Comparison of Early Lung Clearance of Yellowcake Aerosols in Rats With in Vitro Dissolution and IR Analysis

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Abstract
The lung retention of U was determined in rats that inhaled aerosols of commercial yellowcake powders obtained from 2 mills (A and D) and whose chemical composition and solubilities in vitro were significantly different. Analysis by IR absorption indicated mill A yellowcake contained 82% ammonium diuranate (ADU) and 18% U3O8. The mill D powder contained 25% ADU and 75% U3O8. In vitro dissolution studies indicated for the mill A sample, .apprx. 85% of the U had a dissolution half-time (t1/2) of < 1 day, with the remainder dissolving with a half-time of 500 days. For the mill D sample, 25% had t1/2 < 1 day and 75% had t1/2 of 300 days. Groups of 50 rats were exposed by nose-only inhalation to aerosols of the mill A or D yellowcake. Rats were sacrificed in groups of 5 at intervals through 6 mo. after exposure. Selected tissues and excreta samples were assayed by fluorometry to determine their U contents. For the mill A yellowcake, 78% initial lung (bronchoalveolar) burden cleared with t1/2 of 0.5 days and 22% with t1/2 of 240 days. For the mill D yellowcake, 25% initial lung burden cleared with t1/2 of 3.5 days and 75% with t1/2 of 110 days. The lung clearance of U in the rat mimicked the in vitro dissolution data and supported the contention that ADU should be considered as a class D compound (t1/2 = 0.5 days) and U3O8 behaved in the lung as a class Y (t1/2 > 100 days) material.