| Project/Area Number |
16K00625
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Environmental risk control and evaluation
|
|---|
| Research Institution | Josai University (2017-2018)
Tokai University (2016) |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
木村 穣 東海大学, 医学部, 教授 (10146706)
|
|---|
| Research Collaborator |
Miyasaka Muneo
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | シックハウス症候群 / フタル酸エステル / 皮膚内代謝 / 発症リスク評価法 / 有害化学物質 / 環境質定量化・予測 / 薬剤反応性 / 経皮暴露 |
|---|
| Outline of Final Research Achievements |
The purpose of this study was to establish an assessment method for the onset risk of sick house syndrome following dermal exposure of phthalate esters (PE). Several tissues of human neuropathy target esterase (NTE) gene transgenic mice and human were used. The NTE activity in the skin was, the higher PE was metabolized, resulting the higher percutaneous absorption of PE. The NTE activity in the skin correlated to that in the peripheral blood mononuclear cells. Other esterase which mainly determines the esterase activity in the skin was also searched, because the contribution of NTE to the activity was small. Carboxylesterase 2 (CES2) was a probable candidate, because it located in the epidermis, had high affinities to many ester compounds, and distributed large amount with large interindividual difference. The onset risk of sick house syndrome following dermal exposure of PE can be assessed by CES2 activity in the skin.
|
| Academic Significance and Societal Importance of the Research Achievements |
シックハウス症候群（SHS)の原因物質が次々と指摘され、その防御対策も進んでいるにも拘らず、未だ多くの患者がその症状に苦しんでいる。本研究は原因物質の暴露経路として見落とされがちな経皮経路に着目し、原因物質の一つであるフタル酸エステルが皮膚内代謝活性に依存して経皮吸収されることを明らかとした。また、その皮膚内代謝を決定づける酵素を探索し、カルボキシルエステラーゼ２が候補酵素として見出された。今後、この酵素の多型や皮膚内分布量を血液検査等から推定できれば、シックハウス症候群の発症リスクを予測できる可能性がある。また、SHS発症を予防するための行動指針や新たな治療法確立の一助となると考えられる。
|
