Cobalt bioavailability from hard metal particles. Further evidence that cobalt alone is not responsible for the toxicity of hard metal particles.
Hard metal is an alloy of tungsten carbide (WC) in a matrix of cobalt metal (Co). The inhalation of hard metal dust can cause an alveolitis which may progress to interstitial fibrosis. This study was undertaken to compare, both in vivo and in vitro, the bioavailability of cobalt metal when mixed or not with WC and to assess whether this factor had any influence on the cellular toxicity of hard metal particles. In vivo, non-toxic doses of cobalt metal were administered intratracheally in the rat, alone (Co, 0.03 mg/100 g) or mixed with tungsten carbide (WC-Co, 0.5 mg/100 g containing 6.3% of cobalt metal particles). Sequential measurements of cobalt in the lung and in urine demonstrated that the retention time of the metal in the lung was longer in Co- than in WC-Co-treated animals. In vitro, the cellular cobalt uptake was higher when the metal was presented to the macrophages as WC-Co. However, there was no relationship between the cellular uptake of cobalt and the occurrence of toxicity, since the intracellular concentration of cobalt associated with the occurrence of a cytotoxic effect of WC-Co particles was insufficient to exert the same effect when resulting from exposure to Co alone. This clearly indicates that increased bioavailability of cobalt is not the mechanism by which hard metal particles exhibit their cellular toxicity. These observations confirm and extend our previous findings supporting the view that cobalt is not the only component responsible for the toxicity of hard metal particles which should be considered as a specific toxic entity.
Lison
D
D
Industrial Toxicology and Occupational Medicine Unit, Catholic University of Louvain, Brussels, Belgium.
Lauwerys
R
R
D000280:Administration, Inhalation; D000497:Alloys / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001682:Biological Availability; D002478:Cells, Cultured; D003035:Cobalt / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity* / Q000652:urine; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014414:Tungsten / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
D000497:Alloys; C080121:hard metal; D003035:Cobalt; D007770:L-Lactate Dehydrogenase; D014414:Tungsten