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REPRODUCTIVE IMMUNOTOXICITY OF PLASTICISER, DEHP IN RODENTS

Research Project

Project/Area Number 13672381
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

UENO Koichi  CHIBA UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, PROFESSOR, 大学院・薬学研究院, 教授 (60125903)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsENVIRONMENTAL HORMONE / di (2-ethylhexyl)phthalate / PLASITICISER / REPRODUCTIVE TOXICITY / IMMUNITY / RODENTS / HUMORAL IMMUNE RESPONSE / DTH REACTION / ラット
Research Abstract

di-(2-ethylhexyl) phthalate (DEHP) exposure occurring in the medical setting are of particular concern because the amount of exposure can be substantial and because those exposed, such as premature infants and other neonates or adults with life-threatening illnesses, may be particularly vulnerable to the effect of toxic chemicals. The objectives are to determine the impact of DEHP on reproductive immunotoxicity and evaluate potential impacts of immunosuppression and reproductive effects.
We found that DEHP leached from PVC medical device tubing settings into medical solutions. DEHP has been measured in medical solutions at a mean concentration of 1.2mg/L in solutions containing Tween 80. When DEHP was administered orally for a week of gestation in pregnant rats, DEHP and its metabolite were detected in fetuses as well as in maternal plasma, placenta and amniotic fluid, and the offspring showed the immunological alterations. In addition, when DEHP was treated from gestation to lactating period in maternal rats and mice, DEHP and MEHP were measured in maternal milk and the infants.
DEHP was able to cross the placental barrier and influenced the immune system of developing fetuses and neonates. Evidence of immunotoxicity in the DEHP exposed dams in rodents included a significant decrease in humoral immune responses of the female F_1 rat, and in DTH responses and mite antigens induced allergic reactions of female F_1 mice. On the other hands, a significant decrease of testis weights and the activation of cell-mediated immune responses were observed in adult F_1 male mice from the DEHP pretreated maternal mice.
These results indicate that DEHP possesses the abilities to influence the immune response of the next generation in rodents, and there are species differences and sex differences in the mode of action.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] K.Yamaura, K.Ogawa, T.Yonekawa, T.Nakamura, S.Yano, K.Ueno: "Inhibition of the antibody production by acetaminophen independent of liver injury in mice"Biol. Pharm. Bull.. 25(2). 201-205 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomonori Nakamura, Akiko Sakai, Issei Isogami, Kazuhiro Noda, Koichi Ueno, Shingo Yano: "Abatement of Morphine-Induced Slowing in Gastrointestinal Transit by Dai-Kenchu-to, a Traditional Japanese Herbal Medicine"Jpn. J. Pharmacol. 88(2). 217-221 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Narimatsu, M.Mochida, K.Ueno, T.Horie, S.Yamamoto, T.Suzuki: "Induction of cytochrome P450 1A1 in mice by repeated oral administration of propranolol"Drug Metabol. Pharmacokin.. 17(1). 54-59 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] E.Negishi, A.Hirai, N.Yoshizaki, M.Yonezawa, T.Akiba, K.Ueno: "Electronic links between hospitals or clinics and pharmacies : Structure and operation of WAKASHIO pharmacotherapeusis network"YAKUGAKU ZASSHI. 123(3). 191-200 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Yamaura, T.Yonekawa, T.Nakamura, S.Yano, K.Ueno: "The Histamine H2-Receptor Antagonist, Cimetidine Inhibits the Articular Osteopenia in Rats With Adjuvant-Induced Arthritis by Suppressing the Osteoclast Differentiation Induced by Histamine"J. Pharmacol. Sci.. 91(In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 日本トキシコロジー学会教育委員会, 分担執筆者:上野光一: "トキシコロジー"朝倉書店. 327 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Yamaura, K. Ogawa, T. Yonekawa, T. Nakamura, S. Yano and K. Ueno: "Inhibition of the antibody production by acetaminophen independent of liver injury in mice"Biol. Pharm. Bull.. 25(2). 201-205 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Nakamura, A. Sakai, I. Isogami, K. Noda, K. Ueno and S. Yano: "Abatement of Morphine-Induced Slowing in Gastrointestinal Transit by Dai-Kenchu-to, a Traditional Japanese Herbal Medicine"Jpn. J. Pharmacol.. 88(2). 217-221 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S. Narimatsu, M. Mochida, K. Ueno, T. Horie, S. Yamamoto and T. Suzuki: "Induction of cytochrome P450 1A1 in mice by repeated oral administration of propranolol"Drug Metabol. Parmacokin.. 17(1). 54-59 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] E. Negishi, A. Hirai, N. Yoshizaki, M. Yonezawa, T. Akiba and K. Ueno: "Electronic links between hospitals or clinics and pharmacies : Structure and operation of WAKASHIO pharmacotherapeusis network"YAKUGAKU ZASSHI. 123(3). 191-200 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Yamaura, T. Yonekawa, T. Nakamura, S. Yano and K. Ueno: "The Histamine H_2-Receptor Antagonist, Cimetidine, Inhibits the Articular Osteopenia in Rats With Adjuvant-Induced Arthritis by Suppressing the Osteoclast Differentiation Induced by Histamine"J. Pharmacol. Sci.. 91, IN PRESS. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. UENO: "TOXICOLOGY"ASAKURA SHOTEN. 327 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Narimatsu, M.Mochida, K.Ueno, T.Horie, S.Yamamoto, T.Suzuki: "Induction of cytochrome P450 1A1 in mice by repeated oral administration of propranolol"Drug Metabol. Pharmacokin.. Vol.17(1). 54-59 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Yamaura, T.Yonekawa, T.Nakamura, S.Yano, K.Ueno: "The Histamine H_2-Receptor Antagonist, Cimetidine, Inhibits the Articular Osteopenia in Rats With Adjuvant-Induced Arthritis by Suppressing the Osteoclast Differentiation Induced by Histamine"J. Pharmacol. Sci.. Vol.91(In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] E.Negishi, A.Hirai, N.Yoshizaki, M.Yonezawa, T.Akiba, K.Ueno: "Electronic links between hospitals or clinics and pharmacies : Structure and operation of WAKASHIO pharmacotherapeusis network"YAKUGAKU ZASSHI. Vol.123(3). 191-200 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 上野 光一: "薬剤師を取り巻く諸問題と薬剤師教育"神奈川県病院薬剤師会誌. Vol.101. 12-13 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 日本トキシコロジー学会教育委員会 分担執筆者:上野 光一: "トキシコロジー"朝倉書店. 327 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 水谷義勝, 酒井明子, 上野光一, 中村智徳, 高橋英世, 矢野眞吾: "癌患者におけるモルヒネ製剤の使用状況と消化器副作用"日本病院薬剤師会雑誌. 53・2. 223-232 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S. Narimatsu, T. Arai, Y. Masubuchi, T. Horie, M. Hosokawa, K. Ueno, H. Kataoka, S. Yamamoto, T. Ishikawa, A. K. Cho: "Inactivation of Rat Cytochrome P450 2D Enzyme by Further Metabolite of 4-Hydroxypropranolol, the Major and Active Metabolite of Propranolol"Biol.Pharm.Bull.,. 24・8. 988-994 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K. Yamaura, K. Ogawa, T. Yonekawa, T. Nakamura, S. Yano, K. Ueno: "Inhibition of the antibody production by acetaminophen independent of liver injury in mice"Biol. Pharm. Bull.,. 25・2. 201-205 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomonori Nakamura, Akiko Sakai, Issei Isogami, Kazuhiro Noda, Koichi Ueno, Shingo Yano: "Abatement of Morphine-Induced Slowing in Gastrointestinal Transit by Dai-Kenchu-to, a Traditional Japanise Herbal Medicine"Jpn. J. Pharmacol.,. 88・2. 217-221 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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