Development of a novel risk assessment method to detect 'disturbance of stress response systems' by environmental chemicals

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K19406
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: University of Toyama
• Principal Investigator: Tetsushi Hirano 富山大学, 学術研究部薬学・和漢系, 助教 (70804590)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: ストレス応答系 / 化学物質 / AOP / リスク評価

Outline of Final Research Achievements

In this study, we focused on chemical-induced “disturbance of the stress response system”, and through mechanistic analysis using animal models, we were able to elucidate some aspects of a new adverse effect pathway (AOP), with behavioural abnormalities and changes in neural activity as key events during exposure to neonicotinoid pesticides. . Furthermore, omics analysis revealed a set of genes related to neurotransmitter signalling and calcium signalling as candidate biomarkers. In addition, a novel risk assessment system that can efficiently detect synergistic effects of chemicals on neurotoxicity was established using a cellular model, using changes in the activity of proteolytic systems as an indicator.

Free Research Field

毒性学

Academic Significance and Societal Importance of the Research Achievements

従来の中枢神経系における化学物質の毒性評価はげっ歯類の脳組織変性や運動失調等を指標としているため、高次脳機能に及ぼす影響に対する検出感度、スループット、再現性の低さが問題点として指摘されている。そのため、「化学物質の曝露が高次脳機能に対して影響を及ぼすのか否か」を検出可能な新規リスク評価法の開発が切望されている。本研究により明らかになったAOPやリスク評価系は、今後、中枢神経系に対する化学物質のリスク評価の高度化を通じて、動物実験の削減や環境負荷の低減に貢献することで持続可能な開発目標（SDGs2, 12, 15等）の達成に寄与することが期待できる。