Physicochemical Mechanism of the Interaction between Cobalt Metal and Carbide Particles To Generate Toxic Activated Oxygen Species

Abstract

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.

Characteristics of Dusts Encountered during the Production of Cemented Tungsten Carbides

“…If Co particles in the presence of WC particles cause HMD via generation of ROS [4][5][6] , then our characterization of airborne particles may help to explain the inconsistent findings of epidemiological studies, e.g., between Meyer-Bisch et al 1) and Sprince et al 2) ; only Sprince et al 2) showed a higher risk in the later stages of the CTC manufacturing process. We observed that airborne particles potentially available for inhalation in spray drying and all subsequent work areas were a mixture of elemental tungsten and elemental Co particles and/or multi-constituent W/Co particles (ostensibly WC/Co particles, but the relative carbon contribution of the collection substrate and metal carbides is unknown).…”

“…It is interesting to speculate on the potential implications of our results, which suggest more intimate contact between Co and WC in post-screened particles relative to pre-spray dried particles, for generation of ROS and risk of HMD. It has been reported that the Co constituent of pre-sintered WC/Co powder is oxidized in vitro, releasing electrons that are transferred to the surface of WC where atmospheric oxygen is reduced, resulting in generation of ROS [4][5][6] . In pre-sintered powder, metallic Co and WC may be held in contact by weak electrostatic bonds or by van der Waals forces.…”

In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components

“…These synergistic epigenetic effects are further corroborated by statistically significant reduction of H3-Ser10 phosphorylation caused by tungsten-alloy as compared to cobalt concentration (CoA) equivalent to the percentage that was used in the preparation of tungsten-alloy in C2C12 cells. When cobalt and tungsten carbide particles are in close contact, the generation of reactive oxygen species may take place, disturbing signaling pathways involved in proliferation, apoptosis, transformation, and senescence (Lison et al, 1995;Lu, et al, 2005). Tungsten carbide-cobalt mixture has been shown to trigger DNA fragmentation and rearrangements of nucleosome/chromatin assembly in human peripheral blood mononucleated cells thus contributing to apoptosis (Lombaert et al, 2004(Lombaert et al, , 2008.…”

Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure

“…Early data concerning the effects of inhaled WC-Co dusts first emerged in the 1960s and continued through the 1980s, providing researchers the foundation to further explore the toxic effects of hard metal exposure using in vitro [71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] and in vivo 72,[89][90][91][92][93][94][95][96] models. Although cobalt itself was originally considered the causative agent of HMLD, several studies demonstrated that this is not the case and the disease mainly develops due to the simultaneous presence of WC with Co. 71,74,[76][77][78][79]90,91 It is currently understood that the combination of WC-Co is more toxic than Co, W, or WC particles alone, both in vitro and in vivo, 71,72,74,78,79,81,85,90,91,93,94,…”

“…Although cobalt itself was originally considered the causative agent of HMLD, several studies demonstrated that this is not the case and the disease mainly develops due to the simultaneous presence of WC with Co. 71,74,[76][77][78][79]90,91 It is currently understood that the combination of WC-Co is more toxic than Co, W, or WC particles alone, both in vitro and in vivo, 71,72,74,78,79,81,85,90,91,93,94,[97][98][99] but the reason for this enhanced toxicity is still not well defined.…”