title: The in vitro respiratory toxicity of cristobalite-bearing volcanic ash.
abstract: Ash from dome-forming volcanoes poses a unique hazard to millions of people worldwide due to an abundance of respirable cristobalite, a crystalline silica polymorph. Crystalline silica is an established respiratory hazard in other mixed dusts, but its toxicity strongly depends on sample provenance. Previous studies suggest that cristobalite-bearing volcanic ash is not as bio-reactive as may be expected for a dust containing crystalline silica. We systematically address the hazard posed by volcanic cristobalite by analysing a range of dome-related ash samples, and interpret the crystalline silica hazard according to the mineralogical nature of volcanic cristobalite. Samples are sourced from five well-characterized dome-forming volcanoes that span a range of magmatic compositions, specifically selecting samples rich in cristobalite (up to 16wt%). Isolated respirable fractions are used to investigate the in vitro response of THP-1 macrophages and A549 type II epithelial cells in cytotoxicity, cellular stress, and pro-inflammatory assays associated with crystalline silica toxicity. Dome-related ash is minimally reactive in vitro for a range of source compositions and cristobalite contents. Cristobalite-based toxicity is not evident in the assays employed, supporting the notion that crystalline silica provenance influences reactivity. Macrophages experienced minimal ash-induced cytotoxicity and intracellular reduction of glutathione; however, production of IL-1β, IL-6 and IL-8 were sample-dependent. Lung epithelial cells experienced moderate apoptosis, sample-dependent reduction of glutathione, and minimal cytokine production. We suggest that protracted interaction between particles and epithelial cells may never arise due to effective clearance by macrophages. However, volcanic ash has the propensity to incite a low, but significant, and sample-dependent response; the effect of this response in vivo is unknown and prolonged exposure may yet pose a hazard.
authors.affiliation: Institute of Hazard, Risk and Resilience, Department of Earth Sciences, Durham University, Durham, United Kingdom; The University of Edinburgh/MRC Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh, United Kingdom; Department of Earth and Environmental Sciences, Ludwig-Maximilians Universität München, Munich, Germany. Electronic address: david.damby@min.uni-muenchen.de.
authors.forename: David E
authors.initials: DE
authors.lastname: Damby
authors.affiliation: MRC Toxicology Unit, University of Leicester, Leicester, United Kingdom.
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Murphy
authors.affiliation: Institute of Hazard, Risk and Resilience, Department of Earth Sciences, Durham University, Durham, United Kingdom.
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Horwell
authors.affiliation: The University of Edinburgh/MRC Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Raftis
authors.affiliation: The University of Edinburgh/MRC Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Donaldson
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D012137:Respiratory System / Q000187:drug effects*; D012822:Silicon Dioxide / Q000032:analysis / Q000633:toxicity*; D013499:Surface Properties; D018707:Volcanic Eruptions / Q000032:analysis*
chemical_list: D052638:Particulate Matter; D012822:Silicon Dioxide
keywords: Cristobalite; Crystalline silica; Toxicity; Volcanic ash