Effects of Cemented Tungsten Carbide Dust on Rat Lungs Following Intratracheal Injection of Saline Suspension

Abstract

In order to examine the effect of cemented tungsten carbide dust on the animal lung, saline suspensions were intratracheally administered into the lungs of rats in a single dosage. About one‐fifth of the animals died during the first three days. The acute response of the lungs was hemorrhagic edema with intense alveolar congestion. The animals killed at six months all presented pulmonary lesions of patchy fibrosis in the vicinity of the deposited dusts, occasionally associated with focal traction emphysema and broncho‐bronchiolar ectasia. At twelve months, two‐third of the animals had neither fibrosis nor dust deposition, although the remaining animals showed pulmonary lesions similar to those seen in the six‐months responders. Pibrosis of the lungs seemed to consist of collapsed alveoli with condensation of the preexistent reticulin fibers, but without noticeable collagenization. It is supposed that both the early toxic and the late flbrogenic effects of the carbide dust are attributable to the cytotoxic action of cobalt present in the dust particles. It is possible that recovery of the pulmonary lesions results from removal of the dusts from the lesions.

Experimental research into the pathogenesis of cobalt/hard metal lung disease

“…After a single administration, the acute and delayed lung responses to hard metal powder were much more pronounced than those produced by each individual component administered separately. As found by KITAMURA et al [13], the alveolar reaction had completely regressed by 4 months and no fibrosis developed. In a protocol involving repeated intratracheal administrations of the different particles, no effect on the parenchymal architecture was found 1 month after the last dose in the groups treated with tungsten carbide or cobalt alone, whereas clear fibrotic lesions were observed in the group instilled with hard metal [15].…”

“…KITAMURA et al [13] examined the pulmonary response to a single intratracheal administration of a high dose of hard metal powder in the rat. Six months later, the surviving animals presented pulmonary lesions of patchy fibrosis in the vicinity of deposited dust, but there was no evidence of an active inflammatory process in the lung.…”

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,…”

“…72,91,92,95 Significant pulmonary edema, interstitial lung fibrosis, alveolar congestion, and alveolitis were also reported in micro-sized WC-Co-exposed animals at 1 and 6 months following a single IT exposure. 89,90,95 Given this body of literature, the local effects of micro-sized WC-Co following pulmonary exposure have been characterized relatively well, and it is understood that micro-sized WC-Co exerts both acute and chronic effects in vivo.…”

“…5,72,[89][90][91][92]94 As noted in Table 5, the in vivo studies examined the effects of WC-Co particles in the Table 5 Summary of in vivo wC-Co toxicity studies Single IT bolus at 0-500 μg per rat 24 h exposure A consistent lack of acute local pulmonary inflammation was observed in terms of the BAL fluid parameters examined in animals exposed to wC-Co NPs while significant acute pulmonary inflammation was observed in the CeO 2 NP group micron-size range, using the mass-per-body weight dosing scheme (ie, mg/kg or mg/g), although some variation in particle size was noted in most cases (overall, WC-Co size ranging from 0.1 to 6 μm). Specifically, micro-sized WC-Co particle exposure caused significant pulmonary inflammation in rats, marked by increased bronchoalveolar lavage (BAL) fluid parameters such as lactate dehydrogenase (LDH) and albumin content, compared to control animals, in as little as 24 h after delivery the of WC-Co IT bolus.…”