In vitro dissolution of curium oxide using a phagolysosomal simulant solvent system.

Abstract

Detailed study of actinide oxide behavior in alveolar macrophages (AM) in vitro is limited because of the short life span of these cells in culture. We created an in vitro dissolution system that could mimic the acidic phagolysosomal environment for the actinide and be maintained for an indefinite period so that dissolution of more insoluble materials could be measured. The dissolution system for this investigation, consisting of nine different solutions of HCl and the chelating agent diethylenetriamine pentaacetate (DTPA) in distilled water, is called the phagolysosomal simulant solvent (PSS). In this system, both the pH and the amount of DTPA were varied. We could observe the effect of altering pH within a range of 4.0-6.0 (similar to that of the phagolysosome) and the effect of the molar ratio of DTPA to curium at 1000:1, 100:1, or 10:1. We chose curium sequioxide (244Cm2O3) to validate the PSS for actinide dissolution versus that occurring in AM in vitro because it dissolves significantly in less than 1 week. The polydisperse 244Cm2O3) aerosol was generated, collected on filters, resuspended, and added to the PSS solutions and to cultured canine AM. By comparing dissolution in the two systems directly, we hoped to arrive at an optimum PSS for future dissolution studies. PSS and cell culture samples were taken daily for 7 days after exposure and tested for the solubilized curium. The amount of soluble material was determined by ultracentrifugation to separate the insoluble Cm2O3 from the soluble curium in the PSS solutions and filtration for the cell-containing material.(ABSTRACT TRUNCATED AT 250 WORDS)

ICRP Publication 141: Occupational Intakes of Radionuclides: Part 4

“…Curium sesquioxide appeared to dissolve faster than AmO 2 based on more rapid urinary excretion and decrease of whole-body burden in curium-exposed animals compared with americium-exposed animals given the same therapy. The analysis here of curium data for untreated animals gave f r = 0.2 and s s = 0.01 d −1 , consistent with assignment to Type M. (970) Helfinstine et al (1992) investigated the in-vitro dissolution kinetics of curium sesquioxide ( 244 Cm 2 O 3 ). The amount of soluble material was determined over 7 d in a phagolysosomal simulant solvent made of HCl aqueous solution with DTPA at a 10:1000 ratio with curium and pH 4–6, or in cultured dog alveolar macrophages.…”

“…(970) Helfinstine et al (1992) investigated the in-vitro dissolution kinetics of curium sesquioxide ( 244 Cm 2 O 3 ). The amount of soluble material was determined over 7 d in a phagolysosomal simulant solvent made of HCl aqueous solution with DTPA at a 10:1000 ratio with curium and pH 4–6, or in cultured dog alveolar macrophages.…”

Dissolution and biodurability: Important parameters needed for risk assessment of nanomaterials

“…Properties of the simulated fluid also affect the dissolution of particles and fibres and should be tailored to accurately model the biological fluid of interest. For example, the pH of the medium has an effect on the dissolution [ 83 ]. For this reason pulmonary dissolution studies are usually conducted at neutral pH as encountered outside cells and at acidic conditions, representing conditions inside the cell (around pH 4.5) and in lysosomes (around pH = 5.5).…”

ANNEX B: Deposition, characterisation, and sampling of radioactive aerosols

“…Another suitable application arises when a material consists of a mixture of compounds that have distinctly different in vivo dissolution characteristics: an in vitro test may be used to determine the fraction that is absorbed rapidly (Eidson and Griffith, 1984). Hence there are continuing efforts to develop reliable methods for appropriate circumstances (e.g., Eidson and Griffith, 1984;Ansoborlo et al, 1990;Duport et al, 1991;Helfinstine et al, 1992;Metzger et al, 1997;Ansoborlo et al, 1998). The main techniques applied in published papers are described in the following paragraphs.…”

“…(C106) Cellular dissolution systems (AM in culture) offer potential advantages over chemical simulants, but do not yet provide results that consistently agree with dissolution in vivo (Andre´et al, 1989a), possibly because of sensitivity to conditions in the culture medium. Their major limitation, however, is that lavaged alveolar macrophages can only be maintained in culture for about two weeks (Lirsac et al, 1989;Poncy et al, 1992;Helfinstine et al, 1992).…”