ペット動物の化学汚染：有機ハロゲン化合物および代謝物の暴露実態解明とリスク評価

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25241013
• Research Institution: Ehime University
• Principal Investigator: 田辺 信介 愛媛大学, 沿岸環境科学研究センター, 教授 (60116952)
• Co-Investigator(Kenkyū-buntansha): 岩田 久人 愛媛大学, 沿岸環境科学研究センター, 教授 (10271652) ; 野見山 桂 愛媛大学, 沿岸環境科学研究センター, 准教授 (30512686) ; 国末 達也 愛媛大学, 沿岸環境科学研究センター, 教授 (90380287)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 有機ハロゲン化合物 / ペット動物 / 代謝 / 甲状腺ホルモン

Outline of Annual Research Achievements

国内のペットのイヌ・ネコを対象に有機ハロゲン化合物および水酸化代謝物による汚染実態の解明と甲状腺ホルモン（THs）へ及ぼす影響を明らかにするため、血清中有機ハロゲン化合物を分析するとともに、LC-MS/MSを用いてTHs濃度を高精度で測定し、THsの恒常性へ及ぼす影響について検証した｡
1) 分析の結果、ネコのDecaBDEによる高濃度汚染が明らかとなった。日本におけるPBDEs製剤の使用はDeca製剤が主体であり、ペットフードやハウスダストも同様の組成を示したことから、Deca製剤によるペット動物への遍在的な汚染が明らかとなった。
2）イヌ・ネコ血清中のTHsと有機ハロゲン化合物濃度の関係を解析した結果、ネコで複数の汚染物質とTHsの間に有意な負の相関関係が認められた。さらに、PLS解析を用いてこれらの汚染物質がTHsに及ぼす影響の強さを評価した結果、DecaBDEが最も強い影響度を示した。。これらの結果より、恒常的なDecaBDEへの曝露がペットネコの甲状腺機能を撹乱している可能性が示された。
3) イヌおよびネコを対象にPCBs 12異性体のin vivo曝露試験を実施し、体内動態および代謝に関わる酵素や遺伝子を解析した。
曝露開始後から経時採血した血清中PCBsおよびOH-PCBsを分析し、両種を比較した結果、低塩素化異性体と高塩素化異性体の残留パターンに差がみられ、ネコは低塩素化OH-PCBsの毒性影響を受けやすいことが推察された。さらに代謝酵素活性を解析した結果、両種ともにPCBs曝露によりシトクロムP450(CYPs)の活性は上昇するが、ネコのグルクロン酸抱合酵素、硫酸抱合酵素活性は変化せず、PCBs曝露がネコの抱合化能に影響しないことが明らかとなった。ネコは有機ハロゲン化合物に対しても特異な体内動態を示す可能性があり、ネコの代謝能や薬物動態に関してさらなる研究が必要である。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Organohalogen compounds in pet dog and cat: do pets biotransform natural brominated products in food to harmful hydroxlated substances? (2016)
  • Author(s): Mizukawa H, Nomiyama K, Nakatsu S, Iwata H, Yoo J, Kubota A, Yamamoto M, Ishizuka M, Ikenaka Y, Nakayama S M M, Kunisue,T, Tanabe S
  • Journal Title: Environmental Science and Technology Volume: 50 Pages: 444-452
  • DOI: doi: 10.1021/acs.est.5b04216
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] In Vitro and in Silico Analyses for Predicting Hepatic Cytochrome P450-Dependent Metabolic Potencies of Polychlorinated Biphenyls in the Baikal Seal (2015)
  • Author(s): Yoo J, Hirano M, Mizukawa H, Nomiyama K, Agusa T, Kim EY, Tanabe S, Iwata H.
  • Journal Title: Environmental Science and Technology Volume: 49 Pages: 14588-14596
  • DOI: doi: 10.1021/acs.est.5b03890
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Uptake and Tissue Distribution of Pharmaceuticals and Personal Care Products in Wild Fish from Treated-Wastewater-Impacted Streams (2015)
  • Author(s): Tanoue R, Nomiyama K, Nakamura H, Kim JW, Isobe T, Shinohara R, Kunisue T, Tanabe S.
  • Journal Title: Environmental Science and Technology Volume: 49 Pages: 11649-11658
  • DOI: doi: 10.1021/acs.est.5b02478
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Uridine Diphosphate-Glucuronosyltransferase (UGT) Xenobiotic Metabolizing Activity and Genetic Evolution in Pinniped Species (2015)
  • Author(s): Kakehi M, Ikenaka Y, Nakayama SM, Kawai YK, Watanabe KP, Mizukawa H, Nomiyama K, Tanabe S, Ishizuka M
  • Journal Title: Toxicological Science Volume: 147 Pages: 360-369
  • DOI: doi: 10.1093/toxsci/kfv144
  • Peer Reviewed / Open Access
• [Journal Article] Residue profiles of organohalogen compounds in human serum from e-waste recycling sites in North Vietnam: Association with thyroid hormone levels (2015)
  • Author(s): Eguchi A, Nomiyama K, Minh Tue N, Trang PT, Hung Viet P, Takahashi S, Tanabe S
  • Journal Title: Environmental Research Volume: 137 Pages: 440-449
  • DOI: doi: 10.1016/j.envres.2015.01.007
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Uptake and tissue distribution of pharmaceuticals and personal care products in wild fish from treated-waste water impacted streams (2016)
  • Author(s): Rumi Tanoue,Kei Nomiyama,Haruna Nakamura,Joon-Woo Kim,Tomohiko Isobe,Ryota Shinohara,Tatsuya Kunisue,Shinsuke Tanabe
  • Organizer: International Symposium on Environmental Chemistry and Toxicology - To Accelerate a Global Network of Environmental Researchers
  • Place of Presentation: Matsuyama, Japan
  • Year and Date: 2016-03-19 – 2016-03-19
  • Int'l Joint Research
• [Presentation] Biotransformation potencies of polychlorinated biphenyls in cats (2016)
  • Author(s): Hazuki Mizukawa,Misaki Maehara,Nozomu Yokoyama,Osamu Ichii,Mitsuyoshi Takiguchi,Kei Nomiyama,Yoshinori Ikenaka,Shouta M. M. Nakayama,Shinsuke Tanabe,Mayumi Ishizuka
  • Organizer: International Symposium on Environmental Chemistry and Toxicology - To Accelerate a Global Network of Environmental Researchers
  • Place of Presentation: Matsuyama, Japan
  • Year and Date: 2016-03-19 – 2016-03-19
  • Int'l Joint Research
• [Presentation] Toxicological assessment of PCBs and OH-PCBs in cat using metabolomics approach (2016)
  • Author(s): Hiroyuki Nishikawa,Kei Nomiyama,Akifumi Eguchi,Hazuki Mizukawa,Mayumi Ishizuka,Yoshinori Ikenaka,Shouta M. M. Nakayama,Shinsuke Tanabe
  • Organizer: International Symposium on Environmental Chemistry and Toxicology-To Accelerate a Global Network of Environmental Researchers
  • Place of Presentation: Matsuyama, Japan
  • Year and Date: 2016-03-19 – 2016-03-19
  • Int'l Joint Research
• [Presentation] Toxicological assessment of polychlorinated biphenyls and their metabolites in the Baikal seal (Pusa sibirica)Toxicological assessment of polychlorinated biphenyls and their metabolites in the Baikal seal (Pusa sibirica) (2015)
  • Author(s): Kei Nomiyama, Shusaki Hirakawa, Chika Kanbara, Daisuke Imaeda, Jean Yoo, Tatsuya Kunisue, Eun-Young Kim, Hisato Iwata, Shinsuke Tanabe
  • Organizer: Leading Symposium on Chemical Hazard and Adaptability in Animals - The Current Challenge of Young Researchers
  • Place of Presentation: Hokkaido Univ. Sapporo, Japan
  • Year and Date: 2015-12-11 – 2015-12-11
  • Int'l Joint Research / Invited
• [Presentation] Impact of anthropogenic and naturally occurring brominated compounds in veterinary field. (2015)
  • Author(s): Hazuki Mizukawa, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M. Nakayama, Kei Nomiyama, Misaki Maehara, Shinsuke Tanabe, Mayumi Ishizuka
  • Organizer: Leading Symposium on Chemical Hazard and Adaptability in Animals - The Current Challenge of Young Researchers
  • Place of Presentation: Hokkaido Univ. Sapporo, Japan
  • Year and Date: 2015-12-11 – 2015-12-11
  • Int'l Joint Research
• [Presentation] イヌ脳に及ぼす PCBs の影響：プロテオーム解析による評価 (2015)
  • Author(s): 高口倖暉・野見山 桂Claret Lauan Maria・Jean Yoo・水川葉月・岩田久人・国末達也・田辺信介
  • Organizer: 環境ホルモン学会第18回研究発表会
  • Place of Presentation: 栃木県下野市 自治医科大学
  • Year and Date: 2015-12-10 – 2015-12-11
• [Presentation] イヌ脳中 PCBs, OH-PCBs の毒性影響評価：メタボロミクスアプローチ (2015)
  • Author(s): 野見山 桂・江口哲史・水川葉・Jean Yoo・高口倖暉・山本泰央・国末達也・岩田久人・田辺信介
  • Organizer: 環境ホルモン学会第18回研究発表会
  • Place of Presentation: 栃木県下野市 自治医科大学
  • Year and Date: 2015-12-10 – 2015-12-11
• [Presentation] Lipid composition in the brain compartments of striped dolphins (Stenella coeruleoalba) in relation to the accumulation of environmental pollutants (PCBs and OH-PCBs) (2015)
  • Author(s): Mari Ochiai, Kei Nomiyama, Tomohiko Isobe, Tadasu K. Yamada, Yuko Tajima, Hisato Iwata, Masao Amano, Shinsuke Tanabe
  • Organizer: Society of Environmental Toxicology and Chemistry (SETAC) North America 36th Annual Meeting
  • Place of Presentation: San Francisco, California, USA
  • Year and Date: 2015-11-14 – 2015-11-18
  • Int'l Joint Research
• [Presentation] Omics approach of proteomic and metabolomic analysis for PCBs toxicity in the dog brain (2015)
  • Author(s): Kohki Takaguchi, Kei Nomiyama, Maria C. Lauan, Jean Yoo, Hazuki Mizukawa, Hisato Iwata, Tatsuya Kunisue, Shinsuke Tanabe
  • Organizer: Society of Environmental Toxicology and Chemistry (SETAC) North America 36th Annual Meeting
  • Place of Presentation: Salt Lake City, Utah, USA
  • Year and Date: 2015-11-01 – 2015-11-05
  • Int'l Joint Research
• [Presentation] Toxicological assessment of polychlorinated biphenyls (PCBs) and hydroxylated PCBs (OH-PCBs) in the brain of dogs using metabolomics approach (2015)
  • Author(s): Kei Nomiyama, Akifumi Eguchi, Hazuki Mizukawa, Jean Yoo, Kohki Takaguchi, Yasuo Yamamoto, Tomoko Oshihoi, Hisato Iwata, Tatsuya Kunisue, Shisuke Tanabe
  • Organizer: Society of Environmental Toxicology and Chemistry (SETAC) North America 36th Annual Meeting
  • Place of Presentation: Salt Lake City, Utah, USA
  • Year and Date: 2015-11-01 – 2015-11-05
  • Int'l Joint Research
• [Presentation] Metabolism and biotransformation of organohalogen compounds in the liver microsomes of cats and dogs. (2015)
  • Author(s): Hazuki Mizukawa, Kei Nomiyama, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M. Nakayama, Misaki Maehara, Shisuke Tanabe Mayumi Ishizuka
  • Organizer: Society of Environmental Toxicology and Chemistry (SETAC) North America 36th Annual Meeting
  • Place of Presentation: Salt Lake City, Utah, USA
  • Year and Date: 2015-11-01 – 2015-11-05
  • Int'l Joint Research
• [Presentation] Contamination status of organohalogen compounds and their hydroxylated metabolites in pet cats: Effects on thyroid hormones homeostasis (2015)
  • Author(s): Yasuo Yamamoto, Kei Nomiyama, Hazuki Mizukawa, Kohki Takiguchi, Mayumi Ishizuka, Tatsuya Kunisue, Shinsuke Tanabe
  • Organizer: Society of Environmental Toxicology and Chemistry (SETAC) North America 36th Annual Meeting
  • Place of Presentation: Salt Lake City, Utah, USA
  • Year and Date: 2015-11-01 – 2015-11-05
  • Int'l Joint Research
• [Presentation] II 相抱合反応の種差：食肉目におけるグルクロン酸抱合酵素の進化と遺伝子構造 (2015)
  • Author(s): 池中良徳・筧 麻友・中山翔太・川合佑典・渡邊研右・水川葉月・野見山 桂・田辺信介・石塚真由美
  • Organizer: 第24回環境化学討論会
  • Place of Presentation: 北海道札幌市 札幌コンベンションセンター
  • Year and Date: 2015-06-24 – 2015-06-26
• [Presentation] メタボローム解析によるイヌ脳中PCBs, OH-PCBs の毒性影響評価 (2015)
  • Author(s): 野見山桂・江口哲史・水川葉月・Jean Yoo・高口倖暉・山本泰央・忍穂井智子・岩田久人・国末達也・田辺信介
  • Organizer: 第24回環境化学討論会
  • Place of Presentation: 北海道札幌市 札幌コンベンションセンター
  • Year and Date: 2015-06-24 – 2015-06-26
• [Presentation] ポリ塩化ビフェニル（PCBs）を曝露したイヌの脳プロテオーム解析による毒性影響評価 (2015)
  • Author(s): 高口倖暉・野見山 桂・Claret Lauan Maria・草木桃子・Jean Yoo・水川葉月・岩田久人・国末達也・田辺信介
  • Organizer: 第24回環境化学討論会
  • Place of Presentation: 北海道札幌市 札幌コンベンションセンター
  • Year and Date: 2015-06-24 – 2015-06-26
• [Presentation] ペットネコにおける有機ハロゲン化合物および水酸化代謝物の汚染実態と甲状腺ホルモン恒常性への影響 (2015)
  • Author(s): 山本恭央・野見山 桂・水川葉月・滝口満喜・石塚真由美・国末達也・田辺信介
  • Organizer: 第24回環境化学討論会
  • Place of Presentation: 北海道札幌市 札幌コンベンションセンター
  • Year and Date: 2015-06-24 – 2015-06-26
• [Remarks] 研究トピックス
  • URL: https://www.ehime-u.ac.jp/post-1439/
• [Remarks] ACSニュース
  • URL: http://www.acs.org/content/acs/en/pressroom/presspacs/2016/acs-presspac-january-6-2016/fish-flavored-cat-food-could-contribue-to-feline-hyperthyroidism.html