There has been an increase in the number of reported cases of coal workers’ pneumoconiosis (CWP) within Australia in recent years. The initiation and progression of CWP is driven by coalmine dust-induced cytotoxicity, inflammation, oxidative stress and fibrosis. Disease severity is well-known to be correlated with mass concentration, exposure duration and particle size. However, the prevalence and severity of CWP differs geographically, despite comparable exposure to respirable dust. This observation suggests that coal composition plays a key role in determining CWP pathogenesis. This notion is supported by epidemiological studies showing correlations between coal seam geochemistry and the prevalence of CWP and early in vitro studies showing that cell growth is inhibited to a greater extent by leachates of coal collected from areas with a higher incidence of CWP. The aim of this study was to determine if there is association between the detrimental lung cellular response and chemical composition of coal particles to identify key chemical factor(s) contributing to disease development.