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Dose-effect relation and mechanism of effects at central and peripheral nervous system of volatile organic solvents as industrial substance.

Research Project

Project/Area Number 05454233
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Public health/Health science
Research InstitutionTOHO University

Principal Investigator

OMOTO Miyako  Toho University School of Medicine Professer, 医学部, 教授 (20057491)

Co-Investigator(Kenkyū-buntansha) OTAHARA Yumi  Toho University School of Medicine Assistant, 医学部, 助手
IMAI Tsunehiko  Toho University School of Medicine Assistant, 医学部, 助手 (90104215)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥4,400,000 (Direct Cost: ¥4,400,000)
KeywordsOrganic solvents / Toluene / n-Hexane / Receptor / Neuron specific enolase / Cholin acetyl tsansferase / Binding assay / Immunohistochonistry / バインディングアッセイ / toluene トルエン / 中枢神経系 / 抹消神経系 / 化学伝達物質 / receptor assay リセプターアツセイ / 受容器結合能 / 低濃度曝露 / 特異的結合能
Research Abstract

Among the industrial toxic materials some organic solvents are extremely frequently and abundantly employed in the actual industrial field and handled without much care because they have too many uses in dissolving and cleansing. In addition it is known that some organic solvents affect central and peripheral nervous systems even through the exposure at relatively low concentrations. For the purpose of clarifying this mechanism, the rat was examined under various conditions of exposure using different indices concerning the nervous system.
Items examined : (1) Binding of the substance transmitting nerve impulses to receptors in the cerebrum : (2) histological findings of cerebrum ; (3) immunohistochemical findings of cerebral ChAT ; and (4) quantity of nervous apecific protein in the cerebellum and the peripheral nervous systems.
Substances used for exposure : Toluene, n-hexane, and mixture of toluene and n-hexane.
Method of exposure : (1) Inhalation in the perfuse type exposure chamber p … More urchased with this subsidy. This chamber can vary the concentration and the flowing amount of gases and can make precise measurement.
Results and discussion : 1) Effects on specific binding of cerebral nerve tranmitting chemical substance to receptors :
Toluene, high concentration, short single exposure - binding to receptors Adralpha1 -- decrease ; Adralpha2 -- increase ; Cho.Mus.-- increase
Toluene, low concentration, subchronic exposure - binding to receptor Adralpha2 -- decrease ; CABAa -- decreasing tendency
Toluene, high concentration, chronic exposure - binding to receptor Adralpha1 -- decrease
n-Hexane, low concentration, chronic exposure - binding to receptor Adralpha1 -- decrease
Other than above cases, no effects were observed on receptors setotonin 5HT2 and dopamine. 2) Cerebral histological findings : In high concentration exposure group, shrinkage of nerve cell body and axon was observed. In low concentration subchronic exposure group, large changes were not observed. 3) In immunohistological observations of cerebral ChAT,the effects of chronic exposure was not observed. 4) In measurement of neuron specific enolase, toluene of high concentration showed an increase in enolase in cerebellum, and chronic exposure at low concentration, an increase was observed in peripheral nerves (sciatic nerve).
As a results, it was suggested that high concentration acute exposure mainly affects adrenergic receptor and cholinergic receptor in the central nervous system and the low concentration chronic exposure affects the peripheral nervous systems. The subsidy we were granted this time was not enough to purchase many inhalation chambers on the market to make sufficient exposures possible. Furthermore we were not able to handle enough number of subjects for observing many items. We need to increase the observation examples and investigate other markers, too. Less

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] 大本美彌子,今井常彦,野村良治,関久美子,武田秀勝: "トルエン吸入のラット大脳の神経伝達物質受容器結合能への影響観察" 産業医学. 36. 409- (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 大本美彌子,今井常彦,大田原由美,大道正義,木内夏生: "有機溶剤による神経化学的および行動学的生体影響の観察" 産業医学. 36. (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 大本美彌子,今井常彦,野村良治,関久美子,大田原由美: "トルエンの中枢神経系化学伝達物質受容器結合能への影響" アルコール研究と薬物依存. 29. 394-395 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 大本美彌子,今井常彦,大田原由美,野村良治,武田秀勝: "有機溶剤吸入のラット神経系におよぼす影響-tolueneおよびn-hexaneについて-" 産業医学. 37. (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Omoto, M., Imai.T., Nomura.R., Seki, K.and Takeda, H.: "Influence of toluene on receptor binding in rat's brain." Jpn.J.Ind.Health. 36. 409 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Omoto, M., Imai.T., Otahara, Y., Omichi, M.and Kiuchi, N.: "Neurochemical and neurobehavioral effects of organic solvents." Jpn.J.Ind.Health. 37. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Omoto, M., Imai.T., Nomura, R., Seki, K.and Otahara, Y.: "Influence of toluene on receptor specific combinding of various chemical transmitter in rat's brain." Jpn.J.Alcohol & Dependence. 29. 394-395 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Omoto, M., Imai.T., Otahara, Y., Nomura, R.and Takeda, H.: "Neuronal effects of toluene, n-hexane, and mixture of toluene and n-hexane." Jpn.J.Ind.Health. 37. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 大本 美彌子,今井 常彦,野村 良治 関 久美子,武田 秀勝: "トルエン吸入のラット大脳の神経伝達物質受容器結合能への影響観察" 産業医学. 36. 409- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 大本 美彌子,今井 常彦,大田原 由美 大道 正義,木内 夏生: "有機溶剤による神経化学的および行動学的生体影響の観察" 産業医学. 36. (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 大本 美彌子,今井 常彦,野村 良治 関 久美子,大田原 由美: "トルエンの中枢神経系化学伝達物質受容器結合能への影響" アルコール研究と薬物依存. 29. 394-395 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 大本 美彌子,今井 常彦,大田原 由美 野村 良治,武田 秀勝: "有機溶剤吸入のラット神経系におよぼす影響-tolueneおよびn-hexaneについて-" 産業医学. 37. (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 大本美彌子・今井常彦他: "Toluene 吸入のラット大脳神経伝達物質受容器結合能への影響" 産業医学. 36. (1995)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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