Comparative study of the acute lung toxicity of pure cobalt powder and cobalt-tungsten carbide mixture in rat.
Alveolitis progressing to lung fibrosis has been reported in workers exposed to cobalt containing dust (e.g., tungsten carbide-cobalt mixture as produced by the hard metal industry) but rarely following exposure to pure cobalt dust (e.g., in cobalt-producing factories). We have previously demonstrated that tungsten carbide-cobalt mixture is more toxic toward rat alveolar macrophages in vitro than pure cobalt metal powder. The present study was undertaken to compare in female rats the acute pulmonary response (lung weight, lung histology, cellular and biochemical analyses of bronchoalveolar lavage fluid, and mortality) following the intratracheal instillation of pure cobalt (Co) particles (median particle size, d50:4 microns), pure tungsten carbide (WC) particles (d50:2 microns), tungsten carbide-cobalt (WC-Co) powder (d50:2 microns; cobalt 6.3%, tungsten 84%, carbon 5.4%) and crystalline silica (d50 less than 5 micron) used as pneumotoxic reference material. WC alone (15.67 mg/100 g body wt) behaves as an inert dust producing only a mild accumulation of macrophages in the alveolar duct walls. Co alone (1.0 mg/100 g) only causes a moderate inflammatory response. An identical amount of Co given as WC-Co mixture (16.67 mg/100 g; corresponding to 1.0 mg Co/100 g) produces a severe alveolitis and fatal pulmonary edema. Cellular and biochemical characteristics of bronchoalveolar lavage fluid collected 24 hr after the intratracheal instillation of WC (1.0 mg/100 g) or Co (0.06 mg/100 g) are not significantly different from those of control animals instilled with sterile saline. On the contrary, bronchoalveolar lavage fluid changes following administration of the WC-Co mixture (1.0 mg/100 g; corresponding to 0.06 mg Co/100 g) are very similar to those induced by crystalline silica (1.0 mg/100 g). The amount of cobalt excreted in urine is significantly higher when the animals are exposed to WC-Co powder as compared to an equivalent amount of pure cobalt particles, suggesting an increased bioavailability of cobalt metal when combined with tungsten carbide. This study demonstrates that the acute lung toxicity of tungsten carbide-cobalt mixture is much higher than that of each individual component and may explain why lung fibrosis is rarely if ever induced by exposure to pure cobalt dust.
Lasfargues
G
G
Industrial Toxicology and Occupational Medicine Unit, School of Medicine, Catholic University of Louvain, Brussels, Belgium.
Lison
D
D
Maldague
P
P
Lauwerys
R
R
D000818:Animals; D001682:Biological Availability; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003035:Cobalt / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000652:urine; D004391:Dust / Q000009:adverse effects; D005260:Female; D008168:Lung / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014132:Trachea; D014414:Tungsten / Q000009:adverse effects* / Q000494:pharmacology; D017973:Tungsten Compounds
D004391:Dust; D017973:Tungsten Compounds; C002802:tungsten carbide; D003035:Cobalt; D014414:Tungsten