Factors affecting cristobalite toxicity in Soufrière Hills ash
Electron microprobe analyses of in situ vapour-phase cristobalite crystals in dome rock confirmed that the Soufrière Hills cristobalite is not pure SiO2 (theory 1). The fact that Al has been shown to be the dominant substituted cation in cristobalite is critical for understanding its toxic potential.
The toxicological effects of cristobalite surface modification have not been previously studied, but it is known that the structure of cristobalite allows substitutions of Al for Si
. The mechanism by which Al interacts with quartz is not well understood though (it does not have the open lattice structure of cristobalite or tridymite); however, in acidic conditions, Al is thought to insert into the quartz crystal lattice
 at discrete points where defects enable this bonding to occur
. Duffin et al.
 treated laboratory standard DQ12 quartz surfaces with Al lactate which had the effect of inhibiting the production of cytokines from macrophages and epithelial cells. The release of reactive oxygen species, capable of causing mutations in the cells of the lung, a likely mechanism for the development of cancer
, would also be affected if the silica surface were affected by Al. Analogously, the presence of Al in the cristobalite structure and, therefore, at discrete points at its surface, could have similar effects. To test the toxicity side of this structure-toxicity relationship, we are now synthesising cristobalite in the laboratory with controlled levels of Al and Na. The resulting powders will be exposed to alveolar macrophages and cytotoxic, metabolic and pro-inflammatory effects measured to test our theory that structural substitutions in cristobalite affect toxic response.
These structure substitutions may also control crystal morphology. The platy cristobalite contains significantly more Al and Na than prismatic crystals and, hence, at this level of substitution in the crystal structure, prismatic crystal formation may be inhibited. This leads to the possibility that differing cristobalite morphologies may also be variably pathogenic, depending on their Al content (i.e. platy crystals would be less toxic). However, Horwell et al.
 did not observe solely platy crystals in these dome rock samples – they were always seen in association with prismatic and devitrification cristobalite (Table
1) - so it is unlikely that exposure would ever be restricted to the less-toxic variety.
A second mechanism for generation of cristobalite particles with heterogeneous surfaces is through dome-collapse fragmentation processes, generating particles which are mixed phases of cristobalite and other minerals (theory 2). Our results show this to be the case, as particles (in cross-section) are rarely observed to be solely comprised of cristobalite. These mixed-phase particles likely derive from: 1) vapour-phase crystals which were attached to (and will have nucleated from) groundmass or phenocrysts adjacent to the pore spaces, so we may expect that at least one surface of the vapour-phase cristobalite may have a 'rim' composed of other materials; or 2) break up of devitrified patches of glass where we would expect to see particles composed of feathery crystallites of cristobalite, plagioclase and a glassy matrix. These associated phases give an additional explanation as to why Horwell et al.
 found that crystalline silica ash particles contain minor amounts of other elements (by SEM-EDS). It is also likely that many whole particles identified as plagioclase or glass by SEM-EDS e.g. by
 would contain a crystalline silica component.
We did not observe evidence for any cristobalite surfaces being occluded by a thin coating of volcanic glass, clay, or an annealed amorphous layer (theory 3). In studies assessing the toxicity of coal dust, low-rank coals have been observed to contain crystalline silica coated with clays
. The clays, and associated soluble extracts, in the coal mine dust are thought to inhibit the cellular reactivity of quartz
. Fresh volcanic ash does not contain clay; however, old ash deposits, which may be quarried for volcanic aggregate, may well contain clays derived from chemical weathering of feldspar. Therefore, studies assessing the toxicity of crystalline silica-rich volcanic-derived quarry dust should assess whether silica occlusion is occurring.
When considering health, we can now say that, for the Soufrière Hills ash, there are two inherent factors which may act to reduce the toxicity of cristobalite: 1) the cristobalite is not pure SiO2 (theory 1); 2) heterogeneous RCS surfaces will be produced by fragmentation of devitrified areas and will consist of vapour-phase cristobalite and adhered fragments of groundmass (theory 2). All of these processes involve the introduction of Al to the RCS surface.
This evidence of surface modification and heterogeneity provides an explanation as to why the predicted toxicity is not observed in reality e.g.
[28, 29] and also why SHV ash does not generate silica surface radicals (e.g., Si· and Si–O·)
. However, there is also evidence here for the formation of reactive RCS volcanic particulate; the cracked, ‘fish-scale’ cristobalite provides weakened planes for the generation of inhalable sub-particles (< 15 μm diameter) of cristobalite on fragmentation and it appears that these surfaces remain exposed (i.e. no glass coating). The exposed crack intersections and twin planes at the surface of a crystal can be highly reactive
 and may host transition metal ions, giving a possible source area for hydroxyl radical activity (HO·)
. In addition, in areas of extensive devitrification, cristobalite can recrystallize to quartz, which may form up to 5 wt. % of dome rock in altered samples
. The toxicity of quartz particles may be different to cristobalite and, therefore, a variably-altered volcanic dome may produce ash with a range of toxicities.
Considering external factors, the heterogeneity of volcanic ash, with the inevitable close association of cristobalite and Al-rich mineral particles (such as feldspar) in the lung could also contribute to impairment of RCS toxicity (theory 4). Diffusion of elements from dissolving/leaching particles to the RCS surface is a possibility on the lung surface but this is likely to be greatly increased within the acidic lysosomal environment following phagocytosis by macrophages, where several particles may be stored in close proximity. In industry, quartz is also extracted with other minerals (e.g. clays), for example, during quarrying and industrial processing of sedimentary rock. For coal-mine dust, it is believed that, where quartz levels are below 10 wt. %, the total mass dust exposure is the best correlate with coal workers’ pneumoconiosis (CWP)
[51, 52]. However, above 10 wt. %, silicosis and rapid progression of CWP may occur
. The lack of silica reactivity at low concentrations cannot only be due to occlusion of RCS surfaces by clays, as discussed above. When DQ12 quartz is pre-incubated with an extract of coal-mine dust, haemolysis drops from 90% in non-incubated DQ12 quartz to virtually zero in incubated samples, demonstrating that there is an external control, such as diffusion of ions to the quartz surface
Determining if volcanic cristobalite toxicity is affected by external factors such as accompanying minerals is challenging as volcanic cristobalite cannot be isolated from the other minerals without affecting the surfaces of the particles (for example through heavy liquid separation or boiling the ash in phosphoric acid). Additionally, several minerals in volcanic ash are iron rich (e.g. amphiboles, pyroxenes and oxides) and Horwell et al.
[21, 54] have shown that deleterious, iron-catalysed hydroxyl radicals can be generated by these minerals in Soufrière Hills ash, providing a possible separate mechanism for toxicity.
The variable hazard of RCS
Since IARC classified crystalline silica as a carcinogen, with the proviso that hazard was likely to vary depending on the characteristics of the dust
, many authors have attempted to quantify the variability of the silica hazard. Studies have shown how cellular responses related to inflammation and fibrosis vary amongst different polymorphs and dust sources, and even amongst samples from the same source e.g.
[48, 55]. Donaldson and Borm
 have clarified that the surface reactivity of quartz is key, and that the ability of particles to induce oxidative stress could be modified by substances which affect its surface, including those derived from accompanying minerals. Therefore, toxicity could vary dramatically depending on the origin of the silica. Other authors have suggested that transient piezoelectric charges on freshly-fractured surfaces or the hydrophilicity of the surface may play a role in reactivity
In this study, we have investigated the mineralogical features which may modulate RCS toxicity. In the case of volcanic ash, we have shown evidence that the toxicity of RCS is likely affected by ‘inherent characteristics’ of the silica and hypothesized that ‘external factors’ may also act to hinder the reactivity of RCS. However, Fubini
, postulated that the inherent characteristics and external factors may be active at different stages in disease development, or be involved in different disease pathways. There is also evidence that different disease mechanisms (e.g. inflammation and DNA damage) involve different properties of the silica particle
In occupational settings, RCS surfaces may be exposed and activated by grinding or milling
[20, 61, 62], modified by the environment in which they are ground
 and altered by heating (e.g., for fly ash and biogenic silicas)
[63, 64]. These processes will variably alter their size, morphology, crystallinity, surface charges, hydrophilicity and external contaminants. However, the present investigation shows that the original mineralogy of the silica and its host material may also significantly influence its toxicity. Characterisation of these parameters can therefore shed light on the variable toxicity of respirable crystalline silica.