Development of risk evaluation method for environmental chemicals based on the exposure routes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26281028
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Yokohama College of Pharmacy
• Principal Investigator: Hanioka Nobumitsu 横浜薬科大学, 薬学部, 教授 (70228518)
• Co-Investigator(Kenkyū-buntansha): 神野 透人 名城大学, 薬学部, 教授 (10179096) ; 須野 学 岡山大学, 学内共同利用施設等, 准教授 (20621189) ; 重山 昌人 横浜薬科大学, 薬学部, 教授 (90598327)
• Co-Investigator(Renkei-kenkyūsha): MURATA MIKIO 横浜薬科大学, 薬学部, 准教授 (80723478) ; HICHIYA HIROYUKI 横浜薬科大学, 薬学部, 講師 (20548820) ; OKADA KENJI 横浜薬科大学, 薬学部, 講師 (00396673) ; KAGAWA TOSHIKO (TANAKA TOSHIKO) 横浜薬科大学, 薬学部, 教授 (40188313)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 化学物質 / 曝露経路依存的 / リスク評価法 / 異物代謝酵素 / ヒトiPS細胞 / シトクロムP450（CYP） / UDP-グルクロン酸転移酵素（UGT） / フタル酸モノ-2-エチルへキシル（MEHP）

Outline of Final Research Achievements

The purpose of this study was to develop the risk evaluation method for environmental chemicals based on the exposure routes. 1) The expression profile of UGT mRNA of differentiated intestinal epithelial cell-like cells fro Human iPS cells was similar that of human intestine. 2) The inter-individual differences (3.7-136-fold) in the expression levels of CYP and UGT mRNAs in human livers were observed. 3) The hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate (MEHP) in humans, dogs, rats and mice was examined in an in vitro system using microsomal fractions. The metabolic abilities of UGT enzymes expressed in the liver and intestine toward MEHP markedly differed among humans, dogs, rats and mice. Furthermore, UGT1A3, UGT1A7, UGT1A9 and UGT2B7 were suggested to play important roles in the glucuronidation of MEHP in humans.

Free Research Field

衛生化学