Long-term Clearance of Inhaled UO2 Particles from the Pulmonary Region of the Rat

Abstract

This paper reports on an enriched uranium dioxide (UO2) mass clearance study undertaken with Fischer-344 rats. The UO2 had a uranium (U) isotopic composition of 0.79% 234U, 92.8% 235U, 0.34% 236U and 6.06% 238U, by mass, with an alpha-particle activity of 1.91 Bq micrograms-1. Forty-six rats were exposed to an enriched UO2 aerosol that had an activity median particle aerodynamic diameter ranging from 2.7 to 3.2 microns. The rats were killed from 1 to 720 d post-inhalation (PI). The mass of enriched UO2 present in the trachea, lung lobes, thoracic lymph nodes, kidneys, liver, spleen, gut, and the remainder of the carcass was assessed at death. At 720 d after exposure, 82% of the total body burden of enriched UO2 was in the lung, with a further 10% in the thoracic lymph nodes. This represented 17% and 2% of the original (5 d PI) lung burden. The mass clearance of enriched UO2 from the lung was fitted to a single exponential function, normalized to 100% at 5 d PI. The rate constant (k) was 2.8 X 10(-3) d-1, giving a clearance half-time of 247 d. Although statistical comparisons with the majority of published data were not possible, it appeared that both enriched UO2 and natural UO2 particles cleared at rates that were broadly similar, with a t1/2 in the rat lung of 150 to 300 d over the 5- to 720-d PI period. As a consequence of the 234U component in the inhaled UO2 particles, the rats killed at 720 d PI received a total mean accumulated alpha-particle dose averaged over the whole lung of 5.7 Gy. Histologic investigations of the rat lungs found that widespread lung disease was only observed in animals killed at 720 d PI.

Dosimetric implications of pulmonary macrophage clusters observed within lungs of rats that have inhaled enriched UO2 particles.

“…The dose rate within the small macrophage clusters was estimated to be 0.033 ± 0.015 Gy/day (n = 11), and the dose rate within the large macrophage clusters 207 was estimated to be 0.130 ± 0.083 Gy/day (n = 6). In comparison, the dose rate averaged over the whole lung was estimated to be 0.021 Gy/day at 4 days PI, 0.0057 Gy/day at 360 days PI, and 0.0026 Gy/day at 630 days PI (9). If it is assumed that the macrophage clusters remain at the same location within the lung once formed, this suggests the total accumulated dose within small clusters will be 18 Gy over the 180-to 720-day PI period.…”

“…A complete description ofthe exposure F these rats is given by Morris et al (9). The acti aerodynamic diameter ofthe aerosol ranged from 2 with a geometric standard deviation of 1.7.…”

“…At 5 days PI, the mass ofenriched U02 retained in estimated by using a small animal whole-body -y counter (9). The mean initial burden ofall the rats v ,ug (SD), with the lowest burden at 136 jg and the h Mg.…”

“…By 45, 90, 180, 360, 540, and 720 days PI, the animals were estimated to have received a total a-particle dose, averaged over the whole lung, of0.9, 1.6,2.9, 4.4, 5.2, and 5.7 Gy, respectively (9). Thus the large macrophage clusters observed may have occurred too late in the animals' lives to be important in terms of dose to cells at risk ofcancer induction.…”

“…However, as most ofthe particles seen are likely to have originally come from the alveolar region, the unknown residence times in the human alveoli and latterly in the lymphatic tissue must also be taken into account. Also, the majority ofparticles inhaled would normally be cleared from the lung over the individuals lifetime (15), either completely from the individual via the mucociliary escalator or, probably to a much lesser extent, to the thoracic lymph nodes (9). It is likely that a substantial part ofthe total aparticle irradiation ofthe lung will come from those particles that clear in such a manner and leave the lung long before lung disease would be clinically detected.…”