The potential for free radical release has been measured by means of the spin trapping technique on three kinds of iron containing particulate: two asbestos fibers (chrysotile and crocidolite); an iron-exchanged zeolite and two iron oxides (magnetite and haematite). DMPO (5,5'-dimethyl-1-pirroline-N-oxide), used as spin trap in aqueous suspensions of the solids, reveals the presence of the hydroxyl and carboxylate radicals giving rise respectively to the two adducts [DMPO-OH] and [DMPO-CO2], each characterized by a well-defined EPR spectrum. Two target molecules have been considered: the formate ion to evidence potential for hydrogen abstraction in any biological compartment and hydrogen peroxide, always present in the phagosome during phagocytosis. The kinetics of decomposition of hydrogen peroxide has also been measured on all solids. Ferrozine and desferrioxamine, specific chelators of Fe(II) and Fe(III) respectively, have been used to remove selectively iron ions. Iron is implicated in free radical release but the amount of iron at the surface is unrelated to the amount of radicals formed. Only few surface ions in a particular redox and coordination state are active. Three different kinds of sites have been evidenced: one acting as H abstracter, the other as a heterogeneous catalyst for hydroxyl radical release, the third one related to catalysis of hydrogen peroxide disproportionation. In both mechanisms of free radical release, the Fe-exchanged zeolite mimics the behaviour of asbestos whereas the two oxides are mostly inert. Conversely magnetite turns out to be an excellent catalyst for hydrogen peroxide disproportionation while haematite is inactive also in this reaction. The results agree with the implication of a radicalic mechanism in the in vitro DNA damage and in the in vivo toxicity of asbestos.

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Hard metal alloys (or cemented carbides) are made of a mixture of tungsten carbide particles (WC, more than 80%) cemented in cobalt metal powder (Co, 5-10%). The inhalation of hard metal particles may cause an interstitial pulmonary disease, the mechanism of which involves an interaction between Co and WC particles. Some epidemiological data also suggest that hard metal dust can induce lung cancer in workers. In a macrophage culture model, butylated hydroxytoluene (1 mM) protected from the cytotoxicity of hard metal particles, suggesting a possible involvement of lipid peroxidation in the toxicity of these powders. In a biochemical system, a mixture of Co and WC particles, but not Co or WC alone, stimulated the production of thiobarbituric acid-reactive substances from arachidonic acid. Using a spin trapping system applied to aqueous particulate suspensions and electrochemical techniques, we present experimental evidence that the association of Co and carbide particles represents a specific toxic entity producing large amounts of activated oxygen species. The mechanism of this interaction proceeds through the oxidation of cobalt metal catalyzed at the surface of carbide particles and resulting in the reduction of dissolved oxygen. This physicochemical property of hard metal particles provides a new basis for interpreting their inflammatory action and their possible carcinogenic effect on the lung.

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Stable radicals detectable by electron paramagnetic resonance (EPR) may be of use in the investigation of early events in cell-particle toxicity. Piperidine-N-oxyl derivatives (nitroxides), covalently linked to the surface of a high surface area silica (used as model solid for the technique), served as probes in the investigation of the effects of incubation of silica particles with mesothelial cells. A mesoporous silica (MCM-41), prepared by precipitation from a micellar solution, was the most appropriate silica-based particle for this purpose, as its channels allow direct contact with small molecules but not with macromolecules. The cytotoxicity of this amorphous silica is very low, allowing relatively high particle loading in the cell cultures. Both the high surface area of the sample and the large amount of inorganic material extracted from the cell culture provide enough material to run reasonably intense EPR spectra. Computer-aided analysis of the EPR spectra of silica-bound nitroxides provided information on the sensitivity of the labeled silica monitoring different environments, e.g., to follow the path of particles in a mammalian cell culture. Upon contact of the particles with mesothelial cells, the mean distance among the labels at the silica surface decreased as a consequence of the release of oxidizing and/or radical moieties from the cells.

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