Table 5.

Summary of in vivo WC-Co toxicity studies

Method of delivery	Animal model & particle size	WC-Co dosage	Major outcome(s)	References
Intra-tracheal instillation (IT)	Rat Mixed WC-Co dusts ~0.1 to 6 μm	Single IT bolus at high dose (≥1 mg/kg body weight)	At 6 months following single IT WC-Co exposure, rats presented with pulmonary edema, alveolar congestion, and lung fibrosis in regions of deposited WC-Co dusts	89
IT	Rat 5 μm WC-Co	Single IT bolus at 1 mg/100 g body weight	WC-Co caused high mortality with massive pulmonary edema, increased macrophage counts, LDH, albumin and total protein content at 24 h post-exposure	90
IT	Rat 5 μm WC-Co	Single and repeated IT bolus at 1, 5, or 10 mg/kg body weight	Single IT WC-Co exposure caused acute alveolitis which persisted for about 1 month following the IT bolus. Repeated weekly exposure (4× for 1 month) caused interstitial lung fibrosis and increased lung hydroxyproline levels in exposed rats	91
IT	Rat 2 μm WC-Co	Single IT bolus at 16.6 mg/kg body weight	WC-Co exposure caused significant elevation of LDH, total protein & albumin in BAL fluids after 12 h and up to 72 h following exposure. In rat type II pneumocytes isolated after IT exposure, increased induction of micronuclei was observed, indicating genotoxicity and DNA damage	92
IT	Rat 2 μm WC-Co	Single IT bolus at 1 mg/100 g body weight	24 h after single IT WC-Co exposure, significant increases in LDH, total protein, and albumin were found in BAL fluids. WC-Co did not exert any effects on the levels of IL-1, TNFα, fibronectin, or cystatin-C in BAL fluids of exposed animals	72
IT	Rat 3 μm WC-Co	Single IT bolus at 2.5, 5, or 10 mg/100 g body weight	Pulmonary edema, fibrin formation, and increased number of inflammatory cells were observed in WC-Co-exposed rat lungs, along with decreased reactivity to methacholine, increased levels of nitric oxide synthase (NOS), LDH, total protein and albumin in BAL fluids	94
IT	Rat 1 μm WC-Co	Single IT bolus at 1 or 3 mg per rat	A significant increase in LDH was observed after 1, 4, 7, and 30 days of WC-Co exposure and fibrosis alveolitis developed in rats after 30 days post-IT exposure	95
IT	Rat 80 nm WC-Co 190 nm CeO	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 CeO2 NP group	96

Abbreviations: BAL, bronchoalveolar lavage; NP, nanoparticle; LDH, lactate dehydrogenase; WC-Co, tungsten carbide cobalt.