An in vitro system for determining the dissolution of transuranic oxides deposited in the lung

Abstract

Methods currently available to assess dose from inhalation exposures to the transuranic oxides cannot accommodate the variety of exposure materials, nor the dissolution rates of the materials within the lungs. The purpose of this study was to develop an in vitro surrogate to mimic the dissolution of less soluble transuranics deposited in the lung. It is commonly assumed that dissolution occurring in the lung takes place within the alveolar macrophage (AM). A dissolution study with 244Cm2O3 was performed using cultured beagle AM and a series of solutions, created as surrogates for the AM phagolysosome, consisting of dilute HCl with DTPA. Results showed that dissolution in cells was negligible, and that the optimum molar concentration of DTPA to transuranic was 100:1. A series of experiments were conducted to measure phagolysosomal pH of AM in culture and in vivo using FITC-labeled amorphous silica particles. The phagolysosomal pH ([plus or minus] SD) for cultured cells fluctuated over the 14-day study period from 4.4 [plus or minus] 0.1 to 8.7 [plus or minus] 0.1. The AM exposed in vivo to the probe had constant pH of 4.6 [plus or minus] 0.2 and 5.2 [plus or minus] 0.2, depending upon measurement conditions. From the results of the pH measurements, surrogate dissolution measurements were interpolated for the selected surrogate at pH 4.6, with DTPA to transuranic ratio of 100:1. These results were then incorporated into a model proposed to correlate in vitro dissolution measurements with material retention in the lung following inhalation exposure (Guilmette and Kanapilly 1988). The model was derived from basic retention models to address retention and release of solubilized material from the AM. Lung retention predicted by the model for the in vitro dissolution data was similar to retention measured in the in vivo study.