Searching of nuclear receptor-mediated persistent unknown contaminants by an integrated approach of chemical analysis and bioassays

• Project/Area Number: 19K22911
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 63:Environmental analyses and evaluation and related fields
• Research Institution: Ehime University
• Principal Investigator: Kunisue Tatsuya 愛媛大学, 沿岸環境科学研究センター, 教授 (90380287)
• Project Period (FY): 2019-06-28 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 残留性未知物質 / バイオアッセイ / 機器分析 / 核内受容体 / 生物蓄積

Outline of Research at the Start

２次元ガスクロマトグラフ飛行時間型高分解能質量分析計および高分解能ガスクロマトグラフ質量分析計を用いた機器分析技術と細胞内受容体介在活性の評価が可能な in vitro アッセイを駆使し、アジア各地から収集し愛媛大学沿岸環境科学研究センターの生物環境試料バンクに冷凍保存されている多種類の環境・生物試料に適用することで、環境残留性・生物蓄積性未知有害化学物質の探索をおこなう。

Outline of Final Research Achievements

This study evaluated aryl hydrocarbon receptor (AhR)-agonistic activities in sulfuric acid (H2SO4)- or gel permeation chromatography (GCP)-treated liver extracts from 5 wild avian species by using in vitro bioassays. AhR-agonistic activities were observed in all the liver samples, especially with high activities in raptors such as falcon and black kite. The AhR-agonistic activities in GCP-treated liver extracts were higher than those in H2SO4-treated liver extracts, suggesting the presence of acid-labile AhR agonist(s). HPLC (high performance liquid chromatography)-fractionation and instrumental analysis approach indicated the accumulation of not only dioxins but also PAH (polycyclic aromatic hydrocarbon)-related compounds, as possible AhR agonists, in the liver of Japanese wild birds.

Academic Significance and Societal Importance of the Research Achievements

本研究で構築したin vitroバイオアッセイと機器分析のアプローチ手法は、生物蓄積性を示す未知有害化学物質を探索する上で有用なツールとなり得る。本手法により、日本に棲息する野生鳥類の肝臓にダイオキシン類や多環芳香族炭化水素といった既知のAhRアゴニストだけでなく、AhRアゴニスト活性を示す未同定化合物が蓄積していることを示唆した研究成果は学術的にも重要である。従来のターゲット分析では見落とされていた生態リスクが懸念される生物蓄積性化合物の可能性が高いことから、残留性有機汚染物質に関するストックホルム条約等の要監視化学物質として検討すべき基礎データを提示することができた。

Research Products

• [Journal Article] Estrogenic, androgenic, and glucocorticoid activities and major causative compounds in river waters from three Asian countries (2022)
  • Author(s): Tue Nguyen Minh、Matsukami Hidenori、Tuyen Le Huu、Suzuki Go、Viet Pham Hung、Sudaryanto Agus、Subramanian Annamalai、Tanabe Shinsuke、Kunisue Tatsuya
  • Journal Title: Environmental Science and Pollution Research Volume: 30 Issue: 8 Pages: 20765-20774
  • DOI: 10.1007/s11356-022-23674-6
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nontarget Screening of Organohalogen Compounds in the Liver of Wild Birds from Osaka, Japan: Specific Accumulation of Highly Chlorinated POP Homologues in Raptors (2021)
  • Author(s): Tue Nguyen Minh、Goto Akitoshi、Fumoto Mitsuo、Nakatsu Susumu、Tanabe Shinsuke、Kunisue Tatsuya
  • Journal Title: Environmental Science & Technology Volume: 55 Issue: 13 Pages: 8691-8699
  • DOI: 10.1021/acs.est.1c00357
  • Peer Reviewed / Open Access
• [Journal Article] Application of inert gas-mediated ionization for qualitative screening of chlorinated aromatics in house dust by comprehensive two-dimensional gas chromatography?high-resolution time-of-flight mass spectrometry (2021)
  • Author(s): Ieda Teruyo、Hashimoto Shunji、Tanabe Kiyoshi、Goto Akitoshi、Kunisue Tatsuya
  • Journal Title: Journal of Chromatography A Volume: 1657 Pages: 462571-462571
  • DOI: 10.1016/j.chroma.2021.462571
  • Peer Reviewed
• [Journal Article] Nontarget and Target Screening of Organohalogen Compounds in Mussels and Sediment from Hiroshima Bay, Japan: Occurrence of Novel Bioaccumulative Substances (2020)
  • Author(s): Goto Akitoshi、Tue Nguyen Minh、Isobe Tomohiko、Takahashi Shin、Tanabe Shinsuke、Kunisue Tatsuya
  • Journal Title: Environmental Science & Technology Volume: 54 Issue: 9 Pages: 5480-5488
  • DOI: 10.1021/acs.est.9b06998
  • Peer Reviewed
• [Presentation] Methyl-substituted polycyclic hydrocarbons in bivalves from Seto Inland Sea: Levels and AhR agonist activities (2022)
  • Author(s): Nguyen Minh Tue・Kana Kuroishi・Haruka Yukimoto・Akitoshi Goto・Shinsuke Tanabe・Tatsuya Kunisue
  • Organizer: 環境化学物質 3 学会合同大会
• [Presentation] 瀬戸内海のクロダイに蓄積する有機ハロゲン化合物のノンターゲットスクリーニング (2022)
  • Author(s): 後藤哲智・Nguyen Minh Tue・田辺信介・国末達也
  • Organizer: 環境化学物質 3 学会合同大会
• [Presentation] 瀬戸内海の環境および生物相に残留するダイオキシン類縁化合物のターゲットスクリーニングと起源解析 (2022)
  • Author(s): 後藤哲智・Nguyen Minh Tue・田辺信介・国末達也
  • Organizer: 環境化学物質 3 学会合同大会
• [Presentation] Effect-directed analysis of aryl-hydrocarbon receptor agonists reveals contribution of methyl-substituted PAHs in bivalves from Seto Inland Sea, Japan (2022)
  • Author(s): Tue, N. M., Kuroishi, K., Yukimoto, H., Goto, A., Tanabe, S., Kunisue, T.
  • Organizer: SETAC Asia-Pacific Virtual Conference 2022
  • Int'l Joint Research
• [Presentation] Nontarget and suspect screening of bioaccumulative organohalogen compounds in marine fish from Seto Inland Sea, Japan (2022)
  • Author(s): Goto, A., Tue, N. M., Tanabe, S., Kunisue, T.
  • Organizer: SETAC North America 43th Annual Meeting
  • Int'l Joint Research
• [Presentation] 海産二枚貝を用いたバイオモニタリング－未知物質スクリーニングの試み－ (2021)
  • Author(s): 国末達也
  • Organizer: 第24回日本水環境学会シンポジウム
  • Invited
• [Presentation] 海産の魚類を対象とした生物蓄積性有機ハロゲン化合物のサスペクトスクリーニング (2021)
  • Author(s): 後藤哲智・Tue, N. M.・田辺信介・国末達也
  • Organizer: 第69回質量分析総合討論会
• [Presentation] 瀬戸内海の二枚貝と堆積物に残留する既知・未知有機ハロゲン化合物の生物濃縮性評価 (2021)
  • Author(s): 後藤哲智・Nguyen Minh Tue・田辺信介・国末達也
  • Organizer: 第29回環境化学討論会
• [Presentation] 鯨類の脂皮に蓄積する有機ハロゲン化合物の網羅的スクリーニング (2021)
  • Author(s): 須之内 朋哉・後藤哲智・Nguyen Minh Tue・田島 木綿子・山田 格・田辺信介・国末達也
  • Organizer: 第29回環境化学討論会
• [Presentation] Evaluation of biota-sediment accumulation factors (BSAFs) for known and unknown organohalogen compounds in Japanese mussels (2021)
  • Author(s): Goto, A., Tue, N. M., Tanabe, S., Kunisue, T
  • Organizer: 41th International Symposium on Halogenated Persistent Organic Pollutants
  • Int'l Joint Research
• [Presentation] Specific accumulation of C15-based chlordane-related compounds in the liver of wild birds from Japan (2021)
  • Author(s): Tue, N. M., Goto, A., Fumoto, M., Nakatsu, S., Tanabe, S., Kunisue, T
  • Organizer: 41th International Symposium on Halogenated Persistent Organic Pollutants
  • Int'l Joint Research
• [Presentation] 瀬戸内海の二枚貝に残留する多環芳香族炭化水素レベルとAhRアゴニストの活性評価 (2020)
  • Author(s): 黒石佳奈・Tue, N. M.・後藤哲智・田辺信介・国末達也
  • Organizer: 環境科学会2020年会
• [Presentation] Non-target screening for POP-like compounds in Japanese bivalves using GC×GC-HRToFMS (2019)
  • Author(s): Goto, A., Tue, N. M., Tanabe, S., Kunisue, T.
  • Organizer: 39th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN 2019)
  • Int'l Joint Research
• [Presentation] Validation of soft ionization method mediated by inert gas for non-target screening of halogenated compounds and application to crude extract of house dust (2019)
  • Author(s): Ieda, T., Hashimoto, S., Tanabe, K., Goto, A., Kunisue, T.
  • Organizer: 39th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN 2019)
  • Int'l Joint Research
• [Presentation] CALUX activities, flame retardants and polyaromatic hydrocarbons in indoor dust from informal waste recycling sites in Vietnam (2019)
  • Author(s): Tue, N. M., Tuyen, L. H., Suzuki, G., Takahashi, S., Viet, P. H., Tanabe, S., Kunisue, T.
  • Organizer: 39th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN 2019)
  • Int'l Joint Research