School of Public Health, Qingdao University, Qingdao, 266021, Shandong, China.
National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
Arch Toxicol. 2020 Mar;94(3):761-771. doi: 10.1007/s00204-020-02678-6. Epub 2020 Feb 19.
Carbon black (CB) particulates as virtually pure elemental carbon can deposit deep in the lungs of humans. International Agency for Research on Cancer classified CB as a Group 2B carcinogen due to inconclusive human evidence. A molecular epidemiological study was conducted in an established cohort of CB packers (CBP) to assess associations between CB exposure and genomic instability in peripheral lymphocytes using cytokinesis-block micronucleus assay (CBMN). Carbon content in airway macrophages (CCAM) was quantified as a bio-effective dosimeter for chronic CB exposure. Dose-response observed in CBPs was compared to that seen in workers exposed to diesel exhaust. The association between CB exposure status and CBMN endpoints was identified in 85 CBPs and 106 non-CBPs from a 2012 visit and replicated in 127 CBPs and 105 non-CBPs from a 2018 visit. The proportion of cytoplasm area occupied by carbon particles in airway macrophages was over fivefold higher in current CBPs compared to non-CBPs and was associated with CBMN endpoints in a dose-dependent manner. CB aerosol and diesel exhaust shared the same potency of inducing genomic instability in workers. Circulatory pro-inflammatory factors especially TNF-α was found to mediate associations between CB exposure and CBMN endpoints. In vitro functional validation supported the role of TNF-α in inducing genomic instability. An estimated range of lower limits of benchmark dose of 4.19-7.28% of CCAM was recommended for risk assessment. Chronic CB exposure increased genomic instability in human circulation and this provided novel evidence supporting its reclassification as a human carcinogen.
炭黑 (CB) 颗粒实质上是纯元素碳，可以沉积在人体肺部深处。由于人类证据不充分，国际癌症研究机构将 CB 归类为 2B 类致癌物质。在一个已建立的炭黑包装工队列中进行了一项分子流行病学研究，使用胞质分裂阻断微核试验 (CBMN) 评估 CB 暴露与外周血淋巴细胞基因组不稳定性之间的关联。气道巨噬细胞中的碳含量 (CCAM) 被量化为慢性 CB 暴露的生物有效剂量计。在 CBPs 中观察到的剂量反应与暴露于柴油废气的工人中观察到的反应进行了比较。在 2012 年的一次访问中，确定了 85 名 CBPs 和 106 名非 CBPs 之间的 CB 暴露状况与 CBMN 终点之间的关联，并在 2018 年的一次访问中复制了 127 名 CBPs 和 105 名非 CBPs 之间的关联。当前 CBPs 中气道巨噬细胞中碳颗粒占据的细胞质面积比例比非 CBPs 高出五倍以上，并且与 CBMN 终点呈剂量依赖性相关。CB 气溶胶和柴油废气在工人中引起基因组不稳定性的效力相同。循环促炎因子，特别是 TNF-α，被发现介导 CB 暴露与 CBMN 终点之间的关联。体外功能验证支持 TNF-α在诱导基因组不稳定性中的作用。建议将 CCAM 的下限基准剂量范围估计为 4.19%-7.28%，用于风险评估。慢性 CB 暴露增加了人类循环中的基因组不稳定性，这为其重新归类为人类致癌物质提供了新的证据。
