32 Occupational exposure to respirable crystalline silica and its impact on lipid mediators and oxidative stress markers in blood and urine

Abstract Background Respirable crystalline silica (RCS) is a well-established occupational health hazard. Inflammation and oxidative stress are key mechanisms for diseases associated with exposure; however, the role of lipid inflammatory mediators remains unclear. Oxylipins, a diverse group of lipid mediators derived mainly from arachidonic acid or linoleic acid via cyclooxygenases, lipoxygenases or P450 enzymes may contribute to silica-induced pathology. This study investigates the association between RCS exposure and oxylipin/oxidative stress biomarkers in a cohort of foundry workers. Method Plasma levels of 79 lipid mediators, including oxylipins and un- mono- and polyunsaturated fatty acids were quantified in 40 foundry workers sampled twice, using solid-phase extraction and ultra high-pressure liquid chromatography coupled to unispray tandem mass spectrometry (SPE-UHPLC-USI-MS/MS). Lipid levels were correlated with personal exposure measurements to respirable dust and RCS. Analysis of urinary oxylipin and oxidative stress markers are ongoing and these results will also be presented at the conference. Results Adjusted for covariates, seven lipids were significantly correlated with RCS exposure. These lipids were mainly linoleic acid derived oxylipins with 9,10-DiHOME demonstrating the strongest correlation. For respirable dust, five lipids correlated significantly with exposure, mainly eicosanoids, eg 8,9-DiHETrE. In general, there were no, or very few significant correlations between the lipid mediators and other inflammatory markers, such as interleukin-8, C-reactive protein and Serum amyloid A. Conclusions The observed associations between linoleic acid-derived oxylipins and RCS exposure suggest that these lipid mediators may play a previously underrecognized role in silica-induced inflammation and disease.