Simulated Lung Fluid Research Articles

Solubility of Metals in Windblown Dust from Mine Waste Dump Sites

Abstract Threshold limit values for metal compounds are listed for specific salts, for fumes or dusts, or for soluble or insoluble compounds. The values for soluble compounds are usually lower than for insoluble compounds, reflecting the greater ability of the soluble compounds to enter the body and cause systemic toxicity. Neither the chemical composition nor the solubility of metals in windblown dust from mine waste dump sites is usually known. Four such sites in Butte, Montana, were investigated. Arsenic, cadmium, copper, manganese, and lead in windblown dust as a function of particle size and of solubility in simulated fluids of the lungs, stomach, and intestines were measured. Lead compounds showed the poorest solubility except for the samples from the Corra site. Manganese, cadmium, and copper compounds tended to be reasonably soluble in both simulated lung and stomach fluids. Arsenic compounds only had significant solubility in the acidic simulated stomach fluids. Only manganese showed reasonable solubility in simulated intestinal fluid. For the investigation of metals in dust samples of unknown composition, it is recommended that duplicate samples be obtained, one for total metal content and the other for dissolution in acidic simulated stomach fluid. Significant differences in metal content between the two samples should be taken into account to assess the potential hazard for systemic toxicity.

Mineral Fibres–What Research is Still Needed?

Fibre morphology, chemistry and surface properties are recognized as critical to the carcinogenic potential of fibres. Yet there remains uncertainty about which fibre dimensions are safe, what effect variations in chemistry can have, which surface properties are important. The biopersistence of respirable fibres needs to be determined. Clearance has at least five components: solubility; fibre-breaking; phagocytosis; translocation; and sequestration. The contributions of each of these components and their interactions need to be assessed. Existing laboratory tests of durability examine solubility in simulated lung fluids, and have not been shown to be adequate tests of biopersistence. Even if a fibre persists in the lung, its interactions with cells remain poorly understood. There is increasing evidence of important differences in cellular responses between species: man, rat and hamster. Much work is needed not only to unravel the mechanisms of fibre-induced cancer, but also to permit well-based regulatory-decisions to be taken.

In vitro chemical and cellular tests applied to uranium trioxide with different hydration states.

A simple and rapid in vitro chemical solubility test applicable to industrial uranium trioxide (UO3) was developed together with two in vitro cellular tests using rat alveolar macrophages maintained either in gas phase or in alginate beads at 37 degrees C. Industrial UO3 was characterized by particle size, X-ray, and IR spectra, and chemical transformation (e.g., aging and hydration of the dust) was also studied. Solvents used for the in vitro chemical solubility study included carbonates, citrates, phosphates, water, Eagle's basal medium, and Gamble's solution (simulated lung fluid), alone, with oxygen, or with superoxide ions. Results, expressed in terms of the half-time of dissolution, according to International Commission on Radiological Protection (ICRP) classification (D,W,Y), varied for different hydration states of UO3, showing a lower solubility of hydrated UO3 in solvents compared to basic UO3 or UO3 heated at 450 degrees C. Two in vitro cellular tests on cultured rat alveolar macrophages (cells maintained in gas phase and cells immobilized in alginate beads) were used on the same UO3 samples and generally showed a lower solution transfer rate in the presence of macrophages than in the culture medium alone. The results of in vitro chemical and cellular tests were compared, with four main conclusions: a good reproducibility of the three tests in Eagle's basal medium the effect of hydration state on solubility, the classification of UO3 in terms of ICRP solubility criteria, and the ability of macrophages to decrease uranium solubility in medium.

Flow-Through Dissolution of Uranium-Thorium Ore Dust, Uranium Concentrate, Uranium Dioxide, and Thorium Alloy in Simulated Lung Fluid

Flow-Through Dissolution of Uranium-Thorium Ore Dust, Uranium Concentrate, Uranium Dioxide, and Thorium Alloy in Simulated Lung Fluid

Flow-Through Dissolution of Uranium-Thorium Ore Dust, Uranium Concentrate, Uranium Dioxide, and Thorium Alloy in Simulated Lung Fluid

Flow-Through Dissolution of Uranium-Thorium Ore Dust, Uranium Concentrate, Uranium Dioxide, and Thorium Alloy in Simulated Lung Fluid

Lung-clearance classification of radionuclides in coal fly ash.

Lung-clearance classifications for 238U, 232Th, 230Th, 228Th, 226Ra, 210Pb and 210Po in respirable coal fly ash were estimated for use with the lung clearance model proposed by the ICRP Task Group on Lung Dynamics. Estimates were based on measurements of the dissolution rates for these radionuclides from sized fly-ash samples into simulated lung fluid at 37 degrees C. The estimates were expressed in the classification terms of the model, i.e. D, W and Y, indicating lung clearance half-times of 0-10 days, 11-100 days, and more than 100 days, respectively. Ash from eastern bituminous coal, western bituminous coal and mid-western bituminous coal was examined. Both Class-D and Class-Y components of 238U were found in all samples, whereas all the other radionuclides dissolved very slowly and were classified 100% Class Y. The fraction of 238U in Class D increased with decreasing particle size and increased linearly from 0.02 to 0.17 as the concentration of U in the volatile-metal portion of the samples increased. This relationship suggests that a major fraction of the U in coal fly ash may be shielded from exposure to simulated lung fluid by more-abundant metals deposited on the outer surface of fly ash during coal combustion.

Techniques for Yellowcake Dissolution Studies in Vitro and Their Use in Bioassay Interpretation

The high variability in solubility of yellowcake produced by different mills complicates the interpretation of routine bioassay data. A simple in vitro dissolution test is needed for yellowcake to improve this interpretation. A series of experiments was designed to evaluate the relative importance of solvent composition, method, pH and temperature in determining yellowcake dissolution according to a model developed from the known composition of a test yellowcake and data from inhalation exposures of humans to UO3 or U3O8. Useful in vitro dissolution results can be obtained using either simulated serum ultrafiltrate or simulated lung fluid as the solvent if dissolved and undissolved yellowcake are separated by a membrane filter. In vitro dissolution experiments estimated the soluble portion of the test yellowcake within +/- 6% (mean +/- 2 S.E.) and showed that the dissolution rates of the more soluble and less soluble portions corresponded to Class D and Class Y compounds, respectively. It was not necessary to maintain physiological pH or temperature conditions to approximate the "human" model. The greatest utility of in vitro dissolution results was in the estimation of the more soluble fraction of the yellowcake and to indicate whether prior excretion of a Class D uranium compound and possible kidney damage could have occurred before detection of an exposure. Some guidelines for the use of in vitro dissolution data in biassay interpretation are suggested based on ICRP Publication 30 recommendations.

Dissolution rates of uranium compounds in simulated lung fluid

Maximum dissolution rates of uranium into simulated lung fluid were measured at 37°C to estimate clearance rates from the deep lung. The materials tested included: ore and yellowcake, an airborne sample from an industrial site, and purified samples of (NH 4) 2U 2O 7, U 3O 8, UO 2 and UF 4. A batch procedure was developed to test samples containing as little as 10 μg of natural uranium. Values of dissolution halftimes varied from 0.01 day to several thousand days depending on the physical and chemical form of the uranium. Dissolution occurred predominantly by formation of the [UO 2(CO 3) 3] 4−ion; and as a result, tetravalent uranium compounds dissolved slowly. Dissolution rates of size-separated yellowcake aerosols were found to be more closely correlated with specific surface area than with aerodynamic diameter.

Dissolution fractions and half-times of single source yellowcake in simulated lung fluids.

Thirty-five samples of yellowcake, the primary product of uranium milling, were obtained from industry. Samples were selected from the archives of 6 yr of yellowcake production from a single uranium milling operation. Ten representative samples were selected on the basis of color variation and chemical composition. Dissolution fractions and half-times were obtained using both simulated interstitial and simulated surfactant lung fluids maintained in vials submerged in a shaker water bath at 37 degrees C for 26 days. Samples were collected at 12 different time intervals and fresh simulant replaced. Uranium concentrations were analyzed by fluorometric methods using ASTM techniques. The fraction of the uranium undissolved, F, can be well modelled by the sum of three exponential terms: (See formula in text). Dissolution fractions and half-times in the two simulated lung fluids were found to be not significantly different. The point estimates for the six parameters (three fractions of the amount of uranium and the three associated half-times for dissolution) based on the analyses are: f1 equals 16.0% and t1/2(1) equals 3.5 hr, f2 equals 16.5% and t1/2(2) equals 4.4 days, and f3 equals 67.5% and t1/2(3) equals 224 days. The final characterization of yellowcake resulting from this investigation strongly suggests that dissolution rates of yellowcake from a single source may be individually process specific or site specific.

Production of 99mTc-labeled iron oxide aerosols for human lung deposition and clearance studies

Radiolabeled aerosols used in human lung deposition and clearance studies require nontoxic particles firmly tagged with low dose isotopes. An iron oxide sol was prepared by deionizing a ferric nitrate solution. A rapid and efficient method of labeling with 99 m Tc was developed. Initial binding approached 100% and product yields exceeded 90% for iron oxide concentrations greater than 1 mg ml −1. 99 m Tc leakage from both iron oxide aqueous colloids and monodisperse particles was assayed by pressure dialysis. Over 24 h, aqueous colloidal leaching in saline and simulated lung fluid was less than 2%, whereas particle leaching was 15.4% and 6.4%, respectively.

The Solubility of Some Uranium Compounds in Simulated Lung Fluid

Abstract Solubility studies, using a simulated lung fluid, have been carried out on a number of uranium compounds used in the manufacture of nuclear fuel elements in the Springfields Works of British Nuclear Fuels Limited. The work was concerned with those compounds which are sparingly soluble in water, since from operational experience and biological monitoring over many years, the classification of soluble uranium compounds was well established. From the results obtained, it was possible to allocate the compounds investigated to the appropriate biological clearance capacity (days, weeks, years) proposed by the ICRP Task Group on Lung Dynamics. An attempt to relate particle size to solubility, did not in general prove successful, but some evidence was obtained to indicate that thermal history may be as, or more important than particle size, in the particle size ranges investigated.