Study on toxic mechanism of chemical substances eluted from containers and packages and risk assessment

• Project/Area Number: 20390171
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Nagoya University
• Principal Investigator: NASU Tamie 名古屋大学, 大学院・医学系研究科, 教授 (10020794)
• Co-Investigator(Kenkyū-buntansha): MURAKAMI Masami 群馬大学, 大学院・医学系研究科, 教授 (30241871) ; 上島 通浩 名古屋市立大学, 大学院・医学研究科, 教授 (80281070)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2008: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: スチレントリマー / オクタクロロスチレン / アリールハイドロカーボン受容体 / 甲状腺ホルモン / グルクロン酸抱合酵素 / CYP1A1 / ダイオキシン / 妊娠マウス / メカニズム / AAhR / UGT / 3-メチルコラントレン / Hepa-1c1c7 / luciferase活性 / MCF-7 / AhR / 次世代影響 / 環境ホルモン作用 / 薬物代謝酵素 / グルクロン酸転移酵素(UGT) / T4 / T3 / 容器・包装品 / リスク評価

Research Abstract

Wild-type and aromatic hydrocarbon receptor(AhR)-null male mice were orally given 0, 32 and 64. mol/kg styrene trimer or octachloroatyrene for 4 days. Unexpectedly, styrene trimer down-regulated AhR mRNA expression, and accordingly down-regulated CYP1A1 and UGT1A1 and 1A6 mRNA expressions in the liver of wild-type mice. These finding were not observed in AhR-null mice. As a result, styrene trimer increased plasma total and free T4 levels in the wild-type mice.
Octachlorostyrene treatment transactivated AhR and induced CYP1A1 and UGT1A1 in the wild-type mice. However, this chemical did not influence plasma T4 lebels.

Research Products

• [Journal Article] In Identification of research needs to resolve the carcinogenicity of high-priority IARC carcinogens (2010)
  • Author(s): Nakajima T, Hopf NB, Schulte PA
  • Journal Title: Phthalate Volume: 42 Pages: 183-195
  • Peer Reviewed
• [Journal Article] Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol (2010)
  • Author(s): Nakamura D, Yanagiba Y, Duan Z, Ito Y, Okamura A, Asaeda N, Tagawa Y, Li C, Taya K, Zhang SY, Naito H, Ramdhan DH, Kamijima M, Nakajima T
  • Journal Title: Toxicol Lett Volume: 194 Pages: 16-25
  • Peer Reviewed
• [Journal Article] Research Recommendations for Selected IARC-Classified Agents (2010)
  • Author(s): Ward EM, Schulte PA, Straif K, Hopf NB, Caldwell JC, Carreon T, Demarini DM, Fowler BA, Goldstein BD, Hemminki K, Husgafvel Pursiainen K, Kuempel E, Lewtas J, Lunn RM, Lynge E, McElvenny DM, Muhle H, Nakajima T, Robertson LW ; IARC Working Group
  • Journal Title: Environ Health Perspect Volume: 118(10) Pages: 1355-1362
  • Peer Reviewed
• [Journal Article] Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol (2010)
  • Author(s): Nakamura D, Yanagiba Y, Duan Z, Ito Y, Okamura A, Asaeda N, Tagawa Y, Li C, Taya K, Zhang SY, Naito H, Ramdhan DH, Kamijima M, Nakajima T
  • Journal Title: Toxicol Lett (In press)
  • Peer Reviewed
• [Journal Article] Octachlorostyrene Induces Cytochrome P450, UDP-glucuronosyltransferase and Sulfotransferase via the Aryl Hydrocarbon Receptor and Constitutive Androstane Receptor (2009)
  • Author(s): Yanagiba Y, Ito Y, Kamijima M, Gonzalez FJ, Nakajima T
  • Journal Title: Toxicol Sci Volume: 111 Pages: 19-26
  • Peer Reviewed
• [Journal Article] Octachlorostyrene Induces Cytochrome P450, UDP-glucuronosyltransferase and Sulfotransferase via the Aryl Hydrocarbon Receptor and Constitutive Androstane Receptor (2009)
  • Author(s): Yanagiba Y, Ito Y, Kamijima M, Gonzalez FJ, Nakajima T
  • Journal Title: Toxicol Sci 111 Pages: 19-26
  • Peer Reviewed
• [Journal Article] Styrene trimer may increase thyroid hormone levels via down-regulation of the aryl hydrocarbon receptor(AhR) target gene UDP-glucuronosyltransferase (2008)
  • Author(s): Yanagiba Y, Ito Y, Yamanoshita O, Zhang S-Y, Watanabe G, Taya K, Li C, Inotsume Y. Kamijima M, Gonzalez, FJ, Nakajima T
  • Journal Title: Environ Health Perspect Volume: 116(6) Pages: 740-745
  • Peer Reviewed
• [Journal Article] PPARalpha-and DEHP-Induced Cancers (2008)
  • Author(s): Ito Y, Nakajima T
  • Journal Title: PPAR Res Volume: 759716
  • Peer Reviewed
• [Journal Article] Styrene trimer may increase thyroid hormone levels via down-regulation of the aryl hydrocarbon receptor(AhR)target gene UDP-glucuronosyltransferase (2008)
  • Author(s): Yanagiba Y, Ito Y, Yamanoshita O, Zhang SY, Watanabe G, Taya Ka, Li C, Inotsume Y, Kamijima M, Gonzalez, FJ, Nakajima T
  • Journal Title: Environ Health Perspect 116 Pages: 740-745
  • Peer Reviewed
• [Presentation] Octachlorostyrene induces cytochrome P450, UDP-glucuronosyltransferase, and sulfotransferase via the aryl hydrocarbon receptor and constitutive androstane receptor (2010)
  • Author(s): Yukie Yanagiba, Yuki Ito, Michihiro Kamijima, Frank J. Gonzalez, Tamie Nakajima
  • Organizer: XII International Congress of Toxicology, XII International Congress of Toxicology
  • Place of Presentation: Barcelona-Spain Palau de Congressos de Barcelona
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/hygiene/index.html