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Fate of barium sulfate nanoparticles deposited in the lungs of rats

: Molina, Ramon M.; Konduru, Nagarjun V.; Queiroz, Priscila M.; Figueroa, Benjamin; Fu, Dan; Ma-Hock, Lan; Gröters, Sibylle; Schaudien, Dirk; Brain, Joseph D.

American Journal of Respiratory and Critical Care Medicine 199 (2019), Abstract A1844
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2019, Dallas/Tex.>
Fraunhofer ITEM ()

Rationale: We have shown that lung clearance of barium [from BaSO4 nanoparticles (NPs)] was faster than that of other poorly soluble NPs, and that barium translocated mostly to the bone. The mechanism of translocation of barium to the bone is not well understood. Methods: We now studied the biokinetics of barium during 1) Study 1: two-year inhalation exposure of rats to 50 mg/m3 BaSO4 NP aerosols and 2) Study 2: single intratracheal (IT) instillation of BaSO4 NPs or soluble BaCl2. BaCl2 was studied to help determine the contribution of particle dissolution on biokinetics of BaSO4 NPs. Barium concentration of the lungs and other organs were analyzed by inductively-coupled plasma mass spectrometry. These organs were also examined for the presence of BaSO4 particles by transmission electron microscopy (TEM) and stimulated Raman spectroscopy (SRS). Results: (Study1). Our data showed that barium retention in the lungs increased during 360 days of aerosol exposures. A constant value was established from that point until 730 days. During that period, deposition rate equaled clearance rate. Barium concentrations in the BaSO4-exposed animals were in the order (lungs > lymph nodes > hard bone > bone marrow > liver). The clearance half-time of barium for exposures ending on day 90 for an initial burden of 1.6 mg (1.24 mg/g) was 56 days. (Study 2). There was a dose-dependent increase in lung retention of barium post-IT instillation of BaSO4 NPs while barium ions (BaCl2) was cleared almost completely by day 28. More barium was retained in the bones of rats instilled with BaCl2 versus BaSO4 NPs. TEM showed intact BaSO4 NPs in alveolar macrophages and type II epithelial cells in the lungs from Study 1 and 2 and in tracheobronchial lymph nodes in Study 1. No particles were seen in the bone marrow, liver, and lungs of air-exposed control and BaCl2-instilled rat lungs. Using SRS, specific BaSO4 Raman spectra were recorded in the lungs of rats instilled with BaSO4 NPs but not in the bone, liver, spleen or kidneys from BaCl2- and BaSO4-instilled rats. Conclusion: We conclude that barium translocation from the lungs occurs after dissolution of BaSO4 NPs mostly within alveolar macrophages. Some intact BaSO4 particles which were extracellular or in phagocytic cells can translocate to lung-associated lymph nodes. However, the substantial presence of barium in the bone is not from intact BaSO4 NPs but from barium ions incorporated into the bone.