Bioaccessibility, bioavailability and toxicity of commercially relevant iron- and chromium-based particles: in vitro studies with an inhalation perspective

Background: Production of ferrochromium alloys (FeCr), master alloys for stainless steel manufacture, involves casting and crushing processes where particles inevitably become airborne and potentially inhaled. The aim of this study was to assess potential health hazards induced by inhalation of different well-characterized iron-and chromium-based particles, i.e. ferrochromium (FeCr), ferrosiliconchromium (FeSiCr), stainless steel (316L), iron (Fe), chromium (Cr), and chromium(III) oxide (Cr(2)O(3)), in different size fractions using in vitro methods. This was done by assessing the extent and speciation of released metals in synthetic biological medium and by analyzing particle reactivity and toxicity towards cultured human lung cells (A549). Results: The amount of released metals normalized to the particle surface area increased with decreasing particle size for all alloy particles, whereas the opposite situation was valid for particles of the pure metals. These effects were evident in artificial lysosomal fluid (ALF) of pH 4.5 containing complexing agents, but not in neutral or weakly alkaline biological media. Chromium, iron and nickel were released to very low extent from all alloy particles, and from particles of Cr due to the presence of a Cr(III)-rich protective surface oxide. Released elements were neither proportional to the bulk nor to the surface composition after the investigated 168 hours of exposure. Due to a surface oxide with less protective properties, significantly more iron was released from pure iron particles compared with the alloys. Cr was predominantly released as Cr(III) from all particles investigated and was strongly complexed by organic species of ALF. Cr2O3 particles showed hemolytic activity, but none of the alloy particles did. Fine-sized particles of stainless steel caused however DNA damage, measured with the comet assay after 4 h exposure. None of the particles revealed any significant cytotoxicity in terms of cell death after 24 h exposure. Conclusion: It is evident that particle and alloy characteristics such as particle size and surface composition are important aspects to consider when assessing particle toxicity and metal release from alloy particles compared to pure metal particles. Generated results clearly elucidate that neither the low released concentrations of metals primarily as a result of protective and poorly soluble surface oxides, nor non-bioavailable chromium complexes, nor the particles themselves of occupational relevance induced significant acute toxic response, with exception of DNA damage from stainless steel.