatitis patients who were exposed to dioxin. In 2014, we collected liver biopsy samples for histopathological examination from 33 chronic hepatitis patients living around the Da Nang Airbase, which is a dioxin-contaminated area due to the herbicide spraying in Vietnam. Dioxin exposure was measured by its levels in the blood. METAVIR classification was used to clarify the liver fibrosis stage. Laboratory tests included ten biochemical and six hematological indices that were measured in the blood. A regression linear model and binary logistic regression were used for data analysis. The observed alterations in the liver at the histological level mainly comprised hydropic degenerative hepatocytes, lymphocytes and polynuclear leukocytes surrounding the liver cells and granular and lipoic degeneration. In addition, increased TCDD levels were associated with increasing aminotransferase (AST), alanine aminotransferase, protein and total bilirubin levels and liver fibrosis stage. Similarly, increased TEQ-PCDD/Fs levels were associated with higher levels of AST and protein and liver fibrosis stage. In conclusion, dioxin exposure altered the liver histology and increased some biochemical marker indices and the liver fibrosis stage of chronic hepatitis patients living in dioxin-contaminated areas in Da Nang, Vietnam. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

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13 pages, 270 KiB

Open AccessFeature PaperArticle

Perinatal Dioxin Exposure and Attention Deficit Hyperactivity Disorder (ADHD) Symptoms in Children Living in a Dioxin Contamination Hotspot in Vietnam

by Tai Pham-The, Muneko Nishijo, Thao Ngoc Pham, Hoa Thi Vu, Nghi Ngoc Tran, Anh Hai Tran, Luong Van Hoang, Quyet Do, Yoshikazu Nishino and Hisao Nishijo

Toxics 2022, 10(5), 212; https://doi.org/10.3390/toxics10050212 - 24 Apr 2022

Cited by 3 | Viewed by 1826

Abstract

We examined children in Da Nang, a dioxin contamination hotspot in Vietnam, twice at 5 and 8 years of age, and investigated sex- and age-dependent differences in the effects of dioxin exposure on attention deficit hyperactivity disorder (ADHD) symptoms. We also studied autistic [...] Read more.

We examined children in Da Nang, a dioxin contamination hotspot in Vietnam, twice at 5 and 8 years of age, and investigated sex- and age-dependent differences in the effects of dioxin exposure on attention deficit hyperactivity disorder (ADHD) symptoms. We also studied autistic traits in children with ADHD symptoms. A total of 163 children participated in follow-up surveys at 5 and 8 years of age and were included in the present analysis. ADHD symptoms were assessed using an ADHD rating scale with inattention and hyperactivity-and-impulsivity (hyperactivity) subscales. Autistic behaviors were evaluated using the Autism Spectrum Rating Scale (ASRS). Perinatal dioxin exposure was indicated by dioxin levels in maternal breast milk. In boys, hyperactivity scores were significantly higher in the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) group only at 5 years of age. In girls, hyperactivity scores at 8 years of age were significantly higher in the high TCDD group, which was significantly associated with those at 5 years of age. In girls, ASRS unusual behavior scores were significantly higher with higher TCDD exposure and hyperactivity scores at 8 years of age. These results suggest that high perinatal TCDD exposure may increase ADHD likelihood and autistic traits, particularly in girls of 7–8 years of age. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

10 pages, 819 KiB

Open AccessArticle

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

by Ho Dung Manh, Teruhiko Kido, Takumi Takasuga, Michiko Yamashita, Le Minh Giang and Hideaki Nakagawa

Toxics 2022, 10(4), 155; https://doi.org/10.3390/toxics10040155 - 25 Mar 2022

Cited by 2 | Viewed by 2600

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

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15 pages, 706 KiB

Open AccessFeature PaperArticle

Effect of Perinatal Dioxin Exposure Originating from Agent Orange on Gaze Behavior in 3-Year-Old Children Living in the Most Dioxin-Contaminated Areas in Vietnam

by Thao Ngoc Pham, Muneko Nishijo, Tai Pham-The, Nghi Ngoc Tran, Hoa Thi Vu, Anh Hai Tran, Tien Viet Tran, Yoshikazu Nishino and Hisao Nishijo

Toxics 2022, 10(4), 150; https://doi.org/10.3390/toxics10040150 - 22 Mar 2022

Cited by 3 | Viewed by 2604

Abstract

We investigated the effect of perinatal dioxin exposure indicated by dioxins in breast milk on children’s gaze behavior. We studied 142 children aged 3 years from the 2012 Bien Hoa birth cohort in a hotspot of dioxin contamination in Vietnam. Children’s faces were [...] Read more.

We investigated the effect of perinatal dioxin exposure indicated by dioxins in breast milk on children’s gaze behavior. We studied 142 children aged 3 years from the 2012 Bien Hoa birth cohort in a hotspot of dioxin contamination in Vietnam. Children’s faces were viewed using the eye-tracking method. Associations between gaze behavior of faces and neurodevelopmental indices and head circumference were analyzed to determine whether poor gaze behavior indicates increased autistic traits in these children. The gaze fixation duration on facial areas when viewing 10 still images of children was calculated as the gaze behavior index. Autistic behavior was assessed using the Autism Spectrum Rating Scale, and language development was evaluated by the Bayley Scales of Infant and Toddler Development, Ver. 3. The face fixation duration (%) significantly decreased as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations increased in a dose–effect manner in girls, which suggested atypical gaze behavior for watching human faces. Furthermore, these girls with atypical gaze behavior showed lower social communication scores and smaller head sizes, suggesting increased autistic traits in girls. In conclusion, our findings show sex-specific effects (girls > boys) of perinatal TCDD exposure on gaze behavior in young children. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

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14 pages, 6085 KiB

Open AccessArticle

Alterations in Regional Brain Regional Volume Associated with Dioxin Exposure in Men Living in the Most Dioxin-Contaminated Area in Vietnam: Magnetic Resonance Imaging (MRI) Analysis Using Voxel-Based Morphometry (VBM)

by Hoa Thi Vu, Thao Ngoc Pham, Takashi Yokawa, Muneko Nishijo, Tai Pham The, Quyet Do, Yoshikazu Nishino and Hisao Nishijo

Toxics 2021, 9(12), 353; https://doi.org/10.3390/toxics9120353 - 15 Dec 2021

Cited by 5 | Viewed by 3121

Abstract

To clarify the influence of dioxin exposure on brain morphometry, the present study investigated associations between dioxin exposure at high levels and brain structural irregularities in 32 Vietnamese men. Two exposure markers were used: blood dioxin levels, as a marker of exposure in [...] Read more.

To clarify the influence of dioxin exposure on brain morphometry, the present study investigated associations between dioxin exposure at high levels and brain structural irregularities in 32 Vietnamese men. Two exposure markers were used: blood dioxin levels, as a marker of exposure in adulthood, and perinatal dioxin exposure, estimated by maternal residency in a dioxin-contaminated area during pregnancy. All subjects underwent brain magnetic resonance imaging (MRI) scans. We analyzed correlations between regional gray matter volumes and blood dioxin levels, and compared regional volumes between men with and without perinatal dioxin exposure using the voxel-based morphometry (VBM) tool from Statistical Parametric Mapping 12 (SPM12). Blood 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with low volume of the medial temporal pole and fusiform gyrus. Toxic equivalency (TEQ)-PCDDs were correlated with low medial temporal pole volume. However, 1,2,3,4,7,8-HxCDD was associated with high middle frontal gyrus and cerebellum volume. In men with perinatal dioxin exposure, the left inferior frontal gyrus pars orbitalis volume was significantly lower than in those without perinatal exposure. These results suggest that dioxin exposure during the perinatal period and in adulthood may alter regional brain volume, which might lead to cognitive deficits and unusual social emotional behavior in Vietnamese men living in dioxin-contaminated areas. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

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Review

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13 pages, 287 KiB

Open AccessReview

Neurodevelopmental Effects of Perinatal TCDD Exposure Differ from Those of Other PCDD/Fs in Vietnamese Children Living near the Former US Air Base in Da Nang, Vietnam

by Nghi Ngoc Tran, Tai Pham-The, Thao Ngoc Pham, Hoa Thi Vu, Khue Ngoc Luong and Muneko Nishijo

Toxics 2023, 11(2), 103; https://doi.org/10.3390/toxics11020103 - 21 Jan 2023

Cited by 1 | Viewed by 1430

Abstract

This study reports that children exposed to 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), the major toxin in Agent Orange, from the breast milk of mothers residing near the former Da Nang US air base in Vietnam may have specific alterations in higher brain functions, resulting in social [...] Read more.

This study reports that children exposed to 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), the major toxin in Agent Orange, from the breast milk of mothers residing near the former Da Nang US air base in Vietnam may have specific alterations in higher brain functions, resulting in social and communication deficits, including autism spectrum disorder (ASD). After the age of 8 years, girls with high TCDD showed increased attention deficit hyperactivity disorder (ADHD)-like behaviors and altered mirror neuron activity, which is often observed in children with ASD. However, no significant relationship between autistic traits and toxic equivalency values of polychlorinated dibenzodioxins and polychlorinated dibenzofurans (TEQ-PCDD/Fs) was found in these children. Notably, boys with high levels of TEQ-PCDD/Fs showed poor language and motor development in the first 3 years of life, although boys with high TCDD levels did not. However, at 8 years of age, boys with high TCDD showed reading learning difficulties, a neurodevelopmental disorder. These findings suggest that perinatal TCDD exposure impacts social–emotional cognitive functions, leading to sex-specific neurodevelopmental disorders—learning difficulty in boys and ADHD in girls. Future studies with a greater number of children exposed to high levels of TCDD are necessary to estimate the threshold values for neurodevelopmental effects. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

14 pages, 286 KiB

Open AccessReview

Effects of Polychlorinated Dibenzo-p-dioxins, Polychlorinated Dibenzofurans, and Dioxin-like PCBs on Teeth and Bones in Animals and Humans

by Tomoya Takiguchi, Hoa Thi Vu and Yoshikazu Nishino

Toxics 2023, 11(1), 7; https://doi.org/10.3390/toxics11010007 - 21 Dec 2022

Cited by 3 | Viewed by 1431

Abstract

Bone metabolism is regulated by endocrine systems, so people exposed to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) may suffer adverse effects on bones and teeth. We reviewed previous publications in which effects of PCDD/Fs and dioxin-like polychlorinated biphenyls on the teeth and bones of [...] Read more.

Bone metabolism is regulated by endocrine systems, so people exposed to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) may suffer adverse effects on bones and teeth. We reviewed previous publications in which effects of PCDD/Fs and dioxin-like polychlorinated biphenyls on the teeth and bones of animals and humans were found. The aim was to identify future research directions, particularly for epidemiological studies of populations exposed to PCDD/Fs in the environment. Exposure of fetuses to PCDD/Fs may affect odontogenesis, particularly enamel formation, but the effects of PCDD/Fs on bone genesis are limited to palatine bone. Exposure to PCDD/Fs in milk may affect both teeth and bones, but the effects on bones may be reversible. Exposure to high PCDD/F concentrations even during adulthood may adversely affect teeth. Exposure to PCDD/Fs may induce osteogenesis and improve bone properties because the disrupting effects of PCDD/Fs cause bone remodeling and vitamin D activation. More studies involving humans are required to investigate previously found associations between the PCDD/F concentrations humans are exposed to and biological markers for teeth and bones, including metabolites of vitamin D. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

Other

Jump to: Editorial, Research, Review

9 pages, 228 KiB

Open AccessEditor’s ChoiceSystematic Review

Research on the Relationship between Exposure to Dioxins and Cancer Incidence in Vietnam

by Tuong Phi Vuong

Toxics 2022, 10(7), 384; https://doi.org/10.3390/toxics10070384 - 11 Jul 2022

Cited by 5 | Viewed by 2356

Abstract

The aim of this literature review is to discover whether there is a relationship between exposure to dioxins and cancer incidence in the hotspot regions of Vietnam by estimating the risk ratio index. The results of the study show that the incidence of [...] Read more.

The aim of this literature review is to discover whether there is a relationship between exposure to dioxins and cancer incidence in the hotspot regions of Vietnam by estimating the risk ratio index. The results of the study show that the incidence of cancer (soft tissue sarcoma; Hodgkin’s and non-Hodgkin’s lymphoma; lung, prostate, and liver cancer) in the dioxin-exposed Vietnamese population is much higher than the results of studies published in other countries because of the high levels of dioxins in South Vietnam, where Agent Orange was sprayed during the war. Further studies on the health effects of dioxins in the Vietnamese population, including cancer incidence, should be conducted with improved research methods. Full article

(This article belongs to the Special Issue Dioxin and Dioxin-Like Compounds and Human Health)

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