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Development of in vitro and in vivo test methods for evaluation of environmental pharmaceuticals on the aquatic species

Research Project

Project/Area Number 17H01907
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental risk control and evaluation
Research InstitutionKyoto University

Principal Investigator

Ihara Masaru  京都大学, 工学研究科, 特定助教 (70450202)

Co-Investigator(Kenkyū-buntansha) 長江 真樹  長崎大学, 水産・環境科学総合研究科(環境), 教授 (00315227)
田中 宏明  京都大学, 工学研究科, 教授 (70344017)
征矢野 清  長崎大学, 海洋未来イノベーション機構, 教授 (80260735)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
KeywordsGPCR阻害薬 / 抗うつ薬 / in vitroアッセイ / in vivo曝露試験 / 行動異常 / 下水 / 河川水 / 魚 / セロトニントランスポーター / 魚曝露試験 / 環境医薬品 / 魚類 / 行動影響 / 培養細胞試験 / 薬理活性 / 医薬品生理活性 / 細胞培養試験 / 行動試験 / GPCR作用薬 / 魚行動試験 / ジフェンヒドラミン / 環境 / 生物影響評価 / 行動解析 / 下水道
Outline of Final Research Achievements

Pharmaceuticals taken by human flow into the sewage treatment plant, and after sewage treatment process, are released into receiving waters such as rivers. Since many kinds of pharmaceuticals act on nerve cells, it is essential to evaluate from the viewpoint of behavioral abnormalities when fish are exposed to them in river. The purpose of this study was to establish the evaluation methods and to clarify the degree of pharmaceutical contamination of river water and sewage. Specifically, we comprehensively measured and clarified the pharmacological activities of GPCR inhibitors and antidepressants against human and fish receptors by in vitro tests. Furthermore, the degree of pharmacological activity in sewage treatment plants in Japan and the United Kingdom was clarified. In addition, we were able to establish a in vivo testing system that can track the behavior of fish with a video camera and establish the basis for analysis of behavioral abnormalities.

Academic Significance and Societal Importance of the Research Achievements

GPCR阻害薬と抗うつ薬の活性を測定できるin vitro試験系を世界で初めて下水へ適用し、その実態を明らかにした。さらにヒトの受容体と魚の受容体の医薬品に対する感受性の違いも世界で初めてデータを示すことができた。生物毒性研究においてこれまで体系的に調べられてこなかった神経系医薬品の研究の必要性を示す重要な成果である。また、これまで報告されている医薬品曝露による水生生物の行動異常の作用機序の説明につながる重要な成果である。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (40 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (26 results) (of which Int'l Joint Research: 16 results,  Invited: 6 results) Book (3 results) Remarks (2 results)

  • [Int'l Joint Research] Center for Ecology and Hydrology(英国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Proposal for fluorescence-based in vitro assay using human and zebrafish monoamine transporters to detect biological activities of antidepressants in wastewater2021

    • Author(s)
      Masaru Ihara, Han Zhang, Mariko O. Ihara, Daisuke Kato, Hiroaki Tanaka
    • Journal Title

      Science of the Total Environment

      Volume: 770 Pages: 144665-144665

    • DOI

      10.1016/j.scitotenv.2020.144665

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evaluation of pharmaceutical activities of G-protein coupled receptor targeted pharmaceuticals in Chinese wastewater effluent2020

    • Author(s)
      Han Zhang, YingchaoLin, Zhengyu Men, Masaru Ihara, Weizun Li, Kai He
    • Journal Title

      Chinese Chemical Letters

      Volume: 31 Issue: 10 Pages: 2859-2863

    • DOI

      10.1016/j.cclet.2020.08.040

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Biological Activity-Based Prioritization of Pharmaceuticals in Wastewater for Environmental Monitoring: G Protein-Coupled Receptor Inhibitors2020

    • Author(s)
      Zhang Han、Ihara Mariko O.、Nakada Norihide、Tanaka Hiroaki、Ihara Masaru
    • Journal Title

      Environmental Science & Technology

      Volume: 54 Issue: 3 Pages: 1720-1729

    • DOI

      10.1021/acs.est.9b05768

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Characterization of G protein‐coupled estrogen receptors in Japanese medaka, Oryzias latipes2020

    • Author(s)
      Miyaoku Kaori、Ogino Yukiko、Lange Anke、Ono Ayaka、Kobayashi Tohru、Ihara Masaru、Tanaka Hiroaki、Toyota Kenji、Akashi Hiroshi、Yamagishi Genki、Sato Tomomi、Tyler Charles R.、Iguchi Taisen、Miyagawa Shinichi
    • Journal Title

      Journal of Applied Toxicology

      Volume: - Issue: 9 Pages: 1390-1399

    • DOI

      10.1002/jat.4130

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Wastewater‐derived antagonistic activities of G protein‐coupled receptor‐acting pharmaceuticals in river water2020

    • Author(s)
      Ihara Masaru、Hanamoto Seiya、Ihara Mariko O.、Zhang Han、Tanaka Hiroaki
    • Journal Title

      Journal of Applied Toxicology

      Volume: 2020 Issue: 7 Pages: 32077112-32077112

    • DOI

      10.1002/jat.3952

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantification of Pharmaceutical Related Biological Activity in Effluents from Wastewater Treatment Plants in UK and Japan.2018

    • Author(s)
      Han Zhang, Masaru Ihara, Seiya Hanamoto, Norihide Nakada, Monika D. Jurgens, Andrew C. Johnson, Hiroaki Tanaka.
    • Journal Title

      Envrion. Sci. Technol.

      Volume: 52 Pages: 11848-11856

    • DOI

      10.1021/acs.est.8b03013

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection of physiological activity of pharmaceuticals in wastewater and river water.2018

    • Author(s)
      Ihara M, Zhang H, Hanamoto S, Tanaka H
    • Journal Title

      薬学雑誌

      Volume: 38 Pages: 281-287

    • NAID

      130006410647

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 下水,河川水からの医薬品生理活性の検出2018

    • Author(s)
      井原賢, Zhang Han, 花本征也,田中宏明
    • Journal Title

      薬学雑誌

      Volume: 38

    • NAID

      130006410647

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Prediction and management of emerging chemicals in the water environment2020

    • Author(s)
      Hiroaki TANAKA, Masaru IHARA, Norihide NAKADA, Han ZHANG,Hiromasa YAMASHITA, Seiya HANAMOTO
    • Organizer
      The 22nd UK-Japan Annual Scientific Workshop on Research into Environmental Endocrine Disrupting Chemicals
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PPCPsの水生生物への影響:神経系薬を中心に2019

    • Author(s)
      井原賢
    • Organizer
      第33回環境ホルモン学会講演会、水環境中における医薬品及びパーソナルケア製品(PPCPs)に関する最近の動向について
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Prediction and management of emerging chemicals in the water environment2019

    • Author(s)
      Hiroaki TANAKA, Masaru IHARA, Norihide NAKADA, Han ZHANG,Hiromasa YAMASHITA, Seiya HANAMOTO
    • Organizer
      The 21th UK-Japan Annual Scientific Workshop on Research into Environmental Endocrine Disrupting Chemicals
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Investigation of G Protein-Coupled Receptor-acting Pharmaceuticals Responsible for Biological Activities in Wastewater in England2019

    • Author(s)
      Han Zhang, Hiroaki Tanaka, Masaru Ihara
    • Organizer
      11th Micropol & Ecohazard Conference、Seoul, Korea
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel in vitro assays to investigate adverse effects of environmental pharmaceuticals on aquatic species2019

    • Author(s)
      Masaru Ihara, Han Zhang, Mariko O. Ihara, Daisuke Kato, and Hiroaki Tanaka
    • Organizer
      The 5th Asian Symposium on Water Reuse -Technology Renovation and Risk Management, Yokohama, Japan
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biological-activity-based prioritization of pharmaceuticals in wastewater in Japan and England2019

    • Author(s)
      Han Zhang, Hiroaki Tanaka, Masaru Ihara
    • Organizer
      The 21th UK-Japan Annual Scientific Workshop on Research into Environmental Endocrine Disrupting Chemicals, Otsu, Japan
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection of biological activity of antidepressants in wastewater treatment plant effluents in Japan and UK using in vitro assay2019

    • Author(s)
      Daisuke Kato, Mariko Ihara, Han Zhang, Hiroaki Tanaka, Masaru Ihara
    • Organizer
      The 21th UK-Japan Annual Scientific Workshop on Research into Environmental Endocrine Disrupting Chemicals, Otsu, Japan
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biological activity-based prioritization of pharmaceuticals in wastewater of England and Japan2019

    • Author(s)
      Han Zhang, Norihide Nakada, Masaru Ihara, Hiroaki Tanaka
    • Organizer
      The 5th Asian Symposium on Water Reuse -Technology Renovation and Risk Management, Yokohama, Japan
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biological activities of antidepressants in wastewater to fish monoamine transporters2019

    • Author(s)
      Masaru Ihara, Mariko O. Ihara, Daisuke Kato, Han Zhang, and Hiroaki Tanaka
    • Organizer
      Europe 29th Annual Meeting、Helsinki, Finland
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトおよびメダカのトランスポーターを用いたin vitroアッセイによる下水処理水中の抗うつ薬の薬理活性の検出2019

    • Author(s)
      加藤大典, 井原満理子, 張晗, 田中 宏明, 井原賢
    • Organizer
      第53回日本水環境学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] バイオアッセイ、ターゲット分析、予測スクリーニングによる 下水処理水中の各種受容体拮抗作用物質の探索2019

    • Author(s)
      中田典秀, 張晗, 井原賢
    • Organizer
      第53回日本水環境学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 水環境中の汚染医薬品による生態影響の理解にむけて2018

    • Author(s)
      井原賢
    • Organizer
      株式会社フソウ フソウ技術発表会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] How we should manage human pharmaceuticals in in waters to protect aquatic species?2018

    • Author(s)
      Masaru Ihara
    • Organizer
      The 4th Asian Symposium on Water Reuse -Technology Renovation and Risk Management
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Prediction and management of emerging chemicals in the water environment2018

    • Author(s)
      Hiroaki TANAKA, Masaru IHARA, Fumiaki OGAWA
    • Organizer
      The 20th UK-Japan Annual Scientific Workshop on Research into Environmental Endocrine Disrupting Chemicals
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Change of estrogenic activity during wastewater reclamation process2018

    • Author(s)
      Masaru Ihara
    • Organizer
      Engineering Academy of Japan - US National Academy of Engineering, 2018 Japan-America Frontiers of Engineering Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Application of newly developed in vitro assay to detect physiological activities of antidepressants in wastewater2018

    • Author(s)
      Masaru Ihara, Mariko O. Ihara, Daisuke Kato, Han Zhang, Hiroaki Tanaka
    • Organizer
      SETAC Europe 28th Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗うつ薬の検出を目的とする蛍光基質を用いたin vitroアッセイの下水処理水への適用検討2018

    • Author(s)
      加藤大典, 井原賢, 井原満理子, ZHANG Han, 田中宏明
    • Organizer
      第40回環境衛生工学研究
    • Related Report
      2018 Annual Research Report
  • [Presentation] 生理活性に基づく下水処理水中のアンジオテンシンII受容体拮抗作用(薬)のターゲット分析および予測スクリーニング2018

    • Author(s)
      中田典秀, ZHANG Han, 井原賢
    • Organizer
      日本水環境学会年会講演集
    • Related Report
      2018 Annual Research Report
  • [Presentation] 水環境中の汚染医薬品による生態影響の理解にむけて2018

    • Author(s)
      井原賢
    • Organizer
      環境省 平成29年度化学物質の内分泌かく乱作用に関する公開セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Change of estrogenic activity during wastewater reclamation process2017

    • Author(s)
      Masaru Ihara
    • Organizer
      The 3rd Asian Symposium on Water Reuse
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection of physiological activities of antidepressant pharmaceuticals in wastewater by fluorescence based in vitro assay2017

    • Author(s)
      Masaru Ihara
    • Organizer
      Green Technologies for Sustainable Water (GTSW) Conference - 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Detection of physiological activities of antidepressant pharmaceuticals in wastewater by fluorescence based in vitro assay2017

    • Author(s)
      Masaru Ihara
    • Organizer
      SETAC North America 38th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prediction and management of emerging chemicals in the water environment2017

    • Author(s)
      Hiroaki TANAKA, Masaru IHARA, Norihide NAKADA, Han ZHANG
    • Organizer
      The 19th UK-Japan annual scientific workshop on research into environmental endocrine disrupting chemicals
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 水環境中の微量汚染化学物質と病原微生物について2017

    • Author(s)
      井原賢
    • Organizer
      K-CONNEXファーストコンタクト、KRPアイデア・シェアリング・コミュニティ第6回
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 下水処理排水のエストロゲン活性およびエストロゲン遮断効果2017

    • Author(s)
      長江真樹,三島和也,田島英佳,山城加奈子,加島未奈子,征矢野清,高尾雄二
    • Organizer
      第26回環境化学討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] In vitroアッセイによる下水中の抗うつ薬様物質の生理活性の検出2017

    • Author(s)
      井原賢、井原満理子、加藤大典、HanZhang、田中宏明
    • Organizer
      第20回環境ホルモン学会
    • Related Report
      2017 Annual Research Report
  • [Book] 総説 医薬品による水環境への影響について2020

    • Author(s)
      井原賢
    • Total Pages
      5
    • Publisher
      日本病院薬剤師会雑誌
    • Related Report
      2019 Annual Research Report
  • [Book] PPCPsの水生生物への影響:神経系薬を中心に2019

    • Author(s)
      井原賢
    • Total Pages
      1
    • Publisher
      環境ホルモン学会 ニュースレター、Vol22, No2
    • Related Report
      2019 Annual Research Report
  • [Book] 研究最前線 ヒトおよびメダカのトランスポーターを用いたin vitroアッセイによる下水処理水中の抗うつ薬の薬理活性の検出2019

    • Author(s)
      加藤大典, 井原満理子, 張晗, 田中宏明, 井原賢
    • Total Pages
      1
    • Publisher
      環境ホルモン学会 ニュースレター、Vol21, No4
    • Related Report
      2019 Annual Research Report
  • [Remarks] 井原賢研究グループHP

    • URL

      https://ihara-lab.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 井原賢研究グループHP

    • URL

      http://ihara-lab.jp/

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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