Characterization of phagolysosomal simulant fluid for study of beryllium aerosol particle dissolution.

A simulant of phagolysosomal fluid is needed for beryllium particle dissolution research because intraphagolysosomal dissolution is believed to be a necessary step in the cellular immune response associated with development of chronic beryllium disease. Thus, we refined and characterized a potassium hydrogen phthalate (KHP) buffered solution with pH 4.55, termed phagolysosomal simulant fluid (PSF), for use in a static dissolution technique. To characterize the simulant, beryllium dissolution in PSF was compared to dissolution in the J774A.1 murine cell line. The effects of ionic composition, buffer strength, and the presence of the antifungal agent alkylbenzyldimethylammonium chloride (ABDC) on beryllium dissolution in PSF were evaluated. Beryllium dissolution in PSF was not different from dissolution in the J774A.1 murine cell line (p = 0.78) or from dissolution in another simulant having the same pH but different ionic composition (p = 0.73). A buffer concentration of 0.01-M KHP did not appear adequate to maintain pH under all conditions. There was no difference between dissolution in PSF with 0.01-M KHP and 0.02-M KHP (p = 0.12). At 0.04-M KHP, beryllium dissolution was increased relative to 0.02-M KHP (p = 0.02). Use of a 0.02-M KHP buffer concentration in the standard formulation for PSF provided stability in pH without alteration of the dissolution rate. The presence of ABDC did not influence beryllium dissolution in PSF (p = 0.35). PSF appears to be a useful and appropriate model of in vitro beryllium dissolution when using a static dissolution technique. In addition, the critical approach used to evaluate and adjust the composition of PSF may serve as a framework for characterizing PSF to study dissolution of other metal and oxide particles.

[1]  A. Hodgson,et al.  Factors affecting the in vitro dissolution of cobalt oxide. , 1992, Environmental Health Perspectives.

[2]  J. A. Mewhinney,et al.  Cytotoxicity, uptake and dissolution of 241AmO2 particles in dog alveolar macrophages in vitro. , 1992, International journal of radiation biology.

[3]  A. F. Eidson,et al.  IN VITRO SOLUBILITY OF YELLOWCAKE SAMPLES FROM FOUR URANIUM MILLS AND THE IMPLICATIONS FOR BIOASSAY INTERPRETATION* , 1980, Health physics.

[4]  Baron Dn,et al.  Intracellular concentrations of water and of the principal electrolytes determined by analysis of isolated human leucocytes. , 1969 .

[5]  H. Métivier,et al.  Beryllium Metal Solubility in the Lung, Comparison of Metal and Hot-pressed Forms by in vivo and in vitro Dissolution Bioassays , 1987, Human toxicology.

[6]  W. Kreyling,et al.  Phagolysosomal pH and dissolution of cobalt oxide particles by alveolar macrophages. , 1992, Environmental Health Perspectives.

[7]  A. Eklund,et al.  Dissolution of metals by human and rabbit alveolar macrophages. , 1985, British journal of industrial medicine.

[8]  Marcello Pagano,et al.  Principles of Biostatistics , 1992 .

[9]  Mark D. Hoover,et al.  Determination of the oxide layer thickness on beryllium metal particles. , 1989, American Industrial Hygiene Association journal.

[10]  P. Ralph,et al.  Phagocytosis and cytolysis by a macrophage tumour and its cloned cell line , 1975, Nature.

[11]  T. Knudsen,et al.  Dissolution behaviour of biosoluble HT stone wool fibres , 2001 .

[12]  D. Butt,et al.  The Passivity and Breakdown of Beryllium in Aqueous Solutions , 1998 .

[13]  C. L. Sanders,et al.  Pulmonary macrophage and epithelial cells , 1977 .

[14]  W G Kreyling,et al.  In vitro dissolution of uniform cobalt oxide particles by human and canine alveolar macrophages. , 1990, American journal of respiratory cell and molecular biology.

[15]  L. Richeldi,et al.  HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. , 1993, Science.

[16]  S. Y. Helfinstine,et al.  In vitro dissolution of curium oxide using a phagolysosomal simulant solvent system. , 1992, Environmental health perspectives.

[17]  Mark D. Hoover,et al.  Dosimetry of beryllium in cultured canine pulmonary alveolar macrophages. , 1991, Journal of toxicology and environmental health.

[18]  O. Raabe,et al.  Measurement of in vitro dissolution of aerosol particles for comparison to in vivo dissolution in the lower respiratory tract after inhalation. , 1973, Health physics.

[19]  P. Camner,et al.  Intraphagosomal pH in alveolar macrophages studied with fluorescein-labeled amorphous silica particles. , 1989, Experimental lung research.

[20]  A. Black,et al.  Regional deposition of 2.5-7.5 μm diameter inhaled particles in healthy male non-smokers , 1978 .

[21]  R. Dean,et al.  Lysosomes in biology and pathology , 1969 .

[22]  J. A. Mewhinney,et al.  An interspecies comparison of the phagocytosis and dissolution of 241AmO2 particles by rat, dog and monkey alveolar macrophages in vitro. , 1992, International journal of radiation biology.

[23]  P Camner,et al.  Estimation of pH in individual alveolar macrophage phagolysosomes. , 1989, Experimental lung research.

[24]  Mark D. Hoover,et al.  Surface area of respirable beryllium metal, oxide, and copper alloy aerosols and implications for assessment of exposure risk of chronic beryllium disease. , 2003, AIHA journal : a journal for the science of occupational and environmental health and safety.

[25]  W. Kreyling,et al.  Interspecies Comparison of Phagolysosomal pH in Alveolar Macrophages , 1991 .

[26]  James Lawder Gamble,et al.  Chemical anatomy, physiology and pathology of extracellular fluid : a lecture syllabus , 1952 .

[27]  P. Camner,et al.  Ability of rabbit alveolar macrophages to dissolve metals. , 1984, Experimental lung research.

[28]  Mark D. Hoover,et al.  In vitro dissolution characteristics of beryllium oxide and beryllium metal aerosols , 1988 .

[29]  R. Guilmette,et al.  Review and critical analysis of available in vitro dissolution tests. , 1999, Health physics.

[30]  W. Kreyling,et al.  Intraphagolysosomal pH in canine and rat alveolar macrophages: flow cytometric measurements. , 1992, Environmental health perspectives.

[31]  A. Koenig,et al.  Measurement of in- vitro fibre dissolution rate at acidic pH , 1998 .

[32]  E. Marafante,et al.  Dissolution of two arsenic compounds by rabbit alveolar macrophages in vitro. , 1987, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[33]  S. Burastero,et al.  Beryllium chemical speciation in elemental human biological fluids. , 2003, Chemical research in toxicology.

[34]  Mercer Tt On the role of particle size in the dissolution of lung burdens. , 1967 .

[35]  M. L. Laucks,et al.  Aerosol Technology Properties, Behavior, and Measurement of Airborne Particles , 2000 .