Abstract
We have shown that barium [from BaSO4 nanoparticles (NPs)] was cleared from the lungs faster than other poorly soluble NPs and translocated mostly to bone. We now studied barium biokinetics in rats during Study 1: two-year inhalation exposure to 50 mg/m3 BaSO4 NP aerosols, and Study 2: single intratracheal (IT) instillation of increasing doses of BaSO4 NPs or BaCl2. Study 1 showed that lung barium content measured by inductively coupled plasma mass spectrometry increased during 360 days of BaSO4 NP aerosol exposures. An equilibrium was established from that time until 2 years. Barium concentrations in BaSO4-exposed animals were in the order (lungs > lymph nodes > hard bone > bone marrow > liver). In Study 2, there was an increase in lung barium post-IT instillation of BaSO4 NPs while barium from BaCl2 was mostly cleared by day 28. Transmission electron microscopy showed intact BaSO4 NPs in alveolar macrophages and type II epithelial cells, and in tracheobronchial lymph nodes. Using stimulated Raman scattering microscopy, specific BaSO4 Raman spectra were detected in BaSO4 NP-instilled lungs and not in other organs. Thus, we posit that barium from BaSO4 NPs translocates from the lungs mainly after dissolution. Barium ions are then incorporated mostly into the bone and other organs.
Highlights
The toxicity and biokinetics of nanoparticles are influenced by their physicochemical properties[12,13,14,15,16]
Selected physicochemical endpoints for NM-220 and the similar reproduced BaSO4 NPs used in Study 1 are summarized in Table S1 (Supplement)
We have previously reported that lung clearance of barium from BaSO4 was far faster than cerium from CeO2 NPs (9.6 vs. 140 days), despite BaSO4 NPs having low dissolution rates in various simulant fluids[18,20]
Summary
The toxicity and biokinetics of nanoparticles are influenced by their physicochemical properties[12,13,14,15,16]. In the earlier phase of this project, we found that despite the reported low solubility of BaSO4 NPs, barium was cleared from the lungs much more rapidly compared to other poorly soluble nanoparticles, including CeO23,18,20 Since it was established in short-term inhalation studies that BaSO4 does not cause adverse health effects[26,27,28] at the doses studied, a concentration of 50 mg/m3 was selected by BASF SE for the 2-year repeated inhalation exposures, a level at which lung overload might be expected. Neither method could differentiate whether the measured barium was present in intact BaSO4 NPs, ionic barium or new structural forms containing Ba. The aims of our research are: Study 1 to measure retention of barium in multiple organs of rats that inhaled BaSO4 NPs during the 2-year inhalation exposure described earlier and Study 2 to examine the role of BaSO4 particle dissolution in the translocation of barium from the lungs to extra-pulmonary tissues especially the bone and lymph nodes. Our overall goal was to explore the mechanisms of clearance of BaSO4 NPs from the lungs and to quantify and understand the mechanisms for the retention of barium in extrapulmonary organs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
