Title: Biokinetics and effects of barium sulfate nanoparticles.

Authors: Konduru, Nagarjun; Keller, Jana; Ma-Hock, Lan; Gröters, Sibylle; Landsiedel, Robert; Donaghey, Thomas C; Brain, Joseph D; Wohlleben, Wendel; Molina, Ramon M

Published In Part Fibre Toxicol, (2014 Oct 21)

Abstract: 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 (BaSO₄ NPs) was previously published [Part Fibre Toxicol 11:16, 2014]. We performed comprehensive biokinetic studies of ¹³¹BaSO₄ NPs administered via different routes and of acute and subchronic pulmonary responses to instilled or inhaled BaSO₄ in rats.We compared the tissue distribution of ¹³¹Ba over 28 days after intratracheal (IT) instillation, and over 7 days after gavage and intravenous (IV) injection of ¹³¹BaSO₄. Rats were exposed to 50 mg/m³ BaSO₄ 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.Inhaled BaSO₄ 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 BaSO₄ NPs after 4-week exposure (0.84 ± 0.18 mg/lung) decreased by 95% over 34 days. Instilled BaSO₄ NPs caused dose-dependent inflammatory responses in the lungs. Instilled BaSO₄ NPs (0.28 mg/lung) was cleared with a half-life of ≈ 9.6 days. Translocated ¹³¹Ba 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 ¹³¹BaSO₄ 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.Pulmonary exposure to instilled BaSO₄ NPs caused dose-dependent lung injury and inflammation. Four-week and 13-week inhalation exposures to a high concentration (50 mg/m³) of BaSO₄ NPs elicited minimal pulmonary response and no systemic effects. Instilled and inhaled BaSO₄ NPs were cleared quickly yet resulted in higher tissue retention than when ingested. Particle dissolution is a likely mechanism. Injected BaSO₄ NPs localized in the reticuloendothelial organs and redistributed to the bone over time. BaSO₄ NP exhibited lower toxicity and biopersistence in the lungs compared to other poorly soluble NPs such as CeO₂ and TiO₂.

PubMed ID: 25331813

MeSH Terms: Administration, Oral; Air Pollutants/analysis; Air Pollutants/toxicity*; Animals; Barium Radioisotopes; Barium Sulfate/administration & dosage; Barium Sulfate/analysis; Barium Sulfate/chemistry; Barium Sulfate/toxicity*; Dose-Response Relationship, Drug; Female; Half-Life; Inhalation Exposure/adverse effects*; Injections, Intravenous; Intestinal Absorption; Intestinal Elimination; Lung/chemistry; Lung/drug effects*; Lung/immunology; Lung/pathology; Male; Metal Nanoparticles/administration & dosage; Metal Nanoparticles/analysis; Metal Nanoparticles/chemistry; Metal Nanoparticles/toxicity*; Pneumonia/chemically induced*; Pneumonia/immunology; Pneumonia/metabolism; Pneumonia/pathology; Rats, Inbred WKY; Respiratory Mucosa/chemistry; Respiratory Mucosa/drug effects*; Respiratory Mucosa/immunology; Respiratory Mucosa/pathology; Respiratory Tract Absorption; Solubility; Tissue Distribution; Toxicity Tests, Acute; Toxicity Tests, Subchronic; Toxicokinetics