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Coplanar PCBs Health Effects in the Rat: Dose-Effect Relationships and Reproductive Toxicity Endopoint

Research Project

Project/Area Number 11460147
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionAzabu University

Principal Investigator

AKAHORI Fumiaki  Azabu University, Veterinary Medicine, Professor, 獣医学部, 教授 (70063964)

Co-Investigator(Kenkyū-buntansha) SHIROTA Mariko  Hatano Research Institute, Food and Drug Safety Center, 秦野研究所, 客員研究員
SAKAGUTI Kazuko  Azabu University, Environmental Health, Assistant Professor, 環境保健学部, 講師 (40153879)
SHIRAI Mituyuki  Azabu University, Veterinary Medicine, Professor, 獣医学部, 教授 (60235728)
代田 真理子  (財)食品薬品安全センター, 泰野研究所, 客員研究員
池川 直  帝人(株), 医薬品研究所, 研究員
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordscoplanar PCBs / reproductive toxicity / endpoint / hepatic cytochrome P450 / components of complement
Research Abstract

(1) Single injection of 10 or 100 μg/kg of PCB 126 on gestation day (GD) 15 to the dams delayed vaginal opening (VO) of their offspring significantly. In contrast, daily exposure to PCB 126 delayed VO only at a dose of 3 μg/kg/day, although cumulative doses of PCB 126 until chorionic gonandotropin (CG) 15 in the 1 μg/kg/day-group were estimated as much larger than 10 μg/kg. In addition, while a single injection of PCB 126 reduced the number of corpus lutea (CL), daily exposure to 1μg/kg/day did not alter it. These findings indicate that daily exposure may diminish effects of PCB 126 on female offspring as compared to single injection on GD 15. (2) The effects of Co-PCBs on CYP1A1, CYP1A2 and CYP2B1/2 mRNA expression were investigated by semi quantitative RT-PCR analysis in rats. In utero exposure to PCB126 (3μg/kg) or PCB169 (30 μg/kg) induced CYP1A1 and CYP1A2 mRNA expression levels in the liver of both male and female offspring. Exposure to PCB126 (30 μg/kg) or PCB169 (30 μg/kg) to pregnant rats induced CYP1A1, CYP1A2 and CYP2B1/2 mRNA expression levels in the placenta. (1) Proteins in the plasma of the (1-, 3-, 6-, and 15-week-old) rats, which were exposed to PCB126 or PCB169 in the viviparous phase, were analyzed by micro 2-dimensional electrophoresis. The influence of exposure to Co-PCBs on complement components (C3 and C4) in the plasma was observed in the 6- and 15-week-old rats, which were prenatally exposed to Co-PCBs. When toxicity for reproduction and development was considered from the aspect of the influence of Co-PCBs on a living body as an end point, the inactive amount was estimated to be 1 μg/kg. (4) It was also revealed that the exposure in the viviparous phase and milk-mediated exposure of neonates influenced expression of CYP1A1, CYP1A2, and CYP2B1/2 mRNA in the liver and dynamic changes in the complement system of proteins in the plasma.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 赤堀文昭: "コプラナーPCBsの生体毒性"The Japanese Journal of TOXICOLOGY. 12. 241-260 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikuko Teramitsu, Fumiaki Akahori, Shoichi Fujita: "Identification of novel cytochrome P450 1A genes from five marine mammal species"Aquatic Toxicology. 51. 145-153 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Issei Chiba, Fumiaki Akahori, Shoichi Fujita: "Negative correlation between plasma thyroid hormone levels and chlorinated hydrocarbon levels accumulated in seals from the coast of Hokkaido, Japan"Environmental Toxicology and Chemistry. 20. 1092-1097 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroshi Yoshikawa, Mitsuyuki Shirai, Fumiaki Akahori: "Electron paramagnetic resonance analysis of liver and serum in Sprague-Dawley rats exposed subchronically to coplanar pentachlorobiphenyl-congener 3,3',4,4',5"Animal Science Journal. 73. 269-277 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Issei Chiba, Fumiaki Akahori, Shoichi Fujita: "Hepatic microsomal cytochrome P450s and chlorinated hydrocarbons in largha and ribbon seals from Hokkaido, Japan : differential response of seal species to ah receptor agonist exposure"Environmental Toxicology and Chemistry. 21. 794-806 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kentaro Q Sakamoto, Fumiaki Akahori, Shoichi Fujita: "Accumulation patterns of polychlorinated biphenyl congeners and origanochlorine pesticides in steller's sea eagles and white-tailed sea eagles, threatened species, in Hokkaido, Japan"Environmental Toxicology and Chemistry. 21. 842-847 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Shirota, K.Taya, K.Shirota: "Effects of reduction of the number of primordial follicles on follicular development to achieve puberty in female rats"Reproduciton. 125. 85-94 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikuko Teramitsu., Yukio Yamamoto., Issei Chiba., Hisato Iwata., Shinsuke Tanabe., Yoshihiro Fujise., Akio Kazusaka., Fumiaki Akahori., Shoichi Fujita.: "Identification of novel cytochrome P450 1A genes from five marine mammal species"Aquatic Toxicology. 51. 145-153 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shirota M., Kitazawa I., Inoue K., Doyama A., Muaki M., Haishima A., Yamamoto K., Katoh C., Soda S., Kawabata A., Akahori F., and Shirota K.: "Adverse effects of in utero and lactational exposure to 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126) on the first ovulation in rats"Organohalogaen Compounds. 49. 356-358 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Issei Chiba., Akihito Sakakibara., Yoko Goto., Takeomi Isono., Yukie Yamamoto., Hisato Iwata., Shinsuke Tanabe., Kenji Shimazaki., Fumiaki Akahori., Akio Kazusaka., and Shoichi Fujita.: "Negative correlation between plasma thyroid hormone levels and chlorinated hydrocarbon levels accumulated in seals from the coast of Hokkaido Japan"Environmental Toxicology and Chemistry. 20(5). 1092-1097 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroshi Yoshikawa., Hidetoshi Morita., Tetsuya Takizawa., Mitsuyuki Shirai., Fumiaki Akahori., Hoboru Imano., Kenji Nakai., Ryoichi Sakata., and Tetsuhiko Yoshimura.: "Electron paramagnetic resonance analysis of liver and serum in Sprague-Dawley rats exposed subchronically to coplanar pentachlorobiphenyl-congener 3, 3', 4, 4', 5"Animal Science Journal. 73. 269-277 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Issei Chiba., Akihito Sakakibara., Hisato Iwata., Mayumi Ishizuka., Shinsuke Tanabe., Fumiaki Akahori., Akio Kazusaka., and Shoichi Fujita.: "Hepatic microsomal cytochrome P450s and chlorinated hydrocarbons in largha and ribbon seals from Hokkaido, Japan: differential response of seal species to receptor agonist exposure"Environmental Toxicology and Chemistry. 21(4). 794-806 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kentaro Q Sakamoto., Tatsuya Kunisue., Mafumi Watanabe., Yasushi Masuda., Hisato Iwata., Shinsuke Tanabe., Fumiaki Akahori., Mayumi Ishizuka., Akio Kazusaka., and Shoichi Fujita.: "Accumulation patterns of polychlorinated biphenyl congeners and origanochlorine pesticide in steller's sea eagles and white-tailed sea eagles, threatened species, in Hokkaido, Japan"Environmental Toxicology and Chemistry. 21(4). 842-847 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Shirota., S.Soda., C.Katoh., S.Asai., M.Sato., R.Ohta., G.Watanabe., K.Taya., and K.Shirota.: "Effects of reduction of the number of primordial follicles on follicular development to achieve puberty in female rats"Reproduction. 125. 85-94 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Shirota, K.Shirota, et al.: "Effects of reduction of the number of primordial follicles on follicular development to achieve puberty in female rats"Reproduction. 125. 85-94 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamamoto K, Shirota M, Akahori F, et al.: "In vtero exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) induces hypospadias in female rats"ORGANOHALOGEN COMPOUNDS.

    • Related Report
      2001 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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