2018 Fiscal Year Final Research Report

Development of diagnostic methods for subacute and chronic neonicotinoids intoxication and investigation of the pathogenesis of neonicotinoids intoxication

Research Project

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Project/Area Number	15K00559
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Risk sciences of radiation and chemicals
Research Institution	Tokyo Women's Medical University
Principal Investigator	Taira Kumiko 東京女子医科大学, 医学部, 非常勤講師 (10163148)
Co-Investigator(Kenkyū-buntansha)	池中良徳北海道大学, 獣医学研究院, 准教授 (40543509) 中山翔太北海道大学, 獣医学研究院, 助教 (90647629)
Research Collaborator	KOMORI makiko FUJIOKA kazutoshi KAWAKAMI tomonori ARIZONO kouji
Project Period (FY)	2015-04-01 – 2019-03-31
Keywords	ネオニコチノイド / 殺虫剤 / 慢性腎臓病 / バイオマーカー / 尿 / 記憶障害 / 代謝物
Outline of Final Research Achievements	Seven neonicotinoids were separately administered to female NZ white rabbits; and the urine samples were collected after 12-48 hours. More than 20 metabolites, such as hydroxy-imidacloprid, N-desmethyl-acetamiprid, N-desmethyl-colthianidin, N-desmetyl-nitenpyram, and N-desmetyl-dinotefuran, were qualitatively detected from the urine samples by LC-TOFMS. We synthesized 13 metabolites, which were not commercially available, as standards substances and developed quantitative bioanalytical methods using LC-MS/MS. Then we collected urine samples from the general population, e.g. 46 from three- to six-year-old children in Nagano; 102 from Sri Lankan people, some with chronic kidney disease; and 78 from people in Ghana. The following compounds, imidacloprid, acetamiprid, thiacloporid, nitenpyram, thiamethoxam, clothianidin, dinotefuran, hydroxy-imidacloprid, N-desmethyl-acetamiprid, N-desmethyl-colthianidin, and N-desmethyl-nitenpyram were quantitatively detected from those urine samples.
Free Research Field	環境医学
Academic Significance and Societal Importance of the Research Achievements	近年のネオニコチノイド系殺虫剤の使用増加に伴い、食品や飲料、空気を介したネオニコチノイド系殺虫剤の慢性環境暴露による健康影響、例えば発達障害、記憶障害、振戦、辺縁性脳炎、慢性腎臓病、不整脈、免疫不全、不妊、不育、肥満、乳がんへの懸念が高まっている。暴露の指標としての、ネオニコチノイドの代謝物を抽出し、標準物質を合成し、定量できるようにしたことで、フィールドレベルで、随時尿を用いたネオニコチノイド系殺虫剤7種の暴露評価が可能となった。さらにネオニコチノイド系殺虫剤の全血や組織での定量法も確立することができたので、今後、ネオニコチノイド系殺虫剤の薬物動態や病態生理の研究への貢献が期待できる。