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Study on toxicokinetics of PCB and tissue-retainable PCB metabolites in human

Research Project

Project/Area Number 10672116
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionDaiichi College of Pharmaceutical Sciences

Principal Investigator

HARAKUCHI Koichi  Daiichi College of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (00258500)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
KeywordsPCB / methylsulfonyl metabolites / hydroxylated netabolites / human / mammals / tissue distribution
Research Abstract

Toxicokinetics of PCBs and tissue-retainable PCB metabolites (hydroxylated (OH-PCB) and methylsulfonylated (MeSOィイD22ィエD2-PCB)) were studied in human blood, tissues of mammals as well as in laboratory animals exposed to PCBS.
(1) Single administration of each PCB (#105, #118, #126, #138, #146, #153, #167, #187) to rats resulted in the retention of selected OH-PCBs in blood, particularly of 4-OH-PCBs with 3,5-dichlorinated substitution. The levels of OH-PCBs in blood were higher than the parent PCB levels.
(2) Species difference in the biotransformation capacity of PCB to OH-PCBs and MeSOィイD22ィエD2-PCBs was investigated between rats, hamsters and guinea pigs dosed with Kanechlor-500 (PCB mixture). In blood, the selective retention of 3-OH-PCBs derived from #99 and #118 was observed in guinea pigs, although only 4-OH-PCB derived from #118 was retained in rats. In liver, the retention of 3- and 4-MeSOィイD22ィエD2-PCBs derived from e.g. #101 and #132 was largely dependent on the species.
(3) More than ten OH-PCBs and ten MeSOィイD22ィエD2-PCBs were isolated from human blood and tissues of mammals such as seals and cetaceans. The levels of OH-PCBs were 1/100 of total PCBs in human blood, whereas, MeSO2-PCBs were 1/10-1/20 in seals and 1/100 in dolphin liver and human blood.
(4) Administration of nine MeSOィイD22ィエD2-PCBS to rats resulted in the reduction of serum thyroxine hormone levels, indicating that these PCB metabolites act as an endocrine disruptor.
These results give us useful information on the metabolism and toxicokinetics of PCBs and their tissue-retainable PCB metabolites in human.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Troisi, G.M.,: "Methyl sulphone metabolites of polychlorinated biphenyls(PCBs) in cetaceans from the Irish and the Aegean Seas"Arch. Environ. Contam. Toxicol.,. 35. 121-128 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi, K.,: "Hydroxylation and methylthiolation of mono-ortho-substituted polychlorinated biphenyls in rats : Identification of metabolites with tissue affinity"Chem. Res. Toxicol.,. 11. 1508-1515 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi, K.,: "Comparative metabolism of polychlorinated biphenyls with 2, 4,5-trichloro substitution in rats : Regioselective formation of hydroxy metabolites with high blood affinity"Organohalogen Compounds,. 37. 401-404 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato, Y.,: "The role of 3-methyl- sulfonyl-2,2',4',5,5' -pentachlorobiphenyl, a metabolite of 2,2',4,5,5' -pentachlorobi-phenyl, in the induction of hepatic microsomal drug- metabolizing enzymes by 2,2',4,5,5' -pentachlorobiphenyl in rats"Environ. Toxicol. Pharmacol.,. 8. 39-47 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi K.,: "Tissue distribution of methylsulfonyl metabolites derived from 2,4,5,2',5' -pentachlorobiphenyl and 2, 4, 5, 2', 3', 6' -hexachlorobiphenyl in rats"Arch. Environ. Contam. Toxicol.,. 37. 135-142 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi, K.,: "Metabolism of 3,3',4,4',5-penta-and 2,2',3,3',4,4' -hexachlorobiphenyls in rats"Fukuoka Acta Med.,. 90. 210-219 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi, K.,: "Comparative metabolism of polychlorinated biphenyls (Kanechlor-500) in rats, hamsters and guinea pigs"Organohalogen Compounds,. 42. 177-180 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato, Y.,: "Reduction of serum thyroxine concentrations by methylsulfonyl metabolites of tetra-, penta- and hexachlorinated biphenyls in male sprague-dawley rats"Chemosphere,. 40. 1233-1240 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Troisi, G.M: "Methyl sulphone metabolites of polychlorinated biphenyls (PCBs) in cetaceans from the Irish and the Aegean Seas."Arch, Environ, Contam. Toxicol.. 36. 121-128 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi, K.: "Hydroxylation and methylthiolation of mono-ortho-substituted polychlorinated biphenyls in rats : Identification of metabolites with tissue affinity."Chem, Res. Toxicol,. 11. 1508-1515 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi, K.: "Comparative metabolism of polychlorinated biphenyls with 2, 4, 5-trichloro substitution in rats : Regioselective formation of hydroxy metabolites with high blood affinity."Organohalogen Compounds. 37. 401-404 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato, Y.: "The role of 3-methyl- sulfonyl-2, 2', 4', 5, 5'-pentachlorobiphenyl, a metabolite of 2, 2', 4-, 5, 5'-pentachlorobiphenyl-, in the induction of hepatic microsomal drugmetabolizing enzymes by 2, 2', 4, 5, 5'-pentachlorobiphenyl in rats."Environ. Toxicol. Pharmacol.. 8. 39-47 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi, K.: "Tissue distribution of methylsulfonyl metabolites derived from 2, 4, 5, 2', 5'-pentachlorobiphenyl and 2, 4, 5, 2', 3', 6'-hexachlorobi-phenyl in rats."Arch, Environ, Contam. Toxicol.. 37. 135-142 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi, K.: "Metabolism of 3, 3', 4, 4', 51-penta- and 2, 2', 3, 3', 4, 4'-hexachlorobiphenyls in rats."Fukuoka Acta Med.. 90. 210-219 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haraguchi, K.: "Comparative metabolism of polychlorinated biphenyls (Kanechlor-500) in rats, hamsters and guinea pigs."Organohalogen Compounds. 42. 177-180 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato, Y.: "Reduction of serum thyroxine concentrations by methylsulfonyl metabolites of tetra-, penta- and hexachlorinated biphenyls in male sprague-dawley rats."Chemosphere. 40. 1233-1240 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato,Y.: "Reduction of serum thyroxine concentrations by methylsulfonyl metabolites of tetra-,penta- and hexachlorinated biphenyls in male Sprague-dawley rats"Chemosphere. 40. 1233-1240 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Haraguchi,K.: "Comparative metabolism of polychlorinated biphenyls(Kanechlor-500)in rats,hamsters and guinea pigs"Organohalogen Compounds. 42. 177-180 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kato,Y.: "Induction of hapatic microsomal UDP-glucuronosyltransferase by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats"Organohalogen Compounds. 42. 337-340 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koga,N.: "Metabolism of tetrachlorobiphneyls by Chinese hamster liver microsomes"Organohalogen Compounds. 42. 181-184 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Haraguchi,K.: "Metabolism of 3,3',4,4',5-penta-and 2,2',3,3',4,4'-hexachlorobiphenyl"Fukuoka Acta Med.. 90・5. 210-219 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 原口浩一: "3,4,5,3',4'-Penta-および2,3,4,2',3',4'-hexachlorobiphenyl の代謝研究" 福岡医学雑誌. 17. 印刷中 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Haraguchi,K.: "Tissue distribution of methylsulfonyl metabolites derived from 2,2',4,5,5'-Penta-and 2,2',3,4',5',6-hexachlorobiphenyls in rats." Archiv.Environm.Contam.Toxicol.(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Haraguchi,K.: "Hydroxylation and methylthiolation of mono-ortho-substituted polychlorinated biphenyls in rats: Identification of metabolites with tissue affinity." Chem.Res.Toxicol.11. 1508-1515 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Haraguchi,K.: "Comparative metabolism of polychlorinated biphenyls with 2,4,5-trichloro substitution in rats: Regioselective formation of hydroxy metabolites with high blood affinity." Organohalogen Compounds. 37. 401-404 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Troisi,G.M.: "Methyl sulphone metabolites of polychlorinated biphenyls (PCBs)in Cetaceans from the Irish and the Aegean Seas." Arch.Environ.Contam.Toxicol.35. 121-128 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kato,Y.: "Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats." Arch.Toxicol.72. 541-544 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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