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INVESTIGATION ON TOXICITIES OF ALTERNATIVES FOR CHLOROFLUOROCARBONS AND ITS RISK ASSESSMENT USING MOLECULAR AND BIOLOGICAL MARKERS.

Research Project

Project/Area Number 13470088
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Public health/Health science
Research InstitutionNagoya University

Principal Investigator

ICHIHARA Gaku  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90252238)

Co-Investigator(Kenkyū-buntansha) MAEDA Kei-ichiro  Nagoya University, Graduate School of Agricultural Sciences, Professor, 大学院・農学研究科, 教授 (30181580)
SHIBATA Eiji  Aichi Medical University, School of Medicine, Assistant Professor, 医学部, 助教授 (90206128)
KAMIJIMA Michihiro  Nagoya University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (80281070)
TSUKAMURA Hiroko  Nagoya University, Graduate School of Agricultural Sciences, Associate Professor, 大学院・農学研究科, 助教授 (00212051)
山田 哲也  名古屋大学, 大学院・医学研究科, 助手 (90303635)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥10,800,000 (Direct Cost: ¥10,800,000)
Keywords1-bromopropane / alternatives for chlorofluorocarbons / neurotoxicity / reproductive toxicity / biomarker / protein adduct / neuro-specific protein / Mercapturate / バイオマーカー / エノラーゼ / 質量分析 / 連続切片 / 卵巣 / メルカプツレート / N-Acetyl-S-propylcysteine / クレアチンキナーゼ / SH基 / アポトーシス / 神経特異蛋白
Research Abstract

Urine was collected from the rats exposed to 1-bromopropane. One hundred μL of urine was added 400μL of saturated sodium chloride solution, and then extracted with 500μL of ethyl acetate for three times. The collected ethyl acetate layer was dehydrated with dried sodium sulfoxide, and dried with centrifuging evaporator. The dried sample was resolved with 40μL of ethylacetate and derivatized with TBDMS. The result showed the metabolite N-acetyl-S-propylcysteine was dose-dependent and available as an internal exposure marker.
Blood was collected from the rats exposed to 1-bromopropane. Globin was extracted from blood samples using acetone-oxalic acid mixture. Globin was hydrolyzed with acid under nitrogen, and S-propylcysteine was identified using LC-MS/MS.
The cerebrum, cerebellum, brainstem and spinal cord were taken from the rats exposed to 1-bromopropane under deep anesthesia. The tissue was homogenized and the soluble fraction was obtained. Neuro-specific protein γ-enolase and glia-specific protein β-S100 was quantified with a sandwich type enzyme immunoassay. Glutatione (GSH and GSSG) was also measured by enzymatic cycling method. The result showed that gamma-enolase was decreased specifically in the cerebrum and 1-bromopropane has a great adverse effect on the central nervous system.
The testes were taken from the rats exposed to 1-bromopropane under deep anesthesia. Immunostaining with α-enolase showed clearly specific localization of α-enoalse to Sertoli cells in the testis. The quantification with enzyme immunoassay showed dose-dependent increase in alpha-enolase in the testis, suggesting the effects of 1-bromopropane on Sertoli cells.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Ichihara G. et al.: "A survey on exposure level, health status and biomarkers in workers exposed to 1-bromopropane."American Journal of Industrial Medicine. 45. 63-75 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada T.et al.: "Exposure to 1-bromopropane caused ovarian dysfunction in rats."Toxicological Sciences. 71. 96-103 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang H.et al.: "Dose-dependent biochemical changes in rat central nervous system after 12-week exposure to 1-bromopropane."Neurotoxicology. 24. 199-206 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajima T.et al.: "Generalized skin reactions in relation to trichloroethylene exposure : a review from the viewpoint of drug-metabolizing enzymes."Journal of Occupational Health. 45. 8-14 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamijima M.et al.: "A survey of semen indices in insecticide sprayers."Journal of Occupational Health. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajiina T.et al.: "Functional activation of peroxisome proliferators-activated receptor alpha by environmental chemicals in relation to their toxicities."Nagoya Journal of Medical Sciences. 65. 85-94 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 久永 直見 ほか: "トリクロロエチレンおよびテトラクロロエチレンに曝露された労働者に発生する急性肝炎を伴うスチーブンス・ジョンソン症候群"産業衛生学雑誌. 44. 33-49 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takagi A.et al.: "Involvement of caspase 3 mediated apoptosis in hematopoietic cytotoxicity of metabolites of ethylene glycol monomethyl ether."Industrial Health. 40. 371-374 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yu X.et al.: "Neurotoxicity of 2-bromopropaneor and 1-bromopropane, alternative solvents for chlorofluorocarbons."Environmental Research (Section A). 174. 48-52 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yu X.et al.: "Involvement of Bc1-2 family genes and Fas signaling system in primary and secondary male germ cell apoptosis induced by 2-bromopropane in rat."Toxicology and Applied Pharmacology. 43. 35-48 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kanemoto I.et al.: "The effects of ether anesthesia for surface-induced hypothermia on car diopulmonary function in the dog."Jpn.J.Vet.Anesth.Surg.. 34. 43-54 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichihara G.et al.: "Neurological disorders in three workers exposed to 1-bromopropane."Journal of Occupational Health. 44. 1-7 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang H.et al.: "Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for 7 days."Toxicological Sciences. 67. 114-120 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 市原 学 ほか: "有機溶剤中毒"総合臨床. 51. 768-773 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 市原 学 ほか: "毒性学入門"産業衛生学雑誌. 44. 70-71 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gotoh M.et al.: "The changes of cholinesterase activity, nerve conduction velocity, and clinical signs and symptoms in termite control operators exposed to chlorpyrifos."Journal of Occupational Health. 43. 157-164 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 市原 学 ほか: "ブロモプロパンによる神経障害の症例とその機序について"末梢神経. 12. 13-19 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 竹内 康浩 ほか: "荒記俊一編 中毒学-基礎・臨床・社会医学"朝倉書店. 399 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichihara G.et al.: "A survey on exposure level, health status and biomarkers in workers exposed to 1-bromopropane."American Journal of Industrial Medicine. 45. 63-75 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada T.et al.: "Exposure to 1-bromopropane caused ovarian dysfunction in rats."Toxicological Sciences. 71. 96-103 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang H.et al.: "Dose-dependent biochemical changes in rat central nervous system after 12-week exposure to 1-bromopropane."Neurotoxicology. 24. 199-206 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajima T.et al.: "Generalized skin reactions in relation to trichioroethylene exposure : a review from the viewpoint of drug-metabolizing enzymes."Journal of Occupational Health. 45. 8-14 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamijima M.et al.: "A survey of semen indices in insecticide sprayers."Journal of Occupational Health(. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kanemoto I.et al.: "The effects of ether anesthesia for surface-induced hypothermia on cardiopulmonary function in the dog."Jpn.J.Vet.Anesth.Surg. 34. 43-54 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichihara G.et al.: "Neurological disorders in three workers exposed to 1-bromopropane."Journal of Occupational Health. 44. 1-7 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang H.et al.: "Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for 7 days."Toxicological Sciences. 67. 114-120 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichihara G.et al.: "Organic solvents intoxication."Sougou Rinsho. 51. 768-773 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichihara G.et al.: "Introduction to toxicology"Sangyo Eiseigaku Zasshi. 44. 70-71 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajima T.et al.: "Functional activation of peroxisome proliferators-activated receptor alpha by environmental chemicals in relation to their toxicities."Nagoya Journal of Medical Sciences. 65. 85-94 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hisanaga N.et al.: "Stevens Johnson syndrome with acute hepatitis in the workers exposed to trichloroethylene and tetrachloroethylene."Sangyo Eiseigaku Zasshi. 44. 33-49 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takagi A.et al.: "Involvement of caspase 3 mediated apoptosis in hematopoietic cytotoxicity of metabolites of ethylene glycol monomethyl ether."Industrial Health. 40. 371-374 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yu X.et al.: "Neurotoxicity of 2-bromopropane and 1-bromopropane, alternative solvents for chlorofluorocarbons."Environmental Research(Section A). 174. 48-52 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yu X.et al.: "Involvement of Bcl-2 family genes and Fas signaling system in primary and secondary male germ cell apoptosis induced by 2-bromopropane in rat."Toxicology and Applied Pharmacology. 43. 35-48 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gotoh M.et al.: "The changes of cholinesterase activity, nerve conduction velocity, and clinical signs and symptoms in termite control operators exposed to chlorpyrifos."Journal of Occupational Health. 43. 157-164 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichihara G.et al.: "Cases of neurological disorders due to 1-bromopropane exposure and its mechanism."Peripheral Nerve. 12. 13-19 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeuchi Y.et al.: "Araki S.ed. Toxicology-fundamental, clinical and social medicine"Asakura Shoten. 399 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichihara G.et al.: "A survey on exposure level, health status and biomarkers in workers exposed to 1-bromopropane."American Journal of Industrial Medicine. 45. 63-75 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada T.et al.: "Exposure to 1-bromopropane caused ovarian dysfunction in rats."Toxicological Sciences. 71. 96-103 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wang H.et al.: "Dose-dependent biochemical changes in rat central nervous system after 12-week exposure to 1-bromopropane."Neurotoxicology. 24. 199-206 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakajima T.et al.: "Generalized skin reactions in relation to trichloroethylene exposure : a review from the viewpoint of drug-metabolizing enzymes."Journal of Occupational Health. 45. 8-14 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kamijima M.et al.: "A survey of semen indices in insecticide sprayers."Journal of Occupational Health. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanemoto I.et al.: "The effects of ether anesthesia for surface-induced hypothermia on cardiopulmonary function in the dog."Jpn.J.Vet.Anesth.Surg.. 34. 43-54 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ichihara G et al.: "Neurological disorders in three workers exposed to 1-bromopropane"Journal of Occupational Health. 44. 1-7 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wang H et al.: "Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for seven days"Toxicological Sciences. 67. 114-120 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wang H et al.: "Dose-dependent biochemical changes in rat central nervous system after 12 week exposure to 1-bromopropane"Neurotoxiclogy. 24. 199-206 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamada T et al.: "Exposure to 1-bromopropane canses ovarian dysfunction in rats"Toxicological Sciences. 71. 96-103 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 市原学 ほか: "有機溶剤中毒"総合臨牀. 51. 768-773 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 市原学 ほか: "毒性学入門"産業衛生学雑誌. 44. 70-71 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakajima T et al.: "Functional activation of peroxisome proliferator-activated receptor α(PPARα)byenvironmental chemicals in relation to their toxicities"Nagoya Journal of Medical Sciences. 65. 85-94 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakajima T et al.: "Generalized skin reactions in relation to trichloroethylene exposure : A review from the viewpoint of drug-metabolizing enzymes"Journal of Occupational Health. 45. 8-14 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 久永直見 ほか: "トリクロロエチレンおよびテトラクロロエチレンに曝露された労働者に発生する急性肝炎を伴うスチーブンス・ジョンソン症候群"産業衛生学雑誌. 44. 33-49 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takagi A. et al.: "Involvement of caspase 3 mediated apoptosis in hematopoie tic cytotoxicity of metabolites of ethylene glycol monomethyl ether"Industrial Health. 40. 371-374 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ichihara, Gaku: "Neurological Disorders in three workers exposed to 1-bromopropane"Journal of Occupational Health. 44. 1-7 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wang, Hailan: "Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for 7 days"Toxicological Sciences. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 市原 学: "ブロモプロパン中毒による神経障害の症例とその機序について"末梢神経. 12(印刷中). (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yu, Xiaozhong: "Neurotoxicity of 2-bromopropane and 1-bromopropane, alternative solvents for chlorofluorocarbons"Environmental Research (Section A). 85. 48-52 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yu, Xiaozhong: "Involvement of Bcl-2 family genes and Fas signaling system in primary and secondary male germ cell apoptosis induced by 2-bromopropane in rat"Toxicology and Applied Pharmacology. 174. 35-48 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gotoh, Masahiro: "The change of cholinesterase activity nerve conduction velocity, and clinical signs and symptorns in termite control operators exposed to chlorpyrifos"Journal of Occupational Health. 43. 157-164 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 竹内, 康浩: "荒記俊一編. 中毒学-基礎・臨床・社会医学"朝倉書店 (印刷中). (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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