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Analysis of reproductive toxicity and nonlinear reaction mechanism of bisphenol A analogues in food containers

Research Project

Project/Area Number 18H03381
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 63030:Chemical substance influence on environment-related
Research InstitutionGifu Pharmaceutical University

Principal Investigator

Nakanishi Tsuyoshi  岐阜薬科大学, 薬学部, 教授 (50303988)

Co-Investigator(Kenkyū-buntansha) 永瀬 久光  岐阜薬科大学, 薬学部, 名誉教授 (40141395)
木村 朋紀  摂南大学, 理工学部, 准教授 (70340859)
井戸 章子  岐阜薬科大学, 薬学部, 助教 (00336629)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Keywordsフルオレン9-ビスフェノール / エストロゲン作動性 / 内分泌かく乱
Outline of Final Research Achievements

In this study, we conducted a risk assessment of fluorene-9-bisphenol (BHPF), a bisphenol A alternative for which no prior risk assessment has been performed. We evaluated BHPF toxicity using a guideline-based toxicity test and investigated its endocrine-disrupting effects in detail using estrogen-responsive reporter mice that we established. As a result, we identified the no-observed-adverse-effect level (NOAEL) of BHPF and determined a dose range within which it can be safely used. Additionally, although BHPF was detected in human blood at low levels, its presence suggests that humans are exposed to a certain amount of BHPF.

Academic Significance and Societal Importance of the Research Achievements

BHPFは、飲料水用のペットボトル等に使用されているにもかかわらず、これまでその毒性に関する情報が全く存在しなかった。本研究では無毒性量を同定することで、その安全使用に関する用量域を示すことができたことから、学術的意義はもちろんのこと社会的意義も非常に大きい成果であると言える。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (53 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (7 results) Journal Article (15 results) (of which Int'l Joint Research: 10 results,  Open Access: 13 results,  Peer Reviewed: 14 results) Presentation (31 results) (of which Int'l Joint Research: 1 results,  Invited: 12 results)

  • [Int'l Joint Research] Peking University(中国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Porto(ポルトガル)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Peking University(中国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Porto(ポルトガル)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Peking University(中国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Porto(ポルトガル)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Peking University(中国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 内分泌かく乱に起因する生殖発生毒性評価の問題点とその将来展望2022

    • Author(s)
      中西 剛
    • Journal Title

      Farumashia

      Volume: 58 Issue: 1 Pages: 44-49

    • DOI

      10.14894/faruawpsj.58.1_44

    • NAID

      130008138922

    • ISSN
      0014-8601, 2189-7026
    • Related Report
      2021 Annual Research Report
    • Open Access
  • [Journal Article] Discovery of contaminants with antagonistic activity against retinoic acid receptor in house dust.2021

    • Author(s)
      Jia Y, Zhang H, Hu W, Wang L, Kang Q, Liu J, Nakanishi T, Hiromori Y, Kimura T, Tao S, Hu J.
    • Journal Title

      J. Hazard. Mater.

      Volume: 426 Pages: 127847-127847

    • DOI

      10.1016/j.jhazmat.2021.127847

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Triphenyl phosphate delayed pubertal timing and induced decline of ovarian reserve in mice as an estrogen receptor antagonist2021

    • Author(s)
      Ma Haojia、Ishida Keishi、Xu Chenke、Takahashi Kyosuke、Li Yu、Zhang Chenhao、Kang Qiyue、Jia Yingting、Hu Wenxin、Matsumaru Daisuke、Nakanishi Tsuyoshi、Hu Jianying
    • Journal Title

      Environmental Pollution

      Volume: 290 Pages: 118096-118096

    • DOI

      10.1016/j.envpol.2021.118096

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Alginate-coated activated charcoal enhances fecal excretion of 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin in mice, with fewer side effects than uncoated one2021

    • Author(s)
      Dungkokkruad Pinyapach、Tomita Shunsuke、Hiromori Youhei、Ishida Keishi、Matsumaru Daisuke、Mekada Kyoko、Nagase Hisamitsu、Tanaka Keiichi、Nakanishi Tsuyoshi
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 46 Issue: 8 Pages: 379-389

    • DOI

      10.2131/jts.46.379

    • NAID

      130008070936

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Maternal transfer of 2-ethylhexyl diphenyl phosphate leads to developmental toxicity possibly by blocking the retinoic acid receptor and retinoic X receptor in Japanese Medaka (Oryzias latipes).2021

    • Author(s)
      Yu Li, Haojia Ma, Ruichao Chen, Hong Zhang, Tsuyoshi Nakanishi, Jianying Hu
    • Journal Title

      Environmental Science & Technology

      Volume: 55 Issue: 8 Pages: 5056-5064

    • DOI

      10.1021/acs.est.0c06809

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] An ancestral nuclear receptor couple, PPAR-RXR, is exploited by organotins2021

    • Author(s)
      Capit?o Ana M.F.、Lopes-Marques M?nica、P?scoa In?s、Sainath S.B.、Hiromori Youhei、Matsumaru Daisuke、Nakanishi Tsuyoshi、Ruivo Raquel、Santos Miguel M.、Castro L. Filipe C.
    • Journal Title

      Science of The Total Environment

      Volume: 797 Pages: 149044-149044

    • DOI

      10.1016/j.scitotenv.2021.149044

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CpG site-specific regulation of metallothionein-1 gene expression2020

    • Author(s)
      Shoko Ogushi, Yuya Yoshida, Tsuyoshi Nakanishi, Tomoki Kimura
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 17 Pages: 5946-5946

    • DOI

      10.3390/ijms21175946

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tri-substituted organotin compounds, but not retinoic acid, are potent ligands of complement component 8 γ2020

    • Author(s)
      Yamamoto Katsuya、Hiromori Youhei、Matsumaru Daisuke、Ishii Yoichiro、Takeshita Yuki、Tsubakihara Iori、Kimura Tomoki、Nagase Hisamitsu、Nakanishi Tsuyoshi
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 45 Issue: 9 Pages: 581-587

    • DOI

      10.2131/jts.45.581

    • NAID

      130007895029

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo profiling of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced estrogenic/anti-estrogenic effects in female estrogen-responsive reporter transgenic mice.2020

    • Author(s)
      Yoshida I, Ishida K, Yoshikawa H, Kitamura S, Hiromori Y, Nishioka Y, Ido A, Kimura T, Nishikawa JI, Hu J, Nagase H, Nakanishi T.
    • Journal Title

      J Hazard Mater.

      Volume: 385 Pages: 121526-121526

    • DOI

      10.1016/j.jhazmat.2019.121526

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cadmium inhibits all-trans-retinoic acid-induced increase of nitroblue tetrazolium reduction activity and induces metallothionein 1G expression in human acute myelocytic leukemia HL-60 Cells2020

    • Author(s)
      Shoko Ogushi, Shuji Ikemoto, Nobuhiko Miura, Tsuyoshi Nakanishi, Tomoki Kimura
    • Journal Title

      BPB Reports

      Volume: 3 Pages: 34-38

    • NAID

      130007944907

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term cadmium exposure enhances metallothionein-1 induction after subsequent exposure to high concentrations of cadmium in P1798 mouse lymphosarcoma cells2019

    • Author(s)
      Tomoki Kimura, Takuomi Hosaka, Tsuyoshi Nakanishi, Osamu Aozasa
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 44 Issue: 4 Pages: 309-316

    • DOI

      10.2131/jts.44.309

    • NAID

      130007623314

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Screening of House Dust from Chinese Homes for Chemicals with Liver X Receptors Binding Activities and Characterization of Atherosclerotic Activity Using an in Vitro Macrophage Cell Line and ApoE-/- Mice.2019

    • Author(s)
      Hu W, Jia Y, Kang Q, Peng H, Ma H, Zhang S, Hiromori Y, Kimura T, Nakanishi T, Zheng L, Qiu Y, Zhang Z, Wan Y, Hu J.
    • Journal Title

      Environ Health Perspect

      Volume: 127 Issue: 11 Pages: 117003-117003

    • DOI

      10.1289/ehp5039

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An Orthologue of the Retinoic Acid Receptor (RAR) Is Present in the Ecdysozoa Phylum Priapulida.2019

    • Author(s)
      Fonseca ESS, Hiromori Y, Kaite Y, Ruivo R, Franco JN, Nakanishi T, Santos MM, Castro LFC.
    • Journal Title

      Genes (Basel)

      Volume: 10 Issue: 12 Pages: 985-985

    • DOI

      10.3390/genes10120985

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genomic integration and ligand-dependent activation of the human estrogen receptor α in the crustacean Daphnia magna2018

    • Author(s)
      Toerner Kerstin、Nakanishi Tsuyoshi、Matsuura Tomoaki、Kato Yasuhiko、Watanabe Hajime
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 6 Pages: e0198023-e0198023

    • DOI

      10.1371/journal.pone.0198023

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evolutionary Exploitation of Vertebrate Peroxisome Proliferator-Activated Receptor γ by Organotins2018

    • Author(s)
      Capitao Ana M. F.、Lopes-Marques Monica S.、Ishii Yoichiro、Ruivo Raquel、Fonseca Elza S. S.、Piscoa Ines、Jorge Rodolfo P.、Barbosa Melanie A. G.、Hiromori Youhei、Miyagi Takayuki、Nakanishi Tsuyoshi、Santos Miguel M.、Castro L. Filipe C.
    • Journal Title

      Environmental Science & Technology

      Volume: 52 Issue: 23 Pages: 13951-13959

    • DOI

      10.1021/acs.est.8b04399

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] アンドロゲン高産生マウスを用いたアンドロゲン依存的なエンドポイントの同定と毒性試験への応用2022

    • Author(s)
      中西 剛
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] In vivoイメージングを用いたダイオキシンのエストロゲンシグナルかく乱評価2022

    • Author(s)
      石田 慶士、中西 剛
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] アンドロゲン高産生マウスを用いたアンドロゲン作動性に起因するエンドポイントの同定と毒性試験への応用2021

    • Author(s)
      中西 剛
    • Organizer
      第48回日本毒性学会学術年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] In vivoイメージングを応用した新規エストロゲン作動性スクリーニング試験法の確立2021

    • Author(s)
      中西 剛
    • Organizer
      第23回環境ホルモン学会研究発表会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 神経分化トレーサーマウスを用いた新規発達神経毒性評価系の有用性検証2021

    • Author(s)
      南川 祥輝、 石田 慶士、 森 一馬、 辰巳 佳乃子、 松丸 大輔、 田熊 一敞、中西 剛
    • Organizer
      フォーラム2021: 衛生薬学・環境トキシコロジー
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新規発達神経毒性評価系開発に向けた神経分化トレーサーマウスの解析2021

    • Author(s)
      石田 慶士、 南川 祥輝、 森 一馬、 松丸 大輔、 中西 剛
    • Organizer
      第48回日本毒性学会学術年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] In vivo イメージングを応用した新規エストロゲン作動性スクリーニング試験法の確立2021

    • Author(s)
      中西 剛
    • Organizer
      第37回日本毒性病理学会総会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 化学物質の発達神経毒性解明に向けた神経分化トレーサーマウスの構築2021

    • Author(s)
      石田慶士、南川祥輝、森 一馬、松丸大輔、中西 剛
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト型胎盤内分泌機能を持たせたヒト化マウスにおける生殖発生毒性2020

    • Author(s)
      中西 剛
    • Organizer
      第47回日本毒性学会学術年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] リポカリン分子 C8γ の有機スズ化合物との結合性およびその毒性発現に与える影響の解析2020

    • Author(s)
      山本勝也 、松丸大輔、 廣森洋平、永瀬久光、中西 剛
    • Organizer
      生命金属に関する合同年会(Consortium of Metal Biosciences 2020)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 三次元イメージング技術を用いた総排泄腔分割の解析:発生異常メカニズムの解明に向けて2020

    • Author(s)
      松丸大輔、村嶋亜紀、宮川信一、原田理代、山田 源、中西 剛
    • Organizer
      フォーラム2020:衛生薬学・環境トキシコロジー
    • Related Report
      2020 Annual Research Report
  • [Presentation] アンドロゲン高産生マウスを用いた抗アンドロゲン作動性毒性試験の確立と影響評価2020

    • Author(s)
      平野貴大、松丸大輔、伊藤圭祐、目加田京子、西岡 康、永瀬久光、中西 剛
    • Organizer
      フォーラム2020:衛生薬学・環境トキシコロジー
    • Related Report
      2020 Annual Research Report
  • [Presentation] リポカリン分子 C8γはトリフェニルスズの肝臓毒性発現に対し防御的に機能する2020

    • Author(s)
      山本勝也、松丸大輔、椿原伊織、青木 明、廣森洋平、永瀬久光、中西 剛
    • Organizer
      フォーラム2020:衛生薬学・環境トキシコロジー
    • Related Report
      2020 Annual Research Report
  • [Presentation] リポカリン分子C8γの重金属毒性防御機構の解明に向けて:重金属結合性の検討2020

    • Author(s)
      山本勝也、椿原伊織、井戸章子、永瀬久光、松丸大輔、中西 剛
    • Organizer
      第47回日本毒性学会学術年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 重金属によるエストロゲンシグナルのかく乱2019

    • Author(s)
      中西 剛
    • Organizer
      メタルバイオサイエンス研究会2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 核内受容体を介した化学物質の生体影響2019

    • Author(s)
      中西 剛
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 有機スズ化合物による雌性性周期かく乱作用とその分子メカニズム2019

    • Author(s)
      中西 剛
    • Organizer
      第46回 日本毒性学会学術年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] In vivoイメージングを応用したビスフェノールAの低用量エストロゲン作動性評価2019

    • Author(s)
      國谷昌毅、古川誠之、永瀬久光、中西 剛
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アンドロゲン高産生マウスを用いた抗アンドロゲン作動性スクリーニングのための新規エンドポイントの探索2019

    • Author(s)
      平野貴大、伊藤圭祐、目加田京子、西岡 康、松丸大輔、永瀬久光、中西 剛
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Occurrence of fibrates and their metabolites in source and drinking water in Shanghai and Zhejiang, China2019

    • Author(s)
      Nakanishi T, Ido A, Hiromori Y, Nagase H, Jianying Hu
    • Organizer
      15th International Congress of Toxicology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 有機リン系難燃剤Triphenyl phosphateのin vivoエストロゲン作動性と生殖毒性に関する研究2019

    • Author(s)
      髙橋京佑、國谷昌毅、石田慶士、廣森洋平、永瀬久光、Jianying Hu、中西 剛
    • Organizer
      フォーラム2019 衛生薬学・環境トキシコロジー
    • Related Report
      2019 Annual Research Report
  • [Presentation] アンドロゲン高産生マウスを用いた化学物質の新規抗アンドロゲン作用スクリーニング系の構築2019

    • Author(s)
      平野貴大、伊藤圭祐、目加田京子、西岡 康、永瀬久光、中西 剛
    • Organizer
      フォーラム2019 衛生薬学・環境トキシコロジー
    • Related Report
      2019 Annual Research Report
  • [Presentation] エストロゲン応答性レポーターマウスを用いたビスフェノールAの低用量影響評価2019

    • Author(s)
      國谷昌毅、古川誠之、永瀬久光、中西 剛
    • Organizer
      フォーラム2019 衛生薬学・環境トキシコロジー
    • Related Report
      2019 Annual Research Report
  • [Presentation] XX性分化疾患モデルマウスを用いた抗アンドロゲン剤の生殖機能異常の回復効果の解析2019

    • Author(s)
      伊藤圭祐, 目加田京子, 西岡康, 永瀬久光, 中西 剛
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] エストロゲン応答性レポーターマウスを用いたエストロゲン作動性化学物質の非線形応答反応の検出2019

    • Author(s)
      國谷昌毅, 古川誠之, 永瀬久光, 中西 剛
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 重金属による免疫機能の老化2018

    • Author(s)
      中西 剛
    • Organizer
      メタルバイオサイエンス研究会2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 水系環境中に存在する核内受容体作動性ハザードの生体影響2018

    • Author(s)
      中西 剛
    • Organizer
      第21回環境ホルモン学会研究発表会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 水系環境中に存在する核内受容体作動性ハザードの生体影響2018

    • Author(s)
      中西 剛
    • Organizer
      平成30年度地方衛生研究所全国協議会東海・北陸支部 衛生化学部会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 有機リン系難燃剤のヒト胎盤の内分泌機能に対する影響2018

    • Author(s)
      廣森洋平、Wenxin Hu、Fumei Gao、Hong Zhang、荒川脩平、原田均、永瀬久光、中西 剛、Jianying Hu
    • Organizer
      第45回日本毒性学会学術年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 46,XX性分化疾患モデルマウスにおける抗アンドロゲン剤の生殖機能回復効果の解析2018

    • Author(s)
      伊藤圭祐、目加田京子、西岡康、永瀬久光、中西 剛
    • Organizer
      フォーラム2018 衛生薬学・環境トキシコロジー
    • Related Report
      2018 Annual Research Report
  • [Presentation] エストロゲン応答性レポーターマウスを用いたin vivoスクリーニング試験法の構築と非線形応答反応の検出2018

    • Author(s)
      國谷昌毅、古川誠之、永瀬久光、中西 剛
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部 合同学術大会2018
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2025-03-27  

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