The Effect of In Vitro Dissolution System Parameters for Measuring the Solubility of Uranium Aerosols

The use of in vitro dissolution tests for estimating the in vivo solubility of inhaled radioactive aerosols is being increasingly considered for both prospective and retrospective exposure/dose assessments, mainly because such tests are relatively simple to conduct (compared to in vivo experiments) and because current respiratory tract dosimetry models (e.g., ICRP Publication 66, 1994) provide a mechanism for incorporating in vitro dissolution data into calculations of dose. However, there uncertainties continue regarding the accuracy of results obtained with in vitro systems in mimicking in vivo dissolution. We studied the influence of solvent chemical composition and oxidizing potential in altering the in vitro dissolution rates of commercially available UO2 and UO3 powders as well as an industrially derived U3O8 material. Prior to testing, all powders were size-separated using a 5-stage aerosol cyclone separator, so that respirable particles characteristic of workplaces were tested (4.3 μm AD D 10 μm). Each sample was placed in a static test system using the LRRI synthetic ultrafiltrate (SUF) of Kanapilly et al. The composition of the SUF was varied by removing key components, carbonate and phosphate, either singly or together, and adding O2 and/or pyrogallol (generator of superoxide radicals). The results indicated that carbonate and phosphate anions play a major role in determining the rates of dissolution of uranium aerosols, and that the effect increased with increasing intrinsic solubility. In comparison, the presence of O2 and O2 caused only minor increases or decreases in solubility, without a trend in either direction. For the uranium aerosols tested here, the effect of choice of dissolution system parameters on solubility classification and dose coefficients increased with increasing intrinsic solubility. INTRODUCTION The International Commission on Radiological Protection (ICRP), in its recommendations for limiting intakes of radionuclides by workers [1], has consistently recognized that “The behaviour of any specific material may be expected to vary significantly from that of the model employed, and alterations should be made in the application of the model when specific data are available to justify such alterations.” As such, the most recent ICRP respiratory tract dosimetry model (ICRP Publication 66 [2]) provides methods for using material-specific information, e.g., on particle size or solubility of aerosols, for assigning compounds to specific absorption classes and for calculating dose coefficients. Various sources of information can be used to “customize” dose assessments for specific materials. These include 1) direct measurements of the radioelement of interest in humans, 2) observations of the behavior of chemically similar elements in humans; 3) experimental measurements of the behavior of the radioelement in nonhuman species, 4) experimental measurements of chemically similar elements in non-human species, and 5) in vitro studies. This paper concerns the use of in vitro dissolution data for characterizing the in vivo solubility of specific uranium powders. Several parameters used in designing in vitro dissolution systems were also studied as a means of estimating the uncertainty of the data obtained with such systems. Uranium Solubility Large amounts of uranium are handled in the nuclear industry, and in a wide range of physical and chemical forms. These include oxides, inorganic and organic phosphates, carbonates, chlorides, nitrates, sulfates, fluorides (solid and gaseous forms), ammonium diuranates etc. Reviews of the industrial processes involving uranium [3] and the solubility characteristics of the various chemical forms of uranium [4] have been published. Both indicate that workers are often at risk of exposure to more than one physicochemical form of uranium, and that the solubility characteristics of the different forms of uranium can range from very soluble to very insoluble. The potential for such exposures complicates the task of evaluating bioassay data obtained from workers exposed to uranium. Studies of inhaled compounds of uranium have shown that the rapidly dissolved fraction of a uranium aerosol deposited in the lung is absorbed efficiently into the blood where it is transported mainly to the kidneys and bone, or is excreted into the urine. The rate of in vivo dissolution will determine the extent and rate at which the uranium is retained in lung, transferred to blood, deposited in kidney and bone, or excreted in urine and feces (the latter pathway due to clearance of uranium particles from lung to the gastrointestinal tract via mucociliary