Jun Yoshinaga

The University of Tokyo, Edo, Tōkyō, Japan

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Publications (113)196.02 Total impact

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    ABSTRACT: The levels of 25 elements in house dust collected from 100 general Japanese residences were measured. Factor analysis was applied on the multi-element data to explore source of Pb (median concentration 49.1 mg/kg) in house dust. Six factors were extracted and Pb was found to have great loading on the fifth factor with Sb and Sn, suggesting solder (Sn), and plastic and metals (Sb) may be the sources of Pb in the house dust of Japanese residences. No significant loading was found on soil-related factors indicating non-significant contribution of Pb in track-in soil. Seven heavy metals (Cd, Cu, Mo, Pb, Sb, Sn, and Zn) were found in house dust at >10 times more condensed than crustal abundance. Health risk of these elements to children via the ingestion of house dust was estimated based on the comparison with tolerable daily intake and found to be non-significant for most of the elements.
    Environmental Pollution 03/2014; 189C:223-228. · 3.73 Impact Factor
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    ABSTRACT: The associations between serum levels of reproductive hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, sex hormone-binding globulin, inhibin B and calculated free testosterone) and urinary metabolite concentration of pyrethroid insecticides [3-phenoxybenzoic acid (3-PBA)] were explored in 322 male university students in suburban Tokyo. The subjects constituted part of a large cross-sectional survey on the reference value of semen quality of Japanese men. Urinary 3-PBA was detectable in 91% of the subjects demonstrating ubiquitous exposure among the general population. However, there were no associations between urinary 3-PBA and serum hormone levels. This result was inconsistent with those reported in China and the USA for subjects who had similar levels of urinary 3-PBA to the present subjects. One of the possible reasons of the inconsistency might be different composition of pyrethroid insecticides to which the subjects were exposed; 3-PBA is a common metabolite of a number of pyrethroids and thus lacks specificity to compounds that may have different potentials of reproductive toxicity. Another reason might be related to the fact that our subjects were university students who were not aware of their own fertility, whereas the previous study subjects were infertility patients. However, the multiple regression models could explain only a limited fraction of total variance in serum levels of hormones. Identification of other contributors is warranted.
    Andrology. 03/2014;
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    ABSTRACT: The levels of 25 elements in house dust collected from 100 general Japanese residences were measured. Factor analysis was applied on the multi-element data to explore source of Pb (median concentration 49.1 mg/kg) in house dust. Six factors were extracted and Pb was found to have great loading on the fifth factor with Sb and Sn, suggesting solder (Sn), and plastic and metals (Sb) may be the sources of Pb in the house dust of Japanese residences. No significant loading was found on soil-related factors indicating non-significant contribution of Pb in track-in soil. Seven heavy metals (Cd, Cu, Mo, Pb, Sb, Sn, and Zn) were found in house dust at >10 times more condensed than crustal abundance. Health risk of these elements to children via the ingestion of house dust was estimated based on the comparison with tolerable daily intake and found to be non-significant for most of the elements.
    Environmental Pollution. 01/2014; 189:223–228.
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    ABSTRACT: The purpose of this study was to investigate possible associations between concentrations of hydroxylated PCBs (OH-PCBs) and PCBs in the serum of women in the first trimester of pregnancy and thyroid hormone levels and body size of newborn infants in 79 mother-neonate pairs. We measured 16 OH-PCB isomers and 29 PCB isomers in the serum of Japanese women sampled at 11.1±1.9 weeks of gestation. The concentrations of free thyroxine (fT4) and thyroid stimulating hormone (TSH) were measured in whole blood spots on filter papers sampled from the neonates. Dietary and lifestyle information of the mothers were obtained by self-administered questionnaires. Geometric mean (GM) concentrations of the sum of 16 OH-PCB isomers and of 29 PCB isomers were 1.2×10(2)pg/g wet wt. and 69ng/g lipid wt., respectively, in maternal serum. The GM concentrations of neonatal fT4 and TSH were 2.21ng/dL and 1.37μIU/mL, respectively. Multiple regression analysis was performed using measures of neonatal thyroid hormones as dependent variable and serum levels of OH-PCBs/PCBs and other potential covariates (age, pre-pregnancy weight, smoking status, etc.) as independent variables. The results demonstrated a significant positive association between the concentrations of some OH-PCB isomers and that of neonatal TSH. There were no significant associations between levels of PCBs and neonatal fT4, or between OH-PCBs/PCBs and body size of neonates. We conclude that exposure to/body burden of OH-PCBs, but not PCBs, at environmental levels during the first trimester of pregnancy can affect neonatal thyroid hormone status.
    International journal of hygiene and environmental health 11/2013; · 2.64 Impact Factor
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    ABSTRACT: The present study aimed at assessing the relationship between exposure to pyrethroid insecticides and semen quality in 323 university students recruited in a population-based manner in Metropolitan Tokyo. Urinary concentrations of pyrethroid insecticide metabolite, 3-phenoxybenzoic acid (3-PBA), were measured by LC/MS/MS and semen parameters were measured by following internationally harmonized protocols. Median urinary 3-PBA concentration was 0.641ng/mL (specific gravity-adjusted, n=322). Median values of semen volume, sperm concentration, motility, total number of sperm, and total number of motile sperm were 2.5mL, 56×10(6)/mL, 61%, 141×10(6), and 82×10(6), respectively. Urinary concentration of 3-PBA was not selected as significant in multiple regression models indicating, in contrast to previous findings, that environmental exposure to pyrethroid insecticides did not affect semen quality. This inconsistency may be related to exposure to different pyrethroid insecticides and/or levels of exposure as well as to survey design (hospital-vs population-based subject recruitment).
    Reproductive Toxicology 11/2013; · 3.14 Impact Factor
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    ABSTRACT: Possible association between environmental exposure to pyrethroid insecticides and serum thyroid-related measures was explored in 231 pregnant women of 10-12 gestational weeks recruited at a university hospital in Tokyo during 2009-2011. Serum levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and thyroid biding globulin (TBG) and urinary pyrethroid insecticide metabolite (3-phenoxybenzoic acid, 3-PBA) were measured. Obstetrical information was obtained from medical records and dietary and lifestyle information was collected by self-administered questionnaire. Geometric mean concentration of creatinine-adjusted urinary 3-PBA was 0.363 (geometric standard deviation: 3.06)μg/g cre, which was consistent with the previously reported levels for non-exposed Japanese adult females. The range of serum fT4, TSH and TBG level was 0.83-3.41ng/dL, 0.01-27.4μIU/mL and 16.4-54.4μg/mL, respectively. Multiple regression analysis was carried out by using either one of serum levels of thyroid-related measures as a dependent variable and urinary 3-PBA as well as other potential covariates (age, pre-pregnancy BMI, parity, urinary iodine, smoking and drinking status) as independent variables: 3-PBA was not found as a significant predictor of serum level of thyroid-related measures. Lack of association may be due to lower pyrethroid insecticide exposure level of the present subjects. Taking the ability of pyrethroid insecticides and their metabolite to bind to nuclear thyroid hormone (TH) receptor, as well as their ability of placental transfer, into consideration, it is warranted to investigate if pyrethroid pesticides do not have any effect on TH actions in fetus brain even though maternal circulating TH level is not affected.
    Environmental Research 10/2013; · 3.24 Impact Factor
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    ABSTRACT: The concentrations of arsenic (As) species in 19 food composites prepared from 159 food items purchased in Shizuoka city, Japan, were determined (1) to estimate total daily intake of inorganic As (InAs) and some organic As species and (2) to determine food contributing to total daily InAs intake. As analysis included extraction of As species with a synthetic gastric juice (0.07 mol/L HCl + 0.01 % pepsin) from food composite and high-performance liquid chromatography-high efficiency photo-oxidation-hydride generation-inductively coupled plasma mass spectrometry. InAs was detected in 9 of 19 food composites at a concentration of 0.423-450 ng As/g fresh-weight. Daily intake of InAs from cereals was greatest (13 μg/person/day) followed by algae (5.7 μg/person/day), and the intake from the two categories constituted 90 % of the total daily InAs intake of adults (21 μg/person/day on a bioaccessible-fraction basis and 24 μg/person/day on a content basis). Analysis of individual food items showed that rice and hijiki contributed virtually 100 % of InAs from cereals and algae, respectively. The present survey indicated that InAs from rice and hijiki consumption contributed to total daily InAs intake and consequently to significant cancer risk of the general Japanese population. Daily intake of some organic forms of As and their contributing food categories was also estimated.
    Archives of Environmental Contamination and Toxicology 08/2013; · 2.01 Impact Factor
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    ABSTRACT: Objectives: The lead content of excavated bone samples from archaeological sites in Hokkaido was measured to obtain insight into the source of human lead contamination known in the historic Japanese Edo era. Methods: Fifty-seven rib samples excavated from 11 sites of five different eras in Hokkaido were analyzed for lead (Pb), calcium (Ca), and iron (Fe) contents by ICP mass spectrometry and ICP emission spectrometry. Results: The Pb/Ca ratio (mg Pb/kg Ca) was low (approximately 2.0) and constant from the Jomon (approximately 5000 BP) to the Satsumon (approximately 750 BP) eras; however, its median increased to 11 in the Modern era. This elevation of Pb/Ca ratio in the bone samples from sites of the Modern era was not considered to be due to a greater bone contamination with soil particles because of similar Fe concentrations in the bone samples from this era to those in other eras. This historic trend of Pb/Ca ratio was similar to that observed in other parts of Japan. The elevated Pb/Ca ratio in the bone samples excavated from sites in the Modern era in other parts of Japan, that is, Edo era, has been ascribed to the usage of face powder containing Pb; however, people inhabiting Hokkaido in those days, the Ainu, were not considered to have the custom of using face powder. Conclusions: Contamination source(s) other than face powder was postulated in the Modern era of both Hokkaido and other parts of Japan.
    Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) 01/2013; 68(1):53-7.
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    ABSTRACT: OBJECTIVES: The purpose of this study was to investigate the associations between serum concentrations of hydroxylated PCBs (OH-PCBs) and PCBs and measures of thyroid hormone status of Japanese pregnant women. METHODS: The concentrations of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroxine binding globulin (TBG) as well as 16 OH-PCB isomers and 29 PCB isomers were analyzed in the serum of 129 women sampled in the first trimester of gestation. Dietary and lifestyle information of the subjects was obtained by self-administered questionnaire. Multiple regression analysis was performed using measures of thyroid hormones as the dependent variable and serum levels of OH-PCBs/PCBs, urinary iodine concentration, and other potential covariates (age, BMI, smoking, etc.) as independent variables. RESULTS: Geometric mean (GM) concentration of the sum of 16 isomers of OH-PCBs was 120 pg/g wet wt. and that of 29 isomers of PCBs was 68 ng/g lipid wt., respectively, in the serum of the subjects. Iodine nutrition was considered adequate to high from urinary iodine level (GM, 370 μg/g creatinine). The mean concentration of TSH, fT4 and TBG was 1.34 ± 1.37 μIU/mL, 1.22 ± 0.16 ng/dL and 33.0 ± 6.4 μg/mL, respectively, with a small number of subjects who were outside the reference range. Multiple regression analysis revealed that serum concentrations of OH-PCBs/PCBs were not significantly associated with any of the measures of thyroid hormone status. CONCLUSIONS: Exposure/body burden of OH-PCBs and PCBs at environmental levels does not have a measurable effect on thyroid hormones.
    Environmental Health and Preventive Medicine 09/2012;
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    ABSTRACT: Thalidomide is increasingly used in anticancer and anti-inflammation therapies. However, it is known for its teratogenicity and ability to induce peripheral neuropathy, although the mechanisms underlying its neurological effect in humans are unclear. In this study, we investigated the effect of thalidomide on the metabolism and neuronal differentiation of human neural progenitor cells. We found that levels of tyrosine, phenylalanine, methionine and glutathione, which are involved in dopamine and methionine metabolism, were decreased following thalidomide treatment. Morphological analysis revealed that treatment with 100nM thalidomide, which is much lower than clinical doses, significantly decreased the number of dopaminergic (tyrosine hydroxylase-positive) neurons, compared with control cells. Our results suggest that these adverse neurological effects of thalidomide should be taken into consideration prior to its use for the treatment of neurodegenerative and other diseases.
    NeuroToxicology 09/2012; 33(5):1375-80. · 2.65 Impact Factor
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    ABSTRACT: Zinc (Zn) deficiency in utero has been shown to cause a variety of disease states in children in developing countries, which prompted us to formulate the hypothesis that fetal epigenetic alterations are induced by zinc deficiency in utero. Focusing on metallothionein (MT), a protein that contributes to Zn transport and homeostasis, we studied whether and how the prenatal Zn status affects gene expression. Pregnant mice were fed low-Zn (IU-LZ, 5.0 μg Zn/g) or control (IU-CZ, 35 μg Zn/g) diet ad libitum from gestation day 8 until delivery, with a regular diet thereafter. Bisulfite genomic sequencing for DNA methylation and chromatin immunoprecipitation assay for histone modifications were performed on the MT2 promoter region. We found that 5-week-old IU-LZ mice administered cadmium (Cd) (5.0 mg/kg b.w.) have an elevated abundance of MT2 mRNA compared with IU-CZ mice. Alteration of histone modifications in the MT2 promoter region having metal responsive elements (MREs) was observed in 1-day-old and 5-week-old IU-LZ mice compared with IU-CZ mice. In addition, prolongation of MTF1 binding to the MT2 promoter region in 5-week-old IU-LZ mice upon Cd exposure is considered to contribute to the enhanced MT2 induction. In conclusion, we found for the first time that Zn deficiency in utero induces fetal epigenetic alterations and that these changes are being stored as an epigenetic memory until adulthood.
    The Journal of nutritional biochemistry 08/2012; · 4.29 Impact Factor
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    ABSTRACT: Urinary excretion of free and total (free plus conjugated) forms of methyl, ethyl, n-propyl and n-butyl parabens (MP, EP, PP and BP, respectively) and their metabolite p-hydroxybenzoic acid were measured for 111 pregnant Japanese women. Frequent detection of parabens and their metabolite indicated that exposure takes place daily for pregnant Japanese women. The estrogenic potency of PP was 20 times higher than those of the other 3 parabens for the present subjects when both abundance in the urine and the relative estrogenic activity of each compound was considered. Detection of free parabens suggested dermal exposure, probably from their inclusion in personal care products. No statistical association was found between the anogenital index (birth weight-adjusted AGD) of male offspring and the concentrations of any parabens in the urine of the mothers suggesting that the parabens were not apparently estrogenically active at the exposure level of the present subjects.
    Reproductive Toxicology 07/2012; · 3.14 Impact Factor
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    ABSTRACT: We hypothesized that single-nucleotide polymorphisms (SNPs) of genes involved in environmental endocrine disruptors (EEDs) metabolism might influence the risk of male genital malformations. In this study, we explored for association between 384 SNPs in 15 genes (AHR, AHRR, ARNT, ARNT2, NR1I2, RXRA, RXRB, RXRG, CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP3A4, CYP17A1 and CYP19A1) and risk of cryptorchidism (CO) and hypospadias (HS) in 334 Japanese (JPN) males (141 controls, 95 CO and 98 HS) and 187 Italian (ITA) males (129 controls and 58 CO). In the JPN study group, five SNPs from ARNT2 (rs2278705 and rs5000770), CYP1A2 (rs2069521), CYP17A1 (rs4919686) and NR1I2 (rs2472680) were significantly associated at both allelic and genotypic levels with risk of at least one genital malformation phenotype. In the ITA study group, two SNPs in AHR (rs3757824) and ARNT2 (rs1020397) were significantly associated with risk of CO. Interaction analysis of the positive SNPs using multifactor dimensionality reduction demonstrated that synergistic interaction between rs2472680, rs4919686 and rs5000770 had 62.81% prediction accuracy for CO (P=0.011) and that between rs2069521 and rs2278705 had 69.98% prediction accuracy for HS (P=0.001) in JPN population. In a combined analysis of JPN and ITA population, the most significant multi-locus association was observed between rs5000770 and rs3757824, which had 65.70% prediction accuracy for CO (P=0.055). Our findings indicate that genetic polymorphisms in genes involved in EED metabolism are associated with risk of CO and HS.
    Journal of Human Genetics 05/2012; 57(7):434-41. · 2.37 Impact Factor
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    ABSTRACT: The daily dietary intake of inorganic arsenic (InAs) and some of organic arsenic (OrAs) species of Japanese subjects were estimated by determining the concentrations of As species in two different sets of total diet sample: duplicated diet samples collected from 25 subjects in Japan and a certified reference material with total diet matrix (NIES CRM No. 27 Typical Japanese Diet, TJD). The concentration of InAs and OrAs in diet samples were determined by LC-ICP-MS using a photo-oxidation and hydride generation system. The median intake of InAs for the 25 subjects was 3.8 μg day(-1) (2.0-57 μg day(-1)) and intake of 27 μg day(-1) was estimated from TJD. The median intake of MMA, DMA and TMAsO were <0.18, 1.1 and <0.053 μg day(-1) for the 25 subjects and that of MMA, DMA, AB and TMAsO was estimated to be 3.9, 11, 140 and 5.9 μg day(-1), respectively, based on TJD analysis. On the basis of InAs intakes estimated and the oral slope factor of the US EPA and Health Canada, excess cancer risk was estimated to exceed acceptable level. Cancer risk posed by the dietary InAs of the general Japanese may not be negligible.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2012; 50(8):2663-7. · 2.99 Impact Factor
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    ABSTRACT: The establishment of more efficient in vitro approaches has been widely acknowledged as a critical need for toxicity testing. In this study, we examined the effects of methylmercury (MeHg), which is a well-known developmental neurotoxicant, in two neuronal differentiation systems of mouse and human embryonic stem cells (mESCs and hESCs, respectively). Embryoid bodies were generated from gathering of mESCs and hESCs using a micro-device and seeded onto ornithine-laminin-coated plates to promote proliferation and neuronal differentiation. The cells were exposed to MeHg from the start of neuronal induction until the termination of cultures, and significant reductions of mESCs and hESCs were observed in the cell viability assays at 1,10,100 and 1000nM, respectively. Although the mESC derivatives were more sensitive than the hESC derivatives to MeHg exposure in terms of cell viability, the morphological evaluation demonstrated that the neurite length and branch points of hESC derivatives were more susceptible to a low concentration of MeHg. Then, the mRNA levels of differentiation markers were examined using quantitative RT-PCR analysis and the interactions between MeHg exposure and gene expression levels were visualized using a network model based on a Bayesian algorithm. The Bayesian network analysis showed that a MeHg-node was located on the highest hierarchy in the hESC derivatives, but not in the mESC derivatives, suggesting that MeHg directly affect differentiation marker genes in hESCs. Taken together, effects of MeHg were observed in our neuronal differentiation systems of mESCs and hESCs using a combination of morphological and molecular markers. Our study provided possible, but limited, evidences that human ESC models might be more sensitive in particular endpoints in response to MeHg exposure than that in mouse ESC models. Further investigations that expand on the findings of the present paper may solve problems that occur when the outcomes from laboratory animals are extrapolated for human risk evaluation.
    Toxicology Letters 04/2012; 212(1):1-10. · 3.15 Impact Factor
  • Jun Yoshinaga
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    ABSTRACT: Lead has long been known to be a neurotoxic heavy metal, particularly in the context of occupational health. However, its adverse effect on the cognitive development of children at lower exposure levels has only recently received attention. Although the exposure level of contemporary Japanese children is among the lowest in the world, it is desirable to reduce exposure as much as reasonably possible due to the absence of a threshold of exposure for adverse effects. In this review, information on lead levels in milieus of our proximate environment, such as the atmosphere, drinking water, soil, house dust, diet and others, of contemporary Japan was compiled with the aim of updating our knowledge on lead distribution. Monitoring data demonstrates that lead concentrations in the atmosphere and lead intake from food consumption have decreased substantially from the 1970s. Lead was hardly detectable in tap water in a recent nation-wide monitoring survey. To the contrary, elevated lead concentrations were detected in surface soil and house dust in one of the studies on daily exposure to lead from all potential sources, and both of these sources were regarded by the authors as significant contributors of lead exposure to general Japanese children. A similar study indicated that diet is the sole major source of lead for Japanese children. A significant difference was present in the estimated dietary lead intake levels in different studies, resulting in significant discrepancies in the current knowledge on lead in our environment. Further studies are warranted to identify the major source(s) of lead exposure in Japanese children in order to establish an effective countermeasure to reduce lead exposure to children.
    Environmental Health and Preventive Medicine 04/2012;
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    ABSTRACT: The carcinogenic activity of bisphenol A (BPA) is responsible for stimulating growth in estrogen-dependent breast cancer tissues, cell lines and rodent studies. However, it is not fully understood how this compound promotes mammary carcinogenesis. In our study, we examined the effect of BPA on cellular proliferation and senescence in human mammary epithelial cells (HMEC). Exposure to BPA for 1 week at the early stage at passage 8 increased the proliferation and sphere size of HMEC at the later stage up to passage 16, suggesting that BPA has the capability to modulate cell growth in breast epithelial cells. Interestingly, the number of human heterochromatin protein-1γ positive cells, which is a marker of senescence, was also increased among BPA-treated cells. Consistent with these findings, the protein levels of both p16 and cyclin E, which are known to induce cellular senescence and promote proliferation, respectively, were increased in BPA-exposed HMEC. Furthermore, DNA methylation levels of genes related to development of most or all tumor types, such as BRCA1, CCNA1, CDKN2A (p16), THBS1, TNFRSF10C and TNFRSF10D, were increased in BPA-exposed HMEC. Our findings in the HMEC model suggested that the genetic and epigenetic alterations by BPA might damage HMEC function and result in complex activities related to cell proliferation and senescence, playing a role in mammary carcinogenesis.
    Cancer biology & therapy 03/2012; 13(5):296-306. · 3.29 Impact Factor
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    Cancer biology & therapy 01/2012; · 3.29 Impact Factor
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    ABSTRACT: We hypothesized that polymorphic differences among individuals might cause variations in the effect that environmental endocrine disruptors (EEDs) have on male genital malformations (MGMs). In this study, individual variation in the genetic response to low-dose bisphenol A (BPA) was investigated in human foreskin fibroblast cells (hFFCs) derived from child cryptorchidism (CO) and hypospadias (HS) patients. hFFCs were collected from control children without MGMs (n = 5) and child CO and HS patients (n = 8 and 21, respectively). BPA exposure (10 nM) was found to inhibit matrix metalloproteinase-11 (MMP11) expression in the HS group (0.74-fold, P = 0.0034) but not in the control group (0.93-fold, P = 0.84) and CO group (0.94-fold, P = 0.70). Significantly lower levels of MMP11 expression were observed in the HS group compared with the control group (0.80-fold, P = 0.0088) and CO group (0.79-fold, P = 0.039) in response to 10 nM BPA. The effect of single-nucleotide polymorphism rs5000770 (G>A), located within the aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) locus, on individual sensitivity to low-dose BPA was investigated in the HS group. A significant difference in neurotensin receptor 1 (NTSR1) expression in response to 10 nM BPA was observed between AA and AG/GG groups (n = 6 and 15, respectively. P = 0.031). However, no significant difference in ARNT2 expression was observed (P = 0.18). This study advances our understanding of the specificity of low-dose BPA effects on human reproductive health. Our results suggest that genetic variability among individuals affects susceptibility to the effects of EEDs exposure as a potential cause of HS.
    PLoS ONE 01/2012; 7(12):e52756. · 3.73 Impact Factor

Publication Stats

758 Citations
196.02 Total Impact Points


  • 1989–2014
    • The University of Tokyo
      • • Department of Natural Environmental Studies
      • • Graduate School of Frontier Sciences
      • • Department of International Health
      Edo, Tōkyō, Japan
  • 1992–2012
    • National Institute for Environmental Studies
      • • Center for Environmental Health Sciences
      • • Center for Material Cycles and Waste Management Research
      Tsukuba, Ibaraki, Japan
  • 2007–2009
    • Kitasato University
      • School of Allied Health Sciences
      Edo, Tōkyō, Japan