Abstract
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.
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Acknowledgements
The authors would like to thank staff from Luoyang and Jiaozuo Centers for Disease Control and Prevention for their assistance in field study, and thank Mrs. Jianyu Li, Lutang Wei, and Shuo Wang, and Ms. Ge Guan, Xiaoxiao Zhu, Li Lin, and Xue Cao from School of Public Health, Qingdao University for their technical assistance in environmental monitoring, sputum collection, carbon content in airway macrophage analysis, and database management.
Funding
This study was primarily supported by the National Natural Science Foundation of China (91643203 to YZ and 81872600 to SL) and supported in part by Guangdong Provincial Natural Science Foundation Team Project (2018B030312005 to SL) and National Institute of Health of United States (P30 CA11800 to SAB and MJC). The funding organizations played no role in the design and conduct of the study; in collection, management, analysis, and interpretation of the data; or in the presentation, review, or approval of the manuscript.
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YZ and SL: conceived of and designed the study; WC, YL, JT, HD, XW, XZ, and SY: performed the data collection and management; WC: scored all CBMN slides made in the visit of 2018; YL: led the sputum induction and CCAM analysis; WH: supervised the sputum differential cell count; SL: conducted the data analyses and tabulated the results; SL: interpreted the results and drafted the manuscript; and MJC, NR, SAB, QL, YZ, and SL: critically edited the manuscript. All authors have read the manuscript and approved its submission.
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Cheng, W., Liu, Y., Tang, J. et al. Carbon content in airway macrophages and genomic instability in Chinese carbon black packers. Arch Toxicol 94, 761–771 (2020). https://doi.org/10.1007/s00204-020-02678-6
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DOI: https://doi.org/10.1007/s00204-020-02678-6