[Show abstract][Hide abstract] ABSTRACT: Former U.S. air bases are dioxin contamination hotspots in Vietnam. • We determined breast milk dioxin levels in women living around three air bases. • TCDD levels were high from women living close to Bien Hoa and Da Nang air bases. • TCDD levels were not high from women living further from Phu Cat air base. • The levels of other dioxins were not elevated from women living near air bases. We determined polychlorinated dibenzodioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in breast milk of 143 primiparae living around the three most dioxin-contaminated areas of Vietnam. The women sampled lived in the vicinity of former U.S. air bases at Bien Hoa (n = 51), Phu Cat (n = 23), and Da Nang (n = 69), which are known as dioxin hotspots. Breast milk samples from Bien Hoa City, where residents live very close to the air base, showed high levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with 18% of the samples containing N 5 pg TCDD/g lipid. However, Phu Cat residents lived far from the air base and their samples showed lower TCDD levels, with none containing N5 pg TCDD/g lipid. In Da Nang, TCDD levels in mothers from Thanh Khe (close to the air base, n = 43) were significantly higher than those in mothers from Son Tra (far from the air base, n = 26), but not other PCDD and PCDF (PCDD/F) congeners. Although TCDD levels in Bien Hoa were the highest among these hotspots, levels of other PCDD/F congeners as well as the geometric mean concentration of total PCDD/F level in Bien Hoa (9.3 pg toxic equivalents [TEQ]/g lipid) were significantly lower than the level observed in Phu Cat (14.1 pg TEQ/g lipid), Thanh Khe (14.3 pg TEQ/g lipid), and Son Tra (13.9 pg TEQ/g lipid). Our findings indicated that residents living close to former U.S. air bases were exposed to elevated levels of TCDD, but not of other PCDD/F congeners.
Science of The Total Environment 04/2015; 511:416-422. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
The aim of the present study was to evaluate the dose-effect relationship between urinary cadmium (U-Cd as an index of internal Cd exposure) and mortality in a cohort of the Japanese general population.
A 19-year cohort study was conducted in 897 men and 1307 women who lived in two non-polluted areas in Japan. The subjects were categorized into four quartiles (lowest, lower, higher, highest) based on creatinine adjusted U-Cd (μg/g cre). Hazard ratio (HR) and 95% confidence interval (95%CI) of the quartiles of U-Cd for mortality was calculated using a proportional hazards regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness.
The mortality rates per 1000 person years were 27.8 and 12.5 in men and women, respectively. In men, the fourth quartile of U-Cd (≥ 2.919 μg/g cre) showed a significant, positive HR (1.50, 95%CI: 1.11-2.02) for mortality compared to the first quartile (< 1.014). In women, the fourth quartile of U-Cd (≥ 3.943 μg/g cre) also showed a significant HR (1.50, 95%CI: 1.08-2.09) for mortality compared to the first quartile (< 1.140).
The present study clarified that U-Cd was significantly associated with increased mortality, indicating the worsened life prognosis of the general population in Cd non-polluted areas in Japan. These results highlight the importance of further discussion of the health risk assessment of Cd exposure in the general population.
International Journal of Hygiene and Environmental Health 11/2014; · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to estimate the benchmark doses (BMD) for renal effects for health risk assessment of residents living in Cd-polluted and non-polluted areas in a Thai population.
BMC Public Health 07/2014; 14(1):702. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and mortality. A 19-year cohort study was conducted in 900 men and 1313 women in 1993 or 1994 who lived in two cadmium non-polluted areas in Japan. Hazard ratio (HR) and 95% confidence interval (95% CI) of urinary β2-microglobulin (β2-MG) and N-acetyl-β-glucosaminidase (NAG) for mortality were calculated using a proportional hazard regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness. Simultaneously, the dose-effect relationship between renal tubular markers and urinary cadmium at baseline was evaluated using multiple regression analyses. In men, HR was significant for β2-MG (HR corresponding to an increase of 100 μg/g cre: 1.02) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.05). In women, a significant HR was observed for β2-MG (HR corresponding to an increase of 100 μg/g cre: 1.01) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.02). Dose-effect relationships were significant for urinary cadmium and all renal tubular markers in men and women. The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium non-polluted areas in Japan.Journal of Exposure Science and Environmental Epidemiology advance online publication, 18 June 2014; doi:10.1038/jes.2014.44.
Journal of Exposure Science and Environmental Epidemiology 06/2014; · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to clarify the relationship between dioxin concentrations in breast milk and the sister chromatid exchange (SCE) frequency in women from herbicide-sprayed and non sprayed areas. Blood samples were taken from 21 women with high TCDD (tetrachlorodibenzo-p-dioxin) levels from sprayed areas, 23 women with moderate TCDD levels from sprayed areas, and 19 women from non sprayed areas to determine their SCE frequency. The SCE frequencies for the high and moderate TCDD groups from the sprayed area and for the non sprayed area group were 2.40, 2.19, and 1.48 per cell, respectively. Multiple regression analysis showed that the standardized β values for 1,2,3,6,7,8-hexaCDD (β = 0.60), 1,2,3,4,6,7,8-heptaCDD (β = 0.64), and octaCDD (β = 0.65) were higher than those for TCDD (β = 0.34) and 1,2,3,7,8-pentaCDD (β = 0.42). The adjusted R2 value for polyCDDs (R2 = 0.38) was higher than that for polyCDD toxic equivalents (TEQ (toxic equivalents); R2 = 0.23). This study therefore shows that levels of hexa-, hepta-, and octaCDD, which were previously regarded as being less toxic than TCDD, are closely related to SCE frequency and that the level of dioxin (pg/g lipid) is potentially more useful as an indicator than TEQ value for explaining SCE frequency.
International Journal of Molecular Sciences 05/2014; 15(5):7485-7499. · 2.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract A recent study found an inverse correlation between serum TCDD levels and serum testosterone in the US veterans, while there is little known on the dioxin and steroid hormones about Vietnamese men. We collected blood samples from 48 men who had resided in a hotspot when exposure happened and 38 men in a non-sprayed area. Some steroid hormones levels showed significant differences between two areas. There were no correlations between steroid hormones and dioxin TEQ, after ajusting for age and other factors. Our findings indicate that steroid hormones of Vietnamese men did not correlate with dioxin TEQ in two areas.
[Show abstract][Hide abstract] ABSTRACT: Dioxin levels in the breast milk of mothers residing near a contaminated former airbase in Vietnam remain much higher than in unsprayed areas, suggesting high perinatal dioxin exposure for their infants. The present study investigated the association of perinatal dioxin exposure with autistic traits in 153 3-year-old children living in a contaminated area in Vietnam. The children were followed up from birth using the neurodevelopmental battery Bayley-III. The high-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed groups (3.5 pg per g fat) showed significantly higher Autism Spectrum Rating Scale (ASRS) scores for both boys and girls than the mild-TCDD exposed groups, without differences in neurodevelopmental scores. In contrast, the high total dioxin-exposed group, indicated by polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs)-the toxic equivalents (TEQ) levels17.9 pg-TEQ per g fat, had significantly lower neurodevelopmental scores than the mild-exposed group in boys, but there was no difference in the ASRS scores. The present study demonstrates a specific impact of perinatal TCDD on autistic traits in childhood, which is different from the neurotoxicity of total dioxins (PCDDs/Fs).Molecular Psychiatry advance online publication, 18 March 2014; doi:10.1038/mp.2014.18.
[Show abstract][Hide abstract] ABSTRACT: We aimed to investigate the mortality and causes of deaths of inhabitants with renal dysfunction induced by cadmium (Cd) exposure caused by heavy environmental contamination.
We conducted a 26-year follow-up survey targeting 7529 inhabitants of the Cd-polluted Jinzu River basin and 2149 controls from non-polluted areas who participated in urinary examinations for proteinuria and glucosuria conducted in 1979 to 1984. When the residents were divided into 4 groups, no finding group, glucosuria group, proteinuria group, glucoproteinuria group, mortality risk ratios for all and specific causes of these groups in the polluted area were compared with that of controls without glucosuria and/or proteinuria after adjustments for age at baseline, smoking status, and history of hypertension using Cox's proportional hazard model.
The mortality risk ratios for all causes of proteinuria and glucoproteinuria in men and glucosuria, proteinuria, and glucoproteinuria in women of the polluted areas significantly increased compared with those of the controls with no urinary findings. Respiratory, renal, and cardiovascular diseases and diabetes in men, and all diseases except cerebrovascular diseases in women contributed toward an increased mortality of exposed glucoproteinuria groups, which involved chronic Cd toxicosis with renal tubular dysfunction. In women, the mortality risks for cancer of the colon and rectum, uterus and kidney and urinary tract were significantly higher in the exposed proteinuria and glucoproteinuria groups, suggesting associations between renal damage and cancer risk. In exposed women, the no finding group and glucoproteinuria group also showed increased mortality from ischemic heart diseases, indicating that all exposed women may be at risk for ischemic heart diseases. Although the control glucosuria and/or proteinuria group also showed high mortality for diabetes and renal diseases, the increased risk ratio for renal disease mortality was much higher in exposed subjects with urinary findings, particularly in women.
These findings indicate that inhabitants with renal effects caused by Cd exposure had a poor life prognosis over long-term observation in both genders. Particularly in women, renal tubular dysfunction indicated by glucoproteinuria may increase mortality from cancer, ischemic heart diseases, and renal diseases.
Environmental Health 03/2014; 13(1):18. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have found elevated dioxin levels inside some US military former air bases in Vietnam, known as hotspots. Many studies of Agent Orange have been done in the U.S. veterans; however, there is little known about Vietnamese men. In 2010, we collected blood samples from 97 men in a hotspot and 85 men in an unsprayed area in Northern Vietnam. Serum concentrations of not only TCDD but also other dioxins (PCDDs), furans (PCDFs), and non-ortho polychlorinated biphenyls (PCBs) were significantly higher in the hotspot than in the unsprayed area. In the hotspot, three sub-areas were demarcated, based on their proximity to the air base. The total toxic equivalents (TEQ) of PCDDs/PCDFs+PCBs was 41.7 pg/g lipid in the area closest to the air base, while it was around 29 pg/g lipid in the other two sub-areas. In the unsprayed area, the dioxin levels were no different between men who went to the South during the Vietnam War and those who remained in the North, with TEQs PCDDs/PCDFs+PCBs of around 13.6 pg/g lipid. Our findings suggested that people living close to the former US air bases might have been exposed to both Agent Orange and other sources of dioxin-like compounds.
[Show abstract][Hide abstract] ABSTRACT: First, the urinary metabolic profiling by gas chromatography-mass spectrometry (GC-MS), was performed to compare ten cadmium (Cd) toxicosis cases from a Cd-polluted area in Mae Sot (Thailand) with gender-matched healthy controls. Orthogonal partial list square-discrimination analysis was used to identify new biomarker candidates in highly Cd exposed toxicosis cases with remarkable renal tubular dysfunction. The results of the first step of this study showed that urinary citrate was a negative marker and myo-inositol was a positive marker for Cd toxicosis in Thailand. In the second step, we measured urinary citrate in the residents (168 Cd-exposed subjects and 100 controls) and found significantly lower levels of urinary citrate and higher ratios of calcium/citrate and magnesium/citrate, which are risk factors for nephrolithiasis, in highly Cd-exposed residents. Additionally, this inverse association of urinary citrate with urinary Cd was observed after adjustment for age, smoking and renal tubular dysfunction, suggesting a direct effect of Cd on citrate metabolism. These results indicate that urinary citrate is a useful biomarker for the adverse health effects of Cd exposure in a Thai population with a high prevalence of nephrolithiasis.
International Journal of Environmental Research and Public Health 01/2014; 11(4):3661-77. · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study looked to identify determinants of exposure to dioxin in breast milk from breast-feeding women in a hot spot of dioxin exposure in Vietnam. Breast milk was collected from 140 mothers 1 month after delivery. The risk factors investigated included length of residency, drinking of well water and the frequency of animal food consumption. Cluster analysis was performed to identify dietary patterns of fish and meat portions, fish variety and egg variety. Residency, age and parity were clearly associated with increased dioxin levels. Drinking well water and the consumption of marine crab and shrimps were related to higher levels of furans in breast milk. The consumption of quail eggs also appeared to be associated with increased levels of some dioxin isomers in this area. Some mothers who ate no or less meat than fish and mothers who consumed more freshwater fish than marine fish had lower levels of dioxins in their breast milk. However, the type of water and the eating habits of mothers contributed only partly to the increased dioxin levels in their breast milk; the length of residency was the most important risk factor associated with increased dioxin body burdens of mothers.Journal of Exposure Science and Environmental Epidemiology advance online publication, 23 October 2013; doi:10.1038/jes.2013.73.
Journal of Exposure Science and Environmental Epidemiology 10/2013; · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dioxin (PCDDs+PCDFs), is one of the most toxic chemical substances known. Although it is suspected to cause endocrine disruption, very few epidemiological studies into its effects on human steroid hormones have been performed. The aim of this study is to elucidate the association of dioxin exposure with steroid hormone levels in the saliva and serum of lactating Vietnamese women. Two areas, namely Phu Cat (hot-spot) and Kim Bang (non-exposed area), were selected for study. The study subjects consisted of 51 and 58 lactating women, respectively. Saliva, blood and breast milk samples were collected from subjects in both areas. Cortisol, cortisone, dehydroepiandrosterone, androstenedione, estrone and estradiol levels in serum and saliva were determined by liquid-chromatography/tandem mass spectrometry (LC-MS/MS); dioxin levels in breast milk were measured by gas-chromatography-mass spectrometry (GC-MS). The dioxin concentration in breast milk from women in the hot-spot area was 3-4 times higher than in women from the non-exposed area. Good correlations were found between the levels of six steroid hormones in saliva and those in serum, respectively. Salivary and serum cortisol and cortisone levels in women from the hot spot were significantly higher than in those from the non-exposed area (P<0.001) and those in all subjects were positively associated with dioxin levels in Vietnamese women (P<0.01). These results suggest that dioxin influences steroidogenesis in humans. Saliva sample can be used for hormone analysis and are therefore excellent specimens in epidemiological studies.
European Journal of Endocrinology 10/2013; · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies have reported that maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces socioemotional and cognitive disturbances in rat offspring. In the present study, the effects of maternal TCDD exposure on putative inhibitory interneurons were investigated in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), hippocampus (HP), and superior colliculus (SC) in rat offspring. Dams were given TCDD (1.0μg/kg) on gestational day 15. When offspring rats reached adulthood (14 weeks old), parvalbumin (PV)- and calbindin (Calb)-immunoreactive neurons were immunohistochemically investigated. The histological investigations indicated that the mean area of the mPFC had increased, whereas the mean area of the SC decreased in the exposed male rats. In the exposed female rats, the mean SC area increased. Furthermore, the number and area of PV-immunoreactive neurons increased in the mPFC of the female exposed rats. In contrast, the number of PV-immunoreactive neurons in the BLA, HP, and SC decreased in the male and female exposed rats. The number of Calb-immunoreactive neurons decreased in the HP of the male and female exposed rats and the SC of the female exposed rats. Because PV- and Calb-immunoreactive neurons, which are putatively GABAergic, have been implicated in various higher brain functions, the effects of TCDD on socioemotional and cognitive functions might be mediated partly through these alterations in PV- and Calb-immunoreactive neurons in these areas.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: The aim of this study was to explore the impact of Agent Orange exposure for prostate cancer with a comparison of the prostate specific antigen (PSA) levels between a hotspot and a non-sprayed area. METHODS: The study was conducted in Phu Cat district (hotspot) and Kim Bang district (non-sprayed), with a total of 101 men in the hotspot and 97 men in the non-sprayed area older than 50 years of age. About 5 mL of whole blood and a health status questionnaire were collected from each subject in August 2009-2011. RESULTS: The mean age of the subjects in the hotspot (68.0 years old) was significantly higher than that of those in the non-sprayed area (65.0 years old). No significant difference was found between the hotspot area (0.93 ng/mL) and the non-sprayed area (0.95 ng/mL) in terms of PSA levels. Likewise, this was not statistically significant after adjusting for age. The prevalence of high PSA levels (>3 ng/mL) did not differ significantly between the hotspot (14 men; 13.9 %) and non-sprayed area (9 men; 9.3 %). No significant difference was found between the hotspot area and the non-sprayed area in terms of occupation (farmer and others). In control subjects, no significant difference was found between the PSA levels in subjects exposed to Agent Orange and non-exposed subjects. Likewise, no significant difference was found between the PSA levels of combatants and civilians. CONCLUSION: The PSA levels were not significantly different between the hotspot and the non-sprayed area.
Environmental Health and Preventive Medicine 03/2013;
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Previous U.S. population modeling studies have reported that urinary cadmium (Cd) excretion patterns differ with age, sex, and dietary exposure, and associations between Cd exposures and health outcomes also have differed by age and sex. Therefore, it is important to test models used to estimate Cd exposures across an expanded Cd exposure range. OBJECTIVES: Estimate relative Cd exposures from both diet and smoking in low- and high-exposure scenarios to provide data for improving risk assessment calculations. METHODS: We used a Cd toxicokinetic-based model to estimate Cd exposures based on urinary Cd levels measured for 399 persons in a low-exposure (Bangkok) area and 6747 persons in a high-exposure (Mae Sot) area in Thailand. RESULTS: In Bangkok, we estimated dietary Cd exposures of 50-56 µg/day for males and 21-27 µg/day for females 20 to 59 years of age who never smoked. In Mae Sot, we estimated dietary Cd exposures of 188-224 µg/day for males and 99-113 µg/day for females. In Bangkok, we estimated Cd exposures from smoking of 5.5-20.4 µg/day for male smokers 20-59 years of age. In Mae Sot, we estimated Cd exposures from smoking of 9.8-26µg/day for male heavy smokers and 26µg/day for female heavy smokers. CONCLUSION: This study provides estimates of Cd exposures from diet and smoking in low- and high-exposure scenarios. Our findings suggest a relatively small safety margin between the established tolerable Cd reference exposure of 62μg/day and exposure levels previously associated with evidence of kidney and bone effects in Mae Sot residents, where dietary Cd exposures among women were only 1.6- to 2.1-times the reference value.
Environmental Health Perspectives 02/2013; · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: Dioxin levels in the breast milk of mothers residing near hot spots of dioxin contamination areas in South Vietnam remain much higher than in unsprayed areas, suggesting that fetuses and breast-fed infants may be exposed to high levels of dioxins. The present study investigated the association of infant neurodevelopment in early infancy and dioxin exposure during the perinatal period. METHODS: The study involved 216 mother-infant pairs living near the Da Nang airbase, a dioxin contaminated area in Vietnam. Mothers and infants were followed from birth until infants were 4 months old. Dioxin levels in breast milk were measured to estimate the perinatal dioxin exposure, including the infant daily dioxin intake (DDI) via breastfeeding. Infant neurodevelopmental parameters, including cognitive, language and motor domains were assessed at approximately 4 months using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). RESULTS: The level of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated dibenzo-p-dioxins/furans-toxic equivalents in breast milk and the infant DDI showed significant inverse correlations with neurodevelopmental scores. When the subjects were divided into four groups according to dioxin levels in breast milk, the moderate and high DDI groups had significantly lower cognitive, composite motor and fine motor scores, and the high polychlorinated dibenzo-p-dioxins/furans-toxic equivalents group had significantly lower fine motor score than the low exposure group. For all domains, neurodevelopmental scores were decreased with increase in the level of 2,3,7,8-tetrachlorodibenzo-p-dioxin. CONCLUSION: The present study demonstrates a considerable impact of perinatal dioxin exposure on neurodevelopment in 4-month-old infants living in contaminated areas in Vietnam.
Occupational and environmental medicine 02/2013; · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Effects of dioxins on cognitive functions were reported in previous studies conducted in humans and animals. In the present study, we investigated the influence of dioxin exposure during pregnancy on social interaction and on the activity of offspring, which are related to neurodevelopmental disturbances. In addition, we analyzed neurochemical alterations of the limbic system of rat brains to suggest one mechanism of dioxin effects on brain function. We believe that this manuscript is suitable for publication in "Environmental Health Insights" because it provides an interesting topic for a wide global audience. To clarify the relationships between maternal dioxin exposure and socioemotional functions of rat offspring, dams were given TCDD (1.0 μg/kg) on gestational day 15. Social interactions and forced swimming time were compared between TCDD-exposed and control offspring in each gender. Frequency and duration of locomotion were higher, and durations per one behavior of proximity and social contact were significantly lower in the exposed males, while only the duration of proximity was lower in the exposed females. Forced swimming time on the first day was significantly longer in the exposed males. In the limbic system of the rat brain, the levels and/or activity of CaMKIIα were decreased in males and were increased in females in the exposed offspring. These results suggest that prenatal TCDD exposure induces hyperactivity and socioemotional deficits, particularly in the male offspring due to alterations in CaMKIIα activity in the limbic system of the brain.