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上島 通浩カミジマ ミチヒロ

所属部署医学研究科環境労働衛生学分野
職名教授
メールアドレス
ホームページURLhttp://www.med.nagoya-cu.ac.jp/hygiene.dir/index.html
生年月日
Last Updated :2020/06/02

研究者基本情報

学歴

  • 1991年04月 - 1995年03月, 名古屋大学, 大学院医学研究科
  • 1985年04月 - 1991年03月, 東北大学, 医学部

学位

  • 博士(医学), 名古屋大学

所属学協会

  • 日本衛生学会
  • 日本産業衛生学会
  • 国際労働衛生学会
  • International Society for Environmental Epidemiology
  • International Society of Exposure Science
  • 米国毒科学会(SOT)
  • 東海公衆衛生学会
  • 室内環境学会
  • 日本農薬学会
  • 日本公衆衛生学会
  • 日本毒性学会
  • 日本疫学会

委員歴

  •   2019年04月 - 現在, 愛知県, 環境影響評価審査会 委員
  •   2019年04月 - 現在, 国立環境研究所, 子どもの健康と環境に関する全国調査(エコチル調査) 運営委員長(研究代表者)
  •   2018年 - 現在, 名古屋市, 名古屋市保健所運営協議会 委員
  •   2017年12月 - 現在, 環境省, 中央環境審議会 専門委員
  •   2017年05月 - 現在, 日本産業衛生学会 全国理事
  •   2015年 - 現在, 東海公衆衛生学会, 評議員
  •   2014年 - 現在, 日本産業衛生学会, 編集委員(2005-2008, 2014-)、副編集委員長(2008-2011)
  •   2012年 - 現在, 名古屋市, 名古屋市衛生研究所 調査研究に関する懇談会 委員
  •   2012年 - 現在, 愛知県, 健康・快適居住環境専門家会議 構成員・座長
  •   2012年 - 現在, 愛知県, 貝類出荷自主規制解除判定会議 構成員
  •   2012年 - 現在, 名古屋市, 食の安全・安心推進会議 会長
  •   2012年 - 現在, 名古屋市, 環境審議会 委員
  •   2011年04月 - 現在, 環境省, 子どもの健康と環境に関する全国調査(エコチル調査)国際連携調査委員会 委員(2012-18年度 座長)
  •   2009年04月 - 現在, 日本農薬学会, 編集委員(常任編集委員 2009-2010)
  •   2008年 - 現在, 日本毒性学会, 評議員
  •   2007年04月 - 現在, 日本衛生学会, 評議員・評議会員
  •  - 現在, 日本産業衛生学会, 代議員・東海地方会理事
  •   2016年02月 - 2019年12月, 名古屋市, 名古屋市環境審議会大気環境目標値部会 部会長
  •   2017年07月 - 2019年03月, 環境省, 化学物質の人へのばく露量モニタリング調査に関するタスクフォース会合委員
  •   2015年04月 - 2019年03月, 国立環境研究所, 子どもの健康と環境に関する全国調査(エコチル調査)運営委員会 委員
  •   2014年 - 2019年03月, 国立環境研究所, 子どもの健康と環境に関する全国調査(エコチル調査)曝露評価専門委員会 座長
  •   2012年 - 2019年03月, 国立環境研究所, 子どもの健康と環境に関する全国調査(エコチル調査)学術専門委員会 委員
  •   2018年12月 - 2019年02月, 農林水産省, 農薬の使用者への影響評価法に関する検討会 委員
  •   2016年01月 - 2018年03月, 環境省, 第五次環境基本計画の検討に関する研究会 委員
  •   2017年07月 - 2018年, 環境省, 有害大気汚染物質健康リスク評価作業部会委員
  •   2012年 - 2018年, 名古屋市, 土壌及び地下水汚染対策検討委員会 委員
  •   2014年09月 - 2017年03月, 環境省, トリクロロエチレン健康リスク評価作業部会 委員
  •   2014年02月 - 2017年03月, 名古屋市, 六番町駅アスベスト飛散にかかる健康対策等検討会 構成員
  •   2016年 - 2017年, 愛知県, 化学物質に関する調査委員会委員
  •   2010年09月 - 2011年03月, 内閣府, 「ヒトの発達障害と農薬に関する情報収集踏査」に係わる検討会 委員

経歴

  •   2009年04月 - 現在, 名古屋市立大学大学院医学研究科, 環境労働衛生学分野, 教授
  •   2004年04月 - 2009年03月, 名古屋大学大学院医学研究科, 社会生命科学講座環境労働衛生学, 助教授(平成19年4月より准教授)
  •   1998年04月 - 2004年04月, 名古屋大学大学院医学研究科, 社会生命科学講座環境労働衛生学, 講師
  •   1997年04月 - 1999年04月, 米国カリフォルニア大学バークレー校, 自然資源学部環境科学政策管理学講座, 客員研究員
  •   1995年10月 - 1998年03月, 名古屋大学医学部, 衛生学講座, 助手

研究活動情報

研究分野

  • ライフサイエンス, 衛生学、公衆衛生学分野:実験系を含まない
  • ライフサイエンス, 衛生学、公衆衛生学分野:実験系を含む
  • 環境・農学, 化学物質影響

研究キーワード

    リスク評価, 環境化学物質

論文

  • 人間工学ナッジを事例としたCOVID-19による社会不安軽減に向けたリサーチイシューの提案 -CBRNE災害におけるクライシス・エマージェンシー・リスクコミュニケーション-, 庄司直人, 上島通浩, 榎原 毅, 人間工学, 56, (2) 49 - 57,   2020年04月15日, 査読有り, 2020年1月以降,新型コロナウィルス(COVID-19)に対するリスク対応が喫緊の社会課題である.このようなCBRNE災害(Chemical, Biological, Radiological, Nuclear and Explosive)に対し,人間工学が果たせる貢献のひとつにリスクコミュニケーションがあげられる.本稿では次の4視点で人間工学におけるリサーチイシューを整理した:1)CBRNE災害におけるCERC要素とそのリサーチイシュー,2)社会不安へ対応する行動志向型コミュニケーションのリサーチイシュー,3)COVID-19の公衆衛生危機に対する人間工学研究と実践のリサーチイシュー,4)人間工学コミュニティが果たす役割.これら4視点からCOVID-19による社会不安軽減に向けた人間工学研究の方向性を示すこととした
  • Effects of long working hours and shift work during pregnancy on obstetric and perinatal outcomes: a large prospective cohort study - Japan Environment and Children’s Study., Suzumori N, Ebara T, Matsuki T, Yamada Y, Kato S, Omori T, Saitoh S, Kamijima M, Sugiura-Ogasawara M, Japan Environment, Children’s Study Group, Birth, 47, 67 - 79,   2020年03月, 査読有り
  • Organophosphate agent induces ADHD-like behaviors via Inhibition of brain endocannabinoid-hydrolyzing enzyme(s) in adolescent male rats., Yuki Ito, Motohiro Tomizawa, Kazutaka Suzuki, Yuichi Shirakawa, Hiromasa Ono, Keishi Adachi, Himiko Suzuki, Kenji Shimomura, Toshitaka Nabeshima, Michihiro Kamijima, J Agric Food Chem, 68, 2547 - 2553,   2020年02月13日, 査読有り, Anticholinergic organophosphate (OP) agents act on the diverse serine hydrolases, thereby revealing unexpected biological effects. Epidemiological studies indicate a relationship between the OP exposure and development of attention-deficit/hyperactivity disorder (ADHD)-like symptoms, whereas no plausible mechanism for the OP-induced ADHD has been established. The present investigation employs ethyl octylphosphonofluoridate (EOPF) as an OP-probe, which is an extremely potent inhibitor of endocannabinoid (EC, anandamide and 2-arachidonoylglycerol)-hydrolyzing enzymes: that is, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). An ex vivo experiment shows that EOPF treatment decreases FAAH and MAGL activities and conversely increases EC levels in the rat brain. Subsequently, EOPF (treated intraperitoneally once at 0, 1, 2, or 3 mg/kg) clearly induces ADHD-like behaviors (in elevated plus-maze test) in both Wistar and spontaneously hypertensive rats. The EOPF-induced behaviors are reduced by a concomitant administration of cannabinoid receptor inverse agonist SLV-319. Accordingly, the EC system is a feasible target for OP-caused ADHD-like behaviors in adolescent rats.
  • Biomonitoring method for neonicotinoid insecticides in urine of non-toilet-trained children using LC-MS/MS., Jun Ueyama, Arisa Aoi, Yuko Ueda, Naoko Oya, Yuka Sugiura, Yuki Ito, Takeshi Ebara, Michihiro Kamijima, Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 37, (2) 304 - 315,   2020年02月, 査読有り, There is a growing appreciation of the importance of determining chemical exposure levels in early childhood, as well as in embryonic and foetal life, which are now widely believed to be essential for gaining insight into potential health risks associated with these chemicals. To facilitate the assessment of exposure to neonicotinoid insecticides (NEOs) in non-toilet-trained children, a new method using disposable diapers (nappies) was developed for the simultaneous determination of the NEOs acetamiprid and its metabolite N-desmethylacetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, and thiamethoxam (NEO biomarkers). The urine absorbed in disposable diapers was extracted with acetone (diaper urine) and was cleaned using a solid-phase extraction column, before analysis with LC-MS/MS. The absolute recoveries of NEO biomarkers were 19-50%. Good results were observed for the linearity of the matrix-matched calibration curves (r2 = 0.983-0.996; concentration range LOQ-20 µg L-1) and the precision of intra-day (% relative standard deviation (%RSD): 3.3-12.7%) and inter-day (%RSD: 4.3-19.5%) analyses. The lowest and highest limits of detection of the developed method were 0.07 µg L-1 for acetamiprid and 0.75 µg L-1 for clothianidin. The developed method was applied for the evaluation of fifty diapered three-year-old children in Japan. Importantly, the study revealed relatively high detection rates for dinotefuran and N-desmethylacetamiprid; 84% and 78% respectively. The highest geometric mean of dinotefuran urinary concentration was 2.01 µg L-1. Thus, a method for determining NEO biomarkers in urine extracted from disposable diapers was established. This is the first report on the simultaneous quantitative analysis of NEO biomarkers of diaper-absorbed urine samples.
  • Ten-year temporal trends (2006-2015) and seasonal-differences in urinary metabolite concentrations of novel, hygiene-used pyrethroids in Japanese children., Risa Hamada, Yuko Ueda, Keiko Wada, Isao Saito, Hiroshi Nomura, Michihiro Kamijima, Kunihiko Nakane, Chisato Nagata, Takaaki Kondo, Jun Ueyama, Int J Hyg Environ Health, 225, 113448 - 113448,   2020年01月18日, 査読有り, BACKGROUND AND AIM: Metofluthrin, profluthrin, tefluthrin, and transfluthrin are pyrethroid (PYR) insecticides increasingly used to control mosquitoes, flies, and moths in households and public places (hygiene-PYRs). Currently, there is limited data available concerning exposure to these novel hygiene-PYRs. The goal of this study was to monitor exposure to these hygiene-PYRs by analysing their urinary metabolites and to investigate the temporal and seasonal trends in the concentrations of these metabolites. METHODS: First morning urine samples were obtained from 50 Japanese children (four-six years old) in October of 2006, 2011, and 2015 (total = 150 children) in order to investigate temporal trends. Additionally, first-morning urine samples were collected from 44 three-year-old children in August-September of 2012 (summer) and in February of 2013 (winter) to investigate seasonal differences. The urinary concentrations of 2,3,5,6-tetrafluorobenzyl alcohol (FB-Al; a specific metabolite of transfluthrin), 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (CH3-FB-Al; a common metabolite of tefluthrin and profluthrin), 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (CH3OCH2-FB-Al; a specific metabolite of metofluthrin), and 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al; a common metabolite of metofluthrin, tefluthrin, and profluthrin) were measured using GC-MS/MS. RESULTS: For the investigated years, rapid increases in the detection rates of the hygiene-PYR metabolites were observed. In 2015, FB-Al was identified in 64% of the samples, CH3-FB-Al in 46%, CH3OCH2-FB-Al in 50%, and HOCH2-FB-Al in 83%. Significant increasing trends were found for the concentrations of all hygiene-PYR metabolites from 2006 to 2015 (Jonckheere-Terpstra test, p < 0.001). The concentrations of FB-Al and CH3OCH2-FB-Al were higher in summer than in winter (Mann Whitney-U test, p < 0.05). CONCLUSIONS: These findings suggest that, in Japanese children, exposure to hygiene-PYRs has increased over the past decade, and that children are exposed to higher levels of hygiene-PYRs in summer than in winter.
  • Exposure levels of organophosphate pesticides in Japanese diapered children: contributions of exposure-related behaviors and mothers’ considerations of food selection and preparation., Oya N, Ito Y, Ebara T, Kato S, Hioki K, Aoi A, Ueyama J, Oguri T, Shoji N, Sugiura-Ogasawara M, Saitoh S, Kamijima M, Environ Int, 134, 105294 - 105294,   2020年01月, 査読有り
  • Time course of metabolic status in pregnant women: The Japan Environment and Children’s Study, Hatoko Sasaki, Naoko Arata, Ai Tomotaki, Kiwako Yamamoto-Hanada, Hidetoshi Mezawa, Mizuho Konishi, Kazue Ishitsuka, Mayako Saito-Abe, Miori Sato, Minaho Nishizato, Hirohisa Saito, Yukihiro Ohya, Michihiro Kamijima, Shin Yamazaki, Reiko Kishi, Nobuo Yaegashi, Koichi Hashimoto, Chisato Mori, Shuichi Ito, Zentaro Yamagata, Hidekuni Inadera, Takeo Nakayama, Hiroyasu Iso, Masayuki Shima, Youichi Kurosawa, Narufumi Suganuma, Koichi Kusuhara, Takahiko Katoh, Journal of Diabetes Investigation,   2020年, 査読有り, © 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd Aims/Introduction: We aimed to evaluate the metabolic status of pregnant women by assessing metabolic biomarkers of participants in the Japan Environment and Children’s Study, a nationwide, multicenter, pregnancy and birth cohort. Materials and Methods: Pregnant women aged 14–50 years were studied in 15 centers across Japan. Clinical information was obtained using self-administered questionnaires. Blood samples were taken during the first two trimesters to measure metabolic biomarkers. Samples were divided into seven groups according to the weeks of pregnancy. Results: Among 82,972 pregnant women, 43 had only type 1 diabetes, 78 had only type 2 diabetes, 2,315 had only gestational diabetes and 354 had only dyslipidemia. Glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol and triglyceride across all the percentiles increased as prepregnancy body mass index increased, whereas high-density lipoprotein cholesterol levels across all the percentiles decreased as body mass index increased. Glycated hemoglobin was high in participants with type 1 diabetes or type 2 diabetes only, but not in those with gestational diabetes or hyperlipidemia only. Participants with type 2 diabetes or dyslipidemia only had high triglyceride in the first trimester, which then decreased in the second trimester. Participants with type 2 diabetes only also showed low high-density lipoprotein cholesterol, whereas participants with dyslipidemia only showed high total cholesterol and low-density lipoprotein cholesterol throughout. Conclusions: Metabolic biomarkers were affected by blood sample timing and underlying metabolic disease. The Japan Environment and Children’s Study will clarify the influences of metabolic status during pregnancy on the health and development of the offspring in future studies.
  • Prenatal exposure to organophosphate pesticides, maternal paraoxonase 1 genotype, and childhood neurodevelopment at 24 months of age in Shandong, China., Yiwen Wang, Yan Zhang, Lin Ji, Yijun Zhou, Rong Shi, Michihiro Kamijima, Jun Ueyama, Yu Gao, Ying Tian, Environmental science and pollution research international, 27, (2) 1969 - 1977,   2020年01月, 査読有り, Prenatal organophosphate pesticide (OP) exposure was reported to negatively affect childhood neurodevelopment. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of OPs and may affect an individual's susceptibility to OP exposure. However, little is known about its role in the associations of prenatal OP exposure and childhood neurodevelopment. We measured dimethylphosphate (DM), diethylphosphate (DE), and total dialkylphosphate (DAP) metabolites in maternal urine (n = 436) as well as PON1-108C/T and PON1192Q/R genotypes in maternal blood (n = 244). We assessed the modifying effects of maternal PON1-108C/T and PON1192Q/R genotypes on relationships between prenatal OP exposure and developmental quotients (DQs) in 24-month-old children in Shandong, China (n = 172). Among children of mothers carrying PON1-108CC, a tenfold increase in prenatal DMs was associated with a 5.72-point decrease in social domain DQ scores. Among children of mothers carrying PON1192QQ, a tenfold increase in prenatal DMs and DAPs were associated with a 7.68- and 7.67-point decrease in gross motor domain DQ scores, respectively. Among children of mothers carrying PON1192QQ, a tenfold increase in prenatal DMs, DEs, and DAPs were associated with a 7.52-, 9.07-, and 9.60-point decrease in social domain DQ scores, respectively. Maternal PON1 genotype might modify the associations between prenatal OP exposure and children's neurodevelopment at 24 months of age.
  • Cohort profile: Aichi regional sub-cohort of the Japan Environment and Children’s Study (JECS-A), Ebara T, Yamada Y, Shoji N, Ito Y, Nakagawa A, Miyachi T, Ozaki Y, Omori T, Suzuki S, Kojima M, Ueyama J, Tomizawa M, Kato S, Oguri T, Matsuki T, Sato H, Oya N, Sugiura-Ogasawara M, Saitoh S, Kamijima M, BMJ Open, 9, (11) ,   2019年11月12日, 査読有り
  • Identifying characteristics of indicators of sedentary behavior using objective measurements., Kojiro Yamamoto, Fumiko Matsuda, Tsuyoshi Matsukawa, Nao Yamamoto, Kenji Ishii, Takahiro Kurihara, Shota Yamada, Taro Matsuki, Michihiro Kamijima, Takeshi Ebara, J Occup Health,   2019年10月10日, 査読有り, OBJECTIVE: Recent attention has been focused on sedentary behavior (SB) affecting health outcomes, but the characteristics of indicators reflecting SB remain to be identified. This cross-sectional study aims to identify the characteristics of indicators of SB, focusing on the examination of correlations, reliability, and validity of sedentary variables assessed by the smartphone app. METHOD: Objectively measured data of SB of eligible 46 Japanese workers obtained from smartphones were used. We assessed the characteristics of current indicators being used with a 10-minute or 30-minute thresholds, in addition to the conventional indicators of total sedentary time, mean sedentary bout duration, and total number of sedentary bouts. They were evaluated from three perspectives: (a) association among the indicators, (b) reliability of the indicators, and (c) criterion validity. RESULTS: Total sedentary time under 10 minutes (U10) and U30 had negative associations with Total sedentary time (r = -.47 and -.21 respectively). The correlation between Mean sedentary bout duration and Total number of sedentary bouts was -.84, whereas between Mean sedentary bout duration 10, 30 and Total number of sedentary bouts were -.54 and -.21, respectively. The intraclass correlation coefficients of almost all indicators were around .80. Mean sedentary bout duration, Mean sedentary bout duration 10, Total number of sedentary bouts, Total sedentary time 30, U30 and U10 have significant differences between three BMI groups. CONCLUSION: This study comprehensively revealed the rationale of advantage in the current indicator being used with a 10-minute or 30-minute threshold, rather than the conventional total amount of SB.
  • Di(2-ethylhexyl) phthalate-induced toxicity and peroxisome proliferator-activated receptor alpha: a review., Ito Y, Kamijima M, Nakajima T, Environ Health Prev Med, 24,   2019年07月, 査読有り
  • Benefits of cooperation among large-scale cohort studies and human biomonitoring projects in environmental health research: An exercise in blood lead analysis of the Environment and Child Health International Birth Cohort Group., Nakayama SF, Espina C, Kamijima M, Magnus P, Charles MA, Zhang J, Wolz B, Conrad A, Murawski A, Iwai-Shimada M, Zaros C, Caspersen IH, Kolossa-Gehring M, Meltzer HM, Olsen SF, Etzel RA, Schüz J, Int J Hygiene Environ Health,   2019年07月, 査読有り
  • Occupational exposure limits for cumene, 2,4-dichlorophenoxy acetic acid, silicon carbide whisker, benzyl alcohol, and methylamine, and carcinogenicity, occupational sensitizer, and reproductive toxicant classifications, Atsuko Araki, Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Koji Harada, Hajime Hori, Seichi Horie, Masayoshi Ichiba, Gaku Ichihara, Masayuki Ikeda, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Takeyasu Kakumu, Michihiro Kamijima, Kanae Karita, Takahiko Katoh, Toshio Kawai, Toshihiro Kawamoto, Shinji Kumagai, Yukinori Kusaka, Akiko Matsumoto, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Makiko Nakano, Tetsuo Nomiyama, Hirokazu Okuda, Masayuki Okuda, Kazuyuki Omae, Haruhiko Sakurai, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Akito Takeuchi, Ayano Takeuchi, Masatoshi Tanaka, Shigeru Tanaka, Teruomi Tsukahara, Masashi Tsunoda, Susumu Ueno, Jun Ueyama, Yumi Umeda, Kenya Yamamoto, Yuko Yamano, Takenori Yamauchi, Eiji Yano, Journal of Occupational Health, 61, (4) 328 - 330,   2019年07月
  • Simple method to detect triclofos and its metabolites in plasma of children by combined use of liquid chromatography tandem-mass spectrometry and gas chromatography-mass spectrometry., Sato H, Ito Y, Inoue M, Nakahira Y, Hashimoto S, Nakajima T, Kamijima M, Sci Rep, 9,   2019年06月, 査読有り
  • Endometriosis and recurrent pregnancy loss as new risk factors for venous thromboembolism during pregnancy and post-partum: The JECS Birth Cohort., Sugiura-Ogasawara M, Ebara T, Matsuki T, Yamada Y, Omori T, Matsumoto Y, Kato S, Kano H, Kurihara T, Saitoh S, Kamijima M, the Japan Environment, Children's Study, JECS) Group, Thromb Haemost, 119, 606 - 617,   2019年04月, 査読有り
  • For making a declaration of countermeasures against the falling birth rate from the Japanese Society for Hygiene: summary of discussion in the working group on academic research strategy against an aging society with low birth rate., Nomura K, Karita K, Araki A, Nishioka E, Muto G, Iwai-Shimada M, Nishikitani M, Inoue M, Tsurugano S, Kitano N, Tsuji M, Iijima S, Ueda K, Kamijima M, Yamagata Z, Sakata K, Iki M, Yanagisawa H, Kato M, Inadera H, Kokubo Y, Yokoyama K, Koizumi A, Otsuki T, Environmental health and preventive medicine, 24, (1) ,   2019年03月, 査読有り
  • Within-individual and interlaboratory variability analyses of urinary metabolites measurements of organophosphorus insecticides, Ito Y, Ueyama J, Nakayama SF, Isobe T, Oya N, Sato H, Ebara T, Yoshimasu K, Tsuno K, Tatsuta N, Nakai K, Kamijima M, J Expo Sci Environ Epidemiol,   2019年02月, 査読有り
  • Association between maternal blood cadmium and lead concentrations and gestational diabetes mellitus in the Japan Environment and Children’s Study, Oguri T, Ebara T, Nakayama SF, Sugiura-Ogasawara M, Kamijima M, Japan Environment, Children’s Study Group, Int Arch Occup Environ Health, 92, 209 - 217,   2019年02月, 査読有り
  • 日本衛生学会における少子化対策提言に向けて:日本衛生学会少子化対策ワーキンググループによるとりまとめ, 野村 恭子, 苅田 香苗, 荒木 敦子, 西岡 笑子, 武藤 剛, 岩井 美幸, 錦谷 まりこ, 井上 まり子, 鶴ヶ野 しのぶ, 北野 尚美, 辻 真弓, 飯島 佐知子, 上田 佳代, 上島 通浩, 山縣 然太郎, 坂田 清美, 伊木 雅之, 柳澤 裕之, 加藤 昌志, 横山 和仁, 小泉 昭夫, 大槻 剛巳, 日衛誌, 2019,   2019年01月, 査読有り, 招待有り
  • Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan, Hioki K, Ito Y, Oya N, Nakayama SF, Isobe T, Ebara T, Shibata K, Nishikawa N, Nakai K, Kamida T, Ueyama J, Sugiura-Ogasawara M, Kamijima M, Environ Health Prev Med, 24,   2019年01月, 査読有り
  • Comprehensive review of 2-ethyl-1-hexanol as an indoor air pollutant, Wakayama T, Ito Y, Sakai K, Miyake M, Shibata E, Ohno H, Kamijima M, J Occup Health, 61, 19 - 35,   2019年01月, 査読有り
  • Adverse pregnancy and perinatal outcome in patients with recurrent pregnancy loss: Multiple imputation analyses with propensity score adjustment applied to a large-scale birth cohort of the Japan Environment and Children’s Study., Sugiura-Ogasawara M, Ebara T, Yamada Y, Shoji N, Matsuki T, Kano H, Kurihara T, Omori T, Tomizawa M, Miyata M, Kamijima M, Saitoh S, Japan Environment Children's Study Group, Am J Reprod Immunol, 81,   2019年01月, 査読有り
  • 職場における未知の中毒発生事例から今後の環境リスク対応を考える, 上島通浩, 柴田英治, 保健医療科学, 67, 282 - 291,   2018年08月, 査読有り, 招待有り
  • 少子化対策としての生殖毒性研究, 上島通浩, 日衛誌, 73, 330 - 337,   2018年07月, 査読有り, 招待有り
  • A sensitive and efficient procedure for the high-throughput determination of nine urinary metabolites of pyrethroids by GC-MS/MS and its application in a sample of Japanese children, Ueda Y, Oda M, Saito I, Hamada R, Kondo T, Kamijima M, Ueyama J, Anal Bioanal Chem, 410, 6207 - 6217,   2018年07月, 査読有り
  • Exposure reconstruction of trichloroethylene among patients with occupational trichloroethylene hypersensitivity syndrome, Nakajima T, Wang H, Ito Y, Naito H, Wang D, Zhao N, Li H, Qiu X, Xia L, Chen J, Wu Q, Li L, Huang H, Kamijima M, Ind Health, 56, 300 - 307,   2018年06月, 査読有り
  • 幼児向けADH行動評価尺度「行動特徴のチェックリスト(BCL)」の妥当性と信頼性の検討, 津野香奈美, 吉益光一, 林隆, 龍田希, 伊藤由起, 上島通浩, 仲井邦彦, 日衛誌, 73, 225 - 234,   2018年06月, 査読有り
  • Epididymal phospholipidosis is a possible mechanism for spermatotoxicity induced by the organophosphorus insecticide fenitrothion in rats, Miyake M, Ito Y, Suzuki H, Tomizawa M, Sato H, Liu M, Okamura A, Nakajima T, Ohtani K, Takino H, Inagaki H, Kamijima M, Toxicol Lett, 285, 27 - 33,   2018年03月, 査読有り
  • Prenatal and postnatal exposure to organophosphate pesticides and childhood neurodevelopment in Shandong, China, Yiwen Wang, Yan Zhang, Lin Ji, Yi Hu, Jingjing Zhang, Caifeng Wang, Guodong Ding, Limei Chen, Michihiro Kamijima, Jun Ueyama, Yu Gao, Ying Tian, ENVIRONMENT INTERNATIONAL, 108, 119 - 126,   2017年11月, 査読有り, Background: Although studies in laboratory animals demonstrate neurodevelopmental deficits caused by prenatal or postnatal organophosphate pesticide (OP) exposure, there is limited evidence on effects induced by not only prenatal but also postnatal exposure of children to OPs. Methods: We measured diethylphosphate (DE), dimethylphosphate (DM), and total dialkylphosphate (DAP) metabolites in maternal and child urine at 12 and 24 months of age and examined their relationship with developmental quotients (DQs) in 12-month-old infants and 24-month-old children in Shandong, China. Results: The median concentrations of total DAP metabolites (DAPs) in child urine [371.97 nmol/g creatinine (12-month-old infants), 538.64 nmol/g creatinine (24-month-old children)] were higher than those in maternal urine (352.67 nmol/g creatinine). Prenatal OP exposure was negatively associated with 24-month-old children's DQs, especially among boys. A 10-fold increase in prenatal DEs and DAPs was associated with a 2.59- and 2.49-point decrease in social domain DQ scores in 24-month-old children (n = 262), respectively. However, positive association of postnatal exposure to OPs and 24-month-old children's DQs was observed (n = 237). Neither prenatal nor postnatal exposure to OPs was related to 12-month-old infants' DQs. Conclusions: These data suggested that prenatal OP exposure could adversely affect children's neurodevelopment at 24 months of age, especially among boys. The prenatal period might be a critical window of OP exposure. In view of the positive association with postnatal OP exposure, it is necessary to interpret findings with caution.
  • Association Between Organophosphate Pesticide Exposure and Thyroid Hormones in Pregnant Women, Yiwen Wang, Limei Chen, Caifeng Wang, Yi Hum, Yu Gao, Yijun Zhou, Rong Shi, Yan Zhang, Michihiro Kamijima, Jun Ueyama, Ying Tian, Epidemiology, 28, S35 - S40,   2017年10月, 査読有り
  • Quantitative analysis of organophosphate insecticide metabolites in urine extracted from disposable diapers of toddlers in Japan, Naoko Oya, Yuki Ito, Keisuke Hioki, Yuya Asai, Arisa Aoi, Yuka Sugiura, Jun Ueyama, Tomoko Oguri, Sayaka Kato, Takeshi Ebara, Michihiro Kamijima, Int J Hyg Environ Health, 220, (2) 209 - 216,   2017年03月, 査読有り, Background and aim: Epidemiological studies linking insecticide exposure to childhood neurodevelopment have been gaining global attention. Despite the rapid development of the central nervous system in early childhood, studies regarding the biological monitoring of insecticide exposure in diapered children are limited. In this study, we aimed to clarify the concentrations of organophosphate (OP) insecticide metabolites in toddler urine extracted from disposable diapers in Japan. Methods: We recruited diapered children from the Aichi regional subcohort participants of the Japan Environment and Children's Study (JECS) at the time of their 18-month checkup. A total of 116 children wore designated disposable diapers overnight, which were then sent as refrigerated cargo. The urine was extracted from the diapers using acetone and analyzed by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) to determine the concentrations of six dialkyl phosphates (DAPs) (i.e., dimethyl phosphate [DMP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP], diethyl phosphate [DEP], diethyl thiophosphate [DETP], and diethyl dithiophosphate [DEDTP]). DAP absorption into the diapers was quantified to calculate the urinary DAP concentrations. Results: The DAP recovery using the developed method yielded between 54.2% (DEDTP) and 101.4% (DEP). Within-run precision expressed as the relative standard deviation was between 2.4% and 14.7%, and the between-run precision was between 3.1% and 8.5%. A Bland-Altman analysis confirmed the agreement between the results obtained by the developed method and by the measurements for the corresponding urine without diaper absorption. The geometric means (GM) of urinary DMP, DMTP, DMDTP, DEP, DETP, and total DAPs (EDAP) were 3.6, 3.9, 0.9, 6.0, 0.6 mu g/L, and 137.6 nmol/L, respectively. The GM of DEDTP was not calculated due to its low detection rate. Conclusions: We successfully established a method to measure the DAP concentrations in urine extracted from diapers and this is the first report of these pesticide concentrations in diapered children in Japan. (C) 2016 Elsevier GmbH. All rights reserved.
  • Japan Environment and Children’s Study - backgrounds, activities, and future directions in global perspectives, Ishitsuka K, Nakayama SF, Kishi R, Mori C, Yamagata Z, Ohya Y, Kawamoto T, Kamijima M, Environ Health Prev Med, 22, (1) ,   2017年, 査読有り
  • Determinants of polyunsaturated fatty acid concentrations in erythrocytes of pregnant Japanese women from a birth cohort study: study protocol and baseline findings of an adjunct study of the Japan environment & Children's study, Shoji Saito, Terue Kawabata, Nozomi Tatsuta, Fumiko Kimura, Teruo Miyazawa, Satoshi Mizuno, Hidekazu Nishigori, Takahiro Arima, Yasuo Kagawa, Kouichi Yoshimasu, Kanami Tsuno, Yuki Ito, Michihiro Kamijima, Kunihiko Nakai, Nobuo Yaegashi, ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE, 22, (1) ,   2017年, 査読有り, Background: N-3 polyunsaturated fatty acids (n-3 PUFA) may have multiple beneficial effects on the outcome of pregnancy, maternal health and child development. The present study introduced the protocol of a birth cohort study to examine the beneficial effects of n-3 PUFA status in pregnant Japanese women as an adjunct study of the Japan Environment and Children's Study (JECS). Methods: The JECS participants in the coastal areas of Miyagi Prefecture were further invited to participate in this adjunct study, and 1,878 pregnant women were enrolled prior to delivery. Their n-3 PUFA status was evaluated with fatty acid profiles in erythrocytes of maternal blood collected from 1,623 mothers at 24-30 weeks of gestation and cord blood from 1,505 deliveries. Results: The baseline results, including comprehensive data on the fatty acid status and determinants affecting the PUFA status, were analyzed. In stepwise multivariate analyses, the cord blood docosahexaenoic acid (DHA) level was found to be significantly influenced by the DHA level in maternal blood, the child's sex, and the gestational period. The maternal DHA level was influenced by fish intake, maternal age, and the prepregnancy body mass index. While cord blood eicosapentaenoic acid (EPA) was influenced by maternal EPA, fish intake, and season at birth, additional factors such as maternal education, household income, and smoking habits affected the maternal EPA content. Conclusion: Further studies are warranted to clarify the nutritional impacts of n-3 PUFA in pregnant Japanese women of the cohort study.
  • Organophosphorus insecticide dichlorvos inhibits fatty acid amide hydrolase in the male reproductive organs of rats, Oya N, Ito Y, Kamijima M, Fundam Toxicol Sci, 4, 201 - 205,   2017年, 査読有り
  • Nanoparticle-Rich Diesel Exhaust-Induced Liver Damage via Inhibited Transactivation of Peroxisome Proliferator-Activated Receptor Alpha, Yuki Ito, Yukie Yanagiba, Doni Hikmat Ramdhan, Yumi Hayashi, Yufei Li, Akira K. Suzuki, Michihiro Kamijima, Tamie Nakajima, ENVIRONMENTAL TOXICOLOGY, 31, (12) 1985 - 1995,   2016年12月, 査読有り, Diesel exhaust emission contains a high amount of nano-sized particles and is considered to be systemically distributed in the body. However, few studies about the effects of nanoparticle rich-diesel exhaust (NR-DE) on liver have been reported. The present investigation focuses on the effects of NR-DE on livers in rats, especially concerning inflammation and lipid metabolism. Male F344 rats were exposed to fresh air or low (24+/-7 mu g/m(3)), medium (3+/-4 mu g/m(3)) and high (138+/-20 mu g/m(3)) concentrations of NR-DE for 1, 2, or 3 months (5 hours/day, 5 days/week). Exposure to both medium and high concentrations of NR-DE for one month increased plasma asparate aminotransferase and alanine aminotransferase activities, while only high concentrations increased plasma interleukin-6 and hepatic nuclear factor kappa B (NF kappa B), suggesting that activation of hepatic inflammatory signaling took place. Although these exposures elevated peroxisome proliferator-activated receptor (PPAR) alpha levels or its binding activity to the response element, neither activated PPAR alpha-target genes such as beta-oxidative enzymes nor inhibited NF kappa B elevation. Thus, NR-DE may contain some materials that inhibit PPARa activation in relation to lipid metabolism and inflammation. Taken together, NR-DE exposure at one month may cause inflammation; however, this finding may not be observed after a longer exposure period. (C) 2015 Wiley Periodicals, Inc.
  • Subchronic inhalation exposure to 2-ethyl-1-hexanol impairs the mouse olfactory bulb via injury and subsequent repair of the nasal olfactory epithelium, Mio Miyake, Yuki Ito, Masato Sawada, Kiyoshi Sakai, Himiko Suzuki, Tatsuo Sakamoto, Kazunobu Sawamoto, Michihiro Kamijima, Arch Toxicol, 90, (8) 1949 - 1958,   2016年08月, 査読有り, The olfactory system can be a toxicological target of volatile organic compounds present in indoor air. Recently, 2-ethyl-1-hexanol (2E1H) emitted from adhesives and carpeting materials has been postulated to cause "sick building syndrome." Patients' symptoms are associated with an increased sense of smell. This investigation aimed to characterize the histopathological changes of the olfactory epithelium (OE) of the nasal cavity and the olfactory bulb (OB) in the brain, due to subchronic exposure to 2E1H. Male ICR mice were exposed to 0, 20, 60, or 150 ppm 2E1H for 8 h every day for 1 week, or 5 days per week for 1 or 3 months. After a 1-week exposure, the OE showed inflammation and degeneration, with a significant concentration-dependent reduction in the staining of olfactory receptor neurons and in the numbers of globose basal cells at a parts per thousand yen20 ppm. Regeneration occurred at 1 month along with an increase in the basal cells, but lymphocytic infiltration, expanded Bowman's glands, and a decrease in the olfactory receptor neurons were observed at 3 months. Intriguingly, the OB at 3 months showed a reduction in the diameters of the glomeruli and in the number of olfactory nerves and tyrosine hydroxylase-positive neurons, but an increased number of ionized calcium-binding adaptor molecule 1-positive microglia in glomeruli. Accordingly, 2E1H inhalation induced degeneration of the OE with the lowest-observed-adverse-effect level of 20 ppm. The altered number of functional cell components in the OB suggests that effects on olfactory sensation persist after subchronic exposure to 2E1H.
  • Exposure characterization of three major insecticide lines in urine of young children in Japan-neonicotinoids, organophosphates, and pyrethroids, Aya Osaka, Jun Ueyama, Takaaki Kondo, Hiroshi Nomura, Yuka Sugiura, Isao Saito, Kunihiko Nakane, Ayuko Takaishi, Hiroko Ogi, Shinya Wakusawa, Yuki Ito, Michihiro Kamijima, Environ Res, 147, 89 - 96,   2016年05月, 査読有り, The use of neonicotinoid (NEO) insecticides has increased over the past decade not only in Japan but also worldwide, while organophosphate (OP) and pyrethroid (PYR) insecticides are still conventionally used in agriculture and domestic pest control. However, limited data are currently available on the NEO exposure levels, especially in children, who are particularly vulnerable to environmental toxicants. Thus, the purpose of this study was to characterize the exposure to NEOs, as well as OPs and PYRs, in three-year-old Japanese children by assessing the range, distribution, and seasonal differences of the urinary concentrations of seven NEOs (acetamiprid, clothianidin, dinotefuran, thiacloprid, thiamethoxam, imidacloprid, and nitenpyram); four OP metabolites (dialkylphosphates IDAPsp, including dimethylphosphate, dimethylthiophosphate, diethylphosphate, and diethylthiophosphate; and three PYR metabolites (3-phenoxybenzoic acid, trans-chrysanthemumdicarboxylic acid, and 3-(2,2-dichloroviny1)-2,2- dimethylcyclopropane carboxylic acid). Urine samples were collected from 223 children (108 males and 115 females) in the summer and winter months. The detection rates of NEOs were 58% for dinotefuran, 25% for thiamethoxam, 21% for nitenpyram, and <16% for all other NE05. The median and maximum concentrations of the sum of the seven NEOs (NEO) were 4.7 and 370.2 nmol/g creatinine, respectively. Urinary Sigma NEO, dimethylphosphate, and all PYR metabolite concentrations were significantly higher in the summer than in the winter (p < 0.05). The creatinine-adjusted concentration of Sigma NEO significantly correlated with those of all DAPs (p < 0.05) but not with those of the PYR metabolites. Moreover, the NEO-detected group showed higher urinary EDAP (sum of four OP metabolites) concentrations than the group without NEO detection. These findings suggest that children in Japan are environmentally exposed to the three major insecticide lines, and that the daily exposure sources of NEOs are common to those of Ups. (C) 2016 Elsevier Inc. All rights reserved.
  • エコチル調査の意義と地域での子育て支援, 上島通浩, 小栗朋子, 加藤沙耶香, 榎原 毅, 保健師ジャーナル, 72, (4) 291 - 295,   2016年
  • Effects of Paraoxonase 1 gene polymorphisms on organophosphate insecticide metabolism in Japanese pest control workers, Hirotaka Sato, Yuki Ito, Jun Ueyama, Yuya Kano, Tomoya Arakawa, Masahiro Gotoh, Takaaki Kondo, Yuka Sugiura, Isao Saito, Eiji Shibata, Michihiro Kamijima, J Occup Health, 58, (1) 56 - 65,   2016年01月, 査読有り, Objectives: Paraoxonase 1 (PON1) in serum detoxifies organophosphate (OP) insecticides by hydrolysis. The present cross-sectional study aimed to clarify the relationship between PON1 single nucleotide polymorphisms (SNPs) and enzyme activities or OP metabolite concentrations in urine of workers occupationally exposed to low-level OPs. Methods: Among 283 workers in 10 pest control companies located in central Japan who underwent checkups, 230 subjects (male 199, female 31, average age 38.9 +/- 11.1 years old) participated in the study. Q192R and L55M polymorphisms were determined by TaqMan assay. PON1 activity was measured using fenitrothion (FNT) oxon, chlorpyrifos-methyl (CPM) oxon, chlorpyrifos (CP) oxon, and phenyl acetate as substrates. Urinary OP metabolite concentrations were measured with gas chromatography-mass spectrometry. Results: The maximum differences in enzyme activities between individuals were 64.6-, 6.3-, 7.7-, and 2.0-fold for FNT oxonase, CPM oxonase, CP oxonase, and arylesterase (ARE), respectively. The activities of CPM oxonase and ARE in workers having the RR genotype were 53.5% and 18.2% lower than in those with the QQ genotype, respectively. CP oxonase activity was 15.0% lower in those having the M allele (LM + MM compared with LL). Urinary metabolite concentrations were not associated with PON1 polymorphisms, but negative associations were observed between the concentrations and activities of FNT oxonase and ARE. Conclusions: While PON1 SNPs can explain differences in catalytic activities toward some OPs, differences in urinary concentrations of OP metabolites are not attributable to PON1 SNPs but instead are attributable to its serum activities. Its serum activities might be more sensitive biomarkers for estimation of individual susceptibility to OP toxicities.
  • Comparison of different urine pretreatments for biological monitoring of pyrethroid insecticides, Toshima H, Yoshinaga J, Shiraishi H, Ito Y, Kamijima M, Ueyama J, J Anal Toxicol, 39, 133 - 6,   2015年, 査読有り
  • Household pesticide exposure and the risk of childhood acute leukemia in Shanghai, China, Zhang Y, Gao Y, Shi R, Chen D, Wang X, Kamijima M, Sakai K, Nakajima T, Khalequzzaman M, Zhou Y, Zheng Y, Bao P, Tian Y, Environ Sci Pollut Res Int, 22, 11755 - 63,   2015年, 査読有り
  • Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study, Xu J, Alexander DB, Iigo M, Hamano H, Takahashi S, Yokoyama T, Kato M, Usami I, Tokuyama T, Tsutsumi M, Tamura M, Oguri T, Niimi A, Hayashi Y, Yokoyama Y, Tonegawa K, Fukamachi K, Futakuchi M, Sakai Y, Suzui M, Kamijima M, Hisanaga N, Omori T, Nakae D, Hirose A, Kanno J, Tsuda H, Cancer Sci, 106, 825 - 32,   2015年, 査読有り
  • Temporal levels of urinary neonicotinoid and dialkylphosphate concentrations in Japanese women between 1994 and 2011, Ueyama J, Harada KH, Koizumi A, Sugiura Y, Kondo T, Saito I, Kamijima M, Environ Sci Technol, 49, 14522 - 8,   2015年, 査読有り
  • Non-specific psychological distress in women undergoing noninvasive prenatal testing because of advanced maternal age, Nobuhiro Suzumori, Takeshi Ebara, Kyoko Kumagai, Shinobu Goto, Yasuyuki Yamada, Michihiro Kamijima, Mayumi Sugiura-Ogasawara, PRENATAL DIAGNOSIS, 34, (11) 1055 - 1060,   2014年11月, 査読有り, ObjectiveThe objective of our study was to describe our clinical experience in providing noninvasive prenatal testing (NIPT) for fetal aneuploidy to pregnant women, highlighting the degree of non-specific psychological distress. MethodsData were collected from Japanese women who were offered and underwent NIPT after genetic counseling and control pregnant women who did not undergo NIPT as part of the Japan Environment and Children's Study Control A planning. The degree of mental distress was assessed using the Kessler 6 (K6) screening scale with a score of 10 indicating depression or anxiety disorder. ResultsAmong the 505 women who underwent NIPT because of advanced maternal age, 9.1% had a K6 score of 10. Compared with matched controls (n=1010) adjusted for maternal age and gestational age, the NIPT group showed a trend toward higher K6 scores (odds ratio 1.44, 95% confidence interval 0.97-2.13, P=0.07). Higher K6 scores were associated with women whose husbands were the primary decision makers during NIPT counseling (P=0.06). ConclusionsWomen electing NIPT tend to have higher scores of depression/anxiety, and those with higher depression scores tended to defer the decision to their husbands. (c) 2014 John Wiley & Sons, Ltd.
  • A revised method for determination of dialkylphosphate levels in human urine by solid-phase extraction and liquid chromatography with tandem mass spectrometry: application to human urine samples from Japanese children, Jun Ueyama, Isao Saito, Ayuko Takaishi, Hiroshi Nomura, Mai Inoue, Aya Osaka, Yuka Sugiura, Yumi Hayashi, Shinya Wakusawa, Hiroko Ogi, Kimio Inuzuka, Michihiro Kamijima, Takaaki Kondo, ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE, 19, (6) 405 - 413,   2014年11月, 査読有り, Biological monitoring of organophosphorus insecticide (OP) metabolites, specifically dialkylphosphates (DAP) in urine, plays a key role in low-level exposure assessment of OP in individuals. The aims of this study are to develop a simple and sensitive method for determining four urinary DAPs using high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS), and to assess the concentration range of urinary DAP in Japanese children. Deuterium-labeled DAPs were used as internal standards. Urinary dimethylphosphate (DMP) and diethylphosphate (DEP), which passed through the solid-phase extraction (SPE) column, and dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP), which were extracted from a SPE column using 2.5 % NH3 water including 50 % acetonitrile, were prepared for separation analysis. The samples were then injected into LC-MS/MS. The optimized method was applied to spot urine samples from 3-year-old children (109 males and 116 females) living in Aichi Prefecture in Japan. Results from the validation study demonstrated good within- and between-run precisions (< 10.7 %) with low detection limits (0.4 for DMP and DMTP, 0.2 for DEP and 0.1 mu g/L for DETP). The geometric mean values and detection rates of the urinary DAPs in Japanese children were 14.4 mu g/L and 100 % for DMP, 5.3 mu g/L and 98 % for DMTP, 5.5 mu g/L and 99 % for DEP, and 0.6 mu g/L and 80 % for DETP, respectively. The present high-throughput method is simple and reliable, and can thereby further contribute to development of an exposure assessment of OP. The present study is the first to reveal the DAP concentrations in young Japanese children.
  • Biological Monitoring Method for Urinary Neonicotinoid Insecticides Using LC-MS/MS and Its Application to Japanese Adults, Jun Ueyama, Hiroshi Nomura, Takaaki Kondo, Isao Saito, Yuki Ito, Aya Osaka, Michihiro Kamijima, JOURNAL OF OCCUPATIONAL HEALTH, 56, (6) 461 - 468,   2014年11月, 査読有り, Objectives: Agricultural use of neonicotinoid (NEO) insecticides has been increasing in recent years, but their biological monitoring methods have been scarcely reported. In this study, we developed and validated a rapid and sensitive method for quantifying urinary NEO concentrations using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods: After phosphate-induced acidification of a urine sample, urinary NEOs were trapped by a solid-phase extraction column and eluted with methanol for acetamiprid, imidacloprid, thiacloprid, thiamethoxam, clothianidin and dinotefuran and with an acetonitrile and methanol solution (1:1, v/v) containing 5% NH3 for nitenpyram. A separation analysis was performed by LC-MS/MS within 10 minutes for the sample. This method was applied to first morning urine obtained from 52 Japanese (40.9 +/- 10.5 years old, mean standard deviation) without occupational NEO exposure. Results: The linear dynamic ranges and their limit of quantification (LOQ, signal to noise ratio=10) levels were 0.3-20 or 50 mu g/l (r=0.998-0.999) and 0.05-0.36 mu g/l, respectively. The absolute recovery was 64-95%, and the intra- and inter-day precisions were less than 16.4% (relative standard deviation, %RSD). This method was successfully applied for analysis of NEOs in human urine samples obtained from 52 adults. The frequencies of individuals who showed more than LOD levels was above 90% for imidacloprid, thiamethoxam, clothianidin and dinotefuran, more than 50% for acetamiprid and thiacloprid and 29% for nitenpyram. Conclusions: These results indicated that our new method could be applied to biological monitoring of NEO exposure even at environmental exposure levels in Japanese adults without occupational spraying histories.
  • Harmonizing biomarker measurements in longitudinal studies of children’s health and the environment, Etzel R, Charles MA, Dellarco M, Gajeski K, Jöckel KH, Hirschfeld S, Kamijima M, Kawamoto T, Kolossa-Gehring M, Nakayama S, Schmidt B, Tian Y, Wolz B, Zaros C, Zhang J, Biomonitoring, 1, 50 - 62,   2014年10月, 査読有り, Large scale studies of environmental influences on children’s health and development are being planned or conducted in many places, including Japan, France, Shanghai (China), the United States, and Germany. The objective of these “next generation” studies is to better understand a broad range of environmental and social factors that influence the health and well-being of children. Some of these studies are designed to enroll tens of thousands of children and follow them for many years to investigate the influence of the environment on child growth, development and health. Environment is broadlydefinedinthesestudiesandincludesinvestigation of chemical, biological, physical and socioeconomic factors. An international group composed of study teams from Japan, France, Shanghai (China), the United States, and Germany has been meeting since 2011 to exchange information and work towards harmonization of processes that would provide the opportunity to compare methods and develop procedures to conduct combined analyses of results and data pooling procedures. Harmonization of infant health outcomes, biomarkers, environmental measurements, socioeconomic and migration status has been initiated. This manuscript provides an overview of the Environment and Child Health International Birth Cohort Group and its history, describes the progress of work, and discusses the advantages of this international collaborative effort.
  • Fenitrothion action at the endocannabinoid system leading to spermatotoxicity in Wistar rats, Yuki Ito, Motohiro Tomizawa, Himiko Suzuki, Ai Okamura, Katsumi Ohtani, Mari Nunome, Yuki Noro, Dong Wang, Tamie Nakajima, Michihiro Kamijima, Toxicol App Pharmacol, 279, (3) 331 - 337,   2014年09月, 査読有り, Organophosphate (OP) compounds as anticholinesterase agents may secondarily act on diverse serine hydrolase targets, revealing unfavorable physiological effects including male reproductive toxicity. The present investigation proposes that fenitrothion (FNT, a major OP compound) acts on the endocannabinoid signaling system in male reproductive organs, thereby leading to spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) in rats. FNT oxon (bioactive metabolite of FNT) preferentially inhibited the fatty acid amide hydrolase (FAAH), an endocannabinoid anandamide (AEA) hydrolase, in the rat cellular membrane preparation from the testis in vitro. Subsequently, male Wistar rats were treated orally with 5 or 10 mg/kg FNT for 9 weeks and the subchronic exposure unambiguously deteriorated sperm motility and morphology. The activity-based protein profiling analysis with a phosphonofluoridate fluorescent probe revealed that FAAH was selectively inhibited among the FNT-treated cellular membrane proteome in testis. Intriguingly, testicular AEA (endogenous substrate of FAAH) levels were elevated along with the FAAH inhibition caused by the subchronic exposure. More importantly, linear regression analyses for the FNT-elicited spermatotoxicity reveal a good correlation between the testicular FAAH activity and morphological indices or sperm motility. Accordingly, the present study proposes that the FNT-elicited spermatotoxicity appears to be related to inhibition of FAAH leading to over-stimulation of the endocannabinoid signaling system, which plays crucial roles in spermatogenesis and sperm motility acquirement. (C) 2014 Elsevier Inc. All rights reserved.
  • Formation of the Nitrative DNA Lesion 8-Nitroguanine is Associated with Asbestos Contents in Human Lung Tissues: A Pilot Study, Yusuke Hiraku, Kiyoshi Sakai, Eiji Shibata, Michihiro Kamijima, Naomi Hisanaga, Ning Ma, Shosuke Kawanishi, Mariko Murata, JOURNAL OF OCCUPATIONAL HEALTH, 56, (3) 186 - 196,   2014年05月, 査読有り, Objectives: Asbestos causes lung cancer and malignant mesothelioma, and chronic inflammation is considered to participate in carcinogenesis. However, biomarkers to evaluate its carcinogenic risk have not been established. Reactive oxygen/nitrogen species are generated in biological systems under inflammatory conditions and may contribute to carcinogenesis by causing DNA damage. In this study, we examined the relationship between the formation of 8-nitroguanine (8-nitroG), a mutagenic DNA lesion formed during inflammation, and asbestos contents in human lung tissues. Methods: We obtained non-tumor lung tissues from patients with (n=15) and without mesothelioma (n=21). The expression of 8-nitroG and related molecules was examined by immunohistochemistry, and their staining intensities were semiquantitatively evaluated. Asbestos contents in lung tissues were analyzed by analytical transmission electron microscopy. Results: In subjects without mesothelioma, staining intensities of 8-nitroG and apurinic/apyrimidinic endonuclease 1 (APE1) were significantly correlated with total asbestos and amphibole contents (p<0.05), but not with chrysotile content. In mesothelioma patients, their staining intensities were not correlated with asbestos contents. The double immunofluorescence technique revealed that APE1 was expressed in 8-nitroG-positive cells, suggesting that abasic sites were formed possibly due to the removal of 8-nitroG. The staining intensities of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative DNA lesion, and its repair enzyme 8-oxoguanine DNA-glycosylase were correlated with age (p<0.05), but not with asbestos contents in subjects without mesothelioma. Conclusions: This is the first study to demonstrate that 8-nitroG formation is associated with asbestos contents in human lung tissues. This finding raises a possibility that 8-nitroG serves as a biomarker that can be used to evaluate asbestos exposure and carcinogenic risk.
  • Quantitative assessments of indoor air pollution and the risk of childhood acute leukemia in Shanghai, Yu Gao, Yan Zhang, Michihiro Kamijima, Kiyoshi Sakai, Md Khalequzzaman, Tamie Nakajima, Rong Shi, Xiaojin Wang, Didi Chen, Xiaofan Ji, Kaiyi Han, Ying Tian, ENVIRONMENTAL POLLUTION, 187, 81 - 89,   2014年04月, We investigated the association between indoor air pollutants and childhood acute leukemia (AL). A total of 105 newly diagnosed cases and 105 1:1 gender-, age-, and hospital-matched controls were included. Measurements of indoor pollutants (including nitrogen dioxide (NO2) and 17 types of volatile organic compounds (VOCs)) were taken with diffusive samplers for 64 pairs of cases and controls. Higher concentrations of NO2 and almost half of VOCs were observed in the cases than in the controls and were associated with the increased risk of childhood AL The use of synthetic materials for wall decoration and furniture in bedroom was related to the risk of childhood AL Renovating the house in the last 5 years, changing furniture in the last 5 years, closing the doors and windows overnight in the winter and/or summer, paternal smoking history and outdoor pollutants affected VOC concentrations. Our results support the association between childhood AL and indoor air pollution. (C) 2014 Elsevier Ltd. All rights reserved.
  • A non-invasive biomonitoring method for assessing levels of urinary pyrethroid metabolites in diapered children by gas chromatography-mass spectrometry, Shun Saito, Jun Ueyama, Takaaki Kondo, Isao Saito, Eiji Shibata, Masahiro Gotoh, Hiroshi Nomura, Shinya Wakusawa, Kunihiko Nakai, Michihiro Kamijima, JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY, 24, (2) 200 - 207,   2014年03月, The aim of this study was to develop a method for quantitative measurement of urinary metabolites of pyrethroid (PYR) insecticides, trans-chrysanthemumdicarboxylic acid. (CDCA) and 3-phenoxybenzoic acid (3-PBA), extracted from disposable diapers. This study was approved by the university ethics committees, and informed consent was obtained from all the parents for their children and from adult volunteers. After extraction of PYR metabolites in the absorber of diapers with 5 ml acetone, the metabolites in the eluents were extracted with tert-butyl methyl ether, derivatized with 1,1,1,3,3,3-hexafluoroisopropanol and analyzed by gas chromatography-mass spectrometry. The limits of quantitation (LOQs) were 0.55,mu g/l for CDCA and 0.09 mu g/l for 3-PBA in 2 ml urine extracted from diapers. Within-series and between-day precisions were < 14% (CV%) over the concentration range of metabolites from 0.4 to 20.4 mu g/l urine. When concentrations of each metabolite were measured with the developed method after pouring 2 ml urine, which was obtained from adults both in a general population and pest control operators, on diapers, good correlations were shown between the measured results and the concentrations measured directly for the respective urine with the conventional method (Spearman's rank correlation coefficient 0.889 for CDCA and 0.989 for 3-PBA; n = 27-28). The developed method would be applicable to epidemiological studies.
  • Species and inter-individual differences in metabolic capacity of di(2-ethylhexyl)phthalate (DEHP) between human and mouse livers, Yuki Ito, Michihiro Kamijima, Chie Hasegawa, Masahiro Tagawa, Toshio Kawai, Mio Miyake, Yumi Hayashi, Hisao Naito, Tamie Nakajima, Environ Health Prev Med, 19, (2) 117 - 125,   2014年03月, 査読有り, This study was conducted to assess inter-species and inter-individual differences in the metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans and mice. The activities of four DEHP-metabolizing enzymes [lipase, UDP-glucuronocyltransferase (UGT), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)] were measured in the livers of 38 human subjects of various ages and in eight 129/Sv male mice. Microsomal lipase activity was significantly lower in humans than in mice. The V (max)/K (m) value in humans was one-seventh of that in mice, microsomal UGT activity in humans was a sixth of that in mice, and cytosolic ALDH activity for 2-ethylhexanal in humans was one-half of that in mice. In contrast, ADH activity for 2-ethylhexanol was twofold higher in humans than in mice. The total amount of DEHP urinary metabolites and the concentration of mono(2-ethylhexyl)phthalate (MEHP) were much higher in intact mice than in the U.S. general population based on data reported elsewhere, regardless of the similar estimated DEHP intake between these mice and the human reference population. However, mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) levels were higher in the latter than in the former. Of note, inter-subject variability in the activities of all enzymes measured was 10-26-fold. The inter-individual variation in the metabolism of DEHP in humans may be greater than the difference between mice and humans (inter-species variation), and both may affects the risk assessment of DEHP.
  • Organophosphate agents induce plasma hypertriglyceridemia in mouse via single or dual inhibition of the endocannabinoid hydrolyzing enzyme(s), Himiko Suzuki, Yuki Ito, Yuki Noro, Mamoru Koketsu, Michihiro Kamijima, Motohiro Tomizawa, TOXICOLOGY LETTERS, 225, (1) 153 - 157,   2014年02月, Diverse serine hydrolases including endocannabinoid metabolizing enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have been suggested as secondary targets for organophosphate (OP) agents to exert adverse toxic effects such as lipid homeostasis disruption. The goal of this investigation is to verify that a major OP insecticide fenitrothion (FNT) induces plasma hypertriglyceridemia through the inhibition of FAAH and/or MAGL in comparison with that elicited by isopropyl dodecylfluorophosphonate (IDFP), a potent FAAH/MAGL inhibitor. Fasted mice were treated intraperitoneally with FNT or IDFP and were subsequently sacrificed for evaluations of plasma triglyceride (TG) levels and liver FAAH/MAGL activities. Plasma TG levels were significantly enhanced by the FNT or IDFP treatment (1.7- or 4.8-fold, respectively) compared with that of vehicle control. The IDFP exposure reduced the liver FAAH and MAGL activities, whereas the FNT exposure led to the preferential FAAH inhibition. The brain acetylcholinesterase was almost unaffected by the FNT or IDFP treatment, thus leading to no neurotoxic sign. Intriguingly, the TG elevations were averted by concomitant administration with the cannabinoid receptor antagonist AM251. The present findings suggest that OP agents induce plasma hypertriglyceridemia in mouse through single or dual inhibition of FAAH or/and MAGL, apparently leading to overstimulation of cannabinoid signal regulating energy metabolism. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
  • Trends in asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma., Kiyoshi Sakai, Naomi Hisanaga, Eiji Shibata, Michihiro Kamijima, Gaku Ichihara, Yasuhiro Takeuchi, Tamie Nakajima, Ann Occup Hyg, 58, (1) 103 - 20,   2014年01月, 査読有り, OBJECTIVES: We aimed to elucidate changes in asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma over time. METHODS: Lung tissues were obtained from 46 patients with mesothelioma who died or underwent surgery between 1971 and 2005. All of the patients had a history of occupational asbestos exposure. We classified patients into four groups according to the period during which their lung tissue was obtained. Asbestos and non-asbestos fibre concentrations were determined by transmission electron microscopy with energy-dispersive X-ray analysis using a low-temperature ashing procedure. RESULTS: From the 1970s to the 2000s, we observed a decrease in the geometric mean of total asbestos concentration (67.4-1.05 million fibres per gram dry lung), chrysotile concentration (25.0-0.66 million fibres per gram dry lung), amphibole asbestos concentration (21.3-0.76 million fibres per gram dry lung), and non-asbestos fibre concentration (326-19.3 million fibres per gram dry lung). The mean duration of asbestos exposure decreased from 33.7 to 17.6 years, and the mean duration since the last exposure increased from 0.3 to 21.5 years. The percentage of longer fibres to total fibres tended to increase over time, whereas the mean fibre length did not differ significantly. CONCLUSIONS: The present study suggested that asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma who have occupational histories of asbestos exposure may have decreased from the 1970s to the 2000s.
  • 子どもの健康と環境に関する全国調査(エコチル調査)-概要並びに東海地区における実施状況と今度の展望-, 上島通浩, 榎原毅, 宮田麻衣子, 加藤沙耶香, 若林千鶴子, 伊藤由起, 齋藤伸治, 杉浦真弓, 東海産科婦人科学会雑誌, 51, 9 - 15,   2014年, 招待有り
  • Quantitation of neonicotinoid metabolites in human urine using GC-MS, Hiroshi Nomura, Jun Ueyama, Takaaki Kondo, Isao Saito, Katsuyuki Murata, Toyoto Iwata, Shinya Wakusawa, Michihiro Kamijima, JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 941, 109 - 115,   2013年12月, A rapid and sensitive analytical method using gas chromatography-mass spectrometry (GC-MS) was developed for the measurement of neonicotinoid (NEO) metabolites 6-chloronicotinic acid (6CN), 2-chloro-1,3-thiazole-5-carboxylic acid (2CTCA) and 3-furoic acid (3FA) from human urine. After acid hydrolysis, the metabolites were extracted using solid phase extraction (SPE) column (Bond Elute Plexa PCX) and eluted with methanol. N,O-bis (trimethylsilyl) trifluoroacetamide with 1% trimethylchlorosilane (BSTFA-TMCS, 99:1) was used for the derivatization of metabolites and analyzed by GC-MS with the electron ionization mode. The elution solvent, derivatization reagent and its conditions were mainly optimized for improved detection and quantitation of the metabolites based on signal-to-noise ratio, recoveries and reproducibility. Our present method offered a sufficiently low limit of detection (0.1 mu g/L for each metabolite) with satisfactory within-run and between-day accuracy and precision (variability less than 12.3%, R.S.D). This method is simple, sensitive and precise, and has been successfully applied to quantify low concentrations of urinary 6CN, 2CTCA and 3FA for the occupational NEO exposures survey (C) 2013 Elsevier B.V. All rights reserved.
  • Occupational trichloroethylene hypersensitivity syndrome: Human herpesvirus 6 reactivation and rash phenotypes, Michihiro Kamijima, Hailan Wang, Osamu Yamanoshita, Yuki Ito, Lihua Xia, Yukie Yanagiba, Cishan Chen, Ai Okamura, Zhenlie Huang, Xinxiang Qiu, Xiangrong Song, Tingfeng Cai, Lili Liu, Yichen Ge, Yingyu Deng, Hisao Naito, Tetsushi Yoshikawa, Mikiko Tohyama, Laiyu Li, Hanlin Huang, Tamie Nakajima, JOURNAL OF DERMATOLOGICAL SCIENCE, 72, (3) 218 - 224,   2013年12月, Background: Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational ICE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). Objective: This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. Methods: HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. Results: The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (>= 100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p < 0.01). Positive correlations between HHV6 DNA, TNF-alpha, IFN-gamma, IL-6 and IL-10 were significant (p < 0.05) except for that between HHV6 DNA and IFN-gamma. An increase in HHV6 DNA was positively associated with an increase in TNF-alpha on admission (p < 0.01). HHV6 DNA, the antibody titers, TNF-alpha and IL-10 concentrations were significantly higher in ED than in the non-ED type (p < 0.05). Conclusion: Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Sex Differences in Metabolism of Trichloroethylene and Trichloroethanol in Guinea Pigs, Yui Hibino, Hailan Wang, Hisao Naito, Na Zhao, Dong Wang, Xiaofang Jia, Hongling Li, Xiangrong Song, Lili Liu, Yongshun Huang, Yuki Ito, Hanlin Huang, Michihiro Kamijima, Tamie Nakajima, JOURNAL OF OCCUPATIONAL HEALTH, 55, (6) 443 - 449,   2013年11月, 査読有り, Objectives: Trichloroethylene (TRI) has the potential to cause generalized dermatitis complicated with hepatitis. The guinea pig maximization test (GPMT) also suggests that both TRI and its metabolite trichloroethanol (ICE) exhibit immunogenicity and possible sex differences in guinea pigs. However, TRI and TOE metabolisms in guinea pigs have not been elucidated in detail. The first issue to clarify may be the sex differences in relation to the immunogenicity, Methods: We collected urine from Hartley male and female guinea pigs 24 hours after intracutaneous injection of TRI, TCE or trichloroacetic acid (TCA) during a GPMT and measured the urinary metabolites by gas chromatography-mass spectrometry. Results: After TRI treatment, the amount of TCA was significantly greater in females than males, while there was no sex difference in the total amount (TCA + TOE). TCA was only detected in urine after TCA treatment. Interestingly, not only TCE but also TCA was detected in urine of both sexes after TOE treatment, and the amount of TCA was also greater in females than males. An additional experiment showed that TOE treatment did not result in the detection of urinary TCA in cytochrome P450 (CYP)2E1-null mice but did in wild-type mice, suggesting the involvement of CYP2E1 in the metabolism from TOE to TCA. The constitutive expression of CYP2E1 in the liver of guinea pigs was greater in females than males. Conclusions: The sex difference in urinary TCA excretion after TRI and TOE treatments may be due to variation of the constitutive expression of CYP2E1.
  • Anticholinesterase insecticide action at the murine male reproductive system, Yuki Noro, Motohiro Tomizawa, Yuki Ito, Himiko Suzuki, Keisuke Abe, Michihiro Kamijima, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 23, (19) 5434 - 5436,   2013年10月, The present report describes for the first time that anticholinesterase type insecticides specifically inhibit the fatty acid amide hydrolase and/or monoacylglycerol lipase, as secondary target(s), in the murine male reproductive system (testis and epididymis cauda), thereby presumably being involved with spermatotoxicity such as deformity, underdevelopment, and reduced motility. (C) 2013 Elsevier Ltd. All rights reserved.
  • A Potential Target for Organophosphate Insecticides Leading to Spermatotoxicity, Himiko Suzuki, Motohiro Tomizawa, Yuki Ito, Keisuke Abe, Yuki Noro, Michihiro Kamijima, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 61, (41) 9961 - 9965,   2013年10月, Organophosphate (OP) insecticides as an anticholinesterase also act on the diverse serine hydrolase targets, thereby revealing secondary or unexpected toxic effects including male reproductive toxicity. The present investigation detects a possible target molecule(s) for OP-induced spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) from a chemical standpoint. The activity-based protein profiling (ABPP) approach with a phosphonofluoridate fluorescent probe pinpointed the molecular target for fenitrothion (FNT, a major OP insecticide) oxon (bioactive metabolite of FNT) in the mouse testicular membrane proteome, i.e., FNT oxon phosphorylates the fatty acid amide hydrolase (FAAH), which plays pivotal roles in spermatogenesis and sperm motility acquirement. Subsequently, mice were treated orally with vehicle or FNT for 10 days, and FAAH activity in testis or epididymis cauda was markedly reduced by the subacute exposure. ABPP analysis revealed that FAAH was selectively inhibited among the FNT-treated testicular membrane proteome. Accordingly, FAAH is a potential target for OP-elicited spermatotoxicity.
  • Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice, Ryosuke Nakashima, Yumi Hayashi, Khalequzzaman Md, Xiaofang Jia, Dong Wang, Hisao Naito, Yuki Ito, Michihiro Kamijima, Frank J. Gonzalez, Tamie Nakajima, TOXICOLOGY, 309, 52 - 60,   2013年07月, Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPAR alpha), peroxisome proliferator-activated receptor alpha-null (Ppar alpha-null) and humanized PPAR alpha (hPPAR alpha) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, alpha-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPAR alpha mice than in Ppara-null and hPPAR alpha mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPAR alpha mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, alpha-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPAR alpha mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPAR alpha mice, similarly to triglyceride levels. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
  • Sick Building Syndrome by Indoor Air Pollution in Dalian, China, Peng Guo, Kazuhito Yokoyama, Fengyuan Piao, Kiyoshi Sakai, Md Khalequzzaman, Michihiro Kamijima, Tamie Nakajima, Fumihiko Kitamura, INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 10, (4) 1489 - 1504,   2013年04月, This study assessed subjective symptoms related to indoor concentrations of chemicals among residents in a housing estate in Dalian, China, where indoor air pollution by interior decoration materials has recently become a major health problem. Fifty-nine males and 50 females were surveyed for their symptoms related to sick building syndrome. Formaldehyde (HCHO), NO2, and volatile organic compounds (VOCs) in their dwellings were collected using a diffusion sampler and measured by GC/MS. For residents with one or more symptoms in the past, HCHO, butanol or 1,2-dichloroethane concentrations were significantly greater in their bedrooms or kitchens compared with those of subjects without previous symptoms. For residents with one or more symptoms at the time of the study, 1,1,1-trichloroethane, xylene, butanol, methyl isobutyl ketone, and styrene concentrations in their bedrooms or kitchens were significantly greater compared with those of residents without symptoms. HCHO, NO2, and VOCs were detected in all rooms, but their levels were lower than the guideline values except for HCHO in two rooms. Chemical substances from interior decoration materials at indoor air levels lower than their guideline values might have affected the health status of residents.
  • 大学生のアルバイトとワーク・スクール・コンフリクト―多重役割マップ(MRM)を用いたナラティブ・アプローチの展開―, 山田泰行, 水野基樹, 榎原 毅, 芳地泰幸, 上島通浩, 広沢正孝, 産業保健人間工学研究, 14, (1) 7 - 15,   2013年
  • Upregulation of calprotectin and downregulation of retinol binding protein in the serum of workers with trichloroethylene-induced hypersensitivity dermatitis., Huang Z, Yue F, Yang X, Xia L, Chen C, Qiu X, Huang J, Li L, Kamijima M, Nakajima T, Huang H, J Occup Health, 54, 299 - 309,   2013年
  • Pyrethroid Pesticide Exposure and Risk of Childhood Acute Lymphocytic Leukemia in Shanghai, Guodong Ding, Rong Shi, Yu Gao, Yan Zhang, Michihiro Kamijima, Kiyoshi Sakai, Guoquan Wang, Chao Feng, Ying Tian, ENVIRONMENTAL SCIENCE & TECHNOLOGY, 46, (24) 13480 - 13487,   2012年12月, Significant amounts of pyrethroid pesticides are used throughout China. Previous studies have suggested that exposure to pesticides may increase the risk of childhood cancer; however, few studies have focused on pyrethroid metabolites. We investigated five nonspecific metabolites of pyrethroid pesticides found in children's urine and examined the correlation with childhood leukemia. We conducted a hospital-based case-control study of childhood acute lymphocytic leukemia (ALL) in Shanghai between 2010 and 2011. The study included 176 children aged 0-14 years and 180 controls matched for age and sex. Compared with those in the lowest quartiles of total and individual metabolites, the highest quartiles were associated with an approximate 2-fold increased risk of ALL [total metabolites: odds ratio (OR) = 2.75, 95% confidence interval (CI), 1.43-5.29; cis-DCCA: OR = 2.21, 95% CI, 1.16-4.19; trans-DCCA: OR = 2.33, 95% CI, 1.23-4.41; and 3-PBA: OR = 1.84, 95% CI, 1.00-3.38], and most of the positive trends were significant (p < 0.05). Our findings suggest that urinary levels of pyrethroid metabolites may be associated with an elevated risk of childhood ALL and represent a previously unreported quantitative exposure assessment for childhood leukemia.
  • Evidence for diazinon-mediated inhibition of cis-permethrin metabolism and its effects on reproductive toxicity in adult male mice, Dong Wang, Michihiro Kamijima, Ai Okamura, Yuki Ito, Yukie Yanagiba, Xiao-fang Jia, Hisao Naito, Jun Ueyama, Tamie Nakajima, REPRODUCTIVE TOXICOLOGY, 34, (4) 489 - 497,   2012年12月, The potential toxicity resulting from combinatorial effects of organophosphorus and pyrethroid insecticides are not completely known. We evaluated male reproductive toxicity in mice co-exposed to diazinon and cis-permethrin. Nine-week-old male Sv/129 mice were exposed to diazinon (10 mu mol/kg/day) or cis-permethrin (90 mu mol/kg/clay) alone or in combination (100 mu mol/kg/day), or vehicle (corn oil), for 6 weeks. Diazinon and the diazinon-permethrin mixture inhibited plasma and liver carboxylesterase activities. In the mixture group, urinary excretion of cis-permethrin metabolite 3-phenoxybenzoic acid decreased along with increased plasma and testicular concentrations of cis-permethrin, while excretion of diazinon metabolites, diethylphosphate and diethylthiophosphate, did not change, versus mice exposed to each chemical alone, which suggested that inhibition of carboxylesterase decreased the metabolic capacity to cis-permethrin. Though the co-exposure decreased testosterone biosynthesis, increased degenerate germ cells in seminiferous tubule and sperm morphological abnormalities versus controls more clearly than exposure to cis-permethrin alone, the expected potentiation of toxicity was not evident. (C) 2012 Elsevier Inc. All rights reserved.
  • Effect of nanoparticle-rich diesel exhaust on testicular and hippocampus steroidogenesis in male rats, Nozomi Yamagishi, Yuki Ito, Doni Hikmat Ramdhan, Yukie Yanagiba, Yumi Hayashi, Dong Wang, Chun Mei Li, Shinji Taneda, Akira K. Suzuki, Kazuyoshi Taya, Gen Watanabe, Michihiro Kamijima, Tamie Nakajima, INHALATION TOXICOLOGY, 24, (8) 459 - 467,   2012年07月, Background: Nanoparticle-rich diesel exhaust (NR-DE) has potentially adverse effects on testicular steroidogenesis. However, it is unclear whether NR-DE influences steroidogenic systems in the brain. Objective: To investigate the effect of NR-DE on hippocampal steroidogenesis of adult male rats in comparison with its effect on the testis. Methods: F344 male rats (8-week-old) were randomly divided into four groups (n = 8 or 9 per group) and exposed to clean air with 4.6 +/- 3.2 mu g/m(3) in mass concentration, NR-DE with 38 +/- 3 mu g/m(3) (a level nearly equivalent to the environmental standard in Japan (low NR-DE)), NR-DE with 149 +/- 8 mu g/m(3) (high NR-DE), or filtered diesel exhaust with 3.1 +/- 1.9 mu g/m(3) (F-DE), for 5 hours/day, 5 days/week, for 1, 2 or 3 months. F-DE was prepared by removing only particulate matters from high NR-DE with an HEPA filter. Results: Exposures to the high NR-DE for 1 month, and low NR-DE for 2 months, significantly increased or tended to increase plasma and testicular testosterone levels compared to clean air exposure, which might have resulted from the increased expression of mRNA of steroidogenic acute regulatory protein and its protein in the testes of rats. In the hippocampus, high NR-DE exposure for 1 month significantly increased the androstendione level compared to the clean air exposure, while no significant difference was observed in the steroidogenesis between fresh air exposure and any exposure to NR-DE or F-DE. Conclusion: NR-DE may influence steroidogenic enzymes in the testis, but not those in the hippocampus.
  • Neurogenic airway microvascular leakage induced by toluene inhalation in rats, Tatsuo Sakamoto, Michihiro Kamijima, Mio Miyake, EUROPEAN JOURNAL OF PHARMACOLOGY, 685, (1-3) 180 - 185,   2012年06月, Toluene is a representative airborne occupational and domestic pollutant that causes eye and respiratory tract irritation. We investigated whether a single inhalation of toluene elicits microvascular leakage in the rat airway. We also evaluated the effects of CP-99,994, a tachykinin NK1 receptor antagonist, and ketotifen, a histamine H1 receptor antagonist with mast cell-stabilizing properties, on the airway response. The content of Evans blue dye that extravasated into the tissues was measured as an index of plasma leakage. Toluene (18-450 ppm, 10 min) concentration-dependently induced dye leakage into the trachea and main bronchi of anesthetized and mechanically ventilated rats. Toluene at concentrations of >= 50 and >= 30 ppm caused significant responses in the trachea and main bronchi, respectively, which both peaked after exposure to 135 ppm toluene for 10 min. This response was abolished by CP-99,994 (5 mg/kg i.v.), but not by ketotifen (1 mg/kg i.v.). Nebulized phosphoramidon (1 mM, 1 min), a neutral endopeptidase 24.11 inhibitor, significantly enhanced the response induced by toluene (135 ppm, 10 min) compared with nebulized 0.9% saline (1 min). These results show that toluene can rapidly increase airway plasma leakage that is predominantly mediated by tachykinins endogenously released from airway sensory nerves. However, mast cell activation might not be important in this airway response. (C) 2012 Elsevier B.V. All rights reserved.
  • Urinary concentrations of organophosphorus insecticide metabolites in Japanese workers, Jun Ueyama, Isao Saito, Takaaki Kondo, Tomoko Taki, Akiko Kimata, Shun Saito, Yuki Ito, Katsuyuki Murata, Toyoto Iwata, Masahiro Gotoh, Eiji Shibata, Shinya Wakusawa, Michihiro Kamijima, CHEMOSPHERE, 87, (11) 1403 - 1409,   2012年06月, A recent development in analytical chemistry has enabled us to monitor systemic organophosphorus insecticide (OP) exposure at individual levels. At present, however, limited data are currently available on urinary OP metabolite levels worldwide. The purpose of this study was to assess urinary dialkylphosphate (DAP) concentrations in Japanese workers. Urine samples were collected in both summer and winter from 339 Japanese adults who worked as food distributors (FDs, n = 164), apple farmers (AFs, n = 147) and pest control operators (PCOs, n = 28). DAPs were measured by gas chromatography-mass spectrometry after derivatization with pentafluorobenzylbromide. Dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP) were detected in the urine of over 87% of the studied populations in both seasons. The geometric mean values of total DAPs (nmol g(-1) creatinine), DMP, DMTP, DEP and DETP (mu g g(-1) creatinine) in summer and winter were 106.7 and 98.3, 7.0 and 3.8, 3.4 and 4.5, 0.8 and 1.5, and 0.3 and 0.2 for the FDs, 440.8 and 197.7, 33.1 and 10.8, 10.1 and 5.8, 4.2 and 4.7 and 1.6 and 0.8 for the AFs, and 473.4 and 284.6, 28.9 and 22.2, 17.6 and 4.6, 3.5 and 4.4, and 0.5 and 0.6 for the PCOs, respectively, thereby revealing significantly higher concentrations in AFs and PCOs groups than in the FDs in both seasons except for winter DMTP. These DAP concentrations were approximately the same or at lower levels compared with those reported in the previous literature. This is one of the first studies to demonstrate urinary DAP concentrations in Japanese adults. (C) 2012 Elsevier Ltd. All rights reserved.
  • Differences in metabolite burden of di(2-ethylhexyl)phthalate in pregnant and postpartum dams and their offspring in relation to drug-metabolizing enzymes in mice, Yumi Hayashi, Yuki Ito, Yukie Yanagiba, Michihiro Kamijima, Hisao Naito, Tamie Nakajima, ARCHIVES OF TOXICOLOGY, 86, (4) 563 - 569,   2012年04月, Di(2-ethylhexyl)phthalate (DEHP) induced adverse effects on mice offspring, and the metabolite mono(2-ethylhexyl)phthalate (MEHP) may be essential to determine the toxicity. In this experiment, we measured liver MEHP levels and the factors determining the metabolism, two enzyme activities [lipase and uridine 5'-diphosphate-glucuronosyltransferase (UGT)] or expression of cytochrome P450 4A14 (CYP4A14) in dams (on gestational day 18 and postnatal day 2) and their offspring. MEHP concentrations in the liver from pregnant dams were 1.5 times higher than those of postpartum dams at exposure to 0.05% DEHP. Accordingly, MEHP concentrations were 1.7 times higher in fetuses than in pups at the dose. Interestingly, lipase activity was 1.8-fold higher in pregnant dams than postpartum ones, but no such difference was noted in the activity between fetuses and pups. UGT activity was also 1.5-fold higher in pregnant dams than postpartum ones, whereas the activity in the fetuses was 1/2 that of pups. No difference was noted in CYP4A14 levels between pregnant and postpartum mice, whereas the levels in the fetuses were < 1/10 those of pups. DEHP exposure did not influence lipase activity, whereas it slightly enhanced UGT activity and exclusively increased CYP4A14 levels in pregnant and/or postpartum dams. Taken together, the higher MEHP levels in pregnant dams than postpartum ones may be primarily due to higher lipase activities in pregnant dams, which may closely reflect those in fetuses and pups.
  • New analytical method for sensitive quantification of urinary 3-methyl-4-nitrophenol to assess fenitrothion exposure in general population and occupational sprayers, Ai Okamura, Isao Saito, Jun Ueyama, Yuki Ito, Tamie Nakajima, Michihiro Kamijima, TOXICOLOGY LETTERS, 210, (2) 220 - 224,   2012年04月, The measurement of blood cholinesterase (ChE) activities is adopted worldwide for biological monitoring of exposure to organophosphorus insecticides (OPs). Recent development of analytical chemistry has made sensitive quantification possible of non-specific OP metabolites, dialkylphosphates, in urine as a biomarker of low-level OP exposure. In this study, we established a method for quantification of urinary 3-methyl-4-nitrophenol (MNP), a specific metabolite of fenitrothion (FNT), and a parathion metabolite p-nitrophenol (PNP), using gas chromatography-mass spectrometry. The limits of detection of MNP and PNP were 0.3 and 0.5 mu g/L, respectively. The method enabled the quantification of both free and conjugated metabolites. This method was actually applied to monitor human urine in summer and winter in FNT sprayers (N = 29 and 9, respectively) and control workers (N = 17 and 29, respectively). Geometric mean total MNP concentrations (mu g/g creatinine) in the FNT sprayers (28.8 in summer and 8.6 in winter) were significantly higher than those of the controls (3.1 in summer and 2.3 in winter) in both seasons. Among the sprayers, total MNP concentrations in summer were significantly higher than in winter. In contrast, no significant difference in total PNP concentrations was observed between FNT sprayers (geometric mean 3.4 in summer and 3.0 in winter) and controls (3.6 in summer and 2.1 in winter). No seasonal difference was observed in each group. In conclusion, the present new method is sensitive enough for biological monitoring of FNT and parathion metabolites even in a non-spraying population. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor alpha Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver, Yuki Ito, Toshiki Nakamura, Yukie Yanagiba, Doni Hikmat Ramdhan, Nozomi Yamagishi, Hisao Naito, Michihiro Kamijima, Frank J. Gonzalez, Tamie Nakajima, PPAR RESEARCH,   2012年, Dibutylphthalate (DBP), di(2-ethylhexyl) phthalate (DEHP), and di(2-ethylhexyl) adipate (DEHA) are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR) alpha, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPAR alpha by these plasticizers using wild-type (mPPAR alpha) and humanized PPAR alpha (hPPAR alpha) mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control), 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg), DEHP (977, 1953 mg/kg), and DEHA (926, 1853 mg/kg), respectively. Generally, hepatic PPAR alpha of mPPAR alpha mice was more strongly activated than that of hPPAR alpha mice when several target genes involving beta-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR) more in hPPAR alpha mice than in mPPAR alpha mice. Taken together, these plasticizers activated mouse and human hepatic PPAR alpha as well as CAR. The activation of PPAR alpha was stronger in mPPAR alpha mice than in hPPAR alpha mice, while the opposite was true of CAR.
  • Proliferation of sensory C-fibers and subsequent neurogenic inflammation in rat airway induced by inhaled lipopolysaccharide, Masanori Takeda, Mio Miyake, Taichiro Muto, Michihiro Kamijima, Tatsuo Sakamoto, NEUROTOXICOLOGY, 32, (6) 954 - 962,   2011年12月, Lipopolysaccharide (LPS) is associated with the development and exacerbation of airway inflammation. Increases in innervation of sensory C-fibers and tachykinin receptors, which mainly involve overproduction of neurotrophins such as nerve growth factor (NGF), may enhance neurogenic inflammation. Expression of NGF and its receptors in rat lungs is known to decline with age. We examined whether inhaled LPS causes proliferation of sensory C-fibers, increased expression of tachykinin receptors and subsequent enhancement of neurogenic inflammation in the airways of preweaning rats. Wistar male rats aged 2 weeks inhaled aerosolized LPS derived from Escherichia coli (0.1 mg/ml) for 30 min. Evans blue dye leakage into the trachea induced by gaseous formaldehyde or intravenous capsaicin was measured as an index of tachykinin NK1 receptor-mediated vascular permeability. Expression of substance P-immunoreactive nerves, tachykinin NK1 receptors, tumor necrosis factor (TNF)-alpha and NGF in the trachea was also assessed immunohistochemically. Neurogenic plasma leakage in the trachea increased significantly between 7 and 21 days after LPS inhalation. Expression of TNF-alpha, NGF, substance P-immunoreactive nerves and tachykinin NK1 receptors was enhanced, peaking at 28 h, 7 days, 14 days and 14 days after LPS inhalation, respectively. Pretreatment with infliximab, a blocking antibody for TNF-alpha, almost completely abolished the airway changes seen after LPS inhalation. In conclusion, inhaled LPS increased innervation of sensory C-fibers and expression of tachykinin NK1 receptors in the airway, probably resulting in enhancement of neurogenic airway inflammation. These airway responses may be caused by overproduction of neurotrophins including NGF, mainly through a TNF-alpha-mediated pathway. (C) 2011 Elsevier Inc. All rights reserved.
  • Hepatic peroxisome proliferator-activated receptor α may have an important role in the toxic effects of di(2-ethylhexyl)phthalate on offspring of mice., Hayashi Y, Ito Y, Yamagishi N, Yanagiba Y, Tamada H, Wang D, Ramdhan DH, Naito H, Harada Y, Kamijima M, Gonzales FJ, Nakajima T, Toxicology, 289, (1) 1 - 10,   2011年10月
  • Effect of oral exposure to fenitrothion and 3-methyl-4-nitrophenol on splenic cell populations and histopathological alterations in spleen in Wistar rats, Qing Li, Maiko Kobayashi, Hirofumi Inagaki, Yukiyo Hirata, Shigeru Sato, Masamichi Ishizaki, Ai Okamura, Dong Wang, Tamie Nakajima, Michihiro Kamijima, Tomoyuki Kawada, HUMAN & EXPERIMENTAL TOXICOLOGY, 30, (7) 665 - 674,   2011年07月, Fenitrothion (FNT) is used throughout the world as an insecticide in agriculture. To investigate the effect of FNT on the splenocytes and the underlying mechanism, FNT and its main metabolite, 3-methyl-4-nitrophenol (MNP), were administered orally to Wistar rats in daily doses of 0, 5 and 10 mg/kg, 4-5 days/week for 9 weeks. Splenocytes were harvested from control and exposed rats, and the following cell phenotypes were quantified by flow cytometry: (1) B cells (PE-CD45RA), (2) T cells (FITC-CD3), (3) T cell subsets (PE-CD4 and PerCP-CD8), (4) natural killer (NK) cells (FITC-CD161a), (5) macrophages (FITC-CD11b), and (6) granulocyte (PE-granulocyte). Body weight, weight of the spleen, and histopathological alterations of spleens were also examined. The percentage of splenic CD8+ T cells and the ratio of CD8/CD4 in the group receiving 10 mg/kg FNT, and the percentages of splenic CD3+ and CD8+ T cells in the group receiving 10 mg/kg MNP were significantly decreased compared with those in the controls. FNT exposure also significantly decreased the weight of the spleen and body weight. In addition, apoptotic lymphocytes in spleen were observed in FNT-exposed rats under transmission electron microscope. However, FNT and MNP exposures did not affect splenic NK cells, B cells, macrophages, and granulocytes. The above findings indicate that FNT and MNP may selectively affect splenic T cells in rats.
  • Effect of DDVP on urinary excretion levels of pyrethroid metabolite 3-phenoxybenzoic acid in rats, Naoko Hirosawa, Jun Ueyama, Takaaki Kondo, Michihiro Kamijima, Kenji Takagi, Sanae Fujinaka, Ayaka Hirate, Takaaki Hasegawa, Shinya Wakusawa, TOXICOLOGY LETTERS, 203, (1) 28 - 32,   2011年05月, Pyrethroid insecticide (PYR) is used worldwide in agriculture and for indoor extermination of harmful insects. Urinary PYR metabolites (e.g. 3-phenoxybenzoic acid, 3PBA) have been used as the most sensitive biomarker for environmental PYR exposure since the late 1990s. In this study, we examined the effect of organophosphorus insecticide (OP) dichlorvos (DDVP) on excretion levels of urinary cis-permethrin-derived 3PBA in rats. Concentration of urinary 3PBA and cis-permethrin in plasma was monitored using gas chromatography-mass spectrometry and high-performance liquid chromatography after cis-permethrin injection (20 mg/kg) via the tail vein of rats pretreated intraperitoneally with DDVP (low dose, 0.3 mg/kg; high dose, 1.5 mg/kg). The amount of urinary 3PBA excretion over 48 h after cis-permethrin administration in control was 21.5 +/- 5.1 mu g (mean +/- S.D.). In the low- and high-dose DDVP groups, the amounts of urinary 3PBA excretion were decreased to 81.1% (17.4 +/- 2.7 mu g) and 70.3% (15.1 +/- 2.6 mu g) of control, respectively. The plasma concentrations of cis-permethrin-derived 3-phenoxybenzyl alcohol (3PBAlc), which is a metabolite derived following hydrolysis of cis-permethrin, in high-dose DDVP group (0.18 +/- 0.01 mu g) were significantly lower than in control (0.23 +/- 0.03 mu g) 1 h after cis-permethrin injection. Both in the control and high-dose DDVP group, no differences were observed in the excretion levels of urinary 3PBA after injection of 3PBAlc (25 mg/kg, iv.). These results suggested that the effect of DDVP on the amount of urinary 3PBA excretion was caused by the DDVP-induced modification of the cis-permethrin metabolic pathway. In conclusion, the possible decrease in urinary excretion level of 3PBA due to co-exposure to OPs should be considered in the biological monitoring of PYR exposure. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Staphylococcal enterotoxin B causes proliferation of sensory C-fibers and subsequent enhancement of neurogenic inflammation in rat skin, Mihoko Ohshima, Mio Miyake, Masanori Takeda, Michihiro Kamijima, Tatsuo Sakamoto, JOURNAL OF INFECTIOUS DISEASES, 203, (6) 862 - 869,   2011年03月, 査読有り, Methods. SEB was applied intracutaneously to the abdomen of preweaning and adult rats. Evans blue dye leakage into the skin induced by topical 10% formalin was measured as an index of neurogenic skin vascular permeability. Local expression of substance P, tachykinin NK1 receptors, and nerve growth factor was assessed immunohistochemically. In addition, we assessed the effects of topical tacrolimus on these skin responses induced by SEB. Results. Increased neurogenic skin plasma leakage was seen 7 days after SEB treatment in 2 different age groups. Innervation of substance P-immunoreactive nerves and expression of tachykinin NK1 receptors and nerve growth factor were also promoted by SEB, peaking at 7 days, 7 days, and 56 h after SEB treatment, respectively. Tacrolimus markedly inhibited these skin changes. Conclusions. SEB increased the innervation of sensory C-fibers and tachykinin NK1 receptors in rat skin, probably because of upregulated production of neurotrophins, including nerve growth factor, leading to enhancement of neurogenic skin inflammation. T cell activation induced by SEB may initiate these changes.
  • Indoor air pollution and health of children in biomass fuel-using households of Bangladesh: comparison between urban and rural areas., Khalequzzaman M, Kamijima M, Sakai K, Ebara T, Hoque BA, Nakajima T, Environ Health Prev Med, 16, (6) 375 - 83,   2011年
  • ナノ粒子を多く含むディーゼル排気ガス曝露による肝臓への影響, 伊藤由起, ラムダン ドニヒクマット, 柳場由絵, 山岸希, 上島通浩, 那須民江, 日本衛生学雑誌, 66, (4) 638 - 42,   2011年
  • Pleural plaque profiles on the chest radiographs and CT scans of asbestos-exposed Japanese construction workers., Momen Elshazley, Eiji Shibata, Naomi Hisanaga, Gaku Ichihara, Ashraf A Ewis, Michihiro Kamijima, Sahoko Ichihara, Kiyoshi Sakai, Mitsuo Sato, Masashi Kondo, Yoshinori Hasegawa, Industrial health, 49, (5) 626 - 33,   2011年, Pleural plaques are asymptomatic focal thickenings of the pleura and considered the hallmark of asbestos exposure. However, it is often difficult to detect pleural plaques on chest x-rays (CXR). In a retrospective study, using chest CT scans of 140 Japanese asbestos-exposed construction workers who have probable or definite findings of pleural plaque on CXR; firstly, we proposed plaque morphology-based classification for CXR findings, and then we examined if those classified findings could be confirmed as pleural plaques on CT scans. Our morphology-based classification of pleural plaque findings included nine types. The percentages of confirmed pleural plaques on CT scans by type (number of confirmed pleural plaque on CT/number of observed on CXR) were 93% (40/43) for straight, 89% (56/63) for diamond, 88% (7/8) for double, 83% (19/23) for tapered medially, 80% (20/25) for parallel, 77% (23/30) for crescent, 79% (11/14) for tenting, 72% (18/25) for tapered-laterally (long type), and 0% (0/9) for tapered-laterally (short type). When added to the ILO classification, morphology-based classification of CXR pleural plaque findings makes its detection easier and hence chest radiograph continues to be a suitable tool for screening asbestos-related pleural plaques based on its simplicity, low radiation exposure, wide availability and cost-effectiveness.
  • Toxicokinetics of pyrethroid metabolites in male and female rats, Jun Ueyama, Naoko Hirosawa, Aiko Mochizuki, Akiko Kimata, Michihiro Kamijima, Takaaki Kondo, Kenji Takagi, Shinya Wakusawa, Takaaki Hasegawa, ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, 30, (1) 88 - 91,   2010年07月, The toxicokinetic characteristics of 3-phenoxybenzyl alcohol (3PBA1c) and 3-phenoxybenzaldehyde (3PBAld; metabolites of pyrethroid [PYR] after 25 mg/kg, single intravenous administration), were investigated in male and female rats. The systemic clearance (Cl) of 3PBAlc in females (0.403 +/- 0.040 l/h/kg) was significantly larger than that of males (0.227 +/- 0.036 l/h/kg). The plasma concentration-time curve of 3PBAld decreased gradually and then increased again 1 and 2 h after injection, suggesting the effect of enterohepatic circulation. The present study characterized the elimination and distribution of PYR metabolites and suggests that gender-related difference exists in the toxicokinetics of 3PBAlc and 3PBAld in rats. (C) 2010 Elsevier B.V. All rights reserved.
  • Heart rate variability assessment in Japanese workers recovered from depressive disorders resulting from job stress: measurements in the workplace, Mikio Takada, Takeshi Ebara, Michihiro Kamijima, INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, 83, (5) 521 - 529,   2010年06月, 査読有り, The purpose of this study is to clarify workers' autonomic nerve balance after long-term sick leave due to depressive disorders resulting from job stress compared with healthy workers. The participants were 28 Japanese male workers recovered from depressive disorders and 75 healthy male workers. For each participant, the lifestyle and the fatigue within 1 month were assessed by a checklist. Heart rate variability (HRV) was measured at the workplace by acceleration plethysmography (APG). HRV was assessed by the coefficient of variation of rate intervals (CV), the spectral components in the high- and low-frequency areas represented by the normalized HF and LF (nHF and nLF), and the ratio of LF to HF components (LF/HF). There was no significant difference in individual lifestyle and fatigue symptoms between the recovered and the healthy workers. The former workers showed significantly lower CV, higher nLF and log(10)LF/HF, and lower nHF that represent the predominance of sympathetic activity in comparison with the healthy workers. Moreover, the recovered workers who discontinued medications indicated significantly higher nLF and log(10)LF/HF, and lower nHF compared to the recovered workers who continued their medications. Recovered workers in the workplace tended to show the depressive HRV feature that is the dominant sympathetic activity compared with the healthy workers. They might still be showing job stress that was not detected by the checklist. HRV analyses by APG in addition to questionnaire has the potential to become an effective approach for assessing workers' job stress to prevent repeated absences.
  • Revised method for routine determination of urinary dialkyl phosphates using gas chromatography-mass spectrometry, Jun Ueyama, Michihiro Kamijima, Takaaki Kondo, Kenji Takagi, Eiji Shibata, Takaaki Hasegawa, Shinya Wakusawa, Tomoko Taki, Masahiro Gotoh, Isao Saito, JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 878, (17-18) 1257 - 1263,   2010年05月, 査読有り, Among urinary organophosphorus pesticide (OP) metabolites, dialkyl phosphates (DAPs) have been most often measured as a sensitive biomarker in non-occupational and occupational OP exposure risk assessment. In our conventional method, we have employed a procedure including simple liquid-liquid extraction (diethyl ether/acetonitrile), derivatization (pentafluorobenzylbromide, PFBBr) and clean-up (multi-layer column) for gas chromatography-mass spectrometry (GC-MS) analysis starting from 5-mL urine samples. In this study, we introduce a revised analytical method for urinary DAPs; its main modification was aimed at improving the pre-derivatization dehydration procedure. The limits of detection were approximately 0.15 mu g/L for dimethylphosphate (DMP), 0.07 mu g/L for diethylphosphate (DEP), and 0.05 mu g/L for both dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP) in 2.5-mL human urine samples. Within-run precision (percent of relative standard deviation, %RSD) at the DAP levels varying in the range of 0.5-50 mu g/L was 6.0-19.1% for DMP, 3.6-18.3% for DEP, 8.0-25.6% for DMTP and 9.6-27.8% for DETP. Between-run precision at 5 mu g/L was below 15.7% for all DAPs. The revised method proved to be feasible to routine biological monitoring not only for occupational OP exposure but also for environmental background levels in the general population. Compared to our previous method, the revised method underscores the importance of adding pre-derivatization anhydration for higher sensitivity and precision. (C) 2010 Elsevier B.V. All rights reserved.
  • Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol, Daichi Nakamura, Yukie Yanagiba, Zhiwen Duan, Yuki Ito, Ai Okamura, Nobuyuki Asaeda, Yoshiaki Tagawa, ChunMei Li, Kazuyoshi Taya, Shu-Yun Zhang, Hisao Naito, Doni Hikmat Ramdhan, Michihiro Kamijima, Tamie Nakajima, TOXICOLOGY LETTERS, 194, (1-2) 16 - 25,   2010年04月, Bisphenol A (BPA) causes reproductive toxicities, but the mechanisms are still unclear. In the present study, we sought to clarify these mechanisms in comparison with those of 17 beta-estradiol (E2). Prepubertal Wistar/ST male rats (4 weeks old) were subcutaneously administered BPA (0, 20, 100 and 200 mg/kg/day) or E2 (10 and 100 mu g/kg/clay) for 6 weeks. Both BPA and E2 treatments decreased plasma and testicular testosterone levels, and plasma luteinizing hormone (LH), but not E2 and follicle-stimulating hormone levels, though E2 treatment increased its plasma level. In relation to the decreased testosterone levels, BPA and E2 decreased expressions of steroidogenic enzymes and cholesterol carrier protein in Leydig cells. Thus, decreased testosterone levels in plasma might have resulted from decreased expressions of these enzymes and protein as well as from decreased plasma LH levels. Interestingly, the changes in steroidogenic enzymes and carrier protein were observed at lower levels of exposure to BPA or E2 than those inhibiting plasma LH levels. Microscopically, 200 mg/kg BPA and 100 mu g/kg E2 significantly decreased Leydig cell numbers in the testis. In addition, BPA and E2 also decreased expression of estrogen receptor a-mRNA, which might be related to the decreased numbers of Leydig cells. Thus, BPA directly affects not only the Leydig cells but also the pituitary gland, but the former may be impaired at lower exposure concentrations than the latter. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
  • Dermoscopic evaluation of vascular structures of various skin tumors in Japanese patients, Akihiro Sakakibara, Michihiro Kamijima, Shinichi Shibata, Satoshi Yasue, Michihiro Kono, Yasushi Tomita, JOURNAL OF DERMATOLOGY, 37, (4) 316 - 322,   2010年04月, Dermoscopic analysis of skin tumor has been mainly focused on pigmented structures. Recently, several different morphological types of vessels were found to be well associated with pigmented or non-pigmented skin tumors in white subjects. Therefore, the recognition of such vascular structures has been applied for diagnostic purposes. As little statistical information on the various pigmented skin tumor vessels of Japanese patients has been reported, we therefore tried to evaluate the association between various vascular structures and 741 tumor lesions of Japanese patients. Vascular structures were dermoscopically recognized in 41 of 102 cases of melanoma, 104 of 119 basal cell carcinoma (BCC), 86 of 257 seborrheic keratosis (SK), 35 of 210 dermal and compound nevus (DN/CN), six of 12 squamous cell carcinoma (SCC) and 16 of 41 Bowen disease (BD). The structures of arborizing and glomerular vessels statistically revealed diagnostic specificity for BCC and BD, respectively, and hairpin vessels were helpful for differentiating SK from other pigmented tumors, as already reported in white patients. The most common vascular pattern observed in melanoma was the linear-irregular structure, but this pattern in Japanese patients had less diagnostic value than in white patients, because its sensitivity was not significantly higher than in SCC. The most remarkable differences between our study and previous reports with white patients were low frequency and sensitivity of dotted, comma and polymorphous vessels in lesions of melanoma, BCC and DN/CN; these vessels had less diagnostic value for Japanese patients. Finally, the frequency of vascular structures observed in melanoma rose along with the increase of the Breslow's tumor thickness, and 88% of melanomas with vascular vessels revealed tumor thicknesses of more than 2 mm.
  • beta-Glucuronidase activity is a sensitive biomarker to assess low-level organophosphorus insecticide exposure, Jun Ueyama, Tetsuo Satoh, Takaaki Kondo, Kenji Takagi, Eiji Shibata, Masahiro Goto, Akiko Kimata, Isao Saito, Takaaki Hasegawa, Shinya Wakusawa, Michihiro Kamijima, TOXICOLOGY LETTERS, 193, (1) 115 - 119,   2010年03月, Acetylcholinesterase and butyrylcholinesterase (BChE) activities in blood are widely used as the biomarkers for organophosphorus insecticide (OP)exposure In the present Study. we conducted a cross-sectional Study to evaluate plasma beta-glucuronidase (BG), a sensitive biomarker candidate for OP exposure, BChE activities and urinary dialkyl phosphates (DAPs). OP metabolites We assessed the relationship between these biomarker levels in the following groups 32 controls (control), 21 pest control operators and their co-workers who had not sprayed OPs within 3 days prior to sample collection (PCO1), and 21 pest control operators who sprayed OPs within those 3 days (PCO2) Logarithmically transformed age-adjusted means of DAPs were 3.88. 5 62 and 6 45 nmol/g creatinine for control, PCO1 and PCO2, respectively (P < 0 001 for difference, P < 0 001 for trend) Logarithmically transformed age-adjusted means of BG were 1 40, 1 52 and 1.85 mu mol/L/h for control, PCO1 and PCO2, respectively. BG activity, but not BChE, was increased according to their OP exposure level (P = 0 038 for difference, P = 0 026 for trend) It was concluded that plasma BG activity is more sensitive biomarker as well as urinary OP metabolites than BChE for low-level exposure in humans (C) 2009 Elsevier Ireland Ltd All rights reserved.
  • Analysis and evaluation of pyrethroid exposure in human population based on biological monitoring of urinary pyrethroid metabolites, Jun Ueyama, Isao Saito, Michihiro Kamijima, JOURNAL OF PESTICIDE SCIENCE, 35, (2) 87 - 98,   2010年, 査読有り, The current risk assessment of human exposure to low-level pyrethroids (PYRs) is generally based on the estimation of residue intake from diets. Limited data are available on individual exposure levels in human studies, which is partly attributable to the difficulty in biological monitoring of PYR exposure. This obstacle has been overcome in recent years due to the evolution of analytical chemistry. Separation and sensitive identification and quantitation of urinary PYR metabolites are today reliably made with liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. This article gives an overview of the biological monitoring of urinary PYR metabolites, reviews PYR metabolite levels in general populations, and discusses future research perspectives in the field of environmental health. (C) Pesticide Science Society of Japan
  • Interactive Model of Subsidiary Behaviors, Work Performance and Autonomic Nerve Activity during Visual Display Terminal Work, Toshimasa Takanishi, Takeshi Ebara, Gen-i Murasaki, Tomohide Kubo, Norihide Tachi, Toru Itani, Michihiro Kamijima, JOURNAL OF OCCUPATIONAL HEALTH, 52, (1) 39 - 47,   2010年01月, Interactive Model of Subsidiary Behaviors, Work Performance and Autonomic Nerve Activity during Visual Display Terminal Work: Toshimasa TAKANISHI, et al. Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences-Objectives: The aims of the study were to investigate the systematic classification of subsidiary behaviors during visual display terminal (VDT) work and discuss the interpretation of these behaviors through an interactive model of subsidiary behaviors, work performance and autonomic nerve activity Methods: Twelve university students were instructed to perform continuous 120-min English transcription tasks in a sedentary posture Data on subsidiary behaviors, work performance (mean keystroke and mean error rates), and autonomic nervous system balance (log-transformed low frequency (LF) / high frequency (HF) ratio) were recorded every 5 min during VDT work Results: The subsidiary behaviors were categorized into 3 qualitatively independent factors distractive behaviors against monotony (DBM), sleepiness-related behaviors (SRB), and habitual behaviors (HB). A cross-correlation analysis indicated that an increase of DBM, which is considered as a sign of workers' attempt to escape from monotonous task operations, was related to a decline in performance. A decrease in the LF/HF ratio was followed by SRB after 5 min passed (r=-0.57, p<0.05), eventually leading to a restriction of the deterioration in performance An increase of DBM was predictive of an increase in errors (r=0.54, p<0.05), and a significant negative correlation (r=-0.46, p<0.05) between HB and autonomic nerve activity at 10 min after the appearance of HB was observed. Conclusion: It emerged from the results that the factor structure of subsidiary behaviors consists of 3 mutually independent factors The interactive model suggests that subsidiary behaviors are possibly precursory signs of errors and changes in autonomic nervous system balance (J Occup Health 2010; 52 39-47)
  • Occupational Trichloroethylene Hypersensitivity Syndrome with Human Herpesvirus-6 and Cytomegalovirus Reactivation, Hideaki Watanabe, Mikiko Tohyama, Michihiro Kamijima, Tamie Nakajima, Takemi Yoshida, Koji Hashimoto, Masafumi Iijima, DERMATOLOGY, 221, (1) 17 - 22,   2010年, Patients having a generalised rash with severe liver dysfunction associated with exposure to trichloroethylene (TCE) have been reported mainly in Asian countries. However, no case has been reported in Japan since the 1990s. Here, we describe a case of hypersensitivity syndrome (HS) caused by TCE in a 30-year-old Japanese man. The patient developed a rash, fever and liver dysfunction 21 days after he had been exposed to TCE at his workplace. Serum human herpesvirus (HHV)-6 and cytomegalovirus (CMV) DNA were detected 4 and 7 weeks, respectively, after the onset; the IgG antibody titres to HHV-6 and CMV were significantly elevated 6 and 9 weeks, respectively, after the onset. Patch testing was positive for the metabolites of TCE (i.e. trichloroethanol, trichloroacetic acid and chloral hydrate) but not for TCE itself; these results suggest that the TCE metabolites induced this disease. Human leucocyte antigen-B*1301, which has been reported to be strongly associated with TCE-induced HS, was identified in this patient. In addition, the clinical findings, laboratory data and period of virus reactivation after onset were quite similar to those of drug-induced hypersensitivity syndrome (DIHS). We also review TCE-induced HS from the viewpoint of the similarity to DIHS in this article. Copyright (C) 2010 S. Karger AG, Basel
  • Differential response to trichloroethylene-induced hepatosteatosis in wild-type and PPARalpha-humanized mice., Ramdhan DH, Kamijima M, Wang D, Ito Y, Naito H, Yanagiba Y, Hayashi Y, Tanaka N, Aoyama T, Gonzalez FJ, Nakajima T, Environ Health Perspect, 118, (11) 1557 - 63,   2010年
  • Interactive Model of Subsidiary Behaviors, Work Performance and Autonomic Nerve Activity during Visual Display Terminal Work, Toshimasa Takanishi, Takeshi Ebara, Gen-i Murasaki, Tomohide Kubo, Norihide Tachi, Toru Itani, Michihiro Kamijima, JOURNAL OF OCCUPATIONAL HEALTH, 52, (1) 39 - 47,   2010年01月, Interactive Model of Subsidiary Behaviors, Work Performance and Autonomic Nerve Activity during Visual Display Terminal Work: Toshimasa TAKANISHI, et al. Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences-Objectives: The aims of the study were to investigate the systematic classification of subsidiary behaviors during visual display terminal (VDT) work and discuss the interpretation of these behaviors through an interactive model of subsidiary behaviors, work performance and autonomic nerve activity Methods: Twelve university students were instructed to perform continuous 120-min English transcription tasks in a sedentary posture Data on subsidiary behaviors, work performance (mean keystroke and mean error rates), and autonomic nervous system balance (log-transformed low frequency (LF) / high frequency (HF) ratio) were recorded every 5 min during VDT work Results: The subsidiary behaviors were categorized into 3 qualitatively independent factors distractive behaviors against monotony (DBM), sleepiness-related behaviors (SRB), and habitual behaviors (HB). A cross-correlation analysis indicated that an increase of DBM, which is considered as a sign of workers' attempt to escape from monotonous task operations, was related to a decline in performance. A decrease in the LF/HF ratio was followed by SRB after 5 min passed (r=-0.57, p<0.05), eventually leading to a restriction of the deterioration in performance An increase of DBM was predictive of an increase in errors (r=0.54, p<0.05), and a significant negative correlation (r=-0.46, p<0.05) between HB and autonomic nerve activity at 10 min after the appearance of HB was observed. Conclusion: It emerged from the results that the factor structure of subsidiary behaviors consists of 3 mutually independent factors The interactive model suggests that subsidiary behaviors are possibly precursory signs of errors and changes in autonomic nervous system balance (J Occup Health 2010; 52 39-47)
  • Briefhourly exercise during night work can help maintain workers' performance., Sato T, Kubo T, Ebara T, Takeyama H, Inoue T, Iwanishi M, Tachi N, Itani T, Kamijima M, Ind Health, 48, (4) 470 - 7,   2010年
  • Indoor air pollution and the health of childrenin biomass- and fossil-fuel users of Bangladesh: situation in two different seasons., Khalequzzaman M, Kamijima M, Sakai K, Hoque BA, Nakajima T, Environ Health Prev Med, 15, (4) 236 - 43,   2010年
  • 特定建築物における揮発性有機化合物による室内空気汚染 : 2002年建築物衛生法改正後の実態と残された問題点, 酒井 潔, 上島 通浩, 柴田 英治, 大野浩之, 那須 民江, 日本公衆衛生雑誌, 57, (9) 825 - 834,   2010年
  • Comparison of urinary concentrations of 3-phenoxybenzoic acid among general residents in rural and suburban areas and employees of pest control firms, Akiko Kimata, Takaaki Kondo, Jun Ueyama, Kanami Yamamoto, Junko Yoshitake, Kenji Takagi, Koji Suzuki, Takashi Inoue, Yoshinori Ito, Nobuyuki Hamajima, Michiro Kamijima, Masahiro Gotoh, Eiji Shibata, INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, 82, (10) 1173 - 1178,   2009年11月, 査読有り, Objectives The purpose of this study is to determine the levels of urinary 3-phenoxybenzoic acid (3-PBA) among general populations in rural and suburban areas and employees of pest control firms to evaluate the differences in the level of environmental or occupational pyrethroid (PYR) pesticides to which those populations are exposed. Methods Spot urine specimens were collected from male residents in a rural area (n = 143) and male residents in a suburban area (n = 66) in August of 2005 and 2007, respectively. Male employees of pest control firms, who also provided their urine specimens at the time of a health-checkup in August 2007, were classified either as sprayers (n = 14) or as non-sprayers ( n = 16) according to the presence of spraying during the pre-checkup week. Urinary concentrations of 3-PBA were determined using gas chromatography-mass spectrometry and corrected for the urinary creatinine concentrations. An analysis of covariance was used to examine the statistical difference in 3-PBA concentrations between these four groups after adjustment for age, body mass index, and current smoking/drinking habits. Results Multiple comparisons indicated no differences in adjusted 3-PBA concentrations between the groups of general residents from the rural areas (0.33 mu g/g cre in geometric mean) and suburban area (0.51 mu g/g cre). The group of sprayers showed a much higher level of 3-PBA concentrations (25.0 mu g/g cre) than the other three groups. A statistically significant difference, though to a lesser extent, was also exhibited in 3-PBA concentrations between the group of non-sprayers (5.6 mu g/g cre) and that of general residents. Conclusions The results indicated that the levels of background low-dose exposure to PYRs are not likely to differ evidently among general populations according to the area of residence. Moreover, employees of pest control firms, who have been away from PYR spraying operations for a week or more, still retain much higher urinary 3-PBA concentrations than general populations.
  • Octachlorostyrene Induces Cytochrome P450, UDP-glucuronosyltransferase, and Sulfotransferase via the Aryl Hydrocarbon Receptor and Constitutive Androstane Receptor, Yukie Yanagiba, Yuki Ito, Michihiro Kamijima, Frank J. Gonzalez, Tamie Nakajima, TOXICOLOGICAL SCIENCES, 111, (1) 19 - 26,   2009年09月, Octachlorostyrene (OCS) is a byproduct produced in the process of synthesis of chlorinated compounds. There are some reports concerning environmental contamination by OCS, but few on the toxicological effects on human. Drug-metabolizing enzymes may play an important role in toxicity through metabolic activation or deactivation of OCS. In this study, we investigated whether OCS influences these enzymes using wild-type and aryl hydrocarbon receptor (Ahr)-null mice; AhR regulates cytochrome P450 (CYP) 1A, UDP-glucuronosyltransferase (UGT), or sulfotransferase (SULT). Both mouse lines were treated with OCS (0, 32, and 64 mu mol/kg) for 4 days by gavage. As a reference, the mice were treated with 20 mg/kg 3-methylcholanthrene (3MC) for 4 days. OCS treatment increased the expression of CYP 1A1 and CYP1A2 mRNA and ethoxyresorfin O-deethylase activity only in the wild-type mice, similar to that of the AhR activator 3MC. OCS treatment increased expression of UGT1A6 and SULT 1A1 mRNA and their associated enzyme activities only in Ahr-null mice, whereas 3MC still influenced these enzymes only in wild-type mice. OCS induced constitutive androstane receptor (CAR) only in Ahr-null mice, and the target gene CYP2B10 mRNA was induced more strongly in Ahr-null mice than in wild-type mice. 3MC slightly induced CYP2B10 mRNA only in the wild-type mice. These results suggest that CAR is involved in regulation of the UGT and SULT genes by OCS. Thus, OCS may regulate CYP1A via AhR, whereas it controls UGT1A6 and SULT1A via CAR.
  • Identification of the sources of organic compounds that decalcify cement concrete and generate alcohols and ammonia gases, Takashi Tomoto, Akihiro Moriyoshi, Kiyoshi Sakai, Eiji Shibata, Michihiro Kamijima, BUILDING AND ENVIRONMENT, 44, (9) 2000 - 2005,   2009年09月, 査読有り, This study identifies the emission sources of various types of airborne organic compounds, which deteriorate cement concrete by penetrating into the concrete together with moisture. The study used high-performance liquid chromatography and gas chromatograph mass spectrometry. The results show that the types of organic compounds contained in decalcified cement concrete were very similar to those found in the total suspended compounds in the air, and that the source of the emissions was particles of exhaust from diesel vehicles and radial tires used in summer. Such organic compounds include substances suspected of having endocrine disrupting properties. Hydrolysis occurs when these substances penetrate into highly alkaline cement concrete, and leads to deterioration of the cement concrete and the release of alcohols and ammonia gases which pollute indoor air and may be a cause of the sick building syndrome. (C) 2008 Elsevier Ltd. All rights reserved.
  • Nanoparticle-rich diesel exhaust may disrupt testosterone biosynthesis and metabolism via growth hormone, Ramdhan DH, Ito Y, Yanagiba Y, Yamagishi N, Hayashi Y, Li C, Taneda S, Suzuki AK, Watanabe G, Taya K, Kamijima M, Nakajima T, Toxicol Lett, 191, (2-3) ,   2009年08月, 査読有り
  • Urinary excretion of 3-phenoxybenzoic acid in middle-aged and elderly general population of Japan, Jun Ueyama, Akiko Kimata, Michihiro Kamijima, Nobuyuki Hamajima, Yoshinori Ito, Koji Suzuki, Takashi Inoue, Kanami Yamamoto, Kenji Takagi, Isao Saito, Ken-ichi Miyamoto, Takaaki Hasegawa, Takaaki Kondo, ENVIRONMENTAL RESEARCH, 109, (2) 175 - 180,   2009年02月, 査読有り, Limited data are available on the background levels of exposure to synthetic pyrethroid (PYR) in Japan, despite their frequent application for agriculture and indoor extermination and possible effects of chronic and/or low-dose PYR exposure on human health. This study was conducted to describe the level and distribution of one of the major PYR metabolites, 3-phenoxybenzoic acid (3-PBA), in urine samples collected from a general population in Japan. The subjects were 535 individuals (184 men and 351 women; 61.5 +/- 9.8 years of age. mean +/- S.D.) residing in a town in Hokkaido, a dairy and agricultural area. Urinary 3-PBA was found detectable in 98% of samples above the limit of detection of 0.02 mu g/l. The geometric mean values of urinary 3-PBA in occupationally exposed farmers (n = 87) and the remaining general group without occupational exposure (n = 448) were 0.38 and 0.29 mu g/l, respectively, ranging from <LOD to 17.09 mu g/l. No significant differences in urinary 3-PBA concentrations were shown between these two groups. Moreover, 3-PBA concentrations were found comparable to those reported in some countries. The present study is, to our knowledge, the first report of a biological monitoring study of urinary 3-PBA, which elucidated the background environmental exposure level of PYR in the Japanese general population without occupational exposure. Further nationwide studies covering different seasons and age distribution are needed to monitor the urinary 3-PBA levels in Japan. (C) 2008 Elsevier Inc. All rights reserved.
  • Relationship between dietary habits and urinary concentrations of 3-phenoxybonzoic acid in a middle-aged and elderly general population in Japan, Kimata A, Kondo T, Ueyama J, Yamamoto K, Kamijima M, Suzuki K, Inoue T, Ito Y, Hamajima N, Environmental Health and Preventive Medicine, 14, (3) 173 - 179,   2009年, 査読有り
  • Relationship between urinary pesticide metabolites and pest control operation among occupational pesticide sprayers., KIMATA Akiko, KONDO Takaaki, UEYAMA Jun, YAMAMOTO Kanami, MOCHIZUKI Aiko, ASAI Kazumi, TAKAGI Kenji, OKAMURA Ai, WANG Dong, KAMIJIMA Michihiro, NAKAJIMA Tamie, FUKAYA Yukio, SHIBATA Eiji, GOTOH Masahiro, SAITO Isao, J Occup Health, 51, (1) 100 - 105,   2009年
  • Broken sperm, cytoplasmic droplets and reduced sperm motility are principal markers of decreased sperm quality due to organophosphorus pesticides in rats., OKAMURA Ai, KAMIJIMA Michihiro, OHTANI Katsumi, YAMANOSHITA Osamu, NAKAMURA Daichi, ITO Yuki, MIYATA Maiko, UEYAMA Jun, SUZUKI Takayoshi, IMAI Ryota, TAKAGI Kenji, NAKAJIMA Tamie, J Occup Health, 51, (6) 478 - 487,   2009年, 査読有り
  • Annual transition and seasonal variation of indoor air pollution levels of 2-ethyl-1-hexanol in large-scale buildings in Nagoya, Japan, Kiyoshi Sakai, Michihiro Kamijima, Eiji Shibata, Hiroyuki Ohno, Tamie Nakajima, JOURNAL OF ENVIRONMENTAL MONITORING, 11, (11) 2068 - 2076,   2009年, 2-Ethyl-1-hexanol (2E1H) is a possible causative chemical for sick building symptoms; however, thus far, we do not have a clear understanding of the indoor air pollution levels caused by it. In this study, first, airborne 2E1H concentrations were measured during summer and winter from 2004 to 2007 in 67 rooms of 56 large-scale buildings in Nagoya, Japan, in order to show the seasonal variation of indoor air pollution levels of 2E1H. Then, a follow-up survey was conducted in five rooms of five buildings for more than 2 years in order to establish the annual transition of their 2E1H indoor air pollution levels. 2E1H was found to be one of the predominant volatile organic compounds in the indoor air of large-scale buildings. Its geometric mean concentration was significantly higher during summer (55.4 mu g/m(3)) than during winter (13.7 mu g/m(3)) (p < 0.01), although there was a significant difference in the concentrations among the buildings. High 2E1H concentrations may have been caused by high emission rates of 2E1H from floors, because of the hydrolysis of di(2-ethylhexyl) phthalate in polyvinyl chloride flooring materials or of adhesives containing 2-ethylhexyl moieties. Follow-up observations showed little decrease in the indoor air 2E1H concentrations from one year to the next, although they did show seasonal fluctuations, with an evident increase in concentrations during summer and an evident decrease during winter.
  • Molecular mechanism of trichloroethylene-induced hepatotoxicity mediated by CYP2E1., Doni Hikmat Ramdhan, Michihiro Kamijima, Naoyasu Yamada, Yuki Ito, Yukie Yanagiba, Daichi Nakamura, Ai Okamura, Gaku Ichihara, Toshifumi Aoyama, Frank J Gonzalez, Tamie Nakajima, Toxicol App Pharmacol, 231, (3) 300 - 7,   2008年09月15日, 査読有り, Cytochrome P450 (CYP) 2E1 was suggested to be the major enzyme involved in trichloroethylene (TRI) metabolism and TRI-induced hepatotoxicity, although the latter molecular mechanism is not fully understood. The involvement of CYP2E1 in TRI-induced hepatotoxicity and its underlying molecular mechanism were studied by comparing hepatotoxicity in cyp2e1+/+ and cyp2e1-/- mice. The mice were exposed by inhalation to 0 (control), 1000, or 2000 ppm of TRI for 8 h a day, for 7 days, and TRI-hepatotoxicity was assessed by measuring plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histopathology. Urinary metabolites of trichloroethanol and trichloroacetic acid (TCA) were considerably greater in cyp2e1+/+ compared to cyp2e1-/- mice, suggesting that CYP2E1 is the major P450 involved in the formation of these metabolites. Consistent with elevated plasma ALT and AST activities, cyp2e1+/+ mice in the 2000 ppm group showed histopathological inflammation. TRI significantly upregulated PPARalpha, which might function to inhibit NFkappaB p50 and p65 signalling. In addition, TRI-induced NFkappaB p52 mRNA, and significantly positive correlation between NFkappaB p52 mRNA expression and plasma ALT activity levels were observed, suggesting the involvement of p52 in liver inflammation. Taken together, the current study directly demonstrates that CYP2E1 was the major P450 involved in the first step of the TRI metabolism, and the metabolites produced may have two opposing roles: one inducing hepatotoxicity and the other protecting against the toxicity. Intermediate metabolite(s) from TRI to chloral hydrate produced by CYP2E1-mediated oxidation may be involved in the former, and TCA in the latter.
  • Permethrin may induce adult male mouse reproductive toxicity due to cis isomer not trans isomer., NAKAJIMA T, KAMIJIMA M, OKAMURA A, YANAGIBA Y, ITO Y, UEYAMA J, ZHANG Sy, Toxicology, 248, (2-3) 136 - 141,   2008年
  • Effect of the organophosphorus pesticide diazinon on glucose tolerance in type 2 diabetic rats, Ueyama J, Kamijima M, Asai K, Mochizuki A, Wang D, Kondo T, Suzuki T, Takagi K, Takagi K, Kanazawa H, Miyamoto K.-i, Wakusawa S, Hasegawa T, Toxicology Letters, 182, (1-3) 42 - 47,   2008年, 査読有り
  • Characterization of liver injury associated with hypersensitivity skin reactions induced by trichloroethylene in the guinea pig maximization test., TANG Xiaojiang, TANG Xiaojiang, QUE Bingling, SONG Xiangrong, LI Senhua, YANG Xiaojun, WANG Hailan, HUANG Hanlin, KAMIJIMA Michihiro, NAKAJIMA Tamie, LIN Yongcheng, LI Laiyu, J Occup Health, 50, (2) 114 - 121,   2008年
  • Styrene trimer may increase thyroid hormone levels via down-regulation of the aryl hydrocarbon receptor (AhR) target gene UDP-glucuronosyltransferase., YANAGIBA Yukie, ITO Yuki, YAMANOSHITA Osamu, ZHANG Shu‐Yun, WATANABE Gen, WATANABE Gen, TAYA Kazuyoshi, TAYA Kazuyoshi, LI Chun Mei, INOTSUME Yuko, KAMIJIMA Michihiro, GONZALEZ Frank J, NAKAJIMA Tamie, Environ Health Perspect, 116, (6) 740 - 745,   2008年
  • Trichloroethylene causes generalized hypersensitivity skin disorders complicated by hepatitis., Kamijima M, Wang H, Huang H, Li L, Shibata E, LinB, Sakai K, Liu H, Tsuchiyama F, Chen J, Okamura A, Huang X, Hisanaga N, Huang Z, Ito Y, Takeuchi Y, Nakajima T, J Occup Health, 50, 328 - 38,   2008年
  • Biological monitoring of pyrethroid exposure of pest control workers in Japan, Dong Wang, Michihiro Kamijima, Ryota Imai, Takayoshi Suzuki, Yohei Kameda, Kazumi Asai, Ai Okamura, Hisao Naito, Jun Ueyama, Isao Saito, Tarnie Nakajima, Masahiro Goto, Eiji Shibata, Takaaki Kondo, Kenji Takagi, Kenzo Takagi, Shinya Wakusawa, JOURNAL OF OCCUPATIONAL HEALTH, 49, (6) 509 - 514,   2007年11月, 査読有り, Synthetic pyrethroids such as cypermethrin, deltamethrin and permethrin, which are usually used in pest control operations, are metabolized to 3-phenoxybenzoic acid (3-PBA) and excreted in urine. Though 3-PBA can be used to assess exposure to pyrethroids, there are few reports describing urinary 3-PBA levels in Japan. This study aimed to investigate the seasonal variation of the exposure levels of pyrethroids and the concentration of urinary 3-PBA among pest control operators (PCOs) in Japan. The study subjects were 78 and 66 PCOs who underwent a health examination in December 2004 and in August 2005, respectively. 3-PBA was determined using gas chromatography-mass spectrometry. The geometric mean concentration of urinary 3-PBA in winter (3.9 mu g/ g creatinine) was significantly lower than in summer (12.2 mu g/g creatinine) (p<0.05). Geometric mean concentrations of urinary 3-PBA in the spraying workers and the not-spraying workers within 2 d before the survey were 5.4,mu g/g creatinine and 0.9 mu g/g creatinine for winter with a significant difference between the groups (p<0.05), and 12.3,mu g/g creatinine and 8.7 mu g/ g creatinine for summer (p>0.05), respectively. A significant association of 3-PBA levels and pyrethroid spraying was thus observed only in winter. In conclusion, the results of the present study show that the exposure level of pyrethroids among PCOs in Japan assessed by monitoring urinary 3-PBA was higher than that reported in the UK but comparable to that in Germany. Further research should be accumulated to establish an occupational reference value in Japan.
  • Pyrene-induced CYP1A2 and SULT1A1 may be regulated by CAR and not by AhR, Chul-Ho Lee, Yuki Ito, Yukie Yanagiba, Osamu Yamanoshita, Heon Kim, Shu-Yun Zhang, Michihiro Kamijima, Frank J. Gonzalez, Tamie Nakajima, TOXICOLOGY, 238, (2-3) 147 - 156,   2007年09月, Aryl hydrocarbon receptor (AhR) plays important roles in the regulation and induction of xenobiotic-metabolizing enzymes including the cytochromes P450 1 family (CYP1) and UDP-glucuronosyltransferases 1A (UGT1As) by polycyclic aromatic hydrocarbons as well as chlorinated aromatic hydrocarbons. To determine whether pyrene-induced xenobiotic-metabolizing enzymes are regulated by AhR, male AhR (+/+) and (-/-) mice were used. Both genotyped mice were exposed to 0, 205, 300 or 410 mg/(kg day pyrene), once daily, for four consecutive days by gavage. Exposure to pyrene did not influence hepatic CYP1A1-mRNA in mice of both genotypes, whereas it induced hepatic CYP1A2 protein and mRNA expression and associated 7-ethoxyresorufin O-deethylase and pyrene 1-hydroxylation activities in both AhR (+/+) and (-/-) mice. Similar effects were also found with sulfotransferase 1A1 expression and the associated 1-hydroxypyrene sulfation activity. In contrast, pyrene exposure increased expression of the UGT1A1 and 1A6, and glucuronidation activities associated with 1-hydroxypyrene and 1-naphthol in the liver only in AhR (-/-) mice, although pyrene treatment dose-dependently decreased the latter activity. Pyrene exposure did not increase AhR-mRNA expression in AhR (+/+) mice. In contrast, pyrene-induced expression of the hepatic constitutive androstane receptor (CAR) and one of its target genes, CYP2B10, in both AhR (+/+) and (-/-) mice. These results strongly suggest that pyrene-induced CYP1A2 and SULT1A1 are regulated by CAR, not by AhR. However, the mechanisms of UGT1A1 and 1A6 induction by pyrene were not elucidated in this study. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
  • Permethrin may disrupt testosterone biosynthesis via mitochondrial membrane damage of leydig cells in adult male mouse, Shu-Yun Zhang, Yuki Ito, Osamu Yamanoshita, Yukie Yanagiba, Miya Kobayashi, Kazuyoshi Taya, ChunMei Li, Ai Okamura, Maiko Miyata, Jun Ueyama, Chul-Ho Lee, Michihiro Kamijima, Tamie Nakajima, ENDOCRINOLOGY, 148, (8) 3941 - 3949,   2007年08月, Permethrin, a popular synthetic pyrethroid insecticide used to control noxious insects in agriculture, forestry, households, horticulture, and public health throughout the world, poses risks of environmental exposure. Here we evaluate the reproductive toxicity of cis-permethrin in adult male ICR mice that were orally administered cis- permethrin ( 0, 35, or 70 mg/kg center dot d) for 6 wk. Caudal epididymal sperm count and sperm motility in the treated groups were statistically reduced in a dose-dependent manner. Testicular testosterone production and plasma testosterone concentration were significantly and dose-dependently decreased with an increase in LH, and a significant regression was observed between testosterone levels and cis-permethrin residues in individual mice testes after exposure. However, no significant changes were observed in body weight, reproductive organ absolute and relative weights, sperm morphology, and plasma FSH concentration after cis- permethrin treatment. Moreover, cis- permethrin exposure significantly diminished the testicular mitochondrial mRNA expression levels of peripheral benzodiazepine receptor (PBR), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side- chain cleavage (P450scc) and enzyme and protein expression levels of StAR and P450scc. At the electron microscopic level, mitochondrial membrane damage was found in Leydig cells of the exposed mouse testis. Our results suggest that the insecticide permethrin may cause mitochondrial membrane impairment in Leydig cells and disrupt testosterone biosynthesis by diminishing the delivery of cholesterol into the mitochondria and decreasing the conversion of cholesterol to pregnenolone in the cells, thus reducing subsequent testosterone production.
  • Chemopreventive Effect of Selenium-Enriched Japanese Radish Sprout against Breast Cancer Induced by 7,12-Dimethylbenz[a]anthracene in Rats, Yamanoshita O, Ichihara S, Hama H, Ichihara G, Chiba M, Kamijima M, Takeda I, Nakajima T, TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 212, (2) 191 - 198,   2007年06月05日, 査読有り
  • Toxicity of diazinon and its metabolites increases in diabetic rats, Jun Ueyama, Dong Wang, Takaaki Kondo, Isao Saito, Kenji Takagi, Kenzo Takagi, Michihiro Kamijima, Tamie Nakajima, Ken-Ichi Miyamoto, Shinya Wakusawa, Takaaki Hasegawa, TOXICOLOGY LETTERS, 170, (3) 229 - 237,   2007年05月, 査読有り, The effect of diazinon (DZN) on the activities of cholinesterase (ChE) in plasma and acetylcholinesterase (AChE) in erythrocyte and brain was investigated in normal and streptozotocin-induced diabetic rats. Hepatic drug-metabolizing enzyme activity was also estimated by measuring the systemic clearance of antipyrine, and the expression of hepatic cytochrome P450 (CYP) 3A2 and CYP1A2, which is closely related to the metabolism from DZN to DZN-oxon, a strong inhibitor-of both ChE and AChE. No significant differences in the activities of ChE in plasma and AChE in erythrocyte were observed between normal and diabetic rats. Treatment with DZN significantly decreased these activities in diabetic rats more than in normal rats 6h after injection (6.5 mg/kg). Treatment with DZN significantly decreased the activity of AChE in brain of diabetic rats than normal rats 3 h after injection (65 mg/kg), although no significant difference in the activity was found between normal and diabetic rats. The urinary recovery of diethyl phosphate (DEP), a metabolite of DZN-oxon, was significantly increased in diabetic rats, but that of diethylthiophosphate (DETP), a metabolite of DZN, was unchanged. Significant increases in the systemic clearance of antipyrine and protein levels of hepatic CYP1A2, not CYP3A2, were observed in diabetic rats. These results suggest the possibility that a metabolite of DZN, DZN-oxon, causes higher toxicity in diabetic rats due to the enhancement of hepatic CYP1A2-mediated metabolism of DZN. (C) 2007 Published by Elsevier Ireland Ltd.
  • Di(2-ethylhexyl)phthalate induces hepatic tumorigenesis through a peroxisome proliferator-activated receptor alpha-independent pathway., Yuki Ito, Osamu Yamanoshita, Nobuyuki Asaeda, Yoshiaki Tagawa, Chul-Ho Lee, Toshifumi Aoyama, Gaku Ichihara, Koichi Furuhashi, Michihiro Kamijima, Frank J Gonzalez, Tamie Nakajima, Journal of occupational health, 49, (3) 172 - 82,   2007年05月, Di(2-ethylhexyl)phthalate (DEHP), a commonly used industrial plasticizer, causes liver tumorigenesis presumably via activation of peroxisome proliferator-activated receptor alpha (PPARalpha). The mechanism of DEHP tumorigenesis has not been fully elucidated, and to clarify whether DEHP tumorigenesis is induced via PPARalpha, we compared DEHP-induced tumorigenesis in wild-type and Pparalpha-null mice. Mice of each genotype were divided into three groups, and treated for 22 months with diets containing 0, 0.01 or 0.05% DEHP. Surprisingly, the incidence of liver tumors was higher in Pparalpha-null mice exposed to 0.05% DEHP (25.8%) than in similarly exposed wild-type mice (10.0%). These results suggest the existence of pathways for DEHP-induced hepatic tumorigenesis that are independent of PPARalpha. The levels of 8-OHdG increased dose-dependently in mice of both genotypes, but the degree of increase was higher in Pparalpha-null than in wild-type mice. NFkappaB levels also significantly increased in a dose-dependent manner in Pparalpha-null mice. The protooncogene c-jun-mRNA was induced, and c-fos-mRNA tended to be induced only in Pparalpha-null mice fed a 0.05% DEHP-containing diet. These results suggest that increases in oxidative stress induced by DEHP exposure may lead to the induction of inflammation and/or the expression of protooncogenes, resulting in a high incidence of tumorigenesis in Pparalpha-null mice.
  • Occupational trichloroethylene exposure as a cause of idiosyncratic generalized skin disorders and accompanying hepatitis similar to drug hypersensitivities, Michihiro Kamijima, Naomi Hisanaga, Hailan Wang, Tamie Nakajima, INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, 80, (5) 357 - 370,   2007年04月, Objectives Workers exposed to trichloroethylene (TCE) rarely show severe generalized skin disorders and accompanying hepatitis which resemble drug hypersensitivities. The disorders are completely different from solvent-induced irritating contact dermatitis, and their serious consequences have become one of the critical occupational health issues recently in Asia. The present review sheds light on the analogous relationship between the reported patients' clinical manifestations and those of severe drug rash, and provides a comprehensive picture of the disorder occurrences among TCE-exposed workers to date. Methods All literature published in English and ad hoc publications in local languages were reviewed. Results The patients typically showed rash on the extremities, face, neck or trunk with/without fever 2 weeks to 2 months after commencement of occupational TCE exposure. Reported cutaneous manifestations were classified into two hypersensitivity categories, i.e. hypersensitivity syndrome and erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis. Based on this categorization, 124 (52%) cases were classified as the former and 115 (48%) as the latter. According to the two spectra, the prevalence of each clinical finding of TCE-related skin disorders was close to that in drug hypersensitivities except for disease incidence and the prevalence of fever, hepatitis, and lymphadenopathy. Occurrences of the disorders have been reported from the USA, Japan, Spain, Singapore, China, Korea, Thailand, and the Philippines. The case reports from industrialized countries were mostly published up to 1990, whereas cases from Asian industrializing countries appeared thereafter. Conclusions The TCE-related generalized skin disorders are important not only in terms of the number of disease occurrences and severity but from the viewpoint of drug hypersensitivity. Systematic collection of clinical information is necessary in cases diagnosed by the same criteria as those used for drug hypersensitivities. Detailed exposure assessments are also required to establish preventive strategies in these countries.
  • Induction of peroxisome proliferator-activated receptor alpha (PPARα)-related enzymes by di(2-ethylhexyl) phthalate (DEHP) treatment in mice and rats, but not marmosets., ITO Y, YAMANOSHITA O, KURATA Y, KAMIJIMA M, AOYAMA T, NAKAJIMA T, Arch Toxicol, 81, (3) 219 - 226,   2007年03月
  • Indoor air pollution and its impact on under-5 children in Bangladesh., KHALEQUZZAMAN M, KAMIJIMA M, SAKAI K, CHOWDHURY N.A, HAMAJIMA N, NAKAJIMA T, Indoor Air, 17, (4) 297 - 304,   2007年
  • 8-hydroxydeoxyguanosine levels in human leukocyte and urine according to exposure to organophosphorus pesticides and paraoxonase 1 genotype, Chul-Ho Lee, Michihiro Kamijima, Heon Kim, Eiji Shibata, Jun Ueyama, Takayoshi Suzuki, Kenji Takagi, Isao Saito, Masahiro Gotoh, Hatsuki Hibi, Hisao Naito, Tamie Nakajima, INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, 80, (3) 217 - 227,   2007年01月, Objective In order to investigate a role of paraoxonase 1 (PON1) polymorphism in organophosphorus (OP)-induced 8-hydroxydeoxyguanosine (8-OHdG) levels, urinary metabolites of OP, PON1 genotypes, and 8-OHdG levels in leukocyte and urine were measured in OP indoor insecticide sprayers and controls in summer and winter. Methods The study population contained 18 male sprayers and age-matched 18 male controls. Sprayers were primarily exposed to OP insecticides (mainly fenitrothion, dichlorvos, chlorpyrifos, and diazinon), and partially to pyrethroids (mainly permethrin) and carbamates (mainly propoxur). Urinary metabolites of OP were measured by gas chromatography-mass spectrometry. 8-OHdG levels in leukocyte and urine were measured by ELISA kit. PON1 genotype was identified using allele-specific fluorogenic TaqMan probes. Results The mean concentrations of urinary dimethyl phosphate (DMP) and total dialkyl phosphates (DAP) in summer and those of 8-OHdG in summer and winter were significantly higher in OP sprayers than controls. This resulted in a significant positive correlation between 8-OHdG levels and urinary DMP or DAP, suggesting a correlation between OP metabolites and production of oxidative stress. Of PON1 genotypes, incidences of Q/Q, Q/R, and R/R types were 17, 39, and 44% in OP sprayers and controls, respectively. Although PON1 polymorphism did not contribute to the leukocyte and urinary 8-OHdG levels, the urinary OP metabolite concentrations in summer showed a significant decrease as the number Q allele decreased. Conclusion These results indicate that an increase in OP metabolites is associated with a high level of oxidative stress in OP sprayers, although the contribution of the PON1 polymorphism to the metabolism of OP is still unclear.
  • Differential effects of aging, drinking and exercise on serum cholesterol levels dependent on PPARA-V227A polymorphism., NAITO Hisao, KAMIJIMA Michihiro, YAMANOSHITA Osamu, NAKAHARA Ai, KATOH Takahiko, TANAKA Naoki, AOYAMA Toshifumi, GONZALEZ Frank J, NAKAJIMA Tamie, J Occup Health, 49, (5) 353 - 362,   2007年
  • 3-Methyl-4-nitrophenol metabolism by UDP-glucuronosyltransferase and sulfotransferase in liver microsomes of mice, rats and Japanese quail (Coturnix japonica.), LEE Chul‐Ho, KAMIJIMA Michihiro, LI ChunMei, LI ChunMei, TANEDA Shinji, SUZUKI Akira K, NAKAJIMA Tamie, Environmental Toxicology and Chemistry, 26, (9) 1873 - 1878,   2007年
  • Association of V227A PPARα polymorphism with altered serum biochemistry and alcohol drinking in Japanese men, Hisao Naito, Osamu Yamanoshita, Michihiro Kamijima, Takahiko Katoh, Tadashi Matsunaga, Chul Ho Lee, Heon Kim, Toshifumi Aoyama, Frank J. Gonzalez, Tamie Nakajima, Pharmacogenetics and Genomics, 16, (8) 569 - 577,   2006年08月, 査読有り, OBJECTIVES: Peroxisome proliferator-activated receptor (PPAR) α plays a major role in alcoholic liver disease in rodents. The two-fold objective of our study was to determine the presence of PPARα polymorphisms and their frequencies in Japanese populations and then to evaluate the effects of any alleles on metabolic parameters and alcohol drinking. METHODS: Analysis of coding SNP in PPARα was performed in 706 Japanese men; from these subjects 655 men were further studied after exclusion criteria were applied. RESULTS: PPARα-V227A, which has not been reported in Europe and North America as a major polymorphism, was discovered with the frequency of 0.05. PPARα-L162V was found in European and North American populations, but not in Japanese, thus confirming the ethnic differences in PPARα allele frequencies. The A227 allele was associated with increased serum concentrations of gamma glutamyltranspeptidase. In non-drinkers, the total cholesterol (TC) levels were significantly lower in those having the PPARα-V227A polymorphism. In drinkers, however, it was comparable among V227A polymorphisms, and conversely higher in those having both A227 and aldehyde dehydrogenase 2 (ALDH2) variants when further divided according to the ALDH2 polymorphism. Significant interactions between PPARα-V227A polymorphism and drinking were also found for TC, triglyceride levels and AST/ALT ratios. These results suggest that the activity of the A227 allele without drinking may be higher than in wild-type allele, but its activity may become lower during drinking habits. CONCLUSION: PPARα-V227A is a major polymorphism in the Japanese population, and its activity may be greater compared to wild-type, but decreased by alcohol drinking. © 2006 Lippincott Williams & Wilkins.
  • Simultaneous determination of urinary dialkylphosphate metabolites of organophosphorus pesticides using gas chromatography-mass spectrometry, J Ueyama, Saito, I, M Kamijima, T Nakajima, M Gotoh, T Suzuki, E Shibata, T Kondo, K Takagi, K Miyamoto, J Takamatsu, T Hasegawa, K Takagi, JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 832, (1) 58 - 66,   2006年02月, In this study, we developed a safe and sensitive method for the simultaneous determination of urinary dialkylphosphates (DAPs), metabolites of organophosphorus insecticides (OPs), including dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP), and diethylthiophosphate (DETP), using a pentafluorobenzylbromide (PFBBr) derivatization and gas chromatography-mass spectrometry (GC-MS). Several parameters were investigated: pH on evaporation, reaction temperature and time for the derivatization, the use of an antioxidant for preventing oxidation, and a clean-up step. The pH was set at 6, adjusted with K2CO3, and the reaction temperature and time of derivatization were 80 degrees C and 30 min, respectively. Sodium disulfite was chosen as an antioxidant. The clean-up step was performed with a Florisil/PSE mini-column to remove the unreacted PFBBr and sample matrix. This established procedure markedly shortened the sample preparation time to only about 3 h, and completely inhibited the unwanted oxidization of dialkylthiophosphates. The limits of determination (LOD) were approximately 0.3 mu g/L for DMP, and 0.1 mu g/L for DEP, DMTP, and DETP in 5 mL of human urine. Within-series and between-day imprecision for the present method using pooled urine spiked with DAPs was less than 20.6% in the calibration range of 1-300 mu g/L, and the mean recovery was 56.7-60.5% for DMP, 78.5-82.7% for DEP, 88.3-103.9% for DMTP, and 84.2-92.4% for DETP. This method detected geometric mean values of the urinary DAPs in Japanese with and without occupational exposure to OPs, 16.6 or 27.4 for DMP, 1.0 or 0.7 for DEP, 1.3 or 2.3 for DMTP, and 1.0 or 1. 1 mu g/l for DETP, respectively. The present method, which does not require special equipment except for GC-MS, is quick, safe, and sensitive enough to be adopted in routine biological monitoring of non-occupational as well as occupational exposure to OPs. (c) 2006 Elsevier B.V. All rights reserved.
  • Indoor air pollution by 2-ethyl-1-hexanol in non-domestic buildings in Nagoya, Japan, Kiyoshi Sakai, Michihiro Kamijima, Eiji Shibata, Hironobu Ohno, Tamie Nakajima, JOURNAL OF ENVIRONMENTAL MONITORING, 8, (11) 1122 - 1128,   2006年, 2-Ethyl-1-hexanol is a possibly causative chemical in sick building symptoms, although 2-ethyl-1-hexanol has received little attention as a hazardous substance in studies on indoor air pollution. Airborne 2-ethyl-1-hexanol concentrations were measured from 2002 to 2004 in 99 rooms of 42 non-domestic buildings in Nagoya, Japan. The diffusive sampling method is effective for the measurement of a low level of 2-ethyl-1-hexanol in indoor air. The geometric mean ( geometric standard deviation) of 2-ethyl-1-hexanol concentrations was 16.5 ( 5.4) mu g m(-3) in indoor air and 1.9 ( 2.2) mg m(-3) in outdoor air. The maximum concentration of 2-ethyl-1-hexanol in indoor air and outdoor air was 2709 mg m(-3) and 12.4 mg m(-3), respectively. Fewer rooms in a small number of new buildings showed high concentrations of 2-ethyl-1-hexanol, while low concentrations were observed in many rooms of these buildings as well as the other new buildings. The room-to-room concentrations of 2-ethyl-1-hexanol in each building exhibited a wide variation. The geometric mean of the 2-ethyl-1-hexanol concentrations was significantly higher for indoor air than for outdoor air ( p < 0.01). The correlation of the 2-ethyl-1-hexanol concentrations between indoor and outdoor air was not significant. Mechanical ventilation was effective in the temporary reduction of indoor 2-ethyl-1-hexanol level. These results suggest that the predominant source of 2-ethyl-1-hexanol was indoor areas.
  • Human herpesvirus 6 reactivation in trichloroethylene-exposed workers suffering from generalized skin disorders accompanied by hepatic dysfunction., Huang H, Kamijima M, Wang H, Li S, Yoshikawa T, Lai G, Huang Z, Liu H, Chen J, Takeuchi Y, Nakajima T, Li L, J Occup Health, 48, 417 - 23,   2006年, 査読有り
  • A comprehensive evaluation of the testicular toxicity of dichlorvos in Wistar rats, Okamura A, Kamijima M, Shibata E, Ohtani K, Takagi K, Ueyama J, Watanabe Y, Omura M, Wang H, Ichihara G, Kondo T, Nakajima T, TOXICOLOGY, 213, (1-2) 129 - 137,   2005年09月15日, 査読有り
  • A review of hazardous chemical toxicity studies utilizing genetically-modified animals―their applications for risk assessment., NAKAJIMA Tamie, WANG Rui‐Sheng, ITO Yuki, AOYAMA Toshifumi, KAMIJIMA Michihiro, Ind Health, 43, (4) 615 - 622,   2005年
  • Environmental Exposure and p53 Mutations in Esophageal Cancer Patients in Areas of Low and High Incidence of Esophageal Cancer in China., SAKAGUCHI Shigeko, YOKOKAWA Yoshiharu, HOU Jun, ZHANG Xiu-lan, LI Xiang-ping, LI Shao-sen, LI Xiao-xian, ZHU De-chen, KAMIJIMA Michihiro, YAMANOSHITA Osamu, NAKAJIMA Tamie, Tohoku J Exp Med, 207, (4) 313 - 324,   2005年
  • 2-エチル-1-ヘキサノールによる室内空気汚染-室内濃度、発生源、自覚症状について-, 上島通浩, 柴田英治, 酒井潔, 大野浩之, 石原伸哉, 山田哲也, 竹内康浩, 那須民江, 日本公衆衛生雑誌, 52, 1021 - 1031,   2005年
  • Neurologic Abnormalities in Workers of a 1-Bromopropane Factory, Ichihara G, Li W, Shibata E, Ding X, Wang H, Liang Y, Peng S, Itohara S, Kamijima M, Fan Q, Zhang Y, Zhong E, Wu X, Valentine WM, Takeuchi Y, ENVIRONMENTAL HEALTH PERSPECTIVES, 112, (13) 1319 - 1325,   2004年09月, 査読有り
  • A survey of semen indices in insecticide sprayers., Michihiro Kamijima, Hatsuki Hibi, Masahiro Gotoh, Ken-ichi Taki, Isao Saito, Hailan Wang, Seiichiro Itohara, Tetsuya Yamada, Gaku Ichihara, Eiji Shibata, Tamie Nakajima, Yasuhiro Takeuchi, J Occup Health, 46, (2) 109 - 18,   2004年03月, 査読有り, This study aims at clarifying the semen indices of insecticide sprayers who are exposed mainly to organophosphorus and pyrethroid insecticides. Eighteen male sprayers out of 54 working for 9 companies in central Japan and 18 age-matched students or medical doctors as unexposed controls participated in detailed reproductive check-ups conducted in summer and the following winter. The sprayers were exposed to insecticides more in summer, the busiest season, than winter, the off-season (p<0.05). Erythrocyte true cholinesterase activities in the sprayers were lower than in the controls in summer (p<0.05), and decreased in significant association with the increase in exposure frequency. Testicular volumes in the sprayers tended to be smaller than in the controls (p=0.06). The serum testosterone concentration in winter in the sprayers was higher than in the controls (p<0.05), though luteinizing hormone and follicle stimulating hormone concentrations were not significantly different. The sperm counts and vitality were comparable between the groups, but detailed sperm motility analysis in summer revealed that the percentages of slow progressive and nonprogressive motile sperm were twice as high in the sprayers (p<0.05), and that of rapid progressive sperm tended to be lower (p=0.06). Such differences were not observed in winter. Differential sperm morphology counts showed that interaction of group and abstinence effects were significant in sperm with normal morphology and with head deformity only in the summer check-up. Despite possible inherent differences between the groups, the above season-dependent differences suggested that the observed lower semen quality in the sprayers was associated with pesticide spraying work.
  • Generalized skin reactions in relation to trichloroethylene exposure: a review from the viewpoint of drug-metabolizing enzymes., Tamie Nakajima, Osamu Yamanoshita, Michihiro Kamijima, Reiko Kishi, Gaku Ichihara, J Occup Health, 45, (1) 8 - 14,   2003年01月, 査読有り, The literature was reviewed to study cases of intoxication with systemic dermatitis associated with exposure to trichloroethylene. The average age of patients in the reports reviewed to date was twenty-nine; these diseases were found in relatively young persons and no difference was found according to gender. Many cases occurred within one month after the onset of exposure to trichloroethylene, and were accompanied by hepatitis, jaundice, hepatomegaly or hepatosplenomegaly. Most of the patients had no history of drug abuse or herpes infection. The level of exposure to trichloroethylene was not recorded in many cases, but ranged from less than 9 ppm to 800 ppm. In the severest cases, the lesions involved mucous membranes such as the conjunctiva and oral cavity, and the patients were diagnosed with Stevens-Johnson syndrome, but the etiology of the disease after trichloroethylene exposure remains unclear. Since several drugs have also been shown to cause systemic dermatitis with hepatitis, susceptibility factors are discussed. Many patients were found to have the slow acetylator genotype of N-acetyltransferase (NAT) 2, suggesting that the NAT2 genotype is a susceptibility factor. This hypothesis may also be applicable to trichloroethylene because NAT is involved in the glutathione-mediated metabolism.
  • Exposure to 1-bromopropane causes ovarian dysfunction in rats., Tetsuya Yamada, Gaku Ichihara, Hailan Wang, Xiaozhong Yu, Kei-ichiro Maeda, Hiroko Tsukamura, Michihiro Kamijima, Tamie Nakajima, Yasuhiro Takeuchi, Toxicological sciences : an official journal of the Society of Toxicology, 71, (1) 96 - 103,   2003年01月, Although 1-bromopropane has been used in chemical and electronic industries as an alternative to ozone layer-depleting solvents, its toxicity on female reproductive organs has not been fully elucidated. The aim of this experiment was to determine the effect of 1-bromopropane on female reproductive function in rats. Forty female Wistar rats were divided into four equal groups. Each group was exposed daily to 0, 200, 400, or 800 ppm of 1-bromopropane for eight h a day. After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill and were sacrificed during the 8th week. The other dose groups were exposed for 12 weeks. In the 800-ppm group, but not in the other two exposed groups, body weight was significantly less than the control at each time point from 2 to 7 weeks after the beginning of exposure. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus in the 400- and 800-ppm groups. Histopathological examination of the ovary showed a significant dose-dependent reduction of the number of normal antral follicles and a decrease in the number of normal growing follicles in the 400-ppm group. No significant change was found in plasma concentrations of LH or FSH in any group when compared with the control. Our results indicate that 1-bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant female rats associated with disruption in follicular growth process.
  • Functional activation of peroxisome proliferator-activated receptor α (PPARα) by environmental chemicals in relation to their toxicities., NAKAJIMA T, ICHIHARA G, KAMIJIMA M, ITOHARA S, AOYAMA T, Nagoya J Med Sci, 65, (3-4) 85 - 94,   2002年11月
  • 2-ethyl-1-hexanol in indoor air as a possible cause of sick building symptoms, M Kamijima, K Sakai, E Shibata, T Yamada, S Itohara, H Ohno, R Hayakawa, M Sugiura, K Yamaki, Y Takeuchi, JOURNAL OF OCCUPATIONAL HEALTH, 44, (3) 186 - 191,   2002年05月
  • Stevens-Johnson syndrome accompanied by acute hepatitis in workers exposed to trichloroethylene or tetrachloroethylene, Naomi Hisanaga, Hiroshi Jonai, Xiaozhong Yu, Yasutaka Ogawa, Ippei Mori, Michihiro Kamijima, Gaku Ichihara, Eiji Shibata, Yasuhiro Takeuchi, Sangyō eiseigaku zasshi = Journal of occupational health, 44, (2) 33 - 49,   2002年03月, Since the late 1980s, there has been an increasing tendency in the number of case reports on Stevens-Johnson syndrome accompanied by acute hepatitis in workers exposed to trichloroethylene from Asian countries. Recently, mass outbreaks of it have been disclosed in the Philippines and China. Besides trichloroethylene, although the number is small, a similar health disorder has also occurred in workers using tetrachloroethylene. Since the above-mentioned facts are not yet well recognized in the occupational health community, this review is aimed at making clear (1) the clinical features of the health disorder, (2) details of patients' jobs, working environments, and exposure to hazardous chemicals, and (3) the relationship between exposure to trichloroethylene or tetrachloroethylene and the health disorder. Based on a critical review of articles, the following were pointed out. First, it is important to carefully observe the health status of workers exposed to trichloroethylene or tetrachloroethylene and to take countermeasures to reduce exposure. Secondly, circumstantial evidence suggests a cause-effect relationship between the two chemicals and the health disorder; but at the present time it is impossible to rule out the participation of unelucidated factors promoting the occurrence of the health disorder or the existence of a hidden genuine causative substance. Therefore further investigation to trace such a case is needed. Thirdly, the mechanism of the health disorder and the reason why there seems to be a large inter-individual difference in sensitivity to the causative agent should be clarified.
  • Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for seven days, Hailan Wang, Gaku Ichihara, Hidenori Ito, Kanefusa Kato, Junzoh Kitoh, Tetsuya Yamada, Xiaozhong Yu, Seiji Tsuboi, Yoshinori Moriyama, Rie Sakatani, Eiji Shibata, Michihiro Kamijima, Seiichiro Itohara, Yasuhiro Takeuchi, Toxicological Sciences, 67, (1) 114 - 120,   2002年, 査読有り, 1-Bromopropane is used widely as an alternative to ozone-depleting solvents. The neurotoxic effects of this agent have been described in humans and experimental animals. Here we investigated the underlying mechanisms of the neurotoxic effects of 1-bromopropane by examining the initial biochemical changes in the central nervous system. Four groups of 9 Wistar male rats each were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 7 days. At the end of the experiment, the cerebrum, cerebellum, brain stem and lumbar enlargement of the spinal cord were dissected out from each rat (n = 8) for biochemical analyses. Morphological examinations of the nervous system were performed in the remaining rat of each group. 1-Bromopropane dose-dependently decreased neurospecific γ-enolase, total glutathione, and nonprotein sulfhydryl groups in the cerebrum and cerebellum. Creatine kinase activity decreased dose-dependently in the brain and spinal cord. Histopathological examination showed swelling of preterminal axons in gracile nucleus and degeneration of myelin in peripheral nerves. Our results of low levels of γ-enolase suggested that 1-bromopropane might primarily cause functional or cellular loss of neurons in the cerebrum and cerebellum. Glutathione depletion or modification to functional proteins containing a sulfhydryl base as a critical site might be the underlying mechanism of 1-bromopropane neurotoxicity.
  • Changes in cholinesterase activity, nerve conduction velocity, and clinical signs and symptoms in termite control operators exposed to chlorpyrifos, Masahiro Gotoh, Isao Saito, Jian Huang, Yukio Fukaya, Tadao Matsumoto, Naomi Hisanaga, Eiji Shibata, Gaku Ichihara, Michihiro Kamijima, Yasuhiro Takeuchi, Journal of Occupational Health, 43, (3) 157 - 164,   2001年, 査読有り, We have surveyed periodical medical examinations for pest and termite control operators (n=64) exposed to chlorpyrifos and other organophosphate pesticides. Distribution of serum butyrylcholinesterase (BuChE) activities of all workers ranged 0.01-1.18 (ΔpH). Serum BuChE activities in 6 workers in one termite control company were severely depressed and ranged from 0.01 to 0.21 ΔpH. Erythrocyte acetylcholinesterase (AChE) activities in 3 workers were lower than the normal range. Erythrocyte AChE activities and serum BuChE acitivities in chlorpyrifos sprayers were significantly correlated (r=0.720). In other clinical signs, blood urine nitrogen (BUN) in 4 workers and white blood cell (WBC) counts in 4 workers were abnormal. Sensory nerve conduction velocities in the sural nerve of all 6 workers were significantly reduced to 18.8-26.6 m/s in the left leg and 19.2-27.2 m/s in the right leg. In the results of ophthalmic examinations, accommodation time (both eyes) in 4 workers extended over the normal range and electroretinography (ERG) in 2 workers showed abnormal ERG including disappearance of oscillatory potential. Chlorpyrifos residue in blood in 4 operators whose serum BuChE activities ranged from 0.01 to 0.03 ΑpH were detected in the range 2-8 ng/m/. They had sprayed chlorpyrifos daily for 5 d before every blood sampling. It is suggested that serum BuChE activity and sensory nerve conduction velocity are sensitive indicators to evaluate the effects of chlorpyrifos exposure, and may be used effectively to monitor exposure and the effects of chlorpyrifos on health.
  • Neurotoxicity of 2-bromopropane and 1-bromopropane, alternative solvents for chlorofluorocarbons, Xiaozhong Yu, Gaku Ichihara, Junzoh Kitoh, Zhenlin Xie, Eiji Shibata, Michihiro Kamijima, Yasuhiro Takeuchi, Environmental Research, 85, (1) 48 - 52,   2001年, 査読有り, To clarify the neurotoxicity of 2-bromopropane (2-BP) in comparison with 1-bromopropane (1-BP), 36 Wistar strain male rats were divided into 4 groups of 9 and exposed daily to 100-ppm 2-BP, 1000-ppm 2-BP, 1000-ppm 1-BP, or fresh air for 8 h a day. Exposure to 1000 ppm of 1-BP was discontinued after 5 or 7 weeks' exposure because of the unexpected appearance of incomplete hindlimb paralysis followed by serious emaciation. The other groups were sacrificed at the end of 12 weeks' exposure. Exposure to 1000 ppm of 2-BP resulted in significant decreases in body weight and motor nerve conduction velocity (MCV) and elongation in distal latency (DL). A ball-like enlargement of myelin sheaths was observed. Significant reductions in the number of erythrocytes, platelets, and leukocytes, testicular germ cell loss, and seminiferous atrophy were also observed in this group, but not in 100-ppm 2-BP group. Exposure to 1000 ppm of 1-BP for 5 or 7 weeks caused a significant decrease in body weight and MCV and elongation in DL. Linearly arranged ovoid- or bubble-like debris of the axons and myelin sheaths in the teased tibial nerves and axonal swelling in gracilis nucleus were found in this group. No significant changes in hematological indices or histopathological findings of the testis were found in this group. In conclusion, 2-BP is neurotoxic to the peripheral nerves in addition to its toxic effects on the reproductive and hematopoietic systems at 1000 ppm. No noticeable changes were found in the rats exposed to 100 ppm of 2-BP. 1-BP is a potent neurotoxicant at 1000 ppm for 5 or 7 weeks, while testicular and hematopoietic toxicity was not found. © 2001 Academic Press.
  • Chronic occupational exposure to organic solvents and magnetic resonance signal changes in the brain white matter - A case report, Michihiro Kamijima, Eiji Shibata, Hisashi Tanaka, Gaku Ichihara, Yasuhiro Takeuchi, J Occup Health, 42, (1) 47 - 49,   2000年, 査読有り
  • 2-Bromopropane causes ovarian dysfunction by damaging primordial follicles and their oocytes in female rats, Xiaozhong Yu, Michihiro Kamijima, Gaku Ichihara, Wenxin Li, Junzoh Kitoh, Zhenlin Xie, Eiji Shibata, Naomi Hisanaga, Yasuhiro Takeuchi, Toxicol App Pharmacol, 159, (3) 185 - 193,   1999年09月15日, 査読有り, Ovarian dysfunction induced by 2-bromopropane (2-BP) has been described in female factory workers and experimental animals. However, the underlying mechanism is still unclear. To establish the reproductive target site and define mechanisms of 2-BP toxicity in adult female rats, we examined the effects of different doses and duration of exposure to 2-BP in female rats. In the dose-dependent experiments, female rats were exposed to 2-BP at 100, 300, or 1000 ppm or fresh air (n = 9 each) in exposure chambers for 8 h/day for 9 weeks. In the time-course experiments, female rats were exposed to 2-BP at 3000 ppm for 8 h (n = 7 each). The rats were then euthanized 1, 3, 5, and 17 days after exposure. Differential follicle counts and in situ terminal deoxynucleotidyl transferase assay were used to evaluate 2-BP effect on primordial, growing, and antral follicles. Exposure to 2-BP at 300 and 1000 ppm produced a significant reduction in the percentage of primordial, growing, and antral follicles in a dose-dependent manner. Significant reduction in the percentage of primordial follicles at 17 days after exposure was observed in time-course experiments. Exposure to 2-BP at 3000 ppm for 8 h resulted in histological changes in primordial follicles complex at 5 and 17 days after exposure. These changes consisted of distortion of the symmetry of oocytes and their nuclei at Day 5 after exposure and appearance of eccentric pyknotic cells and shrinkage of oocyte nuclei at Day 17 after exposure. In situ end labeling showed increased numbers of apoptotic oocytes and granulosa cells in primordial follicles at Days 5 and 17 after exposure. Our results suggested that ovarian dysfunction induced by 2-BP was caused by the destruction of primordial follicle and its oocyte due to the induction of apoptosis. Our studies also show that the follicle differential count is a more sensitive method than the vaginal smear in monitoring the female reproductive disorders induced by 2-BP.
  • Effect of inhalation exposure to 2-bromopropane on the nervous system in rats, Xiaozhong Yu, Gaku Ichihara, Junzoh Kitoh, Zhenlin Xie, Eiji Shibata, Michihiro Kamijima, Nobuyuki Asaeda, Naomi Hisanaga, Yasuhiro Takeuchi, Toxicology, 135, (2-3) 87 - 93,   1999年07月15日, 査読有り, Exposure to 2-bromopropane (2-BP) is suspected to have adverse effects on the nervous system. The aim of this study was to investigate whether the exposure of rats to 2-BP had neurotoxic effects using histological and electrophysiological studies. Wistar strain male rats were exposed daily to either 100 or 1000 ppm 2-BP or to fresh air for 8 h a day for 12 weeks. Body weight was measured before exposure and every 2 weeks. Motor nerve conduction velocity (MCV) and distal latency (DL) were measured before exposure and every 4 weeks during exposure. Histological examination of the nervous system was also performed. Exposure of rats (n=9) to 1000 ppm resulted in suppression of body weight gain and a significant decrease in brain weight compared to the control (n=9). Electrophysiological measurements showed a significant decrease in MCV in 1000 ppm exposed rats at 8 weeks and significant prolongation of DL at 8 and 12 weeks. Abnormalities of the myelin sheath were detected in the common peroneal nerves. In 100-ppm exposed rats (n=9), no significant changes were noted in body weight and the peripheral nerve. In conclusions, long-term exposure to 1000 ppm of 2-BP may result in peripheral neuropathy in rats. Copyright (C) 1999 Elsevier Science Ireland Ltd.
  • Occupational health survey on workers exposed to 2-bromopropane at low concentrations, Gaku Ichihara, Xuncheng Ding, Xiaozhong Yu, Xiangdong Wu, Michihiro Kamijima, Simeng Peng, Xuezhi Jiang, Yasuhiro Takeuchi, American Journal of Industrial Medicine, 35, (5) 523 - 531,   1999年, 査読有り, Background: Recent case studies in Korea and animal studies revealed the reproductive and hematopoietic toxicity of 2-bromopropane introduced into workplaces as an alternative to ozone-layer depleting chlorofluorocarbons. We aimed to clarify the dose-effect relationship of 2-bromopropane in workers. Method: The exposure concentration of 2-bromopropane and hematological indices, hormonal levels, menstruation status, and sperm indices were examined in 25 workers (11 males, 14 females) at a 2-bromopropane factory. Regression analyses of the examined indices against time-weighted average (TWA) of exposure concentration were conducted. Results: Amenorrhea or polymenorrhea was observed only in older females. Hematological indices had a significant relation with TWA of exposure concentration in females with normal menstruation. However, no other indices showed any significant relation with TWA of 2-bromopropane. Conclusions: No severe cases of reproductive or hematopoietic disorders were found at less than 10 ppm (TWA), but a possible adverse effect of 2-bromopropane on hematopoiesis could not be disproved.
  • Physiologically based pharmacokinetic modeling of metabolic interactions between n-hexane and toluene in humans, Xiaozhong Yu, Gunnar Johanson, Gaku Ichihara, Eiji Shibata, Michihiro Kamijima, Yuichiro Ono, Yasuhiro Takeuchi, Journal of Occupational Health, 40, (4) 293 - 301,   1998年10月, 査読有り, Some animal experiments have shown that mutual metabolic inhibition takes place between n-hexane and toluene, but we have found only one report dealing with their metabolic interaction at occupationally relevant exposure levels (Baelum et al. 1998). In order to evaluate the effect of dose- dependent metabolic interaction between toluene and n-hexane, especially in occupationally relevant exposure conditions such as relevant exposure levels, physical activities and exposure patterns, a physiologically based pharmacokinetic (PBPK) model for co-exposure to n-hexane and toluene was developed. The PBPK model for the binary co-exposure was established by initially validating or refining the existing PBPK models for n-hexane and toluene and then linking the individual solvent models via the hepatic metabolism terms. In reporting previous findings, noncompetitive inhibition was assumed and the inhibition constant of toluene on n-hexane biotransformation and that of n-hexane on toluene biotransformation used in simulation were 7.5, 30 μm, respectively, in previous data. According to the model, 8 h of constant exposure to 50 ppm n-hexane and 25, 50, 100 and 500 ppm toluene will cause about 7%, 18%, 62% and 96% decreases in the urinary excretion of 2,5-hexanedione (2,5-HD) and 4%, 10%, 25% and 30% increases in the n-hexane concentration in blood at the end of the fifth day of exposure simulated in a standard man at a 25 W work load. Simulations of co-exposure to 50 ppm n-hexane and 50 ppm toluene in a standard man who inhaled 50 ppm n- hexane with 0 or 50 ppm toluene for 8 h at different work loads suggest that toluene causes a slight decrease in urinary 2,5-HD in the resting condition, a 17% decrease at 25 W, and a 41% decrease at 50 W work load. The simulations of co-exposure in different exposure patterns with the same time-weighted concentration (TWA) of 50 ppm, i.e. 50 ppm for 8 h, 100 ppm of 4 times for 1 h and 200 ppm of twice for 1 h, showed reductions in urinary 2,5-HD of 17%, 40% and 67%, respectively. These simulations suggest that coexposure to n- hexane and toluene around 50 ppm (TWA) could affect urinary n-hexane metabolites to various degrees depending on the fluctuations in exposure concentrations and variety of work activities in the workplace.
  • Preliminary report on the neurotoxicity of 1-bromopropane, an alternative solvent for chlorofluorocarbons, Xiaozhong Yu, Gaku Ichihara, Junzoh Kitoh, Zhenlin Xie, Eiji Shibata, Michihiro Kamijima, Nobuyuki Asaeda, Yasuhiro Takeuchi, Journal of Occupational Health, 40, (3) 234 - 235,   1998年07月, 査読有り
  • Urinary 2,5-hexanedione increases with potentiation of neurotoxicity in chronic coexposure to n-hexane and methyl ethyl ketone, Gaku Ichihara, Isao Saito, Michihiro Kamijima, Xiaozhong Yu, Eiji Shibata, Machiko Toida, Yasuhiro Takeuchi, International Archives of Occupational and Environmental Health, 71, (2) 100 - 104,   1998年03月, 査読有り, Objective: MEK (methyl ethyl ketone) is widely and frequently used as an ingredient of mixed solvents together with n-hexane. MEK is known to decrease urinary levels of 2,5-hexanedione dose-dependently in an acute or chronic coexposure with a constant level of n-hexane. This change in urinary 2,5-hexanedione appears to contradict the potentiation effect of MEK on n-hexane-induced neurotoxicity because it is believed that the toxicity of n-hexane is activated through n-hexane metabolism. We aimed to clarify how the urinary level of 2,5-hexanedione changes when MEK modifies the degree of n-hexane-induced neurotoxicity. Method: A total of 32 male Wistar rats were divided into 4 groups of 8 each and were then exposed to fresh air only, 2000 ppm n-hexane only, 2000 ppm n-hexane plus 200 ppm MEK, and 2000 ppm n-hexane plus 2000 ppm MEK, respectively. Inhalation exposures were performed 12 h/day, 6 days/week, for 20 weeks. Motor-nerve conduction velocity (MCV), distal latency (DL), and urinary 2,5-hexanedione were measured every 4 weeks. Results: The MCV decreased, the DL increased, and urinary levels of 2,5-hexanedione increased in the 2000-ppm n-hexane plus 2000 ppm MEK group in comparison with the 2000-ppm M-hexane only group following 4 weeks' exposure. On the 1st day of exposure, however, coexposure to MEK decreased urinary levels of 2,5-hexanedione dose-dependently. Conclusions: The present study showed that urinary concentrations of 2,5-hexanedione increased with potentiation of n-hexane neurotoxicity. Urinary 2,5-hexanedione concentration does not necessarily reflect the exposure concentration of n-hexane in coexposure to n-hexane along with MEK or other solvents, but it may be useful as a marker in the assessment of neurotoxicity in coexposure to n-hexane and other solvents.
  • Epicondylitis among cooks in nursery schools, Yuichiro Ono, Ryogo Nakamura, Midori Shimaoka, Shuichi Hiruta, Yoji Hattori, Gaku Ichihara, Michihiro Kamijima, Yasuhiro Takeuchi, Occupational and Environmental Medicine, 55, (3) 172 - 179,   1998年, 査読有り, Objectives - To investigate the prevalence and risk factors of epicondylitis among cooks in nursery schools in a cross sectional study because they are suspected to have strenuous workloads on the hands and arms. Methods - Prevalence of epicondylitis among 209 nursery school cooks and 366 control workers aged 40-59 were studied. Both groups consisted of women workers chosen from 1299 subjects who agreed to participate from 1329 social welfare employees in a city. All workers were interviewed with a questionnaire and had a clinical examination of the tenderness to palpation of epicondyles and epicondylar pain provoked by resisted extension and flexion of the wrist. Results - Nursery school cooks had a significantly higher prevalence of epicondylitis (11.5%) than the controls (2.5%). In a logistic regression model, job title of the cook was also found to have a strong association with epicondylitis (odds ratio (OR) 5.4, 95% confidence interval (95% CI) 2.4 to 11.9) after adjustment for age, body length, and body mass index. Weaker associations were also found between epicondylitis and suspected job stress or workload scores for mechanical workload and psychosocial stressors based on factor analysis. Conclusions - This study supported the hypothesis that nursery school cooks had a higher prevalence of epicondylitis than other workers with less strenuous hand and arm tasks. It was suggested that risk factors of epicondylitis would be multifactorial, including mechanical workload and psychosocial factors.
  • A review on toxicity of 2-bromopropane: Mainly on its reproductive toxicity, Yasuhiro Takeuchi, Gaku Ichihara, Michihiro Kamijima, Journal of Occupational Health, 39, (3) 179 - 191,   1997年07月, 2-Bromopropane has been used mostly as an intermediate for medicines, pesticides and other chemicals in closed systems. Recently it has come to be used as an alternative solvent in open systems instead of ozone layer depleting chlorofluorocarbons. An outbreak of reproductive and hematopoietic disorders occurred in workers exposed to solvents containing 2-bromopropane in a Korean factory in 1995. After that some animal experiments revealed that 2-bromopropane has a severe toxic effect on the female and male reproductive organs and hematopoietic organs. We reviewed the toxicity of 2-bromopropane based on the recent data obtained in epidemiological surveys and animal experiments. Toxicities of structurally related bromopropanes were compared with that of 2-bromopropane and its risk assessment was discussed. The conclusions are as follows: 1. 2-Bromopropane has a specific reproductive and hematopoietic toxicity in both sexes in humans and experimental animals. 2. It could impair the testes, especially spermatogonia in males. 3. It could impair the ovarian function, resulting in a disturbed estrous cycle and loss of oocytes in females. 4. It could impair the bone marrow, resulting in pancytopenia. 5. It has a weak potent mutagenicity in bacterial mutation assays. 6. A risk assessment suggests that around 0.3-10 ppm might be recommended as an occupational exposure limit for 2-bromopropane.
  • A cohort mortality study of construction workers, J. Sun, E. Shibata, N. Hisanaga, M. Kamijima, G. Ichihara, J. Huang, M. Toida, Y. Takeuchi, American Journal of Industrial Medicine, 32, (1) 35 - 41,   1997年07月, 査読有り, This report presents a mortality study among the 17,344 members of the Construction Workers' Health Insurance Society of Mie Prefecture in Japan. The study period was between 1973 and 1993. During this period, 480 members died. Age-specific mortality rates of Mie Prefecture were used as comparison standards. Significantly elevated standardized mortality ratio (SMR) and proportionate mortality ratio (PMR) were observed for 'accidents and adverse effects.' In addition, the PMRs of all cancers and 'cancers of trachea, bronchus and lung' were also significantly elevated. The job classifications were reorganized into three groups, according to the frequency of asbestos exposure the workers experienced on the construction sites. The asbestos exposure was based on job classifications among 7,411 workers who had completed a self-administered survey questionnaire. In the frequent-exposure group, the PMR was significantly elevated for all cancers. In the medium- exposure group, the SMRs were significantly elevated for all cancers and 'cancer of trachea, bronchus and lung.' The PMR was significantly elevated for 'cancer of trachea, bronchus and lung.' In the less-exposure group, the PMR was significantly elevated for 'accidents and adverse effects.' This study provided support for the hypothesis that working in the construction industry might be associated with high risks for asbestos-associated cancers and accidental deaths.
  • 2-bromopropane-induced hypoplasia of bone marrow in male rats, Tamie Nakajima, Shigetaka Shimodaira, Gaku Ichihara, Nobuyuki Asaeda, Toshihiko Kumazawa, Hisakazu Iwai, Ichihito Ichikawa, Michihiro Kamijima, Y. U. Xiaozhong, Zhelin Xie, Hidetaka Kondo, Yasuhiro Takeuchi, Journal of Occupational Health, 39, (3) 228 - 233,   1997年07月, 査読有り, The hematotoxicity of 2-bromopropane was investigated in thirty-six male Wistar rats. The rats were put into four groups: three groups were exposed to 0, 300, and 1,000 ppm 2-bromopropane for 8 hr per day, for 9 weeks, respectively, and the remaining group was exposed to 3,000 ppm only for 9-11 days. Hematotoxicity was assessed by measuring peripheral blood cells as well as cellularity, the number of megakaryocytes and morphological findings in the bone marrow. Exposure to 2-bromopropane decreased the numbers of erythrocytes in the peripheral blood at 300 ppm or higher, leukocytes at 1,000 ppm, and platelets at 300 and 1,000 ppm. Exposure to 300 ppm 2- bromopropane did not influence the indices of bone marrow toxicity. Exposure to 1,000 ppm 2-bromopropane or a higher dose-dependently induced a hypoplastic profile with replacement of fatty spaces in the bone marrow, though the durations of exposure to 3,000 ppm were under one sixth. These exposures also induced dose-dependent decreases in the number of megakaryocytes, with the maintained ratio of granulocytes to erythrocytes in the bone marrow. Residual progenitor cells showed some dysplastic or megaloblastic changes. These results suggest that exposure to 2-bromopropane leads to a reduction in the numbers of hematopoietic cells in the bone marrow, the result being a persistent pancytopenia in male rats.
  • Histopathologic findings of bone marrow induced by 2-bromopropane in male rats, Tamie Nakajima, Shigetaka Shimodaira, Gaku Ichihara, Nobuyuki Asaeda, Toshihiko Kumazawa, Hisakazu Iwai, Ichihito Ichikawa, Michihiro Kamijima, Xiaozhong Yu, Zhelin Xie, Hidetaka Kondo, Yasuhiro Takeuchi, Journal of Occupational Health, 39, (2) 81 - 82,   1997年04月, 査読有り
  • Ovarian toxicity of 2-bromopropane in the non-pregnant female rat, Michihiro Kamijima, Gaku Ichihara, Junzoh Kitoh, Hiroko Tsukamura, Kei Ichiro Maeda, Xiaozhong Yu, Zhenlin Xie, Tamie Nakajima, Nobuyuki Asaeda, Naomi Hisanaga, Yasuhiro Takeuchi, J Occup Health, 39, (2) 144 - 149,   1997年04月, 査読有り, A cluster of patients with amenorrhea, oligospermia and anemia were found among workers in an electronics factory in the Republic of Korea. 2-Bromopropane was suspected to cause the disorders. This study aimed to clarify its ovarian toxicity in the virgin rat. Female Wistar rats were daily exposed to 0, 100, 300, or 1,000 ppm 2-bromopropane for eight hours a day for 9 weeks. During the experimental period, vaginal smears were taken everyday to monitor ovarian cyclicity. Tissues were histopathologically examined and plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined at the end of experiment. The vaginal smear test showed that the number of normal cycles decreased significantly both in the 300 and 1,000 ppm groups. The histopathological examination revealed dose-dependent ovarian follicle atresia accompanied by a decreased number of normal antral and growing follicles in the 300 and 1,000 ppm groups. Especially, in the ovaries of rats with persistent estrous smears in the 1,000 ppm group, most of the follicles were atretic and there were no newly formed corpora lutea. There still remained normal antral follicles and corpora lutea in the ovaries of the remaining rats of the group and of the 300 ppm group with constant diestrous and occasional estrous smears. Hormonal in LH or FSH concentrations between any groups. The results showed that 2-bromopropane has ovarian toxicity in rats, indicating that the secondary amenorrhea in human cases was due to 2-bromopropane exposure.
  • Disruption in ovarian cyclicity due to 2-bromopropane in the rat, M Kamijima, G Ichihara, XZ Yu, ZL Xie, J Kitoh, H Tsukamura, K Maeda, T Nakajima, N Asaeda, N Hisanaga, Y Takeuchi, JOURNAL OF OCCUPATIONAL HEALTH, 39, (1) 3 - 4,   1997年01月, 査読有り
  • Testicular toxicity of 2-bromopropane, Gaku Ichihara, Nobuyuki Asaeda, Toshihiko Kumazawa, Yoshiaki Tagawa, Michihiro Kamijima, Xiaozhong Yu, Hidetaka Kondo, Tamie Nakajima, Junzoh Kitoh, Il Je Yu, Young Hahn Moon, Naomi Hisanaga, Yasuhiro Takeuchi, Journal of Occupational Health, 38, (4) 205 - 206,   1996年10月, 査読有り
  • Effects of asymmetric dynamic and isometric liftings on strength/force and rating of perceived exertion, Yoji Hattori, Yuichiro Ono, Michihiro Kamijima, Eiji Shibata, Gaku Ichihara, Shoko Ando, Maria Beatriz G. Villaneuva, Yasuhiro Takeuchi, Midori Shimaoka, Shuichi Hiruta, Ergonomics, 39, (6) 862 - 876,   1996年06月01日, 査読有り
  • Toxic effects of hexane derivatives on cultured rat Schwann cells, Michihiro Kamijima, Gen Sobue, Gaku Ichihara, Eiji Shibata, Yuichiro Ono, Hidetaka Kondo, Maria Beatriz G. Villanueva, Takayuki Itoh, Terunori Mitsuma, Yasuhiro Takeuchi, Toxicology, 108, (1-2) 25 - 31,   1996年04月, 査読有り, The cytotoxic effects of the following five hexane-related compounds were examined on Schwann cell DNA synthesis: 2,5-hexanedione (2,5-HD), 2-hexanol (2-OH), 2-hexanone (MnBK), 2,5-dimethylfuran (DF), and γ-valerolactone (VL). Schwann cells were isolated from the sciatic nerves of neonatal Sprague-Dawley rats and cultured. [3H]-thymidine incorporation into Schwann cell nuclei was measured by scintillation spectrometry and autoradiography when hexane derivatives were added to the culture medium. All of the hexane-related compounds suppressed [3H]-thymidine incorporation in a concentration-dependent manner. DF was the most cytotoxic for the inhibition of Schwann cell DNA synthesis among the compounds. The finding suggests that DF-mediated cytotoxicity should be taken into account as a possible additional mechanism of hexane intoxication, especially in the impairment of mitotic cells.
  • Toluene induces behavioral activation without affecting striatal dopamine metabolism in the rat: Behavioral and microdialysis studies, Hidetaka Kondo, Jian Huang, Gaku Ichihara, Michihiro Kamijima, Isao Saito, Eiji Shibata, Yuichiro Ono, Naomi Hisanaga, Yasuhiro Takeuchi, Daiichiro Nakahara, Pharmacology, Biochemistry and Behavior, 51, (1) 97 - 101,   1995年05月, 査読有り, We examined the effects of toluene on the release of dopamine (DA) and its metabolites in rat striatum using microdialysis. Intraperitoneal injection of 800 mg/kg toluene significantly increased motor activity in rats, as did methamphetamine (MAP) (1 mg/kg). However, 800 mg/kg toluene did not affect the extracellular levels of DA, 3,4-dihydroxyphenylacetic acid, homovanillic acid, or 5-hydroxyindoleacetic acid. This is in contrast to MAP, which significantly increased extracellular DA and decreased the extracellular levels of its metabolites. These results suggest that toluene-induced behavioral augmentation may not be associated with alterations in DA or serotonin neurochemistry such as are associated with MAP-induced behavioral augmentation. © 1995.
  • METABOLIC-ACIDOSIS AND RENAL TUBULAR INJURY DUE TO PURE TOLUENE INHALATION, M KAMIJIMA, Y NAKAZAWA, M YAMAKAWA, E SHIBATA, M HISANAGA, Y ONO, M TOIDA, Y TAKEUCHI, ARCHIVES OF ENVIRONMENTAL HEALTH, 49, (5) 410 - 413,   1994年09月, 査読有り, A 22-y-old woman was hospitalized for muscle weakness of her lower extremities after she sniffed approximately 6 l of pure toluene during the month prior to admission. The examinations on serum and urine revealed mixed hyperchloremic and high anion gap metabolic acidosis accompanied by impaired urinary acidification. Histopathological changes of the kidney were patchy areas of tubular injury. Acidosis normalized on the fourth day of admission, but both proximal and distal tubular dysfunction persisted. These findings indicate that toluene is a tubular toxin and may contribute to the development of distal renal tubular acidosis.

MISC

  • 一目で分かる!専門用語:室内空気汚染分野, 若山貴成, 伊藤由起, 上島通浩, ビルと環境, 163,   2018年12月, 招待有り
  • 2-エチル-1-ヘキサノールによる室内空気汚染, 若山貴成, 伊藤由起, 上島通浩, ビルと環境, 163,   2018年12月, 招待有り
  • Occupational Exposure Limits for ethylidene norbornene, ethyleneimine, benomyl, and 2,3-epoxypropyl methacrylate, and classifications on carcinogenicity., Atsuko Araki, Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Hajime Hori, Seichi Horie, Hyogo Horiguchi, Masayoshi Ichiba, Gaku Ichihara, Masayuki Ikeda, Tatsuya Ishitake, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Takeyasu Kakumu, Michihiro Kamijima, Kanae Karita, Takahiko Katoh, Toshio Kawai, Toshihiro Kawamoto, Shinji Kumagai, Yukinori Kusaka, Akiko Matsumoto, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Makiko Nakano, Tetsuo Nomiyama, Hirokazu Okuda, Masayuki Okuda, Kazuyuki Omae, Haruhiko Sakurai, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Akito Takeuchi, Ayano Takeuchi, Masatoshi Tanaka, Shigeru Tanaka, Teruomi Tsukahara, Masashi Tsunoda, Susumu Ueno, Jun Ueyama, Yumi Umeda, Kenya Yamamoto, Yuko Yamano, Takenori Yamauchi, Eiji Yano, Journal of occupational health, 60, (4) 333 - 335,   2018年07月25日
  • Occupational exposure limits for ethylene glycol monobutyl ether, isoprene, isopropyl acetate and propyleneimine, and classifications on carcinogenicity, occupational sensitizer and reproductive toxicant., Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Hajime Hori, Seichi Horie, Hyogo Horiguchi, Masayoshi Ichiba, Gaku Ichihara, Masayuki Ikeda, Tatsuya Ishitake, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Michihiro Kamijima, Kanae Karita, Takahiko Katoh, Toshio Kawai, Toshihiro Kawamoto, Reiko Kishi, Shinji Kumagai, Yukinori Kusaka, Akiko Matsumoto, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Tetsuo Nomiyama, Hirokazu Okuda, Kazuyuki Omae, Haruhiko Sakurai, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Akito Takeuchi, Ayano Takeuchi, Masatoshi Tanaka, Shigeru Tanaka, Teruomi Tsukahara, Masashi Tsunoda, Susumu Ueno, Jun Ueyama, Yumi Umeda, Yuko Yamano, Takenori Yamauchi, Eiji Yano, Journal of occupational health, 59, (4) 364 - 366,   2017年07月27日
  • 小児におけるトリクロホスの投与量の最適化, 井上美帆, 佐藤博貴, 糸原光太郎, 加藤祐子, 石井祥代, 伊藤由起, 中平有紀, 那須民江, 上島通浩, 矢野育子, 松原和夫, 佐和貞治, 橋本悟, 臨床薬理の進歩, (38号) 71 - 78,   2017年06月, 招待有り
  • トリクロロエチレン健康リスク評価作業部会報告書 トリクロロエチレンに係る健康リスク評価について, 青木 康展, 上田 佳代, 内山 巌雄, 上島 通浩, 祖父江 友孝, 武林 亨, 中杉 修身, 那須 民江, 新田 裕史, 野見山 哲生, 山崎 新, 朝倉 敬子, 苅田 香苗, 塚原 照臣, 中野 真規子, 道川 武紘, 安達 修一, 高野 裕久, 中島 宏, トリクロロエチレン健康リスク評価作業部会, 大気環境学会誌, 52, (2) A24 - A57,   2017年03月
  • 一般乳幼児における運動バリエーション頻度調査研究の中間報告, 宮地 泰士, 中川 敦子, 鷲見 聡, 今枝 正行, 齋藤 伸治, 上島 通浩, 脳と発達, 48, (Suppl.) S381 - S381,   2016年05月
  • 事例に潜む新しい労働衛生課題を拾うために, 上島通浩, 産業医学ジャーナル, 38, (1) 91 - 2,   2015年, 招待有り
  • エコチル調査の国際連携, 中山祥嗣, 上島通浩, 生活と環境, 694,   2014年, 招待有り
  • 有機溶剤トリクロロエチレンによる職業性過敏症症候群, 上島通浩, 王海蘭, 那須民江, アレルギー・免疫, 19, (8) 1254 - 1260,   2012年07月, 招待有り
  • シックハウス症候群・化学物質過敏症への対応, 上島 通浩, 酒井 潔, 伊藤 由起, 榎原 毅, 柴田 英治, 現代医学, 58,   2010年
  • 劇毒物 有機リン系農薬(ダイアジノン,フェニトロチオン,メタミドホス,ジクロルボスなど) (広範囲 血液・尿化学検査 免疫学的検査(第7版・2)その数値をどう読むか) -- (生化学的検査(2)), 上島 通浩, 上山 純, 高木 健次, 日本臨床, 68,   2010年
  • 予防医学 環境と予防医学 重症薬疹と有機溶剤中毒の接点, 上島 通浩, 王 海蘭, 那須 民江, 現代医学, 56,   2008年
  • 2-エチル-1-ヘキサノールによるシックビル-シックハウス対策の盲点-, 上島通浩, 那須民江, 柴田英治, 酒井潔, ビルと環境, 114,   2006年09月, 招待有り

書籍等出版物

  • シンプル衛生公衆衛生学2017、2018、2019、2020, 上島通浩, 鈴木庄亮, 分担執筆, 6-2 環境の把握とその評価. (p145-151)/10-1 働く人々の健康. 10-2 労働災害・事故. 10-3 職業病. (p273-292), 南江堂,   2020年03月, ISBN:9784524248193
  • 今日の治療指針 2020年版(私はこう治療している), 福井次矢, 高木 誠, 小室一成, 多賀須, 幸男, 尾形, 悦郎, 山口, 徹, 北原, 光夫, 福井, 次矢, 高木, 誠, 小室, 一成, 分担執筆, 17. 環境・職業性因子による疾患 有機溶剤中毒(p1106), 医学書院,   2020年01月10日, ISBN:4260039393
  • 内科学書(改訂第7・8・9版) Vol.1, 那須民江, 上島通浩, 上島通浩, 那須民江, 分担執筆, 内科学総論 2. 病因・病態. 中毒の病態(p69-70)/工業毒中毒(p70-73)., 中山書店,   2019年08月, ISBN:9784521747491
  • New予防医学公衆衛生学(第3版、改訂第4版), 上島通浩, 伊藤由起, 分担執筆, 4部:第3章 産業衛生 生殖発生毒性物質 (p276-281), 南江堂,   2018年11月, ISBN:9784524251162
  • 環境による健康リスク(日本医師会雑誌 第146巻特別号(2)), 上島通浩, 分担執筆, 「環境中における農薬の動態と管理」、「農薬・殺虫剤」, 日本医師会,   2017年10月
  • 上島通浩. 酸素欠乏、塩ビモノマー、ニトログリコール 他4項目. In: 産業保健マニュアル(6版、改訂第7版)(p267-275), 南山堂,   2017年, ISBN:9784525184575
  • Kamijima M, Wang H, Yamanoshita O, Ito Y, Nakajima T. Chapter 3. Hypersensitivity Dermatitis and Hepatitis. In: Gilbert KM and Blossom SJ ed. Trichloroethylene: Toxicity and Health Risks (p37-52), Humana Press,   2014年, ISBN:9781447163107
  • 大森豊緑、上島通浩、荒木俊一 社会医学からみた今後の課題-化学物質過敏症を含む- In:職業アレルギー (p263-270), 永井書店,   2011年, ISBN:9784815918897
  • Satoh T, Inayat-Hussain SH, Kamijima M, Ueyama J. Novel Biomarkers of organophosphate exposure. In: Anticholinesterase pesticide. (p289-302), Wiley,   2010年
  • 上島通浩、伊藤由起、上山純. Ⅲ-14農薬類 In: 分子予防環境医学 改訂版 (p731-739), 本の泉社,   2010年, ISBN:9784780706017
  • 最新臨床検査項目辞典, 上島通浩, 分担執筆, 総三塩化物、三塩化酢酸、三塩化エタノール、馬尿酸、メチル馬尿酸、マンデル酸、N-メチルホルムアミド、2,5-ヘキサンジオン、パラニトロフェノール、フェノール、メタノール、エチレングリコール、エタノール、ニコチン, 医歯薬出版,   2008年03月, ISBN:9784263221655

講演・口頭発表等

  • 陰膳調査における女子大学生の食事摂取状況について, 野正 夏鈴, 大矢 奈穂子, 伊藤 由起, 佐藤 博貴, 北森 一哉, 大島 志織, 峰松 明也子, 湊 京子, 榎原 毅, 上島 通浩, 東海公衆衛生雑誌,   2019年07月, 東海公衆衛生学会
  • 1.5歳児および3歳児における使い捨ておむつを用いた殺虫剤の曝露量評価, 大矢 奈穂子, 伊藤 由起, 榎原 毅, 佐藤 博貴, 日置 啓介, 上山 純, 加藤 沙耶香, 松木 太郎, 杉浦 真弓, 齋藤 伸治, 上島 通浩, 東海公衆衛生雑誌,   2019年07月, 東海公衆衛生学会
  • 2-エチル-1-ヘキサノール吸入曝露中止後のマウス嗅上皮の構造変化と炎症細胞浸潤, 三宅 美緒, 伊藤 由起, 大矢 奈穂子, 佐藤 博貴, 若山 貴成, 上島 通浩, 産業衛生学雑誌,   2019年03月, (公社)日本産業衛生学会
  • 非線形回帰モデルによる有機リン系殺虫剤尿中代謝物のリスク評価 急性毒性の異なる薬剤間での比較検討, 佐藤 博貴, 伊藤 由起, 文堂 生深, 花井 ちなみ, 西村 正也, 上山 純, 上島 通浩, 産業衛生学雑誌,   2019年03月, (公社)日本産業衛生学会
  • 神経発達期における縦断的な有機リン系殺虫剤曝露評価, 大矢 奈穂子, 伊藤 由起, 榎原 毅, 佐藤 博貴, 日置 啓介, 上山 純, 加藤 沙耶香, 松木 太郎, 杉浦 真弓, 齋藤 伸治, 上島 通浩, 産業衛生学雑誌,   2019年03月, (公社)日本産業衛生学会
  • 1歳半児におけるジノテフラン曝露量と生活環境および食意識との関連, 大矢 奈穂子, 伊藤 由起, 上山 純, 加藤 沙耶香, 松木 太郎, 佐藤 博貴, 齋藤 伸治, 杉浦 真弓, 榎原 毅, 上島 通浩, 日本衛生学雑誌,   2019年02月, (一社)日本衛生学会
  • 学術研究からの少子化対策 日本衛生学会からの提言に向けて 日本衛生学会における少子化対策提言に向けて 日本衛生学会少子化対策ワーキンググループによるとりまとめ, 野村 恭子, 苅田 香苗, 荒木 敦子, 西岡 笑子, 武藤 剛, 岩井 美幸, 錦谷 まりこ, 井上 まり子, 鶴ヶ野 しのぶ, 北野 尚美, 辻 真弓, 飯島 佐知子, 上田 佳代, 上島 通浩, 山縣 然太郎, 坂田 清美, 伊木 雅之, 柳澤 裕之, 加藤 昌志, 横山 和仁, 小泉 昭夫, 大槻 剛巳, 日本衛生学雑誌,   2019年, (一社)日本衛生学会, 日本衛生学会では、少子化対策ワーキンググループを設置し、少子化対策シンポジウムを開催し、この問題について様々な角度から議論を重ねてきた。主にそのシンポジウムにおける学術的知見を次の様にまとめた。1)未婚化、晩婚化に対する社会環境整備、2)労働衛生領域における環境整備、3)職場の少子化対策、4)環境化学物質による性成熟、生殖能力への影響、5)社会環境および親のストレスと小児の健全な育ちに関する包括的な研究、として述べた。
  • 愛知県におけるエコチル調査参加児の母親の就労状況と質問票返送日数との関連について, 松木太郎, 松木太郎, 榎原毅, 榎原毅, 加藤沙耶香, 加藤沙耶香, 上島通浩, 上島通浩, 日本公衆衛生学会総会抄録集,   2018年10月09日
  • エコチル調査愛知ユニットセンターにおける参加児の質問票の回収状況と発達について, 加藤沙耶香, 加藤沙耶香, 榎原毅, 榎原毅, 松木太郎, 松木太郎, 伊藤由起, 伊藤由起, 杉浦真弓, 杉浦真弓, 齋藤伸治, 齋藤伸治, 上島通浩, 上島通浩, 東海公衆衛生雑誌,   2018年07月07日
  • DDVP投与Wistarラットにおけるコリンエステラーゼ活性と尿中代謝物の非線形モデル解析, 佐藤博貴, 伊藤由起, 花井ちなみ, 西村正也, 上山純, 上島通浩, 産業衛生学雑誌,   2018年05月16日
  • 2‐エチル‐1‐ヘキサノール慢性吸入曝露とうつ様行動との関係, 伊藤由起, 三宅美緒, 大矢奈穂子, 佐藤博貴, 若山貴成, 若山貴成, 上島通浩, 産業衛生学雑誌,   2018年05月16日
  • 2‐エチル‐1‐ヘキサノール慢性吸入曝露による嗅上皮の病理変化と嗅覚試験への影響, 三宅美緒, 伊藤由起, 大矢奈穂子, 佐藤博貴, 若山貴成, 上島通浩, 産業衛生学雑誌,   2018年05月16日
  • 2‐エチル‐1‐ヘキサノール吸入曝露後のマウス肝臓の脂質解析, 若山貴成, 若山貴成, 伊藤由起, 三宅美緒, 酒井潔, 大矢奈穂子, 佐藤博貴, 大野浩之, 上島通浩, 産業衛生学雑誌,   2018年05月16日
  • Wistarラットを用いたDDVP投与によるコリンエステラーゼ活性抑制と尿中代謝物量の関係の検討, 佐藤 博貴, 伊藤 由起, 花井 ちなみ, 西村 正也, 上山 純, 上島 通浩, 産業衛生学雑誌,   2018年03月, (公社)日本産業衛生学会
  • Wistarラットを用いたジメチル-2,2-ジクロロビニルホスフェイト(DDVP)の影響評価におけるベンチマークドーズ法の適用, 佐藤 博貴, 伊藤 由起, 花井 ちなみ, 上島 通浩, 産業衛生学雑誌,   2018年03月, (公社)日本産業衛生学会
  • フェニトロチオンによるラット精子毒性に精巣上体リン脂質症が関与している, 三宅 美緒, 伊藤 由起, 鈴木 日美子, 冨澤 元博, 佐藤 博貴, 劉 明, 岡村 愛, 那須 民江, 大谷 勝巳, 滝野 寿, 稲垣 宏, 上島 通浩, 産業衛生学雑誌,   2018年03月, (公社)日本産業衛生学会
  • 3歳児の尿中有機リン系殺虫剤代謝物濃度と採尿季節の関係, 伊藤 由起, 大矢 奈穂子, 榎原 毅, 佐藤 博貴, 加藤 沙耶香, 上山 純, 庄司 直人, 松木 太郎, 杉浦 真弓, 斎藤 伸治, 上島 通浩, 産業衛生学雑誌,   2018年03月, (公社)日本産業衛生学会
  • トリクロロエチレンによる過敏症症候群における曝露濃度と感受性因子の交互作用, 那須 民江, 王 海蘭, 伊藤 由起, 内藤 久雄, 柳場 由絵, 八谷 寛, 上島 通浩, 日本衛生学雑誌,   2018年03月, (一社)日本衛生学会
  • バイオモニタリング手法を用いた日本人小児ピレスロイド系殺虫剤曝露レベルの国際比較, 上山 純, 上田 裕子, 伊藤 由起, 榎原 毅, 大矢 奈穂子, 加藤 沙耶香, 小栗 朋子, 庄司 直人, 齋藤 伸治, 上島 通浩, 日本衛生学雑誌,   2018年03月, (一社)日本衛生学会
  • Pelvic Incidence(PI)間接計測のための体表面マーカー添付法の信頼性検討 PIに基づく新しいテーラーメードな腰痛対策の開発を目指して, 山田 翔太, 榎原 毅, 上島 通浩, 上原 徹, 木村 新吾, 庄司 直人, 稲田 充, 産業衛生学雑誌,   2018年03月, (公社)日本産業衛生学会
  • 小児におけるトリクロロエタノールの薬物動態・薬力学の発達・成長に伴う変化の解析, 井上美帆, 糸原光太郎, 佐藤博貴, 加藤祐子, 石井祥代, 伊藤由起, 那須民江, 上島通浩, 矢野育子, 矢野育子, 松原和夫, 佐和貞治, 橋本悟, 臨床薬理,   2017年11月15日, (一社)日本臨床薬理学会
  • 臍帯血ドコサヘキサエン酸と出生児の神経発達 エコチル調査の追加コホート調査より, 仲井 邦彦, 龍田 希, 西浜 柚季子, 津野 香奈美, 吉益 光一, 伊藤 由起, 上島 通浩, 日本公衆衛生学会総会抄録集,   2017年10月, 日本公衆衛生学会
  • 小児におけるトリクロホスの投与量の最適化, 井上美帆, 佐藤博貴, 糸原光太郎, 加藤祐子, 石井祥代, 伊藤由起, 中平有紀, 那須民江, 上島通浩, 矢野育子, 松原和夫, 佐和貞治, 橋本悟, 臨床薬理の進歩,   2017年06月, 招待あり
  • 使い捨てオムツを用いた尿中ネオニコチノイド系殺虫剤のバイオモニタリング手法の開発と小児への実践応用, 上山 純, 青井 亜里沙, 伊藤 由起, 榎原 毅, 大矢 奈穂子, 加藤 沙耶香, 小栗 朋子, 庄司 直人, 佐藤 博貴, 三宅 美緒, 上島 通浩, The Journal of Toxicological Sciences,   2017年06月, (一社)日本毒性学会
  • 妊娠の進行に伴う尿中殺虫剤曝露マーカー濃度の変動についての検討, 上島 通浩, 加藤 沙耶香, 小栗 朋子, 庄司 直人, 大矢 奈穂子, 齋藤 伸治, 杉浦 真弓, 榎原 毅, 伊藤 由起, 上山 純, 青井 亜里沙, 山田 泰行, 冨澤 元博, 若林 千鶴子, 宮田 麻衣子, 日本毒性学会学術年会,   2017年06月, 日本毒性学会, 妊娠中の低用量殺虫剤曝露による児への健康影響リスクを疫学研究で検討する際、一時点の尿中曝露マーカー濃度をもって胎児期の曝露量とみなせるかには議論がある。このため、妊娠中に二回採取(順にT1, T2)した尿中のマーカー濃度を測定した。出生コホート研究「子どもの健康と環境に関する全国調査(エコチル調査)」への愛知県の参加者で、妊娠20週までにT1採尿を行った者の中から66名(平均31.0±SD5.3歳)を抽出し対象者とした。有機リン(OP)代謝物(4種類のジアルキルリン酸(DAP))、ネオニコチノイド (NN)(アセタミプリド、イミダクロプリド、クロチアニジン、チアメトキサム(TM)、チアクロプリド、ジノテフラン(DN))は高速液体クロマトグラフタンデム質量分析計で、また、ピレスロイド(PY)代謝物(3-フェノキシ安息香酸(PBA)、トランス型クリサンテマムジカルボン酸、ジクロロビニルジメチルシクロプロパンカルボン酸(DCCA))はガスクロマトグラフ質量分析計により測定した。各物質の検出率(%)は、DAP 60-100、NN 1 -75、PY 37-100で、T1(平均14.2週)、T2(同25.2週)ともほぼ同じであった。検出率が6割以上だったDAP、TM、DN、PBA、DCCAについて、T1、T2の濃度を比較した結果、DAPとNNでは有意差がない一方、PY(PBAとDCCA)については有意にT2>T1であった(Wilcoxonの符号付順位検定)。また、三分位点濃度で3群に分けた場合の2回の測定のカッパ係数は、OP、NNでは0.40以下であったが、PYでは中等度の一致(PBA 0.50、DCCA 0.48)を示した。さらに、DAPは20パーセンタイル値、PBA、DCCA、NNについては30パーセンタイル値をカットオフ濃度として対象者を2群に分けた時のカッパ係数は、それぞれ0.49、0.59、0.64、0.45-0.71であった。すなわち、1回の採尿で曝露が相対的に少ない人を明らかにできること、PYのマーカーはOP、NNに比べ集団の曝露評価の変数として安定していることが示唆された。
  • 殺虫剤散布作業・関連業務従事者の薬剤使用品目および尿中代謝物量の変遷, 佐藤博貴, 上山純, 伊藤由起, 五藤雅博, 三宅美緒, 大矢奈穂子, 近藤高明, 齋藤勲, 柴田英治, 上島通浩, 日本産業衛生学会講演集(CD-ROM),   2017年05月
  • 2‐エチル‐1‐ヘキサノール吸入曝露中止後のマウス嗅上皮回復の病理学的解析, 三宅美緒, 伊藤由起, 大矢奈穂子, 佐藤博貴, 若山貴成, 上島通浩, 日本産業衛生学会講演集(CD-ROM),   2017年05月
  • 矢状面脊柱骨盤アライメントを外観上で把握する試み:全脊柱撮像から計測される各種パラメーターの信頼性の検討, 山田 翔太, 榎原 毅, 上原 徹, 木村 新吾, 庄司 直人, 稲田 充, 上島 通浩, 理学療法学Supplement,   2017年04月, 公益社団法人 日本理学療法士協会, <p>【はじめに,目的】</p><p></p><p>全脊柱撮像より計測される矢状面脊柱骨盤アライメント(SSPA)は,腰痛の素因と関係しているとの報告がある。X線の曝露がなく,簡便に人の外観上から得られる姿勢パラメーターでSSPAを推定する間接測定法が確立できれば,臨床応用のみならず,腰痛予防対策など公衆衛生上の意義も大きい。そこで,本研究では間接測定法確立の第一段階として,代表的な指標である胸椎後彎角(TKA),腰椎前彎角(LLA),仙骨傾斜角(SS),Sagittal Vertical Axis(SVA),Pelvic Incidence(PI)のX線画像の計測を行い,比較基準値となる計測の信頼性検討を行った。</p><p></p><p></p><p></p><p>【対象と方法】</p><p></p><p>名古屋市立西部医療センターにて頚椎症性脊髄症,腰部脊柱管狭窄症と診断され手術を施行した20名(男性11名,女性9名,平均年齢62.0±15.3歳)とした。診療目的で撮影された全脊柱撮像からSchwabらの計測に基づきTKA,LLA,SS,SVA,Legayeらの提唱したPIをacetabular domes methodを用い計測した。画像検査者は理学療法士の男性3名(平均年齢37.3±7.4歳)である。1回目の計測から24時間以上空けたのちに計測順を変更して再度計測した。統計解析はR2.8.1を用い,検査者内・検査者間信頼性を評価するために級内相関ICC<sub>1</sub>,ICC<sub>3</sub>を求めた。また各測定の系統誤差を評価するためにBland-Altman解析を行った。信頼性の評価はLandis(1977)の基準に従い,ICC>0.8をExcellentとした。</p><p></p><p></p><p></p><p>【結果】</p><p></p><p>各計測値の1回計測の検査者内信頼性ICC<sub>(1,1)</sub>は3名ともTKA,LLA,SS,SVAは全て0.8以上であった。PIのICC<sub>(1,1)</sub>は最大0.89(95%CI:0.74-0.95)から最小0.65(0.31-0.84)となり,検査者毎にばらつきを認めた。PIの2回計測の信頼性ICC<sub>(1,2)</sub>は0.94(0.85-0.98)から0.79(0.48-0.92)であり,PIの信頼性を担保するには2回以上の計測が必要と示唆された。3名の検査者が1回計測した時の検査者間信頼性ICC<sub>(3,1)</sub>は,全計測値とも0.87以上であった。Bland-Altman解析は,3名の検査者とも[1回目の測定-2回目の測定]の差(d)の平均に系統誤差は認められず,また,Bland-Altman Plotの偏回帰係数(β)においても比例誤差は認められなかった。</p><p></p><p></p><p></p><p>【結論】</p><p></p><p>TKA,LLA,SS,SVAは,任意1名の検査者が1回計測することで十分な検査者内・検査者間信頼性を担保している。一方,PIは検査者1名でよいが検査者内信頼性を高めるには複数回測定が必要である。また系統誤差や比例誤差も認めず,検査者の習熟に影響を受けないことが確認できた。</p>
  • 母体血および臍帯血赤血球中の多価不飽和脂肪酸レベルを決定する要因, 仲井 邦彦, 龍田 希, 川端 輝江, 津野 香奈美, 吉益 光一, 伊藤 由起, 上島 通浩, 有馬 隆博, 齋藤 彰治, 八重樫 伸生, 日本衛生学雑誌,   2017年03月, (一社)日本衛生学会
  • ガスクロマトグラフ質量分析計(GC-MS)と液体クロマトグラフタンデム型質量分析計(LC-MS/MS)を併用した血清中トリクロホスおよび代謝物の同時測定法の開発, 佐藤 博貴, 伊藤 由起, 井上 美帆, 中平 有紀, 橋本 悟, 上島 通浩, 産業衛生学雑誌,   2017年01月, (公社)日本産業衛生学会
  • トリクロロエチレンによるHypersensitivity 患者の曝露濃度から許容濃度再考の必要性を考察する, 那須 民江, 王 棟, 王 海蘭, 山ノ下 理, 伊藤 由起, 内藤 久雄, 上島 通浩, 産業衛生学雑誌,   2016年05月, (公社)日本産業衛生学会
  • 胸部X線写真に胸膜プラーク所見がない建設従事者の胸部CTにおける胸膜プラーク頻度, 久永 直見, 柴田 英治, 酒井 潔, 鈴木 隆佳, 内藤 久雄, 上島 通浩, 産業衛生学雑誌,   2016年05月, (公社)日本産業衛生学会
  • エコチル調査の追加調査を活用した出生コホート調査の実施 調査プロトコル, 仲井 邦彦, 龍田 希, 鈴木 朋恵, 津野 香奈美, 吉益 光一, 伊藤 由起, 上島 通浩, 川端 輝江, 木村 ふみ子, 柳沼 梢, 日本衛生学雑誌,   2016年05月, 日本衛生学会
  • 子どものADHD行動評価尺度「行動特徴のチェックリスト」の評価者間信頼性と妥当性, 津野 香奈美, 吉益 光一, 龍田 希, 伊藤 由起, 上島 通浩, 仲井 邦彦, 日本衛生学雑誌,   2016年05月, 日本衛生学会
  • 尿中有機リン系殺虫剤代謝物測定の個人間変動と施設間差についての検討, 伊藤由起, 上山純, 中山祥嗣, 磯部友彦, 佐藤博貴, 大矢奈穂子, 仲井邦彦, 上島通浩, 日本衛生学雑誌(Web),   2016年05月, 日本衛生学会
  • 多価不飽和脂肪酸と子どもの成長と発達に関する出生コホート調査プロトコル エコチル調査の追加調査として実施, 仲井 邦彦, 龍田 希, 鈴木 朋恵, 川端 輝江, 香川 靖雄, 木村 ふみ子, 宮澤 陽夫, 吉益 光一, 津野 香奈美, 伊藤 由起, 上島 通浩, 有馬 隆博, 八重樫 伸生, 日本栄養・食糧学会大会講演要旨集,   2016年04月, (公社)日本栄養・食糧学会
  • 有機リン系殺虫剤分解酵素活性と尿中代謝物の関連, 佐藤博貴, 伊藤由起, 上山純, 加納裕也, 荒川朋弥, 五藤雅博, 近藤高明, 杉浦友香, 斎藤勲, 柴田英治, 上島通浩, 産業衛生学雑誌,   2016年01月20日, (公社)日本産業衛生学会
  • 胸部X線写真に胸膜肥厚斑を認めない建築業従事者における胸部CT上の胸膜肥厚斑有所見率, 久永 直見, 柴田 英治, 酒井 潔, 鈴木 隆佳, 内藤 久雄, 上島 通浩, 産業衛生学雑誌,   2016年01月, (公社)日本産業衛生学会
  • トリクロロエチレンによるHypersensitivity 15年間の日中共同研究による患者の曝露濃度推移の考察, 那須 民江, 王 棟, 王 海蘭, 山ノ下 理, 伊藤 由起, 内藤 久雄, 上島 通浩, 産業衛生学雑誌,   2016年01月, (公社)日本産業衛生学会
  • トリクロロエチレン曝露量とHLA遺伝型に対する皮膚過敏症への影響, 山ノ下 理, 上島 通浩, 王 海蘭, 伊藤 由起, 内藤 久雄, 那須 民江, 産業衛生学雑誌,   2016年01月, (公社)日本産業衛生学会
  • 尿中有機リン系殺虫剤代謝物測定の施設間,個人間変動についての検討, 伊藤由起, 上山純, 中山祥嗣, 磯部友彦, 佐藤博貴, 仲井邦彦, 上島通浩, 産業衛生学雑誌,   2015年11月20日, (公社)日本産業衛生学会
  • 石綿肺がんとして労災認定された建築業従事者36名の職業歴, 久永直見, 柴田英治, 酒井潔, 鈴木隆佳, 内藤久雄, 上島通浩, 日本産業衛生学会講演集(CD-ROM),   2015年05月13日
  • 有機リン系殺虫剤散布作業者におけるパラオキソナーゼ1酵素活性と尿中代謝物濃度の関連, 佐藤博貴, 伊藤由起, 上山純, 五藤雅博, 近藤高明, 杉浦友香, 柴田英治, 上島通浩, 日本産業衛生学会講演集(CD-ROM),   2015年05月13日, (公社)日本産業衛生学会
  • 石綿肺がんとして労災認定された建築業従事者の職業歴, 久永直見, 柴田英治, 酒井潔, 鈴木隆佳, 内藤久雄, 上島通浩, 産業衛生学雑誌,   2015年03月20日
  • 有機リン系殺虫剤曝露者における尿中代謝物濃度および代謝酵素活性の関連について, 佐藤博貴, 伊藤由起, 上山純, 加納裕也, 荒川朋弥, 五藤雅博, 近藤高明, 杉浦友香, 斎藤勲, 柴田英治, 上島通浩, 産業衛生学雑誌,   2015年03月20日, (公社)日本産業衛生学会
  • 殺虫剤散布作業従事者におけるParaoxonase 1遺伝子多型と尿中代謝物の関係, 佐藤博貴, 伊藤由起, 上山純, 加納裕也, 荒川朋弥, 五藤雅博, 近藤高明, 杉浦友香, 斎藤勲, 柴田英治, 上島通浩, 産業衛生学雑誌,   2015年03月20日, (公社)日本産業衛生学会
  • フェニトロチオンとその主要代謝物投与による雄性ラット副生殖器への影響, 三宅美緒, 伊藤由起, 佐藤博貴, 大谷勝己, 榎原毅, 上島通浩, 日本衛生学雑誌,   2015年03月, 日本衛生学会
  • 冬季暖房方式の違いが乳幼児のアレルギー性鼻炎罹患に与える影響, 榎原 毅, 尹 奎英, 横山 清子, 河原 ゆう子, 佐宗 洋子, 成瀬 春美, 上島 通浩, 人間工学,   2014年06月
  • トリクロロエチレンによる重症皮膚肝障害の個体感受性マーカーの解析, 山ノ下理, 内藤久雄, 伊藤由起, 王海蘭, 黄漢林, 上島通浩, 那須民江, 日本産業衛生学会講演集(CD-ROM),   2014年05月01日
  • 害虫防除作業者における,殺虫剤解毒作用へのパラオキソナーゼ1遺伝子多型の影響, 佐藤博貴, 伊藤由起, 荒川朋弥, 加納裕也, 上山純, 五藤雅博, 柴田英治, 近藤高明, 斎藤勲, 上島通浩, 日本産業衛生学会講演集(CD-ROM),   2014年05月01日, (公社)日本産業衛生学会
  • 肺がん患者の肺内石綿濃度の経年推移, 酒井潔, 久永直見, 柴田英治, 上島通浩, 内藤久雄, 市原学, 名取雄司, 田村昭彦, 舟越光彦, 五島雅博, 那須民江, 加藤昌志, 産業衛生学雑誌,   2014年03月20日
  • トリクロロエタノールの代謝におけるCYP2E1の役割, 日比野優衣, 内藤久雄, 王棟, 伊藤由起, 上島通浩, 那須民江, 産業衛生学雑誌,   2013年03月20日
  • トリクロロエチレンとその代謝物のHypersensitivityに関する検討, 日比野優衣, 内藤久雄, 王棟, 趙娜, 宋向栄, 王海蘭, 伊藤由起, 上島通浩, 那須民江, 日本衛生学雑誌,   2013年03月
  • 建設業従事者における石綿曝露職歴,胸膜肥厚斑,肺内石綿・非石綿濃度の関係, 久永直見, 酒井潔, 柴田英治, 鈴木隆佳, 内藤久雄, 上島通浩, 市原学, 産業衛生学雑誌,   2013年01月20日
  • 中皮腫患者の肺内石綿・非石綿繊維量とその表面積, 酒井潔, 久永直見, 柴田英治, 上島通浩, 内藤久雄, 市原学, 那須民江, 産業衛生学雑誌,   2013年01月20日
  • 胎生期フタル酸ジ‐2‐エチルヘキシル曝露がレプチンに及ぼす影響, 林由美, 伊藤由起, 内藤久雄, 近藤高明, 上島通浩, 那須民江, 日本内分泌かく乱化学物質学会研究発表会要旨集,   2012年12月18日
  • トリクロロエチレン曝露による免疫性肝障害に関する研究, 日比野優衣, 内藤久雄, 斉藤優, 王棟, 趙娜, 宋向栄, 王海蘭, 上島通浩, 那須民江, 日本衛生学雑誌,   2012年02月17日
  • 胎生期DEHP曝露による低栄養と摂食行動, 林由美, 伊藤由起, 内藤久雄, 王棟, 賈小芳, 田川雅大, 上島通浩, 那須民江, 日本衛生学雑誌,   2012年02月17日
  • ヒトPPARαトランスジェニックマウスを用いたDEHPの肝発がん性評価, 伊藤由起, 柳場由絵, 林由美, 内藤久雄, 三宅美緒, 上島通浩, 那須民江, 日本産業衛生学会講演集(CD-ROM),   2012年
  • モルモットを用いたトリクロロエチレンによる皮膚・肝障害のメカニズム解析, 内藤久雄, 日比野優衣, 斉藤優, 王棟, 趙娜, 宋向栄, 王海蘭, 上島通浩, 那須民江, 日本産業衛生学会講演集(CD-ROM),   2012年
  • ヒトPPARαトランスジェニックマウスを用いたDEHPの発がん性評価, 伊藤由起, ドニヒクマット ラムダン, 柳場由絵, 林由美, 内藤久雄, 上島通浩, 那須民江, 日本衛生学雑誌,   2011年02月15日
  • 一般生活者集団における子どもとその親の尿中殺虫剤代謝物濃度の比較, 王棟, 上島通浩, 上山純, 内藤久雄, 伊藤由起, 那須民江, 日本産業衛生学会講演集(CD-ROM),   2011年
  • 可塑剤の毒性発現にはPPARαのみならずCARも関与しているかもしれない, 伊藤由起, 柳場由絵, RAMDHAN Doni Hikmat, 内藤久雄, 上島通浩, 那須民江, 日本衛生学雑誌,   2010年04月15日
  • DEHP曝露によるPPARαの活性化で妊娠マウスの血漿中必須脂肪酸濃度が低下する, 中島亮輔, 林由美, 玉棟, 伊藤由起, RAMDHAN Doni Hikat, 内藤久雄, 上島通浩, 那須民江, 日本衛生学雑誌,   2010年04月15日
  • 妊娠マウスのDEHP曝露はPPARαを介して母獣血漿中必須脂肪酸濃度を低下させる, 中島亮輔, 林由美, 王棟, 伊藤由起, HIKMAT Ramdhan Doni, 内藤久雄, 上島通浩, 那須民江, 産業衛生学雑誌,   2010年01月20日
  • 害虫防除作業者集団におけるフェニトロチオン散布とその尿中代謝物量との関連, 岡村愛, 上島通浩, 上山純, 高木健次, 柴田英治, 内藤久雄, 五藤雅博, 斉藤勲, 那須民江, 日本衛生学雑誌,   2009年03月15日
  • 日本人中高齢者における尿中ピレスロイド系殺虫剤代謝物および血中酸化ストレス指標との関連性, 上山 純, 木全 明子, 上島 通浩, 濱島 信之, 鈴木 康司, 伊藤 宜則, 高木 健次, 斎藤 勲, 長谷川 高明, 近藤 高明, 日本衛生学雑誌,   2009年03月, (一社)日本衛生学会
  • 高濃度PFOAはマウスのみならずヒトのPPARαを活性化する, 玉田 葉月, 中川 智彦, ラムダン・ドニヒクマット, 伊藤 由起, 柳場 由絵, 上島 通浩, 那須 民江, 日本衛生学雑誌,   2009年03月, (一社)日本衛生学会
  • 核内受容体PPARαによるフタル酸ジ2-エチルヘキシルの生殖・次世代影響の制御, 林 由美, 伊藤 由起, 玉田 葉月, 山岸 希, 柳場 由絵, 王 棟, 上島 通浩, 那須 民江, 日本衛生学雑誌,   2009年03月, (一社)日本衛生学会
  • ヒトPPARαを介したプラスチック可塑剤の脂質代謝への影響評価, 中村十識, 伊藤由起, 柳場由絵, 中川智彦, 森谷隆, 内藤久雄, 上島通浩, 那須民江, 日本衛生学雑誌,   2007年03月01日
  • 室内揮発性有機化合物濃度低減化のための床材張り替えとその効果に関する検討, 柴田 英治, 酒井 潔, 上島 通浩, 大野 浩之, 那須 民江, 横山 和仁, 小林 章雄, 日本衛生学雑誌,   2007年03月
  • 殺虫剤散布作業集団におけるフェニトロチオン尿中代謝物3‐methyl‐4‐nitrophenolとフェニトロチオン散布との関連, 岡村愛, 上島通浩, 李チュルホ, 内藤久雄, 上山純, 今井亮太, 王棟, 柴田英治, 五藤雅博, 高木健次, 近藤高明, 深谷幸生, 斉藤勲, 那須民江, 産業衛生学雑誌,   2007年01月20日
  • 胸膜肥厚所見を有する建設労働者の職業的石綿曝露歴, 長谷部哲也, 久永直見, 上島通浩, 柴田英治, 内藤久雄, 岡村愛, 酒井潔, 那須民江, 日本産業衛生学会講演集(CD-ROM),   2007年
  • 衛生害虫防除作業者のピレスロイド系薬剤使用と血中ペルメトリン及び尿中3‐フェノキシ安息香酸の定量, 柴田英治, 圓藤陽子, 上山純, 上島通浩, 岡村愛, 内藤久雄, 今井亮太, 王棟, 高木健次, 近藤高明, 五藤雅博, 深谷幸生, 斎藤勲, 日本産業衛生学会講演集(CD-ROM),   2007年
  • PPARA‐V227A遺伝子多型と年齢,運動,飲酒によるコレステロール値への影響について, 内藤久雄, 上島通浩, 山ノ下理, 中原愛, 加藤貴彦, 那須民江, 日本産業衛生学会講演集(CD-ROM),   2007年
  • ビル建築における床からの1-ブタノール放射, 上島 通浩, 酒井 潔, 横山 和仁, 石川 仁, 柴田 英治, 大野 浩之, 那須 民江, 日本衛生学雑誌,   2006年03月
  • 衛生害虫防除作業者のピレスロイド系殺虫剤尿中代謝産物による曝露評価, 今井亮太, 鈴木隆佳, 内藤久雄, 李チュルホ, 岡村愛, 上山純, 斎藤勲, 上島通浩, 五藤雅博, 柴田英治, 深谷幸生, 近藤高明, 高木健次, 産業衛生学雑誌,   2006年
  • 日本人男性におけるPPARα遺伝子多型と脂質代謝との関連, 内藤久雄, LEE C, 上島通浩, 加藤貴彦, 那須民江, 産業衛生学雑誌,   2005年03月20日
  • シックハウス症候群に伴う遺伝毒性影響の検討, 栗原 和生, 石川 仁, 上島 通浩, 酒井 潔, 宮津 優, 那須 民江, 横山 和仁, 産業衛生学雑誌,   2005年03月
  • 精巣腫よう患者の職業性曝露に関する調査検討, 内藤久雄, 上島通浩, 武林亨, 大前和幸, 那須民江, 産業衛生学雑誌,   2004年03月20日

受賞

  •   2015年, 日本学術振興会 科学研究費助成事業 平成27年度審査委員表彰
  •   2009年, 日本産業衛生学会奨励賞

競争的資金

  • 幼児期に摂取する肥満促進性環境化学物質のカクテル効果に関するコホート研究, 日本学術振興会, 科学研究費補助金 基盤研究(A),   2019年04月 - 2023年03月
  • 有機リン化合物曝露評価指標としての尿中ジアルキルリン酸の有効性の検証, 環境再生保全機構, 環境研究総合推進費,   2018年04月 - 2021年03月
  • トリクロロエチレン過敏症症候群(重症薬疹様皮膚肝障害)の発症前診断法開発の試み, 日本学術振興会, 科学研究費補助金 挑戦的研究(萌芽),   2018年04月 - 2020年03月
  • 低用量殺虫剤曝露の代謝物プロファイリング:エクスポソーム導入へのマイルストーン, 日本学術振興会, 科学研究費補助金 基盤研究(B),   2016年04月 - 2019年03月
  • 脳の発達臨界期にあたる幼児期の殺虫剤ばく露量モニタリング, 環境省・環境再生保全機構, 環境研究総合推進費,   2015年04月 - 2018年03月
  • 小児発達障害の環境因子の同定:有機リン殺虫剤の二次標的作用からのアプローチ, 日本学術振興会, 科学研究費補助金 挑戦的萌芽研究,   2013年04月 - 2016年03月
  • 胎児期の非蓄積性殺虫剤曝露の解明と出生児の成長・発達への影響に関するコホート研究, 日本学術振興会, 科学研究費補助金 基盤研究(B),   2013年04月 - 2016年03月
  • トリクロロエチレンによる重症薬疹様皮膚・肝障害の発症リスク評価バッテリーの開発, 日本学術振興会, 科学研究費補助金 基盤研究(B),   2012年04月 - 2016年03月
  • 殺虫剤の生体影響リスク評価へのメタボノミクスの導入, 日本学術振興会, 科学研究費補助金 基盤研究(B),   2008年04月 - 2011年03月
  • セメントによる加水分解反応由来の室内空気汚染物質-生体影響機序及び発生源の探索, 日本学術振興会, 科学研究費補助金 挑戦的萌芽研究,   2008年04月 - 2010年03月
  • 開発途上国における室内空気汚染と居住者の健康状態に関する調査研究, 日本学術振興会, 科学研究費補助金 基盤研究(B),   2007年04月 - 2010年03月

教育活動情報

担当経験のある科目

  • 中毒学, 高知大学
  • 衛生学, 順天堂大学
  • 予防医学(基礎・応用), 名古屋市立大学
  • 衛生学, 名古屋大学

社会貢献活動情報

社会貢献活動

  • 非常勤講師, 講師, 名古屋大学・高知大学・順天堂大学,  - 現在
  • 日本医師会認定産業医制度基礎研修会, 講師, 東北大学医師会,   2013年01月12日 - 2020年01月11日
  • 脳と環境物質の関連を知る, 講師, 名古屋市立大学,   2012年09月25日 - 2019年10月02日
  • からだに取り込まれた化学物質の量を知る―環境化学物質の健康リスクをどう考えるか, 講師, 名古屋市立大学,  - 2019年07月31日
  • 厚生労働大臣登録「建築物環境衛生管理技術者等講習会」教授, 講師, 公益財団法人 日本建築衛生管理教育センター,   2012年10月26日 - 2019年03月31日, 建築物衛生法に基づく建築物環境衛生管理技術者等の講習会講師を務める
  • 気候変動と健康リスク, 講師, 環境省中部地方環境事務所,   2017年06月06日 - 2017年06月06日
  • 農薬, 情報提供, 日本学術会議科学者委員会・科学と社会委員会合同広報・科学力増進分科会,   2015年11月15日 - 2015年11月15日
  • 公述(公益側代表), その他, 厚生労働省,   2012年09月05日 - 2014年07月18日
  • 東海テレビ 放送, 民間企業,   2013年03月27日 - 2013年03月27日, 微小粒子状物質「PM2.5」の健康影響について取材を受け、その内容が放映された。
  • 中日新聞 掲載, 民間企業,   2013年02月28日 - 2013年02月28日, 微小粒子状物質「PM2.5」の健康影響についてコメントを述べ、紙面に掲載された。
  • 名古屋テレビ 放送, 民間企業,   2013年02月18日 - 2013年02月18日, PM2.5が人体にどのような影響を与える可能性があるのかについて取材を受け、放映された。
  • 環境化学物質と健康, 講師, 愛知県・名古屋市,   2012年11月08日 - 2012年11月08日, 環境化学物質と健康について講演
  • 毒を規制する―化学物質の影響を食い止める―, 講師, 名古屋市立大学,   2012年06月08日 - 2012年06月08日
  • 労働者健康福祉機構愛知産業保健推進センター産業保健相談員, 情報提供,   2008年04月01日 - 2012年03月31日


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