The Iron‐Related Molecular Toxicity Mechanism of Synthetic Asbestos Nanofibres: A Model Study for High‐Aspect‐Ratio Nanoparticles

Abstract

Asbestos shares with carbon nanotubes some morphological and physico-chemical features. An asbestos-like behaviour has been recently reported by some authors, though the mechanism of toxicity may be very different. To identify at the atomic level the source of toxicity in asbestos, the effect of progressive iron loading on a synthetic iron-free model nanofibre previously found non-toxic in cellular tests was studied. A set of five synthetic chrysotile nanofibres [(Mg,Fe)3(Si2O5)(OH)4] has been prepared with Fe ranging from 0 to 1.78 wt %. The relationship between fibre-induced free-radical generation and the physico-chemical characteristics of iron active sites was investigated with spin-trapping techniques on an aqueous suspension of the fibres and Mössbauer and EPR spectroscopies on the solids, respectively. The fully iron-free fibre was inert, whereas radical activity arose with even the smallest amount of iron. Surprisingly, such activity decreased upon increasing iron loading. Mössbauer and EPR revealed isolated iron ions in octahedral sites that undergo both axial and rhombic distortion and the occurrence of aggregated iron ions and/or extra-framework clustering. The isolated ions largely prevailed at the lowest loadings. Upon increasing the loading, the amount of isolated iron was reduced and the aggregation increased. A linear relationship between the formation of carbon-centred radicals and the amount of rhombic-distorted isolated iron sites was found. Even the smallest iron contamination imparts radical reactivity, hence toxicity, to any chrysotile outcrop, thereby discouraging the search for non-toxic chrysotile. The use of model solids that only differ in one property at a time appears to be the most successful approach for a molecular understanding of the physico-chemical determinants of toxicity. Such findings could also be useful in the design of safer nanofibres.

Adsorption of bovine serum albumin onto synthetic Fe-doped geomimetic chrysotile

“…In a previous study, it was demonstrated that at the low amount of Fe content in the nanocrystals both biological and radical activity were more significant than the nanocrystal with higher Fe content [8,23]. This higher reactivity could be due to the higher percentage of Fe replacing Mg in octahedral position.…”

“…In fact, octahedral coordinated Fe has been observed in all the substitution range in Fe-doped chrysotile synthesized in absence of metallic Fe. On the contrary, tetrahedral coordinated Fe inducing a flattening of the chrysotile structure appears prevalent in respect of octahedral coordinated Fe in highly Fe-doped chrysotile synthesized when metallic Fe is available in the synthetic environment [19,[21][22][23]. The position of the sites responsible for catalytic and redox activity of Fe of asbestos is currently unknown, even if the fibre surface appears mainly to control the Fe reactivity.…”

The Role of Iron Impurities in the Toxic Effects Exerted by Short Multiwalled Carbon Nanotubes (MWCNT) in Murine Alveolar Macrophages

“…It is well known how asbestos fibers generate free radicals via different mechanisms including a Fenton reaction catalyzed by Fe ions exposed to their surface (Kamp, 2009). Our research group showed a correlation between the coordination and oxidation state of Fe in asbestos and its toxicity in in vitro cellular systems (Aldieri et al, 2001;Gazzano et al, 2007;Turci et al, 2010). It is thus conceivable to postulate a role for Fe also in MWCNT-induced toxic effects.…”

In vitro cellular responses to silicon carbide particles manufactured through the Acheson process: Impact of physico-chemical features on pro-inflammatory and pro-oxidative effects

“…This SiC I atypical profile could be explained on the one hand by the presence of crystallized silica (quartz and cristobalite) with high free carbon levels, and on the other hand by its high content of iron impurities (Table 1) Governa et al, 2005;IARC, 1996). It has been well described in the literature that there is a relationship between the presence of surface transition metal ions (especially iron) and cellular responses (Fubini et al, 1995b;Pritchard et al, 1996;Aust et al, 2000), especially for free radical generation (Fubini and Hubbard, 2003;Fenoglio et al, 2001;van Maanen et al, 1999;Turci et al, 2011;Pourchez et al, 2012). Indeed iron is known to be a catalyst in the formation of several reactive oxygen species (Pierre and Fontecave, 1999) (Halliwell and Gutteridge, 1992).…”