COMPARATIVE-STUDY OF THE ACUTE LUNG TOXICITY OF PURE COBALT POWDER AND COBALT TUNGSTEN CARBIDE MIXTURE IN RAT

被引:85
作者
LASFARGUES, G
LISON, D
MALDAGUE, P
LAUWERYS, R
机构
[1] CATHOLIC UNIV LOUVAIN,SCH MED,IND TOXICOL & OCCUPAT MED UNIT,3054 CLOS CHAPELLE CHAMPS,B-1200 BRUSSELS,BELGIUM
[2] CATHOLIC UNIV LOUVAIN,SCH MED,EXPTL PATHOL & CYTOL UNIT,B-1200 BRUSSELS,BELGIUM
关键词
D O I
10.1016/0041-008X(92)90277-Y
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 μm), pure tungsten carbide (WC) particles (d50:2 μm), tungsten carbide-cobalt (WC-Co) powder (d50:2 μm; cobalt 6.3%, tungsten 84%, carbon 5.4%) and crystalline silica (d50 < 5 μm) 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 10.06 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. © 1992.
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页码:41 / 50
页数:10
相关论文
共 33 条
[11]   PATHOGENESIS OF SILICOSIS - CURRENT CONCEPTS AND HYPOTHESES [J].
DAVIS, GS .
LUNG, 1986, 164 (03) :139-154
[12]  
DEMEDTS M, 1984, AM REV RESPIR DIS, V130, P130
[13]   RESPIRATORY-DISEASES FROM HARD METAL OR COBALT EXPOSURE - SOLVING THE ENIGMA [J].
DEMEDTS, M ;
CEUPPENS, JL .
CHEST, 1989, 95 (01) :2-3
[14]  
GORDON S, 1978, FED PROC, V37, P2754
[15]   EXPRESSION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR BY RAT PULMONARY ALVEOLAR EPITHELIAL-CELLS [J].
GROSS, TJ ;
SIMON, RH ;
SITRIN, RG .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1990, 3 (05) :449-456
[16]   ON THE QUESTION OF THE PATHOGENETIC IMPORTANCE OF COBALT FOR HARD METAL FIBROSIS OF THE LUNG [J].
HARTUNG, M ;
SCHALLER, KH ;
BRAND, E .
INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, 1982, 50 (01) :53-57
[17]   EARLY DAMAGE INDICATORS IN THE LUNG .3. BIOCHEMICAL AND CYTOLOGICAL RESPONSE OF THE LUNG TO INHALED METAL-SALTS [J].
HENDERSON, RF ;
REBAR, AH ;
PICKRELL, JA ;
NEWTON, GJ .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1979, 50 (01) :123-136
[18]   EARLY DAMAGE INDICATORS IN THE LUNGS .4. BIOCHEMICAL AND CYTOLOGIC RESPONSE OF THE LUNG TO LAVAGE WITH METAL-SALTS [J].
HENDERSON, RF ;
REBAR, AH ;
DENICOLA, DB .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1979, 51 (01) :129-135
[19]  
Henderson RF, 1985, IN VITRO EFFECTS MIN, P521
[20]   PLASMINOGEN-ACTIVATOR ACTIVITY OF NORMAL AND RETINOIC ACID-TREATED POSTIMPLANTATION EMBRYOS [J].
KNOOPS, B ;
LISON, D ;
COLLETTE, C ;
LAUWERYS, R ;
PICARD, JJ .
BIOCHEMICAL PHARMACOLOGY, 1990, 39 (10) :1545-1548