Lung Cancer and Inhaled Uranium Ore Dust in Rats

Abstract

Using a nose only inhalation system, 187 nine week old male Sprague-Dawley rats were exposed to two different concentrations of natural uranium ore dust aerosol (44% U) without significant radon content. Inhalation exposures averaged about 4.2 h/day, 5 days/week for 65 weeks at which point lung uranium burdens in the two groups averaged 0.9 and 1.9 mg/g dry weight. Animals (63) exposed to the air stream without dust served as controls. After inhalation exposure ceased, the rats were allowed to live for their natural lifetime, a maximum of about 900 days after the start of dust inhalation. Lung uranium burdens were measured at the time of death of each animal. Lung burdens were found to decline exponentially after dust inhalation ceased, and the rate of decline was independent of the initial lung burden. All lungs were examined at necropsy and histologically for lung tumors. Lung tumors of lung origin were observed in both exposed groups and in the control group. The frequency of primary malignant lung tumors was 0.016,0.175 and 0.328 and primary non-malignant lung tumors 0.016,0.135 and 0.131 in the control, low and high aerosol exposed groups respectively. Absorbed dose to the lung was calculated for each animal in the study. The average maximum doses for all the animals exposed to the low or high concentration of dust aerosol were 0.87 Gy and 1.64 Gy respectively. The average risk of malignant lung tumors from inhaled natural uranium ore dust was therefore about 0.20 tumors/animal/Gy. For animals with lung tumors, the average doses were 0.98 and 1.90 in the exposed groups. In both exposed groups, the frequency of primary malignant or non-malignant lung tumors was significantly greater than in the control group (p < 0.02) and the frequency of primary malignant lung tumors in the two exposed group were significantly different from each other (p = 0.05). The frequency of primary lung tumors (malignant and non-malignant) was calculated as a function of dose increment for both exposed groups individually and combined. The data suggested that, in spite of the above result, lung tumor frequency does not increase with dose even though a risk that doubled with dose could have been detected. However, when malignant lung tumor frequency was calculated as a function of dose rate (as measured by the lung burden at the end of dust inhalation) a positive correlation was seen. suggesting dose rate may be a more important determinant of risk than dose. No strong lobe-to-lobe biases in tumor frequency were found. For the same absolute tumor incidence, lung tumor latency was longer in the group exposed to the low dust aerosol concentration, as compared to the group exposed to the higher concentration but on a relative basis there was no latency change. Uranium particulates in lung were rapidly transferred to bronchial lymph nodes. Lymph node specific burdens were variable, ranging from 1 to 60 fold greater than the specific lung burden in the same animal. No lymph node tumors were observed. We conclude that chronic inhalation of natural uranium ore dust alone in rats creates a risk of primary malignant and non-malignant lung tumor formation. The evidence suggests that risk is not directly proportional to dose and certainly does not double as dose doubles in the range below 1.5 Gy.