Metabolic fate and mechanism of toxicity caused by AhR activation derived from benzotriazole UV stabilizers

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K21710
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hygiene and public health; Risk sciences of radiation and chemicals
• Research Institution: Osaka Institute of Public Health
• Principal Investigator: Nagayoshi Haruna 地方独立行政法人 大阪健康安全基盤研究所, 衛生化学部, 主任研究員 (70516757)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: ベンゾトリアゾール系紫外線吸収剤 / AhR / シトクロムP450 / DNA損傷

Outline of Final Research Achievements

In this study, risk assessment of 4 types of benzotriazole ultraviolet stabilizers (BUVSs) which show AhR ligand activities was attempted. First, oxidation of BUVSs by 8 types of major cytochrome P450s and changes in AhR ligand activity caused by oxidation were evaluated. As a result, BUVSs were oxidized by both AhR-dependent and independent cytochrome P450s, then, lose their original AhR ligand activity. It means that BUVSs would be categorized "no risk AhR ligand". Metabolite search was also conducted using LC-MS/MS, then UV-P and UV-9 confirmed the presence of oxidative metabolites. In addition, when the DNA damage property of BUVSs was evaluated using umu test, all BUVSs except for UV-326 were negative. From above, BUVSs other than UV-326 were considered as harmless low-risk AhR ligands. In the case of UV-326, it showed nearly positive response by umu test, therefore, comprehensive genotoxicity assessment were required.

Free Research Field

環境毒性学