Uranium pulmonary toxicity

The pulmonary toxicity of uranium compounds varies in animals. Reports of pulmonary toxicity in animals after acute-duration exposure to uranium are limited to experiments with uranium hexafluoride. Gasping and severe irritation to the nasal passages were reported after 10 minute exposures at 637 mg U/mg in rats and mice (Spiegl 1949) and nasal hemorrhage in rats after a 5 minute exposure to 54,503 mg/m (Leach et al. 1984). Uranium hexafluoride promptly hydrolyzes on contact with water to uranyl fluoride and hydrofluoric acid. Thus, the animals were potentially exposed to hydrofluoric acid, a potent toxicant to respiratory tract epithelium, which probably contributed to pulmonary tissue destruction (Leach et al. 1984 Spiegl 1949 Stokinger et al. 1953). In addition, exposure to fluoride ions can result in hypocalcemia, hypomagnesemia, pulmonary edema, metabolic acidosis, ventricular arrhythmia, and death (Meditext 1998). 

The acute pulmonary toxicity of inhaled uranium is dependent on the chemical form of the uranium. Uranium hexafluoride is the only uranium compound that has been associated with acute effects after inhalation. Two accidents involving uranium hexafluoride have resulted in the deaths of three workers in the US uranium processing industry. However, the lethal effects were due to liberated hydrogen fluoride rather than the uranium. 

Soluble Compounds Animals repeatedly exposed to dusts of soluble uranium compounds in concentrations from 3 to 20mg/m died of pulmonary and renal damage both feeding and percutaneous toxicity studies on animals indicated that the more soluble compounds are the most toxic. In animals, effects on the liver are a consequence of the acidosis and azotemia induced by renal dysfunction. ... 

Uranium hexafluoride is hydrolyzed to uranyl fluoride and hydrogen fluoride. Hydrogen fluoride is highly toxic in acute exposures and causes pulmonary edema, which may be immediately life-threatening. 

Deaths occurred after accidental releases of uranium hexafluoride at uranium-processing facilities in 1944 and 1986, but these deaths were not attributed to the uranium component of this compound (Kathren and Moore 1986 Moore and Kathren 1985 USNRC 1986). These releases resulted in the generation of concentrated aerosols of highly toxic hydrofluoric acid and uranyl fluoride. In the 1944 incident exposure time was estimated to be only 17 seconds, deaths occurred in 2 of 20 workers within an hour and were attributed to severe chemical burns of the lungs. In the 1986 incident, 1 of 23 workers died from massive pulmonary edema, indicating that inhalation of hydrofluoric acid was responsible for death. Estimated airborne concentrations were 20 mg uranium hexafluoride/m for a 1-minute exposure and 120 mg uranium hexafluoride/m for a 60-minute exposure (15.2 and 91 mg U/m, respectively). 

In acute exposures, respiratory disease may be limited to interstitial inflammation of the alveolar epithelium, leading eventually to emphysema or pulmonary fibrosis (Cooper et al. 1982 Dungworth 1989 Stokinger 1981 Wedeen 1992). In studies of the pulmonary effects of airborne uranium dust in uranium miners and in animals, the respiratory diseases reported are probably aggravated by the inhalable dust particles (the form in which uranium is inhaled) toxicity because most of the respiratory diseases reported in these studies are consistent with the effects of inhaled dust (Dockery et al. 1993). In some of these instances, additional data from the studies show that the workers were exposed to even more potent respiratory tract irritants, such as silica and vanadium pentaoxide (Waxweiler et al. 1983). 

Most studies of respiratory diseases reported for uranium involve noncancerous alveolar epithelium damage in type II cells. These changes are characterized by interstitial inflammahon of the alveolar epithelium leading eventually to emphysema or pulmonary fibrosis in acute exposures or to hyperplasia, hypertrophy, and transdifferentiation (metaplasia) in chronic exposures (Cooper et al. 1982 Dungworth 1989 Stokinger 1981 Wedeen 1992). However, the lack of significant pulmonary injury in most inhalation animal studies indicates that other potentially toxic contaminants such as inhalable dust particles, radium, or radon may contribute to these effects. 

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