Journal
ARCHIVES OF TOXICOLOGY
Volume 94, Issue 3, Pages 761-771Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-020-02678-6
Keywords
Carbon black; Genomic instability; Diesel exhaust; Carbon content in airway macrophages; Dose-response; Potency
Categories
Funding
- National Natural Science Foundation of China [91643203, 81872600]
- Guangdong Provincial Natural Science Foundation Team Project [2018B030312005]
- National Institute of Health of United States [P30 CA11800]
Ask authors/readers for more resources
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-alpha was found to mediate associations between CB exposure and CBMN endpoints. In vitro functional validation supported the role of TNF-alpha 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available