Biokinetics and effects of barium sulfate nanoparticles

BACKGROUND: Nanoparticulate barium sulfate has potential novel applications and wide use in the polymer and paint industries. A short-term inhalation study on barium sulfate nanoparticles (BaSO(4) NPs) was previously published [Part Fibre Toxicol 11:16, 2014]. We performed comprehensive biokinetic studies of (131)BaSO(4) NPs administered via different routes and of acute and subchronic pulmonary responses to instilled or inhaled BaSO(4) in rats. METHODS: We compared the tissue distribution of (131)Ba over 28 days after intratracheal (IT) instillation, and over 7 days after gavage and intravenous (IV) injection of (131)BaSO(4). Rats were exposed to 50 mg/m(3) BaSO(4) aerosol for 4 or 13 weeks (6 h/day, 5 consecutive days/week), and then gross and histopathologic, blood and bronchoalveolar lavage (BAL) fluid analyses were performed. BAL fluid from instilled rats was also analyzed. RESULTS: Inhaled BaSO(4) NPs showed no toxicity after 4-week exposure, but a slight neutrophil increase in BAL after 13-week exposure was observed. Lung burden of inhaled BaSO(4) NPs after 4-week exposure (0.84 ± 0.18 mg/lung) decreased by 95% over 34 days. Instilled BaSO(4) NPs caused dose-dependent inflammatory responses in the lungs. Instilled BaSO(4) NPs (0.28 mg/lung) was cleared with a half-life of ≈ 9.6 days. Translocated (131)Ba from the lungs was predominantly found in the bone (29%). Only 0.15% of gavaged dose was detected in all organs at 7 days. IV-injected (131)BaSO(4) NPs were predominantly localized in the liver, spleen, lungs and bone at 2 hours, but redistributed from the liver to bone over time. Fecal excretion was the dominant elimination pathway for all three routes of exposure. CONCLUSIONS: Pulmonary exposure to instilled BaSO(4) NPs caused dose-dependent lung injury and inflammation. Four-week and 13-week inhalation exposures to a high concentration (50 mg/m(3)) of BaSO(4) NPs elicited minimal pulmonary response and no systemic effects. Instilled and inhaled BaSO(4) NPs were cleared quickly yet resulted in higher tissue retention than when ingested. Particle dissolution is a likely mechanism. Injected BaSO(4) NPs localized in the reticuloendothelial organs and redistributed to the bone over time. BaSO(4) NP exhibited lower toxicity and biopersistence in the lungs compared to other poorly soluble NPs such as CeO(2) and TiO(2). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-014-0055-3) contains supplementary material, which is available to authorized users.