An updated review of the genotoxicity of respirable crystalline silica
- PDF / 717,898 Bytes
- 17 Pages / 595.276 x 790.866 pts Page_size
- 94 Downloads / 216 Views
REVIEW
Open Access
An updated review of the genotoxicity of respirable crystalline silica Paul J. A. Borm1* , Paul Fowler2 and David Kirkland3
Abstract Human exposure to (certain forms of) crystalline silica (CS) potentially results in adverse effects on human health. Since 1997 IARC has classified CS as a Group 1 carcinogen [1], which was confirmed in a later review in 2012 [2]. The genotoxic potential and mode of genotoxic action of CS was not conclusive in either of the IARC reviews, although a proposal for mode of actions was made in an extensive review of the genotoxicity of CS by Borm, Tran and Donaldson in 2011 [3]. The present study identified 141 new papers from search strings related to genotoxicity of respirable CS (RCS) since 2011 and, of these, 17 relevant publications with genotoxicity data were included in this detailed review. Studies on in vitro genotoxic endpoints primarily included micronucleus (MN) frequency and % fragmented DNA as measured in the comet assay, and were mostly negative, apart from two studies using primary or cultured macrophages. In vivo studies confirmed the role of persistent inflammation due to quartz surface toxicity leading to anti-oxidant responses in mice and rats, but DNA damage was only seen in rats. The role of surface characteristics was strengthened by in vitro and in vivo studies using aluminium or hydrophobic treatment to quench the silanol groups on the CS surface. In conclusion, the different modes of action of RCS-induced genotoxicity have been evaluated in a series of independent, adequate studies since 2011. Earlier conclusions on the role of inflammation driven by quartz surface in genotoxic and carcinogenic effects after inhalation are confirmed and findings support a practical threshold. Whereas classic in vitro genotoxicity studies confirm an earlier no-observed effect level (NOEL) in cell cultures of 60-70 μg/cm2, transformation frequency in SHE cells suggests a lower threshold around 5 μg/ cm2. Both levels are only achieved in vivo at doses (2–4 mg) beyond in vivo doses (> 200 μg) that cause persistent inflammation and tissue remodelling in the rat lung. Keywords: Crystalline silica, Quartz, Nanoparticles, Genotoxicity, Risk assessment
Background Prolonged chronic inhalation exposure to respirable crystalline silica (RCS) in the forms of quartz or cristobalite) can induce silicosis and, under certain circumstances, may also cause lung tumours. In 1997, the International Agency for Research on Cancer (IARC) classified crystalline silica (silica) as a Group I human carcinogen [1]. This classification was confirmed in a more recent review [2] but the pathogenesis of CS-induced lung cancer was not clearly identified,
* Correspondence: [email protected] 1 Borm Nanoconsult Holding BV, Proost Willemstraat 1, 6231 CV Meerssen, The Netherlands Full list of author information is available at the end of the article
leaving many open questions about risk assessment of CS-containing particle exposure. At the time of the IARC reviews, most genotoxicity assays
Data Loading...
