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EXPERIMENTAL STUDIES ON MODIFICATION AND MECHANISM OF N-HEXANE NEUROTOXICITY BY CO-EXPOSURE OF OTHER SOLVENTS.

Research Project

Project/Area Number 62480171
Research Category

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

Allocation TypeSingle-year Grants
Research Field Hygiene
Research InstitutionNagoya University

Principal Investigator

TAKEUCHI Yasuhiro  NAGOYA UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (90022805)

Co-Investigator(Kenkyū-buntansha) ONO Yuichiro  NAGOYA UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (80135334)
HISANAGA Naomi  NAGOYA UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (90111856)
Project Period (FY) 1987 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1989: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥4,800,000 (Direct Cost: ¥4,800,000)
KeywordsN-HEXANE / TOLUENE / MEK / CO-EXPOSURE / METABOLITES / 2,5-HEXANEDIONE / NEUROTOXICITY / NERVOUS SYSTEM SPECIFIC PROTEINS / 尿中代謝物 / γ-エノラ-ゼ / S-100蛋白 / nーヘキサン / 曝露装置 / 濃度の自動制禦 / 末梢神経伝導速度 / γーエノラーゼ / Sー100蛋白 / ノルマルヘキサン / メチルエチルケトン / 混合暴露 / 2,5ーヘキサンジオン
Research Abstract

The workers handling organic solvents are often exposed to mixture of them. Neurotoxicity of n-hexane is well known to be enhanced by co-exposure of MEK. We made clear that neurotoxicity of n-hexane was decreased be co- exposure of toluene. The modification and mechanism of neurotoxicity of n-hexane by co-exposure of other solvents were studied and the results are as follows;
1) Urinary 2,5-hexanedione, one of n-hexane metabolites, was decreased by co-exposure of MEK in proportion to the concentration of MEK, 2,5-hexanedione in blood was remarkably decreased by co-exposure of MEK, too. The hypothesis that co-exposure of MEK facilitates metabolism of n- hexane and increase, of production of 2,5-hexanedione resulting in enhancement of neurotoxicity of n-hexane seems doubtful from our results.
2) In order to evaluate the long-term effects of co-exposure of solvents, an automated solvent exposure system for small laboratory animals was devised. Single and mixed exposure of n-hexane and tolue … More ne were successfully conducted for one day exposure and for long-term exposure. But the exposure system was found not to work well in the long-term exposure of MEK. Therefore, the experiment of the long-term co-exposure of n-hexane and MEK was interrupted and the system was improved.
The long-term co-exposure started again and continues now. 3) As indices for neurotoxicity of organic solvents, nervous system specific proteins, analysis and S-100 proteins were determined in the peripheral nerves, cerebrum, cerebellum and brain stem. The results showed that these nervous system specific proteins were useful indices of the effects on the nervous system. 4) The method to determine urinary 2,5-hexanedione was established by us in order to determine it more exactly and specifically. It was revealed that pH of sample urine should be decreased to less than 1 at the pretreatment in order to obtain a stable 2,5-hexanedione, and 2,5- hexanedione was hardly detected in the urine of the person unexposed to n- hexane and the good co-relation between n-hexane exposure and urinary 2,5- hexanedione was obtained using the appropriate column. Less

Report

(4 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] KASAHARA,M.: "N-HEXANE,BENZENE AND OTHER AROMATIC COMPONENTS IN PETROLEUM DISTILLATE SOLVENTS IN JAPAN" IND HEALTH. 25. 205-214 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] HUANG,J.: "EFFECTS OF CHRONIC N-HEXANE EXPOSURE ON NERVOUS SYSTEM-SPECIFIC AND MUSCLESPECIFIC PROTEINS" ARCH TOXICOL. 63. 381-385 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] SHIBATA,E.: "CHANGES IN URINARY N-HEXANE METABOLITES BY CO-EXPOSURE TO VARIOUS CONCENTRATIONS OF METHYL ETHYL KETONE AND FIXED N-HEXANE LEVELS" ARCH TOXICOL(INPRESS).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] HUANG,J.: "EFFECTS OF SUBACUTE TOLUENE EXPOSURE ON NEURONAL AND GLIAL MARKER PROTEINS IN RAT BRAIN" TOXICOL(IN PRESS).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] SHIBATA,E.: "EFFECTS OF MEK ON KINETICS OF N-HEXANE METABOLITES IN SERUM" ARCH TOXICOL(IN PRESS).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] TAKEUCHI,Y.: "AN AUTOMATED SOLVENT EXPOSURE SYSTEM FOR SMALL LABORATORY ANIMALS" ARCH TOXICOL(SUBMITTED).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] KASAHARA,M.: "N-HEXANE, BENZENE AND OTHER AROMATIC COMPONENTS IN PETROLEUM DISTILLATE SOLVENTS IN JAPAN" IND HEALTH 25:205-14, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] TAKEUCHI,Y.: "VISUAL DISORDERS DUE TO ORGANIC SOLVENTS POISONING" JPN J IND HEALTH 30:236-47, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] TAKEUCHI,Y.: "ORAGNIC SOLVENTS POISONING AND ACQUIRED DISORDERS OF COLOR VISION" IGAKU NO AYUMI 148:670, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] TAKEUCHI,Y.: "NERVOUS SYSTEM IMPAIRMENT DUE TO MAIN HAZARDOUS CHEMICALS - N-HEXANE" CLIN NEUROSCI 7:1098-9 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] HUANG,J.: "EFFECTS OF CHRONIC N-HEXANE EXPOSURE ON NERVOUS SYSTEM-SPECIFIC AND MUSCLE-SPECIFIC PROTEINS" ARCH TOXICOL 63:381-5 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] SHIBATA,E.: "CHANGES IN URINARY N-HEXANE METABOLITES BY CO-EXPOSURE TO VARIOUS CONCENTRATIONS OF METHYL ETHYL KETONE AND FIXED N-HEXANE LEVELS" ARCH TOXICOL.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] HUANG,J.: "EFFECTS OF SUBACUTE TOLUENE EXPOSURE ON NEURONAL AND GLIAL MARKER PROTEINS IN RAT BRAIN" TOXICOL.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] SHIBATA,E.: "EFFECTS OF MEK ON KINETICS OF N-HEXANE METABOLITES IN SERUM" ARCH TOXICOL.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] TAKEUCHI,Y.: "AN AUTOMATED SOLVENT EXPOSURE SYSTEM FOR SMALL LABORATORY ANIMALS" ARCH TOXICOL.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] HUANG,J.: "EFFECTS OF CHRONIC N-HEXANE EXPOSURE ON NERVOUS SYSTEM-SPECIFIC AND MUSCLE-SPECIFIC PROTEINS" ARCH TOXICOL. 63. 381-385 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] SHIBATA,E.: "CHANGES IN URINARY N-HEXANE METABOLITES BY CO-EXPOSURE TO VARIOUS CONCENTRATIONS OF METHYL ETHYL KETONE AND FIXED N-HEXANE LEVELS" ARCH TOXICOL.

    • Related Report
      1989 Annual Research Report
  • [Publications] HUANG,J.: "EFFECTS OF SUBACUTE TOLUENE EXPOSURE ON NEURONAL AND GLIAL MARKER PROTEINS IN RAT BRAIN" TOXICOL.

    • Related Report
      1989 Annual Research Report
  • [Publications] SHIBATA,E.: "EFFECTS OF MEK ON KINETICS OF N-HEXANE METABOLITES IN SERUN" ARCH TOXICOL.

    • Related Report
      1989 Annual Research Report
  • [Publications] TAKEUCHI,Y.: "AN AUTOMATED SOLVENT EXPOSURE SYSTEM FOR SMALL LABORATORY ANIMALS" ARCH TOXICOL.

    • Related Report
      1989 Annual Research Report
  • [Publications] 柴田英治: 産業医学. 30. 678-678 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 竹内康浩: 産業医学.

    • Related Report
      1988 Annual Research Report
  • [Publications] 黄健: 産業医学.

    • Related Report
      1988 Annual Research Report
  • [Publications] Eiji SHIBATA: Toxicology.

    • Related Report
      1988 Annual Research Report
  • [Publications] Jian HUANG: Brit.J Ind.Med.

    • Related Report
      1988 Annual Research Report
  • [Publications] 柴田英治他: 産業医学. 29. 623 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] SHIBATA E.et al.: Toxieol.Appl.Pharmacal.

    • Related Report
      1987 Annual Research Report
  • [Publications] 柴田英治他: 産業医学.

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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