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.