was used as a control. Tissue samples were collected at day 1, and at 6, 12, and 18 months after implantation. Bone and kidney were the primary reservoir for the uranium that had dissolved from embedded DU fragments. Dissolved uranium also localized within the central nervous system (CNS), lymph nodes, testes, and spleen (Pellmar et al., 1999a). Low levels of uranium were noted in the serum at all time points. The size of the pellets diminished with time.

Animal and In Vitro Studies

The following section summarizes and highlights a number of key animal and in vitro studies of the toxic effects of uranium. Researchers have examined the health effects of exposure to uranium via the inhalation, oral, and dermal routes; there are also studies on the effects of injected uranium and embedded DU fragments. A more thorough description of these studies and others can be found in the recent ATSDR (1999b) review.

Nonmalignant Respiratory Effects

Acute exposure to uranium (UF6; 10-minute exposure at 637 mg U/m3) resulted in gasping and severe irritation of the nasal passages in rats and mice (Spiegl, 1949); nasal hemorrhage occurred in rats after 5-minute exposure to 54,503 mg/m3 (Leach et al., 1984). These effects were most likely due to the hydrolysis of UF6 to hydrofluoric acid, a potent toxicant to respiratory tract epithelium (Spiegl, 1949; Leach et al., 1984).

Rats, mice, and guinea pigs exposed to uranium hexafluoride for an intermediate duration (6 hours a day for 30 days at 13 mg U/m3) showed pulmonary edema, hemorrhage, emphysema, and inflammation of the bronchi and alveoli (Spiegl, 1949). Cats and dogs exposed for 30 days to 18 mg U/m3 as uranium tetrafluoride or 5 weeks exposure to 9.2 mg U/m3 as uranyl fluoride exhibited rhinitis (Dygert et al., 1949). Notably, uranium dioxide and triuranium octaoxide, insoluble uranium compounds, did not lead to pulmonary toxicity. Hemorrhagic lungs were noted in dogs exposed to carnotite uranium ore, likely reflecting deeper penetration of this material into the dogs’ respiratory tract compared to guinea pigs and mice, which remained asymptomatic in similar exposure studies.

Rats, rabbits, guinea pigs, and dogs exposed to aerosols containing 0.05–10 mg U/m3 of various uranium compounds for 7–13 months did not suffer uranium-related histological damage to the lungs (Cross et al., 1981a,b). In a comprehensive study by Leach and colleagues (1970), lung damage did not occur in rats and dogs exposed to 5 mg U/m3 as uranium dioxide dust for 1–5 years (5.4 hours a day, 5 days a week). Occasional patchy hyaline fibrosis was evident in the tracheobronchial lymph nodes of dogs and monkeys exposed for a minimum of 3 years to the same concentrations of uranium (Leach et al., 1970).

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