ヒトにおける1-ブロモプロパン中枢神経毒性と量-反応関係に関する疫学的研究

2008 年度 研究成果報告書

• 研究課題/領域番号: 17406017
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 海外学術
• 研究分野: 衛生学
• 研究機関: 名古屋大学
• 研究代表者: 市原 学 名古屋大学, 大学院・医学系研究科, 准教授 (90252238)
• 研究分担者: 市原 佐保子 三重大学, 生命科学研究支援センター, 助教 (20378326)
• 連携研究者: 玉腰 暁子 愛知医科大学, 大学院・医学系研究科, 准教授 (90236737) ; 八谷 寛 名古屋大学, 大学院・医学系研究科, 准教授 (30324437) ; 山本 直彦 名古屋大学, 大学院・医学系研究科, 准教授 (40220488) ; 山本 敏充 名古屋大学, 大学院・医学系研究科, 准教授 (50260592)
• 研究期間 (年度): 2005 – 2008
• キーワード: オゾン層 / 代替物質 / ブロモプロパン / 神経毒性 / 疫学 / 健康影響 / 量反応性

研究概要

1-ブロモプロパンに曝露された中国労働者の個人曝露量、曝露期間を調べるとともに、健康調査を行った。健康調査は、下肢の運動神経伝導速度、感覚神経伝導速度、遠位潜時、F波伝導速度、WHO神経行動学的検査、血球検査、生化学検査、振動覚検査であった。その結果、1-ブロモプロパン曝露が遠位潜時を延長することがわかった。一方、同時に調査した米国の重症1-ブロモプロパン症例は中枢神経系障害を示した。

研究成果

• [雑誌論文] In vitro cytotoxicity and oxidative damage effects of multi-wall carbon nanotube on RAW246.7 macrophages (2008)
  • 著者名/発表者名: Liu Y, Song W, Li W, Ichihara G
  • 雑誌名: Wei Sheng Yan Jiu 37 ページ: 281-4
  • 査読あり
• [雑誌論文] Chemopreventive Effect of Selenium-Enriched Japanese Radish Sprout against Breast Cancer Induced by 12 Dimethylbenz[a]anthracene in Rats (2007)
  • 著者名/発表者名: Yamanoshita O, Ichihara S, Hama H, Ichihara G, Chiba M, Kamijima M, Takeda I, Nakajima T
  • 雑誌名: Tohoku J Exp Med 212 ページ: 191-8
  • 査読あり
• [雑誌論文] Di(2-ethylhexyl)phthalate induces hepatic tumorigenesis through a peroxisome proliferator-activated receptor alpha-independent pathway (2007)
  • 著者名/発表者名: 6. Ito Y, Yamanoshita O, Asaeda N, Tagawa Y, Lee C, Aoyama T, Ichihara G, Furuhashi K, Kamijima M, Gonzalez FJ, Nakajima T
  • 雑誌名: J Occup Health 49 ページ: 172-82
  • 査読あり
• [雑誌論文] A role for the aryl hydrocarbon receptor in regulation of ischemia induced angiogenesis (2007)
  • 著者名/発表者名: Ichihara S, Yamada Y, Ichihara G, Nakajima T, Kondo T, Gonzalez FJ, Murohara T
  • 雑誌名: Arterioscler Thromb Vasc Biol 27 ページ: 1297-1304
  • 査読あり
• [雑誌論文] Roles of oxidative stress and Akt signaling in doxorubicin cardiotoxicity (2007)
  • 著者名/発表者名: Ichihara S, Yamada Y, Kawai Y, Osawa T, Furuhashi K, Duan Z, Ichihara G
  • 雑誌名: Biochem Biophys Res Commun 359 ページ: 27-33
  • 査読あり
• [雑誌論文] Differential cardiovascular effects of endotoxin derived from Escherichia coli or Pseudomonas aeruginosa (2007)
  • 著者名/発表者名: Matsushita A, Iwase M, Kato Y, Ichihara S, Ichihara G, Kimata H, Hayashi K, Hashimoto K, Yokoi T, Noda A, Koike Y, Yokota M, Nagata K
  • 雑誌名: Exp Anim 56 ページ: 339-48
  • 査読あり
• [雑誌論文] Globin S-propyl cysteine and urinary N-acetyl-S-propylcysteine as internal biomarkers of 1-bromopropane exposure (2007)
  • 著者名/発表者名: Valentine H, Amarnath K, Amarnath V, Li W, Ding X, Valentine WM, Ichihara G
  • 雑誌名: Toxicological Sciences 98 ページ: 427-35
  • 査読あり
• [雑誌論文] Reversibility of the adverse effects of 1-bromopropane exposure in rats (2007)
  • 著者名/発表者名: Banu S, Ichihara S, Huang F, Ito H, Inaguma Y, Furuhashi K, Fukunaga Y, Wang Q, Kitoh J, Ando H, Kikkawa F, Ichihara G
  • 雑誌名: Toxicol Sci 100 ページ: 504-12
  • 査読あり
• [雑誌論文] Effects of exposure of rat dams to 1-bromopropane during pregnancy and lactation on growth and sexual maturation of their offspring (2006)
  • 著者名/発表者名: Furuhashi K, Kitoh J, Tsukamura H, Maeda K, Wang H, Li W, Ichihara S, Nakajima T, Ichihara G
  • 雑誌名: Toxicology 224 ページ: 219-228
  • 査読あり
• [雑誌論文] A comprehensive evaluation of the testicular toxicity of dichlorvos in Wistar rats (2005)
  • 著者名/発表者名: Okamura A, Kamijima M, Shibata E, Ohtani K, Takagi K, Ueyama J, Watanabe Y, Omura M, Wang H, Ichihara G, Kondo T, Nakajima T
  • 雑誌名: Toxicology 213(1-2) ページ: 129-37
  • 査読あり
• [雑誌論文] Inhibition of ischemia-induced angiogenesis by benzo[a]pyrene in a manner dependent on the aryl hydrocarbon receptor
  • 著者名/発表者名: Ichihara S, Yamada Y, Gonzalez FJ, Nakajima T,Murohara T, Ichihara G
  • 雑誌名: Biochem Biophys Res Commun 2009 (in press)
  • 査読あり
• [雑誌論文] Melatonin pretreatment attenuates 2-bromopropane-induced testicular toxicity in rats
  • 著者名/発表者名: Huang F, Ning H, Xin QQ, Huang Y, Wang H, Zhang ZH, Xu DX, Ichihara G, Ye DQ.
  • 雑誌名: Toxicology 2009 256 ページ: 75-82
  • 査読あり
• [雑誌論文] Carbon Nanotubes in historical and future perspective: summary of an extended session at Carbon 2008 in Nagano (JP)
  • 著者名/発表者名: Endo M, Tsuruoka S, Ichihara G
  • 雑誌名: Part Fibre Toxicol 2008 5 ページ: 21
  • 査読あり
• [雑誌論文] Re : Induction of mesothelioma in p53+/-mouse by intraperitoneal application of multi-wall carbon nanotube
  • 著者名/発表者名: Ichihara G, Castranova V, Tanioka A, Miyazawa K
  • 雑誌名: J Toxicol Sci 2008 33 ページ: 381-2
  • 査読あり
• [雑誌論文] Methylation of dimethyltin in mice and rats
  • 著者名/発表者名: Furuhashi K, Ogawa M, Suzuki Y, Endo Y, Kim Y, Ichihara G
  • 雑誌名: Chemical Research in Toxicology 2008 21 ページ: 467-71
  • 査読あり
• [雑誌論文] Molecular mechanism of trichloroethylene-induced hepatoxicity mediated by CYP2E1
  • 著者名/発表者名: Ramdhan DH, Kamijima M, Yamda N, Ito Y, Yanagiba Y, Nakamura D, Okamura A, Ichihara G, Aoyama T, Gonzalez FJ, Nakajima T
  • 雑誌名: Toxicol Appli Pharmacol 2008 231 ページ: 300-7
  • 査読あり
• [雑誌論文] Attenuation of oxidative stress and cardiac dysfunction by bisoprolol in an animal model of dilated cardiomyopathy
  • 著者名/発表者名: Ichihara S, Yamada Y, Ichihara G, Kanazawa H, Hashimoto K, Kato Y, Matsushita A, Oikawa S, Yokota M, Iwase M
  • 雑誌名: Biochem Biophys Res Commun 2006 ページ: 350105-13
  • 査読あり
• [雑誌論文] PPAR-alpha attenuates left ventricular remodeling and dysfunction by the suppression of the redox-regulated transcription factors activity
  • 著者名/発表者名: Ichihara S, Obata K, Yamada Y, Nagata K, Noda A, Ichihara G, Yomada A, Kato T, Murohara T, Yokota M
  • 雑誌名: Journal of Molecular Cellular Cardiology 2006 41 ページ: 318-329
  • 査読あり
• [雑誌論文] Pravastatin increases survival and suppresses an increase in myocardial MMP activity in a rat model of heart failure
  • 著者名/発表者名: Ichihara S, Noda A, Nagata K, Obata K, Xu J, Ichihara G, Oikawa S, Kawanishi S, Yamada Y, Yokota M
  • 雑誌名: Cardiovascular Research 2006 69 ページ: 726-735
  • 査読あり
• [雑誌論文] Species difference in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets
  • 著者名/発表者名: Ito Y, Yokota H, Wang R, Yamanoshita O, Ichihara G, Wang H, Kurata Y, Takagi K, Nakajima T.
  • 雑誌名: Archives of Toxicology 2005 79 ページ: 147-54
  • 査読あり
• [学会発表] Dose-dependent neurological and hematological effects of 1-bromopropane exposure on workers (2009)
  • 著者名/発表者名: Ichihara G, Li W, Shibata E, Zhou Z, Ichihara S, Wang Q, Li J, Ding X, Takeuchi Y
  • 学会等名: The 29^<th> International Congress on Occupational Health
  • 発表場所: Cape Town, South Africa
  • 年月日: 20090322-27
• [学会発表] Occupational Health Survey on workers handling titanium dioxide (2009)
  • 著者名/発表者名: Ichihara S, Li W, Kobayashi T, Ding X, Fujitani Y, Liu Y, Wang Q, Cui U, Hata N, Ichihara G
  • 学会等名: The 29^<th> International Congress on Occupational Health
  • 発表場所: Cape Town, South Africa
  • 年月日: 20090322-27
• [学会発表] Exposure assessment and health examination of workers handling titanium dioxide (2009)
  • 著者名/発表者名: Ichihara G, Li W, Kobayashi T, Ding X, Fujitani Y, Liu Y, Sai U, Hata N, Wang Q, Ichihara S
  • 学会等名: The 48th Annual Meeting of the Society of Toxicology
  • 発表場所: Baltimore, USA
  • 年月日: 20090315-19
• [学会発表] Inhibition of ischemia-induced angiogenesis by benzo[a]pyrene in a manner dependent on aryl hydrocarbon receptor (2009)
  • 著者名/発表者名: Ichihara S, Yamada Y, Ichihara G, Nakajima T, Gonzalez E.J, Murohara T
  • 学会等名: The 48^<th> Annual Meeting of the Society of Toxicology
  • 発表場所: Baltimore, USA
  • 年月日: 20090315-19
• [学会発表] Assessment of exposure and health status in workers handling titanium dioxide (2008)
  • 著者名/発表者名: Ichihara G, Li W, Kobayashi T, Ding X, Fujitani Y, Liu Y, Wang Q, Cui U, Hata N, Ichihara S.
  • 学会等名: Internatoinal Conference on safe production and use of nanomaterials, NANOSAFE 2008
  • 発表場所: Minatec, Grenoble, France
  • 年月日: 20081103-07
• [学会発表] Occupational Health Survey on workers handling titanium dioxide (2008)
  • 著者名/発表者名: Ichihara G, Li W, Kobayashi T, Ding X, Fujitani Y, Liu Y, Wang Q, Cui U, Hata N, Ichihara S
  • 学会等名: The 45th Congress of the European Societies of Toxicology
  • 発表場所: Rhodes, Greece
  • 年月日: 20081005-08
• [学会発表] Recent studies of bromopropane toxicity-animal studies and newly found human cases in United States (2008)
  • 著者名/発表者名: Ichihara G
  • 学会等名: China-Japan Collaboration Workshop "Environmental Health and Safety Research on new manufactured materials"
  • 発表場所: Shanghai, China
  • 年月日: 20080730-313
• [学会発表] Microarray study on bromopropane toxicity (2008)
  • 著者名/発表者名: Ichihara G
  • 学会等名: China-Japan Collaboration Workshop "Environmental Health and Safety Research on new manufactured materials"
  • 発表場所: Shanghai, China
  • 年月日: 20080730-31
• [学会発表] International collaboration and coordination of nanotoxicology research (2008)
  • 著者名/発表者名: Ichihara G
  • 学会等名: China-Japan Collaboration Workshop "Environmental Health and Safety Research on new manufactured materials"
  • 発表場所: Shanghai, China
  • 年月日: 20080730-31
• [学会発表] Methylation of dimethyltin in mice and rats (2008)
  • 著者名/発表者名: Furuhashi K, Ogawa M, Suzuki Y, Endo Y, Ichihara G
  • 学会等名: The 47^<th> Annual Meeting of Society of Toxicology
  • 発表場所: Seattle, Washington, USA
  • 年月日: 20080316-20
• [学会発表] Effect of 1-bromopropane exposure on gene expression of neurotransmitter receptors in rat (2008)
  • 著者名/発表者名: Sheik Mohideen S, Ichihara S, Liu F, Furuhashi K, Li W, Ichihara G
  • 学会等名: The 47^<th> Annual Meeting of Society of Toxicology
  • 発表場所: Seattle, Washington, USA
  • 年月日: 20080316-20
• [学会発表] Neurotoxicity and reproductive toxicity of 1-bromopropapane, an alternative to ozone-depleting solvents. International Conference on "Toxic Exposure Related Biomarker : Genomes and Health Effects" (2008)
  • 著者名/発表者名: Ichihara G
  • 学会等名: National Environmental Engineering Research Institute
  • 発表場所: Nagpur, India
  • 年月日: 20080110-11
• [学会発表] Animal experiments and human studies in risk assessment of manufactured nanomaterials (2008)
  • 著者名/発表者名: Ichihara G
  • 学会等名: Animal experiments and human studies in risk assessment of manufactured nanomaterials. International Workshop at Nagoya University "Recent Progress in EHS Research on Manufactured Nanomaterials."
  • 発表場所: Nagoya, Japan
  • 年月日: 2008-12-12
• [学会発表] Environment, Health and Safety Research on Manufactured Nanomaterials (2007)
  • 著者名/発表者名: Ichihara G.
  • 学会等名: The 13^<th> International Symposium on Toxicity Assessment
  • 発表場所: Toyama, Japan
  • 年月日: 20070819-243
• [学会発表] DNA microarray study with two dimensional analysis on susceptibility to 1-bromopropane exposure (2007)
  • 著者名/発表者名: Huang F, Ichihara S, Kitagawa E, Mizugami S, Iwahashi H, Kito J, Furuhashi K, Banu S, Iida M, Ichihara G.
  • 学会等名: The 11^<th> International Congress of Toxicology
  • 発表場所: Montreal, Canada
  • 年月日: 20070715-19
• [学会発表] Dose-dependent effects of 1-bromopropane exposure on workers (2007)
  • 著者名/発表者名: Li W, Wang Q, Ding X, Shibata E, Takeuchi Y, Valentine W, Ichihara G
  • 学会等名: The 18th Korea Japan China Joint Conference on Occupational Health
  • 発表場所: Nagoya, Japan
  • 年月日: 20070520-22
• [学会発表] Globin S-propylcysteine and urinary N-acetyl-S-propylcysteine as biomarkers of 1-bromopropane exposure (2007)
  • 著者名/発表者名: Valentine W, Valentine H, Amarnath K, Ding X, Ichihara G
  • 学会等名: The 46^<th> Annual Meeting of Society of Toxicology
  • 発表場所: Charlotte, North Carolina, USA
  • 年月日: 20070325-29
• [学会発表] Susceptibility to 1-bromopropane exposure and alteration of mRNA expression in rats (2007)
  • 著者名/発表者名: Huang F, Ichihara S, Kitagawa E, Mizugami S, Iwahashi H, Fukunaga S, Furuhashi K, Banu S, Iida M, Kitoh J, Ichihara G
  • 学会等名: The 46^<th> Annual Meeting of Society of Toxicology
  • 発表場所: Charlotte, North Carolina, USA
  • 年月日: 20070325-29
• [学会発表] Reversibility of the adverse effects of 1-bromopropane exposure in rats (2007)
  • 著者名/発表者名: Banu S, Ichihara S, Huang F, Ito H, Inaguma Y, Furuhashi K, Fukunaga S, Wang Q, Ichihara G
  • 学会等名: The 46^<th> Annual Meeting of Society of Toxicology
  • 発表場所: Charlotte, North Carolina, USA
  • 年月日: 20070325-29
• [学会発表] Effect of 1-bromopropane exposure on gene expression of neurotransmitter receptors and exploration of biomarkers for the central nervous system toxicity (2007)
  • 著者名/発表者名: Sahabudeen S, Ichihara G
  • 学会等名: The 24th International Neurotoxicology Conference
  • 発表場所: San Antonio, TX, US
  • 年月日: 2007-11-14
• [学会発表] Study on 1-bromopropane neurotoxicity through animal experiments and human studies (2007)
  • 著者名/発表者名: Ichihara G, Li W, Ding X, Valentine W, Kitoh J, Takeuchi Y
  • 学会等名: International Symposium on 1-Bromopropane Toxicity in the 77th annual meeting of the Japanese Society for Hygiene
  • 発表場所: Osaka, Japan
  • 年月日: 2007-03-26
• [学会発表] Exposure to 1-bromopropane causes neurologic deficits in humans (2007)
  • 著者名/発表者名: Li W, Ding X, Valentine W, Shibata E, Takeuchi Y, Ichihara G
  • 学会等名: International Symposium on 1-Bromopropane Toxicity in the 77^<th> annual meeting of the Japanese Society for Hygiene
  • 発表場所: Osaka, Japan
  • 年月日: 2007-03-26
• [学会発表] Study on 1-bromopropane neurotoxicity through animal experiments and human studies (2007)
  • 著者名/発表者名: Ichihara G, Li W, Ding X, Valentine W, Kitoh J, Takeuchi Y
  • 学会等名: International Symposium on 1-Bromopropane Toxicity in the 77^<th> annual meeting of the Japanese Society for Hygiene
  • 発表場所: Osaka, Japan
  • 年月日: 2007-03-26
• [学会発表] EHS research strategies on manufactured nanomaterials in Japan (2007)
  • 著者名/発表者名: Ichihara G
  • 学会等名: The Dialogue between Academia and the Participants of OECD's Working Party on Manufactured Nanomaterials
  • 発表場所: Dortmund, Germany
  • 年月日: 2007-03-21
• [学会発表] Occupational Health Survey on workers handling nano-titanium dioxide (2007)
  • 著者名/発表者名: Ichihara G
  • 学会等名: Roundtable on Nanotechnology and engineered nanoparticles: Research perspectives in Occupational Health and Safety
  • 発表場所: Canadian Embassy, Tokyo, Japan
  • 年月日: 2007-02-12
• [学会発表] Exposure to 1-bromopropane adversely affects vibration sense and nerve conduction velocity of lower limbs and central nervous system in workers (2006)
  • 著者名/発表者名: Ichihara G, Li W, Shibata E, Ding X, Li J, Wang H, Huang F, Peng S, Gu B, Ichihara S, Miyata M, Takeuchi Y.
  • 学会等名: North American Congress of Clinical Toxicology
  • 発表場所: San Francisco, USA
  • 年月日: 20061004-09
• [学会発表] Microarray studies on neuro-reproductive toxicities of bromopropanes, alternatives to ozone-depleting solvents (2006)
  • 著者名/発表者名: Ichihara G.
  • 学会等名: The 3^<rd> International Workshop on Biochips and Environmental Monitoring
  • 発表場所: Ikeda, Osaka, Japan
  • 年月日: 20060817-18
• [学会発表] Adverse effects of exposure to 1-bromopropane on central nervous system and peripheral nerve in human (2006)
  • 著者名/発表者名: Ichihara G, Li W, Shibata E, Ding X, Li J, Wang H, Huang F, Peng S, Gu B, Ichihara S, Tang Y, Shao B, Sun Y, Miyata M, Takeuchi Y
  • 学会等名: 28^<th> International Congress on Occupational Health
  • 発表場所: Milan, Italy
  • 年月日: 20060611-16
• [学会発表] Exposure to 1-bromopropane reduces nerve conduction velocity in human (2006)
  • 著者名/発表者名: Ichihara G. Li W, Shibata E, Ding X, Li J, Peng S, Ichihara S, Wang H, Huang F, Gu B, Tang Y, Shao B, Sun Y, Miyata M, Takeuchi Y
  • 学会等名: The 45^<th> Annual Meeting of Society of Toxicology
  • 発表場所: San Diego, California, USA
  • 年月日: 20060305-09
• [学会発表] Round table discussion in the 2^<nd> Joint Science Council of Japan-Royal Society workshop on the potential health (2006)
  • 著者名/発表者名: Ichihara G
  • 学会等名: environmental and societal impacts of nanotechnologies
  • 発表場所: Tokyo
  • 年月日: 2006-02-23
• [学会発表] Exposure to 1-bromopropane reduces nerve conduction velocity in lower limb of human (2005)
  • 著者名/発表者名: Ichihara G. Li W, Shibata E, Ding X, Wang H, Li Jiefei, Huang F, Peng S, Gu B, Ichihara S, Shao B, Tang Y, Sun Y, Miyata M, Takeuchi Y
  • 学会等名: 9^<th> International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health
  • 発表場所: Gyongiu Neurobehavior meeting in Gyeongju, Korea
  • 年月日: 20050926-29
• [学会発表] Occupational Health in a National University Corporation in Japan (2005)
  • 著者名/発表者名: Ichihara G
  • 学会等名: 16^<th> Japan-China-Korea Joint Conference on Occupational Health
  • 発表場所: Dalian, China
  • 年月日: 20050602-04
• [学会発表] Exposure to 1-bromopropane reduces nerve conduction velocity in lower limb of human (2005)
  • 著者名/発表者名: Li W, Shibata E, Ding X, Li Jiefei, Wang H, Huang F, Peng S, Gu B, Ichihara S, Tang Y, Shao B, Sun Y, Miyata M, Takeuchi Y, Ichihara G
  • 学会等名: 16^<th> Japan-China-Korea Joint Conference on Occupational Health
  • 発表場所: Dalian, China
  • 年月日: 20050602-04
• [学会発表] Neurotoxicity of 1-bromopropane in human.-investigation through human cases/data and animal data (2005)
  • 著者名/発表者名: Ichihara G
  • 学会等名: Symposium in the meeting for young epidemiologists in China
  • 発表場所: Hefei, Anhui, China
  • 年月日: 2005-10-13
• [図書] 有機溶剤IV.中毒各論2.有毒ガス中毒症のすべて-いざという時に役立つ、的確な治療のために-(編集黒川顕) (2006)
  • 著者名/発表者名: 市原学
  • 総ページ数: 177-184
  • 出版者: 永井書店