BackgroundDiatomaceous earth (DE) is mined globally and is potentially of occupational respiratory health concern due to the high crystalline silica content in processed material. DE toxicity, in terms of variability related to global source and processing technique, is poorly understood. This study addresses this variability using physicochemical characterisation and in vitro toxicology assays.MethodsNineteen DE samples sourced from around the world, comprising unprocessed, calcined and flux-calcined DE, were analysed for chemical and mineral composition, particle size and morphology, and surface area. The potential toxicity of DE was assessed by its haemolytic capacity, and its ability to induce cytotoxicity or cytokine release by J774 macrophages.ResultsThe potential toxicity of DE varied with source and processing technique, ranging from non-reactive to as cytotoxic and haemolytic as DQ12. Crystalline silica-rich, flux-calcined samples were all unreactive, regardless of source. The potential toxicity of unprocessed and calcined samples was variable, and did not correlate with crystalline silica content. Calcium-rich phases, iron content, amorphous material, particle size and morphology all appeared to play a role in sample reactivity. An increased surface area was linked to an increased reactivity in vitro for some sample types.ConclusionsOverall, no single property of DE could be linked to its potential toxicity, but crystalline silica content was not a dominant factor. Occlusion of the potentially toxic crystalline silica surface by an amorphous matrix or other minerals and impurities in the crystal structure are suggested to pacify toxicity in these samples. In vivo verification is required, but these data suggest that crystalline silica content alone is not a sufficient indicator of the potential DE hazard.Electronic supplementary materialThe online version of this article (doi:10.1186/s12995-015-0064-7) contains supplementary material, which is available to authorized users.