Investigation into early detection and prevention of trichloroethylene hypersensitivity syndrome

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K19691
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 58:Society medicine, nursing, and related fields
• Research Institution: Nagoya City University
• Principal Investigator: Kamijima Michihiro 名古屋市立大学, 医薬学総合研究院(医学), 教授 (80281070)
• Co-Investigator(Kenkyū-buntansha): 那須 民江 中部大学, 生命健康科学部, 客員教授 (10020794)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Keywords: トリクロロエチレン / 過敏症症候群 / 薬剤性過敏症症候群(DIHS) / 自己抗体 / CYP2E1 / 生物学的モニタリング / 尿中代謝物 / 許容濃度

Outline of Final Research Achievements

Occupational exposure to trichloroethylene (TCE) can cause generalized skin disorder accompanied with severe hepatitis (hypersensitivity syndrome, TCE-HS), which resembles severe adverse cutaneous reactions to drugs. Traditional occupational safety measures focusing on controlling TCE exposure concentrations were considered not effective to enough prevent TCE-HS since a susceptibility gene (HLA-B*13:01) is involved in the occurrence of the disease. This study project clarified that the risk of the occurrence markedly increased at exposure levels higher than 15 mg/L of urinary trichloroacetic acid, regardless of whether the patient had the gene, which means that reduction in the exposure is necessary to prevent TCE-HS. The project also clarified that serum anti-CYP2E1 IgG autoantibody levels increased by the TCE exposure.

Free Research Field

衛生学

Academic Significance and Societal Importance of the Research Achievements

１．本研究によって曝露量の管理がTCE-HSの発生予防に必要なことが明らかになり、日本産業衛生学会がTCEの許容濃度（尿中トリクロロ酢酸の生物学的許容値）を従来の50 mg/Lから10 mg/Lに引き下げる改訂の根拠となった。
２．TCEへの曝露により血清チトクロムP450（CYP2E1）自己抗体が上昇し、CYP2E1との免疫複合体形成がTCE-HS発症の機序である可能性が、感受性遺伝子HLA-B*13:01が自己抗体上昇に関与しないこととともに明らかになった。すなわち、自己抗体を産生させない曝露管理が発症予防に有用であるという、有機溶剤中毒予防の領域で新しい概念を打ち立てた。