2001 Fiscal Year Final Research Report Summary
Reproductive toxicity of endocrine-disrupting chemicals and the mechanism via peroxisome proliferators-activated receptor in relation to the risk assessment
| Project/Area Number |
11470095
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Nagoya University (2001)
Shinshu University (1999-2000) |
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Principal Investigator |
NASU Tamie Graduate School of Medicine, Nagoya University, Professor, 大学院・医学研究科, 教授 (10020794)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA Jun Shinshu University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (10221459)
FUKUSHIMA Yoshimitsu Shinshu University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (70273084)
AOYAMA Toshifumi Shinshu University, School of Medicine, Professor, 医学部, 教授 (50231105)
SASAKI Kazutoshi Nagano Research Institute for Health and Pollution, Head Researcher, 主任研究員
OMURA Minoru Kyushu University, Graduate School of Medicine, Research Associate, 大学院・医学研究科, 助手 (50243936)
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| Project Period (FY) |
1999 – 2001
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| Keywords | di(2-ethylhexyl)phthalate / reproductive toxicity / PPARα / testosterone / Meals / 2,4-dichlorophenoxyacetic acid / endocrine-disrupting chemicals / Intake per day |
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| Research Abstract |
Phthalic acid esters are typical plasticizer, which is recently noted as an endocrine-disrupting chemical. These chemicals are known as a ligand to peroxisome proliferators-activated receptor a (PPARα). Reproductive toxicity of di(2-ethylhexyl) phthalate (DEHP) and the mechanism were investigated using wild-type Sv/129 mice and PPARα-null mice on the same genetic background. A 0.05% DEHP diet was prepared with commercial rodent chow. DEHP treatment increased the resolution of fetus and mortality of new born pups per pair in wild-type mice, but not in the PPARα-null mice. Although PPARα was related to testosterone level in serum of male mice, DEHP also decreased the level in wild-type mice, not in the PPARα-null mice. These results suggest that the reproductive effect of DEHP and effect on testosterone level in serum are closely related to the expression of PPARα. Phthalic acid esters other than DEHP induced PPARα dependently on the lipid solubility. 2,4-Dichlorophenoxyacetic acid, one of herbicides, induced PPARα and decreased testosterone level in male mice, which is due, in part, to downregulate cholesterol-synthetic enzymes.
We also measured DEHP concentration in meals including coffee or tea of 16 persons, and then calculated the total intake per day. DEHP was found in all samples, and the concentration levels were 30〜370ug/kg, and the average was 124ug/kg, which was estimated at 70〜1200ug/day (average 320ug/day).
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