Muneko Nishijo

Chubu University, Касугай, Aichi, Japan

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Publications (137)308.45 Total impact

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    ABSTRACT: We investigated the biological half-life of urinary cadmium concentration (U-Cd) based on a 22-year follow-up study after cessation of environmental Cd pollution. Spot urine samples were obtained from the inhabitants (32 men and 36 women) in the target area in 1986, 1991, 1999, 2003 and 2008. These inhabitants were divided into higher or lower baseline U-Cd group by the cut-off of 5 μg l(-1) or 5 μg g(-1) creatinine. Biological half-life of U-Cd was estimated using a linear mixed model adjusted for the baseline age. In the higher baseline U-Cd groups, the estimated half-life and 95% confidence intervals were 12.4 years (9.3-18.8 years) and 11.4 years (9.3-14.6 years) for unadjusted U-Cd in men and women, respectively. For creatinine-adjusted U-Cd, they were 16.0 years (13.0-20.7 years) and 20.4 years (16.6-26.2 years) in men and women, respectively. In the lower baseline U-Cd groups, biological half-life for unadjusted U-Cd in men was solely significant (23.4 years) and longer than the corresponding half-life in the higher baseline U-Cd group. The biological half-lives of U-Cd obtained in this study were identical with the values for U-Cd or total body burden determined by a different method.
    Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment 06/2015; DOI:10.1080/19440049.2015.1052573 · 2.34 Impact Factor
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    ABSTRACT: Bien Hoa Air Base is the largest dioxin contamination hot spot in Vietnam. In 2012, we recruited 216 mothers who were living in 10 communities around Bien Hoa Air Base and had delivered newborns at a prefecture hospital, and we investigated recent exposure levels of dioxins and nonortho PCBs in their breast milk. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD) was present at 2.6 pg/g lipid in primiparae and 2.2 pg/g lipid in multiparae. Among multiparae and total subjects, significant high prevalence of 2,3,7,8-tetraCDD ≥ 5 pg/g lipid and 2,3,7,8-tetraCDD contribution ≥ 40% were observed in mothers living in the five communities closest to Bien Hoa Air Base. The TEQ for nonortho PCBs was 1.6 pg-TEQ/g lipid for primiparae, and this was even lower than that in the unsprayed area. The length of residency was a strong factor to increase dioxins, including 2,3,7,8-tetraCDD. Residency in the five communities with the highest exposure was a specific risk factor for increased 2,3,7,8-tetraCDD in breast milk. Food intake might contribute partly to the increased levels of dioxin congeners other than 2,3,7,8-tetraCDD in breast milk. These results suggest that Bien Hoa Air Base has led to elevated 2,3,7,8-tetraCDD levels in breast milk of mothers in nearby areas even in the recent years.
    Environmental Science and Technology 05/2015; 49(9):5732-5742. DOI:10.1021/es506211p · 5.48 Impact Factor
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    ABSTRACT: 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 >5pgTCDD/g lipid. However, Phu Cat residents lived far from the air base and their samples showed lower TCDD levels, with none containing >5pgTCDD/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 (9.3pg toxic equivalents [TEQ]/g lipid) were significantly lower than the level observed in Phu Cat (14.1pgTEQ/g lipid), Thanh Khe (14.3pgTEQ/g lipid), and Son Tra (13.9pgTEQ/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. Copyright © 2014 Elsevier B.V. All rights reserved.
    Science of The Total Environment 04/2015; 511:416-422. DOI:10.1016/j.scitotenv.2014.12.083 · 4.10 Impact Factor
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    ABSTRACT: In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that urinary histidine may be a useful marker of dioxin-induced neurodevelopmental deficits and that histaminergic neurotransmission may be an important pathological contributor to dioxin-mediated neurotoxicity.
    PLoS ONE 01/2015; 10(1):e0116778. DOI:10.1371/journal.pone.0116778 · 3.23 Impact Factor
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    ABSTRACT: The aim of this study was to estimate the reference level of cadmium in rice as the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for various renal effects by applying an updated hybrid approach. The participants were 1120 men and 1274 women aged 50 years or older who lived in the environmentally exposed Kakehashi river basin for at least 30 years. As indicators of renal dysfunction, glucose, protein, aminonitrogen, metallothionein and β2 -microgrobulin in urine were measured. Cadmium concentration was determined for rice samples stored in warehouses of the farmers in all of the polluted hamlets. The BMD and BMDL that corresponded to an additional risk of 5% were calculated with background risk at a zero exposure set at 5%. The obtained BMDLs were 0.39 (aminonitrogen), 0.26 (metallothionein), 0.25 (β2 -microgrobulin) mg kg(-1) in men and 0.44 (glucose), 0.32 (protein), 0.33 (aminonitrogen), 0.28 (metallothionein) and 0.24 (β2 -microgrobulin) mg kg(-1) in women. The lowest BMDL was 0.25 and 0.24 mg kg(-1) (β2 -microgrobulin) in men and women respectively. These values were lower than the maximum level (0.4 mg kg(-1) ) determined by the Codex Alimentarius Commission, indicating that these BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 01/2015; 35(1). DOI:10.1002/jat.2982 · 3.17 Impact Factor
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    ABSTRACT: The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd on all-cause mortality in the Japanese general population. A 19-year cohort study was conducted in 1067 men and 1590 women aged 50 years or older who lived in three cadmium non-polluted areas in Japan. The subjects were divided into four quartiles based on creatinine adjusted U-Cd (µg g−1 cre). The hazard ratio (HR) and 95% confidence interval (CI) for continuous U-Cd or the quartiles of U-Cd were estimated for all-cause mortality using a proportional hazards regression.The all-cause mortality rates per 1000 person years were 31.2 and 15.1 in men and women, respectively. Continuous U-Cd (+1 µg g−1 cre) was significantly related to the all-cause mortality in men (HR 1.05, 95% CI: 1.02–1.09) and women (HR 1.04, 95% CI: 1.01–1.07). Furthermore in men, the third (1.96–3.22 µg g−1 cre) and fourth quartile (≥3.23 µg g−1 cre) of U-Cd showed a significant, positive HR (third: HR 1.35, 95% CI: 1.03–1.77, fourth: HR 1.64, 95% CI: 1.26–2.14) for all-cause mortality compared with the first quartile (<1.14 µg g−1 cre). In women, the fourth quartile of U-Cd (≥4.66 µg g−1 cre) also showed a significant HR (1.49, 95% CI 1.11–2.00) for all-cause mortality compared with the first quartile (<1.46 µg g−1 cre).In the present study, U-Cd was significantly associated with increased mortality in the Japanese general population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non-polluted areas in Japan. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 12/2014; 35(7). DOI:10.1002/jat.3077 · 3.17 Impact Factor
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    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. Methods 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. Results 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). Conclusion 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; 217(8). DOI:10.1016/j.ijheh.2014.05.001 · 3.28 Impact Factor
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    ABSTRACT: Background 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. Methods The study participants consisted of inhabitants aged 40 years or older who lived in a non-polluted area (40 men and 41 women) and in the environmentally polluted Mae Sot District (230 men and 370 women) located in northwestern Thailand. We measured urinary and blood cadmium (Cd) as markers of long-term exposure and urinary β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) as renal tubular effect markers. An updated hybrid approach was applied to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) of urinary and blood Cd for Cd-induced renal effects in these subjects. BMD and BMDL corresponding to an additional risk (BMR) of 5% were calculated with the background risk at zero exposure set to 5% after adjusting for age and smoking status. Results The estimated BMDLs of urinary Cd for renal effect markers were 6.9 for urinary β2-MG and 4.4 for NAG in men and 8.1 for β2-MG and 6.1 for NAG μg/g creatinine (Creat) in women. These BMDLs of urinary Cd (μg/g Creat) for NAG were less than the geometric mean urinary Cd in the polluted area (6.5 in men and 7.1 in women). The estimated BMDLs of blood Cd (μg/L) were 6.2 for urinary β2-MG and 5.0 for NAG in men and 5.9 for β2-MG and 5.8 for NAG in women. The calculated BMDLs were similar or less compared with the geometric mean blood Cd (μg/L) in the polluted Thai area (6.9 in men and 5.2 in women). Conclusion The BMDLs of urinary and blood Cd for renal effects were estimated to be 4.4 - 8.1 μg/g Creat and 4.4 - 6.2 μg/L in the Thai population aged ≥ 40 years old, suggesting that more than 40% of the residents were at risk of adverse renal effects induced by Cd exposure in Thailand.
    BMC Public Health 07/2014; 14(1):702. DOI:10.1186/1471-2458-14-702 · 2.32 Impact Factor
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    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; 25(4). DOI:10.1038/jes.2014.44 · 3.05 Impact Factor
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    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. DOI:10.3390/ijms15057485 · 2.86 Impact Factor
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    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 04/2014; 11(4):3661-77. DOI:10.3390/ijerph110403661 · 2.06 Impact Factor
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    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.
    Biomarkers 03/2014; 19(3). DOI:10.3109/1354750X.2014.899626 · 2.52 Impact Factor
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    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) levels17.9 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.
    Molecular Psychiatry 03/2014; 19(11). DOI:10.1038/mp.2014.18 · 15.15 Impact Factor
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    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. DOI:10.1186/1476-069X-13-18 · 2.71 Impact Factor
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    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.
    Environmental Science & Technology 02/2014; 48(6). DOI:10.1021/es404853h · 5.48 Impact Factor
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    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; 24(5). DOI:10.1038/jes.2013.73 · 3.05 Impact Factor

Publication Stats

2k Citations
308.45 Total Impact Points

Institutions

  • 2015
    • Chubu University
      Касугай, Aichi, Japan
  • 1993–2015
    • Kanazawa Medical University
      • • Department of Epidemiology and Public Health
      • • School of Nursing
      Kanazawa, Ishikawa, Japan
  • 2003
    • Chiba University
      • Graduate School of Medicine
      Chiba-shi, Chiba-ken, Japan
  • 2002
    • Kanazawa Gakuin University
      Kanazawa, Ishikawa, Japan
  • 1988
    • Toyama Medical and Pharmaceutical University
      Тояма, Toyama, Japan