Modeling and inter-individual difference of pharmacokinetics of persistent organofluorine compounds

• Project/Area Number: 20590597
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Kyoto University
• Principal Investigator: HARADA Kouji Kyoto University, 大学院・医学研究科, 准教授 (80452340)
• Co-Investigator(Renkei-kenkyūsha): KOIZUMI Akio 京都大学, 大学院・医学研究科, 教授 (50124574) ; MINATA Mutsuko 京都大学, 大学院・医学研究科, 助教 (00456857)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 衛生 / 環境 / 分析化学 / 社会医学 / 薬学 / 薬物動態学 / 分析科学

Research Abstract

Perfluorooctanoic acid (PFOA) is a synthetic fluorochemical. PFOA shows extremely long half-life in humans. Long chain homologues in serum were increased in a decade. We developed toxicokinetics model and modeling of serum levels in general population agreed with observed levels. We found a large renal excretion of PFOA in Abcb4-deficient mice and using a microarray approach ATP-binding cassette, sub-family B, member 1B (Abcb1b) was shown to be a renal transporter of PFOA using abcb1a/1b null mice.

Research Products

• [Journal Article] Environmental ecological modeling of human blood lead levels in East Asia. (2011)
  • Author(s): Niisoe T, Harada KH, Hitomi T, Watanabe T, Hung NN, Ishikawa H, Wang Z, Koizumi A.
  • Journal Title: Environ Sci Technol 45 Pages: 2856-62
  • Peer Reviewed
• [Journal Article] Detection of dicofol and related pesticides in human breast milk from China, Korea and Japan. (2011)
  • Author(s): Fujii Y, Haraguchi K, Harada KH, Hitomi T, Inoue K, Itoh Y, Watanabe T, Takenaka K, Uehara S, Yang HR, Kim MY, Moon CS, Kim HS, Wang P, Liu A, Hung NN, Koizumi A.
  • Journal Title: Chemosphere 82 Pages: 25-31
  • Peer Reviewed
• [Journal Article] Mycotoxin Detection in Urine Samples from Patients with Chronic Kidney Disease of Uncertain Etiology in Sri Lanka. (2011)
  • Author(s): Desalegn B, Nanayakkara S, Harada KH, Hitomi T, Chandrajith R, Karunaratne U, Abeysekera T, Koizumi A.
  • Journal Title: Bull Environ Contam Toxicol
  • Peer Reviewed
• [Journal Article] Historical trends in human dietary intakes of endosulfan and toxaphene in China, Korea and Japan. (2011)
  • Author(s): Desalegn B, Takasuga T, Harada KH, Hitomi T, Fujii Y, Yang HR, Wang P, Senevirathna S, Koizumi A.
  • Journal Title: Chemosphere
  • Peer Reviewed
• [Journal Article] Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: geographic distribution and environmental implications. (2011)
  • Author(s): Chandrajith R, Nanayakkara S, Itai K, Aturaliya TN, Dissanayake CB, Abeysekera T, Harada K, Watanabe T, Koizumi A.
  • Journal Title: Environ Geochem Health DOI : 10.1007/s10653-010-9339-1.
  • Peer Reviewed
• [Journal Article] Detection of dicofol and related pesticides in human breast milk from China, Korea and Japan (2011)
  • Author(s): Fujii, et al.
  • Journal Title: Chemosphere Volume: 82 Pages: 25-31
  • Peer Reviewed
• [Journal Article] Historical trends in human dietary intakes of endosulfan and toxaphene in China, Korea and Japan (2011)
  • Author(s): Desalegn, et al.
  • Journal Title: Chemosphere Volume: (受理済み)
  • Peer Reviewed
• [Journal Article] Long-Term Simulation of Human Exposure to Atmospheric Perfluorooctanoic Acid (PFOA) and Perfluorooctanoate (PFO) in the Osaka Urban Area, Japan. (2010)
  • Author(s): Niisoe T, Harada KH, Ishikawa H, Koizumi A.
  • Journal Title: Environ Sci Technol 44 Pages: 7852-7
  • Peer Reviewed
• [Journal Article] A global transport model of lead in the atmosphere. (2010)
  • Author(s): Niisoe T, Nakamura E, Harada K, Ishikawa H, Hitomi T, Watanabe T, Wang Z, Koizumi A.
  • Journal Title: Atmos Environ 44 Pages: 1806-14
  • Peer Reviewed
• [Journal Article] Levels of perfluorooctane sulfonate and perfluorooctanoic acid in female serum samples from Japan in 2008, Korea in 1994-2008 and Vietnam in 2007-2008. (2010)
  • Author(s): Harada KH, Yang HR, Moon CS, Hung NN, Hitomi T, Inoue K, Niisoe T, Watanabe T, Kamiyama S, Takenaka K, Kim MY, Watanabe K, Takasuga T, Koizumi A.
  • Journal Title: Chemosphere 79 Pages: 314-9
  • Peer Reviewed
• [Journal Article] Role of Peroxisome Proliferator-activated Receptor-alpha in Hepatobiliary Injury Induced by Ammonium Perfluorooctanoate in Mouse Liver. (2010)
  • Author(s): Minata M, Harada KH, Karrman A, Hitomi T, Hirosawa M, Murata M, Gonzalez FJ, Koizumi A.
  • Journal Title: Ind Health 48 Pages: 96-107
  • NAID: 130004828559
  • Peer Reviewed
• [Journal Article] Long-term simulation of human exposure to atmospheric perfluorooctanoic acid (PFOA) and perfluorooctanoate (PFO) in the Osaka urban area, Japan (2010)
  • Author(s): Niisoe T, et al.
  • Journal Title: Environ Sci Technol Volume: 44 Pages: 7852-7857
  • Peer Reviewed
• [Journal Article] Levels of perfluorooctane sulfonate and perfluorooctanoic acid in female serum samples from Japan in 2008, Korea in 1994-2008 and Vietnam in 2007-2008 (2010)
  • Author(s): Harada, et al.
  • Journal Title: Chemosphere Volume: 79 Pages: 314-319
  • Peer Reviewed
• [Journal Article] Levels of perfluorooctane sulfonate and perfluorootanoic acid in female serum samples from Japan in 2008, Korea in 1994-2008 and Vietnam in 2007-2008 (2010)
  • Author(s): Harada KH, et al.
  • Journal Title: Chemosphere 79 Pages: 314-319
  • Peer Reviewed
• [Journal Article] Role of peroxisome proliferator-activated receptor-α in hepatobiliary injury induced by ammonium perfluorooctanoate in mouse liver (2010)
  • Author(s): Minata M, et al.
  • Journal Title: Ind Health 48 Pages: 96-107
  • Peer Reviewed
• [Journal Article] Human organic anion transporter hOAT4 is a transporter of perfluorooctanoic acid. (2009)
  • Author(s): Nakagawa H, Terada T, Harada KH, Inoue K, Inui K, Koizumi A.
  • Journal Title: Basic Clin Pharmacol Toxicol
  • Peer Reviewed
• [Journal Article] Polyfluorinated telomers in precipitation and surface water in an urban area of Japan. (2009)
  • Author(s): Mahmoud MA, Karrman A, Oono S, Harada KH, Koizumi A.
  • Journal Title: Chemosphere 74 Pages: 467-72
  • Peer Reviewed
• [Journal Article] Paradoxical increases in serum levels of highly chlorinated PCBs in aged women in clear contrast to robust decreases in dietary intakes from 1980 to 2003 in Japan. (2009)
  • Author(s): Koizumi A, Harada KH, Eslami B, Fujimine Y, Hachiya N, Hirosawa I, Inoue K, Inoue S, Koda S, Kusaka Y, Murata K, Omae K, Saito N, Shimbo S, Takenaka K, Takeshita T, Todoriki H, Wada Y, Watanabe T, Ikeda M.
  • Journal Title: Environ Health Prev Med 14 Pages: 235-46
  • NAID: 10026959024
  • Peer Reviewed
• [Journal Article] Reconstruction of human exposure to heavy metals using synchrotron radiation microbeams in prehistoric and modern humans. (2009)
  • Author(s): Koizumi A, Azechi M, Shirasawa K, Saito N, Saito K, Shigehara N, Sakaue K, Shimizu Y, Baba H, Yasutake A, Harada K, Yoshinaga T, Ide-Ektessabi A.
  • Journal Title: Environmental Health and Preventive Medicine 14 Pages: 52-9
  • NAID: 10026958210
  • Peer Reviewed
• [Journal Article] Relationship between dietary exposure and serum perfluorochemical (PFC) levels-a case study. (2009)
  • Author(s): Karrman A, Harada KH, Inoue K, Takasuga T, Ohi E, Koizumi A.
  • Journal Title: Environ Int 35 Pages: 712-7
  • Peer Reviewed
• [Journal Article] Levels and regional trends of persistent organochlorines and polybrominated diphenyl ethers in Asian breast milk demonstrate POPs signatures unique to individual countries. (2009)
  • Author(s): Haraguchi K, Koizumi A, Inoue K, Harada KH, Hitomi T, Minata M, Tanabe M, Kato Y, Nishimura E, Yamamoto Y, Watanabe T, Takenaka K, Uehara S, Yang HR, Kim MY, Moon CS, Kim HS, Wang P, Liu A, Hung NN.
  • Journal Title: Environ Int 35 Pages: 1072-9
  • Peer Reviewed
• [Journal Article] Cleft palate caused by perfluorooctane sulfonate is caused mainly by extrinsic factors. (2009)
  • Author(s): Era S, Harada KH, Toyoshima M, Inoue K, Minata M, Saito N, Takigawa T, Shiota K, Koizumi A.
  • Journal Title: Toxicology 256 Pages: 42-7
  • Peer Reviewed
• [Journal Article] Levels and regional trend of persistent organochlorines and polybyominated diphenyl ethers in Asian breast milk demonstrated POPs signatures unique to individual countries (2009)
  • Author(s): Haraguchi K, et al.
  • Journal Title: Environ Int 35 Pages: 1072-1079
  • Peer Reviewed
• [Journal Article] Human organic anion transporter hOAT4 is a transporter of perfluorooc tanoic acid (2009)
  • Author(s): Nakagawa H, et al.
  • Journal Title: Basic Clin Pharmacol Toxicol 105 Pages: 136-138
  • Peer Reviewed
• [Journal Article] Relationship between dietary exposure and serum perfluorochemical (PFC) levels-a case study (2009)
  • Author(s): Karrman A, et al.
  • Journal Title: Environ Int 35 Pages: 712-717
  • Peer Reviewed
• [Journal Article] Human organic anion transporter hOAT4 is a transporter of perfluorooctanoic acid (2009)
  • Author(s): H. Nakagwa, et al.
  • Journal Title: Basic Clin Pharmacol Toxicol.
  • Peer Reviewed
• [Journal Article] Relationship between dietary exposure and serum perfluorocheml (PFC) levels - a case study (2009)
  • Author(s): A. Karrman, et al.
  • Journal Title: Environ Int
  • Peer Reviewed
• [Journal Article] Roles of organic anion transporters in the renal excretion of perfluorooctanoic acid (2008)
  • Author(s): H. Nakgawa, et al.
  • Journal Title: Basic Clin Pharmacol Toxicol. 103 Pages: 1-8
  • Peer Reviewed
• [Presentation] ペルフルオロアルキル化合物の生物モニタリングから毒性研究へ (2011)
  • Author(s): 原田浩二
  • Organizer: 日本薬学会第131回年会シンポジウム
  • Place of Presentation: 静岡県コンベンションアーツセンター(招待講演)
  • Year and Date: 2011-03-31
• [Presentation] ペルフルオロオクタン酸(PFOA)尿中排出に対するマウス腎臓中多剤排出トランスポーターABCB1A/Bの役割検討 (2011)
  • Author(s): 岡本かほり, ほか
  • Organizer: 第10回分子予防環境医学研究会
  • Place of Presentation: 京都府立医科大学
  • Year and Date: 2011-01-21
• [Presentation] 日中韓の食事試料中の短鎖塩素化パラフィン (2011)
  • Author(s): 原田浩二、高菅卓三、藤井由希子、人見敏明、渡辺孝男、王培玉、小泉昭夫
  • Organizer: 第81回日本衛生学会総会
  • Place of Presentation: 東京都
• [Presentation] 日中韓の母乳中の長鎖有機フッ素化合物(Long chain PFCs)分析 (2011)
  • Author(s): 藤井由希子、厳俊霞、原田浩二、Yang Hyeran、王培玉、人見敏明、小泉昭夫
  • Organizer: 第81回日本衛生学会総会
  • Place of Presentation: 東京都
• [Presentation] 日中韓における食事試料中のエンドスルファンおよびトキサフェンの経年変化 (2011)
  • Author(s): Biruck Desalegn、高菅卓三、原田浩二、人見敏明、藤井由希子、Yang Hyeran、王培玉、Senevirathna Lalantha、小泉昭夫
  • Organizer: 第81回日本衛生学会総会
  • Place of Presentation: 東京都
• [Presentation] スリランカの病因不明の慢性腎臓病患者の尿中マイコトキシン (2011)
  • Author(s): Senevirathna Lalantha、Biruck Desalegn、Shanika Nanayakkara、原田浩二、人見敏明、小泉昭夫
  • Organizer: 第81回日本衛生学会総会
  • Place of Presentation: 東京都
• [Presentation] ペルフルオロオクタン酸の腎排出トランスポーターの探索 (2011)
  • Author(s): 岡本かほり、原田浩二、古川和良、皆田睦子、穐友絹美代、小林果、人見敏明、小泉昭夫
  • Organizer: 第81回日本衛生学会総会
  • Place of Presentation: 東京都
• [Presentation] ベトナムハノイ市における小児血中鉛のシミュレーションとリスク評価 (2011)
  • Author(s): 新添多聞、原田浩二、人見敏明、渡辺孝男、Nguyen Ngoc Hung、石川裕彦、小泉昭夫
  • Organizer: 第81回日本衛生学会総会
  • Place of Presentation: 東京都
• [Presentation] ハウスダスト中ペルフルオロアルキルカルボン酸(PFCAs)の分析と関連要因の検討 (2011)
  • Author(s): 陳聖英、原田浩二、小泉昭夫
  • Organizer: 第81回日本衛生学会総会
  • Place of Presentation: 東京都
• [Presentation] ペルフルオロオクタン酸(PFOA)尿中排出に対するマウス腎臓中多剤排出トランスポーターABCB1A/Bの役割検討 (2011)
  • Author(s): 岡本かほり、原田浩二、古川和良、皆田睦子、穐友絹美代、小林果、人見敏明、小泉昭夫
  • Organizer: 第10回分子予防環境医学研究会
  • Place of Presentation: 京都市
• [Presentation] 東アジアにおける血中有機フッ素化合物の変遷 (2010)
  • Author(s): 原田浩二, ほか
  • Organizer: 第80回日本衛生学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2010-05-09
• [Presentation] POPs IN DIETARY SAMPLES FROM CHINA, KOREA AND JAPAN-TRENDS OF LEGACY & NEW POPs COMPARED TO POPs CANDIDATES, DIOXIN2010. (2010)
  • Author(s): Takasuga T, Nouda C, Matsukami H, Takemori H, Harada K, Fujii Y, Hitomi T, Watanabe T, Yang HR, Moon CS, Wang P, Koizumi A
  • Organizer: the 30th International Symposium on Halogenated Environmental Organic Pollutants and Persistent Organic Pollutants (POPs)
  • Place of Presentation: Texas, USA
• [Presentation] 日本人血清中のhydroxy-およびethoxy-PBDEs (2010)
  • Author(s): 伊藤美子、原口浩一、原田浩二、井上佳代子、人見敏明、竹中勝信、加美山茂利、渡辺孝男、小泉昭夫
  • Organizer: フォーラム2010:衛生薬学・環境トキシコロジー
  • Place of Presentation: 東京都
• [Presentation] ベトナムの成人女性における血中有機フッ素化合物の評価 (2010)
  • Author(s): 原田浩二、Moon Chan-Seok、Yang Hye-Ran、人見敏明, 井上佳代子, 新添多聞、渡辺孝男、加美山茂利、竹中勝信、渡邉清彦、高菅卓三、小泉昭夫、日本、韓国
  • Organizer: 第19回日本環境化学会討論会
  • Place of Presentation: 愛知県
• [Presentation] 東アジアにおける血中有機フッ素化合物の変遷 (2010)
  • Author(s): 原田浩二、Moon Chan-Seok、Yang Hye-Ran、人見敏明、井上佳代子、新添多聞、渡辺男、加美山茂利、竹中勝信、小泉昭夫
  • Organizer: 第80回日本衛生学会総会
  • Place of Presentation: 仙台市
• [Presentation] 日中韓の食事試料中の残留性有機汚染物質(POPs)の濃度の特徴的分布 (2010)
  • Author(s): 藤井由希子、王培玉、Moon Chan-Seok、人見敏明、高菅卓三、原田浩二、渡辺孝男、小泉昭夫
  • Organizer: 第80回日本衛生学会総会
  • Place of Presentation: 仙台市
• [Presentation] ペルフルオロオクタン酸の体内動態におけるリン脂質輸送分子Mdr2の役割の検討 (2010)
  • Author(s): 古川和良、皆田睦子、岡本かほり、穐友絹美代、原田浩二、小泉昭夫
  • Organizer: 第80回日本衛生学会総会
  • Place of Presentation: 仙台市
• [Presentation] Blood Level and Dietary Intake of Metals in Asian countries (2010)
  • Author(s): Hye-Ran Yang、原田浩二、人見敏明、渡辺孝男、Moon Chan-Seok、板井一好、小泉昭夫
  • Organizer: 第80回日本衛生学会総会
  • Place of Presentation: 仙台市
• [Presentation] 関西における大気中PFOAの長期シミュレーション (2010)
  • Author(s): 新添多聞、原田浩二、人見敏明、石川裕彦、渡辺孝男、小泉昭夫
  • Organizer: 第80回日本衛生学会総会
  • Place of Presentation: 仙台市
• [Presentation] ハウスダスト中ペルフルオロオクタン酸の分析と関連要因の予備的検討 (2010)
  • Author(s): 陳聖英、藤井由希子、原田浩二、人見敏明、小泉昭夫
  • Organizer: 第80回日本衛生学会総会
  • Place of Presentation: 仙台市
• [Presentation] Endemic Chronic Kidney Disease of Unknown Etiology in North Central Region of Sri Lanka is a Disease Induced by Focal Renal Ischemia. (2010)
  • Author(s): Shanika Nanayakkara、原田浩二、人見敏明、板井一好、和田安彦、渡辺孝男、小泉昭夫
  • Organizer: 第80回日本衛生学会総会
  • Place of Presentation: 仙台市
• [Presentation] 残留性有機フッ素化合物のバイオモニタリング・曝露・体?内動態・?健康影響 (2009)
  • Author(s): 原田浩二
  • Organizer: 日本内分泌撹乱化学物質学会 第12回研究発表会
  • Place of Presentation: 東京大学山上会館
  • Year and Date: 2009-12-07
• [Presentation] 大気中PFOAの数値シミュレーション (2009)
  • Author(s): 新添多聞、原田浩二、人見敏明、石川裕彦、小泉昭夫
  • Organizer: 第49回近畿産業衛生学会
  • Place of Presentation: 仙台市
  • Year and Date: 2009-11-14
• [Presentation] 難分解性有機フッ素化合物による環境汚染と健康影響 (2009)
  • Author(s): 原田浩二, ほか
  • Organizer: 第68回日本公衆衛生学会総会
  • Place of Presentation: 奈良県文化会館
  • Year and Date: 2009-10-21
• [Presentation] 東アジアにおける血中有機フッ素化合物の変遷、日本産業衛生学会 (2009)
  • Author(s): 原田浩二、Moon Chan-Seok、Yang Hye-Ran、人見敏明、井上佳代子、新添多聞、渡辺孝男、加美山茂利、竹中勝信、小泉昭夫
  • Organizer: 第37回有機溶剤中毒研究会・第42回生物学的モニタリング・バイオマーカー研究会
  • Place of Presentation: 京都市
  • Year and Date: 2009-10-17
• [Presentation] 日中韓越の母乳試料中残留性有機塩素化合物と臭素系難燃剤濃度の特徴的分布 (2009)
  • Author(s): 藤井由希子、原口浩一、井上佳代子、原田浩二、人見敏明、Moon Chan-Seok、Yang Hye-Ran、渡辺孝男、竹中勝信、上原茂樹、小泉昭夫
  • Organizer: 日本産業衛生学会第37回有機溶剤中毒研究会・第42回生物学的モニタリング・バイオマーカー研究会
  • Place of Presentation: 京都市
  • Year and Date: 2009-10-17
• [Presentation] 東アジアにおける血中有機フッ素化合物の変遷 (2009)
  • Author(s): 原田浩二, ほか
  • Organizer: 日本産業衛生学会 第37回有機溶剤中毒研究会・第4?2回生物学的モニタリング・バイオマーカー研究会
  • Place of Presentation: 京都大学
  • Year and Date: 2009-10-17
• [Presentation] 炭素・窒素安定同位体比分析によるヒト血清中アミノ酸と食料源の関係評価 (2009)
  • Author(s): 廣野留都、武蔵正明、中下留美子、鈴木彌生子、伊永隆史、原田浩二、小泉昭夫
  • Organizer: 2009年度日本地球化学会年会
  • Place of Presentation: 東広島市
• [Presentation] 受動捕集法による室内空気中フルオロテロマー類の分析とヒト曝露の推定 (2009)
  • Author(s): 原田浩二、高橋慧、桜町惟、古川和良、大野佐代子、小泉昭夫
  • Organizer: 第18回日本環境化学会討論会
  • Place of Presentation: つくば市
• [Presentation] 生体試料中の残留性有機フッ素化合物測定と曝露源の検討 (2008)
  • Author(s): 原田浩二
  • Organizer: 第17回 日本環境化学会討論会
  • Place of Presentation: 神戸市
  • Year and Date: 2008-06-11
• [Book] 残留性有機汚染物質(721-730)(改訂版)分子予防環境医学-生命科学研究の予防・環境医学への統合-(分子予防環境医学研究会編) (2010)
  • Author(s): 原田浩二、小泉昭夫
  • Publisher: 本の泉社
• [Book] 残留性有機汚染物質(改訂版 分子予防環境医学-生命科学研究の予防・環境医学への統合-:721-730) (2010)
  • Author(s): 分子予防環境医学研究会
  • Total Pages: 850
  • Publisher: 本の泉社
• [Remarks] ホームページ等
  • URL: http://hes.med.kyoto-u.ac.jp/
• [Remarks]
  • URL: http://hes.med.kyoto-u.ac.jp/
• [Remarks]
  • URL: http://hes.pbh.med.kyoto-u.ac.jp/